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In geometry, the Murakami–Yano formula , introduced by Murakami & Yano (2005) , is a formula for the volume of a hyperbolic or spherical tetrahedron given in terms of its dihedral angles .
This geometry-related article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Murakami–Yano_formula |
A mural instrument is an angle measuring instrument mounted on or built into a wall. For astronomical purposes, these walls were oriented so they lie precisely on the meridian . A mural instrument that measured angles from 0 to 90 degrees was called a mural quadrant . They were utilized as astronomical devices in ancient Egypt and ancient Greece . Edmond Halley , due to the lack of an assistant and only one vertical wire in his transit , confined himself to the use of a mural quadrant built by George Graham after its erection in 1725 at the Royal Observatory, Greenwich . Bradley 's first observation with that quadrant was made on 15 June 1742. [ 1 ]
The mural quadrant has been called the "quintessential instrument" of 18th century (i.e. 1700s) observatories. [ 2 ] It rose to prominence in the field of positional astronomy at this time. [ 2 ]
Many older mural quadrants have been constructed by marking directly on the wall surfaces. More recent instruments were made with a frame that was constructed with precision and mounted permanently on the wall.
The arc is marked with divisions, almost always in degrees and fractions of a degree. In the oldest instruments, an indicator is placed at the centre of the arc . An observer can move a device with a second indicator along the arc until the line of sight from the movable device's indicator through the indicator at the centre of the arc aligns with the astronomical object . The angle is then read, yielding the elevation or altitude of the object. In smaller instruments, an alidade could be used. More modern mural instruments would use a telescope with a reticle eyepiece to observe the object.
Many mural quadrants were constructed, giving the observer the ability to measure a 90° range of elevation . There were also mural sextants that read 60°.
Mural quadrants of the 17th century were noted for their expense, with Flamsteed's 1689 quadrant costing £120 (equivalent to £27,488 in 2023), and Edmund Halley's 1725 quadrant which cost over £200 (equivalent to £37,619 in 2023). [ 2 ] The large fixed quadrants were more expensive than a typical portable quadrant, with a Bird 2-foot quadrant costing 70 guineas or £73.50 (equivalent to £13,825 in 2023). [ 2 ]
In order to measure the position of, for example, a star, the observer needs a sidereal clock in addition to the mural instrument. With the clock measuring time, a star of interest is observed with the instrument until it crosses an indicator showing that it is transiting the meridian. At this instant, the time on the clock is recorded as well as the angular elevation of the star. This yields the position in the coordinates of the instrument. If the instrument's arc is not marked relative to the celestial equator, then the elevation is corrected for the difference, resulting in the star's declination . If the sidereal clock is precisely synchronized with the stars, the time yields the right ascension directly. [ 3 ] | https://en.wikipedia.org/wiki/Mural_instrument |
Murashige and Skoog medium (or MSO or MS0 (MS-zero) ) is the most popular plant growth medium used in the laboratories worldwide for cultivation of plant cell culture on agar .
MS0 was invented by plant scientists Toshio Murashige and Folke K. Skoog in 1962 during Murashige's search for a new plant growth regulator . A number behind the letters MS is used to indicate the sucrose concentration of the medium. For example, MS0 contains no sucrose and MS20 contains 20 g/L sucrose. Along with its modifications, it is the most commonly used medium in plant tissue culture experiments in the laboratory. [ 1 ]
As Skoog's doctoral student, Murashige originally set out to find an as-yet undiscovered growth hormone present in tobacco juice . No such component was discovered; instead, analysis of juiced tobacco and ashed tobacco revealed higher concentrations of specific minerals in plant tissues than were previously known. A series of experiments demonstrated that varying the levels of these inorganic nutrients enhanced growth substantially over existing formulations. It was determined that nitrogen in particular enhanced growth of tobacco in tissue culture.
According to recent scientific findings, however, MS medium is not suitable as a nutrient solution for deep water culture or hydroponics , [ 2 ] and organic compounds are not required for normal plant nutrition. [ 3 ] | https://en.wikipedia.org/wiki/Murashige_and_Skoog_medium |
In the field of enzymology , murburn is a term coined by Kelath Murali Manoj that explains the catalytic mechanism of certain redox -active proteins. [ 1 ] [ 2 ] [ 3 ] The term describes the equilibrium among m olecules, u nbound ions and r adicals, signifying a process of " m ild u nrestricted r edox catalysis".
Murburn is abstracted from " mur ed bur ning " (connoting a "closed burning", an oxidative process), and implies equilibriums involving diffusible reactive oxygen species (DRS/DROS/ROS). Though akin to the oxygen assisted combustion of fuel, unlike the flames produced in the open burning process, the biological reaction occurs in enclosed premises, is mild and may generate heat alone (and no flames). Such a reaction could also incur selective and specific electron/moiety transfers.
Further, though burning is a reaction that usually involves oxygen (aerobic process), "burning flames" [ 4 ] produced by anoxic oxidants are also well-known. [ 4 ] Therefore, the enzymes working via murburn scheme (aerobic or anaerobic) could be called murzymes and the region around the biomolecule where the DRS interacts with the final ‘substrate’ is called ‘murzone’. [ 5 ]
While enzyme activities are classically defined by the interaction of the protein with its substrate at a defined active site (necessitating a topological recognition of the interactive participants), murburn scheme obligatorily invokes a DRS (or a reactive radical) for carrying out this agenda. [ 6 ] The conventional enzyme-substrate interaction scheme invokes Fischer ’s lock and key type affinity or Koshland ’s induced fit theory . That is, a substrate is identified by the enzyme by virtue of a topographical complementation, and thereafter, the enzyme-substrate complex undergoes a "transition-state," leading to products. [ 7 ]
Such a system shows certainty/determinism, usually abides by the standard models of kinetics (like Michaelis-Menten scheme ) and the inhibitors may be of competitive, non-competitive, uncompetitive, etc. The classical enzymes have a unique substrate or a well defined set of substrates.
In contrast, murburn scheme (as shown in figure) might invoke an enzyme-substrate complementation, but this aspect is not obligatory. The kinetics of the reaction may at times not be traceable with standard models because the diffusible reactive species is subjected to multiple equilibriums and the product of interest may be favorably formed only in discrete concentrations of the protagonists.
Therefore, the outcomes in such systems could be subjected to a lot of uncertainty and the overall reaction scheme might exhibit varying and non-integral stoichiometry. The modulators/influencers (activators or inhibitors) may work by mixed modalities, owing to affects on the protein, substrate or the diffusible species. The murzymes may have a wide variety of substrates, as the reaction scheme is dependent on multiple modalities of interactions and outcomes. These considerations seek us to overcome the aesthetic perspective that DROS are mere manifestations of pathophysiology. [ 8 ] [ 9 ] A relevant comparison is that the presence of knife-racks, cutting boards and gloves in kitchen (analogous to enzymes like superoxide dismutase and catalase, membrane-embedded proteins with one-electron active redox centers, etc.) does not mean that knife is a dangerous component that must be avoided. On the contrary, it is an important tool across the globe that has to be used with adequate care. Quite similarly, the cellular machinery has evolved to harness the reaction potential of DRS. The aesthetic perspective/concern that DRS would wreak havoc in routine physiology is no more relevant because several decades of research has now clearly established that DRS are routinely observed and unavoidable in physiology, and they cannot be just wished away. [ 10 ] It has also been demonstrated that sustained release of DRS could afford selectivity (choice of a particular reactant from a variety, say B from A, B, C and D) and specificity (attack at a specific locus, like alpha- or para- positions of a reactant). Therefore, such a selectivity can be compared to how setting fire to a damp cloth dipped in oil burns the oil first and minimally chars the cloth's fabric. Analogously, murburn activity has cumulative collateral damage, which leads to aging, and ultimately, death. Murburn concept stresses the already well-established fundamental awareness that all molecules/processes in life have spatial, temporal, quantitative and contextual relevance. A comparison of the classical perspectives and murburn concept is given in the figure and the perceptional changes ushered in by murburn concept can be captured in the Table 1. [ 11 ]
The new mechanism has been proposed as an explanation for phenomena involving catalytic electron or moiety transfers, chemico-physical changes and unusual observations in various experimental, ecological, metabolic and physiological scenarios. Fundamentally, murburn concept advocates the thesis that DRS are vital requirements for routine metabolic and physiological functions. This theory is validated by its ability to explain the toxicity of cyanide to a variety of important life processes (particularly, respiration and photosynthesis). [ 12 ] [ 13 ]
The murburn concept has been used to criticize classical perceptions like Peter Mitchell ’s and Paul Boyer ’s chemiosmotic rotary ATP synthesis mechanism. [ 51 ] [ 52 ] [ 53 ] These criticisms have been called into question. [ 54 ] [ 55 ] These criticisms have in turn been responded to. [ 56 ] [ 57 ]
The late Lowell Hager (Member, NAS-USA and Professor of Biochemistry at UIUC) recognized the DRS-mediated murburn selectivity/specificity mechanism in chloroperoxidase. [ 58 ] Two books authored by respected European researchers were published in the UK that favorably discussed murburn concept. [ 59 ] [ 60 ] [ 61 ] Articles based in murburn concept were given cover-page credits in four annual volumes ( 2017 , 2018 , 2019 and 2020 ) of Biomedical Reviews (the official journal of Bulgarian Society for Cell Biology ) and the 167th (December 2021) volume of Progress in Biophysics and Molecular Biology (Elsevier). The advocates of murburn concept have provided precepts and proof of concept for murburn models of diverse life processes (drug metabolism, cellular respiration, thermogenesis, homeostasis, photosynthesis, electrophysiology, photo-transduction in retina, lactate metabolism in liver, role of hemoglobin in erythrocytes, etc.). Their comparative analyses also address the essential theoretical criteria (thermodynamics, kinetics, mechanism, structure-function correlations, evolutionary considerations, Ockham's razor/probability, etc.) and reported experimental findings. These writings also present pan-systemic and holistic appeal of the new theory and call out the untenable nature of several classical perceptions. Thus, murburn concept is poised to expand the classical concepts of biocatalysis, biological electron transfers, metabolism and physiology, leading to the discontinuation of several unrealistic terms/ideas in classical redox enzymology (like - electron transport chain, Z-scheme, Q-cycle, Kok-Joliot cycle, chemiosmosis, proton motive force, rotary ATP synthesis, etc.) that are currently advocated in textbooks. The erstwhile terms were invented to explain redox protein activity when murburn concept was not unraveled and researchers had confined their explorations to active-site and affinity-based logic alone. Incorporating murburn concept in teaching and research is the next step in the sequence of scientific progression.
(i) Post-translational and epigenetic outcomes: Since murburn processes can introduce oxidative and group transfer (halogenation, phosphorylation, hydroxylation, etc.) reactions, the various biomolecules (like proteins, DNA, matrix components, etc.) could be subjected to corresponding modifications, leading to metabolo-proteomic influences. [ 62 ]
(ii) Murburn concept explains the structure-function correlation of Na,K-ATPase. [ 63 ]
(iii) Murburn concept serves as a unifying umbrella for connecting acute-timescale cellular powering, coherence, homeostasis, electro-physiological/mechanical and sensory/response facets. Thus, it should be considered as a fundamental principle of life, along with cell theory and central dogma. [ 49 ] [ 62 ]
(iv) The “auto-assembled molecular rotary” functionalisms in biology is conclusively disclaimed with murburn-centric criticisms, as both Complex V (earlier!) and bacterial flagella-aided motility are shown to be water-mobilizing systems. [ 64 ] [ 65 ]
(v) The relevance of murburn concept in genetic and acquired respiratory diseases was pointed out.[Kelath Murali Manoj. What Is the Relevance of Murburn Concept in Thalassemia and Respiratory Diseases? Thalass. Rep. 2023, 13(2), 144–151; https://doi.org/10.3390/thalassrep13020013 [ 66 ] ].
(vi) American Institute of Physics portal publishes two-part review of murburn concept explaining multiple metabolic and physiological routines. These developments support murburn concept as a fundamental principle explaining diverse cellular functionalisms. [ 67 ] [ 68 ] | https://en.wikipedia.org/wiki/Murburn_concept |
Murexide (NH 4 C 8 H 4 N 5 O 6 , or C 8 H 5 N 5 O 6 ·NH 3 ), also called ammonium purpurate or MX , is the ammonium salt of purpuric acid . It is a purple solid that is soluble in water. The compound was once used as an indicator reagent . [ 1 ] Aqueous solutions are yellow at low pH , reddish-purple in weakly acidic solutions, and blue-purple in alkaline solutions.
Murexide is prepared by treating alloxantin with ammonia to 100 °C, or by treating uramil (5-aminobarbituric acid) with mercury oxide . [ 2 ] It may also be prepared by digesting alloxan with alcoholic ammonia.
Justus von Liebig and Friedrich Wöhler in Giessen, Germany, had investigated the purple product, murexide, obtained from snake excrement in the 1830s, but this was not an abundant raw material, and a method of using it as a dyestuff was not established at that time. [ 3 ] In the 1850s, French colourists and dye-producers, such as Depoully in Paris, succeeded in making murexide from abundant South American guano and of applying it to natural fibres. It was then widely adopted in Britain, France and Germany.
Murexide is used in analytical chemistry as a complexometric indicator for complexometric titrations, most often of calcium ions, [ 4 ] but also for copper , nickel , cobalt , thorium and rare-earth metals. It functions as a tridentate ligand. [ 1 ]
Its use has been eclipsed by calcium- ion selective electrodes .
This article incorporates text from a publication now in the public domain : Chisholm, Hugh , ed. (1911). " Murexide ". Encyclopædia Britannica . Vol. 19 (11th ed.). Cambridge University Press. p. 36. | https://en.wikipedia.org/wiki/Murexide |
The murexide test is an analytical technique to identify the presence of caffeine and other purine derivatives in a sample. These compounds do not respond to the common alkaloid identification tests such as Dragendorff's reagent . In this test, crude drugs (to be identified) are mixed with a tiny amount of potassium chlorate and a drop of hydrochloric acid . The sample is then evaporated to dryness and the resulting residue is exposed to ammonia vapour. Purine alkaloids produce a pinkish-purple color in this test [ 1 ] [ 2 ] due to formation of murexide (ammonium purpurate ; appears purple in pure state), which the test is named after. [ 3 ]
In pure form, murexide appears purple, but when it is produced by reaction of acidified solutions of purines and ammonia, various shades of purple and pink are produced.
Murexide test is a color test for uric acid and some other purines. The (solid) sample is first treated with small volume of a concentrated acid such as hydrochloric acid , nitric acid , which is slowly evaporated away; subsequent addition of ammonia (NH 3 ) gives a purple color if uric acid was present, due to formation of murexide, or a yellow color that turns to red on heating if xanthine or its derivatives are present. | https://en.wikipedia.org/wiki/Murexide_test |
Muri ( 無理 ) is a Japanese word meaning "unreasonableness; impossible; beyond one's power; too difficult; by force; perforce; forcibly; compulsorily; excessiveness; immoderation", [ 1 ] and is a key concept in the Toyota Production System (TPS) as one of the three types of waste ( muda , mura , muri ). [ 2 ]
A direct example of Muri is asking workers to stay focused for a period exceeding 8 hours a day or expecting a machine to produce more than it can in a given time.
Some of the most common reasons why production systems experience overburdening: [ citation needed ]
Muri is one of three types of waste ( muda , mura , muri) identified in the Toyota Production System . Waste reduction is an effective way to increase profitability.
Muri can be avoided through standardized work . To achieve this a standard condition or output must be defined to assure effective judgment of quality. Then every process and function must be reduced to its simplest elements for examination and later recombination.
The process must then be standardized to achieve the defined condition. This is done by taking simple work elements and combining them, one-by-one into standardized work sequences. In manufacturing, this includes:
When everyone knows the standard condition, and the standardized work sequences, the results observed include: | https://en.wikipedia.org/wiki/Muri_(Japanese_term) |
Muriel Kennett Wales (9 Jun 1913 – 8 August 2009) was an Irish-Canadian mathematician, and is believed to have been the first Irish-born woman to earn a PhD in pure mathematics . [ 1 ] [ 2 ]
She was born Muriel Kennett on 9 June 1913 in Belfast . In 1914, her mother moved to Vancouver , British Columbia , and soon remarried; henceforth Muriel was known by her mother's new last name, Wales. [ 3 ]
She was first educated at the University of British Columbia (BA 1934, MA 1937 with the thesis Determination of Bases for Certain Quartic Number Fields ). [ 4 ] In 1941 she was awarded the PhD from the University of Toronto for the dissertation Theory Of Algebraic Functions Based On The Use Of Cycles under Samuel Beatty [ 5 ] (himself the first person to receive a PhD in mathematics in Canada, in 1915). [ 6 ]
She spent most of the 1940s working in atomic energy, in Toronto and Montreal , but by 1949 had retired back to Vancouver where she worked in her step-father's shipping company. [ 3 ] | https://en.wikipedia.org/wiki/Muriel_Kennett_Wales |
In group theory , a branch of mathematics, the Murnaghan–Nakayama rule, named after Francis Murnaghan and Tadashi Nakayama , is a combinatorial method to compute irreducible character values of a symmetric group . [ 1 ] There are several generalizations of this rule beyond the representation theory of symmetric groups, but they are not covered here.
The irreducible characters of a group are of interest to mathematicians because they concisely summarize important information about the group, such as the dimensions of the vector spaces in which the elements of the group can be represented by linear transformations that “mix” all the dimensions. For many groups, calculating irreducible character values is very difficult; the existence of simple formulas is the exception rather than the rule.
The Murnaghan–Nakayama rule is a combinatorial rule for computing symmetric group character values χ λ ρ using a particular kind of Young tableaux .
Here λ and ρ are both integer partitions of some integer n , the order of the symmetric group under consideration. The partition λ specifies the irreducible character, while the partition ρ specifies the conjugacy class on whose group elements the character is evaluated to produce the character value. The partitions are represented as weakly decreasing tuples; for example, two of the partitions of 8 are (5,2,1) and (3,3,1,1).
There are two versions of the Murnaghan-Nakayama rule, one non-recursive and one recursive.
Theorem:
where the sum is taken over the set BST(λ,ρ) of all border-strip tableaux of shape λ and type ρ.
That is, each tableau T is a tableau such that
The height , ht (T), is the sum of the heights of the border strips in T . The height of a border strip is one less than the number of
rows it touches.
It follows from this theorem that the character values of a symmetric group are integers.
For some combinations of λ and ρ, there are no border-strip tableaux. In this case, there are no terms in the sum and therefore the character value is zero.
Consider the calculation of one of the character values for the symmetric group of order 8, when λ is the partition (5,2,1) and ρ is the partition (3,3,1,1). The shape partition λ specifies that the tableau must have three rows, the first having 5 boxes, the second having 2 boxes, and the third having 1 box. The type partition ρ specifies that the tableau must be filled with three 1's, three 2's, one 3, and one 4. There are six such border-strip tableaux:
If we call these T 1 {\displaystyle T_{1}} , T 2 {\displaystyle T_{2}} , T 3 {\displaystyle T_{3}} , T 4 {\displaystyle T_{4}} , T 5 {\displaystyle T_{5}} , and T 6 {\displaystyle T_{6}} , then their heights are
h t ( T 1 ) = 0 + 1 + 0 + 0 = 1 h t ( T 2 ) = 1 + 0 + 0 + 0 = 1 h t ( T 3 ) = 1 + 0 + 0 + 0 = 1 h t ( T 4 ) = 2 + 0 + 0 + 0 = 2 h t ( T 5 ) = 2 + 0 + 0 + 0 = 2 h t ( T 6 ) = 2 + 1 + 0 + 0 = 3 {\displaystyle {\begin{aligned}ht(T_{1})=0+1+0+0=1\\ht(T_{2})=1+0+0+0=1\\ht(T_{3})=1+0+0+0=1\\ht(T_{4})=2+0+0+0=2\\ht(T_{5})=2+0+0+0=2\\ht(T_{6})=2+1+0+0=3\end{aligned}}}
and the character value is therefore
χ ( 3 , 3 , 1 , 1 ) ( 5 , 2 , 1 ) = ( − 1 ) 1 + ( − 1 ) 1 + ( − 1 ) 1 + ( − 1 ) 2 + ( − 1 ) 2 + ( − 1 ) 3 = − 1 − 1 − 1 + 1 + 1 − 1 = − 2 {\displaystyle \chi _{(3,3,1,1)}^{(5,2,1)}=(-1)^{1}+(-1)^{1}+(-1)^{1}+(-1)^{2}+(-1)^{2}+(-1)^{3}=-1-1-1+1+1-1=-2}
Theorem:
where the sum is taken over the set BS(λ,ρ 1 ) of border strips within the Young diagram of shape λ that have ρ 1 boxes and whose removal leaves a valid Young diagram. The notation λ ∖ ξ {\displaystyle \lambda \backslash \xi } represents the partition that results from removing the border strip ξ from λ. The notation ρ ∖ ρ 1 {\displaystyle \rho \backslash \rho _{1}} represents the partition that results from removing the first element ρ 1 from ρ.
Note that the right-hand side is a sum of characters for symmetric groups that have smaller order than that of the symmetric group we started with on the left-hand side. In other words, this version of the Murnaghan-Nakayama rule expresses a character of the symmetric group S n in terms of the characters of smaller symmetric groups S k with k < n .
Applying this rule recursively will result in a tree of character value evaluations for smaller and smaller partitions. Each branch stops for one of two reasons: Either there are no border strips of the required length within the reduced shape, so the sum on the right is zero, or a border strip occupying the entire reduced shape is removed, leaving a Young diagram with no boxes. At this point we are evaluating χ λ ρ when both λ and ρ are the empty partition (), and the rule requires that this terminal case be defined as having character χ ( ) ( ) = 1 {\displaystyle \chi _{()}^{()}=1} .
This recursive version of the Murnaghan-Nakayama rule is especially efficient for computer calculation when one computes character tables for S k for increasing values of k and stores all of the previously computed character tables.
We will again compute the character value with λ=(5,2,1) and ρ=(3,3,1,1).
To begin, consider the Young diagram with shape λ. Since the first part of ρ is 3, look for border strips that consist of 3 boxes. There are two possibilities:
In the first diagram, the border strip has height 0, and removing it produces the reduced shape (2,2,1). In the second diagram, the border strip has height 1, and removing it produces the reduced shape (5). Therefore, one has
χ ( 3 , 3 , 1 , 1 ) ( 5 , 2 , 1 ) = χ ( 3 , 1 , 1 ) ( 2 , 2 , 1 ) − χ ( 3 , 1 , 1 ) ( 5 ) {\displaystyle \chi _{(3,3,1,1)}^{(5,2,1)}=\chi _{(3,1,1)}^{(2,2,1)}-\chi _{(3,1,1)}^{(5)}} ,
expressing a character value of S 8 in terms of two character values of S 5 .
Applying the rule again to both terms, one finds
χ ( 3 , 1 , 1 ) ( 2 , 2 , 1 ) = − χ ( 1 , 1 ) ( 2 ) {\displaystyle \chi _{(3,1,1)}^{(2,2,1)}=-\chi _{(1,1)}^{(2)}}
and
χ ( 3 , 1 , 1 ) ( 5 ) = χ ( 1 , 1 ) ( 2 ) {\displaystyle \chi _{(3,1,1)}^{(5)}=\chi _{(1,1)}^{(2)}} ,
reducing to a character value of S 2 .
Applying again, one finds
χ ( 1 , 1 ) ( 2 ) = χ ( 1 ) ( 1 ) {\displaystyle \chi _{(1,1)}^{(2)}=\chi _{(1)}^{(1)}} ,
reducing to the only character value of S 1 .
A final application produces the terminal character χ ( ) ( ) = 1 {\displaystyle \chi _{()}^{()}=1} :
χ ( 1 ) ( 1 ) = χ ( ) ( ) = 1 {\displaystyle \chi _{(1)}^{(1)}=\chi _{()}^{()}=1}
Working backwards from this known character, the result is χ ( 3 , 3 , 1 , 1 ) ( 5 , 2 , 1 ) = − 2 {\displaystyle \chi _{(3,3,1,1)}^{(5,2,1)}=-2} , as before. | https://en.wikipedia.org/wiki/Murnaghan–Nakayama_rule |
Muromonab-CD3 (brand name Orthoclone OKT3 , marketed by Janssen-Cilag ) is an immunosuppressant medication given to reduce acute rejection in people with organ transplants . [ 1 ] [ 2 ] It is a monoclonal antibody targeted at the CD3 receptor, [ 3 ] a membrane protein on the surface of T cells . It is the first monoclonal antibody to be approved for clinical use in humans. [ 2 ]
Muromonab-CD3 is approved for the therapy of acute, glucocorticoid -resistant rejection of allogeneic kidney , heart , and liver transplants . [ 4 ] Unlike the monoclonal antibodies basiliximab and daclizumab , it is not approved for prophylaxis of transplant rejection, although a 1996 review has found it to be safe for that purpose. [ 5 ]
Except under special circumstances, the drug is contraindicated for patients with an allergy against mouse proteins, as well as patients with uncompensated heart failure , uncontrolled arterial hypertension or epilepsy . It should not be used during pregnancy or lactation . [ 2 ] [ 4 ]
Especially during the first infusion, the binding of muromonab-CD3 to CD3 can activate T cells to release cytokines like tumor necrosis factor and interferon gamma . This cytokine release syndrome , or CRS, includes side effects like skin reactions, fatigue , fever , chills , myalgia , headaches , nausea and diarrhea , [ 6 ] and could lead to life-threatening conditions like apnoea , cardiac arrest , and flash pulmonary edema . [ 4 ] To minimize the risk of CRS and to offset some of the minor side effects patient experience, glucocorticoids (such as methylprednisolone ), acetaminophen , and diphenhydramine are given before the infusion. [ 7 ]
Other adverse effects include leucopenia , as well as an increased risk for severe infections and malignancies typical of immunosuppressive therapies. Neurological side effects like aseptic meningitis and encephalopathy have been observed. Possibly, they are also caused by the T cell activation. [ 4 ]
Repeated application can result in tachyphylaxis (reduced effectiveness) due to the formation of anti-mouse antibodies in the patient, which accelerates elimination of the drug. It can also lead to an anaphylactic reaction against the mouse protein, [ 2 ] which may be difficult to distinguish from a CRS.
T cells recognise antigens primarily via the T cell receptor (TCR). [ 8 ] : 160 CD3 is one of the proteins that make up the TCR complex. [ 8 ] : 166 The TCR transduces the signal for the T cell to proliferate and attack the antigen. [ 8 ] : 160
Muromonab-CD3 is a murine (mouse) monoclonal IgG2a antibody which was created using hybridoma technology . [ 9 ] It binds to the T cell receptor-CD3-complex (specifically the CD3 epsilon chain) on the surface of circulating T cells, initially leading to an activation, [ 7 ] but subsequently inducing the clearance of TCR complex from cell surface and apoptosis of the T cells. [ 10 ] This protects the transplant against the T cells. [ 2 ] [ 4 ] When administered for transplant induction, the drug is administered daily thereafter for up to 7 days. [ 7 ]
Newer monoclonal antibodies in development with the same mechanism of action include otelixizumab (also known as TRX4), teplizumab (also known as hOKT3γ1(Ala-Ala) ), visilizumab and foralumab . They are being investigated for the treatment of other conditions like Crohn's disease , ulcerative colitis , and type 1 diabetes .
Muromonab-CD3 was approved by the U.S. Food and Drug Administration (FDA) in 1986, [ 5 ] making it the first monoclonal antibody to be approved anywhere as a drug for humans. In the European Communities , it is the first drug to be approved under the directive 87/22/EWG, a precursor of the European Medicines Agency (EMA) centralised approval system in the European Union. This process included an assessment by the Committee for Proprietary Medicinal Products (CPMP, now CHMP), and a subsequent approval by the national health agencies; in Germany, for example, in 1988 by the Paul Ehrlich Institute in Frankfurt . However, the manufacturer of muromonab-CD3 has voluntarily withdrawn [ 11 ] it from the United States market in 2010 due to numerous side-effects, better-tolerated alternatives and declining usage. [ 12 ]
Orthoclone OKT3 was withdrawn from the US market in 2010. [ 13 ]
Muromonab-CD3 was developed before the WHO nomenclature of monoclonal antibodies took effect, and consequently its name does not follow this convention. Instead, it is a contraction from " mur ine mon oclonal a nti b ody targeting CD3 ". [ 2 ]
It has also been investigated for use in treating T-cell acute lymphoblastic leukemia . [ 14 ] | https://en.wikipedia.org/wiki/Muromonab-CD3 |
In biophysical fluid dynamics , Murray's law is a potential relationship between radii at junctions in a network of fluid-carrying tubular pipes . Its simplest version proposes that whenever a branch of radius r {\displaystyle r} splits into two branches of radii r 1 {\displaystyle r_{1}} and r 2 {\displaystyle r_{2}} , then the three radii should obey the equation r 3 = r 1 3 + r 2 3 . {\displaystyle r^{3}=r_{1}^{3}+r_{2}^{3}{\text{.}}} If network flow is smooth and leak -free, then systems that obey Murray's law minimize the resistance to flow through the network. For turbulent networks, the law takes the same form but with a different characteristic exponent α .
Murray's law is observed in the vascular and respiratory systems of animals, xylem in plants, and the respiratory system of insects. In principle, Murray's law also applies to biomimetic engineering , but human designs rarely exploit the law.
Murray's law is named after Cecil D. Murray , a physiologist at Bryn Mawr College , who first argued that efficient transport might determine the structure of the human vascular system .
Murray's law assumes material is passively transported by the flow of fluid in a network of tubular pipes , [ 1 ] and that the network requires energy to maintain both flow and structural integrity. [ 2 ] Variation in the fluid viscosity across scales will affect the Murray's law exponent, but is usually too small to matter. [ 3 ]
At least two different conditions are known in which the cube exponent is optimal.
In the first, organisms have free (variable) circulatory volume. Also, maintenance energy is not proportional to the pipe material, but instead the quantity of working fluid. The latter assumption is justified in metabolically active biological fluids, such as blood . [ 4 ] It is also justified for metabolically inactive fluids, such as air, as long as the energetic "cost" of the infrastructure scales with the cross-sectional area of each tube; such is the case for all known biological tubules. [ 5 ]
In the second, organisms have fixed circulatory volume and pressure, but wish to minimize the resistance to flow through the system. Equivalently, maintenance is negligible and organisms with to maximize the volumetric flow rate . [ 6 ]
Although most derivations of Murray's law assume a steady state flow field , the same results apply for flow in tubes that have a moderate to small width, relative to the flow wavelength . [ 7 ]
Murray's original derivation uses the first set of assumptions described above. She begins with the Hagen–Poiseuille equation , which states that for fluid of dynamic viscosity μ , flowing laminarly through a cylindrical pipe of radius r and length l , the volumetric flow rate Q associated with a pressure drop Δ p is Q = π 8 μ r 4 l Δ p {\displaystyle Q={\frac {\pi }{8\mu }}{\frac {r^{4}}{l}}\Delta p} and the corresponding power consumed is [ 1 ] P = 8 μ π l Q 2 r 4 . {\displaystyle P={\frac {8\mu }{\pi }}{\frac {lQ^{2}}{r^{4}}}{\text{.}}} Said pipe contains volume π lr 2 . If the maintenance power density is λ , then the total power consumed (from both flow and upkeep) is ∑ P = 8 μ π l Q 2 r 4 + π λ l r 2 . {\displaystyle \sum {P}={\frac {8\mu }{\pi }}{\frac {lQ^{2}}{r^{4}}}+\pi \lambda lr^{2}{\text{.}}} Minimizing this quantity depends on precisely which variables the organism is free to manipulate, but the minimum invariably occurs when the two terms are proportional to each other. [ 8 ] In that minimal case, the proportionality determines a relationship between Q and r . Canceling common factors and taking a square root,
That is, when using as little energy as possible, the mass flowing through the pipe must be proportional to the cube of the pipe's radius. Since flow is leakless, the total flow rate into a junction must be the total flow rate out: ∑ in Q = ∑ out Q . {\displaystyle \sum _{\text{in}}{Q}=\sum _{\text{out}}{Q}{\text{.}}} Substituting ( 1 ) then gives Murray's law with α =3 . [ 9 ]
If the network does not rely on transported material getting "swept up in the flow", but instead expects it to passively diffuse, then resistance to transport is minimized when α =2 : that is, ∑ in r 2 = ∑ out r 2 . {\displaystyle \sum _{\text{in}}{r^{2}}=\sum _{\text{out}}{r^{2}}{\text{.}}} The same law would apply to a direct-current electrical grid composed of wires of only one material, but varying diameter . [ 10 ]
For turbulent flow , transport resistance is minimized when α = 7 / 3 ; that is: [ 11 ] [ 12 ] ∑ in r 7 3 = ∑ out r 7 3 . {\displaystyle \sum _{\text{in}}{r^{\frac {7}{3}}}=\sum _{\text{out}}{r^{\frac {7}{3}}}{\text{.}}} In general, networks intermediate between diffusion and laminar flow are expected to have characteristic exponents between 2 and 3, at least approximately. [ 13 ] [ 14 ]
Murray's law has been verified in chicks; dog intestines and lungs; cat mesentery ; and human intestines and lung capillaries. [ 15 ] [ 16 ] Mice genetically engineered to lack the blood-vessel-wall protein elastin have smaller and thinner blood vessels, but still obey Murray's law. [ 17 ]
In humans, large vessels, such as the aorta or trachea , do not appear to obey Murray's law, instead obeying a Murray's law with exponent close to 2. [ 16 ] But flow in those vessels is also partially turbulent, and so should exhibit an exponent nearer to 7 / 3 than to 3. [ 18 ]
Insects do not have a fully-fledged circulatory system, instead relying on passive diffusion through the haemocoel . For those networks, Murray's law predicts constant cross-sectional area, which is observed. [ 10 ]
The same arguments that imply Murray's law also imply that the distribution of tubules should exhibit a specific power law scaling with size. Plant xylem is known to exhibit that scaling except in scenarios where the passages double as structural supports . [ 19 ] [ 20 ]
The first phenomenon now recognized as Murray's law is Young 's rule for circulatory systems, which states that two identical subcapillaries should combine to form a capillary with radius about 1.26≈ 3 √ 2 times larger, and dates to the early 19th century . [ 21 ] Bryn Mawr physiologist Cecil D. Murray published the law's modern, general formulation in 1926, [ 22 ] [ 21 ] but it languished in a disciplinary no-man's-land for the next fifty years: too trivial for physicists and too complicated for biologists. [ 21 ] Interest in the law revived in the 1970s. [ 21 ]
In circulatory system governed by Murray's law with α =3 , shear stress on vessel walls is roughly constant. Consequently, variations in shear stress are a sign of deviation from Murray's law; Rodbard and Zamir suggest that such variations stimulate homeostatic growth or contraction. [ 23 ]
Murray's law rarely applies to engineered materials, because man-made transport routes attempt to reduce flow resistance by minimizing branching and maximizing diameter. [ 24 ]
Materials that obey Murray's law at the microscale, known as Murray materials , are expected to have favorable flow characteristics, but their construction is difficult, because it requires tight control over pore size typically over a wide range of scales. [ 14 ] [ 25 ]
Lim et al propose designing microfluidic " labs on a chip " in accord with Murray's law to minimize flow resistance during analysis. Conventional lithography does not support such construction, because it cannot produce channels of varying depth. [ 26 ]
Seeking long-lived lithium battery electrodes , Zheng et al constructed Murray materials out of layers of sintered zinc oxide nanoparticles . The evaporation rate of the dissolved zinc oxide solvent controlled the size of the pores in each layer; the network was then just layers of ZnO with different pore sizes placed atop each other. [ 14 ]
Because power plant working fluids typically funnel into many small tubules for efficient heat transfer , Murray's law may be appropriate for nuclear reactor design. [ 27 ] | https://en.wikipedia.org/wiki/Murray's_law |
The Murray loop bridge is a bridge circuit used for locating faults in underground or underwater cables . [ 1 ] [ 2 ] It has been used for more than 100 years [ 3 ] but is being replaced by the more precise time-domain reflectometer .
One end of the faulted cable is connected through a pair of resistors to the voltage source. Also a null detector is connected. The other end of the cable is shorted. The bridge is brought to balance by changing the values of R B1 and R B2 , which is achieved when:
R x R g + R y = R B 1 R B 2 {\displaystyle {\frac {R_{x}}{R_{g}+R_{y}}}={\frac {R_{B1}}{R_{B2}}}}
which is equivalent to:
R x = ( R g + R y ) ⋅ R B 1 R B 2 {\displaystyle R_{x}=(R_{g}+R_{y})\cdot {\frac {R_{B1}}{R_{B2}}}}
The value of resistance R x is proportional the length L x , thus the location of the fault can be calculated:
L x = 2 ⋅ L ⋅ R B 1 R B 1 + R B 2 {\displaystyle L_{x}=2\cdot L\cdot {\frac {R_{B1}}{R_{B1}+R_{B2}}}}
where L is the total length of the cable under test - a value proportional to R g .
The method assumes a single fault exists, of low resistance compared with the undamaged cable insulation resistance, and that the cable conductors have uniform resistance per unit length.
The similar Varley loop uses fixed resistors for RB1 and RB2, and inserts a variable resistor in the faulted leg. Test sets for cable testing can be connected for either bridge technique. If the fault resistance is high, the sensitivity of the Murray bridge is reduced and the Varley loop may be more suitable. | https://en.wikipedia.org/wiki/Murray_loop_bridge |
Murus Dacicus ( Latin for Dacian Wall) is a construction method for defensive walls and fortifications developed in ancient Dacia sometime before the Roman conquest. It is a mix between traditional construction methods particular to Dacian builders and methods imported from Greek and Roman architecture and masonry, and – although somewhat similar construction techniques were used before, during and long after the period – it has peculiarities that make it unique.
Murus Dacicus consisted of two outer walls made out of stone blocks carved in the shape of a rectangular parallelepiped ; apparently no mortar was used, thus making them examples of ashlar masonry – but typically done with regular sized, bigger-than-average blocks, due to technological requirements. After each layer of the outer walls was completed, the gap between them would be filled with gravel and rocks cemented together with clay and compacted (cf. also rammed earth technique). The structure was strengthened and consolidated at the level of each layer by horizontal, singed/scorched wood tie beams connected to the outer walls by means of a dovetail joint at the upper surface of the stone block (hence the need for big stone blocks of the same size). Due to its higher flexibility, this structure had a distinct advantage over the 'classical', solid dry stone wall (as seen, e. g., in the cyclopean and ashlar walls in Mycenae ): a higher capability of shock absorption and dissipation of kinetic energy from an incoming projectile thrown by a siege weapon. However, archaeological and historical evidence suggests that the wall might have been topped by a wooden palisade instead of stone battlements , which had the obvious disadvantage of being vulnerable to fire.
A properly built Dacian Wall would be both labor-intensive and time-consuming. A typical wall for the late period, hastily built in the years between the two Dacian Wars (when Dacia had to rebuild, repair, enlarge or reinforce the defenses of many of its key fortresses), would be about 3–4 meters thick and 10 m tall, an outstanding achievement in the given conditions.
The Dacian Fortresses of the Orăştie Mountains , UNESCO World Heritage Sites are examples of citadels built using this method. Also the Dacian walls are depicted on the Trajan's column in Rome .
Media related to Dacia and Dacians at Wikimedia Commons | https://en.wikipedia.org/wiki/Murus_Dacicus |
Murus gallicus or Gallic wall is a method of construction of defensive walls used to protect Iron Age hillforts and oppida of the La Tene period in Western Europe.
The distinctive features are:
The technique of construction and the utility of the walls was described by Julius Caesar in his Commentaries on the Gallic War :
But this is usually the form of all the Gallic walls. Straight beams, connected lengthwise and two feet distant from each other at equal intervals, are placed together on the ground; these are morticed on the inside, and covered with plenty of earth. But the intervals which we have mentioned, are closed up in front by large stones. These being thus laid and cemented together, another row is added above, in such a manner, that the same interval may be observed, and that the beams may not touch one another, but equal spaces intervening, each row of beams is kept firmly in its place by a row of stones. In this manner the whole wall is consolidated, until the regular height of the wall be completed. This work, with respect to appearance and variety, is not unsightly, owing to the alternate rows of beams and stones, which preserve their order in right lines; and, besides, it possesses great advantages as regards utility and the defense of cities; for the stone protects it from fire, and the wood from the battering ram, since it [the wood] being mortised in the inside with rows of beams, generally forty feet each in length, can neither be broken through nor torn asunder. [ 1 ]
About 30 structures of this type have been excavated, mainly in Gaul , but extending to the upper reaches of the Rhine and Danube . The example at the sea promontory fort of Le Camp d'Artus, at Huelgoat , was excavated and reported by Mortimer Wheeler .
At Manching an earlier murus gallicus wall was rebuilt in the pfostenschlitzmauer style.
The murus gallicus contrasts with other construction styles: | https://en.wikipedia.org/wiki/Murus_gallicus |
Muscarinic acetylcholine receptors ( mAChRs ) are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons [ 1 ] and other cells . They play several roles, including acting as the main end-receptor stimulated by acetylcholine released from postganglionic fibers . They are mainly found in the parasympathetic nervous system , but also have a role in the sympathetic nervous system in the control of sweat glands . [ 2 ]
Muscarinic receptors are so named because they are more sensitive to muscarine than to nicotine . [ 3 ] Their counterparts are nicotinic acetylcholine receptors (nAChRs), receptor ion channels that are also important in the autonomic nervous system . Many drugs and other substances (for example pilocarpine and scopolamine ) manipulate these two distinct receptors by acting as selective agonists or antagonists . [ 4 ]
Acetylcholine (ACh) is a neurotransmitter found in the brain , neuromuscular junctions and the autonomic ganglia .
Muscarinic receptors are used in the following roles:
ACh is always used as the neurotransmitter within the autonomic ganglion . Nicotinic receptors on the postganglionic neuron are responsible for the initial fast depolarization (Fast EPSP ) of that neuron. As a consequence of this, nicotinic receptors are often cited as the receptor on the postganglionic neurons at the ganglion . However, the subsequent hyperpolarization ( IPSP ) and slow depolarization (Slow EPSP) that represent the recovery of the postganglionic neuron from stimulation are actually mediated by muscarinic receptors, types M 2 and M 1 respectively (discussed below). [ citation needed ]
Peripheral autonomic fibers (sympathetic and parasympathetic fibers) are categorized anatomically as either preganglionic or postganglionic fibers , then further generalized as either adrenergic fibers, releasing noradrenaline, or cholinergic fibers, both releasing acetylcholine and expressing acetylcholine receptors. Both preganglionic sympathetic fibers and preganglionic parasympathetic fibers are cholinergic. Most postganglionic sympathetic fibers are adrenergic: their neurotransmitter is norepinephrine except postganglionic sympathetic fibers to the sweat glands, piloerectile muscles of the body hairs, and the skeletal muscle arterioles do not use adrenaline/noradrenaline.
The adrenal medulla is considered a sympathetic ganglion and, like other sympathetic ganglia, is supplied by cholinergic preganglionic sympathetic fibers: acetylcholine is the neurotransmitter utilized at this synapse. The chromaffin cells of the adrenal medulla act as "modified neurons", releasing adrenaline and noradrenaline into the bloodstream as hormones instead of as neurotransmitters. The other postganglionic fibers of the peripheral autonomic system belong to the parasympathetic division; all are cholinergic fibers, and use acetylcholine as the neurotransmitter.
Another role for these receptors is at the junction of the innervated tissues and the postganglionic neurons in the parasympathetic division of the autonomic nervous system. Here acetylcholine is again used as a neurotransmitter, and muscarinic receptors form the principal receptors on the innervated tissue.
Very few parts of the sympathetic system use cholinergic receptors. In sweat glands the receptors are of the muscarinic type. The sympathetic nervous system also has some preganglionic nerves terminating at the chromaffin cells in the adrenal medulla , which secrete epinephrine and norepinephrine into the bloodstream. Some [ who? ] believe that chromaffin cells are modified postganglionic CNS fibers. In the adrenal medulla, acetylcholine is used as a neurotransmitter, and the receptor is of the nicotinic type.
The somatic nervous system uses a nicotinic receptor to acetylcholine at the neuromuscular junction.
Muscarinic acetylcholine receptors are also present and distributed throughout the local nervous system, in post-synaptic and pre-synaptic positions. There is also some evidence for postsynaptic receptors on sympathetic neurons allowing the parasympathetic nervous system to inhibit sympathetic effects.
It is known that muscarinic acetylcholine receptors also appear on the pre-synaptic membrane of somatic neurons in the neuro-muscular junction, where they are involved in the regulation of acetylcholine release.
Muscarinic acetylcholine receptors belong to a class of metabotropic receptors that use G proteins as their signaling mechanism. In such receptors, the signaling molecule (the ligand ) binds to a monomeric receptor that has seven transmembrane regions ; in this case, the ligand is ACh. This receptor is bound to intracellular proteins, known as G proteins, which begin the information cascade within the cell. [ 5 ]
By contrast, nicotinic receptors form pentameric complexes and use a ligand-gated ion channel mechanism for signaling. In this case, binding of the ligands with the receptor causes an ion channel to open, permitting either one or more specific types of ions (e.g., K + , Na + , Ca 2+ ) to diffuse into or out of the cell.
By the use of selective radioactively labeled agonist and antagonist substances, five subtypes of muscarinic receptors have been determined, named M 1 –M 5 (using an upper case M and subscript number). [ 6 ] M 1 , M 3 , M 5 receptors are coupled with G q proteins , while M 2 and M 4 receptors are coupled with G i/o proteins. [ 5 ] There are other classification systems. For example, the drug pirenzepine is a muscarinic antagonist (decreases the effect of ACh), which is much more potent at M 1 receptors than it is at other subtypes. The acceptance of the various subtypes proceeded in numerical order, therefore, earlier sources may recognize only M 1 and M 2 subtypes, [ citation needed ] while later studies recognize M 3 , M 4 , [1] and most recently M 5 subtypes. [ citation needed ]
Meanwhile, geneticists and molecular biologists have characterised five genes that appear to encode muscarinic receptors, named m1-m5 (lowercase m; no subscript number). They code for pharmacologic types M 1 -M 5 . The receptors m1 and m2 were determined based upon partial sequencing of M 1 and M 2 receptor proteins. The others were found by searching for homology, using bioinformatic techniques.
G proteins contain an alpha-subunit that is critical to the functioning of receptors. These subunits can take a number of forms. There are four broad classes of form of G-protein: G s , G i , G q , and G 12/13 . [ 7 ] Muscarinic receptors vary in the G protein to which they are bound, with some correlation according to receptor type. G proteins are also classified according to their susceptibility to cholera toxin (CTX) and pertussis toxin (PTX, whooping cough). G s and some subtypes of G i (G αt and G αg ) are susceptible to CTX. Only G i is susceptible to PTX, with the exception of one subtype of G i (G αz ) which is immune. Also, only when bound with an agonist, those G proteins normally sensitive to PTX also become susceptible to CTX. [ 8 ]
The various G-protein subunits act differently upon secondary messengers, upregulating Phospholipases, downregulating cAMP, and so on.
Because of the strong correlations to muscarinic receptor type, CTX and PTX are useful experimental tools in investigating these receptors.
The muscarinic acetylcholine receptor subtype sectivities of a large number of antimuscarinic drugs have been reviewed. [ 27 ]
This receptor is found mediating slow EPSP at the ganglion in the postganglionic nerve, [ 28 ] is common in exocrine glands and in the CNS. [ 29 ] [ 30 ]
It is predominantly found bound to G proteins of class G q , [ 31 ] which use upregulation of phospholipase C and, therefore, inositol trisphosphate and intracellular calcium as a signaling pathway. A receptor so bound would not be susceptible to CTX or PTX. However, G i (causing a downstream decrease in cAMP ) and G s (causing an increase in cAMP) have also been shown to be involved in interactions in certain tissues, and so would be susceptible to PTX and CTX, respectively.
The M 2 muscarinic receptors are located in the heart and lungs. In the heart, they act to slow the heart rate down below the normal baseline sinus rhythm , by slowing the speed of depolarization . In humans, under resting conditions, vagal activity dominates over sympathetic activity. Hence, inhibition of M 2 receptors (e.g. by atropine) will cause a raise in heart rate. They also moderately reduce contractile forces of the atrial cardiac muscle , and reduce conduction velocity of the atrioventricular node (AV node). It also serves to slightly decrease the contractile forces of the ventricular muscle.
M 2 muscarinic receptors act via a G i type receptor, which causes a decrease in cAMP in the cell, inhibition of voltage-gated Ca 2+ channels, and increasing efflux of K + , in general, leading to inhibitory-type effects.
The M 3 muscarinic receptors are located at many places in the body. They are located in the smooth muscles of the blood vessels, as well as in the lungs. Because the M 3 receptor is G q -coupled and mediates an increase in intracellular calcium, it typically causes contraction of smooth muscle, such as that observed during bronchoconstriction and bladder voiding . [ 32 ] However, with respect to vasculature, activation of M 3 on vascular endothelial cells causes increased synthesis of nitric oxide , which diffuses to adjacent vascular smooth muscle cells and causes their relaxation , thereby explaining the paradoxical effect of parasympathomimetics on vascular tone and bronchiolar tone. Indeed, direct stimulation of vascular smooth muscle, M 3 mediates vasoconstriction in diseases wherein the vascular endothelium is disrupted. [ 33 ] The M 3 receptors are also located in many glands, which help to stimulate secretion in, for example, the salivary glands, as well as other glands of the body.
Like the M 1 muscarinic receptor, M 3 receptors are G proteins of class G q that upregulate phospholipase C and, therefore, inositol trisphosphate and intracellular calcium as a signaling pathway. [ 5 ]
M 4 receptors are found in the CNS. M 4 receptors are also located in erythroid progenitor cell in peripheral tissue and modulate the cAMP pathway to regulate erythroid progenitor cell differentiation. Therapies targeting the M 4 receptor treats myelodysplastic syndrome and anemia that are refractory to erythropoietin . [ 24 ] [ 25 ] [ 26 ]
M 4 receptors work via G i receptors to decrease cAMP in the cell and, thus, produce generally inhibitory effects. Possible bronchospasm may result if stimulated by muscarinic agonists .
Location of M 5 receptors is not well known.
Like the M 1 and M 3 muscarinic receptor, M 5 receptors are coupled with G proteins of class G q that upregulate phospholipase C and, therefore, inositol trisphosphate and intracellular calcium as a signaling pathway. [ citation needed ]
Ligands targeting the mAChR that are currently approved for clinical use include non-selective antagonists for the treatment of Parkinson's disease , [ 34 ] atropine (to dilate the pupil ), scopolamine (used to prevent motion sickness ), and ipratropium (used in the treatment of COPD ). [ 4 ] [ 35 ]
In 2024, the United States FDA approved the drug KarXT (Cobenfy), which is a combination drug that combines xanomeline (a preferentially acting M1/M4 muscarinic acetylcholine receptor agonist) with trospium (a peripherally-restricted pan-mAChR antagonist for use in schizophrenia. [ 36 ] In early clinical trials of moderate to high severity patients without treatment resistant history, it has demonstrated efficacy about equivalent to that of other anti-psychotics (20-point improvement in PANSS vs 10-point placebo improvement), with a notably different side effect profile (very low rates of metabolic effects, hypotension, weight changes, or EPS) with moderately reported rates of nausea and constipation. No trials have been published to date regarding use in combination with other antipsychotics, use in treatment resistant patients, or head-to-head comparisons with other medications. This is the first anti-psychotic drug approved that uses a muscarinic mechanism of action, and many others are in development. [ 36 ] | https://en.wikipedia.org/wiki/Muscarinic_acetylcholine_receptor |
A bryophilous lichen is one that grows on a bryophyte – that is, on a moss or liverwort . [ 1 ] Those which grow on mosses are known as muscicolous lichens , [ 2 ] while those which grow on liverworts are called hepaticolous lichens . [ 3 ] Muscicolous derives from the Latin muscus meaning moss, [ 4 ] while the suffix colous means "living or growing in or on". [ 5 ] Lichens are slow-growing organisms, and so are far more likely to be overgrown by a bryophyte than to overgrow one. [ 6 ] [ 7 ] However, they are better able to compete if the bryophyte is sickly or decaying and they can be parasitic upon them. [ 1 ] [ 8 ] [ 9 ] Some, rather than overgrowing the bryophyte, instead live among its branches. [ 9 ] Bryophilous lichens are particularly common in heathland and arctic or alpine tundra . [ 9 ] Because many are small and inconspicuous, they are easy to overlook. [ 1 ]
This article about lichens or lichenology is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Muscicolous_lichen |
Muscle atrophy is the loss of skeletal muscle mass. It can be caused by immobility , aging, malnutrition , medications, or a wide range of injuries or diseases that impact the musculoskeletal or nervous system . Muscle atrophy leads to muscle weakness and causes disability.
Disuse causes rapid muscle atrophy and often occurs during injury or illness that requires immobilization of a limb or bed rest. Depending on the duration of disuse and the health of the individual, this may be fully reversed with activity. Malnutrition first causes fat loss but may progress to muscle atrophy in prolonged starvation and can be reversed with nutritional therapy. In contrast, cachexia is a wasting syndrome caused by an underlying disease such as cancer that causes dramatic muscle atrophy and cannot be completely reversed with nutritional therapy. Sarcopenia is age-related muscle atrophy and can be slowed by exercise. Finally, diseases of the muscles such as muscular dystrophy or myopathies can cause atrophy, as well as damage to the nervous system such as in spinal cord injury or stroke . Thus, muscle atrophy is usually a finding ( sign or symptom ) in a disease rather than being a disease by itself. However, some syndromes of muscular atrophy are classified as disease spectrums or disease entities rather than as clinical syndromes alone, such as the various spinal muscular atrophies .
Muscle atrophy results from an imbalance between protein synthesis and protein degradation, although the mechanisms are incompletely understood and are variable depending on the cause. Muscle loss can be quantified with advanced imaging studies but this is not frequently pursued. Treatment depends on the underlying cause but will often include exercise and adequate nutrition. Anabolic agents may have some efficacy but are not often used due to side effects. There are multiple treatments and supplements under investigation but there are currently limited treatment options in clinical practice. Given the implications of muscle atrophy and limited treatment options, minimizing immobility is critical in injury or illness.
The hallmark sign of muscle atrophy is loss of lean muscle mass. This change may be difficult to detect due to obesity, changes in fat mass or edema. Changes in weight, limb or waist circumference are not reliable indicators of muscle mass changes. [ 1 ]
The predominant symptom is increased weakness which may result in difficulty or inability in performing physical tasks depending on what muscles are affected. Atrophy of the core or leg muscles may cause difficulty standing from a seated position, walking or climbing stairs and can cause increased falls. Atrophy of the throat muscles may cause difficulty swallowing and diaphragm atrophy can cause difficulty breathing. Muscle atrophy can be asymptomatic and may go undetected until a significant amount of muscle is lost. [ 2 ]
Skeletal muscle serves as a storage site for amino acids , creatine , myoglobin , and adenosine triphosphate , which can be used for energy production when demands are high or supplies are low. If metabolic demands remain greater than protein synthesis, muscle mass is lost. [ 3 ] Many diseases and conditions can lead to this imbalance, either through the disease itself or disease associated appetite-changes, such as loss of taste due to Covid-19 . Causes of muscle atrophy , include immobility, aging, malnutrition , certain systemic diseases ( cancer , congestive heart failure ; chronic obstructive pulmonary disease ; AIDS , liver disease , etc.), deinnervation, intrinsic muscle disease or medications (such as glucocorticoids ). [ 4 ]
Disuse is a common cause of muscle atrophy and can be local (due to injury or casting) or general (bed-rest). The rate of muscle atrophy from disuse (10–42 days) is approximately 0.5–0.6% of total muscle mass per day although there is considerable variation between people. [ 5 ] The elderly are the most vulnerable to dramatic muscle loss with immobility. Much of the established research has investigated prolonged disuse (>10 days), in which the muscle is compromised primarily by declines in muscle protein synthesis rates rather than changes in muscle protein breakdown. There is evidence to suggest that there may be more active protein breakdown during short term immobility (<10 days). [ 5 ]
Certain diseases can cause a complex muscle wasting syndrome known as cachexia . It is commonly seen in cancer, congestive heart failure , chronic obstructive pulmonary disease , chronic kidney disease and AIDS although it is associated with many disease processes, usually with a significant inflammatory component. Cachexia causes ongoing muscle loss that is not entirely reversed with nutritional therapy. [ 6 ] The pathophysiology is incompletely understood but inflammatory cytokines are considered to play a central role. In contrast to weight loss from inadequate caloric intake, cachexia causes predominantly muscle loss instead of fat loss and it is not as responsive to nutritional intervention. Cachexia can significantly compromise quality of life and functional status and is associated with poor outcomes. [ 7 ] [ 8 ]
Sarcopenia is the degenerative loss of skeletal muscle mass, quality, and strength associated with aging. This involves muscle atrophy, reduction in number of muscle fibers and a shift towards "slow twitch" or type I skeletal muscle fibers over "fast twitch" or type II fibers . [ 3 ] The rate of muscle loss is dependent on exercise level, co-morbidities, nutrition and other factors. There are many proposed mechanisms of sarcopenia, such as a decreased capacity for oxidative phosphorylation, cellular senescence or an altered signaling of pathways regulating protein synthesis, [ 9 ] and is considered to be the result of changes in muscle synthesis signalling pathways and gradual failure in the satellite cells which help to regenerate skeletal muscle fibers, specifically in "fast twitch" myofibers. [ 10 ]
Sarcopenia can lead to reduction in functional status and cause significant disability but is a distinct condition from cachexia although they may co-exist. [ 8 ] [ 11 ] In 2016 an ICD code for sarcopenia was released, contributing to its acceptance as a disease entity. [ 12 ]
Muscle diseases, such as muscular dystrophy , amyotrophic lateral sclerosis (ALS), or myositis such as inclusion body myositis can cause muscle atrophy. [ 13 ]
Damage to neurons in the brain or spinal cord can cause prominent muscle atrophy. This can be localized muscle atrophy and weakness or paralysis such as in stroke or spinal cord injury . [ 14 ] More widespread damage such as in traumatic brain injury or cerebral palsy can cause generalized muscle atrophy. [ 15 ]
Injuries or diseases of peripheral nerves supplying specific muscles can also cause muscle atrophy. This is seen in nerve injury due to trauma or surgical complication, nerve entrapment, or inherited diseases such as Charcot-Marie-Tooth disease . [ 16 ]
Some medications are known to cause muscle atrophy, usually due to direct effect on muscles. This includes glucocorticoids causing glucocorticoid myopathy [ 4 ] or medications toxic to muscle such as doxorubicin . [ 17 ]
Disorders of the endocrine system such as Cushing's disease or hypothyroidism are known to cause muscle atrophy. [ 18 ]
Muscle atrophy occurs due to an imbalance between the normal balance between protein synthesis and protein degradation. This involves complex cell signalling that is incompletely understood and muscle atrophy is likely the result of multiple contributing mechanisms. [ 19 ]
Mitochondrial function is crucial to skeletal muscle health and detrimental changes at the level of the mitochondria may contribute to muscle atrophy. [ 20 ] A decline in mitochondrial density as well as quality is consistently seen in muscle atrophy due to disuse. [ 20 ]
The ATP -dependent ubiquitin / proteasome pathway is one mechanism by which proteins are degraded in muscle. This involves specific proteins being tagged for destruction by a small peptide called ubiquitin which allows recognition by the proteasome to degrade the protein. [ 21 ]
Screening for muscle atrophy is limited by a lack of established diagnostic criteria, although many have been proposed. Diagnostic criteria for other conditions such as sarcopenia or cachexia can be used. [ 3 ] These syndromes can also be identified with screening questionnaires. [ citation needed ]
Muscle mass and changes can be quantified on imaging studies such as CT scans or Magnetic resonance imaging (MRI) . Biomarkers such as urine urea can be used to roughly estimate muscle loss during circumstances of rapid muscle loss. [ 22 ] Other biomarkers are currently under investigation but are not used in clinical practice. [ 3 ]
Muscle atrophy can be delayed, prevented and sometimes reversed with treatment. Treatment approaches include impacting the signaling pathways that induce muscle hypertrophy or slow muscle breakdown as well as optimizing nutritional status. [ citation needed ]
Physical activity provides a significant anabolic muscle stimulus and is a crucial component to slowing or reversing muscle atrophy. [ 3 ] It is still unknown regarding the ideal exercise "dosing." Resistance exercise has been shown to be beneficial in reducing muscle atrophy in older adults. [ 23 ] [ 24 ] In patients who cannot exercise due to physical limitations such as paraplegia, functional electrical stimulation can be used to externally stimulate the muscles. [ 25 ]
Adequate calories and protein is crucial to prevent muscle atrophy. Protein needs may vary dramatically depending on metabolic factors and disease state, so high-protein supplementation may be beneficial. [ 3 ] Supplementation of protein or branched-chain amino acids , especially leucine, can provide a stimulus for muscle synthesis and inhibit protein breakdown and has been studied for muscle atrophy for sarcopenia and cachexia. [ 3 ] [ 26 ] β-Hydroxy β-methylbutyrate (HMB), a metabolite of leucine which is sold as a dietary supplement , has demonstrated efficacy in preventing the loss of muscle mass in several muscle wasting conditions in humans, particularly sarcopenia . [ 26 ] [ 27 ] [ 28 ] Based upon a meta-analysis of seven randomized controlled trials that was published in 2015, HMB supplementation has efficacy as a treatment for preserving lean muscle mass in older adults. [ 29 ] More research is needed to determine the precise effects of HMB on muscle strength and function in various populations. [ 29 ]
In severe cases of muscular atrophy, the use of an anabolic steroid such as methandrostenolone may be administered to patients as a potential treatment although use is limited by side effects. A novel class of drugs, called selective androgen receptor modulators , is being investigated with promising results. They would have fewer side effects , while still promoting muscle and bone tissue growth and regeneration. These effects have yet to be confirmed in larger clinical trials. [ 30 ]
Outcomes of muscle atrophy depend on the underlying cause and the health of the patient. Immobility or bed rest in populations predisposed to muscle atrophy, such as the elderly or those with disease states that commonly cause cachexia , can cause dramatic muscle atrophy and impact on functional outcomes. In the elderly, this often leads to decreased biological reserve and increased vulnerability to stressors known as the " frailty syndrome ." [ 3 ] Loss of lean body mass is also associated with increased risk of infection, decreased immunity, and poor wound healing. The weakness that accompanies muscle atrophy leads to higher risk of falls, fractures, physical disability, need for institutional care, reduced quality of life, increased mortality, and increased healthcare costs. [ 3 ]
Inactivity and starvation in mammals lead to atrophy of skeletal muscle, accompanied by a smaller number and size of the muscle cells as well as lower protein content. [ 31 ] In humans, prolonged periods of immobilization, as in the cases of bed rest or astronauts flying in space, are known to result in muscle weakening and atrophy. Such consequences are also noted in small hibernating mammals like the golden-mantled ground squirrels and brown bats. [ 32 ] A striking example of human-induced atrophy is seen in Amar Bharati , an Indian sadhu who held his arm raised for decades as a spiritual devotion, resulting in severe muscle atrophy and loss of function in the limb.
Bears are an exception to this rule; species in the family Ursidae are famous for their ability to survive unfavorable environmental conditions of low temperatures and limited nutrition availability during winter by means of hibernation . During that time, bears go through a series of physiological, morphological, and behavioral changes. [ 33 ] Their ability to maintain skeletal muscle number and size during disuse is of significant importance. [ citation needed ]
During hibernation, bears spend 4–7 months of inactivity and anorexia without undergoing muscle atrophy and protein loss. [ 32 ] A few known factors contribute to the sustaining of muscle tissue. During the summer, bears take advantage of the nutrition availability and accumulate muscle protein. The protein balance at time of dormancy is also maintained by lower levels of protein breakdown during the winter. [ 32 ] At times of immobility, muscle wasting in bears is also suppressed by a proteolytic inhibitor that is released in circulation. [ 31 ] Another factor that contributes to the sustaining of muscle strength in hibernating bears is the occurrence of periodic voluntary contractions and involuntary contractions from shivering during torpor . [ 34 ] The three to four daily episodes of muscle activity are responsible for the maintenance of muscle strength and responsiveness in bears during hibernation. [ 34 ]
Muscle-atrophy can be induced in pre-clinical models (e.g. mice) to study the effects of therapeutic interventions against muscle-atrophy. Restriction of the diet, i.e. caloric restriction, leads to a significant loss of muscle mass within two weeks, and loss of muscle-mass can be rescued by a nutritional intervention. [ 35 ] Immobilization of one of the hindlegs of mice leads to muscle-atrophy as well, and is hallmarked by loss of both muscle mass and strength. Food restriction and immobilization may be used in mouse models and have been shown to overlap with mechanisms associated to sarcopenia in humans. [ 36 ] | https://en.wikipedia.org/wiki/Muscle_atrophy |
Muscle coactivation occurs when agonist and antagonist muscles (or synergist muscles ) surrounding a joint contract simultaneously to provide joint stability, [ 1 ] [ 2 ] and is suggested to depend crucially on supraspinal processes involved in the control of movement. [ 3 ] It is also known as muscle cocontraction, since two muscle groups are contracting at the same time. It is able to be measured using electromyography (EMG) from the contractions that occur. The general mechanism of it is still widely unknown. It is believed to be important in joint stabilization, as well as general motor control . [ 1 ]
Muscle coactivation allows muscle groups surrounding a joint to become more stable. This is due to both muscles (or sets of muscles) contracting at the same time, which produces compression on the joint. The joint is able to become stiffer and more stable due to this action. [ 4 ] [ 5 ] For example, when the biceps and the triceps coactivate, the elbow becomes more stable. This stabilization mechanism is also important for unexpected loads impeded on the joint, allowing the muscles to quickly coactivate and provide stability to the joint. [ 1 ] [ 4 ] This mechanism is controlled neuromuscularly , which allows the muscle(s) to contract. [ 1 ] This occurs through a motor neuron sending a signal (through creating action potentials ) to the muscle fiber to contract by releasing acetylcholine . [ 6 ] When signals are sent to all muscle fibers in a muscle group, the muscle group will contract as a whole.
In the upper limbs, the stability of muscle coactivation allows for precise low-level physical tasks. [ 1 ] An example of this would be picking up a small object. By protecting the muscles at the end of their range of motion, the direction of the fine movements is able to be changed. [ 4 ] In the lower limbs, stability is important in upright standing balance. The coactivation of different muscle groups allows for proper balance and the ability to adjust weight and to stay upright on uneven ground. [ 7 ] It is also believed to be important for postural control by stabilizing the spine. [ 1 ] Muscle coactivation is absolutely necessary for learning a fine motor skill or for any activity involving stability. [ 7 ] In order for muscle coactivation to occur, it must inhibit reciprocal innervation , which occurs when a muscle contracts and the synergist muscle relaxes. [ 5 ] For muscle coactivation to occur, both the muscle and synergist muscle need to contract.
Muscle coactivation is measured using a technique called electromyography (EMG). [ 1 ] This is performed by using surface EMG that responds to electrical activity of the muscle through the skin. [ 8 ] Electrical activity is only present in the muscle when the muscle voluntarily contracts. [ 9 ] When the muscle is contracted, the EMG is able to display the force of the contraction or how the nerves can respond to stimulation. [ 10 ] An EMG of coactivation would display the agonist and antagonist muscle contracting simultaneously. Although it is believed many muscles are involved in the mechanism of coactivation, methods to measure coactivation are finite to specific instances or two muscle systems. Because of this, little is understood about the role of coactivation in a multiple muscle system. [ 1 ] | https://en.wikipedia.org/wiki/Muscle_coactivation |
Muscle hypertrophy or muscle building involves a hypertrophy or increase in size of skeletal muscle through a growth in size of its component cells . Two factors contribute to hypertrophy: sarcoplasmic hypertrophy, which focuses more on increased muscle glycogen storage; and myofibrillar hypertrophy, which focuses more on increased myofibril size. [ 1 ] It is the primary focus of bodybuilding -related activities.
A range of stimuli can increase the volume of muscle cells. These changes occur as an adaptive response that serves to increase the ability to generate force or resist fatigue in anaerobic conditions.
Strength training (resistance training) causes neural and muscular adaptations which increase the capacity of an athlete to exert force through voluntary muscular contraction: After an initial period of neuro-muscular adaptation, the muscle tissue expands by creating sarcomeres (contractile elements) and increasing non-contractile elements like sarcoplasmic fluid. [ 2 ]
Muscular hypertrophy can be induced by progressive overload (a strategy of progressively increasing resistance or repetitions over successive bouts of exercise to maintain a high level of effort ). [ 3 ] However, the precise mechanisms are not clearly understood; the current accepted theory is mechanical tension. [ 4 ]
Muscular hypertrophy plays an important role in competitive bodybuilding and strength sports like powerlifting , American football, and Olympic weightlifting .
Another form of training that has been researched in terms of inducing muscle hypertrophy is blood flow restriction training (BFR). [ 5 ] BFR training involves the use of cuffs or bands to partially restrict blood flow to the working muscles during low-load resistance exercise. This method has been shown to induce hypertrophy comparable to traditional high-load training, likely due to mechanical tension and muscle fiber recruitment. BFR training is particularly useful for individuals who cannot tolerate high mechanical loads, such as those recovering from injury or older adults.
The best approach to specifically achieve muscle growth remains controversial (as opposed to focusing on gaining strength, power, or endurance); it was generally considered that consistent anaerobic strength training will produce hypertrophy over the long term, in addition to its effects on muscular strength and endurance. Muscular hypertrophy can be increased through strength training and other short-duration, high-intensity anaerobic exercises . Lower-intensity, longer-duration aerobic exercise generally does not result in very effective tissue hypertrophy; instead, endurance athletes enhance storage of fats and carbohydrates within the muscles, [ 6 ] as well as neovascularization . [ 7 ] [ 8 ]
During a workout, increased blood flow to metabolically active areas causes muscles to temporarily increase in size. This phenomenon is referred to as transient hypertrophy, or more commonly known as being "pumped up" or getting "a pump." [ 9 ] About two hours after a workout and typically for seven to eleven days, muscles swell due to an inflammation response as tissue damage is repaired. [ 10 ] Longer-term hypertrophy occurs due to more permanent changes in muscle structure.
Hirono et al. explained the causes of muscle swelling: [ 11 ]
"Muscle swelling occurs as a result of the following:
(a) resistance exercise can increase phosphocreatine and hydrogen ion accumulations due to blood lactate and growth hormone production, and
(b) the high lactate and hydrogen ion concentrations may accelerate water uptake in muscle cells according to cell permeability because the molecular weights of the lactate and hydrogen ions are smaller than that of muscle glycogen."
Biological factors (such as DNA and sex), nutrition, and training variables can affect muscle hypertrophy. [ 12 ]
Individual differences in genetics account for a substantial portion of the variance in existing muscle mass. A classical twin study design (similar to those of behavioral genetics) estimated that about 53% of the variance in lean body mass is heritable, [ 13 ] along with about 45% of the variance in muscle fiber proportion. [ 14 ]
During puberty in males, hypertrophy occurs at an increased rate. Natural hypertrophy normally stops at full growth in the late teens. As testosterone is one of the body's major growth hormones, on average, males find hypertrophy much easier (on an absolute scale) to achieve than females, and, on average, have about 60% more muscle mass than women. [ 15 ] Taking additional testosterone, as in anabolic steroids , will increase results. It is also considered a performance-enhancing drug , the use of which can cause competitors to be suspended or banned from competitions. Testosterone is also a medically regulated substance in most [ 16 ] [ 17 ] countries, making it illegal to possess without a medical prescription . Anabolic steroid use can cause testicular atrophy , cardiac arrest, [ 18 ] and gynecomastia . [ 19 ]
In the long term, a positive energy balance, when more calories are consumed rather than burned, is helpful for anabolism and therefore muscle hypertrophy. An increased requirement for protein can help elevate protein synthesis, which is seen in athletes training for muscle hypertrophy. Protein intakes up to 1.6 grams per kilogram of body weight a day help increase gains in strength and muscle size from resistance training. [ 20 ]
Training variables, in the context of strength training, such as frequency, intensity, and total volume also directly affect the increase of muscle hypertrophy. A gradual increase in all of these training variables will yield muscular hypertrophy. [ 21 ] Range of motion is also seen as another possible factor to induce hypertrophy. Training through a full ROM, particularly at elongated muscle lengths, has been shown to enhance hypertrophy compared to partial ROM. For example, deep squats and full-ROM deadlifts increase mechanical tension on muscle fibers, particularly in the stretched position, which may stimulate greater muscle growth. Partial ROM training at longer muscle lengths has also been found to promote hypertrophy, potentially due to increased muscle damage. [ 22 ]
The message filters down to alter the pattern of gene expression . The additional contractile proteins appear to be incorporated into existing myofibrils (the chains of sarcomeres within a muscle cell). There appears to be some limit to how large a myofibril can become: at some point, they split. These events appear to occur within each muscle fiber. That is hypertrophy results primarily from the growth of each muscle cell rather than an increase in the number of cells. Skeletal muscle cells are however unique in the body in that they can contain multiple nuclei, and the number of nuclei can increase. [ 23 ]
Cortisol decreases amino acid uptake by muscle tissue, and inhibits protein synthesis. [ 24 ] The short-term increase in protein synthesis that occurs subsequent to resistance training returns to normal after approximately 28 hours in adequately fed male youths. [ 25 ] Another study determined that muscle protein synthesis was elevated even 72 hours following training. [ 26 ]
A small study performed on young and elderly found that ingestion of 340 grams of lean beef (90 g protein) did not increase muscle protein synthesis any more than ingestion of 113 grams of lean beef (30 g protein). In both groups, muscle protein synthesis increased by 50%. The study concluded that more than 30 g protein in a single meal did not further enhance the stimulation of muscle protein synthesis in young and elderly. [ 27 ] However, this study didn't check protein synthesis in relation to training; therefore conclusions from this research are controversial. A 2018 review of the scientific literature [ 28 ] concluded that for the purpose of building lean muscle tissue, a minimum of 1.6 g protein per kilogram of body weight is required, which can for example be divided over 4 meals or snacks and spread out over the day. [ citation needed ]
It is not uncommon for bodybuilders to advise a protein intake as high as 2–4 g per kilogram of bodyweight per day. [ 29 ] However, scientific literature has suggested this is higher than necessary, as protein intakes greater than 1.8 g per kilogram of body weight showed to have no greater effect on muscle hypertrophy. [ 30 ] A study carried out by American College of Sports Medicine (2002) put the recommended daily protein intake for athletes at 1.2–1.8 g per kilogram of body weight. [ 30 ] [ 31 ] [ 32 ] Conversely, Di Pasquale (2008), citing recent studies, recommends a minimum protein intake of 2.2 g/kg "for anyone involved in competitive or intense recreational sports who wants to maximize lean body mass but does not wish to gain weight. However athletes involved in strength events (..) may need even more to maximize body composition and athletic performance. In those attempting to minimize body fat and thus maximize body composition, for example in sports with weight classes and in bodybuilding, it's possible that protein may well make up over 50% of their daily caloric intake." [ 33 ]
Microtrauma is tiny damage to the muscle fibers. The precise relation between microtrauma and muscle growth is not entirely understood yet. [ citation needed ]
One theory is that microtrauma plays a significant role in muscle growth. [ 34 ] [ 35 ] When microtrauma occurs (from weight training or other strenuous activities), the body responds by overcompensating, replacing the damaged tissue and adding more, so that the risk of repeat damage is reduced. Damage to these fibers has been theorized as the possible cause for the symptoms of delayed onset muscle soreness (DOMS), and is why progressive overload is essential to continued improvement, as the body adapts and becomes more resistant to stress.
However, other work examining the time course of changes in muscle protein synthesis and their relationship to hypertrophy showed that damage was unrelated to hypertrophy. [ 36 ] In fact, in one study [ 36 ] the authors showed that it was not until the damage subsided that protein synthesis was directed to muscle growth.
In the bodybuilding and fitness community and even in some academic books skeletal muscle hypertrophy is described as being either sarcoplasmic or myofibrillar. [ qualify evidence ] According to this hypothesis, during sarcoplasmic hypertrophy, the volume of sarcoplasmic fluid in the muscle cell increases with no accompanying increase in muscular strength, whereas during myofibrillar hypertrophy, actin and myosin contractile proteins increase in number and add to muscular strength as well as a small increase in the size of the muscle. Sarcoplasmic hypertrophy is greater in the muscles of bodybuilders because studies suggest sarcoplasmic hypertrophy shows a greater increase in muscle size while myofibrillar hypertrophy proves to increase overall muscular strength making it more dominant in Olympic weightlifters . [ 37 ] These two forms of adaptations rarely occur completely independently of one another; one can experience a large increase in fluid with a slight increase in proteins, a large increase in proteins with a small increase in fluid, or a relatively balanced combination of the two.
Examples of increased muscle hypertrophy are seen in various professional sports, mainly strength related sports such as boxing , olympic weightlifting , mixed martial arts , rugby , professional wrestling and various forms of gymnastics. Athletes in other more skill-based sports such as basketball, baseball, ice hockey , and football may also train for increased muscle hypertrophy to better suit their position of play. For example, a center (basketball) may want to be bigger and more muscular to better overpower their opponents in the low post. [ 38 ] Athletes training for these sports train extensively not only in strength but also in cardiovascular and muscular endurance training. [ citation needed ]
Some neuromuscular diseases result in true hypertrophy of one or more skeletal muscles, confirmed by MRI or muscle biopsy. As this muscle hypertrophy is not the result of resistance training nor heavy manual labour, this is why the muscle hypertrophy is described as a pseudoathletic appearance .
As muscle hypertrophy is a response to strenuous anaerobic activity, ordinary everyday activity would become strenuous in diseases that result in premature muscle fatigue (neural or metabolic), or disrupt the excitation-contraction coupling in muscle, or cause repetitive or sustained involuntary muscle contractions ( fasciculations , myotonia , or spasticity ). [ 39 ] [ 40 ] In lipodystrophy , an abnormal deficit of subcutaneous fat accentuates the appearance of the muscles, though the muscles are quantifiably hypertrophic (possibly due to a metabolic abnormality). [ 41 ] [ 42 ]
Diseases that result in true muscle hypertrophy include, but not limited to, select: muscular dystrophies, metabolic myopathies, endocrine myopathies, congenital myopathies, non-dystrophic myotonias and pseudomyotonias, denervation, spasticity, and lipodystrophy. The muscle hypertrophy may persist throughout the course of the disease, or may later atrophy, or become pseudohypertrophic (muscle atrophy with infiltration of fat or other tissue). For instance, Duchenne and Becker muscular dystrophy may start as true muscle hypertrophy, but later develop into pseudohypertrophy. [ 43 ] | https://en.wikipedia.org/wiki/Muscle_hypertrophy |
Muscle tissue engineering is a subset of the general field of tissue engineering , which studies the combined use of cells and scaffolds to design therapeutic tissue implants. Within the clinical setting, muscle tissue engineering involves the culturing of cells from the patient's own body or from a donor, development of muscle tissue with or without the use of scaffolds, then the insertion of functional muscle tissue into the patient's body. Ideally, this implantation results in full regeneration of function and aesthetic within the patient's body. Outside the clinical setting, muscle tissue engineering is involved in drug screening, hybrid mechanical muscle actuators, robotic devices, and the development of cell-cultured meat meat as a new food source. [ 1 ]
Innovations within the field of muscle tissue engineering seek to repair and replace defective muscle tissue, thus returning normal function.The practice begins by harvesting and isolating muscle cells from a donor site, then culturing those cells in media. The cultured cells form cell sheets and finally muscle bundles which are implanted into the patient.
Muscle is a naturally aligned organ, with individual muscle fibers packed together into larger units called muscle fascicles . [ 2 ] The uniaxial alignment of muscle fibers allows them to simultaneously contract in the same direction and properly propagate force on the bones via the tendons . Approximately 45% of the human body is composed of muscle tissue, and this tissue can be classified into three different groups: skeletal muscle , cardiac muscle , and smooth muscle . Muscle plays a role in structure, stability, and movement in mammalian bodies. The basic unit for a muscle is a muscle fiber, which is made up of myofilaments actin and myosin. This muscle fiber contains sarcomeres which generate the force required for contraction.
A major focus of muscle tissue engineering is to create constructs with the functionality of native muscle and ability to contract. To this end, alignment of the tissue engineered construct is extremely important. It has been shown that cells grown on substrates with alignment cues form more robust muscle fibers. [ 3 ] Several other design criteria considered in muscle tissue engineering include the scaffold porosity, stiffness, biocompatibility, and degradation timeline. Substrate stiffness should ideally be in the myogenic range, which has been shown to be 10-15 kPa. [ 4 ]
The purpose of muscle tissue engineering is to reconstruct functional muscular tissue which has been lost via traumatic injury, tumor ablation, or functional damage caused by myopathies. Until now, the only method used to restore muscular tissue function and aesthetic was free tissue transfer. Full function is typically not restored, however, which results in donor site morbidity and volume deficiency. The success of tissue engineering as it pertains to the regeneration of skin, cartilage, and bone indicates that the same success will be found in engineering muscular tissue. [ 5 ] Early innovations in the field yielded in vitro cell culturing and regeneration of muscle tissue which would be implanted in the body, but advances in recent years have shown that there may be potential for in vivo muscle tissue engineering using scaffolding .
The term muscle tissue engineering, while it is a subset of the much larger discipline, tissue engineering, was first coined in 1988 when Herman Vandenburgh, a surgeon, cultured avian myotubes in collagen-coated culture plates. [ 6 ] This started a new era of in vitro tissue engineering. The ideal was officially adopted in 1988 in Vandenburgh's publication titled Maintenance of Highly Contractile Tissue-Cultured Avian Skeletal Myotubes in Collagen Gel. [ 7 ] In 1989, the same group determined that mechanical stimulation of myoblasts in vitro facilitates engineered skeletal muscle growth. [ 8 ]
A rudimentary understanding of muscle tissue began to develop as early as 1835, when embryonic myogenesis was first described. In the 1860s, it was shown that muscle is capable of regeneration and an experimental regeneration was conducted to better understand the specific method by which this was done in vivo. Following this discovery, muscle generation and degeneration in man were described for the first time. Researchers consequently assessed several aspects of muscle regeneration in vivo, including "the continuous or discontinuous regeneration depending on tissue type" to increase functional understanding of the phenomena. [ 9 ] It was not until the 1960s, however, that researchers determined what components were required for muscle regeneration. [ 9 ]
In 1957, it was determined via DNA content that myoblasts proliferate, but myonuclei do not. Following this discovery, the satellite cell was experimentally uncovered by Mauro and Katz [ 10 ] as stem cells which sit on the surface of the myofibre and have the capability to differentiate into muscle cells. Satellite cells provide myoblasts for growth, differentiation, and repair of muscle tissue. Muscle tissue engineering officially began as a discipline in 1988 when Herman Vandenburgh cultured avian myotubes in collagen-coated culture plates. Following this development, it was found in 1989 that mechanical stimulation of myoblasts in vitro facilitates engineered skeletal muscle growth. Most of the modern innovations in the field of muscle tissue engineering are found in the 21st century.
Between 2000 and 2010, the effects of volumetric muscle loss (VML) were assessed as it pertains to muscle tissue engineering. VML can be caused by a variety of injuries or diseases, including general trauma , postoperative damage, cancer ablation, congenital defects , and degenerative myopathy . Although muscle contains a stem cell population called satellite cells that are capable of regenerating small muscle injuries, muscle damage in VML is so extensive that it overwhelms muscle's natural regenerative capabilities. Currently VML is treated through an autologous muscle flap or graft but there are various problems associated with this procedure. Donor site morbidity, lack of donor tissue, and inadequate vascularization all limit the ability of doctors to adequately treat VML. [ 11 ] The field of muscle tissue engineering attempts to address this problem through the design of a functional muscle construct that can be used to treat the damaged muscle instead of harvesting an autologous muscle flap from elsewhere on the patient's body.
Research conducted between 2000 and 2010 informed the conclusion that functional analysis of a tissue engineered muscle construct is important to illustrate its potential to help regenerate muscle. A variety of assays are generally used to evaluate a tissue engineered muscle construct including immunohistochemistry , RT-PCR , electrical stimulation and resulting peak-to-peak voltage , scanning electron microscope imaging, and in vivo response.
The most recent advances in the field include cultured meat, biorobotic systems, and biohybrid impants in regenerative medicine or disease modeling. [ 12 ]
The majority of current advancements in muscle tissue engineering reside in the skeletal muscle category, so the majority of these examples will have to do with skeletal muscle engineering and regeneration. We will review a couple of examples of smooth muscle tissue engineering and cardiac muscle tissue engineering in this section as well.
Muscle tissue engineering methods are consistently categorized across literature into three groups: in situ, in vivo, and in vitro muscle tissue engineering. We will assess each of these categories and detail specific practices used in each one.
“ In situ ” is a latin phrase whose literal translation is “on site.” It is a term that has been used in the English language since the mid-eighteenth century to describe something that is in its original place or position. In the context of muscle tissue engineering, in situ tissue engineering involves the introduction and implantation of an acellular scaffold into the site of injury or degenerated tissue. The goal of in situ muscle tissue engineering is to encourage host cell recruitment, natural scaffold formation, and proliferation and differentiation of host cells. The main idea which in situ muscle tissue engineering is based on is the self-healing, regenerative properties of the mammalian body. [ 26 ] The primary method for in situ muscle tissue engineering is described in the following section:
As described in Biomaterials for In Situ Tissue Regeneration: A Review (Abdulghani & Mitchell, 2019), [ 27 ] in situ muscle tissue engineering requires very specific biomaterials which have the capability to recruit stem cells or progenitor cells to the site of the muscle defect, thus allowing regeneration of tissue without implantation of seed cells. The key to a successful scaffold is the appropriate properties (i.e. biocompatibility, mechanical strength, elasticity, biodegradability) and the correct shape and volume for the specific muscle defect in which they are implanted. This scaffold should effectively mimic the cellular response of the host tissue, and Mann et al. have found that Polyethylene glycol-based hydrogels are very successful as in situ biomaterial scaffolds because they are chemically modified to be degraded by biological enzymes, thus encouraging cell migration and proliferation. [ 28 ] Beyond Polyethylene glycol-based hydrogels, synthetic biomaterials such as PLA and PCL are successful in situ scaffolds as they can be fully customized to each specific patient. These materials' stiffness, degradation, and porosity properties are tailored to the degenerated tissue's topology, volume, and cell type so as to provide the optimal environment for host cell migration and proliferation.
In situ engineering promotes natural regeneration of damaged tissue by effectively mimicking the mammalian body's own wound healing response. The use of both biological and synthetic biomaterials as scaffolds promotes host cell migration and proliferation directly to the defect site, thus decreasing the amount of time required for muscle tissue regeneration. Furthermore, in situ engineering effectively bypasses the risk of implant rejection by the immune system due to the biodegradable qualities in each scaffold.
" In vivo " is a latin phrase whose literal translation is "in a living thing." This term is used in the English language to describe a process which occurs inside of a living organism. In the realm of muscle tissue engineering, this term applies to the seeding of cells into a biomaterial scaffold immediately prior to implantation. The goal of in vivo muscle tissue engineering is to create a cell-seeded scaffold that once implanted into the wound site will preserve cell efficacy. In vivo methods provide a greater amount of control over cell phenotype, mechanical properties, and functionality of the tissue construct. [ 26 ]
As described in Skeletal Muscle Tissue Engineering: Biomaterials-Based Strategies for the Treatment of Volumetric Muscle Loss (Carnes & Pins, 2020), [ 26 ] in vivo muscle tissue engineering builds on the concept of in situ engineering by not only implanting a biomaterial scaffold with specific mechanical and chemical properties, but also seeding the scaffold with the specific cell type needed for regeneration of the tissue. Reid et al. [ 29 ] describe common scaffolds utilized in the in vivo muscle tissue engineering process. These scaffolds include hydrogels infused with hyaluronic acid (HA), gelatin silk fibroin, and chitosan as these materials promote muscle cell migration and proliferation. For example, a biodegradable and renewable material derived from chitin known as chitosan, has unique mechanical properties which support smooth muscle cell differentiation and retention in the tissue regeneration site. When this scaffold is further functionalized with Arginine-Glycine-Aspartic Acid (RGD), it provides a better growth environment for smooth muscle cells. Another scaffold commonly used is decellularized extracellular matrix (ECM) tissue as it is fully biocompatible, biodegradable, and contains all of the necessary protein binding sites for full functional recovery and integration of muscle tissue. Once seeded with cells, this material becomes an optimal environment for cell proliferation and integration with existing tissue as it effectively mimics the environment in which tissue naturally regenerates in the mammalian body.
The in vivo muscle tissue engineering technique provides the wound healing process with a "head start" in development, as the body no longer needs to recruit host cells to begin regeneration. This approach also bypasses the need for cell manipulation prior to implantation, thus ensuring that they maintain all of their mechanical and functional properties. [ 30 ]
" In vitro " is a latin phrase whose literal translation is "within the glass." This term is used in the English language to describe a process which occurs outside of a living organism. Within the context of muscle tissue engineering, the term "in vitro" applies to the seeding of cells into a biomaterial scaffold with growth factors and nutrients, then culturing these constructs until a functional construct, such as myofibres, is developed. These developed constructs are then implanted into the wound site with the expectation that they will continue to proliferate and integrate into host muscle tissue. The goal of in vitro muscle tissue engineering is to increase the functionality of the tissue before it is ever implanted into the body, thus increasing mechanical properties and potential to thrive in the host body.
Abdulghani & Mitchell [ 27 ] describe in vitro muscle tissue engineering as a concept with utilizes the same basic strategies of in vivo tissue engineering. The difference between the two methods, however, is the development of a fully functional tissue engineered muscle graft (TEMG) that occurs in the in vitro technique. In vitro muscle tissue engineering includes the seeding of cells onto a biomaterial scaffold, but goes a step further by adding growth factors and biochemical and biophysical cues to promote cell growth, proliferation, differentiation, and finally regeneration into a functional muscle tissue construct. Typically, in vitro scaffolds contain specific surface features which guide the direction of cell proliferation. They are usually fibrous with aligned pores as these features encourage cell adhesion during regeneration. Beyond the types of scaffolds used in this technique, a largely important aspect of this technique is the electrical and mechanical stimulation which mimic the natural regeneration environment and encourage the expansion of intracellular communication pathways. Before TEMGs are introduced into the wound defect, they musts be vascularized to promote proper integration with the host tissue. To achieve vascularization, researchers typically seed a scaffold with multiple cell types in order to develop both muscle tissue and vascular pathways. This process prevents rejection of the TEMG upon implantation as it is able to effectively thrive in the host tissue environment. There is always a risk of immune rejection when implanting fully developed tissue, though, so this method tissue regeneration is the most closely monitored post-implantation. [ 26 ]
The in vitro muscle tissue engineering technique is used to create muscle tissue with more successful functional and mechanical properties. According to Carnes & Pins in Skeletal Muscle Tissue Engineering: Biomaterials-Based Strategies for the Treatment of Volumetric Muscle Loss, [ 26 ] this approach develops a microenvironment that is more conducive to enhancing tissue regeneration upon implantation, thus restoring full functionality to patients.
Current muscle tissue engineering trends lead towards the development of skeletal muscle regeneration techniques over smooth muscle or cardiac muscle regeneration. A current trend found throughout literature is the treatment of Volumetric Muscle Loss (VML) using muscle tissue engineering techniques. VML is the result of abrupt loss of skeletal muscle due to surgical resection, trauma, or combat injuries. [ 29 ] It has been observed that tissue grafts, the current treatment plan, do not restore full functionality or aesthetic integrity to the site of injury. Muscle tissue engineering offers an optimistic possibility for patients, as in situ, in vivo, and in vitro techniques have been proven to restore functionality to muscle tissue in the wound site. Methods being explored include acellular scaffold implantation, cell-seeded scaffold implantation, and in vitro fabrication of muscle grafts. Preliminary data from each of these methods promises a solution for patients suffering from VML.
Beyond specific technological advances in the field of muscle tissue engineering, researchers are working to establish a connection with the larger umbrella that is tissue engineering. | https://en.wikipedia.org/wiki/Muscle_tissue_engineering |
Museomics is the study of genomic data obtained from ancient DNA (aDNA) and historic DNA (hDNA) specimens in museum collections . [ 1 ] [ 2 ] Early research in this area focused on short sequences of DNA from mitochondrial genes , but sequencing of whole genomes has become possible. [ 1 ] Next-generation sequencing (NGS) and high-throughput sequencing (HTS) methods can be applied to the analysis of genetic datasets extracted from collections materials. [ 3 ] Such techniques have been described as a "third revolution in sequencing technology". [ 4 ] Like radiocarbon dating , the techniques of museomics are a transformative technology. Results are revising and sometimes overturning previously accepted theories about a wide variety of topics such as the domestication of the horse . [ 5 ] [ 6 ]
Museum collections contain unique resources such as natural history specimens, which can be used for genome-scale examinations of species, their evolution, and their responses to environmental change. Ancient DNA provides a unique window into genetic change over time. It enables scientists to directly study evolutionary and ecological processes, comparing ancient and modern populations, identifying distinct populations, and revealing patterns of change such as extinctions and migrations . [ 7 ] [ 8 ] [ 9 ] Research may be used to identify isolated populations and inform conservation priorities. [ 2 ]
However, museum specimens can be poorly preserved and are subject to degradation [ 7 ] and contamination. [ 2 ] [ 10 ] Genomic analyses face considerable challenges as a result of the highly degraded DNA typical of museum specimens. DNA from such samples is often subject to post-mortem nucleotide damage such as the hydrolytic deamination of cytosine (C) to uracil (U) residues. PCR amplification of damaged templates can further substitute uracils with thymine (T), completing a C to T substitution path. Such errors tend to occur towards the ends of molecules, accumulate with time, and can be significant in specimens a century-old or later. Robust genomic and statistical techniques are needed to rigorously detect and avoid errors and genotyping uncertainties when carrying out analyses based on museum collections. [ 7 ] Optimal methods for working with hDNA and aDNA can differ as a result of differences in their DNA degradation history. [ 1 ]
Museomics also involves destructive sampling, irreversibly removing parts of sometimes rare specimens to obtain DNA. [ 11 ] This can be contentious for curators and collection staff, [ 1 ] involving a variety of ethical issues around the handling and destruction of objects, colonial acquisition and repatriation practices, and present-day social and political implications of research. Museums, universities and journals are increasingly developing ethics statements, best practices and guidelines for such work. [ 12 ] [ 13 ] | https://en.wikipedia.org/wiki/Museomics |
Museum architecture [ 1 ] has been of increasing importance over the centuries, especially more recently. [ 2 ] [ 3 ] [ 4 ]
A challenge for museum architecture is the differing purposes of the building. [ citation needed ] The museum collection must be preserved, but it also needs to be made accessible to the public. Climate control may be very important for the objects in the collection.
An early example of architecture for a purpose-built museum is the Museum of the History of Science building in Oxford , England , originally built to house the Ashmolean Museum . [ citation needed ]
In the 20th century, museums have been combined with war memorials to serve multiple purposes. The Australian War Memorial in Canberra , for example, is a place of commemoration as well as for collection and display. It contains a museum, an archive and a shrine. It was designed by Emil Sodersten and John Crust in a contemporary neoclassical style reminiscent of Lutyens with detailing influenced by Art Deco .
The Solomon R. Guggenheim Museum in New York City, USA (opened in 1959), by Frank Lloyd Wright is an important architectural landmark and icon of the 20th century. Another classic 20th century example of iconic museum architecture is the titanium-covered Guggenheim Museum Bilbao in Spain by Frank Gehry (opened in 1997). Gehry has undertaken many major museum architecture projects, including the Experience Music Project in Seattle, USA, the Weisman Art Museum in Minneapolis, USA, the Vitra Design Museum and MARTa Museum in Germany, and the Art Gallery of Ontario in Toronto, Canada.
Successful examples of modern architecture being married with existing museum buildings include the Louvre Pyramid by I. M. Pei in Paris, France (1989), and more recently the Queen Elizabeth II Great Court by Norman Foster at the British Museum , London, England (2000).
David Chipperfield designed many notable museums, including the award-winning River and Rowing Museum in Henley-on-Thames, England, in 1997. [ 5 ] This won in 1999 the RIBA Architecture in Arts and Leisure Award and the Royal Fine Art Commission Trust/ British Sky Broadcasting Best Building Award (England) . [ 6 ] Chipperfield also designed the Figge Art Museum in Davenport, Iowa, USA (2005), the Museum of Modern Literature in Marbach, Germany (2006), and the reconstructed Neues Museum in Berlin, Germany (2009).
Museum architecture sometimes involves the conversion of old buildings that have outlived their usefulness but that are still of historic interest. A notable example is the Dalí Theatre and Museum or the conversion of the Bankside Power Station designed by Sir Giles Gilbert Scott into the Tate Modern in 2000, based on design by Herzog & de Meuron . [ 7 ] Information about the conversion was the basis for a 2008 documentary Architects Herzog and de Meuron: Alchemy of Building & Tate Modern . [ 8 ]
Finegold Alexander Architects , an architecture firm based in Boston, Massachusetts, USA, established in 1962, has undertaken museum architecture projects including Ellis Island National Monument and Museum [ 9 ] (Associated Architects with Beyer Blinder Belle Architects) and the United States Holocaust Memorial Museum (Associated Architects with Pei Cobb Freed & Partners).
As well as the architects mentioned above, other architects notable for their contributions to museum architecture include: | https://en.wikipedia.org/wiki/Museum_architecture |
The Museum of Failure [ 1 ] is a museum that features a collection of failed products and services. The touring exhibition provides visitors with a learning experience about the critical role of failure in innovation . According to its founder, Samuel West, the goal of the museum is to help people recognize the "need to accept failure if we want progress", and to encourage companies to learn more from their failures without resorting to "cliches". [ 2 ]
West's 2016 visit to the Museum of Broken Relationships in Zagreb inspired the concept of the museum. [ 3 ] Museum founder and curator Samuel West reportedly registered a domain name for the museum and later realized he had misspelled the word museum. [ 4 ] The Swedish Innovation Authority (Vinnova) partially funded the museum. [ 5 ]
The exhibition opened on 7 June 2017 in Helsingborg , Sweden . [ 4 ] The exhibit reopened at Dunkers Kulturhus on 2 June 2018, before closing in January 2019. A temporary exhibit opened in Los Angeles in December 2017. [ 6 ] The Los Angeles museum was on Hollywood Boulevard in the Hollywood & Highland Center . [ 7 ] The exhibit opened in January – March 2019 at Shanghai, No.1 Center (上海第一百货). [ 8 ] In December 2019, a smaller version opened in Paris, France at the Cité des Sciences et de l'Industrie along with other interesting failure-related exhibitions for the "Festival of Failures" (Les Foirés festival des flops, des bides, des ratés et des inutiles). [ 9 ]
The collection consists of over 150 [ 1 ] failed products and services worldwide. Some examples of the items on display include the Apple Newton , Bic for Her , [ 10 ] Google Glass , N-Gage , lobotomy instruments , Harley-Davidson Cologne, [ 11 ] Kodak DC-40 , Sony Betamax , Lego Fiber Optics, the My Friend Cayla talking doll, [ 12 ] and Coca-Cola BlāK . [ 13 ]
The museum's package of Colgate lasagna is a replica since the company refused to send a real package of the short-lived 1960s product. [ 14 ] [ 15 ] In May 2020, the museum made most of the collection of artifacts available for viewing on its website. | https://en.wikipedia.org/wiki/Museum_of_Failure |
27 October:
The Musha Incident ( Chinese and Japanese : 霧社事件; pinyin : Wùshè Shìjiàn ; Wade–Giles : Wu 4 -she 4 Shih 4 -chien 4 ; rōmaji : Musha Jiken ; Pe̍h-ōe-jī : Bū-siā Sū-kiāⁿ ), also known as the Wushe Rebellion and several other similar names, began in October 1930 and was the last major uprising against colonial Japanese forces in Japanese Taiwan . In response to long-term oppression by Japanese authorities, the Seediq indigenous group in the settlement of Musha (Wushe) attacked a school, killing 134 Japanese and two Han Taiwanese children. In response, the Japanese led a counter-attack, killing 354 Seediq in retaliation. The handling of the incident by the Japanese authorities was strongly criticised, [ by whom? ] leading to many changes in Aboriginal policy.
Previous armed resistance to Japanese imperial authority had been dealt with harshly, as demonstrated by responses to previous uprisings, such as the Tapani Incident , which resulted in a cycle of rebel attacks and harsh Japanese retaliation. [ 2 ] However, by the 1930s, armed resistance had largely been replaced by organised political and social movements among the younger Taiwanese generation. Direct police involvement in local administration had been relaxed, many harsh punishments were abolished, and some elements of self-government, albeit of questionable effectiveness, had been introduced to colonial Taiwan. [ 3 ]
However, a different approach was used in order to control Taiwan's indigenous peoples . The indigenous peoples of Formosa Island were still designated as seiban ( 生蕃 , "raw barbarians" or "wild tribespeople") , and treated as inferiors, rather than as equal subjects. Tribes were "tamed" through "assimilation", the process of disarming traditional hunting tribes and forcing them to relocate to the plains and lead an agrarian existence. Further resistance was then dealt with by military campaigns, isolation and containment. [ 4 ] In order to access natural resources in mountainous and forested indigenous-controlled areas, Governor-General Sakuma Samata adopted a more aggressive terrain policy , attempting to pacify or eradicate aboriginal groups in areas scheduled for logging within five years' time; by 1915, this policy had been largely successful, although resistance still existed in the more remote areas. [ 5 ]
The Seediq people in the vicinity of Musha village had been considered by the Japanese authorities to be one of the most successful examples of this "taming" approach, with Chief Mona Rudao being one of 43 indigenous leaders selected for a tour of Japan a few years earlier. [ 6 ] However, resentment still lingered, due largely to police misconduct, the ongoing practice of forced labor , and the lack of respect for Indigenous beliefs and customs. [ 5 ]
In the days immediately prior to the incident, Chief Mona Rudao held a traditional wedding banquet for his son, Daho Mona, during which animals were slaughtered and wine was prepared and drunk. A Japanese police officer named Katsuhiko Yoshimura was on patrol in the area, and was offered a cup of wine by Daho Mona as a symbolic gesture. The officer refused, saying that Daho Mona's hands were soiled with blood from the slaughtered animals. Daho Mona attempted to take hold of the officer, insisting he participate, and the officer struck him with his stick. Fighting ensued, and the officer was injured. Mona Rudao attempted to apologize by presenting a flagon of wine at the officer's house, but was turned away. [ 7 ] The simmering resentment among the Seediq in Musha was finally pushed to the limit.
On 27 October 1930, hundreds of Japanese converged on Musha for an athletics meet at the elementary school. Shortly before dawn, Mona Rudao led over 300 Seediq warriors in a raid of strategic police sub-stations to capture weapons and ammunition. They then moved on to the elementary school, concentrating their attack on the Japanese in attendance. A total of 134 Japanese, including women and children, were killed in the attack. Two Han Taiwanese dressed in Japanese clothing were also mistakenly killed, [ 8 ] one of whom was a girl wearing a Japanese kimono . [ 9 ] Most of the victims were beheaded . [ 10 ] The Seediqs had intended to kill only Japanese people. [ 11 ]
The Japanese authorities responded with unprecedentedly harsh military action. A press blackout was enforced, and Governor General Ishizuka Eizō ordered a counter-offensive of two thousand troops to be sent to Musha, forcing the Seediq to retreat into the mountains and carry out guerrilla attacks by night. Unable to root out the Seediq despite their superior numbers and greater firepower, the Japanese faced a political need for a faster solution. Consequently, Japan's army air corps in Taiwan ordered bombing runs over Musha to smoke out the rebels, dropping mustard gas bombs in what was allegedly the first such use of chemical warfare in Asia. [ 12 ] [ 7 ] [ 14 ] The uprising was swiftly quelled, with any remaining resistance suppressed by the third week of December 1930; [ 7 ] Mona Rudao had committed suicide on November 28, but the uprising had continued under other leaders. [ 15 ] Of the 1,200 Seediq directly involved in the uprising, 644 died, 290 of whom committed suicide to avoid dishonour. [ citation needed ] While the Geneva Protocol of 1925 made the wartime use of chemical weapons by land, naval, and air forces a war crime , the treaty does not apply to internal disturbances or conflicts, [ 16 ] and Japan was not a signatory to the treaty until May 21, 1975. [ 17 ]
Due to internal and external criticism of their handling of the incident, Ishizuka and Hitomi Jirō, his chief civil administrator, were forced to resign in January 1931. However, Ishizuka's replacement, Ōta Masahiro , also took a harsh approach to controlling Taiwan's indigenous peoples: certain tribes were disarmed and left unprotected, giving their aboriginal enemies an opportunity to annihilate them on behalf of the Japanese administration. [ 5 ] Around 500 of the Seediq involved in the Musha Incident surrendered and were subsequently confined to a village near Musha. However, on 25 April 1931, indigenous groups working with the Japanese authorities attacked the village, beheading all remaining males over the age of 15. This is known as the "Second Musha Incident". [ citation needed ]
The uprising did effect a change in the authorities' attitudes and approaches towards aboriginals in Taiwan. Musha had been regarded as the most "enlightened and compliant" of the aboriginal territories, and the colonial power's inability to prevent the massacre provoked a fear of similar nationalist movements starting in Taiwan, Korea, and Japan itself. A change in policy was clearly needed. Ching suggests that the institution of empire-building ( kominka 皇民化 ) became the dominant expression of colonial control: aboriginals came to be seen as imperial subjects on equal footing with other ethnic groups in Taiwan, and were upgraded in status from "raw savages" to takasagozoku ( 高砂族 , "tribal peoples of Taiwan") . [ 18 ]
During the Musha Incident, the Seediq under Mona Rudao revolted against the Japanese, while the Truku and Toda did not. The rivalry of the Seediq with the Toda and Truku was aggravated by the Musha Incident, given that the Japanese had long played them off against each other. Following the incident, part of Seediq land was ceded to the Truku and Toda by the authority. [ citation needed ]
The Musha Incident has been depicted three times in movies, in 1957 in the Taiwanese film Qing Shan bi xue ( 青山碧血 ), [ 19 ] in the 2003 TV drama Dana Sakura [ zh ] , and in the 2011 Taiwanese film Seediq Bale .
Wu He 's novel Remains of Life (originally published in Chinese in 2000; published in English translation in 2017) is a fictionalized account of the aftermath of this incident. [ 20 ] | https://en.wikipedia.org/wiki/Musha_Incident |
A mushroom cloud is a distinctive mushroom -shaped flammagenitus cloud of debris, smoke, and usually condensed water vapour resulting from a large explosion. The effect is most commonly associated with a nuclear explosion , but any sufficiently energetic detonation or deflagration will produce a similar effect. They can be caused by powerful conventional weapons , including thermobaric weapons such as the ATBIP and GBU-43/B MOAB . Some volcanic eruptions and impact events can produce natural mushroom clouds.
Mushroom clouds result from the sudden formation of a large volume of lower-density gases at any altitude, causing a Rayleigh–Taylor instability . The buoyant mass of gas rises rapidly, resulting in turbulent vortices curling downward around its edges, forming a temporary vortex ring that draws up a central column, possibly with smoke, debris, condensed water vapor, or a combination of these, to form the "mushroom stem". The mass of gas plus entrained moist air eventually reaches an altitude where it is no longer of lower density than the surrounding air; at this point, it disperses, drifting back down , which results in fallout following a nuclear blast. The stabilization altitude depends strongly on the profiles of the temperature, dew point, and wind shear in the air at and above the starting altitude.
Although the term appears to have been coined in the early 1950s, mushroom clouds generated by explosions were being described centuries before the Atomic Age . A contemporary aquatint by an unknown artist of the 1782 Franco-Spanish attack on Gibraltar shows one of the attacking force's floating batteries exploding with a mushroom cloud after the British defenders set it ablaze by firing heated shot .
In 1798, Gerhard Vieth published a detailed and illustrated account of a cloud in the neighborhood of Gotha that was "not unlike a mushroom in shape". The cloud had been observed by legation counselor Lichtenberg a few years earlier on a warm summer afternoon. It was interpreted as an irregular meteorological cloud and seemed to have caused a storm with rain and thunder from a new dark cloud that developed beneath it. Lichtenberg stated to have later observed somewhat similar clouds, but none as remarkable. [ 1 ]
The 1917 Halifax Explosion produced a mushroom cloud. In 1930 Olaf Stapledon in his novel Last and First Men imagines the first demonstration of an atomic weapon "clouds of steam from the boiling sea.. a gigantic mushroom of steam and debris". The Times published a report on 1 October 1937 of a Japanese attack on Shanghai , China , that generated "a great mushroom of smoke". During World War II , the destruction of the Japanese battleship Yamato produced a mushroom cloud. [ 2 ]
The atomic bomb cloud over Nagasaki , Japan, was described in The Times of London of 13 August 1945 as a "huge mushroom of smoke and dust". On 9 September 1945, The New York Times published an eyewitness account of the Nagasaki bombing, written by William L. Laurence , the official newspaper correspondent of the Manhattan Project , who accompanied one of the three aircraft that made the bombing run. He wrote of the bomb producing a "pillar of purple fire " out of the top of which came "a giant mushroom that increased the height of the pillar to a total of 45,000 feet". [ 3 ]
In 1946, the Operation Crossroads nuclear bomb tests were described as having a " cauliflower " cloud, but a reporter present also spoke of "the mushroom, now the common symbol of the atomic age". Mushrooms have traditionally been associated both with life and death, food and poison, which made them a more powerful symbolic connection than, say, the "cauliflower" cloud. [ 4 ]
Mushroom clouds are formed by many sorts of large explosions under Earth's gravity, but they are best known for their appearance after nuclear detonations . Without gravity, or without a thick atmosphere, the explosive's by-product gases would remain spherical. Nuclear weapons are usually detonated above the ground (not upon impact, because some of the energy would be dissipated by the ground motions), to maximize the effect of their spherically expanding fireball and blast wave . Immediately after the detonation, the fireball begins to rise into the air, acting on the same principle as a hot-air balloon .
One way to analyze the motion, once the hot gas has cleared the ground sufficiently, is as a "spherical cap bubble", [ 5 ] as this gives agreement between the rate of rise and observed diameter.
As it rises, a Rayleigh–Taylor instability is formed, and air is drawn upwards and into the cloud (similar to the updraft of a chimney ), producing strong air currents known as "afterwinds", while, inside the head of the cloud, the hot gases rotate in a toroidal shape. When the detonation altitude is low enough, these afterwinds will draw in dirt and debris from the ground below to form the stem of the mushroom cloud.
Once the mass of hot gases reaches its equilibrium level, the ascent stops, and the cloud begins to flatten into the characteristic mushroom shape, often assisted by surface growth from decaying turbulence.
At the moment of a nuclear explosion, a fireball is formed. The ascending, roughly spherical mass of hot, incandescent gases changes shape due to atmospheric friction, and the surface of the fireball is cooled by energy radiation, turning from a sphere to a violently rotating spheroidal vortex. A Rayleigh–Taylor instability is formed as the cool air underneath initially pushes the bottom fireball gases into an inverted cup shape. This causes turbulence and a vortex that sucks more air into the center, creating external afterwinds and further cooling the fireball. The speed of rotation slows as the fireball cools and may stop entirely during later phases. The vaporized parts of the weapon and ionized air cool into visible gases, forming a cloud; the white-hot vortex core becomes yellow, then dark red, then loses visible incandescence. With further cooling, the bulk of the cloud fills in as atmospheric moisture condenses. As the cloud ascends and cools, its buoyancy lessens, and its ascent slows. If the size of the fireball is comparable to the atmospheric density scale height , the whole cloud rise will be ballistic , overshooting a large volume of overdense air to greater altitudes than the final stabilization altitude. Significantly smaller fireballs produce clouds with buoyancy-governed ascent.
After reaching the tropopause (the bottom of the region of strong static stability) the cloud tends to slow and spread out. If it contains sufficient energy, the central part may continue rising up into the stratosphere as an analog of a standard thunderstorm . [ 6 ] A mass of air ascending from the troposphere to the stratosphere leads to the formation of acoustic gravity waves , virtually identical to those created by intense stratosphere-penetrating thunderstorms. Smaller-scale explosions penetrating the tropopause generate waves of higher frequency, classified as infrasound . The explosion raises a large amount of moisture-laden air from lower altitudes. As the air rises, its temperature drops and its water vapour first condenses as water droplets and later freezes as ice crystals. The phase change releases latent heat , heating the cloud and driving it to yet higher altitudes. The heads of the clouds consist of highly radioactive particles, primarily the fission products and other weapon debris aerosols, and are usually dispersed by the wind, though weather patterns (especially rain) can produce nuclear fallout . [ 7 ] The droplets of condensed water gradually evaporate, leading to the cloud's apparent disappearance. The radioactive particles, however, remain suspended in the air, and the invisible cloud continues depositing fallout along its path.
A mushroom cloud undergoes several phases of formation. [ 8 ]
The shape of the cloud is influenced by the local atmospheric conditions and wind patterns. The fallout distribution is predominantly a downwind plume . However, if the cloud reaches the tropopause, it may spread against the wind, because its convection speed is higher than the ambient wind speed. At the tropopause, the cloud shape is roughly circular and spread out. The initial color of some radioactive clouds can be colored red or reddish-brown, due to presence of nitrogen dioxide and nitric acid , formed from initially ionized nitrogen , oxygen , and atmospheric moisture. In the high-temperature, high-radiation environment of the blast, ozone is also formed. It is estimated that each megaton of yield produces about 5,000 tons of nitrogen oxides. [ 10 ] A higher-yield detonation can carry the nitrogen oxides from the burst high enough in atmosphere to cause significant depletion of the ozone layer . Yellow and orange hues have also been described. This reddish hue is later obscured by the white colour of water/ice clouds, condensing out of the fast-flowing air as the fireball cools, and the dark colour of smoke and debris sucked into the updraft. The ozone gives the blast its characteristic corona discharge -like smell. [ 11 ]
The distribution of radiation in the mushroom cloud varies with the yield of the explosion, type of weapon, fusion –fission ratio, burst altitude, terrain type, and weather. In general, lower-yield explosions have about 90% of their radioactivity in the mushroom head and 10% in the stem. In contrast, megaton-range explosions tend to have most of their radioactivity in the lower third of the mushroom cloud. The fallout may appear as dry, ash-like flakes, or as particles too small to be visible; in the latter case, the particles are often deposited by rain. Large amounts of newer, more radioactive particles deposited on skin can cause beta burns , often presenting as discolored spots and lesions on the backs of exposed animals. [ 13 ] The fallout from the Castle Bravo test had the appearance of white dust and was nicknamed Bikini snow ; the tiny white flakes resembled snowflakes , stuck to surfaces, and had a salty taste. In Operation Wigwam , 41.4% of the fallout consisted of irregular opaque particles, slightly over 25% of particles with transparent and opaque areas, approximately 20% of microscopic marine organisms, and 2% of microscopic radioactive threads of unknown origin. [ 14 ]
With surface and near-surface air bursts, the amount of debris lofted into the air decreases rapidly with increasing burst altitude. At a burst altitude of approximately 7 meters/kiloton 1 ⁄ 3 , a crater is not formed, and correspondingly lower amounts of dust and debris are produced. The fallout-reducing height, above which the primary radioactive particles consist mainly of the fine fireball condensation, is approximately 55 meters/kiloton 0.4 . [ 7 ] However, even at these burst altitudes, fallout may be formed by other mechanisms. Airbursts produce white, steamy stems, while surface bursts produce gray to brown stems because large amounts of dust, dirt, soil, and debris are sucked into the mushroom cloud. Surface bursts produce dark mushroom clouds containing irradiated material from the ground in addition to the bomb and its casing and therefore produce more radioactive fallout, with larger particles that readily deposit locally.
A detonation high above the ground may produce a mushroom cloud without a stem. A double mushroom, with two levels, can be formed under certain conditions. For example, the Buster-Jangle Sugar shot formed the first head from the blast, followed by another one generated by the heat from the hot, freshly formed crater. [ 14 ]
A detonation significantly below ground level or deep below the water (for instance, a nuclear depth charge) does not produce a mushroom cloud, as the explosion causes the vaporization of a huge amount of earth or water, creating a bubble which then collapses in on itself; in the case of a less deep underground explosion, this produces a subsidence crater . An underwater detonation near the surface may produce a pillar of water which collapses to form a cauliflower-like shape, which is easily mistaken for a mushroom cloud (such as in the well-known pictures of the Crossroads Baker test). An underground detonation at low depth produces a mushroom cloud and a base surge , two different distinct clouds. The amount of radiation vented into the atmosphere decreases rapidly with increasing detonation depth.
The cloud contains three main classes of material: the remains of the weapon and its fission products, the material acquired from the ground (only significant for burst altitudes below the fallout-reducing altitude, which depends on the weapon yield), and water vapour. The bulk of the radiation contained in the cloud consists of the nuclear fission products; neutron activation products from the weapon materials, air, and the ground debris form only a minor fraction. Neutron activation starts during the neutron burst at the instant of the blast, and the range of this neutron burst is limited by the absorption of the neutrons as they pass through the Earth's atmosphere.
Thermonuclear weapons produce a significant part of their yield from nuclear fusion . Fusion products are typically non-radioactive. The degree of radiation fallout production is therefore measured in kilotons of fission. The Tsar Bomba , which produced 97% of its 50-megaton yield from fusion, was a very clean weapon compared to what would typically be expected of a weapon of its yield (although it still produced 1.5 megatons of its yield from fission), as its fusion tamper was made of lead instead of uranium-238 ; otherwise, its yield would have been 100 megatons with 51 megatons produced from fission. Were it to be detonated at or near the surface, its fallout would comprise fully one-quarter of all the fallout from every nuclear weapon test , combined.
Initially, the fireball contains a highly ionized plasma consisting only of atoms of the weapon, its fission products, and atmospheric gases of adjacent air. As the plasma cools, the atoms react, forming fine droplets and then solid particles of oxides. The particles coalesce to larger ones, and deposit on surface of other particles. Larger particles usually originate from material aspired into the cloud. Particles aspired while the cloud is still hot enough to melt them mix with the fission products throughout their volume. Larger particles get molten radioactive materials deposited on their surface. Particles aspired into the cloud later, when its temperature is low enough, do not become significantly contaminated. Particles formed only from the weapon are fine enough to stay airborne for a long time and become widely dispersed and diluted to non-hazardous levels. Higher-altitude blasts which do not aspire ground debris, or which aspire dust only after cooling enough and where the radioactive fraction of the particles is therefore small, cause a much smaller degree of localized fallout than lower-altitude blasts with larger radioactive particles formed.
The concentration of condensation products is the same for the small particles and for the deposited surface layers of larger particles. About 100 kg of small particles are formed per kiloton of yield. The volume, and therefore activity, of the small particles is almost three orders of magnitude lower than the volume of the deposited surface layers on larger particles. For higher-altitude blasts, the primary particle forming processes are condensation and subsequent coagulation. For lower-altitude and ground blasts, with involvement of soil particles, the primary process is deposition on the foreign particles.
A low-altitude detonation produces a cloud with a dust loading of 100 tons per megaton of yield. A ground detonation produces clouds with about three times as much dust. For a ground detonation, approximately 200 tons of soil per kiloton of yield is melted and comes in contact with radiation. [ 9 ] The fireball volume is the same for a surface or an atmospheric detonation. In the first case, the fireball is a hemisphere instead of a sphere, with a correspondingly larger radius. [ 9 ]
The particle sizes range from submicrometer- and micrometer-sized (created by condensation of plasma in the fireball), through 10–500 micrometers (surface material agitated by the blast wave and raised by the afterwinds), to millimeter and above (crater ejecta). The size of particles together with the altitude they are carried to, determines the length of their stay in the atmosphere, as larger particles are subject to dry precipitation. Smaller particles can be also scavenged by precipitation, either from the moisture condensing in the cloud or from the cloud intersecting with a rain cloud. The fallout carried down by rain is known as rain-out if scavenged during raincloud formation, washout if absorbed into already formed falling raindrops. [ 15 ]
Particles from air bursts are smaller than 10–25 micrometers, usually in the submicrometer range. They are composed mostly of iron oxides , with smaller proportion of aluminium oxide , and uranium and plutonium oxides . Particles larger than 1–2 micrometers are very spherical, corresponding to vaporized material condensing into droplets and then solidifying. The radioactivity is evenly distributed throughout the particle volume, making total activity of the particles linearly dependent on particle volume. [ 9 ] About 80% of activity is present in more volatile elements, which condense only after the fireball cools to considerable degree. For example, strontium-90 will have less time to condense and coalesce into larger particles, resulting in greater degree of mixing in the volume of air and smaller particles. [ 16 ] The particles produced immediately after the burst are small, with 90% of the radioactivity present in particles smaller than 300 nanometers. These coagulate with stratospheric aerosols. Coagulation is more extensive in the troposphere, and, at ground level, most activity is present in particles between 300 nm and 1 μm . The coagulation offsets the fractionation processes at particle formation, evening out isotopic distribution.
For ground and low-altitude bursts, the cloud contains vaporized, melted and fused soil particles. The distribution of activity through the particles depends on their formation. Particles formed by vaporization-condensation have activity evenly distributed through volume as the air-burst particles. Larger molten particles have the fission products diffused through the outer layers, and fused and non-melted particles that were not heated sufficiently but came in contact with the vaporized material or scavenged droplets before their solidification have a relatively thin layer of high activity material deposited on their surface. The composition of such particles depends on the character of the soil, usually a glass-like material formed from silicate minerals. The particle sizes do not depend on the yield but instead on the soil character, as they are based on individual grains of the soil or their clusters. Two types of particles are present, spherical, formed by complete vaporization-condensation or at least melting of the soil, with activity distributed evenly through the volume (or with a 10–30% volume of inactive core for larger particles between 0.5–2 mm), and irregular-shaped particles formed at the edges of the fireball by fusion of soil particles, with activity deposited in a thin surface layer. The amount of large irregular particles is insignificant. [ 9 ] Particles formed from detonations above, or in, the ocean, will contain short-lived radioactive sodium isotopes, and salts from the sea water . Molten silica is a very good solvent for metal oxides and scavenges small particles easily; explosions above silica-containing soils will produce particles with isotopes mixed through their volume. In contrast, coral debris, based on calcium carbonate , tends to adsorb radioactive particles on its surface. [ 16 ]
The elements undergo fractionation during particle formation, due to their different volatility . Refractory elements ( Sr , Y , Zr , Nb , Ba , La , Ce , Pr , Nd , Pm ) form oxides with high boiling points ; these precipitate the fastest and at the time of particle solidification, at temperature of 1400 °C, are considered to be fully condensed. Volatile elements ( Kr , Xe , I , Br ) are not condensed at that temperature. Intermediate elements have their (or their oxides) boiling points close to the solidification temperature of the particles ( Rb , Cs , Mo , Ru , Rh , Tc , Sb , Te ). The elements in the fireball are present as oxides, unless the temperature is above the decomposition temperature of a given oxide. Less refractory products condense on surfaces of solidified particles. Isotopes with gaseous precursors solidify on the surface of the particles as they are produced by decay.
The largest and therefore most radioactive particles are deposited by fallout in the first few hours after the blast. Smaller particles are carried to higher altitudes and descend more slowly, reaching ground in a less radioactive state as the isotopes with the shortest half-lives decay the fastest. The smallest particles can reach the stratosphere and stay there for weeks, months, or even years, and cover an entire hemisphere of the planet via atmospheric currents. The higher danger, short-term, localized fallout is deposited primarily downwind from the blast site, in a cigar-shaped area, assuming a wind of constant strength and direction. Crosswinds, changes in wind direction, and precipitation are factors that can greatly alter the fallout pattern. [ 17 ]
The condensation of water droplets in the mushroom cloud depends on the amount of condensation nuclei . Too many condensation nuclei actually inhibit condensation, as the particles compete for a relatively insufficient amount of water vapor. Chemical reactivity of the elements and their oxides, ion adsorption properties, and compound solubility influence particle distribution in the environment after deposition from the atmosphere. Bioaccumulation influences the propagation of fallout radioisotopes in the biosphere .
The primary fallout hazard is gamma radiation from short-lived radioisotopes , which represent the bulk of activity. Within 24 hours after a burst, the fallout gamma radiation level drops 60 times. Longer-life radioisotopes, typically caesium-137 and strontium-90 , present a long-term hazard. Intense beta radiation from the fallout particles can cause beta burns to people and animals coming in contact with the fallout shortly after the blast. Ingested or inhaled particles cause an internal dose of alpha and beta radiation, which may lead to long-term effects, including cancer. The neutron irradiation of the atmosphere produces a small amount of activation, mainly as long-lived carbon-14 and short-lived argon -41. The elements most important for induced radioactivity for sea water are sodium -24, chlorine , magnesium , and bromine . For ground bursts, the elements of concern are aluminium -28, silicon -31, sodium-24, manganese -56, iron -59, and cobalt-60 .
The bomb casing can be a significant sources of neutron-activated radioisotopes. The neutron flux in the bombs, especially thermonuclear devices, is sufficient for high-threshold nuclear reactions . The induced isotopes include cobalt-60, 57 and 58, iron-59 and 55, manganese-54, zinc-65, yttrium-88, and possibly nickel-58 and 62, niobium-63, holmium-165, iridium-191, and short-lived manganese-56, sodium-24, silicon-31, and aluminium-28. Europium -152 and 154 can be present, as well as two nuclear isomers of rhodium -102. During the Operation Hardtack , tungsten -185, 181 and 187 and rhenium -188 were produced from elements added as tracers to the bomb casings, to allow identification of fallout produced by specific explosions. Antimony -124, cadmium -109, and cadmium-113m are also mentioned as tracers. [ 9 ]
The most significant radiation sources are the fission products from the primary fission stage, and in the case of fission-fusion-fission weapons, from the fission of the fusion stage uranium tamper. Many more neutrons per unit of energy are released in a thermonuclear explosion in comparison with a purely fission yield influencing the fission products composition. For example, uranium-237 is a unique thermonuclear explosion marker, as it is produced by a (n,2n) reaction from uranium-238 , with the minimal neutron energy needed being about 5.9 MeV. Considerable amounts of neptunium-239 and uranium-237 are indicators of a fission-fusion-fission explosion. Minor amounts of uranium-240 are also formed, and capture of large numbers of neutrons by individual nuclei leads to formation of small but detectable amounts of higher transuranium elements , e.g. einsteinium -255 and fermium -255. [ 9 ]
One of the important fission products is krypton-90 , a radioactive noble gas . It diffuses easily in the cloud and undergoes two decays to rubidium-90 and then strontium-90 , with half-lives of 33 seconds and 3 minutes. The noble gas nonreactivity and rapid diffusion is responsible for depletion of local fallout in Sr-90, and corresponding Sr-90 enrichment of remote fallout. [ 18 ]
The radioactivity of the particles decreases with time, with different isotopes being significant at different timespans. For soil activation products, aluminium-28 is the most important contributor during the first 15 minutes. Manganese-56 and sodium-24 follow until about 200 hours. Iron-59 follows at 300 hours, and after 100–300 days, the significant contributor becomes cobalt-60.
Radioactive particles can be carried for considerable distances. Radiation from the Trinity test was washed out by a rainstorm in Illinois . This was deduced, and the origin traced, when Eastman Kodak found x-ray films were being fogged by cardboard packaging produced in the Midwest . Unanticipated winds carried lethal doses of Castle Bravo fallout over the Rongelap Atoll , forcing its evacuation. The crew of Daigo Fukuryu Maru , a Japanese fishing boat located outside of the predicted danger zone, was also affected. Strontium-90 found in worldwide fallout later led to the Partial Test Ban Treaty . [ 16 ]
The intense radiation in the first seconds after the blast may cause an observable aura of fluorescence , the blue-violet-purple glow of ionized oxygen and nitrogen out to a significant distance from the fireball, surrounding the head of the forming mushroom cloud. [ 19 ] [ 20 ] [ 21 ] This light is most easily visible at night or under conditions of weak daylight. [ 7 ] The brightness of the glow decreases rapidly with elapsed time since the detonation, becoming only barely visible after a few tens of seconds. [ 22 ]
Nuclear mushroom clouds are often accompanied by short-lived vapour clouds, known variously as "Wilson clouds", condensation clouds , or vapor rings. The "negative phase" following the positive overpressure behind a shock front causes a sudden rarefaction of the surrounding medium. This low pressure region causes an adiabatic drop in temperature, causing moisture in the air to condense in an outward moving shell surrounding the explosion. When the pressure and temperature return to normal, the Wilson cloud dissipates. [ 23 ] Scientists observing the Operation Crossroads nuclear tests in 1946 at Bikini Atoll named that transitory cloud a "Wilson cloud" because of its visual similarity to a Wilson cloud chamber ; the cloud chamber uses condensation from a rapid pressure drop to mark the tracks of electrically charged subatomic particles . Analysts of later nuclear bomb tests used the more general term "condensation cloud" in preference to "Wilson cloud".
The same kind of condensation is sometimes seen above the wings of jet aircraft at low altitude in high-humidity conditions. The top of a wing is a curved surface. The curvature (and increased air velocity) causes a reduction in air pressure, as given by Bernoulli's Law . This reduction in air pressure causes cooling, and when the air cools past its dew point , water vapour condenses out of the air, producing droplets of water, which become visible as a white cloud. In technical terms, the "Wilson cloud" is also an example of the Prandtl–Glauert singularity in aerodynamics. [ citation needed ]
The shape of the shock wave is influenced by variation of the speed of sound with altitude, and the temperature and humidity of different atmospheric layers determines the appearance of the Wilson clouds. Condensation rings around or above the fireball are a commonly observed feature. Rings around the fireball may become stable, becoming rings around the rising stem. Higher-yield explosions cause intense updrafts , where air speeds can reach 300 miles per hour (480 km/h). The entrainment of higher-humidity air, combined with the associated drop in pressure and temperature, leads to the formation of skirts and bells around the stem. If the water droplets become sufficiently large, the cloud structure they form may become heavy enough to descend; in this way, a rising stem with a descending bell around it can be produced. Layering of humidity in the atmosphere, responsible for the appearance of the condensation rings as opposed to a spherical cloud, also influences the shape of the condensation artifacts along the stem of the mushroom cloud, as the updraft causes laminar flow . The same effect above the top of the cloud, where the expansion of the rising cloud pushes a layer of warm, humid, low-altitude air upwards into cold, high-altitude air, first causes the condensation of water vapour out of the air and then causes the resulting droplets to freeze, forming ice caps (or icecaps ), similar in both appearance and mechanism of formation to scarf clouds .
The resulting composite structures can become very complex. The Castle Bravo cloud had, at various phases of its development, 4 condensation rings, 3 ice caps, 2 skirts, and 3 bells. | https://en.wikipedia.org/wiki/Mushroom_cloud |
A musical keyboard is the set of adjacent depressible levers or keys on a musical instrument . Keyboards typically contain keys for playing the twelve notes of the Western musical scale , with a combination of larger, longer keys and smaller, shorter keys that repeats at the interval of an octave . Pressing a key on the keyboard makes the instrument produce sounds—either by mechanically striking a string or tine ( acoustic and electric piano , clavichord ), plucking a string ( harpsichord ), causing air to flow through a pipe organ , striking a bell ( carillon ), or activating an electronic circuit ( synthesizer , digital piano , electronic keyboard ). Since the most commonly encountered keyboard instrument is the piano , the keyboard layout is often referred to as the piano keyboard or simply piano keys .
The twelve notes of the Western musical scale are laid out with the lowest note on the left. The longer keys (for the seven "natural" notes of the C major scale : C, D, E, F, G, A, B) jut forward. Because these keys were traditionally covered in ivory they are often called the white notes or white keys . The keys for the remaining five notes—which are not part of the C major scale—(i.e., C ♯ /D ♭ , D ♯ /E ♭ , F ♯ /G ♭ , G ♯ /A ♭ , A ♯ /B ♭ ) (see Sharp and Flat ) are raised and shorter. Because these keys receive less wear, they are often made of black colored wood and called the black notes or black keys . Black keys form a pentatonic scale . The entire pattern repeats at the interval of an octave .
The arrangement of longer keys for C major with intervening, shorter keys for the intermediate semitones date to the 15th century. Many keyboard instruments dating from before the nineteenth century, such as harpsichords and pipe organs, have a keyboard with the colours of the keys reversed: the white notes are made of ebony and the black notes are covered with softer white bone. A few electric and electronic instruments from the 1960s and subsequent decades have also done this; Vox's electronic organs of the 1960s, Farfisa's FAST portable organs, Hohner's Clavinet L, one version of the Korg Poly-800 synthesizer and Roland's digital harpsichords.
Some 1960s electronic organs used reverse colors or gray sharps or naturals to indicate the lower part (or parts) of a single keyboard divided into two parts, each controlling a different registration or sound. Such keyboards accommodate melody and contrasting accompaniment without the expense of a second manual , and were a regular feature in Spanish and some English organs of the renaissance and baroque eras. The break was between middle C and C-sharp , or outside of Iberia between B and C. Broken keyboards reappeared in 1842 with the harmonium , the split occurring at E4 /F4.
The reverse-colored keys on Hammond organs such as the B3, C3 and A100 are latch-style radio buttons for selecting pre-set sounds.
The chromatic range (also called compass ) of keyboard instruments has tended to increase. Harpsichords often extended over five octaves (>60 keys) in the 18th century, while most pianos manufactured since about 1870 have 88 keys. The lowest pitch (frequency: 27.5 Hz) of an 88-key piano is equivalent to a sub contrabass in the range name. Some modern pianos have even more notes (a Bösendorfer 290 "Imperial" has 97 keys, and a Stuart & Sons model has 108 keys [ 1 ] ). While modern synthesizer keyboards commonly have either 61, 76 or 88 keys, small MIDI controllers are available with 25 keys (digital systems allow shifting octaves, pitch, and "splitting" ranges dynamically, which, in some cases, reduce the need for dedicated keys. However, smaller keyboards will typically limit which musical scores can be played). Organs normally have 61 keys per manual, though some spinet models have 44 or 49. An organ pedalboard is a keyboard with long pedals played by the organist's feet. Pedalboards vary in size from 12 to 32 notes or 42 on a touring organ used by Cameron Carpenter.
In a typical keyboard layout, black note keys have uniform width, and white note keys have uniform width and uniform spacing at the front of the keyboard. In the larger gaps between the black keys, the width of the natural notes C, D and E differ slightly from the width of keys F, G, A and B. This allows close to uniform spacing of 12 keys per octave while maintaining uniformity of seven "natural" keys per octave.
Over the last three hundred years, the octave span distance found on historical keyboard instruments (organs, virginals , clavichords , harpsichords , and pianos ) has ranged from as little as 125 mm (4.9 in) to as much as 170 mm (6.7 in). [ citation needed ] Modern piano keyboards ordinarily have an octave span of 164–165 mm (6.46–6.50 in), resulting in the width of black keys averaging 13.7 mm (0.54 in) and white keys about 23.5 mm (0.93 in) at the base, disregarding space between keys.
In recent years, there has been evidence of a correlation between pianists with smaller hand spans and hand or arm injuries. [ 2 ] [ 3 ] Several reduced-size standards have been proposed for these pianists. A 7/8 size (140 mm (5.5 in) octave span) keyboard was developed by Canadian Christopher Donison in the 1970s. This size, along with the 15/16 size (152 mm (6.0 in) octave span) and a smaller size (130 mm (5.1 in) octave span) have since been developed and marketed by Steinbuhler & Company in Pennsylvania. These three sizes are registered as DS6.0, DS5.5 and DS5.1. The company was converted to the non-profit DS Standard Foundation in 2018. Hailun USA manufactures pianos in the two alternative DS6.0 and DS5.5 sizes through an agreement with the DS Standard Foundation. Since 2013, a global network of pianists, teachers and performing arts health professionals has been increasingly advocating for change to the 'one size fits all' approach to piano keyboard manufacturing by major companies. This network is known as PASK ( Pianists for Alternatively Sized Keyboards ). [ 4 ] U.S. pianist Hannah Reimann has promoted piano keyboards with narrower octave spans and has a U.S. patent on the apparatus and methods for modifying existing pianos to provide interchangeable keyboards of different sizes. [ 5 ] Narrower keyboards are available from Steinway & Sons USA in new grand pianos or as a retrofit to existing pianos. [ 6 ]
There have been variations in the design of the keyboard to address technical and musical issues. The earliest designs of keyboards were based heavily on the notes used in Gregorian chant (the seven diatonic notes plus B-flat) and as such would often include B ♭ and B ♮ both as diatonic "white notes", with the B ♮ at the leftmost side of the keyboard and the B ♭ at the rightmost. Thus, an octave would have eight "white keys" and only four "black keys". The emphasis on these eight notes would continue for a few centuries after the "seven and five" system was adopted, in the form of the short octave : the eight aforementioned notes were arranged at the leftmost side of the keyboard, compressed in the keys between E and C (at the time, accidentals that low were very uncommon and thus not needed). During the sixteenth century, when instruments were often tuned in meantone temperament , some harpsichords were constructed with the G ♯ and E ♭ keys split into two. One portion of the G ♯ key operated a string tuned to G ♯ and the other operated a string tuned to A ♭ , similarly one portion of the E ♭ key operated a string tuned to E ♭ , the other portion operating a string tuned to D ♯ . This type of keyboard layout, known as the enharmonic keyboard , extended the flexibility of the harpsichord, enabling composers to write keyboard music calling for harmonies containing the so-called wolf fifth (G-sharp to E-flat), but without producing aural discomfort in the listeners (see Split sharp ). The "broken octave", a variation of the aforementioned short octave, similarly used split keys to add accidentals left out of the short octave. Other examples of variations in keyboard design include the Jankó keyboard and the chromatic keyboard systems on the chromatic button accordion and bandoneón .
Simpler electronic keyboards have switches under each key. Depressing a key connects a circuit, which triggers tone generation. Most keyboards use a keyboard matrix circuit , in which 8 rows and 8 columns of wires cross — thus, 16 wires can provide 8 × 8 = 64 crossings, which the keyboard controller scans to determine which key was pressed. [ 7 ] The problem with this system is that it provides only a crude binary on/off signal for each key. Better electronic keyboards employ two sets of slightly offset switches for each key. By determining the timing between the activation of the first and second switches, the velocity of a key press can be determined, greatly improving the performance dynamic of a keyboard. The best electronic keyboards have dedicated circuits for each key, providing polyphonic aftertouch.
Advanced electronic keyboards may provide hundreds of key touch levels [ 8 ] and have 88 keys, as most pianos do.
Despite their visual similarity, different keyboard instrument types require different techniques. The piano hammer mechanism produces a louder note the faster the key is pressed, while the harpsichord's plectrum mechanism does not perceptibly vary the volume of the note with different touch on the keyboard. The pipe organ 's volume and timbre are controlled by the flow of air from the bellows and the stops preselected by the player. Players of these instruments therefore use different techniques to color the sound. An arranger keyboard may be preset to produce any of a range of voices as well as percussion and other accompaniments that respond to chords played by the left hand.
Even though the keyboard layout is simple and all notes are easily accessible, playing requires skill. A proficient player has undertaken much training to play accurately and in tempo . Beginners seldom produce a passable rendition of even a simple piece due to lack of technique . The sequences of movements of the player's hands can be very complicated. Problems include wide-spanned chords , which can be difficult for people with small hands, chords requiring unusual hand positions that can initially be uncomfortable, and fast scales , trills and arpeggios .
Playing instruments with velocity sensitive (or dynamic ) keyboards (i.e., that respond to varying playing velocity) may require finger independence, so that some fingers play "harder" while others play more softly. Pianists call this control of touch velocity voicing (not to be confused with a piano technician's "voicing" of a piano by modifying the hardness of the hammers). Keyboardists speak of playing harder and softer, or with more or less force. This may accurately describe the player's experience—but in the mechanics of the keyboard, velocity controls musical dynamics. The faster the player depresses the key, the louder the note. Players must learn to coordinate two hands and use them independently. Most music is written for two hands; typically the right hand plays the melody in the treble range, while the left plays an accompaniment of bass notes and chords in the bass range. Examples of music written for the left hand alone include several of Leopold Godowsky 's 53 Studies on Chopin's Etudes , Maurice Ravel 's Piano Concerto for the Left Hand and Sergei Prokofiev 's Piano Concerto No. 4 for the left hand . In music that uses counterpoint technique, both hands play different melodies at the same time.
A number of percussion instruments—such as the xylophone , marimba , vibraphone , or glockenspiel — have pitched elements arranged in the keyboard layout. Rather than pressing a key, the performer typically strikes each element (e.g., a metal or wood bar) with a mallet .
There are some examples of a musical keyboard layout used for non-musical devices. For example, some of the earliest printing telegraph machines used a layout similar to a piano keyboard. [ 9 ] [ 10 ]
There are some rare variations of keyboards with more or fewer than 12 keys per octave, mostly used in microtonal music , after the discoveries and theoretical developments of musician and inventor Julián Carrillo (1875–1965).
Some free-reed instrument keyboards such as accordions and Indian harmoniums include microtones. Electronic music pioneer Pauline Oliveros played one of these. Egyptian belly-dance musicians like Hossam Ramzy use custom-tuned accordions so they can play traditional scales. The small Garmon accordion played in the music of Azerbaijan sometimes has keys that can play microtones when a "shift" key is pressed. | https://en.wikipedia.org/wiki/Musical_keyboard |
Musical notation is any system used to visually represent music. Systems of notation generally represent the elements of a piece of music that are considered important for its performance in the context of a given musical tradition. The process of interpreting musical notation is often referred to as reading music .
Distinct methods of notation have been invented throughout history by various cultures. Much information about ancient music notation is fragmentary. Even in the same time frames, different styles of music and different cultures use different music notation methods.
For example, classical performers most often use sheet music using staves , time signatures , key signatures , and noteheads for writing and deciphering pieces . But even so, there are far more systems just that, for instance in professional country music , the Nashville Number System is the main method, and for string instruments such as guitar , it is quite common for tablature to be used by players.
The symbols used include ancient symbols and modern symbols made upon any media such as symbols cut into stone, made in clay tablets , made using a pen on papyrus or parchment or manuscript paper ; printed using a printing press ( c. 1400 ), a computer printer ( c. 1980 ) or other printing or modern copying technology .
Although many ancient cultures used symbols to represent melodies and rhythms , none of them were particularly comprehensive, which has limited today's understanding of their music. The direct ancestor of the modern Western system of notation emerged in medieval Europe , in the context of the Christian Church 's attempts to standardize the performance of plainsong melodies so that chants could be standardized across different areas. Notation developed further during the Renaissance and Baroque music eras. In the classical period (1750–1820) and the Romantic music era (1820–1900), notation continued to develop as the technology for musical instruments developed. In the contemporary classical music of the 20th and 21st centuries, music notation has continued to develop, with the introduction of graphical notation by some modern composers and the use, since the 1980s, of computer-based scorewriter programs for notating music. Music notation has been adapted to many kinds of music, including classical music , popular music , and traditional music .
The earliest form of musical notation can be found in a cuneiform tablet that was created at Nippur , in Babylonia (today's Iraq ), in about 1400 BCE. The tablet represents fragmentary instructions for performing music, that the music was composed in harmonies of thirds , and that it was written using a diatonic scale . [ 2 ]
A tablet from about 1250 BCE shows a more developed form of notation. [ 3 ] Although the interpretation of the notation system is still controversial, it is clear that the notation indicates the names of strings on a lyre , the tuning of which is described in other tablets. [ 4 ] Research indicates these notations had dual purposes for liturgical and secular musical pieces since music was essential in both religious ceremonies and courtly activities. [ 5 ] Although they are fragmentary, these tablets represent the earliest notated melodies found anywhere in the world. [ 6 ]
Ancient Greek musical notation was in use from at least the 6th century BCE until approximately the 4th century CE; only one complete composition ( Seikilos epitaph ) and a number of fragments using this notation survive.
The notation for sung music consists of letter symbols for the pitches , placed above text syllables. Rhythm is indicated in a rudimentary way only, with long and short symbols. The Seikilos epitaph has been variously dated between the 2nd century BCE to the 2nd century CE.
Three hymns by Mesomedes of Crete exist in manuscript . The Delphic Hymns , dated to the 2nd century BCE also use this notation, but they are not completely preserved.
Ancient Greek notation appears to have fallen out of use around the time of the decline of the Western Roman Empire .
Byzantine music once included music for court ceremonies, but has only survived as vocal church music within various Orthodox traditions of monodic ( monophonic ) chant written down in Byzantine round notation (see Macarie's anastasimatarion with the Greek text translated into Romanian and transliterated into its corresponding Cyrillic script ). [ 7 ]
Since the 6th century, Greek theoretical categories ( melos , genos , harmonia , systema ) played a key role to understand and transmit Byzantine music, especially the tradition of Damascus had a strong impact on the pre-Islamic Near East comparable to the impact coming from Persian music . The earliest evidence are papyrus fragments of Greek tropologia. These fragments just present the hymn text following a modal signature or key (like " ΠΛ Α " for echos plagios protos or " Β " for echos devteros ).
Unlike Western notation, Byzantine neumes used since the 10th century were always related to modal steps (same modal degree, one degree lower, two degrees higher, etc.) in relation to such a clef or modal key ( modal signatures ). Originally this key or the incipit of a common melody was enough to indicate a certain melodic model given within the echos . Next to ekphonetic notation , only used in lectionaries to indicate formulas used during scriptural lessons, melodic notation developed not earlier than between the 9th and the 10th century, when a theta ( θ ), oxeia ( / ) or diple ( // ) were written under a certain syllable of the text, whenever a longer melisma was expected. This primitive form was called "theta" or "diple notation".
Today, one can study the evolution of this notation in Greek monastic chant books like those of the sticherarion and the heirmologion (Chartres notation was rather used on Mount Athos and Constantinople, Coislin notation within the patriarchates of Jerusalem and Alexandria), while there was another gestic notation originally used for the asmatikon (choir book) and kontakarion (book of the soloist or monophonaris) of the Constantinopolitan cathedral rite. The earliest books which have survived, are "kondakars" in Slavonic translation which already show a notation system known as Kondakarian notation . [ 8 ] Like the Greek alphabet notational signs are ordered left to right (though the direction could be adapted like in certain Syriac manuscripts). The question of rhythm was entirely based on cheironomia (the interpretation of so-called great signs which derived from different chant books). These great signs ( μεγάλα σῃμάδια ) indicated well-known melodic phrases given by gestures of the choirleaders of the cathedral rite. They existed once as part of an oral tradition, developed Kondakarian notation and became, during the 13th century, integrated into Byzantine round notation as a kind of universal notation system. [ 9 ]
Today the main difference between Western and Eastern neumes is that Eastern notation symbols are "differential" rather than absolute, i.e., they indicate pitch steps (rising, falling or at the same step), and the musicians know to deduce correctly, from the score and the note they are singing presently, which correct interval is meant. These step symbols themselves, or better "phonic neumes", resemble brush strokes and are colloquially called gántzoi ('hooks') in modern Greek .
Notes as pitch classes or modal keys (usually memorised by modal signatures) are represented in written form only between these neumes (in manuscripts usually written in red ink). In modern notation they simply serve as an optional reminder and modal and tempo directions have been added, if necessary. In Papadic notation medial signatures usually meant a temporary change into another echos.
The so-called "great signs" were once related to cheironomic signs; according to modern interpretations they are understood as embellishments and microtonal attractions (pitch changes smaller than a semitone ), both essential in Byzantine chant. [ 10 ]
Since Chrysanthos of Madytos there are seven standard note names used for "solfège" ( parallagē ) pá, vú, g h á, d h i, ké, zō, nē , while the older practice still used the four enechemata or intonation formulas of the four echoi given by the modal signatures, the authentic or kyrioi in ascending direction, and the plagal or plagioi in descending direction ( Papadic Octoechos ). [ 12 ] With exception of vú and zō they do roughly correspond to Western solmization syllables as re, mi, fa, sol, la, si, do . Byzantine music uses the eight natural, non-tempered scales whose elements were identified by Ēkhoi , "sounds", exclusively, and therefore the absolute pitch of each note may slightly vary each time, depending on the particular Ēkhos used. Byzantine notation is still used in many Orthodox Churches. Sometimes cantors also use transcriptions into Western or Kievan staff notation while adding non-notatable embellishment material from memory and "sliding" into the natural scales from experience, but even concerning modern neume editions since the reform of Chrysanthos a lot of details are only known from an oral tradition related to traditional masters and their experience.
In 1252, Safi al-Din al-Urmawi developed a form of musical notation, where rhythms were represented by geometric representation. Many subsequent scholars of rhythm have sought to develop graphical geometrical notations. For example, a similar geometric system was published in 1987 by Kjell Gustafson, whose method represents a rhythm as a two-dimensional graph. [ 13 ] Rhythmic notation during its early stages developed Eastern musical traditions while simultaneously establishing concepts that Western music used to build its notation systems later on. [ 14 ]
The scholar and music theorist Isidore of Seville , while writing in the early 7th century, considered that "unless sounds are held by the memory of man, they perish, because they cannot be written down." [ 15 ] By the middle of the 9th century, however, a form of neumatic notation began to develop in monasteries in Europe as a mnemonic device for Gregorian chant , using symbols known as neumes ; the earliest surviving musical notation of this type is in the Musica Disciplina of Aurelian of Réôme , from about 850. There are scattered survivals from the Iberian Peninsula before this time, of a type of notation known as Visigothic neumes , but its few surviving fragments have not yet been deciphered. [ 16 ] The problem with this notation was that it only showed melodic contours and consequently the music could not be read by someone who did not know the music already.
Notation had developed far enough to notate melody, but there was still no system for notating rhythm. A mid-13th-century treatise, De Mensurabili Musica , explains a set of six rhythmic modes that were in use at the time, [ 17 ] although it is not clear how they were formed. These rhythmic modes were all in triple time and rather limited rhythm in chant to six different repeating patterns. This was a flaw seen by German music theorist Franco of Cologne and summarised as part of his treatise Ars Cantus Mensurabilis (the art of measured chant, or mensural notation ). He suggested that individual notes could have their own rhythms represented by the shape of the note. Not until the 14th century did something like the present system of fixed note lengths arise. [ citation needed ] The use of regular measures (bars) became commonplace by the end of the 17th century. [ citation needed ]
The founder of what is now considered the standard music staff was Guido d'Arezzo , [ 18 ] an Italian Benedictine monk who lived from about 991 until after 1033. He taught the use of solmization syllables based on a hymn to Saint John the Baptist , which begins Ut Queant Laxis and was written by the Lombard historian Paul the Deacon . The first stanza is:
Guido used the first syllable of each line, Ut, Re, Mi, Fa, Sol, La, and Si, to read notated music in terms of hexachords ; they were not note names, and each could, depending on context, be applied to any note. In the 17th century, Ut was changed in most countries except France to the easily singable, open syllable Do, believed to have been taken either from the name of the Italian theorist Giovanni Battista Do ni , or from the Latin word Do minus , meaning Lord . [ 19 ]
Christian monks developed the first forms of modern European musical notation in order to standardize liturgy throughout the worldwide Church, [ 20 ] and an enormous body of religious music has been composed for it through the ages. This led directly to the emergence and development of European classical music, and its many derivatives. The Baroque style, which encompassed music, art, and architecture, was particularly encouraged by the post-Reformation Catholic Church as such forms offered a means of religious expression that was stirring and emotional, intended to stimulate religious fervor. [ 21 ]
Modern music notation is used by musicians of many different genres throughout the world. The staff (or stave, in British English) consists of 5 parallel horizontal lines which acts as a framework upon which pitches are indicated by placing oval note-heads on (ie crossing) the staff lines, between the lines (ie in the spaces) or above and below the staff using small additional lines called ledger lines . Notation is read from left to right, which makes setting music for right-to-left scripts difficult. The pitch of a note is indicated by the vertical position of the note-head within the staff, and can be modified by accidentals . The duration (note length or note value ) is indicated by the form of the note-head or with the addition of a note-stem plus beams or flags. A stemless hollow oval is a whole note or semibreve, a hollow rectangle or stemless hollow oval with one or two vertical lines on both sides is a double whole note or breve. A stemmed hollow oval is a half note or minim. Solid ovals always use stems, and can indicate quarter notes (crotchets) or, with added beams or flags, smaller subdivisions. Additional symbols such as dots and ties can lengthen the duration of a note.
A staff of written music generally begins with a clef , which indicates the pitch-range of the staff. The treble clef or G clef was originally a letter G and it identifies the second line up on the five line staff as the note G above middle C. The bass clef or F clef identifies the second line down as the note F below middle C. While the treble and bass clef are the most widely used, other clefs, which identify middle C, are used for some instruments, such as the alto clef (for viola and alto trombone ) and the tenor clef (used for some cello , bassoon , tenor trombone , and double bass music). Some instruments use mainly one clef, such as violin and flute which use treble clef , and double bass and tuba which use bass clef . Some instruments, such as piano and pipe organ , regularly use both treble and bass clefs.
Following the clef, the key signature is a group of 0 to 7 sharp ( ♯ ) or flat ( ♭ ) signs placed on the staff to indicate the key of the piece or song by specifying that certain notes are sharp or flat throughout the piece, unless otherwise indicated with accidentals added before certain notes. When a flat ( ♭ ) sign is placed before a note, the pitch of the note is lowered by one semitone. Similarly, a sharp sign ( ♯ ) raises the pitch by one semitone. For example, a sharp on the note D would raise it to D♯ while a flat would lower it to D♭ . Double sharps and double flats are less common, but they are used. A double sharp is placed before a note to make it two semitones higher, a double flat - two semitones lower. A natural sign placed before a note renders that note in its "natural" form, which means that any sharp or flat applied to that note from the key signature or an accidental, is cancelled. Sometimes a courtesy accidental is used in music where it is not technically required, to remind the musician of what pitch is required.
Following the key signature is the time signature . The time signature typically consists of two numbers, with one of the most common being 4 4 . The top "4" indicates that there are four beats per measure (also called bar ). The bottom "4" indicates that each of those beats are quarter notes. Measures divide the piece into groups of beats , and the time signatures specify those groupings. 4 4 is used so often that it is also called " common time ", and it may be indicated with rather than numbers. Other frequently used time signatures are 3 4 (three beats per bar, with each beat being a quarter note); 2 4 (two beats per bar, with each beat being a quarter note); 6 8 (six beats per bar, with each beat being an eighth note) and 12 8 (twelve beats per bar, with each beat being an eighth note; in practice, the eighth notes are typically put into four groups of three eighth notes. 12 8 is a compound time type of time signature). Many other time signatures exist, such as 2 2 or 3 8 .
Many short classical music pieces from the classical era and songs from traditional music and popular music are in one time signature for much or all of the piece. Music from the Romantic music era and later, particularly contemporary classical music and rock music genres such as progressive rock and the hardcore punk subgenre mathcore , may use mixed meter ; songs or pieces change from one meter to another, for example alternating between bars of 5 4 and 7 8 .
Directions to the player regarding matters such as tempo (e.g., Andante ) and dynamics (e.g., forte) appear above or below the staff. Terms indicating the musical expression or "feel" to a song or piece are indicated at the beginning of the piece and at any points where the mood changes (e.g., "Gelassen") For vocal music, lyrics are written near the pitches of the melody. For short pauses (breaths), retakes (retakes are indicated with a ' mark) are added.
In music for ensembles , a " score " shows music for all players together, with the staves for the different instruments and/or voices stacked vertically. The conductor uses the score while leading an orchestra , concert band , choir or other large ensemble. Individual performers in an ensemble play from "parts" which contain only the music played by an individual musician. A score can be constructed from a complete set of parts and vice versa. The process was laborious and time consuming when parts were hand-copied from the score, but since the development of scorewriter computer software in the 1980s, a score stored electronically can have parts automatically prepared by the program and quickly and inexpensively printed out using a computer printer.
Jeongganbo is a traditional musical notation system created during the time of Sejong the Great that was the first East Asian system to represent rhythm, pitch, and time. [ 22 ] [ 23 ] Among various kinds of Korean traditional music, Jeong-gan-bo targets a particular genre, Jeong-ak ( 정악, 正樂 ).
Jeong-gan-bo specifies the pitch by writing the pitch's name down in a box called 'jeong-gan'. One jeong-gan is one beat each, and it can be split into two, three or more to hold half beats and quarter beats, and more.
Also, there are many markings indicating things such as ornaments. Most of these were later created by Ki-su Kim.
The Samaveda text (1200 BCE – 1000 BCE) contains notated melodies, and these are probably the world's oldest surviving ones. [ 24 ] The musical notation is written usually immediately above, sometimes within, the line of Samaveda text, either in syllabic or a numerical form depending on the Samavedic Sakha (school). [ 25 ] The Indian scholar and musical theorist Pingala (c. 200 BCE), in his Chanda Sutra , used marks indicating long and short syllables to indicate meters in Sanskrit poetry.
A rock inscription from circa 7th–8th century CE at Kudumiyanmalai , Tamil Nadu contains an early example of a musical notation. It was first identified and published by archaeologist/epigraphist D. R. Bhandarkar . [ 26 ] Written in the Pallava-grantha script of the 7th century, it contains 38 horizontal lines of notations inscribed on a rectangular rock face (dimension of around 13 by 14 feet). Each line of the notation contains 64 characters (characters representing musical notes), written in groups of four notes. The basic characters for the seven notes, 'sa ri ga ma pa dha ni', are seen to be suffixed with the vowels a, i, u, e. For example, in the place of 'sa', any one of 'sa', 'si', 'su' or 'se' is used. Similarly, in place of ri, any one of 'ra', 'ri', 'ru' or 're' is used. Horizontal lines divide the notation into 7 sections. Each section contains 4 to 7 lines of notation, with a title indicating its musical 'mode'. These modes may have been popular at least from the 6th century CE and were incorporated into the Indian 'raga' system that developed later. But some of the unusual features seen in this notation have been given several non-conclusive interpretations by scholars. [ 27 ]
In the notation of Indian rāga , a solfege-like system called sargam is used. As in Western solfege, there are names for the seven basic pitches of a major scale (Shadja, Rishabha, Gandhara, Madhyama, Panchama, Dhaivata and Nishada, usually shortened to Sa Re Ga Ma Pa Dha Ni). The tonic of any scale is named Sa, and the dominant Pa. Sa is fixed in any scale, and Pa is fixed at a fifth above it (a Pythagorean fifth rather than an equal-tempered fifth). These two notes are known as achala swar ('fixed notes').
Each of the other five notes, Re, Ga, Ma, Dha and Ni, can take a 'regular' (shuddha) pitch, which is equivalent to its pitch in a standard major scale (thus, shuddha Re, the second degree of the scale, is a whole-step higher than Sa), or an altered pitch, either a half-step above or half-step below the shuddha pitch. Re, Ga, Dha and Ni all have altered partners that are a half-step lower (Komal-"flat") (thus, komal Re is a half-step higher than Sa).
Ma has an altered partner that is a half-step higher ( teevra -"sharp") (thus, tivra Ma is an augmented fourth above Sa). Re, Ga, Ma, Dha and Ni are called vikrut swar ('movable notes'). In the written system of Indian notation devised by Ravi Shankar, the pitches are represented by Western letters. Capital letters are used for the achala swar, and for the higher variety of all the vikrut swar. Lowercase letters are used for the lower variety of the vikrut swar.
Other systems exist for non-twelve-tone equal temperament and non-Western music, such as the Indian Swaralipi .
Znamenny Chant is a singing tradition used in the Russian Orthodox Church which uses a "hook and banner" notation. Znamenny Chant is unison , melismatic liturgical singing that has its own specific notation, called the stolp notation. The symbols used in the stolp notation are called kryuki (Russian: крюки , 'hooks') or znamyona (Russian: знамёна , 'banners'). Often the names of the signs are used to refer to the stolp notation. Znamenny melodies are part of a system, consisting of Eight Modes (intonation structures; called glasy); the melodies are characterized by fluency and well-balancedness. [ 28 ] There exist several types of Znamenny Chant: the so-called Stolpovoy , Malyj (Little) and Bolshoy (Great) Znamenny Chant. Ruthenian Chant ( Prostopinije ) is sometimes considered a sub-division of the Znamenny Chant tradition, with the Muscovite Chant (Znamenny Chant proper) being the second branch of the same musical continuum.
Znamenny Chants are not written with notes (the so-called linear notation), but with special signs, called Znamëna (Russian for "marks", "banners") or Kryuki ("hooks"), as some shapes of these signs resemble hooks. Each sign may include the following components: a large black hook or a black stroke, several smaller black 'points' and 'commas' and lines near the hook or crossing the hook. Some signs may mean only one note, some 2 to 4 notes, and some a whole melody of more than 10 notes with a complicated rhythmic structure. The stolp notation was developed in Kievan Rus' as an East Slavic refinement of the Byzantine neumatic musical notation.
The most notable feature of this notation system is that it records transitions of the melody, rather than notes . The signs also represent a mood and a gradation of how this part of melody is to be sung (tempo, strength, devotion, meekness, etc.) Every sign has its own name and also features as a spiritual symbol. For example, there is a specific sign, called "little dove" (Russian: голубчик (golubchik) ), which represents two rising sounds, but which is also a symbol of the Holy Ghost . Gradually the system became more and more complicated. This system was also ambiguous, so that almost no one, except the most trained and educated singers, could sing an unknown melody at sight. The signs only helped to reproduce the melody, not coding it in an unambiguous way.
(See Byzantine Empire )
The earliest known examples of text referring to music in China are inscriptions on musical instruments found in the Tomb of Marquis Yi of Zeng (d. 433 B.C.). Sets of 41 chimestones and 65 bells bore lengthy inscriptions concerning pitches, scales, and transposition. The bells still sound the pitches that their inscriptions refer to. Although no notated musical compositions were found, the inscriptions indicate that the system was sufficiently advanced to allow for musical notation. Two systems of pitch nomenclature existed, one for relative pitch and one for absolute pitch. For relative pitch, a solmization system was used. [ 29 ]
Gongche notation used Chinese characters for the names of the scale.
Japanese music is highly diversified, and therefore requires various systems of notation. In Japanese shakuhachi music, for example, glissandos and timbres are often more significant than distinct pitches, whereas taiko notation focuses on discrete strokes.
Ryukyuan sanshin music uses kunkunshi , a notation system of kanji with each character corresponding to a finger position on a particular string.
Notation plays a relatively minor role in the oral traditions of Indonesia . However, in Java and Bali , several systems were devised beginning at the end of the 19th century, initially for archival purposes. Today the most widespread are cipher notations ("not angka" in the broadest sense) in which the pitches are represented with some subset of the numbers 1 to 7, with 1 corresponding to either highest note of a particular octave, as in Sundanese gamelan , or lowest, as in the kepatihan notation of Javanese gamelan .
Notes in the ranges outside the central octave are represented with one or more dots above or below the each number. For the most part, these cipher notations are mainly used to notate the skeletal melody (the balungan ) and vocal parts ( gerongan ), although transcriptions of the elaborating instrument variations are sometimes used for analysis and teaching. Drum parts are notated with a system of symbols largely based on letters representing the vocables used to learn and remember drumming patterns; these symbols are typically laid out in a grid underneath the skeletal melody for a specific or generic piece.
The symbols used for drum notation (as well as the vocables represented) are highly variable from place to place and performer to performer. In addition to these current systems, two older notations used a kind of staff: the Solonese script could capture the flexible rhythms of the pesinden with a squiggle on a horizontal staff, while in Yogyakarta a ladder-like vertical staff allowed notation of the balungan by dots and also included important drum strokes. In Bali, there are a few books published of Gamelan gender wayang pieces, employing alphabetical notation in the old Balinese script.
Composers and scholars both Indonesian and foreign have also mapped the slendro and pelog tuning systems of gamelan onto the western staff, with and without various symbols for microtones . The Dutch composer Ton de Leeuw also invented a three line staff for his composition Gending . However, these systems do not enjoy widespread use.
In the second half of the twentieth century, Indonesian musicians and scholars extended cipher notation to other oral traditions, and a diatonic scale cipher notation has become common for notating western-related genres (church hymns, popular songs, and so forth). Unlike the cipher notation for gamelan music, which uses a "fixed Do" (that is, 1 always corresponds to the same pitch, within the natural variability of gamelan tuning), Indonesian diatonic cipher notation is "moveable-Do" notation, so scores must indicate which pitch corresponds to the number 1 (for example, "1=C").
Ancient Jewish texts include a series of marks assigning musical cantillation notes. Known in Hebrew as Ta'amim and Yiddish as Trope, there are records of these marks from the 6th and 7th centuries, having been passed down as a tradition for Jewish prayers and texts. Traditionally a series of marks written above and around the accompanying Hebrew texts, Trope marks represent a short musical motif. Throughout the Jewish diaspora there are variations in the accompanying melodies. There are three main systems of Hebrew cantillation: The Babylonian System, The Palestinian System, and the Tiberian System.
Cipher notation systems assigning Arabic numerals to the major scale degrees have been used at least since the Iberian organ tablatures of the 16th-century and include such exotic adaptations as Siffernotskrift . The one most widely in use today is the Chinese Jianpu , discussed in the main article . Numerals can also be assigned to different scale systems, as in the Javanese kepatihan notation described above .
Solfège is a way of assigning syllables to names of the musical scale. In order, they are today: Do Re Mi Fa Sol La Ti Do ' (for the octave). The classic variation is: Do Re Mi Fa Sol La Si Do ' . The first Western system of functional names for the musical notes was introduced by Guido of Arezzo (c. 991 – after 1033), using the beginning syllables of the first six musical lines of the Latin hymn Ut queant laxis . The original sequence was Ut Re Mi Fa Sol La , where each verse started a scale note higher. "Ut" later became "Do". The equivalent syllables used in Indian music are: Sa Re Ga Ma Pa Dha Ni . See also: solfège , sargam , Kodály hand signs .
Tonic sol-fa is a type of notation using the initial letters of solfège.
The notes of the 12-tone scale can be written by their letter names A–G, possibly with a trailing accidental , such as A ♯ or B ♭ .
ABC notation is a compact format using plain text characters, readable by computers and by humans. More than 100,000 tunes are now transcribed in this format. [ 31 ]
Tablature was first used in the Middle Ages for organ music and later in the Renaissance for lute music. [ 32 ] In most lute tablatures, a staff is used, but instead of pitch values, the lines of the staff represent the strings of the instrument. The frets to finger are written on each line, indicated by letters or numbers. Rhythm is written separately with one or another variation of standard note values indicating the duration of the fastest moving part. Few seem to have remarked on the fact that tablature combines in one notation system both the physical and technical requirements of play (the lines and symbols on them and in relation to each other representing the actual performance actions) with the unfolding of the music itself (the lines of tablature taken horizontally represent the actual temporal unfolding of the music). In later periods, lute and guitar music was written with standard notation. Tablature caught interest again in the late 20th century for popular guitar music and other fretted instruments, being easy to transcribe and share over the internet in ASCII format .
Some chromatic systems have been created taking advantage of the layout of black and white keys of the standard piano keyboard. The "staff" is most widely referred to as " piano roll ", created by extending the black and white piano keys.
Klavarskribo (sometimes shortened to klavar ) is a music notation system that was introduced in 1931 by the Dutchman Cornelis Pot. The name means "keyboard writing" in Esperanto . It differs from conventional music notation in a number of ways and is intended to be easily readable. Many klavar readers are from the Netherlands.
Over the past three centuries, hundreds of music notation systems have been proposed as alternatives to traditional western music notation. Many of these systems seek to improve upon traditional notation by using a "chromatic staff" in which each of the 12 pitch classes has its own unique place on the staff. An example is Jacques-Daniel Rochat's Dodeka music notation . [ 33 ] [ 34 ] These notation systems do not require the use of standard key signatures, accidentals, or clef signs. They also represent interval relationships more consistently and accurately than traditional notation, e.g. major 3rds appear wider than minor 3rds. Many of these systems are described and illustrated in Gardner Read's "Source Book of Proposed Music Notation Reforms".
The term 'graphic notation' refers to the contemporary use of non-traditional symbols and text to convey information about the performance of a piece of music. Composers such as Johanna Beyer . Christian Wolff , Carmen Barradas , Earle Brown , Yoko Ono , Anthony Braxton , John Cage , Morton Feldman , Cathy Berberian , Graciela Castillo , Krzysztof Penderecki , Cornelius Cardew , Pauline Oliveros and Roger Reynolds are among the early generation of practitioners. The book Notations , by John Cage and Alison Knowles , is another example of this kind of notation.
Simplified Music Notation is an alternative form of musical notation designed to make sight-reading easier. It is based on classical staff notation , but incorporates sharps and flats into the shape of the note heads . Notes such as double sharps and double flats are written at the pitch they are actually played at, but preceded by symbols called history signs that show they have been transposed .
Modified Stave Notation (MSN) is an alternative way of notating music for people who cannot easily read ordinary musical notation even if it is enlarged.
Parsons code is used to encode music so that it can be easily searched.
Braille music is a complete, well developed, and internationally accepted musical notation system that has symbols and notational conventions quite independent of print music notation. It is linear in nature, similar to a printed language and different from the two-dimensional nature of standard printed music notation. To a degree Braille music resembles musical markup languages [ 35 ] such as MusicXML [ 36 ] or NIFF .
In integer notation , or the integer model of pitch, all pitch classes and intervals between pitch classes are designated using the numbers 0 through 11.
The standard form of rap notation is the "flow diagram", where rappers line up their lyrics underneath "beat numbers". [ 37 ] Hip-hop scholars also make use of the same flow diagrams that rappers use: the books How to Rap and How to Rap 2 extensively use the diagrams to explain rap's triplets, flams, rests, rhyme schemes, runs of rhyme, and breaking rhyme patterns, among other techniques. [ 38 ] Similar systems are used by musicologists Adam Krims in his book Rap Music and the Poetics of Identity [ 39 ] and Kyle Adams in his work on rap's flow. [ 40 ] As rap usually revolves around a strong 4/4 beat, [ 41 ] with certain syllables aligned to the beat, all the notational systems have a similar structure: they all have four beat numbers at the top of the diagram, so that syllables can be written in-line with the beat. [ 41 ]
It is being used for six-hole woodwind instruments, basically for Irish folk songs. Tin whistle tabs are particularly useful for those unfamiliar with sheet music notation.
The Musical Symbols Unicode block encodes an extensive system of formal musical notation.
The Miscellaneous Symbols block has a few of the more common symbols:
The Miscellaneous Symbols and Pictographs block has three emoji that may include depictions of musical notes:
Various computer programs have been developed for creating music notation (called scorewriters or music notation software ). Music may also be stored in various digital file formats for purposes other than graphic notation output.
According to Philip Tagg and Richard Middleton , musicology and to a degree European-influenced musical practice suffer from a 'notational centricity', a methodology slanted by the characteristics of notation. [ 42 ] [ 43 ] A variety of 20th- and 21st-century composers have dealt with this problem, either by adapting standard Western musical notation or by using graphic notation. [ clarification needed ] These include George Crumb , Luciano Berio , Krzystof Penderecki , Earl Brown , John Cage , Witold Lutoslawski , and others. [ 44 ] [ 45 ] | https://en.wikipedia.org/wiki/Musical_notation |
Musicians' medicine deals with physical and mental issues suffered by musicians ('Musicians' illnesses').
It is sometimes also referred to as Music Medicine, which also describes different forms of music therapy . The related field of music physiology consists of research of physiological foundations of making music as well as the prevention of common health problems in musicians. The term Musicians' Health, often used as a synonym for Musicians' Medicine, generally refers to the health maintenance and wellbeing of musicians, as well as preventive measures, such as sufficient and appropriate exercise, a healthy diet, and enough sleep.
The studies also include mental health problems, for instance stage fright .
As early as 1832, Karl Sundelin published his Medical Guidebook for Musicians . Later, around the turn of the century, Adolf Steinhausen (1859–1910) published multiple tracts on music medicine. Then, in the 1920s, Julius Flesch wrote about Berufskrankheiten des Musikers (Occupational Diseases of the Musician) (Celle, 1925). The neurologist Kurt Singer published his book Berufskrankheiten der Musiker (Occupational diseases of musicians). From 1923, Singer taught at the Hochschule für Musik Hanns Eisler Berlin . The Kurt-Singer-Institute for Music Physiology and Musicians’ Health in Berlin (Academy of Arts and Hochschule für Musik Hans Eisler), currently headed by Alexander Schmidt, was named after him. Further institutions for Musicians' Medicine are the Institute of Music Physiology and Musicians' Medicine at the Hanover University of Music, Drama and Media , founded by Christoph Wagner in 1974 and headed by Eckart Altenmüller since 1994, as well as the Freiburg Institute for Musicians’ Medicine, founded in 2005 and headed by Claudia Spahn and Bernhard Richter. In the former GDR, the field was studied at the Occupational Health Clinic of theatres and orchestras in Berlin.
Further institutes and departments for Music Physiology and Musicians' Medicine are located at the Universities of Music in Weimar , Leipzig , Dresden and Frankfurt , as well as the Düsseldorf University Hospital and the Rechts der Isar Hospital in Munich.
In 1994, the German Society for Music Physiology and Musicians' Medicine was founded and holds annual conferences. Similar associations have been established in Switzerland, Austria, France, the UK, the Netherlands, the US and New Zealand since the 1990s.
The most common problems are related to overstressing particular muscles, tendons and joints, especially the arms and hands. Of the 264,000 professional musicians working in the US in 2006, 50-76% (depending on the instrument) suffered work-related muscoskeletal ailments. Women were affected more often than men (70% vs 52%). These problems occur most commonly between the ages of 20 and 40. Risk factors are a general hyperlaxicity, abrupt increase in training and rehearsal times, a change of conductor, bad posture, wrong use of the instrument and general stress. [ 1 ]
Common medical conditions are:
Some illnesses are typical for certain instruments. [ 2 ] For example, playing the violin, the viola or wind instruments often lead to changes in the mouth cavity, jaw, teeth or face. [ 3 ]
Musicians in orchestras are often seated close together in orchestra pits and are exposed to high sound levels. Due to the positioning of the orchestra, sound is often not loud enough and doesn't reach the audience and therefore has to be amplified. Over the course of the last centuries, orchestra music has become increasingly louder. This can lead to lasting hearing loss and tinnitus . [ 4 ] [ 5 ] Such problems emerge slowly and often unnoticed. Musicians suffering from these conditions have to concentrate more while playing their instrument, resulting in insecurities and stress. In some cases even minor hearing problems can hinder their work. [ 6 ]
Musicians medicine is mainly concerned with prevention, which means educating musicians about preventative measures. These can be ergonomic adjustments of the instruments to the musician's body, good chairs, appropriate exercises and basic physiological and anatomical knowledge, as well as healthy eating habits and sufficient sleep. [ citation needed ]
Additionally, relaxation techniques can be helpful, for example progressive muscle relaxation (Jacobsen), autogenic training , meditation , Tai chi and Qigong . Furthermore, movement therapies such as Eutony , Alexander Technique , Feldenkrais Method , Dispokinesis and functional movement therapy are efficient in diagnosing and correcting bad posture. Such measures can not only prevent, but also reduce or even eradicate existing problems. Another commonly used form of therapy is osteopathy .
Currently, there is no cure for hearing damage. Many musicians are not aware of the health risks that come with being a musician. [ 7 ] [ 8 ] According to the German Occupational Safety Law relating to Noise and Vibration ( Lärm- und Vibrations-Arbeitsschutzverordnung ) employees have to be protected from damaging noise. Many employers often are not aware how demanding the job really is, since it includes many different tasks, such as teaching music or a lot of practice. For these instances, Germany set up a training programme to help identify how affected a musician is by being exposed to loud sounds and what preventative measures should be established. Since that exposure can vary significantly, the software related to the programme creates a weekly average. [ 9 ] | https://en.wikipedia.org/wiki/Musicians'_Medicine |
A Musikalisches Würfelspiel (German for "musical dice game") was a system for using dice to randomly generate music from precomposed options. These games were quite popular throughout Western Europe in the 18th century. Several different games were devised, some that did not require dice, but merely choosing a random number .
The earliest example is Johann Kirnberger 's Der allezeit fertige Menuetten- und Polonaisencomponist (German for "The Ever-Ready Minuet and Polonaise Composer") (1757 [1st edition; revised 2nd 1783]). [ 1 ] Examples by well known composers include C. P. E. Bach 's Einfall, einen doppelten Contrapunct in der Octave von sechs Tacten zu machen, ohne die Regeln davon zu wissen (German for "A method for making six bars of double counterpoint at the octave without knowing the rules") (1758) and Maximilian Stadler 's Table pour composer des minuets et des Trios à la infinie; avec deux dez à jouer (French for "A table for composing minuets and trios to infinity, by playing with two dice") (1780). [ 1 ]
In the early 20th century the Kaleidacousticon System, using arbitrarily combinable playing cards , was unsuccessfully marketed in the Boston area as a parlour game . [ 2 ]
According to Lawrence Zbikowski, "In truth, chance played little part in the success of the music produced by such games. Instead, what was required of the compilers...[was] a little knowledge about how to put the game together and an understanding of the formal design of waltzes , etc." [ 3 ]
According to Stephen Hedges, "The 'galant' middle class in Europe was playing with mathematics. In this atmosphere of investigation and cataloguing, a systematic device that would seem to make it possible for anyone to write music was practically guaranteed popularity. [ 4 ]
According to Leonard Meyer , "Eighteenth-century composers constructed musical dice games while nineteenth century composers did not. ... [W]hat constrained the choice of figures [in seventeenth- and eighteenth-century music] were the claims of taste, coherent expression and propriety, given the genre of work being composed, rather than the inner necessity of a gradually unfolding, underlying process [as in nineteenth century music]". [ 5 ] See: musical development .
The way these games work may be understood in analogy to sentence construction .
One rolls one die for each word and selects the word from the appropriate column according to the number. Thus if one rolls 1 2 3 1 2 3 one is given, "The pig ran past the marsh." Each progression is essentially the same, there may be more or less choices for different slots, and the choices offered for each slot are slight variations rather than being entirely different.
The best-known was published in 1792, by Mozart 's publisher Nikolaus Simrock in Berlin ( K. 294d K3 or K. 516f K6 ). On its cover, the game was attributed to Mozart, but this attribution has not been authenticated. [ 6 ]
The dice rolls randomly selected small sections of music, which would be patched together to create a musical piece. All measures except 8 and 16 have different possibilities for each roll ( i.e. 11 different versions), with measure 8 only having one possibility and measure 16 having two. [ 7 ] This gives a total of 2×11 14 = 759,499,667,166,482 different yet similar waltzes. [ 7 ] If the game is played with dice (as intended), then these different pieces are not equally likely due to the different probabilities for different dice sums .
Mozart's manuscript [ clarification needed ] , written in 1787, consisting of 176 one- bar fragments of music, [ 8 ] appears to be some kind of game or system for constructing music out of two-bar fragments, but contains no instructions and there is no evidence that dice were involved.
The titles of the supposed Mozart compositions [ clarification needed ] are: [ 1 ]
Robert Xavier Rodríguez composed his Musical Dice Game for string orchestra based on K. 516f. [ 9 ]
The attribution to Joseph Haydn of Gioco filarmonico o sia maniera facile per comporre un infinito numero de minuetti e trio anche senza sapere il contrappunto (Italian for "The game of harmony, or an easy method for composing an infinite number of minuet-trios, without any knowledge of counterpoint") has not been authenticated either. [ 1 ] | https://en.wikipedia.org/wiki/Musikalisches_Würfelspiel |
The Musolaphone (also marketed as the Multa Musola ), developed by the Automatic Electric Company of Chicago, Illinois , was an audio distribution system that transmitted news and entertainment over telephone lines to subscribing homes and businesses. The company's "Automatic Enunciator" loudspeakers were employed at the receiving end.
A test commercial installation was established in southside Chicago in 1913, but the project was short-lived and did not prove to be financially successful. This was the last significant attempt to set up a " telephone newspaper " to transmit entertainment over telephone lines in the United States, prior to the development of radio broadcasting in the early 1920s.
In 1910, the Automatic Electric Company, an established firm best known for making automatic telephone switchboards, announced its development of a new loudspeaker, called the "Automatic Enunciator", which was envisioned to have multiple potential uses. In part, Joseph Harris, president of the company, predicted: "An automatic enunciator, by which a man talking in New York can be heard in every part of a large room in Chicago... may make it possible for a public speaker to address a million or more people at one time... Running descriptions of baseball games, or prize fights can be sent over long distances for the entertainment of sporting fans of all varieties." [ 2 ]
In 1910 the Automatic Enunciator Company was formed in Chicago to market the invention. [ 3 ] Initially, Automatic Enunciators were employed in public address systems , for making announcements in establishments such as department stores, factories, and railroad stations. In 1913, multiple units were installed throughout the Comiskey Park baseball field in Chicago, both for announcements and to provide musical interludes. [ 4 ]
The next step was to expand the system to distribute programming to multiple sites, initially under the name "Multa Musola". Company publicity included the following description: "The object of the Multa Musola service is to distribute music by telephone wires from an instrument at the central office, so it can be easily heard in any part of a room without having to listen carefully." [ 5 ]
The summer of 1912 saw a series of Multa Musola demonstrations in Portland, Oregon, [ 6 ] and in the spring of the next year, advertisements for the Oregon Enunciator Company appeared, promoting both home and business service. This would have competed with another telephone-based news and entertainment service, the Oregon Telephone Herald Company's "telephone newspaper", but there is no evidence that the Multa Musola system ever began operation. Moreover, later that year, Oregon's Corporation Commissioner, R. A. Watson, acting under the state's "Blue Sky" law, prohibited both the Oregon Enunciator Company and the Oregon Telephone Herald Company from doing business in the state, due to concern about their financial viability. [ 7 ]
However, an experimental commercial Musolaphone service was established in south-side Chicago in 1913, working in conjunction with the Illinois Telephone & Telegraph Co. Two features that were superior to the Telephone Herald "telephone newspaper" systems was that listening was done over loudspeakers instead of headphones, and the system did not need dedicated, separate telephone lines, because "as soon as connection is made in the telephone exchange to the subscriber's line upon which the service is being given, the other equipment is automatically disconnected. When the subscriber desires to use the telephone, disconnection from the Musolaphone service, as it is called, is obtained by the operation of a push button installed at the telephone instrument". [ 1 ] John J. Comer, former General Manager of a similarly designed Tel-musici installation at Wilmington, Delaware, was described as the inventor.
An early 1914 report reviewed the Chicago Musolaphone's daily schedule:
"From eight to twelve in the morning, announcement of special bargain sales at the leading stores is made, and the principal news items are read from the morning papers including the United States weather report, stock market quotations, announcements of special events happening during the day, etc. At twelve o'clock the announcement of standard Western Union time is made. From twelve to one-thirty is given up to a musical program, especially adapted to cafes, restaurants, dining rooms, etc., and following this is a running description of ball games of the home team and scores by innings of other teams in both leagues during the baseball season. In winter lectures by prominent people will be obtainable besides language lessons in French, German, Italian, etc., and a period will be set aside for the reading of children's stories. A half hour's music for dancing will be offered each evening." [ 8 ]
Subscribers were charged $3 a week for the service. [ 9 ] (For comparison, at this time issues of the Chicago Tribune newspaper cost one cent on weekdays and five cents on Sundays.) Eventually interactive communication was established, as one report stated: "There is in Chicago a teacher of languages whose pupils have grown so in number recently that personal attention to each pupil has come to be out of the question. An arrangement was made with the Automatic Company's studio for connections and service and now the lessons are all transmitted by telephones, service can be cut in any time for the purpose of asking questions or more information on certain points and in all ways the telephone service proves as flexible as the ordinary arrangement in a studyroom." [ 10 ]
A challenge was submitted to the Chicago Counsel about the legality of the Musolaphone's operation on Sundays, and the fact that the telephone company was partnering with a service that charged extra beyond the normal telephone rental fees, but a ruling did not sustain either of these objections. [ 9 ] An additional complaint was made to the City of Chicago by "a prominent news bureau... which protested that the music interfered with the news service". Again the city ruled in favor of the Musolaphone operation, while further noting that "The company, however, discontinued the music service." [ 11 ]
In early 1914, it was announced that the Federal Telephone Company of Buffalo, New York was planning to establish its Musolaphone service, but it appears that no other systems were ever established. [ 10 ] However, Automatic Enunciator loudspeakers continued to be marketed, with the emphasis returning to their use in public address systems. The Musolaphone Corporation's Delaware charter was repealed on January 27, 1919 for failure to pay taxes for two years, [ 12 ] and the Automatic Enunciator Company was dissolved in 1926. [ 3 ] | https://en.wikipedia.org/wiki/Musolaphone |
The U.S. National Oceanic and Atmospheric Administration ( NOAA ) National Status and Trends (NS&T) Mussel Watch Program is a water contaminant monitoring program that started in 1986. [ 1 ] .The program was inspired by Dr. Ed Goldberg at Scripps Institute of Oceanography, but was conceived and designed at a workshop sponsored by NOAA, held at Battelle Ocean Sciences in 1984, and led by Dr. Paul D. Boehm. It is the longest running continuous contaminant monitoring program of its kind in the United States . [ 2 ] Mussel Watch monitors the concentration of contaminants in bivalves (mussels and oysters) and sediments in the coastal waters of the U.S., including the Great Lakes , to monitor bivalve health and by extension the health of their local and regional environment. [ 2 ]
Mussel Watch consults with experts to determine appropriate contaminants to monitor; these include dichlorodiphenyltrichloroethane ( DDT ), polycyclic aromatic hydrocarbons ( PAHs ), and polychlorinated biphenyls ( PCBs ). As of 2008, Mussel Watch monitors approximately 140 analytes . [ 3 ] In addition to the effects of contaminants, Mussel Watch is able to assess the effects of natural disasters , such as the 2005 Hurricane Katrina , and environmental disasters , such as the 2010 Deepwater Horizon oil spill . [ 4 ] Data collected by Mussel Watch can also be used to monitor the effectiveness of coastal remediation. [ 3 ] The Mussel Watch Program utilized its 20 years of monitoring data to effectively analyze the impacts of Hurricane Katrina and has affected regulatory decisions based on the data it has collected on bivalve parasites. [ 5 ] [ 6 ] [ 7 ]
NOAA describes the goal of Mussel Watch as "to support ecosystem-based management through an integrated nationwide program of environmental monitoring, assessment and research to describe the status and trends of our nation's estuaries and coasts." [ 3 ] Mussel Watch is a program that monitors the health of bivalves for contaminants along the coasts of the United States. This program was launched in 1986 and since then is the longest government-run monitoring program that has national influence. [ 3 ] It was made in response to a legislative mandate to preserve the marine environment. In 2008 they released an assessment of their data from 1986 through 2005. [ 3 ] In this report, concentrations of many different metals and organic pollutants are shown over the two decades of data collection. Using this set of data, trends can be identified for different coastal areas. Starting in 2000, the scientists that NOAA sent out to collect the mussels changed companies and the Mussel Watch program began employing citizen scientists to collect the mussels; this approach saved a good deal of money for the program. This can be seen on the local level in Washington State where The Snohomish County 's Natural Marine Resources Committee coordinated with the Mussel Watch program in 2007 to employ citizens to collect samples from the nearshore water Snohomish County. [ 8 ] In 2010 and 2012 Western Washington University students assisted Whatcom County Public Works. Mussel Watch originally monitored areas known for contamination where data would be easily found and monitored for trends in the toxicity data. Now the focus is to shift to areas of concern directed by organizations like the Environmental Protection Agency ( EPA ). Instead of focusing just on trends in the data Mussel Watch is looking to see if a given policy has actually made a positive impact on a specific environment. [ 9 ]
Mussel Watch uses a combination of national oversight from NOAA with a network of regional and local groups to monitor coastal health throughout the United States. NOAA and its National Centers for Coastal Ocean Science (NCCOS) has a staff of scientists throughout the United States and partners with other Federal, State, non-governmental organization, and private sector partners throughout the world to work together towards achieving the goals of the Mussel Watch Program. Contamination in one coastal region can lead to effects in areas thousands of miles away and having a nationwide monitoring program enables NOAA to track these effects. [ 3 ] A performance based quality assurance process (QA) is used by the Mussel Watch Program to maintain data quality. The National Institute of Standards and Technology ( NIST ) and the National Research Council of Canada ( NRC ) assist analytic laboratories in exercises to ensure that data collected from all labs have comparable accuracy and precision. [ 3 ] The QA process reduces intralaboratory and interlaboratory variation. [ 10 ]
A complete list of Mussel Watch regions follows.
NOAA currently supports over 65 active citizen science projects, including Mussel Watch. In 2013 a NOAA Citizen Science Community of Practice was formed to help the citizen scientists compile and share best practices, share resources, and provide a searchable database of NOAA's citizen science projects. The community of over 120 members continues to work to aid citizen scientists. [ 11 ] An example of the collaboration between national and local groups is the Washington state 2009/10 Mussel Watch Pilot Project. [ 12 ] The Washington Department of Fish and Wildlife's (WDFW) Puget Sound Assessment and Monitoring Program (PSAMP), Snohomish County Marine Resources Committee (MRC), Snohomish County Public Works-Surface Water Management, Washington Sea Grant, and NOAA's Mussel Watch collaborated to; "conduct field-sampling for the 2009/10 Mussel Watch season in Washington waters, evaluate the possibility of merging field sampling with existing toxic contaminant monitoring in Puget Sound, demonstrate and evaluate the use citizen scientists as a primary resource for conducting field work and investigate the feasibility of Mussel Watch as a monitoring tool in Puget Sound." [ 12 ] This involved a representative from NOAA assisting PSAMP staff and volunteers with a successful sampling of all Mussel Watch sites. The result of this pilot project was a significant reduction in labor time of professional staff in the field due to the assistance and proper training of citizen scientist volunteers. [ 12 ] Proper training of volunteers is necessary to maintain consistent and accurate collection methods. [ 13 ]
More than 140 chemical contaminants (analytes) are monitored by the Mussel Watch Program. The EPA lists many of these analytes as Priority Pollutants under the Clean Water Act. [ 3 ] They have been chosen based on their bioavailability , possible uptake and storage into animal tissues, toxicity to aquatic life, and potential harm to humans.
Metals measured in the Mussel Watch Program include aluminum, antimony, arsenic, cadmium, chromium, copper, iron, lead, manganese, mercury, nickel, selenium, silicon, silver, thallium, tin, and zinc. These metals come from both natural and anthropogenic sources. [ 3 ] Different bivalve species have different bioaccumulation abilities for trace metals , and as a result oysters will accumulate about 10 times more zinc and copper than mussels. Mussels will accumulate about 3 times more lead than oysters. [ 3 ] A report over a 20-year period released by the Mussel Watch Program in 2008 found that higher metal concentrations are found in urbanized and industrialized regions, and there is no significant difference in metal concentrations between the East Coast, the West Coast, and the Great Lakes regions. There is an increase in metal concentrations nationwide over time. [ 3 ]
As of 2008, the organic contaminants monitored by Mussel Watch included 51 PCB congeners (out of a possible 209), [ 10 ] 65 PAHs, DDT, butyltin, chlordane , and dieldrin . A complete list is available at http://NSandT.noaa.gov . [ 3 ] Most of the organic contaminants monitored by Mussel Watch have an anthropogenic source, with PAHs being an exception as they are derived from both natural processes and anthropogenic sources. [ 3 ] PCB congeners were selected based on a list of criteria including that the chosen congeners are already being measured by other scientific organizations. [ 10 ] Organic contaminants can be compared across all sites and all species used by Mussel Watch. [ 3 ] The same 20-year report discussed in "Metals" found that, similar to metals, elevated levels of organic contaminants are also found in urbanized and industrialized regions. Organic contaminants were found at every site. [ 3 ]
"The histopathology component of the Mussel Watch Program, quantifies the stage of gamete development, and the prevalence of nearly 70 diseases and parasites found in mussels and oysters. Trends in histopathology data may help to assess the effects of global warming ." [ 3 ]
In 1986 the Mussel Watch Program only sampled 145 sites, but as of 2008 that amount has grown to approximately 300 active monitoring sites in the continental U.S., Alaska, Puerto Rico and Hawaii. Many of these sites coincide with the 1976-1978 EPA Mussel Watch sites, and new sites have been chosen after consulting with state officials and academic professionals about ideal placement. [ 3 ] Criteria for site selection includes;
The Mussel Watch Program does not use caged mussels, instead it uses naturally occurring bivalves. [ 10 ] Sites were distributed 10–100 km apart to better represent large coastal areas which enable NOAA to more accurately construct a nationwide assessment. As a result, Mussel Watch can be used to "monitor spatial distributions and temporal trends of chemical concentrations in coastal and estuarine regions of the US." [ 13 ]
There is not a single species of mussel or oyster that is common to all US coastal regions, so the species for a given site are chosen based on their abundance and ease of collection. "Mussels ( Mytilus species) are collected from the North Atlantic and Pacific coasts, oysters ( Crassostrea virginica ) from the mid-Atlantic (Delaware Bay) southward and along the Gulf Coast, and zebra mussels ( Dreissena species), an invasive species, are collected from sites in the Great Lakes." [ 3 ]
The majority of field collection and laboratory work is conducted by non-NOAA contract laboratories. [ 10 ] At least once annually between November and March volunteers at each Mussel Watch site collect two groups of 50-100 bivalves. The samples must be collected within three weeks of the date the site was first sampled. [ 10 ] This means that if a sample was first taken on April 15, 1987, then all future samples in subsequent years must be taken within three weeks of April 15. One group is used for testing organic contaminants while the other group is used for trace elements (metals). [ 13 ] Sediment from a site exposed to the same water mass as the corresponding bivalve site and no more than 2 km away is collected concurrently with the bivalves. Sediment criteria measured includes total organic and carbonate carbon, moisture content, particle size, concentration of Clostridium perfringens , and concentration of Coprostanol (this was no longer measured after 1989). [ 10 ] Different methods of bivalve collection are used depending on the site characteristics. A bivalve dredge is used in water deeper than 2 m, stainless steel tongs are used in 2-2.5 m deep water with a soft bottom, stainless steel pitch forks or quahog rakes are used in water less than 1 m deep, and collection by hand is done at some shoreline sites. [ 10 ] The bivalves are then cleaned, packed in iced containers, and shipped to the appropriate analytical laboratory within two days of collection. [ 3 ]
NOAA awarded TDI-Brooks International with a five-year contract to analyze sediment and bivalve tissue chemistry from September 21, 2009 to September 20, 2014. TDI-Brooks has also conducted the testing for the previous ten years from 1999 to 2009. TDI-Brooks and their affiliate B&B Laboratories conducts the organic chemical analysis, Rutgers University is subcontracted to conduct the histopathology analysis, and Texas A&M is subcontracted to conduct the metal and nutrient analysis. [ 14 ] Due to the Deepwater Horizon oil spill the resources at these labs were shifted towards chemical analyses of the high-priority samples for the Gulf of Mexico . This caused significant delays, in some cases of more than a year, of analysis results for the Mussel Watch Program. [ 15 ]
National Tissue and Sediment Sample Archive: Many of NOAA's projects incorporate different programs to obtain the desired information. The National Status and Trends program of NOAA's started using mussel, oyster, and zebra mussel samples collected under the Mussel Watch Program in 1985 as a means to start specimen banking. This bank of samples allows NOAA to take a snapshot of certain contaminants of interest at any point in time allowing, through the use of analytical techniques, the tissue concentrations of the desired compound. This allows regulators to better understand the history of a certain compound. [ 16 ] Another project that took advantage of the Mussel Watch program was the assessment of coastal waters impacted by Hurricane Katrina in 2005. By examining shallow waters for concentrations of DDT, conventional chlorinated pesticides, PCBs, PAHs, and metals after the hurricane NOAA scientists were able to compare results with the past 20 years of monitoring data from the same area. This consistent and historical record of contaminants from the Mussel Watch program proved effective in analyzing the impacts of Hurricane Katrina. [ 7 ] Pathology of parasites in bivalves, using oysters and mussels collected via the Mussel Watch program tissue samples were investigated for parasites. The change in abundance of parasites geographically and over time can be a good indicator of exposure to a contaminant. [ 5 ] The results of these pathology screenings have been used to show levels of contamination and have affected regulatory decisions. [ 6 ]
Mussel Watch publishes reports approximately every 2 years concerning most sites and regions. Some compilations and other notable publications historically produced include:
Arguably the most important publication to come from the Mussel Watch program is "An Assessment of Two Decades of Contaminant Monitoring in the Nation's Coastal Zone". [ 3 ] This publication was intended for use by academics, concerned citizens, and governmental and other regulatory agencies. This report includes trends and relative levels of 140 different chemicals at 300 sampling sites across the US and Puerto Rico . Spanning the years of 1986-2006 this report has served to inform policy makers and interested individuals outside of regulatory agencies. [ 3 ] Another notable publication is the report titled, An Assessment of Polybrominated Diphenyl Ethers (PBDEs) in Sediments and Bivalves of the U.S. Coastal Zone. This report investigated the relatively new class of compounds known as Polybrominated Diphenyl Ethers (PBDEs) which act as flame retardants. These are found in many consumer plastics, textiles, electronics, and furniture cushion material. This report showed the relative levels of contamination geographically and linked high levels of PBDE to areas of high human population density. This has been significant due to the potential threat these compounds pose for global distribution. [ 17 ]
Great Lakes Mussel Watch Supports the President's Great Lakes Restoration Initiative is one of the many ongoing projects by Mussel Watch.
This project, receiving attention and funding from the President's Great Lakes Restoration Initiative (GLRI), is a typical example of the types of projects Mussel Watch is being used for. Looking at Areas of Concern (AOC) in the US Great Lakes, Mussel Watch has increased sampling sizes and rates as well as updated techniques including doing caged mussel testing when shellfish beds are not available. [ 18 ] By looking at both sediment and mussel tissue concentrations researches have been able to better identify remediation efforts at Great Lake AOC. Like many other current Mussel Watch projects, the GLRI is using both historical data from Mussel Watch as well as increasingly more temporally and spatially prioritized data leading to more robust data sets far more applicable to specific AOC. [ 18 ]
Mussels are the organism of choice for monitoring contaminant levels in the coastal regions for a number of reasons. Most mussels are generally sessile and cannot move to another location if their environment has become contaminated; this makes them good measures of environmental pollution. Mussels do not readily metabolize some of the organics that vertebrates do, making them a better choice when tracking substances such as PAHs. In addition, most mussels are filter feeders and filter water through their bodies to feed. This filtration makes them prime targets for picking up contaminants in the water. [ 3 ] Mussels can provide information on if a system is recovering and if a remediation or cleanup effort is effective. In a successful remediation effort a decline of contaminants in the organisms is expected. An example of this is in Lavaca Bay , Texas, which is a site that has been contaminated due to chronic mercury releases from a nearby facility. By monitoring the mercury levels in oysters over several years it was discovered that the mercury content in the bay was decreasing. [ 19 ] Due to the nature of their filter feeding, bivalves allow Mussel Watch to tracks changes in contamination levels in the environment by monitoring bivalve tissue concentrations. This is important because it can show whether a policy that is meant to protect and clean the environment or an ecosystem is actually working. Mussel Watch can be used to evaluate current policies to determine what, if any, changes need to be made to ensure that there is an improvement in environmental health. | https://en.wikipedia.org/wiki/Mussel_Watch_Program |
Mustafa Babanlı ( Azerbaijani : Mustafa Baba oğlu Babanlı ; born February 21, 1968), is an Azerbaijani scientist, Rector of the Azerbaijan State Oil and Industry University .
On September 3, 2015, Mustafa Babanli was appointed Rector of the Azerbaijan State University of Oil and Industry . [ 1 ] [ 2 ] He is a member of the International Association of University Presidents , [ 3 ] serving as Regional Chair for Middle East, Caucasus & Central Asia. [ 4 ] | https://en.wikipedia.org/wiki/Mustafa_Babanli |
The principle of mutability is the notion that any physical property which appears to follow a conservation law may undergo some physical process that violates its conservation. [ 1 ] [ 2 ] [ 3 ] John Archibald Wheeler offered this speculative principle after Stephen Hawking predicted the evaporation of black holes which violates baryon number conservation . [ 4 ]
This article about theoretical physics is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Mutability |
Mutacin 1140 is a bacteriocin produced by Streptococcus mutans . [ 1 ] It has activity against a broad spectrum of Gram-positive bacteria. It is a member of the class of compounds known as lantibiotics .
Mutacin 1140 belongs to the epidermin subset of type Al lantibiotics. Molecules belonging to this family bind to lipid II which is a precursor to bacterial cell wall synthesis. [ 2 ]
While the effects mutacin 1140 has against gram-positive bacteria are known, it remains difficult to study due to it demonstrating poor pharmacokinetics . Besides the poor pharmacokinetics, it is easily vulnerable to proteolytic degradation by interfering with the protein's peptide bonds. [ 2 ]
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Mutacin_1140 |
In genetics , a mutagen is a physical or chemical agent that permanently changes genetic material , usually DNA , in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer in animals, such mutagens can therefore be carcinogens , although not all necessarily are. All mutagens have characteristic mutational signatures with some chemicals becoming mutagenic through cellular processes.
The process of DNA becoming modified is called mutagenesis . Not all mutations are caused by mutagens: so-called "spontaneous mutations" occur due to spontaneous hydrolysis , errors in DNA replication , repair and recombination .
The first mutagens to be identified were carcinogens , substances that were shown to be linked to cancer . Tumors were described more than 2,000 years before the discovery of chromosomes and DNA ; in 500 B.C., the Greek physician Hippocrates named tumors resembling a crab karkinos (from which the word "cancer" is derived via Latin), meaning crab. [ 1 ] In 1567, Swiss physician Paracelsus suggested that an unidentified substance in mined ore (identified as radon gas in modern times) caused a wasting disease in miners, [ 2 ] and in England, in 1761, John Hill made the first direct link of cancer to chemical substances by noting that excessive use of snuff may cause nasal cancer. [ 3 ] In 1775, Sir Percivall Pott wrote a paper on the high incidence of scrotal cancer in chimney sweeps , and suggested chimney soot as the cause of scrotal cancer. [ 4 ] In 1915, Yamagawa and Ichikawa showed that repeated application of coal tar to rabbit's ears produced malignant cancer. [ 5 ] Subsequently, in the 1930s the carcinogen component in coal tar was identified as a polyaromatic hydrocarbon (PAH), benzo[a]pyrene . [ 2 ] [ 6 ] Polyaromatic hydrocarbons are also present in soot, which was suggested to be a causative agent of cancer over 150 years earlier.
The association of exposure to radiation and cancer had been observed as early as 1902, six years after the discovery of X-ray by Wilhelm Röntgen and radioactivity by Henri Becquerel . [ 7 ] Georgii Nadson and German Filippov were the first who created fungi mutants under ionizing radiation in 1925. [ 8 ] [ 9 ] The mutagenic property of mutagens was first demonstrated in 1927, when Hermann Muller discovered that x-rays can cause genetic mutations in fruit flies , producing phenotypic mutants as well as observable changes to the chromosomes, [ 10 ] [ 11 ] visible due to the presence of enlarged "polytene" chromosomes in fruit fly salivary glands. [ 12 ] His collaborator Edgar Altenburg also demonstrated the mutational effect of UV radiation in 1928. [ 13 ] Muller went on to use x-rays to create Drosophila mutants that he used in his studies of genetics . [ 14 ] He also found that X-rays not only mutate genes in fruit flies, [ 10 ] but also have effects on the genetic makeup of humans. [ 15 ] [ better source needed ] Similar work by Lewis Stadler also showed the mutational effect of X-rays on barley in 1928, [ 16 ] and ultraviolet (UV) radiation on maize in 1936. [ 17 ] The effect of sunlight had previously been noted in the nineteenth century where rural outdoor workers and sailors were found to be more prone to skin cancer. [ 18 ]
Chemical mutagens were not demonstrated to cause mutation until the 1940s, when Charlotte Auerbach and J. M. Robson found that mustard gas can cause mutations in fruit flies. [ 19 ] A large number of chemical mutagens have since been identified, especially after the development of the Ames test in the 1970s by Bruce Ames that screens for mutagens and allows for preliminary identification of carcinogens. [ 20 ] [ 21 ] Early studies by Ames showed around 90% of known carcinogens can be identified in Ames test as mutagenic (later studies however gave lower figures), [ 22 ] [ 23 ] [ 24 ] and ~80% of the mutagens identified through Ames test may also be carcinogens. [ 24 ] [ 25 ]
Mutagens are not necessarily carcinogens, and vice versa. Sodium azide for example may be mutagenic (and highly toxic), but it has not been shown to be carcinogenic. [ 26 ] Meanwhile, compounds which are not directly mutagenic but stimulate cell growth which can reduce the effectiveness of DNA repair and indirectly increase the chance of mutations, and therefore that of cancer. [ 27 ] One example of this would be anabolic steroids , which stimulate growth of the prostate gland and increase the risk of prostate cancer among others. [ 28 ] Other carcinogens may cause cancer through a variety of mechanisms without producing mutations, such as tumour promotion , immunosuppression that reduces the ability to fight cancer cells or pathogens that can cause cancer, disruption of the endocrine system (e.g. in breast cancer), tissue-specific toxicity, and inflammation (e.g. in colorectal cancer). [ 29 ]
A DNA damaging agent is an agent that causes a change in the structure of DNA that is not itself replicated when the DNA is replicated . [ 30 ] Examples of DNA damage include a chemical addition or disruption of a nucleotide base in DNA (generating an abnormal nucleotide or nucleotide fragment), or a break in one or both strands in DNA. When duplex DNA containing a damaged base is replicated, an incorrect base may be inserted in the newly synthesized strand opposite the damaged base in the complementary template strand, and this can become a mutation in the next round of replication. Also a DNA double-strand break may be repaired by an inaccurate process leading to an altered base pair, a mutation. However, mutations and DNA damages differ in a fundamental way: mutations can, in principle, be replicated when DNA replicates, whereas DNA damages are not necessarily replicated. Thus DNA damaging agents often cause mutations as a secondary consequence, but not all DNA damages lead to mutation and not all mutations arise from a DNA damage. [ 30 ] The term genotoxic means toxic (damaging) to DNA.
Mutagens can cause changes to the DNA and are therefore genotoxic . They can affect the transcription and replication of the DNA, which in severe cases can lead to cell death. The mutagen produces mutations in the DNA, and deleterious mutation can result in aberrant, impaired or loss of function for a particular gene, and accumulation of mutations may lead to cancer. Mutagens may therefore be also carcinogens. However, some mutagens exert their mutagenic effect through their metabolites, and therefore whether such mutagens actually become carcinogenic may be dependent on the metabolic processes of an organism, and a compound shown to be mutagenic in one organism may not necessarily be carcinogenic in another. [ 31 ]
Different mutagens act on DNA differently. Powerful mutagens may result in chromosomal instability, [ 32 ] causing chromosomal breakages and rearrangement of the chromosomes such as translocation , deletion , and inversion . Such mutagens are called clastogens .
Mutagens may also modify the DNA sequence; the changes in nucleic acid sequences by mutations include substitution of nucleotide base-pairs and insertions and deletions of one or more nucleotides in DNA sequences. Although some of these mutations are lethal or cause serious disease, many have minor effects as they do not result in residue changes that have significant effect on the structure and function of the proteins . Many mutations are silent mutations , causing no visible effects at all, either because they occur in non-coding or non-functional sequences, or they do not change the amino-acid sequence due to the redundancy of codons . [ 33 ] Some mutagens can cause aneuploidy and change the number of chromosomes in the cell. They are known as aneuploidogens. [ 34 ]
In Ames test, where the varying concentrations of the chemical are used in the test, the dose response curve obtained is nearly always linear, suggesting that there may be no threshold for mutagenesis. Similar results are also obtained in studies with radiations, indicating that there may be no safe threshold for mutagens. However, the no-threshold model is disputed with some arguing for a dose rate dependent threshold for mutagenesis. [ 35 ] [ 10 ] Some have proposed that low level of some mutagens may stimulate the DNA repair processes and therefore may not necessarily be harmful. More recent approaches with sensitive analytical methods have shown that there may be non-linear or bilinear dose-responses for genotoxic effects, and that the activation of DNA repair pathways can prevent the occurrence of mutation arising from a low dose of mutagen. [ 36 ]
Mutagens may be of physical, chemical or biological origin. They may act directly on the DNA, causing direct damage to the DNA, and most often result in replication error. Some however may act on the replication mechanism and chromosomal partition. Many mutagens are not mutagenic by themselves, but can form mutagenic metabolites through cellular processes, for example through the activity of the cytochrome P450 system and other oxygenases such as cyclooxygenase . [ 37 ] Such mutagens are called promutagens . [ citation needed ]
Chemical mutagens either directly or indirectly damage DNA. On this basis, they are of 2 types:
They directly damage DNA, but may or may not undergo metabolism to produce promutagens (metabolites that can have higher mutagenic potential than their substrates).
They are not necessarily mutagenic by themselves, but they produce promutagens mutagenic compounds through metabolic processes in cells.
Some chemical mutagens additionally require UV or visible light activation for their mutagenic effect. These are the photomutagens , which include furocoumarins and limettin . [ 45 ]
Many metals, such as arsenic , cadmium , chromium , nickel and their compounds may be mutagenic, but they may act, however, via a number of different mechanisms. [ 46 ] Arsenic, chromium, iron, and nickel may be associated with the production of ROS, and some of these may also alter the fidelity of DNA replication. Nickel may also be linked to DNA hypermethylation and histone deacetylation, while some metals such as cobalt , arsenic, nickel and cadmium may also affect DNA repair processes such as DNA mismatch repair , and base and nucleotide excision repair . [ 47 ]
Antioxidants are an important group of anticarcinogenic compounds that may help remove ROS or potentially harmful chemicals. These may be found naturally in fruits and vegetables . [ 50 ] Examples of antioxidants are vitamin A and its carotenoid precursors, vitamin C , vitamin E , polyphenols , and various other compounds. β-Carotene is the red-orange colored compounds found in vegetables like carrots and tomatoes . Vitamin C may prevent some cancers by inhibiting the formation of mutagenic N-nitroso compounds (nitrosamine). Flavonoids , such as EGCG in green tea , have also been shown to be effective antioxidants and may have anti-cancer properties. Epidemiological studies indicate that a diet rich in fruits and vegetables is associated with lower incidence of some cancers and longer life expectancy, [ 51 ] however, the effectiveness of antioxidant supplements in cancer prevention in general is still the subject of some debate. [ 51 ] [ 52 ]
Other chemicals may reduce mutagenesis or prevent cancer via other mechanisms, although for some the precise mechanism for their protective property may not be certain. Selenium , which is present as a micronutrient in vegetables, is a component of important antioxidant enzymes such as gluthathione peroxidase. Many phytonutrients may counter the effect of mutagens; for example, sulforaphane in vegetables such as broccoli has been shown to be protective against prostate cancer . [ 53 ] Others that may be effective against cancer include indole-3-carbinol from cruciferous vegetables and resveratrol from red wine. [ 54 ]
An effective precautionary measure an individual can undertake to protect themselves is by limiting exposure to mutagens such as UV radiations and tobacco smoke. In Australia, where people with pale skin are often exposed to strong sunlight, melanoma is the most common cancer diagnosed in people aged 15–44 years. [ 55 ] [ 56 ]
In 1981, human epidemiological analysis by Richard Doll and Richard Peto indicated that smoking caused 30% of cancers in the US. [ 57 ] Diet is also thought to cause a significant number of cancer fatalities, and it has been estimated that around 32% of cancer deaths may be avoidable by modification to the diet. [ 58 ] Mutagens identified in food include mycotoxins from food contaminated with fungal growths, such as aflatoxins which may be present in contaminated peanuts and corn; heterocyclic amines generated in meat when cooked at high temperature; PAHs in charred meat and smoked fish, as well as in oils, fats, bread, and cereal; [ 59 ] and nitrosamines generated from nitrites used as food preservatives in cured meat such as bacon ( ascorbate , which is added to cured meat, however, reduces nitrosamine formation). [ 50 ] Overly-browned starchy food such as bread, biscuits and potatoes can generate acrylamide , a chemical shown to cause cancer in animal studies. [ 60 ] [ 61 ] Excessive alcohol consumption has also been linked to cancer; the possible mechanisms for its carcinogenicity include formation of the possible mutagen acetaldehyde , and the induction of the cytochrome P450 system which is known to produce mutagenic compounds from promutagens. [ 62 ]
For certain mutagens, such as dangerous chemicals and radioactive materials, as well as infectious agents known to cause cancer, government legislations and regulatory bodies are necessary for their control. [ 63 ]
Many different systems for detecting mutagen have been developed. [ 64 ] [ 65 ] Animal systems may more accurately reflect the metabolism of human, however, they are expensive and time-consuming (may take around three years to complete), they are therefore not used as a first screen for mutagenicity or carcinogenicity.
Systems similar to Ames test have been developed in yeast. Saccharomyces cerevisiae is generally used. These systems can check for forward and reverse mutations, as well as recombinant events.
Sex-Linked Recessive Lethal Test – Males from a strain with yellow bodies are used in this test. The gene for the yellow body lies on the X-chromosome. The fruit flies are fed on a diet of test chemical, and progenies are separated by sex. The surviving males are crossed with the females of the same generation, and if no males with yellow bodies are detected in the second generation, it would indicate a lethal mutation on the X-chromosome has occurred.
Plants such as Zea mays , Arabidopsis thaliana and Tradescantia have been used in various test assays for mutagenecity of chemicals.
Mammalian cell lines such as Chinese hamster V79 cells, Chinese hamster ovary (CHO) cells or mouse lymphoma cells may be used to test for mutagenesis. Such systems include the HPRT assay for resistance to 8-azaguanine or 6-thioguanine , and ouabain -resistance (OUA) assay .
Rat primary hepatocytes may also be used to measure DNA repair following DNA damage. Mutagens may stimulate unscheduled DNA synthesis that results in more stained nuclear material in cells following exposure to mutagens.
These systems check for large scale changes to the chromosomes and may be used with cell culture or in animal test. The chromosomes are stained and observed for any changes. Sister chromatid exchange is a symmetrical exchange of chromosome material between sister chromatids and may be correlated to the mutagenic or carcinogenic potential of a chemical. In micronucleus Test , cells are examined for micronuclei, which are fragments or chromosomes left behind at anaphase, and is therefore a test for clastogenic agents that cause chromosome breakages. Other tests may check for various chromosomal aberrations such as chromatid and chromosomal gaps and deletions, translocations, and ploidy.
Rodents are usually used in animal test . The chemicals under
test are usually administered in the food and in the drinking water, but sometimes by dermal application, by gavage , or by inhalation, and carried out over the major part of the life span for rodents. In tests that check for carcinogens, maximum tolerated dosage is first determined, then a range of doses are given to around 50 animals throughout the notional lifespan of the animal of two years. After death the animals are examined for sign of tumours. Differences in metabolism between rat and human however means that human may not respond in exactly the same way to mutagen, and dosages that produce tumours on the animal test may also be unreasonably high for a human, i.e. the equivalent amount required to produce tumours in human may far exceed what a person might encounter in real life.
Mice with recessive mutations for a visible phenotype may also be used to check for mutagens. Females with recessive mutation crossed with wild-type males would yield the same phenotype as the wild-type, and any observable change to the phenotype would indicate that a mutation induced by the mutagen has occurred.
Mice may also be used for dominant lethal assays where early embryonic deaths are monitored. Male mice are treated with chemicals under test, mated with females, and the females are then sacrificed before parturition and early fetal deaths are counted in the uterine horns .
Transgenic mouse assay using a mouse strain infected with a viral shuttle vector is another method for testing mutagens. Animals are first treated with suspected mutagen, the mouse DNA is then isolated and the phage segment recovered and used to infect E. coli . Using similar method as the blue-white screen , the plaque formed with DNA containing mutation are white, while those without are blue.
Many mutagens are highly toxic to proliferating cells, and they are often used to destroy cancer cells. Alkylating agents such as cyclophosphamide and cisplatin , as well as intercalating agent such as daunorubicin and doxorubicin may be used in chemotherapy . However, due to their effect on other cells which are also rapidly dividing, they may have side effects such as hair loss and nausea. Research on better targeted therapies may reduce such side-effects. Ionizing radiations are used in radiation therapy .
In science fiction , mutagens are often represented as substances that are capable of completely changing the form of the recipient or granting them superpowers. Powerful radiations are the agents of mutation for the superheroes in Marvel Comics 's Fantastic Four , Daredevil , and Hulk , while in the Ninja Turtles franchise the MUTAGEN "ooze" for Inhumans the mutagen is the Terrigen Mist . Mutagens are also featured in video games such as Cyberia , System Shock , The Witcher , Metroid Prime: Trilogy , Resistance: Fall of Man , Resident Evil , Infamous , Freedom Force , Command & Conquer , Gears of War 3 , StarCraft , BioShock , Fallout , Underrail , and Maneater .
In the "nuclear monster" films of the 1950s, nuclear radiation mutates humans and common insects often to enormous size and aggression; these films include Godzilla , Them! , Attack of the 50 Foot Woman , Tarantula! , and The Amazing Colossal Man . | https://en.wikipedia.org/wiki/Mutagen |
In molecular biology , mutagenesis is an important laboratory technique whereby DNA mutations are deliberately engineered to produce libraries of mutant genes, proteins, strains of bacteria, or other genetically modified organisms . The various constituents of a gene, as well as its regulatory elements and its gene products, may be mutated so that the functioning of a genetic locus, process, or product can be examined in detail. The mutation may produce mutant proteins with interesting properties or enhanced or novel functions that may be of commercial use. Mutant strains may also be produced that have practical application or allow the molecular basis of a particular cell function to be investigated.
Many methods of mutagenesis exist today. Initially, the kind of mutations artificially induced in the laboratory were entirely random using mechanisms such as UV irradiation. Random mutagenesis cannot target specific regions or sequences of the genome; however, with the development of site-directed mutagenesis , more specific changes can be made. Since 2013, development of the CRISPR /Cas9 technology, based on a prokaryotic viral defense system, has allowed for the editing or mutagenesis of a genome in vivo . [ 1 ] Site-directed mutagenesis has proved useful in situations that random mutagenesis is not. Other techniques of mutagenesis include combinatorial and insertional mutagenesis. Mutagenesis that is not random can be used to clone DNA, [ 2 ] investigate the effects of mutagens, [ 3 ] and engineer proteins. [ 4 ] It also has medical applications such as helping immunocompromised patients, research and treatment of diseases including HIV and cancers, and curing of diseases such as beta thalassemia . [ 5 ]
Early approaches to mutagenesis relied on methods which produced entirely random mutations. In such methods, cells or organisms are exposed to mutagens such as UV radiation or mutagenic chemicals, and mutants with desired characteristics are then selected. Hermann Muller discovered in 1927 that X-rays can cause genetic mutations in fruit flies , [ 6 ] and went on to use the mutants he created for his studies in genetics . [ 7 ] For Escherichia coli , mutants may be selected first by exposure to UV radiation, then plated onto an agar medium. The colonies formed are then replica-plated , one in a rich medium , another in a minimal medium, and mutants that have specific nutritional requirements can then be identified by their inability to grow in the minimal medium. Similar procedures may be repeated with other types of cells and with different media for selection.
A number of methods for generating random mutations in specific proteins were later developed to screen for mutants with interesting or improved properties. These methods may involve the use of doped nucleotides in oligonucleotide synthesis, or conducting a PCR reaction in conditions that enhance misincorporation of nucleotides (error-prone PCR), for example by reducing the fidelity of replication or using nucleotide analogues. [ 8 ] A variation of this method for integrating non-biased mutations in a gene is sequence saturation mutagenesis . [ 9 ] PCR products which contain mutation(s) are then cloned into an expression vector and the mutant proteins produced can then be characterised.
In animal studies, alkylating agents such as N -ethyl- N -nitrosourea (ENU) have been used to generate mutant mice. [ 10 ] [ 11 ] Ethyl methanesulfonate (EMS) is also often used to generate animal, plant, and virus mutants. [ 12 ] [ 13 ] [ 14 ]
In a European Union law (as 2001/18 directive), this kind of mutagenesis may be used to produce GMOs but the products are exempted from regulation: no labeling, no evaluation. [ 15 ]
Prior to the development site-directed mutagenesis techniques, all mutations made were random, and scientists had to use selection for the desired phenotype to find the desired mutation. Random mutagenesis techniques has an advantage in terms of how many mutations can be produced; however, while random mutagenesis can produce a change in single nucleotides, it does not offer much control as to which nucleotide is being changed. [ 5 ] Many researchers therefore seek to introduce selected changes to DNA in a precise, site-specific manner. Early attempts uses analogs of nucleotides and other chemicals were first used to generate localized point mutations . [ 16 ] Such chemicals include aminopurine , which induces an AT to GC transition , [ 17 ] while nitrosoguanidine , [ 18 ] bisulfite , [ 19 ] and N 4 -hydroxycytidine may induce a GC to AT transition. [ 20 ] [ 21 ] These techniques allow specific mutations to be engineered into a protein; however, they are not flexible with respect to the kinds of mutants generated, nor are they as specific as later methods of site-directed mutagenesis and therefore have some degree of randomness. Other technologies such as cleavage of DNA at specific sites on the chromosome, addition of new nucleotides, and exchanging of base pairs it is now possible to decide where mutations can go. [ 11 ] [ 8 ]
Current techniques for site-specific mutation originates from the primer extension technique developed in 1978. Such techniques commonly involve using pre-fabricated mutagenic oligonucleotides in a primer extension reaction with DNA polymerase . This methods allows for point mutation or deletion or insertion of small stretches of DNA at specific sites. Advances in methodology have made such mutagenesis now a relatively simple and efficient process. [ 3 ]
Newer and more efficient methods of site directed mutagenesis are being constantly developed. For example, a technique called "Seamless ligation cloning extract" (or SLiCE for short) allows for the cloning of certain sequences of DNA within the genome, and more than one DNA fragment can be inserted into the genome at once. [ 2 ]
Site directed mutagenesis allows the effect of specific mutation to be investigated. There are numerous uses; for example, it has been used to determine how susceptible certain species were to chemicals that are often used In labs. The experiment used site directed mutagenesis to mimic the expected mutations of the specific chemical. The mutation resulted in a change in specific amino acids and the effects of this mutation were analyzed. [ 3 ]
The site-directed approach may be done systematically in such techniques as alanine scanning mutagenesis, whereby residues are systematically mutated to alanine in order to identify residues important to the structure or function of a protein. [ 22 ] Another comprehensive approach is site saturation mutagenesis where one codon or a set of codons may be substituted with all possible amino acids at the specific positions. [ 23 ] [ 24 ]
Combinatorial mutagenesis is a site-directed protein engineering technique whereby multiple mutants of a protein can be simultaneously engineered based on analysis of the effects of additive individual mutations. [ 25 ] It provides a useful method to assess the combinatorial effect of a large number of mutations on protein function. [ 26 ] Large numbers of mutants may be screened for a particular characteristic by combinatorial analysis. [ 25 ] In this technique, multiple positions or short sequences along a DNA strand may be exhaustively modified to obtain a comprehensive library of mutant proteins. [ 25 ] The rate of incidence of beneficial variants can be improved by different methods for constructing mutagenesis libraries. One approach to this technique is to extract and replace a portion of the DNA sequence with a library of sequences containing all possible combinations at the desired mutation site. The content of the inserted segment can include sequences of structural significance, immunogenic property, or enzymatic function. A segment may also be inserted randomly into the gene in order to assess structural or functional significance of a particular part of a protein. [ 25 ]
The insertion of one or more base pairs, resulting in DNA mutations, is also known as insertional mutagenesis . [ 27 ] Engineered mutations such as these can provide important information in cancer research, such as mechanistic insights into the development of the disease. Retroviruses and transposons are the chief instrumental tools in insertional mutagenesis. Retroviruses, such as the mouse mammory tumor virus and murine leukemia virus, can be used to identify genes involved in carcinogenesis and understand the biological pathways of specific cancers. [ 28 ] Transposons, chromosomal segments that can undergo transposition, can be designed and applied to insertional mutagenesis as an instrument for cancer gene discovery. [ 28 ] These chromosomal segments allow insertional mutagenesis to be applied to virtually any tissue of choice while also allowing for more comprehensive, unbiased depth in DNA sequencing. [ 28 ]
Researchers have found four mechanisms of insertional mutagenesis that can be used on humans. the first mechanism is called enhancer insertion. Enhancers boost transcription of a particular gene by interacting with a promoter of that gene. This particular mechanism was first used to help severely immunocompromised patients I need of bone marrow. Gammaretroviruses carrying enhancers were then inserted into patients. The second mechanism is referred to as promoter insertion. Promoters provide our cells with the specific sequences needed to begin translation. Promoter insertion has helped researchers learn more about the HIV virus. The third mechanism is gene inactivation. An example of gene inactivation is using insertional mutagenesis to insert a retrovirus that disrupts the genome of the T cell in leukemia patients and giving them a specific antigen called CAR allowing the T cells to target cancer cells. The final mechanisms is referred to as mRNA 3' end substitution. Our genes occasionally undergo point mutations causing beta-thalassemia that interrupts red blood cell function. To fix this problem the correct gene sequence for the red blood cells are introduced and a substitution is made. [ 5 ]
Homologous recombination can be used to produce specific mutation in an organism. Vector containing DNA sequence similar to the gene to be modified is introduced to the cell, and by a process of recombination replaces the target gene in the chromosome. This method can be used to introduce a mutation or knock out a gene, for example as used in the production of knockout mice . [ 29 ]
Since 2013, the development of CRISPR -Cas9 technology has allowed for the efficient introduction of different types of mutations into the genome of a wide variety of organisms. The method does not require a transposon insertion site, leaves no marker, and its efficiency and simplicity has made it the preferred method for genome editing . [ 30 ] [ 31 ]
As the cost of DNA oligonucleotide synthesis falls, artificial synthesis of a complete gene is now a viable method for introducing mutations into a gene. This method allows for extensive mutation at multiple sites, including the complete redesign of the codon usage of a gene to optimise it for a particular organism. [ 32 ] | https://en.wikipedia.org/wiki/Mutagenesis_(molecular_biology_technique) |
The mutanome is the entirety of somatic cancer mutations in an individual tumor. [ 1 ]
Carcinogenesis is largely driven by changes in the DNA sequence of the genomes of cancer cells. [ 1 ] [ 2 ] This process leads to a unique repertoire of mutations (′the mutanome′) in every patient's tumor. [ 3 ] [ 4 ] The mutanome encodes peptides that can be targets for T cells , which play a central role in the immune response. [ 5 ]
A description of individual mutanomes of human tumors has been made feasible by the introduction of Next Generation Sequencing Technology (NGS). [ 6 ] Cancer mutanomes can be defined by comparing exome sequencing data obtained by NGS of individual healthy tissue with sequences from tumor-derived nucleic acids . [ 7 ] As the vast majority of cancer-associated mutations are patient specific, shared mutations are rare, even within the same type of cancer. [ 7 ] [ 8 ] [ 9 ]
The mutanome encodes a pattern of tumor-specific mutated peptides referred to as neoantigens or m-peptides. Neoantigens are products of mutations that first occur in the course of cancer development. Each and every tumor has its own unique neoantigenic pattern, and even within the same type of cancer, only a small percentage of neoantigens are shared. [ 5 ] [ 10 ]
Neoantigens are presented on major histocompatibility complex (MHC) molecules of tumor cells. [ 8 ] [ 10 ] [ 11 ] The antigenic determinants of neoantigens – neoepitopes – are recognized by the immune system as a target for T cells, thus triggering immune responses against cancer. [ 1 ] [ 12 ]
A neoepitope is an epitope the immune system has not encountered before. Therefore, it is not subject to tolerance mechanisms of the immune system. [ 13 ] Since the mutated gene product is only expressed in tumors, but not on healthy cells, neoepitopes may evoke vigorous T cell response. [ 6 ]
The vast majority of cancer mutations are unique to the individual patient, [ 9 ] and a significant portion of mutations (21-45%) are immunogenic. [ 1 ] Therefore, the patients' individual mutanome and the neoepitopes are used as the basis for a novel strategy against cancer, which is referred to as individualized cancer immunotherapy . [ 14 ] Cancer immunotherapy uses the body's own immune defense system and is based on the recognition by cytotoxic and helper T cells with antitumor activity. [ 10 ]
Strategies to immunotherapeutically address the individual mutanome are currently under investigation. [ 8 ] [ 11 ] [ 14 ] [ 15 ] Ongoing mutanome cancer vaccine trials use synthetic peptides and antigen-encoding DNA or RNA as formats. [ 7 ] For an individualized treatment, neoepitopes that are thought to elicit a strong immune response are selected out of the patient's mutanome. [ 14 ] [ 16 ]
An increasingly explored concept for individualized cancer immunotherapy is the treatment of a patient with immunogenic mRNA vaccines for a given patient's individual cancer mutanome (IVAC - Individualized Vaccine Against Cancer). [ 14 ] [ 16 ] The IVAC concept is based on decoding the individual mutanome by NGS and on-demand mRNA manufacturing for use in single patients to produce therapeutic vaccines against cancer. [ 8 ] [ 14 ] [ 15 ]
Since 2016, the IVAC concept has been developed as Individualized Neoantigen Specific Therapy (iNeST) .
The process of NSG based cancer mutanome mapping, target selection, prioritization approaches, synthetic mRNA vaccine manufacturing and delivery is also referred to as MERIT (mutanome engineered RNA immunotherapy). [ 8 ] [ 17 ] By vaccination with the synthetic mRNA, which contains the blueprint of a mutant tumor peptide, T lymphocytes are activated against the tumor. [ 7 ] [ 17 ] | https://en.wikipedia.org/wiki/Mutanome |
In biology , and especially in genetics , a mutant is an organism or a new genetic character arising or resulting from an instance of mutation , which is generally an alteration of the DNA sequence of the genome or chromosome of an organism . It is a characteristic that would not be observed naturally in a specimen. The term mutant is also applied to a virus with an alteration in its nucleotide sequence whose genome is in the nuclear genome . The natural occurrence of genetic mutations is integral to the process of evolution . The study of mutants is an integral part of biology; by understanding the effect that a mutation in a gene has, it is possible to establish the normal function of that gene. [ 2 ]
Mutants arise by mutations occurring in pre-existing genomes as a result of errors of DNA replication or errors of DNA repair . Errors of replication often involve translesion synthesis by a DNA polymerase when it encounters and bypasses a damaged base in the template strand. [ 3 ] A DNA damage is an abnormal chemical structure in DNA, such as a strand break or an oxidized base, whereas a mutation, by contrast, is a change in the sequence of standard base pairs. Errors of repair occur when repair processes inaccurately replace a damaged DNA sequence. The DNA repair process microhomology-mediated end joining is particularly error-prone. [ 4 ] [ 5 ]
Although not all mutations have a noticeable phenotypic effect, the common usage of the word "mutant" is generally a pejorative term, only used for genetically or phenotypically noticeable mutations. [ 6 ] Previously, people used the word " sport " (related to spurt ) to refer to abnormal specimens. The scientific usage is broader, referring to any organism differing from the wild type . The word finds its origin in the Latin term mūtant- (stem of mūtāns), which means "to change". [ 6 ]
Mutants should not be confused with organisms born with developmental abnormalities , which are caused by errors during morphogenesis . In a developmental abnormality, the DNA of the organism is unchanged and the abnormality cannot be passed on to progeny. Conjoined twins are the result of developmental abnormalities.
Chemicals that cause developmental abnormalities are called teratogens ; these may also cause mutations, but their effect on development is not related to mutations. Chemicals that induce mutations are called mutagens . Most mutagens are also considered to be carcinogens .
Mutations are distinctly different from epigenetic alterations, although they share some common features. Both arise as a chromosomal alteration that can be replicated and passed on to subsequent cell generations. Both, when occurring within a gene, may silence expression of the gene. Whereas mutant cell lineages arise as a change in the sequence of standard bases, epigenetically altered cell lineages retain the sequence of standard bases but have gene sequences with changed levels of expression that can be passed down to subsequent cell generations. Epigenetic alterations include methylation of CpG islands of a gene promoter as well as specific chromatin histone modifications. Faulty repair of chromosomes at sites of DNA damage can give rise both to mutant cell lineages [ 4 ] and/or epigenetically altered cell lineages. [ 7 ] | https://en.wikipedia.org/wiki/Mutant |
In stereochemistry , mutarotation is the change in optical rotation of a chiral material in a solution due to a change in proportion of the two constituent anomers (i.e. the interconversion of their respective stereocenters ) until equilibrium is reached. Cyclic sugars show mutarotation as α and β anomeric forms interconvert. [ 1 ] The optical rotation of the solution depends on the optical rotation of each anomer and their ratio in the solution.
Mutarotation was discovered by French chemist Augustin-Pierre Dubrunfaut in 1844, when he noticed that the specific rotation of aqueous sugar solution changes with time. [ 2 ] [ 3 ]
The α and β anomers are diastereomers of each other and usually have different specific rotations . A solution or liquid sample of a pure α anomer will rotate plane polarised light by a different amount and/or in the opposite direction than the pure β anomer of that compound. The optical rotation of the solution depends on the optical rotation of each anomer and their ratio in the solution. [ 4 ]
For example, if a solution of β- D - glucopyranose is dissolved in water, its specific optical rotation will be +18.7°. Over time, some of the β- D -glucopyranose will undergo mutarotation to become α- D -glucopyranose, which has an optical rotation of +112.2°. The rotation of the solution will increase from +18.7° to an equilibrium value of +52.7° as some of the β form is converted to the α form. The equilibrium mixture is about 64% of β- D -glucopyranose and about 36% of α- D -glucopyranose, though there are also traces of the other forms including furanoses and open chained form.
The observed rotation of the sample is the weighted sum of the optical rotation of each anomer weighted by the amount of that anomer present. Therefore, one can use a polarimeter to measure the rotation of a sample and then calculate the ratio of the two anomers present from the enantiomeric excess , as long as one knows the rotation of each pure anomer. One can monitor the mutarotation process over time or determine the equilibrium mixture by observing the optical rotation and how it changes. | https://en.wikipedia.org/wiki/Mutarotation |
In biology , a mutation is an alteration in the nucleic acid sequence of the genome of an organism , virus , or extrachromosomal DNA . [ 1 ] Viral genomes contain either DNA or RNA . Mutations result from errors during DNA or viral replication , mitosis , or meiosis or other types of damage to DNA (such as pyrimidine dimers caused by exposure to ultraviolet radiation), which then may undergo error-prone repair (especially microhomology-mediated end joining ), [ 2 ] cause an error during other forms of repair, [ 3 ] [ 4 ] or cause an error during replication ( translesion synthesis ). Mutations may also result from substitution , insertion or deletion of segments of DNA due to mobile genetic elements . [ 5 ] [ 6 ] [ 7 ]
Mutations may or may not produce detectable changes in the observable characteristics ( phenotype ) of an organism. Mutations play a part in both normal and abnormal biological processes including: evolution , cancer , and the development of the immune system , including junctional diversity . Mutation is the ultimate source of all genetic variation , providing the raw material on which evolutionary forces such as natural selection can act.
Mutation can result in many different types of change in sequences. Mutations in genes can have no effect, alter the product of a gene , or prevent the gene from functioning properly or completely. Mutations can also occur in non-genic regions . A 2007 study on genetic variations between different species of Drosophila suggested that, if a mutation changes a protein produced by a gene, the result is likely to be harmful, with an estimated 70% of amino acid polymorphisms that have damaging effects, and the remainder being either neutral or marginally beneficial. [ 8 ]
Mutation and DNA damage are the two major types of errors that occur in DNA, but they are fundamentally different. DNA damage is a physical alteration in the DNA structure, such as a single or double strand break, a modified guanosine residue in DNA such as 8-hydroxydeoxyguanosine , or a polycyclic aromatic hydrocarbon adduct. DNA damages can be recognized by enzymes, and therefore can be correctly repaired using the complementary undamaged strand in DNA as a template or an undamaged sequence in a homologous chromosome if it is available. If DNA damage remains in a cell, transcription of a gene may be prevented and thus translation into a protein may also be blocked. DNA replication may also be blocked and/or the cell may die. In contrast to a DNA damage, a mutation is an alteration of the base sequence of the DNA. Ordinarily, a mutation cannot be recognized by enzymes once the base change is present in both DNA strands, and thus a mutation is not ordinarily repaired. At the cellular level, mutations can alter protein function and regulation. Unlike DNA damages, mutations are replicated when the cell replicates. At the level of cell populations, cells with mutations will increase or decrease in frequency according to the effects of the mutations on the ability of the cell to survive and reproduce. Although distinctly different from each other, DNA damages and mutations are related because DNA damages often cause errors of DNA synthesis during replication or repair and these errors are a major source of mutation. [ 9 ]
Mutations can involve the duplication of large sections of DNA, usually through genetic recombination . [ 10 ] These duplications are a major source of raw material for evolving new genes, with tens to hundreds of genes duplicated in animal genomes every million years. [ 11 ] Most genes belong to larger gene families of shared ancestry, detectable by their sequence homology . [ 12 ] Novel genes are produced by several methods, commonly through the duplication and mutation of an ancestral gene, or by recombining parts of different genes to form new combinations with new functions. [ 13 ] [ 14 ]
Here, protein domains act as modules, each with a particular and independent function, that can be mixed together to produce genes encoding new proteins with novel properties. [ 15 ] For example, the human eye uses four genes to make structures that sense light: three for cone cell or colour vision and one for rod cell or night vision; all four arose from a single ancestral gene. [ 16 ] Another advantage of duplicating a gene (or even an entire genome) is that this increases engineering redundancy ; this allows one gene in the pair to acquire a new function while the other copy performs the original function. [ 17 ] [ 18 ] Other types of mutation occasionally create new genes from previously noncoding DNA . [ 19 ] [ 20 ]
Changes in chromosome number may involve even larger mutations, where segments of the DNA within chromosomes break and then rearrange. For example, in the Homininae , two chromosomes fused to produce human chromosome 2 ; this fusion did not occur in the lineage of the other apes , and they retain these separate chromosomes. [ 21 ] In evolution, the most important role of such chromosomal rearrangements may be to accelerate the divergence of a population into new species by making populations less likely to interbreed, thereby preserving genetic differences between these populations. [ 22 ]
Sequences of DNA that can move about the genome, such as transposons , make up a major fraction of the genetic material of plants and animals, and may have been important in the evolution of genomes. [ 23 ] For example, more than a million copies of the Alu sequence are present in the human genome , and these sequences have now been recruited to perform functions such as regulating gene expression . [ 24 ] Another effect of these mobile DNA sequences is that when they move within a genome, they can mutate or delete existing genes and thereby produce genetic diversity. [ 6 ]
Nonlethal mutations accumulate within the gene pool and increase the amount of genetic variation. [ 25 ] The abundance of some genetic changes within the gene pool can be reduced by natural selection , while other "more favorable" mutations may accumulate and result in adaptive changes.
For example, a butterfly may produce offspring with new mutations. The majority of these mutations will have no effect; but one might change the colour of one of the butterfly's offspring, making it harder (or easier) for predators to see. If this color change is advantageous, the chances of this butterfly's surviving and producing its own offspring are a little better, and over time the number of butterflies with this mutation may form a larger percentage of the population. [ 26 ]
Neutral mutations are defined as mutations whose effects do not influence the fitness of an individual. These can increase in frequency over time due to genetic drift . It is believed that the overwhelming majority of mutations have no significant effect on an organism's fitness. [ 27 ] [ 28 ] Also, DNA repair mechanisms are able to mend most changes before they become permanent mutations, and many organisms have mechanisms, such as apoptotic pathways , for eliminating otherwise-permanently mutated somatic cells . [ 29 ]
Beneficial mutations can improve reproductive success. [ 30 ] [ 31 ]
Four classes of mutations are (1) spontaneous mutations (molecular decay), (2) mutations due to error-prone replication bypass of naturally occurring DNA damage (also called error-prone translesion synthesis), (3) errors introduced during DNA repair, and (4) induced mutations caused by mutagens . Scientists may sometimes deliberately introduce mutations into cells or research organisms for the sake of scientific experimentation. [ 32 ]
One 2017 study claimed that 66% of cancer-causing mutations are random, 29% are due to the environment (the studied population spanned 69 countries), and 5% are inherited. [ 33 ]
Humans on average pass 60 new mutations to their children but fathers pass more mutations depending on their age with every year adding two new mutations to a child. [ 34 ]
Spontaneous mutations occur with non-zero probability even given a healthy, uncontaminated cell. Naturally occurring oxidative DNA damage is estimated to occur 10,000 times per cell per day in humans and 100,000 times per cell per day in rats . [ 35 ] Spontaneous mutations can be characterized by the specific change: [ 36 ]
There is increasing evidence that the majority of spontaneously arising mutations are due to error-prone replication ( translesion synthesis ) past DNA damage in the template strand. In mice , the majority of mutations are caused by translesion synthesis. [ 39 ] Likewise, in yeast , Kunz et al. [ 40 ] found that more than 60% of the spontaneous single base pair substitutions and deletions were caused by translesion synthesis.
Although naturally occurring double-strand breaks occur at a relatively low frequency in DNA, their repair often causes mutation. Non-homologous end joining (NHEJ) is a major pathway for repairing double-strand breaks. NHEJ involves removal of a few nucleotides to allow somewhat inaccurate alignment of the two ends for rejoining followed by addition of nucleotides to fill in gaps. As a consequence, NHEJ often introduces mutations. [ 41 ]
Induced mutations are alterations in the gene after it has come in contact with mutagens and environmental causes.
Induced mutations on the molecular level can be caused by:
Whereas in former times mutations were assumed to occur by chance, or induced by mutagens, molecular mechanisms of mutation have been discovered in bacteria and across the tree of life. As S. Rosenberg states, "These mechanisms reveal a picture of highly regulated mutagenesis, up-regulated temporally by stress responses and activated when cells/organisms are maladapted to their environments—when stressed—potentially accelerating adaptation." [ 45 ] Since they are self-induced mutagenic mechanisms that increase the adaptation rate of organisms, they have some times been named as adaptive mutagenesis mechanisms, and include the SOS response in bacteria, [ 46 ] ectopic intrachromosomal recombination [ 47 ] and other chromosomal events such as duplications. [ 45 ]
The sequence of a gene can be altered in a number of ways. [ 48 ] Gene mutations have varying effects on health depending on where they occur and whether they alter the function of essential proteins.
Mutations in the structure of genes can be classified into several types. [ citation needed ]
Large-scale mutations in chromosomal structure include:
Small-scale mutations affect a gene in one or a few nucleotides. (If only a single nucleotide is affected, they are called point mutations .) Small-scale mutations include:
The effect of a mutation on protein sequence depends in part on where in the genome it occurs, especially whether it is in a coding or non-coding region . Mutations in the non-coding regulatory sequences of a gene, such as promoters, enhancers, and silencers, can alter levels of gene expression, but are less likely to alter the protein sequence. Mutations within introns and in regions with no known biological function (e.g. pseudogenes , retrotransposons ) are generally neutral , having no effect on phenotype – though intron mutations could alter the protein product if they affect mRNA splicing.
Mutations that occur in coding regions of the genome are more likely to alter the protein product, and can be categorized by their effect on amino acid sequence:
A mutation becomes an effect on function mutation when the exactitude of functions between a mutated protein and its direct interactor undergoes change. The interactors can be other proteins, molecules, nucleic acids, etc. There are many mutations that fall under the category of by effect on function, but depending on the specificity of the change the mutations listed below will occur. [ 54 ]
In genetics , it is sometimes useful to classify mutations as either harmful or beneficial (or neutral ):
Large-scale quantitative mutagenesis screens , in which thousands of millions of mutations are tested, invariably find that a larger fraction of mutations has harmful effects but always returns a number of beneficial mutations as well. For instance, in a screen of all gene deletions in E. coli , 80% of mutations were negative, but 20% were positive, even though many had a very small effect on growth (depending on condition). [ 60 ] Gene deletions involve removal of whole genes, so that point mutations almost always have a much smaller effect. In a similar screen in Streptococcus pneumoniae , but this time with transposon insertions, 76% of insertion mutants were classified as neutral, 16% had a significantly reduced fitness, but 6% were advantageous. [ 61 ]
This classification is obviously relative and somewhat artificial: a harmful mutation can quickly turn into a beneficial mutations when conditions change. Also, there is a gradient from harmful/beneficial to neutral, as many mutations may have small and mostly neglectable effects but under certain conditions will become relevant. Also, many traits are determined by hundreds of genes (or loci), so that each locus has only a minor effect. For instance, human height is determined by hundreds of genetic variants ("mutations") but each of them has a very minor effect on height, [ 62 ] apart from the impact of nutrition . Height (or size) itself may be more or less beneficial as the huge range of sizes in animal or plant groups shows.
Attempts have been made to infer the distribution of fitness effects (DFE) using mutagenesis experiments and theoretical models applied to molecular sequence data. DFE, as used to determine the relative abundance of different types of mutations (i.e., strongly deleterious, nearly neutral or advantageous), is relevant to many evolutionary questions, such as the maintenance of genetic variation , [ 63 ] the rate of genomic decay , [ 64 ] the maintenance of outcrossing sexual reproduction as opposed to inbreeding [ 65 ] and the evolution of sex and genetic recombination . [ 66 ] DFE can also be tracked by tracking the skewness of the distribution of mutations with putatively severe effects as compared to the distribution of mutations with putatively mild or absent effect. [ 67 ] In summary, the DFE plays an important role in predicting evolutionary dynamics . [ 68 ] [ 69 ] A variety of approaches have been used to study the DFE, including theoretical, experimental and analytical methods.
One of the earliest theoretical studies of the distribution of fitness effects was done by Motoo Kimura , an influential theoretical population geneticist . His neutral theory of molecular evolution proposes that most novel mutations will be highly deleterious, with a small fraction being neutral. [ 27 ] [ 81 ] A later proposal by Hiroshi Akashi proposed a bimodal model for the DFE, with modes centered around highly deleterious and neutral mutations. [ 82 ] Both theories agree that the vast majority of novel mutations are neutral or deleterious and that advantageous mutations are rare, which has been supported by experimental results. One example is a study done on the DFE of random mutations in vesicular stomatitis virus . [ 70 ] Out of all mutations, 39.6% were lethal, 31.2% were non-lethal deleterious, and 27.1% were neutral. Another example comes from a high throughput mutagenesis experiment with yeast. [ 75 ] In this experiment it was shown that the overall DFE is bimodal, with a cluster of neutral mutations, and a broad distribution of deleterious mutations.
Though relatively few mutations are advantageous, those that are play an important role in evolutionary changes. [ 83 ] Like neutral mutations, weakly selected advantageous mutations can be lost due to random genetic drift, but strongly selected advantageous mutations are more likely to be fixed. Knowing the DFE of advantageous mutations may lead to increased ability to predict the evolutionary dynamics. Theoretical work on the DFE for advantageous mutations has been done by John H. Gillespie [ 84 ] and H. Allen Orr . [ 85 ] They proposed that the distribution for advantageous mutations should be exponential under a wide range of conditions, which, in general, has been supported by experimental studies, at least for strongly selected advantageous mutations. [ 86 ] [ 87 ] [ 88 ]
In general, it is accepted that the majority of mutations are neutral or deleterious, with advantageous mutations being rare; however, the proportion of types of mutations varies between species. This indicates two important points: first, the proportion of effectively neutral mutations is likely to vary between species, resulting from dependence on effective population size ; second, the average effect of deleterious mutations varies dramatically between species. [ 25 ] In addition, the DFE also differs between coding regions and noncoding regions , with the DFE of noncoding DNA containing more weakly selected mutations. [ 25 ]
In multicellular organisms with dedicated reproductive cells , mutations can be subdivided into germline mutations , which can be passed on to descendants through their reproductive cells, and somatic mutations (also called acquired mutations), [ 89 ] which involve cells outside the dedicated reproductive group and which are not usually transmitted to descendants.
Diploid organisms (e.g., humans) contain two copies of each gene—a paternal and a maternal allele. Based on the occurrence of mutation on each chromosome, we may classify mutations into three types. A wild type or homozygous non-mutated organism is one in which neither allele is mutated.
A germline mutation in the reproductive cells of an individual gives rise to a constitutional mutation in the offspring, that is, a mutation that is present in every cell. A constitutional mutation can also occur very soon after fertilization , or continue from a previous constitutional mutation in a parent. [ 91 ] A germline mutation can be passed down through subsequent generations of organisms.
The distinction between germline and somatic mutations is important in animals that have a dedicated germline to produce reproductive cells. However, it is of little value in understanding the effects of mutations in plants, which lack a dedicated germline. The distinction is also blurred in those animals that reproduce asexually through mechanisms such as budding , because the cells that give rise to the daughter organisms also give rise to that organism's germline.
A new germline mutation not inherited from either parent is called a de novo mutation .
A change in the genetic structure that is not inherited from a parent, and also not passed to offspring, is called a somatic mutation . [ 89 ] Somatic mutations are not inherited by an organism's offspring because they do not affect the germline . However, they are passed down to all the progeny of a mutated cell within the same organism during mitosis. A major section of an organism therefore might carry the same mutation. These types of mutations are usually prompted by environmental causes, such as ultraviolet radiation or any exposure to certain harmful chemicals, and can cause diseases including cancer. [ 92 ]
With plants, some somatic mutations can be propagated without the need for seed production, for example, by grafting and stem cuttings. These type of mutation have led to new types of fruits, such as the "Delicious" apple and the "Washington" navel orange . [ 93 ]
Human and mouse somatic cells have a mutation rate more than ten times higher than the germline mutation rate for both species; mice have a higher rate of both somatic and germline mutations per cell division than humans. The disparity in mutation rate between the germline and somatic tissues likely reflects the greater importance of genome maintenance in the germline than in the soma. [ 94 ]
In order to categorize a mutation as such, the "normal" sequence must be obtained from the DNA of a "normal" or "healthy" organism (as opposed to a "mutant" or "sick" one), it should be identified and reported; ideally, it should be made publicly available for a straightforward nucleotide-by-nucleotide comparison, and agreed upon by the scientific community or by a group of expert geneticists and biologists , who have the responsibility of establishing the standard or so-called "consensus" sequence. This step requires a tremendous scientific effort. Once the consensus sequence is known, the mutations in a genome can be pinpointed, described, and classified. The committee of the Human Genome Variation Society (HGVS) has developed the standard human sequence variant nomenclature, [ 101 ] which should be used by researchers and DNA diagnostic centers to generate unambiguous mutation descriptions. In principle, this nomenclature can also be used to describe mutations in other organisms. The nomenclature specifies the type of mutation and base or amino acid changes.
Mutation rates vary substantially across species, and the evolutionary forces that generally determine mutation are the subject of ongoing investigation.
In humans , the mutation rate is about 50–90 de novo mutations per genome per generation, that is, each human accumulates about 50–90 novel mutations that were not present in his or her parents. This number has been established by sequencing thousands of human trios, that is, two parents and at least one child. [ 102 ]
The genomes of RNA viruses are based on RNA rather than DNA. The RNA viral genome can be double-stranded (as in DNA) or single-stranded. In some of these viruses (such as the single-stranded human immunodeficiency virus ), replication occurs quickly, and there are no mechanisms to check the genome for accuracy. This error-prone process often results in mutations.
The rate of de novo mutations, whether germline or somatic, vary among organisms. [ 103 ] Individuals within the same species can even express varying rates of mutation. [ 104 ] Overall, rates of de novo mutations are low compared to those of inherited mutations, which categorizes them as rare forms of genetic variation . [ 105 ] Many observations of de novo mutation rates have associated higher rates of mutation correlated to paternal age. In sexually reproducing organisms, the comparatively higher frequency of cell divisions in the parental sperm donor germline drive conclusions that rates of de novo mutation can be tracked along a common basis. The frequency of error during the DNA replication process of gametogenesis , especially amplified in the rapid production of sperm cells, can promote more opportunities for de novo mutations to replicate unregulated by DNA repair machinery. [ 106 ] This claim combines the observed effects of increased probability for mutation in rapid spermatogenesis with short periods of time between cellular divisions that limit the efficiency of repair machinery. [ 107 ] Rates of de novo mutations that affect an organism during its development can also increase with certain environmental factors. For example, certain intensities of exposure to radioactive elements can inflict damage to an organism's genome, heightening rates of mutation. In humans, the appearance of skin cancer during one's lifetime is induced by overexposure to UV radiation that causes mutations in the cellular and skin genome. [ 108 ]
There is a widespread assumption that mutations are (entirely) "random" with respect to their consequences (in terms of probability). This was shown to be wrong as mutation frequency can vary across regions of the genome, with such DNA repair - and mutation-biases being associated with various factors. For instance, Monroe and colleagues demonstrated that—in the studied plant ( Arabidopsis thaliana )—more important genes mutate less frequently than less important ones. They demonstrated that mutation is "non-random in a way that benefits the plant". [ 109 ] [ 110 ] Additionally, previous experiments typically used to demonstrate mutations being random with respect to fitness (such as the Fluctuation Test and Replica plating ) have been shown to only support the weaker claim that those mutations are random with respect to external selective constraints, not fitness as a whole. [ 111 ]
Changes in DNA caused by mutation in a coding region of DNA can cause errors in protein sequence that may result in partially or completely non-functional proteins. Each cell, in order to function correctly, depends on thousands of proteins to function in the right places at the right times. When a mutation alters a protein that plays a critical role in the body, a medical condition can result. One study on the comparison of genes between different species of Drosophila suggests that if a mutation does change a protein, the mutation will most likely be harmful, with an estimated 70 per cent of amino acid polymorphisms having damaging effects, and the remainder being either neutral or weakly beneficial. [ 8 ] Some mutations alter a gene's DNA base sequence but do not change the protein made by the gene. Studies have shown that only 7% of point mutations in noncoding DNA of yeast are deleterious and 12% in coding DNA are deleterious. The rest of the mutations are either neutral or slightly beneficial. [ 112 ]
If a mutation is present in a germ cell , it can give rise to offspring that carries the mutation in all of its cells. This is the case in hereditary diseases. In particular, if there is a mutation in a DNA repair gene within a germ cell, humans carrying such germline mutations may have an increased risk of cancer. A list of 34 such germline mutations is given in the article DNA repair-deficiency disorder . An example of one is albinism , a mutation that occurs in the OCA1 or OCA2 gene. Individuals with this disorder are more prone to many types of cancers, other disorders and have impaired vision.
DNA damage can cause an error when the DNA is replicated, and this error of replication can cause a gene mutation that, in turn, could cause a genetic disorder. DNA damages are repaired by the DNA repair system of the cell. Each cell has a number of pathways through which enzymes recognize and repair damages in DNA. Because DNA can be damaged in many ways, the process of DNA repair is an important way in which the body protects itself from disease. Once DNA damage has given rise to a mutation, the mutation cannot be repaired.
On the other hand, a mutation may occur in a somatic cell of an organism. Such mutations will be present in all descendants of this cell within the same organism. The accumulation of certain mutations over generations of somatic cells is part of cause of malignant transformation , from normal cell to cancer cell. [ 113 ]
Cells with heterozygous loss-of-function mutations (one good copy of gene and one mutated copy) may function normally with the unmutated copy until the good copy has been spontaneously somatically mutated. This kind of mutation happens often in living organisms, but it is difficult to measure the rate. Measuring this rate is important in predicting the rate at which people may develop cancer. [ 114 ]
Point mutations may arise from spontaneous mutations that occur during DNA replication. The rate of mutation may be increased by mutagens. Mutagens can be physical, such as radiation from UV rays , X-rays or extreme heat, or chemical (molecules that misplace base pairs or disrupt the helical shape of DNA). Mutagens associated with cancers are often studied to learn about cancer and its prevention.
Although mutations that cause changes in protein sequences can be harmful to an organism, on occasions the effect may be positive in a given environment. In this case, the mutation may enable the mutant organism to withstand particular environmental stresses better than wild-type organisms, or reproduce more quickly. In these cases a mutation will tend to become more common in a population through natural selection. That said, the same mutation can be beneficial in one condition and disadvantageous in another condition. Examples include the following:
HIV resistance : a specific 32 base pair deletion in human CCR5 ( CCR5-Δ32 ) confers HIV resistance to homozygotes and delays AIDS onset in heterozygotes. [ 115 ] One possible explanation of the etiology of the relatively high frequency of CCR5-Δ32 in the European population is that it conferred resistance to the bubonic plague in mid-14th century Europe . People with this mutation were more likely to survive infection; thus its frequency in the population increased. [ 116 ] This theory could explain why this mutation is not found in Southern Africa , which remained untouched by bubonic plague. A newer theory suggests that the selective pressure on the CCR5 Delta 32 mutation was caused by smallpox instead of the bubonic plague. [ 117 ]
Malaria resistance : An example of a harmful mutation is sickle-cell disease , a blood disorder in which the body produces an abnormal type of the oxygen-carrying substance haemoglobin in the red blood cells . One-third of all indigenous inhabitants of Sub-Saharan Africa carry the allele, because, in areas where malaria is common, there is a survival value in carrying only a single sickle-cell allele ( sickle cell trait ). [ 118 ] Those with only one of the two alleles of the sickle-cell disease are more resistant to malaria, since the infestation of the malaria Plasmodium is halted by the sickling of the cells that it infests.
Antibiotic resistance : Practically all bacteria develop antibiotic resistance when exposed to antibiotics. In fact, bacterial populations already have such mutations that get selected under antibiotic selection. [ 119 ] Obviously, such mutations are only beneficial for the bacteria but not for those infected.
Lactase persistence . A mutation allowed humans to express the enzyme lactase after they are naturally weaned from breast milk, allowing adults to digest lactose , which is likely one of the most beneficial mutations in recent human evolution . [ 120 ]
By introducing novel genetic qualities to a population of organisms, de novo mutations play a critical role in the combined forces of evolutionary change. However, the weight of genetic diversity generated by mutational change is often considered a generally "weak" evolutionary force. [ 104 ] Although the random emergence of mutations alone provides the basis for genetic variation across all organic life, this force must be taken in consideration alongside all evolutionary forces at play. Spontaneous de novo mutations as cataclysmic events of speciation depend on factors introduced by natural selection , genetic flow, and genetic drift . For example, smaller populations with heavy mutational input (high rates of mutation) are prone to increases of genetic variation which lead to speciation in future generations. In contrast, larger populations tend to see lesser effects of newly introduced mutated traits. In these conditions, selective forces diminish the frequency of mutated alleles, which are most often deleterious, over time. [ 121 ]
Compensated pathogenic deviations refer to amino acid residues in a protein sequence that are pathogenic in one species but are wild type residues in the functionally equivalent protein in another species. Although the amino acid residue is pathogenic in the first species, it is not so in the second species because its pathogenicity is compensated by one or more amino acid substitutions in the second species. The compensatory mutation can occur in the same protein or in another protein with which it interacts. [ 122 ]
It is critical to understand the effects of compensatory mutations in the context of fixed deleterious mutations due to the population fitness decreasing because of fixation. [ 123 ] Effective population size refers to a population that is reproducing. [ 124 ] An increase in this population size has been correlated with a decreased rate of genetic diversity. [ 124 ] The position of a population relative to the critical effect population size is essential to determine the effect deleterious alleles will have on fitness. [ 123 ] If the population is below the critical effective size fitness will decrease drastically, however if the population is above the critical effect size, fitness can increase regardless of deleterious mutations due to compensatory alleles. [ 123 ]
As the function of a RNA molecule is dependent on its structure, [ 125 ] the structure of RNA molecules is evolutionarily conserved. Therefore, any mutation that alters the stable structure of RNA molecules must be compensated by other compensatory mutations. In the context of RNA, the sequence of the RNA can be considered as ' genotype' and the structure of the RNA can be considered as its 'phenotype'. Since RNAs have relatively simpler composition than proteins, the structure of RNA molecules can be computationally predicted with high degree of accuracy. Because of this convenience, compensatory mutations have been studied in computational simulations using RNA folding algorithms. [ 126 ] [ 127 ]
Compensatory mutations can be explained by the genetic phenomenon epistasis whereby the phenotypic effect of one mutation is dependent upon mutation(s) at other loci. While epistasis was originally conceived in the context of interaction between different genes, intragenic epistasis has also been studied recently. [ 128 ] Existence of compensated pathogenic deviations can be explained by 'sign epistasis', in which the effects of a deleterious mutation can be compensated by the presence of an epistatic mutation in another loci. For a given protein, a deleterious mutation (D) and a compensatory mutation (C) can be considered, where C can be in the same protein as D or in a different interacting protein depending on the context. The fitness effect of C itself could be neutral or somewhat deleterious such that it can still exist in the population, and the effect of D is deleterious to the extent that it cannot exist in the population. However, when C and D co-occur together, the combined fitness effect becomes neutral or positive. [ 122 ] Thus, compensatory mutations can bring novelty to proteins by forging new pathways of protein evolution : it allows individuals to travel from one fitness peak to another through the valleys of lower fitness. [ 128 ]
DePristo et al. 2005 outlined two models to explain the dynamics of compensatory pathogenic deviations (CPD). [ 129 ] In the first hypothesis P is a pathogenic amino acid mutation that and C is a neutral compensatory mutation. [ 129 ] Under these conditions, if the pathogenic mutation arises after a compensatory mutation, then P can become fixed in the population. [ 129 ] The second model of CPDs states that P and C are both deleterious mutations resulting in fitness valleys when mutations occur simultaneously. [ 129 ] Using publicly available, Ferrer-Costa et al. 2007 obtained compensatory mutations and human pathogenic mutation datasets that were characterized to determine what causes CPDs. [ 130 ] Results indicate that the structural constraints and the location in protein structure determine whether compensated mutations will occur. [ 130 ]
Lunzer et al. [ 131 ] tested the outcome of swapping divergent amino acids between two orthologous proteins of isopropymalate dehydrogenase (IMDH). They substituted 168 amino acids in Escherichia coli IMDH that are wild type residues in IMDH Pseudomonas aeruginosa . They found that over one third of these substitutions compromised IMDH enzymatic activity in the Escherichia coli genetic background. This demonstrated that identical amino acid states can result in different phenotypic states depending on the genetic background. Corrigan et al. 2011 demonstrated how Staphylococcus aureus was able to grow normally without the presence of lipoteichoic acid due to compensatory mutations. [ 132 ] Whole genome sequencing results revealed that when Cyclic-di-AMP phosphodiesterase (GdpP) was disrupted in this bacterium, it compensated for the disappearance of the cell wall polymer, resulting in normal cell growth. [ 132 ]
Research has shown that bacteria can gain drug resistance through compensatory mutations that do not impede or having little effect on fitness. [ 133 ] Previous research from Gagneux et al. 2006 has found that laboratory grown Mycobacterium tuberculosis strains with rifampicin resistance have reduced fitness, however drug resistant clinical strains of this pathogenic bacteria do not have reduced fitness. [ 134 ] Comas et al. 2012 used whole genome comparisons between clinical strains and lab derived mutants to determine the role and contribution of compensatory mutations in drug resistance to rifampicin. [ 133 ] Genome analysis reveal rifampicin resistant strains have a mutation in rpoA and rpoC. [ 133 ] A similar study investigated the bacterial fitness associated with compensatory mutations in rifampin resistant Escherichia coli . [ 135 ] Results obtained from this study demonstrate that drug resistance is linked to bacterial fitness as higher fitness costs are linked to greater transcription errors. [ 135 ]
Gong et al. [ 136 ] collected obtained genotype data of influenza nucleoprotein from different timelines and temporally ordered them according to their time of origin. Then they isolated 39 amino acid substitutions that occurred in different timelines and substituted them in a genetic background that approximated the ancestral genotype. They found that 3 of the 39 substitutions significantly reduced the fitness of the ancestral background. Compensatory mutations are new mutations that arise and have a positive or neutral impact on a populations fitness. [ 137 ] Previous research has shown that populations have can compensate detrimental mutations. [ 122 ] [ 137 ] [ 138 ] Burch and Chao tested Fisher's geometric model of adaptive evolution by testing whether bacteriophage φ6 evolves by small steps. [ 139 ] Their results showed that bacteriophage φ6 fitness declined rapidly and recovered in small steps . [ 139 ] Viral nucleoproteins have been shown to avoid cytotoxic T lymphocytes (CTLs) through arginine-to glycine substitutions. [ 140 ] This substitution mutations impacts the fitness of viral nucleoproteins, however compensatory co-mutations impede fitness declines and aid the virus to avoid recognition from CTLs. [ 140 ] Mutations can have three different effects; mutations can have deleterious effects, some increase fitness through compensatory mutations, and lastly mutations can be counterbalancing resulting in compensatory neutral mutations. [ 141 ] [ 135 ] [ 134 ]
In the human genome, the frequency and characteristics of de novo mutations have been studied as important contextual factors to our evolution. Compared to the human reference genome, a typical human genome varies at approximately 4.1 to 5.0 million loci, and the majority of this genetic diversity is shared by nearly 0.5% of the population. [ 142 ] The typical human genome also contains 40,000 to 200,000 rare variants observed in less than 0.5% of the population that can only have occurred from at least one de novo germline mutation in the history of human evolution. [ 143 ] De novo mutations have also been researched as playing a crucial role in the persistence of genetic disease in humans. With recents advancements in next-generation sequencing (NGS), all types of de novo mutations within the genome can be directly studied, the detection of which provides a magnitude of insight toward the causes of both rare and common genetic disorders. Currently, the best estimate of the average human germline SNV mutation rate is 1.18 x 10^-8, with an approximate ~78 novel mutations per generation. The ability to conduct whole genome sequencing of parents and offspring allows for the comparison of mutation rates between generations, narrowing down the origin possibilities of certain genetic disorders. [ 144 ]
÷⊈⊂⊃⊅ | https://en.wikipedia.org/wiki/Mutation |
A mutation accumulation (MA) experiment is a genetic experiment in which isolated and inbred lines of organisms (so-called MA lines) are maintained such that the effect of natural selection is minimized, with the aim of quantitatively estimating the rates at which spontaneous mutations (mutations not caused by exogenous mutagens ) occur in the studied organism. Spontaneous mutation rates may be directly estimated using molecular techniques such as DNA sequencing , or indirectly estimated using phenotypic assays (observing how an organism’s phenotype changes as mutations accumulate). [ 1 ]
The earliest mutation accumulation experiments were performed by American geneticist Hermann Joseph Muller in the 1920s, using Drosophila melanogaster . [ 1 ]
All MA lines used in a MA experiment are bred from a single common ancestor , and are often propagated by single-progeny descent, where a single offspring is randomly selected to sire the next generation of organisms. [ 2 ] This serves to prevent the loss of mutant alleles through sexual reproduction . Notably, single-progeny descent is only possible if the organism being studied is capable of asexual reproduction or self-fertilization .
A control line is maintained parallel to the MA lines and under the same conditions, except organisms are allowed to reproduce sexually (they are not constrained to single-progeny descent). The assumption underlying this procedure is that the larger, sexually reproducing population of the control line will cause all spontaneous mutations to be ‘weeded out’ by sexual reproduction. [ 1 ] Mutations that arise in MA lines are heterozygous at first, and can become fixed or lost at random in subsequent generations. [ 1 ] Thus, the control line will be relatively free of mutations, and can be compared with the MA lines to assess the impact of the mutations that have accumulated therein. Both the MA lines and the control line are maintained under relaxed natural selection, to minimize the strain that natural selection places on mutant organisms (which may have reduced fitness). [ 3 ] For example, the organisms in a MA experiment may be kept in the ideal environmental conditions and provided with an excess of nutrients.
Mutation accumulation experiments are time-consuming and labor intensive, as a result of the requirement that multiple MA lines be raised parallel to one another for multiple generations, under carefully maintained environmental conditions.
Phenotypic assays may be performed on the organisms within each MA line, to determine the extent to which the accumulated mutations have affected the organism’s various phenotypic traits. The measured changes in phenotype across generations can be used to indirectly estimate the mutation rate for that organism. [ 1 ] With the advent of whole-genome sequencing, the mutation rate of an MA line can be directly estimated by sequencing the MA line and comparing it with sequence data for the control line (i.e., the wild-type organism). [ 4 ]
Historically, most MA experiments have estimated mutation rates by using a phenotypic assay to measure the change in the trait value of a phenotype across generations. [ 1 ] However, the validity of this approach relies on several assumptions: Since the average mutation is thought to be slightly deleterious, [ 5 ] it is assumed that accumulated mutations will cause an organism to become gradually less viable (i.e., that the effect of mutations on the organism’s viability will be unidirectional). It is also assumed that the control line will be free of mutations: since the organisms within the control line are able to freely sexually reproduce, it is thought that most mutations that arise within individuals will be relatively quickly lost during sexual reproduction. [ 1 ]
Furthermore, since the organisms in an MA experiment are raised under relaxed natural selection, it is assumed that all mutations that arise have arisen randomly, and become fixed or lost at random, in the absence of any selective pressure exerted by the environment. [ 1 ]
A mutation accumulation experiment conducted by Ruth Shaw and colleagues serves as a good example of a typical MA experiment: the group sought to measure the effects of spontaneous mutations on the reproductive traits of Arabidopsis thaliana . A.thaliana is an ideal candidate for a MA experiment because it is capable of self-fertilization, has a relatively short life cycle (of about 10 weeks), and is a well-studied model organism in plant biology and genetics. Shaw and colleagues established 120 lines of A.thaliana , and advanced each line 17 generations by single-progeny descent: each generation was propagated by a single individual randomly selected from a number of self-fertilized seeds sown. The reproductive traits measured as part of the phenotypic assay included seed number per fruit, fruit number, and reproductive mass (the total mass of fruits and seeds from a single plant). The group found that each trait diverged significantly between MA lines, suggesting that mutations had accumulated in some lines. [ 6 ]
Single-progeny descent is only possible if the organism being studied is capable of asexual reproduction or self-fertilization. In cases where an organism is only capable of sexual reproduction (such as Drosophila melanogaster, which was the species used in many early MA experiments), [ 1 ] organisms with balancer chromosomes are used.
In MA experiments involving an obligate sexually reproducing species such as Drosophila, mutations are accumulated on only one of a pair of homologous chromosomes. The other homologous chromosome is a modified so-called balancer chromosome. Balancer chromosomes contain a sizable inversion relative to their homologue, which serves to prevent recombination of the balancer chromosome with its homologue during meiosis. Additionally, the balancer chromosome may contain a number of mutations. While the exact mutation(s) may vary, it is important that they achieve two things. First, the mutation(s) must create a physically visible phenotype in heterozygous organisms. This allows organisms that carry a balancer and an unmodified chromosome (organisms that are ideal for the MA experiment) to be easily identified. Second, the mutation(s) must also be homozygous lethal , so that any organism that inherits two balancer chromosomes (i.e. an organism useless to the MA experiment) will not survive. [ 7 ]
Using this system, a proportion of the offspring created by sexual reproduction will inherit a balancer chromosome and its homologue. This homologue is passed down across generations without having its mutations disrupted by recombination during sexual reproduction, allowing it to properly accumulate mutations.
MA experiments allow researchers to study the rates and properties of new mutations. Since mutation is the ultimate source of genetic diversity in all living organisms, researchers are interested in knowing how often mutations arise, and in understanding the phenotypic impacts on newly-arisen mutations, in order to better understand the patterns underlying adaptation and evolution. [ 1 ]
Mutation accumulation experiments are an important means by which to estimate mutational parameters. As the name suggests, these parameters define the rate at which different types of mutations occur in a given organism. Their estimation is important because mutations are the ultimate source of genetic variation as well as being involved in the pathogenesis of many common diseases. [ 8 ] As such, understanding how often they occur, as well as what consequences they are likely to carry when they do occur can yield significant insight into these issues. The mutation rate in the nuclear genome varies quite significantly across species, while that of the mitochondrial genome is much more consistent, with most estimates of this latter parameter in unicellular and multicellular eukaryotes ranging from 0.76 to 1.6 x 10 −7 mutations per site per generation. [ 9 ] Since these parameters have been ascertained for only a small number of species because of how labor intensive this approach can be, a significant amount of this type of work has been done in various model organisms .
For example, in the nuclear genome of Drosophila melanogaster , one study placed the rate of single-nucleotide mutation at 3.5 × 10 −9 mutations per site per generation, [ 10 ] while another study obtained a value of 5.8 × 10 −9 mutations per site per generation for the same parameter. [ 11 ] Estimates of the D. melanogaster mitochondrial genome mutation rate are generally ~10 times higher than that of the nuclear genome, with one estimate being 6.2 x 10 −8 mutations per site per generation. [ 12 ] The rate of occurrence for deleterious mutations per generation (Ud) can be obtained by multiplying the average number of mutations per generation by the proportion of mutations which are expected to be deleterious within a given species. However, it can also be estimated by way of fitness assays using MA lines of known genotype. [ 11 ] In Drosophila melanogaster, one study placed the value of this parameter at 1.2 deleterious mutations per diploid genome per generation, [ 11 ] which matches closely the average value of this parameter within this species across all studies on the subject conducted as of 1999. [ 13 ] However, the putative Ud values obtained by way of similar mutation accumulation-based studies have varied significantly, with some estimates being as low as 0.02 deleterious mutations per diploid genome per generation, a value not much higher than the putative lethal mutation rate of 0.01 mutations per generation. [ 13 ] Uncharacteristically low values such as this are usually obtained in studies that classify mutations as either deleterious or not by screening for quantifiable decreases in viability. This is because these studies are thought to overlook the vast majority of deleterious mutations for which the overall effect on viability is too small in magnitude to be observed by way of such assays. [ 13 ] [ 11 ] Higher Ud values (>1) that are more in line with current scientific consensus regarding the estimation of this parameter in D. melanogaster suggest that selection against these deleterious mutations may play a significant role in shaping patterns of genetic variation in the genome, as well as in maintaining selection for recombination and sexual reproduction. [ 11 ]
For Caenorhabditis elegans , a nematode that is one of the most commonly used model organisms in molecular and developmental biology research, one estimate of the nuclear genome mutation rate is 2.1 x 10 −8 mutations per site per generation. [ 14 ] The value of Ud within the species was in 1997 directly estimated to be 0.0026 deleterious mutations per generation, which is two orders of magnitude smaller than previous indirect estimates. [ 15 ] A newer estimate based on laboratory fitness assays of MA lines placed this parameter at 0.015 deleterious mutations per generation. [ 14 ] However, as previously mentioned, such assays may overlook mutations which produce negative consequences of modest magnitude. These are thought to represent the vast majority of deleterious mutations, and possibly even the majority of all mutations within this species. [ 14 ] Authors have also noted that insertions are the predominant type of mutation observed in MA studies using C. elegans. [ 14 ] The mitochondrial mutation rate in this species has been estimated at 1.05 x 10 −7 mutations per site per generation. [ 9 ]
In the yeast, Saccharomyces cerevisiae, the nuclear genomic rate of single nucleotide mutations was estimated to be 1.67 ± 0.04 × 10 −10 per site per generation, while the rate of small insertions/deletions was estimated to be 5.03 ± 0.99 × 10 −12 per site per generation. [ 16 ] As far as aneuploidy and other large copy number variant events in this organism, the rate of whole-chromosome duplication was found to be 9.7 ± 1.8 × 10 −5 events per diploid genome per generation, while the rate of chromosome loss was estimated at 0.7 ± 0.04 × 10 −5 events per diploid genome per generation. [ 16 ] | https://en.wikipedia.org/wiki/Mutation_accumulation_experiments |
The mutation accumulation theory of aging was first proposed by Peter Medawar in 1952 as an evolutionary explanation for biological aging and the associated decline in fitness that accompanies it. [ 1 ] Medawar used the term ' senescence ' to refer to this process. The theory explains that, in the case where harmful mutations are only expressed later in life, when reproduction has ceased and future survival is increasingly unlikely, then these mutations are likely to be unknowingly passed on to future generations. [ 2 ] In this situation the force of natural selection will be weak, and so insufficient to consistently eliminate these mutations. Medawar posited that over time these mutations would accumulate due to genetic drift and lead to the evolution of what is now referred to as aging.
Despite Charles Darwin 's completion of his theory of biological evolution in the 19th century, the modern logical framework for evolutionary theories of aging wouldn't emerge until almost a century later. Though August Weismann did propose his theory of programmed death, it was met with criticism and never gained mainstream attention. [ 3 ] It wasn't until 1930 that Ronald Fisher first noted the conceptual insight which prompted the development of modern aging theories. This concept, namely that the force of natural selection on an individual decreases with age, was analysed further by J. B. S. Haldane , who suggested it as an explanation for the relatively high prevalence of Huntington's disease despite the autosomal dominant nature of the mutation. Specifically, as Huntington's only presents after the age of 30, the force of natural selection against it would have been relatively low in pre-modern societies. [ 2 ] It was based on the ideas of Fisher and Haldane that Peter Medawar was able to work out the first complete model explaining why aging occurs, which he presented in a lecture in 1951 and then published in 1952 [ 1 ]
Amongst almost all populations, the likelihood that an individual will reproduce is related directly to their age. [ 1 ] Starting at 0 at birth, the probability increases to its maximum in young adulthood once sexual maturity has been reached, before gradually decreasing with age. This decrease is caused by the increasing likelihood of death due to external pressures such as predation or illness, as well as the internal pressures inherent to organisms that experience senescence. In such cases deleterious mutations which are expressed early on are strongly selected against due to their major impact on the number of offspring produced by that individual. [ 3 ] Mutations that present later in life, by contrast, are relatively unaffected by selective pressure, as their carriers have already passed on their genes, assuming they survive long enough for the mutation to be expressed at all. The result, as predicted by Medawar, is that deleterious late-life mutations will accumulate and result in the evolution of aging as it is known colloquially. [ 2 ] This concept is portrayed graphically by Medawar through the concept of a " selection shadow ". The shaded region represents the 'shadow' of time during which selective pressure has no effect. [ 4 ] Mutations that are expressed within this selection shadow will remain as long as reproductive probability within that age range remains low. [ citation needed ]
In populations where extrinsic mortality is low, the drop in reproductive probability after maturity is less severe than in other cases. The mutation accumulation theory therefore predicts that such populations would evolve delayed senescence. [ 5 ] One such example of this scenario can be seen when comparing birds to organisms of equivalent size. It has been suggested that their ability to fly, and therefore lower relative risk of predation, is the cause of their longer than expected life span. [ 6 ] The implication that flight, and therefore lower predation, increases lifespan is further born out by the fact that bats live on average 3 times longer than similarly sized mammals with comparable metabolic rates. [ 7 ] Providing further evidence, insect populations are known to experience very high rates of extrinsic mortality, and as such would be expected to experience rapid senescence and short life spans. The exception to this rule, however, is found in the longevity of eusocial insect queens. As expected when applying the mutation accumulation theory, established queens are at almost no risk of predation or other forms of extrinsic mortality, and consequently age far more slowly than others of their species. [ 8 ]
In the interest of finding specific evidence for the mutation accumulation theory, separate from that which also supports the similar antagonistic pleiotropy hypothesis, an experiment was conducted involving the breeding of successive generations of Drosophila Melanogaster . Genetic models predict that, in the case of mutation accumulation, elements of fitness, such as reproductive success and survival, will show age-related increases in dominance , homozygous genetic variance and additive variance. Inbreeding depression will also increase with age. This is because these variables are proportional to the equilibrium frequencies of deleterious alleles, which are expected to increase with age under mutation accumulation but not under the antagonistic pleiotropy hypothesis. This was tested experimentally by measuring age specific reproductive success in 100 different genotypes of Drosophila Melanogaster, with findings ultimately supporting the mutation accumulation theory of aging. [ 9 ]
Under most assumptions, the mutation accumulation theory predicts that mortality rates will reach close to 100% shortly after reaching post-reproductive age. [ 10 ] Experimental populations of Drosophila Melanogaster, and other organisms, however, exhibit age-specific mortality rates that plateau well before reaching 100%, making mutation accumulation alone an insufficient explanation. It is suggested instead that mutation accumulation is only one factor among many, which together form the cause of aging. In particular, the mutation accumulation theory, the antagonistic pleiotropy hypothesis and the disposable soma theory of aging are all believed to contribute in some way to senescence. [ 11 ] | https://en.wikipedia.org/wiki/Mutation_accumulation_theory |
Mutation breeding , sometimes referred to as " variation breeding ", is the process of exposing seeds to chemicals , radiation , or enzymes [ 1 ] [ 2 ] in order to generate mutants with desirable traits to be bred with other cultivars . Plants created using mutagenesis are sometimes called mutagenic plants or mutagenic seeds.
From 1930 to 2014 more than 3200 mutagenic plant varieties were released [ 3 ] [ 4 ] that have been derived either as direct mutants (70%) or from their progeny (30%). [ 5 ] Crop plants account for 75% of released mutagenic species with the remaining 25% ornamentals or decorative plants. [ 6 ] However, although the FAO / IAEA reported in 2014 that over 1,000 mutant varieties of major staple crops were being grown worldwide, [ 3 ] it is unclear how many of these varieties are currently used in agriculture or horticulture around the world, as these seeds are not always identified or labeled as having a mutagenic provenance. [ 7 ]
According to garden historian Paige Johnson:
After WWII, there was a concerted effort to find 'peaceful' uses for atomic energy . One of the ideas was to bombard plants with radiation and produce lots of mutations, some of which, it was hoped, would lead to plants that bore more heavily or were disease or cold-resistant or just had unusual colors. The experiments were mostly conducted in giant gamma gardens on the grounds of national laboratories in the US but also in Europe and countries of the [then-]USSR. [ 8 ]
There are different kinds of mutagenic breeding such as using chemical mutagens like ethyl methanesulfonate and dimethyl sulfate , radiation or transposons to generate mutants . Mutation breeding is commonly used to produce traits in crops such as larger seeds, new colors, or sweeter fruits, that either cannot be found in nature or have been lost during evolution. [ 9 ]
Exposing plants to radiation is sometimes called radiation breeding and is a sub class of mutagenic breeding. Radiation breeding was discovered in the 1920s when Lewis Stadler of the University of Missouri used X-rays on maize and barley. In the case of barley, the resulting plants were white, yellow, pale yellow and some had white stripes. [ 10 ] In 1928, Stadler first published his findings on radiation-induced mutagenesis in plants. [ 11 ] During the period 1930–2024, radiation-induced mutant varieties were developed primarily using gamma rays (64%) and X-rays (22%), [ 12 ] [ 13 ] [ 14 ] [ 6 ] : 187 although other sources of radiation such as microwaves or high-energy photons and high-energy electrons can be applied. [ 15 ] [ 16 ]
Radiation breeding may take place in atomic gardens ; [ 11 ] and seeds have been sent into orbit in order to expose them to more cosmic radiation. [ 17 ]
Ultraviolet has been used, for example to produce knockouts for the investigation of virulence mechanisms of plant pathogens . [ 18 ]
The ability of plants to develop and thrive is dependent on conditions such as microgravity and cosmic radiation in space. China has been experimenting with this theory by sending seeds into space, testing to see if space flights will cause genetic mutations. Since 1987, China has cultivated 66 mutant varieties from space through their space-breeding program. Chromosomal aberrations greatly increased when seeds were sent into aerospace compared to their earth-bound counterparts. The effect of space flight on seeds depends on their species and variety. For example, space-bred wheat saw a large growth in seed germination in compared to its Earth-bound control, but space-bred rice had no visible advantage compared to its control. For the varieties that were positively mutated by space flight, their growth potential exceeded that of not only their Earth-grown counterparts, but also their irradiated counterparts on Earth. Compared to traditional mutagenic techniques, space-bred mutations have greater efficacy in that they experience positive effects on their first generation of mutation, whereas irradiated crops often see no advantageous mutations in their first generations. Though multiple experiments have shown the positive effects of space flight on seed mutation, there is no clear connection as to what aspect of aerospace has produced such advantageous mutations. There is much speculation around cosmic radiation being the source of chromosomal aberrations, but so far, there has been no concrete evidence of such connection. Though China's space-breeding program has been shown to be very successful, the program requires a large budget and technological support that many other countries are either unwilling or unable to provide, meaning this program is unfeasible outside of China. Due to such restraints, scientists have been trying to replicate space condition on Earth in order to promote the same expedient space-born mutations on Earth. One such replication is a magnetic field -free space (MF), which produces an area with a weaker magnetic field than that of Earth. MF treatment produced mutagenic results, and has been used to cultivate new mutant varieties of rice and alfalfa. Other replications of space conditions include irradiation of seeds by a heavy 7 Li-ion beam or mixed high-energy particles. [ 19 ] These space-bred varieties are already being introduced to the public. In 2011, during the National Lotus Flowers Exhibition in China, a mutant lotus, called the "Outer Space Sun", was shown at the flower show. [ 20 ]
Ion beams mutate DNA by deleting multiple bases from the genome. Compared to traditional sources of radiation, like gamma rays and X-rays, ion beams have been shown to cause more severe breaks in DNA that are more difficult to weave back together, causing the change in DNA to be more drastic than changes caused by traditional irradiation. Ion beams change DNA in a manner that makes it look vastly different than its original makeup, more so than when traditional irradiation techniques are used. Most experimentation, using ion beam technology, has been conducted in Japan. Notable facilities using this technology are TIARA of the Japan Atomic Energy Agency , RIKEN Accelerator Research Facility, and various other Japanese institutions. During the process of ion beam radiation, seeds are wedged between two kapton films and irradiated for roughly two minutes. Mutation frequencies are notably higher for ion beam radiation compared to electron radiation, and the mutation spectrum is broader for ion beam radiation compared to gamma ray radiation. The broader mutation spectrum was revealed through the largely varied amount of flower phenotypes produced by ion beams. Flowers mutated by the ion beams exhibited a variety of colors, patterns, and shapes. Through ion beam radiation, new varieties of plants have been cultivated. These plants had the characteristics of being ultraviolet light-B resistant, disease resistant, and chlorophyll -deficient. Ion beam technology has been used in the discovery of new genes responsible for the creation of more robust plants, but its most prevalent use is commercially for producing new flower phenotypes, like striped chrysanthemums . [ 21 ]
Gamma radiation is used on mature rice pollen to produce parent plants used for crossing. The mutated traits in the parent plants are able to be inherited by their offspring plants. Because rice pollen has a very short lifespan, researchers had to blast gamma rays at cultured spikes from rice plants. Through experimentation, it was revealed that there was a greater variety of mutation in irradiated pollen rather than irradiated dry seeds. Pollen treated with 46Gy of gamma radiation showed an increase in grain size overall and other useful variations. Typically, the length of each grain was longer after the crossing of irradiated parent rice plants. The rice progeny also exhibited a less chalky visage, improving on the appearance of the parent rice plants. This technique was used to develop two new rice cultivars , Jiaohezaozhan and Jiafuzhan, in China. Along with facilitating the creation of these two rice cultivars, the irradiation of mature rice pollen has produced roughly two hundred mutant rice lines. Each of these lines produce rice grains of both a higher quality and larger size. The mutations produced by this technique vary with each generation, meaning further breeding of these mutated plants could produce new mutations. Traditionally , gamma radiation is used on solely adult plants, and not on pollen. The irradiation of mature pollen allows mutant plants to grow without being in direct contact with gamma radiation. This discovery is in contrast to what was previously believed about gamma radiation: that it could only elicit mutations in plants and not pollen. [ 22 ]
High rates of chromosome aberrations resulting from ionizing radiation and the accompanied detrimental effects made researchers look for alternate sources for inducing mutations. As a result, an array of chemical mutagens has been discovered. The most widely used chemical mutagens are alkylating agents . Ethyl methanesulfonate (EMS) is the most popular because of its effectiveness and ease of handling, especially its detoxification through hydrolysis for disposal. Nitroso compounds are the other alkylating agents widely used, but they are light-sensitive and more precautions need to be taken because of their higher volatility. EMS has become a commonly used mutagen for developing large numbers of mutants for screening such as in developing TILLING populations. [ 23 ] Although many chemicals are mutagens, only few have been used in practical breeding as the doses need to be optimised and also because the effectiveness is not high in plants for many. [ citation needed ]
Interest in the use of bacterial restriction endonucleases (RE) – for example Fok1 [ 2 ] and CRISPR/ Cas9 [ 1 ] [ 2 ] – to study double-stranded breaks in plant DNA began in the mid-nineties. These breaks in DNA, otherwise known as DSBs, were found to be the source of much chromosomal damage in eukaryotes, causing mutations in plant varieties. REs induce a result on plant DNA similar to that of ionizing radiation or radiomimetic chemicals. Blunt ended breaks in the DNA, unlike sticky ended breaks, were found to produce more variations in chromosomal damage, making them the more useful type of break for mutation breeding. While the connection of REs to chromosomal aberrations is mostly limited to research on mammalian DNA, success in mammalian studies caused scientists to conduct more studies of RE-induced chromosomal and DNA damage on barley genomes . Due to restriction endonucleases' ability to facilitate damage in chromosomes and DNA, REs have the capability of being used as a new method of mutagenesis to promote the proliferation of mutated plant varieties. [ 24 ] [ 1 ] [ 2 ]
In the debate over genetically modified foods , the use of transgenic processes is often compared and contrasted with mutagenic processes. [ 25 ] While the abundance and variation of transgenic organisms in human food systems, and their effect on agricultural biodiversity, ecosystem health and human health is somewhat well documented, mutagenic plants and their role on human food systems is less well known, with one journalist writing "Though poorly known, radiation breeding has produced thousands of useful mutants and a sizable fraction of the world's crops...including varieties of rice, wheat, barley, pears, peas, cotton, peppermint, sunflowers, peanuts, grapefruit, sesame, bananas, cassava and sorghum." [ 10 ]
In Canada crops generated by mutation breeding face the same regulations and testing as crops obtained by genetic engineering. [ a ] [ 26 ] [ 27 ] [ 28 ] Mutagenic varieties tend to be made freely available for plant breeding, in contrast to many commercial plant varieties or germplasm that increasingly have restrictions on their use [ 6 ] : 187 such as terms of use , patents and proposed genetic user restriction technologies and other intellectual property regimes and modes of enforcement.
The European Union considers crops produced by mutagenesis technically subject to the GM directive, but the traditional (chemical and radiation) [ 29 ] methods are exempt from regulation. [ 30 ]
Unlike genetically modified crops , which typically involve the insertion of one or two target genes, plants developed via mutagenic processes with random, multiple and unspecific genetic changes [ 31 ] have been discussed as a concern [ 32 ] but are not prohibited by any nation's organic standards . Reports from the US National Academy of Sciences state that there is no scientific justification for regulating genetic engineered crops while not doing so for mutation breeding crops. [ 7 ]
Several organic food and seed companies promote and sell certified organic products that were developed using both chemical and nuclear mutagenesis. [ 33 ] Several certified organic brands, whose companies support strict labeling or outright bans on GMO-crops, market their use of branded wheat and other varietal strains which were derived from mutagenic processes without any reference to this genetic manipulation. [ 33 ] These organic products range from mutagenic barley and wheat ingredient used in organic beers [ 34 ] to mutagenic varieties of grapefruits sold directly to consumers as organic. [ 35 ]
The Codex Alimentarius guidelines for organic food production accepts mutation breeding. The IFOAM - Organics International does not accept the use of induced mutagenesis. [ 36 ]
As of 2011 the percentage of all mutagenic varieties released globally, by country, were: [ 6 ] : 187 [ 37 ]
Notable varieties per country include:
Czech Republic
In 2014, it was reported that 17 rice mutant varieties, 10 soybean, two maize and one chrysanthemum mutant varieties had been officially released to Vietnamese farmers. 15% of rice and 50% of soybean was produced from mutant varieties. [ 52 ] | https://en.wikipedia.org/wiki/Mutation_breeding |
Mutation frequency and mutation rates are highly correlated to each other. Mutation frequencies test are cost effective in laboratories [ 1 ] however; these two concepts provide vital information in reference to accounting for the emergence of mutations on any given germ line . [ 2 ] [ 3 ]
There are several test utilized in measuring the chances of mutation frequency and rates occurring in a particular gene pool. Some of the test are as follows:
Mutation frequency and rates provide vital information about how often a mutation may be expressed in a particular genetic group or sex. [ 6 ] Yoon et., 2009 suggested that as sperm donors ages increased the sperm mutation frequencies increased. This reveals the positive correlation in how males are most likely to contribute to genetic disorders that reside within X-linked recessive chromosome. [ 7 ] There are additional factors affecting mutation frequency and rates involving evolutionary influences. Since, organisms may pass mutations to their offspring incorporating and analyzing the mutation frequency and rates of a particular species may provide a means to adequately comprehend its longevity [ 5 ]
The time course of spontaneous mutation frequency from middle to late adulthood was measured in four different tissues of the mouse. [ 8 ] Mutation frequencies in the cerebellum (90% neurons ) and male germ cells were lower than in liver and adipose tissue. Furthermore, the mutation frequencies increased with age in liver and adipose tissue , whereas in the cerebellum and male germ cells the mutation frequency remained constant [ 8 ]
Dietary restricted rodents live longer and are generally healthier than their ad libitum fed counterparts. No changes were observed in the spontaneous chromosomal mutation frequency of dietary restricted mice (aged 6 and 12 months) compared to ad libitum fed control mice. [ 9 ] Thus dietary restriction appears to have no appreciable effect on spontaneous mutation in chromosomal DNA, and the increased longevity of dietary restricted mice apparently is not attributable to reduced chromosomal mutation frequency. | https://en.wikipedia.org/wiki/Mutation_frequency |
In genetics , the mutation rate is the frequency of new mutations in a single gene , nucleotide sequence , or organism over time. [ 2 ] Mutation rates are not constant and are not limited to a single type of mutation; there are many different types of mutations. Mutation rates are given for specific classes of mutations. Point mutations are a class of mutations which are changes to a single base. Missense , nonsense , and synonymous mutations are three subtypes of point mutations. The rate of these types of substitutions can be further subdivided into a mutation spectrum which describes the influence of the genetic context on the mutation rate. [ 3 ]
There are several natural units of time for each of these rates, with rates being characterized either as mutations per base pair per cell division, per gene per generation, or per genome per generation. The mutation rate of an organism is an evolved characteristic and is strongly influenced by the genetics of each organism, in addition to strong influence from the environment. The upper and lower limits to which mutation rates can evolve is the subject of ongoing investigation. However, the mutation rate does vary over the genome . [ 4 ]
When the mutation rate in humans increases certain health risks can occur, for example, cancer and other hereditary diseases. Having knowledge of mutation rates is vital to understanding the future of cancers and many hereditary diseases. [ 5 ]
Different genetic variants within a species are referred to as alleles, therefore a new mutation can create a new allele. In population genetics , each allele is characterized by a selection coefficient, which measures the expected change in an allele's frequency over time. The selection coefficient can either be negative, corresponding to an expected decrease, positive, corresponding to an expected increase, or zero, corresponding to no expected change. The distribution of fitness effects of new mutations is an important parameter in population genetics and has been the subject of extensive investigation. [ 6 ] Although measurements of this distribution have been inconsistent in the past, it is now generally thought that the majority of mutations are mildly deleterious, that many have little effect on an organism's fitness, and that a few can be favorable.
Because of natural selection , unfavorable mutations will typically be eliminated from a population while favorable changes are generally kept for the next generation, and neutral changes accumulate at the rate they are created by mutations. This process happens by reproduction. In a particular generation the 'best fit' survive with higher probability, passing their genes to their offspring. The sign of the change in this probability defines mutations to be beneficial, neutral or harmful to organisms. [ 7 ]
An organism's mutation rates can be measured by a number of techniques.
One way to measure the mutation rate is by the fluctuation test, also known as the Luria–Delbrück experiment . This experiment demonstrated that bacteria mutations occur in the absence of selection instead of the presence of selection. [ 8 ]
This is very important to mutation rates because it proves experimentally mutations can occur without selection being a component—in fact, mutation and selection are completely distinct evolutionary forces . Different DNA sequences can have different propensities to mutation (see below) and may not occur randomly. [ 9 ]
The most commonly measured class of mutations are substitutions, because they are relatively easy to measure with standard analyses of DNA sequence data. However substitutions have a substantially different rate of mutation (10 −8 to 10 −9 per generation for most cellular organisms) than other classes of mutation, which are frequently much higher (~10 −3 per generation for satellite DNA expansion/contraction [ 10 ] ).
Many sites in an organism's genome may admit mutations with small fitness effects. These sites are typically called neutral sites. Theoretically mutations under no selection become fixed between organisms at precisely the mutation rate. Fixed synonymous mutations, i.e. synonymous substitutions , are changes to the sequence of a gene that do not change the protein produced by that gene. They are often used as estimates of that mutation rate, despite the fact that some synonymous mutations have fitness effects. As an example, mutation rates have been directly inferred from the whole genome sequences of experimentally evolved replicate lines of Escherichia coli B. [ 11 ]
A particularly labor-intensive way of characterizing the mutation rate is the mutation accumulation line.
Mutation accumulation lines have been used to characterize mutation rates with the Bateman-Mukai Method and direct sequencing of well-studied experimental organisms ranging from intestinal bacteria ( E. coli ), roundworms ( C. elegans ), yeast ( S. cerevisiae ), fruit flies ( D. melanogaster ), and small ephemeral plants ( A. thaliana ). [ 12 ]
Mutation rates differ between species and even between different regions of the genome of a single species. Mutation rates can also differ even between genotypes of the same species; for example, bacteria have been observed to evolve hypermutability as they adapt to new selective conditions. [ 13 ] These different rates of nucleotide substitution are measured in substitutions ( fixed mutations ) per base pair per generation. For example, mutations in intergenic, or non-coding, DNA tend to accumulate at a faster rate than mutations in DNA that is actively in use in the organism ( gene expression ). That is not necessarily due to a higher mutation rate, but to lower levels of purifying selection . A region which mutates at predictable rate is a candidate for use as a molecular clock .
If the rate of neutral mutations in a sequence is assumed to be constant (clock-like), and if most differences between species are neutral rather than adaptive, then the number of differences between two different species can be used to estimate how long ago two species diverged (see molecular clock ). In fact, the mutation rate of an organism may change in response to environmental stress. For example, UV light damages DNA, which may result in error prone attempts by the cell to perform DNA repair .
The human mutation rate is higher in the male germ line (sperm) than the female (egg cells), but estimates of the exact rate have varied by an order of magnitude or more. This means that a human genome accumulates around 64 new mutations per generation because each full generation involves a number of cell divisions to generate gametes. [ 14 ] Human mitochondrial DNA has been estimated to have mutation rates of ~3× or ~2.7×10 −5 per base per 20 year generation (depending on the method of estimation); [ 15 ] these rates are considered to be significantly higher than rates of human genomic mutation at ~2.5×10 −8 per base per generation. [ 16 ] Using data available from whole genome sequencing, the human genome mutation rate is similarly estimated to be ~1.1×10 −8 per site per generation. [ 17 ]
The rate for other forms of mutation also differs greatly from point mutations . An individual microsatellite locus often has a mutation rate on the order of 10 −4 , though this can differ greatly with length. [ 18 ]
Some sequences of DNA may be more susceptible to mutation. For example, stretches of DNA in human sperm which lack methylation are more prone to mutation. [ 19 ]
In general, the mutation rate in unicellular eukaryotes (and bacteria ) is roughly 0.003 mutations per genome per cell generation. [ 14 ] However, some species, especially the ciliate of the genus Paramecium have an unusually low mutation rate. For instance, Paramecium tetraurelia has a base-substitution mutation rate of ~2 × 10 −11 per site per cell division. This is the lowest mutation rate observed in nature so far, being about 75× lower than in other eukaryotes with a similar genome size, and even 10× lower than in most prokaryotes. The low mutation rate in Paramecium has been explained by its transcriptionally silent germ-line nucleus , consistent with the hypothesis that replication fidelity is higher at lower gene expression levels. [ 20 ]
The highest per base pair per generation mutation rates are found in viruses, which can have either RNA or DNA genomes. DNA viruses have mutation rates between 10 −6 to 10 −8 mutations per base per generation, and RNA viruses have mutation rates between 10 −3 to 10 −5 per base per generation. [ 14 ]
A mutation spectrum is a distribution of rates or frequencies for the mutations relevant in some context, based on the recognition that rates of occurrence are not all the same. In any context, the mutation spectrum reflects the details of mutagenesis and is affected by conditions such as the presence of chemical mutagens or genetic backgrounds with mutator alleles or damaged DNA repair systems. The most fundamental and expansive concept of a mutation spectrum is the distribution of rates for all individual mutations that might happen in a genome (e.g., [ 21 ] ). From this full de novo spectrum, for instance, one may calculate the relative rate of mutation in coding vs non-coding regions. Typically the concept of a spectrum of mutation rates is simplified to cover broad classes such as transitions and transversions (figure), i.e., different mutational conversions across the genome are aggregated into classes, and there is an aggregate rate for each class.
In many contexts, a mutation spectrum is defined as the observed frequencies of mutations identified by some selection criterion, e.g., the distribution of mutations associated clinically with a particular type of cancer, [ 22 ] or the distribution of adaptive changes in a particular context such as antibiotic resistance (e.g., [ 23 ] ).
Whereas the spectrum of de novo mutation rates reflects mutagenesis alone, this kind of spectrum may also reflect effects of selection and ascertainment biases (e.g., both kinds of spectrum are used in [ 24 ] ).
The theory on the evolution of mutation rates identifies three principal forces involved: the generation of more deleterious mutations with higher mutation, the generation of more advantageous mutations with higher mutation, and the metabolic costs and reduced replication rates that are required to prevent mutations. Different conclusions are reached based on the relative importance attributed to each force. The optimal mutation rate of organisms may be determined by a trade-off between costs of a high mutation rate, [ 25 ] such as deleterious mutations, and the metabolic costs of maintaining systems to reduce the mutation rate (such as increasing the expression of DNA repair enzymes. [ 26 ] or, as reviewed by Bernstein et al. [ 27 ] having increased energy use for repair, coding for additional gene products and/or having slower replication). Secondly, higher mutation rates increase the rate of beneficial mutations, and evolution may prevent a lowering of the mutation rate in order to maintain optimal rates of adaptation. [ 28 ] [ 29 ] As such, hypermutation enables some cells to rapidly adapt to changing conditions in order to avoid the entire population from becoming extinct. [ 30 ] Finally, natural selection may fail to optimize the mutation rate because of the relatively minor benefits of lowering the mutation rate, and thus the observed mutation rate is the product of neutral processes. [ 31 ] [ 32 ]
Studies have shown that treating RNA viruses such as poliovirus with ribavirin produce results consistent with the idea that the viruses mutated too frequently to maintain the integrity of the information in their genomes. [ 33 ] This is termed error catastrophe .
The characteristically high mutation rate of HIV (Human Immunodeficiency Virus) of 3 x 10 −5 per base and generation, coupled with its short replication cycle leads to a high antigen variability, allowing it to evade the immune system. [ 34 ] | https://en.wikipedia.org/wiki/Mutation_rate |
Mutatis mutandis is a Medieval Latin phrase meaning "with things changed that should be changed" or "once the necessary changes have been made", literally: having been changed, going to be changed. [ 1 ] [ 2 ] [ 3 ] It continues to be seen as a foreign-origin phrase (and thus, unnaturalized, meaning not integrated as part of native vocabulary) in English and is therefore usually italicized in writing. It is used in many countries to acknowledge that a comparison being made requires certain obvious alterations, which are left unstated. It is not to be confused with the similar ceteris paribus , which excludes any changes other than those explicitly mentioned. Mutatis mutandis is still used in law , economics , mathematics , linguistics and philosophy . In particular, in logic , it is encountered when discussing counterfactuals , as a shorthand for all the initial and derived changes which have been previously discussed.
The phrase mutatis mutandis —now sometimes written mūtātīs mūtandīs to show vowel length —does not appear in surviving classical literature . It is Medieval Latin [ 4 ] in origin and the Feet of fines , kept at The National Archives (United Kingdom) , contains its first use in England on January 20, 1270, at Pedes Finium, 54 Hen. III, Salop. [ 5 ]
Both words are participles of the Latin verb mutare ('to move; to change; to exchange'). Mutatus, -a, -um is its perfect passive participle ('changed; having been changed'). Mutandus, -a, -um is its gerundive , which functions both as a future passive participle ('to be changed; going to be changed') and as a verbal adjective or noun expressing necessity ('needing to be changed; things needing to be changed'). The phrase is an ablative absolute , using the ablative case to show that the clause is grammatically independent ('absolute' literally meaning 'dissolved' or 'separated') from the rest of the sentence.
Mutatis mutandis was first borrowed into English in the 16th century, but continues to be italicized as a foreign phrase. [ 4 ] Although many similar adverbial phrases are treated as part of the sentence, mutatis mutandis is usually set apart by commas or in some other fashion. The nearest English equivalent to an ablative absolute is the nominative absolute , so that a literal translation will either use the nominative case ("things changed which are to be changed") or a preposition ("with the things to be changed having been changed"). More often, the idea is expressed more tersely ("with the necessary changes") or using subordinating conjunctions and a dependent clause ("once the necessary adjustments are made").
The phrase has a technical meaning in mathematics where it is sometimes used to signal that a proof can be more generally applied to other certain cases after making some, presumably obvious, changes. It serves a similar purpose to the more common phrase, " without loss of generality " [ 6 ] (WLOG).
The legal use of the term is somewhat specialized. As glossed by Shira Scheindlin , judge for the Southern District of New York , for a 1998 case: "This Latin phrase simply means that the necessary changes in details, such as names and places, will be made but everything else will remain the same." [ 7 ] In the wake of the Plain English movements , some countries attempted to replace their law codes' legal Latin with English equivalents.
The phrase appears in other European languages as well. A passage of Marcel Proust 's À la recherche du temps perdu includes "...j'ai le fils d'un de mes amis qui, mutatis mutandis, est comme vous..." ("A friend of mine has a son whose case, mutatis mutandis , is very much like yours.") The German Ministry of Justice , similar to the Plain English advocates above, now eschews its use. Their official English translation of the Civil Code now reads: [ 8 ]
"Section 27 (Appointment of and management by the board). ...(3) The management by the board is governed by the provisions on mandate in sections 664 to 670 with the necessary modifications. "
The phrase is used as the motto of Xavier's School for Gifted Youngsters from the X-Men Marvel Comics . [ 9 ] [ 10 ] | https://en.wikipedia.org/wiki/Mutatis_mutandis |
Mutatochrome (5,8-epoxy-β-carotene) is a carotenoid . It is the predominant carotenoid in the cap of the bolete mushroom Boletus luridus . [ 1 ]
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Mutatochrome |
Mutual Aid: A Factor of Evolution is a 1902 collection of anthropological essays by Russian naturalist and anarchist philosopher Peter Kropotkin . The essays, initially published in the English periodical The Nineteenth Century between 1890 and 1896, [ 1 ] explore the role of mutually beneficial cooperation and reciprocity (or " mutual aid ") in the animal kingdom and human societies both past and present. It is an argument against theories of social Darwinism that emphasize competition and survival of the fittest , and against the romantic depictions by writers such as Jean-Jacques Rousseau , who thought that cooperation was motivated by universal love. Instead, Kropotkin argues that mutual aid has pragmatic advantages for the survival of human and animal communities and, along with the conscience , has been promoted through natural selection.
Mutual Aid is considered a fundamental text in anarchist communism . [ 2 ] It presents a scientific basis for communism as an alternative to the historical materialism of the Marxists . Kropotkin considers the importance of mutual aid for prosperity and survival in the animal kingdom, in indigenous and early European societies, in the medieval free cities (especially through the guilds ), and in the late 19th century village, labor movement, and impoverished people. He criticizes the State for destroying historically important mutual aid institutions, particularly through the imposition of private property .
Many biologists [ 3 ] [ 4 ] (including Stephen Jay Gould , one of the most influential evolutionary biologists of his generation) also consider it an important catalyst in the scientific study of cooperation. [ 5 ]
Daniel P. Todes, in his account of Russian naturalism in the 19th century, concludes that Kropotkin's work "cannot be dismissed as the idiosyncratic product of an anarchist dabbling in biology" and that his views "were but one expression of a broad current in Russian evolutionary thought that pre-dated, indeed encouraged, his work on the subject and was by no means confined to leftist thinkers." [ 6 ]
Kropotkin emphasizes the distinction between competitive struggle between individual organisms over limited resources and collective struggle between organisms and the environment. He drew from his firsthand observations of Siberia and Northeast Asia , where he saw that animal populations were limited not by food sources, which were abundant, but rather by harsh weather. For example, predatory birds may compete by stealing food from one another while migratory birds cooperate in order to survive harsh winters by traveling long distances. He did not deny the competitive form of struggle but argued that the cooperative counterpart has been under-emphasized: "There is an immense amount of warfare and extermination going on amidst various species; there is, at the same time, as much, or perhaps even more, of mutual support, mutual aid, and mutual defense... Sociability is as much a law of nature as mutual struggle." [ 7 ]
As a description of biology, Kropotkin's perspective is consistent with contemporary understanding. Stephen Jay Gould admired Kropotkin's observations, noting that cooperation, if it increases individual survival, is not ruled out by natural selection , and is in fact encouraged. [ 3 ] Kropotkin's ideas anticipate the now recognized importance of mutualism (a beneficial relationship between two different species) and altruism (when one member of a species aids another) in biology. Examples of altruism in animals include kin selection and reciprocal altruism . Douglas H. Boucher places Kropotkin's book as a precursor to the development of the biological theory of altruism. [ 4 ] | https://en.wikipedia.org/wiki/Mutual_Aid:_A_Factor_of_Evolution |
In logic and probability theory , two events (or propositions) are mutually exclusive or disjoint if they cannot both occur at the same time. A clear example is the set of outcomes of a single coin toss, which can result in either heads or tails, but not both.
In the coin-tossing example, both outcomes are, in theory, collectively exhaustive , which means that at least one of the outcomes must happen, so these two possibilities together exhaust all the possibilities. [ 1 ] However, not all mutually exclusive events are collectively exhaustive. For example, the outcomes 1 and 4 of a single roll of a six-sided die are mutually exclusive (both cannot happen at the same time) but not collectively exhaustive (there are other possible outcomes; 2,3,5,6).
In logic , two propositions ϕ {\displaystyle \phi } and ψ {\displaystyle \psi } are mutually exclusive if it is not logically possible for them to be true at the same time; that is, ¬ ( ϕ ∧ ψ ) {\displaystyle \lnot (\phi \land \psi )} is a tautology. To say that more than two propositions are mutually exclusive, depending on the context, means either 1. " ¬ ( ϕ 1 ∧ ϕ 2 ) ∧ ¬ ( ϕ 1 ∧ ϕ 3 ) ∧ ¬ ( ϕ 2 ∧ ϕ 3 ) {\displaystyle \lnot (\phi _{1}\land \phi _{2})\land \lnot (\phi _{1}\land \phi _{3})\land \lnot (\phi _{2}\land \phi _{3})} is a tautology" (it is not logically possible for more than one proposition to be true) or 2. " ¬ ( ϕ 1 ∧ ϕ 2 ∧ ϕ 3 ) {\displaystyle \lnot (\phi _{1}\land \phi _{2}\land \phi _{3})} is a tautology" (it is not logically possible for all propositions to be true at the same time). The term pairwise mutually exclusive always means the former.
In probability theory , events E 1 , E 2 , ..., E n are said to be mutually exclusive if the occurrence of any one of them implies the non-occurrence of the remaining n − 1 events. Therefore, two mutually exclusive events cannot both occur. Formally said, X {\displaystyle X} is a set of mutually exclusive events if and only if given any E i , E j ∈ X {\displaystyle E_{i},E_{j}\in X} , if E i ≠ E j {\displaystyle E_{i}\neq E_{j}} then E i ∩ E j = ∅ {\displaystyle E_{i}\cap E_{j}=\varnothing } . As a consequence, mutually exclusive events have the property: P ( A ∩ B ) = 0 {\displaystyle P(A\cap B)=0} . [ 2 ]
For example, in a standard 52-card deck with two colors it is impossible to draw a card that is both red and a club because clubs are always black. If just one card is drawn from the deck, either a red card (heart or diamond) or a black card (club or spade) will be drawn. When A and B are mutually exclusive, P( A ∪ B ) = P( A ) + P( B ) . [ 3 ] To find the probability of drawing a red card or a club, for example, add together the probability of drawing a red card and the probability of drawing a club. In a standard 52-card deck, there are twenty-six red cards and thirteen clubs: 26/52 + 13/52 = 39/52 or 3/4.
One would have to draw at least two cards in order to draw both a red card and a club. The probability of doing so in two draws depends on whether the first card drawn was replaced before the second drawing since without replacement there is one fewer card after the first card was drawn. The probabilities of the individual events (red, and club) are multiplied rather than added. The probability of drawing a red and a club in two drawings without replacement is then 26/52 × 13/51 × 2 = 676/2652 , or 13/51. With replacement, the probability would be 26/52 × 13/52 × 2 = 676/2704 , or 13/52.
In probability theory, the word or allows for the possibility of both events happening. The probability of one or both events occurring is denoted P( A ∪ B ) and in general, it equals P( A ) + P( B ) – P( A ∩ B ). [ 3 ] Therefore, in the case of drawing a red card or a king, drawing any of a red king, a red non-king, or a black king is considered a success. In a standard 52-card deck, there are twenty-six red cards and four kings, two of which are red, so the probability of drawing a red or a king is 26/52 + 4/52 – 2/52 = 28/52.
Events are collectively exhaustive if all the possibilities for outcomes are exhausted by those possible events, so at least one of those outcomes must occur. The probability that at least one of the events will occur is equal to one. [ 4 ] For example, there are theoretically only two possibilities for flipping a coin. Flipping a head and flipping a tail are collectively exhaustive events, and there is a probability of one of flipping either a head or a tail. Events can be both mutually exclusive and collectively exhaustive. [ 4 ] In the case of flipping a coin, flipping a head and flipping a tail are also mutually exclusive events. Both outcomes cannot occur for a single trial (i.e., when a coin is flipped only once). The probability of flipping a head and the probability of flipping a tail can be added to yield a probability of 1: 1/2 + 1/2 =1. [ 5 ]
In statistics and regression analysis , an independent variable that can take on only two possible values is called a dummy variable . For example, it may take on the value 0 if an observation is of a white subject or 1 if the observation is of a black subject. The two possible categories associated with the two possible values are mutually exclusive, so that no observation falls into more than one category, and the categories are exhaustive, so that every observation falls into some category. Sometimes there are three or more possible categories, which are pairwise mutually exclusive and are collectively exhaustive — for example, under 18 years of age, 18 to 64 years of age, and age 65 or above. In this case a set of dummy variables is constructed, each dummy variable having two mutually exclusive and jointly exhaustive categories — in this example, one dummy variable (called D 1 ) would equal 1 if age is less than 18, and would equal 0 otherwise ; a second dummy variable (called D 2 ) would equal 1 if age is in the range 18–64, and 0 otherwise. In this set-up, the dummy variable pairs (D 1 , D 2 ) can have the values (1,0) (under 18), (0,1) (between 18 and 64), or (0,0) (65 or older) (but not (1,1), which would nonsensically imply that an observed subject is both under 18 and between 18 and 64). Then the dummy variables can be included as independent (explanatory) variables in a regression. The number of dummy variables is always one less than the number of categories: with the two categories black and white there is a single dummy variable to distinguish them, while with the three age categories two dummy variables are needed to distinguish them.
Such qualitative data can also be used for dependent variables . For example, a researcher might want to predict whether someone gets arrested or not, using family income or race, as explanatory variables. Here the variable to be explained is a dummy variable that equals 0 if the observed subject does not get arrested and equals 1 if the subject does get arrested. In such a situation, ordinary least squares (the basic regression technique) is widely seen as inadequate; instead probit regression or logistic regression is used. Further, sometimes there are three or more categories for the dependent variable — for example, no charges, charges, and death sentences. In this case, the multinomial probit or multinomial logit technique is used. | https://en.wikipedia.org/wiki/Mutual_exclusivity |
In portfolio theory , a mutual fund separation theorem , mutual fund theorem , or separation theorem is a theorem stating that, under certain conditions, any investor's optimal portfolio can be constructed by holding each of certain mutual funds in appropriate ratios, where the number of mutual funds is smaller than the number of individual assets in the portfolio. Here a mutual fund refers to any specified benchmark portfolio of the available assets. There are two advantages of having a mutual fund theorem. First, if the relevant conditions are met, it may be easier (or lower in transactions costs) for an investor to purchase a smaller number of mutual funds than to purchase a larger number of assets individually. Second, from a theoretical and empirical standpoint, if it can be assumed that the relevant conditions are indeed satisfied, then implications for the functioning of asset markets can be derived and tested.
Portfolios can be analyzed in a mean-variance framework, with every investor holding the portfolio with the lowest possible return variance consistent with that investor's chosen level of expected return (called a minimum-variance portfolio ), if the returns on the assets are jointly elliptically distributed , including the special case in which they are jointly normally distributed . [ 1 ] [ 2 ] Under mean-variance analysis, it can be shown [ 3 ] that every minimum-variance portfolio given a particular expected return (that is, every efficient portfolio) can be formed as a combination of any two efficient portfolios. If the investor's optimal portfolio has an expected return that is between the expected returns on two efficient benchmark portfolios, then that investor's portfolio can be characterized as consisting of positive quantities of the two benchmark portfolios.
To see two-fund separation in a context in which no risk-free asset is available, using matrix algebra , let σ 2 {\displaystyle \sigma ^{2}} be the variance of the portfolio return, let μ {\displaystyle \mu } be the level of expected return on the portfolio that portfolio return variance is to be minimized contingent upon, let r {\displaystyle r} be the vector of expected returns on the available assets, let X {\displaystyle X} be the vector of amounts to be placed in the available assets, let W {\displaystyle W} be the amount of wealth that is to be allocated in the portfolio, and let 1 {\displaystyle 1} be a vector of ones. Then the problem of minimizing the portfolio return variance subject to a given level of expected portfolio return can be stated as
where the superscript T {\displaystyle ^{T}} denotes the transpose of a matrix. The portfolio return variance in the objective function can be written as σ 2 = X T V X , {\displaystyle \sigma ^{2}=X^{T}VX,} where V {\displaystyle V} is the positive definite covariance matrix of the individual assets' returns. The Lagrangian for this constrained optimization problem (whose second-order conditions can be shown to be satisfied) is
with Lagrange multipliers λ {\displaystyle \lambda } and η {\displaystyle \eta } . This can be solved for the optimal vector X {\displaystyle X} of asset quantities by equating to zero the derivatives with respect to X {\displaystyle X} , λ {\displaystyle \lambda } , and η {\displaystyle \eta } , provisionally solving the first-order condition for X {\displaystyle X} in terms of λ {\displaystyle \lambda } and η {\displaystyle \eta } , substituting into the other first-order conditions, solving for λ {\displaystyle \lambda } and η {\displaystyle \eta } in terms of the model parameters, and substituting back into the provisional solution for X {\displaystyle X} . The result is
where
For simplicity this can be written more compactly as
where α {\displaystyle \alpha } and β {\displaystyle \beta } are parameter vectors based on the underlying model parameters. Now consider two benchmark efficient portfolios constructed at benchmark expected returns μ 1 {\displaystyle \mu _{1}} and μ 2 {\displaystyle \mu _{2}} and thus given by
and
The optimal portfolio at arbitrary μ 3 {\displaystyle \mu _{3}} can then be written as a weighted average of X 1 o p t {\displaystyle X_{1}^{\mathrm {opt} }} and X 2 o p t {\displaystyle X_{2}^{\mathrm {opt} }} as follows:
This equation proves the two-fund separation theorem for mean-variance analysis. For a geometric interpretation, see the Markowitz bullet .
If a risk-free asset is available, then again a two-fund separation theorem applies; but in this case one of the "funds" can be chosen to be a very simple fund containing only the risk-free asset, and the other fund can be chosen to be one which contains zero holdings of the risk-free asset. (With the risk-free asset referred to as "money", this form of the theorem is referred to as the monetary separation theorem .) Thus mean-variance efficient portfolios can be formed simply as a combination of holdings of the risk-free asset and holdings of a particular efficient fund that contains only risky assets. The derivation above does not apply, however, since with a risk-free asset the above covariance matrix of all asset returns, V {\displaystyle V} , would have one row and one column of zeroes and thus would not be invertible. Instead, the problem can be set up as
where r f {\displaystyle r_{f}} is the known return on the risk-free asset, X {\displaystyle X} is now the vector of quantities to be held in the risky assets, and r {\displaystyle r} is the vector of expected returns on the risky assets. The left side of the last equation is the expected return on the portfolio, since ( W − X T 1 ) {\displaystyle (W-X^{T}1)} is the quantity held in the risk-free asset, thus incorporating the asset adding-up constraint that in the earlier problem required the inclusion of a separate Lagrangian constraint. The objective function can be written as σ 2 = X T V X {\displaystyle \sigma ^{2}=X^{T}VX} , where now V {\displaystyle V} is the covariance matrix of the risky assets only. This optimization problem can be shown to yield the optimal vector of risky asset holdings
Of course this equals a zero vector if μ = W r f {\displaystyle \mu =Wr_{f}} , the risk-free portfolio's return, in which case all wealth is held in the risk-free asset. It can be shown that the portfolio with exactly zero holdings of the risk-free asset occurs at μ = W r T V − 1 ( r − 1 r f ) 1 T V − 1 ( r − 1 r f ) {\displaystyle \mu ={\tfrac {Wr^{T}V^{-1}(r-1r_{f})}{1^{T}V^{-1}(r-1r_{f})}}} and is given by
It can also be shown (analogously to the demonstration in the above two-mutual-fund case) that every portfolio's risky asset vector (that is, X o p t {\displaystyle X^{\mathrm {opt} }} for every value of μ {\displaystyle \mu } ) can be formed as a weighted combination of the latter vector and the zero vector. For a geometric interpretation, see the efficient frontier with no risk-free asset .
If investors have hyperbolic absolute risk aversion (HARA) (including the power utility function , logarithmic function and the exponential utility function ), separation theorems can be obtained without the use of mean-variance analysis. For example, David Cass and Joseph Stiglitz [ 4 ] showed in 1970 that two-fund monetary separation applies if all investors have HARA utility with the same exponent as each other. [ 5 ] : ch.4
More recently, in the dynamic portfolio optimization model of Çanakoğlu and Özekici, [ 6 ] the investor's level of initial wealth (the distinguishing feature of investors) does not affect the optimal composition of the risky part of the portfolio. A similar result is given by Schmedders. [ 7 ] | https://en.wikipedia.org/wiki/Mutual_fund_separation_theorem |
Mutual knowledge in game theory is information known by all participatory agents. However, unlike common knowledge , a related topic, mutual knowledge does not require that all agents are aware that this knowledge is mutual. [ 1 ] All common knowledge is mutual knowledge, but not all mutual knowledge is common knowledge. Mutual knowledge can arise accidentally, due to a failure to design the game properly, so all players independently discover this mutual knowledge, or deliberately, due to the expected course of the game.
The difference is crucial in a co-operation game. For example, in the game depicted below, with a random event determining the payoff matrix, both players, being fully rational , presume the more likely option to have occurred. However, suppose each player separately finds out that the random number, which was created privately and which determines the payoff matrix, was 1. However, neither are told that the other player is also aware of this.
Player A presumes Player B is not aware the random number is 1. They then observe that if the random number is 2-100, the best choice for B is always b1. So they choose a2, which would give them the best possible payoff in this matrix. Symmetrically, Player B presumes Player A expects the random numbers 2-100 and chooses a1, so B chooses b2. As a result, the players had a final result of (1, a2, b2), with a payoff of 1 for both - the lowest possible payoff (total or individual).
Now suppose that it is common knowledge that the random number is 1 - that is, both players are also aware that the other player knows the random number is 1, in addition to knowing this themselves. Given this, the best choice for A is a1, with an average of 6.5, and the best choice for B is b1, with an average of 6.5 also, giving an outcome of (1, a1, b1) with a payoff of 8 for both - the highest possible total payoff.
Common knowledge tends to lead to co-operative behavior more often than purely mutual knowledge, which can often lead to anti-cooperative behavior as shown in the example above, as the participants are aware that the knowledge is mutual knowledge and can all decide on behalf of this knowledge. [ 2 ] This works best in a symmetric game, like the left matrix below.
This game theory article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Mutual_knowledge |
Mutual knowledge is a fundamental concept about information in game theory , (epistemic) logic , and epistemology . An event is mutual knowledge if all agents know that the event occurred. [ 1 ] : 73 However, mutual knowledge by itself implies nothing about what agents know about other agents' knowledge: i.e. it is possible that an event is mutual knowledge but that each agent is unaware that the other agents know it has occurred. [ 2 ] Common knowledge is a related but stronger notion; any event that is common knowledge is also mutual knowledge.
The philosopher Stephen Schiffer , in his book Meaning , developed a notion he called "mutual knowledge" which functions quite similarly to David K. Lewis 's "common knowledge". [ 3 ]
Communications (verbal or non-verbal ) can turn mutual knowledge into common knowledge. For example, in the Muddy Children Puzzle with two children (Alice and Bob, G = { a , b } {\displaystyle G=\{a,b\}} ), if they both have muddy face (viz. M a ∧ M b {\displaystyle M_{a}\land M_{b}} ), both of them know that there is at least one muddy face. Written formally, let p = [ ∃ x ∈ G ( M x ) ] {\displaystyle p=[\exists x\!\in \!G(M_{x})]} , and then we have K a p ∧ K b p {\displaystyle K_{a}p\land K_{b}p} . However, neither of them know that the other child knows ( ( ¬ K a K b p ) ∧ ( ¬ K b K a p ) {\displaystyle (\neg K_{a}K_{b}p)\land (\neg K_{b}K_{a}p)} ), which makes p = [ ∃ x ∈ G ( M x ) ] {\displaystyle p=[\exists x\!\in \!G(M_{x})]} mutual knowledge . Now suppose if Alice tells Bob that she knows p {\displaystyle p} (so that K a p {\displaystyle K_{a}p} becomes common knowledge , i.e. C G K a p {\displaystyle C_{G}K_{a}p} ), and then Bob tells Alice that he knows p {\displaystyle p} as well (so that K b p {\displaystyle K_{b}p} becomes common knowledge , i.e. C G K b p {\displaystyle C_{G}K_{b}p} ), this will turn p {\displaystyle p} into common knowledge ( C G E G p ⇒ C G p {\displaystyle C_{G}E_{G}p\Rightarrow C_{G}p} ), which is equivalent to the effect of a public announcement "there is at least one muddy face". | https://en.wikipedia.org/wiki/Mutual_knowledge_(logic) |
Mutual shaping suggests that society and technology are not mutually exclusive to one another and, instead, influence and shape each other. [ 1 ] This process is a combination of social determinism and technological determinism . The term mutual shaping was developed through science and technology studies (STS) in an attempt to explain the detailed process of technological design. [ 2 ] Mutual shaping is argued to have a more comprehensive understanding of the development of new media because it considers technological and social change as directly affecting the other. [ 3 ]
Technological determinism (TD), coined by Thorstein Veblen , suggests that technology is the primary catalyst for change in society. Following this theory, the development and implementation of technology is beyond the control of society as it is pervasive in all elements of our lives. Once a technology has been created its influence on society is an inevitable, predetermined path. Technological deterministic view suggests that technology is the cause of societal change, which shapes humans and their environments. [ 4 ] An example that supports technological determinism is the development of the printing press that accelerated the Protestant Reformation . [ 5 ]
In contrast, social determinism (SD), popularized by social theorists Karl Marx and Emile Durkheim , purports that social structure is the driving factor towards change in society. [ 6 ] Following this view, society is the governing force that determines social behaviour, and technology is created and adapted based on society's wants and needs. [ 7 ] Social determinism has been observed as response to technological determinism and explains that it is social and environmental factors which determine how technology is used and progresses. [ 8 ]
Both TD and SD are cause-and-effect theories suggesting that technology and society are mutually exclusive. The theory of mutual shaping suggests that technology design is a result of a synthesis of TD and SD. It sees technology and society working together to facilitate change. Society changes as a direct result of the implementation of technology that has been created based on society's wants and needs. They function collectively to shape one another. [ 1 ]
Technology innovations have long been tied to social changes. The move to an industrial society from an agricultural society meant that people had to adjust their social interactions. Agricultural societies have a few, distant and long-term relationships with people, while industrial societies have more casual, short-term relationships. [ 9 ]
Technological innovations also don't work in isolation from social change and vice versa. For example, while the telephone was initially invented as an extension of the telegraph , with a focus on business, the telephone quickly became a popular way for people to chat socially. Telephone companies then began to make innovations to enhance social interactions. [ 10 ]
Mutual shaping is exemplified through the integration of online social networking platforms into daily life. They are a communications technology designed to complement pre-existing methods of communication, such as the phone or in-person conversations, that have become more convenient and/or affordable than their predecessors. [ 11 ] TD would argue that these communication technologies have directly influenced our networking capabilities due to their accessibility. Without them we would not be able to conduct business or maintain friendships over long distances. SD would argue that these platforms were created as a result of a need to facilitate communication over long distances. [ 1 ] Mutual shaping supports both of these arguments, believing that the two cannot be separated. Social networking platforms display how technology and society are inextricably linked as they work together towards the advancement of one another, exemplifying the theory of mutual shaping.
The impact of mutual shaping has not always been positive. When the printing press was first introduced, many were worried about the information overload it might cause. [ 12 ] Recently, Internet addiction, or problematic internet use (PIU), has become a widespread issue. PIU can cause lack of sleep due to internet usage as well as increasing the risk for certain physical ailments like eyestrain. [ 13 ] Smartphones allow for endless amounts of information to be accessible in the pockets of its users. [ 14 ] However, the social stigma around smartphone use has centered around how technology addiction can lead to increased stress and anxiety for the users. [ 15 ]
Push-Pull-Thinking can be understood by the application of how new technology is created. When new demand for a product is the driving factor behind its creation then it is the "pulled" method, while when a new technology enters the market with new possibilities for application or innovation then it is the "push method." [ 16 ]
According to Michael Haddad, it's easier to understand an example of Push-Pull-Thinking where technology is the driving factor as one from an engineering or research and development background. [ 17 ] Sony's Walkman personal stereo cassette player has also been stated as an example of a technology push where there was no market need. [ 18 ]
In cases of Push-Pull-Thinking, where demand is the driving factor, the needs or requirements of society or market its best to take a market research approach to innovation. [ 17 ] Innovations regarding safety are often seen as pulled innovations with car airbags and new medical advancements are usually listed as examples. [ 18 ] | https://en.wikipedia.org/wiki/Mutual_shaping |
Mutualism describes the ecological interaction between two or more species where each species has a net benefit. [ 1 ] Mutualism is a common type of ecological interaction. Prominent examples are:
Mutualism can be contrasted with interspecific competition , in which each species experiences reduced fitness, and exploitation , and with parasitism , in which one species benefits at the expense of the other. [ 2 ] However, mutualism may evolve from interactions that began with imbalanced benefits, such as parasitism. [ 3 ]
The term mutualism was introduced by Pierre-Joseph van Beneden in his 1876 book Animal Parasites and Messmates to mean "mutual aid among species". [ 4 ] [ 5 ]
Mutualism is often conflated with two other types of ecological phenomena: cooperation and symbiosis . Cooperation most commonly refers to increases in fitness through within-species (intraspecific) interactions, although it has been used (especially in the past) to refer to mutualistic interactions, and it is sometimes used to refer to mutualistic interactions that are not obligate. [ 1 ] Symbiosis involves two species living in close physical contact over a long period of their existence and may be mutualistic, parasitic, or commensal , so symbiotic relationships are not always mutualistic, and mutualistic interactions are not always symbiotic. Despite a different definition between mutualism and symbiosis, they have been largely used interchangeably in the past, and confusion on their use has persisted. [ 6 ]
Mutualism plays a key part in ecology and evolution . For example, mutualistic interactions are vital for terrestrial ecosystem function as:
A prominent example of pollination mutualism is with bees and flowering plants. Bees use these plants as their food source with pollen and nectar. In turn, they transfer pollen to other nearby flowers, inadvertently allowing for cross-pollination. Cross-pollination has become essential in plant reproduction and fruit/seed production. The bees get their nutrients from the plants, and allow for successful fertilization of plants, demonstrating a mutualistic relationship between two seemingly-unlike species.
Mutualism has also been linked to major evolutionary events, such as the evolution of the eukaryotic cell ( symbiogenesis ) and the colonization of land by plants in association with mycorrhizal fungi.
Mutualistic relationships can be thought of as a form of " biological barter" [ 10 ] in mycorrhizal associations between plant roots and fungi , with the plant providing carbohydrates to the fungus in return for primarily phosphate but also nitrogenous compounds. Other examples include rhizobia bacteria that fix nitrogen for leguminous plants (family Fabaceae) in return for energy-containing carbohydrates . [ 11 ] Metabolite exchange between multiple mutualistic species of bacteria has also been observed in a process known as cross-feeding . [ 12 ] [ 13 ]
Service-resource relationships are common. Three important types are pollination , cleaning symbiosis, and zoochory .
In pollination, a plant trades food resources in the form of nectar or pollen for the service of pollen dispersal. However, daciniphilous Bulbophyllum orchid species trade sex pheromone precursor or booster components via floral synomones /attractants in a true mutualistic interactions with males of Dacini fruit flies (Diptera: Tephritidae: Dacinae). [ 14 ] [ 15 ]
Phagophiles feed (resource) on ectoparasites , thereby providing anti-pest service, as in cleaning symbiosis . Elacatinus and Gobiosoma , genera of gobies , feed on ectoparasites of their clients while cleaning them. [ 16 ]
Zoochory is the dispersal of the seeds of plants by animals. This is similar to pollination in that the plant produces food resources (for example, fleshy fruit, overabundance of seeds) for animals that disperse the seeds (service). Plants may advertise these resources using colour [ 17 ] and a variety of other fruit characteristics, e.g., scent. Fruit of the aardvark cucumber (Cucumis humifructus) is buried so deeply that the plant is solely reliant upon the aardvark's keen sense of smell to detect its ripened fruit, extract, consume and then scatter its seeds; [ 18 ] C. humifructus ' s geographical range is thus restricted to that of the aardvark.
Another type is ant protection of aphids , where the aphids trade sugar -rich honeydew (a by-product of their mode of feeding on plant sap ) in return for defense against predators such as ladybugs . [ citation needed ]
Strict service-service interactions are very rare, for reasons that are far from clear. [ 10 ] One example is the relationship between sea anemones and anemone fish in the family Pomacentridae : the anemones provide the fish with protection from predators (which cannot tolerate the stings of the anemone's tentacles) and the fish defend the anemones against butterflyfish (family Chaetodontidae ), which eat anemones. However, in common with many mutualisms, there is more than one aspect to it: in the anemonefish-anemone mutualism, waste ammonia from the fish feeds the symbiotic algae that are found in the anemone's tentacles. [ 19 ] [ 20 ] Therefore, what appears to be a service-service mutualism in fact has a service-resource component. A second example is that of the relationship between some ants in the genus Pseudomyrmex and trees in the genus Acacia , such as the whistling thorn and bullhorn acacia . The ants nest inside the plant's thorns. In exchange for shelter, the ants protect acacias from attack by herbivores (which they frequently eat when those are small enough, introducing a resource component to this service-service relationship) and competition from other plants by trimming back vegetation that would shade the acacia. In addition, another service-resource component is present, as the ants regularly feed on lipid -rich food-bodies called Beltian bodies that are on the Acacia plant. [ 21 ]
In the neotropics , the ant Myrmelachista schumanni makes its nest in special cavities in Duroia hirsuta . Plants in the vicinity that belong to other species are killed with formic acid . This selective gardening can be so aggressive that small areas of the rainforest are dominated by Duroia hirsute . These peculiar patches are known by local people as " devil's gardens ". [ 22 ]
In some of these relationships, the cost of the ant's protection can be quite expensive. Cordia sp. trees in the Amazon rainforest have a kind of partnership with Allomerus sp. ants, which make their nests in modified leaves. To increase the amount of living space available, the ants will destroy the tree's flower buds. The flowers die and leaves develop instead, providing the ants with more dwellings. Another type of Allomerus sp. ant lives with the Hirtella sp. tree in the same forests, but in this relationship, the tree has turned the tables on the ants. When the tree is ready to produce flowers, the ant abodes on certain branches begin to wither and shrink, forcing the occupants to flee, leaving the tree's flowers to develop free from ant attack. [ 22 ]
The term "species group" can be used to describe the manner in which individual organisms group together. In this non-taxonomic context one can refer to "same-species groups" and "mixed-species groups." While same-species groups are the norm, examples of mixed-species groups abound. For example, zebra ( Equus burchelli ) and wildebeest ( Connochaetes taurinus ) can remain in association during periods of long distance migration across the Serengeti as a strategy for thwarting predators. Cercopithecus mitis and Cercopithecus ascanius , species of monkey in the Kakamega Forest of Kenya , can stay in close proximity and travel along exactly the same routes through the forest for periods of up to 12 hours. These mixed-species groups cannot be explained by the coincidence of sharing the same habitat. Rather, they are created by the active behavioural choice of at least one of the species in question. [ 23 ]
Protocooperation is a form of mutualism, but the cooperating species do not depend on each other for survival. The term, initially used for intraspecific interactions, was popularized by Eugene Odum (1953), although it is now rarely used. [ 24 ]
Mutualistic symbiosis can sometimes evolve from parasitism or commensalism . Symbiogenesis , a leading theory on the evolution of Eukaryotes states the origin of the mitochondria and cell nucleus emerged from a parasitic relationship of ancient Archaea and Bacteria . Fungi's relationship to plants in the form of mycelium evolved from parasitism and commensalism. Under certain conditions species of fungi previously in a state of mutualism can turn parasitic on weak or dying plants. [ 25 ] Likewise the symbiotic relationship of clown fish and sea anemones emerged from a commensalist relationship. [ 26 ] [ 27 ] [ 28 ] Once a mutualistic relationship emerges both symbionts are pushed towards co-evolution with each other. [ 29 ] [ 30 ]
Mathematical treatments of mutualisms, like the study of mutualisms in general, have lagged behind those for predation , or predator-prey, consumer-resource, interactions. In models of mutualisms, the terms "type I" and "type II" functional responses refer to the linear and saturating relationships, respectively, between the benefit provided to an individual of species 1 ( dependent variable ) and the density of species 2 (independent variable). [ citation needed ]
One of the simplest frameworks for modeling species interactions is the Lotka–Volterra equations . [ 31 ] In this model, the changes in population densities of the two mutualists are quantified as:
where
Mutualism is in essence the logistic growth equation modified for mutualistic interaction. The mutualistic interaction term represents the increase in population growth of one species as a result of the presence of greater numbers of another species. As the mutualistic interactive term β is always positive, this simple model may lead to unrealistic unbounded growth. [ 32 ] So it may be more realistic to include a further term in the formula, representing a saturation mechanism, to avoid this occurring.
In 1989, David Hamilton Wright modified the above Lotka–Volterra equations by adding a new term, βM / K , to represent a mutualistic relationship. [ 33 ] Wright also considered the concept of saturation, which means that with higher densities, there is a decrease in the benefits of further increases of the mutualist population. Without saturation, depending on the size of parameter α, species densities would increase indefinitely. Because that is not possible due to environmental constraints and carrying capacity, a model that includes saturation would be more accurate. Wright's mathematical theory is based on the premise of a simple two-species mutualism model in which the benefits of mutualism become saturated due to limits posed by handling time. Wright defines handling time as the time needed to process a food item, from the initial interaction to the start of a search for new food items and assumes that processing of food and searching for food are mutually exclusive. Mutualists that display foraging behavior are exposed to the restrictions on handling time. Mutualism can be associated with symbiosis. [ citation needed ]
In 1959, C. S. Holling performed his classic disc experiment that assumed that
where
The equation that incorporates Type II functional response and mutualism is:
where
or, equivalently,
where
This model is most effectively applied to free-living species that encounter a number of individuals of the mutualist part in the course of their existences. Wright notes that models of biological mutualism tend to be similar qualitatively, in that the featured isoclines generally have a positive decreasing slope, and by and large similar isocline diagrams. Mutualistic interactions are best visualized as positively sloped isoclines, which can be explained by the fact that the saturation of benefits accorded to mutualism or restrictions posed by outside factors contribute to a decreasing slope.
The type II functional response is visualized as the graph of b a M 1 + a T H M {\displaystyle {\cfrac {baM}{1+aT_{H}M}}} vs. M .
Mutualistic networks made up out of the interaction between plants and pollinators were found to have a similar structure in very different ecosystems on different continents, consisting of entirely different species. [ 34 ] The structure of these mutualistic networks may have large consequences for the way in which pollinator communities respond to increasingly harsh conditions and on the community carrying capacity. [ 35 ]
Mathematical models that examine the consequences of this network structure for the stability of pollinator communities suggest that the specific way in which plant-pollinator networks are organized minimizes competition between pollinators, [ 36 ] reduce the spread of indirect effects and thus enhance ecosystem stability [ 37 ] and may even lead to strong indirect facilitation between pollinators when conditions are harsh. [ 38 ] This means that pollinator species together can survive under harsh conditions. But it also means that pollinator species collapse simultaneously when conditions pass a critical point. [ 39 ] This simultaneous collapse occurs, because pollinator species depend on each other when surviving under difficult conditions. [ 38 ]
Such a community-wide collapse, involving many pollinator species, can occur suddenly when increasingly harsh conditions pass a critical point and recovery from such a collapse might not be easy. The improvement in conditions needed for pollinators to recover could be substantially larger than the improvement needed to return to conditions at which the pollinator community collapsed. [ 38 ]
Humans are involved in mutualisms with other species: their gut flora is essential for efficient digestion . [ 40 ] Infestations of head lice might have been beneficial for humans by fostering an immune response that helps to reduce the threat of body louse borne lethal diseases. [ 41 ]
Some relationships between humans and domesticated animals and plants are to different degrees mutualistic. [ citation needed ] For example, domesticated cereals that provide food for humans have lost the ability to spread seeds by shattering , a strategy that wild grains use to spread their seeds. [ 42 ]
In traditional agriculture , some plants have mutualistic relationships as companion plants , providing each other with shelter, soil fertility or natural pest control . For example, beans may grow up cornstalks as a trellis, while fixing nitrogen in the soil for the corn, a phenomenon that is used in Three Sisters farming . [ 43 ]
One researcher has proposed that the key advantage Homo sapiens had over Neanderthals in competing over similar habitats was the former's mutualism with dogs. [ 44 ]
The microbiota in the human intestine coevolved with the human species, and this relationship is considered to be a mutualism that is beneficial both to the human host and the bacteria in the gut population. [ 45 ] The mucous layer of the intestine contains commensal bacteria that produce bacteriocins , modify the pH of the intestinal contents, and compete for nutrition to inhibit colonization by pathogens. [ 46 ] The gut microbiota, containing trillions of microorganisms , possesses the metabolic capacity to produce and regulate multiple compounds that reach the circulation and act to influence the function of distal organs and systems. [ 47 ] Breakdown of the protective mucosal barrier of the gut can contribute to the development of colon cancer . [ 46 ]
Every generation of every organism needs nutrients – and similar nutrients – more than they need particular defensive characteristics, as the fitness benefit of these vary heavily especially by environment. This may be the reason that hosts are more likely to evolve to become dependent on vertically transmitted bacterial mutualists which provide nutrients than those providing defensive benefits. This pattern is generalized beyond bacteria by Yamada et al. 2015's demonstration that undernourished Drosophila are heavily dependent on their fungal symbiont Issatchenkia orientalis for amino acids. [ 48 ]
Mutualisms are not static, and can be lost by evolution. [ 49 ] Sachs and Simms (2006) suggest that this can occur via four main pathways:
There are many examples of mutualism breakdown. For example, plant lineages inhabiting nutrient-rich environments have evolutionarily abandoned mycorrhizal mutualisms many times independently. [ 52 ] Evolutionarily, headlice may have been mutualistic as they allow for early immunity to various body-louse borne disease; however, as these diseases became eradicated, the relationship has become less mutualistic and more parasitic. [ 50 ]
Measuring the exact fitness benefit to the individuals in a mutualistic relationship is not always straightforward, particularly when the individuals can receive benefits from a variety of species, for example most plant- pollinator mutualisms. It is therefore common to categorise mutualisms according to the closeness of the association, using terms such as obligate and facultative . Defining "closeness", however, is also problematic. It can refer to mutual dependency (the species cannot live without one another) or the biological intimacy of the relationship in relation to physical closeness ( e.g. , one species living within the tissues of the other species). [ 10 ] | https://en.wikipedia.org/wiki/Mutualism_(biology) |
The hypothesis or paradigm of Mutualism Parasitism Continuum postulates that compatible host-symbiont associations can occupy a broad continuum of interactions with different fitness outcomes for each member.
At one end of the continuum lies obligate mutualism where both host and symbiont benefit from the interaction and are dependent on it for survival. At the other end of the continuum highly parasitic interactions can occur, where one member gains a fitness benefit at the expense of the others survival. Between these extremes many different types of interaction are possible. [ 1 ] [ 2 ]
The degree of change between mutualism or parasitism varies depending on the availability of resources, where there is environmental stress generated by few resources, symbiotic relationships are formed while in environments where there is an excess of resources, biological interactions turn to competition and parasitism. [ 3 ]
Classically the transmission mode of the symbiont can also be important in predicting where on the mutualism-parasitism-continuum an interaction will sit. [ 4 ] Symbionts that are vertically transmitted (inherited symbionts) frequently occupy mutualism space on the continuum, this is due to the aligned reproductive interests between host and symbiont that are generated under vertical transmission. In some systems increases in the relative contribution of horizontal transmission can drive selection for parasitism. [ 5 ]
Studies of this hypothesis have focused on host-symbiont models of plants and fungi, and also of animals and microbes.
This biology article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Mutualism_Parasitism_Continuum |
Conservation is the maintenance of biological diversity . Conservation can focus on preserving diversity at genetic , species , community or whole ecosystem levels. This article will examine conservation at the species level, because mutualisms involve interactions between species. The ultimate goal of conservation at this level is to prevent the extinction of species. However, species conservation has the broader aim of maintaining the abundance and distribution of all species, not only those threatened with extinction (van Dyke 2008). Determining the value of conserving particular species can be done through the use of evolutionary significant units, which essentially attempt to prioritise the conservation of the species which are rarest, fastest declining, and most distinct genotypically and phenotypically (Moritz 1994, Fraser and Bernatchez 2001).
Mutualisms can be defined as "interspecific interactions in which each of two partner species receives a net benefit" (Bronstein et al. 2004). Here net benefit is defined as, a short-term increase in inclusive fitness (IF). Incorporating the concept of genetic relatedness (through IF) is essential because many mutualisms involve the eusocial insects, where the majority of individuals are not reproductively active. The short-term component is chosen because it is operationally useful, even though the role of long-term adaptation is not considered (de Mazancourt et al. 2005). This definition of mutualism should be suffice for this article, although it neglects discussion of the many subtitles of IF theory applied to mutualisms, and the difficulties of examining short-term compared to long-term benefits, which are discussed in Foster and Wenselneers (2006) and de Mazancourt et al. (2005) respectively. Mutualisms can be broadly divided into two categories. Firstly, obligate mutualism, where two mutualistic partners are completely interdependent for survival and reproduction. Secondly, facultative mutualism, where two mutualistic partners both benefit from the mutualism, but can theoretically survive in each other's absence.
Mutualisms are remarkably common, in fact all organisms are believed to be involved in a mutualism at some point during their lives (Bronstein et al. 2004). This is particularly likely to be true for the definition of mutualism adopted here, where herbivory can paradoxically be mutualistic, for example in a situation where a plant overcompensates by producing more biomass when grazed on. Therefore, any species identified as particularly important to conserve will probably have mutualistic partners. It is beyond the purview of this article to discuss all these mutualisms, so the focus will be on specifically animal-plant mutualisms.
A mutualism coextinction event is where a species goes extinct upon the loss of its mutualist (Koh et al. 2004). Models have attempted to predict when the breakdown of a mutualism leads to coextinction, because in this situation protecting the mutualism will be particularly important for conservation. These models are multi-dimensional, so examine complex networks of interactions, rather than just pairs of interacting species. This means that these models incorporate modelling the breakdown of obligate mutualisms (which lead directly to coextinction), but also the breakdown of facultative mutualisms (which can lead indirectly to coextinction). Koh et al. (2004) use a "nomographic model of affiliate extinctions", which estimates the probability that the extinction of a species leads to the extinction of its mutualist, for a given estimate of the specificity of the mutualism. By applying the model to actual species, Koh et al. (2004) estimate that 200 coextinctions have occurred since records of species extinction began in the past few centuries, and 6300 coextinctions are at risk of occurring in the near future. However, these estimates are not exclusively for mutualism coextinctions (e.g. parasitic coextinctions are incorporated), but mutualism coextinctions make up a significant proportion of the number quoted. Additionally the model predicts that these coextinctions can start extinction cascades, where many other species in the surrounding ecosystem go extinct. Other recent models largely agree with this one, predicting that mutualism coextinction is a very significant cause of species loss, and that it can lead to extinction cascades (Dunn et al. 2009).
Surprisingly, given the model predictions, there are very few recorded examples of global mutualism coextinctions actually occurring (Bronstein et al. 2004, Dunn et al. 2009), and many examples often quoted are unconvincing on examination. For example, a well documented case of animal-plant coextinction and an extinction cascade involves a butterfly ( Phengaris arion ) to ant ( Myrmica sabuleti ) interaction. P. arion larvae provide honeydew for the M. sabuleti workers, which raise the caterpillars in their nest. When the Myxoma virus was introduced to control rabbit populations in the UK, the subsequent increase in grassland caused a decrease in soil temperatures at ground level. This caused reductions in the M. sabuleti populations, which led to the extinction of the P. arion populations (Dunn 2005). However, this is actually a relatively weak example, because it was a local (rather than a global) extinction, and the nature of the interaction is often not viewed as mutualistic, because it has been long known that the M. sabuleti caterpillars eat M. sabuleti larvae (Elmes and Thomas 1992).
So, why are there very few documented examples of mutualism coextinctions? There are various possible reasons. Perhaps global mutualism coextinctions are genuinely uncommon, and the model predictions are inaccurate. The models may overestimate the specificity of the mutualisms, because species may only associate with alternative species when their 'normal' mutualist is rare or absent. For example, oligolectic bees visit a small number of flowers for pollen. However, these bees do not generally have strongly specialised anatomy, morphology or physiology. Therefore, in the absence of these usual flowers, many oligolectic bee species are able switch to collecting pollen from flower species they would never normally associate with (Wcislo and Cane 1996). Even some fig wasps , often considered to be in completely obligate relationships, have maintained low population densities when introduced to new areas without their natural mutualist fig tree species (McKey 1989). The models may also underestimate the robustness of the mutualisms. For example, fig trees and fig wasps are coadapted so that the wasps can find the trees from a long distances away (Bronstein et al. 1994).
Alternatively, there may simply be many global mutualism coextinctions that have occurred which we are not yet aware of. This explanation is not unlikely, because mutualisms have generally been understudied as interactions (Bronstein 1994, Richardson et al. 2000). There is additionally the difficulty of defining when a species becomes globally extinct, compared to just extremely rare or maintained exclusively through captive breeding programs. Of course, these stated explanations are not mutually exclusive. However, more research is required to rectify the model predictions of many mutualism coextinctions, with the lack of empirical evidence for such events. Only then can we discover if conserving mutualisms is likely to prevent many global species extinction.
Even if global mutualism coextinctions are genuinely rare, conserving mutualisms may still be important for conservation. As mentioned previously, conservation is not just about preventing extinctions, but also about preventing species decline. Unlike with coextinctions, there are numerous recorded examples of where the decline or extinction of a species has led to the decline of its mutualist ("codeclines"). A documented example of a pollination mutualism breakdown leading to population declines is the Indian rubber tree ( Ficus elastica ) to its pollinator wasp ( Pleistodontes clavigar ) interaction. Habitat fragmentation has led to the F. elastica declining to very low population levels. However, F. Elastic can propagate clonally, so has remained extant. Meanwhile, P. clavigar is virtually extinct globally, because the mutualist relationship is probably obligate for P. clavigar (Mawsdley et al. 1998). An example of a seed dispersal mutualism breakdown causing population declines comes from two endemic species on Menorca Island. A frugivorous lizard ( Podarcis lilfordi ) is a seed disperser of a shrub ( Daphne rodriguezii ). When P. lilfordi became extinct on Menorca, due to the introduction of carnivorous mammals, D. rodriguezii numbers declined significantly to endangered levels. This D. rodriguezii decline could be attributed to the local extinction of P. lilfordi , due to the lack of seedling recruitment on Menorca compared to other nearby islands, where P. lilfordi remained extant and D. rodriguezii populations larger (Traveset and Riera 2005).
However, in some cases it has been shown that declines of one partner in a mutualism do not lead to significant declines in the other. For example, a Hawaiian vine ( Freycinetia arborea ) was pollinated in the nineteenth century by four species of birds. These bird species are all now either locally endangered or extinct. Despite this, F. arborea continues to survive in reasonable abundance, but is now mainly pollinated by the recently introduced white-eye ( Zosterops japonica ) (Cox and Elmqvist 2000). In this case, conservation of the mutualism was not required to maintain the F. arborea population. There are probably no published estimates of how frequently declines of one species do not result in declines of that species' mutualist, due to a 'replacement' mutualist. However, judging by the few examples in the literature where this replacement has been reported to have happened, it seems to be a relatively rare occurrence.
The Hawaiian vine example also illustrates that alien species can be involved in animal-plant mutualisms. In fact, alien species are often dependent on mutualisms to establish themselves in new habitats (particularly on islands), and especially those alien species requiring animal-mediated pollination (Richardson et al. 2000). These alien species will, by definition, be beneficial to the short-term inclusive fitness of the species they form a mutualism with. However, the alien species will negatively impact other species in the ecosystem. For example, through competition for resources (including competition for mutualist partners) (Kaiser-Bunbury et al. 2009). In fact, these negative impacts could theoretically cascade through the ecosystem, and lead to the alien species having an indirect long-term negative impact on its mutualist. This means that mutualisms involving alien species is important in conservation. However, the action taken by a conservation organization could be either to conserve or disrupt the mutualism.
In some situations, a conservation organization will want to conserve the mutualistic relationship. For example, many of the Hawaiian Islands have lost the vast majority of their native seed dispersers, and introduced bird species now act as very major seed dispersers of native species. In fact, these exotic species appear to actually facilitate the re-growth of native forests in some areas (Foster and Robinson 2007). In these situations, conserving the native mutualism may become less important than conserving the new one. Alien species involved in mutualisms may actually be desirable for conservationists to protect in a more general way. Alien species are particularly likely to generate highly generalised and asymmetric mutualisms, which help stabilise communities, making them less vulnerable to decline and extinctions (Aizen et al. 2008).
In other situations, conservation will be facilitated by disrupting mutualisms involving alien species. For example, alien bumblebees ( Bombus terrestris ) have displaced many native pollinators, and pollinated some unwanted weed species, across the globe (Hingston et al. 2002). These mutualisms could lead to a decline in both animal and plant species of particular value to conservation. The empirical evidence would suggest that in the majority of cases a conservation organisation should try to disrupt the mutualisms involving the alien species (Kaiser-Bunbury et al. 2009). | https://en.wikipedia.org/wiki/Mutualisms_and_conservation |
In quantum information theory, a set of bases in Hilbert space C d are said to be mutually unbiased if when a system is prepared in an eigenstate of one of the bases, then all outcomes of the measurement with respect to the other basis are predicted to occur with an equal probability of 1/ d .
The notion of mutually unbiased bases was first introduced by Julian Schwinger in 1960, [ 1 ] and the first person to consider applications of mutually unbiased bases was I. D. Ivanovic [ 2 ] in the problem of quantum state determination.
Mutually unbiased bases (MUBs) and their existence problem is now known to have several closely related problems and equivalent avatars in several other branches of mathematics and quantum sciences, such as SIC-POVMs , finite projective/affine planes, complex Hadamard matrices and more [see section: Related problems ].
MUBs are important for quantum key distribution , more specifically in secure quantum key exchange. [ 3 ] MUBs are used in many protocols since the outcome is random when a measurement is made in a basis unbiased to that in which the state was prepared. When two remote parties share two non-orthogonal quantum states, attempts by an eavesdropper to distinguish between these by measurements will affect the system and this can be detected. While many quantum cryptography protocols have relied on 1- qubit technologies, employing higher-dimensional states, such as qutrits , allows for better security against eavesdropping. [ 3 ] This motivates the study of mutually unbiased bases in higher-dimensional spaces.
Other uses of mutually unbiased bases include quantum state reconstruction , [ 4 ] quantum error correction codes , [ 5 ] [ 6 ] detection of quantum entanglement , [ 7 ] [ 8 ] and the so-called "mean king's problem". [ 9 ] [ 10 ]
A pair of orthonormal bases { | e 1 ⟩ , … , | e d ⟩ } {\displaystyle \{|e_{1}\rangle ,\dots ,|e_{d}\rangle \}} and { | f 1 ⟩ , … , | f d ⟩ } {\displaystyle \{|f_{1}\rangle ,\dots ,|f_{d}\rangle \}} in Hilbert space C d are said to be mutually unbiased , if and only if the square of the magnitude of the inner product between any basis states | e j ⟩ {\displaystyle |e_{j}\rangle } and | f k ⟩ {\displaystyle |f_{k}\rangle } equals the inverse of the dimension d : [ 11 ]
These bases are unbiased in the following sense: if a system is prepared in a state belonging to one of the bases, then all outcomes of the measurement with respect to the other basis are predicted to occur with equal probability.
The three bases
provide the simplest example of mutually unbiased bases in C 2 . The above bases are composed of the eigenvectors of the Pauli spin matrices σ z , σ x {\displaystyle \sigma _{z},\sigma _{x}} and their product σ x σ z {\displaystyle \sigma _{x}\sigma _{z}} , respectively.
For d = 4, an example of d + 1 = 5 mutually unbiased bases where each basis is denoted by M j , 0 ≤ j ≤ 4, is given as follows: [ 12 ]
Let M ( d ) {\displaystyle {\mathfrak {M}}(d)} denote the maximum number of mutually unbiased bases in the d -dimensional Hilbert space C d . It is an open question [ 13 ] how many mutually unbiased bases, M ( d ) {\displaystyle {\mathfrak {M}}(d)} , one can find in C d , for arbitrary d .
In general, if
is the prime-power factorization of d , where
then the maximum number of mutually unbiased bases which can be constructed satisfies [ 11 ]
It follows that if the dimension of a Hilbert space d is an integer power of a prime number, then it is possible to find d + 1 mutually unbiased bases. This can be seen in the previous equation, as the prime number decomposition of d simply is d = p n {\displaystyle d=p^{n}} . Therefore,
Thus, the maximum number of mutually unbiased bases is known when d is an integer power of a prime number, but it is not known for arbitrary d .
The smallest dimension that is not an integer power of a prime is d = 6. This is also the smallest dimension for which the number of mutually unbiased bases is not known. The methods used to determine the number of mutually unbiased bases when d is an integer power of a prime number cannot be used in this case. Searches for a set of four mutually unbiased bases when d = 6, both by using Hadamard matrices [ 11 ] and numerical methods [ 14 ] [ 15 ] have been unsuccessful. The general belief is that the maximum number of mutually unbiased bases for d = 6 is M ( 6 ) = 3 {\displaystyle {\mathfrak {M}}(6)=3} . [ 11 ]
The MUBs problem seems similar in nature to the symmetric property of SIC-POVMs. William Wootters points out that a complete set of d + 1 {\displaystyle d+1} unbiased bases yields a geometric structure known as a finite projective plane , while a SIC-POVM (in any dimension that is a prime power ) yields a finite affine plane , a type of structure whose definition is identical to that of a finite projective plane with the roles of points and lines exchanged. In this sense, the problems of SIC-POVMs and of mutually unbiased bases are dual to one another. [ 16 ]
In dimension d = 3 {\displaystyle d=3} , the analogy can be taken further: a complete set of mutually unbiased bases can be directly constructed from a SIC-POVM. [ 17 ] The 9 vectors of the SIC-POVM, together with the 12 vectors of the mutually unbiased bases, form a set that can be used in a Kochen–Specker proof . [ 18 ] However, in 6-dimensional Hilbert space, a SIC-POVM is known, but no complete set of mutually unbiased bases has yet been discovered, and it is widely believed that no such set exists. [ 19 ] [ 20 ]
Let X ^ {\displaystyle {\hat {X}}} and Z ^ {\displaystyle {\hat {Z}}} be two unitary operators in the Hilbert space C d such that
for some phase factor ω {\displaystyle \omega } . If ω {\displaystyle \omega } is a primitive root of unity , for example ω ≡ e 2 π i d {\displaystyle \omega \equiv e^{\frac {2\pi i}{d}}} then the eigenbases of X ^ {\displaystyle {\hat {X}}} and Z ^ {\displaystyle {\hat {Z}}} are mutually unbiased.
By choosing the eigenbasis of Z ^ {\displaystyle {\hat {Z}}} to be the standard basis , we can generate another basis unbiased to it using a Fourier matrix. The elements of the Fourier matrix are given by
Other bases which are unbiased to both the standard basis and the basis generated by the Fourier matrix can be generated using Weyl groups. [ 11 ] The dimension of the Hilbert space is important when generating sets of mutually unbiased bases using Weyl groups. When d is a prime number, then the usual d + 1 mutually unbiased bases can be generated using Weyl groups. When d is not a prime number, then it is possible that the maximal number of mutually unbiased bases which can be generated using this method is 3.
When d = p is prime , we define the unitary operators X ^ {\displaystyle {\hat {X}}} and Z ^ {\displaystyle {\hat {Z}}} by
where { | k ⟩ | 0 ≤ k ≤ d − 1 } {\displaystyle \{|k\rangle |0\leq k\leq d-1\}} is the standard basis and ω = e 2 π i d {\displaystyle \omega =e^{\frac {2\pi i}{d}}} is a root of unity .
Then the eigenbases of the following d + 1 operators are mutually unbiased: [ 21 ]
For odd d , the t -th eigenvector of the operator X ^ Z ^ k {\displaystyle {\hat {X}}{\hat {Z}}^{k}} is given explicitly by [ 13 ]
When d = p r {\displaystyle d=p^{r}} is a power of a prime, we make use of the finite field F d {\displaystyle \mathbb {F} _{d}} to construct a maximal set of d + 1 mutually unbiased bases. We label the elements of the computational basis of C d using the finite field: { | a ⟩ | a ∈ F d } {\displaystyle \{|a\rangle |a\in \mathbb {F} _{d}\}} .
We define the operators X a ^ {\displaystyle {\hat {X_{a}}}} and Z b ^ {\displaystyle {\hat {Z_{b}}}} in the following way
where
is an additive character over the field and the addition and multiplication in the kets and χ ( ⋅ ) {\displaystyle \chi (\cdot )} is that of F d {\displaystyle \mathbb {F} _{d}} .
Then we form d + 1 sets of commuting unitary operators:
The joint eigenbases of the operators in one set are mutually unbiased to that of any other set. [ 21 ] We thus have d + 1 mutually unbiased bases.
Given that one basis in a Hilbert space is the standard basis, then all bases which are unbiased with respect to this basis can be represented by the columns of a complex Hadamard matrix multiplied by a normalization factor. For d = 3 these matrices would have the form
The problem of finding a set of k +1 mutually unbiased bases therefore corresponds to finding k mutually unbiased complex Hadamard matrices. [ 11 ]
An example of a one parameter family of Hadamard matrices in a 4-dimensional Hilbert space is
There is an alternative characterization of mutually unbiased bases that considers them in terms of uncertainty relations . [ 22 ]
Entropic uncertainty relations are analogous to the Heisenberg uncertainty principle, and Hans Maassen and J. B. M. Uffink [ 23 ] found that for any two bases B 1 = { | a i ⟩ i = 1 d } {\displaystyle B_{1}=\{|a_{i}\rangle _{i=1}^{d}\}} and B 2 = { | b j ⟩ j = 1 d } {\displaystyle B_{2}=\{|b_{j}\rangle _{j=1}^{d}\}} :
where c = max | ⟨ a j | b k ⟩ | {\displaystyle c=\max |\langle a_{j}|b_{k}\rangle |} and H B 1 {\displaystyle H_{B_{1}}} and H B 2 {\displaystyle H_{B_{2}}} is the respective entropy of the bases B 1 {\displaystyle B_{1}} and B 2 {\displaystyle B_{2}} , when measuring a given state.
Entropic uncertainty relations are often preferable [ 24 ] to the Heisenberg uncertainty principle , as they are not phrased in terms of the state to be measured, but in terms of c .
In scenarios such as quantum key distribution , we aim for measurement bases such that full knowledge of a state with respect to one basis implies minimal knowledge of the state with respect to the other bases. This implies a high entropy of measurement outcomes, and thus we call these strong entropic uncertainty relations.
For two bases, the lower bound of the uncertainty relation is maximized when the measurement bases are mutually unbiased, since mutually unbiased bases are maximally incompatible : the outcome of a measurement made in a basis unbiased to that in which the state is prepared in is completely random. In fact, for a d -dimensional space, we have: [ 25 ]
for any pair of mutually unbiased bases B 1 {\displaystyle B_{1}} and B 2 {\displaystyle B_{2}} . This bound is optimal : [ 26 ] If we measure a state from one of the bases then the outcome has entropy 0 in that basis and an entropy of log ( d ) {\displaystyle \log(d)} in the other.
If the dimension of the space is a prime power, we can construct d + 1 MUBs, and then it has been found that [ 27 ]
which is stronger than the relation we would get from pairing up the sets and then using the Maassen and Uffink equation. Thus we have a characterization of d + 1 mutually unbiased bases as those for which the uncertainty relations are strongest.
Although the case for two bases, and for d + 1 bases is well studied, very little is known about uncertainty relations for mutually unbiased bases in other circumstances. [ 27 ] [ 28 ]
When considering more than two, and less than d + 1 {\displaystyle d+1} bases it is known that large sets of mutually unbiased bases exist which exhibit very little uncertainty. [ 29 ] This means merely being mutually unbiased does not lead to high uncertainty, except when considering measurements in only two bases. Yet there do exist other measurements that are very uncertain. [ 27 ] [ 30 ]
While there has been investigation into mutually unbiased bases in infinite dimension Hilbert space, their existence remains an open question. It is conjectured that in a continuous Hilbert space, two orthonormal bases | ψ s b ⟩ {\displaystyle |\psi _{s}^{b}\rangle } and | ψ s ′ b ′ ⟩ {\displaystyle |\psi _{s'}^{b'}\rangle } are said to be mutually unbiased if [ 31 ]
For the generalized position and momentum eigenstates | q ⟩ , q ∈ R {\displaystyle |q\rangle ,q\in \mathbb {R} } and | p ⟩ , p ∈ R {\displaystyle |p\rangle ,p\in \mathbb {R} } , the value of k is
The existence of mutually unbiased bases in a continuous Hilbert space remains open for debate, as further research in their existence is required before any conclusions can be reached.
Position states | q ⟩ {\displaystyle |q\rangle } and momentum states | p ⟩ {\displaystyle |p\rangle } are eigenvectors of Hermitian operators x ^ {\displaystyle {\hat {x}}} and − i ∂ ∂ x {\displaystyle -i{\frac {\partial }{\partial x}}} , respectively. Weigert and Wilkinson [ 31 ] were first to notice that also a linear combination of these operators have eigenbases, which have some features typical for the mutually unbiased bases. An operator α x ^ − i β ∂ ∂ x {\displaystyle \alpha {\hat {x}}-i\beta {\frac {\partial }{\partial x}}} has eigenfunctions proportional to exp ( i ( a x 2 + b x ) ) {\displaystyle \exp(i(ax^{2}+bx))\,} with α + 2 β a = 0 {\displaystyle \alpha +2\beta a=0} and the corresponding eigenvalues b β {\displaystyle b\beta } . If we parametrize α {\displaystyle \alpha } and β {\displaystyle \beta } as cos θ {\displaystyle \cos \theta } and sin θ {\displaystyle \sin \theta } , the overlap between any eigenstate of the linear combination and any eigenstate of the position operator (both states normalized to the Dirac delta) is constant, but dependent on β {\displaystyle \beta } :
where | x ⟩ {\displaystyle |x\rangle } and | x θ ⟩ {\displaystyle |x_{\theta }\rangle } stand for eigenfunctions of x ^ {\displaystyle {\hat {x}}} and cos θ x ^ − i sin θ ∂ ∂ x {\displaystyle \cos \theta {\hat {x}}-i\sin \theta {\frac {\partial }{\partial x}}} . | https://en.wikipedia.org/wiki/Mutually_unbiased_bases |
mwrank is one in a suite of programs for computing elliptic curves over rational numbers . Other programs in the suite compute conductors , torsion subgroups , isogenous and quadratic twists of curves. mwrank is written in C++ and is free software released under the GNU General Public License . | https://en.wikipedia.org/wiki/Mwrank |
The myGrid consortium produces and uses a suite of tools design to “help e-Scientists get on with science and get on with scientists”. The tools support the creation of e-laboratories and have been used in domains as diverse as systems biology , social science , music , astronomy , [ 1 ] multimedia and chemistry . [ 2 ] [ 3 ]
The consortium is led by Carole Goble of the Department of Computer Science at the University of Manchester , UK.
Tools developed by the myGrid consortium include:
The consortium has three distinct phases:
The consortium was formed in 2001, bringing together collaborators at the Universities of Manchester , Southampton , Newcastle , Nottingham and Sheffield , The European Molecular Biology Laboratory - European Bioinformatics Institute [ 22 ] (EMBL-EBI) in Cambridge, and industrial partners GlaxoSmithKline , Merck KGaA , AstraZeneca , Sun Microsystems , IBM , GeneticXchange, Epistemics and Cerebra, (formerly Network Inference). The UK Engineering and Physical Sciences Research Council funded the first phase of the project with £3.5 million. [ 23 ]
To date, Grid development has focused on the basic issues of storage, computation and resource management needed to make a global scientific community's information and tools accessible in a high performance environment. However, from an e-Science viewpoint, the purpose of the Grid is to deliver a collaborative and supportive environment that allows geographically distributed scientists to achieve research goals more effectively. MyGrid will design, develop and demonstrate higher level functionalities over an existing Grid infrastructure that support scientists in making use of complex distributed resources.
The project has developed an e-Science workbench called Taverna [ 4 ] [ 5 ] [ 6 ] that supports:
The myGrid project has also developed myExperiment to allow sharing of scientific workflows from Taverna and other Scientific workflow systems .
The Taverna workbench supports individual scientists by providing personalisation facilities relating to resource selection, data management and process enactment. The design and development activity will be informed by and evaluated using problems in bioinformatics, which is characterised by a highly distributed community, with many shared tools resources. myGrid will develop two application environments, one that supports individual scientists in the analysis of functional genomic data, and another that supports the annotation of a pattern database . Both of these tasks require explicit representation and enactment of scientific processes, and have challenging performance requirements.
In phase 2, from 2006 to 2009, the consortium is funded for £2 million [ 24 ] as part of the Open Middleware Infrastructure Institute . The
membership of the consortium was concentrated in the University of Manchester and EMBL-EBI .
In December 2008, the UK's Engineering and Physical Sciences Research Council approved the team's renewal grant proposal. The grant is for £1.15m [ 25 ] and started in January 2009. The members of the myGrid team for Phase 3 are the University of Manchester and the University of Southampton . The project is organised around 4 themes: Knowledge Management for e-Science, Metadata management in e-Laboratories, Scientific Workflow Design, Management and Enactment, and Social Computing for e-Scientists. The Social Computing theme is oriented around the myExperiment [ 7 ] Virtual research environment (VRE) for the social curation and sharing of scientific Research Objects . | https://en.wikipedia.org/wiki/MyGrid |
MyRIO is a real-time embedded evaluation board made by National Instruments . It is used to develop
applications that utilize its onboard FPGA and microprocessor . It requires LabVIEW . It's geared towards students and basic applications. [ 1 ]
(for myRIO-1900)
cRIO (compactRIO)
myDAQ | https://en.wikipedia.org/wiki/MyRIO |
MySensors is a free and open source DIY ( do-it yourself ) software framework for wireless IoT ( Internet of Things ) devices allowing devices to communicate using radio transmitters . The library was originally developed for the Arduino platform. [ 2 ] [ 3 ]
The MySensors devices create a virtual radio network of nodes that automatically forms a self healing mesh like structure. Each node can relay messages for other nodes to cover greater distances using simple short range transceivers. Each node can have several sensors or actuators attached and can interact with other nodes in the network.
The radio network can consist of up to 254 nodes where one node can act as a gateway to the internet or a home automation controller. The controller adds functionality to the radio network such as id assignment and time awareness.
The framework can natively be run on the following platforms and micro controllers .
MySensors supports wireless communication using the following transceivers:
Wired communication over:
The wireless communication can be signed using truncated HMAC-SHA256 either through hardware with Atmel ATSHA204A or compatible software emulation and optionally encrypted. The implementation is timing neutral with whitened random numbers, attack detection-and-lockout and protects against timing attacks , replay attacks and man in the middle attacks .
The firmware of a MySensor node can be updated over the air using a few different bootloader options: | https://en.wikipedia.org/wiki/MySensors |
My Sky was a personal astronomy tool made by Meade Instruments . When pointed at an area of sky, it was supposed to identify objects based on its built-in database of 30000 objects. It also claimed it could guide the user to a particular object from its database. It has an LCD display, unsuccessfully incorporates GPS technology and cannot be linked to a compatible Meade computer-controllable telescope . Note, however, that my Sky is not a telescope or observing instrument. [ 1 ]
The later model of this device no longer incorporated the GPS functionality. There were many complaints about that feature not working. Now, latitude and longitude are entered manually or selected from a list of cities.
This article about an organization or institute connected with astronomy is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/MySky |
MySyara is a UAE-based online car servicing and repair platform. [ 1 ] [ 2 ]
Founded in 2019 by Chirenj Chandran and Anser Latheef, [ 3 ] the company provides a car maintenance application. [ 4 ] [ 5 ] [ 6 ] 8 months later, MySyara acquired SKKYN Technologies, an on-demand car wash application provider, for $2.8 million. [ 7 ]
In February 2021, Creative Zone, Dubai’s business setup advisory firm, acquired a stake in MySyara. [ 8 ] [ 9 ] [ 10 ] The company secured a $650,000 pre-Series A funding round, [ 11 ] [ 12 ] facilitated by JRC Corporate Consulting with ten investors. [ 13 ] [ 14 ]
In October 2021, MySyara announced a partnership agreement with AutoCentral. [ 15 ] [ 16 ]
In 2021, MySyara acquired a UAE-based auto parts distributor for $2.6 million [ 17 ] [ 18 ] and introduced “MySyara Supply” to streamline and integrate its supply chain operations. [ 19 ] [ 20 ] [ 21 ] The company, also, expanded to Abu Dhabi and Sharjah , with rising demand due to the pandemic . [ 22 ] [ 23 ]
As of September 2022, MySyara had raised a total of $5.5 million in funding. [ 24 ] It has 105,000 users and claims to have helped save over 11.5 million liters of water. [ 3 ]
In September 2024, MySyara partnered with Mobil UAE to launch the first cloud garage network in the UAE, aiming to open 20 locations by the end of 2025. [ 25 ] [ 26 ] | https://en.wikipedia.org/wiki/MySyara |
A myc tag is a polypeptide protein tag derived from the c-myc gene product that can be added to a protein using recombinant DNA technology. It can be used for affinity chromatography , then used to separate recombinant, overexpressed protein from wild type protein expressed by the host organism. It can also be used in the isolation of protein complexes with multiple subunits.
A myc tag can be used in many different assays that require recognition by an antibody and was originally identified in 1985. [ 1 ] If there is no antibody against the studied protein, adding a myc-tag allows one to follow the protein with an antibody against the Myc epitope. Examples are cellular localization studies by immunofluorescence or detection by Western blotting .
The peptide sequence of the myc-tag is (in 1- and 3-letter codes, respectively): EQKLISEEDL and Glu-Gln-Lys-Leu-Ile-Ser-Glu-Glu-Asp-Leu. The tag is approximately 1202 daltons in atomic mass and has 10 amino acids.
It can be fused to the C-terminus and the N-terminus of a protein. It is advisable not to fuse the myc-tag directly behind the signal peptide of a secretory protein, since it can interfere with translocation into the secretory pathway . [ 2 ]
A monoclonal antibody against the myc epitope , named 9E10, is available from the non-commercial Developmental Studies Hybridoma Bank . [ 3 ] | https://en.wikipedia.org/wiki/Myc-tag |
The term mycangium (pl., mycangia ) is used in biology for special structures on the body of an animal that are adapted for the transport of symbiotic fungi (usually in spore form). This is seen in many xylophagous insects (e.g. horntails and bark beetles), which apparently derive much of their nutrition from the digestion of various fungi that are growing amidst the wood fibers. In some cases, as in ambrosia beetles (Coleoptera: Curculionidae: Scolytinae and Platypodinae), the fungi are the sole food, and the excavations in the wood are simply to make a suitable microenvironment for the fungus to grow. In other cases (e.g., the southern pine beetle, Dendroctonus frontalis ), wood tissue is the main food, and fungi weaken the defense response from the host plant. [ 1 ]
Some species of phoretic mites that ride on the beetles, have their own type of mycangium, but for historical reasons, mite taxonomists use the term acarinarium . Apart from riding on the beetles, the mites live together with them in their burrows in the wood. [ 2 ] [ 3 ]
These structures were first systematically described by Helene Francke-Grosmann at 1956. [ 4 ] Then Lekh R. Batra [ 5 ] coined the word mycangia : [ 6 ] modern Latin, from Greek myco 'fungus' + angeion 'vessel'.
The most common function of mycangia is preserving and releasing symbiotic inoculum . Usually, the symbiotic inoculum in mycangia will benefit their vectors (typically insect or mites), helping them to adapt to the new environment or provide nutrients of the vectors themselves and their descendants . [ 7 ]
For example, the ambrosia beetle ( Euwallacea fornicatus ) carries the symbiotic fungus Fusarium . When the beetle bores a host plant, it releases the symbiotic fungus from its mycangium. The symbiotic fungus becomes a plant pathogen, acting to weaken the resistance of host plant. [ 8 ] In the meantime, the fungus grows quickly in the galleries as the main food of beetle. [ 8 ] After reproduction, maturing beetles will fill their mycangia with symbiont before hunting for a new host plant. [ 9 ]
Therefore, mycangia play an important role in protecting the inoculum from degradation and contamination. The structures of mycangia always resemble a pouch or a container, with caps or a small opening that reduce the possibility of contaminants from outside. [ 4 ] How mycangia release their inoculum is still unknown.
Most of the inoculum in mycangia are fungi. The symbiotic inoculum of most bark and ambrosia beetles are fungi belonging to Ophiostomatales ( Ascomycota : Sordariomycetidae ) and Microascales ( Ascomycota : Hypocreomycetidae ). [ 7 ] Symbiotic fungi in mycangia of woodwasps are Amylostereaceae ( Basidiomycota : Russulales ). [ 10 ] Symbiotic fungi in mycangia of lizard beetles are yeast ( Ascomycota : Saccharomycetales ). [ 11 ] Symbiotic fungi in mycangia of ship-timber beetles are Endomyces ( Ascomycota : Dipodascaceae ). [ 12 ] Symbiotic fungi in mycangia of leaf-rolling weevils are Penicillium fungi ( Ascomycota : Trichocomaceae ). [ 13 ] In addition to the above primary symbiotic fungi, secondary fungi and some bacteria have been isolated from mycangia. [ 14 ]
Mycangia of bark and ambrosia beetles ( Curculionidae : Scolytinae and Platypodinae ) are often complex cuticular invaginations for transport of symbiotic fungi. [ 2 ] [ 7 ] Phloem -feeding bark beetles ( Curculionidae : Scolytinae ) have usually numerous small pits on the surface of their body, while ambrosia beetles (many Scolytinae and all Platypodinae), which are completely dependent on their fungal symbiont, have deep and complicated pouches. [ 7 ] These mycangia are often equipped with glands secreting substances to support fungal spores and perhaps to nourish mycelium during transport. [ 15 ] In many cases, the entrance to a mycangium is surrounded by tufts of setae , aiding in scraping mycelium and spores from walls of the tunnels and directing the spores into the mycangium. The mycangia of ambrosia beetle are highly diverse. Different genera or tribes with different kinds of mycangia. Some are oral mycangia in the head, [ 7 ] such as genus Ambrosiodmus and Euwallacea . [ 16 ] Some are pronotal mycangia, such genus Xylosandrus and Cnestus . [ 17 ]
Mycangia of the woodwasps (Hymenoptera: Siricidae) were first described by Buchner. [ 18 ] Different from highly diverse types in bark and ambrosia beetles , woodwasps only have a pair of mycangia on the top of their ovipositor . Then when females deposit their eggs inside the host plant, they inject the symbiotic fungi from mycangia and phytotoxic mucus from another reservoir-like structure. [ 19 ]
One species of lizard beetle Doubledaya bucculenta (Coleoptera: Erotylidae: Erotylidae ) has mycangia on the tergum of the eighth abdominal segment. This ovipositor-associated mycangia is only present in adult females. Before Doubledaya bucculentnta deposit their eggs and inject the symbiotic microorganisms on a recently dead bamboo , they will excavate a small hole through the bamboo culm . [ 11 ]
The ship-timber beetle ( Coleoptera : Lymexylidae ) is another family of wood-boring beetles that live with symbiotic fungi. Buchner first discovered their mycangia located on the ventral side of the long ovipositor. [ 20 ] These mycangia form a pair of integumental pouches at either side near the tip of oviduct. When the female lays the eggs, new eggs are coated with the fungal spores.
Females of the leaf-rolling weevil in the genus Euops ( Coleoptera : Attelabidae ) store symbiotic fungi in the mycangia, which is between the first ventral segment of the abdomen and the thorax. [ 13 ] Different from ovipositor-associate mycangia in woodwasps, lizard beetles, and ship-timber beetles, mycangia of leaf-rolling weevils is a pair of spore incubators at the anterior end of the abdomen. This mycangium is formed by the coxa and the metendosternite at the posterior end of the thorax. [ 10 ]
Mycangia of the stag beetles ( Coleoptera : Lucanidae ) were discovered in Japan only this century. [ 21 ] This ovipositor-associated mycangium is located in a dorsal fold of the integument between the last two tergal plates of the adult females. It has been examined in many species. [ 22 ] [ 23 ] [ 24 ] A female everts the mycangium for the first time soon after eclosion; this is to retrieve the symbionts left by the larva on the pupal chamber when it emptied its gut before pupating. Later, when ovipositing, she everts it to pass on the inoculum to the next generation. [ 25 ] | https://en.wikipedia.org/wiki/Mycangium |
Since their inception, mycelium-based materials , more commonly referred to as mycelium composites, have been explored under diverse niches ranging from experimental to industrial scales. Mycelium , the root-like structure that comprises the main vegetative growth of fungi , has been identified as an ecologically friendly stand-alone / composite substitute to a litany of materials throughout different industries, including but not limited to packaging, design, building, fashion and cosmetics applications. Mycelium composites present a sustainable biodegradable alternative to conventional materials that can convert waste into primary feedstock. [ 1 ] Critical perspectives might situate mycelium composites that are inert (dehydrated or baked, limiting its growth) within the field of biomaterials, in contrast to untreated mycelium applications (subject to evolving growth) falling within the field of engineered living materials. [ 2 ]
Some of the first reported interdisciplinary explorations weaving between art and design date back to the 1990s led by Philip Ross. [ 3 ] The artist started cultivating G. lucidum (reishi) for its medicinal and immune-supporting properties in the context of the HIV outbreak, eventually working with the fungal specie under the sculptural lens as mycotecture, a term he coined referring to the practice of designing and building with fungi. Mycelium was first explored as an eco-friendly commercial material alternative in 2006. Eben Bayer and Gavin McIntyre further popularized the biotechnology by developing mycelium packaging while founding their company, Ecovative (2007), during their time at Rensselaer Polytechnic Institute . Only later in 2013, Philip Ross founded the company MycoWorks alongside storyteller Sophia Wang, best known for their mycelium leather. Shortly after, the italian-based company Mogu, was founded by Maurizio Montalti in 2015, mainly leading the fabrication of wall and acoustics panels, and flooring tiles.
The hyphal network that provides structural cell walls for the fungal organisms' growth are found within three different types that correspond to its sporocarps; generative, skeletal and ligative. Hyphal systems fall under three categories – monomitic, dimitic, and trimitic. [ 5 ] [ 6 ] While monomitic hyphae are generative, dimitic systems have a combination of generative and skeletal (most common) or ligative. As for trimitic systems, they are composed of all three hyphal typologies. These traits are valuable as they have an influence on the resulting mechanical properties of the composite matrix, which can inform the selection of species for targeted applications. [ 7 ]
Mycelium-based composites are made from a fungal culture and a substrate. When introduced to a fibrous substrate, mainly composed of lignocellulose, the fungi begin to break down the fibers into basic nutrients, which enable the organisms' growth. In the case of composites, the substrate is only partially decomposed during this enzymatic process, creating a hybrid intertwined with the mycelium. [ 8 ]
The main components of fungi are chitin, polysaccharides, lipids, and proteins. [ 4 ] Different compositional amounts of these molecules change the properties of the composites. This is also true for different substrates. Substrates that have higher amounts of chitin and are harder for the mycelium to break down and lead to a stiffer composite formation. [ 8 ] [ 4 ]
Commonly used species of fungi to grow mycelium are aerobic basidiomycetes, which include Ganoderma sp., Pleurotus sp., and Trametes sp. [ 9 ] Basidiomycetes have favorable properties as fungi for creating mycelium based composites because they grow at a relatively steady and quick pace, and can use many different types of organic waste as substrates. [ 8 ] Some characteristics that these species differ in are elasticity, water absorption, and strength.
As an example, Trametes hirsuta forms a thicker outer layer of mycelium than Pleurotus ostreatus . This allows the Trametes hirsuta composite to remain flexible and stable in high moisture environments. [ 9 ] Additionally, Ganoderma lucidum exhibited higher elasticity, even with different types of substrates. [ 9 ] Different combinations of fungi, substrate, and environmental conditions can all affect the properties of the resulting composite; this area of research continues to be explored as the applications for mycelium-based composites expand.
The initial step in the production of mycelium-based materials is the growth process. The incubation of fungal mycelium requires a ventilated dark environment operating within a specific range of temperature situating between 25-30 °C and humidity settings around 70-80%. [ 6 ] The selective pairing of specie with substrate will affect the overall time of mycelial growth and will lead to different properties that will be further discussed below. The average time, however will also depend on the size of the composite and can vary anywhere from 6–20 days up until several weeks. [ 6 ]
The growth of the organisms happens is three phases; the lag phase, the exponential phase, and the stationary phase. Initially, the lag phase consists of the mycelium cells' introduction to its new environment with little to no population growth. The exponential phase is where the mycelium can develop, increasing in biomass and cell number, if the conditions are appropriate. Lastly, the stationary phase occurs when the fungal biomass stabilizes and the population growth falls back to zero. [ 10 ] If left past this stage, the mycelium-based material can start to form fruiting bodies, which is ideally avoided to ensure that the shape and heterogeneity are maintained. [ 6 ] The composites must then be dehydrated or baked to become inert and stable. Continued research explores various optimization techniques ensuring foreseeable growth time and material characteristics. [ 11 ]
In order to form the structures of the composites, mycelium needs a substrate to grow into. To fabricate these mycelium based composites outside of natural processes, options for substrates include common “left-over” materials such as wood and straw. [ 12 ] Recycling waste products contributes to the mycelium based composites' low cost and environmental-friendliness over the current methods and materials. [ 12 ]
For most industrial materials there is a high degree of control in the processing methods of the final product leading to standardized properties. Mycelium composites still hold many open variables that can significantly effect the material behaviour ranging growth time and conditions, pH and moisture of substrate, and post-treatments. [ 7 ] At the cellular level, there is a mixture of elements that will provide material rigidity and strength, such as the content of chitin, chitosan, glucans, manoproteins, and cellulose, to name a few. [ 1 ] Research suggests that the concentration of chitin for instance, can be measured by the difficulty of the mycelium to break down the sugars in the substrate, leading to a stiffer material as opposed to one that gets digested very easily by the organism. [ 13 ] A recent study focused on the comparative analysis of substrate granulation to understand the compressive behaviour, where the authors indicate that the orientation of fibres and particle size leading up to ultimate strength. [ 14 ] Between a range of three granulations from small (0.5–1.0 mm), medium (0.75–3.0 mm), and large (4.0–12.0 mm), the 34 x 34 x 140 mm samples using particles in the 0.75–3.0 mm range proved to be stronger and stiffer. [ 14 ]
The mechanical tests included uniaxial tension and compression, conducted using a specific testing machine and performed in ambient conditions. For the tensile tests, dog bone specimens of dimensions 200 mm × 6 mm × 3.5 mm were used. Cuboid specimens of dimensions 20 mm × 20 mm × 16 mm were tested under compression. The strain rate chosen was 4 × 10−4 per second until failure for tensile tests whereas compressive samples were deformed at a rate of 6.25 × 10−3 per second ranging from 2% to 20%. [ 15 ]
IKEA has committed to mycelium packaging, making a deal with Ecovative acknowledging the damage that comes from polystyrene packaging and the time it takes the decompose. [ 16 ] Plastic foams can take hundreds of years to decompose whereas mushroom based materials can decompose in a few weeks. [ 16 ] At Ecovative, they grow mushroom packaging known as MyoComposite which can be grown in less than a week where this manufacturing starts at the Ecovative Design foundry in Green Island, New York. Ecovative partners with multiple local farmers in order to source agricultural products that get turned into packaging. The agricultural materials are cleaned and sorted into molds where the fungi is added and will grow around the material. Once the fungus grows throughout the mold, the final packaging is specially treated to stop the growth process. [ 16 ] According to another company, Grown Bio, mycelium based packaging also has advantages because of the versatility of design shapes as well as having a high shock absorbance and insulation properties. [ 17 ] They use a 3D printed reusable mold made from a biopolymer to template their products which are then filled with agricultural waste, water, and lastly the mycelium. The entire process takes a week and once the packaging has served its use, it breaks down and can be used as fertilizer. [ 17 ]
In 2012 Ecovative partnered with Sealed Air, at the time a $7.6 billion global company best known for bubble wrap and other packaging, [ 18 ] to license their process for making mycelium-based packaging material.
Mycelium based composites have not yet been widely considered as alternatives for wood, or masonry construction. When considering large-scale applications, there are a few avenues for the fabrication of mycelium composites, although the most common consist of external or internal molds for modular units, in-situ monoliths, or myco-welding. [ 19 ] The growth guided with external molds is led with a formwork that will eventually be removed to reveal the material in its desired shape, in contrast to an internal mold, also referred to as a soft mold, which acts as a scaffold that remains embedded in the composite. [ 20 ] [ 21 ] [ 22 ] The in-situ monolithic typology references traditional cast-in-place techniques for casting and growing composites at a larger non-modular scale. Lastly, myco-welding bridges these two techniques as it works with living assembly units to render them monolithic, essentially keeping the organism alive in order to create bonding between a block, a layer, or panel with one another. [ 19 ]
Over the years, we [ who? ] have seen several examples of outdoor pavilions, such as the Homegrown Wonderland designed by Andre Kong studio with the mycelium bricks provided by Ecovative at the New York Botanical Garden (2024); the MycoTemple] by Côme Di Meglio (2021); the [ https://jdovaults.com/El-Monolito-Micelio Mycelium Monolith by the research group at UNC Charlotte led by Jonathan Dessi-Olive (2018); or the Hy-Fi pavilion by the Living at MoMA PS1 (2014).
As a load-bearing building application that exceeds the temporary installation timeframe, one of the first precedents has been realized in 2024 by MycoHAB, a pilot project located in Namibia. It came to exist through the BioHAB; a merging of the Johannesburg-headquartered Standard Bank Group, the Massachusetts Institute of Technology Center for Bits and Atoms, the MIT Label Free Research Group, and the architecture firm redhouse, based in Cleveland. They make use of an invasive bush as feedstock to cultivate gourmet oyster mushrooms, which eventually generates a leftover mycelium mass that gets pressed into structural composites blocks. The stand-alone material is then treated with a mud-plaster finishing on the exterior face to protect it from weathering.
However, there are still some challenges linked with mycelium composites as a choice for building materials. The first is the novelty of these materials. They are not yet accepted as replacements for common construction materials because researchers are still working to understand their properties and how these properties are affected by time, environmental conditions, substrate, and fungal species. Mycelium composites also have issues with water absorption. [ 12 ] Too much water absorption will lead the composites to fail under their mechanical loads. [ 12 ] The relationship between density and water absorption was analyzed to find that composites with a higher density were only slightly affected by the levels of humidity, but remained mechanically sound by the standard necessary for construction materials. [ 23 ]
As with other common building applications, mycelium based materials have also been considered for the application of acoustic dampening. Some species recently under particular consideration include Pleurotus ostreatus (Oyster Mushrooms) and many individual species from the phylum class Basidiomycetes , the latter class being known to have mycelium bodies composed primarily of chitin. [ 24 ] [ 25 ]
In order to construct said acoustic panels, the filamentous hyphae of the fungal body must be isolated, harvested and processed. This can be done through careful control of humidity, temperature (85-95F), atmospheric CO 2 concentration (5-7%) and chemical/hormonal additives ( forskolin /10-oxo-trans-8-decenoic acid (ODA)), in order to not only increase the volume of growth but also encourage the resultant growth to consist of a higher percentage of useful biopolymer material. Fine control over the proportion of cross linkages within the resulting chitin biopolymer is also possible. [ 15 ]
To construct a panel of acoustic dampening material, the fungus can be mechanically suspended within a rigid chamber, and allowed to grow to fill the space. After the space has been filled, the mycelium is compressed and allowed to grow again into the resultant space, after which the product is dried and post processed for specific applications (embossing or decorative purposes). [ 15 ]
Studies have found that the resultant paneling, when compared to conventional acoustic dampening materials like foam , cork , felt , cotton and ceiling tiles , displayed comparable acoustic absorption in frequencies around 3000 Hz and above, while falling short in performance at frequencies below 3000 Hz. [ 25 ] [ 13 ] Performance of any given panel is highly dependent on the mix of substrate, species and other previously mentioned variables, and yield varying absorbance profiles. [ 13 ]
The industry niche of designing mycelium based acoustic damping panels is currently being developed by companies like Mogu, pursuing the market with their FORESTA acoustic panel system. [ 13 ] [ 26 ]
Within the contemporary fashion industry there has been a push for more ethically sourced materials in order to alleviate environmental concerns. [ 27 ] [ 28 ] To fulfil these needs, companies like Mycoworks, Ecovative, and Sqim (Ephea/Mogu), have developed sustainable materials to substitute for leather of varying thicknesses and applications. [ 29 ] [ 30 ] The first mycelium leather wearable garment was produced by Sqim through Ephea in collaboration with the fashion house of Givenchy (2022). Shortly after, Mycoworks followed with their first fashion runway debut in collaboration with Swedish brand Deadwood Studios (2023).
Beyond textiles, mycelium based materials have also found use for substitution in makeup wedges, eye masks and sheet masks. [ 31 ] Fungi contain a multitude of bioactive compounds such as, terpenoids, selenium, phenolics, polyphenolics, vitamins, polysaccharides, and volatile organic compounds. [ 32 ] The extracts provide skin care benefits as moisturizing, anti-aging, anti-oxidant, anti-wrinkle, anti-acne and anti-dandruff agent. [ 32 ] In particular, the specie Ceriporia lacerata was studied for skin aging, effectively increasing collagen while preventing skin barrier damage and wrinkles. [ 33 ] In addition, it demonstrated anti-inflammatory and wound-healing effects presenting itself as a great potential ingredient in cosmeceutical skin care. [ 33 ] | https://en.wikipedia.org/wiki/Mycelium-based_materials |
A mycetome is a specialized organ in a variety of animal species which houses that animal's symbionts , isolating them from the animal's natural cellular defense mechanisms and allowing sustained controlled symbiotic growth. In several species, such as bed bugs and certain families of leech , these symbionts are attached to the gut and aid in the production of vitamin B from ingested meals of blood. [ 1 ] In insects, the organisms that inhabit these structures are either bacteria or yeasts. [ 2 ]
In bed bugs, it has been found that heat stress can cause damage to the mycetome, preventing the symbionts from being successfully passed from the adult female to her eggs at the time of oogenesis , causing the resulting nymphs to develop abnormally or to die prematurely. [ 3 ] | https://en.wikipedia.org/wiki/Mycetome |
Mycobiota ( plural noun , no singular) are a group of all the fungi present in a particular geographic region (e.g. "the mycobiota of Ireland ") or habitat type (e.g. "the mycobiota of cocoa "). [ 1 ] [ 2 ] An analogous term for Mycobiota is funga .
Mycobiota exist on the surface and in the gastrointestinal system of humans. [ 3 ] There are as many as sixty-six genera and 184 species in the gastrointestinal tract of healthy people. Most of these are in the Candida genera. [ 3 ] [ 4 ] [ 5 ]
Though found to be present on the skin and in the gi tract in healthy individuals, the normal resident mycobiota can become pathogenic in those who are immunocompromised . [ 6 ] [ 7 ] Such multispecies infections lead to higher mortalities. [ 8 ] In addition hospital-acquired infections by C. albicans have become a cause of major health concerns. [ 9 ] [ 10 ] A high mortality rate of 40-60% is associated with systemic infection. [ 10 ] [ 11 ] [ 12 ] [ 13 ] [ 14 ] [ 5 ] The best-studied of these are Candida species due to their ability to become pathogenic in immunocompromised and even in healthy hosts. [ 13 ] [ 14 ] [ 5 ] Yeasts are also present on the skin, such as Malassezia species, where they consume oils secreted from the sebaceous glands . [ 15 ] [ 16 ] [ 12 ] Pityrosporum (Malassezia) ovale , which is lipid -dependent and found only on humans. P. ovale was later divided into two species, P. ovale and P. orbiculare , but current sources consider these terms to refer to a single species of fungus, with M. furfur the preferred name. [ 17 ]
There is a peer reviewed mycological journal titled Mycobiota . | https://en.wikipedia.org/wiki/Mycobiota |
Mycocepurus smithii is a species of fungus-growing ant from Latin America . This species is widely distributed geographically and can be found from Mexico in the north to Argentina in the south, as well as on some Caribbean Islands. [ 1 ] [ 2 ] [ 3 ] It lives in a variety of forested habitats and associated open areas. [ 2 ] Two studies published in 2009 demonstrated that some populations of the species consist exclusively of females which reproduce via thelytokous parthenogenesis . [ 4 ] [ 5 ] A detailed study found evidence of sexual reproduction in some populations in the Brazilian Amazon. [ 3 ] Accordingly, M. smithii consists of a mosaic of sexually and asexually reproducing populations. [ 3 ] In asexual populations all ants in a single colony are female clones of the queen . [ 3 ] Inside the colony, the ants cultivate a garden of fungus grown with pieces of dead vegetable matter, dead insects, and insect droppings. [ 6 ] [ 7 ]
Ants of the genus Mycocepurus are distinctly recognizable for the crown-like cluster of spines on their promesonotum, the fused mesonotum and pronotum on the front of their mesosoma or midsection. Mycocepurus smithii has sharp, protruding propodeal (posterior of the alitrunk) spines unlike M. obsoletus whose propodeal spines are blunt. Workers also do not have developed promesonotal spines in the center of their crown, which separates M. smithii from M. goeldii and similar species. [ 1 ] [ 2 ]
Initially, M. smithii was thought to only reproduce asexually because no evidence of male individuals had been found. This led to M. smithii being recognized as the first fungus-growing ant species to reproduce via thelytokous parthenogenesis, where females, the workers and reproductive queens, are produced asexually. [ 5 ] [ 4 ] The cytogenetic mechanism of thelytoky is either apomixis (mitotic parthenogenesis) or automixis with central fusion and low recombination rates. [ 3 ] Automixis with central fusion is the cytogenetic mechanism that was recorded in other asexual ant species. [ 8 ] Nests with multiple dealated queens are often found, suggesting that M. smithii is a polygynous species. [ 5 ] [ 6 ] [ 7 ] This appears to be a case of secondary polygyny, and the queens may be daughters of the foundress. [ 6 ]
A detailed study of many M. smithii populations across their geographic distribution range (Mexico to Argentina) showed that some M. smithii populations in the Brazilian Amazon reproduce sexually. This was demonstrated using highly variable genetic markers . Sperm was also found stored in the spermathecas of queens. Sexual reproduction was suggested as a mechanism for maintaining the genetic diversity seen in this species. [ 3 ] In summary, M. smithii is not purely asexual, but instead consists of a "mosaic" of sexual and asexual populations. Phylogenetic reconstructions and the biology of the species suggest that these sexual populations gave rise to the asexual ones. [ 3 ] The mechanism behind the shift to asexuality is still unknown. However, antibiotic assays and genetic screenings suggest that it is not an endosymbiont such as Wolbachia causing the asexuality. [ 4 ] In fact, a comparative analysis showed that Wolbachia endosymbionts do not seem to cause asexuality in ants in general. [ 8 ]
The nests and colonies of M. smithii were studied in great detail in Puerto Rico and Brazil . [ 6 ] [ 7 ] [ 5 ] On the surface, M. smithii nests can be recognized by their nest mounds consisting of excavated soil and clay. A nest entrance of roughly 1.2 mm in diameter is located in the center of each nest mound. Large M. smithii nests, which are presumably older, can contain up to 7 or so chambers. [ 5 ] [ 6 ] [ 7 ] Some fungus chambers are shallow whereas others can be found in great depths, as deep as 2 meters. [ 7 ] The abandoned chambers are used to deposit waste from the fungus garden and loose soil from chamber construction. The number of nest chambers tends to increase as colonies grow older. [ 7 ] Because M. smithii queens are capable of asexual reproduction, it is believed that colonies can also grow by budding [ 7 ] in addition to independent colony foundation. [ 5 ] Colonies that grow by budding can result in large colony networks. [ 7 ]
Workers of M. smithii ants maintain narrow tunnels (diameter of 1.3 mm), which do not allow two ants to pass each other in the tunnel (head size is around 0.7 mm for workers and 0.9 mm for queens). The tunnels also have a number of slightly larger sections (about 3.6 mm diameter), which would allow passing while also facilitating information exchange. Narrow tunnels are presumably easier (energetically cheaper) to construct and may also aide in leveling the humidity or temperature of the colony or preventing predatory intrusions. [ 6 ] [ 7 ] In general, M. smithii colonies are smaller than the colonies of M. goeldii . [ 5 ] [ 7 ]
When founding a new colony, young queens either shed their wings prior to excavating the nest or just inside. They then excavate a tunnel to a depth of roughly 10 cm (4 in) and create a primary chamber. The dealate, or wingless, queen then carries the wings into the primary chamber and inserts them into the chamber ceiling where the surface of the wings is used as a platform for growing an incipient fungus garden. She will also forage around the nest entrance for caterpillar droppings to feed the fungus garden. The female fore wings of all so-called Paleoattini (the genera Mycocepurus , Apterostigma , and Myrmicocrypta ) have a crescent-shaped spot lacking any veins, hairs, and pigmentation, and is thought to provide an "easy to clean" platform for the fungus garden. [ 6 ] Queens of the socially parasitic species Mycocepurus castrator do not found their colonies independently, and the clear spot is absent from their wings. [ 9 ] This indirectly supports the idea that the wing spot has a function during the early colony founding and fungus cultivation stage of independently founding Mycocepurus queens. [ 9 ] As the colony matures, workers develop and then tend to the fungus garden, feeding it dried leaves, caterpillar droppings, and other debris from the leaf-litter. [ 6 ] [ 7 ]
One trait of M. smithii cultivation is that, unlike higher attines, they use a wide diversity of fungal lineages for their gardens. [ 10 ] [ 11 ] Lineages of M. smithii have undergone many cultivar shifts over time. This tendency to shift cultivars is hypothesized to be a mechanism for helping to offset some of the costs of asexuality. [ 12 ] Also unlike other fungus-growing ants M. smithii has a microbiome that is distinct from the surrounding soil. [ 13 ] A Brazilian population of M. smithii has a fungal cultivar with gongylidia -like structures. This is unusual, because gongylidia are the nutrient rich food bodies produced by the fungi of leaf-cutting ants – and leaf-cutting ants are rather distant relatives of Mycocepurus. [ 14 ] | https://en.wikipedia.org/wiki/Mycocepurus_smithii |
Mycoestrogens are xenoestrogens produced by fungi . They are sometimes referred to as estrogenic mycotoxins . [ 1 ] Some important mycoestrogens are zearalenone , zearalenol and zearalanol . [ 2 ] Although all of these can be produced by various Fusarium species, [ 3 ] [ 4 ] zearalenol and zearalanol may also be produced endogenously in ruminants that have ingested zearalenone. [ 5 ] [ 6 ] Alpha-zearalanol is also produced semisynthetically, for veterinary use; such use is prohibited in the European Union. [ 7 ]
Mycoestrogens act as agonists of the estrogen receptors , ERα and ERβ .
Mycoestrogens are produced by various strains of fungi, many of which fall under the genus Fusarium . Fusarium fungi are filamentous fungi that are found in the soil and are associated with plants and some crops, especially cereals. [ 8 ] Zearalenone is mainly produced by F. graminearum and F. culmorum strains, which inhabit different areas depending on temperature and humidity. F. graminearum prefers to inhabit warmer and more humid locations such as Eastern Europe, Northern America, Eastern Australia, and Southern China in comparison to F. colmorum which is found in colder Western Europe. [ 9 ]
Mycoestrogens mimic natural estrogen in the body by acting as estrogen receptor (ER) ligands. [ 8 ] Mycoestrogens have been identified as endocrine disruptors due to their high binding affinity for ERα and ERβ, exceeding that of well known endocrine disruptors such as bisphenol A and DDT. [ 10 ] Studies have been performed that strongly suggest a relationship between detectable levels of mycoestrogen and growth and pubertal development. More than one study has shown that detectable levels of zearalenone and its metabolite alpha-zearalanol in girls are associated with significantly shorter heights at menarche. [ 1 ] [ 10 ] Other reports have documented premature onset of puberty in girls. Estrogen are known to cause decreased body weight in model animals, and the same effect has been seen in rats exposed to zearalenone. [ 11 ] Interactions of ZEN and its metabolite with human androgen receptors (hAR) have also been documented. [ 9 ]
Zearalenone has two major phase I metabolites: α-zearalenol and β-zearalenol. [ 11 ] [ 9 ] When exposed orally ZEN is absorbed by the intestinal lining and metabolized there as well as in the liver. [ 11 ] Research into the metabolism of ZEN has been difficult because of the significant difference in biotransformation between species making comparison challenging.
The first transformation of metabolism of ZEN will reduce the ketone group to an alcohol via aliphatic hydroxylation and result in the formation of the two zearalenol metabolites. This process is catalyzed by 3 α- and 3 β-hydroxy steroid dehydrogenase (HSD). CYP450 enzymes will then catalyze aromatic hydroxylation at the 13 or 15 position resulting in 13- or 15- catechols. Steric hindrance of at the 13 position is suspected to be the reason that in humans and rats there is more of the 15-catechol present. The catechols are the processed into mono-ethyl esters by catechol-o-methyl transferase (COMT) and S-adenosyl methionine (SAM). After this transformation they may be metabolized further to quinones which can cause the formation of reactive oxygen species (ROS) and cause covalent modification of DNA. [ 12 ]
In phase-II metabolizing includes glucuronidation and sulfation of the mycoestrogen compound. Glucuronidation is the major phase II metabolic pathway. The transferase UGT (5'-diphosphate glucuronosyltransferase) adds a glucuronic acid group sourced from uridine 5'-diphosphate glucuronic acid (UDPGA). [ 12 ]
Mycoestrogens and their metabolites are largely excreted in urine in humans and in feces in other animal systems. [ 12 ]
Mycoestrogens are commonly found in stored grain. They can come from fungi growing on the grain as it grows, or after harvest during storage. Mycoestrogens can be found in silage . [ 13 ] Some estimates state that 25% of global cereal production and 20% of global plant production may be at some point contaminated by mycotoxins of which mycoestrogens, especially those from fusarium strains, may make up a significant portion. [ 9 ] Among mycoestrogens that contaminate plants are ZEN and its phase I metabolites. The limit for ZEN in unprocessed cereals, milling products, and cereal foodstuffs is 20-400 μg/kg (depending on the product in question). [ 9 ]
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Mycoestrogen |
Mycofactocin ( MFT ) is a family of small molecules derived from a peptide of the type known as RiPP (ribosomally synthesized and post-translationally modified peptides), naturally occurring in many types of Mycobacterium . It was discovered in a bioinformatics study in 2011. [ 1 ] All mycofactocins share a precursor in the form of premycofactocin ( PMFT ); they differ by the cellulose tail added. Being redox active, both PMFT and MFT have an oxidized dione (mycofactocinone) form and a reduced diol (mycofactocinol) form, respectively termed PMFTH 2 and MFTH 2 . [ 2 ]
The name "mycofactocin" is derived from three words, the genus name " Mycobacterium " (across which it is nearly universal), " cofactor " because its presence in a genome predicts the co-occurrence of certain families of enzymes as if it is a cofactor they require, and " bacteriocin " because a radical SAM enzyme critical to its biosynthesis, MftC, is closely related to the key enzyme for the biosynthesis of subtilosin A, a bacteriocin, from its precursor peptide.
An MFT with a glucose tail of n units is termed MFT- n ; MFT- n H 2 in the reduced form. [ 2 ] An MFT with a 2-O-methylglucose is termed a methylmycofactocin (MMFT), with analogous numbering. [ 2 ]
Mycofactocin is thought to play a role in redox pathways involving nicotinoproteins, enzymes with non-exchangeable bound nicotinamide adenine dinucleotide (NAD). [ 3 ] This notion comes largely from comparative genomics work that highlighted the many parallels between mycofactocin and pyrroloquinoline quinone (PQQ). [ 4 ] In both cases, maturation of the RiPP requires post-translational modification of a precursor peptide by a radical SAM enzyme, the system appears in very similar form in large numbers of species, the product appears to be used within the cell rather than exported, and several families of enzymes occur exclusively in bacteria with those systems. The number of putatively mycofactocin-dependent oxidoreductases encoded by a single genome can be quite large: at least 19 for Rhodococcus jostii RHA1, and 26 for the short chain dehydrogenase/reductase (SDR) family alone in Mycobacterium avium.
The enzyme LimC ( Q9RA05 ), a nicotinoprotein carveol dehydrogenase (EC 1.1.1.n4), is shown to use both MFT and PMFT in vitro . [ 2 ]
The mycofactocin biosynthesis pathway is one of the most abundant of any RiPP system in the collection of bacterial genomes sequenced to date. However, its species distribution is heavily skewed towards the Actinomycetota , including Mycobacterium tuberculosis , which is the causative agent of tuberculosis and therefore the number one killer among bacterial pathogens of humans. The system is virtually absent from the normal human microbiome , although common in soil bacteria.
Mycofactocin, therefore, is not a single compound, but instead a mixture of closely related electron carriers that differ in the nature of their attached oligosaccharides. | https://en.wikipedia.org/wiki/Mycofactocin |
Mycoforestry is an ecological forest management system implemented to enhance forest ecosystems and plant communities, by introducing the mycorrhizal and saprotrophic fungi . Mycoforestry is considered a type of permaculture [ 1 ] and can be implemented as a beneficial component of an agroforestry system. It can enhance the yields of tree crops and produce edible mushrooms , an economically valuable product. By integrating plant-fungal associations into a forestry management system, native forests can be preserved, wood waste can be recycled back into the ecosystem, carbon sequestration can be increased, planted restoration sites are enhanced, and the sustainability of forest ecosystems are improved. [ 2 ] [ 3 ] Mycoforestry is an alternative to the practice of clearcutting , which removes dead wood from forests, thereby diminishing nutrient availability and reducing soil depth. [ 4 ]
According to Paul Stamets , the first principle for the creation of a mycoforestry system is to utilize native fungal species. Implementing a mycoforestry system provides the potential of improving restoration efforts and the possibility of economic gain through mushroom cropping and harvesting. However to utilize native fungal flora, first the relationships between present fungal species and growth substrate, and habitat need to be studied.
A simple way to introduce a mycoforestry system and enhance out-plantings for crops and forest restoration sites is to "use mycorrhizal spore inoculum when replanting forest lands." [ 2 ] For this process it is best to match native trees with native mycorrhizal fungi. This method keeps and will promote the functioning of the native ecosystem, and native biodiversity.
It is assumed in a functioning forest ecosystem an underground mycelial network persists even if no fruiting bodies are visible. [ 5 ] A period of disappearance of mushrooms from an area should not cause alarm. In order to trigger the formation of fruiting bodies, many fungal species require specific environmental conditions. Most species of fungi do not fruit year round.
Mycoforestry is an emergent scientific field and practice. [ 2 ] Until broadly standardized protocols are created and perfected, the collection of both current and historical ecological site conditions will improve the success of the project. [ 2 ] Therefore, a survey of fungal relations at the site under both prime and poor conditions is beneficial to implementation of a mycoforestry system.
The second principle is to promote saprotrophic fungi in the environment. [ 2 ] Saprophytic fungi are crucial to mycoforestry systems because these are the primary composers breaking down wood and returning nutrients to the soil for use by the rest of the forest ecosystem. This can be accomplished through inoculation of wood debris at site. Spored oils (biodegradable oils containing fungal spores) can be used in chainsaws when problematic or invasive hardwood requires felling. This method is a simple means to inoculate a tree. Additionally plug spawn can be implemented and injected into wood mass again prompting colonization by the selected fungus. Eventually repeated colonization efforts should not be necessary as many fungal life forms are strong and will spread and sustain in the soil on their own. [ 5 ]
In management of the mycoforestry system, it is important that dead wood be in contact with the ground. This allows fungus to reach up from the soil and decompose fallen wood releasing nutrients at a much quicker rate then if the wood is left standing. [ 2 ] Additionally, it is important to leave dead wood on site for decomposition back into the soil. [ 2 ] This philosophy is similarly based to the fact that clearcutting of a forest reduces soil nutrients and thickness. [ 4 ]
The third principle is to implement species known to benefit plant species. [ 2 ] These are commonly mycorrhizal fungus that form long term associations with plants, often extending inside of plants roots, acting as an additional root system, and improving absorption of nutrients and water.
Utilizing mushroom species that attract insects could be a useful source of fish food. This practice makes the mycoforestry a larger system. Unlike most agriculture systems it helps the environment in a number of ways. It ties all biological aspects of the environment together, creating sustainable living and food production as well as sustainable fisheries similar to the ancient Hawaiian Ahupua'a , which utilized sustainable all portions of the land for environmental and food security . [ 6 ]
Additionally fungal species can be implemented that compete with disease-causing agents like Armillaria root rots , [ 2 ] to provide long term protection of the forestry system.
Additionally, the implementation of an agroforestry system performs mycoremediation and mycofiltration activities, cleaning up toxins and restoring the environment. | https://en.wikipedia.org/wiki/Mycoforestry |
Mycological Progress is a peer-reviewed scientific journal covering the study of fungi including lichens . It is published by Springer Science+Business Media on behalf of the German Mycological Society . Its editor in chief is Marco Thines . [ 1 ]
The journal was established in February 2002 by the German Mycological Society under founding editor-in-chief, Franz Oberwinkler ( University of Tübingen ). The current editor-in-chief is Marco Thines, who is also the president of the German Mycological Society. Originally published by botanical publisher, IHW-Verlag ( Eching ), the title transferred to Springer in 2006 by which time it was the official journal of ten European national mycological societies. [ 2 ] [ 3 ] It was published quarterly until 2015 when it converted to continuous publication online and production of the printed version ceased. [ 4 ]
The journal is abstracted and indexed in: [ 5 ]
According to the Journal Citation Reports , the journal has a 2018 impact factor of 2.0. [ citation needed ]
This article about lichens or lichenology is a stub . You can help Wikipedia by expanding it .
This article about a mycology journal is a stub . You can help Wikipedia by expanding it .
See tips for writing articles about academic journals . Further suggestions might be found on the article's talk page . | https://en.wikipedia.org/wiki/Mycological_Progress |
Mycology is the branch of biology concerned with the study of fungi , including their taxonomy , genetics , biochemical properties, and use by humans . [ 1 ] Fungi can be a source of tinder , food , traditional medicine , as well as entheogens , poison , and infection . Yeasts are among the most heavily utilized members of the fungus kingdom, particularly in food manufacturing. [ 2 ]
Mycology branches into the field of phytopathology , the study of plant diseases. The two disciplines are closely related, because the vast majority of plant pathogens are fungi. A biologist specializing in mycology is called a mycologist .
The word mycology comes from the Ancient Greek : μύκης ( mukēs ), meaning "fungus" and the suffix -λογία ( -logia ), meaning "study." [ 3 ] Pioneer mycologists included Elias Magnus Fries , Christiaan Hendrik Persoon , Heinrich Anton de Bary , Elizabeth Eaton Morse , and Lewis David de Schweinitz . Beatrix Potter , author of The Tale of Peter Rabbit , also made significant contributions to the field. [ 4 ]
Pier Andrea Saccardo developed a system for classifying the imperfect fungi by spore color and form, which became the primary system used before classification by DNA analysis . He is most famous for his Sylloge Fungorum , [ 5 ] which was a comprehensive list of all of the names that had been used for mushrooms . Sylloge is still the only work of this kind that was both comprehensive for the botanical kingdom Fungi and reasonably modern. [ 6 ]
Many fungi produce toxins , [ 7 ] antibiotics , [ 8 ] and other secondary metabolites . For example, the cosmopolitan genus Fusarium and their toxins associated with fatal outbreaks of alimentary toxic aleukia in humans were extensively studied by Abraham Z. Joffe . [ 9 ]
Fungi are fundamental for life on earth in their roles as symbionts , e.g. in the form of mycorrhizae , insect symbionts, and lichens . Many fungi are able to break down complex organic biomolecules such as lignin , the more durable component of wood , and pollutants such as xenobiotics , petroleum , and polycyclic aromatic hydrocarbons . By decomposing these molecules, fungi play a critical role in the global carbon cycle .
Fungi and other organisms traditionally recognized as fungi, such as oomycetes and myxomycetes ( slime molds ), often are economically and socially important, as some cause diseases of animals (including humans) and of plants. [ 10 ]
Apart from pathogenic fungi, many fungal species are very important in controlling the plant diseases caused by different pathogens. For example, species of the filamentous fungal genus Trichoderma are considered one of the most important biological control agents as an alternative to chemical-based products for effective crop disease management. [ 11 ]
Field meetings to find interesting species of fungi are known as 'forays', after the first such meeting organized by the Woolhope Naturalists' Field Club in 1868 and entitled "A foray among the funguses [ sic ]". [ 12 ]
Some fungi can cause disease in humans and other animals; the study of pathogenic fungi that infect animals is referred to as medical mycology . [ 13 ]
It is believed that humans started collecting mushrooms as food in prehistoric times. Mushrooms were first written about in the works of Euripides (480–406 BC). The Greek philosopher Theophrastos of Eresos (371–288 BC) was perhaps the first to try to systematically classify plants; mushrooms were considered to be plants missing certain organs. It was later Pliny the Elder (23–79 AD), who wrote about truffles in his encyclopedia Natural History . [ 14 ]
Fungi and truffles are neither herbs, nor roots, nor flowers, nor seeds, but merely the superfluous moisture or earth, of trees, or rotten wood, and of other rotting things. This is plain from the fact that all fungi and truffles, especially those that are used for eating, grow most commonly in thundery and wet weather.
The Middle Ages saw little advancement in the body of knowledge about fungi. However, the invention of the printing press allowed authors to dispel superstitions and misconceptions about the fungi that had been perpetuated by the classical authors. [ 16 ]
The start of the modern age of mycology begins with Pier Antonio Micheli 's 1737 publication of Nova plantarum genera . [ 17 ] Published in Florence , this seminal work laid the foundations for the systematic classification of grasses, mosses and fungi. He originated the still current genus names Polyporus [ 18 ] and Tuber , [ 19 ] both dated 1729 (though the descriptions were later amended as invalid by modern rules).
The founding nomenclaturist Carl Linnaeus included fungi in his binomial naming system in 1753, where each type of organism has a two-word name consisting of a genus and species (whereas up to then organisms were often designated with Latin phrases containing many words). [ 20 ] He originated the scientific names of numerous well-known mushroom taxa , such as Boletus [ 21 ] and Agaricus , [ 22 ] which are still in use today. During this period, fungi were still considered to belong to the plant kingdom, so they were categorized in his Species Plantarum . Linnaeus' fungal taxa were not nearly as comprehensive as his plant taxa, however, grouping together all gilled mushrooms with a stem in genus Agaricus . [ 23 ] [ 24 ] Thousands of gilled species exist, which were later divided into dozens of diverse genera; in its modern usage, Agaricus only refers to mushrooms closely related to the common shop mushroom, Agaricus bisporus . [ 25 ] For example, Linnaeus gave the name Agaricus deliciosus to the saffron milk-cap, but its current name is Lactarius deliciosus . [ 26 ] On the other hand, the field mushroom Agaricus campestris has kept the same name ever since Linnaeus's publication. [ 27 ] The English word " agaric " is still used for any gilled mushroom, which corresponds to Linnaeus's use of the word. [ 25 ]
Although mycology was historically considered a branch of botany , the 1969 discovery [ 28 ] of fungi's close evolutionary relationship to animals resulted in the study's reclassification as an independent field. [ 29 ] The term mycology and the complementary term mycologist are traditionally attributed to M.J. Berkeley in 1836. [ 30 ] However, mycologist appeared in writings by English botanist Robert Kaye Greville as early as 1823 in reference to Schweinitz . [ 31 ]
Lumber and timber products are a key element of international trade , [ 32 ] as they are used for all things from architecture to firewood . The cultivation of forested ecosystems to produce this amount of usable wood is highly dependent on the mycorrhizal symbiotic relationships between plants, specifically trees, and fungi. The fungi provide a great number of benefits to their symbiotic plant partner, such as disease tolerance, improved growth and mineral nutrition, stress tolerance, and even fertilizer utilization. [ 33 ]
Another major component of international trade over recent years has been edible and medicinal mushrooms . While many fungal species can be cultivated in large farming installations, the cultivation of some coveted species has yet to be fully understood, which means that there are many species that can only be found naturally in the wild. [ 32 ] While the demand of wild mushroom species has increased worldwide over recent years, the rarity of these species has not changed. Even still, mushroom hunting has become a key factor in local economies . [ 34 ]
Increased scientific knowledge of fungal diversity has led to biotechnological advances in food manufacturing . [ 35 ] Humans have utilized this knowledge by cultivating various types of fungi, particularly yeasts . There are over 500 species of yeasts that have been cultivated for different purposes, the most common of which is Saccharomyces cerevisiae , also known as baker's yeast. As its common name suggests, S. cerevisiae has been used for winemaking , baking , and brewing since ancient times. [ 2 ]
Fermentation is one of the earliest forms of food preservation, with the earliest recorded use dating back over 13,000 years ago in Israel . [ 36 ] The cultivation of bacteria and fungi, particularly yeasts, have been used for centuries to increase the storage life of meats , vegetables , grains , and other foods. [ 37 ] Fermentation also plays a significant role in the production of various food products and alcoholic beverages such as beer and wine . About 90% of the world's beer production comes from lager beer and 5% from ale beer , while the rest is from spontaneous fermentation of a variety of yeasts and bacteria. [ 32 ] Production of alcoholic beverages play significant roles in the economics of many countries, with beer often being a crucial export . [ 32 ]
Plant pathogenic fungi are a serious threat when it comes to crop availability and food security . These fungi can infiltrate plants and food crops , which can cause serious economic issues for agricultural industries in numerous countries. [ 35 ] Various plant pathogens can cause cash crops to become inedible and virtually useless to the farmer that is growing them. This problem has increased over the years as the usage of monocultures have become more prevalent: a limited variety of plants in one area can lead to the rapid spread of specific pathogens . [ 38 ] Puccinia graminis is a type of stem rust that targets wheat crops worldwide from Africa to Europe . [ 39 ] [ 40 ] Another devastating fungal pathogen is Sarocladium oryzae , which is a type of sheath rot fungus prevalent in India and is a great threat to rice cultivation . [ 41 ] Historically, one of the more well-known cases of plant-fungal pandemics was the potato blight of Ireland, which was caused by a water mold known as Phytophthora infestans . This event is known as the Great Famine of Ireland . [ 42 ]
For centuries, certain mushrooms have been documented as a folk medicine in China , Japan , and Russia . [ 43 ] Although the use of mushrooms in folk medicine is centered largely on the Asian continent, people in other parts of the world like the Middle East , Poland , and Belarus have been documented using mushrooms for medicinal purposes. [ 44 ]
Mushrooms produce large amounts of vitamin D when exposed to ultraviolet (UV) light . [ 45 ] Penicillin , ciclosporin , griseofulvin , cephalosporin and psilocybin are examples of drugs that have been isolated from molds or other fungi. [ 46 ] | https://en.wikipedia.org/wiki/Mycologist |
Mycology is the branch of biology concerned with the study of fungi , including their taxonomy , genetics , biochemical properties, and use by humans . [ 1 ] Fungi can be a source of tinder , food , traditional medicine , as well as entheogens , poison , and infection . Yeasts are among the most heavily utilized members of the fungus kingdom, particularly in food manufacturing. [ 2 ]
Mycology branches into the field of phytopathology , the study of plant diseases. The two disciplines are closely related, because the vast majority of plant pathogens are fungi. A biologist specializing in mycology is called a mycologist .
The word mycology comes from the Ancient Greek : μύκης ( mukēs ), meaning "fungus" and the suffix -λογία ( -logia ), meaning "study." [ 3 ] Pioneer mycologists included Elias Magnus Fries , Christiaan Hendrik Persoon , Heinrich Anton de Bary , Elizabeth Eaton Morse , and Lewis David de Schweinitz . Beatrix Potter , author of The Tale of Peter Rabbit , also made significant contributions to the field. [ 4 ]
Pier Andrea Saccardo developed a system for classifying the imperfect fungi by spore color and form, which became the primary system used before classification by DNA analysis . He is most famous for his Sylloge Fungorum , [ 5 ] which was a comprehensive list of all of the names that had been used for mushrooms . Sylloge is still the only work of this kind that was both comprehensive for the botanical kingdom Fungi and reasonably modern. [ 6 ]
Many fungi produce toxins , [ 7 ] antibiotics , [ 8 ] and other secondary metabolites . For example, the cosmopolitan genus Fusarium and their toxins associated with fatal outbreaks of alimentary toxic aleukia in humans were extensively studied by Abraham Z. Joffe . [ 9 ]
Fungi are fundamental for life on earth in their roles as symbionts , e.g. in the form of mycorrhizae , insect symbionts, and lichens . Many fungi are able to break down complex organic biomolecules such as lignin , the more durable component of wood , and pollutants such as xenobiotics , petroleum , and polycyclic aromatic hydrocarbons . By decomposing these molecules, fungi play a critical role in the global carbon cycle .
Fungi and other organisms traditionally recognized as fungi, such as oomycetes and myxomycetes ( slime molds ), often are economically and socially important, as some cause diseases of animals (including humans) and of plants. [ 10 ]
Apart from pathogenic fungi, many fungal species are very important in controlling the plant diseases caused by different pathogens. For example, species of the filamentous fungal genus Trichoderma are considered one of the most important biological control agents as an alternative to chemical-based products for effective crop disease management. [ 11 ]
Field meetings to find interesting species of fungi are known as 'forays', after the first such meeting organized by the Woolhope Naturalists' Field Club in 1868 and entitled "A foray among the funguses [ sic ]". [ 12 ]
Some fungi can cause disease in humans and other animals; the study of pathogenic fungi that infect animals is referred to as medical mycology . [ 13 ]
It is believed that humans started collecting mushrooms as food in prehistoric times. Mushrooms were first written about in the works of Euripides (480–406 BC). The Greek philosopher Theophrastos of Eresos (371–288 BC) was perhaps the first to try to systematically classify plants; mushrooms were considered to be plants missing certain organs. It was later Pliny the Elder (23–79 AD), who wrote about truffles in his encyclopedia Natural History . [ 14 ]
Fungi and truffles are neither herbs, nor roots, nor flowers, nor seeds, but merely the superfluous moisture or earth, of trees, or rotten wood, and of other rotting things. This is plain from the fact that all fungi and truffles, especially those that are used for eating, grow most commonly in thundery and wet weather.
The Middle Ages saw little advancement in the body of knowledge about fungi. However, the invention of the printing press allowed authors to dispel superstitions and misconceptions about the fungi that had been perpetuated by the classical authors. [ 16 ]
The start of the modern age of mycology begins with Pier Antonio Micheli 's 1737 publication of Nova plantarum genera . [ 17 ] Published in Florence , this seminal work laid the foundations for the systematic classification of grasses, mosses and fungi. He originated the still current genus names Polyporus [ 18 ] and Tuber , [ 19 ] both dated 1729 (though the descriptions were later amended as invalid by modern rules).
The founding nomenclaturist Carl Linnaeus included fungi in his binomial naming system in 1753, where each type of organism has a two-word name consisting of a genus and species (whereas up to then organisms were often designated with Latin phrases containing many words). [ 20 ] He originated the scientific names of numerous well-known mushroom taxa , such as Boletus [ 21 ] and Agaricus , [ 22 ] which are still in use today. During this period, fungi were still considered to belong to the plant kingdom, so they were categorized in his Species Plantarum . Linnaeus' fungal taxa were not nearly as comprehensive as his plant taxa, however, grouping together all gilled mushrooms with a stem in genus Agaricus . [ 23 ] [ 24 ] Thousands of gilled species exist, which were later divided into dozens of diverse genera; in its modern usage, Agaricus only refers to mushrooms closely related to the common shop mushroom, Agaricus bisporus . [ 25 ] For example, Linnaeus gave the name Agaricus deliciosus to the saffron milk-cap, but its current name is Lactarius deliciosus . [ 26 ] On the other hand, the field mushroom Agaricus campestris has kept the same name ever since Linnaeus's publication. [ 27 ] The English word " agaric " is still used for any gilled mushroom, which corresponds to Linnaeus's use of the word. [ 25 ]
Although mycology was historically considered a branch of botany , the 1969 discovery [ 28 ] of fungi's close evolutionary relationship to animals resulted in the study's reclassification as an independent field. [ 29 ] The term mycology and the complementary term mycologist are traditionally attributed to M.J. Berkeley in 1836. [ 30 ] However, mycologist appeared in writings by English botanist Robert Kaye Greville as early as 1823 in reference to Schweinitz . [ 31 ]
Lumber and timber products are a key element of international trade , [ 32 ] as they are used for all things from architecture to firewood . The cultivation of forested ecosystems to produce this amount of usable wood is highly dependent on the mycorrhizal symbiotic relationships between plants, specifically trees, and fungi. The fungi provide a great number of benefits to their symbiotic plant partner, such as disease tolerance, improved growth and mineral nutrition, stress tolerance, and even fertilizer utilization. [ 33 ]
Another major component of international trade over recent years has been edible and medicinal mushrooms . While many fungal species can be cultivated in large farming installations, the cultivation of some coveted species has yet to be fully understood, which means that there are many species that can only be found naturally in the wild. [ 32 ] While the demand of wild mushroom species has increased worldwide over recent years, the rarity of these species has not changed. Even still, mushroom hunting has become a key factor in local economies . [ 34 ]
Increased scientific knowledge of fungal diversity has led to biotechnological advances in food manufacturing . [ 35 ] Humans have utilized this knowledge by cultivating various types of fungi, particularly yeasts . There are over 500 species of yeasts that have been cultivated for different purposes, the most common of which is Saccharomyces cerevisiae , also known as baker's yeast. As its common name suggests, S. cerevisiae has been used for winemaking , baking , and brewing since ancient times. [ 2 ]
Fermentation is one of the earliest forms of food preservation, with the earliest recorded use dating back over 13,000 years ago in Israel . [ 36 ] The cultivation of bacteria and fungi, particularly yeasts, have been used for centuries to increase the storage life of meats , vegetables , grains , and other foods. [ 37 ] Fermentation also plays a significant role in the production of various food products and alcoholic beverages such as beer and wine . About 90% of the world's beer production comes from lager beer and 5% from ale beer , while the rest is from spontaneous fermentation of a variety of yeasts and bacteria. [ 32 ] Production of alcoholic beverages play significant roles in the economics of many countries, with beer often being a crucial export . [ 32 ]
Plant pathogenic fungi are a serious threat when it comes to crop availability and food security . These fungi can infiltrate plants and food crops , which can cause serious economic issues for agricultural industries in numerous countries. [ 35 ] Various plant pathogens can cause cash crops to become inedible and virtually useless to the farmer that is growing them. This problem has increased over the years as the usage of monocultures have become more prevalent: a limited variety of plants in one area can lead to the rapid spread of specific pathogens . [ 38 ] Puccinia graminis is a type of stem rust that targets wheat crops worldwide from Africa to Europe . [ 39 ] [ 40 ] Another devastating fungal pathogen is Sarocladium oryzae , which is a type of sheath rot fungus prevalent in India and is a great threat to rice cultivation . [ 41 ] Historically, one of the more well-known cases of plant-fungal pandemics was the potato blight of Ireland, which was caused by a water mold known as Phytophthora infestans . This event is known as the Great Famine of Ireland . [ 42 ]
For centuries, certain mushrooms have been documented as a folk medicine in China , Japan , and Russia . [ 43 ] Although the use of mushrooms in folk medicine is centered largely on the Asian continent, people in other parts of the world like the Middle East , Poland , and Belarus have been documented using mushrooms for medicinal purposes. [ 44 ]
Mushrooms produce large amounts of vitamin D when exposed to ultraviolet (UV) light . [ 45 ] Penicillin , ciclosporin , griseofulvin , cephalosporin and psilocybin are examples of drugs that have been isolated from molds or other fungi. [ 46 ] | https://en.wikipedia.org/wiki/Mycology |
A mycophycobiosis (composed of myco -, from the Ancient Greek : μύκης (mukês , "mushroom"), phyco -, from Ancient Greek: φῦκος , (phûkos, fucus , used for algae ), and - biose , from ancient Greek: βιόω (bióô, "to spend one's life") is a symbiotic organism made up of a multicellular algae and an ascomycete fungus housed inside the algae (in the thallus for example). The algae and fungus involved in this association are called mycophycobionts .
The essential role of the algae is to carry out photosynthesis , while that of the fungus is less obvious, but it could be linked to the transfer of minerals within the thallus, to a repellent effect on herbivores and, above all, to resistance to desiccation of this living organism in the intertidal zone . [ 1 ]
Such symbioses have been reported in a few green algae ( Prasiola , Blidingia ) and red algae ( Apophlaea ), both in seawater and in freshwater.
Although compared to lichens by certain authors, [ 2 ] mycophycobioses carry out an association of the opposite type: the algal partner is multicellular and forms the external structure of the symbiotic organization. Moreover, the reproduction of the two partners is always disjoint (the algae and the fungus reproduce separately). [ 3 ] To explain the nuances of this duality, the ecologists Chantal Delzenne-Van Haluwyn and Michel Lerond propose the analogy of the two symbionts with an "ideal couple". In a lichen, the host is compared to a "macho fungus"; in mycophycobiosis, the host is "the algae that wears the panties". [ 4 ]
According to Hawksworth [ 2 ] the physiology of this symbiosis could well be comparable to that of lichens, but it remains to be better explored. Unlike lichens, mycophycobioses look like an algal partner, which remains fertile. These associations appear to be less coevolved than lichens, as they exhibit neither joint asexual multiplication of partners nor do they contain the equivalent lichen products . [ 3 ]
The term mycophycobiosis was introduced by Jan and Erika Kohlmeyer in 1972, based on the case of the brown algal species Ascophyllum nodosum , which regularly harbours the ascomycete Mycosphaerella ascophylli . [ 5 ]
Another example of mycophycobiosis occurs in the genus Turgidosculum (synonym: Mastodia ), which associates a green alga of the genus Prasiola with an ascomycete pyrenomycete of the genus Kohlmeyera . [ 6 ] While the only alga of the genus Prasiola remains subservient to a certain at least temporary marine cover, the mycophycobiotic association allows a more terrestrial conquest outside the intertidal zone.
Some authors [ 7 ] hypothesize that vascular plants may have evolved from such a type of association and that this symbiosis may have helped land plants to conquer continents (similar to the association that gave rise to lichens). [ 3 ]
The major groups of carbon phototrophs , prokaryotes and eukaryotes , arose in the marine environment. The establishment of symbioses has made it possible to make a macroevolutionary leap to conquer the more hostile terrestrial environment. Various mutualistic associations (mycophycobioses, lichens, then mycorrhizae ) have been simultaneously or successively used. [ 3 ]
In fresh water, the fungus Phaeospora lemaneae grows inside Lemanea fluviatilis . [ 2 ]
In the marine environment, the fungus Blodgettia confervoides can associate with several species of Cladophora . [ 2 ] The fungus Mycophycias ascophylli associates with Ascophyllum nodosum (black seaweed) or another Fucaceae , Pelvetia canaliculata . [ 2 ] | https://en.wikipedia.org/wiki/Mycophycobiosis |
Mycoplasma genitalium Tully et al. 1983 [ 2 ]
Mycoplasma genitalium (also known as MG [ 3 ] , Mgen , or since 2018, Mycoplasmoides genitalium [ 1 ] ) is a sexually transmitted , [ 4 ] small and pathogenic bacterium that lives on the mucous epithelial cells of the urinary and genital tracts in humans. [ 5 ] Medical reports published in 2007 and 2015 state that Mgen is becoming increasingly common. [ 6 ] [ 7 ] Resistance to multiple antibiotics , including the macrolide azithromycin , which until recently was the most reliable treatment, is becoming prevalent. [ 6 ] [ 8 ] The bacterium was first isolated from the urogenital tract of humans in 1981, [ 9 ] and was eventually identified as a new species of Mycoplasma in 1983. [ 2 ] It can cause negative health effects in men and women. It also increases the risk for HIV spread [ 10 ] with higher occurrences in those previously treated with the azithromycin antibiotics . [ 6 ] [ 11 ]
Mgen is a bacterium recognized for causing urethritis in both men and women along with cervicitis and pelvic inflammation in women. [ 12 ] It presents clinically similar symptoms to that of Chlamydia trachomatis infection and has shown higher incidence rates, compared to both Chlamydia trachomatis and Neisseria gonorrhoeae infections in some populations. [ 13 ]
Infection with Mgen can be symptomatic or asymptomatic . Both men and women may experience inflammation in the urethra ( urethritis ), characterized by mucopurulent discharge in the urinary tract , and burning while urinating . In women, it causes cervicitis and pelvic inflammatory diseases (PID) , including endometritis and salpingitis . [ 12 ] Women may also experience bleeding after sex and it is also linked with tubal factor infertility . [ 5 ] [ 14 ] [ 15 ] For men, the most common signs are painful urination or a watery discharge from the penis. [ 16 ]
There is a consistent association of M. genitalium infection and female reproductive tract syndromes. M. genitalium infection was significantly associated with increased risk of preterm birth, spontaneous abortion, cervicitis, and pelvic inflammatory disease. In addition, this pathogen may latently infect the chorionic villi tissues of pregnant women, thereby impacting pregnancy outcome. [ 17 ] Infertility risk is also strongly associated with infection with M. genitalium , although evidence suggests it is not associated with male infertility. [ 18 ] When M. genitalium is a co-infectious agent risk associations are stronger and statistically significant. [ 19 ]
Polymerase chain reaction analyses indicated that it is a cause of acute non-gonococcal urethritis (NGU) and probably chronic NGU. It is strongly associated with persistent and recurring non-gonococcal urethritis (NGU), responsible for 15 percent to 20 percent of symptomatic NGU cases in men. [ 20 ] Unlike other mycoplasmas, the infection is not associated with bacterial vaginosis . [ 21 ] It is highly associated with the intensity of HIV infection. [ 22 ] Some scientists are performing research to determine if Mgen could play a role in the development of prostate and ovarian cancers and lymphomas in some individuals. These studies have yet to find conclusive evidence to suggest a link. [ 23 ]
The genome of M. genitalium strain G37 T consists in one circular DNA molecule of 580,070 base pairs . [ 24 ] Scott N. Peterson and his team at the University of North Carolina at Chapel Hill reported the first genetic map using pulsed-field gel electrophoresis in 1991. [ 25 ] They performed an initial study of the genome using sequencing in 1993, by which they found 100,993 nucleotides and 390 protein-coding genes. [ 26 ] Collaborating with researchers at The Institute for Genomic Research (TIGR; now the J. Craig Venter Institute), which included Craig Venter , they made the complete genome sequence in 1995 using shotgun sequencing . [ 24 ] Only 470 predicted coding regions were identified in 1995, including genes required for DNA replication , transcription and translation , DNA repair , cellular transport , and energy metabolism . It was the second complete bacterial genome ever sequenced, after Haemophilus influenzae . [ 24 ] Later data from KEGG reports 476 protein-coding genes and 43 RNA genes , totaling 519. [ 27 ] It is unclear where the "525" gene count for the G37 T stems from and what gene calling procedure was used. [ 28 ]
In 2006, the team at the J. Craig Venter Institute reported that only 382 genes are essential for biological functions. [ 29 ] The small genome of M. genitalium made it the organism of choice in The Minimal Genome Project , a study to find the smallest set of genetic material necessary to sustain life . [ 30 ]
There is limited divergence among clinical strains of M. genitalium . All strains retain the small genome size. [ 31 ]
Recent research shows that prevalence of Mgen is currently higher than other commonly occurring sexually transmitted infections (STIs). [ 32 ] Mgen is a fastidious organism with prolonged growth durations. This makes detection of the pathogen in clinical specimens and subsequent isolation extremely difficult. [ 33 ] Lacking a cell wall , Mycoplasma remains unaffected by commonly used antibiotics . [ 34 ] The absence of specific serological assays leaves nucleic acid amplification tests (NAAT) as the only viable option for detection of Mgen DNA or RNA . [ 35 ] However, samples with positive NAAT for the pathogen should be tested for macrolide resistance mutations , which are strongly correlated to azithromycin treatment failures, owing to rapid rates of mutation of the pathogen. [ 6 ] Mutations in the 23S rRNA gene of Mgen have been linked with clinical treatment failure and high level in vitro macrolide resistance. [ 36 ] Macrolide resistance mediating mutations have been observed in 20-50% of cases in the UK, Denmark, Sweden, Australia, and Japan. [ 6 ] Resistance is also developing towards the second-line antimicrobials like fluoroquinolone . [ 37 ]
According to the European guidelines, the indication for commencement of diagnosis for Mgen infection are: [ 35 ]
Screening for Mgen with a combination of detection and macrolide resistance mutations will provide the adequate information required to develop personalised antimicrobial treatments, in order to optimise patient management and control the spread of antimicrobial resistance (AMR). [ 35 ] [ 38 ]
Owing to the widespread macrolide resistance , samples that are positive for Mgen should ideally be followed up with an assay capable of detecting mutations that mediate antimicrobial resistance. The European Guideline on Mgen infections recommend complementing the molecular detection of Mgen with an assay capable of detecting macrolide resistance-associated mutations. Furthermore, molecular assays for quinolone resistance-associated mutations are available at specialised laboratories in suspected treatment failure due to treatment with moxifloxacin. [ 39 ]
The U.S. Centers for Disease Control and Prevention recommends a step-wise treatment approach for Mycoplasma genitalium with doxycycline for seven days followed immediately by a seven-day course of moxifloxacin as the preferred therapy due to high rates of macrolide resistance. [ 40 ] [ 41 ] [ 42 ] If resistance assay testing is available, and the Mgen is sensitive to macrolides, the CDC recommends a seven-day course of doxycycline followed by a four-day course of azithromycin . [ 40 ] Although the majority of M. genitalium strains are sensitive to moxifloxacin, resistance has been reported, and potential for serious, adverse side effects should be considered with this regimen. [ 43 ] Floroquinolones, including moxifloxacin, have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together including: [ citation needed ]
and other serious side effects detailed in the FDA black box warning. Moxifloxacin/Avelox should be reserved for use when patients have no other treatment options. [ 44 ]
In settings without access to resistance testing, or if moxifloxacin cannot be used, the CDC recommends as an alternative regimen: seven days of doxycycline followed by the four-day course of azithromycin, with a test of cure 21 days after treatment being required due to the high rate of macrolide resistance. Beta lactam antibiotics are not effective against Mgen as the organism lacks a cell wall. [ 42 ]
In the UK the British Association for Sexual Health and HIV (BASHH) guidelines for treatment are: [ 45 ]
Treatment of Mycoplasma genitalium infections is becoming increasingly difficult due to rapidly growing antimicrobial resistance . [ 46 ] Diagnosis and treatment is further hampered by the fact that Mycoplasma genitalium infections are not routinely tested. [ 47 ] Studies have demonstrated that a 5-day course of azithromycin has a superior cure rate compared to a single, larger dose. Further, a single dose of azithromycin can lead to the bacteria becoming resistant to azithromycin. [ 48 ] Among Swedish patients, doxycycline was shown to be relatively ineffective (with a cure rate of 48% for women and 38% for men); and treatment with a single dose of azithromycin is not prescribed due to it inducing antimicrobial resistance. The five-day treatment with azithromycin showed no development of antimicrobial resistance. [ 49 ] Based on these findings, UK doctors are moving to the 5-day azithromycin regimen. Doxycycline is also still used, and moxifloxacin is used as a second-line treatment in case doxycyline and azithromycin are not able to eradicate the infection. [ 50 ] [ 51 ] In patients where doxycycline, azithromycin and moxifloxacin all failed, pristinamycin has been shown to still be able to eradicate the infection. [ 50 ]
Mycoplasma genitalium was originally isolated in 1980 from urethral specimens of two male patients with non-gonococcal urethritis in the genitourinary medicine (GUM) clinic at St Mary's Hospital, Paddington , London. [ 52 ] [ 53 ] It was reported in 1981 by a team led by Joseph G. Tully. [ 9 ] Under electron microscopy , it appears as a flask-shaped cell with a narrow terminal portion that is crucial for its attachment to the host cell surfaces. [ 54 ] The bacterial cell is slightly elongated, somewhat like a vase, and measures 0.6–0.7 μm in length, 0.3–0.4 μm at the broadest region, and 0.06–0.08 μm at the tip. The base is broad while the tip is stretched into a narrow neck, which terminates with a cap. The terminal region has a specialised region called nap, which is absent in other mycoplasmas. Serological tests indicated that the bacterium was not related to known species of Mycoplasma . The comparison of genome sequences with other urinogenital bacteria, such as M. hominis and Ureaplasma parvum , revealed that M. genitalium is significantly different, especially in the energy-generating pathways , although it shared a core genome of ~250 protein-encoding genes. [ 55 ]
In 2018, Gupta et al. proposed to change the name of Mycoplasma genitalium to Mycoplasmoides genitalium on phylogenetic grounds, reflecting the existing knowledge that M. genitalium is not very related to other Mycoplasma . [ 1 ] The change became correct name under the International Code of Nomenclature of Prokaryotes (ICNP, "Code") with Validation List 184, published by the ICSP ("Committee"). [ 56 ] Mycoplasmaologists working in the field generally oppose this renaming. In 2019, they published an opinion paper arguing that even though the phylogenetic methods are valid, Gupta's renaming scheme causes too many changes, which is impractical and confusing. [ 57 ] They cite some essential principles of the Code, such as "no unnecessary new names", "aim at stability of names", and "avoid or reject the use of names which may cause error or confusion". [ 57 ] However, the 2019 argument for preserving old names was rejected by the Committee in Opinion 122 of 2022, [ 58 ] where it was ruled that the argument incorrectly cited the Code. [ 56 ] The Opinion emphasizes that use of an older validly published name remains acceptable under the Code. [ 58 ]
On 6 October 2007, Craig Venter announced that a team of scientists led by Nobel laureate Hamilton Smith at the J. Craig Venter Institute had successfully constructed synthetic DNA with which they planned to make the first synthetic genome. Reporting in The Guardian , Venter said that they had stitched together a DNA strand containing 381 genes, consisting of 580,000 base pairs, based on the genome of M. genitalium . [ 59 ] On 24 January 2008, they announced the successful creation of a synthetic bacterium, which they named Mycoplasma genitalium JCVI-1.0 (the name of the strain indicating J. Craig Venter Institute with its specimen number). [ 60 ] They synthesised and assembled the complete 582,970-base pair genome of the bacterium. The final stages of synthesis involved cloning the DNA into the bacterium E. coli for nucleotide production and sequencing. This produced large fragments of approximately 144,000 base pairs or 1/4th of the whole genome. Finally, the products were cloned inside the yeast Saccharomyces cerevisiae to synthesize the 580,000 base pairs. [ 61 ] [ 62 ] The molecular size of the synthetic bacterial genome is 360,110 kilodaltons (kDa). Printed in 10-point font, the letters of the genome cover 147 pages. [ 63 ]
On 20 July 2012, Stanford University and the J. Craig Venter Institute announced successful simulation of the complete life cycle of a Mycoplasma genitalium cell, in the journal Cell . [ 64 ] The entire organism is modeled in terms of its molecular components, integrating all cellular processes into a single model. Using object oriented programming to model the interactions of 28 categories of molecules, including DNA, RNA, proteins, and metabolites, and running on a 128 computer Linux cluster, the simulation takes 10 hours for a single M. genitalium cell to divide once—about the same time the actual cell takes—and generates half a gigabyte of data. [ 65 ]
The discovery of Protein M , a protein produced by M. genitalium , was announced in February 2014. [ 66 ] The protein was identified during investigations on the origin of multiple myeloma , a B-cell hematologic neoplasm. To understand the long-term Mycoplasma infection, it was found that antibodies from multiple myeloma patients' blood were recognised by M. genitalium . The antibody reactivity was due to a protein, designated Protein M, that is chemically responsive to all types of human and nonhuman antibodies available. The protein is about 50 kDa in size, and composed of 556 amino acids. [ 67 ]
Mgen evolved from a gram-positive ancestor that was clostridium-like but has lost the genes to code for the enzymes involved in de novo nucleic acid synthesis, amino acid synthesis, and synthesis of fatty acids. [ 68 ] This means that Mgen needs the host's growth factors to keep reproducing. Although Mgen has abilities that help it adhere to cells, it is still unknown how the bacteria can maintain an infection inside the epithelial cells of the ectocervix and vagina when shedding of the apical layer of cells occur. The organism's ability to have adhesion to host cells relies of two proteins, P110 and P140. Adhesion is an important step in beginning an infection in a cell and Mgen can adhere to spermatozoa, erythrocytes, and epithelial cells. The terminal organelle relies on these proteins as well because without them the organelle was not present. The segmented pair plates of Mgen [ vague ] is a core of dense electrons which is anchored to the cell membrane. The end of this core is in contact with the wheel complex and the wheel complex contains the proteins MG219, MG200, MG386, and MG491 which aid in the gliding motility of the bacteria. Although Mgen lacks secreted virulence factors, the protein MG186 degrades host nucleic acids due to it being a calcium-dependent membrane-associated nuclease. [ citation needed ] | https://en.wikipedia.org/wiki/Mycoplasma_genitalium |
Mycoplasma laboratorium Reich, 2000
Mycoplasma laboratorium or Synthia [ b 1 ] refers to a synthetic strain of bacterium . The project to build the new bacterium has evolved since its inception. Initially the goal was to identify a minimal set of genes that are required to sustain life from the genome of Mycoplasma genitalium , and rebuild these genes synthetically to create a "new" organism. Mycoplasma genitalium was originally chosen as the basis for this project because at the time it had the smallest number of genes of all organisms analyzed. Later, the focus switched to Mycoplasma mycoides and took a more trial-and-error approach. [ b 2 ]
To identify the minimal genes required for life, each of the 482 genes of M. genitalium was individually deleted and the viability of the resulting mutants was tested. This resulted in the identification of a minimal set of 382 genes that theoretically should represent a minimal genome. [ a 3 ] In 2008 the full set of M. genitalium genes was constructed in the laboratory with watermarks added to identify the genes as synthetic. [ b 3 ] [ a 4 ] However M. genitalium grows extremely slowly and M. mycoides was chosen as the new focus to accelerate experiments aimed at determining the set of genes actually needed for growth. [ b 4 ]
In 2010, the complete genome of M. mycoides was successfully synthesized from a computer record and transplanted into an existing cell of Mycoplasma capricolum that had had its DNA removed. [ b 5 ] It is estimated that the synthetic genome used for this project cost US$40 million and 200 man-years to produce. [ b 4 ] The new bacterium was able to grow and was named JCVI-syn1.0, or Synthia. After additional experimentation to identify a smaller set of genes that could produce a functional organism, JCVI-syn3.0 was produced, containing 473 genes. [ b 2 ] 149 of these genes are of unknown function. [ b 2 ] Since the genome of JCVI-syn3.0 is novel, it is considered the first truly synthetic organism.
The production of Synthia is an effort in synthetic biology at the J. Craig Venter Institute by a team of approximately 20 scientists headed by Nobel laureate Hamilton Smith and including DNA researcher Craig Venter and microbiologist Clyde A. Hutchison III . The overall goal is to reduce a living organism to its essentials and thus understand what is required to build a new organism from scratch. [ a 3 ] The initial focus was the bacterium M. genitalium , an obligate intracellular parasite whose genome consists of 482 genes comprising 582,970 base pairs , arranged on one circular chromosome (at the time the project began, this was the smallest genome of any known natural organism that can be grown in free culture). They used transposon mutagenesis to identify genes that were not essential for the growth of the organism, resulting in a minimal set of 382 genes. [ a 3 ] This effort was known as the Minimal Genome Project . [ a 5 ]
Mycoplasma is a genus of bacteria of the class Mollicutes in the division Mycoplasmatota (formerly Tenericutes), characterised by the lack of a cell wall (making it Gram negative ) due to its parasitic or commensal lifestyle.
In molecular biology , the genus has received much attention, both for being a notoriously difficult-to-eradicate contaminant in mammalian cell cultures (it is immune to beta-lactams and other antibiotics ), [ a 6 ] and for its potential uses as a model organism due to its small genome size. [ a 7 ] The choice of genus for the Synthia project dates to 2000, when Karl Reich coined the phrase Mycoplasma laboratorium . [ a 2 ]
As of 2005, Pelagibacter ubique (an α-proteobacterium of the order Rickettsiales ) has the smallest known genome (1,308,759 base pairs) of any free living organism and is one of the smallest self-replicating cells known. It is possibly the most numerous bacterium in the world (perhaps 10 28 individual cells) and, along with other members of the SAR11 clade , are estimated to make up between a quarter and a half of all bacterial or archaeal cells in the ocean. [ a 8 ] It was identified in 2002 by rRNA sequences and was fully sequenced in 2005. [ a 9 ] It is extremely hard to cultivate a species which does not reach a high growth density in lab culture. [ a 10 ] [ a 11 ] Several newly discovered species have fewer genes than M. genitalium , but are not free-living: many essential genes that are missing in Hodgkinia cicadicola , Sulcia muelleri , Baumannia cicadellinicola (symbionts of cicadas ) and Carsonella ruddi (symbiote of hackberry petiole gall psyllid, Pachypsylla venusta [ a 12 ] ) may be encoded in the host nucleus. [ a 13 ] The organism with the smallest known set of genes as of 2013 is Nasuia deltocephalinicola , an obligate symbiont . It has only 137 genes and a genome size of 112 kb. [ a 14 ] [ b 6 ]
Several laboratory techniques had to be developed or adapted for the project, since it required synthesis and manipulation of very large pieces of DNA.
In 2007, Venter's team reported that they had managed to transfer the chromosome of the species Mycoplasma mycoides to Mycoplasma capricolum by:
The term transformation is used to refer to insertion of a vector into a bacterial cell (by electroporation or heatshock). Here, transplantation is used akin to nuclear transplantation .
In 2008 Venter's group described the production of a synthetic genome, a copy of M. genitalium G37 sequence L43967 , by means of a hierarchical strategy: [ a 16 ]
The genome of this 2008 result, M. genitalium JCVI-1.0, is published on GenBank as CP001621.1 . It is not to be confused with the later synthetic organisms, labelled JCVI-syn, based on M. mycoides . [ a 16 ]
In 2010 Venter and colleagues created Mycoplasma mycoides strain JCVI-syn1.0 with a synthetic genome. [ a 1 ] Initially the synthetic construct did not work, so to pinpoint the error—which caused a delay of 3 months in the whole project [ b 4 ] —a series of semi-synthetic constructs were created. The cause of the failure was a single frameshift mutation in DnaA , a replication initiation factor . [ a 1 ]
The purpose of constructing a cell with a synthetic genome was to test the methodology, as a step to creating modified genomes in the future. Using a natural genome as a template minimized the potential sources of failure. Several differences are present in Mycoplasma mycoides JCVI-syn1.0 relative to the reference genome, notably an E.coli transposon IS1 (an infection from the 10kb stage) and an 85bp duplication, as well as elements required for propagation in yeast and residues from restriction sites. [ a 1 ]
There has been controversy over whether JCVI-syn1.0 is a true synthetic organism. While the genome was synthesized chemically in many pieces, it was constructed to match the parent genome closely and transplanted into the cytoplasm of a natural cell. DNA alone cannot create a viable cell: proteins and RNAs are needed to read the DNA, and lipid membranes are required to compartmentalize the DNA and cytoplasm . In JCVI-syn1.0 the two species used as donor and recipient are of the same genus, reducing potential problems of mismatches between the proteins in the host cytoplasm and the new genome. [ a 17 ] Paul Keim (a molecular geneticist at Northern Arizona University in Flagstaff ) noted that "there are great challenges ahead before genetic engineers can mix, match, and fully design an organism's genome from scratch". [ b 4 ]
A much publicized feature of JCVI-syn1.0 is the presence of watermark sequences. The 4 watermarks (shown in Figure S1 in the supplementary material of the paper [ a 1 ] ) are coded messages written into the DNA, of length 1246, 1081, 1109 and 1222 base pairs respectively. These messages did not use the standard genetic code , in which sequences of 3 DNA bases encode amino acids, but a new code invented for this purpose, which readers were challenged to solve. [ b 7 ] The content of the watermarks is as follows:
In 2016, the Venter Institute used genes from JCVI-syn1.0 to synthesize a smaller genome they call JCVI-syn3.0, that contains 531,560 base pairs and 473 genes. [ b 8 ] In 1996, after comparing M. genitalium with another small bacterium Haemophilus influenzae , Arcady Mushegian and Eugene Koonin had proposed that there might be a common set of 256 genes which could be a minimal set of genes needed for viability. [ b 9 ] [ a 19 ] In this new organism, the number of genes can only be pared down to 473, 149 of which have functions that are completely unknown. [ b 9 ] As of 2022 the unknown set has been narrowed to about 100. [ b 10 ] In 2019 a complete computational model of all pathways in Syn3.0 cell was published, representing the first complete in silico model for a living minimal organism. [ a 20 ]
On Oct 6, 2007, Craig Venter announced in an interview with UK's The Guardian newspaper that the same team had synthesized a modified version of the single chromosome of Mycoplasma genitalium chemically . The synthesized genome had not yet been transplanted into a working cell. The next day the Canadian bioethics group, ETC Group issued a statement through their representative, Pat Mooney , saying Venter's "creation" was "a chassis on which you could build almost anything. It could be a contribution to humanity such as new drugs or a huge threat to humanity such as bio-weapons". Venter commented "We are dealing in big ideas. We are trying to create a new value system for life. When dealing at this scale, you can't expect everybody to be happy." [ b 11 ]
On May 21, 2010, Science reported that the Venter group had successfully synthesized the genome of the bacterium Mycoplasma mycoides from a computer record and transplanted the synthesized genome into the existing cell of a Mycoplasma capricolum bacterium that had had its DNA removed. The "synthetic" bacterium was viable, i.e. capable of replicating. [ b 1 ] Venter described it as "the first species.... to have its parents be a computer". [ b 12 ]
The creation of a new synthetic bacterium, JCVI-3.0 was announced in Science on March 25, 2016. It has only 473 genes. Venter called it “the first designer organism in history” and argued that the fact that 149 of the genes required have unknown functions means that "the entire field of biology has been missing a third of what is essential to life". [ a 21 ]
The project received a large amount of coverage from the press due to Venter's showmanship, to the degree that Jay Keasling , a pioneering synthetic biologist and founder of Amyris commented that "The only regulation we need is of my colleague's mouth". [ b 13 ]
Venter has argued that synthetic bacteria are a step towards creating organisms to manufacture hydrogen and biofuels , and also to absorb carbon dioxide and other greenhouse gases . George M. Church , another pioneer in synthetic biology , has expressed the contrasting view that creating a fully synthetic genome is not necessary since E. coli grows more efficiently than M. genitalium even with all its extra DNA; he commented that synthetic genes have been incorporated into E.coli to perform some of the above tasks. [ b 14 ]
The J. Craig Venter Institute filed patents for the Mycoplasma laboratorium genome (the "minimal bacterial genome") in the U.S. and internationally in 2006. [ b 15 ] [ b 16 ] [ a 22 ] The ETC group, a Canadian bioethics group, protested on the grounds that the patent was too broad in scope. [ b 17 ]
From 2002 to 2010, a team at the Hungarian Academy of Science created a strain of Escherichia coli called MDS42, which is now sold by Scarab Genomics of Madison, WI under the name of "Clean Genome. E.coli", [ b 18 ] where 15% of the genome of the parental strain (E. coli K-12 MG1655) were removed to aid in molecular biology efficiency, removing IS elements , pseudogenes and phages, resulting in better maintenance of plasmid-encoded toxic genes, which are often inactivated by transposons. [ a 23 ] [ a 24 ] [ a 25 ] Biochemistry and replication machinery were not altered. | https://en.wikipedia.org/wiki/Mycoplasma_laboratorium |
Mycoremediation (from ancient Greek μύκης ( mukēs ), meaning "fungus", and the suffix -remedium , in Latin meaning 'restoring balance') is a form of bioremediation in which fungi -based remediation methods are used to decontaminate the environment . [ 1 ] Fungi have been proven to be a cheap, effective and environmentally sound way for removing a wide array of contaminants from damaged environments or wastewater . These contaminants include heavy metals , organic pollutants, textile dyes , leather tanning chemicals and wastewater, petroleum fuels, polycyclic aromatic hydrocarbons , pharmaceuticals and personal care products, pesticides and herbicides [ 2 ] in land, fresh water, and marine environments.
The byproducts of the remediation can be valuable materials themselves, such as enzymes (like laccase ), [ 3 ] edible or medicinal mushrooms, [ 4 ] making the remediation process even more profitable. Some fungi are useful in the biodegradation of contaminants in extremely cold or radioactive environments where traditional remediation methods prove too costly or are unusable.
Fungi, thanks to their non-specific enzymes, are able to break down many kinds of substances including pharmaceuticals and fragrances that are normally recalcitrant to bacteria degradation, [ 5 ] such as paracetamol (also known as acetaminophen). For example, using Mucor hiemalis , [ 6 ] the breakdown of products which are toxic in traditional water treatment, such as phenols and pigments of wine distillery wastewater, [ 7 ] X-ray contrast agents, and ingredients of personal care products, [ 8 ] can be broken down in a non-toxic way.
Mycoremediation is a cheaper method of remediation, and it doesn't usually require expensive equipment. For this reason, it is often used in small scale applications, such as mycofiltration of domestic wastewater , [ 9 ] and industrial effluent filtration. [ 10 ]
According to a 2015 study, mycoremediation can even help with the polycyclic aromatic hydrocarbons (PAH) soil biodegradation. Soils soaked with creosote contain high concentrations of PAH and in order to stop the spread, mycoremediation has proven to be the most successful strategy. [ 11 ]
Pollution from metals is very common, as they are used in many industrial processes such as electroplating , textiles , [ 12 ] paint and leather . The wastewater from these industries is often used for agricultural purposes, so besides the immediate damage to the ecosystem it is spilled into, the metals can enter creatures and humans far away through the food chain. Mycoremediation is one of the cheapest, most effective and environmental-friendly solutions to this problem. [ 13 ] Many fungi are hyperaccumulators , therefore they are able to concentrate toxins in their fruiting bodies for later removal. This is usually true for populations that have been exposed to contaminants for a long time, and have developed a high tolerance. Hyperaccumulation occurs via biosorption on the cellular surface, where the metals enter the mycelium passively with very little intracellular uptake. [ 14 ] A variety of fungi, such as Pleurotus , Aspergillus , Trichoderma has proven to be effective in the removal of lead , [ 15 ] [ 16 ] cadmium , [ 16 ] nickel , [ 17 ] [ 16 ] chromium , [ 16 ] mercury , [ 18 ] arsenic , [ 19 ] copper , [ 15 ] [ 20 ] boron , [ 21 ] iron and zinc [ 22 ] in marine environments , wastewater and on land . [ 15 ] [ 16 ] [ 17 ] [ 18 ] [ 19 ] [ 20 ] [ 21 ] [ 22 ]
Not all the individuals of a species are effective in the same way in the accumulation of toxins. The single individuals are usually selected from an older polluted environment, such as sludge or wastewater, where they had time to adapt to the circumstances, and the selection is carried on in the laboratory [ citation needed ] . A dilution of the water can drastically improve the ability of biosorption of the fungi. [ 23 ]
The capacity of certain fungi to extract metals from the ground also can be useful for bioindicator purposes, and can be a problem when the mushroom is of an edible variety. For example, the shaggy ink cap ( Coprinus comatus ), a common edible mushroom found in the Northern Hemisphere, can be a very good bioindicator of mercury. [ 24 ] However, as the shaggy ink cap accumulates mercury in its body, it can be toxic to the consumer. [ 24 ]
The capacity of metals uptake of mushroom has also been used to recover precious metals from medium. For example, VTT Technical Research Centre of Finland reported an 80% recovery of gold from electronic waste using mycofiltration techniques. [ 25 ]
Fungi are amongst the primary saprotrophic organisms in an ecosystem , as they are efficient in the decomposition of matter. Wood-decay fungi , especially white rot , secrete extracellular enzymes and acids that break down lignin and cellulose , the two main building blocks of plant fiber. These are long-chain organic ( carbon -based) compounds, structurally similar to many organic pollutants. They achieve this using a wide array of enzymes. In the case of polycyclic aromatic hydrocarbons (PAHs), complex organic compounds with fused, highly stable, polycyclic aromatic rings , fungi are very effective [ 26 ] in addition to marine environments . [ 27 ] The enzymes involved in this degradation are ligninolytic and include lignin peroxidase , versatile peroxidase , manganese peroxidase , general lipase , laccase and sometimes intracellular enzymes, especially the cytochrome P450 . [ 28 ] [ 29 ]
Other toxins fungi are able to degrade into harmless compounds include petroleum fuels , [ 30 ] phenols in wastewater, [ 31 ] polychlorinated biphenyl (PCB) in contaminated soils using Pleurotus ostreatus , [ 32 ] polyurethane in aerobic and anaerobic conditions, [ 33 ] such as conditions at the bottom of landfills using two species of the Ecuadorian fungus Pestalotiopsis , [ 34 ] and more. [ 35 ]
The mechanisms of degradation are not always clear, [ 36 ] as the mushroom may be a precursor to subsequent microbial activity rather than individually effective in the removal of pollutants. [ 37 ]
Pesticide contamination can be long-term and have a significant impact on decomposition processes and nutrient cycling . [ 38 ] Therefore, their degradation can be expensive and difficult. The most commonly used fungi for helping in the degradation of such substances are white rot fungi, which, thanks to their extracellular ligninolytic enzymes like laccase and manganese peroxidase , are able to degrade high quantity of such components. Examples includes the insecticide endosulfan , [ 39 ] imazalil , thiophanate methyl , ortho-phenylphenol , diphenylamine , chlorpyrifos [ 40 ] in wastewater, and atrazine in clay-loamy soils. [ 41 ]
Dyes are used in many industries, like paper printing or textile. They are often recalcitrant to degradation and in some cases, like some azo dyes , carcinogenic or otherwise toxic. [ 42 ]
The mechanism by which the fungi degrade dyes is via their lignolytic enzymes, especially laccase, therefore white rot mushrooms are the most commonly used. [ citation needed ]
Mycoremediation has proven to be a cheap and effective remediation technology for dyes such as malachite green , nigrosin and basic fuchsin with Aspergillus niger and Phanerochaete chrysosporium [ 43 ] and Congo red , a carcinogenic dye recalcitrant to biodegradative processes, [ 44 ] direct blue 14 (using Pleurotus ). [ 45 ]
Phytoremediation is the use of plant-based technologies to decontaminate an area.
Most land plants can form a symbiotic relationship with fungi which is advantageous for both organisms. This relationship is called mycorrhiza . Researchers found that phytoremediation is enhanced by mycorrhizae. [ 46 ] Mycorrhizal fungi's symbiotic relationships with plant roots help with the uptake of nutrients and the plant's ability to resist biotic and abiotic stress factors such as heavy metals bioavailable in the rhizosphere. Arbuscular mycorrhizal fungi (AMF) produce proteins that bind heavy metals and thereby decrease their bioavailability. [ 47 ] [ 48 ] The removal of soil contaminants by mycorrhizal fungi is called mycorrhizoremediation. [ 49 ]
Mycorrhizal fungi, especially AMF, can greatly improve the phytoremediation capacity of some plants. This is mostly due to the stress the plants suffer because of the pollutants is greatly reduced in the presence of AMF, so they can grow more and produce more biomass. [ 50 ] [ 48 ] The fungi also provide more nutrition, especially phosphorus , and promote the overall health of the plants. The mycelium's quick expansion can also greatly extend the rhizosphere influence zone ( hyphosphere ), providing the plant with access to more nutrients and contaminants. [ 51 ] Increasing the rhizosphere overall health also means a rise in the bacteria population, which can also contribute to the bioremediation process. [ 52 ]
This relationship has been proven useful with many pollutants, such as Rhizophagus intraradices and Robinia pseudoacacia in lead contaminated soil, [ 53 ] Rhizophagus intraradices with Glomus versiforme inoculated into vetiver grass for lead removal, [ 54 ] AMF and Calendula officinalis in cadmium and lead contaminated soil, [ 55 ] and in general was effective in increasing the plant bioremediation capacity for metals, [ 56 ] [ 57 ] petroleum fuels, [ 58 ] [ 59 ] and PAHs. [ 52 ] In wetlands AMF greatly promote the biodegradation of organic pollutants like benzene-, methyl tert-butyl ether- and ammonia from groundwater when inoculated into Phragmites australis . [ 60 ]
Antarctic fungi species such as Metschnikowia sp., Cryptococcus gilvescens, Cryptococcus victoriae , Pichia caribbica and Leucosporidium creatinivorum can withstand extreme cold and still provide efficient biodegradation of contaminants. [ 61 ] Due to the nature of colder, remote environments like Antarctica , usual methods of contaminant remediation, such as the physical removal of contaminated media, can prove costly. [ 62 ] [ 63 ] Most species of psychrophilic Antarctic fungi are resistant to the decreased levels of ATP ( adenosine triphosphate ) production causing reduced energy availability, [ 64 ] decreased levels of oxygen due to the low permeability of frozen soil, and nutrient transportation disruption caused by freeze-thaw cycles. [ 65 ] These species of fungi are able to assimilate and degrade compounds such as phenols , n-Hexadecane , toluene , and polycyclic aromatic hydrocarbons in these harsh conditions. [ 66 ] [ 61 ] These compounds are found in crude oil and refined petroleum .
Some fungi species, like Rhodotorula taiwanensis, are resistant to the extremely low pH (acidic) and radioactive medium found in radioactive waste and can successfully grow in these conditions, unlike most other organisms. [ 67 ] They can also thrive in the presence of high concentrations of mercury and chromium . [ 67 ] Fungi such as Rhodotorula taiwanensis can possibly be used in the bioremediation of radioactive waste due to their low pH and radiation resistant properties. [ 67 ] Certain species of fungi are able to absorb and retain radionuclides such as 137 Cs , 121 Sr , 152 Eu , 239 Pu and 241 Am . [ 68 ] [ 10 ] In fact, cell walls of some species of dead fungi can be used as a filter that can adsorb heavy metals and radionuclides present in industrial effluents, preventing them from being released into the environment. [ 10 ]
Mycoremediation can even be used for fire management with the encapsulation method. This process consists of using fungal spores coated with agarose in a pellet form, which is introduced to a substrate in the burnt forest, breaking down toxins and stimulating growth. [ 69 ] | https://en.wikipedia.org/wiki/Mycoremediation |
Mycorestoration is the use of fungi to restore degraded environments. It is a multi-method approach to restore damaged habitats such as oil spill sites and logging roads , while also restoring the health of targeted forest sites that have been compromised in development. Mycorestoration is also used to control insect populations. It generally uses a four-tier approach of mycofiltration , mycoforestry , mycoremediation , and mycopesticides . The mycelia of a number of different gilled fungi are used in some of these applications. [ 1 ] | https://en.wikipedia.org/wiki/Mycorestoration |
A mycorrhiza (from Ancient Greek μύκης ( múkēs ) ' fungus ' and ῥίζα ( rhíza ) ' root ' ; pl. mycorrhizae , mycorrhiza , or mycorrhizas ) [ 1 ] is a symbiotic association between a fungus and a plant . [ 2 ] The term mycorrhiza refers to the role of the fungus in the plant's rhizosphere , the plant root system and its surroundings. Mycorrhizae play important roles in plant nutrition , soil biology , and soil chemistry .
In a mycorrhizal association, the fungus colonizes the host plant's root tissues, either intracellularly as in arbuscular mycorrhizal fungi , or extracellularly as in ectomycorrhizal fungi. [ 3 ] The association is normally mutualistic . In particular species, or in particular circumstances, mycorrhizae may have a parasitic association with host plants. [ 4 ]
A mycorrhiza is a symbiotic association between a green plant and a fungus. The plant makes organic molecules by photosynthesis and supplies them to the fungus in the form of sugars or lipids, while the fungus supplies the plant with water and mineral nutrients, such as phosphorus , taken from the soil. Mycorrhizas are located in the roots of vascular plants, but mycorrhiza-like associations also occur in bryophytes [ 5 ] and there is fossil evidence that early land plants that lacked roots formed arbuscular mycorrhizal associations. [ 6 ] Most plant species form mycorrhizal associations, though some families like Brassicaceae and Chenopodiaceae cannot. Different forms for the association are detailed in the next section. The most common is the arbuscular type that is present in 70% of plant species, including many crop plants such as cereals and legumes. [ 7 ]
Fossil and genetic evidence indicate that mycorrhizae are ancient, potentially as old as the terrestrialization of plants . Genetic evidence indicates that all land plants share a single common ancestor, [ 8 ] which appears to have quickly adopted mycorrhizal symbiosis, and research suggests that proto-mycorrhizal fungi were a key factor enabling plant terrestrialization. [ 9 ] The 400 million year old Rhynie chert contains an assemblage of fossil plants preserved in sufficient detail that arbuscular mycorrhizae have been observed in the stems of Aglaophyton major , giving a lower bound for how late mycorrhizal symbiosis may have developed. [ 6 ] Ectomycorrhizae developed substantially later, during the Jurassic period, while most other modern mycorrhizal families, including orchid and ericoid mycorrhizae, date to the period of angiosperm radiation in the Cretaceous period. [ 10 ] There is genetic evidence that the symbiosis between legumes and nitrogen-fixing bacteria is an extension of mycorrhizal symbiosis. [ 11 ] The modern distribution of mycorrhizal fungi appears to reflect an increasing complexity and competition in root morphology associated with the dominance of angiosperms in the Cenozoic Era , characterized by complex ecological dynamics between species. [ 12 ]
Mycorrhizal relationships were likely crucial in terrestrial plant colonization some 450-500 million years ago, suggesting that mycorrhizal relationships are coincident with the evolution of terrestrial flora. [ 13 ] Mycorrhizal relationships have independently evolved from saprotrophic fungi a number of times, and in effect mycorrhizae have developed multiple modes of exchange between root cells and hyphae. There are three major forms of mycorrhizal relationships which have evolved independently of one another, the oldest being arbuscular mycorrhizae, followed by ectomycorrhizal relationships, and most recently ericoid mycorrhizal relationships.
Arbuscular Mycorrhizae
Arbuscular mycorrhizae are the oldest and most frequent form of mycorrhizal relationship. [ 14 ] Arbuscular mycorrhizae establish nutrient exchange through penetrating the root cortical cells of the host plant, making the relationship endomycorrhizal (inside the cell) as opposed to the later developed ectomycorrhizae (external nutrient exchange). Arbuscular mycorrhizae leave behind arbuscules, tree-like structures formed through hyphal penetration into the cell. Arbuscular mycorrhizae take on most angiosperms, some gymnosperms, pteridophytes, and nonvascular plants as plant hosts. [ 15 ]
Arbuscular mycorrhizas likely evolved alongside terrestrial plants approximately 450-500 million years ago when plants first began to colonize land. [ 16 ] Some scholars suggest arbuscular mycorrhizal relationships originated between fungus-like protists and algae during this time. [ 17 ] Paramycorrhizae, mycorrhiza-like structures, have been observed in the Rhynie Chert, a 407 million-year-old piece of fossilized earth found in Scotland, [ 18 ] setting a lower bound for mycorrhizal relationships. The earliest root-confined arbuscular mycorrhizae observed come from a fossil where hyphae are seen colonizing the rootlet of an arborescent clubmoss, forming arbuscules. [ 19 ]
There is a strong consensus among paleomycologists that mycorrhizal fungi served as a primitive root system for early terrestrial plants. This is because, prior to plant colonization of land, soils were nutrient sparse and plants had yet to develop root systems. [ 20 ] Without complex root systems, early terrestrial plants would have been incapable of absorbing recalcitrant ions from mineral substrates, such as phosphate, a key nutrient for plant growth. [ 21 ] There are a number of indicators that all land plants evolved from arbuscular mycorrhizal symbiosis. One strong indicator is that arbuscular mycorrhizae have been observed in the seedling stage of otherwise ectomycorrhizal partners, suggesting that arbuscular mycorrhizae may be able to infect almost any land plant given proper circumstances. [ 22 ] Arbuscular mycorrhizal symbiosis occurs between plants and fungi in the division glomeromycota, which has been observed in almost every seed plant taxonomic division, or around 67% of species. [ 23 ] As arbuscular mycorrhizae show minimal host plant specificity, and described mycorrhizae species are likely capable of forming relationships with most host plant taxa, this also suggests that terrestrial plants and arbuscular mycorrhizae evolved with one another.
Ectomycorrhizae
Ectomycorrhizae are mycorrhizal relationships formed without the hyphae of the fungi penetrating the root cells of the host plant, instead forming a sheath around the root of the symbiont for nutrient exchange. The earliest confirmed ectomycorrhizal fossil dates back to the eocene approximately 48 million years ago, [ 24 ] However it’s believed that the first ectomycorrhizal relationships evolved in the stem group Pinaceae around the radiation of the Pinaceae crown group in the mid Jurassic, 175 million or so years ago. [ 25 ]
Ectomycorrhizal relationships have evolved a number of times, in both plants and fungi. In angiosperms, it is believed that ectomycorrhizal partnerships have evolved independently at least 18 times, and in fungi 78-82 times. [ 26 ] The main evolutionary driver for ectomycorrhizae is switching of nutritional modes from saprotrophs. [ 27 ] Phylogenomic analysis of various ectomycorrhizal fungal genomes has confirmed the
convergent evolution of ectomycorrhizal fungi from white and brown-rot fungi, as well as from soil saprotrophs – Ectomycorrhizal fungi likely evolved convergently from saprotrophic origins several times. [ 28 ] [ 29 ] Some lineages of ectomycorrhizae have likely evolved from endophytic ancestors, fungi that live within plants without damaging them, while others such as Amanitaceae evolved from saprotrophs. [ 30 ] Some ectomycorrhizal fungi have gone through apparent evolutionary reversal back into saprotrophic ecology. This is possible because ectomycorrhizal fungi retain enzymes for breaking down lignin. [ 31 ] Most ectomycorrhizal relationships are formed between basidiomycetes or ascomycetes and woody trees or shrubs. [ 32 ]
Ericoid Mycorrhizae
Ericoid mycorrhizae evolved from a monophyletic origin around 140 million years ago. [ 33 ] The earliest ericoid mycorrhizae evolved from saprotrophic ascomycetes. [ 34 ] Ericoid mycorrhizae are only present in the Ericales order for plant hosts, and the Leotiales order of fungi. [ 35 ] This specialization suggests that ericoid mycorrhizal partners evolved in parallel with one another in response to environmental change, rather than through reciprocal species-to-species level selection. [ 36 ]
Ericoid mycorrhizal relationships are found in extremely nutrient poor soils in the northern and southern hemispheres. [ 37 ] These environments of low mineral nutrient availability have led to native plants developing sclerophylly, where plants become high in lignin and low in phosphorus and nitrogen. [ 38 ] As a result, decaying plant matter in these areas has an abnormally high carbon to nitrogen ratio, making it resistant to microbial decay. Ericoid mycorrhizae have apparently evolved to conserve minerals in nutrient deficient sclerophyllous litter by directly cycling these nutrients throughout the mycorrhiza system. [ 39 ] Ericoid mycorrhizae also retain saprotrophic abilities, allowing them to extract nitrogen and phosphorus from unmineralized organic material, and resist negative outcomes from high concentrations of toxic cations in the acidic soil environment. [ 40 ]
The mycorrhizal lifestyle has independently convergently evolved multiple times in the history of Earth. [ 41 ] There are multiple ways to categorize mycorrhizal symbiosis. One major categorization is the division between ectomycorrhizas and endomycorrhizas . The two types are differentiated by the fact that the hyphae of ectomycorrhizal fungi do not penetrate individual cells within the root, while the hyphae of endomycorrhizal fungi penetrate the cell wall and invaginate the cell membrane . [ 42 ] [ 43 ]
Some forms of plant-fungal symbiosis are similar to mycorrhizae, but considered distinct. One example is fungal endophytes. Endophytes are defined as organisms that can live within plant cells without causing harm to the plant. They are distinguishable from mycorrhizal fungi by the absence of nutrient-transferring structures for bringing in nutrients from outside the plant. [ 41 ] Some lineages of mycorrhizal fungi may have evolved from endophytes into mycorrhizal fungi, [ 44 ] and some fungi can live as mycorrhizae or as endophytes.
Ectomycorrhizae are distinct in that they do not penetrate into plant cells, but instead form a structure called a Hartig net that penetrates between cells. [ 45 ] Ectomycorrhizas consist of a hyphal sheath, or mantle, covering the root tip and the Hartig net of hyphae surrounding the plant cells within the root cortex . In some cases the hyphae may also penetrate the plant cells, in which case the mycorrhiza is called an endomycorrhiza. Outside the root, ectomycorrhizal extramatrical mycelium forms an extensive network within the soil and leaf litter . Other forms of mycorrhizae, including arbuscular, ericoid, arbutoid, monotropoid, and orchid mycorrhizas, are considered endomycorrhizae. [ 46 ]
Ectomycorrhizas, or EcM, are symbiotic associations between the roots of around 10% of plant families, mostly woody plants including the birch , dipterocarp , eucalyptus , oak , pine , and rose [ 47 ] families, orchids , [ 48 ] and fungi belonging to the Basidiomycota , Ascomycota , and Zygomycota . Ectomycorrhizae associate with relatively few plant species, only about 2% of plant species on Earth, but the species they associate with are mostly trees and woody plants that are highly dominant in their ecosystems, meaning plants in ectomycorrhizal relationships make up a large proportion of plant biomass. [ 49 ] Some EcM fungi, such as many Leccinum and Suillus , are symbiotic with only one particular genus of plant, while other fungi, such as the Amanita , are generalists that form mycorrhizas with many different plants. [ 50 ] An individual tree may have 15 or more different fungal EcM partners at one time. [ 51 ] While the diversity of plants involved in EcM is low, the diversity of fungi involved in EcM is high. Thousands of ectomycorrhizal fungal species exist, hosted in over 200 genera. A recent study has conservatively estimated global ectomycorrhizal fungal species richness at approximately 7750 species, although, on the basis of estimates of knowns and unknowns in macromycete diversity, a final estimate of ECM species richness would probably be between 20,000 and 25,000. [ 52 ] Ectomycorrhizal fungi evolved independently from saprotrophic ancestors many times in the group's history. [ 53 ]
Nutrients can be shown to move between different plants through the fungal network. Carbon has been shown to move from paper birch seedlings into adjacent Douglas-fir seedlings, although not conclusively through a common mycorrhizal network, [ 54 ] thereby promoting succession in ecosystems . [ 55 ] The ectomycorrhizal fungus Laccaria bicolor has been found to lure and kill springtails to obtain nitrogen, some of which may then be transferred to the mycorrhizal host plant. In a study by Klironomos and Hart, Eastern White Pine inoculated with L. bicolor was able to derive up to 25% of its nitrogen from springtails. [ 56 ] [ 57 ] When compared with non-mycorrhizal fine roots, ectomycorrhizae may contain very high concentrations of trace elements, including toxic metals (cadmium, silver) or chlorine. [ 58 ]
The first genomic sequence for a representative of symbiotic fungi, the ectomycorrhizal basidiomycete L. bicolor , was published in 2008. [ 59 ] An expansion of several multigene families occurred in this fungus, suggesting that adaptation to symbiosis proceeded by gene duplication. Within lineage-specific genes those coding for symbiosis-regulated secreted proteins showed an up-regulated expression in ectomycorrhizal root tips suggesting a role in the partner communication. L. bicolor is lacking enzymes involved in the degradation of plant cell wall components (cellulose, hemicellulose, pectins and pectates), preventing the symbiont from degrading host cells during the root colonisation. By contrast, L. bicolor possesses expanded multigene families associated with hydrolysis of bacterial and microfauna polysaccharides and proteins. This genome analysis revealed the dual saprotrophic and biotrophic lifestyle of the mycorrhizal fungus that enables it to grow within both soil and living plant roots. Since then, the genomes of many other ectomycorrhizal fungal species have been sequenced further expanding the study of gene families and evolution in these organisms. [ 60 ]
This type of mycorrhiza involves plants of the Ericaceae subfamily Arbutoideae . It is however different from ericoid mycorrhiza and resembles ectomycorrhiza, both functionally and in terms of the fungi involved. [ 61 ] It differs from ectomycorrhiza in that some hyphae actually penetrate into the root cells, making this type of mycorrhiza an ectendomycorrhiza . [ 62 ]
Arbuscular mycorrhizas , (formerly known as vesicular-arbuscular mycorrhizas), have hyphae that penetrate plant cells, producing branching, tree-like structures called arbuscules within the plant cells for nutrient exchange. Often, balloon-like storage structures, termed vesicles, are also produced. In this interaction, fungal hyphae do not in fact penetrate the protoplast (i.e. the interior of the cell), but invaginate the cell membrane , creating a so-called peri-arbuscular membrane. The structure of the arbuscules greatly increases the contact surface area between the hypha and the host cell cytoplasm to facilitate the transfer of nutrients between them. Arbuscular mycorrhizas are obligate biotrophs, meaning that they depend upon the plant host for both growth and reproduction; they have lost the ability to sustain themselves by decomposing dead plant material. [ 63 ] Twenty percent of the photosynthetic products made by the plant host are consumed by the fungi, the transfer of carbon from the terrestrial host plant is then exchanged by equal amounts of phosphate from the fungi to the plant host. [ 64 ]
Contrasting with the pattern seen in ectomycorrhizae, the species diversity of AMFs is very low, but the diversity of plant hosts is very high; an estimated 78% of all plant species associate with AMFs. [ 49 ] Arbuscular mycorrhizas are formed only by fungi in the division Glomeromycota . Fossil evidence [ 6 ] and DNA sequence analysis [ 65 ] suggest that this mutualism appeared 400-460 million years ago , when the first plants were colonizing land. Arbuscular mycorrhizas are found in 85% of all plant families, and occur in many crop species. [ 47 ] The hyphae of arbuscular mycorrhizal fungi produce the glycoprotein glomalin , which may be one of the major stores of carbon in the soil. [ 66 ] Arbuscular mycorrhizal fungi have (possibly) been asexual for many millions of years and, unusually, individuals can contain many genetically different nuclei (a phenomenon called heterokaryosis ). [ 67 ]
Mycorrhizal fungi belonging to Mucoromycotina , known as “fine root endophytes" (MFREs), were mistakenly identified as arbuscular mycorrhizal fungi until recently. While similar to AMF, MFREs are from subphylum Mucoromycotina instead of Glomeromycotina. Their morphology when colonizing a plant root is very similar to AMF, but they form fine textured hyphae. [ 45 ] Effects of MFREs may have been mistakenly attributed to AMFs due to confusion between the two, complicated by the fact that AMFs and MFREs often colonize the same hosts simultaneously. Unlike AMFs, they appear capable of surviving without a host. This group of mycorrhizal fungi is little understood, but appears to prefer wet, acidic soils and forms symbiotic relationships with liverworts, hornworts, lycophytes, and angiosperms. [ 68 ]
Ericoid mycorrhizae , or ErMs, involve only plants in Ericales and are the most recently evolved of the major mycorrhizal relationships. Plants that form ericoid mycorrhizae are mostly woody understory shrubs; hosts include blueberries, bilberries, cranberries, mountain laurels, rhododendrons, heather, neinei, and giant grass tree. ErMs are most common in boreal forests , but are found in two-thirds of all forests on Earth. [ 49 ] Ericoid mycorrhizal fungi belong to several different lineages of fungi. Some species can live as endophytes entirely within plant cells even within plants outside the Ericales, or live independently as saprotrophs that decompose dead organic matter. This ability to switch between multiple lifestyle types makes ericoid mycorrhizal fungi very adaptable. [ 41 ]
Plants that participate in these symbioses have specialized roots with no root hairs, which are covered with a layer of epidermal cells that the fungus penetrates into and completely occupies. [ 45 ] The fungi have a simple intraradical (growth in cells) phase, consisting of dense coils of hyphae in the outermost layer of root cells. There is no periradical phase and the extraradical phase consists of sparse hyphae that don't extend very far into the surrounding soil. They might form sporocarps (probably in the form of small cups), but their reproductive biology is poorly understood. [ 43 ]
Plants participating in ericoid mycorrhizal symbioses are found in acidic, nutrient-poor conditions. [ 41 ] Whereas AMFs have lost their saprotrophic capabilities, and EcM fungi have significant variation in their ability to produce enzymes needed for a saprotrophic lifestyle, [ 49 ] fungi involved in ErMs have fully retained the ability to decompose plant material for sustenance. Some ericoid mycorrhizal fungi have actually expanded their repertoire of enzymes for breaking down organic matter. They can extract nitrogen from cellulose, hemicellulose, lignin, pectin, and chitin. This would increase the benefit they can provide to their plant symbiotic partners. [ 70 ]
All orchids are myco-heterotrophic at some stage during their lifecycle, meaning that they can survive only if they form orchid mycorrhizae . Orchid seeds are so small that they contain no nutrition to sustain the germinating seedling, and instead must gain the energy to grow from their fungal symbiont. [ 45 ] The OM relationship is asymmetric; the plant seems to benefit more than the fungus, and some orchids are entirely mycoheterotrophic, lacking chlorophyll for photosynthesis. It is actually unknown whether fully autotrophic orchids that do not receive some of their carbon from fungi exist or not. [ 71 ] Like fungi that form ErMs, OM fungi can sometimes live as endophytes or as independent saprotrophs. In the OM symbiosis, hyphae penetrate into the root cells and form pelotons (coils) for nutrient exchange.
This type of mycorrhiza occurs in the subfamily Monotropoideae of the Ericaceae , as well as several genera in the Orchidaceae . These plants are heterotrophic or mixotrophic and derive their carbon from the fungus partner. This is thus a non-mutualistic, parasitic type of mycorrhizal symbiosis. [ citation needed ]
Mycorrhizal fungi form a mutualistic relationship with the roots of most plant species. In such a relationship, both the plants themselves and those parts of the roots that host the fungi, are said to be mycorrhizal. Relatively few of the mycorrhizal relationships between plant species and fungi have been examined to date, but 95% of the plant families investigated are predominantly mycorrhizal either in the sense that most of their species associate beneficially with mycorrhizae, or are absolutely dependent on mycorrhizae. The Orchidaceae are notorious as a family in which the absence of the correct mycorrhizae is fatal even to germinating seeds. [ 72 ]
Recent research into ectomycorrhizal plants in boreal forests has indicated that mycorrhizal fungi and plants have a relationship that may be more complex than simply mutualistic. This relationship was noted when mycorrhizal fungi were unexpectedly found to be hoarding nitrogen from plant roots in times of nitrogen scarcity. Researchers argue that some mycorrhizae distribute nutrients based upon the environment with surrounding plants and other mycorrhizae. They go on to explain how this updated model could explain why mycorrhizae do not alleviate plant nitrogen limitation, and why plants can switch abruptly from a mixed strategy with both mycorrhizal and nonmycorrhizal roots to a purely mycorrhizal strategy as soil nitrogen availability declines. [ 73 ] It has also been suggested that evolutionary and phylogenetic relationships can explain much more variation in the strength of mycorrhizal mutualisms than ecological factors. [ 74 ]
To successfully engage in mutualistic symbiotic relationships with other organisms , such as mycorrhizal fungi and any of the thousands of microbes that colonize plants, plants must discriminate between mutualists and pathogens, allowing the mutualists to colonize while activating an immune response towards the pathogens. Plant genomes code for potentially hundreds of receptors for detecting chemical signals from other organisms. Plants dynamically adjust their symbiotic and immune responses, changing their interactions with their symbionts in response to feedbacks detected by the plant. [ 75 ] In plants, the mycorrhizal symbiosis is regulated by the common symbiosis signaling pathway (CSSP), a set of genes involved in initiating and maintaining colonization by endosymbiotic fungi and other endosymbionts such as Rhizobia in legumes . The CSSP has origins predating the colonization of land by plants, demonstrating that the co-evolution of plants and arbuscular mycorrhizal fungi is over 500 million years old. [ 76 ] In arbuscular mycorrhizal fungi, the presence of strigolactones , a plant hormone, secreted from roots induces fungal spores in the soil to germinate, stimulates their metabolism, growth and branching, and prompts the fungi to release chemical signals the plant can detect. [ 77 ] Once the plant and fungus recognize one another as suitable symbionts, the plant activates the common symbiotic signaling pathway, which causes changes in the root tissues that enable the fungus to colonize. [ 78 ]
Experiments with arbuscular mycorrhizal fungi have identified numerous chemical compounds to be involved in the "chemical dialog" that occurs between the prospective symbionts before symbiosis is begun. In plants, almost all plant hormones play a role in initiating or regulating AMF symbiosis, and other chemical compounds are also suspected to have a signaling function. While the signals emitted by the fungi are less understood, it has been shown that chitinaceous molecules known as Myc factors are essential for the formation of arbuscular mycorrhizae. Signals from plants are detected by LysM-containing receptor-like kinases, or LysM-RLKs. AMF genomes also code for potentially hundreds of effector proteins, of which only a few have a proven effect on mycorrhizal symbiosis, but many others likely have a function in communication with plant hosts as well. [ 79 ]
Many factors are involved in the initiation of mycorrhizal symbiosis, but particularly influential is the plant's need for phosphorus . Experiments involving rice plants with a mutation disabling their ability to detect P starvation show that arbuscular mycorrhizal fungi detection, recruitment and colonization is prompted when the plant detects that it is starved of phosphorus. [ 80 ] Nitrogen starvation also plays a role in initiating AMF symbiosis. [ 81 ]
The mechanisms by which mycorrhizae increase absorption include some that are physical and some that are chemical. Physically, most mycorrhizal mycelia are much smaller in diameter than the smallest root or root hair, and thus can explore soil material that roots and root hairs cannot reach, and provide a larger surface area for absorption. Chemically, the cell membrane chemistry of fungi differs from that of plants. For example, they may secrete organic acids that dissolve or chelate many ions, or release them from minerals by ion exchange . [ 82 ] Mycorrhizae are especially beneficial for the plant partner in nutrient-poor soils. [ 83 ]
The mycorrhizal mutualistic association provides the fungus with relatively constant and direct access to carbohydrates , such as glucose and sucrose . [ 84 ] The carbohydrates are translocated from their source (usually leaves) to root tissue and on to the plant's fungal partners. In return, the plant gains the benefits of the mycelium 's higher absorptive capacity for water and mineral nutrients, partly because of the large surface area of fungal hyphae, which are much longer and finer than plant root hairs , and partly because some such fungi can mobilize soil minerals unavailable to the plants' roots. The effect is thus to improve the plant's mineral absorption capabilities. [ 85 ]
Unaided plant roots may be unable to take up nutrients that are chemically or physically immobilised ; examples include phosphate ions and micronutrients such as iron. One form of such immobilization occurs in soil with high clay content, or soils with a strongly basic pH . The mycelium of the mycorrhizal fungus can, however, access many such nutrient sources, and make them available to the plants they colonize. [ 86 ] Thus, many plants are able to obtain phosphate without using soil as a source. Another form of immobilisation is when nutrients are locked up in organic matter that is slow to decay, such as wood, and some mycorrhizal fungi act directly as decay organisms, mobilising the nutrients and passing some onto the host plants; for example, in some dystrophic forests, large amounts of phosphate and other nutrients are taken up by mycorrhizal hyphae acting directly on leaf litter , bypassing the need for soil uptake. [ 87 ] Inga alley cropping , an agroforestry technique proposed as an alternative to slash and burn rainforest destruction, [ 88 ] relies upon mycorrhiza within the root system of species of Inga to prevent the rain from washing phosphorus out of the soil. [ 89 ]
In some more complex relationships, mycorrhizal fungi do not just collect immobilised soil nutrients, but connect individual plants together by mycorrhizal networks that transport water, carbon, and other nutrients directly from plant to plant through underground hyphal networks. [ 90 ]
Suillus tomentosus , a basidiomycete fungus, produces specialized structures known as tuberculate ectomycorrhizae with its plant host lodgepole pine ( Pinus contorta var. latifolia ). These structures have been shown to host nitrogen fixing bacteria which contribute a significant amount of nitrogen and allow the pines to colonize nutrient-poor sites. [ 91 ]
Mycorrhizal plants are often more resistant to diseases, such as those caused by microbial soil-borne pathogens . These associations have been found to assist in plant defense both above and belowground. Mycorrhizas have been found to excrete enzymes that are toxic to soil borne organisms such as nematodes. [ 92 ] More recent studies have shown that mycorrhizal associations result in a priming effect of plants that essentially acts as a primary immune response. When this association is formed a defense response is activated similarly to the response that occurs when the plant is under attack. As a result of this inoculation, defense responses are stronger in plants with mycorrhizal associations. [ 93 ] Ecosystem services provided by mycorrhizal fungi may depend on the soil microbiome. [ 94 ] Furthermore, mycorrhizal fungi was significantly correlated with soil physical variable, but only with water level and not with aggregate stability [ 95 ] [ 96 ] and can lead also to more resistant to the effects of drought. [ 97 ] [ 98 ] [ 99 ] Moreover, the significance of mycorrhizal fungi also includes alleviation of salt stress and its beneficial effects on plant growth and productivity. Although salinity can negatively affect mycorrhizal fungi, many reports show improved growth and performance of mycorrhizal plants under salt stress conditions. [ 100 ]
Plants connected by mycorrhizal fungi in mycorrhizal networks can use these underground connections to communicate warning signals. [ 101 ] [ 102 ] For example, when a host plant is attacked by an aphid , the plant signals surrounding connected plants of its condition. Both the host plant and those connected to it release volatile organic compounds that repel aphids and attract parasitoid wasps , predators of aphids. [ 101 ] This assists the mycorrhizal fungi by conserving its food supply. [ 101 ]
Plants grown in sterile soils and growth media often perform poorly without the addition of spores or hyphae of mycorrhizal fungi to colonise the plant roots and aid in the uptake of soil mineral nutrients. [ 103 ] The absence of mycorrhizal fungi can also slow plant growth in early succession or on degraded landscapes. [ 104 ] The introduction of alien mycorrhizal plants to nutrient-deficient ecosystems puts indigenous non-mycorrhizal plants at a competitive disadvantage. [ 105 ] This aptitude to colonize barren soil is defined by the category Oligotroph .
Fungi have a protective role for plants rooted in soils with high metal concentrations, such as acidic and contaminated soils . Pine trees inoculated with Pisolithus tinctorius planted in several contaminated sites displayed high tolerance to the prevailing contaminant, survivorship and growth. [ 106 ] One study discovered the existence of Suillus luteus strains with varying tolerance of zinc . Another study discovered that zinc-tolerant strains of Suillus bovinus conferred resistance to plants of Pinus sylvestris . This was probably due to binding of the metal to the extramatricial mycelium of the fungus, without affecting the exchange of beneficial substances. [ 105 ]
Mycorrhizas are present in 92% of plant families studied (80% of species), [ 47 ] with arbuscular mycorrhizas being the ancestral and predominant form, [ 47 ] and the most prevalent symbiotic association found in the plant kingdom. [ 84 ] The structure of arbuscular mycorrhizas has been highly conserved since their first appearance in the fossil record, [ 6 ] with both the development of ectomycorrhizas and the loss of mycorrhizas, evolving convergently on multiple occasions. [ 47 ]
Associations of fungi with the roots of plants have been known since at least the mid-19th century. However, early observers simply recorded the fact without investigating the relationships between the two organisms. [ 107 ] This symbiosis was studied and described by Franciszek Kamieński in 1879–1882. [ 108 ] [ 109 ]
CO 2 released by human activities is causing climate change and possible damage to mycorrhizae, but the direct effect of an increase in the gas should be to benefit plants and mycorrhizae. [ 110 ] In Arctic regions, nitrogen and water are harder for plants to obtain, making mycorrhizae crucial to plant growth. [ 111 ] Since mycorrhizae tend to do better in cooler temperatures, warming could be detrimental to them. [ 112 ] Gases such as SO 2 , NO-x, and O 3 produced by human activity may harm mycorrhizae, causing reduction in " propagules , the colonization of roots, degradation in connections between trees, reduction in the mycorrhizal incidence in trees, and reduction in the enzyme activity of ectomycorrhizal roots." [ 113 ]
A company in Israel , Groundwork BioAg, has discovered a method of using mycorrhizal fungi to increase agricultural crops while sequestering greenhouse gases and eliminating CO2 from the atmosphere. [ 114 ]
In 2021, the Society for the Protection of Underground Networks was launched. SPUN is a science-based initiative to map and protect the mycorrhizal networks regulating Earth’s climate and ecosystems. Its stated goals are mapping, protecting, and harnessing mycorrhizal fungi. | https://en.wikipedia.org/wiki/Mycorrhiza |
Mycorrhiza helper bacteria ( MHB ) are a group of organisms that form symbiotic associations with both ectomycorrhiza and arbuscular mycorrhiza . [ 1 ] MHBs are diverse and belong to a wide variety of bacterial phyla including both Gram-negative and Gram-positive bacteria . [ 1 ] Some of the most common MHBs observed in studies belong to the genera Pseudomonas and Streptomyces . [ 1 ] MHBs have been seen to have extremely specific interactions with their fungal hosts at times, but this specificity is lost with plants. [ 2 ] MHBs enhance mycorrhizal function, growth, nutrient uptake to the fungus and plant , improve soil conductance, aid against certain pathogens , and help promote defense mechanisms . [ 1 ] These bacteria are naturally present in the soil, and form these complex interactions with fungi as plant root development starts to take shape. [ 2 ] The mechanisms through which these interactions take shape are not well-understood and needs further study. [ 1 ] [ 2 ] [ 3 ]
MHBs consist of a diverse group of bacteria , often gram-negative and gram-positive bacteria . Most of the bacteria are associated with both ectomycorrhiza and arbuscular mycorrhiza , but some show specificity to a particular type of fungus. [ 1 ] The common phyla that MHB belong to will be addressed in the following sections, as well as common genera .
The Pseudomonadota (formerly Proteobacteria) are a large and diverse group of gram-negative bacteria containing five classes . Pseudomonas is in the gammaproteobacteria class. Specific bacteria within this genus are strongly associated as being MHBs in the rhizosphere of both ectomycorrhiza and arbuscular mycorrhiza. [ 1 ] Pseudomonas fluorescens has been examined in several studies to understand how they work in benefiting the mycorrhiza and plant. [ 1 ] In one study, they found that the bacteria helped ectomycorrhizal fungi promote a symbiotic relationship with the plant by examining an increase in formation of mycorrhiza when Pseudomonas fluorescens was applied to the soil. [ 4 ] Some bacteria improve root colonization and plant growth when associated with arbuscular mycorrhiza. [ 5 ] It has been hypothesized that MHBs aid the plant in pathogenic defense by improving the nutrient uptake from the soil, allowing plants to allocate more resources to broad defense mechanisms. [ 6 ] However, the mechanism these species use to help both fungi is still unknown and needs to be further investigated. [ 5 ]
Actinomycetota are gram-positive bacteria and are naturally found in the soil. In this phylum, Streptomyces is the largest genus of bacteria, and are often associated with MHBs. [ 1 ] Streptomyces have been a model organism of study in biological research on MHBs. In one study, it has been reported that Streptomyces are responsible for increasing root colonization, plant biomass growth, mycorrhizal colonization, and fungal growth. [ 7 ] [ 8 ] However, there is not just a single mechanism that the MHBs participate in. [ 1 ] [ 7 ] [ 8 ] It has also been found that Streptomyces interact with ectomycorrhiza and arbuscular mycorrhiza. [ 1 ] While these interactions need further understanding, they seem to be extremely common in natural soil. [ 8 ]
Bacillota are gram-positive bacteria, many of which have a low GC content in their DNA . There are a few genera that act as MHBs, but one of the most common is Bacillius . [ 1 ] Bacillius belong to the class Bacilli , and are rod-shaped organisms that can be free-living or pathogenic. However, in the presence of mycorrhiza some species can be beneficial and are considered to be MHBs. [ 1 ] Since they are common, they can form a relationship with ectomycorrhiza and arbuscular mycorrhiza, similar to the previous genera. [ 1 ] Bacillius aids in the establishment and growth of mycorrhiza, and helps with the fixation of nitrogen in the rhizosphere. [ 9 ] [ 10 ] [ 11 ]
MHBs are known to have several functions when interacting with the roots of plants and growth of fungi. In several studies it has been reported that MHBs can help fungi by increasing mycelial growth and aid in nutrient intake. [ 3 ] The mycelial increase allows for fungi to absorb more nutrients, increasing its surface area. [ 9 ]
Some MHBs are known to help break down molecules to a more usable form. [ 1 ] MHBs can obtain both inorganic and organic nutrients in the soil through a direct process known as mineral-weathering which aids in the recycling of nutrients throughout the environment. [ 12 ] The process of mineral-weathering releases protons and iron into the soil. [ 12 ] This results in a lowering of the pH . [ 12 ] A diverse group of bacteria can participate in the mineral- weathering process, such as Pseudomonas , Burkholderia , and Collimonas . [ 12 ] The acidification of the soil by MHBs is hypothesized to be linked to their glucose metabolism . [ 12 ]
MHBs also help gather unavailable phosphorus from the surrounding soil. [ 13 ] Phosphate solubilizing rhizobacteria are the most common MHB that aids in phosphorus uptake. [ 13 ] The bacteria are involved in this process by releasing phosphate-degrading compounds in the soil to break down organic and inorganic phosphate. [ 14 ] As a result, the MHB create a pool of phosphate that the mycorrhiza then use. [ 14 ] [ 15 ] The bacteria work in phosphorus-limited conditions to help the mycorrhiza establish and grow. [ 13 ] Streptomyces can assist arbuscular mycorrhiza in phosphorus-limited conditions through a similar process. [ 8 ] [ 13 ]
MHBs in the rhizosphere often have the capability to acquire nitrogen that the plant can use. The MHBs are able to fix nitrogen in the soil, and create pools of available nitrogen. [ 16 ] However, MHBs do not cause plant modifications as legumes do, to help with nitrogen-fixation . [ 16 ] Nitrogen-fixation is done only in the surrounding soil in relation to the mycorrhiza. [ 16 ] In one study, researchers reported that a Bacillius MHB contributed to the nitrogen-fixation, and among other factors helped the plant grow when inoculated with a fungus. [ 11 ]
It has been proposed (Kaska et al., 1994) that MHBs induce growth hormones in a plant , which helps the mycorrhiza interact with the lateral roots in soil. [ 17 ] An increase of root formation was also observed when Pseudomonas putida produced growth hormones, and was inoculated with the arbuscular mycorrhiza Gigaspora rosea on a cucumber plant. [ 18 ] The inoculation of both the MHB and the fungus allowed for an increase in root elongation and growth in the soil, similar to the previous study. [ 18 ] In another study, it was found that MHB can release gaseous compounds to attract and aid in the growth of fungi. [ 19 ] The introduction of growth hormones and gaseous compounds produced by MHBs was only discovered recently, and requires further study on how MHBs influence the mycorrhiza symbiotic relationship and root growth.
Researchers have reported that fungal genes can be altered in the presence of an MHB. [ 20 ] In one study, it was hypothesized that in the presence of a fungus, an MHB will promote an increase in the expression of a gene that helps to promote growth in the fungus. [ 20 ] The fungus changes its genes expression after the MHB has promoted growth of the fungus, thus the alteration of the gene is an indirect effect. [ 20 ] This is likely the cause of certain compounds or signals released by the MHBs, and further analysis is needed to better understand this communication. [ 20 ]
Only certain bacteria are specific to mycorrhizal fungi groups. [ 15 ] Results have shown that the indigenous arbuscular mycorrhizal fungi of the clover plant could only grow in the presence Pseudomonas putida , but in fact, the plant could grow with the presence of multiple bacteria. [ 15 ] It has been hypothesized that rhizosphere helper bacteria, in the soil, have developed traits to aid them in competition for inoculating fungi in their environment. [ 8 ] Thus, it is plausible that MHBs select for certain fungi and developed some specificity towards a fungus that favors the bacteria. [ 8 ] [ 1 ]
MHBs help mycorrhiza establish symbiotic associations in stressful environments such as those high in toxic metals . [ 21 ] In harsh environments, the bacteria assist in acquiring more nutrients such as nitrogen and phosphorus . [ 22 ] [ 23 ] MHBs help to prevent the uptake of toxic metals including lead , zinc , and cadmium . [ 22 ] [ 23 ] The bacteria decrease the amount of metals taken up by the plant through blockade mechanisms. [ 22 ] [ 23 ] The blockade of the toxic metals by the bacteria allows the fungus to form a stronger symbiotic association with the plant, and promotes the growth of both. [ 22 ] [ 23 ] Another proposed mechanism of MHBs in toxic environments is that the bacteria aid the mycorrhiza by compensating for the negative effects the toxic metal imposed. [ 24 ] The MHBs help by increasing the plant nutrition uptake, and creating a balance between the macronutrients and micronutrients . [ 23 ] [ 24 ] Thus, MHBs have mechanisms to help the plant tolerate harsh and otherwise unsuitable environments. This relationship makes them great candidates for bioremediation .
In the presence of a pathogenic fungus , most studies show that MHBs aid in fighting off pathogens. [ 2 ] However, there have been a few cases where MHBs help to promote pathogenic effects of a fungus. [ 2 ]
There have been a few studies that have found that MHBs aid pathogenic fungi. One study showed that MHBs aided in colonization of a type of fungal pathogen because the surrounding environment was unsuitable for the symbiotic mycorrhiza. [ 25 ] Thus the MHB became more harmful under certain conditions to increase their own fitness. [ 25 ] [ 2 ] Researchers have also found that MHBs help the pathogenic fungus to colonize on the surface of the plant. [ 25 ] This has a negative effect on the plant, by increasing the deleterious effects of the fungus. Another proposed mechanism is that MHBs alter the defense mechanism of the plant, by shutting off degrading peroxidase enzymes, and allowing the pathogenic fungus to inoculate the plant. [ 26 ]
In several studies, researchers have proposed numerous ways MHBs defend against pathogens. In one experiment researchers observed that MHBs produced acid in the surrounding environment, which helped to fight off various pathogens. [ 27 ] It has also been hypothesized that the defense mechanism against pathogens is from a combination of both fungi and plant. [ 27 ] Another study found that MHBs release antifungal metabolites into the soil. [ 28 ] The anti-fungal metabolites produce antagonistic effects towards the pathogenic fungi. [ 28 ] However, MHBs can help defend a pathogen depending on the nutrient availability and space in the rhizosphere. [ 1 ] [ 27 ] Further research is still necessary to understand the mechanism of how MHBs aid mycorrhiza in order to defeat pathogens, and if this role is symbiotic or more mutualistic in nature. | https://en.wikipedia.org/wiki/Mycorrhiza_helper_bacteria |
Mycorrhizal amelioration of heavy metals or pollutants is a process by which mycorrhizal fungi in a mutualistic relationship with plants can sequester toxic compounds from the environment, as a form of bioremediation . [ 1 ] [ 2 ] [ 3 ]
These symbiotic relationships are generally between plants and arbuscular mycorrhizae in the Glomeromycota clade of fungi. [ 3 ] [ 4 ] Other types of fungi have been documented. For example, there is a case where zinc phytoextraction from willows was increased after the Basidiomycete fungus Paxillus involutus was inoculated in the soil. [ 5 ]
The mycorrhizae allow the plants to increase their biomass, which increases their tolerance to heavy metals . The fungi also stimulate the uptake of heavy metals (such as manganese and cadmium ) with the enzymes and organic acids (such as acetic acid and malic acid ) that they excrete into their surroundings in order to digest them. [ 5 ] [ 6 ]
The fungi can prevent heavy metals from traveling past the roots of the plant. [ 6 ] They can also store heavy metals in their vacuoles. However, in some cases, the fungi do not decrease the uptake of heavy metals by plants but increase their tolerance. In some cases, this is done by increasing the overall biomass of the plant so that there is a lower concentration of metals. They can also modify the response of the plant to heavy metals at the level of plant transcription and translation. [ 3 ] [ 7 ]
Mycorrhizae remain functional underground following extreme conditions, such as a forest fire. Researchers believe that this allows them to obtain minerals and nutrients that are released during a fire before they are leached out of the soil. This likely increases the ability to recover quickly after forest fires. [ 8 ]
Serpentine soils are in part characterized by a low calcium-to-magnesium ratio. Studies indicate that arbuscular mycorrhiza helps plants increase their magnesium uptake in soils with low amounts of magnesium. However, plants in serpentine soils inoculated with fungus either showed no effect on magnesium concentration or decreased magnesium uptake. [ 9 ]
Studies show that mycorrhizal symbionts of poplar seedlings are capable of preventing heavy metals reaching vulnerable parts of the plant by keeping the toxins in the rhizosphere . [ 10 ] Another study demonstrates that Arctostaphylos uva-ursi plants in symbiotic relationships were more resistant to toxins because the fungi helped the plants grow below toxic layers of soil. [ 11 ]
In China's provinces of Guizhou , Yunnan and Guangxi , rocky desertification is expanding and is not well controlled. This area is characterized by soil depletion, soil erosion and droughts. It is very difficult for plants to grow in this region, and it is mostly filled with drought-resistant plants , lithophytes and calciphilopteris plants. Morus alba , commonly known as a mulberry, is a drought-resistant tree that can tolerate barren soils. It has been found that mulberry inoculated with arbuscular mycorrhiza has increased survivability in karst desert areas and, therefore, an increased rate of soil improvement and reduced erosion. [ 12 ]
In 1993, artist Mel Chin collaborated with USDA agronomist Dr. Rufus Chaney in an effort to detoxify Pigs Eye Landfill, a superfund site in Saint Paul , Minnesota . The team planted Thlaspi , which had been selected for increased uptake and sequestration of heavy metals. Analysis showed elevated cadmium concentrations in Thlaspi biomass. [ 13 ] It has been found that Thlaspi has a significant arbuscular mycorrhiza association. [ citation needed ]
Slovakia has many heavy metal mines, which have caused significant regional soil contamination . Samples of Thlaspi harvested in Slovakia from contaminated soils near a lead mine showed increased levels of cadmium, lead, and zinc. Furthermore, Thlaspi growing in contaminated regions had higher rates of certain arbuscular mycorrhizal fungi when compared to non-contaminated Thlaspi . [ 14 ] Since manual clean-up is usually inefficient and expensive, mycorrhiza colonized Thlaspi may be useful in bioremediation efforts. [ citation needed ] | https://en.wikipedia.org/wiki/Mycorrhizal_bioremediation |
Soil carbon storage is an important function of terrestrial ecosystems . Soil contains more carbon than plants and the atmosphere combined. [ 1 ] Understanding what maintains the soil carbon pool is important to understand the current distribution of carbon on Earth, and how it will respond to environmental change. While much research has been done on how plants, free-living microbial decomposers , and soil minerals affect this pool of carbon, it is recently coming to light that mycorrhizal fungi —symbiotic fungi that associate with roots of almost all living plants—may play an important role in maintaining this pool as well. [ 2 ] Measurements of plant carbon allocation to mycorrhizal fungi have been estimated to be 5 to 20% of total plant carbon uptake, [ 3 ] [ 4 ] and in some ecosystems the biomass of mycorrhizal fungi can be comparable to the biomass of fine roots. [ 5 ] Recent research has shown that mycorrhizal fungi hold 50 to 70 percent of the total carbon stored in leaf litter and soil on forested islands in Sweden. [ 6 ] Turnover of mycorrhizal biomass into the soil carbon pool is thought to be rapid [ 7 ] and has been shown in some ecosystems to be the dominant pathway by which living carbon enters the soil carbon pool. [ 8 ]
Outlined below are the leading lines of evidence for how different aspects of mycorrhizal fungi may alter soil carbon decomposition and storage. Evidence is presented for arbuscular and ectomycorrhizal fungi separately as they are phylogenetically distinct and often function in very different ways.
Based on the magnitude of mycorrhizal fungal inputs to the soil carbon pool, some have suggested that variation in the recalcitrance of mycorrhizal biomass may be important for predicting soil carbon storage, as it would affect the rate at which the contribution of mycorrhizal fungi to soil carbon is returned to the atmosphere. [ 9 ] The compound glomalin , produced only by arbuscular mycorrhizal fungi, has been found to accumulate in some soils, and may be a substantial fraction of the soil carbon pool in these ecosystems. [ 10 ] However, a recent set of experiments demonstrates the presence of arbuscular mycorrhizal fungi results in net losses of soil carbon, [ 11 ] calling into question the role of glomalin produced by arbuscular mycorrhizal fungi leading to increased soil carbon storage. [ 12 ] Proteomic work has revealed that most of the proteins isolated in the glomalin extraction are not of mycorrhizal origin, and therefore the contribution of this molecule to soil C storage has likely been overestimated. [ 13 ]
Using a similar line of argument, Langley and Hungate (2003) [ 14 ] argued that the abundance of chitin in ectomycorrhizal tissues may reduce decomposition rates of these fungi, under the assumption that chitin is recalcitrant. This possibility was tested and refuted recently. Fernandez and Koide (2012) show that chitin does not decompose more slowly than other chemical compounds in ectomycorrhizal tissues, and that chitin concentrations positively correlated with mycorrhizal biomass decomposition rates, rather than negatively. [ 15 ]
Mycorrhizal fungi are nutrient rich structures compared to the roots they colonize, and it is possible that mycorrhizal colonization of roots leads to increased rates of root decomposition because decomposers would have greater access to nutrients. Evidence is equivocal on this point, as ectomycorrhizal colonization does increase fine root decomposition rates substantially compared to uncolonized roots in some ecosystems, [ 16 ] while Pinus edulis roots colonized predominately by ectomycorrhizal fungi from the Ascomycota group have been found to decompose more slowly than uncolonized controls. [ 17 ]
In an experiment where the effect of arbuscular mycorrhizal colonization on plant decomposition was tested, [ 18 ] only aboveground plant material was found to have decomposed faster after 3 months while root decomposition remained unchanged, even though arbuscular mycorrhizal fungi are confined to roots.
Soil aggregation can physically protect organic carbon from decay by soil microbes. [ 19 ] More aggregate formation can result in more soil carbon storage. There is much evidence that arbuscular mycorrhizal fungi increase soil aggregate formation, and that aggregate formation may be mediated by the arbuscular mycorrhizal protein glomalin . [ 20 ] Therefore, even if glomalin itself is not exceptionally recalcitrant and chemically resistant to decomposition (as described above) it may still contribute to soil carbon storage by physically protecting other organic matter from decomposition by promoting soil aggregation.
There is little information regarding the role of ectomycorrhizal fungi in soil aggregate stability. There are anecdotal accounts of ectomycorrhizal fungi increasing aggregation in sand in-growth bags commonly used to trap these fungi, [ 21 ] but no current evidence that they promote aggregate formation or stability in field soils.
Arbuscular mycorrhizal fungi have been shown to increase soil carbon decomposition in nutrient rich patches. [ 22 ] Since arbuscular mycorrhizal fungi are thought to lack the ability to produce the enzymes to catalyze this decomposition [ 23 ] it is generally thought that they stimulate free-living decomposer communities to increase activity by exuding labile energy substrates, a process termed priming. Recent lab experiments have shown that the presence of arbuscular mycorrhizal fungi increases losses of soil carbon compared to soils where arbuscular mycorrhizal fungi are excluded, and that the difference is greater under elevated CO 2 when the abundance of arbuscular mycorrhizal fungi is greater. [ 24 ] The evidence for ectomycorrhizal priming is so far inconclusive. Field evidence suggests that ectomycorrhizal fungi may be increasing the rate of soil carbon degradation, [ 25 ] [ 26 ] however lab tests show that exudation from fine roots decreases with increasing ectomycorrhizal colonization, [ 27 ] which suggests that abundance of ectomycorrhizal fungi should reduce priming effects. Brzostek et al. (2012) report variation in form of nitrogen produced in the rhizosphere of trees that vary in mycorrhizal type, however the effects of root and mycorrhizal priming could not be separated. [ 28 ]
The first report of mycorrhizal inhibition of decomposition was in 1971 and came from ectomycorrhizal Pinus radiata plantations in New Zealand. Authors show that excluding roots and mycorrhizal fungi resulted in net carbon loss, and that the result could not be explained by soil disturbance effects. [ 29 ] The mechanism presented is that ectomycorrhizal fungi can compete with free-living decomposers for nutrients, and thereby limit the rate of total decomposition. Since then there have been several other reports of ectomycorrhizal fungi reducing activity and decomposition rates of free-living decomposers and thereby increasing soil carbon storage. [ 30 ] [ 31 ] [ 32 ] A theoretical ecosystem model recently demonstrated that greater access to organic nitrogen by mycorrhizal fungi should slow decomposition of soil carbon by free-living decomposers by inducing nutrient limitation. [ 33 ] Koide and Wu (2003) made a strong case that the effect of ectomycorrhizal fungi on reducing decomposition may have more to do with competition for soil water than soil nutrients. [ 34 ]
It is possible that arbuscular mycorrhizal fungi may be outcompeting free-living decomposers for either water or nutrients in some systems as well; however, to date there is no demonstration of this, and it seems that arbuscular mycorrhizal fungi may more often increase, rather than decrease rates of decomposition by free-living microbial decomposers. [ 35 ] [ 36 ]
Further reading on the role of arbuscular and ectomycorrhizal fungi in soil carbon storage and decomposition can be found in Zhu and Miller 2003, [ 37 ] Ekblad et al. 2013, [ 38 ] respectively, and the 2019 paper "Climatic controls of decomposition drive the global biogeography of forest-tree symbioses". [ 39 ] | https://en.wikipedia.org/wiki/Mycorrhizal_fungi_and_soil_carbon_storage |
The mycorrhizosphere includes "roots, hyphae of the directly connected mycorrhizal fungi, associated microorganisms
and the soil within their direct influence". [ 1 ] It is the region in which nutrients released from the root and the fungus increase the microbial population and its activities. The roots of most terrestrial plants, including most crop plants and almost all woody plants , are colonized by mycorrhiza-forming symbiotic fungi. In this relationship, the plant roots are infected by a fungus, but the rest of the fungal mycelium continues to grow through the soil, digesting and absorbing nutrients and water and sharing these with its plant host . The fungus in turn benefits by receiving photosynthetic sugars from its host.
The mycorrhizosphere involves a community of microorganisms. There are three divisions of fungi that can form mycorrhizae, the Glomeromycota , Ascomycota , and Basidiomycota . Glomeromycota can form arbuscular mycorrhizae with angiosperms (flowering plants), gymnosperms (seed-producing plants), pteridophytes , mosses , lycopods , and Psilotales . Ascomycota fungi form ericoid mycorrhizas with plants of the order Ericales , and ectomycorrhizas with trees. Basidiomycota fungi form ecto-, orchid , monotropoid, arbutoid, and some ericoid mycorrhizae. Fungal hyphae are thinner than plant roots, which allows them to penetrate areas in the soil with moisture and nutrient that are inaccessible to roots. In some cases, mycorrhizal fungi in the mycorrhizosphere may ward off fungal plant pathogens . For example, the arbuscular mycorrhizal fungus Glomus intraradices reduces germination of the pathogen Fusarium oxysporum , but stimulates germination of a non-pathogenic fungus Trichoderma harzianum . [ 1 ]
Soil bacteria in the mycorrhizosphere influence plant growth in several ways: by affecting the uptake of nutrients, providing protection against pathogens, contributing to nitrogen fixation , and contributing to mineral weathering . Archaea are also known to exist in mycorrhizosphere. They may contribute to nitrogen fixation and produce antibiotic compounds, but the extent of their interactions with other organisms and their overall function is not well known. [ 1 ] Soil protozoa feed on bacteria, and, in some cases, hyphae. The type of mycorrhizae greatly influences the protozoal population in a mycorrhizosphere. For example, a Paxillus involutus – conifer mycorrhiza seems to reduce the density of protozoa in the resulting mycorrhizosphere, but mycorrhizae formed with Lactarius rufus and Suillus bovinus have the opposite effect. Other soil organisms that influence the mycorrhizosphere community include soil animals such as nematodes , mites , and earthworms , which forage on roots, hyphae and their associated microorganisms. [ 1 ] | https://en.wikipedia.org/wiki/Mycorrhizosphere |
D -Mycosamine is an amino sugar found in several polyene antimycotics . Structural analogs of these agents lacking this monosaccharide component do not exhibit substantial antifungal activity. [ 1 ]
This biochemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Mycosamine |
Mycotaxon was a peer-reviewed scientific journal that covers the nomenclature and taxonomy of fungi, including lichens . The journal was founded by Grégoire L. Hennebert and Richard P. Korf in 1974. [ 1 ] They were frustrated that papers submitted to journals such as Mycologia took a year or longer from submission to publication. Korf and Hennebert introduced a number of innovations to make their journal more efficient and accessible than its contemporaries. Mycotaxon reduced the wait time between submission and publication by requiring authors to submit camera-ready copy. Linotype was the industry standard at the time; Mycotaxon used photo-offset lithography to expedite publication. [ 2 ] A quarterly journal, Mycotaxon aimed to publish papers within four months of submission. [ 3 ]
Mycotaxon took an unusual non-blind approach to refereeing: authors were required to enlist a reviewer outside their institution to peer-review their manuscript prior to its submission. [ 2 ] Initially Mycotaxon did not demand page charges from authors, rather relying on subscription fees to finance publication. Papers of all lengths were accepted. [ 3 ] The journal published its last issue (volume 137, issue 4) on November 11, 2023. [ 4 ]
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Mycotoxicology is the branch of mycology that focuses on analyzing and studying the toxins produced by fungi , known as mycotoxins . [ 1 ] In the food industry it is important to adopt measures that keep mycotoxin levels as low as practicable, especially those that are heat-stable. These chemical compounds are the result of secondary metabolism initiated in response to specific developmental or environmental signals. This includes biological stress from the environment, such as lower nutrients or competition for those available. Under this secondary path the fungus produces a wide array of compounds in order to gain some level of advantage, such as incrementing the efficiency of metabolic processes to gain more energy from less food, or attacking other microorganisms and being able to use their remains as a food source.
Mycotoxins are made by fungi and are toxic to vertebrates and other animal groups in low concentrations. Low-molecular-weight fungal metabolites such as ethanol that are toxic only in high concentrations are not considered mycotoxins. Mushroom poisons are fungal metabolites that can cause disease and death in humans and other animals; they are rather arbitrarily excluded from discussions of mycotoxicology. Molds make mycotoxins; mushrooms and other macroscopic fungi make mushroom poisons. The distinction between a mycotoxin and a mushroom poison is based not only on the size of the producing fungus, but also on human intention. Mycotoxin exposure is almost always accidental. In contrast, with the exception of the victims of a few mycologically accomplished murderers, mushroom poisons are usually ingested by amateur mushroom hunters who have collected, cooked, and eaten what was misidentified as a harmless, edible species. [ 2 ]
Mycotoxins are hard to define and are also very difficult to classify. Mycotoxins have diverse chemical structures, biosynthetic origins, myriad biological effects, and produce numerous different fungal species. Classification generally reflects the training of the categorizer and does not adhere to any set system. Mycotoxins are often arranged by physicians depending on what organ they effect. Mycotoxins can be categorized as nephrotoxins, hepatoxins, immunotoxins, neurotoxins, etc. Generic groups created by cell biologist are teratogens, mutagens, allergens, and carcinogens. Organic chemists have attempted to classify them by their chemical structures (e.g., lactones, coumarins); biochemists according to their biosynthetic origins (polyketides, amino acid-derived, etc.); physicians by the illnesses they cause (e.g., St. Anthony's fire, stachybotryotoxicosis), and mycologists by the fungi that produce them (e.g., Aspergillus toxins, Penicillium toxins). None of these classifications is entirely satisfactory. Aflatoxin, for example, is a hepatotoxic, mutagenic, carcinogenic, difuran-containing, polyketide-derived Aspergillus toxin. Zearalenone is a Fusarium metabolite with potent estrogenic activity; hence, in addition to being called (probably erroneously) a mycotoxin, it also has been labeled a phytoestrogen, a mycoestrogen, and a growth promotant. [ 3 ]
Citrinin was first isolated from Penicillium citrinum prior to World War II; [ 4 ] subsequently, it was identified in over a dozen species of Penicillium and several species of Aspergillus (e.g., Aspergillus terreus and Aspergillus niveus ), including certain strains of Penicillium camemberti (used to produce cheese) and Aspergillus oryzae (used to produce sake, miso, and soy sauce). [ 5 ] More recently, citrinin has also been isolated from Monascus ruber and Monascus purpureus, industrial species used to produce red pigments. [ 6 ]
The aflatoxins were isolated and characterized after the death of more than 100,000 turkey poults ( turkey X disease ) was traced to the consumption of a mold-contaminated peanut meal. [ 7 ] [ 8 ] The four major aflatoxins are called B1, B2, G1, and G2 based on their fluorescence under UV light (blue or green) and relative chromatographic mobility during thin-layer chromatography. Aflatoxin B1 is the most potent natural carcinogen known [ 9 ] and is usually the major aflatoxin produced by toxigenic strains. It is also the best studied: in a large percentage of the papers published, the term aflatoxin can be construed to mean aflatoxin B1. However, well over a dozen other aflatoxins (e.g., P1. Q1, B2a, and G2a) have been described, especially as mammalian biotransformation products of the major metabolites. [ 10 ] The classic book Aflatoxin: Scientific Background, Control, and Implications, published in 1969, is still a valuable resource for reviewing the history, chemistry, toxicology, and agricultural implications of aflatoxin research.
Fumonisins were first described and characterized in 1988. [ 11 ] The most abundantly produced member of the family is fumonisin B1. They are thought to be synthesized by condensation of the amino acid alanine into an acetate-derived precursor. [ 12 ] Fumonisins are produced by a number of Fusarium species, notably Fusarium verticillioides (formerly Fusarium moniliforme = Gibberella fujikuroi), Fusarium proliferatum, and Fusarium nygamai, as well as Alternaria alternata f. sp. lycopersici. [ 13 ] [ 14 ] These fungi are taxonomically challenging, with a complex and rapidly changing nomenclature which has perplexed many nonmycologists (and some mycologists, too). [ 15 ] [ 16 ] The major species of economic importance is Fusarium verticillioides, which grows as a corn endophyte in both vegetative and reproductive tissues, often without causing disease symptoms in the plant. However, when weather conditions, insect damage, and the appropriate fungal and plant genotype are present, it can cause seedling blight, stalk rot, and ear rot. [ 17 ] Fusarium verticillioides is present in virtually all corn samples. [ 18 ] Most strains do not produce the toxin, so the presence of the fungus does not necessarily mean that fumonisin is also present. [ 19 ] Although it is phytotoxic, fumonisin B1 is not required for plant pathogenesis. [ 20 ] [ 21 ]
Ochratoxin A was discovered as a metabolite of Aspergillus ochraceus in 1965 during a large screen of fungal metabolites that was designed specifically to identify new mycotoxins. [ 22 ] Shortly thereafter, it was isolated from a commercial corn sample in the United States [ 23 ] and recognized as a potent nephrotoxin. Members of the ochratoxin family have been found as metabolites of many different species of Aspergillus, including Aspergillus alliaceus, Aspergillus auricomus, Aspergillus carbonarius, Aspergillus glaucus, Aspergillus melleus, and Aspergillus niger. [ 24 ] [ 25 ] [ 26 ] Because Aspergillus niger is used widely in the production of enzymes and citric acid for human consumption, it is important to ensure that industrial strains are nonproducers. [ 27 ] [ 28 ] Although some early reports implicated several Penicillium species, it is now thought that Penicillium verrucosum, a common contaminant of barley, is the only confirmed ochratoxin producer in this genus. [ 29 ] [ 30 ] Nevertheless, many mycotoxin reviews reiterate erroneous species lists.
Patulin is produced by many different molds but was first isolated as an antimicrobial active principle during the 1940s from Penicillium patulum (later called Penicillium urticae , now Penicillium griseofulvum ). The same metabolite was also isolated from other species and given the names clavacin, claviformin, expansin, mycoin C, and penicidin. [ 31 ] A number of early studies were directed towards harnessing its antibiotic activity. For example, it was tested as both a nose and throat spray for treating the common cold and as an ointment for treating fungal skin infections [ 32 ] However, during the 1950s and 1960s, it became apparent that, in addition to its antibacterial, antiviral, and antiprotozoal activity, patulin was toxic to both plants and animals, precluding its clinical use as an antibiotic. During the 1960s, patulin was reclassified as a mycotoxin.
The trichothecenes constitute a family of more than sixty sesquiterpenoid metabolites produced by a number of fungal genera, including Fusarium , Myrothecium , Phomopsis , Stachybotrys , Trichoderma , Trichothecium , and others. [ 33 ] [ 34 ] [ 35 ] The term trichothecene is derived from trichothecin, which was one of the first members of the family identified. All trichothecenes contain a common 12,13-epoxytrichothene skeleton and an olefinic bond with various side chain substitutions. They are commonly found as food and feed contaminants, and consumption of these mycotoxins can result in alimentary hemorrhage and vomiting; direct contact causes dermatitis. [ 36 ] [ 37 ] [ 38 ]
Zearalenone , a secondary metabolite from Fusarium graminearum (teleomorph Gibberella zeae), was given the trivial name zearalenone as a combination of G. zeae, resorcylic acid lactone, -ene (for the presence of the C-1′ to C-2 double bond), and -one, for the C-6′ ketone. [ 39 ] Almost simultaneously, a second group isolated, crystallized, and studied the metabolic properties of the same compound and named it F-2. [ 40 ] [ 41 ] Much of the early literature uses zearalenone and F-2 as synonyms; the family of analogues are known as zearalenones and F-2 toxins, respectively. Perhaps because the original work on these fungal macrolides coincided with the discovery of aflatoxins, chapters on zearalenone have become a regular fixture in monographs on mycotoxins (see, for example, Mirocha and Christensen [ 42 ] and Betina [ 43 ] ). Nevertheless, the word toxin is almost certainly a misnomer because zearalenone, while biologically potent, is hardly toxic; rather, it sufficiently resembles 17β-estradiol, the principal hormone produced by the human ovary, to allow it to bind to estrogen receptors in mammalian target cells [ 44 ] Zearalenone is better classified as a nonsteroidal estrogen or mycoestrogen. Sometimes it is called a phytoestrogen. For the structure-activity relationships of zearalenone and its analogues, see Hurd [ 45 ] and Shier. [ 46 ] | https://en.wikipedia.org/wiki/Mycotoxicology |
A mycotroph is a plant that gets all or part of its carbon, water, or nutrient supply through symbiotic association with fungi . The term can refer to plants that engage in either of two distinct symbioses with fungi:
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Mycoviruses ( Ancient Greek : μύκης mykes ("fungus") + Latin virus ), also known as mycophages , are viruses that infect fungi . The majority of mycoviruses have double-stranded RNA (dsRNA) genomes and isometric particles, but approximately 30% have positive-sense, single-stranded RNA (+ssRNA) genomes. [ 1 ] [ 2 ]
True mycoviruses demonstrate an ability to be transmitted to infect other healthy fungi. Many double-stranded RNA elements that have been described in fungi do not fit this description, and in these cases they are referred to as virus-like particles or VLPs. Preliminary results indicate that most mycoviruses co-diverge with their hosts, i.e. their phylogeny is largely congruent with that of their primary hosts. [ 3 ] However, many virus families containing mycoviruses have only sparsely been sampled. Mycovirology [ 4 ] is the study of mycoviruses. It is a special subdivision of virology and seeks to understand and describe the taxonomy, host range, origin and evolution, transmission and movement of mycoviruses and their impact on host phenotype.
The first record of an economic impact of mycoviruses on fungi was recorded in cultivated mushrooms ( Agaricus bisporus ) in the late 1940s and was called the La France disease. [ 5 ] Hollings found more than three different types of viruses in the abnormal sporophores . This report essentially marks the beginning of mycovirology. [ 4 ]
The La France Disease is also known as X disease, watery stripe, dieback and brown disease. Symptoms include:
Mushrooms have shown no resistance to the virus, and so control has been limited to hygienic practises to stop the spread of the virus.
Perhaps the best known mycovirus is Cryphonectria parasitica hypovirus 1 (CHV1). CHV1 is exceptional within mycoviral research for its success as a biocontrol agent against the fungus C. parasitica , the causative agent of chestnut blight , in Europe, but also because it is a model organism for studying hypovirulence in fungi. However, this system is only being used in Europe routinely because of the relatively small number of vegetative compatibility groups (VCGs) on the continent. By contrast, in North America the distribution of the hypovirulent phenotype is often prevented because an incompatibility reaction prevents fungal hyphae from fusing and exchanging their cytoplasmic content. In the United States, at least 35 VCGs were found. [ 7 ] A similar situation seems to be present in China and Japan, where 71 VCGs have been identified so far. [ 8 ]
The majority of mycoviruses have double-stranded RNA (dsRNA) genomes and isometric particles, but approximately 30% have positive-sense, single-stranded RNA (+ssRNA) genomes. [ 1 ] [ 2 ] However, negative single-stranded RNA viruses and single-stranded DNA viruses have also been described. [ 9 ] [ 10 ] [ 11 ] The updated 9th ICTV report on virus taxonomy [ 12 ] lists over 90 mycovirus species covering 10 viral families, of which 20% were not assigned to a genus or, in some cases, not even to a family.
Isometric forms predominate mycoviral morphologies in comparison to rigid rods, flexuous rods, club-shaped particles, enveloped bacilliform particles, and Herpesvirus-like viruses. [ 13 ] The lack of genomic data often hampers a conclusive assignment to already established groups of viruses or makes it impossible to erect new families and genera. The latter is true for many unencapsidated dsRNA viruses, which are assumed to be viral, but missing sequence data has prevented their classification so far. [ 1 ] So far, viruses of the families Partitiviridae , Totiviridae , and Narnaviridae are dominating the "mycovirus sphere". [ 4 ]
Mycoviruses are common in fungi (Herrero et al., 2009) and are found in all four phyla of the true fungi: Chytridiomycota , Zygomycota , Ascomycota and Basidiomycota . Fungi are frequently infected with two or more unrelated viruses and also with defective dsRNA and/or satellite dsRNA. [ 14 ] [ 15 ] There are also viruses that simply use fungi as vectors and are distinct from mycoviruses because they cannot reproduce in the fungal cytoplasm. [ 16 ]
It is generally assumed that the natural host range of mycoviruses is confined to closely related vegetability compatibility groups or VCGs which allow for cytoplasmic fusion, [ 17 ] but some mycoviruses can replicate in taxonomically different fungal hosts. [ 4 ] Good examples are mitoviruses found in the two fungal species S. homoeocarpa and Ophiostoma novo-ulmi . [ 18 ] Nuss et al. (2005) described that it is possible to extend the natural host range of C. parasitica hypovirus 1 (CHV1) to several fungal species that are closely related to C. parasitica using in vitro virus transfection techniques. [ 19 ] CHV1 can also propagate in the genera Endothia and Valsa , [ 14 ] which belong to the two distinct families Cryphonectriaceae and Diaporthaceae , respectively. Furthermore, some human pathogenic fungi are also found to be naturally infected with mycoviruses, including AfuPmV-1 of Aspergillus fumigatus [ 20 ] and TmPV1 of Talaromyces marneffei [ 21 ] (formerly Penicillium marneffei ).
In one study, forty patients with acute lymphoblastic leukemia were found to have antibodies to a mycovirus-containing Aspergillus flavus.In another research report, exposure of mononuclear cells from patients with acute lymphoblastic leukemia in full remission resulted in the re-development of the genetic and cell surface phenotypes characteristic of acute lymphoblastic leukemia. [ citation needed ]
Viruses consisting of dsRNA as well as ssRNA are assumed to be very ancient and presumably originated from the " RNA world " as both types of RNA viruses infect bacteria as well as eukaryotes . [ 22 ] Although the origin of viruses is still not well understood, [ 23 ] recently presented data suggest that viruses may have invaded the emerging "supergroups" of eukaryotes from an ancestral pool during a very early stage of life on earth. According to Koonin, [ 23 ] RNA viruses colonized eukaryotes first and subsequently co-evolved with their hosts. This concept fits well with the proposed "ancient co-evolution hypothesis", which also assumes a long co-evolution of viruses and fungi. [ 1 ] [ 13 ] The "ancient co-evolution hypothesis" could explain why mycoviruses are so diverse. [ 13 ] [ 24 ]
It has also been suggested that it is very likely that plant viruses containing a movement protein evolved from mycoviruses by introducing an extracellular phase into their life cycle rather than eliminating it. Furthermore, the recent discovery of an ssDNA mycovirus has tempted some researchers [ 10 ] to suggest that RNA and DNA viruses might have common evolutionary mechanisms. However, there are many cases where mycoviruses are grouped together with plant viruses. For example, CHV1 showed phylogenetic relatedness to the ssRNA genus Potyvirus , [ 25 ] and some ssRNA viruses, which were assumed to confer hypovirulence or debilitation, were often found to be more closely related to plant viruses than to other mycoviruses. [ 1 ] Therefore, another theory arose that these viruses moved from a plant host to a plant pathogenic fungal host or vice versa. This "plant virus hypothesis" may not explain how mycoviruses developed originally, but it could help to understand how they evolved further. [ citation needed ]
A significant difference between the genomes of mycoviruses to other viruses is the absence of genes for ‘cell-to-cell movement’ proteins. It is therefore assumed that mycoviruses only move intercellularly during cell division (e.g. sporogenesis) or via hyphal fusion. [ 14 ] [ 26 ] Mycoviruses might simply not need an external route of infection as they have many means of transmission and spread due to their fungal host's life style:
However, there are potential barriers to mycovirus spread due to vegetative incompatibility and variable transmission to sexual spores. Transmission to sexually produced spores can range from 0% to 100% depending on the virus-host combination. [ 14 ] Transmission between species of the same genus sharing the same habitat has also been reported including Cryphonectria ( C. parasitica and C. sp), Sclerotinia ( Sclerotinia sclerotiorum and S. minor ), and Ophiostoma ( O. ulmi and O. novo-ulmi ). [ 28 ] [ 29 ] Intraspecies transmission has also been reported [ 30 ] between Fusarium poae and black Aspergillus isolates. However, it is not known how fungi overcome the genetic barrier; whether there is some form of recognition process during physical contact or some other means of exchange, such as vectors. Research [ 31 ] using Aspergillus species indicated that transmission efficiencies might depend on the hosts viral infection status (infected with no, different, or same virus), and that mycoviruses might play a role in the regulation of secondary mycoviral infection. Whether this is also true for other fungi is not yet known. In contrast to acquiring mycoviruses spontaneously, the loss of mycoviruses seems very infrequent [ 31 ] and suggests that either viruses actively moved into spores and new hyphal tips, or the fungus might facilitate the mycoviral transport in some other way.
Although it is not known yet whether viral transport is an active or passive process, it is generally assumed that fungal viruses move forward by plasma streaming. [ 32 ] Theoretically they could drift with the cytoplasm as it extends into new hyphae, or attach to the web of microtubuli, which would drag them through the internal cytoplasmic space. That might explain how they pass through septa and bypass woronin bodies . However, some researchers have found them located next to septum walls, [ 2 ] [ 33 ] which could imply that they ‘got stuck’ and were not able to move actively forward themselves. Others have suggested that the transmission of viral mitochondrial dsRNA may play an important role in the movement of mitoviruses found in Botrytis cinerea . [ 34 ]
Phenotypic effects of mycoviral infections can vary from advantageous to deleterious, but most of them are asymptomatic or cryptic. The connection between phenotype and mycovirus presence is not always straightforward. Several reasons may account for this. First, the lack of appropriate infectivity assays often hindered the researcher from reaching a coherent conclusion. [ 35 ] Secondly, mixed infection or unknown numbers of infecting viruses make it very difficult to associate a particular phenotypic change with the investigated virus. [ citation needed ]
Although most mycoviruses often do not seem to disturb their host's fitness, this does not necessarily mean they are living unrecognized by their hosts. A neutral co-existence might just be the result of a long co-evolutionary process. [ 36 ] [ 37 ] Accordingly, symptoms may only appear when certain conditions of the virus-fungus-system change and get out of balance. This could be external (environmental) as well as internal (cytoplasmic). It is not known yet why some mycoviruses-fungus-combinations are typically detrimental while others are asymptomatic or even beneficial. Nevertheless, harmful effects of mycoviruses are economically interesting, especially if the fungal host is a phytopathogen and the mycovirus could be exploited as biocontrol agent. The best example is represented by the case of CHV1 and C. parasitica . [ 14 ] Other examples of deleterious effects of mycoviruses are the ‘La France’ disease of A. bisporus [ 5 ] [ 38 ] and the mushroom diseases caused by Oyster mushroom spherical virus [ 39 ] and Oyster mushroom isometric virus. [ 38 ]
In summary, the main negative effects of mycoviruses are:
Hypovirulent phenotypes do not appear to correlate with specific genome features and it seems there is not one particular metabolic pathway causing hypovirulence but several. [ 44 ] In addition to negative effects, beneficial interactions do also occur. Well described examples are the killer phenotypes in yeasts [ 45 ] and Ustilago . [ 46 ] Killer isolates secrete proteins that are toxic to sensitive cells of the same or closely related species while the producing cells themselves are immune. Most of these toxins degrade the cell membrane. [ 45 ] There are potentially interesting applications of killer isolates in medicine, food industry, and agriculture. [ 24 ] [ 45 ] A three-part system involving a mycovirus of an endophytic fungus ( Curvularia protuberata ) of the grass Dichanthelium lanuginosum has been described, which provides a thermal tolerance to the plant, enabling it to inhabit adverse environmental niches. [ 47 ] In medically important fungi, an uncharacterized A78 virus of A. fumigatus causes mild hypervirulent effect on pathogenicity when tested on Galleria mellonella (Greater wax moth). [ 42 ] Furthermore, TmPV1, a dsRNA partitivirus, of Talaromyces marneffei (formerly Penicillium marneffei) was found to cause hypervirulence phenotype on T. marneffei when tested on a mouse model. [ 21 ] These could imply mycoviruses may play important roles in the pathogensis of human pathogenic fungi. [ citation needed ]
Most fungal viruses belong to double-stranded RNA viruses , but about 30% belong to positive-strand RNA virus . [ 1 ] However, negative single-stranded RNA viruses and single-stranded DNA viruses have also been described. [ 9 ] [ 11 ] [ 48 ] [ 10 ] The ninth edition of the report of the International Committee on Taxonomy of Viruses lists more than 90 fungal viruses belonging to 10 families , of which about 20% of the viruses have not been incertae sedis due to insufficient sequence data and have not yet been determined. [ 12 ] The shape of most fungal viruses is isometric. [ 13 ] | https://en.wikipedia.org/wiki/Mycovirus |
Mycroft was a free and open-source software virtual assistant that uses a natural language user interface . [ 2 ] [ 3 ] [ 4 ] Its code was formerly copyleft , but is now under a permissive license . [ 1 ] It was named after a fictional computer from the 1966 science fiction novel The Moon Is a Harsh Mistress . [ 5 ]
Unusually for a voice-controlled assistant, Mycroft did all of its processing locally, not on a cloud server belonging to the vendor. It could access online resources, but it could also function without an internet connection.
In early 2023, Mycroft AI ceased development. [ 6 ] A community-driven platform continues with OpenVoiceOS.
Inspiration for Mycroft came when Ryan Sipes and Joshua Montgomery were visiting a makerspace in Kansas City, MO , where they came across a simple and basic intelligent virtual assistant project. They were interested in the technology, but did not like its inflexibility. [ 7 ] [ 8 ] Montgomery believes that the burgeoning industry of intelligent personal assistance poses privacy concerns for users, and has promised that Mycroft will protect privacy through its open source machine learning platform. [ 9 ]
Mycroft AI, Inc., has won several awards, including the prestigious Techweek's KC Launch competition in 2016. [ 10 ] They were part of the Sprint Accelerator 2016 class in Kansas City and joined 500 Startups Batch 20 in February 2017. [ 11 ] [ 12 ] The company accepted a strategic investment from Jaguar Land Rover during this same time period. [ 13 ] The company had raised more than $2.5 million from institutional investors before they opted to offer shares of the company to the public through StartEngine , an equity crowdfunding platform. [ 14 ]
In early 2023, Mycroft AI ceased development. [ 6 ]
Mycroft provides free software for most [ clarification needed ] parts of the voice stack.
Mycroft does Wake Word spotting, also called keyword spotting , through its Precise Wake Word engine. [ 15 ] Prior to Precise becoming the default Wake Word engine, Mycroft employed PocketSphinx. Instead of being based on phoneme recognition, Precise uses a trained recurrent neural network to distinguish between sounds which are, and which aren't Wake Words.
Mycroft had partnered with Mozilla 's Common Voice Project to leverage their DeepSpeech speech to text software. [ 16 ]
Mycroft uses an intent parser called Adapt to convert natural language into machine-readable data structures. Adapt undertakes intent parsing by matching specific keywords in an order within an utterance. They also have a parser, Padatious . Padatious, in contrast, uses example-based inference to determine intent.
For speech synthesis Mycroft uses Mimic, which is based on the Festival Lite speech synthesis system. [ 17 ]
Mycroft was designed to be modular, so users are able to change its components. For example, espeak can be used instead of Mimic. [ 18 ] [ 19 ] [ 20 ] [ 21 ]
The Mycroft project had created smart speakers that run its software. All of its hardware is open-source, released under the CERN Open Hardware Licence . [ 22 ]
Its first hardware project was the Mark I , targeted primarily at developers. Its production was partially funded through a Kickstarter campaign, which finished successfully. Units started shipping out in April 2016. [ 23 ]
Its second hardware project is the Mark II , intended for general usage, not just for developers. Unlike the Mark I, the Mark II would be equipped with a screen, being able to relay information both visually and acoustically. As with the Mark I, the Mark II's production was partially funded through a Kickstarter campaign, which wrapped up in February 2018, hitting almost 8 times its original goal. Mark II shipping started to crowdfunders in the end of 2022. In February 2023, a post on the Kickstarter page announced that they "will not be able to fulfill any remaining Mark II rewards", however they "will still be shipping all orders that are made through the Mycroft website". [ 24 ]
Mycroft had undertaken several commercial collaborations. In May 2018, the company partnered with WorkAround, an impact sourcing provider who broker work opportunities for refugees, to undertake bulk machine learning training. [ 25 ] In October 2018, Mycroft collaborated with disease surveillance and forecasting company, SickWeather, to identify the frequency of coughing on public transport, funded by the City of Kansas City, Missouri . [ 26 ] | https://en.wikipedia.org/wiki/Mycroft_(software) |
A myelinoid or myelin organoid is a three dimensional in vitro cultured model derived from human pluripotent stem cells (hPSCs) that represents various brain regions, the spinal cord or the peripheral nervous system in early fetal human development. [ 1 ] [ 2 ] [ 3 ] Myelinoids have the capacity to recapitulate aspects of brain developmental processes, microenvironments, cell to cell interaction, structural organization and cellular composition. [ 2 ] [ 3 ] The differentiating aspect dictating whether an organoid is deemed a cerebral organoid /brain organoid or myelinoid is the presence of myelination and compact myelin formation that is a defining feature of myelinoids. Due to the complex nature of the human brain, there is a need for model systems which can closely mimic complicated biological processes. Myelinoids provide a unique in vitro model through which myelin pathology, neurodegenerative diseases, developmental processes and therapeutic screening can be accomplished. [ 1 ] [ 2 ]
In vitro models have been a critical component of many biological studies. Monolayers , or 2D cultures, have been widely used in the past, however, they are limited by their lack of complexity and fail to recapitulate tissue architecture involved in biological processes occurring in vivo. [ 4 ] Model organisms, such as Mus musculus , Caenorhabditis elegans , Drosophila melanogaster , and Saccharomyces cerevisiae , recapitulate biological complexity better than 2D monolayer cultures. [ 5 ] [ 6 ] However, these model organisms do not perfectly capture human biology. Specifically, there are stark differences in brain development between mice and humans. Major developmental differences include variability in division patterns of neural stem cells and localization and types of glial cells that occur at specific stages in development. [ 7 ] [ 8 ]
Leveraging pluripotent stem cell technologies, brain organoids and cerebral organoids were developed to fill the gap in model systems to study human specific brain development and pathology in vitro. The first cerebral organoid was established in 2013. [ 9 ] Since then, various protocols have emerged for generating organoids for different brain regions such as cerebellar , [ 10 ] hippocampal , [ 11 ] midbrain , [ 12 ] forebrain , [ 13 ] and hypothalamic [ 14 ] organoids. Cerebral organoids provide a neurological model through which diseases, development and therapeutics can be studied. [ 15 ] However, a major constraint of cerebral organoids is that they lack robust myelin formation and are therefore not well suited to studies investigating white matter .
This limitation of cerebral organoids was addressed in 2018 when brain organoids containing a robust population of myelinating oligodendrocytes were generated. The process of generating these myelinated brain organoids lasted 210 days and involved the addition of various growth factors and media at specific time points. [ 2 ] Due to the prolonged duration of the 2018 protocol, there were efforts to speed up and streamline the differentiation and generation of these myelinated organoids. A similar protocol which differed slightly in growth factors added and timing of media changes was described in 2019. This protocol was able to generate organoids with compact myelin formation by day 160. [ 16 ]
Another protocol developed in 2019 demonstrated that myelinated organoid generation could be accelerated further. Using a novel protocol, myelin basic protein (MBP), a marker for oligodendrocyte differentiation and myelination in the CNS, was detectable as early as day 63 (9 weeks) and myelinated axons were observed by day 105 (15 weeks), effectively halving the duration of the protocol. [ 17 ] [ 18 ]
A protocol of similar duration was established in 2021, however, the resulting organoids differ slightly in their biological context. This protocol leveraged the fact that spinal cord myelination is observed prior to cortical myelination. [ 1 ] This protocol generated organoids with robust myelination with a ventral caudal cell fate. [ 1 ] These organoids, although not technically brain organoids, can also be used to study myelin disease pathology, validated in the study through generating organoids recapitulating the disease pathology observed in Nfasc 155-/- patients. In this protocol, they referred to their myelinated organoids as "myelinoids" thus creating the category of organoids referred to as myelinoids. [ 1 ]
In 2021, a group of researchers aimed to address the fact that the lengthy differentiation protocols renders myelinoids less practical for high throughput experimentation such as drug screening. [ 19 ] To do this, scientists developed a human induced pluripotent stem cell (hiPSC) line that relies on early expression of an oligodendroglial gene which enabled the accelerated generation of myelinated organoids in just 42 days. [ 19 ] To date, this is the fastest protocol for generating mature oligodendrocytes in a brain organoid. [ 19 ]
To generate organoids, human pluripotent stem cells (hPSCs) are allowed to aggregate into embryoid bodies (EBs) in low attachment plates (in suspension), which are then cultivated in a rotating bioreactor with lineage specific factors to promote cell amplification, growth and differentiation. [ 2 ] [ 20 ] [ 21 ] EBs have the capacity to differentiate into all embryonic germ layers, mesoderm, endoderm and ectoderm. In vivo , the nervous system, including myelin, is generated from the ectoderm. [ 21 ] To recapitulate this in vitro and generate myelin organoids, the EBs are cultured in media with specific growth factors and supplements that lead to ectodermal differentiation specifically, followed by subsequent neural induction. [ 21 ] More specifically, neural induction factors are added to induce the formation of neural progenitor cells which give rise to neurons and glial cells, including oligodendrocytes, in vivo . [ 2 ]
A well established method used to efficiently differentiate hPSC into neural cells is by dual inhibition of SMAD signaling using dorsomorphin (also known as compound C) and SB431542. [ 1 ] [ 2 ] [ 22 ] [ 23 ] To promote further proliferation of neural precursor cells specific growth factors are added to the media such as epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF-2). [ 2 ] [ 23 ] [ 24 ] Before neural and glial induction, the spheroids are generally embedded in an extracellular matrix , such as Matrigel, and transferred to a rotating bioreactor where different small molecules and growth factors are continuously supplemented to promote the differentiation of cells into specific structures and cell types. [ 2 ] [ 20 ] [ 23 ]
In vivo , neuronal induction precedes oligodendrocyte formation. [ 25 ] Therefore, in culture, neuronal induction factors are added first to induce neuro-cortical patterning of the spheroids, followed by factors that induce oligodendrocyte precursor cell (OPC) formation and differentiation into oligodendroglia. [ 2 ] [ 23 ] To promote formation of neurons from neural precursor cells, brain-derived neurotrophic factor (BDNF) and neurotrophic factor 3 (NT3) can be added to the media. [ 2 ] [ 23 ] Subsequently, factors such as platelet-derived growth factor AA (PDGF-AA) and insulin-like growth factor 1 (IGF-1) are added to the media to result in an expansion of the OPC populations present within the organoid by promoting OPC proliferation and survival. [ 1 ] [ 2 ]
Finally, factors that induce OPC differentiation into oligodendrocytes, and ultimately myelinating oligodendrocytes, are added. [ 1 ] [ 2 ] This includes thyroid hormone (T3), which has been shown to induce oligodendrocyte generation from OPCs in vivo. [ 1 ] [ 2 ] The organoids are maintained in suspension where they grow and mature until required for analysis. The fundamentals of this workflow are generally used to obtain myelin organoids; however, various protocols that rely on it have introduced multiple modifications for different purposes. Madhavan et al. was the first to establish a reproducible protocol that allowed for generating organoids with robust OPC and oligodendrocytes populations, and therefore myelination; they are referred to as myelin organoids, or myelinoids. [ 2 ]
The generation of myelin organoids generally relies on neurocortical patterning factors that establish the structural and cellular framework necessary for the induction of oligodendrogenesis later on in the differentiation protocol. [ 2 ] Therefore, the properties and components of myelin organoids in the early stages of differentiation are very similar to that observed in cerebral organoids where populations of neural progenitor cells, precursors of neurons and glial cells, start to emerge and self-organize into distinct layers that recapitulate features of the cortex during early embryogenesis. [ 3 ]
At such early stages, myelin organoids start to form large continuous neuroepithelial that encompass a fluid filled cavity representative of a brain ventricle. [ 9 ] The progenitor cells surrounding the putative ventricle organize into distinct layers defined by specific neural markers that become more defined as the organoid matures. [ 9 ] The layers include a ventricular zone surrounding the cavity with cells expressing PAX6, SOX2 and Ki67, followed by the outer subventricular zone and intermediate zone with cells expressing Ki-67 and TBR2, and finally cortical plate layer with cells expressing CTIP2 , MAP2 and TBR1 . [ 3 ]
Following neurocortical patterning, the oligodendrocyte lineage growth factors drive the expansion of native populations of OPCs distributed causing a substantial increase in their numbers which express SOX6 , SOX10 and OLIG2 , markers of glial induction and OPC specification. [ 2 ] As the myelin organoid matures, the OPC cells differentiate into oligodendrocytes that express proteolipid protein 1 ( PLP1 ), the predominant component of myelin, and MYRF25, an oligodendrocyte specific transcription factor . [ 2 ] The oligodendrocytes are distributed throughout the neuronal layers, where upon maturation, their processes express MBP and CNP (an early myelination marker), begin extending to wrap and myelinate the axons surrounding them. The myelin undergoes maturation, refinement and compaction eventually leading to the formation of functional neuronal networks with compactly wrapped myelin lamellae. [ 1 ] [ 2 ] Further myelin maturation leads to distinct axonal subdomains with a paranodal axo-glial junction (PNJ) and node of Ranvier . The observation of paranodal and nodal assembly is protocol dependent, some observe paranodal and nodal assembly, some do not. Overall, the oligodendrocytes in myelin organoids demonstrate the ability to form compact myelin that wraps and organizes around neuronal axons recapitulating the three dimensional architecture of myelinated axonal networks in humans.
Myelinoids recapitulate various fundamental aspects of brain development and myelination, and therefore related disease and pathology. Given that, they can be used to model various diseases and understand disease mechanisms associated with myelin defects including neurodegenerative diseases, CNS injury, PMD, and NFASC. [ 1 ] [ 2 ] [ 17 ]
PMD is a rare monogenic disease caused by various mutations of the X-linked proteolipid protein 1 gene (PLP1). [ 26 ] PLP1 is a critical protein for myelin formation. PMD is classified as a leukodystrophy, meaning that it is a disease affecting the white matter of the brain. Madhavan et al. tested how well their myelinoid system could recapitulate the established cellular pathology of PMD. Organoids were derived from three patients with varying disease severity where the subject with a deletion, a duplication, and a point mutation had mild, moderate and severe phenotypes respectively. [ 2 ] Their results demonstrated that the myelinating oligocortical spheroids generated recapitulated the degrees of cellular pathology associated with the genetic variants, therefore can serve as models for understanding the relationships between PMD genotypes and phenotypes, which have not been fully characterized yet, therefore can serve as models for understanding the relationships between PMD genotypes and phenotypes, which have not been fully characterized yet. [ 2 ]
The NFASC gene encodes a cell adhesion molecule that is involved in neurite outgrowth and fasciculation . [ 27 ] Additionally, NFASC is involved in the organization of axonal initiation segment and the nodes of Ranvier during development. [ 27 ] Patients with nonsense mutations in NFASC have abnormalities in the paranodal axo-glial junction (PNJ). [ 1 ] James et al. demonstrated that patient derived myelinoids had widespread formation of myelinoids of both patient and control; however, as expected, the PNJ in patient derived myelinoids had disrupted paranode formation. [ 1 ]
Myelin structure and integrity is inherently hard to study in humans at a molecular level. MRI can shed light on myelin abnormalities in a human brain, however, many studies utilize animal models to study myelin related changes in response to genetic variants. Myelinoids provide a 3D human derived system to study myelin structure. [ 2 ] Measuring the number and length of myelin sheaths, paranodal/nodal organization and structure, myelin volume and compaction, cellular identity and composition, and cellular organization are all methods for quantifying myelin changes. [ 1 ]
Studies have shown that in myelinoids, human myelination can be pharmacologically manipulated in a quantifiable manner at both cellular and global levels across the myelinoids. [ 1 ] Therefore, myelin organoids can be used as a preclinical model for evaluating myelin associated candidate therapeutics and drugs in a human physiologically relevant context. [ 2 ]
Myelin organoids can be used to study the therapeutic potential of possible myelination strategies for individuals with diseases associated with demyelination such as leukodystrophies and multiple sclerosis , an auto-immune demyelinating disease affecting the CNS. [ 2 ] [ 28 ] [ 29 ] Clemastine and ketoconazole are promyelinating drugs that function as potent stimulators of oligodendrocyte generation and myelination in rodent models. The previously known effects of both drugs have been recapitulated using myelin organoids as they enhanced and accelerated the extent and rate of oligodendrocyte generation, maturation and myelination in organoids. [ 2 ]
Certain classes of Pelizaeus-Merzbacher disease (PMD), proteolipid protein 1 (PLP1) show perinuclear retention in oligodendrocytes. [ 30 ] Perinuclear retention of misfolded proteins is a hallmark of endoplasmic reticulum (ER) stress, which might be implicated in the pathology observed in PMD. [ 30 ] In a myelinoid model of Pelizaeus-Merzbacher disease (PMD) developed in 2018, treatment with a modulator of ER stress pathways called GSK2656157, an inhibitor of protein-kinase-R-like ER kinase, partially rescued PLP1 perinuclear retention mobilizing it away from the ER and into the processes of oligodendrocytes. [ 2 ] In addition, treatment resulted in an increase in the number of cells that show MYRF expression, an oligodendrocyte specific transcription factor, which has been observed to be reduced in PMD oligodendrocytes compared to control. [ 2 ]
In a myelinoid model of PMD caused by point mutations in proteolipid protein 1 (PLP1), a CRISPR correction to the wildtype sequence in the hPSCs used to generate it rescued some aspects of PMD pathology. [ 2 ] The treatment restored the perinuclear retention of PLP1 and mobilization into oligodendrocyte processes and increased the amount of oligodendrocytes that express MYRF, an oligodendrocyte specific marker, to levels observed in healthy controls. [ 2 ] The myelin organoids derived from hPSC after the CRISPR correction of PLP1 point mutations generated myelin after 20 weeks in culture. [ 2 ]
'Omics' has a broad application to organoids and since the development of organoid technology, transcriptome, epigenome, proteome, and metabolome analysis have been used. [ 31 ] Additionally, targeted gene editing and host-microbiome interactions have been studied using organoids. [ 31 ]
It is not possible to study gene expression patterns of the brain in human subjects, so the ability to recapitulate some of the complexity of the human brain in vitro allows for aspects of human development and disease to be investigated. Single-cell omics is a powerful tool that has been used to identify different subpopulations of oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes in mouse models which were previously undefined. [ 32 ] The heterogeneity of oligodendrocytes was previously thought to be functionally homogeneous; however, distinct cell populations can be characterized through specific transcriptional signatures and gene ontology profiles.
Single-cell RNA sequencing (scRNA seq) analysis of myelinoids generated in 2018, confirmed that there were distinct populations of oligodendrocytes throughout multiple stages of development in oligocortical spheroids which closely matched the single-cell transcriptome data obtained from human fetal cortex. [ 2 ] Due to their close transcriptomic resemblance to human fetal brain data, the regulatory landscape of cells within cerebral organoids can inform on the underlying regulatory mechanisms governing human brain development. [ 33 ]
In 2020, researchers described an approach to obtain meaningful scRNA seq and assay for transposase-accessible chromatin using sequencing (ATAC-seq) data from brain organoids. [ 33 ] The protocol can likely translate to myelin organoids due to the similar biology between cerebral organoids and myelinoids.
Orgo-seq is a framework through which bulk RNA (bRNA) and scRNA sequencing data of organoids can be integrated. [ 34 ] This platform was developed to address challenges associated with phenotyping organoids and demonstrated its ability to identify critical cell types and cell type specific driver genes involved with neurodevelopmental disorders and disease manifestation. [ 34 ]
Using the Orgo-Seq framework, three datasets (bRNA-seq from donor derived organoids, scRNA-seq data from cerebral organoids and fetal brains in precious studies, and bRNA-seq from the BrainSpan Project of human post-mortem brains) were used to study copy number variants in autism spectrum disorder. They leveraged several datasets to identify the types of cells present and cell specific driver genes in patient derived organoids.
Brain organoids serve as a human-derived model through which genetic variation and its impact on cell specific processes and association with neurodevelopmental and neurodegenerative disorders can be studied. [ 34 ] Specifically, myelinoids provide a system to study the cell type specific effects in oligodendrocytes that are disrupted by genetic variants. Overall, Orgo-Seq provides a quantitative and validated framework for investigating driver genes and their role in neurological and neurological disorders. [ 34 ] In the future, Lim et al., aim to develop a precision medicine framework to identify gene networks and effects of genetic variants in an organoid system, which would include myelinoids, that recapitulates the patient's exact genetic background. [ 34 ]
With the absence of human brain tissue, myelinoids offer unprecedented opportunities for studying oligogenesis and myelination. [ 17 ] While animal models are valuable for studying human diseases, they do not fully recapitulate human brain development and show many discrepancies affecting their translatability to human physiology. [ 20 ] Considering resemblance of myelin organoids to the human brain, they have been proposed as models bridging between animal models and human physiology. [ 3 ]
Other hPSC derived oligodendrocytes systems have been established, such as the two dimensional (2D) monolayer oligodendrocytes models. [ 2 ] However, when compared to 2D systems, myelin organoids more faithfully recapitulate the structure and functionality of the developing human brain containing a more physiologically relevant microenvironment including their 3D cytoarchitecture, neural circuits, cell interactions and an overall more physiologically relevant microenvironment. [ 2 ] [ 3 ]
While cerebral organoids form the brain cytoarchitecture and composition, they generally lack oligodendrocytes, the cells responsible for myelination in the central nervous system. [ 2 ] The myelinoid protocol pioneered in 2018, and subsequently modified by others, offer a reproducible method for generating organoids with robust OPC and oligodendrocytes populations that track the endogenous neurons forming functional neuronal networks ensheathed with myelin. [ 2 ] [ 19 ]
Finally, the ability to generate myelinoids from patient derived hPSCs (induced-PSCs) offer major advantages and opportunities to explore patient-specific pathogenesis over the developmental and maturation stages of oligodendrocytes. This allows for the development of personalized therapeutic approaches. [ 2 ] [ 18 ]
As is the case with every model system, myelinoids have their limitations. Due to the methods involved with generating the organoids, there can be a large degree of experimental variability. [ 18 ] Additionally, due to the long duration over which myelination occurs, optimizing the dosage of molecules and treatments involved in myelin development can be difficult. [ 1 ] The advantage of drug screening in this model comes with its own limitations. It can be difficult to scale myelinoid experiment to an appropriate scale for high throughput screening due to the long duration of protocols and limited efficiency. [ 18 ]
Myelinoids capture a large number of cell types found in vivo, however, they fail to capture all cell types. Microglia are absent in some myelinoids as was observed in the 2021 protocol. [ 1 ] Myelinoids also do not capture any behavioral abnormalities.
Finally, a challenge with all organoid cultures is that they rely on diffusion for nutrients to reach cells. Therefore, many organoids will develop a necrotic center due to a lack of nutrients making their way to the innermost cells. [ 35 ] Recently, developing vascularized organoids has been of interest and may potentially alleviate this issue. [ 36 ] However, myelinoids as described in current protocols are not vascularized. | https://en.wikipedia.org/wiki/Myelinoid |
Myeloid-derived suppressor cells ( MDSC ) are a heterogeneous group of immune cells from the myeloid lineage (a family of cells that originate from bone marrow stem cells).
MDSCs expand under pathologic conditions such as chronic infection and cancer, as a result of altered haematopoiesis . [ 1 ] MDSCs differ from other myeloid cell types in that they have immunosuppressive activities, as opposed to immune-stimulatory properties. Similar to other myeloid cells, MDSCs interact with immune cell types such as T cells , dendritic cells , macrophages and natural killer cells to regulate their functions. Tumors with high levels of infiltration by MDSCs have been associated with poor patient outcome and resistance to therapies. [ 2 ] [ 3 ] [ 4 ] [ 5 ] MDSCs can also be detected in the blood. In patients with breast cancer, levels of MDSC in blood are about 10-fold higher than normal. [ 6 ] The size of the myeloid suppressor compartment is considered to be an important factor in the success or failure of cancer immunotherapy , highlighting the importance of this cell type for human pathophysiology. [ 7 ] A high level of MDSC infiltrate in the tumor microenvironment correlates with shorter survival times of patients with solid tumors and could mediate resistance to checkpoint inhibitor therapy. [ 8 ] Studies are needed to determine whether MDSCs are a population of immature myeloid cells that have stopped differentiation or a distinct myeloid lineage.
MDSCs are formed from bone marrow precursors when myelopoietic processes are interrupted, caused by several illnesses. [ 9 ] [ 10 ] Cancer patients' growing tumors produce cytokines and other substances that affect MDSC development. Tumor cell lines overexpress colony-stimulating factors ( G-CSF and GM-CSF ) and IL6 , which promote development of MDSCs that have immune suppressive function in vivo. Other cytokines, including IL10 , IL1 , VEGF , and PGE2 have been associated with the formation and regulation of MDSCs. GM-CSF promotes synthesis of MDSCs from bone marrow, and the transcription factor c/EBP regulates development of MDSCs in bone marrow and in tumors. STAT3 also promotes development of MDSCs, whereas IRF8 could counteract MDSC-inducing signals. [ 11 ]
MDSCs migrate as immature cells from the bone marrow to peripheral tissues (or tumors), where they differentiate into mature macrophages, dendritic cells, and neutrophils without suppressive phenotypes under homeostatic conditions, but become polarized when exposed to pro-inflammatory compounds, chemokines, and cytokines. In the tumor microenvironment, they suppress the anti-tumor immune response. The presence of MDSCs has been associated with progression of colon cancer, tumor angiogenesis, and metastases. In addition to producing NO and ROS , MDSCs secrete immune-regulatory cytokines such as TNF , TGFB , and IL10 . There are subpopulations of MDSC that have some common suppressive characteristics but also have their own unique features; different subpopulations can be found in different areas of the same tissue or tumor. [ 12 ] Tumor-infiltrating MDSCs develop in response to environmental factors, upregulating CD38 (which removes NAD from the environment and is necessary for mitochondrial biosynthesis), PDL-1 (an immune checkpoint protein) and LOX1 (promotes fatty acid consumption and fatty acid oxidation ). Tumor-infiltrating MDSCs also secrete exosomes that can inhibit the anti-tumor immune response.
Myeloid-derived suppressor cells (MDSCs) are a recently discovered bone-marrow-derived cell type. They have characteristic of immature stem cells with immunomodulatory properties. In fact, they are used in research to develop therapeutic strategies against both autoimmune diseases and exacerbate inflammation, which has special interest in the central nervous system. The main inconvenient of MDSCs is that they are only formed during inflammatory conditions, thus being commonly gathered from diseased subjects. [ 13 ] [ 14 ] [ 15 ]
However, a recent research of the University of Salamanca has demonstrated that immature myeloid cells (IMCs), the precursors of MDSCs, have also potential immunosuppressive activity under pathological conditions. [ 16 ] IMCs can be directly gathered from healthy bone marrow, which is a more clinically feasible source. Then, IMCs under pathological conditions behave as MDSCs exerting immunomodulation. In this sense, IMCs can be directly used thus avoiding their gathering from diseased subjects. [ 17 ]
In addition, IMCs are promising adjuvants when performing neurosurgery. They application in an intracranial surgery almost completely prevented the impairments caused by this procedure in mice, probably by the modulation of the inflammatory patterns. [ 18 ] In this sense, IMCs have a direct pre-clinical application to minimize the secondary effects inherent to every single intracranial surgery, especially in a diseased environment.
MDSCs derive from bone marrow precursors usually as the result of a perturbed myeloipoiesis caused by different pathologies. In cancer patients, growing tumors secrete a variety of cytokines and other molecules which are key signals involved in the generation of MDSC. Tumor cell lines overexpressing colony stimulating factors (e.g. G-CSF and GM-CSF) have long been used in vivo models of MDSC generation. GM-CSF , G-CSF and IL-6 allow the in vitro generation of MDSC that retain their suppressive function in vivo. In addition to CSF, other cytokines such as IL-6, IL-10 , VEGF , PGE2 and IL-1 have been implicated in the development and regulation of MDSC. [ 2 ] [ 19 ] The myeloid-differentiation cytokine GM-CSF is a key factor in MDSC production from bone marrow, [ 20 ] [ unreliable medical source? ] and it has been shown that the c/EBPβ transcription factor plays a key role in the generation of in vitro bone marrow-derived and in vivo tumor-induced MDSC. Moreover, STAT3 promotes MDSC differentiation and expansion and IRF8 has been suggested to counterbalance MDSC-inducing signals.
Murine MDSCs show two distinct phenotypes which discriminate them into either monocytic MDSCs or granulocytic MDSCs. The relationship between these two subtypes remains controversial, as they closely resemble monocytes and neutrophils respectively. While monocyte and neutrophil differentiation pathways within the bone marrow are antagonistic and dependent on the relative expression of IRF8 and c/EBP transcription factors (and hence there is not a direct precursor-progeny link between these two myeloid cell types), this seems not to be the case for MDSCs. Monocytic MDSCs seem to be precursors of granulocytic subsets demonstrated both in vitro and in vivo. [ 20 ] [ 21 ] This differentiation process is accelerated upon tumor infiltration and possibly driven by the hypoxic tumor microenvironment.
The depletion of MDSCs from mice with liver cancer significantly increases natural killer (NK) cell cytotoxicity, NKG2D expression, and IFNg (IFNg) production and induces NK cell energy. [ 22 ] MDSC depletion restored the function of impaired hepatic NK cells. An MDSC derived from chronic inflammation caused T and NK-cell dysfunction along with downregulation of the TCR z chain (CD247). The immunosuppressive milieu directly affects CD247, which is crucial in initiating immune responses. MDSCs, acting through membrane-bound TGF-b1, inhibit NK cells in tumor-bearing hosts due to the activity of TGF-b1 on MDSCs. Therefore, MDSCs constitutively suppress hepatic NK cells in tumor-bearing hosts through TGF-b1 on MDSCs. [ 23 ]
A number of studies have reported MDSC regulation of B-cell responses to activators and mitogens that are not MHC-regulated, as well as antigen-specific T cell responses. An infection with the LP-BM5 retrovirus can cause acquired immune deficiency in mice, which causes highly immunosuppressive CD11bCGr-1CLy6CC MDSCs. These cells suppress T and B cells by signaling via nitric oxide (NO). [ 24 ]
Immune responses against tumors and infections are regulated by myeloid-derived suppressor cells and dendritic cells (DCs). The combination of LPS and IFNg treatment of bone marrow-derived MDSCs limits DC formation and improves MDSC suppressive action. MDSCs have been shown to reduce the effectiveness of DC vaccinations. MDSC frequency has no effect on DC production or survivability, but it does cause a dose-dependent reduction in DC maturation. High CD14 CHLA-DR/low cell frequencies can stifle DC maturation and decrease DC function, both of which are critical for vaccination effectiveness. As a result, the balance between MDSCs and DCs might be crucial in tumor and infection treatment. Thus, the balance between MDSCs and DCs may play an important role in tumor and infection therapy. [ 25 ] [ 26 ]
MDSCs are immune suppressive and play a role in tumor maintenance and progression. MDSCs also obstruct therapies that seek to treat cancer through both immunotherapy and other non-immune means. [ 27 ] MDSC activity was originally described as suppressors of T cells , in particular of CD8+ T-cell responses. The spectrum of action of MDSC activity also encompasses NK cells , dendritic cells and macrophages .
Suppressor activity of MDSC is determined by their ability to inhibit the effector function of lymphocytes . Inhibition can be caused by different mechanisms. It is primarily attributed to the effects of the metabolism of L-arginine . Another important factor influencing the activity of MDSC is oppressive ROS . [ 2 ] [ 28 ]
MDSCs can also play a positive regulatory role. It is stated that MMR vaccine stimulates MDSC populations in people taking the vaccine , inhibiting septic inflammation and mortality that is broadly applicable not only to measles, mumps, and rubella, but extends to covid-19 induced cytokine inflammation. [ 29 ] This vaccine stimulation of MDSCs appears to be neither permanent nor chronic. Despite MDSCs being immunosuppressive in certain instances, the MMR vaccine itself is immunostimulatory.
In addition to host-derived factors, pharmacologic agents also have profound impact on MDSC. Chemotherapeutic agents belonging to different classes have been reported to inhibit MDSC. Although this effect may well be secondary to inhibition of hematopoietic progenitors, there may be grounds for search of selectivity based on long-known differential effects of these agents on immunocompetent cells and macrophages . [ 2 ] In 2015, MDSCs were compared to immunogenic myeloid cells highlighting a group of core signaling pathways that control pro-carcinogenic MDSC functions. [ 30 ] [ unreliable medical source? ] Many of these pathways are known targets of chemotherapy drugs with strong anti-cancer properties.
As of May 2018 [update] there are no FDA approved drugs developed to target MDSCs but experimental INB03 has entered early clinical trials . [ 31 ] [ 32 ]
There is promising evidence for inhibiting Galectin-3 as a therapeutic target to reduce MDSCs. [ 33 ] [ 34 ] In a Phase 1b clinical trial of GR-MD-02 developed by Galectin Therapeutics, investigators observed a significant decrease in the frequency of suppressive myeloid-derived suppressor cells following treatment in responding melanoma patients. [ 35 ]
The term myeloid-derived suppressor cell originated in a 2007 journal article published in Cancer Research by Gabrilovich et al. Publications in 2008 established that there are two subpopulations of MDSC: mononuclear MDSC (M-MDSC) and polymorphonuclear or granulocytic MDSC (PMN-MDSC). M-MDSC are similar to monocytes found in blood, while PMN-MDSC are physically akin to neutrophils . [ 27 ] | https://en.wikipedia.org/wiki/Myeloid-derived_suppressor_cell |
In organic chemistry , the Myers allene synthesis is a chemical reaction that converts a propargyl alcohol into an allene by way of an arene sulfonyl hydrazine as a key intermediate . [ 1 ] This name reaction is one of two discovered by Andrew Myers that are named after him; both this reaction and the Myers deoxygenation reaction involve the same type of intermediate. [ 2 ]
The reaction is a three-step process in which the alcohol first undergoes a Mitsunobu reaction with an arenesulfonylhydrazine in the presence of triphenylphosphine and diethyl azodicarboxylate . Unlike hydrazone -synthesis reactions, this reaction occurs on the same nitrogen of the hydrazine that has the arenesulfonyl substituent. Upon warming, this product undergoes an elimination of aryl sulfinic acid to give an unstable diazene as a reactive intermediate . The diazene extrudes N 2 to give isolated allene product. The authors describe this last step as a [3,3]- sigmatropic reaction in the original report but call it a retro- ene reaction in another publication. [ 3 ] [ 1 ] ( Note: The IUPAC defines a sigmatropic rearrangement as a pericyclic reaction involving both breaking and formation of a new σ bond in which the total number of π and σ bonds do not change, [ 4 ] whereas a retro-ene reaction involves the fragmentation of a molecule to a fragment with a double bond with allylic hydrogen (the 'ene') and a multiple-bonded species (the 'enophile') via a cyclic transition state . [ 5 ] In this case, the reaction occurs with the net gain of a π bond and loss of a σ bond, so strictly speaking, only the description of the reaction as a retro-ene reaction is apt.)
Both the first step (Mitsunobu reaction) and third step (sigmatropic reaction) are stereospecific , so the chirality of the propargyl alcohol controls the chirality of the resulting allene. [ 6 ]
The use of ortho -nitrobenzenesulfonylhydrazine gives reactants and intermediates with appropriate relative stability to enable the whole process to be performed as a one-pot reaction, though the order in which the reagents are mixed is important. [ 6 ] Mechanistic studies suggest that the diazene is formed as mixture of cis and trans isomers that easily interconvert, and that the cis is what reacts most readily to form the allene. [ 3 ] | https://en.wikipedia.org/wiki/Myers_allene_synthesis |
In organic chemistry , the Myers deoxygenation reaction is an organic redox reaction that reduces an alcohol into an alkyl position by way of an arene sulfonyl hydrazine as a key intermediate . This name reaction is one of four discovered by Andrew Myers that are named after him; this reaction and the Myers allene synthesis reaction involve the same type of intermediate. [ 1 ] The other reactions are Myers' asymmetric alkylation [ 2 ] and Myers-Saito Cycloaromatization. [ 3 ]
The reaction is a three-step one-pot process in which the alcohol first undergoes a Mitsunobu reaction with ortho - nitrobenzenesulfonylhydrazine in the presence of triphenylphosphine and diethyl azodicarboxylate . Unlike hydrazone -synthesis reactions, this reaction occurs on the same nitrogen of the hydrazine that has the arenesulfonyl substituent. Upon warming, this product undergoes an elimination of aryl sulfinic acid to give an unstable diazene as a reactive intermediate . A radical process then promptly occurs with loss of dinitrogen to give the final alkyl product. [ 4 ]
The alkyl-radical intermediate can instead undergo an intramolecular reaction with various other suitably-positioned functional groups within the molecule, such as alkenes or cyclopropanes , leading to alternate products. [ 1 ]
If the diazene intermediate is able to undergo a sigmatropic rearrangement, this process occurs in preference to the simple radical reduction to give a hydrocarbon with a transposed π bond . For example, in the Myers allene synthesis, one of the two π bonds of the alkyne of a propargyl alcohol shifts, forming an allene . [ 1 ] Likewise, the benzylic alcohol 1-naphthylmethanol rearranges to give a methylene -cyclohexyl product with loss of aromaticity . [ 4 ]
This organic chemistry article is a stub . You can help Wikipedia by expanding it . | https://en.wikipedia.org/wiki/Myers_deoxygenation |
Myfox is a privately held French company that designs and produces connected, sensor-driven, and wireless home security equipment.
The focus is on home automation products that integrate with category eco-systems ( IFTTT , [ 1 ] Works with Nest [ 2 ] ). Myfox's flagship products are the Myfox Home Alarm and the Myfox Security Camera. [ 3 ] [ 4 ]
The company has its headquarters located in Labège , France, and Campbell , California, in the United States. Its products are available for sale in several European countries, such as France, Germany, Spain, Italy, Sweden, Switzerland, and the United Kingdom. The company launched in North America (United States and Canada) in June 2015. [ 5 ] [ 6 ] [ 7 ]
In 2016, Somfy acquired MyFox. [ 8 ]
Myfox was founded in 2005 by entrepreneur Jean Prunet, with the creation of the IntelliTAG smart sensor. This technology is based on the concept of “proactive deterrence.” The vibration sensor attaches to doors and windows to alert users in case of an attempted break-in, with the capacity to differentiate between break-in attempts and normal, everyday events. The end result is a DYI security solution that can catch intruders before they can enter the home. [ citation needed ]
The brand launched the first connected alarm solution on the market in 2009. The same year, Jean-Marc Prunet, Jean Prunet's son, took the helm of the company as chief executive officer. [ citation needed ]
The company grew from its roots in Toulouse, France, to become an international company in 2014. Alongside the launch of the third generation of IntelliTAG, it expanded distribution to Belgium, the Netherlands, Germany, Switzerland and Spain. [ citation needed ]
In 2015, Myfox launched two new products, the Myfox Home Alarm and Security Camera. [ citation needed ]
In June 2015, the company entered the North American market. [ citation needed ]
In September 2015, Myfox announced the Myfox Home Alarm's compatibility with the Nest Learning Thermostat and Nest Protect: Smoke and Carbon Monoxide alarm. [ citation needed ]
In October 2015, Myfox announced their Security Channel on IFTTT that connects their Home Alarm and Security Camera with software that allowed for interaction between the products, apps and IoT devices. In 2016, the company announced the availability of 24/7 professional monitoring. [ 9 ] The company reached an agreement with Apple in February 2016 and is now available for sale at Apple stores in France, Germany, Spain, Italy, the United Kingdom, Sweden and Switzerland, as well as online in over twenty more countries. [ citation needed ]
Myfox Home Alarm is a DIY security system that works with a Bluetooth key fob to recognize users and automatically disarm the alarm.
The system's IntelliTAG can detect break-in attempts by analyzing and differentiating vibrations and impacts. Myfox Home Alarm also allows the user to invite people from his/her network (friends, neighbors, family) to keep an eye on his/her home through what it calls a “community”.
The system includes an IntelliTAG, a 110 dB siren, a Bluetooth key fob to disarm the alarm, and a Link to ensure Wi-Fi connection.
Myfox Home Alarm is wireless; it connects to Wifi and can be controlled through the Myfox app. When a break-in attempt is detected, a smartphone notification is sent to the user and/or their community, including the option to call a designated emergency contact, which can be local authorities. The application also informs users about who is in the home. [ citation needed ]
Myfox Security Camera is equipped with a motorized shutter to respect users' privacy needs. The camera's integrated infrared detector registers movement and records it while the user is away, but the motorized shutter automatically covers the camera lens for privacy when the user comes home. Additionally, the shutter can also be closed remotely with just a click on the smartphone application. [ citation needed ] | https://en.wikipedia.org/wiki/Myfox |
In the theory of formal languages , the Myhill–Nerode theorem provides a necessary and sufficient condition for a language to be regular . The theorem is named for John Myhill and Anil Nerode , who proved it at the University of Chicago in 1957 ( Nerode & Sauer 1957 , p. ii).
Given a language L {\displaystyle L} , and a pair of strings x {\displaystyle x} and y {\displaystyle y} , define a distinguishing extension to be a string z {\displaystyle z} such that
exactly one of the two strings x z {\displaystyle xz} and y z {\displaystyle yz} belongs to L {\displaystyle L} .
Define a relation ∼ L {\displaystyle \sim _{L}} on strings as x ∼ L y {\displaystyle x\;\sim _{L}\ y} if there is no distinguishing extension for x {\displaystyle x} and y {\displaystyle y} . It is easy to show that ∼ L {\displaystyle \sim _{L}} is an equivalence relation on strings, and thus it divides the set of all strings into equivalence classes .
The Myhill–Nerode theorem states that a language L {\displaystyle L} is regular if and only if ∼ L {\displaystyle \sim _{L}} has a finite number of equivalence classes, and moreover, that this number is equal to the number of states in the minimal deterministic finite automaton (DFA) accepting L {\displaystyle L} . Furthermore, every minimal DFA for the language is isomorphic to the canonical one ( Hopcroft & Ullman 1979 ).
Myhill, Nerode (1957) — (1) L {\displaystyle L} is regular if and only if ∼ L {\displaystyle \sim _{L}} has a finite number of equivalence classes.
(2) This number is equal to the number of states in the minimal deterministic finite automaton (DFA) accepting L {\displaystyle L} .
(3) The minimal DFA is unique up to unique isomorphism. That is, for any minimal DFA acceptor, there exists exactly one isomorphism from it to the following one:
Generally, for any language, the constructed automaton is a state automaton acceptor. However, it does not necessarily have finitely many states. The Myhill–Nerode theorem shows that finiteness is necessary and sufficient for language regularity.
Some authors refer to the ∼ L {\displaystyle \sim _{L}} relation as Nerode congruence , [ 1 ] [ 2 ] in honor of Anil Nerode .
(1) If L {\displaystyle L} is regular, construct a minimal DFA to accept it. Clearly, if x , y {\displaystyle x,y} end up in the same state after running through the DFA, then x ∼ L y {\displaystyle x\sim _{L}y} , thus the number of equivalence classes of ∼ L {\displaystyle \sim _{L}} is at most the number of DFA states, which must be finite.
Conversely, if ∼ L {\displaystyle \sim _{L}} has a finite number of equivalence classes, then the state automaton constructed in the theorem is a DFA acceptor, thus the language is regular.
(2) By the construction in (1).
(3) Given a minimal DFA acceptor A {\displaystyle A} , we construct an isomorphism to the canonical one.
Construct the following equivalence relation: x ∼ A y {\displaystyle x\sim _{A}y} if and only if x , y {\displaystyle x,y} end up on the same state when running through A {\displaystyle A} .
Since A {\displaystyle A} is an acceptor, if x ∼ A y {\displaystyle x\sim _{A}y} then x ∼ L y {\displaystyle x\sim _{L}y} . Thus each ∼ L {\displaystyle \sim _{L}} equivalence class is a union of one or more equivalence classes of ∼ A {\displaystyle \sim _{A}} . Further, since A {\displaystyle A} is minimal, the number of states of A {\displaystyle A} is equal to the number of equivalence classes of ∼ L {\displaystyle \sim _{L}} by part (2). Thus ∼ A = ∼ L {\displaystyle \sim _{A}=\sim _{L}} .
Now this gives us a bijection between states of A {\displaystyle A} and the states of the canonical acceptor. It is clear that this bijection also preserves the transition rules, thus it is an isomorphism of DFA. The isomorphism is unique, since for both DFA, any state is reachable from the starting state for some word x {\displaystyle x} .
The Myhill–Nerode theorem may be used to show that a language L {\displaystyle L} is regular by proving that the number of equivalence classes of ∼ L {\displaystyle \sim _{L}} is finite. This may be done by an exhaustive case analysis in which, beginning from the empty string , distinguishing extensions are used to find additional equivalence classes until no more can be found.
For example, the language consisting of binary representations of numbers that can be divided by 3 is regular. Given two binary strings x , y {\displaystyle x,y} , extending them by one digit gives 2 x + b , 2 y + b {\displaystyle 2x+b,2y+b} , so 2 x + b ≡ 2 y + b mod 3 {\displaystyle 2x+b\equiv 2y+b\mod 3} iff x ≡ y mod 3 {\displaystyle x\equiv y\mod 3} . Thus, 00 {\displaystyle 00} (or 11 {\displaystyle 11} ), 01 {\displaystyle 01} , and 10 {\displaystyle 10} are the only distinguishing extensions, resulting in the 3 classes. The minimal automaton accepting our language would have three states corresponding to these three equivalence classes.
Another immediate corollary of the theorem is that if for a language L {\displaystyle L} the relation ∼ L {\displaystyle \sim _{L}} has infinitely many equivalence classes, it is not regular. It is this corollary that is frequently used to prove that a language is not regular.
The Myhill–Nerode theorem can be generalized to tree automata . [ 3 ] | https://en.wikipedia.org/wiki/Myhill–Nerode_theorem |
Mykhailo Andriiovych Holubets ( Ukrainian : Михайло Андрійович Голубець ; 30 October 1930 – 14 August 2016) was a Ukrainian environmental scientist and politician who served as a People's Deputy of Ukraine from Kalush between 1990 and 1994. He was a member of the National Academy of Sciences of Ukraine . [ 1 ]
Holubets was a laureate of the State Prize of Ukraine in Science and Technology , and he served as the vice-president of the Forestry Academy of Sciences of Ukraine. He held the position of honorary director of the NASU Institute of Ecology of the Carpathians. [ 2 ] He also was an honorary doctor of Ivan Franko National University of Lviv . [ 3 ] [ 4 ]
Mykhailo Holubets was born on 30 October 1930, in the village of Velykyi Liubin , then part of the Second Polish Republic (now in Lviv Oblast , Ukraine). In 1953, he obtained a higher education degree from Lviv Agricultural Institute with a specialization in ecology and forestry and the qualification of forestry engineer. He embarked on his scientific career in 1953 as a postgraduate student and later, from 1954 to 1957, as a lecturer at Lviv Agricultural Institute and Ukrainian National Forestry University . [ 5 ]
In 1960, Holubets defended his dissertation to obtain the degree of Candidate of Agricultural Sciences. Until 1962, he worked as a junior and senior researcher at the Research Institute of Agriculture and Animal Husbandry of the Western Regions of the Ukrainian SSR. From 1962, Mykhailo Holubets worked in scientific institutions of the Academy of Sciences of the Ukrainian SSR. He initially served as a senior researcher at the Research Institute of Natural Sciences, and later as a senior researcher in the Department of Experimental Ecology and Biocenology at the M.G. Kholodny Institute of Botany of the Ukrainian SSR Academy of Sciences. He also held positions as the head of a department and director of the State Museum of Natural History. [ 6 ]
In 1969, he defended his dissertation titled "Spruce Forests of the Ukrainian Carpathians" to earn a Doctor of Biological Sciences degree with a specialization in botany. He defended his dissertation at the M.V. Lomonosov Moscow State University. From 1974, Mykhailo Holubets served as the deputy director for Scientific Work at the M.G. Kholodny Institute of Botany of the Ukrainian SSR Academy of Sciences and led the Lviv branch of this institute. Simultaneously, from 1974 to 1995, he worked as a professor at the Department of Plant Morphology and Systematics at Ivan Franko Lviv State University. [ 3 ]
In 1978, Holubets became a professor and was elected a corresponding member of the Academy of Sciences of Ukraine. From 1991 to 2007, he headed NASU Institute of Ecology of the Carpathians, and from 2008, he held the honorary position of director of the research institution.
In 1990, Holubets became an academician of the National Academy of Sciences of Ukraine. [ 7 ] He educated specialists in the fields of ecology, botany, and forestry. Holubets was a member of the editorial boards of several scientific journals, including Studia Biologica , Ecology and Noosphereology , Scientific Works of the Forestry Academy of Sciences of Ukraine , and the Ukrainian Botanical Journal . [ 8 ] [ 9 ]
Holubets' primary research focus included the structural and functional organization of terrestrial ecosystems and geosociosystems, as well as prospects for managing sociospheric processes. He supervised postgraduate students starting from 1965. Under his guidance, 5 doctoral and 17 candidate dissertations were defended.
He paid significant attention to various issues in eidology.
Mykhailo Holubets authored approximately 500 scientific papers, including 19 monographs, and served as the editor for nearly thirty collective monographs.
Selected scientific works by Mykhailo Andriiovych Holubets include:
Holubets joined the People's Movement of Ukraine , an anti-communist opposition movement, in 1989. He later left the organisation in 1990. [ 9 ] From 1990 to 1994 he was a People's Deputy of Ukraine from the city of Kalush in Ivano-Frankivsk Oblast . He was chairman of the Subcommittee on Ecology and Environmental Protection and participated in the development and signing of the Belovezha Accords . [ 11 ] He later joined the Congress of National-Democratic Forces [ uk ] . [ 12 ]
Between 1995 and 1996 Holubets was a member of the Lviv Oblast Council . He served on the Lviv City Council from 1996 to 2002, and was deputy chairman of the Lviv Oblast Organisation of the Congress of Ukrainian Intelligentsia. [ 3 ]
He published journalistic works about the People's Movement of Ukraine (1998), the Belovezha Accords (2001), the consequences of russification of the Ukrainian language (2006), "The Tree of Life" (2008) and others. [ 13 ]
He was the Ukrainian curator of the MAB-6a project within the Man and the Biosphere Programme and chaired sections on Fundamental and Applied Problems of Ecology of the Scientific Council on Environmental Protection and Sustainable Development of the National Academy of Sciences of Ukraine and Ecology, General Biology, and Nature Conservation of the Scientific Council of the Ministry of Education and Science of Ukraine . Holubets passed away on 14 August 2016, at the age of 86 and was buried in the family grave at the 59th Field of Yaniv Cemetery in Lviv. [ 9 ] [ 11 ] | https://en.wikipedia.org/wiki/Mykhailo_Holubets |
Mykola Andriyovych Yankovsky (born 12 August 1944 in Pokotilovo, Ukrainian SSR ) is a former Ukrainian businessman who has influenced Ukraine’s chemical production landscape and made it environmentally friendly. [ 1 ] Candidate of Economic Sciences (1998), Professor, Head of the Department of Advanced Technologies in Management of Donetsk State Academy of Management (since 1999); Academician of AINU (1992), AENU (1995). Member of the Academy of Russian Entrepreneurs (1997). Professor Emeritus of the Ukrainian State University of Chemical Technology . Hero of Ukraine ( 2003 ).
Mykola Yankovsky was born on August 12, 1944, in ( Pokotilovo village , Novoarkhangelsk district , Kirovohrad Oblast ); wife Galina (1949) - housewife; daughters Irina (1967) and Tatiana (1973); son Igor (1974).
Yankovsky is now retired, spending time with his family and friends. He has lived a private life for some years, but during his career as an entrepreneur, Yankovsky has impacted Ukraine’s chemical production landscape and brought in inventions and business practices that were largely unknown when the Soviet Union came to an end. He transformed Donetsk’s industry to meet accepted social and ecological standards. [ 1 ]
Mykola Yankovsky studied at Dneprodzerzhinsk Crafts School from 1961 to 1963; and later on at Dnepropetrovsk Chemical Technology Institute (1963-1969) as a chemical engineer technologist with a specialization of "Technology of inorganic substances and mineral fertilizers"; PhD thesis "Model of foreign economic activity of chemical enterprises". His Doctoral dissertation is "Management of enterprise competitiveness in world markets" (Institute of Industrial Economics of NASU, 2005). [ 2 ]
Yankovsky is a Doctor of Economics, Professor, and Head of Department Advanced Management Technologies since 1999 at Donetsk State University of Management . He has been an incumbent member of the Academy of Engineering Science of Ukraine since 1992 as well as an honorary Professor of the Ukrainian State University of Chemical Technology. He is an honorary Doctor of Odesa State Academy of Technical Regulation and Quality as well as a member of the International Academy of Standardization. [ 3 ]
Yankovsky is an author of more than 150 scientific works and academic publications, including more than 10 monographs and textbooks published in Ukraine and abroad. His monographs include: “Model of the foreign economic activity of chemical industry enterprises” (1997), “Forecasting the development of a large industrial complex: theory and practice” (1999), “Improving the efficiency of foreign economic activity of a large industrial complex” (2000), and “Innovative and classical theories of catastrophes and economic crises” (2010). [ 4 ]
In total, Yankovsky published more than 100 papers and manuals on production management, the chemical industry, international economy and bulk chemicals technology. Some of his monographies and manuals on chemical science are highly regarded and recommended by professors, and are used for teaching in higher and secondary specialized educational institutions of Ukraine [ 3 ]
In 1982, Yankovsky became the director at the Dneprodzerzhinsk production plant. Two years later in 1984, he took on the responsibility as the director at “Azot”. [ 5 ] From 1986 to 1987 he was deputy director at Pershamaiski machine factory. In 1987, he joined Gorlovka ON “Stirol” as chief engineer and took on the position of general director in 1988. He led the construction from scratch of two of the ten currently existing Ukrainian factories specialized in the production of ammonia. Another three of the ten currently existing plants were modernized under the supervision and active involvement of Mykola Yankovsky. [ 5 ]
In 1995, Yankovsky and his son Igor took an active part in the development of Trading House of the Corporate Group "Stirol" (city of Gorlovka, Donetsk Region). To date, the company is the largest chemical complex of Ukraine, specializing in the production of polymers, fertilizers, ammonia, pharmaceuticals. [ 6 ] With Stirol becoming one of the major chemical production businesses in Eastern Europe. Yankovsky was able to gain ownership of Stirol by the end of the 1990s.
In accordance with internationally recognized standards, the Big Four international audit firms have for many years audited OJSC “Stirol”, which allowed it to be one of the first Ukrainian joint-stock companies to issue Euro 125 million Eurobonds aimed at modernizing production. [ 5 ]
Under Yankovsky’s leadership, OSJC Stirol became the most valuable brand in the Ukrainian chemical industry. His efforts were recognized with the honorary title of “Hero of Ukraine”, awarded to him in 2003 for his extraordinary personal contribution to the development of the Ukrainian chemical industry and the production of internationally competitive products. [ 5 ]
OSJC Stirol also was one of the first companies in Eastern Europe and CIS countries to produce granulated carbamide and the first in Europe to use a closed water supply cycle for its production processes without the use of river water and with complete cessation of runoff into the environment. [ 5 ]
Prior to the sale of OSJC Stirol, the company prepared for an IPO, though this failed due to uncertainties on the natural gas markets. [ 5 ]
The company was highly successful and in 2010 the majority of Stirol shares were sold to Ostchem Holdings. According to the Kyiv Post, Yankovsky was among the wealthiest Ukrainians in 2010. [ 5 ]
Yankovsky also takes the following positions: Chairman of the Union of Donbass Chemists, Chairman of the Board of Directors of Gorlovka; Member of the Exporters Council under the CM of Ukraine (since 02.1999); Member of the Committee on State Prizes of Ukraine in Science and Technology (since 03.1997). Trustee of the candidate for the post of President of Ukraine Viktor Yanukovych in ballot paper # 48 (2004-2005). [ 4 ]
As Igor Sharov notes in his book, Mykola Andriyovych was a fervent supporter of the privatization of large industrial enterprises. He said that "Our" failing "enterprises should be privatized, at least for the hryvnia. As soon as possible." He considered every privatization case to be specific and did not see anything wrong with the growth of foreign capital, if investors wanted to develop the economy of the enterprise. Member of the Board and representative of the International Organization of Mineral Fertilizer Manufacturers and Traders (IFA) in Ukraine. [ 7 ]
Yankovsky is a member of Ukraine's national council on philanthropy. [ 8 ]
During his time as CEO of OJSC Stirol, Yankovsky reformed the standards under which chemical plants in Ukraine were run. Working conditions and production methods were significantly improved, leading to greater safety for employees and notably increasing efficiency and production quality. [ 9 ]
Yankovsky further improved working conditions by adopting environmentally friendly production processes and greatly reducing the environmental footprint of OJSC Stirol. He said that, “we want to create an environment in which even rare animals would like to live”. He managed this by opening a zoo with over 500 animals and birds living on the territory of the production plant. [ 9 ]
Mykola Yankovsky supported the diocese of the Ukrainian Orthodox Church, facilitating the construction of temples in Gorlovka and other cities of Ukraine. [ 9 ]
Yankovsky’s sense of social responsibility and desire to care for his employees led him into the world of politics. [ 9 ] From 1994 to 1998, he served as Deputy of Donetsk Regional Council . This was followed by four consecutive terms as People’s Deputy of Ukraine . [ 10 ] from 1998 to 2012. [ 2 ]
In the 1998 elections, he was elected People's Deputy of the Verkhovna Rada of Ukraine of the III convocation [ 11 ] [ circular reference ] in a single-mandate constituency in the Donetsk region (received 44.9% of the vote). [ 2 ]
In the 2002 elections, he was elected People's Deputy of the Verkhovna Rada of Ukraine of the IV convocation [ 12 ] [ circular reference ] in a single-mandate constituency in the Donetsk region (nominated from the electoral bloc " For United Ukraine! ", Received 34.45% of the vote). [ 2 ]
In the 2006 elections, he was elected People's Deputy of the Verkhovna Rada of Ukraine of the V convocation [ 13 ] [ circular reference ] (was No. 17 on the list of the Party of Regions). [ 2 ]
In the 2007 election, he was elected People's Deputy of the Verkhovna Rada of Ukraine of the VI convocation [ 14 ] [ circular reference ] (was No. 15 on the list of the Party of Regions). [ 2 ]
Yankovsky is married to Galina (born 1949). Together they have three children: Irene (born 1967), Tatiana (born 1973) and Igor (born 1974).
His son Yankovskyi Igor has been prominently involved in his business activities. [ 15 ] [ 6 ] | https://en.wikipedia.org/wiki/Mykola_Yankovsky |
Mylan N.V. was a global generic and specialty pharmaceuticals company. In November 2020, Mylan merged with Upjohn , Pfizer 's off-patent medicine division, to form Viatris . [ 2 ] Previously, the company was domiciled in the Netherlands , with principal executive offices in Hatfield, Hertfordshire , UK [ 3 ] and a "Global Center" in Canonsburg, Pennsylvania , US.
In 2007, the company acquired a controlling interest in India -based Matrix Laboratories Limited, a top producer of active pharmaceutical ingredients (APIs) for generic drugs, [ 4 ] and the generics business of Germany -based Merck KGaA . [ 5 ] Through these acquisitions, the company grew from the third-largest generic and specialty pharmaceuticals company in the United States to the second-largest generic and specialty pharmaceuticals company in the world. [ 6 ]
Mylan went public on the OTC market in February 1973. [ 7 ] It was listed on the NASDAQ, [ 8 ] and its shares were a component of the NASDAQ Biotechnology [ 9 ] and the S&P 500 indices. [ 10 ]
The company was founded in 1961 and developed and produced medicines for a wide range of medical disciplines, including oncology , anaphylaxis , antiretrovirals , cardiovascular , respiratory , dermatology , immunology , anesthesia and pain management , infectious disease , gastroenterology , diabetology/ endocrinology , and women's healthcare. [ 11 ]
Founded in 1961, the company was located in an abandoned skating rink in White Sulphur Springs , West Virginia . [ 12 ] [ 13 ] The facility was moved to Pennsauken, New Jersey in 1962, [ 14 ] to Princeton, West Virginia in 1963, and then Morgantown , West Virginia, in 1965, and in 1976 it relocated its corporate headquarters to the Pittsburgh suburb Canonsburg , Pennsylvania . Finally in 2004 it moved to a new office center in nearby Southpointe , a suburban business park located in the Pittsburgh suburb of Cecil Township . [ 15 ]
On February 23, 1973, Mylan had its initial public offering (IPO), [ 16 ] when it became a publicly traded company on the OTC market under the ticker symbol MYLN. In 1976 the stock moved to the National Association of Securities Dealers Automated Quotations ( NASDAQ ). Their final stock move was in 1986, when their stock became available for trade on the New York Stock Exchange under the ticker symbol MYL. Prior to the Viatris combination, the stock was traded on the NASDAQ .
Mylan Pharmaceuticals was founded as a drug distributor in 1961 by Milan Puskar and Don Panoz . [ 12 ] In 1966, the company began manufacturing penicillin G tablets as well as vitamins and other dietary supplements. [ 12 ] [ 17 ]
Panoz left the company in 1969 and Puskar quit the company in 1973, as it grew and experienced financial difficulties. The board hired Roy McKnight as board chairman, who convinced Puskar to return in 1976. [ 17 ]
The company discontinued operating as a contract manufacturing organization in 1980 and instead chose to market their products under their own "Mylan-labeled" brand. [ 18 ]
With the passage of the Hatch-Waxman Act in 1984, the company and other small generic companies gained value; in the eighteen months following passage of the law the company's earnings grew 166% to $12.5 million and its stock value rose 800%. [ 19 ]
In the 1980s one of the most prescribed drugs in the US was Dyazide, a diuretic that was a combination drug containing triamterene and hydrochlorothiazide ; it had been on the market since 1965 and its patents had expired in 1980. [ 20 ] Complications arose with the introductions of generics versions, because the formulation of Dyazide resulted in variable batches that made it impossible for generic manufacturers to show that their versions were bioequivalent. [ 21 ] [ 22 ]
Some generic companies committed fraud trying to bring a generic version of Dyazide. Bolar Pharmaceutical had the first generic version approved in 1987, but it turned out that Bolar had fraudulently substituted Dyazide for its own version to conduct studies that were submitted to the FDA. By 1989 the FDA rescinded its approval based on its suspicions and filed criminal charges against Bolar, to which Bolar eventually pled guilty in 1991. [ 23 ] [ 24 ] [ 25 ]
The company chose to develop a new version of a triamterene/hydrochlorothiazide combination drug instead of going the generic route; it developed a different, more stable formulation [ 22 ] and used different dosages of each active ingredient (50 mg hydrochlorothiazide and 75 mg triamterene, compared with Dyazide's 25 mg hydrochlorothiazide and 50 mg triamterene). [ 26 ] This drug had to get approval as a new drug, as opposed to a generic. Their product was called Maxzide and was approved in 1984. [ 26 ] [ 27 ] The higher dose allowed once per day dosing, which the company and its marketing partner, Lederle, believed would help it compete against Dyazide, which had $210M in sales in 1983. [ 26 ] However, the company's patents on the drug were declared invalid in court, and its marketing exclusivity expired in 1987, prompting a rush of generic competition. [ 28 ]
The company had concerns about the practices of its competitors and the FDA in general, and also with regard to companies seeking to bring generic versions of Maxzide. The company hired private investigators to examine its competitors' practices, and when it found evidence of corruption, it submitted it to the House Oversight and Investigations Committee , which investigated and found fraud and corruption within the Food and Drug Administration 's generic drugs division and at other generic companies. [ 17 ] Two of the companies that had gotten approval to market generic versions of Maxzide, Vitarine Pharmaceutical and Par Pharmaceutical , were targets of the company's initial investigation and were found to have used Maxzide to obtain their bioequivalence data, leading both companies to withdraw its generic competitor to Mylan's product. [ 17 ] [ 29 ]
The corruption in the nascent generics industry and at the office in the FDA regulating it was widely covered in the media, and led to widespread concern among doctors and the public in the late 1980s and early 1990s that generic drugs were not really the same as the branded drugs they were meant to replace. [ 23 ] [ 30 ] [ 21 ]
In 1987, the company entered into a joint venture with Bolar to buy Somerset Pharmaceuticals; Mylan wanted access to Somersets' drug discovery capabilities as well as its new drug for Parkinson's, selegiline ; the deal was completed in 1988 but its consummation was dependent on FDA approval of selegiline, which came in 1989. [ 17 ] [ 31 ] [ 32 ]
The company acquired Bertek Inc. in 1993 for its transdermal patch technologies, and kept it as a subsidiary. In 1999, the company renamed Bertek as Mylan Technologies Inc. (MTI). [ 33 ] MTI eventually came to be the contract manufacturer for the selegiline transdermal patch and was the first company to market generic nitroglycerin, estradiol, clonidine, and fentanyl transdermal patches. [ 33 ]
In 1996, the company acquired UDL Laboratories, a supplier of unit dose generic medications to institutional and long-term care facilities. [ 34 ]
In 1998 when it was the world's second largest generics company, the company came under investigation from the Federal Trade Commission after it raised the prices of its products, tripling them in the case of lorazepam . The company had entered into an exclusive agreement with Profarmica, an Italian company that supplied drug ingredients, after which the company's competitors had higher prices and a diminished supply of raw ingredients for lorazepam and other drugs. [ 35 ] Before the round of price increases the price of generic drugs had been 5 - 10% of the price of branded drugs and afterwards it was around 50%. [ 35 ] The FTC filed suit at the end of 1998 and 32 states filed parallel actions. The case was settled in 2000, with the company paying a total of $147M -- $100M in disgorged profits into a fund to reimburse consumers and state agencies that had overpaid, $8 million in attorney's fees to the State Attorneys General, $35 million, plus $4 million in attorney's fees, to settle certain class actions with insurers and managed care organizations—and Mylan and three ingredient suppliers ( Cambrex Corporation , Profarmaco S.R.L., and Gyma Laboratories) also agreed to an injunction barring them from entering into similar anticompetitive agreements in the future. [ 36 ] [ 37 ]
In 2004, the company and King Pharmaceuticals began discussing a deal in which Mylan would acquire King for $4 billion; Mylan wanted to expand its presence in branded pharmaceuticals and to acquire King's sales force. [ 38 ] The deal was complicated by a number of factors, and included an SEC investigation into King's accounting and Carl Icahn obtaining a 9.8% interest in Mylan and becoming its largest stakeholder in order to kill the deal. The parties called off the deal in February 2005. [ 38 ] Afterwards, Icahn offered to buy Mylan for $5.4 billion [ 39 ] and nominated a slate of board members to change the direction of Mylan; he won three seats in May 2005. [ 40 ] In June, the company bought back 25% of its shares in order to fend off Icahn. [ 41 ] In July, Icahn gave up his bid and sold his shares. [ 42 ]
In January 2007, the company acquired a controlling interest in Matrix Laboratories, an Indian supplier of active pharmaceutical ingredients , for approximately $736 million, with the takeover including all of Matrix's subsidiary firms, for example Docpharma. It was at the time the largest-ever takeover in the Indian pharma industry [ 43 ] and also gave access to markets in China, India, and Africa. [ 44 ] [ 45 ]
In October 2007, the company acquired the generics division of Merck KGaA for $6.6 billion. [ 46 ] [ 47 ] [ 48 ] The company acquired the rights to market the EpiPen in the transaction. At that time annual sales were around $200 million [ 49 ] and the EpiPen had about 90% of the market. [ 50 ]
In 2009, the company filed two lawsuits against the Pittsburgh Post-Gazette after the newspaper ran an article that was critical of the quality control procedures used at the company's Morgantown plant. [ 51 ] [ 52 ] The company had earlier quality control issues involving the FDA. [ 53 ] The lawsuits were dropped in 2012 without any damages paid by the Post-Gazette, which stated "The Post-Gazette did not find and did not intend to report that Mylan had manufactured or distributed any defective drugs. The Post-Gazette regrets if any reader of the article thought otherwise." [ 54 ]
Also in 2009, the company and its subsidiary UDL agreed to pay $118 million to settle a suit filed under the False Claims Act in which Mylan/UDL and two other companies were accused of underpaying states under the Medicaid Drug Rebate Program . The program requires drug companies to give rebates to states under Medicaid and the rebates are higher for new drugs than for generics; the suit said that the companies sold new drugs but paid rebates as if they were generics. [ 55 ]
In 2011, the company entered into an agreement with Pfizer for the exclusive worldwide rights to develop, manufacture and commercialize Pfizer's generic equivalent to GlaxoSmithKline 's Advair (US)/Seretide (UK) Diskus incorporating Pfizer's proprietary dry powder inhaler delivery platform. [ 56 ] The company launched the product in the UK in 2015 [ 57 ] and in February 2016 the FDA accepted its ANDA, putting it in line behind Hikma and Sandoz to launch a generic version in the US. [ 58 ]
In 2012, the company launched a program called EpiPen4Schools to sell EpiPens in bulk and with discounts to schools. To participate in the program schools had to agree not to buy epinephrine autoinjectors from any other company for a year, a requirement which a company spokesperson said is no longer part of its program. [ 59 ]
In December 2012, the National Association of State Boards of Education launched a policy initiative designed to "help state boards of education as they develop student health policies regarding anaphylaxis and epinephrine auto-injector access and use," and advocated for state laws protecting schools from legal liability for stocking and using epinephrine autoinjectors. Gayle Manchin , the mother of the company's CEO, Heather Bresch, had become president of the association in 2010, and shortly after had discussed donations from her "daughter's company" to the association. Manchin had been appointed to the West Virginia state school board by her husband, then-governor of the state Joe Manchin , in 2007. In a statement, the company said, "There is no truth to the suggestion that the company's efforts were anything but straightforward or that we are aware of anyone advocating inappropriately for the right of schoolchildren to have access to potential life-saving medicine." [ 60 ]
After successful lobbying from the company, [ 49 ] in 2013, the "School Access to Emergency Epinephrine Act" became law after passing Congress with broad and bipartisan support; it protected anyone from liability if they administered epinephrine to a child in a school (previously, only trained professionals or the affected person were allowed to administer the drug, and were open to liability), and it provided some financial incentives for schools that didn’t already stock epinephrine autoinjector to start stocking them. [ 61 ] Joe Manchin , the father of Mylan's CEO, was a senator at that time. [ 60 ]
In 2013, the company acquired an Indian generic injectable drugs company, Agila Specialties Private, for $1.6 billion. [ 62 ] In 2015, three plants acquired in that deal were issued warning letters by the FDA. [ 63 ]
In February 2015, in a tax inversion , the company acquired the generic drugs business in developed markets of Abbott Laboratories for $5.3 billion in stock. [ 64 ] [ 65 ]
Also in February 2015, the company acquired Mumbai-based Famy Care and expand its presence in the market for women's contraceptives at about $750 million. [ 66 ] [ 67 ]
In April 2015, the company attempted a hostile takeover of Perrigo , offering to buy $26 billion in shares directly from shareholders. Too few shareholders agreed to sell their stock by the deadline set in November 2015 and the effort failed. [ 68 ] [ 69 ] [ 70 ]
Two weeks after the company made its first offer for Perrigo, Teva Pharmaceuticals offered to buy the company for $40 billion; the combined companies would have been the world's largest generic company and the 9th biggest drug company in the world. [ 71 ] In July, Teva dropped its bid for Mylan and instead acquired Allergan 's generic drug business for about the same price. [ 72 ] [ 73 ]
In June 2015, the company agreed to work with Pulmatrix, a company with a proprietary inhaled drug delivery platform, to co-develop a product to treat for chronic obstructive pulmonary disease (COPD); the product was PUR0200, a generic drug in a Pulmatrix device. [ 74 ]
In February 2016, the company announced it would acquire Meda AB for $9.9 billion. [ 75 ] In May 2016, the company announced it would acquire Renaissance Acquisition Holdings dermatology division for up to $1 billion. [ 76 ]
In December 2016, the State attorneys general of 20 states filed a civil complaint accusing the company of a coordinated scheme to artificially maintain high prices for a generic antibiotic and diabetes drug. The complaint alleged price collusion schemes between six pharmaceutical firms including informal gatherings, telephone calls, and text messages. [ 77 ]
In October 2017, the company announced the launch of the first FDA-approved generic of Teva’s long-acting Copaxone . Approximately three months later, Credit Suisse analyst Vamil Divan cited IMS Health data which showed that the new generic accounted for 10% of the market. [ 78 ]
In May 2018, the company announced a collaboration with West Virginia University to provide children across West Virginia with STEM education. [ 79 ]
In 2018, valsartan manufactured by the company was voluntarily recalled due to the detection of trace amounts of N -nitrosodiethylamine (NDEA) which is a probable human carcinogen. [ 80 ]
In January 2019, the FDA announced its approval of the company's Wixela Inhub , the first approved generic version of GlaxoSmithKline 's Advair Diskus. [ 81 ]
In late July 2019, the company and Pfizer announced that Pfizer would spin off and merge its off-patent medicine division, Upjohn, with Mylan. [ 82 ] [ 83 ]
In November 2019, Mylan & Upjohn announced that the name of the new company would be Viatris . [ 84 ] [ 85 ] The company continued sales of Mylan's more than 7,500 products, including biosimilars, generics, brand and over-the-counter remedies, with brands including the Epi-Pen , Viagra , Lipitor and Celebrex . [ 86 ] [ 87 ] [ 88 ]
The deal was structured as an all-stock, Reverse Morris Trust transaction.
Pfizer shareholders owned 57% of the combined new company and Mylan shareholders owned 43%. [ 89 ]
On February 23, 1973, the company became a public company via an initial public offering (IPO), [ 34 ] on the OTC market. In 1976, the stock moved to NASDAQ and in 1986, it moved to the New York Stock Exchange , then later back to NASDAQ.
The following is an illustration of the company's major mergers and acquisitions and historical predecessors:
Mylan acquired the right to market and distribute the EpiPen line of epinephrine autoinjector devices from Merck KGaA as part of their 2007 deal; [ 90 ] that right had formerly been held by Dey LP, a wholly owned subsidiary of Merck. [ 91 ] According to Bloomberg News , the devices deliver about $1 worth of drug. [ 49 ] At that time annual sales were around $200 million. [ 49 ] Bresch, the company's CEO, saw an opportunity to increase sales through marketing and advocacy, and the company launched a marketing campaign to increase awareness of the dangers of anaphylaxis for people with severe allergies that made the brand "EpiPen" as identified with its product as "Kleenex" is with facial tissue. The company also successfully lobbied the FDA to broaden the label to include risk of anaphylaxis and in parallel, successfully lobbied Congress to generate legislation making EpiPens available in schools and in public places like defibrillators are, and hired the same people that Medtronic had worked with on defibrillator legislation to do so. [ 49 ] Mylan's efforts to gain market dominance were aided when Sanofi 's competing product was recalled in November 2015 and further when Teva's generic competitor was rejected by the FDA in March 2016. [ 92 ]
By the first half of 2015, Mylan had an 85% market share of such devices in the US [ 49 ] and in that year sales reached around $1.5 billion and accounted for 40% of Mylan's profit. [ 93 ] Those profits were also due in part to Mylan's continually raising the price of EpiPens starting in 2009; in 2009 the wholesale price of two EpiPens was about $100, by July 2013 the price was about $265, in May 2015 it was around $461, and in May 2016 the price rose again to around $609, [ 90 ] around a 500% jump from the price in 2009. [ 94 ]
Starting in 2014, according to a 2017 report in the New York Times , mid-level executives began questioning the rate at which the company had increased and was planning to continue to increase the price of the Epi-Pen, and raising concerns that the price increases were unethical; the Times reported that when these concerns were brought to Robert Coury, the chairman of the board, Coury "replied that he was untroubled. He raised both his middle fingers and explained, using colorful language, that anyone criticizing Mylan, including its employees, ought to go copulate with themselves. Critics in Congress and on Wall Street, he said, should do the same. And regulators at the Food and Drug Administration? They, too, deserved a round of anatomically challenging self-fulfillment." The Times reported that Bresch provided similarly dismissive responses. [ 95 ] The reporter noted that "Those top leaders’ responses are a far cry from the message on Mylan’s website, which says that 'we challenge every member of every team to challenge the status quo,' and that 'we put people and patients first, trusting that profits will follow'", and also noted that "The firm is a case study in the limits of what consumer and employee activism, as well as government oversight, can achieve." [ 95 ] [ 96 ] [ 97 ] [ 98 ]
In the summer of 2016, as parents prepared to send their children back to school and went to pharmacies to get new EpiPens, people began to express outrage at the cost of the EpiPen and the company was widely and harshly criticized, [ 99 ] [ 100 ] including criticism from Martin Shkreli , "poster boy for grasping pharma greed," letters from two senators and initiation of Congressional investigations. [ 93 ] [ 101 ] Mylan's pricing of the EpiPen was widely referred to as price gouging . [ 102 ] [ 103 ] [ 104 ] The last price increase coincided with the company's airing of a new line of TV commercials that were described as "shocking" and "no holds barred", depicting an anaphylactic reaction from the point of view of the young woman having it at a party, and ending with the young woman seeing her swollen and hive-covered face in the mirror before she collapses. [ 105 ] In response to criticism, the company increased financial assistance available for some patients to purchase EpiPens, [ 106 ] a gesture that was called a "classic public relations move" by Harvard Medical School professor Aaron Kesselheim. [ 107 ] The up to $300 saving cards can only be used by a small number of people who need the drug, and no one on Medicaid . They do nothing about the high price, he said, which is still being paid by insurers, who ultimately pass the cost onto consumers. [ 107 ] The company further responded by releasing the first authorized generic version of the EpiPen in December 2016 at a more than 50% discount. [ 108 ]
In September 2016, the New York State Attorney General began an investigation into the company's EpiPen4Schools program in New York to determine if the program's contracts violated antitrust law [ 109 ] and the West Virginia State Attorney General opened an investigation into whether Mylan had given the state the correct discount under the Medicaid Drug Rebate Program and subpoenaed the company when it refused to provide the documentation the state requested. [ 110 ]
In October 2016, the CEO of the company testified to Congress that Pfizer/King charged the company about $34.50 for one device. [ 111 ] In September 2016, a Silicon Valley engineering consultancy performed a teardown analysis of the EpiPen and estimated the manufacturing and packaging costs at about $10 for a two-pack. [ 112 ]
According to the Department of Health and Human Services' Office of Inspector General analysis, the U.S. government may have overpaid "as much as $1.27 billion between 2006 and 2016" to the company for the EpiPen emergency allergy treatment. This represents three times the proposed settlement of $465 million announced by the company in October 2016. In October 2016, the company announced a settlement with the US Department of Justice over rebates paid by the company to states under the Medicaid Drug Rebate Program. [ 113 ] Questions had been raised by Congress and others about why EpiPen had been classified as a generic rather a proprietary product in the program since 1997; generic drugs have lower rebates (13%) than proprietary drugs (23%), and price hikes for generic drugs cannot be passed onto states, and a common form of pharmaceutical fraud involves misclassifying proprietary drugs as generic under the program. [ 114 ] Under the agreement, the company agreed to pay a $465 million payment and to sign a corporate integrity agreement requiring it to perform better in the future; [ 113 ] the settlement also resolved cases brought by states related to the rebates. [ 115 ] Simultaneously with the settlement, the company also announced it was being investigated by the Securities and Exchange Commission related to the drug rebate program. [ 116 ] Republican Senator Chuck Grassley , chair of the Senate Judiciary Committee that launched the "probe of EpiPen pricing probe in 2016, released the analysis on May 30, 2017. [ 117 ]
In a report published on June 12, 2017 Institutional Shareholder Services criticized the company for the "outsized compensation" of its directors. Former CEO Robert Coury received a $98 million 2016 pay package in spite of shareholder losses and the perceived harm to the company inflicted by the EpiPen controversies. The report urged the company's shareholders to oust all of the existing directors. [ 118 ] [ 117 ]
The company manufactures rocuronium bromide , which is approved by the state of Alabama for use in executions by lethal injection . European manufacturers refuse to sell drugs which can be used for executions to the United States, except to distributors or users who sign legally binding agreements that the drug will not be used for executions down the delivery chain. [ 119 ]
In September 2014, the London -based human rights organisation Reprieve told Mylan that it was the only FDA -approved manufacturer of rocuronium bromide without legal controls in place to prevent its use in executions, and there was "a very real risk that Mylan may soon become the go-to provider of execution drugs for states across the country". German asset manager DJE Kapital [ de ] divested itself of $70 million in Mylan shares for that reason. The company said that its distribution was "legally compliant," [ 119 ] and that their restrictions did "prohibit resale to correctional facilities for use in lethal injections." [ 120 ]
Heather Bresch was an Executive Director and the CEO of Mylan from 2012 until the Viatris combination in 2020. [ 128 ] Robert Coury was Chairman, [ 129 ] and Rajiv Malik was President. [ 130 ] | https://en.wikipedia.org/wiki/Mylan |
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