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score before showing him the movie; instead, he would give him relevant cues like "falling into a black hole" or "event horizon." === Soundtrack === == Reception == A Brief History of Time received largely positive reviews. On review aggregator website Rotten Tomatoes, the film holds a 93% rating based on 15 reviews. On Metacritic, the film has a 78 out of 100 rating based on 12 critics, indicating "generally favorable" reviews. == Availability == The film was released on VHS in the early 1990s, but remained unreleased on DVD or Blu-ray until The Criterion Collection issued a release on April 15, 2014. == See also == List of films about mathematicians == References == == External links == A Brief History of Time at IMDb A Brief History of Time at Box Office Mojo A Brief History of Time at Rotten Tomatoes A Brief History of Time at Metacritic A Brief History of Time from ErrolMorris.com A Brief History of Time: Macrobiography an essay by David Sterritt at the Criterion Collection
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"title": "A Brief History of Time (film)"
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Facial symmetry is one specific measure of bodily symmetry. Along with traits such as averageness and youthfulness, it influences judgments of aesthetic traits of physical attractiveness and beauty. For instance, in mate selection, people have been shown to have a preference for symmetry. Facial bilateral symmetry is typically defined as fluctuating asymmetry of the face comparing random differences in facial features of the two sides of the face. The human face also has systematic, directional asymmetry: on average, the face (mouth, nose and eyes) sits systematically to the left with respect to the axis through the ears, the so-called aurofacial asymmetry. == Directional asymmetry == Directional asymmetry is systematic. The average across the population is not "symmetric", but statistically significantly biased on one direction. That means, that individuals of a species can be symmetric, or even asymmetric to the opposite side (see, e.g., handedness), but most individuals are asymmetric to the same side. The relation between directional and fluctuating asymmetry is comparable to the concepts of accuracy and precision in empirical measurements. There are examples from the brain (Yakovlevian torque) and spine, and inner organs (see axial twist theory), but also from various animals (see Symmetry in biology). === Aurofacial asymmetry === Aurofacial asymmetry (from Latin auris 'ear' and facies 'face') is an example of directed asymmetry of the face. It refers to the left-sided offset of the face (i.e. eyes, nose, and mouth) with respect to the ears. On average, the face's offset is slightly to the left, meaning that the right side of the face appears larger than the left side. The offset is larger in newborns and reduces gradually during growth. ==== Anatomy and definition ==== In contrast to fluctuating asymmetry, directional asymmetry is systematic, i.e. across the population it is systematically more often in one direction
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"page_id": 1967292,
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"title": "Facial symmetry"
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than in the other. It means that across the population a deviation is more often to one direction than to the other, i.e., there is a statistically significant bias to one direction. In case of directional asymmetry, most individuals of a species are asymmetric to the same side, even though some individuals can be symmetric, or even asymmetric to the opposite side (cf., e.g., handedness). The relation between directional and fluctuating asymmetry is comparable to the concepts of accuracy and precision in empirical measurements. The aurofacial asymmetry is defined as the position of the face (mouth, nose and eyes) with respect to the mid plane of the axis through the ears. The asymmetry is expressed as an angle (degrees), i.e. by how many degrees facial landmarks (e.g. tip of the nose) or pairs of landmarks (e.g. inner corners of the eyes (endocanthions are rotated away from the mid plane between the ears. ==== Magnitude across the face and development ==== On average, the aurofacial asymmetry is slightly larger for the eyes than for the nose, as shown by the figure. In humans asymmetric growth leads to a gradual reduction of the aurofacial asymmetry. As shown in the graph, the asymmetry decreases from about 2° at birth to about 0.5° in adults. ==== Theory and evolution ==== The aurofacial asymmetry was discovered after it was predicted by the axial twist theory. According to the theory the facial asymmetry is related to the Yakovlevian torque of the cerebrum, asymmetric heart and bowels and the spine. It is predicted to be common in vertebrates, but this has never been tested. The axial twist occurs in the early embryo. Shortly after the neurulation, the anterior head region makes a half-turn around the body axis in anti-clockwise direction (looking from tail to head), whereas the
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"page_id": 1967292,
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rest of the body (except heart and bowels) make a half-turn in clockwise direction. Since the axial twist is located between the ear-region and the forebrain-face-region, it is predicted that the face grows from the left to the midline, as is indeed the case. == Fluctuating asymmetry == Fluctuating asymmetry is the non-systematic variation of individual facial landmarks with respect to the facial midline, i.e., the line perpendicular to the line through the eyes, which crosses the tip of the nose and the chin. A wide variety of methods have been used to examine the claim that facial symmetry plays a role in judgments of beauty. Blending of multiple faces to create a composite and face-half mirroring have been among the techniques used. Conclusions derived from face mirroring, however, have been called into question, because it has been shown that mirroring face-halves creates artificial features. For example, if the nose of an individual is slightly bent to the right side, then mirroring the right side of the face will lead to an over-sized nose, while mirroring the left side will lead to an unnaturally small nose. === Attractiveness === Facial symmetry has been found to increase ratings of attractiveness in human faces. More symmetrical faces are perceived as more attractive in both males and females, although facial symmetry plays a larger role in judgments of attractiveness concerning female faces. Studies have shown that nearly symmetrical faces are considered highly attractive as compared to asymmetrical ones. === Dynamic asymmetries === Highly conspicuous directional asymmetries can be temporary ones. For example, during speech, most people (76%) tend to express greater amplitude of movement on the right side of their mouth. This is most likely caused by the uneven strengths of contralateral neural connections between the left hemisphere of the brain (linguistic localization)
|
{
"page_id": 1967292,
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and the right side of the face. === Facial averageness vs. symmetry === Experiments suggest that symmetry and averageness make independent contributions to attractiveness. === Aging === Facial symmetry is also a valid marker of cognitive aging. Progressive changes occurring throughout life in the soft tissues of the face will cause more prominent facial asymmetry in older faces. Therefore, symmetrical transformation of older faces generally increases their attractiveness while symmetrical transformation in young adults and children will decrease their attractiveness. == Physiognomy == Physiognomy or face reading is the practice of assessing a person's character or personality from their outer appearance—especially the face. Physiognomy as a practice meets the contemporary definition of pseudoscience and is regarded as such by academics because of its unsupported claims. Nevertheless, the subject is topic of serious scientific research. Statistical correlations does not inform anout possible causal dependence, so if observers judge the personality of (pictures of) symmetric faces differently than asymmetric ones, this might be due to cultural prejudice. Research indicates that a correlation exists between facial symmetry and the 'big-five' model of personality. The five factors are: Openness to experience (inventive/curious vs. consistent/cautious) Conscientiousness (efficient/organized vs. easy-going/careless) Extraversion (outgoing/energetic vs. solitary/reserved) Agreeableness (friendly/compassionate vs. challenging/detached) Neuroticism (sensitive/nervous vs. secure/confident) Accordingly, a positive correlation was found between facial symmetry and extraversion, as judged by others from photographs, as well as by the subjects themselves. More symmetrical faces are also judged to be lower on neuroticism but higher on conscientiousness and agreeableness (asymmetrical faces were rated as less agreeable than normal ones, but the more symmetrical were again rated as somewhat less agreeable than the normal). More symmetrical faces are also more likely to have more desirable social attributes assigned to them, such as sociable, intelligent or lively. The correlation of facial symmetry and neuroticism,
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{
"page_id": 1967292,
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openness, agreeableness and conscientiousness has remained unclear. Openness and agreeableness appear to be significantly negatively correlated to facial symmetry, while neuroticism and conscientiousness do not seem to be correlated to facial symmetry. With respect to trustworthiness it has been found that the facial muscles become imbalanced when lying. == Evolution and sexual selection == Sexual selection is a theoretical construct within evolution theory. According to sexual selection, mate choice can have profound influence on the preferred features. Sexual selection can only influence features that potential mates can perceive, such as smell, audition (e.g. song) and vision. Such features might be reliable indicators of hidden fitness parameters such as a good immune system or developmental stability. It has been argued that more symmetric faces are preferred because symmetry might be a reliable sign of such hidden fitness parameters. However it is possible that high facial symmetry in an individual is not due to their superior genetics but due to a lack of exposure to stressors, such as alcohol, during prenatal development. It has been found that more symmetrical faces are rated as healthier than less symmetrical faces. Indeed, facial symmetry was found to be positively associated with the perceived healthiness of the facial skin. Also, facial asymmetry was found to be correlated with physiological, psychological and emotional distress. Some evidence suggests that face preferences in adults might be correlated to infections in childhood. == See also == Beauty Symmetry in nature Patterns in nature Physical attractiveness == References == == External links == FaceResearch – Online studies on facial symmetry by researchers affiliated with University of Aberdeen (Scotland) School of Psychology, and University of St. Andrews (Scotland). "A facial symmetry plugin for the GIMP Archived 2019-04-05 at the Wayback Machine"—Try experimenting with facial symmetry, using open source software. "Psychological Image Collection
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{
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at Stirling (PICS) Free Database of pictures of faces "FaceBase An interdisciplinary research consortium for facial symmetry "Tübinger Face Database An open research database of 200 merged 3-D faces "A facial symmetry app for iPhone Experiment with facial symmetry, using a free iPhone app. AI-Driven Facial Symmetry Tool by FaceAuraAI – interactive analysis and visualization of human facial symmetry.
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{
"page_id": 1967292,
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"title": "Facial symmetry"
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The Gateway cloning method is a method of molecular cloning invented and commercialized by Invitrogen since the late 1990s, which makes use of the integration and excision recombination reactions that take place when bacteriophage lambda infects bacteria. This technology provides a fast and highly efficient way to transport DNA sequences into multi-vector systems for functional analysis and protein expression using Gateway att sites and two proprietary enzyme mixes called BP Clonase and LR Clonase. In vivo, these recombination reactions are facilitated by the recombination of attachment sites from the lambda/phage chromosome (attP) and the bacteria (attB). As a result of recombination between the attP and attB sites, the phage integrates into the bacterial genome flanked by two new recombination sites (attLeft and attRight). The removal of the phage from the bacterial chromosome and the regeneration of attP and attB sites can both result from the attL and attR sites recombining under specific circumstances. DNA sequences of interest are added to modified versions of these special Gateway Att sites. Two enzyme reactions take place, BP Clonase and LR Clonase. The BP Clonase occurs between the attB sites surrounding the insert and the attP sites of the donor vector. This reaction is catalyzed by the BP Clonase enzyme mixture and produces the entry clone containing the DNA of interest flanked by attL domains. As a byproduct of the reaction, the lethal ccdB gene is excised from the donor vector. The LR Clonase occurs between the attL regions of the generated entry clone and the attR regions of the target vector and is catalyzed by the LR Clonase enzyme mix. As a result, an expression clone with DNA of interest flanked by attB regions is produced. As in the BP reaction, a DNA sequence containing the ccdB gene is cut from the target
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"page_id": 20579517,
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"title": "Gateway Technology"
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vector. Large archives of Gateway Entry clones, containing the vast majority of human, mouse, and rat ORFs (open reading frames) have been cloned from human cDNA libraries or chemically synthesized to support the research community using NIH (National Institutes of Health) funding (e.g. Mammalian Gene Collection, http://mgc.nci.nih.gov/ Archived 2015-02-25 at the Wayback Machine). The availability of these gene cassettes in a standard Gateway cloning plasmid helps researchers quickly transfer these cassettes into plasmids that facilitate the analysis of gene function. Gateway cloning does take more time for initial set-up, and is more expensive than traditional restriction enzyme and ligase-based cloning methods, but it saves time and offers simpler and highly efficient cloning for downstream applications. The technology has been widely adopted by the life science research community especially for applications that require the transfer of thousands of DNA fragments into one type of plasmid (e.g., one containing a CMV promoter for protein expression in mammalian cells), or for the transfer of one DNA fragment into many different types of plasmids (e.g., for bacterial, insect, and mammalian protein expression). == Basic procedure == The first step in Gateway cloning is the preparation of a Gateway Entry clone. There are a few different ways to make entry clone. Gateway attB1 and attB2 sequences are added to the 5' and 3' end of a gene fragment, respectively, using gene-specific PCR primers and PCR amplification. The PCR amplification products are then mixed with a proprietary mixture of plasmids called Gateway "Donor vectors" (Invitrogen terminology) and proprietary "BP Clonase" enzymes. The enzyme mix catalyzes the recombination and insertion of the PCR product containing the attB sequence into the attP recombination sites in the Gateway Donor vector. When the cassette is part of the target plasmid, it is referred to as an "Entry clone" in Gateway
|
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"page_id": 20579517,
"source": null,
"title": "Gateway Technology"
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nomenclature and the recombination sequences are referred to as Gateway "attL" type. A short end containing attL is added using the TOPO method, a technique in which DNA fragments are cloned into specific vectors without the need for DNA ligases. The desired DNA sequence can be cloned into a multicloning site containing attL using restriction enzyme. The second step in Gateway cloning is the preparation of a Gateway Destination vector. It is important to choose the target vector that best suits your target when preparing the expression clone. The gene cassette in the Gateway Entry clone can then be simply and efficiently transferred into any Gateway Destination vector (Invitrogen nomenclature for any Gateway plasmid that contains Gateway “attR” recombination sequences and elements such as promoters and epitope tags, but not ORFs) using the proprietary enzyme mix, “LR Clonase”. Thousands of Gateway Destination plasmids have been made and are freely shared amongst researchers across the world. Gateway Destination vectors are similar to classical expression vectors containing multiple cloning sites, before the insertion of a gene of interest, using restriction enzyme digestion and ligation. Gateway Destination vectors are commercially available from Invitrogen, EMD (Novagen) and Covalys. The third step in Gateway cloning is the preparation of express your gene of interest. Make sure to use sequencing or a restriction digest to check the integrity of your expression clone. Once your construct is working, you can transform or transfect the cells you intend to employ in your investigations. Since Gateway cloning uses patented recombination sequences, and proprietary enzyme mixes available only from Invitrogen, the technology does not allow researchers to switch vendors and contributes to the lock-in effect of all such patented procedures. To summarize the different steps involved in Gateway cloning: Gateway BP reaction: PCR-product with flanking attB sites (this step can
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"page_id": 20579517,
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also use other methods of DNA isolation, such as restriction-digestion) + Donor vector containing attP sites + BP clonase => Gateway Entry clone, containing attL sites, flanking gene of interest Gateway LR reaction: Entry clone containing attL sites + Destination vector containing attR sites, and promoters and tags + LR clonase => Expression clone containing attB sites, flanking gene of interest, ready for gene expression. == Advantages == Flexibility: Your DNA sequence of interest can be moved across any expression system in just one recombination step when you create the entry clone with it. Speed: Instead of taking two or more days with conventional restriction and ligation cloning, the Gateway approach allows for the creation of the expression construct in just one day. The attB-PCR products can also be immediately cloned into the target vectors by performing the BP and LR reactions in the same tube. There are no procedures for restriction, ligation, or gel purification during the cloning process. Multiple fragment cloning: Gateway cloning can be used to simultaneously insert several DNA pieces into numerous vectors in a single tube. To create the necessary expression clone, up to four DNA segments can be cloned into a single Gateway vector in a precise order and orientation in a single tube. The design of the Gateway vectors makes this possible. High efficiency: The Gateway Cloning Method uses positive and negative selection markers to increase the chance of successfully cloning a gene. This means that the process is more efficient, meaning it is more likely to produce successful results. Universality: All types of DNA fragments can be cloned using PCR techniques. Cloning is available for many different kinds of organisms, from mammals to bacteria. == See also == Cloning Gateway cassette Subcloning == References ==
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"page_id": 20579517,
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"title": "Gateway Technology"
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Isoamyl formate, also known as isopentyl formate, is an ester formed from isoamyl alcohol and formic acid, with the formula C6H12O2. It is a colorless liquid with a fruity odor of plum or blackcurrant. == Natural occurrence == Isoamyl formate is found in nature in the plant Plectranthus glabratus. It occurs in the following foods and drinks: avocado, beer, cheese, grape brandy, honey, pineapple, Mangifera (a plant genus including mangos), plum, quince, cider, rum, sea buckthorn, strawberry, tea, tequila, vinegar, and wine. == Preparation == Isoamyl formate may be prepared by the Fischer esterification of isoamyl alcohol and formic acid. Fischer esterifications of formic acid use an excess of formic acid as the solvent, and formic acid is a strong enough acid to self-catalyze the reaction without any other acid catalyst added. == Uses == Isoamyl formate is used as an aroma compound and artificial flavoring, for its odor of plum or blackcurrant. == Safety == Isoamyl formate has not been shown to be mutagenic or genotoxic in tests such as the Ames test. == References ==
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{
"page_id": 76088511,
"source": null,
"title": "Isoamyl formate"
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Immunogenic cell death is any type of cell death eliciting an immune response. Both accidental cell death and regulated cell death can result in immune response. Immunogenic cell death contrasts to forms of cell death (apoptosis, autophagy or others) that do not elicit any response or even mediate immune tolerance. The name 'immunogenic cell death' is also used for one specific type of regulated cell death that initiates an immune response after stress to endoplasmic reticulum. == Types == Immunogenic cell death types are divided according to molecular mechanisms leading up to, during and following the death event. The immunogenicity of a specific cell death is determined by antigens and adjuvant released during the process. === Accidental cell death === Accidental cell death is the result of physical, chemical or mechanical damage to a cell, which exceeds its repair capacity. It is an uncontrollable process, leading to loss of membrane integrity. The result is the spilling of intracellular components, which may mediate an immune response. === Immunogenic cell death or ICD === ICD or immunogenic apoptosis is a form of cell death resulting in a regulated activation of the immune response. This cell death is characterized by apoptotic morphology, maintaining membrane integrity. Endoplasmic reticulum (ER) stress is generally recognised as a causative agent for ICD, with high production of reactive oxygen species (ROS). Two groups of ICD inducers are recognised. Type I inducers cause stress to the ER only as collateral damage, mainly targeting DNA or chromatin maintenance apparatus or membrane components. Type II inducers target the ER specifically. ICD is induced by some cytostatic agents such as anthracyclines, oxaliplatin and bortezomib, or radiotherapy and photodynamic therapy (PDT). Some viruses can be listed among biological causes of ICD. Just as immunogenic death of infected cells induces immune response to the
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{
"page_id": 40436928,
"source": null,
"title": "Immunogenic cell death"
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infectious agent, immunogenic death of cancer cells can induce an effective antitumor immune response through activation of dendritic cells (DCs) and consequent activation of specific T cell response. This effect is used in antitumor therapy. ICD is characterized by secretion of damage-associated molecular patterns (DAMPs).There are three most important DAMPs which are exposed to the cell surface during ICD. Calreticulin (CRT), one of the DAMP molecules which is normally in the lumen of the endoplasmic reticulum, is translocated after the induction of immunogenic death to the surface of dying cell. There it functions as an "eat me" signal for professional phagocytes. Other important surface exposed DAMPs are heat-shock proteins (HSPs), namely HSP70 and HSP90, which under stress condition also translocate to the plasma membrane. On the cell surface they have an immunostimulatory effect, based on their interaction with number of antigen-presenting cell (APC) surface receptors like CD91 and CD40 and also facilitate crosspresentation of antigens derived from tumour cells on MHC class I molecule, which then leads to the CD8+ T cell response. Other important DAMPs, characteristic for ICD are secreted HMGB1 and ATP. HMGB1 is considered to be a marker of late ICD and its release to the extracellular space seems to be required for the optimal presentation of antigens by dendritic cells. It binds to several pattern recognition receptors (PRRs) such as Toll-like receptors (TLR) 2 and 4, which are expressed on APCs. ATP released during immunogenic cell death functions as a "find-me" signal for phagocytes when secreted and induces their attraction to the site of ICD. Also, binding of ATP to purinergic receptors on target cells has immunostimulatory effect through inflammasome activation. DNA and RNA molecules released during ICD activate TLR3 and cGAS responses, both in the dying cell and in phagocytes. The concept of using ICD
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{
"page_id": 40436928,
"source": null,
"title": "Immunogenic cell death"
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in antitumor therapy has started taking shape with the identification of some inducers mentioned above, which have a potential as anti-tumor vaccination strategies. The use of ICD inducers alone or in combination with other anticancer therapies (targeted therapies, immunotherapies) has been effective in mouse models of cancer and is being tested in the clinic. === Necroptosis === Another type of regulated cell death that induces an immune response is necroptosis. Necroptosis is characterized by necrotic morphology. This type of cell death is induced by extracellular and intracellular microtraumas detected by death or damage receptors. For example, FAS, TNFR1 and pattern recognition receptors may initiate necroptosis. These activation inducers converge on receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and mixed lineage kinase domain like pseudokinase (MLKL). Sequential activation of these proteins leads to membrane permeabilization. === Pyroptosis === Pyroptosis is a distinct type of regulated cell death, exhibiting a necrotic morphology and cellular content spilling. This type of cell death is induced most commonly in response to microbial pathogen infection, such as infection with Salmonella, Francisella, or Legionella. Host factors, such as those produced during myocardial infarction, may also induce pyroptosis. Cytosolic presence of bacterial metabolites or structures, termed pathogen associated molecular patterns (PAMPs), initiates the pyroptotic response. Detection of such PAMPs by some members of Nod-like receptor family (NLRs), absent in melanoma 2 (AIM2) or pyrin leads to the assembly of an inflammasome structure and caspase 1 activation. So far, the cytosolic PRRs that are known to induce inflammasome formation are NLRP3, NLRP1, NLRC4, AIM2 and Pyrin. These proteins contain oligomerization NACHT domains, CARD domains and some also contain similar pyrin (PYR) domains. Caspase 1, the central activator protease of pyroptosis, attaches to the inflammasome via the CARD domains or a CARD/PYR-containing adaptor protein called apoptosis-associated speck-like protein (ASC). Activation of caspase
|
{
"page_id": 40436928,
"source": null,
"title": "Immunogenic cell death"
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1 (CASP1) is central to pyroptosis and when activated mediates the proteolytic activation of other caspases. In humans, other involved caspases are CASP3, CASP4 and CASP5, in mice CASP3 and CASP11. Precursors of IL-1β and IL-18 are among the most important CASP1 substrates, and the secretion of the cleavage products induces the potent immune response to pyroptosis. The release of IL-1β and IL-18 occurs before any morphological changes occur in the cell. The cell dies by spilling its contents, mediating the distribution of further immunogenic molecules. Among these, HMGB1, S100 proteins and IL-1α are important DAMPs. Pyroptosis has some characteristics similar with apoptosis, an immunologically inert cell death. Primarily, both these processes are caspase-dependent, although each process utilizes specific caspases. Chromatin condensation and fragmentation occurs during pyroptosis, but the mechanisms and outcome differ from those during apoptosis. Contrasting with apoptosis, membrane integrity is not maintained in pyroptosis, while mitochondrial membrane integrity is maintained and no spilling of cytochrome c occurs. === Ferroptosis === Ferroptosis is also a regulated form of cell death. The process is initiated in response to oxidative stress and lipid peroxidation and is dependent on iron availability. Necrotic morphology is typical of ferroptotic cells. Peroxidation of lipids is catalyzed mainly by lipoxygenases, but also by cyclooxygenases. Lipid peroxidation can be inhibited in the cell by glutathione peroxidase 4 (GPX4), making the balance of these enzymes a central regulator of ferroptosis. Chelation of iron also inhibits ferroptosis, possibly by depleting iron from lipoxygenases. Spilling of cytoplasmic components during cell death mediates the immunogenicity of this process. === MPT-driven necrosis === Mitochondria permeability transition (MPT)- driven cell death is also a form of regulated cell death and manifests a necrotic morphology. Oxidative stress or Ca2+ imbalance are important causes for MPT-driven necrosis. The main event in this process is
|
{
"page_id": 40436928,
"source": null,
"title": "Immunogenic cell death"
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the loss of inner mitochondrial membrane (IMM) impermeability. The precise mechanisms leading to the formation of permeability-transition pore complexes, which assemble between the inner and outer mitochondrial membranes, are still unknown. Peptidylprolyl isomerase F (CYPD) is the only known required protein for MPT-driven necrosis. The loss of IMM impermeability is followed by membrane potential dissipation and disintegration of both mitochondrial membranes. === Parthanatos === Parthanatos is also a regulated form of cell demise with necrotic morphology. It is induced under a variety of stressing conditions, but most importantly as a result of long-term alkylating DNA damage, oxidative stress, hypoxia, hypoglycemia and inflammatory environment. This cell death is initiated by the DNA damage response components, mainly poly(ADP-ribose) polymerase 1(PARP1). PARP1 hyperactivation leads to ATP depletion, redox and bioenergetic collapse as well as accumulation of poly(ADPribose) polymers and poly(ADP-ribosyl)ated proteins, which bind to apoptosis inducing factor mitochondria associated 1 (AIF). The outcome is membrane potential dissipation and mitochondrial outer membrane permeabilization. Chromatin condensation and fragmentation by AIF is characteristic of parthanatos. Interconnection of the prathanotic process with some members of the necroptotic apparatus has been proposed, as RIPK3 stimulates PARP1 activity. This type of cell death has been linked to some pathologies, such as some cardiovascular and renal disorders, diabetes, cerebral ischemia, and neurodegeneration. === Lysosome-dependent cell death === Lysosome dependent cell death is a type of regulated cell death that is dependent on permeabilization of lysosomal membranes. The morphology of cells dying by this death is variable, with apoptotic, necrotic or intermediate morphologies observed. It is a type of intracellular pathogen defense, but is connected with several pathophysiological processes, like tissue remodeling or inflammation. Lysosome permeabilization initiates the cell death process, sometimes along with mitochondrial membrane permeabilization. === NETotic cell death === NETotic cell death is a specific type of cell
|
{
"page_id": 40436928,
"source": null,
"title": "Immunogenic cell death"
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death typical for neutrophils, but also observed in basophils and eosinophils. The process is characterized by extrusion of chromatin fibers bound into neutrophil extracellular traps (NETs). NET formation is generally induced in response to microbial infections, but pathologically also in sterile conditions of some inflammatory diseases. ROS inside the cell trigger release of elastase (ELANE) and myeloperoxidase (MPO), their translocation to the nucleus and cytoskeleton remodeling. Some interaction with the necroptotic apparatus (RIPK and MLKL) has been suggested. == References ==
|
{
"page_id": 40436928,
"source": null,
"title": "Immunogenic cell death"
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|
Octanone may refer to any of three isomeric chemical compounds: 2-Octanone 3-Octanone 4-Octanone
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{
"page_id": 42861759,
"source": null,
"title": "Octanone"
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The term glycosynthase refers to a class of proteins that have been engineered to catalyze the formation of a glycosidic bond. Glycosynthase are derived from glycosidase enzymes, which catalyze the hydrolysis of glycosidic bonds. They were traditionally formed from retaining glycosidase by mutating the active site nucleophilic amino acid (usually an aspartate or glutamate) to a small non-nucleophilic amino acid (usually alanine or glycine). More modern approaches use directed evolution to screen for amino acid substitutions that enhance glycosynthase activity. == The first glycosynthase == Two discoveries led to the development of glycosynthase enzymes. The first was that a change of the active site nucleophile of a glycosidase from a carboxylate to another amino acid resulted in a properly folded protein that had no hydrolase activity. The second discovery was that some glycosidase enzymes were able to catalyze the hydrolysis of glycosyl fluorides that had the incorrect anomeric configuration. The enzymes underwent a transglycosidation reaction to form a disaccharide, which was then a substrate for hydrolase activity. The first reported glycosynthase was a mutant of the Agrobacterium sp. β-glucosidase / galactosidase in which the nucleophile glutamate 358 was mutated to an alanine by site directed mutagenesis. When incubated with α-glycosyl fluorides and an acceptor sugar it was found to catalyze the transglycosidation reaction without any hydrolysis. This glycosynthase was used to synthesize a series of di- and trisaccharide products with yields between 64% and 92%. == Reaction mechanism == The mechanism of a glycosynthase is similar to the hydrolysis reaction of retaining glycosidases except no covalent-enzyme intermediate is formed. Mutation of the active site nucleophile to a non-nucleophilic amino acid prevents the formation of a covalent intermediate. An activated glycosyl donor with a good anomeric-leaving group (often a fluorine) is required. The leaving group is displaced by an alcohol of
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{
"page_id": 7013570,
"source": null,
"title": "Glycosynthase"
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the acceptor sugar aided by the active site general base amino acid of the enzyme. == Modern extensions == The first glycosynthase was a retaining exoglycosidase that catalyzed the formation of β 1-4 linked glycosides of glucose and galactose. Glycosynthase enzymes have since been expanded to include mutants of endoglycosidase, as well as mutants of inverting glycosidase. Substrates of glycosynthase include glucose, galactose, mannose, xylose, and glucuronic acid. Modern methods to prepare glycosynthase use directed evolution to introduce modifications, which improve the enzymes function. This process was made available due to the development of high throughput screens for glycosynthase activity. == Limitations == Glycosynthase have been useful for the preparation of oligosaccharides; however, their use suffers from certain limitations. First, glycosynthase can only be used to synthesize glycosidic linkages for which there is a known glycosidase. That glycosidase must also be first converted into a glycosynthase, which is not always possible. Second, the product of the glycosynthase reaction is often a better substrate for the glycosynthase then the starting material, resulting in the formation of multiple products of varying lengths. Finally, glycosynthase are specific for the donor sugar but often have loose specificity for the acceptor sugar. This can result in different regioselectivity depending on the acceptor resulting in products with different glycosidic linkages. One example is the Agrobacterium sp. β-glucosynthase, which forms a β-1,4-glycoside with glucose as the acceptor, but forms a β-1,3-glycoside with xylose as the acceptor. == See also == Glucosidase Glycoside hydrolase family 1 == References ==
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{
"page_id": 7013570,
"source": null,
"title": "Glycosynthase"
}
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The Ray–Dutt twist is a mechanism proposed for the racemization of octahedral complexes containing three bidentate chelate rings. Such complexes typically adopt an octahedral molecular geometry in their ground states, in which case they possess helical chirality. The pathway entails formation of an intermediate of C2v point group symmetry. An alternative pathway that also does not break any metal-ligand bonds is called the Bailar twist. Both of these mechanism product complexes wherein the ligating atoms (X in the scheme) are arranged in an approximate trigonal prism. This pathway is called the Ray–Dutt twist in honor of Priyadaranjan Ray (not Prafulla Chandra Ray) and N. K. Dutt, inorganic chemists at the Indian Association for the Cultivation of Science abbr. IACS who proposed this process. == See also == Pseudorotation Bailar twist Bartell mechanism Berry mechanism Fluxional molecule Indian Association for the Cultivation of Science (IACS) == References ==
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{
"page_id": 12518595,
"source": null,
"title": "Ray–Dutt twist"
}
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This page provides supplementary chemical data on vitexin. == Material Safety Data Sheet == The handling of this chemical may incur notable safety precautions. It is highly recommend that you seek the Material Safety Datasheet (MSDS) for this chemical from a reliable source such as eChemPortal, and follow its directions. Sigma Aldrich MSDS from SDSdata.org == Spectral data == == References == Yi-Pei Lin, Tai-Yuan Chen, Hsiang-Wen Tseng, Mei-Hsien Lee and Shui-Tein Chen (2009). "Neural cell protective compounds isolated from Phoenix hanceana var. formosana". Phytochemistry. 70 (9): 1173–1181. doi:10.1016/j.phytochem.2009.06.006. PMID 19628235. S2CID 28636157.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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{
"page_id": 30278857,
"source": null,
"title": "Vitexin (data page)"
}
|
Pink flowers are used as a symbol of love and awareness. For decades, pink flowers have been used to decorate weddings as a symbol of love. They can also be used as a display of love at funerals, as demonstrated at the funeral for Anna Nicole Smith. More recently, pink flowers have come to symbolize breast cancer awareness. They may also be used as an expression of thanks, or just enjoyed for their aesthetic beauty. == Species == Species of pink flowers include: Allium (flowering onion) Astilbe Azalea Begonias Butterfly bush Camellia Carambola tree (starfruit) Carnation Cherry Clematis Coneflower (Echinacea) Cypripedium acaule (lady's slipper orchids) Dahlia Dianthus family (carnation, pink, and sweet william, and especially garden pink, whence the colour got its name) Flowering plum tree Hibiscus Hyacinth Hydrangea growing in alkaline (basic) soil Oriental lily Papaver orientale (Oriental poppy) Peony / paeony Petunia Rhododendron and Azalea Roses Sabatia angularis (rosepink or bitterbloom) Tulips Vinca Alumroot Aster Forget-me-not (Myosotis) Orchid == References ==
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{
"page_id": 33293519,
"source": null,
"title": "Pink flowers"
}
|
Mark Douglas Norman (1960s to present) is a scientist living in southern Australia. He works as a Chief Conservation Scientist with Parks Victoria. Prior to 2016 he worked as a curator and marine biologist through the University of Melbourne and Museum Victoria. For over a decade in this role, Norman worked exclusively with cephalopods and was a leading scientist in the field, having discovered over 150 new species of octopuses. The best known of these is probably the mimic octopus. == Notable publications == Norman M., Reid A. (2000) A Guide to Squid, Cuttlefish and Octopuses of Australasia (The Gould League of Australia and CSIRO Publishing: Melbourne). Norman M. (2000) Cephalopods: A World Guide (ConchBooks: Hackenheim, Germany). This book contains over 800 color photographs of cephalopods in their natural habitat. == Species described by Mark Norman == The following species have been described by M. Norman either individually or with co-authors. Ameloctopus litoralis Norman, 1992 Cistopus platinoidus Sreeja, Norman & Biju Kumar, 2015 Microeledone mangoldi Norman, Hochberg & Boucher-Rodoni, 2004 Octopus (Abdopus) capricornicus Norman & Finn, 2001 Octopus abaculus Norman & Sweeney, 1997 Octopus aspilosomatis Norman, 1993 Octopus berrima Stranks & Norman, 1992 Octopus exannulatus Norman, 1993 Octopus mototi Norman, 1993 Octopus neglectus Nateewathana & Norman, 1999 Octopus nocturnus Norman & Sweeney, 1997 Octopus rex Nateewathana & Norman, 1999 Octopus siamensis Nateewathana & Norman, 1999 Scaeurgus nesisi Norman, Hochberg & Boucher-Rodoni, 2005 Thaumoctopus mimicus Norman & Hochberg, 2005 == References ==
|
{
"page_id": 4064464,
"source": null,
"title": "Mark Norman (marine biologist)"
}
|
The molecular formula C27H27NO2 (molar mass: 397.51 g/mol, exact mass: 397.204179 u) may refer to: JWH-367 CHM-081
|
{
"page_id": 79168724,
"source": null,
"title": "C27H27NO2"
}
|
Indium bromide may refer to: Indium(I) bromide, InBr Indium(III) bromide, InBr3; when molten it is dimeric, In2Br6, and it is predominantly dimeric in the gas phase
|
{
"page_id": 10159318,
"source": null,
"title": "Indium bromide"
}
|
Hydrogenlyase may refer to: Ferredoxin hydrogenase, an enzyme Hydrogenase (acceptor), an enzyme
|
{
"page_id": 38339799,
"source": null,
"title": "Hydrogenlyase"
}
|
A hemihelix is a curved geometric shape consisting of a series of helices with alternating chirality, connected by a perversion at the reversals. The formation of hemihelices with periodic distributions of perversions in slender structures is understood in terms of competing buckling instabilities generated by in-plane stresses. == References == == External links == The dictionary definition of hemihelix at Wiktionary
|
{
"page_id": 42599642,
"source": null,
"title": "Hemihelix"
}
|
The molecular formula C12H20N2 (molar mass: 192.30 g/mol, exact mass: 192.1626 u) may refer to: Amiflamine (FLA-336) Tremorine
|
{
"page_id": 26608859,
"source": null,
"title": "C12H20N2"
}
|
Infrared Control Freak 360 (IRCF360) is a 360-degree proximity sensor and a motion sensing devices, developed by ROBOTmaker. The sensor is in BETA developers release as a low cost (software configurable) sensor for use within research, technical and hobby projects. == Overview == The 360-degree sensor was originally designed as a short range micro robot proximity sensor and mainly intended for Swarm robotics, Ant robotics, Swarm intelligence, autonomous Qaudcopter, Drone, UAV, multi-robot simulations e.g. Jasmine Project where 360 proximity sensing is required to avoid collision with other robots and for simple IR inter-robot communications. To overcome certain limitation with Infra-red (IR) proximity sensing (e.g. detection of dark surfaces) the sensing module includes ambient light sensing and basic tactile sensing functionality during forward movement sensing/probing providing photovore and photophobe robot swarm behaviours and characteristics. A project named Sensorium Project was started aimed at broadening the Sensors audience beyond its typical robot sensor usage. To demonstrate the sensor's functionality, opensource Java based Integrated Development Environments (IDE) are used, such as Arduino and Processing (programming language). == References == == External links == Official Websites Dean Camera development of USB interface for Arduino Details of the Sensorium and 360 degree sensor development
|
{
"page_id": 35456221,
"source": null,
"title": "IRCF360"
}
|
Rupa Sarkar is the Editor-in-Chief of The Lancet Digital Health, a gold open access medical journal in the Lancet family published by Elsevier. She conducted her doctoral research at Imperial College London, where she studied RNA biology and its role in human stem cell differentiation. After earning her PhD, she did postdoctoral research at the Albert Einstein College of Medicine, then worked as an associate editor at Nature Protocols, a senior editor at Genome Biology, and Chief Editor at Nature Protocols. She has been Editor-in-Chief at The Lancet Digital Health since its founding in 2018. == References ==
|
{
"page_id": 62981341,
"source": null,
"title": "Rupa Sarkar"
}
|
Metatranscriptomics is the set of techniques used to study gene expression of microbes within natural environments, i.e., the metatranscriptome. While metagenomics focuses on studying the genomic content and on identifying which microbes are present within a community, metatranscriptomics can be used to study the diversity of the active genes within such community, to quantify their expression levels and to monitor how these levels change in different conditions (e.g., physiological vs. pathological conditions in an organism). The advantage of metatranscriptomics is that it can provide information about differences in the active functions of microbial communities that would otherwise appear to have similar make-up. == Introduction == The microbiome has been defined as a microbial community occupying a well-defined habitat. These communities are ubiquitous and can play a key role in maintenance of the characteristics of their environment, and an imbalance in these communities can negatively affect the activities of the setting in which they reside. To study these communities, and to then determine their impact and correlation with their niche, different omics approaches have been used. While metagenomics can help researchers generate a taxonomic profile of the sample, metatranscriptomics provides a functional profile by analysing which genes are expressed by the community. It is possible to infer what genes are expressed under specific conditions, and this can be done using functional annotations of expressed genes. == Function == Since metatranscriptomics focuses on what genes are expressed, it enables the characterization of the active functional profile of the entire microbial community. The overview of the gene expression in a given sample is obtained by capturing the total mRNA of the microbiome and performing whole-metatranscriptomics shotgun sequencing. == Tools and techniques == Although microarrays can be exploited to determine the gene expression profiles of some model organisms, next-generation sequencing and third-generation sequencing are
|
{
"page_id": 46204126,
"source": null,
"title": "Metatranscriptomics"
}
|
the preferred techniques in metatranscriptomics. The protocol that is used to perform a metatranscriptome analysis may vary depending on the type of sample that needs to be analysed. Indeed, many different protocols have been developed for studying the metatranscriptome of microbial samples. Generally, the steps include sample harvesting, RNA extraction (different extraction methods for different kinds of samples have been reported in the literature), mRNA enrichment, cDNA synthesis and preparation of metatranscriptomic libraries, sequencing and data processing and analysis. mRNA enrichment is one of the most technically challenging steps, for which different strategies have been proposed: removing rRNA through Ribosomal RNA capture using a 5-3 exonuclease to degrade processed RNAs (mostly rRNA and tRNA) adding poly(A) to mRNAs by using a polyA polymerase (in E. coli) using antibodies to capture mRNAs that bind to specific proteins The last two strategies are not recommended as they have been reported to be highly biased. == Computational analysis == A typical metatranscriptome analysis pipeline: maps reads to a reference genome, or performs de novo assembly of the reads into transcript contigs and supercontigs The first strategy maps reads to reference genomes in databases, to collect information that is useful to deduce the relative expression of the single genes. Metatranscriptomic reads are mapped against databases using alignment tools, such as Bowtie2, BWA, and BLAST. Then, the results are annotated using resources, such as GO, KEGG, COG, and Swiss-Prot. The final analysis of the results is carried out depending on the aim of the study. One of the latest metatranscriptomics techniques is stable isotope probing (SIP), which has been used to retrieve specific targeted transcriptomes of aerobic microbes in lake sediment. The limitation of this strategy is its reliance on the information of reference genomes in databases. The second strategy retrieves the abundance in the
|
{
"page_id": 46204126,
"source": null,
"title": "Metatranscriptomics"
}
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expression of the different genes by assembling metatranscriptomic reads into longer fragments called contigs using different software. The Trinity software for RNA-seq, in comparison with other de novo transcriptome assemblers, was reported to recover more full-length transcripts over a broad range of expression levels, with a sensitivity similar to methods that rely on genome alignments. This is particularly important in the absence of a reference genome. A quantitative pipeline for transcriptomic analysis was developed by Li and Dewey and called RSEM (RNA-Seq by Expectation Maximization). It can work as stand-alone software or as a plug-in for Trinity. RSEM starts with a reference transcriptome or assembly along with RNA-Seq reads generated from the sample and calculates normalized transcript abundance (meaning the number of RNA-Seq reads cor-responding to each reference transcriptome or assembly). Although both Trinity and RSEM were designed for transcriptomic datasets (i.e., obtained from a single organism), it may be possible to apply them to metatranscriptomic data (i.e., obtained from a whole microbial community). == Bioinformatics == The use of computational analysis tools has become more important as DNA sequencing capabilities have grown, particularly in metagenomic and metatranscriptomic analysis, which can generate a huge volume of data. Many different bioinformatic pipelines have been developed for these purposes, often as open source platforms such as HUMAnN and the more recent HUMAnN2, MetaTrans, SAMSA, Leimena-2013 and mOTUs2. === HUMAnN2 === HUMAnN2 is a bioinformatic pipeline designed from the previous HUMAnN software, which was developed during the Human Microbiome Project (HMP), implementing a “tiered search” approach. In the first tier, HUMAnN2 screens DNA or RNA reads with MetaPhlAn2 in order to identify already-known microbes and constructing a sample-specific database by merging pangenomes of annotated species; in the second tier, the algorithm performs a mapping of the reads against the assembled pangenome database; in
|
{
"page_id": 46204126,
"source": null,
"title": "Metatranscriptomics"
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|
the third tier, non-aligned reads are used for a translated search against a protein database. === MetaTrans === MetaTrans is a pipeline that exploits multithreading to improve efficiency. Data is obtained from paired-end RNA-Seq, mainly from 16S RNA for taxonomy and mRNA for gene expression levels. The pipeline is divided in 4 major steps. Firstly, paired-end reads are filtered for quality control purposes, then sorted and filtered for taxonomic analysis (by removal of tRNA sequences) or functional analysis (by removal of both tRNA and rRNA reads). For the taxonomic analysis, sequences are mapped against 16S rRNA Greengenes v13.5 database using SOAP2, while for functional analysis sequences are mapped against a functional database such as MetaHIT-2014 always by using SOAP2 tool. This pipeline is highly flexible, since it offers the possibility to use third-party tools and improve single modules as long as the general structure is preserved. === SAMSA === This pipeline is designed specifically for metatranscriptomics data analysis, by working in conjunction with the MG-RAST server for metagenomics. This pipeline is simple to use, requires low technical preparation and computational power and can be applied to a wide range of microbes. First, sequences from raw sequencing data are filtered for quality and then submitted to MG-RAST (which performs further steps such as quality control, gene calling, clustering of amino acid sequences and use of sBLAT on each cluster to detect the best matches). Matches are then aggregated for taxonomic and functional analysis purposes. === Leimena-2013 === This pipeline does not have an official name and is usually referred to using the first author of the article in which it is described. This algorithm foresees the implementation of alignment tools such as BLAST and MegaBLAST. Reads are clustered in groups of identical sequences and then processed for in-silico removal of tRNA
|
{
"page_id": 46204126,
"source": null,
"title": "Metatranscriptomics"
}
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and rRNA sequences. Remaining reads are then mapped to NCBI databases using BLAST and MegaBLAST, then classified by their bitscore. Sequences with higher bitscores are used to predict phylogenetic origin and function, and lower-score reads are aligned with the more sensitive BLASTX and eventually can be aligned in protein databases so that their function can be characterized. === mOTUs2 === The mOTUs2 profiler, which is based on essential housekeeping genes, is demonstrably well-suited for quantification of basal transcriptional activity of microbial community members. Depending on environmental conditions, the number of transcripts per cell varies for most genes. An exception to this are housekeeping genes that are expressed constitutively and with low variability under different conditions. Thus, the abundance of transcripts from such genes strongly correlate with the abundance of active cells in a community. == Microarrays == Another method that can be exploited for metatranscriptomic purposes is tiling microarrays. In particular, microarrays have been used to measure microbial transcription levels, to detect new transcripts and to obtain information about the structure of mRNAs (for instance, the UTR boundaries). Recently, it has also been used to find new regulatory ncRNA. However, microarrays are affected by some pitfalls: requirement of probe design low sensitivity prior knowledge of gene targets. RNA-Seq can overcome these limitations: it does not require any previous knowledge about the genomes that have to be analysed and it provides high throughput validation of genes prediction, structure, expression. Thus, by combining the two approaches it is possible to have a more complete representation of bacterial transcriptome. == Limitations == With its dominating abundance, ribosomal RNA strongly reduces the coverage of mRNA (usually the main focus of transcriptomic studies) in the total collected RNA. Extraction of high-quality RNA from some biological or environmental samples (such as feces) can be difficult. Instability
|
{
"page_id": 46204126,
"source": null,
"title": "Metatranscriptomics"
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|
of mRNA that compromises sample integrity even before sequencing. Experimental issues can affect the quantification of differences in expression among multiple samples: They can influence integrity and input RNA, as well as the amount of rRNA remaining in the samples, size section and gene models. Moreover, molecular base techniques are very prone to artefacts. Difficulties in differentiating between host and microbial RNA, although commercial kits for microbial enrichment are available. This may also be done in silico if a reference genome is available for the host. Transcriptome reference databases are limited in their coverage. Generally, large populations of cells are exploited in metatranscriptomic analysis, so it is difficult to resolve important variances that can exist between subpopulations. High variability in pathogen populations was demonstrated to affect disease progression and virulence. Both for microarray and RNA-Seq, it is difficult to set a real threshold to classify genes as “expressed”, due to the high dynamic range in gene expression. The presence of mRNA is not always associated with the actual presence of the respective protein. == Applications == === Human gut microbiome === The gut microbiome has emerged in recent years as an important player in human health. Its prevalent functions are related to the fermentation of indigestible food components, competitions with pathogen, strengthening of the intestinal barrier, stimulation and regulation of the immune system. Although much has been learnt about the microbiome community in the last years, the wide diversity of microorganisms and molecules in the gut requires new tools to enable new discoveries. By focusing on changes in the expression of the genes, metatrascriptomics can generate a more dynamic picture of the state and activity of the microbiome than metagenomics. It has been observed that metatranscriptomic functional profiles are more variable than what might have been reckoned only by metagenomic
|
{
"page_id": 46204126,
"source": null,
"title": "Metatranscriptomics"
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information. This suggests that non-housekeeping genes are not stably expressed in situ One example of metatranscriptomic application is in the study of the gut microbiome in inflammatory bowel disease. Inflammatory bowel disease (IBD) is a group of chronic diseases of the digestive tract that affects millions of people worldwide. Several human genetic mutations have been linked to an increased susceptibility to IBD, but additional factors are needed for the full development of the disease. Regarding the relationship between IBD and gut microbiome, it is known that there is a dysbiosis in patients with IBD but microbial taxonomic profiles can be highly different among patients, making it difficult to implicate specific microbial species or strains in disease onset and progression. In addition, the gut microbiome composition presents a high variability over time among people, with more pronounced variations in patient with IBD. The functional potential of an organism, meaning the genes and pathways encoded in its genome, provides only indirect information about the level or extent of activation of such functions. So, the measurement of functional activity (gene expression) is critical to understand the mechanism of the gut microbiome dysbiosis. Alterations in transcriptional activity in IBD, established on the rRNA expression, indicate that some bacterial populations are active in patients with IBD, while other groups are inactive or latent. A metatranscriptomics analysis measuring the functional activity of the gut microbiome reveals insights only partially observable in metagenomic functional potential, including disease-linked observations for IBD. It has been reported that many IBD-specific signals are either more pronounced or only detectable on the RNA level. These altered expression profiles are potentially the result of changes in the gut environment in patients with IBD, which include increased levels of inflammation, higher concentrations of oxygen and a diminished mucous layer. Metatranscriptomics has the advantage of
|
{
"page_id": 46204126,
"source": null,
"title": "Metatranscriptomics"
}
|
allowing researchers to skip the assaying of biochemical products in situ (like mucus or oxygen) and enables evaluation of effects of environmental changes on microbial expression patterns in vivo for large human populations. In addition, it can be coupled with longitudinal sampling to associate modulation of activity with the disease progression. Indeed, it has been shown that while a particular path may remain stable over time at the genomic level, the corresponding expression varies with the disease severity. This suggests that microbial dysbiosis affect the gut health through changing in the transcriptional programmes in a stable community. In this way, metatranscriptomic profiling emerges as an important tool for understanding the mechanisms of that relationship. Some technical limitations of the RNA measurements in stool are related to the fact that the extracted RNA can be degraded and, if not, it still represents only the organisms presents in the stool sample. === Other === Directed culturing: has been used to understand nutritional preferences of organisms in order to allow the preparation of a proper culture medium, resulting in a successful isolation of microbes in vitro. Identify potential virulence factors: through comparative transcriptomics, in order to compare different transcriptional responses of related strains or species after specific stimuli. Identify host-specific biological processes and interactions For this purpose, it's important to develop new technologies which allow the detection, at the same time, of changes in the expression levels of some genes. Examples of techniques applied: Microarrays: allow the monitoring of changes in the expression levels of many genes in parallel for both host and pathogen. First microarray approaches have shown the first global analysis of gene expression changes in pathogens such as Vibrio cholerae, Borrelia burgdorferi, Chlamydia trachomatis, Chlamydia pneumoniae and Salmonella enterica, revealing the strategies that are used by these microorganisms to adapt
|
{
"page_id": 46204126,
"source": null,
"title": "Metatranscriptomics"
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|
to the host. In addition, microarrays only provide the first global insights about the host innate immune response to PAMPs, as the effects of bacterial infection on the expression of various host factor. Anyway, the detection through microarrays of both organisms at the same time could be problematic. Problems: Probe selection (hundreds of millions of different probes) Cross-hybridization Need of expensive chips (with the proper design; high-density arrays) Require the pathogen and host cells to be physically separated before gene expression analysis (eukaryotic cells’ transcriptomes are larger in comparison to the pathogens’ ones, so could happen that the signal from pathogens’ RNAs is hidden). Loss of RNA molecules during the eukaryotic cells lysis. Dual RNA-Seq: this technique allows the simultaneous study of both host and pathogen transcriptomes as well. It is possible to monitor the expression of genes at different time points of the infection process; in this way could it be possible to study the changes in cellular networks in both organisms starting from the initial contact until the manipulation of the host (interplay host-patogen). Potential: No need of expensive chips Probe-independent approach (RNA-seq provides transcript information without prior knowledge of mRNA sequences) High sensitivity. Possibility of studying the expression levels of even unknown genes under different conditions Moreover, RNA-Seq is an important approach for identifying coregulated genes, enabling the organization of pathogen genomes into operons. Indeed, genome annotation has been done for some eukaryotic pathogens, such as Candida albicans, Trypanosoma brucei and Plasmodium falciparum. Despite the increasing sensitivity and depth of sequencing now available, there are still few published RNA-Seq studies concerning the response of the mammalian host cell to the infection. == References ==
|
{
"page_id": 46204126,
"source": null,
"title": "Metatranscriptomics"
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The iron–sulfur world hypothesis is a set of proposals for the origin of life and the early evolution of life advanced in a series of articles between 1988 and 1992 by Günter Wächtershäuser, a Munich patent lawyer with a degree in chemistry, who had been encouraged and supported by philosopher Karl R. Popper to publish his ideas. The hypothesis proposes that early life may have formed on the surface of iron sulfide minerals, hence the name. It was developed by retrodiction (making a "prediction" about the past) from extant biochemistry (non-extinct, surviving biochemistry) in conjunction with chemical experiments. == Origin of life == === Pioneer organism === Wächtershäuser proposes that the earliest form of life, termed the "pioneer organism", originated in a volcanic hydrothermal flow at high pressure and high (100 °C) temperature. It had a composite structure of a mineral base with catalytic transition metal centers (predominantly iron and nickel, but also perhaps cobalt, manganese, tungsten and zinc). The catalytic centers catalyzed autotrophic carbon fixation pathways generating small molecule (non-polymer) organic compounds from inorganic gases (e.g. carbon monoxide, carbon dioxide, hydrogen cyanide and hydrogen sulfide). These organic compounds were retained on or in the mineral base as organic ligands of the transition metal centers with a flow retention time in correspondence with their mineral bonding strength thereby defining an autocatalytic "surface metabolism". The catalytic transition metal centers became autocatalytic by being accelerated by their organic products turned ligands. The carbon fixation metabolism became autocatalytic by forming a metabolic cycle in the form of a primitive sulfur-dependent version of the reductive citric acid cycle. Accelerated catalysts expanded the metabolism and new metabolic products further accelerated the catalysts. The idea is that once such a primitive autocatalytic metabolism was established, its intrinsically synthetic chemistry began to produce ever more complex organic
|
{
"page_id": 394464,
"source": null,
"title": "Iron–sulfur world hypothesis"
}
|
compounds, ever more complex pathways and ever more complex catalytic centers. === Nutrient conversions === The water–gas shift reaction (CO + H2O → CO2 + H2) occurs in volcanic fluids with diverse catalysts or without catalysts. The combination of ferrous sulfide (FeS, troilite) and hydrogen sulfide (H2S) as reducing agents (both reagents are simultaneously oxidized in the reaction here under creating the disulfide bond, S–S) in conjunction with pyrite (FeS2) formation: FeS + H2S → FeS2 + 2 H+ + 2 e− or with H2 directly produced instead of 2 H+ + 2 e− FeS + H2S → FeS2 + H2 has been demonstrated under mild volcanic conditions. This key result has been disputed. Nitrogen fixation has been demonstrated for the isotope 15N2 in conjunction with pyrite formation. Ammonia forms from nitrate with FeS/H2S as reductant. Methylmercaptan [CH3-SH] and carbon oxysulfide [COS] form from CO2 and FeS/H2S, or from CO and H2 in the presence of NiS. === Synthetic reactions === Reaction of carbon monoxide (CO), hydrogen sulfide (H2S) and methanethiol CH3SH in the presence of nickel sulfide and iron sulfide generates the methyl thioester of acetic acid [CH3-CO-SCH3] and presumably thioacetic acid (CH3-CO-SH) as the simplest activated acetic acid analogues of acetyl-CoA. These activated acetic acid derivatives serve as starting materials for subsequent exergonic synthetic steps. They also serve for energy coupling with endergonic reactions, notably the formation of (phospho)anhydride compounds. However, Huber and Wächtershäuser reported low 0.5% acetate yields based on the input of CH3SH (methanethiol) (8 mM) in the presence of 350 mM CO. This is about 500 times and 3700 times the highest CH3SH and CO concentrations respectively measured to date in a natural hydrothermal vent fluid. Reaction of nickel hydroxide with hydrogen cyanide (HCN) (in the presence or absence of ferrous hydroxide, hydrogen sulfide or
|
{
"page_id": 394464,
"source": null,
"title": "Iron–sulfur world hypothesis"
}
|
methyl mercaptan) generates nickel cyanide, which reacts with carbon monoxide (CO) to generate pairs of α-hydroxy and α-amino acids: e.g. glycolate/glycine, lactate/alanine, glycerate/serine; as well as pyruvic acid in significant quantities. Pyruvic acid is also formed at high pressure and high temperature from CO, H2O, FeS in the presence of nonyl mercaptan. Reaction of pyruvic acid or other α-keto acids with ammonia in the presence of ferrous hydroxide or in the presence of ferrous sulfide and hydrogen sulfide generates alanine or other α-amino acids. Reaction of α-amino acids in aqueous solution with COS or with CO and H2S generates a peptide cycle wherein dipeptides, tripeptides etc. are formed and subsequently degraded via N-terminal hydantoin moieties and N-terminal urea moieties and subsequent cleavage of the N-terminal amino acid unit. Proposed reaction mechanism for reduction of CO2 on FeS: Ying et al. (2007) have shown that direct transformation of mackinawite (FeS) to pyrite (FeS2) on reaction with H2S till 300 °C is not possible without the presence of critical amount of oxidant. In the absence of any oxidant, FeS reacts with H2S up to 300 °C to give pyrrhotite. Farid et al. have experimentally shown that mackinawite (FeS) has ability to reduce CO2 to CO at temperature higher than 300 °C. They reported that the surface of FeS is oxidized, which on reaction with H2S gives pyrite (FeS2). It is expected that CO reacts with H2O in the Drobner experiment to give H2. == Early evolution == Early evolution is defined as beginning with the origin of life and ending with the last universal common ancestor (LUCA). According to the iron–sulfur world theory it covers a coevolution of cellular organization (cellularization), the genetic machinery and enzymatization of the metabolism. === Cellularization === Cellularization occurs in several stages. It may have begun with
|
{
"page_id": 394464,
"source": null,
"title": "Iron–sulfur world hypothesis"
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the formation of primitive lipids (e.g. fatty acids or isoprenoids) in the surface metabolism. These lipids accumulate on or in the mineral base. This lipophilizes the outer or inner surfaces of the mineral base, which promotes condensation reactions over hydrolytic reactions by lowering the activity of water and protons. In the next stage lipid membranes are formed. While still anchored to the mineral base they form a semi-cell bounded partly by the mineral base and partly by the membrane. Further lipid evolution leads to self-supporting lipid membranes and closed cells. The earliest closed cells are pre-cells (sensu Kandler) because they allow frequent exchange of genetic material (e.g. by fusions). According to Woese, this frequent exchange of genetic material is the cause for the existence of the common stem in the tree of life and for a very rapid early evolution. Nick Lane and coauthors state that "Non-enzymatic equivalents of glycolysis, the pentose phosphate pathway and gluconeogenesis have been identified as well. Multiple syntheses of amino acids from α-keto acids by direct reductive amination and by transamination reactions can also take place. Long-chain fatty acids can be formed by hydrothermal Fischer-Tropsch-type synthesis which chemically resembles the process of fatty acid elongation. Recent work suggests that nucleobases might also be formed following the universally conserved biosynthetic pathways, using metal ions as catalysts". Metabolic intermediates in glycolysis and the pentose phosphate pathway such as glucose, pyruvate, ribose 5-phosphate, and erythrose-4-phosphate are spontaneously generated in the presence of Fe(II). Fructose 1,6-biphosphate, a metabolic intermediate in gluconeogenesis, was shown to have been continuously accumulated but only in a frozen solution. The formation of fructose 1,6-biphosphate was accelerated by lysine and glycine which implies the earliest anabolic enzymes were amino acids. It had been reported that 4Fe-4S, 2Fe-2S, and mononuclear iron clusters are spontaneously formed in
|
{
"page_id": 394464,
"source": null,
"title": "Iron–sulfur world hypothesis"
}
|
low concentrations of cysteine and alkaline pH. Methyl thioacetate, a precursor to acetyl-CoA can be synthesized in conditions relevant to hydrothermal vents. Phosphorylation of methyl thioacetate leads to the synthesis of thioacetate, a simpler precursor to acetyl-CoA. Thioacetate in more cooler and neutral conditions promotes synthesis of acetyl phosphate which is a precursor to adenosine triphosphate and is capable of phosphorylating ribose and nucleosides. This suggests that acetyl phosphate was likely synthesized in thermophoresis and mixing between the acidic seawater and alkaline hydrothermal fluid in interconnected micropores. It is possible that it could promote nucleotide polymerization at mineral surfaces or at low water activity. Thermophoresis at hydrothermal vent pores can concentrate polyribonucleotides, but it remains unknown as to how it could promote coding and metabolic reactions. In mathematical simulations, autocatalytic nucleotide synthesis is proposed to promote protocell growth as nucleotides also catalyze CO2 fixation. Strong nucleotide catalysis of fatty acids and amino acids slow down protocell growth and if competition between catalytic function were to occur, this would disrupt the protocell. Weak or moderate nucleotide catalysis of amino acids via CO2 fixation would favor protocell division and growth. In 2017, a computational simulation of a protocell at an alkaline hydrothermal vent environment showed that "Some hydrophobic amino acids chelate FeS nanocrystals, producing three positive feedbacks: (i) an increase in catalytic surface area; (ii) partitioning of FeS nanocrystals to the membrane; and (iii) a proton-motive active site for carbon fixing that mimics the enzyme Ech". Maximal ATP synthesis would have occurred at high water activity in freshwater and high concentrations of Mg2+ and Ca2+ prevented synthesis of ATP, however the concentrations of divalent cations in Hadean oceans were much lower than in modern oceans and alkaline hydrothermal vent concentrations of Mg2+ and Ca2+ are typically lower than in the ocean. Such
|
{
"page_id": 394464,
"source": null,
"title": "Iron–sulfur world hypothesis"
}
|
environments would have generated Fe3+ which would have promoted ADP phosphorylation. The mixture of seawater and alkaline hydrothermal vent fluid can promote cycling between Fe3+ and Fe2+. Experimental research of biomimetic prebiotic reactions such as the reduction of NAD+ and phosphoryl transfer also support an origin of life occurring at an alkaline hydrothermal vent . === Proto-ecological systems === William Martin and Michael Russell suggest that the first cellular life forms may have evolved inside alkaline hydrothermal vents at seafloor spreading zones in the deep sea. These structures consist of microscale caverns that are coated by thin membraneous metal sulfide walls. Therefore, these structures would resolve several critical points germane to Wächtershäuser's suggestions at once: the micro-caverns provide a means of concentrating newly synthesised molecules, thereby increasing the chance of forming oligomers; the steep temperature gradients inside the hydrothermal vent allow for establishing "optimum zones" of partial reactions in different regions of the vent (e.g. monomer synthesis in the hotter, oligomerisation in the cooler parts); the flow of hydrothermal water through the structure provides a constant source of building blocks and energy (chemical disequilibrium between hydrothermal hydrogen and marine carbon dioxide); the model allows for a succession of different steps of cellular evolution (prebiotic chemistry, monomer and oligomer synthesis, peptide and protein synthesis, RNA world, ribonucleoprotein assembly and DNA world) in a single structure, facilitating exchange between all developmental stages; synthesis of lipids as a means of "closing" the cells against the environment is not necessary, until basically all cellular functions are developed. This model locates the "last universal common ancestor" (LUCA) within the inorganically formed physical confines of an alkaline hydrothermal vent, rather than assuming the existence of a free-living form of LUCA. The last evolutionary step en route to bona fide free-living cells would be the synthesis of
|
{
"page_id": 394464,
"source": null,
"title": "Iron–sulfur world hypothesis"
}
|
a lipid membrane that finally allows the organisms to leave the microcavern system of the vent. This postulated late acquisition of the biosynthesis of lipids as directed by genetically encoded peptides is consistent with the presence of completely different types of membrane lipids in archaea and bacteria (plus eukaryotes). The kind of vent at the foreground of their suggestion is chemically more similar to the warm (ca. 100 °C) off ridge vents such as Lost City than to the more familiar black smoker type vents (ca. 350 °C). In an abiotic world, a thermocline of temperatures and a chemocline in concentration is associated with the pre-biotic synthesis of organic molecules, hotter in proximity to the chemically rich vent, cooler but also less chemically rich at greater distances. The migration of synthesized compounds from areas of high concentration to areas of low concentration gives a directionality that provides both source and sink in a self-organizing fashion, enabling a proto-metabolic process by which acetic acid production and its eventual oxidization can be spatially organized. In this way many of the individual reactions that are today found in central metabolism could initially have occurred independent of any developing cell membrane. Each vent microcompartment is functionally equivalent to a single cell. Chemical communities having greater structural integrity and resilience to wildly fluctuating conditions are then selected for; their success would lead to local zones of depletion for important precursor chemicals. Progressive incorporation of these precursor components within a cell membrane would gradually increase metabolic complexity within the cell membrane, whilst leading to greater environmental simplicity in the external environment. In principle, this could lead to the development of complex catalytic sets capable of self-maintenance. Russell adds a significant factor to these ideas, by pointing out that semi-permeable mackinawite (an iron sulfide mineral) and silicate
|
{
"page_id": 394464,
"source": null,
"title": "Iron–sulfur world hypothesis"
}
|
membranes could naturally develop under these conditions and electrochemically link reactions separated in space, if not in time. == Alternative environment == The 6 of the 11 metabolic intermediates in reverse Krebs cycle promoted by Fe, Zn2+, and Cr3+ in acidic conditions imply that protocells possibly emerged in locally metal-rich and acidic terrestrial hydrothermal fields. The acidic conditions are seemingly consistent with the stabilization of RNA. These hydrothermal fields would have exhibited cycling of freezing and thawing and a variety of temperature gradients that would promote nonenzymatic reactions of gluconeogenesis, nucleobase synthesis, nonenzymatic polymerization, and RNA replication. ATP synthesis and oxidation of ferrous iron via photochemical reactions or oxidants such as nitric oxide derived from lightning strikes, meteorite impacts, or volcanic emissions could have also occurred at hydrothermal fields. Wet-dry cycling of hydrothermal fields would polymerize RNA and peptides, protocell aggregation in a moist gel phase during wet-dry cycling would allow diffusion of metabolic products across neighboring protocells. Protocell aggregation could be described as a primitive version of horizontal gene transfer. Fatty acid vesicles would be stabilized by polymers in the presence of Mg2+ required for ribozyme activity. These prebiotic processes might have occurred in shaded areas that protect the emergence of early cellular life under ultraviolet irradiation. Long chain alcohols and monocarboxylic acids would have also been synthesized via Fischer–Tropsch synthesis. Hydrothermal fields would also have precipitates of transition metals and concentrated many elements including CHNOPS. Geothermal convection could also be a source of energy for the emergence of the proton motive force, phosphoryl group transfer, coupling between oxidation-reduction, and active transport. It's noted by David Deamer and Bruce Damer that these environments seemingly resemble Charles Darwin's idea of a "warm little pond". The problems with the hypothesis of a subaerial hydrothermal field of abiogenesis is that the proposed
|
{
"page_id": 394464,
"source": null,
"title": "Iron–sulfur world hypothesis"
}
|
chemistry doesn't resemble known biochemical reactions. The abundance of subaerial hydrothermal fields would have been rare and offered no protection from either meteorites or ultraviolet irradiation. Clay minerals at subaerial hydrothermal fields would absorb organic reactants. Pyrophosphate has low solubility in water and can't be phosphorylated without a phosphorylating agent. It doesn't offer explanations for the origin of chemiosmosis and differences between Archaea and Bacteria. == See also == Abiogenesis Iron–sulfur protein RNA world RNP world Miller–Urey experiment == References ==
|
{
"page_id": 394464,
"source": null,
"title": "Iron–sulfur world hypothesis"
}
|
Glutaryl-coenzyme A is an intermediate in the metabolism of lysine and tryptophan. == See also == Glutaryl-CoA dehydrogenase == References ==
|
{
"page_id": 11470048,
"source": null,
"title": "Glutaryl-CoA"
}
|
Forest genetic resources or forest tree genetic resources are genetic resources (i.e., genetic material of actual or future value) of forest shrub and tree species. Forest genetic resources are essential for forest-depending communities who rely for a substantial part of their livelihoods on timber and non-timber forest products (for example fruits, gums and resins) for food security, domestic use and income generation. These resources are also the basis for large-scale wood production in planted forests to satisfy the worldwide need for timber and paper. Genetic resources of several important timber, fruit and other non-timber tree species are conserved ex situ in genebanks or maintained in field collections. Nevertheless, in situ conservation in forests and on farms is in the case of most tree species the most important measure to protect their genetic resources. == Understanding diversity == A better understanding of the diversity of these species is crucial for their sustainable use and conservation. Monitoring patterns of distribution and genetic diversity of these species allows the prioritization of populations for in situ conservation, identification of populations and species most at risk and existing gaps in genebank collections. This is vital information which helps tackle global challenges such as food security and climate change. == The State of the World's Forest Genetic Resources == In 2014, the Food and Agriculture Organization of the United Nations published the first State of the World's Forest Genetic Resources. The publication addressed the conservation, management and sustainable use of forest tree and other woody plant genetic resources of actual and potential value for human well-being in the broad range of management systems. It was prepared based on information provided by 86 countries, outcomes from regional and subregional consultations, and commissioned thematic studies. Amongst the ten key findings, half of the forest species reported as regularly
|
{
"page_id": 23266530,
"source": null,
"title": "Forest genetic resources"
}
|
utilized by countries are threatened by the conversion of forests to pastures and farmland, overexploitation, and the impacts of climate change. On the basis of the information and knowledge compiled by FAO for The State of World’s Forest Genetic Resources, the Commission on Genetic Resources for Food and Agriculture developed the Global Plan of Action for the Conservation, Sustainable Use and Development of Forest Genetic Resources. This Global Plan of Action identifies 27 strategic priorities grouped into 4 areas: improving the availability of, and access to, information on forest genetic resources; conservation of forest genetic resources (in situ and ex situ) sustainable use, development and management of forest genetic resources policies, institutions and capacity-building. == Forest genetic resources and climate change == Even though this is a field with many uncertainties, it is evident that during the next 50–100 years climate changes will have an effect on the distribution of forest tree species and the composition of forests. Diversity of forest genetic resources enables the potential for a species (or a population) to adapt to climatic changes and related future challenges such as temperature changes, drought, pests, diseases and forest fires. Though forest trees are known for showing great plasticity in their response to climate changes, not all species are naturally capable to adapt at the pace necessary. For that reason human interventions, such as transfer of forest reproductive material, may be needed. This is particular important for rare and scattered distributed species and species found on the edge of its distribution range. == See also == Environmental DNA Plant genetic resources == References == == External links == Forest Genetic Resources Program of FAO Bioversity International - Forest and Tree Genetic Diversity Research Program Bioversity International - Why forest and tree genetic diversity matters EUFORGEN European Forest Genetic Resources
|
{
"page_id": 23266530,
"source": null,
"title": "Forest genetic resources"
}
|
Programme Training guide on forest genetic resources for global foresters - Bioversity International
|
{
"page_id": 23266530,
"source": null,
"title": "Forest genetic resources"
}
|
Neuroenhancement or cognitive enhancement is the experimental use of pharmacological or non-pharmacological methods intended to improve cognitive and affective abilities in healthy people who don't have any mental illness. Agents or methods of neuroenhancement are intended to affect cognitive, social, psychological, mood, or motor benefits beyond normal functioning. Pharmacological neuroenhancement agents may include compounds thought to be nootropics, such as modafinil, caffeine, and other drugs used for treating people with neurological disorders. Non-pharmacological measures of cognitive enhancement may include behavioral methods (activities, techniques, and changes), non-invasive brain stimulation, which has been used with the intent to improve cognitive and affective functions, and brain-machine interfaces. == Potential agents == There are many supposed nootropics, most having only small effect sizes in healthy individuals. Neuroenhancement's most common pharmacological agents include modafinil and methylphenidate (Ritalin). Stimulants in general and various dementia treatments or other neurological therapies may affect cognition. Neuroenhancement may also occur from: mood ('mood enhancement') motivation sociability (e.g., talking-related or empathy) creativity cognitive endurance psychological resilience Enhancers are multidimensional and can be clustered into biochemical, physical, and behavioral enhancement strategies. === Modafinil === Approved for treating narcolepsy, obstructive sleep apnea, and shift work sleep disorder, modafinil is a wakefulness-promoting drug used to decrease fatigue, increase vigilance, and reduce daytime sleepiness. Modafinil improves alertness, attention, long-term memory, and daily performance in people with sleep disorders. In sustained sleep deprivation, repeated use of modafinil helped individuals maintain higher levels of wakefulness than a placebo, but did not help attention and executive function. Modafinil may impair one's self-monitoring ability; a common trend found in research studies indicated that participants rated their performances on cognitive tests higher than it was, suggesting an "overconfidence" effect. === Methylphenidate === Methylphenidate (MPH), also known as Ritalin, is a stimulant that is used to treat attention-deficit hyperactivity disorder (ADHD).
|
{
"page_id": 40568034,
"source": null,
"title": "Neuroenhancement"
}
|
MPH is abused by a segment of the general population, especially college students. A comparison between the sales of MPH to the number of people for whom it was prescribed revealed a disproportionate ratio, indicating high abuse. MPH may impair cognitive performance. === Others === Studies are too preliminary to determine whether there are any cognitive-enhancing effects of agents such as memantine or acetylcholinesterase inhibitors (examples: donepezil, galantamine). === Possible adverse effects === Common drugs intended for neuroehancement are typically well-tolerated by healthy people. These drugs are already in mainstream use to treat people with different kinds of psychiatric disorders. Assessment to determine potential adverse effects are drop-out rates and subjective rating. The drop-out rates were minimal or non-existent for donepezil, memantine, MPH, and modafinil. In the drug trials, participants reported the following adverse reactions to use of donepezil, memantine, MPH, modafinil or caffeine: gastrointestinal complaints (nausea), headache, dizziness, nightmares, anxiety, drowsiness, nervousness, restlessness, sleep disturbances, and insomnia, diuresis. The side effects normally ceased in the course of treatment. Various factors, such as dosage, timing and concurrent behavior, may influence the onset of adverse effects. == Non-pharmacological == === Neurostimulation === Neurostimulation methods are being researched and developed. Results indicate that details of the stimulation procedures are crucial, with some applications impairing rather than enhancing cognition and questions are being raised about whether this approach can deliver any meaningful results for cognitive domains. Stimulation methods include electrical stimulation, magnetic stimulation, optical stimulation with lasers, several forms of acoustic stimulation, and physical methods like forms of neurofeedback. === Software and media === Applications of augmented reality technologies may affect general memory enhancement, extending perception and learning-assistance. The Internet may be considered a tool for enabling or extending cognition. However, it is not "a simple, uniform technology, [n]either in its composition, [n]or
|
{
"page_id": 40568034,
"source": null,
"title": "Neuroenhancement"
}
|
in its use" and, as "an informational resource, currently fails to enhance cognition", partly due to issues that include information overload, misinformation and persuasion. == Quality and social issues == === Validation and quality control === Quality standards, validation and authentication, sampling and lab testing are commonly substandard or absent for products thought to be cognitive enhancers, including dietary supplements. === Well-being and productivity === Neuroenhancement products or methods are used with the intent to: improve well-being possibly encourage societal productivity increase incentives to develop potential therapies for various brain diseases, such as Alzheimer's disease. === In popular culture === Neuroenhancement products are mentioned in entertainment productions, such as Limitless (2011), which may to some degree probe and explore opportunities and threats of using such products. == Prevalence == In general, people under the age of 25 feel that neuroenhancement agents are acceptable or that the decision to use them is to be made individually. Healthcare officials and parents feel concerned due to safety factors, lack of complete information on these agents, and possible irreversible adverse effects; such concerns may reduce the willingness to take such agents. A 2024 study based on a representative sample of more than 20,000 adults in Germany showed that around 70% of those surveyed had taken substances with the aim of improving mental performance within a year, without a medical prescription. The consumption of caffeinated drinks, such as coffee and energy drinks, was widespread (64% of users), expressly with the aim of improving performance, followed by dietary supplements and home remedies, such as ginkgo biloba (31%). Around 4% stated that they had taken prescription drugs for cognitive enhancement (lifetime prevalence of 6%), corresponding to around 2.5 million users in Germany. A 2016 German study among 6,454 employees found a rather low life-time prevalence of cognitive
|
{
"page_id": 40568034,
"source": null,
"title": "Neuroenhancement"
}
|
enhancement prescription drug use (namely 3%), while the willingness to take such drugs was found in 10% of respondents. A survey of some 5,000 German university students found a relatively low 30-day prevalence of 1%, while 2% of those sampled used such drugs within the last 6 months, 3% within the last 12 months, and 5% of others used the drugs over their lifetimes. Of those students who used such substances during the last 6 months, 39% reported their use once in this period, 24% twice, 12% three times, and 24% more than three times. Consumers of neuroenhancement drugs are more willing to use them again in the future due to positive experiences or a tendency towards addiction. == See also == Alertness Cognitive development Cosmetic pharmacology Deep brain stimulation Intelligence amplification Neurohacking Neuromarketing Neuroregeneration Performance enhancement Transcranial magnetic stimulation == References ==
|
{
"page_id": 40568034,
"source": null,
"title": "Neuroenhancement"
}
|
Occipital cryoneurolysis is a procedure used to treat nerve pain generated by peripheral nerves (nerves located outside of the spinal column and skull) commonly due to the condition occipital neuralgia. A probe (no larger than a small needle) is carefully placed adjacent to the specific nerve. Once in the appropriate area the probe is first used to stimulate the affected nerve helping to verify positioning. Once certain of proper placement, the tip is cooled by nitrous oxide to temperatures between −50 and −70 °C (−58 and −94 °F) to envelope the nerve in an ice ball, thereby interrupting transmission. The nerve is still functional and returns to its normal (un-frozen) state immediately after the procedure is completed. Side effects and adverse reactions are rare. Potential side effects or complications could include soreness from the procedure for a few days, trauma to the nerve, which may cause worsening of the pain or loss of nerve function, as well as infection or bleeding complications. == References ==
|
{
"page_id": 6685921,
"source": null,
"title": "Occipital cryoneurolysis"
}
|
Cytoplasmic streaming, also called protoplasmic streaming and cyclosis, is the flow of the cytoplasm inside the cell, driven by forces from the cytoskeleton. It is likely that its function is, at least in part, to speed up the transport of molecules and organelles around the cell. It is usually observed in large plant and animal cells, greater than approximately 0.1 mm. In smaller cells, the diffusion of molecules is more rapid, but diffusion slows as the size of the cell increases, so larger cells may need cytoplasmic streaming for efficient function. The green alga genus Chara possesses some very large cells, up to 10 cm in length, and cytoplasmic streaming has been studied in these large cells. Cytoplasmic streaming is strongly dependent upon intracellular pH and temperature. It has been observed that the effect of temperature on cytoplasmic streaming created linear variance and dependence at different high temperatures in comparison to low temperatures. This process is complicated, with temperature alterations in the system increasing its efficiency, with other factors such as the transport of ions across the membrane being simultaneously affected. This is due to cells homeostasis depending upon active transport which may be affected at some critical temperatures. In plant cells, chloroplasts are transported within the cytoplasmic stream to optimize their exposure to light for photosynthesis. This rate of motion is influenced by several factors including light intensity, temperature, and pH levels. Cytoplasmic streaming is most efficient at a neutral pH and tends to decrease in efficiency under conditions of both low and high pH. Several methods exist to halt the flow of cytoplasm within cells. One approach involves the introduction of Lugol's iodine solution, which effectively immobilizes the cytoplasmic streaming. Alternatively, the compound Cytochalasin D, dissolved in dimethyl sulfoxide, can be employed to achieve a similar effect by
|
{
"page_id": 656613,
"source": null,
"title": "Cytoplasmic streaming"
}
|
disrupting the actin microfilaments responsible for facilitating cytoplasmic movement. == Mechanism == What is clearly visible in plants cells which exhibit cytoplasmic streaming is the motion of the chloroplasts moving with the cytoplasmic flow. This motion results from fluid being entrained by moving motor molecules of the plant cell. Myosin filaments connect cell organelles to actin filaments. These actin filaments are generally attached to the chloroplasts and/or membranes of plant cells. As the myosin molecules "walk" along the actin filaments dragging the organelles with them, the cytoplasmic fluid becomes entrained and is pushed/pulled along. Cytoplasmic flow rates can range between 1 and 100 micron/sec. === In Chara corallina === Chara corallina exhibits cyclic cytoplasmic flow around a large central vacuole. The large central vacuole is one of the largest organelles in a plant cell and is generally used for storage. In Chara coralina, cells can grow up to 10 cm long and 1 mm in diameter. The diameter of the vacuole can occupy around 80% of the cell's diameter. Thus for a 1 mm diameter cell, the vacuole can have a diameter of 0.8 mm, leaving only a path width of about 0.1 mm around the vacuole for cytoplasm to flow. The cytoplasm flows at a rate of 100 microns/sec, the fastest of all known cytoplasmic streaming phenomena. === Characteristics === The flow of the cytoplasm in the cell of Chara corallina is belied by the "barber pole" movement of the chloroplasts. Two sections of chloroplast flow are observed with the aid of a microscope. These sections are arranged helically along the longitudinal axis of the cell. In one section, the chloroplasts move upward along one band of the helix, while in the other, the chloroplasts move downwardly. The area between these sections are known as indifferent zones. Chloroplasts are
|
{
"page_id": 656613,
"source": null,
"title": "Cytoplasmic streaming"
}
|
never seen to cross these zones, and as a result it was thought that cytoplasmic and vacuolar fluid flow are similarly restricted, but this is not true. First, Kamiya and Kuroda, experimentally determined that cytoplasmic flow rate varies radially within the cell, a phenomenon not clearly depicted by the chloroplast movement. Second, Raymond Goldstein and others developed a mathematical fluid model for the cytoplasmic flow which not only predicts the behavior noted by Kamiya and Kuroda, but predicts the trajectories of cytoplasmic flow through indifferent zones. The Goldstein model ignores the vacuolar membrane, and simply assumes that shear forces are directly translated to the vacuolar fluid from the cytoplasm. The Goldstein model predicts there is net flow toward one of the indifferent zones from the other. This actually is suggested by the flow of the chloroplasts. At one indifferent zone, the section with the chloroplasts moving at a downward angle will be above the chloroplasts moving at an upward angle. This section is known as the minus indifferent zone (IZ-). Here, if each direction is broken into components in the theta (horizontal) and z (vertical) directions, the sum of these components oppose each other in the z direction, and similarly diverges in theta direction. The other indifferent zone has the upwardly angled chloroplast movement on top and is known as the positive indifferent zone (IZ+). Thus, while the z directional components oppose each other again, the theta components now converge. The net effect of the forces is cytoplasmic/vacuolar flow moves from the minus indifferent zone to the positive indifferent zone. As stated, these directional components are suggested by chloroplast movement, but are not obvious. Further, the effect of this cytoplasmic/vacuolar flow from one indifferent zone to the other demonstrates that cytoplasmic particles do cross the indifferent zones even if the
|
{
"page_id": 656613,
"source": null,
"title": "Cytoplasmic streaming"
}
|
chloroplasts at the surface do not. Particles, as they rise in the cell, spiral around in a semicircular manner near the minus indifferent zone, cross one indifferent zone, and end up near a positive indifferent zone. Further experiments on the Characean cells support of the Goldstein model for vacuolar fluid flow. However, due to the vacuolar membrane (which was ignored in the Goldstein model), the cytoplasmic flow follows a different flow pattern. Further, recent experiments have shown that the data collected by Kamiya and Kuroda which suggested a flat velocity profile in the cytoplasm are not fully accurate. Kikuchi worked with Nitella flexillis cells, and found an exponential relationship between fluid flow velocity and distance from cell membrane. Although this work is not on Chara cells, the flows between Nitella flexillis and Chara coralina are visually and structurally similar. == Advantages == === Enhanced nutrient transport === The Goldstein model predicts enhanced transport (over transport characterized by strictly longitudinal cytoplasmic flow) into the vacuolar cavity due to the complicated flow trajectories arising from the cytoplasmic streaming. Although, a nutrient concentration gradient would result from longitudinally uniform concentrations and flows, the complicated flow trajectories predicted produce a larger concentration gradient across the vacuolar membrane. By Fick's laws of diffusion, it is known that larger concentration gradients lead to larger diffusive flows. Thus, the unique flow trajectories of the cytoplasmic flow in Chara coralina lead to enhanced nutrient transport by diffusion into the storage vacuole. This allows for higher concentrations of nutrients inside the vacuole than would be allowed by strictly longitudinal cytoplasmic flows. Goldstein also demonstrated the faster the cytoplasmic flow along these trajectories, the larger the concentration gradient that arises, and the larger diffusive nutrient transport into the storage vacuole that occurs. The enhanced nutrient transport into the vacuole leads
|
{
"page_id": 656613,
"source": null,
"title": "Cytoplasmic streaming"
}
|
to striking differences in growth rate and overall growth size. Experiments have been performed in Arabidopsis thaliana. Wild type versions of this plant exhibit cytoplasmic streaming due to the entrainment of fluid similar to Chara coralina, only at slower flow rates. One experiment removes the wild type myosin motor molecule from the plant and replaces it with a faster myosin molecule which moves along the actin filaments at 16 microns/sec. In another set of plants, the myosin molecule is replaced with the slower homo sapiens Vb myosin motor molecule. Human myosin Vb only moves at a rate of .19 microns/sec. Resulting cytoplasmic flows rates are 4.3 microns/sec for the wild type and 7.5 microns/sec for the plants implanted with the rapidly moving myosin protein. The plants implanted with human myosin Vb do not exhibit continuous cytoplasmic streaming. The plants are then allowed to grow under similar conditions. Faster cytoplasmic rates produced larger plants with larger and more abundant leaves. This suggests that the enhanced nutrient storage demonstrated by the Goldstein model allows for plants to grow larger and faster. === Increased photosynthetic activity === Photosynthesis converts light energy into chemical energy in the form of adenosine triphosphate (ATP). This occurs in the chloroplasts of plants cells. Light photons interact with various intermembrane proteins of the cholorplast to accomplish this. However, these proteins can become saturated with photons, making them unable to function until the saturation is alleviated. This is known as the Kautsky effect and is a cause of inefficiency on the ATP production mechanism. Cytoplasmic streaming in Chara corallina, however, enables chloroplasts to move around the stem of the plant. Thus, the chloroplasts move into lighted regions and shaded regions. This intermittent exposure to photons due to cytoplasmic streaming actually increases the photosynthetic efficiency of chloroplasts. Photosynthetic activity is
|
{
"page_id": 656613,
"source": null,
"title": "Cytoplasmic streaming"
}
|
generally assessed using chlorophyll fluorescence analysis. === Gravisensing === Gravisensing is the ability to sense the gravitational force and react to it. Many plants use gravisensing to direct growth. For example, depending on root orientation, amyloplasts will settle within a plant cell differently. These different settling patterns cause the protein auxin to be distributed differently within the plant. This differences in the distribution pattern direct roots to grow downward or outward. In most plants, gravisensing requires a coordinated multi-cellular effort, but in Chara corallina, one cell detects gravity and responds to it. The barber pole chloroplast motion resulting from cytoplasmic streaming has one flow upward and another downward. The downward motion of the chloroplasts moves a bit faster than the upward flow producing a ratio of speeds of 1.1. This ratio is known as the polar ratio and depends on the force of gravity. This increase in speed is not a direct result of the force of gravity, but an indirect result. Gravity causes the plant protoplast to settle within the cell wall. Thus, the cell membrane is put into tension at the top, and into compression at the bottom. The resulting pressures on the membrane allow for gravisensing which result in the differing speeds of cytoplasmic flow observed in Chara coralina. This gravitational theory of gravisensing is directly opposed to the statolith theory exhibited by the settling of amyloplasts. === Natural emergence === Cytoplasmic streaming occurs due to the motion of organelles attached to actin filaments via myosin motor proteins. However, in Chara corallina, the organization of actin filaments is highly ordered. Actin is a polar molecule, which means that myosin only moves in one direction along the actin filament. Thus, in Chara corallina, where motion of the chloroplasts and the myosin molecule follow a barber pole pattern, the
|
{
"page_id": 656613,
"source": null,
"title": "Cytoplasmic streaming"
}
|
actin filaments must all be similarly oriented within each section. In other words, the section where the chloroplasts move upward will have all of the actin filaments oriented in the same upward direction, and the section where the chloroplasts move downward will have all the actin filaments oriented in the downward direction. This organization emerges naturally from basic principles. With basic, realistic assumptions about the actin filament, Woodhouse demonstrated that the formation of two sets of actin filament orientations in a cylindrical cell is likely. His assumptions included a force keeping the actin filament in place once set down, an attractive force between filaments leading them to be more likely align as a filament already in place, and a repulsive force preventing alignment perpendicular to the length of the cylindrical cell. The first two assumptions derive from the molecular forces within the actin filament, while the last assumption was made due to the actin molecule's dislike of curvature. Computer simulations run with these assumptions with varying parameters for the assumptive forces almost always leads to highly ordered actin organizations. However, no order was as organized and consistent as the barber pole pattern found in nature, which suggests this mechanism plays role, but is not wholly responsible for the organization of actin filaments in Chara corallina. == Created by pressure gradients == Cytoplasmic streaming in some species is caused by pressure gradients along the length of the cell. === In Physarum polycephalum === Physarum polycephalum is a single-celled protist, belonging to a group of organisms informally referred to as 'slime molds'. Biological investigations into the myosin and actin molecules in this amoeboid have demonstrated striking physical and mechanistic similarities to human muscle myosin and actin molecules. Contraction and relaxation of these molecules leads to pressure gradients along the length of the
|
{
"page_id": 656613,
"source": null,
"title": "Cytoplasmic streaming"
}
|
cell. These contractions force cytoplasmic fluid in one direction and contributes to growth. It has been demonstrated that while the molecules are similar to those in humans, the molecule blocking the binding site of myosin to actin is different. While, in humans, tropomyosin covers the site, only allowing contraction when calcium ions are present, in this amoeboid, a different molecule known as calmodulin blocks the site, allowing relaxation in the presence of high calcium ion levels. === In Neurospora crassa === Neurospora crassa is a multicellular fungus with many off shooting hyphae. Cells can be up to 10 cm long, and are separated by a small septum. Small holes in the septum allow cytoplasm and cytoplasmic contents to flow from cell to cell. Osmotic pressure gradients occur through the length of the cell to drive this cytoplasmic flow. Flows contribute to growth and the formation of cellular subcompartments. ==== Contribution to growth ==== Cytoplasmic flows created through osmotic pressure gradients flow longitudinally along the fungal hyphae and crash into the end causing growth. It has been demonstrated that the greater pressure at the hyphal tip corresponds to faster growth rates. Longer hyphae have greater pressure differences along their length allowing for faster cytoplasmic flow rates and larger pressures at the hyphal tip. This is why longer hyphae grow faster than shorter ones. Tip growth increases as cytoplasmic flow rate increases over a 24-hour period until a max rate of 1 micron/second growth rate is observed. Offshoots from the main hyphae are shorter and have slower cytoplasmic flow rates and correspondingly slower growth rates. ==== Formation of cellular subcompartments ==== Cytoplasmic flow in Neurospora crassa carry microtubules. The presence of microtubules create interesting aspects to the flow. Modelling the fungal cells as a pipe separated at regular points with a septum
|
{
"page_id": 656613,
"source": null,
"title": "Cytoplasmic streaming"
}
|
with a hole in the center should produce very symmetrical flow. Basic fluid mechanics suggest that eddies should form both before and after each septum. However, eddies only form before the septum in Neurospora crassa. This is because when microtubules enter the septal hole, they are arranged parallel to flow and contribute very little to flow characteristics, however, as the exit the septal hole, the orient themselves perpendicular to flow, slowing acceleration, and preventing eddy formation. The eddies formed just before the septum allow for the formation of subcompartments where nuclei spotted with special proteins aggregate. These proteins, one of which is called SPA-19, contribute to septum maintenance. Without it, the septum would degrade and the cell would leak large amounts of cytoplasm into the neighboring cell leading to cell death. == In mouse oocytes == In many animal cells, centrioles and spindles keep nuclei centered within a cell for mitotic, meiotic, and other processes. Without such a centering mechanism, disease and death can result. While mouse oocytes do have centrioles, they play no role in nucleus positioning, yet, the nucleus of the oocyte maintains a central position. This is a result of cytoplasmic streaming. Microfilaments, independent of microtubules and myosin 2, form a mesh network throughout the cell. Nuclei, positioned in non-centered cell locations, have been demonstrated to migrate distances greater than 25 microns to the cell center. They will do this without going off course by more than 6 microns when the network is present. This network of microfilaments has organelles bound to it by the myosin Vb molecule. Cytoplasmic fluid is entrained by the motion of these organelles, however, no pattern of directionality is associated with the movement of the cytoplasm. In fact, the motion has been demonstrated to fulfill Brownian motion characteristics. For this reason, there
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"page_id": 656613,
"source": null,
"title": "Cytoplasmic streaming"
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is some debate as to whether this should be called cytoplasmic streaming. Nonetheless, directional movement of organelles does result from this situation. Since the cytoplasm fills the cell, it is geometrically arranged into the shape of a sphere. As the radius of a sphere increases, surface area increases. Further, the motion in any given direction is proportional to the surface area. So thinking of the cell as a series of concentric spheres, it is clear that spheres with larger radii produce a greater amount of movement than spheres with smaller radii. Thus, the movement toward the center is greater than the movement away from the center, and net movement pushing the nucleus towards a central cellular location exists. In other words, the random motion of the cytoplasmic particles create a net force toward the center of the cell. Additionally, the increased motion with the cytoplasm reduces cytoplasmic viscosity allowing the nucleus to move more easily within the cell. These two factors of the cytoplasmic streaming center the nucleus in the oocyte cell. == See also == Amoeboid movement – Mode of locomotion in eukaryotic cells == References == == Sources == == External links == Video of Cyclosis (Elodea).
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"title": "Cytoplasmic streaming"
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John French (1616–1657) was an English physician known for his contributions to chemistry (in particular, distillation) as well as for his English translations of Latin and German works. == Life == He was born in 1616 at Broughton, near Banbury, Oxfordshire. He obtained a B.A. degree from Oxford University in 1637 and an M.A. in 1640, qualifying as a physician with an MD in 1648. He died in 1657 near Boulogne while serving as a physician to the English army. He left a widow, Mary, and a son, John. He lived at a time when the new science of chemistry was developing from alchemy and was an enthusiast for its application to medicine. He was known for his extensive knowledge of chemistry and was respected by scientists of the time such as Robert Boyle. == Works == John French is chiefly remembered for publishing in 1651 The Art of Distillation, a detailed handbook of knowledge and practice at the time, said to be possibly the earliest definitive book on distillation. However, it has been claimed that much of it was a translation of an earlier (1500) German text by Hieronymus Brunschwig. John French was also the translator of Three Books of Occult Philosophy in 1651 (original: De Occulta Philosophia libri tres by Heinrich Cornelius Agrippa, although he was only identified as J.F. in that work. All other English translations of the book available have been merely edited versions of his work. == References == == Further reading == Elmer, Peter. "French, John". Oxford Dictionary of National Biography (online ed.). Oxford University Press. doi:10.1093/ref:odnb/10164. (Subscription or UK public library membership required.) == External links == John French: The Art of Distillation (1651) (online text) Media related to John French (physician) at Wikimedia Commons Works by or about John French at Wikisource
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In biochemistry, glycoside hydrolases (also called glycosidases or glycosyl hydrolases) are a class of enzymes which catalyze the hydrolysis of glycosidic bonds in complex sugars. They are extremely common enzymes, with roles in nature including degradation of biomass such as cellulose (cellulase), hemicellulose, and starch (amylase), in anti-bacterial defense strategies (e.g., lysozyme), in pathogenesis mechanisms (e.g., viral neuraminidases) and in normal cellular function (e.g., trimming mannosidases involved in N-linked glycoprotein biosynthesis). Together with glycosyltransferases, glycosidases form the major catalytic machinery for the synthesis and breakage of glycosidic bonds. == Occurrence and importance == Glycoside hydrolases are found in essentially all domains of life. In prokaryotes, they are found both as intracellular and extracellular enzymes that are largely involved in nutrient acquisition. One of the important occurrences of glycoside hydrolases in bacteria is the enzyme beta-galactosidase (LacZ), which is involved in regulation of expression of the lac operon in E. coli. In higher organisms glycoside hydrolases are found within the endoplasmic reticulum and Golgi apparatus where they are involved in processing of N-linked glycoproteins, and in the lysosome as enzymes involved in the degradation of carbohydrate structures. Deficiency in specific lysosomal glycoside hydrolases can lead to a range of lysosomal storage disorders that result in developmental problems or death. Glycoside hydrolases are found in the intestinal tract and in saliva where they degrade complex carbohydrates such as lactose, starch, sucrose and trehalose. In the gut they are found as glycosylphosphatidyl anchored enzymes on endothelial cells. The enzyme lactase is required for degradation of the milk sugar lactose and is present at high levels in infants, but in most populations will decrease after weaning or during infancy, potentially leading to lactose intolerance in adulthood. The enzyme O-GlcNAcase is involved in removal of N-acetylglucosamine groups from serine and threonine residues in the cytoplasm
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"page_id": 7013607,
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and nucleus of the cell. The glycoside hydrolases are involved in the biosynthesis and degradation of glycogen in the body. == Classification == Glycoside hydrolases are classified into EC 3.2.1 as enzymes catalyzing the hydrolysis of O- or S-glycosides. Glycoside hydrolases can also be classified according to the stereochemical outcome of the hydrolysis reaction: thus they can be classified as either retaining or inverting enzymes. Glycoside hydrolases can also be classified as exo or endo acting, dependent upon whether they act at the (usually non-reducing) end or in the middle, respectively, of an oligo/polysaccharide chain. Glycoside hydrolases may also be classified by sequence or structure-based methods. === Sequence-based classification === Sequence-based classifications are one of the most powerful predictive methods for suggesting function for newly sequenced enzymes for which function has not been biochemically demonstrated. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of more than 100 different families. This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. The database provides a series of regularly updated sequence based classification that allow reliable prediction of mechanism (retaining/inverting), active site residues and possible substrates. The online database is supported by CAZypedia, an online encyclopedia of carbohydrate active enzymes. Based on three-dimensional structural similarities, the sequence-based families have been classified into 'clans' of related structure. Recent progress in glycosidase sequence analysis and 3D structure comparison has allowed the proposal of an extended hierarchical classification of the glycoside hydrolases. == Mechanisms == === Inverting glycoside hydrolases === Inverting enzymes utilize two enzymic residues, typically carboxylate residues, that act as acid and base respectively, as shown below for a β-glucosidase. The product of the reaction has an axial position on C1, but some spontaneous changes of conformation can appear. === Retaining glycoside hydrolases === Retaining glycosidases
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"page_id": 7013607,
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operate through a two-step mechanism, with each step resulting in inversion, for a net retention of stereochemistry. Again, two residues are involved, which are usually enzyme-borne carboxylates. One acts as a nucleophile and the other as an acid/base. In the first step, the nucleophile attacks the anomeric centre, resulting in the formation of a glycosyl enzyme intermediate, with acidic assistance provided by the acidic carboxylate. In the second step, the now deprotonated acidic carboxylate acts as a base and assists a nucleophilic water to hydrolyze the glycosyl enzyme intermediate, giving the hydrolyzed product. The mechanism is illustrated below for hen egg white lysozyme. An alternative mechanism for hydrolysis with retention of stereochemistry can occur that proceeds through a nucleophilic residue that is bound to the substrate, rather than being attached to the enzyme. Such mechanisms are common for certain N-acetylhexosaminidases, which have an acetamido group capable of neighboring group participation to form an intermediate oxazoline or oxazolinium ion. This mechanism proceeds in two steps through individual inversions to lead to a net retention of configuration. A variant neighboring group participation mechanism has been described for endo-α-mannanases that involves 2-hydroxyl group participation to form an intermediate epoxide. Hydrolysis of the epoxide leads to a net retention of configuration. == Nomenclature and examples == Glycoside hydrolases are typically named after the substrate that they act upon. Thus glucosidases catalyze the hydrolysis of glucosides and xylanases catalyze the cleavage of the xylose based homopolymer xylan. Other examples include lactase, amylase, chitinase, sucrase, maltase, neuraminidase, invertase, hyaluronidase and lysozyme. == Uses == Glycoside hydrolases are predicted to gain increasing roles as catalysts in biorefining applications in the future bioeconomy. These enzymes have a variety of uses including degradation of plant materials (e.g., cellulases for degrading cellulose to glucose, which can be used for ethanol
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production), in the food industry (invertase for manufacture of invert sugar, amylase for production of maltodextrins), and in the paper and pulp industry (xylanases for removing hemicelluloses from paper pulp). Cellulases are added to detergents for the washing of cotton fabrics and assist in the maintenance of colours through removing microfibres that are raised from the surface of threads during wear. In organic chemistry, glycoside hydrolases can be used as synthetic catalysts to form glycosidic bonds through either reverse hydrolysis (kinetic approach) where the equilibrium position is reversed; or by transglycosylation (kinetic approach) whereby retaining glycoside hydrolases can catalyze the transfer of a glycosyl moiety from an activated glycoside to an acceptor alcohol to afford a new glycoside. Mutant glycoside hydrolases termed glycosynthases have been developed that can achieve the synthesis of glycosides in high yield from activated glycosyl donors such as glycosyl fluorides. Glycosynthases are typically formed from retaining glycoside hydrolases by site-directed mutagenesis of the enzymic nucleophile to some other less nucleophilic group, such as alanine or glycine. Another group of mutant glycoside hydrolases termed thioglycoligases can be formed by site-directed mutagenesis of the acid-base residue of a retaining glycoside hydrolase. Thioglycoligases catalyze the condensation of activated glycosides and various thiol-containing acceptors. Various glycoside hydrolases have shown efficacy in degrading matrix polysaccharides within the extracellular polymeric substance (EPS) of microbial biofilms. Medically, biofilms afford infectious microorganisms a variety of advantages over their planktonic, fre-floating counterparts, including greatly increased tolerances to antimicrobial agents and the host immune system. Thus, degrading the biofilm may increase antibiotic efficacy, and potentiate host immune function and healing ability. For example, a combination of alpha-amylase and cellulase was shown to degrade polymicrobial bacterial biofilms from both in vitro and in vivo sources, and increase antibiotic effectiveness against them. == Inhibitors == Many compounds are
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known that can act to inhibit the action of a glycoside hydrolase. Nitrogen-containing, 'sugar-shaped' heterocycles have been found in nature, including deoxynojirimycin, swainsonine, australine and castanospermine. From these natural templates many other inhibitors have been developed, including isofagomine and deoxygalactonojirimycin, and various unsaturated compounds such as PUGNAc. Inhibitors that are in clinical use include the anti-diabetic drugs acarbose and miglitol, and the antiviral drugs oseltamivir and zanamivir. Some proteins have been found to act as glycoside hydrolase inhibitors. == See also == Mucopolysaccharidoses Glucosidase Lysozyme Glycosyltransferase List of glycoside hydrolase families Clans of glycoside hydrolases Hierarchical classification of the TIM-barrel type glycoside hydrolases == References == == External links == Cazypedia, an online encyclopedia of the "CAZymes," the carbohydrate-active enzymes and binding proteins involved in the synthesis and degradation of complex carbohydrates Carbohydrate-Active enZYmes Database ExPASy classification Archived 2011-04-30 at the Wayback Machine Glycoside+hydrolases at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
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Tetrahymena is a genus of free-living ciliates, examples of unicellular eukaryotes. The genus Tetrahymena is the most widely studied member of its phylum.: 59 It can produce, store and react with different types of hormones. Tetrahymena cells can recognize both related and hostile cells. They can also switch from commensalistic to pathogenic modes of survival. They are common in freshwater lakes, ponds, and streams.: 277 Tetrahymena species used as model organisms in biomedical research are T. thermophila and T. pyriformis. == T. thermophila: a model organism in experimental biology == As a ciliated protozoan, Tetrahymena thermophila exhibits nuclear dimorphism: two types of cell nuclei. They have a bigger, non-germline macronucleus and a small, germline micronucleus in each cell at the same time and these two carry out different functions with distinct cytological and biological properties. This unique versatility allows scientists to use Tetrahymena to identify several key factors regarding gene expression and genome integrity. In addition, Tetrahymena possess hundreds of cilia and has complicated microtubule structures, making it an optimal model to illustrate the diversity and functions of microtubule arrays. Because Tetrahymena can be grown in a large quantity in the laboratory with ease, it has been a great source for biochemical analysis for years, specifically for enzymatic activities and purification of sub-cellular components. In addition, with the advancement of genetic techniques it has become an excellent model to study the gene function in vivo. The recent sequencing of the macronucleus genome should ensure that Tetrahymena will be continuously used as a model system. Tetrahymena thermophila exists in seven different sexes (mating types) that can reproduce in 21 different combinations, and a single tetrahymena cannot reproduce sexually with itself. Each organism "decides" which sex it will become during mating, through a stochastic process. Studies on Tetrahymena have contributed to several
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scientific milestones including: First cell which showed synchronized division, which led to the first insights into the existence of mechanisms which control the cell cycle. Identification and purification of the first cytoskeleton based motor protein such as dynein. Aid in the discovery of lysosomes and peroxisomes. Early molecular identification of somatic genome rearrangement. Discovery of the molecular structure of telomeres, telomerase enzyme, the templating role of telomerase RNA and their roles in cellular senescence and chromosome healing (for which a Nobel Prize was won). Nobel Prize–winning co-discovery (1989, in Chemistry) of catalytic RNA (ribozyme). Discovery of the function of histone acetylation. Demonstration of the roles of posttranslational modification such as acetylation and glycylation on tubulins and discovery of the enzymes responsible for some of these modifications (glutamylation) Crystal structure of 40S ribosome in complex with its initiation factor eIF1 First demonstration that two of the "universal" stop codons, UAA and UAG, code for the amino acid glutamine in some eukaryotes, leaving UGA as the only termination codon in these organisms. == Life cycle == The life cycle of T. thermophila consists of an alternation between asexual and sexual stages. In nutrient rich media during vegetative growth cells reproduce asexually by binary fission. This type of cell division occurs by a sequence of morphogenetic events that results in the development of duplicate sets of cell structures, one for each daughter cell. Only during starvation conditions will cells commit to sexual conjugation, pairing and fusing with a cell of opposite mating type. Tetrahymena has seven mating types; each of which can mate with any of the other six without preference, but not its own. Typical of ciliates, T. thermophila differentiates its genome into two functionally distinct types of nuclei, each specifically used during the two different stages of the life cycle. The
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diploid germline micronucleus is transcriptionally silent and only plays a role during sexual life stages. The germline nucleus contains 5 pairs of chromosomes which encode the heritable information passed down from one sexual generation to the next. During sexual conjugation, haploid micronuclear meiotic products from both parental cells fuse, leading to the creation of a new micro- and macronucleus in progeny cells. Sexual conjugation occurs when cells starved for at least 2hrs in a nutrient-depleted media encounter a cell of complementary mating type. After a brief period of co-stimulation (~1hr), starved cells begin to pair at their anterior ends to form a specialized region of membrane called the conjugation junction. It is at this junctional zone that several hundred fusion pores form, allowing for the mutual exchange of protein, RNA and eventually a meiotic product of their micronucleus. This whole process takes about 12 hours at 30 °C, but even longer than this at cooler temperatures. The sequence of events during conjugation is outlined in the accompanying figure. The larger polyploid macronucleus is transcriptionally active, meaning its genes are actively expressed, and so it controls somatic cell functions during vegetative growth. The polyploid nature of the macronucleus refers to the fact that it contains approximately 200–300 autonomously replicating linear DNA mini-chromosomes. These minichromosomes have their own telomeres and are derived via site-specific fragmentation of the five original micronuclear chromosomes during sexual development. In T. thermophila each of these minichromosomes encodes multiple genes and exists at a copy number of approximately 45-50 within the macronucleus. The exception to this is the minichromosome encoding the rDNA, which is massively upregulated, existing at a copy number of approximately 10,000 within the macronucleus. Because the macronucleus divides amitotically during binary fission, these minichromosomes are un-equally divided between the clonal daughter cells. Through natural or
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artificial selection, this method of DNA partitioning in the somatic genome can lead to clonal cell lines with different macronuclear phenotypes fixed for a particular trait, in a process called phenotypic assortment. In this way, the polyploid genome can fine-tune its adaptation to environmental conditions through gain of beneficial mutations on any given mini-chromosome whose replication is then selected for, or conversely, loss of a minichromosome which accrues a negative mutation. However, the macronucleus is only propagated from one cell to the next during the asexual, vegetative stage of the life cycle, and so it is never directly inherited by sexual progeny. Only beneficial mutations that occur in the germline micronucleus of T. thermophila are passed down between generations, but these mutations would never be selected for environmentally in the parental cells because they are not expressed. == Behavior == Free swimming cells of Tetrahymena are attracted to certain chemicals by chemokinesis. The major chemo-attractants are peptides and/or proteins. A 2016 study found that cultured Tetrahymena have the capacity to 'learn' the shape and size of their swimming space. Cells confined in a droplet of a water for a short time were, upon release, found to repeat the circular swimming trajectories 'learned' in the droplet. The diameter and duration of these swimming paths reflected the size of the droplet and time allowed to adapt. == DNA repair == It is common among protists that the sexual cycle is inducible by stressful conditions such as starvation. Such conditions often cause DNA damage. A central feature of meiosis is homologous recombination between non-sister chromosomes. In T. thermophila this process of meiotic recombination may be beneficial for repairing DNA damages caused by starvation. Exposure of T. thermophila to UV light resulted in a greater than 100-fold increase in Rad51 gene expression. Treatment with
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the DNA alkylating agent methyl methanesulfonate also resulted in substantially elevated Rad 51 protein levels. These findings suggest that ciliates such as T. thermophila utilize a Rad51-dependent recombinational pathway to repair damaged DNA. The Rad51 recombinase of T. thermophila is a homolog of the Escherichia coli RecA recombinase. In T. thermophila, Rad51 participates in homologous recombination during mitosis, meiosis and in the repair of double-strand breaks. During conjugation, Rad51 is necessary for completion of meiosis. Meiosis in T. thermophila appears to employ a Mus81-dependent pathway that does not use a synaptonemal complex and is considered secondary in most other model eukaryotes. This pathway includes the Mus81 resolvase and the Sgs1 helicase. The Sgs1 helicase appears to promote the non-crossover outcome of meiotic recombinational repair of DNA, a pathway that generates little genetic variation. == Phenotypic and genotypic plasticity == Many species of Tetrahymena are known to display unique response mechanisms to stress and various environmental pressures. The unique genomic architecture of the ciliates (presence of a MIC, high ploidy, large number of chromosomes, etc.) allows for differential gene expression, as well as increased genomic flexibility. The following is a non-exhaustive list of examples of phenotypic and genotypic plasticity in the Tetrahymena genus. === Inducible trophic polymorphisms === T. vorax is known for its inducible trophic polymorphisms, an ecologically offensive tactic that allows it to change its feeding strategy and diet by altering its morphology. Normally, T. vorax is a bacterivorous microstome around 60 μm in length. However, it has the ability to switch into a carnivorous macrostome around 200 μm in length that can feed on larger competitors. If T. vorax cells are too nutrient starved to undertake transformation, they have also been recorded as transforming into a third "tailed"-microstome morph, thought to be a defense mechanism in response to
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cannibalistic pressure. While T. vorax is the most well studied Tetrahymena that exhibits inducible trophic polymorphisms, many lesser known species are able to undertake transformation as well, including T. paulina and T. paravorax. However, only T. vorax has been recorded as having both a macrostome and tailed-microstome form. These morphological switches are triggered by an abundance of stomatin in the environment, a mixture of metabolic compounds released by competitor species, such as Paramecium, Colpidium, and other Tetrahymena. Specifically, chromatographic analysis has revealed that ferrous iron, hypoxanthine, and uracil are the chemicals in stomatin responsible for triggering the morphological change. Many researchers cite "starvation conditions" as inducing the transformation, as in nature, the compound inducers are in highest concentration after microstomal ciliates have grazed down bacterial populations, and ciliate populations are high. When the chemical inducers are in high concentration, T. vorax cells will transform at higher rates, allowing them to prey on their former trophic competitors. The exact genetic, and structural mechanisms that underlie T. vorax transformation are unknown. However, some progress has been made in identifying candidate genes. Researchers from the University of Alabama have used cDNA subtraction to remove actively transcribed DNA from microstome and macrostome T. vorax cells, leaving only differentially transcribed cDNA molecules. While nine differentiation-specific genes were found, the most frequently expressed candidate gene was identified as a novel sequence, SUBII-TG. The sequenced region of SUBII-TG was 912 bp long and consists of three largely identical 105 bp open-reading frames. A northern blot analysis revealed that low levels of transcription are detected in microstome cells, while high levels of transcription occur in macrostome cells. Furthermore, when the researchers limited SUBII-TG expression in the presence of stomatin (using antisense oligonucleotide methods), a 55% reduction in SUBII-TG mRNA correlated with a 51% decrease in transformation, supporting the
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"page_id": 66793,
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notion that the gene is at least partially responsible for controlling the transformation in T. vorax. However, very little is known about the SUBII-TG gene. Researchers were only able to sequence a portion of the entire open-reading frame, and other candidate genes have not been investigated thoroughly. mRNA and amino acid sequencing indicate that ubiquitin may play a crucial role in allowing transformation to take place as well. However, no known genes in the ubiquitin family have been identified in T. vorax. Finally, the genetic mechanisms of the "tailed" microstome morph are completely unknown. === Metal resistance, gene and genome amplification === Other related species exhibit their own unique responses to various stressors. In T. thermophila, chromosome amplification and gene expansion are inducible responses to common organometallic pollutants such as cadmium, copper, and lead. Strains of T. thermophila that were exposed to large quantities of Cd2+ over time were found to have a 5-fold increase of MTT1, and MTT3 (metallothionein genes that code for Cadmium and Lead binding proteins) as well as CNBDP, an unrelated gene that lies just upstream of MTT1 on the same chromosome. The fact that a non-metallothionein gene on the same locus as MTT1 and MTT3 increased copy number indicates that the entire chromosome had been amplified, as opposed to just specific genes. Tetrahymena species are 45-ploid for their macronucleus, meaning that the wild type of T. thermophila normally contains 45 copies of each chromosome. While the actual number of unique chromosomes are unknown, the number is thought to be around 187 in the MAC, and 5 in the MIC. Thus, the Ca2+ adapted strain contained 225 copies of the specific chromosome in question. This resulted in a nearly 28-fold increase in detected expression levels of MTT1, and slightly less in MTT3. When researchers grew a
|
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sample of the T. thermophila population in normal growth medium (lacking Cd2+) for one month, the number of MTT1, MTT3, and CNBDP genes decreased to an average of three copies (135C). By seven months in normal growth medium, the T. thermophila cells were found reduced to just the wild type copy number (45C). When researchers returned cells from the same colony to Cd2+ medium, within a week MTT1, MTT3, and CNBDP genes increased to three copies once again (135C). Thus, the authors argue that chromosome amplification is an inducible and reversible mechanism in the Tetrahymena genetic response to metal stress. Researchers also used gene-knockdown experiments, where the copy number of another metallothionein gene on a different chromosome, MTT5, was dramatically reduced. Within a week, the new strain was found to have developed four novel genes from at least one duplication of MTT1. However, chromosome duplication had not taken place, as indicated by the wild-type ploidy and the normal quantity of other genes on the same chromosomes. Rather, researchers believe that the duplication resulted from homologous recombination events, producing transcriptionally active, upregulated genes that carry repeated MTT1. === Enhanced motility and dispersal === T. thermophila also undergoes phenotypic changes when faced with limited resource availability. Cells are capable of changing their shape and size, along with behavioral swimming strategies in response to starvation. The more motile cells that change in response to starvation are known as dispersers, or disperser cells. While rates and levels of phenotypic change differ between strains, disperser cells form in nearly all strains of T. thermophila when faced with starvation. Dispersers, and non-dispersing cells both become dramatically thinner and smaller, increasing the basal body and cilia density, allowing them to swim between two and three times faster than normal cells. Some strains of T. thermophila have also
|
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been found to develop a single, non-beating, enlarged cilia that assists the cell in steering or directing movement. While the behavior has been shown to correlate with faster dispersal and form as a reversible trait in Tetrahymena cells, little is known about the genetic or cellular mechanisms that allow for its development. Furthermore, other studies show that when genetically variable populations of T. thermophila were starved, dispersal cells actually increased in cell length, despite still becoming thinner. More research is needed to determine the genetic mechanisms that underlie disperser formation. == Species in genus == Species in this genus include. Tetrahymena americanis Tetrahymena asiatica Tetrahymena australis Tetrahymena bergeri Tetrahymena borealis Tetrahymena canadensis Tetrahymena capricornis Tetrahymena caudata Tetrahymena chironomi Tetrahymena corlissi Tetrahymena cosmopolitanis Tetrahymena dimorpha Tetrahymena edaphoni Tetrahymena elliotti Tetrahymena empidokyrea Tetrahymena farahensis Tetrahymena farleyi Tetrahymena furgasoni Tetrahymena glochidiophila Tetrahymena hegewischi Tetrahymena hyperangularis Tetrahymena leucophrys Tetrahymena limacis Tetrahymena lwoffi Tetrahymena malaccensis Tetrahymena mimbres Tetrahymena mobilis Tetrahymena nanneyi Tetrahymena nipissingi Tetrahymena paravorax Tetrahymena patula Tetrahymena pigmentosa Tetrahymena pyriformis Tetrahymena rostrata Tetrahymena rotunda Tetrahymena setifera Tetrahymena setigera Tetrahymena setosa Tetrahymena shanghaiensis Tetrahymena sialidos Tetrahymena silvana Tetrahymena skappus Tetrahymena sonneborni Tetrahymena stegomyiae Tetrahymena thermophila Tetrahymena tropicalis Tetrahymena vorax == In education == Cornell University offers a National Institutes of Health (NIH) funded program through the Science Education Partnership Award (SEPA) Program called Advancing Secondary Science Education thru Tetrahymena (ASSET). The group develops stand-alone labs or lessons using Tetrahymena as training modules that teachers can use in classes. == References == == Further reading == == External links == Tetrahymena Stock Center at Cornell University ASSET: Advancing Secondary Science Education thru Tetrahymena Tetrahymena Genome Database Biogeography and Biodiversity of Tetrahymena Tetrahymena thermophila Genome Project at The Institute for Genomic Research Tetrahymena thermophila Genome Sequence Synopsis Tetrahymena thermophila genome paper Tetrahymena experiments on Journal of Visualized
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Experiments (JoVE) website Microbial Digital Specimen Archives: Tetrahymena image gallery All Creatures Great and Small: Elizabeth Blackburn
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}
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Neural facilitation, also known as paired-pulse facilitation (PPF), is a phenomenon in neuroscience in which postsynaptic potentials (PSPs) (EPPs, EPSPs or IPSPs) evoked by an impulse are increased when that impulse closely follows a prior impulse. PPF is thus a form of short-term synaptic plasticity. The mechanisms underlying neural facilitation are exclusively pre-synaptic; broadly speaking, PPF arises due to increased presynaptic Ca2+ concentration leading to a greater release of neurotransmitter-containing synaptic vesicles. Neural facilitation may be involved in several neuronal tasks, including simple learning, information processing, and sound-source localization. == Mechanisms == === Overview === Ca2+ plays a significant role in transmitting signals at chemical synapses. Voltage-gated Ca2+ channels are located within the presynaptic terminal. When an action potential invades the presynaptic membrane, these channels open and Ca2+ enters. A higher concentration of Ca2+ enables synaptic vesicles to fuse to the presynaptic membrane and release their contents (neurotransmitters) into the synaptic cleft to ultimately contact receptors in the postsynaptic membrane. The amount of neurotransmitter released is correlated with the amount of Ca2+ influx. Therefore, short-term facilitation (STF) results from a build up of Ca2+ within the presynaptic terminal when action potentials propagate close together in time. Facilitation of excitatory post-synaptic current (EPSC) can be quantified as a ratio of subsequent EPSC strengths. Each EPSC is triggered by pre-synaptic calcium concentrations and can be approximated by: EPSC = k([Ca2+]presynaptic)4 = k([Ca2+]rest + [Ca2+]influx + [Ca2+]residual)4 Where k is a constant. Facilitation = EPSC2 / EPSC1 = (1 + [Ca2+]residual / [Ca2+]influx)4 - 1 === Experimental evidence === Early experiments by Del Castillo & Katz in 1954 and Dudel & Kuffler in 1968 showed that facilitation was possible at the neuromuscular junction even if transmitter release does not occur, indicating that facilitation is an exclusively presynaptic phenomenon. Katz and Miledi proposed the
|
{
"page_id": 5637355,
"source": null,
"title": "Neural facilitation"
}
|
residual Ca2+ hypothesis. They attributed the increase in neurotransmitter release to residual or accumulated Ca2+ ("active calcium") within the axon membrane that remains attached to the membrane's inner surface. Katz and Miledi manipulated the Ca2+ concentration within the presynaptic membrane to determine whether or not residual Ca2+ remaining within the terminal after the first impulse caused an increase in neurotransmitter release following the second stimulus. During the first nerve impulse, Ca2+ concentration was either significantly below or nearing that of the second impulse. When Ca2+ concentration was approaching that of the second impulse, facilitation was increased. In this first experiment, stimuli were presented in intervals of 100 ms between the first and second stimuli. An absolute refractory period was reached when intervals were about 10 ms apart. To examine facilitation during shorter intervals, Katz and Miledi directly applied brief depolarizing stimuli to nerve endings. When increasing the depolarizing stimulus from 1-2 ms, neurotransmitter release greatly increased due to accumulation of active Ca2+. Therefore, the degree of facilitation depends on the amount of active Ca2+, which is determined by the reduction in Ca2+ conductance over time as well as the amount of removed from axon terminals after the first stimulus. Facilitation is greatest when the impulses are closest together because Ca2+ conductance would not return to baseline prior to the second stimulus. Therefore, both Ca2+ conductance and accumulated Ca2+ would be greater for the second impulse when presented shortly after the first. In the Calyx of Held synapse, short term facilitation (STF) has been shown to result from the binding of residual Ca2+ to neuronal Ca2+ sensor 1 (NCS1). Conversely, STF has been shown to decrease when Ca2+ chelators are added to the synapse (causing chelation) which reduce residual Ca2+. Therefore, "active Ca2+" plays a significant role in neural facilitation. In
|
{
"page_id": 5637355,
"source": null,
"title": "Neural facilitation"
}
|
the synapse between Purkinje cells, short-term facilitation has been shown to be entirely mediated by the facilitation of Ca2+ currents through the voltage-dependent calcium channels. == Relation to other forms of short-term synaptic plasticity == === Augmentation and potentiation === Short-term synaptic enhancement is often differentiated into categories of facilitation, augmentation, and potentiation (also referred to as post-tetanic potentiation or PTP). These three processes are often differentiated by their time scales: facilitation usually lasts for tens of milliseconds, while augmentation acts on a time scale on the order of seconds and potentiation has a time course of tens of seconds to minutes. All three effects increase the probability of neurotransmitter release from the presynaptic membrane, but the underlying mechanism is different for each. Paired-pulse facilitation is caused by the presence of residual Ca2+, augmentation likely arises due to increased action of the presynaptic protein munc-13, and post-tetanic potentiation is mediated by presynaptic activation of protein kinases. The type of synaptic enhancement seen in a given cell is also related to variant dynamics of Ca2+ removal, which is in turn dependent upon the type of stimuli; a single action potential leads to facilitation, while a short tetanus generally causes augmentation and a longer tetanus leads to potentiation. === Short-term depression (STD) === Short-term depression (STD) operates in the opposite direction of facilitation, decreasing the amplitude of PSPs. STD occurs due to a decrease in the readily releasable pool of vesicles (RRP) as a result of frequent stimulation. The inactivation of presynaptic Ca2+ channels after repeated action potentials also contributes to STD. Depression and facilitation interact to create short-term plastic changes within neurons, and this interaction is called the dual-process theory of plasticity. Basic models present these effects as additive, with the sum creating the net plastic change (facilitation - depression =
|
{
"page_id": 5637355,
"source": null,
"title": "Neural facilitation"
}
|
net change). However, it has been shown that depression occurs earlier on in the stimulus-response pathway than facilitation, and therefore plays into the expression of facilitation. Many synapses exhibit properties of both facilitation and depression. In general, however, synapses with low initial probability of vesicle release are more likely to exhibit facilitation, and synapses with high probability of initial vesicle release are more likely to exhibit depression. == Relation to information transmission == === Synaptic filtering === Because the probability of vesicle release is activity-dependent, synapses can act as dynamic filters for information transmission. Synapses with a low initial probability of vesicle release act as high-pass filters: because the release probability is low, a higher-frequency signal is needed to trigger release, and the synapse thus selectively responds to high-frequency signals. Likewise, synapses with high initial release probabilities serve as low-pass filters, responding to lower-frequency signals. Synapses with an intermediate probability of release act as band-pass filters that selectively respond to a specific range of frequencies. These filtering characteristics may be affected by a variety of factors, including both PPD and PPF, as well as chemical neuromodulators. In particular, because synapses with low release probabilities are more likely to experience facilitation than depression, high-pass filters are often converted to band-pass filters. Likewise, because synapses with high initial release probabilities are more likely to undergo depression than facilitation, it is common for low-pass filters to become band-pass filters, as well. Neuromodulators, meanwhile, may affect these short-term plasticities. In synapses with intermediate release probabilities, properties of the individual synapse will determine how the synapse changes in response to stimuli. These changes in filtration affect information transmission and encoding in response to repeated stimuli. === Sound-source localization === In humans, sound localization is primarily accomplished using information about how the intensity and timing of
|
{
"page_id": 5637355,
"source": null,
"title": "Neural facilitation"
}
|
a sound vary between each ear. Neuronal computations involving these interaurual intensity differences (IIDs) and interaural time differences (ITDs) are typically carried out in different pathways in the brain. Short-term plasticity likely assists in differentiating between these two pathways: short-term facilitation dominates in intensity pathways, while short-term depression dominates in temporal pathways. These different types of short-term plasticity allow for different kinds of information filtration, thus contributing to the division of the two kinds of information into distinct processing streams. The filtering capabilities of short-term plasticity may also assist with encoding information related to amplitude modulation (AM). Short-term depression can dynamically adjust the gain on high-frequency inputs, and may thus allow for an expanded high-frequency range for AM. A mixture of facilitation and depression may also assist in AM coding by leading to rate filtering. == See also == Long-term potentiation Synaptic plasticity Neuroplasticity Post-tetanic potentiation Sensitization Synaptic augmentation == References == == Further reading == Johnston, Daniel; Wu, Samuel Miao-Sin (1994), Foundations of Cellular Neurophysiology, MIT Press, ISBN 978-0-262-29349-5. Kandel, Eric; Schwartz, James; Jessell, Thomas M. (2000). Principles of Neuroscience (4th ed.). McGraw-Hill. pp. 1247–53. ISBN 978-0-8385-7701-1.
|
{
"page_id": 5637355,
"source": null,
"title": "Neural facilitation"
}
|
Avishai Dekel (Hebrew: אבישי דקל; born 1951) is a professor of physics at the Hebrew University of Jerusalem, holding the Andre Aisenstadt Chair of Theoretical Physics. His primary research interests are in astrophysics and cosmology. == Academic career == Dekel earned his Ph.D. from the Hebrew University in 1980, and was a research fellow at Caltech and assistant professor at Yale University before joining the faculty of the Hebrew University in 1986. He served as the Head of The Racah Institute of Physics (1997–2001), the Dean of the Authority for the Community and Youth at the Hebrew University (2005–2011), and the President of the Israel Physical Society (2008–11). He headed the university computing committee, was a member of the executive committee of the board of trustees and a member of the standing committee of the Hebrew University. Dekel was awarded a Visiting Miller Professorship at UC Berkeley, a Blaise Pascal International Chair of Research by the École Normale Supérieure in Paris (2004–06), and a Lagrange fellowship in IAP Paris (2015–16). He has been elected as a fellow of the Israel Physical Society (2019), and has been awarded the Landau Prize for Arts and Sciences (2020). Dekel is known for his contributions to research in cosmology, especially the study of the formation of galaxies and large-scale structure in the Universe, which is dominated by dark energy and dark matter. His expertise is dwarf galaxies and supernova feedback (1986, 2003), large-scale cosmic flows and early estimates of fundamental cosmological parameters (1989-2001), the structure of dark-matter galactic halos (2000–2003), and the theory of galaxy formation (2003–2012). His research focuses on galaxy formation in its most active phase at the early universe, using analytic models and computer simulations. He studies how continuous streams of cold gas and merging galaxies from the cosmic web lead
|
{
"page_id": 7210219,
"source": null,
"title": "Avishai Dekel"
}
|
to star-forming disks and drive violent gravitational disk instability, and how this instability leads to the formation of compact spheroidal galactic components with central massive black holes. His recent work focuses on the formation of the first galaxies as observed by the James Webb Space Telescope, proposing a unique phase of feedback-free starbursts in the early Universe. Dekel is the most highly cited astrophysicist in Israel, with 60,000 citations and H-index 120. == References == == External links == Scholarly Works by Avishai Dekel from the Astrophysical Data System
|
{
"page_id": 7210219,
"source": null,
"title": "Avishai Dekel"
}
|
A tetramer assay (also known as a tetramer stain) is a procedure that uses tetrameric proteins to detect and quantify T cells that are specific for a given antigen within a blood sample. The tetramers used in the assay are made up of four major histocompatibility complex (MHC) molecules, which are found on the surface of most cells in the body. MHC molecules present peptides to T-cells as a way to communicate the presence of viruses, bacteria, cancerous mutations, or other antigens in a cell. If a T-cell's receptor matches the peptide being presented by an MHC molecule, an immune response is triggered. Thus, MHC tetramers that are bioengineered to present a specific peptide can be used to find T-cells with receptors that match that peptide. The tetramers are labeled with a fluorophore, allowing tetramer-bound T-cells to be analyzed with flow cytometry. Quantification and sorting of T-cells by flow cytometry enables researchers to investigate immune response to viral infection and vaccine administration as well as functionality of antigen-specific T-cells. Generally, if a person's immune system has encountered a pathogen, the individual will possess T cells with specificity toward some peptide on that pathogen. Hence, if a tetramer stain specific for a pathogenic peptide results in a positive signal, this may indicate that the person's immune system has encountered and built a response to that pathogen. == History == This methodology was first published in 1996 by a lab at Stanford University. Previous attempts to quantify antigen-specific T-cells involved the less accurate limiting dilution assay, which estimates numbers of T-cells at 50-500 times below their actual levels. Stains using soluble MHC monomers were also unsuccessful due to the low binding affinity of T-cell receptors and MHC-peptide monomers. MHC tetramers can bind to more than one receptor on the target T-cell, resulting
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{
"page_id": 10290414,
"source": null,
"title": "Tetramer assay"
}
|
in an increased total binding strength and lower dissociation rates. == Uses == === CD8+ T-cells === Tetramer stains usually analyze cytotoxic T lymphocyte (CTL) populations. CTLs are also called CD8+ T-cells, because they have CD8 co-receptors that bind to MHC class I molecules. Most cells in the body express MHC class I molecules, which are responsible for processing intracellular antigens and presenting at the cell's surface. If the peptides being presented by MHC class I molecules are foreign—for example, derived from viral proteins instead of the cell's own proteins—the CTL with a receptor that matches the peptide will destroy the cell. Tetramer stains allow for the visualization, quantification, and sorting of these cells by flow cytometry, which is extremely useful in immunology. T-cell populations can be tracked over the duration of a virus or after the application of a vaccine. Tetramer stains can also be paired with functional assays like ELIspot, which detects the number of cytokine secreting cells in a sample. ==== MHC Class I Tetramer Construction ==== MHC tetramer molecules developed in a lab can mimic the antigen presenting complex on cells and bind to T-cells that recognize the antigen. Class I MHC molecules are made up of a polymorphic heavy α-chain associated with an invariant light chain beta-2 microglobulin (β2m). Escherichia coli are used to synthesize the light chain and a shortened version of the heavy chain that includes the biotin 15 amino acid recognition tag. These MHC chains are biotinylated with the enzyme BirA and refolded with the antigenic peptide of interest. Biotin is a small molecule that forms a strong bond with another protein called streptavidin. Fluorophore tagged streptavidin is added to the bioengineered MHC monomers, and the biotin-streptavidin interaction causes four MHC monomers to bind to the streptavidin and create a tetramer. When
|
{
"page_id": 10290414,
"source": null,
"title": "Tetramer assay"
}
|
the tetramers are mixed with a blood sample, they will bind to T-cells expressing the appropriate antigen specific receptor. Any MHC tetramers that are not bound are washed out of the sample before it is analyzed with flow cytometry. Recent advancements within recombinant MHC molecules have democratised peptide MHC complex formulation and subsequent multimerisation. Highly active formulations of a broad range of MHC class I molecules now allows non-experts users to make their own custom peptide-MHC complexes from day-to-day in any lab without special equipment. === CD4+ T-cells === Tetramers that bind to helper T-cells have also been developed. Helper T-cells or CD4+ T-cells express CD4 co-receptors. They bind to class II MHC molecules, which are only expressed in professional antigen-presenting cells like dendritic cells or macrophages. Class II MHC molecules present extracellular antigens, allowing helper T-cells to detect bacteria, fungi, and parasites. Class II MHC tetramer use is becoming more common, but the tetramers are more difficult to create than class I tetramers and the bond between helper T-cells and MHC molecules is even weaker. === Natural Killer T-cells === Natural killer T-cells (NKT cells) can also be visualized with tetramer technology. NKT cells bind to proteins that present lipid or glycolipid antigens. The antigen presenting complex that NKT cells bind to involves CD1 proteins, so tetramers made of CD1 can be used to stain for NKT cells. == Examples == An early application of tetramer technology focused on the cell-mediated immune response to HIV infection. MHC tetramers were developed to present HIV antigens and used to find the percentage of CTLs specific to those HIV antigens in blood samples of infected patients. This was compared to results of cytotoxic assays and plasma RNA viral load to characterize the function of CTLs in HIV infection. The CTLs that bound
|
{
"page_id": 10290414,
"source": null,
"title": "Tetramer assay"
}
|
to tetramers were sorted into ELIspot wells for analysis of cytokine secretion. Another study utilized MHC tetramer complexes to investigate the effectiveness of an influenza vaccine delivery method. Mice were given subcutaneous and intranasal vaccinations for influenza, and tetramer stains coupled with flow cytometry were used to quantify the CTLs specific to the antigen used in the vaccine. This allowed for comparison of the immune response (the number of T-cells that target a virus) in two different vaccine delivery methods. == References == == Further reading ==
|
{
"page_id": 10290414,
"source": null,
"title": "Tetramer assay"
}
|
RNU4-2 Syndrome or ReNU syndrome is a neurodevelopmental disorder caused by de novo variants in the human gene RNU4-2, which encodes an RNA component of the major spliceosome. It is characterized by hypotonia, global developmental delay, severely impaired intellectual development with poor or absent speech, delayed walking or inability to walk, feeding difficulties with poor overall growth, dysmorphic facial features, and brain anomalies, including ventriculomegaly. The syndrome is an autosomal dominant genetic disorder caused by de novo variants in RNU4-2, a gene on chromosome 12, which encodes the small nuclear RNA (snRNA) U4. U4 is a component of the major spliceosome, a complex of proteins and non-coding RNAs that is necessary for RNA splicing. Most cases of RNU4-2 / ReNU syndrome are explained by a 1-bp insertion (n.64_65insT, NR_003137.2), which is thought to disrupt the interactions of snRNA U4 with the snRNA U6, affecting the stability of the ACAGAGA loop of U6 sRNA which binds 5' splice sites and induces splicing after U4-U6 unwinding. Disrupted splicing, in particular a change in 5' splice site usage, has been reported in individuals with variants in RNU4-2. The genetic etiology of RNU4-2 / ReNU syndrome was identified independently by two research groups, both of which used data collected by Genomics England. The statisticians Daniel Greene and Ernest Turro at the Icahn School of Medicine at Mount Sinai, used a Bayesian approach to identify the genetic association. The other team involved a global collaboration led by Yuyang Chen and Nicola Whiffin of the University of Oxford. Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language (NEDHAFA) was a suggested name for this syndrome, however, ReNU syndrome (pronounced 'renew') was chosen through a collaboration between researchers and the families of those impacted by variants in RNU4-2. The name symbolises that this diagnosis “renews”
|
{
"page_id": 77333746,
"source": null,
"title": "RNU4-2 syndrome"
}
|
hope for a brighter future for all those affected. == Etiologically related disorder == An etiologically related disorder RNU2-2 syndrome has been identified by Greene and Turro. RNU2-2 syndrome is a major spliceosome disorder with similar symptoms to RNU4-2 / ReNU syndrome but it is five times less prevalent. == References == == Further reading == "Mutations in the U4 snRNA gene RNU4-2 cause one of the most prevalent monogenic neurodevelopmental disorders". Read by QxMD. Retrieved 22 July 2024.
|
{
"page_id": 77333746,
"source": null,
"title": "RNU4-2 syndrome"
}
|
Biopreservation is the use of natural or controlled microbiota or antimicrobials as a way of preserving food and extending its shelf life. The biopreservation of food, especially utilizing lactic acid bacteria (LAB) that are inhibitory to food spoilage microbes, has been practiced since early ages, at first unconsciously but eventually with an increasingly robust scientific foundation. Beneficial bacteria or the fermentation products produced by these bacteria are used in biopreservation to control spoilage and render pathogens inactive in food. There are a various modes of action through which microorganisms can interfere with the growth of others such as organic acid production, resulting in a reduction of pH and the antimicrobial activity of the un-dissociated acid molecules, a wide variety of small inhibitory molecules including hydrogen peroxide, etc. It is a benign ecological approach which is gaining increasing attention. == Biopreservative agents and modes of action == === Lactic acid bacteria === Of special interest are lactic acid bacteria (LAB). Lactic acid bacteria have antagonistic properties which make them particularly useful as biopreservatives. When LABs compete for nutrients, their metabolites often include active antimicrobials such as lactic and acetic acid, hydrogen peroxide, and peptide bacteriocins. Some LABs produce the antimicrobial nisin which is a particularly effective preservative. These days LAB bacteriocins are used as an integral part of hurdle technology. Using them in combination with other preservative techniques can effectively control spoilage bacteria and other pathogens, and can inhibit the activities of a wide spectrum of organisms, including inherently resistant Gram-negative bacteria." Lactic acid bacteria and propionibacteria have been extensively studied for their efficiency against spoilage causing yeasts and molds in food spoilage. === Yeast === In addition to lactic acid bacteria, yeasts also have been reported to have a biopreservation effect due to their antagonistic activities relying on the competition
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{
"page_id": 31196402,
"source": null,
"title": "Biopreservation"
}
|
for nutrients, production and tolerance of high concentrations of ethanol, as well as the synthesis of a large class of antimicrobial compounds exhibiting large spectrum of activity against food spoilage microorganisms, but also against plant, animal and human pathogen. A bacterium/yeast that is a suitable candidate for use as a biopreservative does not necessarily have to ferment the food. However, if conditions are suitable for microbial growth, then a biopreservative bacterium will compete well for nutrients with the spoilage and pathogenic bacteria in the food. As a product of its metabolism, it should also produce acids and other antimicrobial agents, particularly bacteriocins. Biopreservative bacteria, such as lactic acid bacteria, must be harmless to humans. === Bacteriophages === Bacteriophages (Greek for 'bacteria eater'), or simply phages, are viruses which infect bacteria. The idea of using phages against unwanted bacteria developed shortly after their discovery. With the improvements in organic chemistry during the 1950s, exploration and development of broad spectrum antibiotics displaced interest in bacteriophage research. Several laboratories have been testing suitability of bacteriophage isolates to control certain bacterial pathogens. Significant advancements in this research have been made at the Bacteriophage Institute in Tbilisi, Georgia, where phage therapy is routinely applied in medicine research. Today treatment of antibiotic resistant bacteria is a challenging task. Recently, research on bacteriophages has gained additional momentum in light of the identification of antibiotic-resistant pathogens of infectious diseases, wherein the application of antibiotics is not effectively working, therefore research on the application of bacteriophages is being reviewed intensely. Bacteriophages have recently received a generally recognized as safe status based on their lack of toxicity and other detrimental effects to human health for application in meat products in the USA. Phage preparations specific for L. monocytogenes, E. coli O157:H7, and S. enterica serotypes have been commercialized and approved
|
{
"page_id": 31196402,
"source": null,
"title": "Biopreservation"
}
|
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