text stringlengths 11 1.65k | source stringlengths 38 44 |
|---|---|
Physical geography Among these is who is considered the patriarch of Russian geography, Mikhail Lomonosov. In the mid-1750s Lomonosov began working in the Department of Geography, Academy of Sciences to conduct research in Siberia. They showed the organic origin of soil and developed a comprehensive law on the movement of the ice, thereby founding a new branch of geography: glaciology. In 1755 on his initiative was founded Moscow University where he promoted the study of geography and the training of geographers. In 1758 he was appointed director of the Department of Geography, Academy of Sciences, a post from which would develop a working methodology for geographical survey guided by the most important long expeditions and geographical studies in Russia. The contributions of the Russian school became more frequent through his disciples, and in the nineteenth century we have great geographers such as Vasily Dokuchaev who performed works of great importance as a "principle of comprehensive analysis of the territory" and "Russian Chernozem". In the latter, he introduced the geographical concept of soil, as distinct from a simple geological stratum, and thus found a new geographic area of study: pedology. Climatology also received a strong boost from the Russian school by Wladimir Köppen whose main contribution, climate classification, is still valid today. However, this great geographer also contributed to the paleogeography through his work "The climates of the geological past" which is considered the father of paleoclimatology | https://en.wikipedia.org/wiki?curid=23263 |
Physical geography Russian geographers who made great contributions to the discipline in this period were: NM Sibirtsev, Pyotr Semyonov, K.D. Glinka, Neustrayev, among others. The second important process is the theory of evolution by Darwin in mid-century (which decisively influenced the work of Friedrich Ratzel, who had academic training as a zoologist and was a follower of Darwin's ideas) which meant an important impetus in the development of Biogeography. Another major event in the late nineteenth and early twentieth centuries took place in the United States. William Morris Davis not only made important contributions to the establishment of discipline in his country but revolutionized the field to develop cycle of erosion theory which he proposed as a paradigm for geography in general, although in actually served as a paradigm for physical geography. His theory explained that mountains and other landforms are shaped by factors that are manifested cyclically. He explained that the cycle begins with the lifting of the relief by geological processes (faults, volcanism, tectonic upheaval, etc.). Factors such as rivers and runoff begin to create V-shaped valleys between the mountains (the stage called "youth"). During this first stage, the terrain is steeper and more irregular. Over time, the currents can carve wider valleys ("maturity") and then start to wind, towering hills only ("senescence") | https://en.wikipedia.org/wiki?curid=23263 |
Physical geography Finally, everything comes to what is a plain flat plain at the lowest elevation possible (called "baseline") This plain was called by Davis' "peneplain" meaning "almost plain" Then river rejuvenation occurs and there is another mountain lift and the cycle continues. Although Davis's theory is not entirely accurate, it was absolutely revolutionary and unique in its time and helped to modernize and create a geography subfield of geomorphology. Its implications prompted a myriad of research in various branches of physical geography. In the case of the Paleogeography, this theory provided a model for understanding the evolution of the landscape. For hydrology, glaciology, and climatology as a boost investigated as studying geographic factors shape the landscape and affect the cycle. The bulk of the work of William Morris Davis led to the development of a new branch of physical geography: Geomorphology whose contents until then did not differ from the rest of geography. Shortly after this branch would present a major development. Some of his disciples made significant contributions to various branches of physical geography such as Curtis Marbut and his invaluable legacy for Pedology, Mark Jefferson, Isaiah Bowman, among others. | https://en.wikipedia.org/wiki?curid=23263 |
Outline of physical science Physical science is a branch of natural science that studies non-living systems, in contrast to life science. It in turn has many branches, each referred to as a "physical science", together called the "physical sciences". Physical science can be described as all of the following: History of physical science – history of the branch of natural science that studies non-living systems, in contrast to the life sciences. It in turn has many branches, each referred to as a "physical science", together called the "physical sciences". However, the term "physical" creates an unintended, somewhat arbitrary distinction, since many branches of physical science also study biological phenomena (organic chemistry, for example). Physics – branch of science that studies matter and its motion through space and time, along with related concepts such as energy and force. Physics is one of the "fundamental sciences" because the other natural sciences (like biology, geology etc.) deal with systems that seem to obey the laws of physics. According to physics, the physical laws of matter, energy and the fundamental forces of nature govern the interactions between particles and physical entities (such as planets, molecules, atoms or the subatomic particles). Some of the basic pursuits of physics, which include some of the most prominent developments in modern science in the last millennium, include: Astronomy – science of celestial bodies and their interactions in space | https://en.wikipedia.org/wiki?curid=23638 |
Outline of physical science Its studies includes the following: Chemistry – branch of science that studies the composition, structure, properties and change of matter. Chemistry is chiefly concerned with atoms and molecules and their interactions and transformations, for example, the properties of the chemical bonds formed between atoms to create chemical compounds. As such, chemistry studies the involvement of electrons and various forms of energy in photochemical reactions, oxidation-reduction reactions, changes in phases of matter, and separation of mixtures. Preparation and properties of complex substances, such as alloys, polymers, biological molecules, and pharmaceutical agents are considered in specialized fields of chemistry. Earth science – the science of the planet Earth, the only identified life-bearing planet. Its studies include the following: | https://en.wikipedia.org/wiki?curid=23638 |
Polymerase chain reaction (PCR) is a method widely used in molecular biology to rapidly make millions to billions of copies of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it to a large enough amount to study in detail. PCR was invented in 1983 by the American biochemist Kary Mullis at Cetus Corporation. It is fundamental to much of genetic testing including analysis of ancient samples of DNA and identification of infectious agents. Using PCR, copies of very small amounts of DNA sequences are exponentially amplified in a series or cycles of temperature changes. PCR is now a common and often indispensable technique used in medical laboratory and clinical laboratory research for a broad variety of applications including biomedical research and criminal forensics. The majority of PCR methods rely on thermal cycling. Thermal cycling exposes reactants to repeated cycles of heating and cooling to permit different temperature-dependent reactions – specifically, DNA melting and enzyme-driven DNA replication. PCR employs two main reagents – primers (which are short single strand DNA fragments known as oligonucleotides that are a complementary sequence to the target DNA region) and a DNA polymerase. In the first step of PCR, the two strands of the DNA double helix are physically separated at a high temperature in a process called Nucleic acid denaturation. In the second step, the temperature is lowered and the primers bind to the complementary sequences of DNA | https://en.wikipedia.org/wiki?curid=23647 |
Polymerase chain reaction The two DNA strands then become templates for DNA polymerase to enzymatically assemble a new DNA strand from free nucleotides, the building blocks of DNA. As PCR progresses, the DNA generated is itself used as a template for replication, setting in motion a chain reaction in which the original DNA template is exponentially amplified. Almost all PCR applications employ a heat-stable DNA polymerase, such as Taq polymerase, an enzyme originally isolated from the thermophilic bacterium "Thermus aquaticus". If the polymerase used was heat-susceptible, it would denature under the high temperatures of the denaturation step. Before the use of Taq polymerase, DNA polymerase had to be manually added every cycle, which was a tedious and costly process. Applications of the technique include DNA cloning for sequencing, gene cloning and manipulation, gene mutagenesis; construction of DNA-based phylogenies, or functional analysis of genes; diagnosis and monitoring of hereditary diseases; amplification of ancient DNA; analysis of genetic fingerprints for DNA profiling (for example, in forensic science and parentage testing); and detection of pathogens in nucleic acid tests for the diagnosis of infectious diseases. PCR amplifies a specific region of a DNA strand (the DNA target). Most PCR methods amplify DNA fragments of between 0.1 and 10 kilo base pairs (kbp) in length, although some techniques allow for amplification of fragments up to 40 kbp | https://en.wikipedia.org/wiki?curid=23647 |
Polymerase chain reaction The amount of amplified product is determined by the available substrates in the reaction, which become limiting as the reaction progresses. A basic PCR set-up requires several components and reagents, including: The reaction is commonly carried out in a volume of 10–200 μL in small reaction tubes (0.2–0.5 mL volumes) in a thermal cycler. The thermal cycler heats and cools the reaction tubes to achieve the temperatures required at each step of the reaction (see below). Many modern thermal cyclers make use of the Peltier effect, which permits both heating and cooling of the block holding the PCR tubes simply by reversing the electric current. Thin-walled reaction tubes permit favorable thermal conductivity to allow for rapid thermal equilibration. Most thermal cyclers have heated lids to prevent condensation at the top of the reaction tube. Older thermal cyclers lacking a heated lid require a layer of oil on top of the reaction mixture or a ball of wax inside the tube. Typically, PCR consists of a series of 20–40 repeated temperature changes, called thermal cycles, with each cycle commonly consisting of two or three discrete temperature steps (see figure below). The cycling is often preceded by a single temperature step at a very high temperature (>), and followed by one hold at the end for final product extension or brief storage | https://en.wikipedia.org/wiki?curid=23647 |
Polymerase chain reaction The temperatures used and the length of time they are applied in each cycle depend on a variety of parameters, including the enzyme used for DNA synthesis, the concentration of bivalent ions and dNTPs in the reaction, and the melting temperature ("T") of the primers. The individual steps common to most PCR methods are as follows: To check whether the PCR successfully generated the anticipated DNA target region (also sometimes referred to as the amplimer or amplicon), agarose gel electrophoresis may be employed for size separation of the PCR products. The size(s) of PCR products is determined by comparison with a DNA ladder, a molecular weight marker which contains DNA fragments of known size run on the gel alongside the PCR products. As with other chemical reactions, the reaction rate and efficiency of PCR are affected by limiting factors. Thus, the entire PCR process can further be divided into three stages based on reaction progress: In practice, PCR can fail for various reasons, in part due to its sensitivity to contamination causing amplification of spurious DNA products. Because of this, a number of techniques and procedures have been developed for optimizing PCR conditions. Contamination with extraneous DNA is addressed with lab protocols and procedures that separate pre-PCR mixtures from potential DNA contaminants | https://en.wikipedia.org/wiki?curid=23647 |
Polymerase chain reaction This usually involves spatial separation of PCR-setup areas from areas for analysis or purification of PCR products, use of disposable plasticware, and thoroughly cleaning the work surface between reaction setups. Primer-design techniques are important in improving PCR product yield and in avoiding the formation of spurious products, and the usage of alternate buffer components or polymerase enzymes can help with amplification of long or otherwise problematic regions of DNA. Addition of reagents, such as formamide, in buffer systems may increase the specificity and yield of PCR. Computer simulations of theoretical PCR results (Electronic PCR) may be performed to assist in primer design. PCR allows isolation of DNA fragments from genomic DNA by selective amplification of a specific region of DNA. This use of PCR augments many ways, such as generating hybridization probes for Southern or northern hybridization and DNA cloning, which require larger amounts of DNA, representing a specific DNA region. PCR supplies these techniques with high amounts of pure DNA, enabling analysis of DNA samples even from very small amounts of starting material. Other applications of PCR include DNA sequencing to determine unknown PCR-amplified sequences in which one of the amplification primers may be used in Sanger sequencing, isolation of a DNA sequence to expedite recombinant DNA technologies involving the insertion of a DNA sequence into a plasmid, phage, or cosmid (depending on size) or the genetic material of another organism | https://en.wikipedia.org/wiki?curid=23647 |
Polymerase chain reaction Bacterial colonies "(such as E. coli)" can be rapidly screened by PCR for correct DNA vector constructs. PCR may also be used for genetic fingerprinting; a forensic technique used to identify a person or organism by comparing experimental DNAs through different PCR-based methods. Some PCR 'fingerprints' methods have high discriminative power and can be used to identify genetic relationships between individuals, such as parent-child or between siblings, and are used in paternity testing (Fig. 4). This technique may also be used to determine evolutionary relationships among organisms when certain molecular clocks are used (i.e., the 16S rRNA and recA genes of microorganisms). Because PCR amplifies the regions of DNA that it targets, PCR can be used to analyze extremely small amounts of sample. This is often critical for forensic analysis, when only a trace amount of DNA is available as evidence. PCR may also be used in the analysis of ancient DNA that is tens of thousands of years old. These PCR-based techniques have been successfully used on animals, such as a forty-thousand-year-old mammoth, and also on human DNA, in applications ranging from the analysis of Egyptian mummies to the identification of a Russian tsar and the body of English king Richard III. Quantitative PCR or Real Time PCR (qPCR, not to be confused with RT-PCR) methods allow the estimation of the amount of a given sequence present in a sample—a technique often applied to quantitatively determine levels of gene expression | https://en.wikipedia.org/wiki?curid=23647 |
Polymerase chain reaction Quantitative PCR is an established tool for DNA quantification that measures the accumulation of DNA product after each round of PCR amplification. qPCR allows the quantification and detection of a specific DNA sequence in real time since it measures concentration while the synthesis process is taking place. There are two methods for simultaneous detection and quantification. The first method consists of using fluorescent dyes that are retained nonspecifically in between the double strands. The second method involves probes that code for specific sequences and are fluorescently labeled. Detection of DNA using these methods can only be seen after the hybridization of probes with its complementary DNA takes place. An interesting technique combination is real-time PCR and reverse transcription. This sophisticated technique, called RT-qPCR, allows for the quantification of a small quantity of RNA. Through this combined technique, mRNA is converted to cDNA, which is further quantified using qPCR. This technique lowers the possibility of error at the end point of PCR, increasing chances for detection of genes associated with genetic diseases such as cancer. Laboratories use RT-qPCR for the purpose of sensitively measuring gene regulation. Prospective parents can be tested for being genetic carriers, or their children might be tested for actually being affected by a disease | https://en.wikipedia.org/wiki?curid=23647 |
Polymerase chain reaction DNA samples for prenatal testing can be obtained by amniocentesis, chorionic villus sampling, or even by the analysis of rare fetal cells circulating in the mother's bloodstream. PCR analysis is also essential to preimplantation genetic diagnosis, where individual cells of a developing embryo are tested for mutations. PCR allows for rapid and highly specific diagnosis of infectious diseases, including those caused by bacteria or viruses. PCR also permits identification of non-cultivatable or slow-growing microorganisms such as mycobacteria, anaerobic bacteria, or viruses from tissue culture assays and animal models. The basis for PCR diagnostic applications in microbiology is the detection of infectious agents and the discrimination of non-pathogenic from pathogenic strains by virtue of specific genes. Characterization and detection of infectious disease organisms have been revolutionized by PCR in the following ways: The development of PCR-based genetic (or DNA) fingerprinting protocols has seen widespread application in forensics: PCR has been applied to many areas of research in molecular genetics: PCR has a number of advantages. It is fairly simple to understand and to use, and produces results rapidly. The technique is highly sensitive with the potential to produce millions to billions of copies of a specific product for sequencing, cloning, and analysis. qRT-PCR shares the same advantages as the PCR, with an added advantage of quantification of the synthesized product | https://en.wikipedia.org/wiki?curid=23647 |
Polymerase chain reaction Therefore, it has its uses to analyze alterations of gene expression levels in tumors, microbes, or other disease states. PCR is a very powerful and practical research tool. The sequencing of unknown etiologies of many diseases are being figured out by the PCR. The technique can help identify the sequence of previously unknown viruses related to those already known and thus give us a better understanding of the disease itself. If the procedure can be further simplified and sensitive non radiometric detection systems can be developed, the PCR will assume a prominent place in the clinical laboratory for years to come. One major limitation of PCR is that prior information about the target sequence is necessary in order to generate the primers that will allow its selective amplification.<ref name="10.1038/jid.2013.1"></ref> This means that, typically, PCR users must know the precise sequence(s) upstream of the target region on each of the two single-stranded templates in order to ensure that the DNA polymerase properly binds to the primer-template hybrids and subsequently generates the entire target region during DNA synthesis. Like all enzymes, DNA polymerases are also prone to error, which in turn causes mutations in the PCR fragments that are generated. Another limitation of PCR is that even the smallest amount of contaminating DNA can be amplified, resulting in misleading or ambiguous results | https://en.wikipedia.org/wiki?curid=23647 |
Polymerase chain reaction To minimize the chance of contamination, investigators should reserve separate rooms for reagent preparation, the PCR, and analysis of product. Reagents should be dispensed into single-use aliquots. Pipetters with disposable plungers and extra-long pipette tips should be routinely used. A 1971 paper in the "Journal of Molecular Biology" by and co-workers in the laboratory of H. Gobind Khorana first described a method of using an enzymatic assay to replicate a short DNA template with primers "in vitro". However, this early manifestation of the basic PCR principle did not receive much attention at the time and the invention of the polymerase chain reaction in 1983 is generally credited to Kary Mullis. When Mullis developed the PCR in 1983, he was working in Emeryville, California for Cetus Corporation, one of the first biotechnology companies, where he was responsible for synthesizing short chains of DNA. Mullis has written that he first conceived the idea for PCR while cruising along the Pacific Coast Highway one night in his car. He was playing in his mind with a new way of analyzing changes (mutations) in DNA when he realized that he had instead invented a method of amplifying any DNA region through repeated cycles of duplication driven by DNA polymerase. In "Scientific American", Mullis summarized the procedure: "Beginning with a single molecule of the genetic material DNA, the PCR can generate 100 billion similar molecules in an afternoon. The reaction is easy to execute | https://en.wikipedia.org/wiki?curid=23647 |
Polymerase chain reaction It requires no more than a test tube, a few simple reagents, and a source of heat." DNA fingerprinting was first used for paternity testing in 1988. Mullis was awarded the Nobel Prize in Chemistry in 1993 for his invention, seven years after he and his colleagues at Cetus first put his proposal to practice. Mullis's 1985 paper with R. K. Saiki and H. A. Erlich, “Enzymatic Amplification of β-globin Genomic Sequences and Restriction Site Analysis for Diagnosis of Sickle Cell Anemia”—the polymerase chain reaction invention (PCR) – was honored by a Citation for Chemical Breakthrough Award from the Division of History of Chemistry of the American Chemical Society in 2017. Some controversies have remained about the intellectual and practical contributions of other scientists to Mullis' work, and whether he had been the sole inventor of the PCR principle (see below). At the core of the PCR method is the use of a suitable DNA polymerase able to withstand the high temperatures of > required for separation of the two DNA strands in the DNA double helix after each replication cycle. The DNA polymerases initially employed for in vitro experiments presaging PCR were unable to withstand these high temperatures. So the early procedures for DNA replication were very inefficient and time-consuming, and required large amounts of DNA polymerase and continuous handling throughout the process | https://en.wikipedia.org/wiki?curid=23647 |
Polymerase chain reaction The discovery in 1976 of Taq polymerase—a DNA polymerase purified from the thermophilic bacterium, "Thermus aquaticus", which naturally lives in hot () environments such as hot springs—paved the way for dramatic improvements of the PCR method. The DNA polymerase isolated from "T. aquaticus" is stable at high temperatures remaining active even after DNA denaturation, thus obviating the need to add new DNA polymerase after each cycle. This allowed an automated thermocycler-based process for DNA amplification. The PCR technique was patented by Kary Mullis and assigned to Cetus Corporation, where Mullis worked when he invented the technique in 1983. The "Taq" polymerase enzyme was also covered by patents. There have been several high-profile lawsuits related to the technique, including an unsuccessful lawsuit brought by DuPont. The Swiss pharmaceutical company Hoffmann-La Roche purchased the rights to the patents in 1992 and currently holds those that are still protected. A related patent battle over the Taq polymerase enzyme is still ongoing in several jurisdictions around the world between Roche and Promega. The legal arguments have extended beyond the lives of the original PCR and Taq polymerase patents, which expired on March 28, 2005. | https://en.wikipedia.org/wiki?curid=23647 |
Plasma ashing In semiconductor manufacturing plasma ashing is the process of removing the photoresist (light sensitive coating) from an etched wafer. Using a plasma source, a monatomic (single atom) substance known as a reactive species is generated. Oxygen or fluorine are the most common reactive species. The reactive species combines with the photoresist to form ash which is removed with a vacuum pump. Typically, monatomic oxygen plasma is created by exposing oxygen gas at a low pressure (O) to high power radio waves, which ionise it. This process is done under vacuum in order to create a plasma. As the plasma is formed, many free radicals are created which could damage the wafer. Newer, smaller circuitry is increasingly susceptible to these particles. Originally, plasma was generated in the process chamber, but as the need to get rid of free radicals has increased, many machines now use a downstream plasma configuration, where plasma is formed remotely and the desired particles are channeled to the wafer. This allows electrically charged particles time to recombine before they reach the wafer surface, and prevents damage to the wafer surface. Two forms of plasma ashing are typically performed on wafers. High temperature ashing, or stripping, is performed to remove as much photo resist as possible, while the "descum" process is used to remove residual photo resist in trenches. The main difference between the two processes is the temperature the wafer is exposed to while in an ashing chamber | https://en.wikipedia.org/wiki?curid=23731 |
Plasma ashing Monatomic oxygen is electrically neutral and although it does recombine during the channeling, it does so at a slower rate than the positively or negatively charged free radicals, which attract one another. This means that when all of the free radicals have recombined, there is still a portion of the active species available for process. Because a large portion of the active species is lost to recombination, process times may take longer. To some extent, these longer process times can be mitigated by increasing the temperature of the reaction area. | https://en.wikipedia.org/wiki?curid=23731 |
Pharmacology is a branch of pharmaceutical sciences which is concerned with the study of drug or medication action, where a drug can be broadly or narrowly defined as any man-made, natural, or endogenous (from within the body) molecule which exerts a biochemical or physiological effect on the cell, tissue, organ, or organism (sometimes the word pharmacon is used as a term to encompass these endogenous and exogenous bioactive species). More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function. If substances have medicinal properties, they are considered pharmaceuticals. The field encompasses drug composition and properties, synthesis and drug design, molecular and cellular mechanisms, organ/systems mechanisms, signal transduction/cellular communication, molecular diagnostics, interactions, chemical biology, therapy, and medical applications and antipathogenic capabilities. The two main areas of pharmacology are pharmacodynamics and pharmacokinetics. Pharmacodynamics studies the effects of a drug on biological systems, and pharmacokinetics studies the effects of biological systems on a drug. In broad terms, pharmacodynamics discusses the chemicals with biological receptors, and pharmacokinetics discusses the absorption, distribution, metabolism, and excretion (ADME) of chemicals from the biological systems. is not synonymous with pharmacy and the two terms are frequently confused | https://en.wikipedia.org/wiki?curid=24354 |
Pharmacology Pharmacology, a biomedical science, deals with the research, discovery, and characterization of chemicals which show biological effects and the elucidation of cellular and organismal function in relation to these chemicals. In contrast, pharmacy, a health services profession, is concerned with the application of the principles learned from pharmacology in its clinical settings; whether it be in a dispensing or clinical care role. In either field, the primary contrast between the two is their distinctions between direct-patient care, pharmacy practice, and the science-oriented research field, driven by pharmacology. The word "pharmacology" is derived from Greek , "pharmakon", "drug, poison, (paranormal)|, "-logia" "study of", "knowledge of" (cf. the etymology of "pharmacy"). Pharmakon is related to pharmakos, the ritualistic sacrifice or exile of a human scapegoat or victim in Ancient Greek religion. The origins of clinical pharmacology date back to the Middle Ages, with pharmacognosy and Avicenna's "The Canon of Medicine", Peter of Spain's "Commentary on Isaac", and John of St Amand's "Commentary on the Antedotary of Nicholas". Early pharmacology focused on herbalism and natural substances, mainly plant extracts. Medicines were compiled in books called pharmacopoeias. Crude drugs have been used since prehistory as a preparation of substances from natural sources. However, the active ingredient of crude drugs are not purified and the substance is adulterated with other substances | https://en.wikipedia.org/wiki?curid=24354 |
Pharmacology Traditional medicine varies between cultures and may be specific to a particular culture, such as in traditional Chinese, Mongolian, Tibetan and Korean medicine. However much of this has since been regarded as pseudoscience. Pharmacological substances known as entheogens may have spiritual and religious use and historical context. In the 17th century, the English physician Nicholas Culpeper translated and used pharmacological texts. Culpeper detailed plants and the conditions they could treat. In the 18th century, much of clinical pharmacology was established by the work of William Withering. as a scientific discipline did not further advance until the mid-19th century amid the great biomedical resurgence of that period. Before the second half of the nineteenth century, the remarkable potency and specificity of the actions of drugs such as morphine, quinine and digitalis were explained vaguely and with reference to extraordinary chemical powers and affinities to certain organs or tissues. The first pharmacology department was set up by Rudolf Buchheim in 1847, in recognition of the need to understand how therapeutic drugs and poisons produced their effects. Subsequently, the first pharmacology department in England was set up in 1905 at University College London. developed in the 19th century as a biomedical science that applied the principles of scientific experimentation to therapeutic contexts. The advancement of research techniques propelled pharmacological research and understanding | https://en.wikipedia.org/wiki?curid=24354 |
Pharmacology The development of the organ bath preparation, where tissue samples are connected to recording devices, such as a myograph, and physiological responses are recorded after drug application, allowed analysis of drugs' effects on tissues. The development of the ligand binding assay in 1945 allowed quantification of the binding affinity of drugs at chemical targets. Modern pharmacologists use techniques from genetics, molecular biology, biochemistry, and other advanced tools to transform information about molecular mechanisms and targets into therapies directed against disease, defects or pathogens, and create methods for preventative care, diagnostics, and ultimately personalized medicine. The discipline of pharmacology can be divided into many sub disciplines each with a specific focus. can also focus on specific systems comprising the body. Divisions related to bodily systems study the effects of drugs in different systems of the body. These include neuropharmacology, in the central and peripheral nervous systems; immunopharmacology in the immune system. Other divisions include cardiovascular, renal and endocrine pharmacology. Psychopharmacology, is the study of the effects of drugs on the psyche, mind and behavior, such as the behavioral effects of psychoactive drugs. It incorporates approaches and techniques from neuropharmacology, animal behavior and behavioral neuroscience, and is interested in the behavioral and neurobiological mechanisms of action of psychoactive drugs | https://en.wikipedia.org/wiki?curid=24354 |
Pharmacology The related field of neuropsychopharmacology focuses on the effects of drugs at the overlap between the nervous system and the psyche. Pharmacometabolomics, also known as pharmacometabonomics, is a field which stems from metabolomics, the quantification and analysis of metabolites produced by the body. It refers to the direct measurement of metabolites in an individual's bodily fluids, in order to predict or evaluate the metabolism of pharmaceutical compounds, and to better understand the pharmacokinetic profile of a drug. Pharmacometabolomics can be applied to measure metabolite levels following the administration of a drug, in order to monitor the effects of the drug on metabolic pathways. Pharmacomicrobiomics studies the effect of microbiome variations on drug disposition, action, and toxicity. Pharmacomicrobiomics is concerned with the interaction between drugs and the gut microbiome. Pharmacogenomics is the application of genomic technologies to drug discovery and further characterization of drugs related to an organism's entire genome. For pharmacology regarding individual genes, pharmacogenetics studies how genetic variation gives rise to differing responses to drugs. Pharmacoepigenetics studies the underlying epigenetic marking patterns that lead to variation in an individual's response to medical treatment. can be applied within clinical sciences | https://en.wikipedia.org/wiki?curid=24354 |
Pharmacology Clinical pharmacology is the basic science of pharmacology focusing on the application of pharmacological principles and methods in the medical clinic and towards patient care and outcomes. An example of this is posology, which is the study of how medicines are dosed. is closely related to toxicology. Both pharmacology and toxicology are scientific disciplines that focus on understanding the properties and actions of chemicals. However, pharmacology emphasizes the therapeutic effects of chemicals, usually drugs or compounds that could become drugs, whereas toxicology is the study of chemical's adverse effects and risk assessment. Pharmacological knowledge is used to advise pharmacotherapy in medicine and pharmacy. Drug discovery is the field of study concerned with creating new drugs. It encompasses the subfields of drug design and development. Drug discovery starts with drug design, which is the inventive process of finding new drugs. In the most basic sense, this involves the design of molecules that are complementary in shape and charge to a given biomolecular target. After a lead compound has been identified through drug discovery, drug development involves bringing the drug to the market. Drug discovery is related to pharmacoeconomics, which is the sub-discipline of health economics that considers the value of drugs Pharmacoeconomics evaluates the cost and benefits of drugs in order to guide optimal healthcare resource allocation | https://en.wikipedia.org/wiki?curid=24354 |
Pharmacology The techniques used for the discovery, formulation, manufacturing and quality control of drugs discovery is studied by pharmaceutical engineering, a branch of engineering. Safety pharmacology specialises in detecting and investigating potential undesirable effects of drugs. Development of medication is a vital concern to medicine, but also has strong economical and political implications. To protect the consumer and prevent abuse, many governments regulate the manufacture, sale, and administration of medication. In the United States, the main body that regulates pharmaceuticals is the Food and Drug Administration; they enforce standards set by the United States Pharmacopoeia. In the European Union, the main body that regulates pharmaceuticals is the EMA, and they enforce standards set by the European Pharmacopoeia. The metabolic stability and the reactivity of a library of candidate drug compounds have to be assessed for drug metabolism and toxicological studies. Many methods have been proposed for quantitative predictions in drug metabolism; one example of a recent computational method is SPORCalc. A slight alteration to the chemical structure of a medicinal compound could alter its medicinal properties, depending on how the alteration relates to the structure of the substrate or receptor site on which it acts: this is called the structural activity relationship (SAR) | https://en.wikipedia.org/wiki?curid=24354 |
Pharmacology When a useful activity has been identified, chemists will make many similar compounds called analogues, to try to maximize the desired medicinal effect(s). This can take anywhere from a few years to a decade or more, and is very expensive. One must also determine how safe the medicine is to consume, its stability in the human body and the best form for delivery to the desired organ system, such as tablet or aerosol. After extensive testing, which can take up to six years, the new medicine is ready for marketing and selling. Because of these long timescales, and because out of every 5000 potential new medicines typically only one will ever reach the open market, this is an expensive way of doing things, often costing over 1 billion dollars. To recoup this outlay pharmaceutical companies may do a number of things: The inverse benefit law describes the relationship between a drugs therapeutic benefits and its marketing. When designing drugs, the placebo effect must be considered to assess the drug's true therapeutic value. Drug development uses techniques from medicinal chemistry to chemically design drugs. This overlaps with the biological approach of finding targets and physiological effects. can be studied in relation to wider contexts than the physiology of individuals. For example, pharmacoepidemiology is the study of the effects of drugs in large numbers of people and relates to the broader fields of epidemiology and public health | https://en.wikipedia.org/wiki?curid=24354 |
Pharmacology Pharmacoenvironmentology or environmental pharmacology is a field intimately linked with ecology and public health. Human health and ecology are intimately related so environmental pharmacology studies the environmental effect of drugs and pharmaceuticals and personal care products in the environment. Drugs may also have ethnocultural importance, so ethnopharmacology studies the ethnic and cultural aspects of pharmacology. Photopharmacology is an emerging approach in medicine in which drugs are activated and deactivated with light. The energy of light is used to change for shape and chemical properties of the drug, resulting in different biological activity. This is done to ultimately achieve control when and where drugs are active in a reversible manner, to prevent side effects and pollution of drugs into the environment. The study of chemicals requires intimate knowledge of the biological system affected. With the knowledge of cell biology and biochemistry increasing, the field of pharmacology has also changed substantially. It has become possible, through molecular analysis of receptors, to design chemicals that act on specific cellular signaling or metabolic pathways by affecting sites directly on cell-surface receptors (which modulate and mediate cellular signaling pathways controlling cellular function). Chemicals can have pharmacologically relevant properties and effects. Pharmacokinetics describes the effect of the body on the chemical (e.g | https://en.wikipedia.org/wiki?curid=24354 |
Pharmacology half-life and volume of distribution), and pharmacodynamics describes the chemical's effect on the body (desired or toxic). is typically studied with respect to particular systems, for example endogenous neurotransmitter systems. The major systems studied in pharmacology can be categorised by their ligands and include acetylcholine, adrenaline, glutamate, GABA, dopamine, histamine, serotonin, cannabinoid and opioid. Molecular targets in pharmacology include receptors, enzymes and membrane transport proteins. Enzymes can be targeted with enzyme inhibitors. Receptors are typically categorised based on structure and function. Major receptor types studied in pharmacology include G protein coupled receptors, ligand gated ion channels and receptor tyrosine kinases. Pharmacological models include the Hill equation, Cheng-Prusoff equation and Schild regression. Pharmacological theory often investigates the binding affinity of ligands to their receptors. Medication is said to have a narrow or wide "therapeutic index," certain safety factor or "therapeutic window". This describes the ratio of desired effect to toxic effect. A compound with a narrow therapeutic index (close to one) exerts its desired effect at a dose close to its toxic dose. A compound with a wide therapeutic index (greater than five) exerts its desired effect at a dose substantially below its toxic dose | https://en.wikipedia.org/wiki?curid=24354 |
Pharmacology Those with a narrow margin are more difficult to dose and administer, and may require therapeutic drug monitoring (examples are warfarin, some antiepileptics, aminoglycoside antibiotics). Most anti-cancer drugs have a narrow therapeutic margin: toxic side-effects are almost always encountered at doses used to kill tumors. The effect of drugs can be described with Loewe additivity. Pharmacokinetics is the study of the bodily absorption, distribution, metabolism, and excretion of drugs. When describing the pharmacokinetic properties of the chemical that is the active ingredient or active pharmaceutical ingredient (API), pharmacologists are often interested in "L-ADME": Drug metabolism is assessed in pharmacokinetics and is important in drug research and prescribing. In the United States, the Food and Drug Administration (FDA) is responsible for creating guidelines for the approval and use of drugs. The FDA requires that all approved drugs fulfill two requirements: Gaining FDA approval usually takes several years. Testing done on animals must be extensive and must include several species to help in the evaluation of both the effectiveness and toxicity of the drug. The dosage of any drug approved for use is intended to fall within a range in which the drug produces a therapeutic effect or desired outcome. The safety and effectiveness of prescription drugs in the U.S. are regulated by the federal Prescription Drug Marketing Act of 1987 | https://en.wikipedia.org/wiki?curid=24354 |
Pharmacology The Medicines and Healthcare products Regulatory Agency (MHRA) has a similar role in the UK. Medicare Part D is a prescription drug plan in the U.S. The Prescription Drug Marketing Act (PDMA) is an act related to drug policy. Prescription drugs are drugs regulated by legislation. The International Union of Basic and Clinical Pharmacology, Federation of European Pharmacological Societies and European Association for Clinical and Therapeutics are organisations representing standardisation and regulation of clinical and scientific pharmacology. Systems for medical classification of drugs with pharmaceutical codes have been developed. These include the National Drug Code (NDC), administered by Food and Drug Administration.; Drug Identification Number (DIN), administered by Health Canada under the Food and Drugs Act; Hong Kong Drug Registration, administered by the Pharmaceutical Service of the Department of Health (Hong Kong) and National Pharmaceutical Product Index in South Africa. Hierarchical systems have also been developed, including the Anatomical Therapeutic Chemical Classification System (AT, or ATC/DDD), administered by World Health Organization; Generic Product Identifier (GPI), a hierarchical classification number published by MediSpan and SNOMED, C axis. Ingredients of drugs have been categorised by Unique Ingredient Identifier. The study of pharmacology overlaps with biomedical sciences and is study of the effects of drugs on living organisms | https://en.wikipedia.org/wiki?curid=24354 |
Pharmacology Pharmacological research can lead to new drug discoveries, and promote a better understanding of human physiology. Students of pharmacology must have detailed working knowledge of aspects in physiology, pathology and chemistry. Modern pharmacology is interdisciplinary and relates to biophysical and computational sciences, and analytical chemistry. Whereas a pharmacy student will eventually work in a pharmacy dispensing medications, a pharmacologist will typically work within a laboratory setting. Pharmacological research is important in academic research (medical and non-medical), private industrial positions, science writing, scientific patents and law, consultation, biotech and pharmaceutical employment, the alcohol industry, food industry, forensics/law enforcement, public health, and environmental/ecological sciences. is often taught to pharmacy and medicine students as part of a Medical School curriculum. | https://en.wikipedia.org/wiki?curid=24354 |
Outline of physics The following outline is provided as an overview of and topical guide to physics: Physics – natural science that involves the study of matter and its motion through spacetime, along with related concepts such as energy and force. More broadly, it is the general analysis of nature, conducted in order to understand how the universe behaves. Physics can be described as all of the following: History of physics – history of the physical science that studies matter and its motion through space-time, and related concepts such as energy and force Physics – branch of science that studies matter and its motion through space and time, along with related concepts such as energy and force. Physics is one of the "fundamental sciences" because the other natural sciences (like biology, geology etc.) deal with systems that seem to obey the laws of physics. According to physics, the physical laws of matter, energy and the fundamental forces of nature govern the interactions between particles and physical entities (such as planets, molecules, atoms or the subatomic particles) | https://en.wikipedia.org/wiki?curid=24489 |
Outline of physics Some of the basic pursuits of physics, which include some of the most prominent developments in modern science in the last millennium, include: Gravity, light, physical system, physical observation, physical quantity, physical state, physical unit, physical theory, physical experiment Theoretical concepts Mass–energy equivalence, particle, physical field, physical interaction, physical law, fundamental force, physical constant, wave Physics This is a list of the primary theories in physics, major subtopics, and concepts. Index of physics articles | https://en.wikipedia.org/wiki?curid=24489 |
RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. and DNA are nucleic acids, and, along with lipids, proteins and carbohydrates, constitute the four major macromolecules essential for all known forms of life. Like DNA, is assembled as a chain of nucleotides, but unlike DNA, is found in nature as a single strand folded onto itself, rather than a paired double strand. Cellular organisms use messenger (mRNA) to convey genetic information (using the nitrogenous bases of guanine, uracil, adenine, and cytosine, denoted by the letters G, U, A, and C) that directs synthesis of specific proteins. Many viruses encode their genetic information using an genome. Some molecules play an active role within cells by catalyzing biological reactions, controlling gene expression, or sensing and communicating responses to cellular signals. One of these active processes is protein synthesis, a universal function in which molecules direct the synthesis of proteins on ribosomes. This process uses transfer (tRNA) molecules to deliver amino acids to the ribosome, where ribosomal (rRNA) then links amino acids together to form coded proteins. Like DNA, most biologically active RNAs, including mRNA, tRNA, rRNA, snRNAs, and other non-coding RNAs, contain self-complementary sequences that allow parts of the to fold and pair with itself to form double helices. Analysis of these RNAs has revealed that they are highly structured | https://en.wikipedia.org/wiki?curid=25758 |
RNA Unlike DNA, their structures do not consist of long double helices, but rather collections of short helices packed together into structures akin to proteins. In this fashion, RNAs can achieve chemical catalysis (like enzymes). For instance, determination of the structure of the ribosome—an RNA-protein complex that catalyzes peptide bond formation—revealed that its active site is composed entirely of RNA. Each nucleotide in contains a ribose sugar, with carbons numbered 1' through 5'. A base is attached to the 1' position, in general, adenine (A), cytosine (C), guanine (G), or uracil (U). Adenine and guanine are purines, cytosine and uracil are pyrimidines. A phosphate group is attached to the 3' position of one ribose and the 5' position of the next. The phosphate groups have a negative charge each, making a charged molecule (polyanion). The bases form hydrogen bonds between cytosine and guanine, between adenine and uracil and between guanine and uracil. However, other interactions are possible, such as a group of adenine bases binding to each other in a bulge, or the GNRA tetraloop that has a guanine–adenine base-pair. An important structural component of that distinguishes it from DNA is the presence of a hydroxyl group at the 2' position of the ribose sugar. The presence of this functional group causes the helix to mostly take the A-form geometry, although in single strand dinucleotide contexts, can rarely also adopt the B-form most commonly observed in DNA | https://en.wikipedia.org/wiki?curid=25758 |
RNA The A-form geometry results in a very deep and narrow major groove and a shallow and wide minor groove. A second consequence of the presence of the 2'-hydroxyl group is that in conformationally flexible regions of an molecule (that is, not involved in formation of a double helix), it can chemically attack the adjacent phosphodiester bond to cleave the backbone. is transcribed with only four bases (adenine, cytosine, guanine and uracil), but these bases and attached sugars can be modified in numerous ways as the RNAs mature. Pseudouridine (Ψ), in which the linkage between uracil and ribose is changed from a C–N bond to a C–C bond, and ribothymidine (T) are found in various places (the most notable ones being in the TΨC loop of tRNA). Another notable modified base is hypoxanthine, a deaminated adenine base whose nucleoside is called inosine (I). Inosine plays a key role in the wobble hypothesis of the genetic code. There are more than 100 other naturally occurring modified nucleosides. The greatest structural diversity of modifications can be found in tRNA, while pseudouridine and nucleosides with 2'-O-methylribose often present in rare the most common. The specific roles of many of these modifications in are not fully understood. However, it is notable that, in ribosomal RNA, many of the post-transcriptional modifications occur in highly functional regions, such as the peptidyl transferase center and the subunit interface, implying that they are important for normal function | https://en.wikipedia.org/wiki?curid=25758 |
RNA The functional form of single-stranded molecules, just like proteins, frequently requires a specific tertiary structure. The scaffold for this structure is provided by secondary structural elements that are hydrogen bonds within the molecule. This leads to several recognizable "domains" of secondary structure like hairpin loops, bulges, and internal loops. Since is charged, metal ions such as Mg are needed to stabilise many secondary and tertiary structures. The naturally occurring enantiomer of is -composed of -ribonucleotides. All chirality centers are located in the -ribose. By the use of -ribose or rather -ribonucleotides, -can be synthesized. -is much more stable against degradation by RNase. Like other structured biopolymers such as proteins, one can define topology of a folded molecule. This is often done based on arrangement of intra-chain contacts within a folded RNA, termed as circuit topology. Synthesis of is usually catalyzed by an enzyme—polymerase—using DNA as a template, a process known as transcription. Initiation of transcription begins with the binding of the enzyme to a promoter sequence in the DNA (usually found "upstream" of a gene). The DNA double helix is unwound by the helicase activity of the enzyme. The enzyme then progresses along the template strand in the 3’ to 5’ direction, synthesizing a complementary molecule with elongation occurring in the 5’ to 3’ direction. The DNA sequence also dictates where termination of synthesis will occur | https://en.wikipedia.org/wiki?curid=25758 |
RNA Primary transcript RNAs are often modified by enzymes after transcription. For example, a poly(A) tail and a 5' cap are added to eukaryotic pre-mand introns are removed by the spliceosome. There are also a number of RNA-dependent polymerases that use as their template for synthesis of a new strand of RNA. For instance, a number of viruses (such as poliovirus) use this type of enzyme to replicate their genetic material. Also, RNA-dependent polymerase is part of the interference pathway in many organisms. Messenger (mRNA) is the that carries information from DNA to the ribosome, the sites of protein synthesis (translation) in the cell. The coding sequence of the mdetermines the amino acid sequence in the protein that is produced. However, many RNAs do not code for protein (about 97% of the transcriptional output is non-protein-coding in eukaryotes). These so-called non-coding RNAs ("ncRNA") can be encoded by their own genes (genes), but can also derive from mintrons. The most prominent examples of non-coding RNAs are transfer (tRNA) and ribosomal (rRNA), both of which are involved in the process of translation. There are also non-coding RNAs involved in gene regulation, processing and other roles. Certain RNAs are able to catalyse chemical reactions such as cutting and ligating other molecules, and the catalysis of peptide bond formation in the ribosome; these are known as ribozymes. According to the length of chain, includes small and long RNA | https://en.wikipedia.org/wiki?curid=25758 |
RNA Usually, small RNAs are shorter than 200 nt in length, and long RNAs are greater than 200 nt long. Long RNAs, also called large RNAs, mainly include long non-coding (lncRNA) and mRNA. Small RNAs mainly include 5.8S ribosomal (rRNA), 5S rRNA, transfer (tRNA), micro(miRNA), small interfering (siRNA), small nucleolar (snoRNAs), Piwi-interacting (piRNA), tRNA-derived small (tsRNA) and small rDNA-derived (srRNA). Messenger (mRNA) carries information about a protein sequence to the ribosomes, the protein synthesis factories in the cell. It is coded so that every three nucleotides (a codon) corresponds to one amino acid. In eukaryotic cells, once precursor m(pre-mRNA) has been transcribed from DNA, it is processed to mature mRNA. This removes its introns—non-coding sections of the pre-mRNA. The mis then exported from the nucleus to the cytoplasm, where it is bound to ribosomes and translated into its corresponding protein form with the help of tRNA. In prokaryotic cells, which do not have nucleus and cytoplasm compartments, mcan bind to ribosomes while it is being transcribed from DNA. After a certain amount of time, the message degrades into its component nucleotides with the assistance of ribonucleases. Transfer (tRNA) is a small chain of about 80 nucleotides that transfers a specific amino acid to a growing polypeptide chain at the ribosomal site of protein synthesis during translation | https://en.wikipedia.org/wiki?curid=25758 |
RNA It has sites for amino acid attachment and an anticodon region for codon recognition that binds to a specific sequence on the messenger chain through hydrogen bonding. Ribosomal (rRNA) is the catalytic component of the ribosomes. Eukaryotic ribosomes contain four different rmolecules: 18S, 5.8S, 28S and 5S rRNA. Three of the rmolecules are synthesized in the nucleolus, and one is synthesized elsewhere. In the cytoplasm, ribosomal and protein combine to form a nucleoprotein called a ribosome. The ribosome binds mand carries out protein synthesis. Several ribosomes may be attached to a single mat any time. Nearly all the found in a typical eukaryotic cell is rRNA. Transfer-messenger (tmRNA) is found in many bacteria and plastids. It tags proteins encoded by mRNAs that lack stop codons for degradation and prevents the ribosome from stalling. The earliest known regulators of gene expression were proteins known as repressors and activators, regulators with specific short binding sites within enhancer regions near the genes to be regulated. More recently, RNAs have been found to regulate genes as well. There are several kinds of RNA-dependent processes in eukaryotes regulating the expression of genes at various points, such as RNAi repressing genes post-transcriptionally, long non-coding RNAs shutting down blocks of chromatin epigenetically, and enhancer RNAs inducing increased gene expression | https://en.wikipedia.org/wiki?curid=25758 |
RNA In addition to these mechanisms in eukaryotes, both bacteria and archaea have been found to use regulatory RNAs extensively. Bacterial small and the CRISPR system are examples of such prokaryotic regulatory systems. Fire and Mello were awarded the 2006 Nobel Prize in Physiology or Medicine for discovering microRNAs (miRNAs), specific short molecules that can base-pair with mRNAs. Post-transcriptional expression levels of many genes can be controlled by interference, in which miRNAs, specific short molecules, pair with meregions and target them for degradation. This antisense-based process involves steps that first process the so that it can base-pair with a region of its target mRNAs. Once the base pairing occurs, other proteins direct the mto be destroyed by nucleases. Fire and Mello were awarded the 2006 Nobel Prize in Physiology or Medicine for this discovery. Next to be linked to regulation were Xist and other long noncoding RNAs associated with X chromosome inactivation. Their roles, at first mysterious, were shown by Jeannie T. Lee and others to be the silencing of blocks of chromatin via recruitment of Polycomb complex so that messenger could not be transcribed from them. Additional lncRNAs, currently defined as RNAs of more than 200 base pairs that do not appear to have coding potential, have been found associated with regulation of stem cell pluripotency and cell division. The third major group of regulatory RNAs is called enhancer RNAs | https://en.wikipedia.org/wiki?curid=25758 |
RNA It is not clear at present whether they are a unique category of RNAs of various lengths or constitute a distinct subset of lncRNAs. In any case, they are transcribed from enhancers, which are known regulatory sites in the DNA near genes they regulate. They up-regulate the transcription of the gene(s) under control of the enhancer from which they are transcribed. At first, regulatory was thought to be a eukaryotic phenomenon, a part of the explanation for why so much more transcription in higher organisms was seen than had been predicted. But as soon as researchers began to look for possible regulators in bacteria, they turned up there as well, termed as small (sRNA). Currently, the ubiquitous nature of systems of regulation of genes has been discussed as support for the World theory. Bacterial small RNAs generally act via antisense pairing with mto down-regulate its translation, either by affecting stability or affecting cis-binding ability. Riboswitches have also been discovered. They are cis-acting regulatory sequences acting allosterically. They change shape when they bind metabolites so that they gain or lose the ability to bind chromatin to regulate expression of genes. Archaea also have systems of regulatory RNA. The CRISPR system, recently being used to edit DNA "in situ", acts via regulatory RNAs in archaea and bacteria to provide protection against virus invaders. Many RNAs are involved in modifying other RNAs | https://en.wikipedia.org/wiki?curid=25758 |
RNA Introns are spliced out of pre-mby spliceosomes, which contain several small nuclear RNAs (snRNA), or the introns can be ribozymes that are spliced by themselves. can also be altered by having its nucleotides modified to nucleotides other than A, C, G and U. In eukaryotes, modifications of nucleotides are in general directed by small nucleolar RNAs (snoRNA; 60–300 nt), found in the nucleolus and cajal bodies. snoRNAs associate with enzymes and guide them to a spot on an by basepairing to that RNA. These enzymes then perform the nucleotide modification. rRNAs and tRNAs are extensively modified, but snRNAs and mRNAs can also be the target of base modification. can also be methylated. Like DNA, can carry genetic information. viruses have genomes composed of that encodes a number of proteins. The viral genome is replicated by some of those proteins, while other proteins protect the genome as the virus particle moves to a new host cell. Viroids are another group of pathogens, but they consist only of RNA, do not encode any protein and are replicated by a host plant cell's polymerase. Reverse transcribing viruses replicate their genomes by reverse transcribing DNA copies from their RNA; these DNA copies are then transcribed to new RNA. Retrotransposons also spread by copying DNA and from one another, and telomerase contains an that is used as template for building the ends of eukaryotic chromosomes | https://en.wikipedia.org/wiki?curid=25758 |
RNA Double-stranded (dsRNA) is with two complementary strands, similar to the DNA found in all cells, but with the replacement of thymine by uracil. dsforms the genetic material of some viruses (double-stranded viruses). Double-stranded RNA, such as viral or siRNA, can trigger interference in eukaryotes, as well as interferon response in vertebrates. In the late 1970s, it was shown that there is a single stranded covalently closed, i.e. circular form of expressed throughout the animal and plant kingdom (see circRNA). circRNAs are thought to arise via a "back-splice" reaction where the spliceosome joins a downstream donor to an upstream acceptor splice site. So far the function of circRNAs is largely unknown, although for few examples a microsponging activity has been demonstrated. Research on has led to many important biological discoveries and numerous Nobel Prizes. Nucleic acids were discovered in 1868 by Friedrich Miescher, who called the material 'nuclein' since it was found in the nucleus. It was later discovered that prokaryotic cells, which do not have a nucleus, also contain nucleic acids. The role of in protein synthesis was suspected already in 1939. Severo Ochoa won the 1959 Nobel Prize in Medicine (shared with Arthur Kornberg) after he discovered an enzyme that can synthesize in the laboratory. However, the enzyme discovered by Ochoa (polynucleotide phosphorylase) was later shown to be responsible for degradation, not synthesis | https://en.wikipedia.org/wiki?curid=25758 |
RNA In 1956 Alex Rich and David Davies hybridized two separate strands of to form the first crystal of whose structure could be determined by X-ray crystallography. The sequence of the 77 nucleotides of a yeast twas found by Robert W. Holley in 1965, winning Holley the 1968 Nobel Prize in Medicine (shared with Har Gobind Khorana and Marshall Nirenberg). During the early 1970s, retroviruses and reverse transcriptase were discovered, showing for the first time that enzymes could copy into DNA (the opposite of the usual route for transmission of genetic information). For this work, David Baltimore, Renato Dulbecco and Howard Temin were awarded a Nobel Prize in 1975. In 1976, Walter Fiers and his team determined the first complete nucleotide sequence of an virus genome, that of bacteriophage MS2. In 1977, introns and splicing were discovered in both mammalian viruses and in cellular genes, resulting in a 1993 Nobel to Philip Sharp and Richard Roberts. Catalytic molecules (ribozymes) were discovered in the early 1980s, leading to a 1989 Nobel award to Thomas Cech and Sidney Altman. In 1990, it was found in "Petunia" that introduced genes can silence similar genes of the plant's own, now known to be a result of interference. At about the same time, 22 nt long RNAs, now called microRNAs, were found to have a role in the development of "C. elegans" | https://en.wikipedia.org/wiki?curid=25758 |
RNA Studies on interference gleaned a Nobel Prize for Andrew Fire and Craig Mello in 2006, and another Nobel was awarded for studies on the transcription of to Roger Kornberg in the same year. The discovery of gene regulatory RNAs has led to attempts to develop drugs made of RNA, such as siRNA, to silence genes. Adding to the Nobel prizes awarded for research on in 2009 it was awarded for the elucidation of the atomic structure of the ribosome to Venki Ramakrishnan, Tom Steitz, and Ada Yonath. In 1967, Carl Woese hypothesized that might be catalytic and suggested that the earliest forms of life (self-replicating molecules) could have relied on both to carry genetic information and to catalyze biochemical reactions—an world. In March 2015, complex DNA and nucleotides, including uracil, cytosine and thymine, were reportedly formed in the laboratory under outer space conditions, using starter chemicals, such as pyrimidine, an organic compound commonly found in meteorites. Pyrimidine, like polycyclic aromatic hydrocarbons (PAHs), is one of the most carbon-rich compounds found in the Universe and may have been formed in red giants or in interstellar dust and gas clouds. | https://en.wikipedia.org/wiki?curid=25758 |
Restriction enzyme A restriction enzyme, restriction endonuclease, or " restrictase " is an enzyme that cleaves DNA into fragments at or near specific recognition sites within molecules known as restriction sites. Restriction enzymes are one class of the broader endonuclease group of enzymes. Restriction enzymes are commonly classified into five types, which differ in their structure and whether they cut their DNA substrate at their recognition site, or if the recognition and cleavage sites are separate from one another. To cut DNA, all restriction enzymes make two incisions, once through each sugar-phosphate backbone (i.e. each strand) of the DNA double helix. These enzymes are found in bacteria and archaea and provide a defence mechanism against invading viruses. Inside a prokaryote, the restriction enzymes selectively cut up "foreign" DNA in a process called "restriction digestion"; meanwhile, host DNA is protected by a modification enzyme (a methyltransferase) that modifies the prokaryotic DNA and blocks cleavage. Together, these two processes form the restriction modification system. Over 3,000 restriction enzymes have been studied in detail, and more than 600 of these are available commercially. These enzymes are routinely used for DNA modification in laboratories, and they are a vital tool in molecular cloning. The term restriction enzyme originated from the studies of phage λ, a virus that infects bacteria, and the phenomenon of host-controlled restriction and modification of such bacterial phage or bacteriophage | https://en.wikipedia.org/wiki?curid=26194 |
Restriction enzyme The phenomenon was first identified in work done in the laboratories of Salvador Luria, Weigle and Giuseppe Bertani in the early 1950s. It was found that, for a bacteriophage λ that can grow well in one strain of "Escherichia coli", for example "E. coli" C, when grown in another strain, for example "E. coli" K, its yields can drop significantly, by as much as 3-5 orders of magnitude. The host cell, in this example "E. coli" K, is known as the restricting host and appears to have the ability to reduce the biological activity of the phage λ. If a phage becomes established in one strain, the ability of that phage to grow also becomes restricted in other strains. In the 1960s, it was shown in work done in the laboratories of Werner Arber and Matthew Meselson that the restriction is caused by an enzymatic cleavage of the phage DNA, and the enzyme involved was therefore termed a restriction enzyme. The restriction enzymes studied by Arber and Meselson were type I restriction enzymes, which cleave DNA randomly away from the recognition site. In 1970, Hamilton O. Smith, Thomas Kelly and Kent Wilcox isolated and characterized the first type II restriction enzyme, "Hin"dII, from the bacterium "Haemophilus influenzae". Restriction enzymes of this type are more useful for laboratory work as they cleave DNA at the site of their recognition sequence and are the most commonly used as a molecular biology tool | https://en.wikipedia.org/wiki?curid=26194 |
Restriction enzyme Later, Daniel Nathans and Kathleen Danna showed that cleavage of simian virus 40 (SV40) DNA by restriction enzymes yields specific fragments that can be separated using polyacrylamide gel electrophoresis, thus showing that restriction enzymes can also be used for mapping DNA. For their work in the discovery and characterization of restriction enzymes, the 1978 Nobel Prize for Physiology or Medicine was awarded to Werner Arber, Daniel Nathans, and Hamilton O. Smith. The discovery of restriction enzymes allows DNA to be manipulated, leading to the development of recombinant DNA technology that has many applications, for example, allowing the large scale production of proteins such as human insulin used by diabetics. Restriction enzymes likely evolved from a common ancestor and became widespread via horizontal gene transfer. In addition, there is mounting evidence that restriction endonucleases evolved as a selfish genetic element. Restriction enzymes recognize a specific sequence of nucleotides and produce a double-stranded cut in the DNA. The recognition sequences can also be classified by the number of bases in its recognition site, usually between 4 and 8 bases, and the number of bases in the sequence will determine how often the site will appear by chance in any given genome, e.g., a 4-base pair sequence would theoretically occur once every 4^4 or 256bp, 6 bases, 4^6 or 4,096bp, and 8 bases would be 4^8 or 65,536bp.<ref name="http://bioweb.uwlax.edu/genweb/molecular/seq_anal/restriction_map/restriction_map | https://en.wikipedia.org/wiki?curid=26194 |
Restriction enzyme htm">Restriction Map</ref> Many of them are palindromic, meaning the base sequence reads the same backwards and forwards. In theory, there are two types of palindromic sequences that can be possible in DNA. The "mirror-like" palindrome is similar to those found in ordinary text, in which a sequence reads the same forward and backward on a single strand of DNA, as in GTAATG. The "inverted repeat" palindrome is also a sequence that reads the same forward and backward, but the forward and backward sequences are found in complementary DNA strands (i.e., of double-stranded DNA), as in GTATAC (GTATAC being complementary to CATATG). Inverted repeat palindromes are more common and have greater biological importance than mirror-like palindromes. EcoRI digestion produces "sticky" ends, whereas SmaI restriction enzyme cleavage produces "blunt" ends: Recognition sequences in DNA differ for each restriction enzyme, producing differences in the length, sequence and strand orientation (5' end or 3' end) of a sticky-end "overhang" of an enzyme restriction. Different restriction enzymes that recognize the same sequence are known as neoschizomers. These often cleave in different locales of the sequence. Different enzymes that recognize and cleave in the same location are known as isoschizomers | https://en.wikipedia.org/wiki?curid=26194 |
Restriction enzyme Naturally occurring restriction endonucleases are categorized into four groups (Types I, II III, and IV) based on their composition and enzyme cofactor requirements, the nature of their target sequence, and the position of their DNA cleavage site relative to the target sequence. DNA sequence analyses of restriction enzymes however show great variations, indicating that there are more than four types. All types of enzymes recognize specific short DNA sequences and carry out the endonucleolytic cleavage of DNA to give specific fragments with terminal 5'-phosphates. They differ in their recognition sequence, subunit composition, cleavage position, and cofactor requirements, as summarised below: Type I restriction enzymes were the first to be identified and were first identified in two different strains (K-12 and B) of "E. coli". These enzymes cut at a site that differs, and is a random distance (at least 1000 bp) away, from their recognition site. Cleavage at these random sites follows a process of DNA translocation, which shows that these enzymes are also molecular motors. The recognition site is asymmetrical and is composed of two specific portions—one containing 3–4 nucleotides, and another containing 4–5 nucleotides—separated by a non-specific spacer of about 6–8 nucleotides. These enzymes are multifunctional and are capable of both restriction digestion and modification activities, depending upon the methylation status of the target DNA | https://en.wikipedia.org/wiki?curid=26194 |
Restriction enzyme The cofactors S-Adenosyl methionine (AdoMet), hydrolyzed adenosine triphosphate (ATP), and magnesium (Mg) ions, are required for their full activity. Type I restriction enzymes possess three subunits called HsdR, HsdM, and HsdS; HsdR is required for restriction digestion; HsdM is necessary for adding methyl groups to host DNA (methyltransferase activity), and HsdS is important for specificity of the recognition (DNA-binding) site in addition to both restriction digestion (DNA cleavage) and modification (DNA methyltransferase) activity. Typical type II restriction enzymes differ from type I restriction enzymes in several ways. They form homodimers, with recognition sites that are usually undivided and palindromic and 4–8 nucleotides in length. They recognize and cleave DNA at the same site, and they do not use ATP or AdoMet for their activity—they usually require only Mg as a cofactor. These enzymes cleave the phosphodiester bond of double helix DNA. It can either cleave at the center of both strands to yield a blunt end, or at a staggered position leaving overhangs called sticky ends. These are the most commonly available and used restriction enzymes. In the 1990s and early 2000s, new enzymes from this family were discovered that did not follow all the classical criteria of this enzyme class, and new subfamily nomenclature was developed to divide this large family into subcategories based on deviations from typical characteristics of type II enzymes. These subgroups are defined using a letter suffix | https://en.wikipedia.org/wiki?curid=26194 |
Restriction enzyme Type IIB restriction enzymes (e.g., BcgI and BplI) are multimers, containing more than one subunit. They cleave DNA on both sides of their recognition to cut out the recognition site. They require both AdoMet and Mg cofactors. Type IIE restriction endonucleases (e.g., NaeI) cleave DNA following interaction with two copies of their recognition sequence. One recognition site acts as the target for cleavage, while the other acts as an allosteric effector that speeds up or improves the efficiency of enzyme cleavage. Similar to type IIE enzymes, type IIF restriction endonucleases (e.g. NgoMIV) interact with two copies of their recognition sequence but cleave both sequences at the same time. Type IIG restriction endonucleases (e.g., Eco57I) do have a single subunit, like classical Type II restriction enzymes, but require the cofactor AdoMet to be active. Type IIM restriction endonucleases, such as DpnI, are able to recognize and cut methylated DNA. Type IIS restriction endonucleases (e.g., "Fok"I) cleave DNA at a defined distance from their non-palindromic asymmetric recognition sites; this characteristic is widely used to perform in-vitro cloning techniques such as Golden Gate cloning. These enzymes may function as dimers. Similarly, Type IIT restriction enzymes (e.g., Bpu10I and BslI) are composed of two different subunits. Some recognize palindromic sequences while others have asymmetric recognition sites. Type III restriction enzymes (e.g | https://en.wikipedia.org/wiki?curid=26194 |
Restriction enzyme , EcoP15) recognize two separate non-palindromic sequences that are inversely oriented. They cut DNA about 20–30 base pairs after the recognition site. These enzymes contain more than one subunit and require AdoMet and ATP cofactors for their roles in DNA methylation and restriction digestion, respectively. They are components of prokaryotic DNA restriction-modification mechanisms that protect the organism against invading foreign DNA. Type III enzymes are hetero-oligomeric, multifunctional proteins composed of two subunits, Res () and Mod (). The Mod subunit recognises the DNA sequence specific for the system and is a modification methyltransferase; as such, it is functionally equivalent to the M and S subunits of type I restriction endonuclease. Res is required for restriction digestion, although it has no enzymatic activity on its own. Type III enzymes recognise short 5–6 bp-long asymmetric DNA sequences and cleave 25–27 bp downstream to leave short, single-stranded 5' protrusions. They require the presence of two inversely oriented unmethylated recognition sites for restriction digestion to occur. These enzymes methylate only one strand of the DNA, at the N-6 position of adenosyl residues, so newly replicated DNA will have only one strand methylated, which is sufficient to protect against restriction digestion | https://en.wikipedia.org/wiki?curid=26194 |
Restriction enzyme Type III enzymes belong to the beta-subfamily of N6 adenine methyltransferases, containing the nine motifs that characterise this family, including motif I, the AdoMet binding pocket (FXGXG), and motif IV, the catalytic region (S/D/N (PP) Y/F). Type IV enzymes recognize modified, typically methylated DNA and are exemplified by the McrBC and Mrr systems of "E. coli". Type V restriction enzymes (e.g., the cas9-gRNA complex from CRISPRs) utilize guide RNAs to target specific non-palindromic sequences found on invading organisms. They can cut DNA of variable length, provided that a suitable guide RNA is provided. The flexibility and ease of use of these enzymes make them promising for future genetic engineering applications. Artificial restriction enzymes can be generated by fusing a natural or engineered DNA binding domain to a nuclease domain (often the cleavage domain of the type IIS restriction enzyme "Fok"I). Such artificial restriction enzymes can target large DNA sites (up to 36 bp) and can be engineered to bind to desired DNA sequences. Zinc finger nucleases are the most commonly used artificial restriction enzymes and are generally used in genetic engineering applications, but can also be used for more standard gene cloning applications. Other artificial restriction enzymes are based on the DNA binding domain of TAL effectors. In 2013, a new technology CRISPR-Cas9, based on a prokaryotic viral defense system, was engineered for editing the genome, and it was quickly adopted in laboratories | https://en.wikipedia.org/wiki?curid=26194 |
Restriction enzyme For more detail, read CRISPR (Clustered regularly interspaced short palindromic repeats). In 2017 a group in Illinois announced using an Argonaute protein taken from Pyrococcus furiosus (PfAgo) along with guide DNA to edit DNA as artificial restriction enzymes. The authors, however, retracted their study later that year. Artificial ribonucleases that act as restriction enzymes for RNA are also being developed. A PNA-based system, called PNAzymes, has a Cu(II)-2,9-dimethylphenanthroline group that mimics ribonucleases for specific RNA sequence and cleaves at a non-base-paired region (RNA bulge) of the targeted RNA formed when the enzyme binds the RNA. This enzyme shows selectivity by cleaving only at one site that either does not have a mismatch or is kinetically preferred out of two possible cleavage sites. Since their discovery in the 1970s, many restriction enzymes have been identified; for example, more than 3500 different Type II restriction enzymes have been characterized. Each enzyme is named after the bacterium from which it was isolated, using a naming system based on bacterial genus, species and strain. For example, the name of the EcoRI restriction enzyme was derived as shown in the box. Isolated restriction enzymes are used to manipulate DNA for different scientific applications. They are used to assist insertion of genes into plasmid vectors during gene cloning and protein production experiments | https://en.wikipedia.org/wiki?curid=26194 |
Restriction enzyme For optimal use, plasmids that are commonly used for gene cloning are modified to include a short "polylinker" sequence (called the multiple cloning site, or MCS) rich in restriction enzyme recognition sequences. This allows flexibility when inserting gene fragments into the plasmid vector; restriction sites contained naturally within genes influence the choice of endonuclease for digesting the DNA, since it is necessary to avoid restriction of wanted DNA while intentionally cutting the ends of the DNA. To clone a gene fragment into a vector, both plasmid DNA and gene insert are typically cut with the same restriction enzymes, and then glued together with the assistance of an enzyme known as a DNA ligase. Restriction enzymes can also be used to distinguish gene alleles by specifically recognizing single base changes in DNA known as single-nucleotide polymorphisms (SNPs). This is however only possible if a SNP alters the restriction site present in the allele. In this method, the restriction enzyme can be used to genotype a DNA sample without the need for expensive gene sequencing. The sample is first digested with the restriction enzyme to generate DNA fragments, and then the different sized fragments separated by gel electrophoresis. In general, alleles with correct restriction sites will generate two visible bands of DNA on the gel, and those with altered restriction sites will not be cut and will generate only a single band | https://en.wikipedia.org/wiki?curid=26194 |
Restriction enzyme A DNA map by restriction digest can also be generated that can give the relative positions of the genes. The different lengths of DNA generated by restriction digest also produce a specific pattern of bands after gel electrophoresis, and can be used for DNA fingerprinting. In a similar manner, restriction enzymes are used to digest genomic DNA for gene analysis by Southern blot. This technique allows researchers to identify how many copies (or paralogues) of a gene are present in the genome of one individual, or how many gene mutations (polymorphisms) have occurred within a population. The latter example is called restriction fragment length polymorphism (RFLP). Artificial restriction enzymes created by linking the "Fok"I DNA cleavage domain with an array of DNA binding proteins or zinc finger arrays, denoted zinc finger nucleases (ZFN), are a powerful tool for host genome editing due to their enhanced sequence specificity. ZFN work in pairs, their dimerization being mediated in-situ through the "Fok"I domain. Each zinc finger array (ZFA) is capable of recognizing 9–12 base pairs, making for 18–24 for the pair. A 5–7 bp spacer between the cleavage sites further enhances the specificity of ZFN, making them a safe and more precise tool that can be applied in humans. A recent Phase I clinical trial of ZFN for the targeted abolition of the CCR5 co-receptor for HIV-1 has been undertaken | https://en.wikipedia.org/wiki?curid=26194 |
Restriction enzyme Others have proposed using the bacteria R-M system as a model for devising human anti-viral gene or genomic vaccines and therapies since the RM system serves an innate defense-role in bacteria by restricting tropism by bacteriophages. There is research on REases and ZFN that can cleave the DNA of various human viruses, including HSV-2, high-risk HPVs and HIV-1, with the ultimate goal of inducing target mutagenesis and aberrations of human-infecting viruses. The human genome already contains remnants of retroviral genomes that have been inactivated and harnessed for self-gain. Indeed, the mechanisms for silencing active L1 genomic retroelements by the three prime repair exonuclease 1 (TREX1) and excision repair cross complementing 1(ERCC) appear to mimic the action of RM-systems in bacteria, and the non-homologous end-joining (NHEJ) that follows the use of ZFN without a repair template. Examples of restriction enzymes include: Key: <nowiki>*</nowiki> = blunt ends N = C or G or T or A W = A or T | https://en.wikipedia.org/wiki?curid=26194 |
Leonard McCoy Leonard H. "Bones" McCoy is a character in the American science fiction franchise "Star Trek". McCoy was most famously portrayed by actor DeForest Kelley in the from 1966 to 1969, and he also appears in the , six "Star Trek" movies, the pilot episode of "", and in numerous books, comics, and video games. After Kelley's death, actor Karl Urban assumed the role of McCoy in the "Star Trek" reboot film in 2009. McCoy was born in Atlanta, Georgia on 2227. The son of David, he attended the University of Mississippi and is a divorcé. McCoy later married Natira, the priestess of Yonada, characterized in the episode, "For the World Is Hollow and I Have Touched the Sky". In 2266, McCoy was posted as chief medical officer of the USS "Enterprise" under Captain James T. Kirk, who often calls him "Bones". McCoy and Kirk are good friends, even "brotherly". The passionate, sometimes cantankerous McCoy frequently argues with Kirk's other confidante, science officer Spock, and occasionally is prejudiced against Spock's Vulcan heritage. McCoy often plays the role of Kirk's conscience, offering a counterpoint to Spock's logic. McCoy is suspicious of technology, especially the transporter. As a physician, he prefers less intrusive treatment and believes in the body's innate recuperative powers. The character's nickname, "Bones", is a play on "sawbones", an epithet for physicians qualified as surgeons. When Kirk orders McCoy's commission reactivated in "" (1979); a resentful McCoy complains of being "drafted" | https://en.wikipedia.org/wiki?curid=27105 |
Leonard McCoy Spock transfers his "katra"—his knowledge and experience—into McCoy before dying in "" (1982). This causes mental anguish for McCoy, who in "" (1984) helps restore Spock's katra to his reanimated body. McCoy continues to serve on Kirk's crew aboard the captured Klingon ship in "" (1986). In "" (1989), McCoy (through the intervention of Spock's half-brother Sybok) reveals that he helped his father commit suicide to relieve him of his pain. Shortly after the suicide, a cure was found for his father's disease, and McCoy had carried the guilt about it with him until Sybok's intervention. In "" (1991), McCoy and Kirk escape from a Klingon prison world, and the "Enterprise" crew stops a plot to prevent peace between the United Federation of Planets and the Klingon Empire. Kelley reprised the role for the "Encounter at Farpoint" pilot episode of "" (1987), insisting upon no more than the minimum Screen Actors Guild payment for his appearance. In the "" episode "", McCoy mentions he has a daughter, Joanna. Although Chekov's friend Irina in the original series episode "The Way to Eden" was originally written as McCoy's daughter, it was changed before the episode was shot. In the 2009 "Star Trek" film, which takes place in an alternate, parallel reality, McCoy and Kirk become friends at Starfleet Academy, which McCoy joins after a divorce that he says "left [him] nothing but [his] bones." This line, improvised by Urban, explains how McCoy earned the nickname "Bones" | https://en.wikipedia.org/wiki?curid=27105 |
Leonard McCoy McCoy later helps get Kirk posted aboard the USS "Enterprise". He later becomes the chief medical officer after Doctor Puri is killed during an attack by Nero. McCoy remains aboard to see the "Enterprise" defeat Nero and his crew, with Kirk becoming the commanding officer of the ship. "The Guardian" called Urban's portrayal of McCoy in the 2009 film an "unqualified success", and "The New York Times" called the character "wild-eyed and funny". Slate.com said Urban came closer than the other actors to impersonating a character's original depiction. Kelley had worked with "Star Trek" creator Gene Roddenberry on previous television pilots, and he was Roddenberry's first choice to play the doctor aboard the USS "Enterprise". However, for the rejected pilot "" (1964), Roddenberry went with director Robert Butler's choice of John Hoyt to play Dr. Philip Boyce. For the second pilot, "Where No Man Has Gone Before" (1966), Roddenberry accepted director James Goldstone's decision to have Paul Fix play Dr. Mark Piper. Although Roddenberry wanted Kelley to play the character of ship's doctor, he did not put Kelley's name forward to NBC; the network never "rejected" the actor as Roddenberry sometimes suggested. Kelley's first broadcast appearance as Doctor was in "The Man Trap" (1966). Despite his character's prominence, Kelley's contract granted him only a "featuring" credit; it was not until the second season that he was given "starring" credit, at the urging of producer Robert Justman | https://en.wikipedia.org/wiki?curid=27105 |
Leonard McCoy Kelley was apprehensive about "Star Trek"s future, telling Roddenberry that the show was "going to be the biggest hit or the biggest miss God ever made". Kelley portrayed McCoy throughout the original "Star Trek" series and voiced the character in the animated "Star Trek". Kelley, who in his youth wanted to become a doctor like his uncle, but whose family could not pay for a medical education, in part drew upon his real-life experiences in creating McCoy: a doctor's "matter-of-fact" delivery of news of Kelley's mother's terminal cancer was the "abrasive sand" Kelley used in creating McCoy's demeanor. "Star Trek" writer D. C. Fontana said that while Roddenberry created the series, Kelley essentially created McCoy; everything done with the character was done with Kelley's input. "Exquisite chemistry" among Kelley, William Shatner and Leonard Nimoy manifested itself in their performances as McCoy, Captain James T. Kirk and science officer Spock, respectively. Nichelle Nichols, who played Uhura, referred to Kelley as her "sassy gentleman friend"; the friendship between the African-American Nichols and Southern Kelley was a real-life demonstration of the message Roddenberry hoped to convey through "Star Trek". For the 2009 "Star Trek" film, writers Roberto Orci and Alex Kurtzman saw McCoy as an "arbiter" in Kirk and Spock's relationship | https://en.wikipedia.org/wiki?curid=27105 |
Leonard McCoy While Spock represented "extreme logic, extreme science" and Kirk symbolized "extreme emotion and intuition", McCoy's role as "a very colorful doctor, essentially a very humanistic scientist" represented the "two extremes that often served as the glue that held the trio together". They chose to reveal that McCoy befriended Kirk first, explaining the "bias" in their friendship and why he would often be a "little dismissive" of Spock. Urban said the script was "very faithful" to the original character, including the "great compassion for humanity and that sense of irascibility" with which Kelley imbued the character.New Zealand-born Urban trained with a dialect coach to create McCoy's accent and reprised the role in its sequels "Star Trek Into Darkness" and "Star Trek Beyond". McCoy is someone to whom Kirk unburdens himself, but is a foil to Spock. He is Kirk's "friend, personal bartender, confidant, counselor, and priest". Spock and McCoy's bickering became so popular that Roddenberry wrote in a 1968 memo "we simply didn't realize ... how much the fans loved the bickering between our Arrowsmith and our Alien". Urban said McCoy has a "sense of irascibility with real passion for life and doing the right thing", and that "Spock's logic and McCoy's moral standing gave Kirk the benefit of having three brains instead of just one." Kelley said that his greatest thrill at "Star Trek" conventions was the number of people who told him they entered the medical profession because of the McCoy character | https://en.wikipedia.org/wiki?curid=27105 |
Leonard McCoy He received two or three letters a month from others reporting similar experiences. A friend observed that despite not becoming a doctor as he had hoped, Kelley's portrayal of McCoy had helped create many doctors. According to Kelley, "You can win awards and that sort of thing, but to influence the youth of the country ... is an award that is not handed out by the industry". In a humor column for the "Canadian Medical Association Journal", the ethicist Michael Yeo described the character of McCoy as "TV’s only true physician" and "someone who has broken free from the yoke of ethics and practises the art and science of medicine beyond the stultifying opposition of paternalism and autonomy". Twenty times on the original "Star Trek", McCoy declares someone or something deceased with the line, "He's dead", "He's dead, Jim", or something similar. The phrase so became a catchphrase of the character that Kelley joked that the line would appear on his tombstone—and it appeared in the first sentence of at least one obituary—but disliked repeating such lines and refused to say it in "" when Spock is near death, since the levity brought by the catchphrase seemed in poor taste for the gravitas of the moment. Kelley and James Doohan (Scotty) agreed to swap their lines, so McCoy warns Kirk against opening the engineering doors while Scotty says, "He's dead already". University of Southern California literature professor Henry Jenkins cites Dr | https://en.wikipedia.org/wiki?curid=27105 |
Leonard McCoy McCoy's "He's dead, Jim" line as an example of fans actively participating in the creation of an underground culture in which they derive pleasure by repeating memorable lines as part of constructing new mythologies and alternative social communities. Another of McCoy's catchphrases is his "I'm a doctor, (Jim) not a(n)..." statements, delivered by Kelley 11 times, and three times (by Karl Urban) in later films. McCoy repeats the line when he must perform some task beyond his medical skills, such as the "classic moment" when he is confronted with the unusual silicon-based Horta alien in "The Devil in the Dark" (1967), saying, "I'm a doctor, not a bricklayer." Kelley himself parodied the phrase in a brief 1992 commercial for Trivial Pursuit's 10th Anniversary Edition, in which the question is asked "How many chambers are there in a human heart?" Kelley appears on screen and replies "How should I know? I'm an actor, not a doctor!". In 2012, IGN ranked the character Doctor McCoy, as depicted in the original series, its films, and the 2009 film "Star Trek", as the 5th top character of the "Star Trek" universe, behind Data, Picard, Spock, and Kirk. In 2016, Doctor McCoy was ranked as the fifth most important character of Starfleet within the "Star Trek" science fiction universe by "Wired" magazine. In 2016, SyFy ranked McCoy 3rd of the six main-cast space doctor's of the "Star Trek" Franchise | https://en.wikipedia.org/wiki?curid=27105 |
Leonard McCoy In 2017, Screen Rant ranked the Kelvin timeline McCoy, played by actor Karl Urban, as the 17th most attractive person in the "Star Trek" universe. In 2018, "The Wrap" placed Doctor McCoy as 6th out 39 in a ranking of main cast characters of the "Star Trek" franchise. In 2018, CBR ranked McCoy as the 11th best Starfleet character of "Star Trek." | https://en.wikipedia.org/wiki?curid=27105 |
Stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and divide indefinitely to produce more of the same stem cell. They are the earliest type of cell in a cell lineage. They are found in both embryonic and adult organisms, but they have slightly different properties in each. They are usually distinguished from progenitor cells, which cannot divide indefinitely, and precursor or blast cells, which are usually committed to differentiating into one cell type. In mammals, the roughly 50–150 cells that make up the inner cell mass during the blastocyst stage of embryonic development, around days 5–14, have stem-cell capability. "In vivo", they eventually differentiate into all of the body's cell types (i.e., they are pluripotent). This process starts with the differentiation into the three germ layers – the ectoderm, mesoderm and endoderm – at the gastrulation stage. However, when they are isolated and cultured "in vitro", they can be kept in the stem-cell stage and are known as embryonic stem cells (ESCs). Adult stem cells are found in a few select locations in the body, known as niches, such as those in the bone marrow or gonads. They exist to replenish rapidly lost cell types and are multipotent or unipotent, meaning they only differentiate into a few cell types or one cell type | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell In mammals, they include, among others, hematopoietic stem cells, which replenish blood and immune cells, basal cells, which maintain the skin epithelium, and mesenchymal stem cells, which maintain bone, cartilage, muscle and fat cells. Adult stem cells constitute a small minority of cells; they are vastly outnumbered by the progenitor cells and terminally differentiated cells that they differentiate into. Research into stem cells grew out of findings by Canadian biologists Ernest A. McCulloch and James E. Till at the University of Toronto in the 1960s. , the only established medical therapy using stem cells is hematopoietic stem cell transplantation, first performed in 1958 by French oncologist Georges Mathé. Since 1998, it has been possible to culture and differentiate human embryonic stem cells (in stem-cell lines). The process of isolating these cells has been controversial, because it typically results in the destruction of the embryo. Sources for isolating ESCs have been restricted in some European countries and Canada, but others such as the UK and China have promoted the research. Somatic cell nuclear transfer is a cloning method that can be used to create a cloned embryo for the use of its embryonic stem cells in stem cell therapy. In 2006, a Japanese team led by Shinya Yamanaka discovered a method to convert mature body cells back into stem cells. These were termed induced pluripotent stem cells (iPSCs) | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell The key properties of a stem cell were first defined by Ernest McCulloch and James Till in the early 1960s. They discovered the blood-forming stem cell, the hematopoietic stem cell (HSC), through their pioneering work in mice. McCulloch and Till began a series of experiments in which bone marrow cells were injected into irradiated mice. They observed lumps in the spleens of the mice that were linearly proportional to the number of bone marrow cells injected. They hypothesized that each lump (colony) was a clone arising from a single marrow cell (stem cell). In subsequent work, McCulloch and Till, joined by graduate student Andy Becker and senior scientist Lou Siminovitch, confirmed that each lump did in fact arise from a single cell. Their results were published in "Nature" in 1963. In that same year, Siminovitch was a lead investigator for studies that found colony-forming cells were capable of self-renewal, which is a key defining property of stem cells that Till and McCulloch had theorized. The first therapy using stem cells was a bone marrow transplant performed by French oncologist Georges Mathé in 1958 on five workers at the Vinča Nuclear Institute in Yugoslavia who had been affected by a criticality accident. The workers all survived. In 1981, embryonic stem (ES) cells were first isolated and successfully cultured using mouse blastocysts by British biologists Martin Evans and Matthew Kaufman | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell This allowed the formation of murine genetic models, a system in which the genes of mice are deleted or altered in order to study their function in pathology. By 1998, embryonic stem cells were first isolated by American biologist James Thomson, which made it possible to have new transplantation methods or various cell types for testing new treatments. In 2006, Shinya Yamanaka’s team in Kyoto, Japan converted fibroblasts into pluripotent stem cells by modifying the expression of only four genes. The feat represents the origin of induced pluripotent stem cells, known as iPS cells. The classical definition of a stem cell requires that it possesses two properties: Two mechanisms ensure that a stem cell population is maintained (doesn't shrink in size): 1. Asymmetric cell division: a stem cell divides into one mother cell, which is identical to the original stem cell, and another daughter cell, which is differentiated. When a stem cell self-renews, it divides and does not disrupt the undifferentiated state. This self-renewal demands control of cell cycle as well as upkeep of multipotency or pluripotency, which all depends on the stem cell. 2. Stochastic differentiation: when one stem cell grows and divides into two differentiated daughter cells, another stem cell undergoes mitosis and produces two stem cells identical to the original. Stem cells use telomerase, a protein that restores telomeres, to protect their DNA and extend their cell division limit (the Hayflick limit) | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell. In practice, stem cells are identified by whether they can regenerate tissue. For example, the defining test for bone marrow or hematopoietic stem cells (HSCs) is the ability to transplant the cells and save an individual without HSCs. This demonstrates that the cells can produce new blood cells over a long term. It should also be possible to isolate stem cells from the transplanted individual, which can themselves be transplanted into another individual without HSCs, demonstrating that the stem cell was able to self-renew. Properties of stem cells can be illustrated "in vitro", using methods such as clonogenic assays, in which single cells are assessed for their ability to differentiate and self-renew. Stem cells can also be isolated by their possession of a distinctive set of cell surface markers. However, "in vitro" culture conditions can alter the behavior of cells, making it unclear whether the cells shall behave in a similar manner "in vivo". There is considerable debate as to whether some proposed adult cell populations are truly stem cells. Embryonic stem cells (ESCs) are the cells of the inner cell mass of a blastocyst, formed prior to implantation in the uterus. In human embryonic development the blastocyst stage is reached 4–5 days after fertilization, at which time it consists of 50–150 cells | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell ESCs are pluripotent and give rise during development to all derivatives of the three germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the extraembryonic membranes or to the placenta. During embryonic development the cells of the inner cell mass continuously divide and become more specialized. For example, a portion of the ectoderm in the dorsal part of the embryo specializes as 'neurectoderm', which will become the future central nervous system. Later in development, neurulation causes the neurectoderm to form the neural tube. At the neural tube stage, the anterior portion undergoes encephalization to generate or 'pattern' the basic form of the brain. At this stage of development, the principal cell type of the CNS is considered a neural stem cell. The neural stem cells self-renew and at some point transition into radial glial progenitor cells (RGPs). Early-formed RGPs self-renew by symmetrical division to form a reservoir group of progenitor cells. These cells transition to a neurogenic state and start to divide asymmetrically to produce a large diversity of many different neuron types, each with unique gene expression, morphological, and functional characteristics. The process of generating neurons from radial glial cells is called neurogenesis | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell The radial glial cell, has a distinctive bipolar morphology with highly elongated processes spanning the thickness of the neural tube wall. It shares some glial characteristics, most notably the expression of glial fibrillary acidic protein (GFAP). The radial glial cell is the primary neural stem cell of the developing vertebrate CNS, and its cell body resides in the ventricular zone, adjacent to the developing ventricular system. Neural stem cells are committed to the neuronal lineages (neurons, astrocytes, and oligodendrocytes), and thus their potency is restricted. Nearly all research to date has made use of mouse embryonic stem cells (mES) or human embryonic stem cells (hES) derived from the early inner cell mass. Both have the essential stem cell characteristics, yet they require very different environments in order to maintain an undifferentiated state. Mouse ES cells are grown on a layer of gelatin as an extracellular matrix (for support) and require the presence of leukemia inhibitory factor (LIF) in serum media. A drug cocktail containing inhibitors to GSK3B and the MAPK/ERK pathway, called 2i, has also been shown to maintain pluripotency in stem cell culture. Human ESCs are grown on a feeder layer of mouse embryonic fibroblasts and require the presence of basic fibroblast growth factor (bFGF or FGF-2). Without optimal culture conditions or genetic manipulation, embryonic stem cells will rapidly differentiate | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell A human embryonic stem cell is also defined by the expression of several transcription factors and cell surface proteins. The transcription factors Oct-4, Nanog, and Sox2 form the core regulatory network that ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency. The cell surface antigens most commonly used to identify hES cells are the glycolipids stage specific embryonic antigen 3 and 4, and the keratan sulfate antigens Tra-1-60 and Tra-1-81. The molecular definition of a stem cell includes many more proteins and continues to be a topic of research. By using human embryonic stem cells to produce specialized cells like nerve cells or heart cells in the lab, scientists can gain access to adult human cells without taking tissue from patients. They can then study these specialized adult cells in detail to try to discern complications of diseases, or to study cell reactions to proposed new drugs. Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for regenerative medicine and tissue replacement after injury or disease., however, there are currently no approved treatments using ES cells. The first human trial was approved by the US Food and Drug Administration in January 2009. However, the human trial was not initiated until October 13, 2010 in Atlanta for spinal cord injury research | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell On November 14, 2011 the company conducting the trial (Geron Corporation) announced that it will discontinue further development of its stem cell programs. Differentiating ES cells into usable cells while avoiding transplant rejection are just a few of the hurdles that embryonic stem cell researchers still face. Embryonic stem cells, being pluripotent, require specific signals for correct differentiation – if injected directly into another body, ES cells will differentiate into many different types of cells, causing a teratoma. Ethical considerations regarding the use of unborn human tissue are another reason for the lack of approved treatments using embryonic stem cells. Many nations currently have moratoria or limitations on either human ES cell research or the production of new human ES cell lines. Mesenchymal stem cells (MSC) are known to be multipotent, which can be found in adult tissues, for example, in the muscle, liver, bone marrow. Mesenchymal stem cells usually function as structural support in various organs as mentioned above, and control the movement of substances. MSC can differentiate into numerous cell categories as an illustration of adipocytes, osteocytes, and chondrocytes, derived by the mesodermal layer. Where the mesoderm layer provides an increase to the body’s skeletal elements, such as relating to the cartilage or bone | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell The term “meso” means middle, infusion originated from the Greek, signifying that mesenchymal cells are able to range and travel in early embryonic growth among the ectodermal and endodermal layers. This mechanism helps with space-filling thus, key for repairing wounds in adult organisms that have to do with mesenchymal cells in the dermis (skin), bone, or muscle. Mesenchymal stem cells are known to be essential for regenerative medicine. They are broadly studied in clinical trials. Since they are easily isolated and obtain high yield, high plasticity, which makes able to facilitate inflammation and encourage cell growth, cell differentiation, and restoring tissue derived from immunomodulation and immunosuppression. MSC comes from the bone marrow, which requires an aggressive procedure when it comes to isolating the quantity and quality of the isolated cell, and it varies by how old the donor. When comparing the rates of MSC in the bone marrow aspirates and bone marrow stroma, the aspirates tend to have lower rates of MSC than the stroma. MSC are known to be heterogeneous, and they express a high level of pluripotent markers when compared to other types of stem cells, such as embryonic stem cells. Embryonic stem cells (ESCs) have the ability to divide indefinitely while keeping their pluripotency, which is made possible through specialized mechanisms of cell cycle control | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell Compared to proliferating somatic cells, ESCs have unique cell cycle characteristics—such as rapid cell division caused by shortened G1 phase, absent G0 phase, and modifications in cell cycle checkpoints—which leaves the cells mostly in S phase at any given time. ESCs’ rapid division is demonstrated by their short doubling time, which ranges from 8 to 10 hours, whereas somatic cells have doubling time of approximately 20 hours or longer. As cells differentiate, these properties change: G1 and G2 phases lengthen, leading to longer cell division cycles. This suggests that a specific cell cycle structure may contribute to the establishment of pluripotency. Particularly because G1 phase is the phase in which cells have increased sensitivity to differentiation, shortened G1 is one of the key characteristics of ESCs and plays an important role in maintaining undifferentiated phenotype. Although the exact molecular mechanism remains only partially understood, several studies have shown insight on how ESCs progress through G1—and potentially other phases—so rapidly. The cell cycle is regulated by complex network of cyclins, cyclin-dependent kinases (Cdk), cyclin-dependent kinase inhibitors (Cdkn), pocket proteins of the retinoblastoma (Rb) family, and other accessory factors. Foundational insight into the distinctive regulation of ESC cell cycle was gained by studies on mouse ESCs (mESCs). mESCs showed a cell cycle with highly abbreviated G1 phase, which enabled cells to rapidly alternate between M phase and S phase | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell In a somatic cell cycle, oscillatory activity of Cyclin-Cdk complexes is observed in sequential action, which controls crucial regulators of the cell cycle to induce unidirectional transitions between phases: Cyclin D and Cdk4/6 are active in the G1 phase, while Cyclin E and Cdk2 are active during the late G1 phase and S phase; and Cyclin A and Cdk2 are active in the S phase and G2, while Cyclin B and Cdk1 are active in G2 and M phase. However, in mESCs, this typically ordered and oscillatory activity of Cyclin-Cdk complexes is absent. Rather, the Cyclin E/Cdk2 complex is constitutively active throughout the cycle, keeping retinoblastoma protein (pRb) hyperphosphorylated and thus inactive. This allows for direct transition from M phase to the late G1 phase, leading to absence of D-type cyclins and therefore a shortened G1 phase. Cdk2 activity is crucial for both cell cycle regulation and cell-fate decisions in mESCs; downregulation of Cdk2 activity prolongs G1 phase progression, establishes a somatic cell-like cell cycle, and induces expression of differentiation markers. In human ESCs (hESCs), the duration of G1 is dramatically shortened. This has been attributed to high mRNA levels of G1-related Cyclin D2 and Cdk4 genes and low levels of cell cycle regulatory proteins that inhibit cell cycle progression at G1, such as p21, p27, and p57. Furthermore, regulators of Cdk4 and Cdk6 activity, such as members of the Ink family of inhibitors (p15, p16, p18, and p19), are expressed at low levels or not at all | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell Thus, similar to mESCs, hESCs show high Cdk activity, with Cdk2 exhibiting the highest kinase activity. Also similar to mESCs, hESCs demonstrate the importance of Cdk2 in G1 phase regulation by showing that G1 to S transition is delayed when Cdk2 activity is inhibited and G1 is arrest when Cdk2 is knocked down. However unlike mESCs, hESCs have a functional G1 phase. hESCs show that the activities of Cyclin E/Cdk2 and Cyclin A/Cdk2 complexes are cell cycle dependent and the Rb checkpoint in G1 is functional. ESCs are also characterized by G1 checkpoint non-functionality, even though the G1 checkpoint is crucial for maintaining genomic stability. In response to DNA damage, ESCs do not stop in G1 to repair DNA damages but instead depend on S and G2/M checkpoints or undergo apoptosis. The absence of G1 checkpoint in ESCs allows for removal of cells with damaged DNA, hence avoiding potential mutations from inaccurate DNA repair. Consistent with this idea, ESCs are hypersensitive to DNA damage to minimize mutations passed onto the next generation. The primitive stem cells located in the organs of fetuses are referred to as fetal stem cells. There are two types of fetal stem cells: Adult stem cells, also called somatic (from Greek σωματικóς, "of the body") stem cells, are stem cells which maintain and repair the tissue in which they are found. They can be found in children, as well as adults | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell There are three known accessible sources of autologous adult stem cells in humans: Stem cells can also be taken from umbilical cord blood just after birth. Of all stem cell types, autologous harvesting involves the least risk. By definition, autologous cells are obtained from one's own body, just as one may bank his or her own blood for elective surgical procedures. Pluripotent adult stem cells are rare and generally small in number, but they can be found in umbilical cord blood and other tissues. Bone marrow is a rich source of adult stem cells, which have been used in treating several conditions including liver cirrhosis, chronic limb ischemia and endstage heart failure. The quantity of bone marrow stem cells declines with age and is greater in males than females during reproductive years. Much adult stem cell research to date has aimed to characterize their potency and self-renewal capabilities. DNA damage accumulates with age in both stem cells and the cells that comprise the stem cell environment. This accumulation is considered to be responsible, at least in part, for increasing stem cell dysfunction with aging (see DNA damage theory of aging). Most adult stem cells are lineage-restricted (multipotent) and are generally referred to by their tissue origin (mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, dental pulp stem cell, etc.) | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell Muse cells (multi-lineage differentiating stress enduring cells) are a recently discovered pluripotent stem cell type found in multiple adult tissues, including adipose, dermal fibroblasts, and bone marrow. While rare, muse cells are identifiable by their expression of SSEA-3, a marker for undifferentiated stem cells, and general mesenchymal stem cells markers such as CD105. When subjected to single cell suspension culture, the cells will generate clusters that are similar to embryoid bodies in morphology as well as gene expression, including canonical pluripotency markers Oct4, Sox2, and Nanog. Adult stem cell treatments have been successfully used for many years to treat leukemia and related bone/blood cancers through bone marrow transplants. Adult stem cells are also used in veterinary medicine to treat tendon and ligament injuries in horses. The use of adult stem cells in research and therapy is not as controversial as the use of embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo. Additionally, in instances where adult stem cells are obtained from the intended recipient (an autograft), the risk of rejection is essentially non-existent. Consequently, more US government funding is being provided for adult stem cell research | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell With the increasing demand of human adult stem cells for both research and clinical purposes (typically 1–5 million cells per kg of body weight are required per treatment) it becomes of utmost importance to bridge the gap between the need to expand the cells in vitro and the capability of harnessing the factors underlying replicative senescence. Adult stem cells are known to have a limited lifespan in vitro and to enter replicative senescence almost undetectably upon starting in vitro culturing. Multipotent stem cells are also found in amniotic fluid. These stem cells are very active, expand extensively without feeders and are not tumorigenic. Amniotic stem cells are multipotent and can differentiate in cells of adipogenic, osteogenic, myogenic, endothelial, hepatic and also neuronal lines. Amniotic stem cells are a topic of active research. Use of stem cells from amniotic fluid overcomes the ethical objections to using human embryos as a source of cells. Roman Catholic teaching forbids the use of embryonic stem cells in experimentation; accordingly, the Vatican newspaper "Osservatore Romano" called amniotic stem cells "the future of medicine". It is possible to collect amniotic stem cells for donors or for autologous use: the first US amniotic stem cells bank was opened in 2009 in Medford, MA, by Biocell Center Corporation and collaborates with various hospitals and universities all over the world | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell Adult stem cells have limitations with their potency; unlike embryonic stem cells (ESCs), they are not able to differentiate into cells from all three germ layers. As such, they are deemed multipotent. However, reprogramming allows for the creation of pluripotent cells, induced pluripotent stem cells (iPSCs), from adult cells. These are not adult stem cells, but somatic cells (e.g. epithelial cells) reprogrammed to give rise to cells with pluripotent capabilities. Using genetic reprogramming with protein transcription factors, pluripotent stem cells with ESC-like capabilities have been derived. The first demonstration of induced pluripotent stem cells was conducted by Shinya Yamanaka and his colleagues at Kyoto University. They used the transcription factors Oct3/4, Sox2, c-Myc, and Klf4 to reprogram mouse fibroblast cells into pluripotent cells. Subsequent work used these factors to induce pluripotency in human fibroblast cells. Junying Yu, James Thomson, and their colleagues at the University of Wisconsin–Madison used a different set of factors, Oct4, Sox2, Nanog and Lin28, and carried out their experiments using cells from human foreskin. However, they were able to replicate Yamanaka's finding that inducing pluripotency in human cells was possible. Induced pluripotent stem cells differ from embryonic stem cells | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell They share many similar properties, such as pluripotency and differentiation potential, the expression of pluripotency genes, epigenetic patterns, embryoid body and teratoma formation, and viable chimera formation, but there are many differences within these properties. The chromatin of iPSCs appears to be more "closed" or methylated than that of ESCs. Similarly, the gene expression pattern between ESCs and iPSCs, or even iPSCs sourced from different origins. There are thus questions about the "completeness" of reprogramming and the somatic memory of induced pluripotent stem cells. Despite this, inducing somatic cells to be pluripotent appears to be viable. As a result of the success of these experiments, Ian Wilmut, who helped create the first cloned animal Dolly the Sheep, has announced that he will abandon somatic cell nuclear transfer as an avenue of research. IPSCs has helped the field of medicine significantly by finding numerous ways to cure diseases. Since human IPSCc has given the advantage to make vitro models to study toxins and pathogenesis. Furthermore, induced pluripotent stem cells provide several therapeutic advantages. Like ESCs, they are pluripotent. They thus have great differentiation potential; theoretically, they could produce any cell within the human body (if reprogramming to pluripotency was "complete"). Moreover, unlike ESCs, they potentially could allow doctors to create a pluripotent stem cell line for each individual patient | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell Frozen blood samples can be used as a valuable source of induced pluripotent stem cells. Patient specific stem cells allow for the screening for side effects before drug treatment, as well as the reduced risk of transplantation rejection. Despite their current limited use therapeutically, iPSCs hold create potential for future use in medical treatment and research. The key factors controlling the cell cycle also regulate pluripotency. Thus, manipulation of relevant genes can maintain pluripotency and reprogram somatic cells to an induced pluripotent state. However, reprogramming of somatic cells is often low in efficiency and considered stochastic. With the idea that a more rapid cell cycle is a key component of pluripotency, reprogramming efficiency can be improved. Methods for improving pluripotency through manipulation of cell cycle regulators include: overexpression of Cyclin D/Cdk4, phosphorylation of Sox2 at S39 and S253, overexpression of Cyclin A and Cyclin E, knockdown of Rb, and knockdown of members of the Cip/Kip family or the Ink family. Furthermore, reprogramming efficiency is correlated with the number of cell divisions happened during the stochastic phase, which is suggested by the growing inefficiency of reprogramming of older or slow diving cells. Lineage is an important procedure to analyze developing embryos. Since cell lineages shows the relationship between cells at each division | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell This helps in analyzing stem cell lineages along the way which helps recognize stem cell effectiveness, lifespan, and other factors. With the technique of cell lineage mutant genes can be analyzed in stem cell clones that can help in genetic pathways. These pathways can regulate how the stem cell perform To ensure self-renewal, stem cells undergo two types of cell division (see "division and differentiation" diagram). Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and a progenitor cell with limited self-renewal potential. Progenitors can go through several rounds of cell division before terminally differentiating into a mature cell. It is possible that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells. An alternative theory is that stem cells remain undifferentiated due to environmental cues in their particular niche. Stem cells differentiate when they leave that niche or no longer receive those signals. Studies in "Drosophila" germarium have identified the signals decapentaplegic and adherens junctions that prevent germarium stem cells from differentiating. therapy is the use of stem cells to treat or prevent a disease or condition. Bone marrow transplant is a form of stem cell therapy that has been used for many years without controversy | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell implantation may help in strengthening the left-ventricle of the heart, as well as retaining the heart tissue to patients who have suffered from heart attacks in the past. treatments may lower symptoms of the disease or condition that is being treated. The lowering of symptoms may allow patients to reduce the drug intake of the disease or condition. treatment may also provide knowledge for society to further stem cell understanding and future treatments. treatments may require immunosuppression because of a requirement for radiation before the transplant to remove the person's previous cells, or because the patient's immune system may target the stem cells. One approach to avoid the second possibility is to use stem cells from the same patient who is being treated. Pluripotency in certain stem cells could also make it difficult to obtain a specific cell type. It is also difficult to obtain the exact cell type needed, because not all cells in a population differentiate uniformly. Undifferentiated cells can create tissues other than desired types. Some stem cells form tumors after transplantation; pluripotency is linked to tumor formation especially in embryonic stem cells, fetal proper stem cells, induced pluripotent stem cells. Fetal proper stem cells form tumors despite multipotency. Some of the fundamental patents covering human embryonic stem cells are owned by the Wisconsin Alumni Research Foundation (WARF) – they are patents 5,843,780, 6,200,806, and 7,029,913 invented by James A. Thomson | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell WARF does not enforce these patents against academic scientists, but does enforce them against companies. In 2006, a request for the US Patent and Trademark Office (USPTO) to re-examine the three patents was filed by the Public Patent Foundation on behalf of its client, the non-profit patent-watchdog group Consumer Watchdog (formerly the Foundation for Taxpayer and Consumer Rights). In the re-examination process, which involves several rounds of discussion between the USPTO and the parties, the USPTO initially agreed with Consumer Watchdog and rejected all the claims in all three patents, however in response, WARF amended the claims of all three patents to make them more narrow, and in 2008 the USPTO found the amended claims in all three patents to be patentable. The decision on one of the patents (7,029,913) was appealable, while the decisions on the other two were not. Consumer Watchdog appealed the granting of the '913 patent to the USPTO's Board of Patent Appeals and Interferences (BPAI) which granted the appeal, and in 2010 the BPAI decided that the amended claims of the '913 patent were not patentable. However, WARF was able to re-open prosecution of the case and did so, amending the claims of the '913 patent again to make them more narrow, and in January 2013 the amended claims were allowed | https://en.wikipedia.org/wiki?curid=27783 |
Stem cell In July 2013, Consumer Watchdog announced that it would appeal the decision to allow the claims of the '913 patent to the US Court of Appeals for the Federal Circuit (CAFC), the federal appeals court that hears patent cases. At a hearing in December 2013, the CAFC raised the question of whether Consumer Watchdog had legal standing to appeal; the case could not proceed until that issue was resolved. Diseases and conditions where stem cell treatment is being investigated include: Research is underway to develop various sources for stem cells, and to apply stem cell treatments for neurodegenerative diseases and conditions, diabetes, heart disease, and other conditions. Research is also underway in generating organoids using stem cells, which would allow for further understanding of human development, organogenesis, and modeling of human diseases. In more recent years, with the ability of scientists to isolate and culture embryonic stem cells, and with scientists' growing ability to create stem cells using somatic cell nuclear transfer and techniques to create induced pluripotent stem cells, controversy has crept in, both related to abortion politics and to human cloning. Hepatotoxicity and drug-induced liver injury account for a substantial number of failures of new drugs in development and market withdrawal, highlighting the need for screening assays such as stem cell-derived hepatocyte-like cells, that are capable of detecting toxicity early in the drug development process. | https://en.wikipedia.org/wiki?curid=27783 |
Sociobiology is a field of biology that aims to examine and explain social behavior in terms of evolution. It draws from disciplines including psychology, ethology, anthropology, evolution, zoology, archaeology, and population genetics. Within the study of human societies, sociobiology is closely allied to Darwinian anthropology, human behavioral ecology and evolutionary psychology. investigates social behaviors such as mating patterns, territorial fights, pack hunting, and the hive society of social insects. It argues that just as selection pressure led to animals evolving useful ways of interacting with the natural environment, so also it led to the genetic evolution of advantageous social behavior. While the term "sociobiology" originated at least as early as the 1940s, the concept did not gain major recognition until the publication of E. O. Wilson's book "" in 1975. The new field quickly became the subject of controversy. Critics, led by Richard Lewontin and Stephen Jay Gould, argued that genes played a role in human behavior, but that traits such as aggressiveness could be explained by social environment rather than by biology. Sociobiologists responded by pointing to the complex relationship between nature and nurture. E. O. Wilson defined sociobiology as "the extension of population biology and evolutionary theory to social organization". is based on the premise that some behaviors (social and individual) are at least partly inherited and can be affected by natural selection | https://en.wikipedia.org/wiki?curid=27919 |
Sociobiology It begins with the idea that behaviors have evolved over time, similar to the way that physical traits are thought to have evolved. It predicts that animals will act in ways that have proven to be evolutionarily successful over time. This can, among other things, result in the formation of complex social processes conducive to evolutionary fitness. The discipline seeks to explain behavior as a product of natural selection. Behavior is therefore seen as an effort to preserve one's genes in the population. Inherent in sociobiological reasoning is the idea that certain genes or gene combinations that influence particular behavioral traits can be inherited from generation to generation. For example, newly dominant male lions often kill cubs in the pride that they did not sire. This behavior is adaptive because killing the cubs eliminates competition for their own offspring and causes the nursing females to come into heat faster, thus allowing more of his genes to enter into the population. Sociobiologists would view this instinctual cub-killing behavior as being inherited through the genes of successfully reproducing male lions, whereas non-killing behavior may have died out as those lions were less successful in reproducing. The philosopher of biology Daniel Dennett suggested that the political philosopher Thomas Hobbes was the first sociobiologist, arguing that in his 1651 book "Leviathan" Hobbes had explained the origins of morals in human society from an amoral sociobiological perspective | https://en.wikipedia.org/wiki?curid=27919 |
Sociobiology The geneticist of animal behavior John Paul Scott coined the word "sociobiology" at a 1948 conference on genetics and social behaviour which called for a conjoint development of field and laboratory studies in animal behavior research. With John Paul Scott's organizational efforts, a "Section of Animal Behavior and Sociobiology" of the ESA (acronym stands for?) was created in 1956, which became a Division of Animal Behavior of the American Society of Zoology in 1958. In 1956, E. O. Wilson came in contact this emerging sociobiology through his PhD student Stuart A. Altmann, who had been in close relation with the participants to the 1948 conference. Altmann developed his own brand of sociobiology to study the social behavior of rhesus macaques, using statistics, and was hired as a "sociobiologist" at the Yerkes Regional Primate Research Center in 1965. Wilson's sociobiology is different from John Paul Scott's or Altmann's, insofar as he drew on mathematical models of social behavior centered on the maximisation of the genetic fitness by W. D. Hamilton, Robert Trivers, John Maynard Smith, and George R. Price. The three sociobiologies by Scott, Altmann and Wilson have in common to place naturalist studies at the core of the research on animal social behavior and by drawing alliances with emerging research methodologies, at a time when "biology in the field" was threatened to be made old-fashioned by "modern" practices of science (laboratory studies, mathematical biology, molecular biology) | https://en.wikipedia.org/wiki?curid=27919 |
Sociobiology Once a specialist term, "sociobiology" became widely known in 1975 when Wilson published his book "Sociobiology: The New Synthesis", which sparked an intense controversy. Since then "sociobiology" has largely been equated with Wilson's vision. The book pioneered and popularized the attempt to explain the evolutionary mechanics behind social behaviors such as altruism, aggression, and nurturance, primarily in ants (Wilson's own research specialty) and other Hymenoptera, but also in other animals. However, the influence of evolution on behavior has been of interest to biologists and philosophers since soon after the discovery of evolution itself. Peter Kropotkin's "", written in the early 1890s, is a popular example. The final chapter of the book is devoted to sociobiological explanations of human behavior, and Wilson later wrote a Pulitzer Prize winning book, "On Human Nature", that addressed human behavior specifically. Edward H. Hagen writes in "The Handbook of Evolutionary Psychology" that sociobiology is, despite the public controversy regarding the applications to humans, "one of the scientific triumphs of the twentieth century." "is now part of the core research and curriculum of virtually all biology departments, and it is a foundation of the work of almost all field biologists" Sociobiological research on nonhuman organisms has increased dramatically and continuously in the world's top scientific journals such as "Nature" and "Science" | https://en.wikipedia.org/wiki?curid=27919 |
Sociobiology The more general term behavioral ecology is commonly substituted for the term sociobiology in order to avoid the public controversy. Sociobiologists maintain that human behavior, as well as nonhuman animal behavior, can be partly explained as the outcome of natural selection. They contend that in order to fully understand behavior, it must be analyzed in terms of evolutionary considerations. Natural selection is fundamental to evolutionary theory. Variants of hereditary traits which increase an organism's ability to survive and reproduce will be more greatly represented in subsequent generations, i.e., they will be "selected for". Thus, inherited behavioral mechanisms that allowed an organism a greater chance of surviving and/or reproducing in the past are more likely to survive in present organisms. That inherited adaptive behaviors are present in nonhuman animal species has been multiply demonstrated by biologists, and it has become a foundation of evolutionary biology. However, there is continued resistance by some researchers over the application of evolutionary models to humans, particularly from within the social sciences, where culture has long been assumed to be the predominant driver of behavior. is based upon two fundamental premises: uses Nikolaas Tinbergen's four categories of questions and explanations of animal behavior. Two categories are at the species level; two, at the individual level | https://en.wikipedia.org/wiki?curid=27919 |
Sociobiology The species-level categories (often called "ultimate explanations") are The individual-level categories (often called "proximate explanations") are Sociobiologists are interested in how behavior can be explained logically as a result of selective pressures in the history of a species. Thus, they are often interested in instinctive, or intuitive behavior, and in explaining the similarities, rather than the differences, between cultures. For example, mothers within many species of mammals – including humans – are very protective of their offspring. Sociobiologists reason that this protective behavior likely evolved over time because it helped the offspring of the individuals which had the characteristic to survive. This parental protection would increase in frequency in the population. The social behavior is believed to have evolved in a fashion similar to other types of nonbehavioral adaptations, such as a coat of fur, or the sense of smell. Individual genetic advantage fails to explain certain social behaviors as a result of gene-centred selection. E.O. Wilson argued that evolution may also act upon groups. The mechanisms responsible for group selection employ paradigms and population statistics borrowed from evolutionary game theory. Altruism is defined as "a concern for the welfare of others" | https://en.wikipedia.org/wiki?curid=27919 |
Sociobiology If altruism is genetically determined, then altruistic individuals must reproduce their own altruistic genetic traits for altruism to survive, but when altruists lavish their resources on non-altruists at the expense of their own kind, the altruists tend to die out and the others tend to increase. An extreme example is a soldier losing his life trying to help a fellow soldier. This example raises the question of how altruistic genes can be passed on if this soldier dies without having any children. Within sociobiology, a social behavior is first explained as a sociobiological hypothesis by finding an evolutionarily stable strategy that matches the observed behavior. Stability of a strategy can be difficult to prove, but usually, it will predict gene frequencies. The hypothesis can be supported by establishing a correlation between the gene frequencies predicted by the strategy, and those expressed in a population. Altruism between social insects and littermates has been explained in such a way. Altruistic behavior, behavior that increases the reproductive fitness of others at the apparent expense of the altruist, in some animals has been correlated to the degree of genome shared between altruistic individuals. A quantitative description of infanticide by male harem-mating animals when the alpha male is displaced as well as rodent female infanticide and fetal resorption are active areas of study | https://en.wikipedia.org/wiki?curid=27919 |
Sociobiology In general, females with more bearing opportunities may value offspring less, and may also arrange bearing opportunities to maximize the food and protection from mates. An important concept in sociobiology is that temperament traits exist in an ecological balance. Just as an expansion of a sheep population might encourage the expansion of a wolf population, an expansion of altruistic traits within a gene pool may also encourage increasing numbers of individuals with dependent traits. Studies of human behavior genetics have generally found behavioral traits such as creativity, extroversion, aggressiveness, and IQ have high heritability. The researchers who carry out those studies are careful to point out that heritability does not constrain the influence that environmental or cultural factors may have on those traits. Criminality is actively under study, but extremely controversial. There are arguments that in some environments criminal behavior might be adaptive. The novelist Elias Canetti also has noted applications of sociobiological theory to cultural practices such as slavery and autocracy. Genetic mouse mutants illustrate the power that genes exert on behaviour. For example, the transcription factor FEV (aka Pet1), through its role in maintaining the serotonergic system in the brain, is required for normal aggressive and anxiety-like behavior | https://en.wikipedia.org/wiki?curid=27919 |
Sociobiology Thus, when FEV is genetically deleted from the mouse genome, male mice will instantly attack other males, whereas their wild-type counterparts take significantly longer to initiate violent behaviour. In addition, FEV has been shown to be required for correct maternal behaviour in mice, such that offspring of mothers without the FEV factor do not survive unless cross-fostered to other wild-type female mice. A genetic basis for instinctive behavioural traits among non-human species, such as in the above example, is commonly accepted among many biologists; however, attempting to use a genetic basis to explain complex behaviours in human societies has remained extremely controversial. Steven Pinker argues that critics have been overly swayed by politics and a fear of biological determinism, accusing among others Stephen Jay Gould and Richard Lewontin of being "radical scientists", whose stance on human nature is influenced by politics rather than science, while Lewontin, Steven Rose and Leon Kamin, who drew a distinction between the politics and history of an idea and its scientific validity, argue that sociobiology fails on scientific grounds. Gould grouped sociobiology with eugenics, criticizing both in his book "The Mismeasure of Man". Noam Chomsky has expressed views on sociobiology on several occasions. During a 1976 meeting of the Study Group, as reported by Ullica Segerstråle, Chomsky argued for the importance of a sociobiologically informed notion of human nature | https://en.wikipedia.org/wiki?curid=27919 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.