C-myc internal ribosome entry site (IRES)

The c-myc internal ribosome entry site (IRES) is an RNA element present in the 5' UTR of the mRNA of C-myc and allows cap-independent translation. The mammalian c-myc gene is a proto-oncogene which is required for cell proliferation, transformation and death. c-myc mRNA has an alternative method of translation via internal ribosome entry where ribosomes are recruited to the IRES located in the 5' UTR thus bypassing the typical eukaryotic cap-dependent translation pathway.


Eldrac


Leukotriene B4 receptor

The leukotriene B4 receptors (BLTRs) include the following two receptors:


Gluten exorphin

Gluten exorphins are a group of opioid peptides formed during the digestion of the gluten protein. These peptides work as external regulators for gastrointestinal movement and hormonal release. The breakdown of gliadin, a polymer of wheat proteins, creates amino acids that stop the gluten epitopes from entering the immune system to activate inflammatory reactions. During this process, gluten does not fully break down, thus increasing the presence of gluten exorphins. Because of this, researchers think this is what might lead to various diseases.
Research shows the benefits of gluten- and casein-free diets for people with diseases and disorders connected to gluten exorphins. The mechanism behind this is still unknown. There is a possibility that gluten has deleterious effects on the human digestive system. When people are more susceptible to gluten and casein allergies, the weakened intestinal lining allows gluten exorphin to flow.
Categorization.
There are four known gluten exorphins with known structure:
Clinical significance.
Recent research surrounding gluten exorphins has revolved around how the peptides might play a role in various diseases and disorders.
Celiac disease.
In response to gluten, people with celiac disease will release gluten exorphins as part of the allergic immune response. Due to the weakening of intestinal walls caused by celiac disease, some of these gluten exorphins can make their way through the lining of the intestines and are then absorbed into the bloodstream. Once in the bloodstream, gluten exorphins can reach the brain and cause issues with neurological functions, like in the disorders discussed below.
Autism.
Autism spectrum disorder (ASD) may be associated with the immune response to gluten and a number of clinical trials have been run to determine the effectiveness of a gluten-free and casein-free (GFCF) diet to alleviate the symptoms of ASD. However reviews of the available clinical evidence found little evidence to support the use of CFCF to treat ASD.
Schizophrenia.
Although a rare disorder, schizophrenia can involve debilitating symptoms for those diagnosed with it. It has been found that celiac disease is twice as likely to occur in people with schizophrenia than in the general population, so it is assumed that there is a connection between the two. Given the knowledge of the gut-brain axis, research has looked into the connection between schizophrenia disorder and gluten allergies. One study gathered that when gluten increases the gut’s permeability, an immune response is sent out in the form of gluten exorphins.
Another study hypothesized that a defect in the gastrointestinal tract could cause gluten-associated antigens to enter the bloodstream more easily. Gluten exorphins may be detrimental to mental processing and functionality if they reach the brain, however the available evidence to support this hypothermia is mixed.


M30-Apoptosense ELISA

M30 Apoptosense® ELISA is an enzyme-linked immunosorbent assay developed for the detection of soluble caspase-cleaved keratin 18 (ccK18, K18-Asp396, formerly cytokeratin 18, ccCK18 or CK18-Asp396).
History.
The M30 Apoptosense® ELISA is a PEVIVA product owned by VLVbio (Nacka, Sweden) and was developed in collaboration with the Karolinska Institute in 2000.
Distributors:
Uses.
The M30 Apoptosense® ELISA is a non-invasive test for the detection of apoptosis of epithelially derived cells. Caspases are activated in apoptotic cells and cleave intracellular protein substrates. Keratin 18 (K18) is one such substrate, expressed by many epithelial cells (e.g. hepatocytes, intestinal cells, breast cells, prostate cells). Cleaved K18 is released into the circulation after cell death. The main uses of M30 Apoptosense® ELISA are to:
Biology.
Caspases cleave keratin 18 at two sites during apoptosis. Cleavage at Asp396 generates a neo-epitope recognized by the monoclonal antibody M30®. This antibody does not recognize uncleaved K18 and is therefore specific for apoptotic epithelial cells. M30 Apoptosense® ELISA utilizes a second monoclonal antibody (M5) which recognizes an epitope N-terminal from the M30® epitope.
M30 Apoptosense® ELISA can be combined with the M65® ELISA (uncleaved K18) (PEVIVA®, VLVbio) to determine cell death mode (apoptosis versus necrosis).
Trademarks.
There has been some confusion in the literature on the use of the term “M30”. Although it should be very clear that “M30” is a monoclonal antibody (“M”) that detects the antigen “ccK18”/“K18-Asp396” people sometimes refer to the antigen as “M30”. This is incorrect.
It is clear that the use of the term “M30” in connection with “keratin” means the monoclonal antibody M30® or (possibly, but erroneously) the neo-epitope DALD396 on K18 recognized by the M30® monoclonal. "“M30” is not a biological entity expressed in cells but a (patent protected) monoclonal antibody."
Caspase-cleaved fragment of keratin 18 = ccK18
Keratin 18 = K18 (or CK18)
M30® = the antibody that recognizes a neoepitope on ccK18
M65® ELISA = an ELISA composed of two antibodies (M5 and M6) for conventional epitopes of K18
M30®, Apoptosense®, M65®, EpiDeath®, and PEVIVA® are registered trademarks, including U.S. Trademarks 4,577,969, 2,749,204, 1,009,048, and 896,269. Additionally, VLVBio™ holds additional Trademarks in most countries worldwide.


Herpetosiphon giganteus

Herpetosiphon giganteus is a species of bacteria in the genus "Herpetosiphon" known to produce 16 restriction enzymes.
"H. giganteus" has been studied for its gliding motility.


4-HO-MET

4-HO-MET (4-hydroxy-"N"-methyl-"N"-ethyltryptamine, metocin, or methylcybin), is a lesser-known psychedelic drug. It is a structural− and functional analog of psilocin as well as the 4-hydroxyl analog of methylethyltryptamine (MET). 4-HO-MET was first synthesized by Alexander Shulgin. In his book "TiHKAL" ("Tryptamines I Have Known and Loved"), the dosage is listed as 10-20 mg. 4-HO-MET produces psilocin-like distortion of color, sound, and form. Very little data exists about the pharmacological properties, metabolism, and toxicity of 4-HO-MET. There have been no reports of deaths from 4-HO-MET, even though people have reported taking doses up to 150 mg, more than an order of magnitude above the effective dose.
Effects.
Users report similar effects to psilocin, including mydriasis, closed and open eye visuals, euphoria, time dilation and general change in thought processes. These effects occur in a wavelike pattern such as that of psilocybin with near-normal perception and high effect varying rapidly. The effects last for about 4–6 hours.
Drug prohibition laws.
Sweden.
"Sveriges riksdag" added 4-HO-MET to schedule I ("substances, plant materials and fungi which normally do not have medical use") as narcotics in Sweden as of May 1, 2012, published by "Medical Products Agency" in their regulation LVFS 2012:6 listed as 4-HO-MET 3-[2-[etyl(metyl)amino]etyl]-1H-indol-4-ol.
United Kingdom.
4-HO-MET is a class A drug in the UK, as a result of the tryptamine catch-all clause.
United States.
4-HO-MET is not scheduled at the federal level in the United States, but it is possible that it could be considered an analogue of psilocin, in which case purchase, sale, or possession could be prosecuted under the Federal Analogue Act.


Shri Mohan Jain

Prof. Dr. Shri Mohan Jain is an Indian-born plant biotechnology scientist. He worked several years for the International Atomic Energy Agency in Vienna. He has done research on genetically modified food, mutation breeding, ornamental plants, date palm, and tropical fruit, such as banana. He has edited 44 internationally sold books.
He was listed in Marquis Who's Who in the World 13th edition, 1996 and Who's Who in Science & Engineering, 4th edition, 1997.
Education.
Dr. Jain completed his bachelor's degree at the Chaudhary Charan Singh Haryana Agricultural University in Hisar, Haryana, India (1966–1970). After that he continued his studies to receive a Master of Science from the Genetics department at the G.B. Pant University of Agriculture and Technology in Pantnagar, Nainital, India (1970–1972).
In 1972 he started his studies in Master of Philosophy in Jawaharlal Nehru University in New Delhi, India and finally completed his studies with PhD from the same university in 1978.
Research areas.
Dr. Jain's research interests include Date palm, Arbequina, and Bananas and plantains to make a more stable and profitable crop by innovative approaches and conventional breeding. Other significant research areas are potato and ornamental plants, such as rose, begonia, orchids, African violets, and brassicas.


Zeng Rong

Zeng Rong () is a Chinese biochemist researching and developing technology for proteomics research. She is currently a professor at the Institute of Biochemistry and Cell Biology at the Shanghai Institutes for Biological Sciences.
Education.
Zeng graduated from the Biology department at Hunan Normal University in China in 1995, with a Bachelor's degree. She then got her doctoral degree in biochemistry and molecular biology in 2000, at the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. She was mentored by a famous protein analyst Xia Qichang.
Career.
Zeng has been working at the Institute of Biochemistry and Cell Biology where she got her doctoral degree since 2000 after her graduation. She works as a doctoral supervisor, and she is also the principal investigator of her research group. She was offered to be an editor of the magazine "Proteomics" in January 2005, and "Molecular and Cell Proteomics" in 2006. Zeng was also accepted as a committee member of HUPO in September 2009.
She has received honors and awards including the National Science Fund in 2004 and the Chinese Young Women in Science Fellowship Award in 2005.
Research focus.
Zeng's main focus is on proteomics and the dynamic behavior of proteins. She leads a research team at the Institute of Biochemistry and Cell Biology at the Shanghai Institute for Biological Sciences to make progress in methodology development, application of quantitative proteomics, and regulation mechanism of protein dynamic behavior.
Her team developed novel methods for proteomics research including multi-dimensional LC-MS/MS that can aid protein profiling, phosphopeptide enrichment, and multiplex quantitation. They applied quantitative proteomics in cell signaling and biomarker discovery of diabetes. Their work on proteins in and around cancer cells in human liver achieved better understanding of liver cancer. In order to regulate the mechanisms involved in the dynamic behavior of proteins, Zeng and her team utilized epigenetic, transcriptomic, and MiRNA data along with proteomic data to find out how biological molecules interact on a systematic level.
Contributions to science.
Zeng has published multiple papers in journals including but not limited to "Electrophoresis", "Nature", "Science", "Proteomics", "BMC Genomics", "Journal of Proteome Research," the "Journal of Molecular Cell Biology", and "Molecular & Cellular Proteomics". Some selected work listed below:


Endothelin

Endothelins are peptides with receptors and effects in many body organs. Endothelin constricts blood vessels and raises blood pressure. The endothelins are normally kept in balance by other mechanisms, but when overexpressed, they contribute to high blood pressure (hypertension), heart disease, and potentially other diseases.
Endothelins are 21-amino acid vasoconstricting peptides produced primarily in the endothelium having a key role in vascular homeostasis. Endothelins are implicated in vascular diseases of several organ systems, including the heart, lungs, kidneys, and brain. As of 2018, endothelins remain under extensive basic and clinical research to define their roles in several organ systems.
Etymology.
Endothelins derived the name from their isolation in cultured endothelial cells.
Isoforms.
There are three isoforms of the peptide (identified as ET-1, -2, -3), each encoded by a separate gene, with varying regions of expression and binding to at least four known endothelin receptors, ETA, ETB1, ETB2 and ETC.
The human genes for endothelin-1 (ET-1), endothelin-2 (ET-2), and endothelin-3 (ET-3) are located on chromosomes 6, 1, and 20, respectively.
Mechanism of action and function.
Endothelin functions through activation of two G protein-coupled receptors, endothelinA and endothelinB receptor (ETA and ETB, respectively). These two subtypes of endothelin receptor are distinguished in the laboratory by the order of their affinity for the three endothelin peptides: the ETA receptor is selective for ET-1, whereas the ETB receptor has the same affinity for all three ET peptides. The two types of ET receptor are distributed across diverse cells and organs, but with different levels of expression and activity, indicating a multiple-organ ET system.
Endothelin-1 is the most powerful endogenous chemical affecting vascular tone across organ systems. Secretion of endothelin-1 from the vascular endothelium signals vasoconstriction and influences local cellular growth and survival. ET-1 has been implicated in the development and progression of several cardiovascular diseases, such as atherosclerosis and hypertension. Endothelin also has roles in mitogenesis, cell survival, angiogenesis, bone growth, nociceptor function, and cancer onset mechanisms. Clinically, anti-ET drugs are used to treat pulmonary arterial hypertension.
Physiological effects.
Endothelins are the most potent vasoconstrictors known. Overproduction of endothelin in the lungs may cause pulmonary hypertension, which was treatable in preliminary research by bosentan, sitaxentan or ambrisentan.
Endothelins have involvement in cardiovascular function, fluid-electrolyte homeostasis, and neuronal mechanisms across diverse cell types. Endothelin receptors are present in the three pituitary lobes which display increased metabolic activity when exposed to ET-1 in the blood or ventricular system.
ET-1 contributes to the vascular dysfunction associated with cardiovascular disease, particularly atherosclerosis and hypertension. The ETA receptor for ET-1 is primarily located on vascular smooth muscle cells, mediating vasoconstriction, whereas the ETB receptor for ET-1 is primarily located on endothelial cells, causing vasodilation due to nitric oxide release.
The binding of platelets to the endothelial cell receptor LOX-1 causes a release of endothelin, which induces endothelial dysfunction.
Clinical significance.
The ubiquitous distribution of endothelin peptides and receptors implicates involvement in a wide variety of physiological and pathological processes among different organ systems. Among numerous diseases potentially occurring from endothelin dysregulation are:
In insulin resistance the high levels of blood insulin results in increased production and activity of ET-1, which promotes vasoconstriction and elevates blood pressure.
ET-1 impairs glucose uptake in the skeletal muscles of insulin resistant subjects, thereby worsening insulin resistance.
In preliminary research, injection of endothelin-1 into a lateral cerebral ventricle was shown to potently stimulate glucose metabolism in specified interconnected circuits of the brain, and to induce convulsions, indicating its potential for diverse neural effects in conditions such as epilepsy. Receptors for endothelin-1 exist in brain neurons, indicating a potential role in neural functions.
Antagonists.
Earliest antagonists discovered for ETA were BQ123, and for ETB, BQ788. An ETA-selective antagonist, ambrisentan was approved for treatment of pulmonary arterial hypertension in 2007, followed by a more selective ETA antagonist, sitaxentan, which was later withdrawn due to potentially lethal effects in the liver. Bosentan was a precursor to macitentan, which was approved in 2013.


Succinate dehydrogenase

Succinate dehydrogenase (SDH) or succinate-coenzyme Q reductase (SQR) or respiratory complex II is an enzyme complex, found in many bacterial cells and in the inner mitochondrial membrane of eukaryotes. It is the only enzyme that participates in both the citric acid cycle and the electron transport chain. Histochemical analysis showing high succinate dehydrogenase in muscle demonstrates high mitochondrial content and high oxidative potential.
In step 6 of the citric acid cycle, SQR catalyzes the oxidation of succinate to fumarate with the reduction of ubiquinone to ubiquinol. This occurs in the inner mitochondrial membrane by coupling the two reactions together.
Structure.
Subunits.
Mitochondrial and many bacterial SQRs are composed of four structurally different subunits: two hydrophilic and two hydrophobic. The first two subunits, a flavoprotein (SdhA) and an iron-sulfur protein (SdhB), form a hydrophilic head where enzymatic activity of the complex takes place. SdhA contains a covalently attached flavin adenine dinucleotide (FAD) cofactor and the succinate binding site and SdhB contains three iron-sulfur clusters: [2Fe-2S], [4Fe-4S], and [3Fe-4S]. The second two subunits are hydrophobic membrane anchor subunits, SdhC and SdhD. Human mitochondria contain two distinct isoforms of SdhA (Fp subunits type I and type II), these isoforms are also found in "Ascaris suum" and "Caenorhabditis elegans". The subunits form a membrane-bound cytochrome b complex with six transmembrane helices containing one heme b group and a ubiquinone-binding site. Two phospholipid molecules, one cardiolipin and one phosphatidylethanolamine, are also found in the SdhC and SdhD subunits (not shown in the image). They serve to occupy the hydrophobic space below the heme b. These subunits are displayed in the attached image. SdhA is green, SdhB is teal, SdhC is fuchsia, and SdhD is yellow. Around SdhC and SdhD is a phospholipid membrane with the intermembrane space at the top of the image.
Ubiquinone binding site.
Two distinctive ubiquinone binding sites can be recognized on mammalian SDH – matrix-proximal QP and matrix-distal QD. Ubiquinone binding site Qp, which shows higher affinity to ubiquinone, is located in a gap composed of SdhB, SdhC, and SdhD. Ubiquinone is stabilized by the side chains of His207 of subunit B, Ser27 and Arg31 of subunit C, and Tyr83 of subunit D. The quinone ring is surrounded by Ile28 of subunit C and Pro160 of subunit B. These residues, along with Il209, Trp163, and Trp164 of subunit B, and Ser27 (C atom) of subunit C, form the hydrophobic environment of the quinone-binding pocket Qp. In contrast, ubiquinone binding site QD, which lies closer to inter-membrane space, is composed of SdhD only and has lower affinity to ubiquinone.
Succinate binding site.
SdhA provides the binding site for the oxidation of succinate. The side chains Thr254, His354, and Arg399 of subunit A stabilize the molecule while FAD oxidizes and carries the electrons to the first of the iron-sulfur clusters, [2Fe-2S]. This can be seen in image 5.
Redox centers.
The succinate-binding site and ubiquinone-binding site are connected by a chain of redox centers including FAD and the iron-sulfur clusters. This chain extends over 40 Å through the enzyme monomer. All edge-to-edge distances between the centers are less than the suggested 14 Å limit for physiological electron transfer. This electron transfer is demonstrated in image 8.
Subunit E.
In molecular biology, the protein domain named Sdh5 is also named SdhE which stands for succinate dehydrogenase protein E. In the past, it has also been named YgfY and DUF339. Another name for SdhE is succinate dehydrogenase assembly factor 2 (Sdhaf2). This protein belongs to a group of highly conserved small proteins found in both eukaryotes and prokaryotes, including NMA1147 from "Neisseria meningitidis" and YgfY from "Escherichia coli". The SdhE protein is found on the mitochondrial membrane is it is important for creating energy via a process named the electron transport chain.
Function.
The function of SdhE has been described as a flavinator of succinate dehydrogenase. SdhE works as a co-factor chaperone that incorporates FAD into SdhA. This results in SdhA flavinylation which is required for the proper function succinate dehydrogenase. Studies indicate that SdhE is required by bacteria in order to grow on succinate, using succinate as its only source of carbon and additionally for the function, of succinate dehydrogenase, a vital component of the electron transport chain which produces energy.
Structure.
The structure of these proteins consists of a complex bundle of five alpha-helices, which is composed of an up-down 3-helix bundle plus an orthogonal 2-helix bundle.
Protein interactions.
SdhE interacts with the catalytic subunit of the succinate dehydrogenase (SDH) complex.
Human disease.
The human gene named "SDH5", encodes for the SdhE protein. The gene itself is located in the chromosomal position 11q13.1. Loss-of-function mutations result in paraganglioma, a neuroendocrine tumour.
History.
The recent studies which suggest SdhE is required for bacterial flavinylation contradict previous thoughts on SdhE. It was originally proposed that FAD incorporation into bacterial flavoproteins was an autocatalytic process. Recent studies now argue that SdhE is the first protein to be identified as required for flavinylation in bacteria. Historically, the SdhE protein was once considered a hypothetical protein. YgfY was also thought to be involved in transcriptional regulation.
Assembly and maturation.
All subunits of human mitochondrial SDH are encoded in nuclear genome. After translation, SDHA subunit is translocated as apoprotein into the mitochondrial matrix. Subsequently, one of the first steps is covalent binding of the FAD cofactor (flavinylation). This process seems to be regulated by some of the tricarboxylic acid cycle intermediates. Specifically, succinate, isocitrate and citrate stimulate flavinylation of the SDHA. In case of eukaryotic Sdh1 (SDHA in mammals), another protein is required for process of FAD incorporation – namely Sdh5 in yeast, succinate dehydrogenase assembly factor 2 (SDHAF2) in mammal cells.
Before forming a heterodimer with subunit SDHB, some portion of SDHA with covalently bound FAD appears to interact with other assembly factor – SDHAF4 (Sdh8 in yeast). Unbound flavinylated SDHA dimerizes with SDHAF4 which serves as a chaperone. Studies suggest that formation of SDHA-SDHB dimer is impaired in absence of SDHAF4 so the chaperon-like assembly factor might facilitate interaction of the subunits. Moreover, SDHAF4 seems to prevent ROS generation via accepting electrons from succinate which can be still oxidized by unbound monomeric SDHA subunit.
Fe-S prosthetic groups of the subunit SDHB are being preformed in the mitochondrial matrix by protein complex ISU. The complex is also thought to be capable of inserting the iron-sulphur clusters in SDHB during its maturation. The studies suggest that Fe-S cluster insertion precedes SDHA-SDHB dimer forming. Such incorporation requires reduction of cysteine residues within active site of SDHB. Both reduced cysteine residues and already incorporated Fe-S clusters are highly susceptible to ROS damage. Two more SDH assembly factors, SDHAF1 (Sdh6) and SDHAF3 (Sdh7 in yeast), seem to be involved in SDHB maturation in way of protecting the subunit or dimer SDHA-SDHB from Fe-S cluster damage caused by ROS.
Assembly of the hydrophobic anchor consisting of subunits SDHC and SDHD remains unclear. Especially in case of heme b insertion and even its function. Heme b prosthetic group does not appear to be part of electron transporting pathway within the complex II. The cofactor rather maintains the anchor stability.
Mechanism.
Succinate oxidation.
Little is known about the exact succinate oxidation mechanism. However, the crystal structure shows that FAD, Glu255, Arg286, and His242 of subunit A (not shown) are good candidates for the initial deprotonation step. Thereafter, there are two possible elimination mechanisms: E2 or E1cb. In the E2 elimination, the mechanism is concerted. The basic residue or cofactor deprotonates the alpha carbon, and FAD accepts the hydride from the beta carbon, oxidizing the bound succinate to fumarate—refer to image 6. In E1cb, an enolate intermediate is formed, shown in image 7, before FAD accepts the hydride. Further research is required to determine which elimination mechanism succinate undergoes in Succinate Dehydrogenase. Oxidized fumarate, now loosely bound to the active site, is free to exit the protein.
Electron tunneling.
After the electrons are derived from succinate oxidation via FAD, they tunnel along the [Fe-S] relay until they reach the [3Fe-4S] cluster. These electrons are subsequently transferred to an awaiting ubiquinone molecule within the active site. The Iron-Sulfur electron tunneling system is shown in image 9.
Ubiquinone reduction.
The O1 carbonyl oxygen of ubiquinone is oriented at the active site (image 4) by hydrogen bond interactions with Tyr83 of subunit D. The presence of electrons in the [3Fe-4S] iron sulphur cluster induces the movement of ubiquinone into a second orientation. This facilitates a second hydrogen bond interaction between the O4 carbonyl group of ubiquinone and Ser27 of subunit C. Following the first single electron reduction step, a semiquinone radical species is formed. The second electron arrives from the [3Fe-4S] cluster to provide full reduction of the ubiquinone to ubiquinol. This mechanism of the ubiquinone reduction is shown in image 8.
Heme prosthetic group.
Although the functionality of the heme in succinate dehydrogenase is still being researched, some studies have asserted that the first electron delivered to ubiquinone via [3Fe-4S] may tunnel back and forth between the heme and the ubiquinone intermediate. In this way, the heme cofactor acts as an electron sink. Its role is to prevent the interaction of the intermediate with molecular oxygen to produce reactive oxygen species (ROS). The heme group, relative to ubiquinone, is shown in image 4.
It has also been proposed that a gating mechanism may be in place to prevent the electrons from tunneling directly to the heme from the [3Fe-4S] cluster. A potential candidate is residue His207, which lies directly between the cluster and the heme. His207 of subunit B is in direct proximity to the [3Fe-4S] cluster, the bound ubiquinone, and the heme; and could modulate electron flow between these redox centers.
Proton transfer.
To fully reduce the quinone in SQR, two electrons as well as two protons are needed. It has been argued that a water molecule (HOH39) arrives at the active site and is coordinated by His207 of subunit B, Arg31 of subunit C, and Asp82 of subunit D. The semiquinone species is protonated by protons delivered from HOH39, completing the ubiquinone reduction to ubiquinol. His207 and Asp82 most likely facilitate this process. Other studies claim that Tyr83 of subunit D is coordinated to a nearby histidine as well as the O1 carbonyl oxygen of ubiquinone. The histidine residue decreases the pKa of tyrosine, making it more suitable to donate its proton to the reduced ubiquinone intermediate.
Inhibitors.
There are two distinct classes of inhibitors of complex II: those that bind in the succinate pocket and those that bind in the ubiquinone pocket. Ubiquinone type inhibitors include carboxin and thenoyltrifluoroacetone. Succinate-analogue inhibitors include the synthetic compound malonate as well as the TCA cycle intermediates, malate and oxaloacetate. Indeed, oxaloacetate is one of the most potent inhibitors of Complex II. Why a common TCA cycle intermediate would inhibit Complex II is not entirely understood, though it may exert a protective role in minimizing reverse-electron transfer mediated production of superoxide by Complex I. Atpenin 5a are highly potent Complex II inhibitors mimicking ubiquinone binding.
Ubiquinone type inhibitors have been used as fungicides in agriculture since the 1960s. Carboxin was mainly used to control disease caused by basidiomycetes such as stem rusts and "Rhizoctonia" diseases. More recently, other compounds with a broader spectrum against a range of plant pathogens have been developed including boscalid, penthiopyrad and fluopyram. Some agriculturally important fungi are not sensitive towards members of the new generation of ubiquinone type inhibitors
Role in disease.
The fundamental role of succinate-coenzyme Q reductase in the electron transfer chain of mitochondria makes it vital in most multicellular organisms, removal of this enzyme from the genome has also been shown to be lethal at the embryonic stage in mice.
Mammalian succinate dehydrogenase functions not only in mitochondrial energy generation, but also has a role in oxygen sensing and tumor suppression; and, therefore, is the object of ongoing research.
Reduced levels of the mitochondrial enzyme succinate dehydrogenase (SDH), the main element of complex II, are observed post mortem in the brains of patients with Huntington's Disease, and energy metabolism defects have been identified in both presymptomatic and symptomatic HD patients.


Victor A. McKusick

Victor Almon McKusick (October 21, 1921 – July 22, 2008) was an American internist and medical geneticist, and Professor of Medicine at the Johns Hopkins Hospital, Baltimore. He was a proponent of the mapping of the human genome due to its use for studying congenital diseases. He is well known for his studies of the Amish. He was the original author and, until his death, remained chief editor of Mendelian Inheritance in Man (MIM) and its online counterpart Online Mendelian Inheritance in Man (OMIM). He is widely known as the "father of medical genetics".
Personal life.
Victor and his identical twin Vincent L. McKusick were born on October 21, 1921. Victor was one of five children. His father was a graduate of Bates College. Before deciding to work as a dairy farmer, Victor's father served as a high school principal in Chester, Vermont. Victor's mother had been an elementary school teacher before marrying. Victor and his siblings were raised on a dairy farm in Parkman, Maine.
During the summer of 1937, Victor suffered a severe microaerophilic "Streptococcus" infection in his axilla. As a result, Victor spent time in two hospitals, one of which was Massachusetts General Hospital. He finally saw a successful diagnosis and course of treatment, using sulfanilamide during his ten weeks at Massachusetts General. Since none of his close family were doctors, the events of 1937 represented McKusick's first substantial experience with the medical community. He stated, "Perhaps I would have ended up a lawyer if it weren't for the "microaerophilic streptococcus"."
Victor married Anne Bishop McKusick in 1949. Anne served Johns Hopkins Hospital as Associate Professor of Medicine in the Division of Rheumatology. The couple had two sons, Victor and Kenneth, and a daughter, Carol.
Medical career.
Education.
After high school, Victor chose to study at Tufts University, and studied there for six semesters from the fall of 1940 to the summer of 1942. Although Tufts had an associated medical school, Victor was fascinated by Johns Hopkins and by its dedication to medical research, and chose to attend Hopkins Medical School instead.
The history and research environment of Hopkins excited McKusick, and during World War II The Johns Hopkins University School of Medicine could not fill its classes. Therefore, the school temporarily discontinued requiring a baccalaureate degree as for admission for the first time since the school's founding in 1893. Victor applied during his sixth semester at Tufts, and began in the fall of 1942, as one of the first, of very few, who ever entered the school without a bachelor's degree. Victor never earned a baccalaureate degree, although he has been awarded over 20 honorary degrees. He earned his Doctor of Medicine through an accelerated program in only three years. He was offered the prestigious William Osler Internship in Internal Medicine at Johns Hopkins Hospital, and chose to remain at Hopkins for his residency. He completed his residency training as a cardiologist, since the department of genetics did not exist at the time. McKusick specialized in heart murmurs, and utilized spectroscopy to analyze heart sounds.
Work at Hopkins.
In 1956 McKusick traveled to Copenhagen to speak about the heritable disorders of connective tissue at the first international congress of human genetics. The meeting looms as the birthplace of the medical genetics field. In the following decades, McKusick went on to head the Chronic Disease Clinic and created and chaired a new Division of Medical Genetics at Hopkins beginning in 1957. In 1973, he served as Physician-in-Chief, William Osler Professor of Medicine, and Chairman of the Department of Medicine at Johns Hopkins Hospital and School of Medicine. McKusick resigned the appointments in 1985, but continued to teach, conduct research, and practice medicine in the Departments of Medicine and Medical Genetics. He held concurrent appointments as University Professor of Medical Genetics at the McKusick–Nathans Institute of Genetic Medicine, Professor of Medicine at the Johns Hopkins School of Medicine, Professor of Epidemiology at the Johns Hopkins Bloomberg School of Public Health, and Professor of Biology at Johns Hopkins University.
McKusick played a role in the development of the HeLa cell line that has been instrumental in biomedical research, although he did not reveal to the Lacks family all the details about subsequent blood draws which were for genotyping HeLa.
He held numerous faculty appointments while remaining at Johns Hopkins until his death in 2008.
Organizations.
In 1960, McKusick founded and co-directed the Annual Short Course in Medical and Experimental Mammalian Genetics at the Jackson Laboratory in Bar Harbor, Maine. He published "Mendelian Inheritance in Man" "(MIM)", which was the first published catalog of all known genes and genetic disorders, in 1966. The complete text of "MIM "was made available online free of charge beginning in 1987, and titled "Online Mendelian Inheritance in Man (OMIM)". The 12th and final print edition was published in 1998. The online database is continually updated, and linked with the National Center for Biotechnology Information. "OMIM" is distributed through the National Library of Medicine, and has been a part of the Entrez database network system since 1995. At the time of McKusick's death, "OMIM" contained 18,847 entries. He also led the Annual Course in Medical Genetics at the University of Bologna Residential Center in Bertinoro di Romagna, Italy in 1987. McKusick was founding president of the Human Genome Organization in 1989.
Publications and research.
McKusick wrote extensively on the history of medicine, genetics, medical genetics, and about Parkman, Maine. He co-founded "Genomics" in 1987 with Dr. Frank Ruddle, and served as an editor. He led a Congressionally-chartered committee examining the ethics of testing Abraham Lincoln's tissue for the presence of Marfan syndrome genes.
His well-known published articles include:
In a 2005 paper presented by M.I. Poling, McKusick said:
I have always told my students, residents, and fellows, if you want to really get on top of some topic, you need to know how it got from where it was to how it is now. I was always strong on eponyms, too—like Marfan syndrome, Freeman–Sheldon syndrome, Down syndrome, Tay–Sachs disease, etc. On rounds, the resident or student would present a patient with some particular condition, and I would always ask, so who is so and so for whom the disease was named. This prompts thought and research into the disease or condition itself to find out who first described it and, therefore, for whom it was named.
Study of genes among the Amish.
McKusick's study of genetics among the Amish is perhaps his most famous research. On his first trip to Amish homes, he was accompanied by Dr. David Krusen who had an extensive medical practice among the Amish in Lancaster, Pennsylvania. McKusick spoke about his introduction to Krusen's work, stating, "He [Krusen] indicated to the author of the article—in a slick-paper, pharmaceutical company 'throw-away'—that achondroplasia is frequent among the Amish. Initial study led to the identification of two recessive conditions named Ellis–van Creveldsyndrome syndrome and cartilage-hair hypoplasia (later named metaphyseal chondrodysplasia, McKusick type).
McKusick listed fifteen advantages to studying genetics among the Amish. Today, these fifteen reasons are argued to be true as well. McKusick's findings led many other researchers to study hereditary related diseases in the 1960s and 1970s. Other researchers and McKusick cite the Amish as working cooperatively with researchers to determine the reason for inherited diseases. McKusick published his official findings from working with the Amish in 1978, titled "Medical Genetic Studies of the Amish".
Awards and honors.
McKusick received more than 20 honorary degrees throughout and after his career.
Some of the awards he won are listed below:
Death.
McKusick died of cancer at the age of 86, on July 22, 2008. He died at his home right outside of Baltimore, in Towson, Maryland. On the 21st, the day before he died, he watched a live-stream of a course on medical genetics from Bar Harbor, Maine, which he helped found and direct in 1960.


Cellular component

Cellular components are the complex biomolecules and structures of which cells, and thus living organisms, are composed. Cells are the structural and functional units of life. The smallest organisms are single cells, while the largest organisms are assemblages of trillions of cells. DNA is found in nearly all living cells; each cell carries chromosome(s) having a distinctive DNA sequence.
Examples include macromolecules such as proteins and nucleic acids, biomolecular complexes such as a ribosome, and structures such as membranes, and organelles. While the majority of cellular components are located within the cell itself, some may exist in extracellular areas of an organism.
Cellular components may also be called biological matter or biological material. Most biological matter has the characteristics of soft matter, being governed by relatively small energies. All known life is made of biological matter. To be differentiated from other theoretical or fictional life forms, such life may be called "carbon-based", "cellular", "organic", "biological", or even simply "living" – as some definitions of life exclude hypothetical types of biochemistry.


Amphiorycteropus

Amphiorycteropus is a genus of mammals in the family Orycteropodidae within Tubulidentata. The genus is known from Middle Miocene to Early Pliocene of Africa, Asia and Europe.
Species.
Five species are recognized:
Other two species are assigned to the genus provisionally until new material are found and confirm the relationship:


Samir Mitragotri

Samir Mitragotri (born 28 May 1971 in Solapur, India) is an Indian American professor at Harvard University, an inventor, an entrepreneur, and a researcher in the fields of drug delivery and biomaterials. He is currently the Hiller Professor of Bioengineering and Hansjörg Wyss Professor of Biologically Inspired Engineering at Harvard John A. Paulson School of Engineering and Applied Sciences and the Wyss Institute for Biologically Inspired Engineering. Prior to 2017, he was the Duncan and Suzanne Mellichamp Chair Professor at University of California, Santa Barbara.
Mitragotri is widely recognized for his contributions to the field of drug delivery. He is considered a pioneer of many novel drug delivery technologies, especially in the fields of transdermal, oral and targeted systems. He invented techniques to deliver drugs transdermally using low-frequency ultrasound, pulsed microjet injector, high throughput skin experimentation, skin penetrating peptides and ionic liquids. He also invented intestinal patches and ionic liquids for oral delivery of proteins. Mitragotri also pioneered nanoparticle-enabled cell therapies which use drug-loaded nanoparticles that hitch a ride on red blood cells, monocytes and other circulatory cells for tissue-specific delivery. Mitragotri’s technologies are used to develop next generation therapies against diabetes, cancer, psoriasis, hemorrhage, trauma and infections.
Mitragotri has published over 300 research publications, has given over 500 presentations worldwide, and is an inventor on over 180 patents/applications. His publications are cited with an h-index of 102. Mitragotri is a member of U.S. National Academy of Engineering, National Academy of Medicine, and National Academy of Inventors. He is a co-founder of several companies that are developing products based on his inventions. He received his PhD in Chemical Engineering at MIT and BS in Chemical Engineering from the Institute of Chemical Technology. Mitragotri serves on the editorial boards of several journals and currently serves as Editor-in-Chief of Bioengineering and Translational Medicine.
Awards and honors.
Mitragotri's national and international awards include:
Biotech Companies.
Samir Mitragotri has co-founded several companies:


Propylphenidate

Propylphenidate (also known as PPH) is a piperidine based stimulant drug, closely related to methylphenidate, but with the methyl ester replaced by a propyl ester. It was banned in the UK as a Temporary Class Drug from April 2015 following its unapproved sale as a designer drug.
Legal status.
Propylphenidate is illegal in Sweden as of 26. January 2016.


Dietzia psychralcaliphila

Dietzia psychralcaliphila is a facultatively psychrophilic alkaliphile that grows on hydrocarbons. It is aerobic, non-motile and gram-positive. The type strain is ILA-1T (= JCM 10987T = IAM14896T = NCIMB 13777T).


Science Signaling

Science Signaling is a peer-reviewed scientific journal that is published weekly by the American Association for the Advancement of Science (AAAS). The editor-in-chief (Chief Scientific Editor) is Michael B. Yaffe (Massachusetts Institute of Technology), and the journal is part of the Science Family of Journals of which Jeremy Berg is the Editor-in-Chief.
Scope.
The journal covers research on cell signaling and the processes of cellular regulation. In addition, the journal covers signaling networks, synthetic biology, systems biology, drug discovery, and computation and modeling of regulatory pathways. Besides full length articles, it also publishes reviews, perspectives, meeting reports, presentations (for a wider audience), protocols, book reviews, teaching resources, a glossary, and a Journal Club section.
History.
The journal was established in 1999 as Science's STKE. On January 8, 2008, it obtained its current name and volume numbering restarted at 1. As "Science's STKE", the journal's last issue was volume 2007, issue 417, on December 18, 2007.
Abstracting and indexing.
"Science Signaling" is abstracted and indexed by:
According to the "Journal Citation Reports", the journal has a 2016 impact factor of 6.494.


Muriel Wheldale Onslow

Muriel Wheldale Onslow (31 March 1880 – 19 May 1932) was a British biochemist, born in Birmingham, England. She studied the inheritance of flower colour in the common snapdragon Antirrhinum and the biochemistry of anthocyanin pigment molecules. She attended the King Edward VI High School in Birmingham and then matriculated at Newnham College, Cambridge in 1900. At Cambridge she majored in botany. Onslow later worked within Bateson's genetic group and then Frederick Gowland Hopkins biochemical group in Cambridge, providing her with expertise in biochemical genetics for investigating the inheritance and biosynthesis of petal colour in Antirrhinum. She was one of the first women appointed as a lecturer at Cambridge, after moving to the Biochemistry department.
Education and personal life.
She was the only child of her parents John and Fannie (née Hayward) Wheldale. Her father was a solicitor. She attended King Edward VI High School in Birmingham, which was well known amongst single-sex schools for its strong science teaching to girls. In 1900, she entered Newnham College, Cambridge and achieved a First Class result in Part I of the Natural Sciences Tripos in 1902. She took Part II (Botany) in 1904 and again achieved a First Class result but was not awarded a degree since University of Cambridge did not award degrees to women until 1948.
In 1919 she married biochemist Victor Alexander Herbert Huia Onslow, second son of the 4th Earl of Onslow. They had no children. He had recently entered the field of chemical genetics, and their work was closely associated. Victor Onslow was paralysed from the waist down following a diving accident and died in 1922. In her memoir for her husband she wrote that he was a man of amazing courage and mental vitality enabling him to gain a career in biochemistry despite his physical circumstances, and with her encouragement and assistance.
She was very keen on travel and took a particular interest in the Balkans and other parts of Eastern Europe, especially in her later years.
She died at her home in Cambridge on 19 May 1932.
Career.
Her work was funded initially by a Bathurst studentship in 1904 and then Newnham College fellowship for 6 years, starting in 1909.
In 1903, she joined William Bateson's genetics group at Cambridge where she began her study focusing on the inheritance of petal colour in Antirrhinum (snapdragons). William Bateson was the English biologist who was the first person to use the term genetics to describe the study of heredity, and the chief populariser of the ideas of Gregor Mendel following their rediscovery in 1900. Bateson and Onslow, alongside a research group mainly made up of Newnham College graduates, carried out a series of breeding experiments in various plant and animal species between 1903 and 1910.
By 1906 she had enough data to formulate a rudimentary factorial analysis on snapdragon inheritance. In 1907, Wheldale published a full explanation what became termed epistasis, the phenomenon of dominant-like relationship between different pairs of nonallelomorphic factors. Wheldale's study of genetics on flower colouration ultimately gained her the most recognition, with the 1907 publication of a full factorial analysis of flower colour inheritance in snapdragons and the four subsequent papers she published from 1909 to 1910. Her interest was in the biochemistry underlying the petal colours, rather than understanding inheritance itself. Her study of the chemistry of the anthocyanin pigments culminated in publication of her first book in 1916, "The Anthocyanin Pigments of Plants". This application of chemical analysis to explain genetic data led to international recognition since it was among the first attempts at syntheses of these two areas.
She was an assistant lecturer in Newnham College between 1906 and 1908.
She left Cambridge University between 1911 and 1914 because she held a studentship at the John Innes Horticultural Institution where, in addition to her laboratory work, she was valued as the Institution's leading botanical artist, able to capture the exact colours of plants. During this time in 1913 she became one of the first three women to be elected to the Biochemical Club (later to be known as the Biochemical Society) after the club's initial exclusion of women in 1911.
She joined the biochemistry lab of Frederick Gowland Hopkins at Cambridge University in 1914, where she pursued the biochemical aspects of petal colour, whose genetics she had elucidated during her work with Bateson. She worked on oxidase systems which were also involved in additional areas of plant biology. This led her to work for the Food Investigation Board from 1917 onward and then, and from 1922 leading a team working on fruit ripening at the Cambridge Low Temperature Station from 1922. Between 1917 and 1922 she collaborated with Victor Onslow on the colour and iridescence in insect scales. In 1925 she produced a second, substantially revised edition of her book "The Anthocyanin Pigments of Plants", updated for the substantial developments in the field since the first 1916 edition.
In combining genetics and biochemistry she became one of the first biochemical geneticists and paved the way for the later successes of such seminal investigators as Edward Tatum and George Beadle.
In 1926 she was one of the first women appointed as a University Lecturer at Cambridge, in plant biochemistry in the biochemistry department. Students considered that she was an inspiring teacher and her course in plant biochemistry was an important part of the advanced botany curriculum.
Amongst her followers was Rose Scott-Moncrieff who went on to identify the first crystalline form of primulin in about 1930. This was the first crystalline anthocyanin pigment ever identified. Onslow and Scott-Moncrieff have been credited with founding biochemical genetics, although Scott-Moncrieff is thought to have the stronger claim.
Legacy.
There is a prize and research fellowship named after her at Newnham College, University of Cambridge.
In 2010 the Royal Institution of Great Britain staged a play, entitled "Blooming Snapdragons", about four early-20th-century women biochemists, one of whom was Onslow. Written by Liz Rothschild and directed by Sue Mayo, it had been commissioned by the John Innes Centre where Onslow worked.


Methyl-MMDA-2

"N"-Methyl-2-methoxy-4,5-methylenedioxyamphetamine (methyl-MMDA-2; 6-methoxy-MDMA) is a psychedelic drug of the amphetamine class. It is the "N"-methylated derivative of MMDA-2, and it is also an analog of MDMA and 6-methyl-MDA.
Methyl-MMDA-2 was first synthesized by Alexander Shulgin and was described in his book "PiHKAL". He states that it is essentially inactive at a dose of 70 mg, and he did not try any higher; however, Methyl-MMDA-2 is still likely to be active, perhaps in the 125-250 mg range. This reduction in hallucinogenic activity relative to MMDA-2 parallels that of MDA and MDMA, indicating that with phenethylamines, "N"-methylation substantially reduces 5-HT2A receptor affinity.


ATAC-seq

ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) is a technique used in molecular biology to assess genome-wide chromatin accessibility. In 2013, the technique was first described as an alternative advanced method for MNase-seq, FAIRE-Seq and DNase-Seq. ATAC-seq is a faster and more sensitive analysis of the epigenome than DNase-seq or MNase-seq.
Description.
ATAC-seq identifies accessible DNA regions by probing open chromatin with hyperactive mutant Tn5 Transposase that inserts sequencing adapters into open regions of the genome. While naturally occurring transposases have a low level of activity, ATAC-seq employs the mutated hyperactive transposase. In a process called "tagmentation", Tn5 transposase cleaves and tags double-stranded DNA with sequencing adaptors. The tagged DNA fragments are then purified, PCR-amplified, and sequenced using next-generation sequencing. Sequencing reads can then be used to infer regions of increased accessibility as well as to map regions of transcription factor binding sites and nucleosome positions. The number of reads for a region correlate with how open that chromatin is, at single nucleotide resolution. ATAC-seq requires no sonication or phenol-chloroform extraction like FAIRE-seq; no antibodies like ChIP-seq; and no sensitive enzymatic digestion like MNase-seq or DNase-seq. ATAC-seq preparation can be completed in under three hours.
Applications.
ATAC-Seq analysis is used to investigate a number of chromatin-accessibility signatures. The most common use is nucleosome mapping experiments, but it can be applied to mapping transcription factor binding sites, adapted to map DNA methylation sites, or combined with sequencing techniques.
The utility of high-resolution enhancer mapping ranges from studying the evolutionary divergence of enhancer usage (e.g. between chimps and humans) during development and uncovering a lineage-specific enhancer map used during blood cell differentiation.
ATAC-Seq has also been applied to defining the genome-wide chromatin accessibility landscape in human cancers, and revealing an overall decrease in chromatin accessibility in macular degeneration. Computational footprinting methods can be performed on ATAC-seq to find cell specific binding sites and transcription factors with cell specific activity.
Single-cell ATAC-seq.
Modifications to the ATAC-seq protocol have been made to accommodate single-cell analysis. Microfluidics can be used to separate single nuclei and perform ATAC-seq reactions individually. With this approach, single cells are captured by either a microfluidic device or a liquid deposition system before tagmentation. An alternative technique that does not require single cell isolation is combinatorial cellular indexing. This technique uses barcoding to measure chromatin accessibility in thousands of individual cells; it can generate epigenomic profiles from 10,000-100,000 cells per experiment. But combinatorial cellular indexing requires additional, custom-engineered equipment or a large quantity of custom, modified Tn5. Recently, a pooled barcode method called sci-CAR was developed, allowing joint profiling of chromating accessibility and gene expression of single cells.
Computational analysis of scATAC-seq is based on construction of a count matrix with number of reads per open chromatin regions. Open chromatin regions can be defined, for example, by standard peak calling of pseudo bulk ATAC-seq data. Further steps include data reduction with PCA and clustering of cells. scATAC-seq matrices can be extremely large (hundreds of thousands of regions) and is extremely sparse, i.e. less than 3% of entries are non-zero. Therefore, imputation of count matrix is another crucial step. As with bulk ATAC-seq, scATAC-seq allows finding regulators like transcription factors controlling gene expression of cells. This can be achieved by looking at the number of reads around TF motifs or footprinting analysis.


Isomescaline

Isomescaline (2,3,4-trimethoxyphenethylamine) is a lesser-known compound based on a well-known psychedelic drug. It is an isomer of mescaline, as well as an analog of TIM-2, TIM-3, and TIM-4. Isomescaline was first synthesized by Alexander Shulgin. In his book "PIHKAL", it is suggested that any potentially active dose would be "greater than 400 mg". Despite its structural similarity to mescaline, isomescaline has produced no effects in humans. Very little data exists about the pharmacological properties, metabolism, and toxicity of isomescaline.


Putative gene

A putative gene is a segment of DNA that is believed to be a gene. Putative genes can share sequence similarities to already characterized genes and thus can be inferred to share a similar function, yet the exact function of putative genes remains unknown. Newly identified sequences are considered putative gene candidates when homologs of those sequences are found to be associated with the phenotype of interest.
Examples.
Examples of studies involving putative genes include the discovery of 30 putative receptor genes found in rat vomeronasal organ (VNO) and the identification of 79 putative TATA boxes found in many plant genomes.
Practical importance.
In order to define and characterize a biosynthetic gene cluster, all the putative genes within said cluster must first be identified and their functions must be characterized. This can be performed by complementation and knock out experiments. In the process of characterizing putative genes, the genome under study becomes increasingly well understood as more interactions can be identified. Identification of putative genes is necessary to study genomic evolution, as significant proportion of genomes make up larger families of related genes. Genomic evolution occurs by processes such as duplication of individual genes, genome segments, or entire genomes. These processes can result in loss of function, altered function, or gain of function, and have drastic affects on the phenotype.
DNA mutations outside of a putative gene can act by positional effect, in which they alter the gene expression. These alterations leave the transcription unit and promoter of the gene intact, but may involve distal promoters, enhancer/silencer elements, or the local chromatin environment. These mutations can be associated with diseases or disorders associated with the gene.
Identification.
Putative genes can be identified by clustering large groups of sequences by patterns and arranging by mutual similarity or can be inferred by potential TATA boxes.
Putative genes can also be identified by recognizing differences between well-known gene clusters and gene clusters with a unique profiling.
Software tools have been developed in order to automatically identify putative genes. This is done by searching for gene families and testing the validity of uncharacterized genes by comparison to already identified genes.
Protein products can be identified and used to characterize the putative gene that codes for it.


Only My Railgun

"Only My Railgun" (stylized as "only my railgun") is a Japanese single released by the pop and trance duo fripSide, the first single by fripSide to feature Yoshino Nanjō as its new lead vocalist. It was released on November 4, 2009 under the label Geneon. The track is used as the opening theme for the anime television series "A Certain Scientific Railgun", which is a spin-off of the series "A Certain Magical Index". This is fripSide's first tie-in with the said anime series.
The single debuted at number three on the Oricon Singles Chart, selling 26,000 copies in its first week.
Track listing.
[CD]
[DVD]


P. Ananda Kumar

P. Ananda Kumar is an Indian plant molecular biologist and biotechnologist.
Education.
Born in a small village Kuchipudi, near Tenali, Guntur district of South Indian state of Andhra Pradesh Dr Kumar studied in the local S K V High School, VSR and NVR College, Tenali and Siver Jubilee Government College, Kurnool. He acquired M.Sc degree in Botany from Sri Venkateswara University, Tirupati. He joined Agricultural Research Service in 1978 He started his research career at Central Tobacco Research Institute, Rajahmundry.
Career.
Kumar moved to the Indian Agricultural Research Institute, New Delhi in 1979 and started working in the area of Plant Nitrogen Metabolism. His research contributions lead to the finding that the photorespiratory nitrogen cycle is an open process. He discovered that nitrate reductase enzyme derives its reducing power from photorespiration, considered a wasteful process by many plant physiologists. Kumar acquired Ph.D degree in plant physiology for his research on photorespiratory ammonia assimilation in crop species. Kumar worked as Alexander von Humboldt Fellow in the University of Hannover, Germany in 1991 and 1992. Chloroplast targeting of cyanobacterial nitrate reducase was achieved in order to link nitrate reduction to photosynthetic electron transport.
Biotechnology.
Having acquired experience in molecular biology, Kumar started working on transgenic crops for insect resistance at Biotechnology Centre of IARI. He developed Bt brinjal and field-tested it in 1995. The "Event 142" that expresses a Bt insecticidal protein Cry1Fa1 is highly effective against Brinjal Shoot and Fruit Borer. The Event 142 was licensed to private companies for commercialization. Another "Event 25" was developed in tomato for protection against Tomato Fruit Borer ("Helicoverpa armigera"). Event 25 was also licensed to a private company. He also worked in the areas of "Bacillus thuringiensis", gene discovery, tissue specific promoters, protein purification and functional genomics of cotton, Ragi and brinjal.
Bt Genes.
Dr Kumar constructed three codon modified genes encoding insecticidal proteins of "Bacillus thuringiensis" (Bt) viz., CryAc-F, Cry1Fa1 and Cry2Aa. Indian patents were granted for the first two genes. The patent application for "cry2Aa" gene was published in 2011. Several genetically modified events were generated in major crops by scientists in public research institutions and private companies. These events are currently being tested for biosafety under the GMO regulatory System of India.
Genomics.
Dr Kumar also works in the area of plant genomics. He collaborated with Canadian institutions to sequence the Flax genome. Extensive work was carried out to unravel the genomics of cotton in relation to fibre development and the effect of abiotic and biotic stresses on cotton boll development.
NRCPB.
Dr Kumar was Director of National Research Centre for Plant Biotechnology (NRCPB) located on the campus of Indian Agricultural Research Institute, New Delhi, India. NRCPB reached great heights during his tenure (2007-2012). The institute unveiled genome sequences of tomato, Pigeonpea and Linseed. Public-Private Partnership (PPP) was given impetus and several technologies were commercialized. The institute was conferred with 'Sardar Patel Best ICAR Institution Award' by ICAR and 'Mahindra Krishi Sansthan Award' by Mahindra and Mahindra.
SPBB.
Dr Kumar is Secretary of the Society for Plant Biochemistry and Biotechnology (SPBB). The society publishes a highly rated journal 'Journal of plant Biochemistry and Biotechnology' in collaboration with Springer.
Dr Kumar organized a highly successful international conference at New Delhi (21–24 February 2012) on behalf of SPBB. The conference was inaugurated by Prof. M.S. Swaminathan and attended by more than 600 national and international delegates.
ANGRAU.
Dr Kumar took over the responsibility of heading the 'Institute of Biotechnology' located in Acharya N.G. Ranga Agricultural University (ANGRAU), Hyderabad, India, as Director in August 2013.
IIRR (DRR).
Dr Kumar moved back to Indian Council of Agricultural Research after the university deputation was completed. He joined Directorate of Rice Research at Hyderabad in April 2015. The institute is currently known as Indian Institute of Rice Reseaech. His research focuses on the root genomics of rice under aerobic and anaerobic conditions.
Director, IIRR.
Dr Kumar has taken charge of Director, IIRR with effect from 1 July 2017. He superannuated from ICAR service on 30 November 2017.
Humboldt Fellow.
After retirement, Dr Kumar joined the Institute of Botany, Leibniz University, Hannover as Alexander von Humboldt Senior Fellow. He worked on regeneration "in vitro" of a single cell C4 plant species "Bienertia sinupersici". He successfully regenerated it via somatic embryogenesis.
Scientist Emeritus.
Dr Kumar joined ICAR-Indian Institute of Rice Research (IIRR) as Scientist Emeritus on October 1, 2018 to continue his research on genomics of rice under aerobic conditions.


Masterpiece (Mami Kawada song)

"masterpiece" is the seventh single released by the J-pop singer, Mami Kawada, and was released on February 4, 2009. The title track was used as the second opening theme for the anime series "A Certain Magical Index" which is her third tie-in with the anime series. This is also Kawada's first single to be produced by a female composer/arranger of I've Sound, which is Maiko Iuchi.
The coupling song jellyfish was used as an insert song on the twenty-third episode of "A Certain Magical Index" making this Kawada's 4th tie-in with the said anime series.
The single will come in a limited CD+DVD edition (GNCV-0013) and a regular edition (GNCV-0014). The DVD will contain the Promotional Video for masterpiece.
Reception.
It peak ranked 12th on the weekly Oricon singles chart and remained on the chart for nine weeks.


Greater long-tailed shrew tenrec

The greater long-tailed shrew tenrec ("Microgale principula") is an afrotherian species of mammal in the family Tenrecidae. It is endemic to Madagascar, where its natural habitats are subtropical or tropical moist lowland forests or moist montane forests. Habitat loss threatens its survival.
Distribution and habitat.
The greater long-tailed shrew tenrec is found in eastern Madagascar at altitudes between above sea level, its range extending from Marojejy southwards to Andohahela. It is an arboreal species and is found in both primary and somewhat degraded humid forests.
Andrahomana Cave.
The greater long-tailed shrew tenrec is one of eight species of "Microgale" tenrecs whose remains have been found in deposits in caverns at Andrahomana on the southern coast of Madagascar alongside the bones of extinct birds including elephant birds and Malagasy sheldgoose. The latter, a waterbird, indicates that a large body of fresh water may have been nearby and moister conditions were probably present in the past. The creatures may have fallen into the cave system through "skylights" in the roof. The cave is outside the present day range of the greater long-tailed shrew tenrec.
Status.
Besides the risk of wildfire, the main threats faced by the greater long-tailed shrew tenrec are destruction of its forest habitat by logging and by its conversion into agricultural land. However the animal's range is wide, it is common in many places and presumably has a large total population, and it is present in a number of protected areas, so the International Union for Conservation of Nature has assessed its conservation status as being of "least concern".


KIX domain

In biochemistry, the KIX domain (kinase-inducible domain (KID) interacting domain) or CREB binding domain is a protein domain of the eukaryotic transcriptional coactivators CBP and P300. It serves as a docking site for the formation of heterodimers between the coactivator and specific transcription factors. Structurally, the KIX domain is a globular domain consisting of three α-helices and two short 310-helices.
The KIX domain was originally discovered in 1996 as the specific and minimal region in CBP that binds and interacts with phosphorylated CREB to activate transcription. It was thus first termed CREB-binding domain. However, when it was later discovered that it also binds many other proteins, the more general name KIX domain became favoured. The KIX domain contains two separate binding sites: the "c-Myb site", named after the oncoprotein c-Myb, and the "MLL site", named after the proto-oncogene MLL (Mixed Lineage Leukemia, KMT2A).
The paralogous coactivators CBP (CREBBP) and P300 (EP300) are recruited to DNA-bound transcription factors to activate transcription. Coactivators can associate with promoters and enhancers in the DNA only indirectly through protein-protein contacts with transcription factors. CBP and P300 activate transcription synergistically in two ways: first, by remodelling and relaxing chromatin through their intrinsic histone acetyltransferase activity, and second, by recruiting the basal transcription machinery, such as RNA polymerase II.
The KIX domain belongs to the proposed GACKIX domain superfamily. GACKIX comprises structurally and functionally highly homologous domains in related proteins. It is named after the protein GAL11 / ARC105 (MED15), the plant protein CBP-like, and the KIX domain from CBP and P300. Additional instances include RECQL5 and related plant proteins. All of these contain a KIX domain or KIX-related domain that interacts with the transactivation domain of many different transcription factors. The distinction between a KIX domain, a KIX-related domain and a GACKIX domain is subject to an ongoing debate and not clearly defined.
The full CBP/P300 protein.
Aside from the KIX domain, CBP and P300 contain many other protein binding domains that should not be confused (numbers are aa numberings):
All three CH (cysteine/histidine-rich) domains are zinc fingers.
Interactions.
Human and animal proteins:
Yeast proteins:
Viral proteins:


Gerronema viridilucens

Gerronema viridilucens is a species of agaric fungus in the family Marasmiaceae. Found in South America, the mycelium and fruit bodies of the fungus are bioluminescent.


Gaylord Harnwell

Gaylord Probasco Harnwell CBE (September 29, 1903 – April 18, 1982), was an American educator and physicist, who was president of the University of Pennsylvania from 1953 to 1970. He also held a great number of positions in a wide variety of national political and educational boards and committees, as well as senior positions in both the Office of the Governor of Pennsylvania and the United States Navy. In the later part of his life he also toured both the Soviet Union and Iran as a promoter of higher education.
Career.
Early life.
Harnwell was born in Evanston, Illinois to Chicago born lawyer Frederick William and Anna Jane Wilcox Harnwell. After attending Evanston Township High School and Haverford College in Haverford, Pennsylvania in 1924, Harnwell attended both Cambridge University and then Princeton University, gaining an M.A. and Ph.D. in physics in 1926 and 1927 respectively. From 1927 until 1928 Harnwell taught physics at the California Institute of Technology and then from 1928 to 1938 he taught at Princeton, becoming associate professor by 1936. Then in 1938 Harnwell took over the physics department at the University of Pennsylvania.
After the outbreak of the Second World War, Harnwell was given a leave of absence to serve as director of the University of California Division of War Research for the U.S. Navy Radio and Sound Laboratory in San Diego, California from 1942 until 1946, earning the Medal for Merit the following year.
University of Pennsylvania.
Harnwell returned to the university's physics department until 1953 when he was elected as the university's president, a position he held until 1970. During his term he oversaw rapid expansion of the university during a period that is cited as "a new milestone in the history of the development of the University."
During his time as president, Harnwell also served in a number of positions within the United States Navy, including chairman of the Ordnance Committee of the Research and Development Board of the Department of Defense and chairman of the Committee on Undersea Warfare of the National Research Council. He was also a member of the Advisory Panel on Ordnance, Transport and Supply of the Department of Defense, Advisory Board of the U. S. Navy Ordnance Laboratory, Science Information Council of the National Science Foundation and congressional Subcommittee on Military Applications of Atomic Energy. In 1958, Harnwell was awarded the Navy Distinguished Public Service Award.
Harnwell also toured educational facilities in the Soviet Union and Iran in 1958 and then 1960 and 1961, discussing the proposal to found an American-style university in Shiraz. These tours gave Harnwell material for a number of published works, and fostered relationships between University of Pennsylvania and Pahlavi University in Iran. From 1958 until 1970 he was also a member of the Pennsylvania Railroad Company board, and in 1971 became president of the Penn Central Company. He also held a number of other influential positions, including Public Governor of the New York Stock Exchange, director of the Chamber of Commerce of Greater Philadelphia, First Pennsylvania Banking and Trust Company, Philadelphia CARE Committee, Rore-Amchem, Inc., the United Fund of the Philadelphia Area, the Food Distribution Center Corporation, the National Society of Scabbard and Blade, and the Institute for Educational Management in Boston.
Later life.
Harnwell was also involved in the office of the state governor, as chairman of the Council of Science and Technology, Committee on Tax Administration, Tax Study and Revision Commission and Commonwealth Priorities Commission at various times in the last decade of his time as president of the University of Pennsylvania. His influence in the university and governor's office continued after his retirement, until his death in April 1982.
Published works and honors.
Harnwell received over 34 honorary degrees, as well as the title of Commander of the National Order of the Ivory Coast, Honorary Commander of the Order of the British Empire and Honorary Fellow of the Royal Society of Edinburgh. In May 1965 he became the 42nd recipient of the Philadelphia Award, and the University of Pennsylvania contains a Harnwell College House named in his honor.
In honor of Harnwell's support of and dedication to The Penn Glee Club both during and after his time at Penn, on May 15, 1970 he was awarded the prestigious University of Pennsylvania Glee Club Award of Merit. Beginning in 1964, this award "established to bring a declaration of appreciation to an individual each year that has made a significant contribution to the world of music and helped to create a climate in which our talents may find valid expression." In addition, Harnwell was supportive of Penn's chapter of Alpha Phi Omega, a national service fraternity. The chapter inducted him as an honorary Brother in 1955.
A member of several academic institutions, including the American Physical Society, the Acoustical Society, the American Philosophical Society, the Newcomen Society of North America, and the National Education Association, many of which he was chairman, Harnwell published a number of works during his life.


GOLLD RNA motif

Giant, Ornate, Lake- and Lactobacillales-Derived (GOLLD) RNA is a conserved RNA structure present in bacteria. GOLLD RNAs were originally detected based on metagenome sequences of DNA isolated from Lake Gatun in Panama. However, they are known to be present in at least eight strains of cultivated bacteria. GOLLD RNAs are extraordinarily large compared to other RNAs with a conserved, complex secondary structure, and average roughly 800 nucleotides. Such large, complex RNAs are often ribozymes, although the biochemical function of GOLLD RNAs remains unknown. The discovery of large RNAs like GOLLD RNAs among bacteria that are mostly uncultivated under laboratory conditions suggests that many other unusually large RNAs might be found in bacteria that have not yet been studied.
The GOLLD RNA in "Lactobacillus brevis" ATCC 367 was studied experimentally. This GOLLD RNA is apparently encoded by a prophage, and its transcription is increased during the phage lytic cycle. Therefore, this GOLLD RNA presumably serves a function that is useful to the phage during this process. GOLLD RNAs are often located near transfer RNAs (tRNAs), and in some cases a tRNA is predicted to be inside the GOLLD RNA structure itself. However, the biological reason underlying this association is not understood.
A more recently discovered large bacterial RNA, named the ROOL RNA motif, shares properties with GOLLD RNAs. In addition to the relatively large size and high degree of structural complexity of these RNA motifs, they both are only sometimes located in prophages and often located nearby to tRNAs. However, the sequence and structures of GOLLD and ROOL RNAs are not related.
The Rfam model of GOLLD RNA uses only the 3' half of GOLLD, as this region of the full RNA is highly consistent in its structure.


Combined bisulfite restriction analysis

Combined Bisulfite Restriction Analysis (or COBRA) is a molecular biology technique that allows for the sensitive quantification of DNA methylation levels at a specific genomic locus on a DNA sequence in a small sample of genomic DNA. The technique is a variation of bisulfite sequencing, and combines bisulfite conversion based polymerase chain reaction with restriction digestion. Originally developed to reliably handle minute amounts of genomic DNA from microdissected paraffin-embedded tissue samples, the technique has since seen widespread usage in cancer research and epigenetics studies.
Procedure.
Bisulfite Treatment.
Genomic DNA of interest is treated with sodium bisulfite, which introduces methylation-dependent sequence differences. During sodium bisulfite treatment, unmethylated cytosine residues are converted to uracil, while methylated cytosine residues are unaffected.
PCR Amplification.
Bisulfite treated DNA is then PCR amplified, resulting in cytosine residues at originally methylated positions, and thymine residues at originally unmethylated position (that were converted to uracil). Primers used during this step do not contain CpG sites (the common target of cytosine methylation), so the amplification process does not discriminate between templates based on methylation status. PCR products are purified to ensure complete digestion in the following step.
Restriction Digest.
The above steps lead to the methylation dependent retention or loss of CpG-containing restriction enzyme sites, such as those for TaqI (TCGA) and BstUI (CGCG), depending on whether the cytosine residue was originally methylated or not, respectively. Due to the methylation-independent amplification in the above step, the resulting PCR products will be a mixed population of fragments that have lost or retained CpG-containing restriction enzyme sites, whose respective percentages will be directly correlated to the original level of DNA methylation in the sample DNA.
PCR products are then treated with a restriction enzyme ("e.g." BstUI), which will only cleave sites that were originally methylated (CGCG), while leaving sites that were originally unmethylated (TGTG). To ensure that all CpG sites are retained due to originally being methylated, and not a remnant of incomplete bisulfite conversion, a control digestion is performed, with enzymes such as Hsp92II which recognizes the sequence CATG, none of which should be remaining after bisulfite conversion (with the rare exception of non-CpG methylation) and thus no cleavage should occur if bisulfite conversion was complete.
Quantification.
The digested fragments are then separated by polyacrylamide gel electrophoresis with the expected appearance of bands corresponding to a single large undigested fragment, and multiple smaller bands corresponding to digested fragments. Quantitative amount of DNA in these bands can be determined with a device such as a phosphoimager, after which the methylation percentage of the original sample can be calculated by:
Usage and Applications.
COBRA has been used extensively in many research-based applications such as screening for DNA methylation changes at gene promoters in cancer studies, detecting altered methylation patterns at imprinted genes, and characterizing methylation patterns in the genome during development in mammals.
In medicine, COBRA has been used as a tool to help diagnose human disease involving aberrant DNA methylation. Researchers utilized COBRA in conjunction with denaturing high performance liquid chromatography in the diagnosis of the genetic imprinting disorder Russell-Silver syndrome where of the imprinted gene H19 is responsible for the disorder in up to 50% of patients.
Alternatives.
In general, COBRA is often combined with other DNA methylation analyses and is frequently used in the initial screening of a loci of interest. If COBRA suggests altered methylation patterns, then more rigorous, labor-intensive techniques can be applied, such as bisulfite sequencing or MeDIP. Also PacBio sequencing can be used to detect DNA methylation.


RU-24,969

RU-24,969 is a drug and research chemical widely used in scientific studies. It is a selective agonist at the 5-HT1A and 5-HT1B receptors, with preference for the latter. As with other 5-HT1B agonists such as CP-94,253, RU-24,969 has been found to increase the reinforcing properties of cocaine, suggesting a role for 5-HT1B receptors in cocaine addiction.


Epitope

An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. For example, the epitope is the specific piece of the antigen to which an antibody binds. The part of an antibody that binds to the epitope is called a paratope. Although epitopes are usually non-self proteins, sequences derived from the host that can be recognized (as in the case of autoimmune diseases) are also epitopes.
The epitopes of protein antigens are divided into two categories, conformational epitopes and linear epitopes, based on their structure and interaction with the paratope. Conformational and linear epitopes interact with the paratope based on the 3-D conformation adopted by the epitope, which is determined by the surface features of the involved epitope residues and the shape or tertiary structure of other segments of the antigen. A conformational epitope is formed by the 3-D conformation adopted by the interaction of discontiguous amino acid residues. In contrast, a linear epitope is formed by the 3-D conformation adopted by the interaction of contiguous amino acid residues. A linear epitope is not determined solely by the primary structure of the involved amino acids. Residues that flank such amino acid residues, as well as more distant amino acid residues of the antigen affect the ability of the primary structure residues to adopt the epitope's 3-D conformation. The proportion of epitopes that are conformational is unknown.
Function.
T cell epitopes.
T cell epitopes are presented on the surface of an antigen-presenting cell, where they are bound to major histocompatibility complex (MHC) molecules. In humans, professional antigen-presenting cells are specialized to present MHC class II peptides, whereas most nucleated somatic cells present MHC class I peptides. T cell epitopes presented by MHC class I molecules are typically peptides between 8 and 11 amino acids in length, whereas MHC class II molecules present longer peptides, 13–17 amino acids in length, and non-classical MHC molecules also present non-peptidic epitopes such as glycolipids.
B cell epitopes.
The part of the antigen that immunoglobulin or antibodies bind to is called a B-cell epitope. Similar to T cell epitopes, B cell epitopes can be divided into two groups: conformational or linear. B cell epitopes are mainly conformational. There are additional epitope types when the quaternary structure is considered. Epitopes that are masked when protein subunits aggregate are called cryptotopes. Neotopes are epitopes that are only recognized while in a specific quaternary structure and the residues of the epitope can span multiple protein subunits. Neotopes are not recognized once the subunits dissociate.
Cross-activity.
Epitopes are sometimes cross-reactive. This property is exploited by the immune system in regulation by anti-idiotypic antibodies (originally proposed by Nobel laureate Niels Kaj Jerne). If an antibody binds to an antigen's epitope, the paratope could become the epitope for another antibody that will then bind to it. If this second antibody is of IgM class, its binding can upregulate the immune response; if the second antibody is of IgG class, its binding can downregulate the immune response.
Epitope mapping.
T cell epitopes.
MHC class I and II epitopes can be reliably predicted by computational means alone, although not all in-silico T cell epitope prediction algorithms are equivalent in their accuracy. There are two main methods of predicting peptide-MHC binding: data-driven and structure-based. Structure based methods model the peptide-MHC structure and require great computational power. Data-driven methods have higher predictive performance than structure-based methods. Data-driven methods predict peptide-MHC binding based on peptide sequences that bind MHC molecules. By identifying T-cell epitopes, scientists can track, phenotype, and stimulate T-cells.
B cell epitopes.
There are two main methods of epitope mapping: either structural or functional studies. Methods for structurally mapping epitopes include X-ray crystallography, nuclear magnetic resonance, and electron microscopy. X-ray crystallography of Ag-Ab complexes is considered an accurate way to structurally map epitopes. Nuclear magnetic resonance can be used to map epitopes by using data about the Ag-Ab complex. This method does not require crystal formation but can only work on small peptides and proteins. Electron microscopy is a low-resolution method that can localize epitopes on larger antigens like virus particles.
Methods for functionally mapping epitopes often use binding assays such as western blot, dot blot, and/or ELISA to determine antibody binding. Competition methods look to determine if two monoclonal antibodies (mABs) can bind to an antigen at the same time or compete with each other to bind at the same site. Another technique involves high-throughput mutagenesis, an epitope mapping strategy developed to improve rapid mapping of conformational epitopes on structurally complex proteins. Mutagenesis uses randomly/site-directed mutations at individual residues to map epitopes. B-cell epitope mapping can be used for the development of antibody therapeutics, peptide-based vaccines, and immunodiagnostic tools.
Epitope tags.
Epitopes are often used in proteomics and the study of other gene products. Using recombinant DNA techniques genetic sequences coding for epitopes that are recognized by common antibodies can be fused to the gene. Following synthesis, the resulting epitope tag allows the antibody to find the protein or other gene product enabling lab techniques for localisation, purification, and further molecular characterization. Common epitopes used for this purpose are Myc-tag, HA-tag, FLAG-tag, GST-tag, 6xHis, V5-tag and OLLAS. Peptides can also be bound by proteins that form covalent bonds to the peptide, allowing irreversible immobilisation. These strategies have also been successfully applied to the development of "epitope-focused" vaccine design.
Epitope-based vaccines.
The first epitope-based vaccine was developed in 1985 by Jacob et al. Epitope-based vaccines stimulate humoral and cellular immune responses using isolated B-cell or T-cell epitopes. These vaccines can use multiple epitopes to increase their efficacy. To find epitopes to use for the vaccine, in silico mapping is often used. Once candidate epitopes are found, the constructs are engineered and tested for vaccine efficiency. While epitope-based vaccines are generally safe, one possible side effect is cytokine storms.
Neoantigenic determinant.
A neoantigenic determinant is an epitope on a neoantigen, which is a newly formed antigen that has not been previously recognized by the immune system. Neoantigens are often associated with tumor antigens and are found in oncogenic cells. Neoantigens and, by extension, neoantigenic determinants can be formed when a protein undergoes further modification within a biochemical pathway such as glycosylation, phosphorylation or proteolysis. This, by altering the structure of the protein, can produce new epitopes that are called neoantigenic determinants as they give rise to new antigenic determinants. Recognition requires separate, specific antibodies.


Structured digital abstract

A Structured Digital Abstract (SDA) is a method of describing relationships between biological entities in a structured, but human-readable, format. It is added below the abstract of scientific articles published in FEBS Letters and FEBS Journal. Current SDAs describe protein-protein interactions.
History.
Many scientific manuscripts describe relationships between entities such as genes and proteins. However, this information cannot be used efficiently because of the difficulties in retrieving it automatically from unstructured text. In a six-month pilot project that started in January 2008, FEBS Letters began publishing manuscripts with “structured digital abstracts” (SDAs). The SDAs were added to the end of abstracts in a structured, but human-readable, format and digitally linked to interaction databases. In the pilot project, the journal concentrated on protein-protein interactions. After six months, this “experiment” was evaluated. As it was a success, all appropriate FEBS Letters manuscripts are now given an SDA.
In 2009, FEBS Journal also started publishing manuscripts with SDAs.
The SDA initiative continues to be funded by FEBS, a not-for-profit organisation.
Recent BioCreative challenges have focused on protein-protein interaction extraction by automatic text mining, using FEBS Letters and FEBS Journal articles.
Format.
An SDA comprises a series of sentences each of which contains a relationship between two biological entities, mentioning the method used to study the relationship. To provide a simplified example: protein A interacts with protein B, by method X. Each sentence in an SDA is followed by one or more identifiers pointing to the corresponding database entries that contain all the details of the structured information. Although most of the sentences currently point to the MINT Molecular INTeraction Database, the proposed structure can easily be extended to contain identifiers from other databases storing protein interactions or different types of relationships between biological entities. Each entity is also linked to the appropriate explanatory database. e.g. UniProtKB for proteins and the European Bioinformatics Institute ontology look up service for other entities.


Cytochrome-c3 hydrogenase

In enzymology, a cytochrome-c3 hydrogenase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are H2 and ferricytochrome c3, whereas its two products are H+ and ferrocytochrome c3.
This enzyme belongs to the family of oxidoreductases, specifically those acting on hydrogen as donor with a cytochrome as acceptor. The systematic name of this enzyme class is hydrogen:ferricytochrome-c3 oxidoreductase. Other names in common use include H2:ferricytochrome c3 oxidoreductase, cytochrome c3 reductase, cytochrome hydrogenase, and hydrogenase [ambiguous]. It has 3 cofactors: iron, Nickel, and Iron-sulfur.
Structural studies.
As of late 2007, 19 structures have been solved for this class of enzymes, with PDB accession codes , , , , , , , , , , , , , , , , , , and .


Capsinolol

Capsinolol is a beta blocker derived from nonivamide. It is the first beta blocker with an associated calcitonin gene-related peptide releasing activity in the heart.


Povia

Giuseppe Povia (}, born November 19, 1972), better known just as Povia , is an Italian rock singer-songwriter.
Biography.
Born in Milan, he began teaching himself guitar. He taught himself how to play music by ear; by the time he was 20, he began to compose music. In 1999 he enrolled in the Academy of Sanremo where he met Giancarlo Bigazzi.
In his songs, Povia frequently takes on social issues. In 2003 he addressed bulimia with his song "Mia sorella". In 2005 his single "Avamposto 55" talked about the children of Darfur. In 2005 he produced the single "I bambini fanno: ooh..." from which the proceeds were used in a campaign he started to build hospitals in Darfur. The single sold 150,000 copies in Italy and received special accolades from Sony BMG.
In 2009 he won second place in the 59th Sanremo Music Festival with his song "Luca era gay". Despite the media initially thinking that the song was about Luca Tolve, a man who allegedly has been reversing his homosexuality following the therapies of Joseph Nicolosi., Povia has declared the song is about a man called Massimiliano whom he met on a train from Milan to Rome. During the train ride the man told Povia his personal story about having been gay, but now being married with children.
Personal life.
He has been married since 2007 to Teresa, with whom he has two daughters, Emma (2005) and Amelia (2007). He has lived in Florence for many years.
Always considering himself to be close to right-wing positions, from around 2013 the singer-songwriter began to publicly express Eurosceptic and sovereign ideas. He has repeatedly declared himself a sympathizer of Silvio Berlusconi, Matteo Salvini, Riscossa Italia, and the People of the Family, while he has often criticized the Democratic Party.
Statements against immigration.
In May 2013, Povia criticized Cécile Kyenge on Facebook stating that "if you take the problems of non-EU citizens to heart by giving them priority in a country like Italy, then it annoys me too. Italy must be managed by Italians. [...] If this continues, Italy will go to the Chinese."
In July 2017, Povia praised the launch of a Molotov cocktail against a hotel property of the Italian entrepreneur Valerio Ponchiardi guilty of hosting 35 refugees. Povia called this action a patriotic act.
Povia also supported the existence of a "Kalergi plan" for the substitution of the European peoples through also false quotations to Kalergi himself.
Misinformation allegations.
Chemtrails.
Povia declared that chemtrails exist and reported their danger.
Earthquakes.
Povia proposed, on several occasions, a pseudoscientific theory to explain why earthquakes occur. The theory in question asserts that the large number of people on earth (7 billion) can produce earthquakes with their movement. But it has been repeatedly demonstrated, scientifically, that even if each person on the planet were clustered together, this would not lead to any earthquake, given that the total weight has a mass that is too dilated and distributed to cause an earthquake.
Vaccines.
Povia has repeatedly expressed opposition to the vaccines and, in addition to believing in the correlation between vaccines and autism (mistakenly described by him as "brain damage"), justifies its use only by virtue of social emergencies as (according to him) mass immigration or poor food.
Povia himself has supported the free vax movement (which many associate with a gimmick to avoid being accused of antivaccinism).
Discography.
2005 – "Evviva i pazzi... che hanno capito cos'è l'amore"

2006 – "I bambini fanno "ooh..." la storia continua..."

2007 – "La storia continua... la tavola rotonda"

2008 – "Uniti (Povia-Baccini)"

2009 – "Centravanti di mestiere"

2009 – "Non basta un sorriso"

2010 – "Scacco matto"

2011 – "Il mondo è di tutti"

2012 – "I "bambini" fanno rock"

2016 – "Nuovo Contrordine Mondiale"
Awards.
2003 Premio Musicultura per la canzone Mia sorella

2005 Premio Mei "etichette indipendenti"

2005 Premio Lunezia nuove stelle 2005

2006 Primo premio al Festival della Canzone Italiana

2008 Leone d'argento alla carriera per la musica

2009 Premio Sala Stampa RadioTv al Festival della Canzone Italiana

2009 Premio Mogol per il testo della canzone Luca era gay

2011 Music Awards – Premio Confindustria Cultura Italia FIMI, AFI e PMI

2011 Targa nella Strada del Festival di Sanremo in Via Matteotti a Sanremo, per il brano Vorrei avere il becco


RNA uridylyltransferase

In enzymology, a RNA uridylyltransferase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are UTP and RNAn, whereas its two products are diphosphate and RNAn+1.
This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing nucleotide groups (nucleotidyltransferases). The systematic name of this enzyme class is UTP:RNA uridylyltransferase. Other names in common use include terminal uridylyltransferase, and TUT.
Structural studies.
As of late 2007, 8 structures have been solved for this class of enzymes, with PDB accession codes , , , , , , , and .