Christine P. Hendon

Christine P. Hendon is an Electrical Engineer and Computer Scientist and an Associate Professor in the Department of Electrical Engineering at Columbia University in New York City. Hendon is a pioneer in medical imaging. She develops biomedical optics technologies, using optical coherence tomography and near infrared spectroscopy systems, that enable physicians to perform guided interventional procedures and allow for structure-function dissection of human tissues and organs. Her advances in imaging technologies have led to improved diagnostic abilities and treatments for cardiac arrhythmias as well as breast cancer and preterm birth. She has been recognized for her development of optical imaging catheters for cardiac wall imaging by Forbes 30 under 30, the MIT Technology Review’s 35 Innovators Under 35, and by President Obama with the Presidential Early Career Awards in 2017.
Early life and education.
Hendon (born Christine Fleming), wanted to pursue a career as a teacher during her childhood. In high school, she enjoyed math and science, and participated in the Institute for Climate and Planets program, hosted by the NASA Goddard Institute for Space studies. This program inspired her to pursue a career in science.
In 2000, Hendon pursued her undergraduate education at the Massachusetts Institute of Technology, in Cambridge, Massachusetts. She majored in Electrical Engineering and Computer Science and became immediately involved in undergraduate research. Hendon graduated with her Bachelors of Science in 2004.
Hendon then pursued her Master’s of Science and her PhD training at Case Western Reserve University in Biomedical Engineering. She completed her M.S. in 2007, and her Ph.D. in 2010. During her PhD, Hendon worked under the mentorship of Andrew M. Rollins where she began using and optimizing Optical Coherence Tomography (OCT) techniques to create volumetric images of human tissues and organs for use in treatment of cardiac arrhythmias. She developed an automated algorithm for fiber orientation in the plane parallel to the wall surface of cardiac tissue in order to properly characterize early structural changes in the myocardium due to disease and injury to guide treatment. Her work showed that OCT can help to visualize real time ablation (RFA) therapy to guide physicians treatment progression and thus improve the outcomes of RFA therapy.
Following her Ph.D., Hendon moved back to Massachusetts and pursued her Postdoctoral research fellowship at Harvard Medical School and Massachusetts General Hospital in the Biomedical Optics Wellman Center for Photomedicine. During this time, Hendon optimized the depth resolved spectral analysis of OCT. She completed her postdoctoral fellowship in 2012.
Career and research.
In 2012, Hendon was recruited to Columbia University as an Assistant Professor in the School of Engineering and Applied Sciences in the Department of Electrical Engineering. In 2018, Hendon was promoted to Associate Professor with tenure. Hendon is the Principal Investigator of the Structure-Function Imaging Laboratory. Her lab focuses on developing novel biomedical technologies for guided imaging of biological tissues and improved diagnosis and treatment of cancer and cardiac arrhythmias. Her work integrates real-time processing algorithms to extract physiological information from Optical Coherence Tomography (OCT) imaging data. Hendon is also a member of the National Society of Black Engineers (NSBE), The International Society for Optics and Photonics (SPIE and The Optical Society (OSA).
OCT guided atrial fibrillation treatment.
Hendon helped to improve and guide ablation treatment of atrial fibrillation using a near-infrared spectroscopy (NIRS) guided catheter implantation. Her results showed improved results of radio-frequency ablation therapy. Hendon then used her knowledge and expertise in OCT to characterize the structure-function relationship of heart tissue. She showed that she was able to image, with high resolution, elastic fibers, Purkinje fibers, and collagen fiber bundles, as well as observe tissue pathology. Since the composition of atrial tissue impacts disease pathology, diagnosis, and recovery, Hendon and her team developed an automated method to classify tissue composition of the atria using a relevance vector machine model. The classification accuracy was over 80% showing its utility in classifying tissue composition and guiding diagnosis and treatment. With Hendon’s technology, physicians that previously treated cardiac arrhythmias essentially blind to the tissue changes, can now observe tissue changes and improvements in realtime to enhance treatment accuracy and recovery.
OCT for breast cancer.
Hendon began adapting her OCT algorithms for use in the diagnosis and treatment of breast cancer. The imaging technique has been nicknamed “optical ultrasound” and, using ultra-high resolution OCT, she was able to improve the characterization and diagnosis of breast cancer.
OCT imaging and preterm birth.
Hendon then became interested in exploring the structure-function relationship of the cervix and how characterizing this relationship could provide insight into causes of preterm birth and possible prevention strategies. Hendon first found that collagen fiber dispersion and directionality had an impact on cervical remodelling and thus propensity for preterm birth. Since this remodelling results in shortening of the cervix, which is thought to result in preterm birth, Hendon sought to further understand the structural properties that underlie shortening and elucidate approaches to prevent preterm birth. By assessing the collagen fiber orientation through her material modelling framework, Hendon was able to determine the basis for cervical deformation using OCT and biomechanically explore the causes of preterm birth at the level of tissue microstructure.


Pteridine oxidase

In enzymology, a pteridine oxidase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are 2-amino-4-hydroxypteridine and O2, whereas its product is 2-amino-4,7-dihydroxypteridine.
This enzyme belongs to the family of oxidoreductases, specifically those acting on CH or CH2 groups with oxygen as acceptor. The systematic name of this enzyme class is 2-amino-4-hydroxypteridine:oxygen oxidoreductase (7-hydroxylating).


Dopamine antagonist

A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and as such they have found use in treating schizophrenia, bipolar disorder, and stimulant psychosis. Several other dopamine antagonists are antiemetics used in the treatment of nausea and vomiting.
Receptor pharmacology.
Dopamine receptors are all G protein–coupled receptors, and are divided into two classes based on which G-protein they are coupled to. The D1-like class of dopamine receptors is coupled to Gαs/olf and stimulates adenylate cyclase production, whereas the D2-like class is coupled to Gαi/o and thus inhibits adenylate cyclase production.
D1-like receptors: D1 and D5.
D1-like receptors – D1 and D5 are always found post-synaptically. The genes coding these receptors lack introns, so there are no splice variants.
D2-like receptors: D2, D3 and D4.
D2-like receptors unlike the D1-like class, these receptors are found pre and post-synaptically. The genes that code these receptors have introns, leading to many alternately spliced variants.
Implications in disease.
The dopaminergic system has been implicated in a variety of disorders. Parkinson's disease results from loss of dopaminergic neurons in the striatum. Furthermore, most effective antipsychotics block D2 receptors, suggesting a role for dopamine in schizophrenia. Additional studies hypothesize dopamine dysregulation is involved in Huntington's disease, ADHD, Tourette's syndrome, major depression, manic depression, addiction, hypertension and kidney dysfunction. Dopamine receptor antagonists are used for some diseases such as schizophrenia, bipolar disorder, nausea and vomiting.
Side effects.
They may include one or more of the following and last indefinitely even after cessation of the dopamine antagonist, especially after long-term or high-dosage use:
Examples.
First-generation antipsychotics (typical).
First generation antipsychotics are used to treat schizophrenia and are often accompanied by extrapyramidal side effects.
Second-generation antipsychotics (atypical).
These drugs are not only dopamine antagonists at the receptor specified, but also act on serotonin receptor 5HT2A. (Citation inappropriate) These drugs have less extrapyramidal side effects and are less likely to affect prolactin levels when compared to typical antipsychotics.


Heterotachy

Heterotachy refers to variations in lineage-specific evolutionary rates over time. In the field of molecular evolution, the principle of heterotachy states that the substitution rate of sites in a gene can change through time. It has been proposed that the positions that show switches in substitution rate over time (that is, heterotachous sites) are good indicators of functional divergence. However, it appears that heterotachy is a much more general process, since most variable sites of homologous proteins with no evidence of functional shift are heterotachous.
The covarion hypothesis is a specific form of heterotachy. Some studies have proposed functional divergence models that are also heterotachous. Additionally, some mixture models that do not explicitly account for rate-shift, but site-partitions evolving at different relative substitution rates across lineages are mathematically heterotachous.
Failure to take heterotachy into account in phylogenetic reconstructions may lead to incorrect phylogenetic trees. Thus Zhong et al. (2011) say that heterotachy is one of the reasons for variability in reconstructions of the origin of gnetophytes.


Zhang Mingjie

Zhang Mingjie (; born September 1966) is a Chinese structural biologist. He is Kerry Holdings Professor of Science and the Chair Professor of Biochemistry in the Department of Biochemistry at Hong Kong University of Science and Technology (HKUST). He was an overseas assessor of the Chinese Academy of Science. His research is focusing on molecular mechanisms of organization and regulation of neuronal signaling complexes and machineries in controlling cell polarity by using protein crystallography and NMR spectroscopy. In 2006, his structural and biochemical studies in signal transduction complex organization was rewarded for the State Natural Science Award (Second Prize), which is one of the most important national awards of science in China.
Biography.
Zhang was born in Ningbo, Zhejiang in September 1966, when the Cultural Revolution broke out. He obtained his B.Sc. in Chemistry from Fudan University in 1988 and earned his Ph.D. in Biochemistry from University of Calgary in 1993. On December 4, 2020, he was recruited as dean of the newly founded College of Life Science, Southern University of Science and Technology.


Janin Plot

In biochemistry, a Janin plot, like a Ramachandran plot, is a way to visualize dihedral angle distributions in protein structures. While a Ramachandran plot relates the two backbone dihedral angles, a Janin plot relates the first side chain dihedral angle χ-1 against χ-2. Because not all amino acids have these dihedral angles, a Janin plot is not applicable to all such acids.
This correlation is different for the various amino acids and can depend on the type of secondary structure (Helix, Sheet, etc.) local to that residue. The plot is named for Joël Janin, who studied these correlations in 1978 with Shoshana Wodak.


Minigastrin

Minigastrin (also mini gastrin) is a form of gastrin. Its sequence is H-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2.
Minigastrin has shown to be a potential therapeutic agent for thyroid carcinoma by targeting cancer-promoting cholecystokinin receptors.
A 2018 study further elaborates by using radiochemical labeling to show that Indium-111 labeled minigastrin peptides showing to have stronger affinity to cholecystokinin B receptors (CCK2) in neuroendocrine cancers.


Pyrimidodiazepine synthase

In enzymology, a pyrimidodiazepine synthase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are pyrimidodiazepine, glutathione disulfide, and H2O, whereas its two products are 6-pyruvoyltetrahydropterin and glutathione.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with a disulfide as acceptor. The systematic name of this enzyme class is pyrimidodiazepine:glutathione-disulfide oxidoreductase (ring-opening, cyclizing). Other names in common use include PDA synthase, pyrimidodiazepine:oxidized-glutathione oxidoreductase (ring-opening, and cyclizing). This enzyme participates in glutathione metabolism.


Malcolm Dole

Malcolm Dole (March 4, 1903 – November 29, 1990) was an American chemist known for the Dole Effect in which he proved that the atomic weight of oxygen in air is greater than that of oxygen in water and for his work on electrospray ionization, polymer chemistry, and electrochemistry.
Dole effect.
The Dole effect is the inequality in the ratio of heavy oxygen isotope 18O to the more abundant 16O in the earth's atmosphere and in seawater.
This effect was reported by Dole in 1935. The effect is due to slightly different reaction rates for the two isotopes in respiration in plants and in animals which tends to retain the lighter 16O, which increases the relative concentration of 18O in the atmosphere.
Electrospray.
Electrospray is a process in which a high voltage is applied to a liquid to create an aerosol containing highly charged droplets. Dole in 1968 was the first to use electrospray ionization with mass spectrometry.


Gorgon (Inhuman)

Gorgon is a fictional character appearing in American comic books published by Marvel Comics. Gorgon is also a member of the Royal Family of the Inhumans, a race of superpowered beings that inhabit the hidden city of Attilan.
Gorgon was portrayed by Eme Ikwuakor in the 2017 Marvel Cinematic Universe "Inhumans" TV series.
Publication history.
The character debuted in "Fantastic Four" #44 (Nov. 1965) and was created by Stan Lee and Jack Kirby.
Fictional character biography.
The son of archivist Milena and architect Korath (brother of the previous king Agon), Gorgon Petragon is a cousin of king Black Bolt and a member of the Royal Family of the Inhumans. As is custom among the Inhumans, Gorgon was exposed to the Terrigen Mists as a teenager, gaining increased strength, while his feet were transformed to hooves, capable of generating highly destructive seismic waves. As an adult, Gorgon became Black Bolt's personal bodyguard and is responsible for training youths recently exposed to the Terrigen Mists in the use of their newly acquired powers and abilities.
Gorgon first leaves the Inhuman city of Attilan to rescue Medusa (suffering from amnesia at the time), who became lost in the outside world. This leads to a battle with the Fantastic Four, who rescued Medusa from the supervillain team the Frightful Four. After making contact with the outside world, Gorgon and the rest of the Royal Family have several encounters with the Fantastic Four over the years, seeking their aid against foes such as Black Bolt's brother Maximus, Psycho-Man, and the Sphinx.
With several other Inhumans, Gorgon also battles the master villain Mandarin, helps free Maximus, journeys to America to search for the missing Black Bolt, and battles Magneto. Over the years, and with continued exposure to the outside world, Gorgon has many adventures, usually taking place in the company of fellow members of the Royal Family.
Significant moments for Gorgon include defying the Attilan Genetics Council and helping to hide the pregnant Medusa (with Black Bolt's child) on Earth; and arguing with Black Bolt over the use of Alpha Primitives as slaves. He leads an Inhuman force down to Earth to gain the return of the Terrigen Mists. This goes badly as many human captives are slain by an impatient Inhuman named Jolen. This sparks a war between Earth and the Inhumans, and Gorgon is captured. He is subjected to the Terrigen Mists again. This amplifies Gorgon's powers and change him into a true beast with a lion-like head, claws, and uncontrollable rages. As with the other Inhumans, he leaves the Moon to assist them in taking over the Kree empire. He is later seen with his more humanoid appearance.
In the "Inhuman" storyline, he is shot in the spine by NuHuman named Lineage, he is paralyzed waist down and cannot use his powers.
As part of the "All-New, All-Different Marvel", Gorgon joined the diplomatic mission created by Medusa to oversee the diplomatic relations and handle the recovery efforts of the newly transformed Inhumans. During this time, Gorgon rode around in a special wheelchair. His paralysis is later cured by NuHuman Panacea.
During the "Inhumans vs. X-Men" storyline, Gorgon and Crystal are ambushed by Magneto.
Powers and abilities.
Gorgon's superhuman powers are a result of exposure to the mutagenic Terrigen Mist. Gorgon now has bull's legs and hooves and can create intense shockwaves equivalent to a powerful earthquake. He also possesses enhanced strength and durability, although like all Inhumans he has a weaker immune system than that of an average human.
Gorgon was exposed to Terrigen Mists a second time by Pentagon officials. He then appeared larger and stronger and behaved more brutishly. These changes gradually faded.
Other versions.
Amalgam Comics.
In "Amalgam Comics", Big Gorgon – a combination of DC Comics' Big Bear and Marvel's Gorgon – is a member of the superhero group the Un-People in the Amalgam Comics universe.
Earth X.
In "Earth X", like many of his fellow Inhumans, the Gorgon of Earth X has undergone a further mutation and possesses the head of a bull.
Marvel Zombies.
In "Marvel Zombies", the first time the zombified Gorgon is seen, he is part of a horde of super-zombies attempting to eat the last few known humans left on Earth. They fail; the humans are safely escorted to another reality. Later, it is seen that the entire Inhuman Royal Family has been zombified and has traveled to Kingpin's domain to eat of his human clones. Machine Man attacks and Gorgon tries to retaliate by stamping the ground, but his leg instantly falls off.
Ultimate Marvel.
In the "Ultimate Marvel" reality, Gorgon is female (the sister of Medusa and Crystal) and possesses the added ability to hypnotize people.


Serotonin receptor agonist

A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin (5-hydroxytryptamine; 5-HT), a neurotransmitter and hormone and the endogenous ligand of the serotonin receptors.
Non-selective agonists.
Serotonergic psychedelics such as tryptamines (e.g., psilocybin, psilocin, , 5-MeO-DMT, bufotenin), lysergamides (e.g., , ergine ()), phenethylamines (e.g., mescaline, 2C-B, 25I-NBOMe), and amphetamines (e.g., , ) are non-selective agonists of serotonin receptors. Their hallucinogenic effects are specifically mediated by activation of the 5-HT2A receptor.
Drugs that increase extracellular serotonin levels such as serotonin reuptake inhibitors (e.g., fluoxetine, venlafaxine), serotonin releasing agents (e.g., fenfluramine, ), and monoamine oxidase inhibitors (e.g., phenelzine, moclobemide) are indirect non-selective serotonin receptor agonists. They are used variously as antidepressants, anxiolytics, antiobsessionals, appetite suppressants, and entactogens.
5-HT1 receptor agonists.
5-HT1A receptor agonists.
Azapirones such as buspirone, gepirone, and tandospirone are 5-HT1A receptor partial agonists marketed primarily as anxiolytics, but also as antidepressants. The antidepressants vilazodone and vortioxetine are 5-HT1A receptor partial agonists. Flibanserin, a drug used for female sexual dysfunction, is a 5-HT1A receptor partial agonist. Many atypical antipsychotics, such as aripiprazole, asenapine, clozapine, lurasidone, quetiapine, and ziprasidone, are 5-HT1A receptor partial agonists, and this action is thought to contribute to their beneficial effects on negative symptoms in schizophrenia.
5-HT1B receptor agonists.
Triptans such as sumatriptan, rizatriptan, and naratriptan are 5-HT1B receptor agonists that are used to abort migraine and cluster headache attacks. The ergoline antimigraine agent ergotamine also acts on this receptor.
Serenics such as batoprazine, eltoprazine, and fluprazine are agonists of the 5-HT1B receptor and other serotonin receptors, and have been found to produce antiaggressive effects in animals, but have not been marketed. Eltoprazine is under development for the treatment of aggression and for other indications.
5-HT1D receptor agonists.
In addition to being 5-HT1B agonists, triptans (i.e. sumatriptan, almotriptan, zolmitriptan, naratriptan, eletriptan, frovatriptan and rizatriptan) are also agonists at the 5-HT1D receptor, which contributes to their antimigraine effect caused by vasoconstriction of blood vessels in the brain. The same is true for ergotamine.
5-HT1E receptor agonists.
The triptan eletriptan is an agonist of the 5-HT1E receptor. BRL-54443 is a selective 5-HT1E and 5-HT1F receptor agonist which is used in scientific research.
5-HT1F receptor agonists.
Triptans such as eletriptan, naratriptan, and sumatriptan are agonists of the 5-HT1F receptor. Lasmiditan is a selective 5-HT1F agonist that is under development by Eli Lilly and Company for the treatment of migraine.
5-HT2 receptor agonists.
5-HT2A receptor agonists.
Serotonergic psychedelics like psilocybin, LSD, and mescaline act as 5-HT2A receptor agonists. Their actions at this receptor are thought to be responsible for their hallucinogenic effects. Most of these drugs also act as agonists of other serotonin receptors. Not all 5-HT2A receptor agonists are psychoactive.
The 25-NB (NBOMe) series is a family of phenethylamine serotonergic psychedelics that, unlike other classes of serotonergic psychedelics, act as highly selective 5-HT2A receptor agonists. The most well-known member of the 25-NB series is 25I-NBOMe. (2"S",6"S")-DMBMPP is an analogue of the 25-NB compounds and is the most highly selective agonist of the 5-HT2A receptor that has been identified to date. O-4310 (1-isopropyl-6-fluoropsilocin) is a tryptamine derivative that is a highly selective agonist of the 5-HT2A receptor.
Selective 5-HT2A receptor agonists like the 25-NB compounds, specifically those which can behave as full agonists at this receptor, can cause serotonin syndrome-like adverse effects such as hyperthermia, hyperpyrexia, tachycardia, hypertension, clonus, seizures, agitation, aggression, and hallucinations which has ended in death on numerous occasions despite these particular drugs only being available to drug users for about 2–3 years, being widely in use mostly in the period from 2010-2012. Bans were put in place around 2012-2013 by countries where they had risen to popularity. They quickly and often accidentally lead to overdose. In contrast to the aforementioned drugs's potent, selective, and most importantly, full agonism (meaning the drug can fully activate the receptor to 100% of its activation potential, and does so even with minuscule amounts due to high potency, LSD, like the other "safe" psychedelics which are almost impossible to overdose fatally on, is a partial agonist, and this means it has a limit of how much it can activate the receptor, a limit which is basically impossible to exceed even with exponentially larger amounts of the drug. These partial agonists have proven relatively safe after having seen widespread abuse by drug users for many decades. Activation of the 5-HT2A receptor is also implicated in serotonin syndrome caused by indirect serotonin receptor agonists like serotonin reuptake inhibitors, serotonin releasing agents, and monoamine oxidase inhibitors. Antagonists of the 5-HT2A receptor like cyproheptadine and chlorpromazine are able to reverse and mediate recovery from serotonin syndrome.
5-HT2B receptor agonists.
Agonists of the 5-HT2B receptor are implicated in the development of cardiac fibrosis. Fenfluramine, pergolide, and cabergoline have been withdrawn from some markets for this reason. Many serotonergic psychedelics, such as LSD and psilocin, have been shown to activate this receptor directly. MDMA has been reported to be both a potent direct agonist and have an indirect effect by increasing plasma serotonin levels.
5-HT2C receptor agonists.
Lorcaserin is an appetite suppressant and anti-obesity drug which acts as a selective 5-HT2C receptor agonist. "meta"-Chlorophenylpiperazine (mCPP) is a 5-HT2C-preferring serotonin receptor agonist that induces anxiety and depression and can cause panic attacks in susceptible individuals.
5-HT3 receptor agonists.
2-Methyl-5-hydroxytryptamine (2-methylserotonin) and quipazine are moderately selective agonists of the 5-HT3 receptor that are used in scientific research. Agonists of this receptor are known to induce nausea and vomiting, and are not used medically.
5-HT4 receptor agonists.
Cisapride and tegaserod are 5-HT4 receptor partial agonists that were used to treat disorders of gastrointestinal motility. Prucalopride is a highly selective 5-HT4 receptor agonist that can be used to treat certain disorders of gastrointestinal motility. Other 5-HT4 receptor agonists have shown potential to be nootropic and antidepressant drugs, but have not been marketed for such indications.
5-HT5A receptor agonists.
Valerenic acid, a constituent of valerian root, has been found to act as a 5-HT5A receptor agonist, and this action could be involved in the sleep-promoting effects of valerian.
5-HT6 receptor agonists.
No selective agonists of the 5-HT6 receptor have been approved for medical use. Selective 5-HT6 receptor agonists like E-6801, E-6837, EMDT, WAY-181,187, and WAY-208,466 show antidepressant, anxiolytic, antiobsessional, and appetite suppressant effects in animals, but also impair cognition and memory.
5-HT7 receptor agonists.
AS-19 is a 5-HT7 receptor agonist that has been used in scientific research.


ViroCap

ViroCap is a test announced in 2015 by researchers at Washington University in St. Louis which can detect most of the infectious viruses which affect both humans and animals. It was demonstrated to be as sensitive as the various Polymerase chain reaction assays for the viruses. It will not be available for clinical use until validation studies are done, which may take years. The test examines two million sequences of genetic data from viruses. The research was published in September 2015 in the online journal Genome Research.


Differentiation (journal)

Differentiation is a peer-reviewed academic journal covering cell differentiation and cell development. It was established in 1973 and is published 10 times per year by Elsevier, on behalf of the International Society of Differentiation. The editor-in-chief is Colin Stewart (Agency for Science, Technology and Research). According to the "Journal Citation Reports", the journal has a 2016 impact factor of 2.567.


Two-dimensional gel electrophoresis

Two-dimensional gel electrophoresis, abbreviated as 2-DE or 2-D electrophoresis, is a form of gel electrophoresis commonly used to analyze proteins. Mixtures of proteins are separated by two properties in two dimensions on 2D gels. 2-DE was first independently introduced by O'Farrell and Klose in 1975.
Basis for separation.
2-D electrophoresis begins with electrophoresis in the first dimension and then separates the molecules perpendicularly from the first to create an electropherogram in the second dimension. In electrophoresis in the first dimension, molecules are separated linearly according to their isoelectric point. In the second dimension, the molecules are then separated at 90 degrees from the first electropherogram according to molecular mass. Since it is unlikely that two molecules will be similar in two distinct properties, molecules are more effectively separated in 2-D electrophoresis than in 1-D electrophoresis.
The two dimensions that proteins are separated into using this technique can be isoelectric point, protein complex mass in the native state, or protein mass.
Separation of the proteins by isoelectric point is called isoelectric focusing (IEF). Thereby, a pH gradient is applied to a gel and an electric potential is applied across the gel, making one end more positive than the other. At all pH values other than their isoelectric point, proteins will be charged. If they are positively charged, they will be pulled towards the more negative end of the gel and if they are negatively charged they will be pulled to the more positive end of the gel. The proteins applied in the first dimension will move along the gel and will accumulate at their isoelectric point; that is, the point at which the overall charge on the protein is 0 (a neutral charge).
For the analysis of the functioning of proteins in a cell, the knowledge of their cooperation is essential. Most often proteins act together in complexes to be fully functional. The analysis of this sub organelle organisation of the cell requires techniques conserving the native state of the protein complexes. In native polyacrylamide gel electrophoresis (native PAGE), proteins remain in their native state and are separated in the electric field following their mass and the mass of their complexes respectively. To obtain a separation by size and not by net charge, as in IEF, an additional charge is transferred to the proteins by the use of Coomassie Brilliant Blue or lithium dodecyl sulfate. After completion of the first dimension the complexes are destroyed by applying the denaturing SDS-PAGE in the second dimension, where the proteins of which the complexes are composed of are separated by their mass.
Before separating the proteins by mass, they are treated with sodium dodecyl sulfate (SDS) along with other reagents (SDS-PAGE in 1-D). This denatures the proteins (that is, it unfolds them into long, straight molecules) and binds a number of SDS molecules roughly proportional to the protein's length. Because a protein's length (when unfolded) is roughly proportional to its mass, this is equivalent to saying that it attaches a number of SDS molecules roughly proportional to the protein's mass. Since the SDS molecules are negatively charged, the result of this is that all of the proteins will have approximately the same mass-to-charge ratio as each other. In addition, proteins will not migrate when they have no charge (a result of the isoelectric focusing step) therefore the coating of the protein in SDS (negatively charged) allows migration of the proteins in the second dimension (SDS-PAGE, it is not compatible for use in the first dimension as it is charged and a nonionic or zwitterionic detergent needs to be used).
In the second dimension, an electric potential is again applied, but at a 90 degree angle from the first field. The proteins will be attracted to the more positive side of the gel (because SDS is negatively charged) proportionally to their mass-to-charge ratio. As previously explained, this ratio will be nearly the same for all proteins. The proteins' progress will be slowed by frictional forces. The gel therefore acts like a molecular sieve when the current is applied, separating the proteins on the basis of their molecular weight with larger proteins being retained higher in the gel and smaller proteins being able to pass through the sieve and reach lower regions of the gel.
Detecting proteins.
The result of this is a gel with proteins spread out on its surface. These proteins can then be detected by a variety of means, but the most commonly used stains are silver and Coomassie Brilliant Blue staining. In the former case, a silver colloid is applied to the gel. The silver binds to cysteine groups within the protein. The silver is darkened by exposure to ultra-violet light. The amount of silver can be related to the darkness, and therefore the amount of protein at a given location on the gel. This measurement can only give approximate amounts, but is adequate for most purposes. Silver staining is 100x more sensitive than Coomassie Brilliant Blue with a 40-fold range of linearity.
Molecules other than proteins can be separated by 2D electrophoresis. In supercoiling assays, coiled DNA is separated in the first dimension and denatured by a DNA intercalator (such as ethidium bromide or the less carcinogenic chloroquine) in the second. This is comparable to the combination of native PAGE /SDS-PAGE in protein separation.
Common techniques.
IPG-DALT.
A common technique is to use an Immobilized pH gradient (IPG) in the first dimension. This technique is referred to as IPG-DALT. The sample is first separated onto IPG gel (which is commercially available) then the gel is cut into slices for each sample which is then equilibrated in SDS-mercaptoethanol and applied to an SDS-PAGE gel for resolution in the second dimension. Typically IPG-DALT is not used for quantification of proteins due to the loss of low molecular weight components during the transfer to the SDS-PAGE gel.
IEF SDS-PAGE.
See Isoelectric focusing
2D gel analysis software.

In quantitative proteomics, these tools primarily analyze bio-markers by quantifying individual proteins, and showing the separation between one or more protein "spots" on a scanned image of a 2-DE gel. Additionally, these tools match spots between gels of similar samples to show, for example, proteomic differences between early and advanced stages of an illness. Software packages include Delta2D, ImageMaster, Melanie, PDQuest, Progenesis and REDFIN – among others. While this technology is widely utilized, the intelligence has not been perfected. For example, while PDQuest and Progenesis tend to agree on the quantification and analysis of well-defined well-separated protein spots, they deliver different results and analysis tendencies with less-defined less-separated spots.
Challenges for automatic software-based analysis include incompletely separated (overlapping) spots (less-defined and/or separated), weak spots / noise (e.g., "ghost spots"), running differences between gels (e.g., protein migrates to different positions on different gels), unmatched/undetected spots, leading to missing values, mismatched spots
, errors in quantification (several distinct spots may be erroneously detected as a single spot by the software and/or parts of a spot may be excluded from quantification), and differences in software algorithms and therefore analysis tendencies
Generated picking lists can be used for the automated in-gel digestion of protein spots, and subsequent identification of the proteins by mass spectrometry. Mass spectrometry analysis can identify precise mass measurements along with the sequencing of peptides that range from 1000-4000 atomic mass units.
For an overview of the current approach for software analysis of 2DE gel images see or.


Fluorescence recovery protein

Fluorescence recovery protein (FRP) is a small protein involved in regulating non-photochemical quenching in cyanobacteria. It prevents accumulation of the red photoactivated form of orange carotenoid protein (OCP), thereby reducing the amount of fluorescence quenching that occurs between the OCP and the phycobilisome antenna complexes. It interacts with the C-terminal domain of OCP, which shares homology with the NTF2 superfamily.
Function.
FRP is constitutively active, both "in vivo" and "in vitro". It is able to prevent quenching of phycobilin fluorescence by OCP "in vitro".
Overexpression of FRP in Synechocystis PCC 6803 leads to an absence of fluorescence quenching. Deletion mutants of FRP show a slightly larger degree of fluorescence quenching induced by strong blue-green light, but was unable to restore fluorescence levels when transferred to low-light or darkness.
Structure.
The protein is all alpha-helical, and the protein structure from "Synechocystis" was solved in 2013, showing both a dimer as well as a tetramer form in the same crystal used for X-ray diffraction. It is believed that the dimer is the active form. In the tetramer structure, one of the alpha helices is extended, disrupting the structure of a conserved patch of amino acids that is suggested to be an active site. Among these conserved residues, a histidine at position 53 and an arginine residue at position 60 have been shown to be essential for activity. Mutations in several other residues within this patch led to poor expression and precipitation, as well as loss of activity.
Genomics.
The gene for FRP is commonly found immediately downstream of OCP, although a CrtW-like B-carotene ketolase gene is occasionally found between the OCP and FRP. The FRP gene is transcribed independently from OCP in "Synechocystis 6803" and thus the OCP/FRP locus is not considered an operon.


Coprinopsis neophlyctidospora

Coprinopsis neophlyctidospora is a species of mushroom-forming fungus in the family Psathyrellaceae. It was described as new to science in 2011 by Jay Raut, Toshimitsu Fukiharu, and Akira Suzuki. An ammonia fungus, the species is known only from the boreal forest region of Alberta, Canada, where it was found growing on urea-treated soil. The specific epithet "neophlyctidospora" alludes to its distribution in the New World ("neo") and its close resemblance to "Coprinellus phlyctidospora".


Melior Discovery

Melior Discovery, Inc. is a private biopharmaceutical company based in Exton, Pennsylvania, USA. The company specializes in drug repositioning and has established a proprietary phenotypic screening platform that it uses for this purpose. Melior also offers certain contract research organization (CRO) services comprising animal models representing different disease conditions. The Company has issued press releases disclosing partnerships with Pfizer, Merck & Co., Johnson & Johnson, and AstraZeneca, all citing the use of the company’s drug repositioning technology. Melior Discovery has also used its technology to discover its own drug candidates.
In March 2009, the Food and Drug Administration (FDA) approved the company’s Investigational New Drug (IND) application for a type 2 diabetes therapeutic candidate, MLR-1023. In 2013, the company reported a licensing partnership with Bukwang Pharmaceutical Company LTD and the initiation of clinical trials in March 2015. In June 2016, the company reported positive results from their Phase 2a clinical study in diabetic subjects.
History.
Melior Discovery was co-founded in 2005 by Dr. Andrew Reaume (President and CEO) and Dr. Michael Saporito (Vice President of Research). Its investors include Cammeby’s Capital Group, VenturEast, Osage Ventures, Mid-Atlantic Angel Group, and BioAdvance.


Methylosphaera hansonii

Methylosphaera hansonii, also called Antarctic budding methanotroph AM6, is a species of psychrophilic, group I methanotrophs, named after microbiologist Richard S. Hanson. It is non-motile, coccoidal in morphology, does not form resting cells, reproduces by constriction, and requires seawater for growth. Its type strain is ACAM 549.
The cells are round and 1.5–2.0 μm in diameter. They are Gram-negative, non-motile, and strictly aerobic. They use methane and methanol as substrates to produce energy, and they can fix atmospheric nitrogen.
Nomenclature.
The name has French and Greek roots. "Methyl" for its methyl group and "sphaera" for sphere. Overall the name means "methyl sphere."


Judith G. Voet

Judith Greenwald Voet (born March 10, 1941) is a James Hammons Professor, Emerita in the Department of Chemistry and Biochemistry at Swarthmore College. Her research interests include enzyme reaction mechanisms and enzyme inhibition. She and her husband, Donald Voet, are authors of biochemistry textbooks that are widely used in undergraduate and graduate curricula.
Education.
Voet earned her B.S. degree from Antioch College and her Ph.D. from Brandeis University.
Career.
Voet participated in postdoctoral research at the University of Pennsylvania, Haverford College, and the Fox Chase Cancer Center before securing her faculty position at Swarthmore in 1979. Voet and her husband are coeditors-in-chief of the journal "Biochemical and Molecular Biology Education".


Phosphonate dehydrogenase

In enzymology, a phosphonate dehydrogenase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are phosphonate, NAD+, and H2O, whereas its 3 products are phosphate, NADH, and H+.
This enzyme belongs to the family of oxidoreductases, specifically those acting on phosphorus or arsenic in donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is phosphonate:NAD+ oxidoreductase. Other names in common use include NAD:phosphite oxidoreductase, and phosphite dehydrogenase.


Grylloblatta campodeiformis

Grylloblatta campodeiformis, also known as the Northern Rock Crawler, is an omnivorous species of insect in family Grylloblattidae. Like other species in the genus "Grylloblatta", it is endemic to North America.
Taxonomy.
This species was the first grylloblatid discovered and formally described in the scientific literature by Edmund Walker in 1914. It was originally placed in the order Orthoptera but has since been placed in the order Notoptera.
There are currently four subspecies:
Description.
Adults are typically long, excluding ovipositors and cerci, and are fairly elongate, wingless insects. They are a uniform honey-yellow in colour and covered with very short hair. Unlike some other species of grylloblatid, "G. campodeiformis" has eyes which have roughly 70 facets. The head is fairly flat and rounded. The thorax is elongate and over a third of the body length. The abdomen is composed of 10 segments and over half the body length. The legs are long and narrow (cursorial) with stout coxae and long femora. Their antennae are long ~ and thread-like. In adults the number of antennal subsegments is variable ranging from 24 to 27.
Biology.
Diet
Rock crawlers are nocturnal predators and scavengers that actively search for small, invertebrate prey. They also venture onto snowfields, foraging for “insect-fallout” carried and deposited there by wind.
Distribution and habitat.
This species was originally discovered on Sulphur Mountain, Alberta in the Canadian Rockies at an altitude of . Subsequently it has been recorded from British Columbia (Canada), Montana, Washington (USA).
They are ground dwelling animals, living between small stones and debris during the day. While they can survive warmer temperatures of up to they are typically nocturnal, becoming active on snow fields at cooler temperatures of around making them psychrophilic.
Like other North American grylloblatids, "G. campodeiformis" is at some risk of extinction due to its habitat requirements and reduced mobility.


Black and rufous elephant shrew

The black and rufous elephant shrew, ("Rhynchocyon petersi") the black and rufous sengi, or the Zanj elephant shrew is one of the 17 species of elephant shrew found only in Africa. It is native to the lowland montane and dense forests of Kenya and Tanzania. Like other members of the genus "Rhynchocyon", it is a relatively large species, with adults averaging about 28 cm (11 in) in length and 450-700 g (1.0-1.5 lb) in weight.
Distribution and habitat.
The forests of the Eastern Arc Mountains are critical habitats for "R. petersi". The Chome Forest Reserve in Tanzania is an isolated, and largely undisturbed, habitat for the shrews. Populations densities in the Chome area are significantly lower than the surrounding areas, home to approximately 2700 "R. petersi", and is thought to be the result of restricted migration and illegal human activity. It was once listed by the IUCN Red List as vulnerable, but has since been changed to a status of least concern. However, its numbers are reportedly declining; suffering from severe forest fragmentation and degradation from human expansion.
Diet and behaviour.
It eats insects such as beetles, termites, and centipedes, using its proboscis to dig them from the soil and its tongue to lick them up. Like most elephant shrews, it lives in monogamous pairs, defending hectare-sized territories. It typically builds ground level nests for shelter requiring dry leaf litter often at the base of trees.
Elephant shrews in zoological gardens.
Several zoos have begun breeding this elephant shrew, including seven in Europe, such as the Prague and Wrocław zoos, as well as zoos in the United States like the Philadelphia Zoo. Two black and rufous elephant shrew males were born on February 4, 2007, at the National Zoo in Washington, D.C.


Phosphofructokinase 2

Phosphofructokinase-2 (6-phosphofructo-2-kinase, PFK-2) or fructose bisphosphatase-2 (FBPase-2), is an enzyme indirectly responsible for regulating the rates of glycolysis and gluconeogenesis in cells. It catalyzes formation and degradation of a significant allosteric regulator, fructose-2,6-bisphosphate (Fru-2,6-P2) from substrate fructose-6-phosphate. Fru-2,6-P2 contributes to the rate-determining step of glycolysis as it activates enzyme phosphofructokinase 1 in the glycolysis pathway, and inhibits fructose-1,6-bisphosphatase 1 in gluconeogenesis. Since Fru-2,6-P2 differentially regulates glycolysis and gluconeogenesis, it can act as a key signal to switch between the opposing pathways. Because PFK-2 produces Fru-2,6-P2 in response to hormonal signaling, metabolism can be more sensitively and efficiently controlled to align with the organism's glycolytic needs.This enzyme participates in fructose and mannose metabolism. The enzyme is important in the regulation of hepatic carbohydrate metabolism and is found in greatest quantities in the liver, kidney and heart. In mammals, several genes often encode different isoforms, each of which differs in its tissue distribution and enzymatic activity. The family described here bears a resemblance to the ATP-driven phospho-fructokinases, however, they share little sequence similarity, although a few residues seem key to their interaction with fructose 6-phosphate.
PFK-2 is known as the "bifunctional enzyme" because of its notable structure: though both are located on one protein homodimer, its two domains act as independently functioning enzymes. One terminus serves as a kinase domain (for PFK-2) while the other terminus acts as a phosphatase domain (FBPase-2).
In mammals, genetic mechanisms encode different PFK-2 isoforms to accommodate tissue specific needs. While general function remains the same, isoforms feature slight differences in enzymatic properties and are controlled by different methods of regulation; these differences are discussed below.
Structure.
The monomers of the bifunctional protein are clearly divided into two functional domains. The kinase domain is located on the N-terminal. It consists of a central six-stranded β sheet, with five parallel strands and an antiparallel edge strand, surrounded by seven α helices. The domain contains nucleotide-binding fold (nbf) at the C-terminal end of the first β-strand. The PFK-2 domain appears to be closely related to the superfamily of mononucleotide binding proteins including adenylate cyclase.
On the other hand, the phosphatase domain is located on the C-terminal. It resembles the family of proteins that include phosphoglycerate mutases and acid phosphatases. The domain has a mixed α/ β structure, with a six-stranded central β sheet, plus an additional α-helical subdomain that covers the presumed active site of the molecule. Finally, the N-terminal region modulates PFK-2 and FBPase2 activities, and stabilizes the dimer form of the enzyme.
While this central catalytic core remains conserved in all forms of PFK-2, slight structural variations exist in isoforms as a result of different amino acid sequences or alternative splicing. With some minor exceptions, the size of PFK-2 enzymes is typically around 55 kDa.
Researchers hypothesize that the unique bifunctional structure of this enzyme arose from a gene fusion event between a primordial bacterial PFK-1 and a primordial mutase/phosphatase.
Function.
This enzyme's main function is to synthesize or degrade allosteric regulator Fru-2,6-P2 in response to glycolytic needs of the cell or organism, as depicted in the accompanying diagram.
In enzymology, a 6-phosphofructo-2-kinase () is an enzyme that catalyzes the chemical reaction:
Thus, the kinase domain hydrolyzes ATP to phosphorylate the carbon-2 of fructose-6-phosphate, producing Fru-2,6-P2 and ADP. A phosphohistidine intermediate is formed within the reaction.
Because of the enzyme's dual functions, it can be categorized into multiple families. Through categorization by the kinase reaction, this enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing groups (phosphotransferases) with an alcohol group as acceptor. On the other hand, the phosphatase reaction is characteristic of the family of hydrolases, specifically those acting on phosphoric monoester bonds.
Regulation.
In almost all isoforms, PFK-2 undergoes covalent modification through phosphorylation/dephosphorylation based on the cell's hormonal signaling. Phosphorylation of a specific residue may prompt a shift that stabilizes either kinase or phosphatase domain function. This regulation signal thus controls whether F-2,6-P2 will be synthesized or degraded.
Furthermore, the allosteric regulation of PFK2 is very similar to the regulation of PFK1. High levels of AMP or phosphate group signifies a low energy charge state and thus stimulates PFK2. On the other hand, a high concentration of phosphoenolpyruvate(PEP) and citrate signifies that there is a high level of biosynthetic precursor and hence inhibits PFK2. Unlike PFK1, PFK2 is not affected by ATP concentration.
Isozymes.
Protein isozymes are enzymes that catalyze the same reaction but are encoded with different amino acid sequences and as such, display slight differences in protein characteristics. In humans, the four genes that encode phosphofructokinase 2 proteins include PFKFB-1, PFKFB2, PFKFB3 and PFKFB4.
Multiple mammalian isoforms of the protein have been reported to date, difference rising by either the transcription of different enzymes or alternative splicing. While the structural core that catalyzes the PFK-2/FBPase-2 reaction is highly conserved across isoforms, the major differences arise from highly variable flanking sequences in the isoform amino and carboxyl terminals. Because these areas often contain phosphorylation sites, changes in amino acid composition or terminal length may result in vastly different enzyme kinetics and characteristics. Each variant differs in their primary tissue of expression, response to protein kinase regulation, and ratio of kinase/phosphatase domain activity. While multiple types of isozymes may consist in a tissue, isozymes are identified by their primary tissue expression and tissue of discovery below.
PFKB1: Liver, muscle, and fetal.
Located on the X chromosome, this gene is the most well-known of the four genes particularly because it encodes the highly researched liver enzyme. Variable mRNA splicing of PFKB1 yields three different promoters (L, M and F) and therefore, three tissue-specific variants that differ in regulation:
PFKB2: Cardiac (H-Type).
The PFKB2 gene is located on chromosome 1. When greater concentrations of adrenaline and/or insulin hormone are circulated, a Protein Kinase A pathway is activated which phosphorylates either Serine 466 or Serine 483 in the C-terminus. Alternatively, Protein Kinase B may also phosphorylate these regulatory sites, which are part of the FBPase-2 domain. When this serine residue is phosphorylated, FBPase-2 function is inactivated and greater PFK-2 activity is stabilized.
PFKB3: Brain, placental, and inducible.
PFKB3 is located on chromosome 10 and transcribes two major isoforms, inducible type and ubiquitous type. These forms differ in alternative splicing of Exon 15 in their C-terminus. However, they are similar in that for both, glucagon activates a cyclic AMP pathway; this results in Protein Kinase A, Protein Kinase C, or AMP-activated Protein Kinase phosphorylating a regulatory residue on Serine 461 in the C-terminus to stabilize PFK-2 kinase function. Furthermore, both isoforms transcribed from this gene are noted for having a particularly high, dominant rate of kinase activity as indicated by a kinase/phosphatase activity ratio of 700 (whereas the liver, heart, and testis isozymes respectively have PFK-2/FBPase-2 ratios of 1.5, 80, and 4). Therefore, PFKB3 in particular consistently produces large amounts of F-2,6-P2 and sustains high rates of glycolysis.
PFKB4: Testis (T-Type).
Gene PFKB4, located on chromosome 3, expresses PFK-2 in human testis tissue. PFK-2 enzymes encoded by PFK-4 are comparable to the liver enzyme in size at around 54kDa, and like the muscle tissue, do not contain a protein kinase phosphorylation site. While less research has clarified regulation mechanisms for this isoform, studies have confirmed that modification from multiple transcription factors in the 5' flanking region regulates the amount of PFK-2 expression in developing testis tissue. This isoform has been particularly implicated as being modified and hyper-expressed for prostate cancer cell survival.
Clinical significance.
Because this enzyme family maintains rates of glycolysis and gluconeogenesis, it presents great potential for therapeutic action for control of metabolism particularly in diabetes and cancer cells. Data also demonstrates that all of the PFK-2 genes (although the PFKB3 gene response remains the most drastic) were activated by limitations in oxygen. The control of PFK-2/FBP-ase2 activity was found to be linked to heart functioning, particularly for ischemia, and the control against hypoxia. Researchers hypothesize that this responsive characteristic of the PFK-2 genes may be a strong, evolutionary physiological adaptation. However, many human cancer cell types (including leukemia, lung, breast, colon, pancreatic, and ovarian cancers) demonstrate over-expression of PFK3 and/or PFK4; this change in metabolism likely plays a role in the Warburg effect.
Lastly, the "Pfkfb2" gene encoding PFK2/FBPase2 protein is linked to the predisposition to schizophrenia.
External links.
"This article incorporates text from the public domain Pfam and InterPro IPR013079"


CAMP receptor protein

cAMP receptor protein (CRP; also known as catabolite activator protein, CAP) is a regulatory protein in bacteria. CRP protein binds cAMP, which causes a conformational change that allows CRP to bind tightly to a specific DNA site in the promoters of the genes it controls. CRP then activates transcription through direct protein–protein interactions with RNA polymerase.
The genes regulated by CRP are mostly involved in energy metabolism, such as galactose, citrate, or the PEP group translocation system. In "Escherichia coli", cyclic AMP receptor protein (CRP) can regulate the transcription of more than 100 genes.
The signal to activate CRP is the binding of cyclic AMP. Binding of cAMP to CRP leads to a long-distance signal transduction from the N-terminal cAMP-binding domain to the C-terminal domain of the protein, which is responsible for interaction with specific sequences of DNA.
At "Class I" CRP-dependent promoters, CRP binds to a DNA site located upstream of core promoter elements and activates transcription through protein–protein interactions between "activating region 1" of CRP and the C-terminal domain of RNA polymerase alpha subunit. At "Class II" CRP-dependent promoters, CRP binds to a DNA site that overlaps the promoter -35 element and activates transcription through two sets of protein–protein interactions: (1) an interaction between "activating region 1" of CRP and the C-terminal domain of RNA polymerase alpha subunit, and (2) an interaction between "activating region 2" of CRP and the N-terminal domain of RNA polymerase alpha subunit. At "Class III" CRP-dependent promoters, CRP functions together with one or more "co-activator" proteins.
At most CRP-dependent promoters, CRP activates transcription primarily or exclusively through a "recruitment" mechanism, in which protein–protein interactions between CRP and RNA polymerase assist binding of RNA polymerase to the promoter.


L-lysine 6-oxidase

In enzymology, a L-lysine 6-oxidase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are L-lysine, O2, and H2O, whereas its 3 products are 2-aminoadipate 6-semialdehyde, H2O2, and NH3.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH2 group of donors with oxygen as acceptor. The systematic name of this enzyme class is L-lysine:oxygen 6-oxidoreductase (deaminating). Other names in common use include L-lysine-epsilon-oxidase, Lod, LodA, and marinocine.


Oxidase

An oxidase is an enzyme that catalyzes an oxidation-reduction reaction, especially one involving dioxygen (O2) as the electron acceptor. In reactions involving donation of a hydrogen atom, oxygen is reduced to water (H2O) or hydrogen peroxide (H2O2). Some oxidation reactions, such as those involving monoamine oxidase or xanthine oxidase, typically do not involve free molecular oxygen.
The oxidases are a subclass of the oxidoreductases.
Examples.
An important example is cytochrome c oxidase, the key enzyme that allows the body to employ oxygen in the generation of energy and the final component of the electron transfer chain. Other examples are:
Oxidase test.
In microbiology, the oxidase test is used as a phenotypic characteristic for the identification of bacterial strains; it determines whether a given bacterium produces cytochrome oxidases (and therefore utilizes oxygen with an electron transfer chain).
Oxidase test is used to determine whether a bacterium is an aerobe or anaerobe.


NADPH dehydrogenase

In enzymology, a NADPH dehydrogenase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are NADPH, H+, and acceptor, whereas its two products are NADP+ and reduced acceptor.
This enzyme belongs to the family of oxidoreductases, specifically those acting on NADH or NADPH with other acceptors. The systematic name of this enzyme class is NADPH:acceptor oxidoreductase. Other names in common use include NADPH2 diaphorase, NADPH diaphorase, OYE, diaphorase, dihydronicotinamide adenine dinucleotide phosphate dehydrogenase, NADPH-dehydrogenase, NADPH-diaphorase, NADPH2-dehydrogenase, old yellow enzyme, reduced nicotinamide adenine dinucleotide phosphate dehydrogenase, TPNH dehydrogenase, TPNH-diaphorase, triphosphopyridine diaphorase, triphosphopyridine nucleotide diaphorase, NADPH2 dehydrogenase, and NADPH:(acceptor) oxidoreductase. It has 2 cofactors: FAD, and FMN.


5-Deoxyinositol

5-Deoxyinositol (quercitol) is a cyclitol. It can be found in wines aged in oak wood barrels. It can also be found in "Quercus" sp. (oaks) and in "Gymnema sylvestre". It is different from , a synonym of quercetin.


Jane Grande-Allen

Katie Jane Grande-Allen (born December 15) is an American bioengineer currently the Isabel C. Cameron Professor at Rice University. She is currently chair of the Department of Bioengineering at Rice University. Her research focuses on an engineering approach to heart disease.
Early life and education.
Grande-Allen earned her Bachelor of Arts in Mathematics and Biology from Transylvania University. She then moved to the University of Washington for her Phd in Bioengineering. She subsequently conducted her postdoctoral fellowship in biomedical engineering with the Cleveland Clinic Foundation.
Career.
Grande-Allen joined the faculty at Rice University in 2003 and began conducting research on the biochemical composition of heart valves in patients with congestive heart failure. She earned the 2011 A.J. Durelli Award by the Society for Experimental Mechanics Inc. as a result of her experimental test on tissue function, strength, growth and abnormalities.
By 2011, she earned the Established Investigator Award from the American Heart Association and received a $1.2 million grant from the National Institutes of Health to research replacement heart valves. A few years later, she was elected a Fellow of the American Association for the Advancement of Science for her contributions to the field of heart-valve biomechanics and mechanobiolog.
In 2017, Grande-Allen was chosen to replace Rebecca Richards-Kortum as director of the Rice Institute of Biosciences and Bioengineering. In the same year, she was elected a Fellow of the Biomedical Engineering Society and named chair of the bioengineering department.
She has also been elected a Fellow of the American Heart Association and Society for Experimental Mechanics.


PHA-57378

PHA-57378 is a drug which acts as an agonist at serotonin 5-HT2 receptors, having a binding affinity of 4.1 nM at the 5-HT2A subtype and 4.3 nM at 5-HT2C. It has anxiolytic effects in animal studies.


Signal peptide

A signal peptide (sometimes referred to as signal sequence, targeting signal, localization signal, localization sequence, transit peptide, leader sequence or leader peptide) is a short peptide (usually 16-30 amino acids long) present at the N-terminus (or occasionally C-terminus) of most newly synthesized proteins that are destined toward the secretory pathway.
These proteins include those that reside either inside certain organelles (the endoplasmic reticulum, Golgi or endosomes), secreted from the cell, or inserted into most cellular membranes. Although most type I membrane-bound proteins have signal peptides, the majority of type II and multi-spanning membrane-bound proteins are targeted to the secretory pathway by their first transmembrane domain, which biochemically resembles a signal sequence except that it is not cleaved. They are a kind of target peptide.
Function (translocation).
Signal peptides function to prompt a cell to translocate the protein, usually to the cellular membrane. In prokaryotes, signal peptides direct the newly synthesized protein to the SecYEG protein-conducting channel, which is present in the plasma membrane. A homologous system exists in eukaryotes, where the signal peptide directs the newly synthesized protein to the Sec61 channel, which shares structural and sequence homology with SecYEG, but is present in the endoplasmic reticulum. Both the SecYEG and Sec61 channels are commonly referred to as the translocon, and transit through this channel is known as translocation. While secreted proteins are threaded through the channel, transmembrane domains may diffuse across a lateral gate in the translocon to partition into the surrounding membrane.
Signal peptide structure.
The core of the signal peptide contains a long stretch of hydrophobic amino acids (about 5–16 residues long) that has a tendency to form a single alpha-helix and is also referred to as the "h-region". In addition, many signal peptides begin with a short positively charged stretch of amino acids, which may help to enforce proper topology of the polypeptide during translocation by what is known as the positive-inside rule. Because of its close location to the N-terminus it is called the "n-region". At the end of the signal peptide there is typically a stretch of amino acids that is recognized and cleaved by signal peptidase and therefore named cleavage site. However this cleavage site is absent from transmembrane-domains that serve as signal peptides, which are sometimes referred to as signal anchor sequences. Signal peptidase may cleave either during or after completion of translocation to generate a free signal peptide and a mature protein. The free signal peptides are then digested by specific proteases.
Moreover, different target locations are aimed by different types of signal peptides. For example, the structure of a target peptide aiming for the mitochondrial environment differs in terms of length and shows an alternating pattern of small positively charged and hydrophobic stretches. Nucleus aiming signal peptides can be found at both the N-terminus and the C-terminus of a protein and are in the majority of the cases retained in the mature protein.
It is possible to determine the amino acid sequence of the N-terminal signal peptide by Edman degradation, a cyclic procedure that cleaves off the amino acids one at a time.
Co-translational versus post-translational translocation.
In both prokaryotes and eukaryotes signal sequences may act co-translationally or post-translationally.
The co-translational pathway is initiated when the signal peptide emerges from the ribosome and is recognized by the signal-recognition particle (SRP). SRP then halts further translation (translational arrest only occurs in Eukaryotes) and directs the signal sequence-ribosome-mRNA complex to the SRP receptor, which is present on the surface of either the plasma membrane (in prokaryotes) or the ER (in eukaryotes). Once membrane-targeting is completed, the signal sequence is inserted into the translocon. Ribosomes are then physically docked onto the cytoplasmic face of the translocon and protein synthesis resumes.
The post-translational pathway is initiated after protein synthesis is completed. In prokaryotes, the signal sequence of post-translational substrates is recognized by the SecB chaperone protein that transfers the protein to the SecA ATPase, which in turn pumps the protein through the translocon. Although post-translational translocation is known to occur in eukaryotes, it is poorly understood. It is however known that in yeast post-translational translocation requires the translocon and two additional membrane-bound proteins, Sec62 and Sec63.
Signal peptides determine secretion efficiency.
Signal peptides are extremely heterogeneous and many prokaryotic and eukaryotic signal peptides are functionally interchangeable even between different species however the efficiency of protein secretion is strongly determined by the signal peptide.
Nucleotide level features.
In vertebrates, the region of the mRNA that codes for the signal peptide (i.e. the signal sequence coding region, or SSCR) can function as an RNA element with specific activities. SSCRs promote nuclear mRNA export and the proper localization to the surface of the endoplasmic reticulum. In addition SSCRs have specific sequence features: they have low adenine-content, are enriched in certain motifs, and tend to be present in the first exon at a frequency that is higher than expected.
Signal peptide-less secretion.
Proteins without signal peptides can also be secreted by unconventional mechanisms. E.g. Interleukin, Galectin. The process by which such secretory proteins gain access to the cell exterior is termed unconventional protein secretion (UPS). In plants, even 50% of secreted proteins can be UPS dependent.
Nomenclature.
Signal peptides are not to be confused with the leader peptides sometimes encoded by leader mRNA, although both are sometimes ambiguously referred to as "leader peptides." These other leader peptides are short polypeptides that do not function in protein localization, but instead may regulate transcription or translation of the main protein, and are not part of the final protein sequence. This type of leader peptide primarily refers to a form of gene regulation found in bacteria, although a similar mechanism is used to regulate eukaryotic genes, which is referred to as uORFs (upstream open reading frames).


Class I PI 3-kinases

Class I PI 3-kinases are a subgroup of the enzyme family, phosphoinositide 3-kinase that possess a common protein domain structure, substrate specificity, and method of activation. Class I PI 3-kinases are further divided into two subclasses, class IA PI 3-kinases and class IB PI 3-kinases.
Class IA PI 3-kinases.
Class IA PI 3-kinases are activated by receptor tyrosine kinases (RTKs).
There are three catalytic subunits that are classified as class IA PI 3-kinases:
There are currently five regulatory subunits that are known to associate with class IA PI 3-kinases catalytic subunits:
Class IB PI 3-kinases.
Class IB PI 3-kinases are activated by G-protein-coupled receptors (GPCRs).
The only known class IB PI 3-kinase catalytic subunit is p110γ.
There are two known regulatory subunits for p110γ:


Carsten Carlberg

Carsten Carlberg (born December 13, 1963) is a German biochemist. He is professor of biochemistry at the University of Eastern Finland in Kuopio, Finland.
Biography.
Carlberg was born in Hamburg, Germany. He attended school at Bremen, Germany, graduating in 1981 with Abitur at the Gymnasium an der Bördestrasse. From 1982 to 1987, he studied Physics and Biochemistry at the Free University of Berlin, Germany, finishing with a diploma in biochemistry. Thereafter he worked in the team of Burghardt Wittig and in 1989 received his PhD (Dr. rer. nat.) for his studies on the interaction of polymerases with DNA secondary structures at the Free University of Berlin.
From 1989 to 1992, Carlberg was a post-doctoral fellow in the team of Willi Hunziker at the Central Research Units of Hoffmann-La Roche in Basel, Switzerland, and started his work on the gene regulation of Vitamin D. From 1992 to 1997, he worked in the Dermatology Department of Jean-Hilaire Saurat at the University of Geneva, where he continued his studies of gene regulation by nuclear receptors. In 1997, Carlberg received his Habilitation at the University of Düsseldorf, Germany, and was research group leader in the Department of Physiological Chemistry of .
In 2000, Carlberg was appointed full professor of biochemistry at the University of Kuopio, which in 2010 merged with the University of Joensuu to form the University of Eastern Finland. In 2006, he took a second affiliation at the University of Luxembourg, in order to create the Master program in Integrated Systems Biology there. From 2008–2013 he was one of 4 principal investigators at the Finnish Center of Excellence in Cardiovascular Diseases and Type 2 Diabetes Research.
Work and publications.
Carlberg's research is focused on epigenetics with special focus on Vitamin D.
Over 280 of his publications are listed in the Science Citation Index. These have been cited more than 10,500 times, according to ResearcherID. Carsten Carlberg's h-index is 57.
Carsten Carlberg published textbooks on "Mechanisms of Gene Regulation", "Nutrigenomics," and "Human Epigenomics."


Changsheng Bio-Technology

Changsheng Bio-Technology Co., Ltd. () is a biotechnology company based in Changchun Jilin, China, specializing in vaccines. It was founded in 1992 as a state-owned enterprise but became a family-owned private company in 2003.
It reported 566 million yuan in net profits in 2017.
A sales representative was found, in July 2018, to have paid 164,000 yuan (US$24,200) in bribes to the head of the Changling County disease control centre.
Its DPT vaccines, sold to the Shandong Centre for Disease Control and Prevention, which had been given to 215,184 children were found to be ineffective. It was fined 3.4 million yuan.
In October 2018, it was fined 9.1 billion yuan ($1.32 billion) for falsifying data for a rabies vaccine and producing an ineffective vaccine for babies. 14 of its executives were banned from working in the drugs sector. It was separately fined 600,000 yuan by the China Securities and Regulatory Commission and four executives were banned for life four of Changsheng Bio-technology’s executives and banned them from the securities market because of violation of information disclosure rules. It proposes to pay compensation of between 200,000-650,000 yuan per person to those who have suffered from the vaccine.
It lost nearly half of its share value after the China Food and Drug Administration uncovered its data forgery and was publicly condemned by Chinese Communist Party general secretary Xi Jinping and State Council premier Li Keqiang.
Police planned to arrest 18 people, including the chairwoman Gao Junfang, on suspicion of producing and selling substandard drugs.


Hydrogenase (acceptor)

In enzymology, a hydrogenase (acceptor) () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are H2 and A, whereas its product is AH2.
This enzyme belongs to the family of oxidoreductases, specifically those acting on hydrogen as donor with other acceptors. The systematic name of this enzyme class is hydrogen:acceptor oxidoreductase. Other names in common use include H2 producing hydrogenase[ambiguous], hydrogen-lyase[ambiguous], hydrogenlyase[ambiguous], uptake hydrogenase[ambiguous], and hydrogen:(acceptor) oxidoreductase.


Ada Wells

Ada Wells (née Pike, 29 April 1863 – 22 March 1933) was a feminist and social worker in New Zealand.
Biography.
Ada Pike was born near Henley-on-Thames, South Oxfordshire, England. Her parents emigrated to New Zealand with their four girls and one boy in 1873, arriving on the "Merope" in Lyttelton on 31 October of that year. She attended Avonside School from 1874, and Christchurch West High School in 1876, where she then worked as a pupil-teacher from 1877 to 1881.
Wells attended Canterbury College. In 1884, aged 20, she married Harry Wells, the cathedral organist and choirmaster. Twelve years Ada's senior, with a violent temper and fondness for alcohol, he was a poor financial manager. Ada's marital experience – where she was, at times, the family breadwinner – strengthened her belief that women should have economic independence.
Wells was a teacher at St. Albans School which was situated in a poor working class part of Christchurch. With her husband's help, Ada put on concerts in aid of the school prize fund. In 1892, Ada, pregnant, sought two months' leave of absence. The North Canterbury Education Board was inclined to grant this. However, Ada was opposed by the headmaster, James Speight, who wrote a long letter on 'the delinquencies of Mrs. Wells'. Rather than being granted leave of absence, Ada was dismissed.
In the 1880s, working within the Women's Christian Temperance Union New Zealand (WCTU NZ), Ada was active in the women's suffrage movement. While Kate Sheppard was the public face of the WCTU NZ campaign for the enfranchisement of women, Ada was an organiser. In 1893 New Zealand became the first self-governing country in the world in which all women had the right to vote in parliamentary elections.
In 1892, Ada established the Canterbury Women's Institute, an organization similar to the Women's Franchise Leagues in other parts of the country; for many years, she was president. In 1896 when the National Council of Women of New Zealand was formed, she became its first secretary.
From 1899 to 1906, Ada was an elected member of the Ashburton and North Canterbury United Charitable Aid Board. She was associated with the Prison Gate Mission for the rehabilitation of ex-prisoners. A founding member of the National Council of Women in 1896, she was the first secretary.
She had three daughters and a son. Harry Wells died in 1918. Ada died in Christchurch on 22 March 1933 and was buried at the Waimairi Cemetery.
The Ministry for Culture and Heritage now offers an Ada Wells Memorial Prize for Undergraduate Students.
Activism.
As a member of the National Peace Council, Ada spoke out strongly against conscription and war, and helped World War I conscientious objectors.
Wells advocated a meatless diet and was a vegetarianism activist. At the 1897 conference of the National Council of Women, Wells promoted an ovo-lacto vegetarian diet. She authored magazine articles supportive of naturopathy and vegetarianism. Wells was an anti-vaccinationist and opposed vivisection.
She also campaigned for the corollary to women's suffrage, women's right to stand for Parliament. This was granted in 1919, though no woman was elected until 1933. A member of the Labour Party, Ada was, between 1917–19, the first woman member of the Christchurch City Council.


Max Bergmann

Max Bergmann (12 February 1886 – 7 November 1944) was a Jewish-German biochemist. Together with Leonidas Zervas, the discoverer of the group, they were the first to use the carboxybenzyl protecting group for the synthesis of oligopeptides.
Life and work.
Bergmann was born in Fürth, Bavaria, Germany on February 12, 1886, the seventh child of coal wholesalers Salomon and Rosalie Bergmann.
Bergmann started studying Biology at the Ludwig Maximilian University of Munich, but lectures by Adolf von Baeyer captured his interest and eventually persuaded him to switch to Organic Chemistry. He continued his chemical studies at the Friedrich Wilhelm University of Berlin, where he was taught by Emil Fischer. After receiving his PhD under the supervision of Ignaz Bloch in 1911 for his thesis on acyl(polysulfides), he became the assistant to Fischer at the University of Berlin, where he stayed until Fischer's death in 1919. He received his habilitation in 1921.
In 1922 Bergmann was made the first director of the Kaiser Wilhelm Institute for Leather Research in Dresden, which was created in 1921 and from which the Max Planck Institute of Biochemistry descends. It was there that he worked with his former doctoral student, Leonidas Zervas, who eventually rose to vice-director of the institute and briefly succeeded Bergmann as director. In the early 1930s, the two scientists developed the Bergmann-Zervas carbobenzoxy method for the synthesis of polypeptides, which started the field of controlled peptide chemical synthesis and remained the dominant method in it for the next 20 years. Bergmann and Zervas gained international academic fame as a result.
Bergmann was nonetheless forced to abandon his institute due to his Jewish origin after the passage of the Civil Service Law and emigrated from Nazi Germany in 1933. He moved to the USA and was thereafter active as a senior researcher at the Rockefeller Institute for Medical Research in New York. There, he was the main specialist in protein chemistry and contributed to the great progress of the US in the area of molecular biology. Two eventual Nobel Prize winners (William Howard Stein and Stanford Moore), as well as numerous postdoctoral students (including Klaus H. Hofmann) worked in his laboratory.
Bergmann is considered an important figure in synthetic organic chemistry and biochemistry. He specialized in decoding peptide structures, while also researching their synthesis.
He died in the Mount Sinai Hospital, New York City, on November 7, 1944.
Since 1980, the Max-Bergmann-Kreis (MBK) company of German peptide chemists awards the Bergmann golden medal for peptide science, with the first medal given to Zervas. In 2002 the Max Bergmann Center was created in Dresden.


Deamination

Deamination is the removal of an amino group from a molecule. Enzymes that catalyse this reaction are called deaminases.
In the human body, deamination takes place primarily in the liver, however it can also occur in the kidney. In situations of excess protein intake, deamination is used to break down amino acids for energy. The amino group is removed from the amino acid and converted to ammonia. The rest of the amino acid is made up of mostly carbon and hydrogen, and is recycled or oxidized for energy. Ammonia is toxic to the human system, and enzymes convert it to urea or uric acid by addition of carbon dioxide molecules (which is not considered a deamination process) in the urea cycle, which also takes place in the liver. Urea and uric acid can safely diffuse into the blood and then be excreted in urine.
Deamination reactions in DNA.
Cytosine.
Spontaneous deamination is the hydrolysis reaction of cytosine into uracil, releasing ammonia in the process. This can occur in vitro through the use of bisulfite, which deaminates cytosine, but not 5-methylcytosine. This property has allowed researchers to sequence methylated DNA to distinguish non-methylated cytosine (shown up as uracil) and methylated cytosine (unaltered).
In DNA, this spontaneous deamination is corrected for by the removal of uracil (product of cytosine deamination and "not" part of DNA) by uracil-DNA glycosylase, generating an abasic (AP) site. The resulting abasic site is then recognised by enzymes (AP endonucleases) that break a phosphodiester bond in the DNA, permitting the repair of the resulting lesion by replacement with another cytosine. A DNA polymerase may perform this replacement via nick translation, a terminal excision reaction by its 5'⟶3' exonuclease activity, followed by a fill-in reaction by its polymerase activity. DNA ligase then forms a phosphodiester bond to seal the resulting nicked duplex product, which now includes a new, correct cytosine (Base excision repair).
5-methylcytosine.
Spontaneous deamination of 5-methylcytosine results in thymine and ammonia. This is the most common single nucleotide mutation. In DNA, this reaction, if detected prior to passage of the replication fork, can be corrected by the enzyme thymine-DNA glycosylase, which removes the thymine base in a G/T mismatch. This leaves an abasic site that is repaired by AP endonucleases and polymerase, as with uracil-DNA glycosylase.
Cytosine deamination increases C-To-T mutations.
A known result of cytosine methylation is the increase of C-to-T transition mutations through the process of deamination. Cytosine deamination has been seen needed for many regulatory functions in the genome; many regulatory functions are related to the loss in CPG sites due to the presence of transposable elements. TEs have been proposed to accelerate the mechanism of enhancer creation by providing extra DNA that is compatible with the host transcription factors that eventually have an impact on C-to-T mutations.
Guanine.
Deamination of guanine results in the formation of xanthine. Xanthine, however, still pairs with cytosine.
Adenine.
Deamination of adenine results in the formation of hypoxanthine. Hypoxanthine, in a manner analogous to the imine tautomer of adenine, selectively base pairs with cytosine instead of thymine. This results in a post-replicative transition mutation, where the original A-T base pair transforms into a G-C base pair.


Myogenin

Myogenin (myogenic factor 4), also known as MYOG, is a gene.
Myogenin is a muscle-specific basic-helix-loop-helix (bHLH) transcription factor involved in the coordination of skeletal muscle development or myogenesis and repair. Myogenin is a member of the MyoD family of transcription factors, which also includes MyoD, Myf5, and MRF4.
In mice, myogenin is essential for the development of functional skeletal muscle. Myogenin is required for the proper differentiation of most myogenic precursor cells during the process of myogenesis. When the DNA coding for myogenin was knocked out of the mouse genome, severe skeletal muscle defects were observed. Mice lacking both copies of myogenin (homozygous-null) suffer from perinatal lethality due to the lack of mature secondary skeletal muscle fibers throughout the body.
In cell culture, myogenin can induce myogenesis in a variety of non-muscle cell types.
Interactions.
Myogenin has been shown to interact with:


SecA

The SecA protein is a cell membrane associated subunit of the eubacterial Sec or Type II secretory pathway, a system which is responsible for the secretion of proteins through the cell membrane. Within this system SecA has the functional properties of an ATPase and is required to power the movement of the protein substrate across the translocon channel.
The translocase system encompasses an array of proteins which are functionally centred on the translocon channel which mediates the export of proteins across the bacterial cytoplasmic membrane and the insertion of membrane proteins into it. Regardless of the chosen targeting route, preprotein eventually reach the cytoplasmic membrane and make contact with the translocase. This translocase consists of the peripheral membrane ATPase SecA and the translocon membrane channel, which itself is composed of the proteins SecY, SecE, and SecG. Conformational changes within the SecA structure are the effect of its ATP-hydrolyzing behaviour and possibly lead to the stepwise export of the preprotein substrate through the SecYEG channel.
Structure.
SecA is a complex protein whose structure consists of six characterized domains that can explain SecA's capabilities to bind substrates and to move them. The following five domains seem to be present in all SecA proteins that have been structurally analyzed so far.
DEAD motor domain.
This amino acid domain is subdivided into the two nucleotide binding folds 1 and 2 (NBF1 and NBF2) where ATP is bound and hydrolyzed. The chemical energy from the phosphodiester bonds results in a conformational change which is transferred to other domains (especially the HWD and the PPXD domains) which consequently mechanically move the preprotein across the membrane. However, these conformational changes are partly regulated by other protomer domains described below.
C-terminal linker domain.
The capability to bind to the SecB chaperone during post-translational translocation, the ribosome (during both post-translational translocation and co-translational translocation ) and the phospholipid bilayer is important for SecA functioning and is achieved by the C-terminal linker domain.
Helical wing domain (HWD).
Located at the C-terminal portion of the molecule, this domain is in contact with the HSD and PPXD domains. Likely it plays a role in transferring molecular conformational motion, which it receives from HSD and which originates from ATP hydrolysis in the DEAD motor domain, to the PPXD domain.
Peptide cross linking domain (PPXD).
Since SecA's essential function is the transport of preprotein across the membrane the ability to actually bind preprotein must be given. The PPXD domain fulfils this function upon substrate binding.
Helical scaffold domain (HSD).
This domain lies in the center of the SecA protomer and contacts via α-helical interactions all other subdomains. In addition it contains the intramolecular regulator of ATP hydrolysis 1 (IRA1) subdomain which seems to prevent unwanted ATP hydrolysis when SecA is not bound to SecYEG. Together with IRA1, a conserved salt bridge called Gate 1 might function to prevent unnecessary conformational change. Gate 1 seems to functionally connect the nucleotide (ATP) binding site of the DEAD motor domain with the PPXD domain which results in regulation of ATP hydrolysis only upon preprotein binding. However, this coordinative behaviour has only been shown to occur when SecA is bound to SecYEG.


Operation Polka Dot

Operation Polka Dot was a U.S. Army test of a biological cluster bomb during the early 1950s.
Operation.
Operation Polka Dot was a field test of the E133 cluster bomb undertaken at Dugway Proving Ground in Utah during the early 1950s. The operation was detailed in a July 18, 1955 U.S. Army report that also detailed Operation Trouble Maker. The operation was classified "secret" and involved filling the munitions with the biological agent simulant, "Bacillus globigii".


Rhodobacter sphaeroides

Rhodobacter sphaeroides is a kind of purple bacterium; a group of bacteria that can obtain energy through photosynthesis. Its best growth conditions are anaerobic phototrophy (photoheterotrophic and photoautotrophic) and aerobic chemoheterotrophy in the absence of light. "R. sphaeroides" is also able to fix nitrogen. It is remarkably metabolically diverse, as it is able to grow heterotrophically via fermentation and aerobic and anaerobic respiration. Such a metabolic versatility has motivated the investigation of "R. sphaeroides" as microbial cell factory for biotechnological applications.
"Rhodobacter sphaeroides" has been isolated from deep lakes and stagnant waters.
"Rhodobacter sphaeroides" is one of the most pivotal organisms in the study of bacterial photosynthesis. It requires no unusual conditions for growth and is incredibly efficient. The regulation of its photosynthetic machinery is of great interest to researchers, as "R. sphaeroides" has an intricate system for sensing O2 tensions. Also, when exposed to a reduction in the partial pressure of oxygen, "R. sphaeroides" develops invaginations in its cellular membrane. The photosynthetic apparatus is housed in these invaginations. These invaginations are also known as chromatophores.
The genome of "R. sphaeroides" is also somewhat intriguing. It has two chromosomes, one of 3 Mb (CI) and one of 900 Kb (CII), and five naturally occurring plasmids. Many genes are duplicated between the two chromosomes but appear to be differentially regulated. Moreover, many of the open reading frames (ORFs) on CII seem to code for proteins of unknown function. When genes of unknown function on CII are disrupted, many types of auxotrophy result, emphasizing that the CII is not merely a truncated version of CI.
Small non-coding RNA.
Bacterial small RNAs have been identified as components of many regulatory networks. Twenty sRNAs were experimentally identified in "Rhodobacter spheroids," and the abundant ones were shown to be affected by singlet oxygen (1O2) exposure. 1O2 which generates photooxidative stress, is made by bacteriochlorophyll upon exposure to oxygen and light. One of the 1O2 induced sRNAs SorY (1O2 resistance RNA Y) was shown to be induced under several stress conditions and conferred resistance against 1O2 by affecting a metabolite transporter. SorX is the second 1O2 induced sRNA that counteracts oxidative stress by targeting mRNA for a transporter. It also has an impact on resistance against organic hydroperoxides. A cluster of four homologous sRNAs called CcsR for conserved CCUCCUCCC motif stress-induced RNA has been shown to play a role in photo-oxidative stress resistance as well. PcrZ (photosynthesis control RNA Z) identified in "R. sphaeroides," is a "trans"-acting sRNA which counteracts the redox-dependent induction of photosynthesis genes, mediated by protein regulators.
Metabolism.
"R. sphaeroides" encodes several terminal oxidases which allow electron transfer to oxygen and other electron acceptors (e.g. DMSO or TMAO). Therefore, this microorganism can respire under oxic, micro-oxic and anoxic conditions under both light and dark conditions.
Moreover, it is capable to accept a variety of carbon substrates, including C1 to C4 molecules, sugars and fatty acids. Several pathways for glucose catabolism are present in its genome, such as the Embden–Meyerhof–Parnas pathway (EMP), the Entner–Doudoroff pathway (ED) and the Pentose phosphate pathway (PP). The ED pathway is the predominant glycolytic pathway in this microorganism, whereas the EMP pathway contributing only to a smaller extent. Variation in nutrient availability has important effects on the physiology of this bacterium. For example, decrease in oxygen tensions activates the synthesis of photosynthetic machinery (including photosystems, antenna complexes and pigments). Moreover, depletion of nitrogen in the medium triggers intracellular accumulation of polyhydroxybutyrate, a reserve polymer.
Biotechnological applications.
A genome-scale metabolic model exists for this microorganism, which can be used for predicting the effect of gene manipulations on its metabolic fluxes. For facilitating genome editing in this species, a CRISPR/Cas9 genome editing tool was developed and expanded. Moreover, partitioning of intracellular fluxes has been studied in detail, also with the help of 13C-glucose isotopomers. Altogether, these tools can be employed for improving "R. sphaeroides" as cell factory for industrial biotechnology.
Knowledge of the physiology of "R. sphaeroides" allowed the development of biotechnological processes for the production of some endogenous compounds. These are hydrogen, polyhydroxybutyrate and isoprenoids (e.g. coenzyme Q10 and carotenoids). Moreover, this microorganism is used also for wastewater treatment. Hydrogen evolution occurs via the activity of the enzyme nitrogenase, whereas isoprenoids are synthesized naturally via the endogenous MEP pathway. Ths native pathway has been optimized via genetic engineering for improving coenzyme Q10 synthesis. Alternatively, improvement of isoprenoid synthesis was obtained via the introduction of a heterologous mevalonate pathway. Synthetic biology-driven engineering of the metabolism of "R. sphaeroides", in combination to the functional replacement the MEP pathway with mevalonate pathway, allowed to further increase bioproduction of isoprenoids in this species.


Chryseobacterium haifense

Chryseobacterium haifense is a psychrotolerant bacteria from the genus of Chryseobacterium which has been isolated from raw milk in Israel.


(Formate-C-acetyltransferase)-activating enzyme

In enzymology, a [formate-C-acetyltransferase]-activating enzyme () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are S-adenosyl-L-methionine, dihydroflavodoxin, and formate C-acetyltransferase-glycine, whereas its 4 products are 5'-deoxyadenosine, L-methionine, flavodoxin semiquinone, and formate C-acetyltransferase-glycin-2-yl radical.
This radical SAM enzyme belongs to the family of oxidoreductases. The systematic name of this enzyme class is [formate C-acetyltransferase]-glycine dihydroflavodoxin:S-adenosyl-L-methionine oxidoreductase (S-adenosyl-L-methionine cleaving). Other names in common use include PFL activase, PFL-glycine:S-adenosyl-L-methionine H transferase (flavodoxin-oxidizing, S-adenosyl-L-methionine-cleaving), formate acetyltransferase activating enzyme, formate acetyltransferase-glycine dihydroflavodoxin:S-adenosyl-L-methionine oxidoreductase (S-adenosyl-L-methionine cleaving).


Locus of enterocyte effacement

The locus of enterocyte effacement (LEE) is a moderately conserved pathogenicity island consisting of 35,000 base pairs in the bacteria "Escherichia coli" genome. The LEE encodes the Type III secretion system and associated chaperones and effector proteins responsible for attaching and effacing (AE) lesions in the large intestine. These proteins include intimin, Tir, EspC, EspF, EspH, and Map protein. The LEE has a 38% G+C ratio.


Collosphaera

Collosphaera is a radiolarian genus in the family Collosphaeridae. The genus contains bioluminescent species. It is a genus of colonial radiolarians (as opposed to solitary).
Species.
The following species are recognized:


Sam Hulbert

Samuel Foster Hulbert (April 12, 1936 – January 29, 2016) was an American scientist working in Ceramics Science and Biomaterials. He carried out biomaterial work in artificial knees, hips, and dental prostheses. He served as president of Rose-Hulman Institute of Technology for 28 years. He was born at Adams Center, New York.
Early life.
Hulbert grew up in Adams Center New York, where he spent most of his time in extracurricular activities and helping out on his family's milk delivery business. Hulbert described helping the milk delivery business as difficult and busy. In part due to his enjoyment of being active and as an effort to cope, he engaged in a wide variety of school activities including: baseball, football, and basketball and believed that it increased his knowledge about how to interact with others and his confidence. Hulbert's passion for sports even led him to try out for the Philadelphia Phillies; the try out ended with his receiving a concussion as result of a lack of protection and a hit from a professional pitcher. While he was grateful for his family, he felt driven to set his own course away from the strenuous life style he grew up with and thus wanted to pursue higher education. He was influenced to go to Alfred University by his chemistry teacher, Lyle Cady, who showed him the campus and helped convince his parents to let him go there.
Education.
Hulbert earned a B.S. in Ceramic Engineering in 1958 and a Ph.D. in Ceramic Science in 1964 both from Alfred University
Career.
Hulbert joined the faculty of Clemson University in 1964, eventually becoming the Associate Dean for Engineering Research and Interdisciplinary Studies in 1970. During his time at Clemson, he along with C. Clifford Fain and Michael J. Eitel, was given a grant by the Environmental Protection Agency to investigate the viability of water disposable/biodegradable glass and conducted a multiple year study that culminated in a report made to the EPA in 1971. 1973 he joined Tulane University as the Dean of Engineering. While at Tulane, Hulbert helped create their biomedical engineering program.
Hulbert was President of Rose-Hulman, situated in Terre Haute, Indiana, from 1976 to 2004, also teaching bioengineering classes. During this period, student enrollment doubled, $90 million in new buildings were constructed, the endowment increased to $180 million, and the school became co-educational. A campaign raised $250 million. Rose-Hulman was ranked at the top of the U.S. News & World Report rankings of undergraduate engineering programs whose highest degree is a Bachelor's or Master's.
He also became President of the Association of Independent Technological Universities, Chairman of the Second World Congress on Biomaterials, and Chairman of the 3rd International Symposium on Ceramics in Medicine, and founded the Society for Biomaterials.
Awards.
Hulbert is a member of the Indiana Academy, the International Academy of Ceramics, a fellow of the American Institute for Medical and Biological Engineering, and a fellow of biomaterials science and engineering from the World Biomaterials Congress.
Family.
Hulbert married Joy E. Husband 1960; they have three children: Greg (b. 1961); Samantha (b. 1962); Jeff (b. 1968) and ten grandchildren.


A-77636

A-77636 is a synthetic drug which acts as a selective D1 receptor full agonist. It has nootropic, anorectic, rewarding and antiparkinsonian effects in animal studies, but its high potency and long duration of action causes D1 receptor downregulation and tachyphylaxis, and unlike other D1 full agonists such as SKF-82,958, it does not produce place preference in animals. A-77636 partially substituted for cocaine in animal studies, and has been suggested for use as a possible substitute drug in treating addiction, but it is better known for its use in studying the role of D1 receptors in the brain.