FNDC5

Fibronectin type III domain-containing protein 5, the precursor of irisin, is a type I transmembrane glycoprotein that is encoded by the FNDC5 gene. Irisin is a cleaved version of FNDC5, named after the Greek messenger goddess Iris.
Fibronectin domain-containing protein 5 is a membrane protein comprising a short cytoplasmic domain, a transmembrane segment, and an ectodomain consisting of a ~100 kDa fibronectin type III (FNIII) domain.
History.
FNDC5 was first discovered in 2002 during a genome search for fibronectin type III domains and independently, in a search for peroxisomal proteins.
The ectodomain was proposed to be cleaved to give a soluble peptide hormone named irisin. Separately it was proposed that irisin is secreted from muscle in response to exercise, and may mediate some beneficial effects of exercise in humans and the potential for generating weight loss and blocking diabetes has been suggested. Others questioned these findings. A recent review highlights new discoveries of irisin in brain function and bone remodeling, but criticizes all studies using commercial antibody assays to measure irisin concentrations. It also raises a question of how an exercise hormone could arise in evolution.  Endocrine Reviews, 2021, Vol. XX, No. XX, 1–21  Maak S,  Norheim F, Drevon CA, Erickson HP. Progress and Challenges in the Biology of FNDC5 and Irisin. doi:10.1210/endrev/bnab003
Biosynthesis and secretion.
The FNDC5 gene encodes a prohormone, a single-pass type I membrane protein (human, 212 amino acids; mouse and rat, 209 amino acids) that is upregulated by muscular exercise and undergoes post-translational processing to generate irisin. The sequence of the protein includes a signal peptide, a single fibronectin type III domain, and a C-terminal hydrophobic domain that is anchored in the cell membrane.
The production of irisin is similar to the shedding and release of other hormones and hormone-like polypeptides, such as epidermal growth factor and TGF alpha, from transmembrane precursors. After the N-terminal signal peptide is removed, the peptide is proteolytically cleaved from the C-terminal moiety, glycosylated and released as a hormone of 112 amino acids (in human, amino acids 32-143 of the full-length protein; in mouse and rat, amino acids 29-140) that comprises most of the FNIII repeat region. The protease/enzyme responsible for the cleavage of FNDC5 to its secreted form, Irisin, has not been identified.
The sequence of irisin is highly conserved in mammals; the human and murine sequences are identical. However, the start codon of human FNDC5 is mutated to ATA, which causes it to be expressed at only 1% the level of other animals with the normal ATG start. A mass spectrometry study reported irisin levels ~3 ng/ml in human plasma, a level on par with other key human hormones, such as insulin. There is no comparable study of irisin levels in other animals, where the ATG vs ATA start codon would predict a 100x higher concentration.
A difference in the nucleotide sequence of human FNDC5 from that of mouse Fndc5 creates a different initiation codon, potentially generating a protein that begins at methionine-76 (Met-76). A protein initiated at Met-76 would be missing the signal peptide and would be trapped in the cytoplasm. Via mass spectrometry, irisin has been found to circulate in humans in levels similar to other key hormones, such as insulin.
Function.
Exercise causes increased expression in muscle of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1alpha), which is involved in adaptation to exercise. In mice, this causes production of the FNDC5 protein which is cleaved to give a new product irisin. Due to its production through a mechanism initiated by muscular contraction, irisin has been classified as a myokine.
Based on the findings that FNDC5 induces thermogenin expression in fat cells, overexpression of FNDC5 in the liver of mice prevents diet-induced weight gain, and "FNDC5" mRNA levels are elevated in human muscle samples after exercise, it has been proposed that irisin promotes the conversion of white fat to brown fat in humans which would make it a health promoting hormone. While this proposal has been challenged by evidence finding "FNDC5" is upregulated only in highly active elderly humans, more recent literature has supported the hypothesis of FNDC5 and irisin having a necessary role in exercise related benefits.
In mice, irisin is released from skeletal muscle during exercise acts directly on bone by increasing cortical bone mineral density, bone perimeter and polar moment of inertia. Irisin regulates bone remodeling and bone metabolism in animal models and humans.
Molecular Interactions.
FNDC5 is known to interact with various different molecules. In exercise related effects, PGC-1alpha induces FNDC5 gene expression through ERRα availability and that exercise leads to increased transcription of Pgc-1α and Errα, thus increased transcription of Fndc5. Additionally, FNDC5 is a positive regulator of BDNF expression and can influence BDNF expression in the brain even when peripherally delivered by adenoviral vectors.
Irisin promotes conversion of white adipose tissue (WAT) to brown adipose tissue (BAT) by increasing UCP1 expression. A 2016 "in vitro" study of white and brown fat cell tissue found dose-related upregulation of a protein called UCP1 that contributes to the browning of white fat and found other markers that would indicate that the white cells were browning and that fat cells were more metabolically active. Many of the stem cells became a type of cell that matures into bone. The tissue treated with irisin produced about 40 percent fewer mature fat cells.
Irisin also interacts with BDNF in terms of regulating its levels in the brain. In a recent study, expression of BDNF in the primary hippocampal nerve cells was observed to decrease as glucose concentration and glucose exposure time increased, or in the diabetic rat conditions. The vitality of these primary hippocampal nerve cells from diabetic rats was markedly decreased when BDNF levels were low but improved following irisin treatment. Thus, irisin was found to positively regulate the expression of BDNF and negatively influence the levels of GHbA1c (human glycated hemoglobin A1c) and AGEs, suggesting that irisin influences cognitive dysfunction in rats with type 2 diabetes by regulating the expression of BDNF and glycometabolism. It appears that these proteins are connected and related to each other in terms of cardiovascular/metabolic diseases, such as hypertension and diabetes.


Diethylaluminium cyanide

Diethylaluminum cyanide ("Nagata's reagent") is the organoaluminum compound with formula ((C2H5)2AlCN)n. This colorless compound is usually handled as a solution in toluene. It is a reagent for the hydrocyanation of α,β-unsaturated ketones.
Synthesis.
Diethylaluminum cyanide was originally generated by treatment of triethylaluminum with a slight excess of hydrogen cyanide. The product is typically stored in ampoules because it is highly toxic. It dissolves in toluene, benzene, hexane and isopropyl ether. It undergoes hydrolysis readily and is not compatible with protic solvents.
Structure.
Diethylaluminum cyanide has not been examined by X-ray crystallography, although other diorganoaluminum cyanides have been. Diorganylaluminum cyanides have the general formula (R2AlCN)"n", and they exist as cyclic trimers ("n" = 3) or tetramers ("n" = 4). In these oligomers, one finds AlCN---Al linkages. One compound similar to diethylaluminum cyanide is bis[di(trimethylsilyl)methyl]aluminium cyanide, ((Me3Si)2CH)2AlCN, which has been shown crystallographically to exist as a trimer with the following structure:
Bis("tert"-butyl)aluminium cyanide, "t"Bu2AlCN exists as a tetramer in the crystalline phase:
Uses.
Diethylaluminum cyanide is used for the stoichiometric hydrocyanation of α,β-unsaturated ketones. The reaction is influenced by the basicity of the solvent. This effect arises from the Lewis acidic qualities of the reagent.
The purpose of this reaction is to generate alkylnitriles, which are precursors to amines, amides, carboxylic acids esters and aldehydes.


Psychroserpens burtonensis

Psychroserpens burtonensis is a species of psychrophilic, yellow-pigmented bacteria. It is non-motile and nutritionally fastidious. Its type strain is ACAM 188.


Enzyme-thiol transhydrogenase (glutathione-disulfide)

In enzymology, an enzyme-thiol transhydrogenase (glutathione-disulfide) () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are xanthine dehydrogenase and glutathione disulfide, whereas its two products are xanthine oxidase and glutathione.
This enzyme belongs to the family of oxidoreductases, specifically those acting on a sulfur group of donors with a disulfide as acceptor. The systematic name of this enzyme class is [xanthine-dehydrogenase]:glutathione-disulfide S-oxidoreductase. Other names in common use include [xanthine-dehydrogenase]:oxidized-glutathione S-oxidoreductase, enzyme-thiol transhydrogenase (oxidized-glutathione), glutathione-dependent thiol:disulfide oxidoreductase, and thiol:disulfide oxidoreductase. This enzyme participates in glutathione metabolism.


Diprafenone

Diprafenone is an antiarrhythmic beta adrenergic antagonist.


San (comics)


Euornithes

Euornithes (from Greek "" meaning "true birds") is a natural group which includes the most recent common ancestor of all avialans closer to modern birds than to "Sinornis".
Description.
Clarke "et al". (2006) found that the most primitive known euornithians (the Yanornithiformes) had a mosaic of advanced and primitive features. These species retained primitive features like gastralia (belly ribs) and a pubic symphysis. They also showed the first fully modern pygostyles, and the type specimen of "Yixianornis" (IVPP 13631) preserves eight elongated rectrices (tail feathers) in a modern arrangement. No earlier pygostylians are known which preserve a fan of tail feathers of this sort; instead, they showed only paired plumes or a tuft of short feathers.
Classification.
The name Euornithes has been used for a wide variety of avialan groups since it was first named by Edward Drinker Cope in 1889. It was first defined as a clade in 1998 by Paul Sereno, who made it the group of all animals closer to birds than to Enantiornithes (represented by "Sinornis"). This definition currently includes similar content as another widely used name, Ornithuromorpha, named and defined by Luis Chiappe in 1999 as the common ancestor of "Patagopteryx", "Vorona", and Ornithurae, plus all of its descendants. Because one definition is node-based and the other branch-based, Ornithuromorpha is a slightly less inclusive group.
Relationships.
The cladogram below follows the results of a phylogenetic analysis by Lee "et al.", 2014:
Other genera.
The following is a list of primitive euornithian genera and those that cannot be confidently referred to any subgroups, following Holtz (2011) unless otherwise noted.
Note that Holtz also included the genera "Eurolimnornis" and "Piksi" as euornitheans, though they have since been re-identified as pterosaurs.


Spirendolol

Spirendolol is a beta adrenergic receptor antagonist.


Apocholate citrate agar

Apocholate Citrate Agar or ACA is a selective environment used to isolate Shigella and Salmonella bacteria.
The name comes for apocholate and citrate in agar.


Vibrio regulatory RNA of OmpA

VrrA (Vibrio regulatory RNA of OmpA) is a non-coding RNA that is conserved across all "Vibrio" species of bacteria and acts as a repressor for the synthesis of the outer membrane protein OmpA. This non-coding RNA was initially identified from Tn5 transposon mutant libraries of "Vibrio cholerae" and its location within the bacterial genome was mapped to the intergenic region between genes VC1741 and VC1743 by RACE analysis.
Outer membrane vesicles are secreted from the surface of gram-negative bacteria, where they are thought to aid in virulence. Little is known about how these vesicles aid virulence but it has been speculated that they may contribute by secreting toxins and help in the evasion of the immune system.
Recent studies showed that VrrA expression is activated by the alternative stress sigma factor, sigma E; unlike other strains of bacteria such as "E. coli" and "Salmonella", it does not require the Hfq protein to regulate the sigma factor. It was also shown that VrrA transcription increases on exposure to UV light and that over expression of VrrA resulted in an increase in outer membrane vesicles secreted. From these studies it has been suggested that VrrA acts to relieve outer membrane stress by limiting the synthesis of OmpA protein and that outer membrane vesicles provide the bacteria physical protect against UV light.


Antiglucocorticoid

An antiglucocorticoid is a drug which reduces glucocorticoid activity in the body. They include direct glucocorticoid receptor antagonists such as mifepristone and synthesis inhibitors such as metyrapone, ketoconazole, and aminoglutethimide. They are used to treat Cushing's syndrome.
Antiglucocorticoids could be effective antidepressants for a subset of specific mood disorders, but their use is limited by side effects.


Microtrol

Microtrol is an extended-release drug delivery system. It is used in certain medications like Adderall and incorporates two types of beads. The first dissolves immediately, releasing half of the medication, while the second type dissolves much more slowly releasing the remaining medication four hours later. Maximum plasma concentration is achieved in seven hours, compared to instant-release which reaches maximum concentration in three hours. Microtrol is manufactured by Supernus Pharmaceuticals, Inc.


Fort Terry

Fort Terry was a coastal fortification on Plum Island, a small island just off Orient Point, New York, United States. This strategic position afforded it a commanding view over the Atlantic entrance to the commercially vital Long Island Sound. It was established in 1897 and used intermittently through the end of World War II. In 1952, it became a military animal and biological warfare (BW) research facility, moving to civilian control in 1954 as the Plum Island Animal Disease Center. However, the biological warfare mission continued under civilian control until 1969, when the US ended offensive BW research. The island is now being considered for sale or conversion to a wildlife refuge. Fort Terry was listed on the National Register of Historic Places in 2021.
History.
Early history.
First “owned” by the Corchaug and Montaukett Indian tribes the Plum Island was sold to Samuel Wyllys for a coat, a barrel of biscuits and 100 fishhooks. The original fort was constructed after the federal government acquired Plum Island from Abraham S. Hewitt, a former mayor of New London, Connecticut, for $25,000. It is not clear how Hewitt became owner of the property.
Endicott period (1895-1916).
Fort Terry, named for Major General Alfred Terry, began construction in 1897 under the Endicott Program as part of the Harbor Defenses of Long Island Sound, and was expanded several times from the time of the Spanish–American War through World War II. The initial federal purchase was for 150 acres; however, the rest of the island was turned over to the federal government in 1901.
In 1898, before any of Fort Terry's batteries were completed, the Spanish–American War broke out. It was feared the Spanish fleet would bombard the US east coast. A number of weapons were purchased from the UK and hastily mounted to give the nascent fort system some modern armament. By March 1898 a 4.7 inch/45 caliber gun was mounted at Battery Kelly under this program. It was later transferred to the Sandy Hook Proving Ground in New Jersey, possibly in 1903. A pair of emplacements for modern 8-inch M1888 guns on modified 1870s-era Rodman carriages were also built at nearby Fort Tyler, but these seem to have not been armed.
Between 1897 and 1906 the following batteries were constructed at Fort Terry:
Battery Stoneman was named in honor of Brevet (Bvt.) Major General (MG) George Stoneman, who served with distinction during the U.S. Civil War, died 5 Sep 1894. Battery Steele was named in honor of Bvt. MG Frederick Steele, U.S. Army, who served with distinction during the Mexican–American War and the U.S. Civil War, and who died on 12 Jan 1868. Battery Bradford was named on March 13, 1902 in honor of Captain James Bradford, U.S. Artillery, who was killed on November 4, 1791, in action with hostile Indians at Fort Recovery, Ohio. Battery Floyd was named in honor of 2nd Lt. Robert Floyd, 3rd US Artillery, mortally wounded in the Battle of Chickamauga, GA, died on 23 Sep 1863. Battery Dimick was named in honor of Justin E. Dimick, an artillery officer mortally wounded in the Battle of Chancellorsville, VA, died on 5 May 1863. Battery Eldridge was named in honor of Capt. Bogardus Eldridge, U.S. Infantry, who was killed in action at Bocoor, Philippine Islands, 2 Oct 1899. Battery Dalliba was named in honor of Bvt. Major James Dalliba, assistant commissary of ordnance, who served 1811-1824 and died 8 Nov 1832. Battery Greble was named in honor of 1st Lt. John Greble, 2nd US Artillery, killed in action at the Battle of Big Bethel, 10 Jun 1861.
Battery Steele was unusual in that the two 10-inch gun emplacements are on different levels on a hillside.
As an artillery post, Fort Terry was heavily armed as part of the Coast Defenses of Long Island Sound. The Army's forts of this type were garrisoned by the Coast Artillery Corps. By 1914 the fort had 11 gun batteries and facilities to control an underwater minefield. In addition the post was home to an advanced fire control system for both the guns and the minefield. The grounds also had a functional 36" gauge railroad built in 1914. The Porter locomotive was used to haul munitions from bunkers to the artillery batteries.
Fort Terry served as an artillery post during the Spanish–American War, and it was intended to attack enemy ships as they headed toward New York City. Organized in 1907, it was initially manned by the 133rd Company, Coast Artillery Corps, organized in 1907. In 1916, they were re-designated as the 3d Company, and continued to serve in that capacity throughout World War I. Lieutenant Colonel Andrew Hero, Jr was in command of the post in August, 1915.
World War I.
Following the American entry into World War I in April 1917, changes were made at the stateside forts with a view to putting some coast artillery weapons into the fight on the Western Front. The Coast Artillery Corps manned almost all US heavy and railway artillery in that war, with stateside forts reduced to a minimum garrison to provide gun crews in France. The forts were also important as mobilization and training centers. The four 6-inch guns of Batteries Floyd and Dimick were dismounted in 1917, to be mounted on field carriages for service in France. The pair of 5-inch guns of Battery Kelly were apparently remounted at Fort H. G. Wright until scrapped in 1919. The 6-inch guns appear to have arrived in France, but for lack of training time none of the 5-inch or 6-inch batteries saw action in that war. The guns were never returned to Fort Terry. In 1918 four of Battery Stoneman's mortars were removed; this was to improve reloading time as reloading four mortars simultaneously in one pit was cumbersome. Many of the mortars removed under this program became railway artillery, but none of these were shipped to France during the war.
Between the wars.
Following the end of World War I, Fort Terry was declared surplus and put under the control of personnel at Fort H.G. Wright in caretaker status. Two anti-aircraft batteries with two guns each were built in 1920, probably armed with the 3-inch gun M1917. In 1924, Fort Terry was used by the Portsmouth (NH) National Guard Armory (the 197th Coast Artillery Regiment (Antiaircraft)) as their summer encampment and training location. The gun and machine gun battalions worked on night firing solutions at aerial balloon targets, tracked by the searchlight battalion. In 1930 the federal census for New York identified 133 people living on Fort Terry. In 1930 the Justice Department conducted a study on building a 1000-cell prison on the island, but it was deemed impractical and was not built. In 1932-34, the 3-inch gun batteries Hagner, Greble, and Campbell were disarmed.
World War II.
During World War II, the post was put to use as a training facility and supply depot. and as a look-out for German U-boats and planes. On 7 December 1941, the fort was listed as manned by the 242nd Coast Artillery Regiment (Harbor Defense) of the Connecticut Army National Guard. Today, on the east side of Plum Island, a network of trenches remains from the area's tenure as an artillery post. Fort Terry's guns were superseded by the pair of 16-inch batteries at Camp Hero in Montauk by 1944, so all except the four 3-inch guns of Batteries Eldridge and Dalliba were scrapped.
During World War II the following batteries were built at Fort Terry:
After World War II it was determined that gun coast defenses were obsolete. In 1948, the fort was once again declared surplus and disarmed with all guns scrapped.
Animal disease center.
Beginning April 15, 1952, it served as a U.S. Army Chemical Corps facility. As such, it was under the control of the First Army. It was small and focused primarily on anti-animal biological warfare (BW) research aimed at enemy livestock. Anti-animal agents rinderpest and foot and mouth disease were the main areas of research. When the decision to use the Fort as a research facility was planned, it was envisioned that it would be staffed by less than 20 personnel.
Fort Terry's Chemical Corps installation covered three acres and included many of the amenities traditionally associated with U.S. military installations. Included on the grounds were various administration buildings, laboratories, a dock, a motor pool, a commissary, a hospital, a fire station, staff housing and animal housing.
When the Chemical Corps took control of Fort Terry, in 1952, it required the remodeling of 18 original buildings on post. The Army had been developing plans for the animal disease facility at Fort Terry since 1951. A laboratory was planned for the circa 1911 Building 257, originally known as Combined Torpedo Storehouse and Cable Tanks building. The lab was not completed by the time the Chemical Corps transferred the fort to the USDA but it and the rest of the remodeled buildings were eventually incorporated into the civilian facility.
In 1954, the U.S. Department of Agriculture (USDA) took over the island, and began to use it as the Plum Island Animal Disease Center. It was then staffed by at least 9 military and 8 civilian employees.
Most of the disease research done by the USDA focused on biological warfare until Richard Nixon ended the U.S. bio-weapons program in 1969. Most of the original buildings and batteries still stand today and in many cases have been incorporated in one way or another into the island's new role as a disease research center.
2000-2016.
As of August 2001, the fort and all of Plum Island was listed for sale with the Government Accounting Office under FORT TERRY POW SUB-STA number C02NY0619 as accepting bids, with $12,000 "cost up to date" for historical clean up. It is listed as "no further action", that is, no cleanup is needed under the FUDS cleanup program, no DOD-related hazards present.
In June 2003, the responsibility for Plum Island facilities was transferred from the USDA to the U.S. Department of Homeland Security.
A 2008 DHS report recommended that the remnants of Fort Terry, its buildings and batteries, be opened to the public and preserved. The Town of Southold, New York formed a Local Waterfront Revitalization Program (LWRP) which noted that many of the island's structures, including those at Fort Terry, could qualify for listing on the U.S. National Register of Historic Places.
On 16 May 2016, the House unanimously passed “Save, Don’t Sell Plum Island”, Bill H.R. 1887 reversing the 2008 decision to put the island up for sale, which would lead to the destruction of the island, and lead to future development.
Biological warfare research.
The original anti-animal biological warfare research mission at Fort Terry was "to establish and pursue a program of research and development of certain anti-animal biological warfare agents". The first agent that was a candidate for development was foot and mouth disease (FMD). Besides FMD, five other top secret BW projects were commissioned on Plum Island. The other four programs researched included Rift Valley fever (RVF), rinderpest, African swine fever, and a slew of miscellaneous exotic animal diseases. Among the miscellaneous diseases were 11 other animal pathogens. Shortly before the handover of the facility to the Department of Agriculture in 1954, Fort Terry's mission was altered. The number of pathogens studied was reduced to two, rinderpest and FMD, and the mission was changed to "defensive" research of those two diseases.


Operator (biology)


Dalbraminol

Dalbraminol is a beta blocker.


Laccase

Laccases () are multicopper oxidases found in plants, fungi, and bacteria. Laccases oxidize a variety of phenolic substrates, performing one-electron oxidations, leading to crosslinking. For example, laccases play a role in the formation of lignin by promoting the oxidative coupling of monolignols, a family of naturally occurring phenols. Other laccases, such as those produced by the fungus "Pleurotus ostreatus", play a role in the degradation of lignin, and can therefore be classed as lignin-modifying enzymes. Other laccases produced by fungi can facilitate the biosynthesis of melanin pigments. Laccases catalyze ring cleavage of aromatic compounds.
Laccase was first studied by Hikorokuro Yoshida in 1883 and then by Gabriel Bertrand in 1894 in the sap of the Japanese lacquer tree, where it helps to form lacquer, hence the name laccase.
Active site.
The active site consists of four copper centers, which adopt structures classified as type I, type II, and type III. A tricopper ensemble contains types II and III copper (see figure). It is this center that binds O2 and reduces it to water. Each Cu(I,II) couple delivers one electron required for this conversion. The type 1 copper does not bind O2, but functions solely as an electron transfer site. The type I copper center consists of a single copper atom that is ligated to a minimum of two histidine residues and a single cysteine residue, but in some laccases produced by certain plants and bacteria, the type I copper center contains an additional methionine ligand. The type III copper center consists of two copper atoms that each possess three histidine ligands and are linked to one another via a hydroxide bridging ligand. The final copper center is the type II copper center, which has two histidine ligands and a hydroxide ligand. The type II together with the type III copper center forms the tricoppper ensemble, which is where dioxygen reduction takes place. The type III copper can be replaced by Hg(II), which causes a decrease in laccase activity. Cyanide removes all copper from the enzyme, and re-embedding with type I and type II copper has been shown to be impossible. Type III copper, however, can be re-embedded back into the enzyme. A variety of other anions inhibit laccase.
Laccases affects the oxygen reduction reaction at low overpotentials. The enzyme has been examined as the cathode in enzymatic biofuel cells. They can be paired with an electron mediator to facilitate electron transfer to a solid electrode wire. Laccases are some of the few oxidoreductases commercialized as industrial catalysts.
Activity in wheat dough.
Laccases have the potential to cross link food polymers such as proteins and nonstarch polysaccharides in dough. In non starch polysaccharides, such as arabinoxylans (AX), laccase catalyzes the oxidative gelation of feruloylated arabinoxylans by dimerization of their ferulic esters. These cross links have been found to greatly increased the maximum resistance and decreased extensibility of the dough. The resistance was increased due to the crosslinking of AX via ferulic acid and resulting in a strong AX and gluten network. Although laccase is known to cross link AX, under the microscope it was found that the laccase also acted on the flour proteins. Oxidation of the ferulic acid on AX to form ferulic acid radicals increased the oxidation rate of free SH groups on the gluten proteins and thus influenced the formation of S-S bonds between gluten polymers. Laccase is also able to oxidize peptide bound tyrosine, but very poorly. Because of the increased strength of the dough, it showed irregular bubble formation during proofing. This was a result of the gas (carbon dioxide) becoming trapped within the crust and could not diffuse out (like it would have normally) and causing abnormal pore size. Resistance and extensibility was a function of dosage, but at very high dosage the dough showed contradictory results: maximum resistance was reduced drastically. The high dosage may have caused extreme changes in structure of dough, resulting in incomplete gluten formation. Another reason is that it may mimic overmixing, causing negative effects on gluten structure. Laccase treated dough had low stability over prolonged storage. The dough became softer and this is related to laccase mediation. The laccase mediated radical mechanism creates secondary reactions of FA-dervived radicals that result in breaking of covalent linkages in AX and weakening of the AX gel.
Biotechnology.
The ability of laccases to degrade various aromatic polymers has led to research into their potential for bioremediation and other industrial applications. Studies utilizing both fungal and bacterial laccases have determined that these enzymes are capable of degrading and detoxifying various synthetic compounds, including azo dyes, bisphenol A and pharmaceuticals.


WHP Posttranscriptional Response Element

Woodchuck Hepatitis Virus (WHV) Posttranscriptional Regulatory Element (WPRE) is a DNA sequence that, when transcribed, creates a tertiary structure enhancing expression. The sequence is commonly used in molecular biology to increase expression of genes delivered by viral vectors. WPRE is a tripartite regulatory element with gamma, alpha, and beta components. The alpha component is 80bp long:
GCCACGGCGGAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTGTTGGGCACTGACAATTCCGTGGT
When used alone without the gamma and beta WPRE components, the alpha component is only 9% as active as the full tripartite WPRE. The sequence for full tripartite WPRE is:
This sequence has 100% homology with base pairs 1093 to 1684 of the Woodchuck hepatitis B virus (WHV8) genome. When used in the 3' untranslated region (UTR) of a mammalian expression cassette, it can significantly increase mRNA stability and protein yield.


Homokaryotic

Monokaryotic (adj.) is a term used to refer to multinucleate cells where all nuclei are genetically identical. In multinucleate cells, nuclei share one common cytoplasm, as is found in hyphal cells or mycelium of filamentous fungi.


Epic Sciences

Epic Sciences is a company that was founded to develop medical diagnostics characterizing circulating tumor cells; its initial product offering was a non-medical service offering analysis services to companies developing drugs.
Epic was founded in 2008, and technology was licensed from Scripps Research Institute, based on inventions made by Peter Kuhn's lab at Scripps. The company's approach involves getting a blood sample, removing red blood cells, putting the remaining cells on a microscope slide, staining the cells with antibodies for a few cancer markers, imaging the slide, then using proprietary image analysis software that counts the stained cells and analyzes the cells based on morphophology and other factors; as of 2014 it took the software around two and a half hours to analyze a single slide; around 12 slides are generated from a standard 7.5 mL blood sample. As of 2014 it was offering its analysis services to drug companies as a way to measure outcomes in clinical trials.
David Nelson was the first President and CEO and in 2012 Epic raised $13M in 2012 from Domain Associates, Roche Venture Fund and Pfizer Venture Investments.
By 2014 Murali Prahalad was president and CEO and in July of that year the company raised an additional $30M. In April 2017, Epic raised another $40 million and as of that date had raise a total of $85.5 million.
In March 2019, Lloyd Sanders joined the company as president and chief executive officer after serving at Myriad Genetics as the president of the oncology segment, overseeing the oncology, urology and dermatology commercial organizations.


Stefan Lanka


Dan Reneau

Daniel Dugan Reneau, Jr. (born June 11, 1940) is the former president of Louisiana Tech University in Ruston, Louisiana, a position which he filled from July 1, 1987, until his retirement effective June 30, 2013. He was succeeded by Dr. Les Guice.
Background.
A native of Woodville in southwestern Mississippi, Reneau graduated from Louisiana Tech in 1963 with a bachelor's degree in chemical engineering. He earned a master's degree in 1964 from the same institution. He received his Ph.D. in 1966 from Clemson University in Clemson, South Carolina. Reneau returned to Louisiana Tech in 1967 to serve as an assistant professor of chemical engineering. He became an associate professor in 1969 and was promoted to full professor in 1973. In 1972, Reneau established the Louisiana Tech biomedical engineering department, only the fifth undergraduate program of its kind, and was named its head. He founded the national biomedical engineering honor society Alpha Eta Mu Beta in 1979.
Reneau's research interests focused upon the application of engineering principles to living systems, the understanding of cerebral palsy, and the use of technology to help people with disabilities. He has published eighty technical papers in books and journals, edited five books, and attended more than one hundred international meetings and conferences.
In 1980, he was promoted to vice president of academic affairs at Louisiana Tech. He had served already for seven years as the university vice-president under President F. Jay Taylor.
University president.
On February 20, 1987, Reneau was selected to succeed the retiring Taylor as the 13th president of the institution and assumed the office on July 1 of that year.
In recent years Reneau has struggled with state-mandated cutbacks in higher education:
Louisiana Tech is now a state-assisted university rather than a state-supported university, and that is sad. Not only have we had to do away with programs like the school's dairy and beef herds , but we've had to shift the load to the students in the form of higher fees and tuition.
Despite the funding problems, the institution has received high academic rankings from national organizations. It is one of only two public institutions in Louisiana on the 2012 "U.S. News and World Report" ranking of Best Colleges. Louisiana Tech ranks in the top 10 nationally for students with the least debt. Louisiana Tech freshmen have consistently had the highest American College Testing scores, and the school has the best graduation rates in the University of Louisiana System, even for a university with a football team. The publication "Kiplinger" rates the university as one of the "Top 100 Best Values in Public Colleges".
Reneau was succeeded by Leslie K. Guice, a Tech vice-president, whose appointment was confirmed on December 4, 2012, by the University of Louisiana System Board of Supervisors in a special meeting in Baton Rouge. Guice took the helm on July 1, 2013.
In December 2015, Reneau was appointed interim president of the University of Louisiana System. He will succeed temporarily Sandra Woodley, who announced her resignation the preceding month.
Personal life.
Reneau married Linda Digby, a native of Bernice in Union Parish. The couple has a weekend retreat there with a main house and two cabins. They have two grown children, Dana Reneau Bernhard of Baton Rouge, who is married to Jim Bernhard of The Shaw Group, and Dr. John Reneau of Las Vegas, Nevada, a physician specializing in physical therapy.


Muscarinic toxin 2

Muscarinic toxin 2 (MT2) is one member of a family of small peptides of 65 amino acid residues of around 7076 daltons in molecular weight derived from the venom of African mamba snakes (Dendroaspis angusticeps), which target the different muscarinic receptor subtypes. Muscarinic toxins like the nicotinic toxins have the three-finger fold structure, characteristic of the large superfamily of toxins that act at cholinergic synapses.
The interactions of muscarinic toxins studied using tritiated 3H-N-methyl scopolamine (NMS) with human muscarinic receptor subtypes m1, m2, m3 and m4 has shown that MT2 and the related MT1 toxin are specific for M1 (Ki=630 nM) and M4 (Ki=1900 nM) receptors, but have little effect on binding to M2 and M3 receptors. The interaction at M1 receptors appears to be essentially irreversible like for muscarinic toxin 7.


DOV Pharmaceutical

DOV Pharmaceutical was a biotechnology company that focused on therapies primarily for central nervous system conditions. It was founded in 1995 by former employees of American Cyanamid (which was acquired by Wyeth in 1994), and in 1998 it in-licensed drugs discovered at American Cyanamid for further development. It held an IPO on NASDQ in 2002, and its shares plunged days later after negative details about a past relationship between Élan and DOV emerged.
Phil Skolnick served as CSO from 2001 to 2009. Euthymics had been founded by Anthony McKinney and Frank Bymaster, a chemist who had worked at Eli Lilly on discovery and development of Prozac, Cymbalta, and Symbyax; the company was funded with $24 million from Novartis Venture Funds among others.
After several failed clinical trials, in 2010 Dov was acquired by Euthymics Bioscience which intended to continue development of Dov's antidepressant, amitifadine (DOV 21,947, renamed EB-1010).
Its drug candidates included:


DNA (Red Dwarf)

"DNA" is the second episode of the science fiction sitcom "Red Dwarf" Series IV and the twentieth episode in the series' run. It was first broadcast on the British television channel BBC2 on 21 February 1991, although it was planned to be broadcast as the fifth episode, it was moved forward in the schedule by the BBC. Written by Rob Grant and Doug Naylor, and directed by Ed Bye, the episode revolves around the genetic engineering technology that the crew discover.
Plot.
"Red Dwarf" encounters a drifting spacecraft which Arnold Rimmer, Dave Lister, Kryten, and Cat decide to investigate. Once onboard, the group split into pairs. While Rimmer and Kryten find the remains of a mutated human with three heads, Cat accidentally activates a machine that turns Lister into a chicken. When the others arrive, Kryten determines that the ship's crew were researching DNA modifications and that the machine Cat used can rewrite the DNA of anything with organic matter. When an attempt to reverse the effect on Lister changes him into a hamster, Cat repeats the actions he did to change him. However, while Lister is restored to his human body, Kryten finds himself turned into a human, due to his brain being part-organic.
Returning to "Red Dwarf", Kryten is initially ecstatic at being human, but finds he cannot conduct certain functions that he did as a mechanoid, and soon regrets the change after he insults his mechanoid spare heads, as well as revealing his sexual arousal to machines in a machine catalogue that he reads. The group agree to help him return to his original form, but Rimmer suggests they use a test subject first on the DNA modifier as a precaution. Lister opts to have the machine change the meat in his vindaloo, but the modifier changes it into a living mutant beast that proves to be indestructible to their weapons. Lister opts to be changed into a powerful fighting machine and becomes a cyborg that he calls "Man Plus", only to be a foot in height. However, he soon discovers that the creature is weak to lager when it stands in some spilled from a can, and so throws another into its mouth and shoots the can, killing the creature explosively.
Production.
"DNA", official full title "Do Not Alter", changed the continuity of the relationship between Lister and Kristine Kochanski. It is established that they had been dating and that she broke up with him, an idea which had been introduced in the novel "". Doug Naylor and Craig Charles explained that Lister's infatuation with Kochanski, despite barely knowing her, was unrealistic.
With the tail end of production and finances running low the DNA ship's set was rushed and was not as had been expected. However, the grungy-looking corridors and rooms were better than nothing which may have been the case.
Paul McGuinness, a member of the effects team, wore the Vindaloo Mutant outfit. He also produced the three-headed corpse that Kryten and Rimmer discover on board the DNA ship. Richard Ridings voices the D.N.A. Ship Computer.
A cast-inspired gag came in at the end of the scene with Rimmer planning to clone himself from his own dandruff. Timing it just right into the rehearsals, Danny John-Jules sneezed on the microscope at the right moment.
Blue-screen techniques was used to produce the transformation of Lister to a "super-human" man plus. Craig Charles was shot in front of a bluescreen to make him appear one foot tall, while this was added to the other crew's footage, who were also involved in blue screen, as they run by the small Lister.
Cultural references.
The 1935 film "Bride of Frankenstein" is referenced by the Cat regarding the way he looks when he cannot use an electrical socket to blow-dry his hair.
Rimmer initially concludes that the spacecraft encountered is alien and that it is attempting to contact the Red Dwarf crew in order to return Glenn Miller. This references the alien abduction myth of Miller, whose plane went missing in 1944 and was never found.
Lister attributes Popeye the Sailor Man's saying "I am what I am" to Descartes (in reference to the latter's famous line, "I think, therefore I am"), but the attribution is corrected by Rimmer. (Kryten later makes the same mistake.)
Using the DNA modifier, Holly turns Lister into a super-human fighting machine "Man Plus". The result transforms Lister into a small replica hybrid of RoboCop from the 1987 film of the same name.
When Lister is being chased by the vindaloo mutation he parodies Bruce Willis' line from "Die Hard 2" (1990); "How can the same smeg happen to the same guy twice?", referencing the previous series when he was attacked by what he thought to be a shami kebab in "Polymorph". "Jaws" is then parodied in the final scene when Lister disposes of the vindaloo mutation by throwing a lager can into its mouth and then shooting at the can, making it explode along with the mutation.
Reception.
"DNA" was first broadcast on the British television channel BBC2 on 21 February 1991 in the 9:00 p.m. evening time slot, although it was intended to be broadcast fifth in the series run—as seen in the repeat showings in 1992 and 1994. The change in the scheduling was affected by the Gulf War hostilities at the time, which meant that "Dimension Jump", originally the series' opener, and "Meltdown" were held back.
The episode was considered to be one of the better episodes from the fourth series; however, it did receive some criticism for moving the humour away from the characters and into situation-based comedy.


Nitrite reductase (NAD(P)H)

In enzymology, a nitrite reductase [NAD(P)H] () is an enzyme that catalyzes the chemical reaction
The 4 substrates of this enzyme are ammonium hydroxide, NAD+, NADP+, and H2O, whereas its 4 products are nitrite, NADH, NADPH, and H+.
This enzyme belongs to the family of oxidoreductases, specifically those acting on other nitrogenous compounds as donors with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is ammonium-hydroxide:NAD(P)+ oxidoreductase. Other names in common use include nitrite reductase (reduced nicotinamide adenine dinucleotide, (phosphate)), NADH-nitrite oxidoreductase, NADPH-nitrite reductase, assimilatory nitrite reductase, nitrite reductase [NAD(P)H2], and NAD(P)H2:nitrite oxidoreductase. This enzyme participates in nitrogen metabolism. It has 3 cofactors: FAD, Iron, and Siroheme.
Structural studies.
As of late 2007, only one structure has been solved for this class of enzymes, with the PDB accession code .


Bizarro (Supergirl)

"Bizarro" is the twelfth episode in the first season of the CBS television series "Supergirl", which aired on February 1, 2016. It was written by Roberto Aguirre-Sacasa and Rachel Shukert, and directed by John Showalter.
The episode centers on Maxwell Lord's plot to destroy Supergirl with a Bizarro-version of the Girl of Steel, while Kara begins romancing Cat Grant's son Adam.
Plot.
In Maxwell's Lab 52, Lord puts the final touches on his new creation - a female version of Bizarro - created to look exactly like Supergirl and follow Maxwell's orders. Max brainwashes the doppelgänger into thinking she is Supergirl and wanting to kill the real one, insisting she is evil. That night, Kara excuses herself from a date with Cat's son Adam to rescue a tram car in danger, unaware that it is a trap set by Bizarro. By rescuing the tram's occupants she confuses Bizarro making her wonder if Supergirl is good, not evil.
At the DEO, Kara tells Alex and J'onn that Bizarro isn't a gynoid but is genetically similar, suggesting the only way to deal with her is by using kryptonite. Kara and Adam go on a second date, only to be interrupted by Bizarro, who kidnaps Kara and the two fight each other at a park, matching each other's powers. The DEO arrive and hit Bizarro with kryptonite, causing her skin become cracked and gray. She now hates Supergirl, truly believing her to be evil and flies off.
Kara tells Alex that Maxwell knew she was Supergirl and sent Bizarro after her. She also learns that kryptonite made Bizarro more powerful than ever, prompting Hank to look for an anti-kryptonite mineral to stop Bizarro. Kara decides that she cannot have a relationship with Adam and they break up. Back at Lord Technologies, a deranged Maxwell sends Bizarro, now dark-suited and displaying a reverse shield, to destroy Kara's loved ones. Alex arrives with the DEO and arrests him. Bizarro kidnaps James as bait who stalls her by trying to convince Bizarro that Supergirl is good and in the process finally confesses he is in love with her. Supergirl arrives, and the two fight, being equally matched until Alex shoots Bizarro with the synthesized kryptonite, knocking her out. Bizarro is subsequently put back into an artificial coma until she can be treated.
Back at Kara's apartment she finds an alien plant on her coffee table. As she investigates she is attacked by a Black Mercy parasite which overpowers her, although this is not revealed to the viewer until the next episode.
Reception.
Ratings.
The episode attracted 546,000 viewers for its British premiere, making it the 10th most watched programme on Sky One for the week.
Critical response.
Eric Goldman of IGN gave the episode a 4.8/10: "The interesting twists of 'Bizarro' – Alex arresting Lord, Lord knowing Supergirl's secret identity, James confessing his love for Kara – are undercut by the unbearably relationship drama and the over-the-top characterization of Maxwell Lord. While the portrayal of Bizarro and Supergirl's compassion for her was spot-on, this episode was a failure on all other fronts."
Jeff Jensen of "Entertainment Weekly" noted: "This week, Supergirl asks if Kara can be Supergirl and still have a life. If you’ve seen any other superhero show, particularly ones in the Berlanti-verse, then you probably know where this episode goes. There are several frustrating parts of the episode, particularly Kara’s answer to the 'can she have it all question,' but there are also moments where the show redeems itself and makes you fall in love with it, its heroine, and what she stands for even more."
Stacy Glanzman of TV Fanatic gave the episode a 4.0 out of 5 stars.


FGF-2 internal ribosome entry site (IRES)

The FGF-2 internal ribosome entry site is an RNA element present in the 5' UTR of the mRNA of fibroblast growth factor-2. It has been found that the FGF-2 internal ribosome entry site (IRES) activity is strictly controlled and highly tissue specific. It is thought that translational IRES dependent activation of FGF-2 plays a vital role in embryogenesis and in the adult brain [1]. When expressed the fibroblast growth factor 2 FGF-2 protein plays a pivotal role in cell proliferation, differentiation and survival as well as being involved in wound-healing [1,2].


Louis, Hereditary Prince of Lorraine

Louis, Hereditary Prince of Lorraine (28 January 170410 May 1711) was heir apparent to the throne of the sovereign Duchy of Lorraine.
His father was the reigning Duke of Lorraine and his mother a member of the House of Bourbon, then ruling the Kingdom of France. He became the "Hereditary Prince" at his birth in 1704, but died of smallpox in 1711 at the age of seven, unmarried and without descendants.
Biography.
He was born at the Château de Lunéville to Léopold, Duke of Lorraine and his wife Élisabeth Charlotte d'Orléans.
Louis was the fifth child but second son born to his parents. Also, Louis was the second of the four heirs of his father: his older brother Prince Léopold, Duke of Bar (26 August 16992 April 1700) died aged eight months; his younger brother Léopold Clément Charles (25 April 17074 June 1723) died aged sixteen and his younger brother François Etienne/Stephen lived to adulthood, became the Duke of Lorraine and also, by union, became Holy Roman Emperor and founded the House of Habsburg-Lorraine.
Soon after his birth, on 24 June 1704, the young prince was baptised as a Roman Catholic at the Château de Lunéville. He did not see the deaths of two of his siblings: Louis, Duke of Bar (26 August 16992 April 1700) and Princess Louise Christine (13 November 170118 November 1701) both died before reaching the age of one. By the time of his birth, however, two sisters had survived.
An epidemic of smallpox was going around Europe in the Spring of 1711. It had already killed people like the Holy Roman Emperor Joseph I (who died on 17 April) and the "Grand Dauphin", Louis (who died on 14 April). Unfortunately, against all efforts, Princess Élisabeth Charlotte of Lorraine, Louis' older sister, contracted smallpox and died on 4 May. Before this, she passed on to Louis and Princess Marie Gabrièle Charlotte. Louis died on 10 May and Marie Gabrièle Charlotte died the very next day. They were both buried in the ducal crypt at the Église Saint-François-des-Cordeliers. At Louis' death, his younger brother Léopold Clement Charles became Hereditary Prince, but he, too died of smallpox in 1723, at the age of sixteen.


W. Mark Saltzman

William Mark Saltzman was named the Goizueta Foundation Professor of Biomedical and Chemical Engineering at Yale University on July 1, 2002 and became the founding chair of Yale's Department of Biomedical Engineering in 2003. Saltzman's research aims to promote new methods for drug delivery and develop new biotechnologies to combat human disease. A pioneer in the fields of biomaterials, nanobiotechnology, and tissue engineering, Saltzman has contributed to the design and implementation of a number of clinical technologies that have become essential to medical practice today. His popular course Frontiers of Biomedical Engineering is available to everyone through Open Yale Courses.
Biography.
Saltzman received a B.S. in Chemical Engineering in 1981 from Iowa State University, followed by a M.S. in Chemical Engineering in 1984 and a Ph.D. in Medical Engineering in 1987, both at the Massachusetts Institute of Technology.
As a graduate student at the Massachusetts Institute of Technology (MIT), Saltzman built scaffolds that could be seeded with cells to sculpt new replacement tissues. He also created drug-impregnated implants from polymers that slowly and steadily release medicines for long periods—work that now helps patients in the form of GLIADEL, a chemotherapy-loaded polymer wafer that neurosurgeons implant in the brain to combat glioblastoma multiforme (GBM), one of the most aggressive types of malignant brain tumors.
He was appointed Assistant Professor of Chemical Engineering at The Johns Hopkins University in 1987 and received a joint appointment in the Department of Biomedical Engineering at The Johns Hopkins School of Medicine in 1990. He was promoted to Associate Professor in 1992 and to Professor in 1995. In 1996, he moved to Cornell University, holding the first BP Amoco/H. Laurance Fuller Chair in Chemical Engineering.
He joined the faculty at Yale University, as the Goizueta Foundation Professor of Chemical and Biomedical Engineering, in July 2002 and became the first chair of Yale's Department of Biomedical Engineering in 2003. Since he arrived at Yale in 2002 to form the new department, he has seen his faculty group grow to 19 members. He hired slowly, knowing that each new person would have a significant effect on the overall department culture. Saltzman settled on four areas to excel in: imaging, biomolecular engineering, biomechanics, and systems biology. The department has developed largely as its founders envisioned—multidisciplinary, collegial, integrated with the medical school, and committed to undergraduate education.
As of July 1, 2016, Saltzman serves as Head of Jonathan Edwards College at Yale University.
Research.
Saltzman's research focuses on developing the most economical, transportable and accessible methods for disease prevention and methods to more effectively deliver chemotherapy to the most aggressive forms of brain tumors. Dr. Saltzman's research interests include controlled drug delivery to the brain, polymers for supplementing or stimulating the immune system, cell interactions with polymers, and tissue engineering. He studies how to create safer and more effective medical and surgical therapy based on tissue engineering. Dr. Saltzman worked with an interdisciplinary team to develop what is now the standard of care for treating brain tumors.
Works.
Books
Selected Publications


Arthrobacter flavus

Arthrobacter flavus is a species of psychrophilic bacteria. It is aerobic, gram-positive, non-spore-forming, non-motile, exhibits a rod-coccus growth cycle and produces a yellow pigment. Its type strain is CMS 19YT (= MTCC 3476T).


Green sulfur bacteria

The green sulfur bacteria (Chlorobiaceae) are a family of obligately anaerobic photoautotrophic bacteria. Together with the non-photosynthetic Ignavibacteriaceae, they form the phylum Chlorobi.
Green sulfur bacteria are nonmotile (except "Chloroherpeton thalassium", which may glide) and capable of anoxygenic photosynthesis. In contrast to plants, green sulfur bacteria mainly use sulfide ions as electron donors. They are autotrophs that utilize the reverse tricarboxylic acid cycle to perform carbon fixation. Green sulfur bacteria have been found in depths of up to 145m in the Black Sea, with low light availability.
Characteristics of green-Sulfur bacteria:
Major photosynthetic pigment: Bacteriochlorophylls a plus c, d or e
Location of photosynthetic pigment: Chlorosomes and plasma membranes
Photosynthetic electron donor: H2, H2S, S
Sulfur deposition: Outside of the cell
Metabolic type: Photolithoautotrophs
Habitat.
The Black Sea, an extremely anoxic environment, was found to house a large population of green sulfur bacteria at about 100 m depth. Due to the lack of light available in this region of the sea, most bacteria were photosynthetically inactive. The photosynthetic activity detected in the sulfide chemocline suggests that the bacteria need very little energy for cellular maintenance.
A species of green sulfur bacteria has been found living near a black smoker off the coast of Mexico at a depth of 2,500 m in the Pacific Ocean. At this depth, the bacterium, designated GSB1, lives off the dim glow of the thermal vent since no sunlight can penetrate to that depth.
Phylogeny.
The currently accepted phylogeny is based on 16S rRNA-based LTP release 123 by The All-Species Living Tree Project.
Taxonomy.
The currently accepted taxonomy is based on the List of Prokaryotic names with Standing in Nomenclature.(LSPN)
Metabolism.
Photosynthesis in the green sulfur bacteria.
The green sulfur bacteria use a Type I reaction center for photosynthesis. Type I reaction centers are the bacterial homologue of photosystem I (PSI) in plants and cyanobacteria. The GSB reaction centers contain bacteriochlorophyll a and are known as P840 reaction centers due to the excitation wavelength of 840 nm that powers the flow of electrons. In green sulfur bacteria the reaction center is associated with a large antena complex called the chlorosome that captures and funnels light energy to the reaction center. The chlorosomes have a peak absorption in the far red region of the spectrum between 720-750 nm because they contain bacteriocholorophyll c, d and e. A protein complex called the Fenna-Matthews-Olson complex (FMO) is physically located between the chlorosomes and the P840 RC. The FMO complex helps efficiently transfer the energy absorbed by the antena to the reaction center.
PSI and Type I reaction centers are able to reduce ferredoxin (Fd), a strong reductant that can be used to fix and reduce NADPH. Once the reaction center (RC) has given an electron to Fd it becomes an oxidizing agent (P840+) with a reduction potential of around +300 mV. While this is not positive enough to strip electrons from water to synthesize ( = +820 mV), it can accept electrons from other sources like , thiosulphate or ions. This transport of electrons from donors like to the acceptor Fd is called linear electron flow or linear electron transport. The oxidation of sulfide ions leads to the production of sulfur as a waste product that accumulates as globules on the extracellular side of the membrane.These globules of sulfur give green sulfur bacteria their name. When sulfide is depleted, the sulfur globules are consumed and further oxidized to sulfate. However, the pathway of sulfur oxidation is not well-understood.
Instead of passing the electrons onto Fd, the Fe-S clusters in the P840 reaction center can transfer the electrons to menaquinone (MQ:) which returns the electrons to the P840+ via an electron transport chain (ETC). On the way back to the RC the electrons from MQH2 pass through a cytochrome bc1 complex (similar to the complex III of mitochondria) that pumps ions across the membrane. The electrochemical potential of the protons across the membrane is used to synthesize ATP by the FoF1 ATP synthase. This cyclic electron transport is responsible for converting light energy into cellular energy in the form of ATP.
Carbon fixation of green sulfur bacteria.
Green sulfur bacteria are photoautotrophs: they not only get energy from light, they can grow using carbon dioxide as their sole source of carbon. They fix carbon dioxide using the reverse tricarboxylic acid cycle (rTCA) cycle where energy is consumed to reduce carbon dioxide in order to synthesize pyruvate and acetate. These molecules are used as the raw materials to synthesize all the building blocks a cell needs to generate macromolecules. The rTCA cycle is highly energy efficient enabling the bacteria to grow under low light conditions. However it has several oxygen sensitive enzymes that limits it's efficiency in aerobic conditions.
The reactions of reversal of the oxidative tricarboxylic acid cycle are catalyzed by four enzymes:
Mixotrophy in green sulfur bacteria.
Green sulfur bacteria are obligate photoautotrophs: they cannot grow in the absence of light even if they are provided with organic matter. However they exhibit a form of mixotrophy where they can consume simple organic compounds in the presence of light and CO2.
Nitrogen fixation.
The majority of green sulfur bacteria are diazotrophs: they can reduce nitrogen to ammonia which is then used to synthesize amino acids.


Short-tailed shrew tenrec

The short-tailed shrew tenrec ("Microgale brevicaudata") is a species of mammal in the family Tenrecidae. It is endemic to Madagascar. Its natural habitats are subtropical or tropical dry forest and subtropical or tropical moist lowland forest. It is threatened by habitat loss.


Rimiterol

Rimiterol (INN/USAN) is a third-generation short-acting β2 agonist.


Phenylalanine adenylyltransferase

In enzymology, a phenylalanine adenylyltransferase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are ATP and L-phenylalanine, whereas its two products are diphosphate and N-adenylyl-L-phenylalanine.
This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing nucleotide groups (nucleotidyltransferases). The systematic name of this enzyme class is ATP:L-phenylalanine adenylyltransferase. This enzyme is also called L-phenylalanine adenylyltransferase.


Pablo DT Valenzuela

Pablo Valenzuela (; born June 13, 1941) is a Chilean biochemist dedicated to biotechnology development. He is known for his genetic studies of hepatitis viruses; participated as R&D Director in the discovery of hepatitis C virus and the invention of the world's first recombinant vaccine (against hepatitis B virus). He is one of the cofounders of the biotechnology company Chiron Corporation and of Fundacion Ciencia para la Vida, a private non profit institution where he is currently working.
Biography.
Pablo Valenzuela studied biochemistry at Universidad de Chile and earned his Ph.D. degree (1970) in Chemistry at Northwestern University, did a postdoctoral training at University of California, San Francisco and held a position as Professor in the Biochemistry Department of that institution. In 1981, together with William J. Rutter and Edward Penhoet founded the biotechnology company Chiron Corporation that in 1997 was the second-largest biotechnology company in the world, after Amgen. As Research Director Pablo Valenzuela developed a variety of biotechnological products, specially in the blood banking industry. The invention of the recombinant vaccine against Hepatitis B virus was chosen by Business Week as one of the three most innovative technological products of the year 1986. In Chile Pablo Valenzuela founded Bios Chile, the first biotechnology company in that country, and in 1997 together with Bernardita Mendez he cofounded Fundacion Ciencia Para la Vida a non profit foundation that carries out scientific and technological research. He is the father of Chilean American singer/songwriter, Francisca Valenzuela.
Work.
Pablo DT Valenzuela is the scientist responsible for the development of biotechnology products in USA and Chile in the area of international diagnostics, blood banking and pharmaceutical. He is cofounder and responsible of early activities of biotechnology Start-ups in USA and Chile. Pablo Valenzuela is also Professor and Investigator in graduate programs, generating scientific publications and patents.
Pablo Valenzuela was recipient of the Chilean National Prize for Applied Sciences and Technologies in 2002 and is a member of the Chilean Academy of Sciences. He was awarded the UCSF medal in 2014.


ATP2A2

ATP2A2 is an ATPase associated with Darier's disease and Acrokeratosis verruciformis.
This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in calcium sequestration associated with muscular excitation and contraction. Alternative splicing results in multiple transcript variants encoding different isoforms.


ACT Biotech Inc

ACT Biotech Inc is a San Francisco-based, privately held biopharmaceutical company focused on the development and commercialization of targeted cancer drugs. It was founded in 2008.
The Company's clinical stage pipeline includes:
Other pipeline products include an oral Aurora A and B kinase inhibitor at the pre-IND stage, and an ABL tyrosine kinase inhibitor targeting the T315I mutant enzyme in pre-clinical development.


Methylarsonate reductase

In enzymology, a methylarsonate reductase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are methylarsonate and glutathione, whereas its 3 products are methylarsonite, glutathione disulfide, and H2O.
This enzyme belongs to the family of oxidoreductases, specifically those acting on phosphorus or arsenic in donor with disulfide as acceptor. The systematic name of this enzyme class is gluthathione:methylarsonate oxidoreductase. This enzyme is also called MMA(V) reductase.


Hyphomonas

In taxonomy, Hyphomonas is a genus of the Hyphomonadaceae.


Dimetotiazine

Dimetotiazine (INN) is a phenothiazine drug used for the treatment of migraine. It is a serotonin antagonist and histamine antagonist.


Exorphin

Exorphins are exogenous opioid peptides, distinguished from endorphins, or endogenous opioid peptides.
Exorphins include opioid food peptides like gluten exorphin and microbial opioid peptides and any other opioid peptide foreign to a host that have metabolic efficacy for that host. Exorphins can be converted from plants and animals but also dairy products and certain vegetables like spinach and soy.
Exorphins can be released for many different kinds of proteins and thus can be isolated from various sources such as from plant proteins or from enzymes of the digestive system of animals. The study of exorphins as a bioactive peptide can be a source of discovery for new kinds of food and drugs to treat and prevent diseases associated with the accumulation of exorphins.
Connection and treatment of autism.
Effective therapies to manage autism remain scarce. According to the exorphin theory of autism, an increase in the levels of exorphin is linked to symptoms of autism. Based on this concept, experiments have attempted to reduce the symptoms of autism by using large amounts of protease to break down exorphins before they are absorbed. Experiments have also attempted to enhance and utilize enzymes existing in the gut to break down exorphins in a similar fashion, since the production of exorphins within the gut is inevitable.
Connection with schizophrenia.
Exorphins can cause various symptoms of schizophrenia if mutation occurs at a few selected loci. Genetic mutation at one of these loci can lead to increased absorption of exorphins via receptor mediated endocytosis. Another possibility from these particular loci is that catabolization of exorphins can be disrupted thus allowing the exorphin to persist in the body. This would lead to exorphins entering the brain capillary, bypassing the blood brain barrier, and inflicting negative repercussion on the brain. This does not mean that exorphin will necessarily cause schizophrenia, as susceptibility to the disease is dependent on an individual's genetic makeup. However, by increasing the probability that exorphins enter the brain, it will also increase the chance of an individual displaying schizophrenic symptoms.


Laurence R. Young

Laurence R. Young is an American physicist currently the Apollo Program Professor Emeritus of Astronautics at Massachusetts Institute of Technology and an Elected Fellow of the Institute of Electrical and Electronics Engineers, the Biomedical Engineering Society and the American Institute for Medical and Biological Engineering. He received an A.B. from Amherst College in 1957; a Certificate in Applied Mathematics from the Sorbonne, Paris as a French Government Fellow in 1958; S.B. and S.M. degrees in Electrical Engineering and the Sc.D. degree in Instrumentation from MIT, from 1957-1962.


Glycine dehydrogenase

In enzymology, a glycine dehydrogenase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are glycine, H2O, and NAD+, whereas its 4 products are glyoxylate, NH3, NADH, and H+.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH2 group of donors with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is glycine:NAD+ oxidoreductase (deaminating).
This should not be confused with:
the glycine dehydrogenase (decarboxylating), which is another name for the Glycine cleavage system P-protein ().
or the glycine dehydroganse (cyanide forming)().
or the glycine dehydrogenase (cytochrome) ().


Cato T. Laurencin

Cato T. Laurencin, M.D., Ph.D. (born January 15, 1959), is an American engineer, physician, scientist, innovator and a University Professor of the University of Connecticut (one of two at the University).
He is currently the Chief Executive Officer of The Connecticut Convergence Institute for Translation in Regenerative Engineering.
Dr. Laurencin is regarded as the founder of the field of Regenerative Engineering. He is the Editor-in-Chief of the journal "Regenerative Engineering and Translational Medicine" and Founder and President of the Regenerative Engineering Society. In engineering, medicine, science, and innovation, he is an elected member of the National Academy of Engineering, an elected member of the National Academy of Medicine, an elected member of the National Academy of Sciences, and an elected Fellow of the National Academy of Inventors. He is the first surgeon in history to be elected to all four academies. He is the first person to receive both the oldest/highest awards from the National Academy of Engineering (the Simon Ramo Founder's Award) and the oldest/highest National Academy of Medicine (the Walsh McDermott Medal).
In science, Dr. Laurencin received the Philip Hague Abelson Prize, the highest honor of the American Association for the Advancement of Science, for "signal contributions to the advancement of science in the United States" for his work in Regenerative Engineering.
In innovation, Laurencin was awarded the National Medal of Technology and Innovation, America's highest honor for technological advancement, awarded by President Barack Obama in ceremonies at the White House.
Background and personal life.
Laurencin was born and raised in the inner city of North Philadelphia. He is an alumnus of Central High School. He then earned a B.S.E. in chemical engineering from Princeton University. He earned an M.D., magna cum laude, from the Harvard Medical School, and received the Robinson Award for Surgery. Simultaneously he earned his Ph.D. in biochemical engineering/biotechnology from MIT, where he was named a Hugh Hampton Young Fellow. Laurencin and his wife have three children.
Contributions to engineering and medicine.
Laurencin is known as a world leader in biomaterials, polymeric materials science, nanotechnology, stem cell science, drug delivery systems, and a field he has pioneered, regenerative engineering. Laurencin's papers and patents have had broad impact on human health, launching the use of nanotechnology in musculoskeletal regeneration and ushering in a new era in orthopaedic therapies. He and his colleagues were the first to develop nanofiber technologies for tissue regeneration. He pioneered the development of polymer-cermaic systems for bone regeneration, and inspired technologies on the market for bone repair/regeneration and for bioceramic implants such as interference screws for musculoskeletal repair.
Laurencin has worked in the development of systems for soft tissue regeneration. He invented the Laurencin-Cooper ligament (LC ligament) for ACL regeneration, and engineered grafts for shoulder rotator cuff tendon repair and regeneration. National Geographic named the LC Ligament one of its "100 Scientific Discoveries that Changed the World" in 2012.
He is a highly cited researcher and has authored over 500 scientific papers and patents.
Selected awards and honors.
Laurencin received the National Institute of Health NIH Director's Pioneer Grant Award and the National Science Foundation NSF Emerging Frontiers in Research and Innovation Grant Award, the agencies' highest grant awards for innovation and breakthrough research.
Dr. Laurencin is an Academician and Member (foreign) of the Chinese Academy of Engineering. He is a Fellow of the African Academy of Sciences, a Fellow of the World Academy of Sciences, a Fellow of the Indian National Academy of Sciences and a Fellow of the Indian National Academy of Engineering.
Works in engineering.
Chemical engineering.
Dr. Laurencin is a Professor of Chemical and Biomolecular Engineering at the University of Connecticut. In Chemical Engineering, Dr. Laurencin was named one of the 100 Engineers of the Modern Era by the American Institute of Chemical Engineers for his work in pioneering polymer-ceramic systems for musculoskeletal use. A Fellow of the American Institute of Chemical Engineers, he won the William Grimes Award from the American Institute of Chemical Engineersand serves on the Board of Directors of the American Institute of Chemical Engineers with a term from 2018–21. He is the Founder and President of the Regenerative Engineering Society, a community within the American Institute of Chemical Engineers, and is the Editor-in-Chief of "Regenerative Engineering and Translational Medicine", published by Springer/Nature. He is the recipient of the James Bailey Award of the American Institute of Chemical Engineers and received the Percy Julian Medal, the highest award of the National Organization of Black Chemists and Chemical Engineers. He is a fellow of the American Chemical Society.
Materials science and engineering.
Dr. Laurencin is a Professor of Materials Science and Engineering at the University of Connecticut. In Materials Science and Engineering, he is a Fellow of the Materials Research Society and has been the Fred Kavli Distinguished Lecturer and Plenary Speaker for the Materials Research Society. He is a life member of the American Ceramic Society and has delivered two of their most prestigious lectures. He has served as the Edward Orton, Jr., Memorial Lecturerand the Rustum Roy Lecturer for the American Ceramic Society. He has been named one of the most highly cited researchers in Material Science and Engineering (Scopus) and his work on engineered materials for soft tissue regeneration was highlighted by National Geographic magazine in its 100 Scientific Discoveries that Changed the World edition.
Biomedical engineering.
Dr. Laurencin is a Professor of Biomedical Engineering. His work has been honored at the White House, receiving the Presidential Faculty Fellow Award from President Bill Clinton. He is a Fellow of the International Academy of Medical and Biological Engineering. He is an International Fellow in Biomaterials Science and Engineering and a Fellow of the American Institute for Medical and Biomedical Engineering, and a Fellow of the Biomedical Engineering Society. His work was honored by Scientific American magazine as one of the "50 Greatest Achievements in Science" in 2007.
Dr. Laurencin was named the 2009 winner of the Pierre Galletti Award, medical and biological engineering's highest honor. Dr. Laurencin is active in technology development. In 2012, his work in musculoskeletal tissue regeneration was featured in National Geographic magazine's "100 Discoveries that Changed Our World" edition.
In addition, he received the Technology, Innovation and Development Award from the Society for Biomaterials in 2013 for key scientific and technical innovation and leadership in translational research. In Connecticut, he was named Academic Entrepreneur of the Year by Connecticut Cure. He received the Connecticut Medal of Technology from the Connecticut Academy of Science and Engineering.
Work in medicine.
Dr. Laurencin is the Albert and Wilda Van Dusen Distinguished Endowed Professor of Orthopaedic Surgery at the University of Connecticut. He completed residency training at the Harvard Combined Orthopaedic Surgery Program, where he was Chief Resident in Orthopaedic Surgery at the Beth Israel Hospital, Harvard Medical School. He served as Vice President for Health Affairs and Dean of the School of Medicine at the University of Connecticut. Previous to that, he served as the Lillian T. Pratt Distinguished Professor of Orthopaedic Surgery and Orthopaedic Surgeon-In-Chief at the University of Virginia Health System.
A board certified shoulder and knee surgeon, Dr. Laurencin has been named to America's Top Doctors (15th consecutive year) from Castle Connolly and he has been named to "America's Leading Physicians" by Black Enterprise magazine. He has served as a ringside boxing physician and has been a physician for the USA Boxing men's elite team. He has been a member of the USA Boxing National Medical Advisory Board. Dr. Laurencin also serves as the Commissioner of Boxing for the state of Connecticut. Dr. Laurencin is a Fellow of the American Academy of Orthopaedic Surgeons, a Fellow of the American Orthopaedic Association, a Fellow of the American College of Surgeons, and a member of the American's Leading Doctors edition. He received the Nicolas Andry Award, the highest honor of the Association of Bone and Joint Surgeons. He is currently the only living orthopaedic surgeon elected to the American Academy of Arts and Sciences. He received an honorary degree from the Mount Sinai School of Medicine in 2018.
Work in equity and justice.
Dr. Laurencin is active in mentoring, especially underrepresented minority students. In 2020, the Association of American Medical Colleges (AAMC) announced Dr. Laurencin as the recipient of the Herbert W. Nickens Award. The award was bestowed upon Dr. Laurencin for his groundbreaking work in social justice, equity and fairness.
He received the American Association for the Advancement of Science (AAAS) Mentor Award, the Beckman Award for Mentoring, and the Presidential Award for Excellence in Science, Math and Engineering Mentoring in ceremonies at the White House. The Society for Biomaterials established The Cato T. Laurencin, M.D., Ph.D., Travel Fellowship in his honor, given to underrepresented minority students pursuing research. He received an honorary degree from Lincoln University, one of the oldest historically Black colleges in the country.
Dr. Laurencin is an expert in public health, especially as it pertains to ethnic minority health and health disparities. Academically, he completed the Program in African-American Studies at Princeton University. He is a core faculty member of the Africana Studies Institute at the University of Connecticut, and is Editor-in-Chief of the "Journal of Racial and Ethnic Health Disparities", published by Springer/Nature, a leading journal in the field. He has written landmark papers, including the first paper in the referred literature showing high levels of COVID-19 cases and deaths in Blacks. He has served as the Chair of the National Academy of Sciences Roundtable on Black Men and Black Women in Science, Engineering, and Medicine.
Dr. Laurencin co-founded the W. Montague Cobb/NMA Health Institute, dedicated to addressing racial health disparities, and served as its first Chair of the Board. He served on the board of trustees of the National Medical Association for over a decade and was Speaker of the House of Delegates of the National Medical Association. The W. Montague Cobb/NMA Health Institute created the Cato T. Laurencin Lifetime Achievement Award in his honor. It is bestowed at the opening ceremonies of the annual meeting of the National Medical Association.


Pyruvate dehydrogenase kinase

Pyruvate dehydrogenase kinase (also pyruvate dehydrogenase complex kinase, PDC kinase, or PDK; ) is a kinase enzyme which acts to inactivate the enzyme pyruvate dehydrogenase by phosphorylating it using ATP.
PDK thus participates in the regulation of the pyruvate dehydrogenase complex of which pyruvate dehydrogenase is the first component. Both PDK and the pyruvate dehydrogenase complex are located in the mitochondrial matrix of eukaryotes. The complex acts to convert pyruvate (a product of glycolysis in the cytosol) to acetyl-coA, which is then oxidized in the mitochondria to produce energy, in the citric acid cycle. By downregulating the activity of this complex, PDK will decrease the oxidation of pyruvate in mitochondria and increase the conversion of pyruvate to lactate in the cytosol.
The opposite action of PDK, namely the dephosphorylation and activation of pyruvate dehydrogenase, is catalyzed by a phosphoprotein phosphatase called pyruvate dehydrogenase phosphatase.
Phosphorylation Sites.
PDK can phosphorylate a serine residue on pyruvate dehydrogenase at three possible sites. Some evidence has shown that phosphorylation at site 1 will nearly completely deactivate the enzyme while phosphorylation at sites 2 and 3 had only a small contribution to complex inactivation. Therefore, it is phosphorylation at site 1 that is responsible for pyruvate dehydrogenase deactivation.
Isozymes.
There are four known isozymes of PDK in humans:
The primary sequencing between the four isozymes are conserved with 70% identity. The greatest differences occur near the N-terminus.
PDK1 is the largest of the four with 436 residues while PDK2, PDK3 and PDK4 have 407, 406, and 411 residues respectively. The isozymes have different activity and phosphorylation rates at each site. At site 1 in order from fastest to slowest, PDK2 > PDK4 ≈ PDK1 > PDK3. For site 2, PDK3 > PDK4 > PDK2 > PDK1. Only PDK1 can phosphorylate site 3. However, it has been shown that these activities are sensitive to slight changes in pH so the microenvironment of the PDK isozymes may change the reaction rates.
Isozyme abundance has also been shown to be tissue specific. PDK1 is ample in heart cells. PDK3 is most abundant in testis. PDK2 is present in most tissues but low in spleen and lung cells. PDK4 is predominantly found in skeletal muscle and heart tissues.
Mechanism.
Pyruvate dehydrogenase is deactivated when phosphorylated by PDK. Normally, the active site of pyruvate dehydrogenase is in a stabilized and ordered conformation supported by a network of hydrogen bonds. However, phosphorylation by PDK at site 1 causes steric clashes with another nearby serine residue due to both the increased size and negative charges associated with the phosphorylated residue. This disrupts the hydrogen bond network and disorders the conformation of two phosphorylation loops. These loops prevent the reductive acetylation step, thus halting overall activity of the enzyme. The conformational changes and mechanism of deactivation for phosphorylation at sites 2 and 3 are not known at this time.
Regulation.
Pyruvate dehydrogenase kinase is activated by ATP, NADH and acetyl-CoA. It is inhibited by ADP, NAD+, CoA-SH and pyruvate.
Each isozyme responds to each of these factors slightly differently. NADH stimulates PDK1 activity by 20% and PDK2 activity by 30%. NADH with acetyl-CoA increases activity in these enzymes by 200% and 300% respectively. In similar conditions, PDK3 is unresponsive to NADH and inhibited by NADH with acetyl-CoA. PDK4 has a 200% activity increase with NADH, but adding acetyl-CoA does not increase activity further.
Disease relevance.
Some studies have shown that cells that lack insulin (or are insensitive to insulin) overexpress PDK4. As a result, the pyruvate formed from glycolysis cannot be oxidized which leads to hyperglycaemia due to the fact that glucose in the blood cannot be used efficiently. Therefore, several drugs target PDK4 hoping to treat type II diabetes.
PDK1 has shown to have increased activity in hypoxic cancer cells due to the presence of HIF-1. PDK1 shunts pyruvate away from the citric acid cycle and keeps the hypoxic cell alive. Therefore, PDK1 inhibition has been suggested as an antitumor therapy since PDK1 prevents apoptosis in these cancerous cells. Similarly, PDK3 has been shown to be overexpressed in colon cancer cell lines. Three proposed inhibitors are AZD7545 and dichloroacetate which both bind to PDK1, and Radicicol which binds to PDK3.
Mutations in the PDK3 gene are a rare cause of X-linked Charcot-Marie-Tooth disease (CMTX6).
In dogs, specifically Doberman Pinschers, a mutation in the PDK4 gene is associated with dilated cardiomyopathy (DCM).


Deoxyribonuclease IV

Deoxyribonuclease IV (phage-T4-induced) (, "endodeoxyribonuclease IV (phage T4-induced)", "E. coli endonuclease IV", "endodeoxyribonuclease", "redoxyendonuclease", "deoxriboendonuclease", "Escherichia coli endonuclease II", "endonuclease II", "DNA-adenine-transferase") is a kind of Endonuclease that catalyzes the degradation nucleotides in DsDNA by attacking the 5'-terminal end.
Deoxyribonuclease IV is a type of deoxyribonuclease that functions at abasic or apurinic-apyrimidininc sites when the cell is undergoing nucleotide excision repair pathway. In addition, the endonuclease IV consists of several activities such as AP endonuclease, 3'-diesterase, 3'->5' exonuclease, and 3'phosphatase.
The endonuclease IV is encoded by denB of bacteriophage T4 and its binding sequence is 5′-dT||dCdAdCdTdTdC-3′. It has been discovered that serine 176 residue plays a crucial role in increasing the hydrolysis rate of the endonuclease of a consensus sequence containing cytidine. The endonuclease IV falls under a structurally resembling members with apyrimidininc endonuclease I (APE1).
Discovery.
Deoxyribonuclease IV was first isolated from rabbit tissues in 1968, and its molecular weight was determined to be 42,000 dalton. It was discovered that this enzyme resembels several microbial endonuclease activities of DNA polymerase I found in Escherichia coli, which appear to be necessary for DNA repair and recombination.
Structure.
DNase IV is coomposed of 185 amino acid residues with magnesium ions acting as a cofactor. Diavalent metal ion such as Mg²⁺ which acting as cofactor during the cleavage of 5'-mononucleotides. Its TIM beta barrel core surrounded by helices with three metal ions —either three Zn2+ or two Zn2+ and one Mn2+ which plays crucial role in AP excision repair.
Enzyme Activities in cell environment and DNA.
70% of the total DNase IV activitiy was found in the cytoplasm while 30% was found in cell nuclei. In human body, DNase IV was required for cleavage of a reaction intermediate generated by template strand displacement during gap-filling.
During the endonuclease activity, conformational change in DNA occurs in a way that exposes the abasic site by benting the DNA by 90 degrees, which inovles flipping out the sugar moiety into a small pocket that would not form watson-crick base pair.


Mycena olivaceomarginata

Mycena olivaceomarginata is a species of agaric fungus in the family Mycenaceae. Originally described as "Agaricus olivaceomarginata" by English mycologist George Edward Massee in 1890, he transferred it to "Mycena" in 1893. Found in Europe and North America, the mycelium of the fungus is bioluminescent.
It was described from Great Britain.


Sulfinalol

Sulfinalol is a beta adrenergic receptor antagonist.
Synthesis.
The methyl group on a sulfoxide is sufficiently acidic to substitute for phenolic hydroxyl.
The preparation of this combined α- and β-blocker sulfinalol begins by protection of the phenolic hydroxyl as its benzoate ester. Bromination followed by condensation with 4-(4-methoxyphenyl)butan-2-amine (not PMA) gives the aminoketone 3. Successive catalytic reduction and saponification affords aminoalcohol 4. Oxidation of the sulfide to the sulfoxide with a reagent such as metaperiodate gives sulfinalol (5).


Microfluidic diffusional sizing

Microfluidic diffusional sizing (MDS) is a method to measure the size of particles based on the degree to which they diffuse within a microfluidic laminar flow. It allows size measurements to be taken from extremely small quantities of material (nano-grams) and is particularly useful when sizing molecules which may vary in size depending on their environment - e.g. protein molecules which may unfold or become denatured in unfavourable conditions.
Applications.
MDS is primarily used in protein analyses, where size, concentration and interactions are important.
Protein size measurement.
Measuring the size of a protein molecule is useful as an overall quality indicator, since misfolding, unfolding, oligomerization, aggregation or degradation can all affect size.
The literature specifically demonstrates the use of MDS in sizing protein-nanobody complexes, monitoring the formation of α-synuclein amyloid fibrils. and in observing protein assembly into oligomers
MDS can also be used to size membrane proteins, as the use of a protein specific labelling and detection system allows other species present in the solution (such as free lipid micelles or detergents) to be ignored.
Protein interactions.
MDS has been used to characterise interactions between biomolecules under native conditions, and has been demonstrated to detect specific interactions within complex mixtures. It has also been used in detecting and quantifying protein-ligand interactions and protein-lipid interactions.
Protein concentration.
The concentration of purified protein solutions in the laboratory is useful in determining yield and measuring the success of a prep. MDS reports concentration as well as size for each test.
Since the detection is not based on inherent fluorescence of tryptophan or tyrosine residues, MDS has been used as an alternative to A280 UV-Vis quantification.
Advantages.
If protein specific labelling is applied, MDS allows membrane proteins to be sized. This is particularly useful as it is an area where other biophysical techniques can struggle - for example dynamic light scattering (DLS) is of limited use, since free detergent molecules may also scatter light and affect the results.
Furthermore, as the size reported is an average of all detectable species present there is no bias towards large species, as is found in DLS measurements.
Another key advantage is that results can be obtained with very small quantities of material which may be particularly important where samples are scarce or expensive.
With commercially available MDS instruments, testing is very simple and there is no need to input test parameters or sample conditions. This makes it a very repeatable method of testing as most of the functions such as flow rates, detector settings etc. are automated by the instrument rather than set by the operator.
In addition to size, MDS is able to calculate concentration so two parameters can be assessed in one test.
Finally the method does not require calibration, as it relies on a ratio-metric measurement to determine diffusion rate.
Theory.
In an MDS analysis, a stream of liquid containing the particles to be sized is introduced alongside an auxiliary stream in a laminar flow in a microfluidic channel. Because there is no convective mixing of the two streams, the only way particles can move to the auxiliary stream is by diffusion. The rate of this diffusion is dependent on the particle's size, as determined by the Stokes–Einstein equation, so small particles diffuse quicker than large particles.
After a period of diffusion the original and auxiliary streams are split and the degree of diffusion is fixed. The number of particles in each stream can then be detected (in the case of proteins this is achieved by addition of an amine reactive fluorogenic dye). The ratio between the two streams is used to determine the diffusion co-efficient, which is used to calculate the hydrodynamic radius. The sum of particles in both streams can also be used to measure the concentration of the analyte.


Proline dehydrogenase

In enzymology, a proline dehydrogenase (, formerly ) is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are L-proline and ubiquinone, whereas its two products are (S)-1-pyrroline-5-carboxylate and ubiquinol.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with a quinone or similar compounds as acceptors. The systematic name of this enzyme class is L-proline:quinone oxidoreductase. Other names in common use include L-proline dehydrogenase, and L-proline:(acceptor) oxidoreductase. This enzyme participates in arginine and proline metabolism. It employs one cofactor, FAD.
Structural studies.
As of late 2007, 9 structures have been solved for this class of enzymes, with PDB accession codes , , , , , , , , and .


5-MeO-2-TMT

5-Methoxy-2,"N","N"-trimethyltryptamine (5-MeO-2,"N","N"-TMT, 5-MeO-TMT) is a psychoactive drug of the tryptamine chemical class which acts as a psychedelic. It was first synthesized by Alexander Shulgin and reported in his book TiHKAL ("Tryptamines i Have Known And Loved"). 5-MeO-TMT is claimed to show psychoactive effects at a dosage of 75–150 mg orally, but these are relatively mild compared to those of other similar compounds. This suggests that while the methyl group on the 2-position of the molecule has impaired the binding of metabolic enzymes like monoamine oxidase (MAO), it is also interfering with binding to and/or activation of the serotonin 5-HT2A receptor, the target responsible for mediating the hallucinogenic effects of such compounds.


Ortho-Methylphenylpiperazine

"ortho"-Methylphenylpiperazine (oMPP, oMePP), or 1-(2-methylphenyl)piperazine (2-MPP, 2-MePP), is a psychoactive and designer drug of the phenylpiperazine group. It acts as a serotonin–norepinephrine–dopamine releasing agent (SNDRA), with EC50 values for induction of monoamine release of 175 nM for serotonin, 39.1 nM for norepinephrine, and 296–542 nM for dopamine. As such, it has about 4.5-fold preference for induction of norepinephrine release over serotonin, and about 7.6- to 13.9-fold preference for induction of norepinephrine release over dopamine.
The 2,3-methyl and 4-methyl analogues show diminished activity as dopamine releasing agents with respective EC50 values of 1,207 nM and 9,523 nM. However, at the same time, induction of serotonin and norepinephrine release is retained and more balanced in the 2,3-methyl analogue, with respective EC50 values of 26 nM and 56 nM.


Banu Onaral

Banu Onaral is H.H. Sun Professor of Biomedical Engineering and Electrical Engineering at Drexel University, Philadelphia, Pennsylvania. She holds a Ph.D. 1978 in Biomedical Engineering from the University of Pennsylvania and BSEE 1973 and MSEE [1974] in Electrical Engineering from Bogazici University, Istanbul, Turkey. Dr. Onaral joined the faculty of the Department of Electrical and Computer Engineering and the Biomedical Engineering and Science Institute in 1981. She held two sabbatical leaves at Bogazici University in the academic years 1980-81 and 1987-88. Since 1997, she has served as the founding Director of the School of Biomedical Engineering Science and Health Systems.
Her academic focus both in research and teaching is centered on information engineering with special emphasis on complex systems and biomedical signal processing in ultrasound and optics. She has led major research and development projects sponsored by the National Science Foundation (NSF), National Institutes of Health (NIH), Office of Naval Research (ONR), DARPA and Department of Homeland Security (DHS). She supervised a large number of graduate students to degree completion and has an extensive publication record in biomedical signals and systems. She is the recipient of a number of faculty excellence awards including the 1990 Lindback Distinguished Teaching Award of Drexel University, the EDUCOM Best educational Software award and the NSF Faculty Achievement Award.
Dr. Onaral’s translational research efforts for rapid commercialization of biomedical technologies developed at Drexel and its partner institutions have resulted in the creation of the Translational Research in Biomedical Technologies program. This initiative brings together academic technology developers with entrepreneurs, regional economic development agencies, local legal, business and investment communities. Under her leadership, the program has been recognized by the Coulter Translational Research Partnership award following a highly competitive selection process among 63 institutions in North America. At the end of the five-year term, universities successful in institutionalizing translational research will receive an endowment to ensure the perpetuity of the program.
Dr. Onaral’s professional services include chair and membership on advisory boards and strategic planning bodies of several universities and funding agencies, including service on the National Science Foundation's Engineering Advisory Board, and on the proposal review panels and study sections. She has served on the strategic planning team charged with the creation of Sabanci University in Istanbul, Turkey.
Her professional responsibilities have included service on the Editorial Board of journals and the CRC Biomedical Engineering Handbook as Section Editor for Biomedical Signal Analysis. She served as President of the IEEE Engineering in Medicine and Biology Society (EMBS), the largest member-based biomedical engineering society in the world. She organized and chaired the 1990 Annual International Conference of the EMBS and Co-Chaired the 2004 Annual Conference of the Biomedical Engineering. She is a Fellow of the IEEE Engineering in Medicine and Biology Society, the American Association for the Advancement of Science (AAAS) and a Founding Fellow of American Institute for Medical and Biological Engineering (AIMBE). She served on the inaugural Board of the AIMBE as publications chair and as Chair of the Academic Council and as the President of the Turkish American Scientists and Scholars Association.