Kevin Granata

Kevin P. Granata (December 29, 1961 – April 16, 2007) was an American professor in multiple departments including the Departments of Engineering, Science and Mechanics (in which he was tenured) and Mechanical Engineering at Virginia Polytechnic Institute and State University (Virginia Tech), in Blacksburg, Virginia. Granata held an additional academic appointment as a professor in the Virginia Tech-Wake Forest School of Biomedical Engineering and was an adjunct professor at the University of Virginia in the Department of Orthopedic Surgery. During the Virginia Tech shooting, he shepherded students into his office in order to safeguard them. He was then killed by Seung-Hui Cho after he went to investigate and intervene.
Education and career.
A native of Toledo, Ohio, Granata attended St. Francis de Sales High School in Toledo, where he played football and served on the debate team for four years, graduating in 1980 with a 4.0 GPA. Granata was awarded a bachelor's degree in engineering physics & electrical engineering from Ohio State University in 1984, a master's degree in physics from Purdue University in 1986, and a doctorate in biomechanics from Ohio State in 1993. He began his bachelor's degree in physics at John Carroll University in Cleveland, where he also played football, before transferring to Ohio State to finish the degree.
After earning his master's degree from Purdue, Granata worked for three years as a research scientist in the Applied Physics Lab at Johns Hopkins University. While there, he was contracted by the military and conducted research for the US Navy.
Granata stayed at Ohio State for four years as a research scientist in the Biodynamics Laboratory after earning his doctorate degree there in 1993.
In 1997, Granata arrived at the University of Virginia as an assistant professor in two departments, Orthopedics and Biomedical Engineering, where he published two journals and collaborated on a study with the Curry School of Education to determine why female athletes experience more knee injuries than their male counterparts. From 1997 to 2003, he also served as the Research Director of the Motion Analysis Laboratory at Virginia. In 2002, he was promoted to the position of associate professor for the orthopedics and biomedical engineering departments. While at Virginia, he worked at the university's Kluge Children's Rehabilitation Center with children who had cerebral palsy.
He remained an adjunct professor at Virginia after leaving for Virginia Tech in 2003.
Virginia Tech.
Granata was among the leading U.S. researchers on biomechanics and movement dynamics in cerebral palsy, in his work with the Musculoskeletal Biomechanics Laboratory at Virginia Tech. His research focused on muscle and reflex control and its relation to legged robotics, neuromuscular control of musculoskeletal movement, biomechanical stability and muscle dynamics, control of low-back pain, and computer simulation and clinical interpretation of pathologic walking and running. Professor Granata was recruited to the Department of Engineering Science and Mechanics to continue his distinguished teaching and research. In particular, he developed innovative methods to quantify low back stability that are considered cutting edge by other leaders in the field. He served as mentor for numerous students and junior professors. When Granata was promoted to the rank of professor, one of these professors conveyed, "Countless times he has provided me with valuable guidance on research-related matters such as student advising, experimental issues, and manuscript preparation."
Darin Padua of the University of North Carolina at Chapel Hill, who earned his doctorate under Granata's tutelage at the University of Virginia, said that Granata particularly excelled at encouraging collaboration among experts in various fields, resulting in research that crossed many disciplines and areas of expertise.
While focusing primarily on research into cerebral palsy, biomimetric robotics and biomechanics, Granata helped develop mobility aids for the elderly such as the MARC Robotic Walker. The MARC Walker is named for the Medical Automation Research Center at the University of Virginia, where Granata had taught until January 10, 2003. He presented a paper on the elderly walker at the 2003 International Conference on Robots and Systems in Las Vegas. Granata was an associate professor at Virginia Tech and in 2005, he achieved the honor of Virginia Tech College of Engineering Faculty Fellow. In 2006, he was awarded the Dean's Award for Excellence in Research for his work on lower back pain. In announcing the Dean's Award given to Granata, Virginia Tech stated he had "established a major research program, developing innovative methods to quantify low back stability that are considered cutting edge." He was additionally honored as the Virginia Tech Scholar of the Week for his published work concerning lower back pain. His friends and colleagues at Virginia Tech called him "a man with a sharp intellect who answered a call to serve the cause of scholarship and higher education".
Granata was a member of many professional societies and served as Associate Editor of the "Journal of Applied Biomechanics" and "Journal of Electromyography & Kinesiology". Granata was a co-chair of the American Society of Biomechanics' annual meeting in 2006, hosted at Virginia Tech.
At the time of his death, he was awaiting publication of four more articles in his name.
Personal life.
Granata lived in Blacksburg with his wife, Linda Ankenman, whom he met at Purdue while they both participated in the Crew Club and married in May 1991. She is a research specialist in the Food Science Department at Virginia Tech. He enjoyed working with the Boy Scouts and other activities with his three children, and he was an avid athlete, participating in triathlons and biathlons for years. On the crew club at Purdue, he was on the JV rowing team that won a bronze medal at the Dad Vail Regatta in 1986. He loved to play golf and was a fan of Ohio State athletics. Granata was also a member of Triangle Fraternity, inducted at Ohio State.
Death.
Granata was a victim of the Virginia Tech shooting on April 16, 2007. Upon hearing a commotion from his office on the third floor of Norris Hall, he brought 20 students from a nearby classroom into his office, where the door could be locked. He and another professor, Wally Grant, then went downstairs to investigate the situation when they were both shot by Seung-Hui Cho; Grant was wounded and survived from a shoulder injury, but Granata died from an injury to his temple. He was 45 years old. None of the students locked in Granata's office were injured or killed.
One of Granata's fellow Virginia Tech engineering professors, Dr. Liviu Librescu, was also killed in the shootings. The Engineering Science and Mechanics Department Head, Dr. Ishwar Puri, remembered Granata and Librescu in a statement as "world-class" researchers. Dr. Puri stated about Granata, "The use of his research by other scholars worldwide had put him on a trajectory to become a notable star in these fields."
Memorial services were held in Blacksburg and a funeral Mass at Christ the King Church in Toledo, Ohio, where his parents, Joseph and Mildred, and siblings live, was later held.


Desulfofrigus fragile

Desulfofrigus fragile is a bacterium. It is a psychrophilic Gram-negative and sulfate-reducing bacteria with type strain Lsv21T.


Methanosarcina-phenazine hydrogenase

In enzymology, a Methanosarcina-phenazine hydrogenase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are H2 and 2-(2,3-dihydropentaprenyloxy)phenazine, whereas its product is 2-dihydropentaprenyloxyphenazine.
This enzyme belongs to the family of oxidoreductases, specifically those acting on hydrogen as donor with other, known, acceptors. The systematic name of this enzyme class is hydrogen:2-(2,3-dihydropentaprenyloxy)phenazine oxidoreductase. Other names in common use include methanophenazine hydrogenase, and methylviologen-reducing hydrogenase.


Evolution of the feather


Dan Olmsted

Dan Olmsted (died January 23, 2017) was a journalist and former senior editor for United Press International (UPI), a news agency of the Unification Church company News World Communications. Olmsted wrote a series of reports suggesting a link between vaccination and autism, a hypothesis which has been disproven. His columns on health and medicine appeared regularly in "The Washington Times" and were syndicated nationally from UPI's Washington D.C. bureau. He owned and edited the "Age of Autism" website, a site he described as the "Daily Web Newspaper of the Autism Epidemic", where writers question the safety of vaccines. Olmsted wrote an article in 2002, along with reporter Mark Benjamin, which drew links between the drug Lariam given to military personnel and mental health disorders in soldiers. In 2013, the FDA issued its most serious "boxed" warning for that drug, warning that Lariam's serious psychiatric side effects may be permanent for some.
He co-wrote four books with Mark Blaxill, co-founder of Age of Autism. The last, "Denial: How Refusing to Face the Facts about Our Autism Epidemic Hurts Children, Families, and Our Future" was released posthumously in 2017.
"The Age of Autism".
From 2005 to July 2007, Olmsted wrote about his investigative findings concerning the apparent global epidemic of autism in a series of columns titled "The Age of Autism". Though some scientific research suggests that autism is a primarily genetic disorder and that reported increases are mainly due to changes in diagnostic practices, Olmsted, claimed that the increases are due to mercury poisoning, particularly from vaccines, and that the genetics is mostly secondary. Though Olmsted continued to make this claim, thimerosal, the mercury-containing preservative blamed by Olmsted, was removed from most vaccines as a precaution beginning in the late 1990s, with no effect on autism diagnosis rates.
Congressional action.
Citing Olmsted's reports, on March 30, 2006, Rep. Carolyn Maloney (NY) announced that she would be drafting legislation calling for scientific studies investigating thiomersal and autism, additional to the many already conducted. The bill was introduced in the U. S. House of Representatives in April 2006. Maloney made the announcement at a National Press Club press conference in Washington, D.C., along with Olmsted and David Kirby.
Criticism.
Scientific studies have found no credible evidence that thimerosal-containing vaccines and the MMR vaccine cause autism, and the MMR vaccine controversy is largely seen as the result of an "elaborate fraud" by British researcher Andrew Wakefield.
In a critical assessment by the "Columbia Journalism Review" of the thimerosal controversy, Olmsted's reporting on unvaccinated populations has been characterized as "misguided" by two anonymous reporters. Both sources "believed that Olmsted has made up his mind on the question and is reporting the facts that support his conclusions". In 2011 Brian Dunning listed the Age of Autism website as #2 on his "Top 10 Worst Anti-Science Websites" list.
Death.
Olmsted died on January 23, 2017, from an overdose of prescription medication, according to his spouse Mark Milett.


Umespirone

Umespirone (KC-9172) is a drug of the azapirone class which possesses anxiolytic and antipsychotic properties. It behaves as a 5-HT1A receptor partial agonist (Ki = 15 nM), D2 receptor partial agonist (Ki = 23 nM), and α1-adrenoceptor receptor antagonist (Ki = 14 nM), and also has weak affinity for the sigma receptor (Ki = 558 nM). Unlike many other anxiolytics and antipsychotics, umespirone produces minimal sedation, cognitive/memory impairment, catalepsy, and extrapyramidal symptoms.


Methylhippuric acid

Methylhippuric acid is a carboxylic acid and organic compound. Methylhippuric acid has three isomers. The isomers include 2-, 3-, and 4-methylhippuric acid.
Methylhippuric acids are metabolites of the isomers of xylene. The presence of methylhippuric acid can be used as a biomarker to determine exposure to xylene.


Shikimate pathway

The shikimate pathway (shikimic acid pathway) is a seven-step metabolic pathway used by bacteria, archaea, fungi, algae, some protozoans, and plants for the biosynthesis of folates and aromatic amino acids (tryptophan, phenylalanine, and tyrosine). This pathway is not found in animal cells.
The seven enzymes involved in the shikimate pathway are DAHP synthase, 3-dehydroquinate synthase, 3-dehydroquinate dehydratase, shikimate dehydrogenase, shikimate kinase, EPSP synthase, and chorismate synthase. The pathway starts with two substrates, phosphoenol pyruvate and erythrose-4-phosphate, and ends with chorismate, a substrate for the three aromatic amino acids. The fifth enzyme involved is the shikimate kinase, an enzyme that catalyzes the ATP-dependent phosphorylation of shikimate to form shikimate 3-phosphate (shown in the figure below). Shikimate 3-phosphate is then coupled with phosphoenol pyruvate to give 5-enolpyruvylshikimate-3-phosphate via the enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase.
Then 5-enolpyruvylshikimate-3-phosphate is transformed into chorismate by a chorismate synthase.
Prephenic acid is then synthesized by a Claisen rearrangement of chorismate by chorismate mutase.
Prephenate is oxidatively decarboxylated with retention of the hydroxyl group to give "p"-hydroxyphenylpyruvate, which is transaminated using glutamate as the nitrogen source to give tyrosine and α-ketoglutarate.


3-Methoxy-4-ethoxyphenethylamine

MEPEA, or 3-methoxy-4-ethoxyphenethylamine, is a lesser-known psychedelic drug. MEPEA was first synthesized by Alexander Shulgin. In his book "PiHKAL (Phenethylamines i Have Known And Loved)", the minimum dosage is listed as 300 mg, and the duration unknown. MEPEA produces a light lifting feeling and a +1 on the Shulgin Rating Scale. Very little data exists about the pharmacological properties, metabolism, and toxicity of MEPEA.


Nocturnal (novel)

Nocturnal is a novel and podcast by author Scott Sigler. The novel was originally released in 2007 in podcast format, with a print format releasing in 2012 by Crown Publishing with some elements from the original version altered.
Plot.
The book is set in San Francisco and is narrated from multiple perspectives, largely that of Bryan Clauser, a homicide detective known for his calm, cold demeanor. This is in stark contrast to the personality of his partner Lawrence "Pookie" Chang, who spends much of his time making wise-cracks and writing the series bible for a TV series he's developing. The two come across a series of ritualistic murders that appear to be initially unconnected but eventually prove to be related to a teenager by the name of Rex Deprovdechuk. During all of the murders Bryan and Rex both have a series of dreams where they see bizarre, monstrous people murdering the victims in the name of an as yet unknown king. Unbeknownst to the others, the monsters have kidnapped multiple individuals including the homeless junkie Aggie James.
Rex is extremely unpopular at his school and was frequently the subject of physical abuse by his mother and by a gang of bullies called "BoyCo". He's initially unaware that he is the reason for the murders but finds himself genuinely enjoying the murder dreams, not only because he's witnessing his bullies' suffering but also because he finds the violence sexually appealing. Meanwhile, Bryan and Pookie investigate the crimes with the help of Pookie's former partner John "Black Mr. Burns" Smith and find that the murders are being committed by a group called "Marie's Children". The group is steeped in mystery as any records of the group- and their opponents "The Saviors"- have been expunged from multiple places. Rex is eventually approached by Sly and a few members of Marie's Children, who tell him that he is their king and is destined to lead them to a glorious new future. Sly and the others help Rex murder his abusive mother and then take him to a series of hiding places before taking him to "Home". During this Bryan finds that Marie's Children are a humanoid species separate from humanity and that he is one of them. He also reconnects with his ex-girlfriend Robin, a medical examiner for San Francisco.
Bryan and Pookie's investigations lead them to Jebidiah Erickson, but the two are fired by police Chief Amy Zou because they wouldn't leave the investigation alone. Despite this, they break into Erickson's house and find multiple stuffed monsters. They are also caught by Erickson and Bryan ends up stabbing the other man as his Marie's Children DNA, paired with the dreams he'd been having, cause him to see Erickson as a threat. Heavily wounded, Erickson is taken to the hospital and Bryan finds that rather than the older man being the reason for the murders, he was actually hunting Marie's Children and was the reason why there were not more deaths in the city. Meanwhile, Rex returns home and is told that all of Marie's Children are born from the same woman: Marie, who serves as a queen bee and is also Rex's birth mother. He is also told that he must have sex with her in order to create a new queen so the colony can spread to other areas. During this Aggie is told that his life is going to be spared so he can smuggle an infant king out of "Home", as some of the Children do not want the colony to spread and will kill any kings that Marie produces. Knowing that the alternative is death, Aggie readily agrees and later absconds with the infant.
The book culminates with Bryan teaming up with Erickson to invade "Home" and kill off Marie's Children. They ultimately succeed in killing Marie and most of the Children, but the attempt comes at the price of multiple lives, including Erickson's. Robin is also murdered in the process, which leaves him grief-stricken. He decides that he will take on Erickson's role as a Savior (as there are still Children in San Francisco) and assumes his identity, as he feels that he has nothing tying him to his old life. The book ends with the revelation that Hillary, a female leader of the Children, has become a new queen after Marie's death and is being cared for by some of the remaining Children.
Reception.
Critical reception for the 2012 release of "Nocturnal" has been mostly positive, with Kirkus Reviews saying the hardback release was "red meat for readers who wish Harry Potter had swapped his YA credentials for a badge and gun." The Huntington News praised the 2012 release, calling it "a treat". The Nerdist also positively reviewed the book, praising the characters and Sigler's research for the novel.
The Daily Texan praised Sigler's use of science as "believable" but stated that "Sigler could use a bit more work is his characterizations".


Bacitracin

Bacitracin is a mixture of related cyclic peptides produced by organisms of the licheniformis group of "Bacillus subtilis" "var" Tracy, first isolated in 1945. These peptides disrupt Gram-positive bacteria by interfering with cell wall and peptidoglycan synthesis.
Bacitracin is primarily used as a topical preparation, as it can cause kidney damage when used internally.
Antibiotics such as bacitracin have been shown to act as dermatological irritants and may slow healing in otherwise sterile wounds.
Medical uses.
 Bacitracin is used in human medicine as a polypeptide antibiotic and is "approved by the U.S. Food and Drug Administration (FDA) for use in chickens and turkeys," though use in animals contributes to antibiotic resistance.
As bacitracin zinc salt, in combination with other topical antibiotics (usually polymyxin B and neomycin) as an ointment ("triple antibiotic ointment," with the common brand name Neosporin), it is used for topical treatment of a variety of localized skin and eye infections, as well as for the prevention of wound infections. A non-ointment form of ophthalmic solution is also available for eye infections.
Although allergic cross-reaction with sulfa drugs has been occasionally reported, bacitracin-containing topical preparations remain a possible alternative to silver sulfadiazine (Silvadene) for burn patients with a sulfa allergy.
Bacitracin can also be bought in pure form for those with allergies to the usual polymyxin B and neomycin components of the combination product.
Bacitracin is also commonly used as an aftercare antibiotic on tattoos and circumcision. It is preferred over combination products such as Neosporin because of its fewer ingredients, which lowers chances of an allergic reaction.
In 2005–06, it was the sixth-most-prevalent allergen in patch tests (9.2%).
It was voted Allergen of the Year in 2003 by the American Contact Dermatitis Society.
In infants, bacitracin is rarely administered intramuscularly for the treatment of staphylococcal pneumonia and empyema when due to organisms shown susceptible to bacitracin. This use is extremely limited, since bacitracin is nephrotoxic and its concentration in the blood must be followed closely.
Bacitracin can be used to distinguish "Streptococcus pyogenes" from other streptococci, with "S. pyogenes" being sensitive to bacitracin and others resistant. In this case bacitracin is used to distinguish "S. pyogenes" from other "β-hemolytic streptococci".
It is also commonly used to distinguish "Haemophilus influenzae" colonies amongst respiratory flora; since "H. influenzae" is intrinsically resistant to bacitracin, colonies form within the zone of inhibition.
Spectrum of activity and susceptibility data.
Bacitracin is a narrow-spectrum antibiotic. It targets Gram-positive organisms, especially those that cause skin infections. The following represents susceptibility data for a few medically significant microorganisms.
Mechanism of action.
Bacitracin interferes with the dephosphorylation of C55-isoprenyl pyrophosphate, and a related molecule known as bactoprenol pyrophosphate; both of these lipids function as membrane carrier molecules that transport the building-blocks of the peptidoglycan bacterial cell wall outside of the inner membrane.
Some have claimed that bacitracin is a protein disulfide isomerase inhibitor, but this is disputed by "in vitro" studies.
History.
Bacitracin was isolated by Balbina Johnson, a bacteriologist at the Columbia University College of Physicians and Surgeons. Its name derives from the fact that a compound produced by a microbe in young Margaret Treacy's (1936–1994) leg injury showed antibacterial activity. The surname was misspelled and the name shortened to the more common spelling "Tracy."
"One strain isolated from tissue debrided from a compound fracture of the tibia was particularly active. We named this growth-antagonistic strain for the patient, "Tracy I." When cell-free filtrates of broth cultures of this bacillus proved to possess strong antibiotic activity and to be non-toxic, further study seemed warranted. We have called this active principle "Bacitracin."
Bacitracin was approved by FDA in 1948.
Synthesis.
Bacitracin is synthesised via nonribosomal peptide synthetases (NRPSs), which means that ribosomes are not directly involved in its synthesis.
bacABC is involved in synthesis.
Bacitracin is commercially manufactured by growing the bacteria "Bacillus subtilis var Tracy I" in a container of liquid growth medium. Over time, the bacteria synthesizes the antibiotic and secretes the antibiotic into the medium. The antibiotic is then extracted from the medium using chemical processes.
Composition.
Bacitracin is composed of a mixture of related compounds with varying degrees of antibacterial activity. Notable fractions include bacitracin A, A1, B, B1, B2, C, D, E, F, G, and X. Bacitracin A has been found to have the most antibacterial activity. Bacitracin B1 and B2 have similar potencies and are approximately 90% as active as bacitracin A. Other bacitracin components including F and X do not appear to be extensively studied.


Glutamicibacter soli

Glutamicibacter soli, also known as Arthrobacter soli, is a species of Gram-positive bacteria. Its type strain is SYB2T (= KCTC 19291T = DSM 19449T).
Since 2016, this species is one of the member of Glutamicibacter genus, instead of Arthrobacter genus.


PNU-22394

PNU-22394 is a drug which acts as an agonist at serotonin 5-HT2 receptors, with strongest binding affinity for 5-HT2A and 5-HT2C and slightly weaker at 5-HT2B, although it is only a full agonist at 5-HT2C, but partial agonist at 5-HT2A and 5-HT2B. It has anorectic effects in both animal studies and human trials, along with "Pro-Cognitive Properties", although it has never been developed for medical use.


Blackbird (Omaha leader)

Chief Blackbird (Wash-ing-guh Sah-ba) (ca. 1750 – 1800) was the leader of the Omaha Native American Indian tribe who commanded the trade routes used by Spanish, French, British and later American traders until the late 18th century. He was one of the first of the Plains Indian chiefs to trade with white explorers and also believed to be the first of the Plains Indian chiefs to openly question white encroachment. Blackbird used trade as a means to prosperity for his people and as a way to ensure white explorers were aware that they were the guests. The Omaha were not warlike people, yet they were the first on the Great Plains to have mastered equestrianism around 1770 and were at one point, while Chief Blackbird was alive, the most powerful Indian tribe in the Great Plains.
Chief Blackbird died during a smallpox epidemic in 1800. In 1804, the Lewis and Clark Expedition members were led to Chief Blackbird's burial site, which sits on a bluff on the west side of the Missouri River, in present-day Nebraska.
Blackbird Bend in western Iowa is named for Blackbird.


Orycteropodidae

Orycteropodidae is a family of afrotherian mammals. Although there are many fossil species, the only species surviving today is the aardvark, "Orycteropus afer" also known as "Qarandi" or "seddex-suulay" in the Somali language. Orycteropodidae is recognized as the only family within the order Tubulidentata, so the two are effectively synonyms.
Evolution.
The first aardvark fossil discovered was originally named "Orycteropus gaudryi" (now "Amphiorycteropus") and was found in Turolian deposits on the island of Samos. Since then, representatives of the order Tubulidentata have been located from the Oligocene in what is now Europe, and it is believed that the order probably originated around 65–70 million years ago or in the Paleocene. They are thought to be closely related to the now extinct Ptolemaiida, a lineage of carnivorous afrotheres. The family arose in Africa in the Early Miocene epoch, and spread to Eurasia later in the Miocene. Most of the family's diversity had become extinct by the end of the Pliocene.
Characteristics.
Aardvarks had originally been categorized as relatives of American anteaters in the order Edentata. But their unique type of teeth and other morphological characteristics had made it clear that aardvarks are not closely related to any other living mammals. Since the end of the 19th century, they are placed in their own separate order Tubulidentata. Both the fossil record and genetic studies have corroborated that separate status. All similarities to American anteaters have evolved independently as adaptations to eating ants.
One of the most distinctive features of the animals is that their teeth have a "tubulidentate" microstructure, lacking enamel, and are just rounded structures of dentine. They lack incisors and canines, and have 20–22 teeth, which are evergrowing, unrooted, and diphyodont. Another unique trait is that their small milk teeth are lost before the animal is born.
A few anatomical characters unite the Orycteropodidae and Tubulidentata. The occipital region of the skull has extensive mastoid exposure, the femur has a pectineal tubercle, and the diaphysis of the tibia is curved mediolaterally.
Modern aardvarks are polygynous, the females providing care for the young. They are territorial, and only cross paths to breed. The males' genitals create a musk while females create this musk from glands in their elbows, this scent helps mating occur. The gestation period lasts about seven months, and they are dependent upon the mother until they are six months of age, becoming sexually mature at two years of age. Breeding occurs once a year, they produce one offspring, and will have maybe one to two more in their lifetime. Aardvarks are myrmecophagous, feeding almost exclusively on termites and ants. They rely on their sense of smell to find most of their food and hunt at night.
Classification.
This classification follows Lehmann 2009.


Peptide

Peptides (from Greek language πεπτός, "peptós" "digested"; derived from πέσσειν, "péssein" "to digest") are short chains of between two and fifty amino acids, linked by peptide bonds. Chains of fewer than ten or fifteen amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A polypeptide is a longer, continuous, unbranched peptide chain of up to approximately fifty amino acids. Hence, peptides fall under the broad chemical classes of biological polymers and oligomers, alongside nucleic acids, oligosaccharides, polysaccharides, and others.
A polypeptide that contains more than approximately fifty amino acids is known as a protein. Proteins consist of one or more polypeptides arranged in a biologically functional way, often bound to ligands such as coenzymes and cofactors, or to another protein or other macromolecule such as DNA or RNA, or to complex macromolecular assemblies.
Amino acids that have been incorporated into peptides are termed residues. A water molecule is released during formation of each amide bond. All peptides except cyclic peptides have an N-terminal (amine group) and C-terminal (carboxyl group) residue at the end of the peptide (as shown for the tetrapeptide in the image).
Classes.
Many kinds of peptides are known. They have been classified or categorized according to their sources and functions. According to the Handbook of Biologically Active Peptides, some groups of peptides include plant peptides, bacterial/antibiotic peptides, fungal peptides, invertebrate peptides, amphibian/skin peptides, venom peptides, cancer/anticancer peptides, vaccine peptides, immune/inflammatory peptides, brain peptides, endocrine peptides, ingestive peptides, gastrointestinal peptides, cardiovascular peptides, renal peptides, respiratory peptides, opiate peptides, neurotrophic peptides, and blood–brain peptides.
Some ribosomal peptides are subject to proteolysis. These function, typically in higher organisms, as hormones and signaling molecules. Some organisms produce peptides as antibiotics, such as microcins and bacteriocins.
Peptides frequently have post-translational modifications such as phosphorylation, hydroxylation, sulfonation, palmitoylation, glycosylation, and disulfide formation. In general, peptides are linear, although lariat structures have been observed. More exotic manipulations do occur, such as racemization of L-amino acids to D-amino acids in platypus venom.
Nonribosomal peptides are assembled by enzymes, not the ribosome. A common non-ribosomal peptide is glutathione, a component of the antioxidant defenses of most aerobic organisms. Other nonribosomal peptides are most common in unicellular organisms, plants, and fungi and are synthesized by modular enzyme complexes called "nonribosomal peptide synthetases".
These complexes are often laid out in a similar fashion, and they can contain many different modules to perform a diverse set of chemical manipulations on the developing product. These peptides are often cyclic and can have highly complex cyclic structures, although linear nonribosomal peptides are also common. Since the system is closely related to the machinery for building fatty acids and polyketides, hybrid compounds are often found. The presence of oxazoles or thiazoles often indicates that the compound was synthesized in this fashion.
 are derived from animal milk or meat digested by proteolysis. In addition to containing small peptides, the resulting material includes fats, metals, salts, vitamins, and many other biological compounds. Peptones are used in nutrient media for growing bacteria and fungi.
Peptide fragments refer to fragments of proteins that are used to identify or quantify the source protein. Often these are the products of enzymatic degradation performed in the laboratory on a controlled sample, but can also be forensic or paleontological samples that have been degraded by natural effects.
Example families.
The peptide families in this section are ribosomal peptides, usually with hormonal activity. All of these peptides are synthesized by cells as longer "propeptides" or "proproteins" and truncated prior to exiting the cell. They are released into the bloodstream where they perform their signaling functions.
Terminology.
Length.
Several terms related to peptides have no strict length definitions, and there is often overlap in their usage.
Number of amino acids.
Peptides of defined length are named using IUPAC numerical multiplier prefixes.


OP9 cell

OP9 cells are a cell line derived from mouse bone marrow stromal cells (mesenchyme). These cells are now characterized as stem cells.
When co-culture with embryonic stem cells (ESC), OP9 cells can induce ESC to differentiate into blood cells.


Avinash K. Dorle

Avinash K. Dorle (A. K. Dorle) (22 March 1935 – 14 November 2015) was an Indian scientist and professor of pharmaceutical sciences. He was formerly the head of the University Department of Pharmaceutical Sciences, Nagpur University, India. He also served as the president of Maharashtra Pharmacy Council (1982–98), and Indian Pharmaceutical Association. He received an emeritus professorship from All India Council for Technical Education (AICTE)(1995–1997). He continues to serve as President of Central India Pharmacy Promotion and Research Association (CIPPARA) and as faculty at Department of Cosmetic Technology, Nagpur University.
He was widely recognized and cited researcher in pharmaceutical sciences, especially in the areas of drug delivery and King of pharmacology. His specific areas of excellent contributions include rosin, zeta potential, adrenergic mechanisms, emulsion stability, herbal panchgavya formulations and alternate medicine.
Dorle was a recipient of several awards including G.P.Shrivastava Memorial Award (APTI), Indian Pharmaceutical Association Award for excellence, and Bhojraj Panjamool Memorial Award. Dorle has mentored several well-known scientists for their doctoral programs.


Coronavirus packaging signal

The Coronavirus packaging signal is a conserved cis-regulatory element found in Betacoronavirus (part of the Coronavirus subfamily of viruses). It has an important role in regulating the packaging of the viral genome into the capsid. As part of the viral life cycle, within the infected cell, the viral genome becomes associated with viral proteins and assembles into new infective progeny viruses. This process is called packaging and is vital for viral replication.
The packaging signal is found in the positive-sense single-stranded RNA genome. It interacts with the viral proteins (M and N) and ensures the selective packaging of viral RNA into virions.
This RNA element is conserved in Embecovirus (previously known as lineage A Betacoronavirus), which includes mouse hepatitis virus (MHV), bovine coronavirus (BCoV), and human coronaviruses like HCoV-HKU1 and HCoV-OC43. Notably, this element is absent from the other viral lineages which have evolved separate packaging signals. For example, it is not found in SARS-CoV and SARS-CoV-2 (contrary to previous claims that have been refuted).
The packaging signal has a conserved RNA secondary structure featuring four AGC/GUAAU internal loop motifs. Within the viral genome the packaging signal is located in the nonstructural protein 15 (nsp15) and encodes a polypeptide which is found on the surface of the nsp15 protein. Deleting the packaging signal or introducing mutations that disrupt its secondary structure but not the encoded peptide lead to the loss of packaging specificity. At the same time, relocating the packaging signal to a different part of the genome did not have a negative effect on packaging.
Other RNA families identified in the coronavirus include the SL-III cis-acting replication element (CRE), the coronavirus frameshifting stimulation element, the coronavirus 3′ stem-loop II-like motif (s2m), as well as the 5′- and 3′ UTR pseudoknot.


Jens Nielsen

Jens Nielsen is the CEO of BioInnovation Institute, Copenhagen, Denmark and Professor of Systems Biology at Chalmers University of Technology, Gothenburg, Sweden. He is Adjunct Professor at the Technical University of Denmark. He is the most cited researcher in the field of metabolic engineering, and he is the founding president of the International Metabolic Engineering Society. Jens Nielsen is the founder of several biotech companies.
Education and academic career.
Nielsen has an MSc degree in Chemical Engineering and a PhD degree (1989) in Biochemical Engineering from the Danish Technical University (DTU). He took his dr.techn. degree also from DTU. Following his PhD degree he established his independent research group at DTU and was appointed full Professor there in 1998. He was Fulbright visiting professor at MIT in 1995–1996. At DTU he founded and directed Center for Microbial Biotechnology.
In 2008 he was recruited as Professor and Director to Chalmers University of Technology, Sweden, where he built a research group of more than 60 people. At Chalmers he established the Area of Advance Life Science Engineering, a cross departmental strategic research initiative and was founding Head of the Department of Biology and Biological Engineering, which now encompass about 200 people.
Nielsen has published so far more than 700 research papers, co-authored more than 40 books and he is inventor of more than 50 patents. He was identified by Thompson Reuter/Clarivate as a highly cited researcher in 2015-2019, and according to Google Scholar he is the most cited researcher in Metabolic Engineering and top five in Synthetic Biology. He is co-author of several textbooks, and his textbook on Bioreaction Engineering Principles has been published in three editions and his textbook on Metabolic Engineering has been translated to both Chinese and Japanese.
In 2019 Jens Nielsen was recruited as CEO of BioInnovation Institute (BII), an initiative by the Novo Nordisk Foundation to support innovation and translation of science for use in society. BII support start-up companies financially and with business development, and operates an incubator that is open for early stage start-up companies in life science.
Research.
Nielsen has been studying and engineering metabolism for almost 30 years. His work has produced, among other, natural rare molecules, antibiotics and biofuels. The scope of this work is to be able to produce valuable compounds in an environmentally friendly and sustainable way that does not depend on petrol processing or extraction from endangered plant species. He is also using his unique approach and methods to study metabolism in humans, with specific interest in metabolic diseases such as type 2 diabetes, obesity, cardiovascular disease and various cancers.
Industrial microbiology.
Nielsen has worked on studying and improving many different industrial biotechnological processes. Initially he worked on physiological characterization of the filamentous fungus "Penicillium chrysogenum" that is used for penicillin production. This resulted in continued work, together with the Dutch company DSM, on development of a novel process for production of adipoyl-7-ADCA, a precursor for cephalexin. He also worked on characterization of many other fermentation processes used for antibiotics production, and through the use of his experimental and modelling techniques he assisted several companies with improving their production process. Nielsen also worked on improving fermentation processed used for production of industrial enzymes, both using fungi and bacteria.
Metabolic engineering.
In connection with his work on improving many classical and new fermentation processed Nielsen developed a number of experimental and computational tools that today is the foundation for metabolic engineering, the directed genetic modification of cells with the objective of improving the phenotype. He was the first to use gas-chromatography mass-spectrometry (GC-MS) as an experimental tool for measurement of C13-labelled metabolites with the objective to perform flux analysis. Through metabolic engineering Nielsen has developed and improved a number of biotechnological processes, e.g. 1) improved ethanol production by yeast and reduced glycerol formation as a by-product, 2) improved the temperature tolerance of yeast which has enabled ethanol production at elevated temperatures and thereby reduced costs, 3) production of a range of different chemicals using engineered yeast such as resveratrol, 3-hydroxypropionic acid, human haemoglobin, fatty acid ethyl esters, short chain fatty acids, alkanes, fatty alcohols, santalene, farnesene, coumaric acid and ornithine.
Systems biology of industrial microorganisms.
Nielsen has pioneered the development of systems biology tools for industrial microorganisms. He has developed genome-scale metabolic models (GEMs) for many important industrial microorganisms, including yeast ("Saccharomyces cerevisiae"), "Lactococcus lactis", "Streptomyces coelicolor", "Aspergillus oryzae", "Aspergillus niger", "Penicilium chrysogenum" and "Pichia pastoris". Nielsen has also developed a number of tools for performing integrative omics analysis, and he was the first to demonstrate how transcriptome data could be integrated in the context of GEMs in order to gain insight into co-regulation. He has also developed methods for performing quantitative metabolome analysis of many microorganisms as well as he has been involved in genome-sequencing of several key industrial microorganisms.
Human metabolism.
Using his systems biology toolbox developed for microorganisms, Nielsen initiated work on human metabolism. In connection with this he developed a comprehensive genome-scale metabolic model for human cells and he was the first to use a human GEM to illustrate the metabolic heterogeneity of cancer metabolism. His work on human metabolism has involved studies of different diseases such as obesity, NAFLD and NASH, and hepatocellular carcinoma. Nielsen further used human GEMs to identify that combined measurements of several glycosaminoglycans can be used as a very strong biomarker for clear cell renal cell carcinoma, probably the first systems biomarker.
Gut microbiota.
Nielsen has also used his systems biology competence to study the metabolism of the gut microbiota. He was involved in early studies on using metagenome sequencing for characterization of the gut microbiota and demonstrate that variations are associated with cardiovascular disease and type 2 diabetes. He also used his advanced metabolic modelling skills to gain further functional insight into how the gut microbiota impacts changes in plasma metabolomics in response to dietary changes.
Companies.
Nielsen founded Fluxome A/S that raised more than M20EUR in venture capital. This company metabolically engineered yeast for production of resveratrol and used this yeast for commercial production of this compound. This process was acquired by the company Evolva. Nielsen has founded several other biotech companies, including Metabogen AB, Biopetrolia AB and Elypta AB, and he has served in the scientific advisory board of a range of different biotech companies in the US and Europe.
Personal.
Nielsen is originally from Horsens in Denmark. He has a daughter named Anna-mathilde.


Mevalonate pathway

The mevalonate pathway, also known as the isoprenoid pathway or HMG-CoA reductase pathway is an essential metabolic pathway present in eukaryotes, archaea, and some bacteria. The pathway produces two five-carbon building blocks called isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are used to make isoprenoids, a diverse class of over 30,000 biomolecules such as cholesterol, vitamin K, coenzyme Q10, and all steroid hormones.
The mevalonate pathway begins with acetyl-CoA and ends with the production of IPP and DMAPP. It is best known as the target of statins, a class of cholesterol lowering drugs. Statins inhibit HMG-CoA reductase within the mevalonate pathway.
Upper mevalonate pathway.
The mevalonate pathway of eukaryotes, archaea, and eubacteria all begin the same way. The sole carbon feed stock of the pathway is acetyl-CoA. The first step condenses two acetyl-CoA molecules to yield acetoacetyl-CoA. This is followed by a second condensation to form HMG-CoA (3-hydroxy-3- methyl-glutaryl-CoA). Reduction of HMG-CoA yields (R)-mevalonate. These first 3 enzymatic steps are called the upper mevalonate pathway.
Lower mevalonate pathway.
The lower mevalonate pathway which converts (R)-mevalonate into IPP and DMAPP has 3 variants. In eukaryotes, mevalonate is phosphorylated twice in the 5-OH position, then decarboxylated to yield IPP. In some archaea such as "Haloferax volcanii", mevalonate is phosphorylated once in the 5-OH position, decarboxylated to yield isopentenyl phosphate (IP), and finally phosphorylated again to yield IPP (Archaeal Mevalonate Pathway I). A third mevalonate pathway variant found in "Thermoplasma acidophilum", phosphorylates mevalonate at the 3-OH position followed by phosphorylation at the 5-OH position. The resulting metabolite, mevalonate-3,5-bisphosphate, is decarboxylated to IP, and finally phosphorylated to yield IPP (Archaeal Mevalonate Pathway II).
Regulation and feedback.
Several key enzymes can be activated through DNA transcriptional regulation on activation of SREBP (sterol regulatory element-binding protein-1 and -2). This intracellular sensor detects low cholesterol levels and stimulates endogenous production by the HMG-CoA reductase pathway, as well as increasing lipoprotein uptake by up-regulating the LDL-receptor. Regulation of this pathway is also achieved by controlling the rate of translation of the mRNA, degradation of reductase and phosphorylation.
Pharmacology.
A number of drugs target the "mevalonate pathway":
Diseases.
A number of diseases affect the "mevalonate pathway":
Alternative pathway.
Plants, most bacteria, and some protozoa such as malaria parasites have the ability to produce isoprenoids using an alternative pathway called the methylerythritol phosphate (MEP) or non-mevalonate pathway. The output of both the mevalonate pathway and the MEP pathway are the same, IPP and DMAPP, however the enzymatic reactions to convert acetyl-CoA into IPP are entirely different. Interaction between the two metabolic pathways can be studied by using 13C-glucose isotopomers. In higher plants, the MEP pathway operates in plastids while the mevalonate pathway operates in the cytosol. Examples of bacteria that contain the MEP pathway include "Escherichia coli" and pathogens such as "Mycobacterium tuberculosis".


Primer walking

Primer walking (or Directed Sequencing) is a sequencing method of choice for sequencing DNA fragments between 1.3 and 7 kilobases. Such fragments are too long to be sequenced in a single sequence read using the chain termination method. This method works by dividing the long sequence into several consecutive short ones. The DNA of interest may be a plasmid insert, a PCR product or a fragment representing a gap when sequencing a genome. The term "primer walking" is used where the main aim is to sequence the genome. The term "chromosome walking" is used instead when the sequence is known but there is no clone of a gene. For example, the gene for a disease may be located near a specific marker such as an RFLP on the sequence.
The fragment is first sequenced as if it were a shorter fragment. Sequencing is performed from each end using either universal primers or specifically designed ones. This should identify the first 1000 or so bases. In order to completely sequence the region of interest, design and synthesis of new primers (complementary to the final 20 bases of the known sequence) is necessary to obtain contiguous sequence information.
Process.
The overall process is as follows:
The method can be used to sequence entire chromosomes (hence "chromosome walking"). Primer walking was also the basis for the development of shotgun sequencing, which uses random primers instead of specifically chosen ones.


Specificity factor

A specificity factor is an amino acid sequence that mediates target recognition in RNA polymerase. An example is the sigma subunit of the "Escherichia coli" RNA polymerase holoenzyme which regulates a binding σ subunit of molecular weight 70 kDa. Under some conditions, some of the 70-kDa subunits are replaced by one of the other, more-specific factors. For instance, when bacteria are subjected to heat stress, some of the 70-kDa subunits are replaced by a 32-kDa subunit; when bound to σ32, RNA polymerase is directed to a specialized set of promoters with a different consensus sequence.


Butofilolol

Butofilolol (trade name Cafide) is a beta-blocker drug for the treatment of essential hypertension (high blood pressure). It is not known to be marketed anywhere.


Nature Reviews Molecular Cell Biology

Nature Reviews Molecular Cell Biology is a peer-reviewed monthly review journal that was established in October 2000 and is published by Springer Nature. It covers all aspects of molecular and cell biology.
The journal had a 2019 impact factor of 55.47, ranking it first in the category "Cell Biology", and an h-index of 411.


Francis Folger Franklin

Francis Folger Franklin (October 20, 1732 November 21, 1736) was the eldest son of Founding Father of the United States Benjamin Franklin and Deborah Read.
In 1736, four-year-old Francis contracted the smallpox virus and died shortly thereafter.
Benjamin Franklin, who had been inoculated earlier in his own life, had intended for his son to be inoculated as well. However, due to an illness affecting Francis at the time planned for his inoculation, the procedure was postponed.
His death devastated both his parents, who doted upon Francis, and after this incident, Franklin became "the most eloquent advocate of smallpox inoculation."
Life.
Francis Folger Franklin was born on October 20, 1732, in Philadelphia, Pennsylvania (then a colony in British America). He was the oldest legitimate child of Benjamin Franklin, then the publisher of the Pennsylvania Gazette, and Deborah Read. Franklin also had an illegitimate son, William (born ), whose mother may have been a maid in the household, perhaps a woman named Barbara, or even Deborah Read herself. It has been suggested that William was Franklin's son by Deborah, but was acknowledged as illegitimate because he had been conceived before the marriage of his parents. Some accounts argue that William's birth was legitimized sometime after Francis' death, possibly due to the lack of an heir.
The baby's middle name, Folger, was the maiden name of Franklin's mother, Abiah. Franklin was proud of his maternal family (one of the first settlers of New England) and thus, in an era when a middle name was unusual for ordinary people to receive, Francis was baptized as Francis Folger. Francis' baptism took place on September 16, 1733, while Franklin was away, at the Anglican Christ Church in Philadelphia, which Deborah attended.
Francis, affectionately called "Franky" by his parents, was described as a "precocious, curious and special" child by Franklin, "a golden child, his smiles brighter, his babblings more telling and his tricks more magical than all the other infants in the colonies combined" by historian of medicine Howard Markel and as "a most engaging child, of singular beauty and wonderful knowingness" by biographer James Parton. Given that Franklin considered Francis to be a "healthy child who thrived from the start," and "very clever," he advertised for a tutor for his two sons in December 1734. By all accounts, Francis was doted on by his parents; his portrait was painted while he was still a baby. By 1734, Franklin's business as a writer, publisher and founder of the Library Company of Philadelphia was going well enough that he was able to build a house for his family of four, at 318 Market Street.
Death and aftermath.
Franklin and his brother, James, criticized smallpox inoculation, which was performed by drawing a string, previously in contact with the pustules of a smallpox victim, through a small incision on the person being inoculated. At the time, inoculation offered a mortality chance of 2%, while smallpox contracted naturally was fatal to 15% of the infected. Later, while James still opposed inoculation, Franklin came to support it, believing it was a "safe and beneficial practice." In 1736, however, Francis contracted smallpox and died on November 21 of that year, without having been inoculated. Both Franklin and Deborah were devastated, and their devastation was compounded because they were unsure they could have another child. Franklin had written his paper, "On the Death of Infants", while Francis was still alive, and was inspired by his youngest son when writing about the beauty of babies. Francis was buried on the same day he died, his tombstone reading "The delight of all who knew him."
Rumors quickly surfaced that Francis had died after being inoculated, and so, Franklin wrote in the "Pennsylvania Gazette", on December 30, that "[he] intended to get [Francis] inoculated as soon as he should have recovered sufficient strength from a flux with which he had been long afflicted," and that the boy "received the distemper in the common way of infection." However, the choice of having his son inoculated was a difficult one for Franklin, as Francis could die either way. Inoculation would become a real choice only if there was a high chance of smallpox being contracted naturally. In this case, the choice of having Francis inoculated was justified, even with its 2% mortality rate.
After Francis' death, Franklin became involved in promoting inoculation in Philadelphia: he published many studies on its value, working with several physicians, including the famed William Heberden at the Pennsylvania Hospital, which he helped found. In 1774, he founded the "Society for Inoculating the Poor Gratis", in order to help the poor people of Philadelphia afford inoculation. In his autobiography, Franklin writes: "In 1736 I lost one of my sons, a fine boy of four years old, by the smallpox taken in the common way. I long regretted bitterly and still regret that I had not given it to him by inoculation. This I mention for the sake of the parents who omit that operation, on the supposition that they should never forgive themselves if a child died under it; my example showing that the regret may be the same either way, and that, therefore, the safer should be chosen."
Seven years after Francis' death, Deborah gave birth to Sarah, who was Franklin's only surviving, legitimate child. In 1772, Franklin's sister Jane Franklin Mecom, wrote him with news of his grandsons. Franklin replied that it "brings often afresh to my mind the idea of my son Franky, though now dead thirty-six years, whom I have seldom since seemed equaled in everything, and whom to this day I cannot think of without a sigh."


Arylsulfatase

Arylsulfatase (, "sulfatase", "nitrocatechol sulfatase", "phenolsulfatase", "phenylsulfatase", "p-nitrophenyl sulfatase", "arylsulfohydrolase", "4-methylumbelliferyl sulfatase", "estrogen sulfatase") is a type of sulfatase enzyme with systematic name "aryl-sulfate sulfohydrolase". This enzyme catalyses the following chemical reaction
This group of enzymes has similar specificities.
Types include:


Nanodomain

A nanodomain is a nanometer-sized cluster of proteins found in a cell membrane. They are associated with the signal which occurs when a single calcium ion channel opens on a cell membrane, allowing an influx of calcium ions (Ca) which extend in a plume a few tens of nanometres from the channel pore. In a nanodomain, the coupling distance, that is, the distance between the calcium-binding proteins which sense the calcium, and the calcium channel, is very small, less than , which allows rapid signalling. The formation of a nanodomain signal is virtually instantaneous following the opening of the calcium channel, as calcium ions move rapidly into the cell along a steep concentration gradient. The nanodomain signal collapses just as quickly when the calcium channel closes, as the ions rapidly diffuse away from the pore. Formation of a nanodomain signal requires the influx of only approximately 1000 calcium ions.
Coupling distances greater than , mediated by a larger number of channels, are referred to as microdomains. nanodomain
Properties.
Nanodomain signals are thought to improve the temporal precision of fast exocytosis of vesicles due to two specific properties:
Single channels are able to cause vesicular release, however, the cooperativity of different calcium channels is synapse-specific. The release driven by a single calcium ion channel minimizes the total calcium ion influx, overlapping domains can provide greater reliability and temporal fidelity.


7,N,N-TMT

7,"N","N"-Trimethyltryptamine (7-methyl-DMT, 7-TMT), is a tryptamine derivative which acts as an agonist of 5-HT2 receptors. In animal tests, both 7-TMT and its 5-methoxy derivative 5-MeO-7-TMT produced behavioural responses similar to those of psychedelic drugs such as DMT, but the larger 7-ethyl and 7-bromo derivatives of DMT did not produce psychedelic responses despite having higher 5-HT2 receptor affinity "in vitro" (cf. DOBU, DOAM). 7-TMT also weakly inhibits reuptake of serotonin but with little effect on dopamine or noradrenaline reuptake.


Methyl-DOB

Methyl-DOB, or 4-bromo-2,5-dimethoxy-N-methylamphetamine, is a lesser-known psychedelic drug. It is similar in structure to DOB. Methyl-DOB was first synthesized by Alexander Shulgin. In his book "PiHKAL (Phenethylamines i Have Known And Loved)", the minimum dosage is listed as 8 mg, and the effects onset begin after 3 hours and last up to 36 hours. Methyl-DOB produces many physical effects, such as mydriasis and muscle tenseness, but few psychoactive effects. Very little data exists about the pharmacological properties, metabolism, and toxicity of Methyl-DOB.


Benjamin Weiss (scientist)

Benjamin Weiss (January 26, 1937) is an American neuropharmacologist, Emeritus Professor of Pharmacology and Physiology at Drexel University College of Medicine. He is best known for his work with cyclic nucleotide phosphodiesterases. He was the first to propose, based on his experimental work, that selective inhibition of phosphodiesterases which are expressed differentially in all tissues, could be used as a target for drug development. His work is the basis for many marketed and developmental human drugs that selectively inhibit cyclic nucleotide phosphodiesterases.
His investigations on the modulation of adrenergic responses in the pineal gland have resulted in the formation of new concepts that may explain the phenomena of drug tolerance and drug hypersensitivity. He and his laboratory were also instrumental in the development of antisense oligonucleotides and antisense RNA as pharmacological tools to study calmodulin and dopamine receptors, and as pharmacological agents for antisense therapy in brain and other tissue.
Early life and education.
Weiss was born in The Bronx in 1937 and was raised on a chicken farm in New Jersey where his immigrant parents moved in 1946. Weiss went to Toms River High School, graduating in 1954. He received his undergraduate degree in Pharmacy in 1958 from the Philadelphia College of Pharmacy and Science (now, University of the Sciences), where he also earned a M.Sc. in 1960 and a Ph.D. in Pharmacology in 1963, under the tutelage of G. Victor Rossi. From 1963-1966 he had a Postdoctoral Fellowship and a Staff Fellowship at the National Heart Institute, National Institute of Health, where he studied under Bernard B. Brodie. He did further training as a Research Associate at Columbia University, College of Physicians and Surgeons, with Erminio Costa from 1966-1968.
Personal life.
In 1959 Weiss married Joyce Zelnick. They have three children and five grandchildren.
Scientific career.
From 1968 to 1972 Weiss worked at the National Institute of Mental Healthat St Elizabeths Hospital, Washington, D.C., where he held the position of Chief of the Section on Neuroendocrinology. In 1972 he accepted the position of Professor of Pharmacologyat the Medical College of Pennsylvania (MCP), where he held the positions of Professor of Pharmacology and Psychiatry, and Chief of the Division of Neuropsychopharmacology. He was also a Visiting Scientist at the Mario Negri Institute for Pharmacological Researchin Milan, Italy, and a Visiting Scientist at the Weizman Institute of Science in Israel. On retirement in 1999 he became an Emeritus Professor of Pharmacology and Psychiatry. In 2002, when Drexel University assumed leadership of MCP, he was given the position of Emeritus Professor of Pharmacology and Physiology at Drexel University College of Medicine, the position he now holds.
Publications.
Weiss edited two books: one on the potential therapeutic application of cyclic nucleotides: (Weiss, Benjamin, ed., Cyclic Nucleotides in Disease[1]), and another on the development and use of antisense oligonucleotides and antisense RNA as pharmacological tools and gene therapy Antisense Oligodeoxynucleotides and Antisense RNA: Novel Pharmacological and Therapeutic Agents[2)). He has also published over 300 scientific articles, reviews and abstracts on his research in the fields of Molecular Biology and Molecular Pharmacology.
Research.
Cyclic Nucleotide Phosphodiesterases:
Weiss and co-workers developed rapid phosphodiesterease assays [3, 4], separated different isozymes of phosphodiesterase in various tissues by electrophoretic methods [5,6]and showed that drugs could selectively inhibit the several isozymes of phosphodiesterase (link) isozymes. He showed that a single cell type may contain more than one form of phosphodiesterase [6,7] and that different forms of phosphodiesterase could be induced or activated by certain neurohormones(e.g. norepinephrine) [7]and intracellular proteins (e.g. calmodulin) [8,9]. He demonstrated that there are different forms of phosphodiesterase in different tissues including the mammalian brain [5,6]and lung [10].
Weiss was the first to show that phosphodiesterase activity is altered in certain disease states [11, 13, 14, 15,16]and to propose that selective inhibition of phosphodiesterase could be the basis of drug selectivity [17,18,19,20]. Weiss and co-workers did extensive work which demonstrated that certain neuropeptides [21,22], alpha adrenergic antagonists [23]and phenothiazineantipsychotic drugs were potent inhibitors of calmodulin activated enzymes [24,25,26,27,28].
Modulation of Adrenergic Receptor-Linked Adenylate Cyclase System: Using the pineal gland as a model, Weiss and his colleagues were the first to show that the beta-adrenergic receptor-linked adenylate cyclasesystem is modified chronically by a variety of physiological factors and pharmacological perturbations [reviewed in 29]. His laboratory demonstrated that this system is influenced by sympathetic neuronal input, in that a long-term decrease in sympathetic input results in an increased responsiveness to adrenergic stimuli [30, 31]; by environmental lighting, in that darkness, which increased sympathetic input to the pineal gland decreases the response to adrenergic input[32]; by hormonal status, in that low estrogen levels increase the responsiveness to norepinephrine[33]and by the age of the animal, in that older animals evidence a decrease in beta-adrenergic receptors and a reduced response to adrenergic stimuli [34,35,36].
Weiss showed additionally that the responses to adrenergic stimuli are also altered by a variety of pharmacological agents that chronically change adrenergic input. For example, long term treatment with agents that reduce sympathetic input, like reserpine[37], 6-hydroxydopamine[38], guanethidine[39], and certain phenothiazine antipsychotic drugs [40]all increase the density of beta-adrenergic receptors and increase the responsiveness to adenylate cyclase. By contrast, treatment with drugs such as the anti-depressant desmethyimipramine, which increases adrenergic input, reduces the adrenergic receptors [41].These studies show that long-term changes ollowing physiological or pharmacological alterations in adrenergic input may be explained by a common biological principle: the degree to which an adrenergically-innervated structure can be stimulated is inversely related to the degree to which it had been previously stimulated. This hypothesis may provide a biochemical basis for explaining the altered responsiveness of the adrenergic system seen in aging and in males vs. females, and may explain the mechanism for drug supersensitivity and drug tolerance.
Antisense Oligonucleotidesand Antisense RNA:Weiss’ laboratory made discoveries on: 1) The role of calmodulin in neuronal differentiation and proliferation; 2) Behavioral and biochemical correlates of dopamineresponses in brain; 3) Development of antisense oligonucleotides and antisense RNA as pharmacological tools to study calmodulin and dopamine receptors, and as pharmacological agents for gene therapy in brain; and 4) Reversal of dopaminergic supersensitivity: preclinical mechanisms and clinical applications. 6) The studies laid the foundation for the therapeutic use of antisense oligonucleotides and antisense RNA in a variety of disease states. A number of drugs are currently on the market and many others are in clinical development using the concept of antisense therapy, including in cancer, Huntington’s Disease, and other neurological diseases.
Weiss and his group, assisted by Genoveva Uzunova (Davidkova), who carried out a significant part of the antisense RNA studies in his group, used molecular biological, biochemical, pharmacological, cell biological techniques (cell cultures, fluorescence microscopy), and mouse models, to develop antisense oligonucleotides to the D1 and D2 dopamine receptors. They showed for the first time that intracerebroventricular (i.c.v.) and intrastriatal injection oligonucleotides targeted to the D1 or D2 dopamine receptor in mouse brain can block the biological effects of the targeted receptor with very high specificity and, importantly, without inducing receptor supersensitivity, which is a significant drawback to the conventional neuroleptic drugs such as haloperidol[42,43,44]. Therefore, these novel pharmacological agents would not likely induce the debilitating motor side effects resulting from conventional pharmacological agents..
Since the effects of the oligonucleotides are relatively short-lasting (up to 2–3 days) and it is necessary to inject them repeatedly in mouse brain in order to achieve a long-term reduction in the D2 dopamine receptor mRNA and the dopamine receptor protein, and the concomitant long-term blockade of the behaviors modulated by these receptors, Weiss’ group developed a second approach – expression of D2 dopamine antisense RNA in brain by a non-viral plasmid vector. This approach was the first to show that a single intrastriatal injection of D2dopamine receptor antisense RNA (targeted to the long isoform of the murine D2 dopamine receptor) can effectively block D2 dopamine-mediated behaviors for up to one month [45]. Moreover, this did not induce D2 receptor supersensitivity, unlike the conventional neuroleptic haloperidol, which blocks D2 dopamine receptors and several other subtypes of dopamine receptors [46]. These studies opened up the possibility to develop a new gene therapeutic approachto treat neurologic and psychiatric conditions associated with D2 receptor hyperactivity such as chorea and addiction to alcohol [47]. In a broader perspective, a similar gene therapeutic approach targeting other central nervous system (CNS) neuroreceptors and proteins may prove useful for treating other disorders of the CNS . The antisense RNA approach is an alternative to the RNA interference approach. RNA interference.
During this period, the studies of Weiss and his group were also focused on the use of antisense oligonucleotides [48]and antisense RNA expression vectors to calmodulin [49] ,which is a ubiquitous calcium binding protein in brain encoded by three different genes that give rise to several transcripts. These studies helped to elucidate the essential role of calmodulin in the proliferation and differentiation of nerve cells and suggest a novel approach with the potential for gene therapy of tumors that express high levels of calmodulin, such as gliomas and certain forms of breast cancer. [50,51].
Honors and awards.
In 2001, Drexel University College of Medicine established a Graduate Student Fellowship in his name.
References.
1. Weiss, B.: Editor, Cyclic Nucleotides in Disease, University Park Press, Baltimore, MD. 1975.
2. Weiss, B.: Editor: Antisense Oligodeoxynucleotides and Antisense RNA: Novel Pharmacological and Therapeutic Agents CRC Press, Boca Raton, FL. 1997.
3.Weiss B, Lehne R, Strada S. Rapid microassay of adenosine 3',5'-monophosphate phosphodiesterase activity. Anal Biochem. 1972 Jan;45(1):222-35. .
4. Fertel R, Weiss B.: A microassay for guanosine 3',5'-monophosphate phosphodiesterase activity. Anal Biochem. 1974 Jun;59(2):386-98. .
5. Uzunov, P. and Weiss, B.: Separation of multiple molecular forms of cyclic adenosine 3',5'‑monophosphate phosphodiesterase in rat cerebellum by polyacrylamide gel electrophoresis. Biochim. Biophys. Acta 284:220‑226, 1972.
6. Uzunov, P., Shein, H.M. and Weiss, B.: Multiple forms of cyclic 3',5'‑AMP phosphodiesterase of rat cerebrum and cloned astrocytoma and neuroblastoma cells. Neuropharmacology 13:377‑391, 1974.
7. Uzunov, P., Shein, H.M. and Weiss, B.: Cyclic AMP phosphodiesterase in cloned astrocytoma cells: norepinephrine induces a specific enzyme form. Science 180:304‑306, 1973.
8. Weiss, B., Prozialeck, W., Cimino, M., Barnette, M.S. and Wallace, T.L.: Pharmacological regulation of calmodulin. In: Calmodulin and Cell Functions, Ann. N.Y. Acad. Sci. 356:319‑345, 1980.
9. Weiss, B., Prozialeck, W.C. and Wallace, T.L.: Interaction of drugs with calmodulin: Biochemical, pharmacological and clinical implications. Biochem. Pharmacol. 31:2217‑2226, 1982.
10. Fertel, R. and Weiss, B.: Properties and drug responsiveness of cyclic nucleotide phosphodiesterases of rat lung. Mol. Pharmacol. 12:678‑687, 1976. Hait, W.N. and Weiss, B.: Increased cyclic nucleotide phosphodiesterase activity in leukemic lymphocytes. Nature 259:321‑323, 1976.
11. Hait, W.N. and Weiss, B.: Characteristics of the cyclic nucleotide phosphodiesterases of normal and leukemic lymphocytes. Biochim. Biophys. Acta 497:86‑100, 1977.
12. Hait, W.N. and Weiss, B.: Increased cyclic nucleotide phosphodiesterase activity in leukemic lymphocytes. Nature 259:321‑323, 1976.
13. Levin, R.M. and Weiss, B.: Characteristics of the cyclic nucleotide phosphodiesterases in a transplantable pheochromocytoma and adrenal medulla of the rat. Cancer Res. 38:915‑920, 1978.
14. Weiss, B. and Winchurch, R.A.: Analyses of cyclic nucleotide phosphodiesterases in lymphocytes from normal and aged leukemic mice. Cancer Res. 38:1274‑1280, 1978.
15. Winchurch, R., Hait, W. and Weiss, B.: Cyclic AMP phosphodiesterase activity of murine T and
B lymphocytes. Cell. Immunol. 41:421‑426, 1978.
16. Hait, W.N. and Weiss, B.: Cyclic nucleotide phosphodiesterase of normal and leukemic lymphocytes: kinetic properties and selective alteration of the activity of the multiple molecular forms. Mol. Pharmacol. 16:851‑864, 1979.
17. Levin, R.M. and Weiss, B.: Mechanism by which psychotropic drugs inhibit adenosine cyclic 3',5'‑monophosphate phosphodiesterase of brain. Mol. Pharmacol. 12:581‑589, 1976.
18. Levin, R.M. and Weiss, B.: Binding of trifluoperazine to the calcium‑dependent activator of cyclic nucleotide phosphodiesterase. Mol. Pharmacol. 13:690‑697, 1977. (a)
19. Levin, R.M. and Weiss, B.: Selective binding of antipsychotics and other psychoactive agents to the calcium‑dependent activator of cyclic nucleotide phosphodiesterase. J. Pharmacol. Exp. Ther. 208:454‑459, 1979.
20. Levin, R.M. and Weiss, B.: Specificity of the binding of trifluoperazine to the calcium‑dependent activator of phosphodiesterase and to a series of other calcium‑binding proteins. Biochim. Biophys. Acta 540:197‑204, 1978. (b)
21. Sellinger‑Barnette, M. and Weiss, B.: Interaction of beta‑endorphin and other opioid peptides with calmodulin. Mol. Pharmacol. 21:86‑91, 1982.
22. Barnette, M.S. and Weiss, B.: Interaction of neuropeptides with calmodulin. A structure‑activity study. Psychopharmacol. Bull., 19:387‑392, 1983.
23. Earl CQ, Prozialeck WC, Weiss B.: Interaction of alpha adrenergic antagonists with calmodulin. Life Sci. 1984 Jul 30;35(5):525-34. .
24. Weiss, B. and Hait, W.N.: Selective cyclic nucleotide phosphodiesterase inhibitors as potential therapeutic agents. Ann. Rev. Pharmacol. Toxicol. 17:441‑477, 1977.
25. Weiss, B. and Levin, R.M.: Mechanism for selectively inhibiting the activation of cyclic nucleotide phosphodiesterase and adenylate cyclase by antipsychotic agents. Adv. Cycl. Nucl. Res. 9:285‑304, 1978.
26. Prozialeck, W.C. and Weiss, B.: Inhibition of calmodulin by phenothiazines and related drugs; structure‑activity relationships. J. Pharmacol. Exptl. Therap. 222:509‑516, 1982.
27. Weiss, B., Earl, C. and Prozialeck, W.C.: Biochemical and possible neuropsychopharmacological implications of inhibiting calmodulin activity. Psychopharmacol. Bull., 19:378‑386, 1983.
28. Weiss, B., Prozialeck, W.C. and Roberts‑Lewis, J.M.: Development of selective inhibitors of calmodulin‑dependent phosphodiesterase and adenylate cyclase; in Design of Enzyme Inhibitors as Drugs, ed. M. Sandler and H.J. Smith, Oxford University Press, New York, pp. 650‑697, 1989.
29. Weiss, B., Greenberg, L.H. and Clark, M.B.: Physiological and pharmacological modulation of the beta-adrenergic receptor-linked adenylate cyclase system: supersensitivity and subsensitivity. In: Dynamics of Neurotransmitter Function, ed. I. Hanin, Raven Press, New York, pp. 319–330, 1984.
30. Weiss, B. and Costa, E.: Adenyl Cyclase activity in rat pineal gland: Effects of chronic denervation and norepinephrine. Science 156:1750-1752, 1967.
31. Strada, S.J. and Weiss, B.: Increased response to catecholamines of the cyclic AMP system of rat pineal gland induced by decreased sympathetic activity. Arch. Biochem. Biophys. 160:197- 204, 1974.
32. Weiss, B.: Effects of environmental lighting and chronic denervation on the activation of adenyl cyclase of rat pineal gland by norepinephrine and sodium fluoride. J. Pharmacol. Exp. Ther. 168:146-152, 1969.
33. Weiss, B. and Crayton, J.: Gonadal hormones as regulators of pineal adenyl cyclase activity. Endocrinology 87:527-533, 1970.
34. Greenberg, L.H., Dix, R.K. and Weiss, B.: Age-related changes in the binding of dihydroalprenolol in rat brain. In: Pharmacological Intervention in the Aging Process, eds. J. Roberts, R.C. Adelman and V.J. Cristofalo, Plenum Press, New York, pp. 245–249, 1978.
35. Greenberg, L.H. and Weiss, B.: Beta adrenergic receptors in aged rat brain: reduced number and capacity of pineal gland to develop supersensitivity. Science 201:61-63, 1978.
36. Weiss, B., Greenberg, L.H. and Cantor, E.: Denervation supersensitivity and beta-adrenergic receptors as a function of age. In: Receptors for Neurotransmitters and Peptide Hormones, eds. G. Pepeu, M.J. Kuhar and S.J. Enna, Raven Press, New York, p 461-472, 1980.
37. Greenberg, L.H. and Weiss, B.: Ability of aged rats to alter beta-adrenergic receptors of brain in response to repeated administration of reserpine and desmethylimipramine. J. Pharmacol. Exp. Ther. 211:309-316, 1979.
38. Strada, S.J., Uzunov, P. and Weiss, B.: Increased sensitivity to norepinephrine (NE) of the cyclic 3',5'-AMP (cAMP) system of rat brain following 6-hydroxydopamine (6-HDM). Pharmacologist 13:257, 1971.
39. Glaubiger, G., Tsai, B.S., Lefkowitz, R.J., Johnson, E.M., Jr. and Weiss, B.: Chronic guanethidine treatment increases cardiac beta-adrenergic receptors. Nature 273:240-242, 1978.
40. Weiss, B. and Greenberg, L.H.: Modulation of beta-adrenergic receptors and calmodulin following acute and chronic treatment with neuroleptics. In: Adv. Biochem. Psychopharmacol., Vol. 24 - Long-Term Effects of Neuroleptics, eds. F. Cattabeni, G. Racagni, P.F. Spano and E. Costa, Raven Press, New York, pp. 139–146, 1980.
41. Moyer, J.A., Greenberg, L.H., Frazer, A., Brunswick, D.J., Mendels, J. and Weiss, B.: Opposite effects of acute and repeated administration of desmethylimipramine on adrenergic responsiveness in rat pineal gland. Life Sci. 24:2237-2244, 1979.
42. Weiss, Benjamin; Long-Wu, Zhou; Zhang, Sui-Po; Qin Z-H. (1993). “Antisense oligodeoxynucleotide inhibits D2 dopamine receptor-mediated behavior and D2 messenger RNA” "Neuroscience"55(3): 607-612. https:// doi:10.1016/0306-4522(93)90426-G
43. Zhang, Sui-Po; Long-Wu, Zhou; Weiss, Benjamin (1994). “Oligodeoxynucleotide to the D1 dopamine receptor mRNA inhibits D1 dopamine receptor-mediated behaviors in normal mice and in mice lesioned with 6-hydroxydopamine” "J. Pharmacol. Experimental Ther."271(3): 1462- 1470.
44. Weiss, Benjamin; Zhang, Sui-Po; Zhou, Long-Wu (1997) “Antisense strategies in dopamine receptor pharmacology” "Life Sciences"60(7): 433-455. doi:10.1016/S0024-3205(96)00566-8
45. Weiss, Benjamin; Davidkova, Genoveva; Zhou, Long-Wu, Zhang, Sui-Po, Morabito, Mark (1997). “Expression of a D2 dopamine receptor antisense RNA in brain inhibits D2-mediated behaviors” "Neurochemistry International"31(4): 571-580. doi:10.1016/S0197-0186(97)00025-9
46. Davidkova, Genoveva; Zhou, Long-Wu; Morabito, Mark; Zhang, Sui-Po; Weiss, Benjamin (1998). “D2 dopamine antisense RNA expression vector, unlike haloperidol, produces long-term inhibition of D2 dopamine-mediated behaviors without causing up-regulation of D2 dopamine receptors” J. Pharmacol. Exper. Therapeutics 285(3): 1187-1196.
47. Weiss, Benjamin; Davidkova, Genoveva; Zhou, Long-Wu (1999).”Antisense RNA gene therapy for studying and modulating biological processes” "Cell Mol. Life Sci."55(3): 334-358. doi:10.1007/s000180050296
48. Hou, Wang-Fang; Zhang, Sui-Po; Davidkova, Genoveva; Nichols, Robert; Weiss, Benjamin (1998) “Effects on antisense oligonucleotides directed to individual calmodulin gene transcripts on the proliferation and differentiation of PC12 cells” "Antisense Nucleic Acids Drug Dev". 8(4): 295-308. doi:10.1089/oli.1.1998.8.295
49. Davidkova, Genoveva; Zhang, Sui-Po; Nichols, Robert; Weiss, Benjamin (1996) “Reduced level of calmodulin in PC12 cells induced by stable expression of calmodulin antisense RNA inhibits cell proliferation and induces neurite outgrowth” "Neuroscience"75(4): 1003-1019. doi:10.1016/0306-4522(96)00230-8
50. Hait, W.N. and Lazo, J.S.: Calmodulin: a potential target for cancer chemotherapeutic agents. J. Clin. Oncol. 4:994-1012, 1986.
51. Mayur, Y.C., Jagadeesh, S. and Thimmaiah, K.N.: Targeting calmodulin in reversing multi drug resistance in cancer cells. Mini Rev. Med. Chem. 6:1383-1389, 2006.


William Henry Johnson (valet)

William Henry Johnson (March 4, 1833 – January 28, 1864) was a free African American and the personal valet of Abraham Lincoln. Having first worked for Lincoln in Springfield, Illinois, Johnson accompanied the President-Elect to Washington, D.C. for his first inauguration (1861).
Once there, he was employed in various jobs, part-time as President's valet and barber, and later, following strife with others on the White House staff, as a messenger for the Treasury Department at $600 () per year. He traveled with Lincoln in November 1863 to Gettysburg, Pennsylvania, where Lincoln gave the Gettysburg Address. While traveling, Lincoln experienced symptoms of the onset of smallpox. At that time, an epidemic was spreading through Washington, D.C. and Lincoln's son Tad Lincoln had smallpox. Johnson tended to Lincoln and became quite ill by January 12, 1864, when he was admitted to a hospital. Johnson died within the next couple of weeks.
Personal life.
Johnson's mother was an enslaved woman. He had a growing family while living in Washington, D.C. Dick Hart, past president of the Abraham Lincoln Association and historian who focuses on black history in Springfield, has been unsuccessful in finding any information about Johnson in Springfield. Lincoln guaranteed the mortgage on a house for Johnson.
Career.
Abraham Lincoln employed Johnson as a valet and driver in Springfield, Illinois during the time of the 1860 United States presidential election. The Lincolns hosted an event for the Republican Presidential Nomination Notification Committee on May 19, 1860 at their house in Springfield, Illinois. Johnson announced people as they entered the house and directed them to the parlour to meet Abraham and Mary Todd Lincoln. Either before or while working for Lincoln, he was also a bootblack and barber.
Lincoln brought Johnson with him to the White House for his first inauguration. During the train trip, Johnson was observed by reporters to be attentive with untiring vigilance and acted as if he was an unofficial bodyguard. Lincoln said that Johnson was a worthy man of integrity and faithfulness. To evade an assassination attempt (called the Baltimore Plot), Lincoln left the train he was expected to arrive on in Washington. He boarded another train that took him from Harrisburg, Pennsylvania to Washington, transferring under cover of darkness in Baltimore. Lincoln's lawyer friend, Ward Hill Lamon, was the only person from Lincoln's Illinois entourage known to have traveled from Harrisburg through Baltimore to Washington with Lincoln to elude potential assassins of the Baltimore Plot, and there is no record that Johnson was present on this dangerous stretch of the journey. [Lamon, 42–47; Holzer, 392–396].
Johnson worked for Lincoln as a barber, valet, handyman, messenger, and bodyguard. The president said of him, "although not exactly the most prominent, [he] is yet the most useful member of the presidential party." Lincoln trusted him to convey messages, and at times significant sums of money.
He was shunned and treated miserably by other White House servants, because they were not welcoming of newcomers, did not want a change in the established pecking order among staff, and disliked that he was a particularly dark-skinned African-American. Until that point, all servants of the White House were light-skinned. It was clear within the first week that an employment change was needed for Johnson. Lincoln first wrote to the Secretary of the Navy Gideon Welles, but a suitable position was not found. In the meantime, Johnson continued his position, running errands some days that would take him out of the mansion for part or all of the day. At Lincoln's request, Secretary of the Treasury Salmon P. Chase gave him a job in November or December, 1861, first as a laborer, and soon after as a messenger. [Roy P. Basler, ed., Collected Works of Abraham Lincoln, V, 33].
If Lincoln needed Johnson's assistance for errands or tasks, he would send a message to his supervisor, Samuel Yorke At Lee, at the Treasury. Before working at the Treasury each workday morning, Johnson went to the White House and shaved and dressed Lincoln, which provided extra income.
Besides both men having felt free to ask favors of one another, it is assumed that Johnson was treated equitably as any other man. Frederick Douglass, the black abolitionist, said of Lincoln, "He was the first great man that I talked with in the United States freely, who in no single instance reminded me of the difference between himself and myself, of the difference of color…" When he referred to him in letters, though, Lincoln called the 27 year-old Johnson a "colored boy." [Basler, Collected Works, V, 33]
In 1862, Johnson accompanied Lincoln to the Antietam Battlefield after the battle and the Confederate Army had left the area. He went with Lincoln on other trips.
Smallpox.
There was a smallpox epidemic in Washington, D.C. during the winter of 1863–1864. On November 18, 1863, Johnson traveled by train with Lincoln to Gettysburg, Pennsylvania, for the dedication of the Soldiers' National Cemetery where Lincoln would deliver the Gettysburg Address. On the train ride to Gettysburg, Lincoln looked "sallow, sunken-eyed, thin, [and] careworn".
Lincoln's son, Tad Lincoln, had smallpox on the day that Lincoln left for Gettysburg, which prevented Mary Todd Lincoln from traveling with the President.
During Lincoln's speech, he was described by newspaper reporters as "listless", "sweating", and "discouraged". On the return trip Lincoln went to bed in the Presidential train car with a bad headache. Johnson kept his forehead cool by bathing his forehead in cold water.
Lincoln's illness was diagnosed as "Varioloid" which is a mild form of smallpox. Long thought to have been only a mild case, recent work suggests it was a serious illness. He was bedridden and finally recovering on December 15.
Johnson cared for Lincoln during his illness. Johnson contracted the disease and ultimately died in mid-January 1864. Lincoln paid off the mortgage on the Johnson family's house and sent money to his family. He paid off half of a loan that he had cosigned; the banker insisted on canceling the other half of the debt.
Burial.
Lincoln also paid for Johnson's burial at an unknown location. While many modern accounts have placed Johnson's grave in Arlington National Cemetery, all such claims are ultimately based on the same, almost certainly incorrect assumption by the historian Roy P. Basler.
In 1972, Basler claimed that Lincoln had buried Johnson in grave no. 3346 in Section 27 of Arlington National Cemetery, where there is indeed a headstone for one "William H. Johnson, Citizen." In 1977, Basler admitted, however, that he had originally decided to search Arlington "on a hunch," and that he had no evidence connecting the occupant of that grave (or even the cemetery at large) to Lincoln's valet of the same name. In 2006, Gabor Boritt repeated Basler's original anecdote, adding, without substantiation, that Lincoln himself had ordered that Johnson's headstone be inscribed with the epitaph, "Citizen." In 2010, Eric Foner in turn cited Boritt's work, further adding, also without substantiation, that Lincoln "chose the one-word-inscription [as] a direct refutation of the "Dred Scott" decision."
In 2012, Phillip W. Magness and Sebastian N. Page challenged all the above "embellishments" to the simple fact of Lincoln having paid for Johnson's coffin. Magness and Page observed that "Citizen" appears on all headstones in Section 27 at Arlington, having been used as a synonym for "Civilian" in the brief period before the cemetery became an exclusively military one. Moreover, they noted that the headstone visible today is a 1990s replacement for an original erected only in the 1870s, thus precluding Lincoln's involvement with any inscription; that Johnson's name, even with his middle initial, was too common for historians to reasonably assume the relevant grave his; and that, when Johnson died, the official conversion of the Arlington estate to a cemetery lay some months in the future. Instead, the single likeliest resting-place for an early 1864 black victim of smallpox was Columbian Harmony Cemetery, cleared in 1959 for redevelopment.
In popular culture.
William H. Johnson was a character in the 2012 film "", played by actor Anthony Mackie. In the film, Lincoln and Johnson are portrayed as childhood friends. In the film's opening scene, a young Lincoln rushes to the aid of a young Johnson, who is being whipped by a slaver. Johnson then goes on to work in the Lincoln White House and assist President Lincoln in his fight against the vampiric forces of the Confederate Army.


Photosynthetic pigment

A photosynthetic pigment (accessory pigment; chloroplast pigment; antenna pigment) is a pigment that is present in chloroplasts or photosynthetic bacteria and captures the light energy necessary for photosynthesis.
Plants pigments (in order of increasing polarity):
Chlorophyll "a" is the most common of the six, present in every plant that performs photosynthesis. The reason that there are so many pigments is that each absorbs light more efficiently in a different part of the electromagnetic spectrum. well at a wavelength of about 400–450 nm and at 650–700 nm; chlorophyll "b" at 450–500 nm and at 600–650 nm. Xanthophyll absorbs well at 400–530 nm. However, none of the pigments absorbs well in the green-yellow region, which is responsible for the abundant green we see in nature.
Bacteria.
Like plants, the cyanobacteria use water as an electron donor for photosynthesis and therefore liberate oxygen; they also use chlorophyll as a pigment. In addition, most cyanobacteria use phycobiliproteins, water-soluble pigments which occur in the cytoplasm of the chloroplast, to capture light energy and pass it on to the chlorophylls. (Some cyanobacteria, the prochlorophytes, use chlorophyll b instead of phycobilin.) It is thought that the chloroplasts in plants and algae all evolved from cyanobacteria.
Several other groups of bacteria use the bacteriochlorophyll pigments (similar to the chlorophylls) for photosynthesis. Unlike the cyanobacteria, these bacteria do not produce oxygen; they typically use hydrogen sulfide rather than water as the electron donor.
Recently, a very different pigment has been found in some marine γ-proteobacteria: proteorhodopsin. It is similar to and probably originated from bacteriorhodopsin (see below: under #Archaea).
Bacterial chlorophyll b has been isolated from Rhodopseudomonas spp. but its structure is not yet known to us.
Archaea.
Halobacteria use the pigment bacteriorhodopsin which acts directly as a proton pump when exposed to light.


FtsK

FtsK is a 1329 amino acid protein involved in bacterial cell division and chromosome segregation. FtsK stands for "Filament temperature sensitive mutant K" because at high temperatures the mutant bacterial cell fails to divide and long filaments develop instead. FtsK, and specifically its C-domain, functions as DNA pump, interacts with other cell division proteins, and intervenes in the regulation of the Xer recombination process. FtsK belongs to the AAA (ATPase Associated with various cellular Activities) superfamily and is present in most bacteria.
Structure.
FtsK is a transmembrane protein composed of three domains: FtsKN, FtsKL, and FtsKC. Through its N- domain and C-domain FtsK works to coordinate cell division and chromosome differentiation. The FtsKN domain is embedded in the cellular membrane by four transmembrane α-helices. The FtsKL domain extends from the membrane into the cytoplasm. This linking domain varies in length across many bacteria. Found at the cytoplasmic end of the linker domain, the FtsKC segment of the protein is responsible for enabling the activity of the Xer recombination system upon the formation of a chromosome dimer.
Additionally, the FtsKC domain is composed of three subdomains: α, β, and γ. The α and β subunits aggregate to form a hexamer that possesses the ability to translocate DNA through ATP hydrolysis. The ATP hydrolysis sites are found on the β subunits of the hexamer. The γ domain is responsible for the control of the hexamer. It mediates the attachment of the hexamer to double-stranded DNA, controls the directionality of the translocase, and initiates chromosome dimer segregation.
Mechanism of Action.
The "dif" Site.
The "dif" site is found at the intersection between the monomers of the chromosome dimer. It corresponds to where chromosomal replication ceased and is also the site of Xer mediated segregation. Translocation of the FtsKC hexamer stops when it reaches the location of the Xer recombinase complex that is associated with the "dif" site.
Binding Site.
Guanosine rich areas of DNA, which are found at the ends of the "dif" region, are the sites of translocation initiation. These sites are referred to as KOPS motifs. Upon binding a KOPS motif, the FtsK hexamer forms and proceeds towards the "dif" region. Movement toward the "dif" region is facilitated by the polarity of the KOPS motif.
Translocation.
There are three proposed mechanisms of DNA translocation: the rotary inchworm, the staircase, and the revolution mechanism. The rotary inchworm mechanism involves two points of contact between DNA and the subunits of the FtsKC hexamer. These points of contact correspond to an α and a β domain. A conformational change in the α subunit can cause the DNA to shift. This shift is followed by a conformational change in the β subunit (which also causes the DNA to move). The repeated conformational changes lead to the translocation of DNA.
Conversely, the staircase mechanism sees the α and β subunits of the hexamer interacting with the double-stranded DNA in a sequential and overlapping manner. Conformational changes in each subunit cause movement in the spatial position of the DNA strand. Additionally, the revolution mechanism entails the passing of DNA through a channel formed by the hexameric FtsKC domain. In general, the chromosome dimer is translocated so that the site of resolution is near the divisome and so one copy of the genetic material ends up in each daughter cell. FtsK is the fastest DNA translocation pump, with rates of up to 7 kb s−1 it is also a very efficient one.
Recombinase (Xer D) Activation.
During bacterial replication, in the presence of a dimer the XerCD mechanism is introduced to divide the dimer into two monomers. FtsK is responsible for the activity of the Xer recombination reaction. Specifically, FtsKc is summoned if a chromosome dimer is present at the mid-cell point. The Xer mechanism is activated by overexpression of FtsK, therefore it appears that FtsK activates the Xer recombination. FtsK turns on the activity of XerCD upon expenditure of ATP.
The recombination apparatus is made up of four monomers, two being Xer D and two being Xer C, that belong to a family of tyrosine recombinases. The interaction of Xer D and the γ subunit of FtsKC results in the activation of the recombinase. Contact between Xer D and the γ subunit is facilitated by the translocation of DNA. Specifically, translocation stops when the FtsKc hexamer reaches the "dif" site.
Role in Cell Division.
FtsK has been shown to be a part of the divisome of bacteria and couple cell division with the resolution of dimers. FtsKN is thought to both stabilize the septum and aid in the recruitment of other proteins to the site of cell division. Recent research has shed light on the role of FtsK in membrane synthesis and has discovered that the L-domain is also important in the building of the septum. There is evidence to suggest that the N terminus is not the only part of FtsK that is involved in cell division. In an experiment done by Dubarry, a suppressor mutation allowed the cells to survive without FtsKN. Parts of FtsK were linked to integral membrane proteins. Subsequently, only those proteins that contained the linker region were able to restore normal cell growth, thus providing convincing evidence that the linker region of FtsK plays an important role in cell division. Other studies have shown that part of the FtsKN domain (which is in the periplasm) is involved in the construction of the cell wall.
Phylogeny.
FtsK is part of the AAA motor ATPases. The phylogeny tree of FtsK ties back to the split between ssDNA and dsDNA translocases where TraB, FtsK, T4CPs and VirB4s arise. Each of these show structural similarities and the parent branch of FtsK arose along with other branches of TraB, TcpA, and FtsK. Although FtsK has its own phylogeny specifications and branches within, TraB is similar to a sister protein branch that can trace back to the timeline of FtsK. A common protein that derives from one of the phylogeny branches of FtsK is SpoIIIE which is essential during chromosome segregation. FtsK is found in most bacteria including "E. coli" , "Staphyloccus", and "Streptomycetes" and in a select amount of Archaea and the phylogenetic tree is similar to that of bacteria. However the difficulty within exact dating of the diversification within its phylogeny is that proteins have variety in their branch lengths which makes it difficult to follow an exact timeline. The phylogeny of FtsK can therefore be compared to the time that protein groups VirB4/VirD4 diversified and slightly earlier than TraB and TcpA as they only occur in Actinobacteria and Firmicutes.


Collozoum

Collozoum is a radiolarian genus formerly reported in the subfamily Sphaerozoidae, now reported descending from the order Collodaria. The genus contains bioluminescent species. It is a genus of colonial radiolarians (as opposed to solitary).
Species.
The following species are recognized:


Qarunavus

Qarunavus is an extinct genus of mammals in the order Ptolemaiida. A single species, Qarunavus meyeri is known from the Lower Oligocene Jebel Qatrani Formation of modern-day Egypt. Described by Elwyn Simons & Philip Gingerich in 1974, the genus name is a combination of "Qarun", the Arabic term for Lake Moeris, and -"avus", Latin for "ancestor". The specific epithet honors Grant E. Mayer of the Yale Peabody Museum.


Widanelfarasia

Widanelfarasia is an extinct genus of placental mammals known from the Late Eocene Jebel Qatrani Formation of Egypt. Two species are known: "W. bowni" and the smaller "W. rasmusseni". Described in 2000 by E. R. Seiffert and Elwyn L. Simons, "Widanelfarasia" was initially classified as uncertain position ("incertae sedis") within placentals, but was later placed within the afrosoricidan suborder Tenrecomorpha (tenrecs and otter shrews). The genus name derives from Widan el-Faras (Arabic for "Ears of the Mare"), two prominent hills in the area where the fossils were recovered.