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SUMMARY / RELATED TOPICS

Exocytosis

Exocytosis is a form of active transport and bulk transport in which a cell transports molecules out of the cell by secreting them through an energy-dependent process. Exocytosis and its counterpart, are used by all cells because most chemical substances important to them are large polar molecules that cannot pass through the hydrophobic portion of the cell membrane by passive means. Exocytosis is in process a large amount of molecules are released thus making it a form of bulk transport. In exocytosis, membrane-bound secretory vesicles are carried to the cell membrane, their contents are secreted into the extracellular environment; this secretion is possible. In the context of neurotransmission, neurotransmitters are released from synaptic vesicles into the synaptic cleft via exocytosis. Exocytosis is a mechanism by which cells are able to insert membrane proteins and other components into the cell membrane. Vesicles containing these membrane components fuse with and become part of the outer cell membrane.

The term was proposed by De Duve in 1963. In eukaryotes there are two types of exocytosis: 1) Ca2+ triggered non-constitutive and 2) non-Ca2+ triggered constitutive. Ca2+ triggered non-constitutive exocytosis requires an external signal, a specific sorting signal on the vesicles, a clathrin coat, as well as an increase in intracellular calcium. Exocytosis in neuronal chemical synapses is Ca2 + serves interneuronal signalling. Constitutive exocytosis is performed by all cells and serves the release of components of the extracellular matrix or delivery of newly synthesized membrane proteins that are incorporated in the plasma membrane after the fusion of the transport vesicle. Vesicular exocytosis in prokaryote gram negative bacteria is a third mechanism and latest finding in exocytosis; the periplasm is pinched off as bacterial outer membrane vesicles for translocating microbial biochemical signals into eukaryotic host cells or other microbes located nearby, accomplishing control of the secreting microbe on its environment - including invasion of host, competing with other microbes for nutrition, etc.

This finding of membrane vesicle trafficking occurring at the host-pathogen interface dispels the myth that exocytosis is purely a eukaryotic cell phenomenon. Five steps are involved in exocytosis: Certain vesicle-trafficking steps require the transportation of a vesicle over a moderately small distance. For example, vesicles that transport proteins from the Golgi apparatus to the cell surface area, will be to use motor proteins and a cytoskeletal track to get closer to their target. Before tethering would have been appropriate, many of the proteins used for the active transport would have been instead set for passive transport, because the Golgi apparatus does not require ATP to transport proteins. Both the actin- and the microtubule-base are implicated in these processes, along with several motor proteins. Once the vesicles reach their targets, they come into contact with tethering factors that can restrain them, it is useful to distinguish between the initial, loose tethering of vesicles to their objective from the more stable, packing interactions.

Tethering involves links over distances of more than about half the diameter of a vesicle from a given membrane surface. Tethering interactions are to be involved in concentrating synaptic vesicles at the synapse. Tethered vesicles are involved in regular cell's transcription processes. Secretory vesicles transiently dock at the cell plasma membrane, preceding the formation of a tight t-/v-SNARE complex. In neuronal exocytosis, the term priming has been used to include all of the molecular rearrangements and ATP-dependent protein and lipid modifications that take place after initial docking of a synaptic vesicle but before exocytosis, such that the influx of calcium ions is all, needed to trigger nearly instantaneous neurotransmitter release. In other cell types, whose secretion is constitutive there is no priming. Transient vesicle fusion is driven by SNARE proteins, resulting in release of vesicle contents into the extracellular space; the merging of the donor and the acceptor membranes accomplishes three tasks: The surface of the plasma membrane increases.

This is important for the regulation of cell size, e.g. during cell growth. The substances within the vesicle are released into the exterior; these might be waste products or toxins, or signaling molecules like hormones or neurotransmitters during synaptic transmission. Proteins embedded in the vesicle membrane are now part of the plasma membrane; the side of the protein, facing the inside of the vesicle now faces the outside of the cell. This mechanism is important for the regulation of transmembrane and transporters. Retrieval of synaptic vesicles occurs by endocytosis; some synaptic vesicles are recycled without a full fusion into the membrane, while others require a complete reformation of synaptic vesicles from the membrane by a specialized complex of proteins. Non-constitutive exocytosis and subsequent endocytosis are energy expending processes, thus, are dependent on mitochondria. Examination of cells following secretion using electron microscopy demonstrate increased presence of empty vesicles followi

Trevor Senior

Trevor Senior is a former professional football striker who played at Reading. He is the assistant manager of Dorchester Town. Senior started his career at Dorchester, he joined Portsmouth in 1981 for £35,000, moved to Reading where he scored 184 goals in 362 league and cup appearances in two spells between 1983 and 1992. In season 1983–84, when Reading won promotion from the Fourth Division, Senior was top scorer in all four divisions of the Football League with 36 goals in the league and a total of 41 in all competitions. Two years he scored 27 times in the Third Division campaign as Reading won another promotion, this time as champions of their division. In March 1988 Senior signed for Middlesbrough on transfer deadline day for a fee of £200,000 from Watford, where he had moved in July 1987. After making just 10 league appearances for Boro and being part of their Second Division promotion winning team, Senior moved back to Reading in October 1988. Despite his time on Teesside being seen as a disappointment, Senior was instrumental in Boro's promotion in May 1988 after scoring two important goals in the play-offs.

After he left Reading for a second time in 1992, making his last Football League appearance at the age of 30, Senior spent a season with non-league Woking, a short spell at Dorchester Town before signing in November 1993 for Farnborough Town. The following season Senior became manager of Weymouth and subsequently during 1995–96 had another spell at Farnborough, his last job was manager of Bridgwater Town in the Western Football League, before joining Dorchester, becoming the Under 18's manager. His last game as U-18's manager was in May 2008 Senior was appointed manager of Western League Division One Bridport on 15 June 2009 following the resignation of Ian Hutchinson

Todd Spitzer

Todd Spitzer is the District Attorney of Orange County, California. He is former California State Assembly Member, he led the successful campaign to start a committee in support of Marsy's Law for All, the organization formed after the 2008 passage of California's Victims' Bill of Rights Act of 2008: Marsy's Law. As an Assistant District Attorney in Orange County, Spitzer handled criminal matters and supervised line prosecutors prior to being fired, he has prosecuted felonies including attempted murder, attempted rape, robbery and reckless driving causing serious bodily injury. Spitzer has tried about 100 jury trials to verdict. Spitzer joined the Orange County DA's Office in 1990 and served until he was fired in 1997 for inappropriate behavior in the work place and intimidating other workers. During this period Spitzer developed his interest in victims' rights; the local chapter of Mothers Against Drunk Driving honored Spitzer with its Outstanding Prosecutor Award, he was voted Outstanding Prosecutor by the Orange County DA's office.

Spitzer ran against incumbent Tony Rackauckas. On November 6, 2018, Spitzer defeated incumbent District Attorney Tony Rackauckas. Spitzer was born in Whittier and raised in nearby Montebello, 10 miles east of downtown Los Angeles, he excelled in academics, student government and theatre, graduated from Schurr High School in 1978. On November 7, 2008, Spitzer was inducted into the Schurr High School Hall of Fame for his achievements in law and politics. Spitzer earned his bachelor's degree from UCLA, a master's degree in Public Policy from UC Berkeley, a Law Degree from UC Hastings School of Law. While at Hastings, Spitzer was awarded the George Moscone Fellowship, for the law student dedicating his career to public service; this scholarship provided full tuition and expenses while at Hastings. At Berkeley, Spitzer received a full academic scholarship. In 1984-85, Spitzer worked as an English teacher at Theodore Roosevelt High School in the Los Angeles Unified School District. Spitzer's first elective office was as a Trustee to the Brea Olinda School Board, where he investigated a grading scandal at Brea Olinda High School involving a former registrar changing students' grades to enhance their chances of getting into college.

As a result, the school's principal was terminated and the Superintendent forced into early retirement. In 1996, Spitzer was first elected to the Orange County Board of Supervisors. While serving on the board, he established the first County restaurant rating system. On November 6, 2018, Spitzer won the Orange County District Attorney election against incumbent Tony Rackauckas. In April 2015, CBS Los Angeles and the Voice of OC reported Spitzer retrieved a gun and handcuffs from his vehicle, handcuffed a man who he felt was behaving aggressively towards him called 911 at a Wahoo's Fish Taco restaurant in Foothill Ranch, CA The handcuffed man was questioned about the incident, but was released by OC Sheriff's Department deputies. Video footage of the event was released. In August 2017, as the result of a Superior Court lawsuit, Orange County was required to reimburse $121,000 in legal fees that the news site Voice of OC had spent in order to get Spitzer to release emails and other documents he had withheld that related to this event.

In September 2017, taxpayers paid $150,000 settlement to an ex Playboy Playmate and former aid, Christine Richters, who sued Spitzer for having a “raging temper” and work place harassment. On October 30, 2018, the Chairman of the Orange County Board of Supervisor declared, during Item 10 at hour thirty five minutes into the board meeting, Supervisor Spitzer used extortionary tactics in campaign fundraising from the dais during the Oct. 30, 2018, Orange County Board of Supervisor’s meeting. The Chairman of the Board of Supervisors stated that Spitzer brought in throngs of television crews to forcefully announce the termination of GTL’s contract with the County of Orange during a previous Board of Supervisor’s meeting. Within days following of said meeting, GTL lobbyists made a $40,000 plus contribution to a Political Action Committee supporting Supervisor Spitzer and sent out mailers on his behalf during the 2018 election cycle. Spitzer serves as an Honorary Board Member of the Doris Tate Crime Victims Bureau and as a Board Member of Crime Survivors, Inc. and the Orange County's Trauma Intervention Program.

He served as a member of the Orange County Bar Association Administration of Justice Committee. He is on the Advisory Board for the Orange County Council along with Ca. Assemblyman James Silva, former State Senator Van Tran Boy Scouts of America. In 2003, he received that organization's Visionary Award, given annually to a person who exemplifies the attributes of the Scout Oath and Law, who has demonstrated leadership and philanthropy in the Hispanic and Latino communities. From 1990 to 2000, Spitzer served as a Level 1 Line Reserve Police Officer in the Los Angeles Police Department's Hollenbeck Division in East Los Angeles, where he founded the Driving Under the Influence Task Force. Official website of Todd Spitzer

Neutrophil elastase

Neutrophil elastase is a serine proteinase in the same family as chymotrypsin and has broad substrate specificity. Secreted by neutrophils and macrophages during inflammation, it destroys bacteria and host tissue, it localizes to Neutrophil extracellular traps, via its high affinity for DNA, an unusual property for serine proteases. As with other serine proteinases it contains a charge relay system composed of the catalytic triad of histidine and serine residues that are dispersed throughout the primary sequence of the polypeptide but that are brought together in the three dimensional conformation of the folded protein; the gene encoding neutrophil elastase, ELA2, consists of five exons. Neutrophil elastase is related to other cytotoxic immune serine proteases, such as the granzymes and cathepsin G, it is more distantly related to the digestive CELA1. The neutrophil form of elastase is 218 amino acids long, with two asparagine-linked carbohydrate chains, it is present in azurophil granules in the neutrophil cytoplasm.

There appear to be two forms of termed IIa and IIb. In humans, neutrophil elastase is encoded by the ELANE gene, which resides on chromosome 19. Elastases form a subfamily of serine proteases. Humans have six elastase genes that encode the structurally similar proteins elastase 1, 2, 2A, 2B, 3A, 3B. Neutrophil elastase hydrolyzes proteins within specialized neutrophil lysosomes, called azurophil granules, as well as proteins of the extracellular matrix following the protein's release from activated neutrophils. Neutrophil elastase may play a role in degenerative and inflammatory diseases by its proteolysis of collagen-IV and elastin of the extracellular matrix; this protein degrades the outer membrane protein A of E. coli as well as the virulence factors of such bacteria as Shigella and Yersinia. Mutations in this gene are associated with severe congenital neutropenia; this gene is clustered with other serine protease gene family members, azurocidin 1 and proteinase 3 genes, at chromosome 19pter.

All 3 genes are expressed coordinately and their protein products are packaged together into azurophil granules during neutrophil differentiation. Neutrophil elastase is an important protease enzyme that when expressed aberrantly can cause emphysema or emphysematous changes; this involves breakdown of increased airspaces. Mutations of the ELANE gene cause cyclic and severe congenital neutropenia, a failure of neutrophils to mature. In order to minimize damage to tissues, there are few inhibitors of neutrophil elastase. One group of inhibitors are the Serpins. Neutrophil elastase has been shown to interact with Alpha 2-antiplasmin, which belongs to the Serpin family of proteins. Elastase GeneReviews/NCBI/NIH/UW entry on ELANE-Related Neutropenias Neutrophil+Elastase at the US National Library of Medicine Medical Subject Headings Overview of all the structural information available in the PDB for UniProt: P08246 at the PDBe-KB

Jim Weir

James McIntosh Weir is a Scottish professional football player and coach. Weir played in the senior Scottish leagues for Hamilton Hearts and St. Johnstone, he has worked as manager of Montrose, Brechin City, Elgin City and Forfar Athletic. After starting in youth football with his hometown boys club, Motherwell Orbiston, Weir signed professionally with Hamilton Accies in 1987, he spent six years at Douglas Park, making close to 200 league appearances for the club, before joining Premier League Hearts under the guidance of Sandy Clark. Weir's stay at Tynecastle was brief and he moved to St. Johnstone within a year, signed by Paul Sturrock in a swap deal that saw Colin Miller move in the other direction, he ruptured his Achilles tendon during the final game of the 1997/98 season, which ruled him out of most of the following season. He returned to the starting line-up, as a right-back, on 4 April 1999, against Rangers, scored the first of Saints' three goals in a 3–1 victory. Following a knee operation, Weir was preparing to return to first-team action against Aberdeen when he broke his nose in a training-ground collision with teammate Paddy Connolly.

After getting back into the team, he was again injured in training which meant he missed more of the campaign. A serious knee injury put Weir out of action until January 2004, he managed seven appearances before being injured again, but was able to play against Newcastle United in his own testimonial match in May, featuring as a young Newcastle side won 2–1 in front of just under 3,000 spectators. Despite his numerous injuries, club captain for the majority of his time at St. Johnstone, made over 200 appearances for the Perth club, received an award when he achieved the 200 mark in August 2001. With his playing days near an end, Weir became assistant manager, firstly, to John Connolly and Owen Coyle. After his senior career, Perth-based Weir played Junior football for local sides Bankfoot Athletic and Kinnoull in between managerial appointments. After thirteen years with St. Johnstone, Weir became the manager of Montrose on 8 February 2007. In his first game in charge, on 10 February, the Gable Endies lost 1–0 at Berwick Rangers.

Just over a year after signing a contract extension, Weir was sacked towards the end of September 2008 with Montrose third in the league. After the resignation of John McGlashan, Weir became the manager of Arbroath on 1 November 2009. Weir failed to save Arbroath from relegation in the 2009–10 Scottish Second Division, as they finished ninth and were beaten by Forfar Athletic in the play-offs; the Lichties lost to junior club Irvine Meadow in the 2009–10 Scottish Cup. Weir joined Brechin City on 24 May 2010. Brechin finished fourth in the 2010–11 Scottish Second Division, qualifying for the promotion play-offs, but lost in the final to Ayr United. Weir was sacked by Brechin in September 2012 after the club had made a bad start to the 2012–13 Scottish Second Division. Weir was appointed manager of Scottish League Two club Elgin City in November 2014. After nearly three years in charge, Weir moved to Forfar Athletic in October 2017. Weir was involved in a car crash after a training session in September 2019.

He left the club on 3 November, as he struggled to combine his work commitments and recovery from the car crash. As of match played 2 November 2019 Jim Weir at Post War English & Scottish Football League A–Z Player's Database Jim Weir at Soccerbase Jim Weir management career statistics at Soccerbase

Benjamin Downing

Benjamin Brackett Downing is a Democratic former member of the Massachusetts Senate, representing the Berkshire and Franklin district from 2007-2013, before being redistricted to the Berkshire, Hampshire and Hampden district. The oldest of four children, Benjamin Downing was born in Pittsfield to Gerard, the late Berkshire County District Attorney, Pamela Downing, he attended Providence College in Rhode Island, graduated with a Bachelor of Arts degree in political science in 2003. He moved to Washington, D. C. where he worked for U. S. Representatives Bill Delahunt and Richard Neal before joining the staff of John Olver, he served as Olver's senior advisor on housing, tax, homeland security, foreign affairs for two years. In 2004, he began his graduate studies at Tufts University. While a student at Tufts, he ran for an open seat in the Massachusetts Senate in 2006, he won re-election in 2008. He received a Master of Arts degree in Urban & Environmental Policy from Tufts in 2008. Official policy and constituent services website Massachusetts General Court - State Senator Benjamin B. Downing official MA House website Project Vote Smart - Representative Benjamin Brackett Downing profile Follow the Money - Benjamin Brackett Downing 2006 campaign contributions