Protein ITFG3 also known as family with sequence similarity 234 member A (FAM234A) is a protein that in humans is encoded by the ITFG3 gene.  Here, the gene is explored as encoded by mRNA found in Homo sapiens.  The FAM234A gene is conserved in mice, rats, chickens, zebrafish, dogs, cows, frogs, chimpanzees, and rhesus monkeys. Orthologs of the gene can be found in at least 220 organisms including the tropical clawed frog, pandas, and Chinese hamsters. The gene is located at 16p13.3 and has a total of 19 exons.  The mRNA has a total of 3224 bp and the protein has 552 aa.  The molecular mass of the protein produced by this gene is 59660 Da.  It is expressed in at least 27 tissue types in humans, with the greatest presence in the duodenum, fat, small intestine, and heart.

A “Newfoundland deletion” or a0-thalassemia deletion has been found within the second intervening sequence of the FAM234A gene. The gene is associated with multiple red blood cell phenotypes in African Americans – though the exact function or effect of the gene was not entirely clear.  Review of GeneCards’ current database on the FAM234A gene provided no additional elucidation on the function of the gene.

Gene
FAM234A is located on Chromosome 16 (234,546 - 269, 943). It is 35,398 bases long, contains 11 exons, and is oriented on the plus strand in the 5' to 3' direction. Other aliases include ITFG3, C16orf9, and gs19.

There are no known paralogs of FAM234A.

The FAM234A gene is conserved in at least 220 organisms, with no evidence for conservation of the gene in single-celled organisms. Listed below is a selection of orthologs with the estimated date of divergence from human lineage in million years ago (MYA), the accession number, and the % identity to human FAM234A. This list does not contain all of the known orthologs.

mRNA
There are at least 11 FAM234A isoforms. Aside from the longest transcript, the other isoforms differ by truncation, primarily at the 3' end. This results in a wide variation in sequence length between isoforms.

Protein

The FAM234A gene encodes a serine and leucine rich protein titled the "FAM234A Protein" or ITFG3. The encoded protein is 552 amino acids in length with a predicted molecular weight of 59,660Da and a basal isoelectric point of 5.84. The FAM234A protein has a notable hydrophobic region from position 49-70 in the amino acid sequence that correlates with one of the two trans-membrane regions found on FAM234A. FAM234A has membrane topology type 3a, indicating multiple trans-membrane regions with its N-terminus facing the cytosol. The protein is predicted to be located in the endoplasmic reticulum, with portions of it found within the endoplasmic reticulum lumen. Within the cell, FAM234A has also been localized to the ribosomes and nucleus.

References

Further reading


Cortactin-binding protein 2 is a protein that in humans is encoded by the CTTNBP2 gene.

Function

This gene encodes a protein with six ankyrin repeats and several proline-rich regions. A similar gene in rat interacts with a central regulator of the actin cytoskeleton.

Interactions

CTTNBP2 has been shown to interact with:
 MOBKL3,
 PPP2CA,
 RP6-213H19.1,
 STRN3,  and
 STRN.

Model organisms
Model organisms have been used in the study of CTTNBP2 function. A conditional knockout mouse line called Cttnbp2tm1b(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed:  - In-depth immunological phenotyping

References

External links

Further reading


Kin of IRRE-like protein 2, also known as NEPH3, is a protein that in humans is encoded by the KIRREL2 gene. It is primarily expressed in β cells of the pancreatic islets.

KIRREL2 is a member of the NEPH protein family, which includes NEPH1 (KIRREL) and NEPH2 (KIRREL3). NEPH proteins bind the

References

Further reading


Estudillo House may refer to;

 Estudillo House, a city landmark in Riverside, California; see List of landmarks in Riverside, California#Estudillo House
 Casa de Estudillo, in San Diego, California
 Casa de Estudillo (San Leandro, California)
 Estudillo Mansion, in San Jacinto, California

See also
Estudillo family of California


James Ross Jack (born 21 March 1959) is a Scottish football player and manager.

Playing career
A striker, Jack began his career with Ross County, where he played in the Highland Football League at the age of 14. He then joined Everton, initially as an apprentice before graduating to the professional ranks. He made only a solitary, goalscoring appearance, for Everton and, after a loan spell at Cardiff City, he joined Norwich City for £20,000 in December 1979. He would have to wait almost a year before making his Norwich debut against Ipswich Town in the League Cup in September 1980. In the 1981–82 season, he scored 10 league goals for Norwich and, with two in the FA Cup and two more in the Football League Cup, was the club's leading scorer for the season. In the summer of 1983, a fee of £15,000 secured his transfer to Lincoln City where he remained for the next two seasons. His last game for Lincoln, and in England, was in May 1985, against Bradford City, in a game overshadowed by the Bradford City stadium fire, which killed 56 spectators.
In July 1985, he returned to Scotland to join Dundee.

In October 1987, Dunfermline Athletic's manager Jim Leishman paid £15,000 to secure Jack's services and he made an instant impression, scoring on his debut in a 3–2 away defeat to Motherwell. In each of his three seasons at the club, Jack would finish as Dunfermline's leading scorer, his most successful season being the 1989–1990 campaign when he was the second highest goalscorer in the Scottish Premier League, his 16 league goals placing him just one goal behind John Robertson. In July 1991 a fee of £45,000 was sufficient to see Jack move to Kilmarnock. Following a brief loan to Sligo Rovers (January – March 1993), Jack was appointed player-manager of Montrose in March 1993. His spell would last only six months and in October 1993 he moved on to Ayr United before retiring from the professional game at the end of the 1993–1994 season.

Coaching career

Post retirement, Jack moved into coaching, primarily focusing with work with the Scottish Football Association (SFA), first as the SFA's Highlands and Islands area community development officer and then as the SFA's North of Scotland Football Development Officer. In October 2001 it was announced that he would leave this role to take up the position of High Performance Football Coach at the Scottish Institute of Sport, a role he commenced in December 2001. On his appointment, Jack was quoted as saying "this new role is one where I hope we can make a difference to the future prospects of Scottish football." He continued to play football at a junior level, particularly in the North Caledonian Football League with Alness United and, in the summer months, with hometown Avoch.

In October 2007 there was speculation that Jack may make a return to management with Ross County with The Scotsman quoting Jack as saying "the time could be right for me to get back into the game. I could think of no better club than Ross County to do that with. I'm a local boy and County have played a big part in my life." but the return did not materialise. In April 2008, his post as the Scottish Institute of Sport's high-performance football coach was axed after the Scottish FA decided that the coaching of young players was best done by the individual clubs. Jack finally made his return to Ross County when he was appointed assistant coach in July 2008. In December 2008 Ross lost his job with Ross County due to the managerial team wanting to take a "new direction".

In January 2009, Jack was appointed manager of Elgin City in the Scottish Third Division. After five years with the club, Jack left Elgin City in January 2014 by mutual consent.

On 23 April 2014, Jack was appointed manager of Turriff United a Scottish Highland Football League club from Aberdeenshire.
 After 4 years in that position Jack left the team after helping them reach 2nd place in the Highland League, their highest ranking ever.

In September 2019, Jack was appointed manager of Rothes. He is currently in a two and a half year contract with them. and combines this with work as a coach in the Inverness Caledonian Thistle Youth Academy.

References

1959 births
Men's association football forwards
Ayr United F.C. players
Cardiff City F.C. players
Dundee F.C. players
Dunfermline Athletic F.C. players
Elgin City F.C. managers
Everton F.C. players
Kilmarnock F.C. players
League of Ireland players
Lincoln City F.C. players
Living people
Montrose F.C. managers
Montrose F.C. players
Norwich City F.C. players
Ross County F.C. players
Scottish expatriate men's footballers
Scottish Football League managers
Scottish Football League players
Scottish men's footballers
Scottish Professional Football League managers
Expatriate men's association footballers in the Republic of Ireland
Scottish expatriate sportspeople in Ireland
Sligo Rovers F.C. players
English Football League players
Highland Football League players
Scottish football managers
Highland Football League managers
Sportspeople from Highland (council area)
People from the Black Isle
Ross County F.C. non-playing staff
Association football coaches


Transmembrane protein 222 is a protein that in humans is encoded by the TMEM222 gene. One notable feature of the protein encoded by this gene is the presence of three predicted transmembrane domains. The TMEM222 protein is predicted to most likely localize to the secretory vesicles.

Gene Features

TMEM222 has a domain of unknown function (DUF778). Aliases of this gene include DKFZP564D0478, RP11-4K3__A.4, C1orf160, and MGC111002. Accession NM_032125.2, the longest coding sequence (1629 bp), encodes a protein of 208 amino acid residues (23230 Daltons), which is considered the consensus coding sequence (CCDS297.2). There are two isoforms of the protein encoded by this gene. They are similar except the second (Q9H0R3-2) is lacking the first 96 amino acid residues that are present in the first (Q9H0R3-1).

Gene Expression

ACEVIEW has labeled TMEM222 as highly expressed with 3.8 times more expression than the average gene in the database. There is expression evidence from 166 tissues including brain, lung, colon, kidney, and placenta.

Homology

Orthologs and distant homologs of the human TMEM222 have been identified throughout Eukaryota especially in plants and animals. No paralogs of this gene have been found in the human genome.

Distant Homolog

A distant homolog of TMEM222, RTH (RTE1-Homolog), is a homolog of RTE1 (Reversion-to-Ethylene Perception 1), which is known to induce conformational changes in ETR1 (Ethylene receptor 1) that result in negative regulation corresponding with loss of ethylene perception.

Protein Interactions

Evidence from yeast two-hybrid screening exists for two protein interactions with this gene. One is a serine protease (PRSS23) that has been identified to be involved in mouse ovulation and is excreted into the extracellular matrix. The other protein is an ab-hydrolase (HLA-B associated transcript 5)  that is integral to the membrane, and its corresponding gene is located in the genome near Tumor Necrosis Factor (TNF)-alpha and TNF-beta.

References

Further reading

Uncharacterized proteins


The Edwin H. Armstrong House, in Yonkers in Westchester County, New York, is unusual for having achieved listing on the National Register of Historic Places and even designation as a National Historic Landmark, only to be demolished.  Its subsequent removal from National Historic Landmark status is the only such occurrence for a New York State site.

It was the home of Edwin H. Armstrong, inventor of two circuits that are the basis of modern telecommunication systems, and also inventor of wide-band frequency modulation (FM) radio.

The home, a Queen Anne house, was located at 1032 Warburton Avenue in Yonkers.

It was designated a National Historic Landmark on January 7, 1976. It was demolished in 1983 after suffering fire damage. It was subsequently de-designated as a National Historic Landmark and delisted from the National Register of Historic Places in 1986.

References

Armstrong House
Armstrong House
Armstrong House
Armstrong House
Armstrong House
Armstrong House
Armstrong House
Queen Anne architecture in New York (state)
Buildings and structures demolished in 1983


Transketolase-like protein 2 is an enzyme that in humans is encoded by the TKTL2 gene.

References

Further reading


William L. Read was the director of the National Hurricane Center from 2008 to 2012. He has served the United States Navy and the National Weather Service (NWS) during his career. His weather service career began in 1977, and he has worked in Sterling, Virginia, Fort Worth, Texas, San Antonio, Texas, Silver Spring, Maryland, Houston, Texas, and Miami, Florida over the years. He was appointed as the Deputy Director of the National Hurricane Center (NHC) From August 2007 until he was selected for the position of director on January 25, 2008.

Career
Read served in the U.S. Navy, where he served as an on-board meteorologist with the Hurricane Hunters. He began his weather service career in 1977 with the National Weather Service test and evaluation division in Sterling, Virginia. He then served as a forecaster in the Fort Worth and San Antonio, Texas offices before becoming the severe thunderstorm and flash flood program leader at the National Weather Service headquarters in Silver Spring, Maryland.

Read was appointed to direct the Houston/Galveston weather forecast office in 1992 and led it through the National Weather Service modernization and restructuring program of the mid-1990s. He was also part of the Hurricane Liaison Team at the National Hurricane Center in Miami when Hurricane Isabel came ashore on the Outer Banks of North Carolina in September 2003.

Read became the director of the Tropical Prediction Center (TPC), which includes the National Hurricane Center and two other divisions, in Miami, Florida, in January 2008 and served until June 4, 2012 when relieved by Richard Knabb. Read had previously served as the center's acting deputy director between August 2007 and January 2008.

Awards
Read received the National Hurricane Conference Public Education Award in Spring 2004 for hurricane preparedness efforts. Under his leadership, the Houston/Galveston forecast office conducted an annual Houston/Galveston Hurricane Workshop, which was considered the largest meeting of its kind in the United States.

References

American meteorologists
Living people
Texas A&M University alumni
National Weather Service people
Year of birth missing (living people)


Kelch repeat and BTB domain-containing protein 7 is a protein that in humans is encoded by the KBTBD7 gene.

References

Further reading

Kelch proteins


The Singing Machine Company is a public company listed on Nasdaq under the ticker symbol MICS. The Singing Machine Company is primarily engaged in the karaoke business including the development, production, marketing, and distribution of consumer karaoke audio equipment, accessories, music, musical instruments, and licensed youth electronic products.

History
The Singing Machine Company (SMC) was originally incorporated in California in 1982 with a focus on professional and semi-professional karaoke equipment. In 1988 the company began marketing karaoke equipment for home use. It is believed that SMD was the first company to introduce home karaoke products to the United States. In 2001, SMC entered into a multi-year license agreement with MTV. As a part of a shift in strategy, SMC approached the mass market through large retailers. In the following year, Business Week Magazine named The Singing Machine Company #1 on their list of Hot Growth Companies.

Products

Karaoke Machines
The core of SMC's business is the distribution and sale of its karaoke machines to retailers and wholesalers such as Wal-Mart, Sam's Club, Best Buy, and Costco.

In the fall of 2015 The Singing Machine introduced its new digital line of products, no CD-G required allowing users to create playlists on the company's branded site and chose their favorite songs, download them to a USB, giving them the freedom of mixing and matching genres, singers, and enjoying the songs they want to sing.

Music
SMC has a music library thousands of recordings, which are licensed from their publishers for karaoke use. The library spans a variety of genres including: pop, rock, rap, country, Christian, Latin, motown, and oldies.

Bratz Licensed Products
In 2007 SMC signed a deal with MGA Entertainment to license the popular Bratz franchise. Such licensed products include karaoke products, digital drum sets, clock radios, TV/DVD combos, and portable DVD players.

Motown Licensed Products
Following a 2003 agreement between SMC and Universal Music Enterprises, the company released the "Motown Original Artist Karaoke" compilation series, which features karaoke tracks of Motown classic songs made from the original master recordings of the songs instead of cover versions, like most karaoke tracks. In addition, a Motown-themed karaoke machine has also been released.

Musical Instruments
SMC has a line of electronic drum sets under the brand name "SoundX".

References

Companies based in California
Karaoke
Companies established in 1982
1982 establishments in California


Enkurin domain-containing protein 1 is a protein that in humans is encoded by the ENKD1 gene.

References

Further reading


Pterin-4-alpha-carbinolamine dehydratase 2 is an enzyme that in humans is encoded by the PCBD2 gene.

References

Further reading


Tak Matsumoto Group (often abbreviated as TMG) was a supergroup consisting of members from several bands around the world. It includes Tak Matsumoto, Eric Martin, and Jack Blades. From July to September 2004, it presented its "Dodge the Bullet Tour" of Japan.

After a single, an album, 20 shows and some videos, the band never performed again. In a 2016 interview with Rolling Stone India, Martin said he asked Matsumoto every year about a possible reunion, to which Matsumoto always answered, "Let me think about it".

Lineup
Official members
 Tak Matsumoto (B'z) – guitar, leader
 Eric Martin (Mr. Big) – lead vocals
 Jack Blades (Night Ranger, Damn Yankees, Shaw/Blades) – bass, backing vocals

Support members
 Brian Tichy (Billy Idol, Ozzy Osbourne, Seether, Whitesnake, Foreigner, Pride & Glory, Glenn Hughes, Sass Jordan, Slash's Snakepit) – studio drums
 Cindy Blackman (Lenny Kravitz) – studio drums
 Chris Frazier (Whitesnake, Foreigner) – live drums

Discography

Albums
TMG I (June 23, 2004) Oricon ranking: No. 1

Singles
"Oh Japan (Our Time Is Now)" (March 31, 2004) No. 3

Videos
Dodge the Bullet (December 15, 2004) No. 8

References
Notes

Sources

Rock music supergroups
Musical groups established in 2004
Japanese hard rock musical groups
Being Inc. artists


Moringa peregrina is a species of flowering plant in the family Moringaceae that is native to the Horn of Africa, Sudan, Egypt, the Arabian Peninsula, and as far north as Syria. It grows on rocky wadis and on cliffs in drier areas.

Description
Moringa peregrina is a small deciduous tree, 6-10 m tall, with large leaves and thin pendulous branches. The tree blossoms twice a year; in Spring and in Autumn. Its flowers are five petaled, white or streaked red or pink. Its fruits are distinctive and can be seen hanging from its branches throughout the year. The fruits are narrowly cylindrical, up to 30 cm long and marked with deep longitudinal grooves. When ripe they split into three valves shedding the large whitish seed, known as the behen-nut.

Range and habitat
Moringa peregrina ranges across northeastern Africa and southwestern Asia. In Africa it is found in Egypt, Sudan, and the countries of the Horn of Africa – Eritrea, Ethiopia, Djibouti, Somalia and also in Libya. It occurs further across the Arabian Peninsula, and in Israel, Jordan, Palestine, and Syria. It has an estimated extent of occurrence (EOO) of over 5,791,000 km2.

It grows on the rocky slopes of wadis and gullies and in Acacia–Commiphora woodland.

In Israel, the tree is protected by law and grows along rugged, desert rock-faces and canyons along the Dead Sea, especially where there are watercourses, such as in Ein Gedi and in Naḥal Gob (near the lower Naḥal Sīn), as well as near the springs of al-Ḥama at the entrance to Wadi Qelt.

Uses
Moringa peregrina were traditionally used for home construction and fires, and its leaves consumed as food and livestock feed. In eastern Oman, young Moringa peregrina saplings would be dug up and its roots slowly roasted in a fire for food. In Oman, oil extracted from pods was used in traditional medicine and in perfumery.

The seed contains a fragranced light oil, with the precious quality that it does not grow rancid. In the Middle Ages, it was used as a base oil for certain perfumes.

Bedouins in Egypt would supply the Cairo market with behen-nut seeds, from which a fine, lubricant oil was extracted for use in mechanical watches. The manner in which the Bedouins extracted the oil from the behen-nut for their own personal use in cooking was marked with superstitious practices. After collecting the seeds from the pods, they would boil the seeds in water, and when the oil surfaced, it was skimmed off. The fire that they used for this process was made from yasaar wood (Moringa peregrina) only. The person or persons doing the extracting were always alone, as they believed that if they were being watched, the yield obtained from the seeds would be far less in quantity, or none at all.

A high quality behen oil was produced from the seeds of Moringa peregrina growing in Saudi Arabia (the Hijaz) and in Yemen. The best seeds were those whose peel inclined to be blackish in color, while the white seed would cause frothing on the surface of the liquid when it is cooked.

Bedouins have traditionally made use of the solidified resin extracted from the seeds to rosin the strings of the Arab violin (rebābah).

Method of extraction
A primitive method of extraction of the Moringa oil (behen oil, also Ben nut oil) is described in the writings of Al-Nuwayri, who cites the Arab physician, Al-Tamimi. The seeds, he says, were taken from the pods and ground in a special quern or millstone made for the purpose. Afterwards, the ground pulp was placed inside a large brass-copper cauldron that held a capacity of a little over 19 Syrian kiljah, equivalent to about , the cauldron being filled to  of its capacity. Water was then poured over the ground pulp so that it completely covered it, with an excess of 4 fingerbreadths of water. The cauldron was stoked from beneath with thick logs of wood, and the water and pulp brought to a boil. In this state, the ground behen-nut seeds were allowed to cook for a half-day, while all evaporated water was being restored to the cauldron by degrees. After a half-day of cooking, the cauldron was removed from the fire and allowed to cool down. The oil which then floated on the surface of the water was scooped out and stored in a prepared vessel.

References

peregrina
Flora of Egypt
Flora of Israel
Flora of the Arabian Peninsula
Flora of Northeast Tropical Africa
Flora of the Hajar Mountains


Luis Asprilla (born 6 December 1977) is a retired Colombian football defender.

He played for the Colombia national team in 2001. He has played outside Colombia for Olimpo de Bahía Blanca in Argentina and Emelec in Ecuador.

External links

1977 births
Living people
Footballers from Cali
Colombian men's footballers
Colombia men's international footballers
Men's association football defenders
Deportivo Pereira footballers
Deportes Tolima footballers
Real Cartagena footballers
América de Cali footballers
Club Olimpo footballers
Millonarios F.C. players
Atlético Bucaramanga footballers
C.S. Emelec footballers
Cúcuta Deportivo footballers
Atlético Cali footballers
Alianza Atlético footballers
Bogotá F.C. footballers
Categoría Primera A players
Argentine Primera División players
Colombian expatriate men's footballers
Expatriate men's footballers in Argentina
Expatriate men's footballers in Ecuador
Expatriate men's footballers in Peru

Asprilla family


U3 small nucleolar RNA-associated protein 15 homolog is a protein that in humans is encoded by the UTP15 gene.

See also

 Fibrillarin
 Small nucleolar RNA U3
 RCL1
 RRP9
 UTP6
 UTP11L
 UTP14A

References

Further reading


The Night Owls is a twice weekly webcomic by cartoonists Peter and Bobby Timony which appears every Tuesday and Thursday on DC Comics Zuda imprint. It was selected as Zuda's Instant Winner in December 2007. The Timony brothers have been based out of New Providence, New Jersey, a suburb of New York City.

Set in 1920s New York City, the strip follows the adventures of a group of detectives who solve supernatural crimes in the tradition of occult detective fiction. The strip alternates between single gags and longer story arcs, though each episode is designed to stand on its own. Although it often deals with bizarre and disturbing themes, the strip maintains a light-hearted tone that is generally suited for all ages. Each strip is usually six to eight panels long, has an art deco banner across the top and is colored in warm sepia hues.

Characters
 Professor Ernest Baxter is a bookwormish and kind of shy fellow who uses his vast knowledge of the supernatural world to try to help people.
 Mindy Markus is a feisty flapper with a modern "liberated" outlook on life who is not afraid to get into a scrap with the forces of evil.
 Roscoe the Gargoyle is a gargoyle from Coney Island with an insatiable appetite; he provides additional comic relief with his flippant and lighthearted approach to things.
 Detective Bill McRory is an honest cop who occasionally seeks help from the Night Owls on cases involving the supernatural.
 Mr. You is a faceless man who steals the faces of others.
 Mable the Gargoyle is Roscoe's sister who, when first introduced, looks inexplicably like a gorgeous blonde human.
 Filthy the Rat is The Professor's underworld informant. Filthy is a rat who is a "Were-Human": by the light of the full moon, he turns into a tiny human.
 Helaku is an Apache girl who met Professor Baxter when he was younger. Baxter helped the tribe defeat a giant monster named Big Owl.
 Ikshu is Helaku's older brother. He went to prison for bootlegging where he met Mr. You, who stole his face and escaped.

Print
Bayou and High Moon were the first two Zuda titles to be published as graphic novels, in June and October 2009, respectively by DC Comics. "Night Owls" was the third title to be released from the imprint and was released on March 30, 2010.

Awards
 Night Owls was nominated for three 2009 Harvey Awards, for Best New Series, Best Online Work, and Best New Talent for artist Bobby Timony.
 Night Owls''' character Mindy Markus was nominated for the 2010 Lulu Awards for BEST FEMALE CHARACTER 'for a lead female character from an ongoing or limited comic book series or comic strip, original graphic novel or novella, whether in print or online'.
 Night Owls'' was nominated as a finalist in the 2010 Cybil Awards for its achievements as one of the 'best children's and young adult titles' of the year.

References

External links
 Read Night Owls on Zuda
 Twin Comics Blog
 Twin Comics Website
 Mook Productions, LLC.
 Twin Comics at IndyPlanet
 Twin Comics at ComicSpace
 The Night Owls animated on Youtube

Interviews
 The Timony Twins, in a podcast interview on Comics Coast to Coast
 The Knave of Krypton interviews the Night Owls
 The Independent Press interviews the Timony Twins.
 Amalgamated Artist's interviews with the Timony Twins about The Night Owls.

Comics set in the 1920s
Comics set in New York City
Detective comics
Occult detective fiction
Flappers
Zuda Comics titles
2000s webcomics
Horror webcomics
American comedy webcomics
2007 webcomic debuts


Uncharacterized protein KIAA1109 is a protein that in humans is encoded by the KIAA1109 gene.

This protein has a function that is not yet understood.  KIAA1109 has 3 aliases, FSA (fragile site-associated) protein, MGC110967 and DKFZp781P0474.

Gene

Location
KIAA1109 is found on the long arm of chromosome 4 (4q27), with the genomic sequence starting at 118,818,167 bp and ending at 119,010,362 bp

Gene Neighborhood
The gene neighborhood of KIAA1109 involves 4 other genes.
KIAA1109 is a part of the KIAA1109/Tenr/IL2/IL21 gene region. This region consists of the three genes to the right of KIAA1109; ADAD1, IL2 and IL21.
Another gene located in the neighborhood of KIAA1109 is TRPC3. This gene is to the left of KIAA1109 on the opposite side of the genes described above.

Expression
According to data on NCBI’s EST Abundance Profile page for KIAA1109, the gene is expressed in many different tissues in humans. Human expression is seen most predominately in parathyroid, muscle, ear, eye, mammary gland, lymph node, thymus in addition to 27 other tissues.   KIAA1109 is also expressed in various disease states including 12 different tumors as well as bladder carcinoma, chondrosarcoma, glioma, leukemia, lymphoma, non-neoplasia, retinoblastoma tissues.  KIAA1109 is expressed in all stages of development from embryoid body to adult, except in infants. No expression of my gene is seen during the infant stage of development.

Promoter
According to Genomatix’s ElDorado program the promoter region of KIAA1109 is predicted to be 601 base pairs in length. The promoter region starts 500 base pairs upstream of the 5’ UTR of KIAA1109 mRNA transcript and contains part of this 5’ UTR.

Homology
KIAA1109 is conserved throughout many species. Orthologs have been found in many mammals and other vertebrates. More distant homologs have been identified in animals such as insects. See the mRNA and protein conservation sections below for more details.  No human paralogs for KIAA1109 have been identified.

mRNA

Splice Variants
KIAA1109 has 13 mRNA splice variants and 6 unspliced variants. Variant A is the longest and most commonly occurring variant of the gene and is the subject of this article. KIAA1109 variant A is made up of 84 exons and is 15,592 base pairs in length. The accession number for this nucleotide is NM_015312.3.

Conservation
The mRNA sequence of KIAA1109 is highly conserved throughout mammals. The mRNA sequence identity to mammals is no less than 81.9% (in platypus) and ranging up to 99.5% (in chimpanzees).   Birds also show fairly high conservation with mRNA sequence identities around 78% in zebra finches.
The table blow shows information on the mRNA orthologs.

Protein

General Properties
KIAA1109 protein is 5005 amino acids in length,  and has a predicted molecular weight of 555519.38 daltons.   The isoelectirc point of KIAA1109 protein is predicted to be 6.12.

Composition
The amino acid composition of KIAA1109 protein showed amino acid frequencies within 1.5% of that of normal human proteins for all but Alanine, Serine and Threonine. Alanine has a lower frequency in KIAA1109 than in that of a normal human protein while Serine and Threonine both have a higher frequency in KIAA1109 than in the average human protein.

Conservation
The amino acid sequence of KIAA1109 is highly conserved throughout mammals. The protein identity ranges from 93.2% in Opossum to 99.8% in Chimpanzees and protein similarity is no less than 97% in all mammals included. Birds continue to show fairly high conservation with protein identities around 90% and proteins similarities at a high 96%. While conservation is still high the lower numbers may be due to small truncations on either, the 5’ and 3’ ends of these sequences.

As we move to the more distant species of zebra fish and then the red four beetle and carpenter ant the conservations drops. In the insects the protein identities are down to around 34%.

Conserved Domains
NCBI conserved domains search identified two domains in KIAA1109. The first is the fragile site associated C-terminus, which is said to be linked to celiac disease susceptibility according to genome-wide-association studies and may also be associated with polycystic kidney disease.   The second conserved region identified by NCBI in KIAA1109 is an uncharacterized conserved protein (DUF2246), whose function is unknown and is conserved in various species from humans to worms.

Post Translation Modifications
KIAA1109 is predicted to undergo various types of post translational modifications including glycate, N-glycosylation, O-GlcNAc, O Glycosylation, Sulfonation and Phosphorylation.

Subcellular Localization
KIAA1109 contains one transmembrane domain from amino acids 26-46.
No signal peptides, mitochondrial targeting sequences or chloroplast peptides were predicted for my protein and it is therefore not predicted to localize to secretory pathway, mitochondria or chloroplast.

Interacting Proteins
MADH2 and Beta-catenin were both found to have a physical interaction with my protein as detached by display technonloy by Miyamoto-Sato et al. 2010.

References

Further reading

Uncharacterized proteins


Assail may refer to:

 Assail (Malazan), a continent in the Malazan Book of the Fallen series
 HMAS Assail (P 89), an Attack-class patrol boat
 USS Assail (AM-147), an Admirable-class minesweeper

See also

 Assail Bank
 Assailant


The Billy Gebbie Arena, occupies a portion of the Glengarry Sports Palace (which also includes a branch of the SD&G County Library, a community hall, two baseball diamonds, and a soccer field), has been the home of the Alexandria Glens since 1976. The arena is also home for the Alexandria & District Minor Hockey Association, Glengarry Girls Hockey Association, and the Alexandria Ladies Ball Hockey League. It is located in Alexandria, Ontario, and has a capacity of 500+ for hockey games.

When the ice is out (typically from April through August), the arena floor hosts a number of events, including the Alexandria & District Chamber of Commerce Trade Show and once every three years the Glengarry Sports Hall of Fame induction dinner/ceremony. The community hall attached to the rink is rented throughout the year for numerous events, public and private.

Events
The final games of the 7-game 2007 EOJBHL championship series were held at the Billy Gebbie Arena, where the Glens won game 7, defeating Gatineau Mustangs 4-0 and won the series 4 games to 3. The arena also host the Annual Little Nashville Tabc Jr. Country Festival and the 1st Annual Rideau-St. Lawrence Showcase for the Alexandria Glens in 2008. The Alexandria Jr.B Glens will be hosting the EOJHL Fall Classic on October 17, 18 and 19, 2013.

The public address announcer for the Alexandria Glens games is Paul Lalonde.

Tenants
 Alexandria Glens (CCHL2)  (1976–present)
 Alexandria Minor Hockey Association  (ODMHA)  (1976–present)
 Glengarry Girls Hockey Association  (-present)
 Alexandria Figure Skating Club  (1976-2010)

Championships

 1984 EOJCHL Champions
 2006-2007 EOJBHL Branch Champions
 2007 Boxing Day Tournaments Champions
 2007-2008 EOJBHL Branch Champions

Retired jerseys
The following numbers are retired by the Alexandria Jr.B Glens and hang from the rafters:
 4 Marc Ménard
 3 Brian Filion

External links
Alexandria Glens
Alexandria Minor Hockey Association

Sports venues in Ontario


USS Kaula (AG-33) was built in 1938 by Henry Robb Ltd, in Leith, Scotland. She was acquired by the U.S. Navy as Cubahama 3 January 1941 from her owner, Balboa Shipping Company of New York and  renamed Kaula 15 January then commissioned at Baltimore, Maryland 22 January.

Sailing to Hampton Roads, Virginia, 25 January, Kaula departed 4 February for Hawaii, via the Panama Canal and the West Coast, reaching Pearl Harbor 17 March. Prior to the outbreak of war in the Pacific, she carried cargo from Pearl Harbor and Honolulu to various islands in the Hawaiian chain and to Johnston and Palmyra Islands. During the Japanese raid on Pearl Harbor 7 December, she was en route to Palmyra Island.

Throughout the war with the Japanese Empire, Kaula operated out of Pearl Harbor and Honolulu to principal Hawaiian Islands and to outlying islands west to Midway and south to Palmyra. Usually sailing in convoy, she ranged the Hawaiian Sea frontier carrying military equipment, ammunition, and contingents of Seabees until she sailed for the United States on 18 May 1945, arriving at Seattle, Washington on 26 May.

Following 2 months of overhaul, Kaula departed Seattle 31 July on the first of several voyages to Alaska. Assigned to the 13th Naval District, she steamed for the US Coast Guard to Ketchikan, Juneau, Seward, Kodiak, and Dutch Harbor before returning to Seattle 18 September. She operated in Puget Sound and the Strait of Juan de Fuca before steaming to Blake Island Anchorage, Washington, 6 December and decommissioning 14 January 1946. Struck from the Naval Vessel Register on 12 March, Kaula was transferred to the Maritime Commission 15 July for sale to her former owner.

References

External links
 photo gallery at navsource.org

World War II auxiliary ships of the United States
Ships built in Leith
1938 ships
Cargo ships of the United States Navy


Shoal Bay is a community on Fogo Island in the province of Newfoundland and Labrador. It is part of the municipality of Town of Fogo Island, with which it amalgamated on March 1, 2011.

References

Fogo Island, Newfoundland and Labrador


Dual specificity tyrosine-phosphorylation-regulated kinase 2 is an enzyme, in particular a dual-specificity kinase, that in humans is encoded by the DYRK2 gene.

DYRK2 belongs to a family of protein kinases whose members are presumed to be involved in cellular growth and development.  The family is defined by structural similarity of their kinase domains and their capability to autophosphorylate on tyrosine residues.  DYRK2 has demonstrated tyrosine autophosphorylation and catalyzed phosphorylation of histones H3 and H2B in vitro.  Two isoforms of DYRK2 have been isolated.  The predominant isoform, isoform 1, lacks a 5' terminal insert.

See also
DYRK1A

References

Further reading

EC 2.7.12


Tammany Young (September 9, 1886 – April 26, 1936) was an American stage and film actor.

Early life
Born in New York City, Young appeared on Broadway in The Front Page (1928) by Ben Hecht and The New Yorkers (1930) by Herbert Fields and Cole Porter. He was considered a "good luck actor" by Broadway producers. He was often cast in bit parts by the likes of The Shuberts, Jed Harris and David Belasco to bring luck to their productions. His reputation in the theater business was such that his likeness was drawn in caricature by Alex Gard for Sardi's restaurant. That picture is now part of the collection of the New York Public Library.

Career
In Hollywood, Young started out in silent films and then was cast in talkies. He often played the stooge (straight man) to W.C. Fields, with whom he appeared in seven films: Sally of the Sawdust (1925), Six of a Kind (1934), You're Telling Me! (1934), The Old Fashioned Way (1934), It's a Gift (1934), Man on the Flying Trapeze (1935), and Poppy (1936).

Gatecrashing
Young also had a reputation as a gate crasher. By claiming to be an ice man, he worked his way into the 1921 Dempsey–Carpentier prize fight in New Jersey, and in 1932 found his way into the Los Angeles Olympics. His exploits were frequently reported by sportswriters of the era.

Death
After a long illness, Young died in his sleep on April 26, 1936  in Hollywood, California, at the age of 49. At the news of Young's death, W.C. Fields fell into a depression and stopped eating and sleeping.

Partial filmography

 The Escape (1914)
 Driven by Fate (1915 short)
 The Foundling (1915)
 The Foundling (1916)
 The Lost Bridegroom (1916)
 Destiny's Toy (1916)
 The Big Sister (1916)
 The Great Secret (1917)
 The Service Star (1918)
 A Regular Girl (1919)
 The Right Way (1921)
 Bits of Life (1921)
 The Man Who (1921)
 The Man Worth While (1921)
 Rainbow (1921)
 When the Desert Calls (1922)
 The Seventh Day (1922)
 John Smith (1922)
 Till We Meet Again (1922)
 The Heart of a Siren (1925)
 The White Monkey (1925)
 The Police Patrol (1925)
 Sally of the Sawdust (1925) (uncredited)
 The Wrongdoers (1925)
 Camille of the Barbary Coast (1925)
 The Unguarded Hour (1925)
 Womanhandled (1925)
 The Highbinders (1926)
 Blind Alleys (1927)
 The Perfect Sap (1927)
 Roadhouse Nights (1930)
 Follow the Leader (1930)
 The Kid from Spain (1932)
 She Done Him Wrong (1933)
 Hallelujah, I'm a Bum (1933)
 Gold Diggers of 1933 (1933) (uncredited)
 Tugboat Annie (1933)
 Six of a Kind (1934) (uncredited)
 You're Telling Me! (1934)
 The Old Fashioned Way (1934)
 It's a Gift (1934)
 The Mighty Barnum (1934)
 The Glass Key (1935)
 Man on the Flying Trapeze (1935)
 Little Big Shot (1935)
 Poppy (1936)

See also
Double act
List of caricatures at Sardi's restaurant

References
Notes

Bibliography
Brantley, Ben. The New York Times Book of Broadway. New York: St. Martin's Press, 2001.
Burdick, Loraine. The Shirley Temple Scrapbook. Middle Village, N.Y.: Jonathan David Publishers, 1975.
Curtis, James. W.C. Fields A Biography. New York: A.A. Knopf, 2003.
Goldman, Herbert G. Fanny Brice The Original Funny Girl. New York: Oxford University Press, 1992.
Langman, Larry. American Film Cycles The Silent Era. Bibliographies and indexes in the performing arts, no. 22. Westport, Conn: Greenwood Press, 1998.
Louvish, Simon. Mae West It Ain't No Sin. New York: Thomas Dunne Books/St Martin's Griffin, 2007.
Louvish, Simon. Man on the Flying Trapeze The Life and Times of W.C. Fields. New York: W.W. Norton, 1999.
Mast, Gerald. The Comic Mind; Comedy and the Movies. Indianapolis: Bobbs-Merrill, 1973.
Rhodes, Gary. Lugosi His Life in Films, on Stage, and in the Hearts of Horror Lovers. Jefferson, N.C.: McFarland & Company, 1997.

External links

1886 births
1936 deaths
American male film actors
American male stage actors
American male silent film actors
20th-century American male actors
Male actors from New York City


Double C2-like domain-containing protein alpha is a protein that in humans is encoded by the DOC2A gene.

There are at least two protein isoforms of the Double C2 protein,  namely alpha (DOC2A) and beta (DOC2B), which contain two C2-like domains.  DOC2A and DOC2B are encoded by different genes; these genes are at times confused with the unrelated DAB2 gene which was initially named DOC-2. DOC2A is mainly expressed in brain and is suggested to be involved in Ca(2+)-dependent neurotransmitter release.

Interactions

DOC2A has been shown to interact with UNC13B and UNC13A.

References

Further reading


{{DISPLAYTITLE:M1G}}

M1G (pyrimido[1,2-a]purin-10(3H)-one) is a heterocyclic compound which is a by-product of base excision repair (BER) of a specific type of DNA adduct called M1dG. The M1dG adduct in turn is formed by a condensation reaction between guanosine nucleotides in DNA and either malondialdehyde (propanedial)  or acrolein. If not repaired, these adducts are mutagenic and carcinogenic.

Malondialdehyde is an end product of lipid peroxidation while acrolein is a result of DNA peroxidation.

M1dG is the major endogenous DNA adduct in humans. M1dG adducts have been detected in cell DNA in liver, leucocytes, pancreas and breast in concentrations of 1-120 per 108 nucleotides. Detection and quantification of M1dG adducts in the body as measured by free M1G is a tool for detecting DNA damage that may lead to cancer. Free M1G is also biomarker for oxidative stress.

References

External links

Biochemistry
Carcinogenesis
Purines


Forkhead box protein N1 is a protein that in humans is encoded by the FOXN1 gene.

Function

Mutations in the winged-helix transcription factor gene at the nude locus in mice and rats produce the pleiotropic phenotype of hairlessness and athymia, resulting in a severely compromised immune system. This gene is orthologous to the mouse and rat genes and encodes a similar DNA-binding transcription factor that is thought to regulate keratin gene expression. A mutation in this gene has been correlated with T-cell immunodeficiency, the skin disorder congenital alopecia, and nail dystrophy. Alternative splicing in the 5' UTR of this gene has been observed. In the chick embryo, the FOXN1 gene is expressed in the developing thymus, claws and feathers. The expression of FOXN1 in feathers and claws indicates that it may regulate the feather outgrowth. In feather and claws, FOXN1 can potentially regulate expression of keratins similar to mammalian orthologs.  In thymic epithelial cells, FOXN1 has been shown to bind to and regulate genes involved in T-cell maturation and antigen presentation.

References

Further reading

Forkhead transcription factors


SLIT and NTRK-like protein 6 is a protein that in humans is encoded by the SLITRK6 gene.

Function

Members of the SLITRK family, such as SLITRK6, are integral membrane proteins with 2 N-terminal leucine-rich repeat (LRR) domains similar to those of SLIT proteins (see SLIT1). Most SLITRKs, including SLITRK6, also have C-terminal regions that share homology with neurotrophin receptors (see NTRK1). SLITRKs are expressed predominantly in neural tissues and have neurite-modulating activity.

Clinical significance

Mutations in SLITRK6 cause high myopia and deafness in humans and mice.

As a drug target

The protein is the target for the antibody-drug conjugate ASG-15ME which is in phase 1 clinical trials for urothelial cancer.

References

Further reading


Methylthioribose-1-phosphate isomerase is an enzyme that in humans is encoded by the MRI1 gene.

References

Further reading


Trichoplein keratin filament-binding protein is a protein that in humans is encoded by the TCHP gene.

Model organisms

Model organisms have been used in the study of TCHP function. A conditional knockout mouse line called Tchptm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed:  - In-depth immunological phenotyping

References

Further reading


RING finger protein 135 is a protein that in humans is encoded by the RNF135 gene.

The protein encoded by this gene contains a RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. This gene is located in a chromosomal region known to be frequently deleted in patients with neurofibromatosis. Alternatively spliced transcript variants encoding distinct isoforms have been reported.

Interactions
RNF135 has been shown to interact with RARRES3.

References

Further reading

RING finger proteins


Biox is an American medical technology company known for the development of the first widely used pulse oximeter.

History
Michael Hickey, Scott Wilber, and Bill Moe founded Biox Technology in 1979. Hickey served as the company's CEO, Wilber was the company's Chief Engineer and Scientist, and Moe was the company's Executive Vice President. Enervest, a Denver-based venture fund, funded the company.

Wilber invented the company's technology and developed the first oximeter patent.  Wilber's development of a "normalization circuitry" proved to be a significant, long-lasting innovation in pulse oximetry.

Wilber led the company's product development for the Biox II, Biox IIa and Biox III product lines. He led the team of pulse oximeter engineers which later developed the Ohmeda Biox 3700 which was widely used in the anesthesia market in the mid-1980s.

The first commercially available oximeters were produced by Hewlett-Packard, and were large, cumbersome, and expensive. These devices were of limited value because they were largely focused on research in the respiratory care field. Biox introduced the first pulse oximeter to commercial distribution in 1980. Initially, the company focused its marketing on the respiratory care market. Later the company established a national, independent distribution network market of respiratory care physicians.

Unbeknownst to the company, the pulse oximeter was also being used to monitor oxygen deprivation in patients under anesthesia in operating rooms.  Reports of this application reached the company's management in late 1982, and the company began to focus time and resources in developing operating room applications to help anesthesiologists monitor oxygenation levels in patients on the operating table.

The company began to experience competition in the anesthesia market from a new entry into the field, Nellcor. In order to enter the anesthesia market and to mitigate competitive pressures, the company retained Kidder Peabody to assist it in developing a strategic alliance with large corporations in the medical field. As a result of this effort, the BOC Group purchased Biox Technology in the summer of 1984. The company became a business unit of BOC's Medical Group, Ohmeda. The product was renamed to Ohmeda Biox 3700.

At the time of acquisition, Hickey, Moe, and Evans stayed on with the company as managers of the business unit; Wilber left the corporation. Under BOC management, the pulse oximeter market expanded significantly.  The Ohmeda business unit remains in Boulder, Colorado as a medical device manufacturer. It is currently under the ownership of GE Healthcare.

References

External links
Ohmeda business unit

Companies based in Boulder, Colorado
Medical technology companies of the United States
Technology companies established in 1979
1979 establishments in Colorado


Vacuolar protein-sorting-associated protein 25 is a protein that in humans is encoded by the VPS25 gene.

It is a component of the endosome-associated complex ESCRT-II (Endosomal Sorting Complexes Required for Transport protein II). ESCRT (ESCRT-I, -II, -III) complexes orchestrate efficient sorting of ubiquitinated transmembrane receptors to lysosomes via multivesicular bodies (MVBs). ESCRT-II recruits the transport machinery for protein sorting at MVB. In addition, the human ESCRT-II has been shown to form a complex with RNA polymerase II elongation factor ELL in order to exert transcriptional control activity. ESCRT-II transiently associates with the endosomal membrane and thereby initiates the formation of ESCRT-III, a membrane-associated protein complex that functions immediately downstream of ESCRT-II during sorting of MVB cargo. ESCRT-II in turn functions downstream of ESCRT-I, a protein complex that binds to ubiquitinated endosomal cargo.

ESCRT-II is a trilobal complex composed of two copies of vps25, one copy of vps22 and the C-terminal region of vps36. The crystal structure of vps25 revealed two winged-helix domains, the N-terminal domain of vps25 interacting with vps22 and vps36.

References

Further reading

Protein families


Polycomb group RING finger protein 5 is a protein that in humans is encoded by the PCGF5 gene.

References

Further reading


MKI67 FHA domain-interacting nucleolar phosphoprotein is a protein that in humans is encoded by the MKI67IP gene.

MKI67 FHA domain-interacting nucleolar phosphoprotein contains an RNA recognition motif (RRM) near to the N-terminus and a FHA Ki67 binding domain near to the C-terminus. There are two conserved sequence motifs within the FHA Ki67 binding domain: TPVCTP and LERRKS, this domain binds to the forkhead-associated domain of human Ki67. High-affinity binding requires sequential phosphorylation by two kinases, CDK1 and GSK3, yielding pThr238, pThr234 and pSer230. This interaction is involved in cell cycle regulation.

References

Further reading

External links
 PDBe-KB provides an overview of all the structure information available in the PDB for Human MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP)

Protein domains


Raymond Slater Brock (14 October 1936 – 1 January 2008) was a leading English bridge player and then a long-time administrator. He was a member of the Great Britain team that finished second in both the 1987 European Bridge League championship and the 1987 Bermuda Bowl world championship, and fifth in the 1988 World Team Olympiad. This success came during his partnership with Tony Forrester, which lasted from 1982 to 1990. He achieved the rank of World International Master through his performances.

Brock was educated at Manchester University and became a physics teacher at a Manchester school. A subsequent job as a computer manager with Honeywell took him to Glasgow from 1968 to 1975. While living there he played seven matches for Scotland; three times during that span the team won the Camrose Trophy, for which England, Scotland, Wales and Northern Ireland compete (subsequently Ireland too). Before and afterward he played for England, with 26 appearances for the country in all. Additionally on four occasions he was non-playing captain of the England team, as well as serving as a selector. He won the Gold Cup, the premier British domestic competition, seven times.

He was twice President of the British Bridge League and was non-playing captain of many Great Britain teams, including the bronze medal winning Women in the 1980 World Team Olympiad and the gold medal winning Juniors at the 1989 World Championships. He did much coaching of the best young players, and in 1994 was non-playing captain of the British Junior team that won the European Championships and went on to win the World title the following year.

He wrote several books, in particular on defence, a part of the game at which he was especially expert. These include Planning the Defence (1996) and Expert Defence (1997). While with Honeywell at Brentford, Middlesex in the late seventies and early eighties, some of his early bridge writing included chapters on the Stayman convention. His vacations during this time were spent at Monte Carlo playing bridge with the likes of Omar Sharif.

He died of cancer. His widow Sally Brock is an international bridge player. Together they won the England Mixed Teams event on six occasions and the British Mixed Pairs twice.

Books

 Step-by-step Planning the Defence (London: B. T. Batsford, 1996)
 Step By Step Expert Defence (Batsford, 1997)
 No Trump Play (Batsford, 1998)
 Expert Tuition for Tournament Bridge, Brock and Brock (Batsford, 1998)
 Slams, Brock and Brock (Batsford, 1999), Bridge Quiz series
 Defence, Brock and Brock (Batsford, 2000), Bridge Quiz series
 Great Hands I Wish I Had Played, Sally and Raymond Brock (Batsford, 2002)

References

Obituary on the English Bridge Union site
Obituary in The Times

External links

1936 births
2008 deaths
British and Irish contract bridge players
Contract bridge writers
Bermuda Bowl players
Alumni of the University of Manchester
Place of birth missing
Place of death missing
Deaths from cancer in England
Fellows of the American Physical Society


Jammit is a 1994 video game for the 3DO, MS-DOS, Sega Genesis and Super Nintendo Entertainment System. It was developed by GTE Vantage and published by GTE Entertainment.

Gameplay
The game features arcade-styled 1-on-1 street basketball, like NBA Jam or Arch Rivals. Player can choose from three playable characters.

Reception
Quick-Draw McGraw of GamePro reviewed that the 3DO version has better graphics and audio than the earlier Genesis and SNES versions, but not to the extent that one would expect from the far more powerful hardware. He also criticized the jerkiness of the characters' moves, but acknowledged that there were very few street-ball games to offer competition, especially on the 3DO. A reviewer for Next Generation gave it two out of five stars, likewise stating that the 3DO version fails to offer significant enhancement over the versions on less powerful consoles. He added that "in the end though, what kills this one is that the controls are so sluggish you'd think your Nikes had melted to the blacktop".

References

External links

1994 video games
3DO Interactive Multiplayer games
Basketball video games
DOS games
GTE Interactive Media games
North America-exclusive video games
Sega Genesis games
Super Nintendo Entertainment System games
Multiplayer and single-player video games
Video games developed in the United States
Virgin Interactive games


Moelv Station () is a railway station located in Moelv in Ringsaker, Norway on the Dovre Line. The station was opened in 1894 with the construction of the railway between Hamar and Tretten. A station building was first constructed in 1981. Moelv is only served by regional trains by Vy and night trains by SJ Norge.

External links

Railway stations on the Dovre Line
Railway stations in Hedmark
Railway stations opened in 1894
1894 establishments in Norway
Ringsaker
Railway stations in Norway opened in the 1890s


DOT1-like (Disruptor of telomeric silencing 1-like), histone H3K79 methyltransferase (S. cerevisiae), also known as DOT1L, is a protein found in humans, as well as other eukaryotes.
The methylation of histone H3 lysine 79 (H3K79) by DOT1L which is a conserved epigenetic mark in many eukaryotic epigenomes, increases progressively along the aging process, suggesting that "DOT1L might function as a vital clock, ticking the hours impassively".

DOT1L has been reported to play an important role in the processes of mixed-lineage leukemia (MLL)-rearranged leukemias

Small molecule inhibitors of Dot1L catalytic activity have been developed.

All three forms of H3K79 methylation (H3K79me1; H3K79me2; H3K79me3) are catalyzed by DOT1 in yeast or DOT1L in mammals.  H3K79 methylation participates in the DNA damage response and has multiple roles in nucleotide excision repair and sister chromatid recombinational repair.

References

Further reading

External links


Ligand-dependent corepressor is a protein that in humans is encoded by the LCOR gene.

Function

LCOR is a transcriptional corepressor widely expressed in fetal and adult tissues that is recruited to agonist-bound nuclear receptors through a single LxxLL motif, also referred to as a nuclear receptor (NR) box.

References

Further reading

External links
 PDBe-KB provides an overview of all the structure information available in the PDB for Human Ligand-dependent corepressor

Transcription coregulators


, also known as , are a class of homeless people in Japan who do not own or rent a residence (thus having no permanent address) and sleep in 24-hour Internet cafés or manga cafés. Although such cafés originally provided only Internet services, some have expanded their services to include food, drink, and showers. The term was coined in 2007 by a Nippon News Network documentary show NNN Document. The net café refugee trend has seen large numbers of people using them as their homes. The shifting definition of the industry partly reflects the dark side of Japanese economy, whose precarity has been noted since the downfall of the national economy that has lasted for decades.

Prevalence
A Japanese government study estimated that over 5,400 people are spending at least half of their week staying in net cafés. It has been alleged that this phenomenon is part of an increasing wealth gap in Japan, which has historically boasted of having an economically equal society.

A cultural anthropological perspective suggests that net cafe refugee is one of the phenomena that arose amid Japan's "lost decades" associated with the 1989 Bubble Burst and the 2011 Triple Disaster that left a long-lasting sense of "precarity." Alongside other youth crises like freeter and irregular employment, net cafe refugee can be seen as exemplifying the collective insecurity and hopelessness shared among the contemporary Japanese society.

As of 2020, it was estimated 15,000 people stay overnight in internet cafés in Tokyo. The vast majority of net café refugees are young men. Most net café refugees are urban working class, driven to an unstable form of residence by the high cost of living amid the long-term economic difficulties in Japan.

The closure of internet cafés during the COVID-19 pandemic in Japan made the homelessness problem more obvious. The coronavirus-related coverage of net café refugees address that the 24-hour feature of net cafés and manga cafés was originally used by businesspeople, but these venues turned into shelters for the urban poor, and the closure due to the pandemic is driving them homeless, even more literally.

Economics

According to the Japanese government survey, the homeless staying have little interest in manga or the Internet, and are instead using the place because of the low price relative to any of the competition for temporary housing, business hotels, capsule hotels, hostels, or any other option besides sleeping on the street.  It was also estimated that about half of those staying have no job, while the other half work in low-paid temporary jobs, which paid around 100,000 yen per month – lower than what is needed to rent an apartment and pay for transportation in a city like Tokyo.

While net cafés basically charge hourly rates, most venues promote overnight packages with discounts. The price varies by cities, but 6- or 9-hour packages typically cost around 2,000 yen. Compared to capsule hotels and dormitories (around 3,500 yen) and business hotels, the relatively cheap price made net cafés an attractive "housing option." Although they are not officially considered as accommodation facilities, their hostel-like function has taken over their primary purposes, internet service and mangas. One net café franchise's name "Net Maru" exemplifies this shifting paradigm of the entire industry, a compound word of net (ネット, netto) and stay (泊まる, tomaru).

Facilities
Some internet cafés offer free showers and sell underwear and other personal items, enabling net café refugees to use the internet cafés like a hotel or hostel. Most venues offer complimentary soft drinks and soup varieties at the lounge, and some venues sell a wide variety of restaurant-quality food items, that are likely sold by family restaurants in Japan.

Net cafés offer different seat types at different rates. Seats range from a regular chair, a reclining chair in booth, and a flat seat in booth (フラット, furatto). In addition to the night package and accommodations, this implies that the industry is expanding in accordance with the constant demand of net cafe refugees. In sum, the industry is moving away from its original intention and trying to attract customers with low budget, just like hotels and hostels.

Cyber-homeless
Another word for Net café refugees is cyber-homeless, a Japanese word based on English. Typically, the cyber-homeless are unemployed or underemployed and cannot afford to rent even the cheapest apartment, which is more than the cost per month to rent an internet booth daily. The cyber-homeless may even use the address of the internet café on resumes when applying for jobs to conceal their present form of accommodation.

The fee of around ¥1400 to ¥2400 yen for a night – which may include free soft drinks, TV, comics and internet access – is less than for capsule hotels. Some cyber-homeless may also be freeters. To elaborate, the low income earned through their unstable freeter labor hinders them from settling in traditional forms of residence and drives them to net cafés, contrary to their initial purpose as temporary stations.

See also

 Boomerang Generation
Freeter
Lost Decade
 McRefugee
 NEET
 Twixter

References

External links
Travel Video – The Cyber-Homeless of Japan

Poverty in Japan
Society of Japan
Homelessness
 Net cafe refugee
Economy of Japan
Welfare in Japan
Japanese values
Japanese family structure
Demographics
Japanese subcultures
Demographics of Japan


Protein MAK16 homolog is a protein that in humans is encoded by the MAK16 gene.

References

Further reading


Spermatogenic leucine zipper protein 1 is a protein that in humans is encoded by the SPZ1 gene.

References

Further reading


Tripartite motif-containing protein 55 is a protein that in humans is encoded by the TRIM55 gene.

The protein encoded by this gene contains a RING zinc finger, a motif known to be involved in protein-protein interactions. This protein associates transiently with microtubules, myosin, and titin during muscle sarcomere assembly. It may act as a transient adaptor and plays a regulatory role in the assembly of sarcomeres. Four alternatively spliced transcript variants encoding distinct isoforms have been described.

References

Further reading


Myosin-XVIIIb is a protein that in humans is encoded by the MYO18B gene.

The protein encoded by this gene may regulate muscle-specific genes when in the nucleus and may influence intracellular trafficking when in the cytoplasm. The encoded protein functions as a homodimer and may interact with F actin. Mutations in this gene are associated with lung cancer.

References

Further reading


tRNA modification GTPase GTPBP3, mitochondrial is an enzyme that in human is encoded by the GTPBP3 gene on chromosome 19.

The GTPBP3 gene encodes a GTP-binding protein that is evolutionarily conserved from bacteria to mammals  and which is localized to the mitochondrion and functions in tRNA modification. At least two major isoforms due to alternative splicing are known In addition, a polymorphism on valine 250 is known and may influence aminoglydoside-induced deafness.

Structure

The GTPBP3 gene contains 10 exons, and encodes a ~44 kDa GTP-binding protein that is evolutionarily conserved from bacteria to mammals. The N-terminal domain of mitochondrial tRNA modification GTPase mediates the dimerization of the protein in a potassium-independent manner, which is thought to be related to the construction of the binding site for the one-carbon-unit donor in its tRNA modification reaction function.

Function

Mitochondrial tRNA modification GTPase is thought to catalyze the formation of 5-taurinomethyluridine (τm(5)U) in the anticodon wobble position of five mitochondrial tRNA. The gene was first discovered yeast where the mutation of the yeast homolog of human GTPBP3, MSS1, is found to elicit respiratory defect in yeast only when the mitochondrial 155 rRNA P(R)454 is present. The latter is equivalent to the human 12 rRNA A1555G mutation which has been found to associate with deafness. Hence GTPBP3 and its yeast homolog function in modification of mitochondrial function. In human, GTPBP3 is ubiquitously expressed in multiple tissues in multiple transcripts.  As a tRNA modification enzyme, it is thought to function to modify codon-anticodon interaction, which is consistent with its modification of the severity of phenotypes in 12S rRNA A1555G mutation..

Clinical Significance

Mutations in GTPBP3 are known to cause hypertrophic cardiomyopathy and mitochondrial defects. Individuals with homozygous or compound heterozygous mutations in GTPBP3 present with combined deficiency of respiratory chain complexes in skeletal muscle, which require mitochondrial translation of mitochondrial-encoded complex subunits to assemble. GTPBP3 mutations cause severe mitochondrial translation defect. The majority of characterized subjects presented with lactic acidosis and hypertrophic cardiomyopathy.

The valine 250 polymorphisms on GTPBP3 is associated with severity of aminoglycoside-induced deafness in human, a disease associated with homoplasmic A1555G mutation in the mitochondrial-encoded 12S rRNA and is characterized by deafness, varying from profond congenital hearing loss to normal hearing.

References

Further reading

Enzymes


Protein BEX2 also known as brain-expressed X-linked protein 2 is a protein that in humans is encoded by the BEX2 gene.

References

Further reading


The Tamaulipas Institute of Higher Education (), or IEST for its acronym in Spanish, is a private university in Altamira, Tamaulipas, Mexico founded in 1974. It is one of the most recognized universities along with ITESM Campus Tampico in the southern area of the state of Tamaulipas. It serves all the metropolitan area of Tampico, Ciudad Madero and Altamira, the northern part of the state of Veracruz and the eastern part of the state of San Luis Potosí. Its campus consist of Campus Altamira, and Campus Cd. Valles located in Ciudad Valles, San Luís Potosí.

Since 2005, it has been officially allied with the Anahuac Universities Network.

Organization
IEST's divisions consists of academic departments rather than faculties. Both undergraduate and graduate studies are available. IEST also provides the Preparatoria IEST (Secondary school), at campus Ciudad Valles, which consists of Upper and Lower Secondary Education (Preparatoria and Secundaria), with no undergraduate or graduate services.

Undergraduate
The academic departments, with their respective majors at campus Altamira for undergraduate level are:

Humanities
Architecture
Graphic Design
Law
Languages
Philosophy
Psychology
Exact Sciences
Chemistry
Information Technology and Telecommunications
Industry for Direction
Mechatronics
Petroleum and Renewable energy
Management and Economics
Finance and Accounting
International Business
Gastronomy
Direction and Management
Marketing
Tourist Management

Graduate
The academic departments, with their respective masters at campus Altamira for graduate level are:

Humanities
Education
Private law
Management and Economics
Corporate finance
Direction and quality education
Logistics and international business
Management
Marketing management
Administration of human capital
Taxes
Quality

Private universities and colleges in Mexico
Catholic universities and colleges in Mexico
Universities and colleges in Tamaulipas
Educational institutions established in 1974
Regnum Christi
Legion of Christ
Anahuac universities


Protein BAT2-like is a protein that in humans is encoded by the BAT2L gene.

Interactions

KIAA0515 has been shown to interact with EHMT2.

References

Further reading


Transmembrane protein 25 is a protein that in humans is encoded by the TMEM25 gene.

References

Further reading


The 17th César Awards ceremony, presented by the Académie des Arts et Techniques du Cinéma, honoured the best French films of 1991 and took place on 22 February 1992 at the Palais des Congrès in Paris. The ceremony was chaired by Michèle Morgan and hosted by Frédéric Mitterrand. Tous les matins du monde won the award for Best Film.

Winners and nominees
The winners are highlighted in bold:

Best Film:Tous les matins du monde, directed by Alain CorneauMerci la vie, directed by Bertrand BlierLa Belle Noiseuse, directed by Jacques RivetteVan Gogh, directed by Maurice Pialat
Best Foreign Film:Toto le Héros, directed by Jaco Van DormaelAlice, directed by Woody AllenDances with Wolves, directed by Kevin CostnerThe Silence of the Lambs, directed by Jonathan DemmeThelma & Louise, directed by Ridley ScottUrga, directed by Nikita Mikhalkov
Best Debut:Delicatessen, directed by Marc Caro, Jean-Pierre JeunetLes Arcandiers, directed by Manuel SanchezL'Autre, directed by Bernard GiraudeauFortune Express, directed by Olivier SchatzkyLune froide, directed by Patrick Bouchitey
Best Actor:Jacques Dutronc, for Van GoghMichel Piccoli, for La Belle NoiseuseHippolyte Girardot, for Hors la vieJean-Pierre Marielle, for Tous les matins du mondeGérard Jugnot, for Une époque formidable...
Best Actress:Jeanne Moreau, for La vieille qui marchait dans la merAnouk Grinberg, for Merci la vieJuliette Binoche, for Les Amants du Pont-NeufEmmanuelle Béart, for La Belle NoiseuseIrène Jacob, for La Double vie de Véronique
Best Supporting Actor:Jean Carmet, for Merci la vieJean-Claude Dreyfus, for DelicatessenTicky Holgado, for Une époque formidable...Bernard Le Coq, for Van GoghGérard Séty, for Van Gogh
Best Supporting Actress:Anne Brochet, for Tous les matins du mondeCatherine Jacob, for Merci la vieJane Birkin, for La Belle NoiseuseHélène Vincent, for J'embrasse pasValérie Lemercier, for L'Opération Corned-Beef
Most Promising Actor:Manuel Blanc, for J'embrasse pasLaurent Grévill, for L'Année de l'éveilThomas Langmann, for Paris s'éveilleGuillaume Depardieu, for Tous les matins du mondeChick Ortega, for Une époque formidable...
Most Promising Actress:Géraldine Pailhas, for La Neige et le feuMarie-Laure Dougnac, for Delicatessen Marie Gillain, for Mon père, ce hérosAlexandra London, for Van GoghElsa Zylberstein, for Van Gogh
Best Director:Alain Corneau, for Tous les matins du mondeBertrand Blier, for Merci la vieJacques Rivette, for La Belle NoiseuseAndré Téchiné, for J'embrasse pasMaurice Pialat, for Van Gogh
Best Writing:Gilles Adrien, Marc Caro, Jean-Pierre Jeunet, for DelicatessenBertrand Blier, for Merci la vieAlain Corneau, Pascal Quignard, for Tous les matins du mondeMaurice Pialat, for Van Gogh
Best Cinematography:Yves Angelo, for Tous les matins du mondeDarius Khondji, for DelicatessenGilles Henry, Emmanuel Machuel, for Van Gogh
Best Costume Design:Corinne Jorry, for Tous les matins du mondeValérie Pozzo di Borgo, for DelicatessenÉdith Vesperini, for Van Gogh
Best Sound:Anne Le Campion, Pierre Gamet, Gérard Lamps, Pierre Verany, for Tous les matins du mondeVincent Arnardi, Jérôme Thiault, for Delicatessen Jean-Pierre Duret, François Groult, for Van Gogh
Best Editing:Hervé Schneid, for DelicatessenClaudine Merlin, for Merci la vieMarie-Josèphe Yoyotte, for Tous les matins du monde
Best Music:Jordi Savall, for Tous les matins du mondeCarlos D'Alessio, for DelicatessenZbigniew Preisner, for La Double vie de VéroniqueJean-Claude Petit, for Mayrig
Best Production Design:Jean-Philippe Carp, Miljen Kreka Kljakovic, for DelicatessenMichel Vandestien, for Les Amants du Pont-NeufPhilippe Pallut, Katia Wyszkop, for Van Gogh
Best Animated Short:J'entends plus la guitare, directed by Bernard PalaciosLa Saga des glaises, directed by David Ferre, Olivier Théry-Lapiney
Best Fiction Short:25 décembre 58, 10h36, directed by Diane Bertrand
Best Documentary Short:Hermann Heinzel, ornithologue, directed by Jacques Mitsch
Honorary César:Michèle MorganSylvester Stallone

See also
 64th Academy Awards
 45th British Academy Film Awards

External links
 Official website

 17th César Awards at AlloCiné

1992
1992 film awards
Cesar


Colniza is a municipality in the state of Mato Grosso, Brazil.

Demographics

Colniza has the highest homicide rate in Brazil with 165 deaths per year per 100 thousand inhabitants.
It is the westernmost and largest (by area) municipality of the state.

Conservation

The municipality of Colniza has a mosaic of conservation units consisting of the Rio Madeirinha Ecological Station, the Rio Roosevelt Ecological Station, the Tucumã State Park and the Guariba-Roosevelt Extractive Reserve.

Satellite monitoring showed that Colniza had the highest level of deforestation in Mato Grosso in the six years from 2010 to 2016, with  cleared, most of it illegally. Rates of deforestation rose successively in 2013, 2014 and 2015.

The  Rio Madeirinha Ecological Station is a fully protected environmental unit created in 1997.
The  Rio Roosevelt Ecological Station is a strictly protected conservation unit created in 1997.
The  Guariba-Roosevelt Extractive Reserve is a sustainable use unit created in 1996.
The municipality also contains  of the Campos Amazônicos National Park, a  protected area created in 2006 that protects an unusual enclave of cerrado vegetation in the Amazon rainforest.
It contains 44% of the  Igarapés do Juruena State Park, created in 2002.

References

Sources

Municipalities in Mato Grosso
Populated places established in 1998


Protein tyrosine phosphatase non-receptor type 5 is an enzyme that in humans is encoded by the PTPN5 gene.

Protein tyrosine phosphatase (PTP), non-receptor type 5, also known as STEP (STriatal-Enriched protein tyrosine Phosphatase), was the first brain-specific PTP discovered. The human STEP locus maps to chromosome 11p15.2-p15.1 and the murine STEP gene to chromosome 7B3-B5. The single STEP gene is alternatively spliced to produce several isoforms, the best characterized of which are the cytosolic STEP46 protein and the membrane-associated STEP61 protein.

Substrates

Seven known targets of STEP have been identified as of 2015, including ERK1/2, p38, Fyn, Pyk2, PTPα, and the glutamate receptor subunits GluN2B and GluA2. STEP dephosphorylation of the kinases (ERK1/2, p38, Fyn, and Pyk2) occurs at a regulatory tyrosine within the kinase activation loop and leads to their inactivation. Dephosphorylation of a regulatory tyrosine on PTPα prevents the translocation of PTPα from the cytosol to lipid rafts, where it normally activates Fyn. STEP thereby directly inactivates Fyn and also prevents the translocation of PTPα to compartments where it activates Fyn. STEP dephosphorylation of GluN2B and GluA2 leads to the internalization of NMDARs (GluN1/GluN2B) and AMPARs (GluA1/GluA2). Thus, one function of STEP is to oppose synaptic strengthening by inactivating kinases and internalizing receptors that are critical for the development of synaptic strengthening.

Clinical significance

STEP levels are disrupted in several diseases. Alzheimer’s disease (AD) was the first illness to be associated with elevated STEP expression both in human cortex and in several mouse models of AD. STEP is also increased in fragile X syndrome, schizophrenia, and Parkinson’s disease. In AD and FXS mouse models, genetic reduction of STEP expression reverses many of the cognitive and behavioral deficits.
Other laboratories have now shown that STEP activity is also reduced in several additional disorders. Thus, STEP levels or activity is decreased in Huntington’s disease, cerebral ischemia, alcohol abuse, and stress disorders. The emergent model suggests that an optimal level of STEP is required at synaptic sites, and that both high and low levels disrupt synaptic function.

Inhibition

Several STEP inhibitors have now been discovered. GlaxoSmithKline chose STEP as a new project for their Discovery Partnerships with Academia (DPAc) in 2014. This is a relatively new program in drug discovery and brings together the academic world with the drug discovery expertise of GSK to discover new inhibitors of validated targets.

 TC-2153

References

Further reading


Major facilitator superfamily domain-containing protein 2 (MFSD2 or MFSD2A) -- also known as sodium-dependent lysophosphatidylcholine symporter 1 --  is a protein that in humans is encoded by the MFSD2A gene. MFSD2A is a membrane transport protein that is expressed in the endothelium of the blood–brain barrier (BBB) and has an essential role in BBB formation and function. Genetic ablation of MFSD2A results in leaky BBB and increases central nervous system endothelial cell vesicular transcytosis without otherwise affecting tight junctions. MFSD2A is an atypical SLC, thus a predicted SLC transporter. It clusters phylogenetically to AMTF8.

In addition to transport of other lysophosphatidylcholines across the BBB, MSFD2A is the primary mechanism for docosahexaenoic acid (DHA, an omega-3 fatty acid) uptake and transport into the brain. It may also be responsible for uptake and transport of tunicamycin.

Complete loss of MFSD2A in human leads to a recessive lethal microcephaly syndrome consisting of enlarged lateral ventricles and underdevelopment of the cerebellum and brainstem.  This is presumably due to loss of uptake of essential polyunsaturated fatty acids by the brain endothelial cells, which utilize MFSD2A as a transporter for these fats.  Serum from patients showed elevated levels of essential polyunsaturated fatty acids, presumably due to the inability of vascular cells to uptake these lipids in the absence of protein function. Without the ability to uptake these fats into endothelial cells, there is breakdown of the blood-brain-barrier and loss of brain volume.  This was demonstrated in a zebrafish model by intracardiac injection of dye, which was found to extravasate into the brain parenchyma following  inactivating one of the paralogues of MSFD2A known as mfsd2aa.

References

Further reading


Leucine rich repeat and Immunoglobin-like domain-containing protein 1 also known as LINGO-1 is a protein which is encoded by the LINGO1 gene in humans. It belongs to the family of leucine-rich repeat proteins which are known for playing key roles in the biology of the central nervous system. LINGO-1 is a functional component of the Nogo (neurite outgrowth inhibitor) receptor also known as the reticulon 4 receptor.

It has been suggested that LINGO-1 antagonists such as BIIB033 could significantly improve and regulate survival after neural injury caused by the protein.

Structure

The human LINGO-1 is a single-pass type 1 transmembrane protein of 614 amino acids. It contains a signal sequence of 34 residues, followed by a LRR (leucine-rich repeat) domain, an Ig (immunoglobulin-like) domain, a stalk domain, a transmembrane region and a short cytoplasmic tail. As a transmembrane protein, it can mostly be found on the cell membrane.

The LINGO-1 structure has been shown to be highly stable both in its crystal form and in solution, thanks to its leucine-rich repeat Ig-composite fold. Since the tetramer has a very large surface area into the cell membrane, it is thought that this may serve as an efficient and stable binding platform, facilitating the interaction with NgR, p75, TROY complex.

Extracellular domain

The extracellular domain consists of the signal sequence, 11 LRR motifs comprised between an N-terminal and C-terminal capping domains, and the Immunoglobulin-like (IgC2) domain. The C-terminal LRR domain is essential for the protein's function with its screening for proteins that interact with this domain. The structure, together with biophysical analysis of LINGO-1 properties have revealed that the protein's LRR-Ig composite fold of the protein can drive it to associate with itself in a circular ring-like form, creating a closed and stable tetramer in solution and in crystal.

Intracellular domain

The intracellular part of the protein is formed by the transmembrane region and a cytoplasmic tail of 38 residues. It contains a canonical Epidermal Growth Factor Receptor (EGFR)-like tyrosine phosphorylation site on the 591 residue that is critical for intracellular signals.

Co-receptor

LINGO-1 is a co-receptor that interacts with the ligand-binding Nogo-66 receptor (NogoR) in the Nogo receptor signaling complex. The Nogo receptor complex is formed when Nogo-66 binds to its receptor.

LINGO-1 is an homotetramer which forms a ternary complex with RTN4R/NGFR and RTN4R/TNFRSF19.

Post-translational modifications

LINGO-1 contains several N-glycosylation sites that could have a negative effect on its capacity to self-interact with cis or trans, with other partners, or gangliosides. It also contains high-mannose glycans.

Tissue distribution

LINGO-1 is expressed almost exclusively in the central nervous system (CNS). It can be found in the brain and in neurons and oligodendrocytes. LINGO-1 mRNA is expressed in an almost exclusive manner in the central nervous system during both embryonic and postnatal stages. It is targeted to the plasma membrane of neurons, but it is possible that a smaller quantities of the protein may be found in other intracellular compartments. Its highest expression is in specific adult human brain regions such as the cerebral cortex, a region involved in sensory-motor function, cognition and working memory; the hippocampus, responsible for long-term memory and the encoding and retrieval of multi-sensory information; the amygdala, implicated in the stress response; as well as the thalamus, with a more constant and basal level of expression across the remainder of the brain.

Function and mode of action

Since LINGO-1 is a leucine-rich repeat protein, which are known for their important role in protein-protein interactions in a wide variety of cellular processes and their implication in important functions like neuronal differentiation and growth or the regulation of axon guidance and regeneration processes, it is logical to deduce that its functions are linked with the nervous system.

LINGO-1 is an essential negative regulator of myelination. It has been implicated in the inhibition of axon regeneration through a ternary complex formed with NgR1/Nogo-66 (ligand-binding subunit) and p75 (signal transducing subunit). NgR1 relies on its co-receptors for transmembrane signalling. The three major myelin-associated inhibitory factors are Nogo, oligodendrocyte myelin glycoprotein, and myelin-associated glycoprotein which all share this trimolecular receptor complex. The inhibitory action is achieved through RhoA-GTP upregulation in response to the presence of MOG, MAG or Nogo-66 in the central nervous system.  LINGO-1 also inhibits oligodendrocyte precursor differentiation and myelination, by a mechanism that also involves activation of RhoA, but which apparently does not require p75 or NgR1.

LINGO-1 is involved in the regulation of neural apoptosis by inhibiting WNK3 kinase activity. It has been shown that blocking the extracellular domain of LINGO-1 disrupts the interaction between receptor kinases and LINGO-1 which directly attenuates inhibition of neuronal survival. However among the four WNK family members, only WNK3 has been shown to regulate and increase cell survival in a caspase-3-dependent pathway.

To be able to understand how these components regulate signalling processes an experiment has been set up "model of serum deprivation" (SD) to prompt neuronal apoptosis. Research shows that treatments either with a construct containing the IgC2 or EGFR domains in the LINGO1 protein or with Nogo66 which act like a NgR1 agonist, therefore initiating a physiological response when combined with the receptor, resulting in an increased rate of apoptosis in primary cultured cortical neurons under SD.

In addition, reducing the expression levels of the serine/threonine Kinase WNK3 (using gene silencing via RNA interference (ShRNA)) or inhibiting its kinase activity had similar effects on the survival of such neurons. The adverse effects of Nogo66 have proved to enhance the co-association of LINGO1 and WNK3, causing the binding of WNK3 to the intracellular domain of LINGO1 leading to reduced WNK3 kinase activity. LINGO1 promotes neural apoptosis by inhibiting WNK3 kinase activity.

Signaling pathways

LINGO-1 is able to interact with different co-factors and co-receptors, which can lead to the activation o signaling pathways that can have an effect on the regulation of neuronal survival, axon regeneration, oligodendrocyte differentiation, or myelination processes in the brain.

Known interactions are with proteins such as Oligodendrocyte-myelinn glycoprotein, Nogo-A (neurotic outgrowth inhibitor), and myelin associated glycoproteins. LINGO-1 also interacts with transmembrane proteins: EFGR, along with its ligand epidermal growth factor (EFG); brain derived neurotrophic factor (BNDF) and its receptor, amyloid precursor protein (APP), and tropomyosin receptor kinase A (TrkA). There are other interactions with proteins that are implicated in neurological and psychiatric disorders: WNK lysine deficient protein in kinase 1 (WNK1), mitogen activated protein kinase 2/3 (MEK 2/3), extracellular signal reduced kinase 5 (ERK5), RhoA, and others.

Neurological and psychiatric disorders

LINGO-1 is coded by the LINGO-1 gene, which is located on the human chromosome 15, more precisely on the locus 15q24-26, which is a region that has a primordial implication in number of psychiatric, addictive and anxiety related disorders. Genomic alterations of this regions can be factors for disorders such as schizophrenia, depression, autism, panic disorder or anxiety.

Brain regions identified as highly expressing Lingo-1 transcripts have also been heavily implicated in both neurological and psychiatric disorders such as spinal cord injury, traumatic brain injury, multiple sclerosis (MS), Parkinson's disease, essential tremor (ET), Alzheimer's disease, epilepsy and glaucoma (central nervous system diseases); as well as stress and panic disorders, schizophrenia, amnesia, etc. The role of Lingo-1 in these neurological disorders consists on its inhibitory role in neurite outgrowth, oligodendrocyte differentiation and myelination, making it difficult for the nervous system to regenerate the injured areas, whether these injuries come from endogenous or exogenous processes.

Spinal cord injury

Spinal cord injury results in the damage of the axonal tracts whose function is to control motor and sensory activity. This protein has been found in this axonal tracts of adolescent rat spinal cords following injury. Furthermore, a five time increase in Lingo-1 mRNA levels was detected 14 days post injury. Lingo-1-Fc, a soluble form of Lingo-1, has also been shown to antagonize Lingo-1 signaling pathways by inhibiting the binding of Lingo-1 to NgR, in consequence, vast improvements in the functional recovery of rats following lateral hemisection of the spinal cord were observed.

Essential tremor and Parkinson

Essential tremor, one of the most common neurological diseases, is characterized by postural and action tremor. Recent research shows that around the 20% of people who suffer this disease have an increase of the protein LINGO1 in their cerebellum, therefore linking LINGO1 to essential tremor would result in the development of more effective symptomatic therapies and treatment.

It has been found that there is a marker in LINGO-1 genome, a variant (rs9652490) that is significantly associated with essential tremor, increasing the risk of having the pathology.

As for Parkinson's disease, which is also an age-related movement disorder, it was discovers that levels of LINGO-1 are more elevated in the substantia nigra and cerebellum of post-mortem Parkinson's disease brains compared to control groups. Dudem et al., (2020) also demonstrated that LINGO1 is a novel regulatory subunit of large conductance, Ca2+ activated (BK) channels. It is thought that dopamine neuron survival and behavioral abnormalities are due to the over expression of LINGO-1 in Parkinson's patients.

Traumatic brain injury

Traumatic brain injury involves the necrotic and apoptotic death of brain cells in vulnerable and delicate areas such as the cerebral cortex and hippocampus, where it is known that there is an expression of Lingo-1 in both development and the adult stage of life. RhoA signaling is largely responsible for the neuronal response to neuronal inhibitory proteins and the regeneration (or lack of in case of its activation) of damaged axons. Receptor Lingo-1 stimulates RhoA, which activates ROCK (RhoA kinase) which, in turn, stimulates LIM kinase, which then stimulates cofilin, which effectively reorganizes the actin cytoskeleton of the cell. In the case of neurons, activation of this pathway results in growth cone collapse, therefore inhibits the growth and repair of neural pathways and axons. Inhibition of this pathway by its various components usually results in some level of improved re-myelination. The use of Lingo-1-Fc as an antagonist for Lingo-1 shows the inhibition of RhoA activation. Since this soluble form of Lingo-1 is able to block the interactions between Lingo-1 and NgR, it is reasonable to think that the blockade of RhoA occurs at the level of Lingo-1/NgR/p75 or TROY complex, leading to the conclusion that Lingo-1plays a very important part in the lack of re-myelination, repair of neural and axon injuries, etc.

Schizophrenia

Schizophrenia is a chronic, severe and disabling brain disorder.

As said before, leucine-rich repeat and immunoglobulin domain-containing protein (Lingo-1) is an essential negative regulator of myelination and neurite extension. Both myelination and neurite outgrowth occur during brain maturation, and it is during this late period of brain development (adolescence and early adulthood) when schizophrenia is first expressed. In fact, myelination peaks during late adolescence, coinciding with the onset of schizophrenia. Consequently, an excessive action of Lingo-1 through demyelination and blocking neurite extension may be one of the possible causes of this disorder.

The brain regions which are highly disrupted in the pathophysiology of this disease are hippocampus and dorsolateral prefrontal cortex. Therefore, clinical studies have been developed in order to study these brain regions in people who suffer schizophrenia. To investigate the hypothesis that myelin fraction is lower in schizophrenia patients than in healthy subjects, a technique called magnetic resonance spectroscopy (MRS), which allows analysis of myelin, is used. This studies reported that there was in fact, a dysfunctional profile of myelination in these two areas of the brain in schizophrenia sufferers.

Post-mortem studies were then realized in order to compare the levels of the protein Lingo-1 in these two brain regions (hippocampus and dorsolateral prefrontal cortex) between schizophrenia and healthy subjects. Effectively, it was shown that the levels of Lingo-1 where significantly higher in schizophrenia than in control groups.

Taking this into account, there is a clear relationship in between schizophrenia and demyelination, therefore, this disease is linked with Lingo-1 protein. Very possibly, an effective treatment of this disease would be the use of Lingo-1 antagonists, such as Anti-Lingo-1, which would offset the lack of myelin and hopefully avoid the disease. Thus, this treatment is still in ways of development and research.

Multiple sclerosis

Multiple sclerosis is among the most common neurological disorders in young adults and it consists in the destructions and damage of the central nervous system (CNS) myelin due to persistent inflammation in the brain and spinal cord. This demyelination is shown to cause mitochondrial dysfunction in axons, leading to their degeneration. These damages disrupt the ability and capacity of the CNS to communicate, causing, therefore, a wide range of symptoms including physical, mental and even psychiatric ones. The best way of re-myelination is encouraging the differentiation of endogenous adult precursor cells into mature oligodendrocytes in the injured regions. These precursor cells are called oligodendrocyte precursor cells (OPCs). It is known that in early stages of MS re-myelination can be achieved successfully and efficiently whereas it cannot in late and progressive stages. Regarding Lingo-1, we know that its signaling pathway is a negative regulator of OPCs differentiation, as well as Notch's and Wnt's.

Lingo-1 antagonists are able to promote re-myelination in CNS by means of stimulating OPCs differentiation which was before blocked by this protein. This has been seen in several experiments that resulted in significant increases of oligodendrocytes differentiation by targeting Lingo-1 with its antagonists, such as the antibody Anti-LINGO-1 (BIIB033).

Glaucoma

Glaucoma is a group of eye diseases characterized by features including morphological changes in the optic nerve head and therefore in the visual fields of the patients. There are two main types; open-angle and closed-angle glaucoma. The loss of RGCs (retinal ganglion cells) and their axons results in visual field loss. Increasing evidence also supports the existence of compartmentalized degeneration in synapses. It has been shown that the first symptoms of this disease are usually ocular hypertension. Elevated IOP (intraocular pressure) has been identified as the etiology of glaucoma which causes neural RCG degeneration in the retina.

LINGO1 was found to be expressed in the normal retina and was up regulated in RCGs after the induction of ocular hypertension in a rat chronic glaucoma model. Hence LINGO1 functions as a negative regulator of neuronal survival, axonal regeneration and oligodendrocyte differentiation. LINGO1 binds with TrkA and inhibits myelination by oligodendrocytes in vitro. Further more it binds to BDNF receptor and TrkB inhibiting the activation of TkrB by binding of BNDF after the induction of ocular hypertension.

Neuroprotection of RCGs

Even though BDNF is an important survival factor for RGCs both during development and adult life,  BDNF can only slightly increase the survival rate of RCGs, and does not significantly “rescue” injured RCGs in hypertensive eyes after episcleral vein cauterization. The negative regulatory function of LINGO1 may be involved in the limited neuroprotective effect of BDNF and it could be reversed after blocking LINGO1 function.

LINGO 1 negatively regulates TrkB activation through the signalling pathway of BDNF/TrKB, and anti-LINGO-1 exerts neuroprotective effects via activation of BDNF/TrkB.

Better than BDNF and BII003 (LINGO1 antagonist) alone, the combined treatment of both provides long term RCG neuroprotection after the induction of ocular hypertension. In conclusion BII033 may provide an attractive therapeutic strategy to promote neuroprotection in glaucoma.

Antagonists

Blocking the activity of lingo-1 has several potential applications in the treatment of neurodegenerative diseases.

(A myelin sheath is a lipid protective coating that covers and protects nerve cells (axons). These sheaths makes possible rapid and accurate transmission of nerve signals. Multiple sclerosis destroys these myelin sheaths, leading to a deterioration in nerve signal transmission. Once this protective myelin coating is stripped away, it leads to apoptosis of the neuron; axons gradually die, causing the muscle spasms and paralysis that are characteristic of the disease.)

Anti-lingo-1 (BIIB033)
Anti-lingo-1 (BIIB033) is a monoclonal antibody specific to the lingo-1 protein and is designed to promote remyelination (the formation of new myelin on axons) and neuroprotection.  The protein lingo-1 inhibits the action of myelin-making cells, oligodendrocytes, which are surrounding the axons. Its antagonist, the antibody anti-lingo-1 would block this protein and even would be capable of myelin repair.

A number of clinical trials of the anti-lingo-1 antibody drug (BIIB033) have either been completed or are underway. Acute optic neuritis (AON) is a disease which involves damage within the nerve fibers and loss of myelin within the optic nerve (it normally involves one eye and it's characterized by inflammation). One clinical trial studying the effects on BIIB033 on acute optic neuritis. Throughout the study, optic nerve conduction latency was measured (the time for a signal to travel from the retina to the brain's visual cortex). As about half of patients with optic neuritis will later develop multiple sclerosis, BIIB033 antibody treatment is also being considered for the former disease. It is thought that Anti-Lingo-1 would produce the necessary myelin to avoid neurodegeneration.

References

Further reading

External links