Aryl hydrocarbon receptor nuclear translocator-like protein 1 or Brain and Muscle ARNT-Like 1 is a protein that in humans is encoded by the Bmal1 gene known as ARNTL, MOP3, less BHLHE5, BMAL, BMAL1C, JAP3, PASD3, TIC. BMAL1 encodes a transcription factor with two PAS domains; the human Arntl gene is located on the p15 band of the 11th chromosome. The BMAL1 protein is 626 amino acids long and plays a key role as one of the positive elements in the mammalian auto-regulatory transcription-translation negative feedback loop, responsible for generating molecular circadian rhythms. Research has revealed that Bmal1 is the only clock gene without which the circadian clock fails to function in humans. Bmal1 has been identified as a candidate gene for susceptibility to hypertension and obesity, mutations in Bmal1 have been linked to infertility and lipogenesis problems, altered sleep patterns. BMAL1, according to genome-wide profiling, is estimated to target more than 150 sites in the human genome, including all of the clock genes and genes encoding for proteins that regulate metabolism.
The Arntl gene was discovered in 1997 by two groups of researchers, John B. Hogenesch et al. in March under the name Mop3 and Ikeda and Nomura in April as part of a superfamily of PAS domain transcription factors. In 1998, Hogenesch's additional characterization of MOP3 revealed that its role as the partner of bHLH-PAS transcription factor CLOCK was essential to mammalian circadian clock function; the MOP3 protein, as it was known by the Hogenesch group, was found to dimerize with MOP4, CLOCK, hypoxia-inducible factors. The names BMAL1 and ARNTL were adopted in papers. One of ARNTL protein's earliest discovered functions in circadian regulation was related to the CLOCK-BMAL1 heterodimer, which would bind through an E-box enhancer to activate the transcription of the gene encoding vasopressin. However, the gene's importance in circadian rhythms was not realized until the knockout of the gene in mice showed complete loss of circadian rhythms in locomotion and other behaviors. SIRT1 regulates PER protein degradation by inhibiting transcriptional activity of the BMAL1:CLOCK heterodimer in a circadian manner through deacetylation.
The degradation of PER proteins prevents the formation of the large protein complex, thus disinhibits the transcriptional activity of the BMAL1:CLOCK heterodimer. The CRY protein is signaled for degradation by poly-ubiquitination from the FBXL3 protein resulting in the disinhibition of BMAL1:CLOCK heterodimer activity. In addition to the circadian regulatory TTFL loop, Bmal1 transcription is regulated by competitive binding to the retinoic acid-related orphan receptor response element-binding site within the promoter of Bmal1; the CLOCK/BMAL1 heterodimer binds to E-box elements in promoter regions of Rev-Erbα and RORα/ß genes, upregulating transcription and translation of REV-ERB and ROR proteins. REV-ERBα and ROR proteins regulate BMAL1 expression through a secondary feedback loop and compete to bind to Rev-Erb/ROR response elements in the Bmal1 promoter, resulting in BMAL1 expression repressed by REV-ERBα and activated by ROR proteins. Other nuclear receptors of the same families have been shown to act on Bmal1 transcriptional activity in a similar manner.
Several posttranslational modifications of BMAL1 dictate the timing of the CLOCK/BMAL1 feedback loops. Phosphorylation of BMAL1 targets it for ubiquitination and degradation, as well as deubiquitination and stabilization. Acetylation of BMAL1 recruits CRY1 to suppress the transactivation of CLOCK/BMAL1; the sumoylation of BMAL1 by small ubiquitin-related modifier 3 signals its ubiquitination in the nucleus, leading to transactivation of the CLOCK/BMAL1 heterodimer. CLOCK/BMAL1 transactivation, is activated by phosphorylation by casein kinase 1ε and inhibited by phosphorylation by MAPK. Phosphorylation by CK2α regulates BMAL1 intracellular localization and phosphorylation by GSK3B controls BMAL1 stability and primes it for ubiquitination. In 2004, Rora was discovered to be an activator of Bmal1 transcription within the suprachiasmatic nucleus, regulated by its core clock. Rora was found to be required for normal Bmal1 expression as well as consolidation of daily locomotor activity; this suggests that the opposing activities of the orphan nuclear receptors RORA and REV-ERBα, the latter of which represses Bmal1 expression, are important in the maintenance of circadian clock function.
Rora is under investigation for its link to autism, which may be a consequence of its function as a circadian regulator. Along with mammals such as humans and mice, orthologs of the Arntl gene are found in fish, reptiles and Drosophila. Unlike mammalian Arntl, circadian regulated, the Drosophila Cycle is constitutively expressed. In humans, three transcript variants encoding two different isoforms have been found for this gene; the importance of these transcript variants is unknown. The Arntl gene is located within the hypertension susceptibility loci of chromosome 1 in rats. A study of single nucleotide polymorphisms within this loci found two polymorphisms that occurred in the sequence encoding for Arntl and were associated with type II diabetes and hypertension; when translated from a rat model to a human model, this research suggests a causative role of Arntl gene variation in the pathology of type II diabetes. Recent phenotype data suggest this gene and its part
Bernard Johannes "Joost" Eerdmans is a Dutch politician of the Livable Rotterdam party. He has been an Alderman and the Deputy mayor of Rotterdam since 15 May 2014. Bernard Johannes Eerdmans was born on 9 January 1971 in Harderwijk in the Dutch Province of Gelderland in a Reformed family. Eerdmans studied Management Science at the Erasmus Universiteit in Rotterdam. In 1995 he received his master's degree, having undertaken postgraduate studies at the Public administration School for Public and Environmental Affairs at Indiana University in Bloomington, Indiana in 1993. After working for some time on projects for the Christian Democratic Appeal, Eerdmans worked at the Ministry of Justice from 1997 until 1999. In 1999 he became secretary to the mayor of Rotterdam. In 2002 Eerdmans contacted Pim Fortuyn, who at that time was busy assembling a list of candidates for his new political party, Pim Fortuyn List. Eerdmans is placed 19th on the list and after the 2002 elections he became a member of the House of Representatives, while his party joined the First Balkenende cabinet.
After the fall of the cabinet, new elections were called. This time the LPF won only 8 seats, but since Eerdmans was second on the list he remained in Parliament, he was removed from the party's parliamentary faction after it was definitively announced that Eerdmans would be on the Eén NL candidate list for the 2006 elections. For the 2006 Dutch general election, Eerdmans split with the LPF to form a new political party called One NL with Marco Pastors of Livable Rotterdam. After the dismal result of One NL in the 2006 elections, Eerdmans left Dutch politics. Eerdmans was elected lijsttrekker of Leefbaar Rotterdam on 6 October 2013. In the local elections of 2014 Leefbaar Rotterdam became the biggest party in Rotterdam, meaning the party would get the chance to lead the formation of a new coalition; the party subsequently formed a coalition with CDA, in which Eerdmans is an alderman. Eerdmans was a television host on the Dutch channel Het Gesprek, he was one of the hosts of the Dutch program TROS Regelrecht.
Official Drs. B. J. Eerdmans Parlement & Politiek
Michelle Christensen is a U. S. car designer. She was Acura's first female exterior designer. Since 2005 Christensen has worked for Acura and was the lead designer of the second generation Honda NSX. Christensen grew up in California, she learned about the mechanics of cars from her father, into hot rods and muscle cars. In school she developed an interest in drawing and fine art and at community college she learned about car design and went on to study at Art Center College of Design in Pasadena. Christensen said that car design is the ideal blend of her passions, "art and making things for people."Christensen undertook an internship at Volvo's Camarillo studio in California before joining Acura in 2005. She worked for General Motors in 2010 before returning to Acura as Lead Principal Designer at Honda R&D; the 2016 Honda NSX was her first project as the lead designer. Christensen received the Woman on Top award from Marie Claire magazine. Acura ZDX 2009 Acura RDX Acura RL sedan facelift Acura RLX sedan Honda NSX 2015
USS Picket was a Chimo-class minelayer of the United States Navy during World War II. Picket was completed 15 April 1942 by Marietta Manufacturing Co. Point Pleasant, West Virginia, as the U. S. Army mine planter USAMP-1 General Henry Knox as the first of the WW II period planters built for the U. S. Army Mine Planter Service. USAMP Knox was transferred to the U. S. Navy 2 January 1945. Picket departed Charleston, South Carolina on 11 March 1945, arrived Little Creek, Virginia, 13 March. Following shakedown, she reported for duty 3 April to Commander, Service Force, Norfolk, Virginia. Loaded with minesweeping equipment, she departed Norfolk 26 April, transited the Panama Canal 7 May, arrived San Diego, 20 May. Following training, Picket departed San Diego 9 June, proceeded via Pearl Harbor, Eniwetok and Saipan to Okinawa, arriving 28 July to serve as minesweeper tender. Picket departed Okinawa on 16 August, following rendezvous with Task Force 31 on the 21st, she entered Tokyo Bay on the 28th. With minesweepers, she departed Tokyo Bay on 12 September, arrived at Wakayama, Japan, on the 14th.
Sailing from Kii Suido on 20 September, she entered the Inland Sea on the 22nd. Through 31 October she operated with minesweepers to clear the approaches to Hiro, Gunchū, Matsuyama for U. S. Army landings. Following postwar occupation duties, Picket returned to the United States, she decommissioned 24 June 1946, was transferred to the U. S. Coast Guard that date, she was struck from the Naval Vessel Register 19 July 1946. The ex-Picket ex-General Henry Knox was commissioned 20 September 1947 as USCGC Willow; the ship was converted to a buoy tender and assigned to San Juan, Puerto Rico from 23 July 1947 until transfer to San Francisco, California during June 1949. Willow's area of responsibility extended from San Luis Obispo Bay to the Golden Gate, northern San Francisco Bay, San Pablo Bay and Suisun and shared logistics support of the Farallon Island Light Station and the San Francisco Lightship with USCGC Magnolia. On 10 October 1969 Willow was decommissioned and stored at the Coast Guard Training Support Center in Alameda, California.
As a buoy tender, the largest in the Coast Guard at time of conversion, duties were tending navigational aids and conducting search and rescue and law enforcement as needed. List of ships of the United States Army List of United States Navy ships World War II U. S. Army mine planter Minelayer Minesweeper This article incorporates text from the public domain Dictionary of American Naval Fighting Ships; the entry can be found here. Photo gallery of USS Picket at NavSource Naval History ACM-8 USS Picket at Ships of the U. S. Navy, 1940-1945 Minecraft at Ships of the U. S. Navy, 1940–1945 Allied Ships Present in Tokyo Bay During the Surrender Ceremony, 2 September 1945
The Nebraskan is a 1953 3-D Technicolor Western film directed by Fred F. Sears starring Phil Carey and Roberta Haynes; the Nebraskan was one of seven feature films from prolific director Fred Sears that were released that year. Set in 1867 in the newly formed state of Nebraska, cavalry scout Wade Harper attempts to make peace with the Sioux Indians, who demand the handover of Wingfoot, an Indian scout, believed to be responsible for the murder of their chief Thundercloud. While being held in the guardhouse at Fort Kearny, Wingfoot escapes with Reno, an army private awaiting trial for murder. Philip Carey as Wade Harper Roberta Haynes as Paris Wallace Ford as McBride Richard Webb as Ace Eliot Lee Van Cleef as Reno Maurice Jara as Wingfoot Regis Toomey as Col. Markham Jay Silverheels as Spotted Bear Pat Hogan as Yellow Knife Dennis Weaver as Capt. DeWitt Boyd "Red" Morgan as Sgt. Phillips The Nebraskan at the TCM Movie Database The Nebraskan on IMDb The Nebraskan at the American Film Institute Catalog Dvdtalk - The Nebraskan 1953
Tjenare kungen is a Swedish drama film, released to cinemas in Sweden on 16 September 2005. The film is set in 1982. Josefin Neldén as Abra Cecilia Wallin as Millan Joel Kinnaman as Dickan Malin Larsson as Isa Johanna Strömberg as Gloria Kjell Bergqvist as factory manager Fyr Thorwald as Bar-Jonny at Errols Morgan Alling as Stefan Erica Carlson as Abra's sister Jessica Persson as "Karin", Dickan's sister Ralph Carlsson as Leif Anders Lönnbro Daniel Gustavsson Markus Holmberg as Piffen Ebba Grön Tjenare kungen Tjenare kungen on IMDb