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  • Brain protein may be a target for fast-acting antidepressants | Newswire
    and Cellular Neuroscience and coauthor Per Svenningsson established p11 as a key signaling molecule for a neurotransmitter known as serotonin which has long been linked to mood They also showed that the interaction between p11 and serotonin influences an individual s susceptibility to depression and his or her response to antidepressant treatments They later showed that p11 and serotonin also play a role in the symptoms of advanced Parkinson s disease These earlier studies focused on the serotonin 1B receptor For the new study Greengard Svenningsson and their colleagues looked at p11 s interaction with another receptor known as serotonin 4 which has been shown to produce a rapid antidepressant response in rodent models of depression Because serotonin 4 is expressed outside the brain particularly in the gastrointestinal system scientists have had difficulty homing in on it to evaluate its potential as an effective therapeutic target Using transgenic mice that express a green fluorescent protein when the serotonin 4 receptor is switched on the researchers showed that p11 and serotonin 4 are expressed together in regions of the brain that are associated with depression Previous studies by Greengard s team showed that p11 is required for the antidepressant actions of a molecule called an agonist which activates the serotonin 1B receptor To determine whether p11 is required for the action of a serotonin 4 agonist the researchers injected two groups of mice with a compound called RS67333 which has been shown to produce antidepressant like effects They found that the antidepressant activity of RS67333 was normal in normal mice but absent in mice that were lacking p11 Together these findings confirm the essential role played by p11 in modulating signaling through the serotonin 4 receptor and support the concept that this protein may be a key determinant of vulnerability to

    Original URL path: http://newswire.rockefeller.edu/2009/02/24/brain-protein-may-be-a-target-for-fast-acting-antidepressants/ (2016-02-13)
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  • Silence of the genes | Newswire
    structure that contains coiled DNA and histones A role for histones in gene activation first became known in the 1960s when the late Vincent G Allfrey Ph D and colleagues at Rockefeller made seminal contributions to understanding how histones control gene activation in higher organisms Allfrey s experiments provided evidence that histones are modified by enzymes that attach acetyl phosphoryl or methyl chemical groups to them Many scientists including Allis theorize that these chemical modifications are in part responsible for passing on inherited traits without changing the sequence of DNA an area of research called epigenetics It is now widely accepted that such non DNA encoded heritable information has important implications for human biology and human disease especially cancer An internationally recognized leader in epigenetics Allis joined Rockefeller in March 2003 Allis and other researchers over the last decade have identified many of the enzymes that attach and remove these modification marks methyl phosphate or acetyl to specific amino acids in the tail The phosphate and acetyl modifications can be reversed by separate enzymes which strip the mark off the amino acid The methyl mark on lysine residues however appears to be more permanent and may be irreversible While scientists know several enzymes that attach methyl chemical groups to different amino acids on the histones no one has yet identified an enzymatic activity that can remove a methyl mark Because of this lack of dynamic addition and removal methyl marks are considered to be static and might be heritable That s an attractive possibility says Allis If methyl groups get put on and then are never removed they would be perfect epigenetic marks especially if they were propagated or inherited from one cell to the next Research in the last few years by Allis group at Rockefeller and at the University of Virginia where he was a faculty member before moving to Rockefeller has focused on methylation of the amino acid lysine and the role of methylation in silencing genes According to recent findings by Allis team methylated lysines on the histone tails recruit proteins that the researchers call effectors Effectors if they are repressive in character pull the histones together and therefore glue the chromatin shut This effectively prevents the cell s machinery from getting near DNA where it would normally read and copy the genetic information stored there in a complex process called transcription But the effector glue essentially shuts down any gene activity If a repressive effector binds to a methylated lysine how does the cell remove the effector when it needs to activate or reactive a gene asks Allis Our model proposes that phosphorylation which is a readily reversible reaction serves as the ejector button or switch Allis and his colleagues analyzed the sequence of amino acids that make up the histone tail and noticed an interesting pattern adjacent to essentially every known methylated lysine residue in histones was a serine or a threonine Both of these amino acids can accept a phosphate in a process

    Original URL path: http://newswire.rockefeller.edu/2003/10/01/silence-of-the-genes/ (2016-02-13)
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  • Scientists discover master regulator of motor neuron firing | Newswire
    transcript To many a key question that remained was which splicing factor is responsible for slipping in this extra piece the Z exon In their work Darnell and Ruggiu not only unmask the splicing factor but also reveal that this factor not Z agrin is the master regulator that orchestrates the formation of the neuromuscular junction Past experiments had led scientists to conclude that Z agrin might be necessary and sufficient for the neuromuscular junction to form properly but Darnell and Ruggiu show that while Z agrin is necessary other proteins are also needed The splicing factor the scientists identified is a well studied protein called NOVA which comes in two varieties The team found that mice that were genetically engineered to lack both varieties NOVA1 and NOVA2 and thus Z agrin were born paralyzed They couldn t move a muscle says Darnell So that s when we decided to look at the neuromuscular junction The researchers found that the receptor clusters on the muscle were few and sparse and those that remained did not form very many connections with nerve ends Based on the reigning doctrine they expected that restoring Z agrin in mice that lacked NOVA would be enough to rescue the mice But that was not the case says Ruggiu And that was very surprising because when we looked at the morphology of the neuromuscular junction it looked normal The Z agrin restored the receptor clusters and synapses but that didn t do the animals any good They remained paralyzed So that s a paradox says Darnell who is also a Howard Hughes Medical Institute investigator And that s a good place to be in science That s where you want to be because it means that the dogma in the field is wrong Since the muscle

    Original URL path: http://newswire.rockefeller.edu/2009/03/13/scientists-discover-master-regulator-of-motor-neuron-firing/ (2016-02-13)
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  • Discovery could help scientists stop the ‘death cascade’ of neurons after a stroke | Newswire
    terrible side effects you get by blocking the whole thing says Sidney Strickland head of the Laboratory of Neurobiology and Genetics who directed the research Now we can start exploring potential drugs to do that in humans The neuronal panic that occurs when a clot or other insult blocks the flow of blood to part of the brain is called excitotoxic neurodegeneration It results in the brain cells spitting out glutamate which then accumulates in the synapses between neurons and stimulates the release of more glutamate It s a vicious cycle that kills the cells quickly and continues until blood flow is restored Doctors often treat stroke victims by administering a heavy dose of a clot buster called tissue plasminogen activator tPA a protein that can stimulate the dissolution of clots Ironically however the same drug that does this crucial clot busting also accelerates the panicky process that kills neurons research by Strickland and others has shown Investigating exactly how tPA does that is what led Strickland s team to the recent discovery Neurons are typically couched in laminin an extracellular matrix protein known to be involved with tPA in the neuronal death cascade The Strickland lab s experiments published in The Journal of Cell Biology show that tPA produces an enzyme that degrades laminin into toxic products that kill the neurons in their midst specifically by stimulating the production of one of five subunits for a particular kind of glutamate receptor The overproduction of this specific subunit KA1 makes the cells hypersensitive to glutamate which fans the glutamate frenzy leading to their death To better understand the process Zu Lin Chen and other colleagues at Rockefeller in the Strickland lab and at the University of Leicester in England designed lines of genetically modified mice that lacked either tPA or

    Original URL path: http://newswire.rockefeller.edu/2009/01/15/discovery-could-help-scientists-stop-the-death-cascade-after-a-stroke/ (2016-02-13)
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  • stroke | Newswire
    oxygen It doesn t take long before the brain cells drown in their own salts Now a team of scientists at Rockefeller University have for the first time found a way to slow cell death by blocking a specific subunit of the glutamate receptor a method that avoids the devastating side effects of disrupting the receptor as a whole More Tags Neurons Sidney Strickland stroke Search for Categories Science News

    Original URL path: http://newswire.rockefeller.edu/tag/stroke/ (2016-02-13)
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  • Protein is linked to functional development of brain neurons | Newswire
    1 regulates neuronal development provides us with a new way about thinking about treatment of brain disorders caused by loss of nerve cells says the study s lead investigator Pallavi Sachdev a postdoc in the Sakmar lab A small molecule that promotes the binding of Tctex1 and the G protein could push new neuronal development and this strategy might help treat disorders such as Alzheimer s disease and Parkinson s disease Using a small molecule to block binding of Tctex 1 and the G protein could maintain the integrity of neuronal stem cells she says The Rockefeller laboratory is now screening compounds to find both inhibitors and enhancers of the Gβγ Tctex 1 interaction she says The researchers conducted the study after noticing that Tctex 1 was highly expressed in young neurons but not in adult nerve cells They also knew that aberrant overexpression of Tctex 1 resulted in increased growth of neurites small projections that form axons and dendrites and that this activity of Tctex 1 was not dependent on the activity of dyenin motor molecules So they asked what was Tctex 1 doing in the young neurons outside of its role in dyenin To find out they cultured neurons taken from the hippocampus of a rat brain during its early development The researchers grew the neurons in culture and then either inhibited or over expressed proteins to study neuronal development They found that in order for neuronal outgrowth to occur Tctex 1 had to be present in a complex with Gβγ subunit If you have these two proteins the number of neurites increases but if you inhibit either of them they do not send out any neurites Sachdev says They also found that if Gβγ is taken away stem cells produce more neurons Tctex 1 is yet another

    Original URL path: http://newswire.rockefeller.edu/2007/06/14/protein-is-linked-to-functional-development-of-brain-neurons/ (2016-02-13)
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  • Thomas P. Sakmar | Newswire
    encasing single membrane proteins from living cells allowing investigators to individually stimulate key proteins with specific molecules and signals in order to precisely define the biological reactions that result More Tags NABB nano Thomas P Sakmar June 14 2007 Science News Protein is linked to functional development of brain neurons Rockefeller University investigators say that a molecule that helps transport cargo inside nerve cells may have another critically important role related to how developing neurons sprout the projections that relay electrical signals within the brain More Tags Neurons Thomas P Sakmar March 29 2006 Science News Lizard s third eye sheds light on how vision evolved A primitive third eye found in many types of lizards used to detect changes in light and dark and to regulate the production of certain hormones may help explain how vision evolved and how signals are transmitted from the eyes to the brain Now new experiments show that the molecular mechanisms that underlie this parietal eye s responses to light are similar to those that transmit responses from rod and cone cells in the eye to the brain More Tags lizards third eye Thomas P Sakmar September 3 2002 Science News Dinosaur ancestor s vision possibly nocturnal Call it Triassic Park with statistics instead of amber preserved DNA researchers at the Howard Hughes Medical Institute at The Rockefeller University and Yale University recreated in the test tube a functional pigment that would have characterized the eyes of archosaurs ruling reptiles and allowed these direct ancestors to dinosaurs to see in dim light More Tags dinosaur rhodopsin Thomas P Sakmar March 17 2000 Campus News Science Outreach H S student in top 10 of Intel Science Talent Search Science Outreach student Eugene Simuni was awarded a 25 000 scholarship for his fifth place win in

    Original URL path: http://newswire.rockefeller.edu/tag/thomas-p-sakmar/ (2016-02-13)
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  • Campus News | Newswire | Page 3
    science degrees to two respected scholars Richard Axel of Columbia University and Linda B Buck of the Fred Hutchinson Cancer Research Center More Tags convocation March 16 2011 Campus News Marc Tessier Lavigne becomes Rockefeller s tenth president Marc Tessier Lavigne a leading neuroscientist and the former chief scientific officer of Genentech takes over as president of The Rockefeller University today replacing Paul Nurse who has left to become president of the Royal Society in London More Tags Laboratory of Brain Development and Repair Marc Tessier Lavigne Paul Nurse January 26 2011 Campus News Rockefeller joins Pfizer s Global Centers For Therapeutic Innovation A new partnership will mimic a venture capital funded biotechnology start up model whereby Pfizer funds pre clinical and clinical development programs in return for the opportunity to potentially broaden its pipeline with novel and highly differentiated candidate drugs More Tags Barry S Coller Pfizer s Global Centers For Therapeutic Innovation January 20 2011 Campus News Amy C Falls appointed chief investment officer and vice president for investments Amy C Falls will be The Rockefeller University s chief investment officer and vice president for investments effective April 4 2011 Falls will oversee the University s Office of Investments and manage the institution s endowment which has an estimated value of 1 8 billion More Tags Amy C Falls University s Office of Investments November 16 2010 Campus News 2010 Pearl Meister Greengard Prize goes to two pioneers of cancer genetics Janet Davison Rowley and Mary Claire King pioneering cancer geneticists are the recipients of the 2010 Pearl Meister Greengard Prize awarded by The Rockefeller University Established by Nobel Prize winner Paul Greengard and his wife sculptor Ursula von Rydingsvard the prize honors women who have made extraordinary contributions to biomedical science a group that historically has not received appropriate recognition and acclaim More Tags Janet Davison Rowley Mary Claire King Paul Greengard Pearl Meister Greengard Prize November 12 2010 Campus News New Rockefeller University lab building opens The Collaborative Research Center a 125 000 square foot 500 million building designed specifically to help foster scientific collaboration and encourage interactions between scientists has opened on Rockefeller s campus More Tags Collaborative Research Center Flexner Hall Maurice R and Corinne P Greenberg Building Theobald Smith Hall October 7 2010 Campus News Paul Nurse named top of the list of 100 most important people in British science Rockefeller University President Paul Nurse has been named the top British scientist in a new list of the 100 most important contemporary figures in British science More Tags Eureka Paul Nurse The Times September 13 2010 Campus News Paul Bieniasz promoted to professor A retrovirologist at Rockefeller who studies the mechanisms that viruses use to assemble new viral particles and the resistance of certain cell types to infection has been awarded tenure and promoted to professor Paul Bieniasz has reanimated extinct retroviruses elucidated defenses evolved by organisms to fend off attacking viruses and made key strides toward developing a monkey model of HIV

    Original URL path: http://newswire.rockefeller.edu/category/campus-news/page/3/ (2016-02-13)
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