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  • SNP | Newswire
    of analgesia and addiction do as well The findings reported by researchers from The Rockefeller University Indiana University School of Medicine and University of Cincinnati College of Medicine in the August 4 Proceeding of the National Academy of Sciences show for the first time that these altered molecules are distributed differently among ethnic groups and have implications for normal physiology therapeutics and vulnerability to develop or protect from diverse diseases

    Original URL path: http://newswire.rockefeller.edu/tag/snp/ (2016-02-13)
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  • Messing With Your Head: Cocaine Found to Affect Endorphin Gene in Brain | Newswire
    binge model in 1988 Following the model the rats received 45 milligrams of the drug per kilogram of their weight daily for 14 days The drug is given in equal doses one hour apart for three hours each day For comparison some rats received injections of salt solution When the rats received the drug expression of the KOR gene in nerve cells in part of the midbrain the substantia nigra decreased However the gene s activity remained unchanged in nerve cells of another linked brain region the caudate putamen These two brain regions are hardwired together by the nerves that communicate using chemicals particularly dopamine that is needed for signals involving movement and small proteins such as dynorphin which binds to KOR Dynorphin belongs to the endorphin family of proteins that can numb pain create feelings of euphoria or increase energy which cocaine does as well Normally substantia nigra nerve cells make dopamine and it is released at their endings in the caudate putamen As part of nature s recycling program dopamine is transported back into these nerve endings for repacking and future use Cocaine interferes in this dopamine feedback loop When the drug decreases the expression of KOR genes in the substantia nigra not enough KOR may be available to respond to the feedback signals Dopamine production then continues for a short time and it accumulates in the caudate putamen but the amount of dopamine eventually plateaus When the cocaine later wears off the addict may feel badly because not enough dopamine is available for normal cell functions From our new data we now know that cocaine s effects on dopamine also change the KOR gene activity thus altering the intricate process of nerve cell communication in the midbrain explains first author Rudolph Spangler Ph D research associate in

    Original URL path: http://newswire.rockefeller.edu/1996/05/06/messing-with-your-head-cocaine-found-to-affect-endorphin-gene-in-brain/ (2016-02-13)
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  • cocaine | Newswire
    The effects of the addictive drug cocaine result in part from altering the activity of a gene in the brain report scientists from The Rockefeller University in the May Molecular Brain Research More Tags addiction cocaine endorphin KOR Mary Jeanne Kreek Search for Categories Science News Awards and Honors Campus News Grants Gifts Topics Video Archive 2015 2014 2013 2012 2011 more About Contact Follow rockefelleruniv Like The Rockefeller University

    Original URL path: http://newswire.rockefeller.edu/tag/cocaine/ (2016-02-13)
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  • Loss of epigenetic regulators causes mental retardation | Newswire
    These modifications are established by specific enzymes that add well defined chemical residues to the amino acids localized within the tails of the histone proteins Histone modifications were first identified in the early 1960s by Rockefeller scientist Vincent Allfrey and his colleagues During the past two decades research by Rockefeller University s C David Allis suggested that histone modification could generate a unique epigenetic code that regulates the specific recruitment of gene expression activators and repressors to individual genes The research program of the Greengard and Tarakhovsky labs focuses on GLP G9a an enzyme pair responsible for inducing an epigenetic mark widely known to silence gene expression in mammals including humans By attaching two methyl chemical groups to a specific amino acid on a specific histone GLP G9a suppresses gene activity Tarakhovsky and his colleagues who study GLP G9a and its role in epigenetic regulation of inflammatory responses created a strain of mice that enables conditional removal of this complex in various cell types including neurons in the adult brain First author Anne Schaefer a senior research associate in Greengard s lab subjected these mice to a battery of behavioral tests and determined that they behave much like humans with a mental retardation syndrome called the 9q34 deletion syndrome in which the region of chromosome 9 that codes for the GLP genes is missing The mice lacking GLP G9a unlike their normal counterparts were not afraid of open space were lethargic and as a result obese and had problems learning to adapt to their environment The researchers compared the brains of normal mice and the conditional knockouts and found that there were no structural differences between them In other words the behavioral and learning problems associated with the conditional knockouts were not due to any kind of damage to the brain s structure or to the individual neurons This suppressive epigenetic mark completely disappears in these mice but the neurons themselves do not die and appear normal says Schaefer The mice maintain many of their basal behavioral functions such as eating and breeding but they display abnormal behavior in response to various environmental signals Schaefer and her colleagues also found that loss of GLP G9a resulted in increased expression of genes usually found in muscles and the heart In addition to their analysis of genes that change in the different brain regions they used a cellular analysis technique developed in labs headed by Rockefeller scientist Nathaniel Heintz and Paul Greengard called TRAP which reveals transcriptional profiles by isolating the RNA messages from structurally and functionally defined individual cell populations We found that several nonneuronal genes normally suppressed by the epigenetic mark became upregulated in the GLP G9a conditional knockouts says Schaefer According to Schaefer and her colleagues it s also possible that genetically predetermined or environmentally induced changes of the epigenetic regulators controlling the methylation mark on histone H3 may be responsible for individual differences in learning and social adaptation The Greengard and Tarakhovsky labs have taken these findings a

    Original URL path: http://newswire.rockefeller.edu/2010/01/08/loss-of-epigenetic-regulators-causes-mental-retardation/ (2016-02-13)
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  • New nucleotide could revolutionize epigenetics | Newswire
    the diverse organs tissues and systems of the body Recent research has shown however that environmental factors and experiences such as the type of care a rat pup receives from its mother can also result in methylation patterns and corresponding behaviors that are heritable for several generations Thousands upon thousands of scientific papers have focused on the role of 5 methylcytosine in development The discovery of a new nucleotide may make biologists rethink their approaches to investigating DNA methylation Ironically the latest addition to the DNA vocabulary was found by chance during investigations of the level of 5 methylcytosine in the very large nuclei of Purkinje cells says Skirmantas Kriaucionis a postdoctoral associate in the Heintz lab who did the research We didn t go looking for this modification he says We just found it Kriaucionis was working to compare the levels of 5 methylcytosine in two very different but connected neurons in the mouse brain Purkinje cells the largest brain cells and granule cells the most numerous and among the smallest Together these two types of cells coordinate motor function in the cerebellum After developing a new method to separate the nuclei of individual cell types from one another Kriaucionis was analyzing the epigenetic makeup of the cells when he came across substantial amounts of an unexpected and anomalous nucleotide which he labeled x The nucleotide accounted for roughly 40 percent of the methylated cytosine in Purkinje cells and 10 percent in granule neurons He then performed a series of tests on x including mass spectrometry which determines the elemental components of molecules by breaking them down into their constituent parts charging the particles and measuring their mass to charge ratio He repeated the experiments more than 10 times and came up with the same result x was 5 hydroxymethylcytosine a stable nucleotide previously observed only in the simplest of life forms bacterial viruses A number of other tests showed that x could not be a byproduct of age DNA damage during the cell type isolation procedure or RNA contamination It s stable and it s abundant in the mouse and human brain Kriaucionis says It s really exciting What this nucleotide does is not yet clear Initial tests suggested that it may play a role in demethylating DNA but Kriaucionis and Heintz believe it may have a positive role in regulating gene expression as well The reason that this nucleotide had not been seen before the researchers say is because of the methodologies used in most epigenetic experiments Typically scientists use a procedure called bisulfite sequencing to identify the sites of DNA methylation But this test cannot distinguish between 5 hydroxymethylcytosine and 5 methylcytosine a shortcoming that has kept the newly discovered nucleotide hidden for years the researchers say Its discovery may force investigators to revisit earlier work The Human Epigenome Project for example is in the process of mapping all of the sites of methylation using bisulfite sequencing If it turns out in the future that 5

    Original URL path: http://newswire.rockefeller.edu/2009/04/16/new-nucleotide-could-revolutionize-epigenetics/ (2016-02-13)
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  • nucleotide | Newswire
    much different isn t the amount of DNA they carry which is about the same but rather the dynamic regulation of those genes by nongenetic factors epigenetics New research at The Rockefeller University has now uncovered a novel system of epigenetic regulation one that adds a new nucleotide to the mammalian DNA code More Tags Nathaniel Heintz nucleotide Search for Categories Science News Awards and Honors Campus News Grants Gifts

    Original URL path: http://newswire.rockefeller.edu/tag/nucleotide/ (2016-02-13)
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  • Breakthrough in cell-type analysis offers new way to study development and disease | Newswire
    the research in his lab now employs the new technique to study the biochemical basis of Parkinson s Alzheimer s and Huntington s diseases as well as the still mysterious ways in which psychoactive drugs fight schizophrenia and depression TRAP should fundamentally change biochemical studies of the brain and the speed at which they yield results he says We can look at a thousand genes instead of one at a time so things should clear a thousand times faster says Greengard who won the Nobel Prize in Physiology or Medicine in 2000 for research into how neurons communicate Glowing review Fluorescing Purkinje cells just one of hundreds of types of neurons have given up their biomolecular secrets thanks to a breakthrough in cellular analysis The TRAP method grew out of a project known as GENSAT for Genetic Expression Nervous System Atlas that Heintz and Rockefeller professor Mary Beth Hatten launched in 2000 to visualize the contributions of individual genes to the mouse brain Heintz and his colleagues had developed a technique to engineer large pieces of DNA carried in bacterial artificial chromosomes BACs which can insinuate themselves into the genomes of other organisms They were able to insert the genetic code for green fluorescent protein EGFP within the regulatory domain of any gene of interest When one of these modified BACs is transferred into mice expression of the EGFP mimics that of the gene of interest lighting up cells with a green glow that shows researchers all of the cells in which that particular gene functions The GENSAT database laid out in glowing green myriad cell types of the mouse brain And it provided genetic markers for each kind But it was an accomplishment that was also a taunt Ultimately the researchers wanted to go deeper to understand the precise biochemical characteristics of the cell types they had brought into focus to learn what makes cells vulnerable to attack and possibly how to protect them from it by discovering what s unique to the susceptible cells and the ones that are resistant Enter TRAP Heintz postdoctoral fellow Myriam Heiman and colleagues attached an EGFP to the surface of the ribosome and used it as a handle to pick out the cell s protein factories and the genetic messages passing through them called messenger RNAs mRNAs Using the GENSAT techniques and findings they designed new mouse lines that made tagged ribosomes in each of four different cell types Heiman and colleagues focused on the brain cells that respond to dopamine an important neurotransmitter involved in muscle movement and emotion regulation among other things They used the handle they had made to pluck out the ribosomes and mRNAs from these brain cells and freeze them within minutes of dissection preserving the messages largely as they were inside the living animal and minimizing degradation Alternative approaches to getting the profiles of cell types in complex tissues have been disappointing because they require the physical isolation of whole cells from the tissues in which

    Original URL path: http://newswire.rockefeller.edu/2008/11/13/breakthrough-in-cell-type-analysis-offers-new-way-to-study-development-and-disease/ (2016-02-13)
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  • Three Rockefeller scientists elected AAAS fellows | Newswire
    Genetics and Hematology was elected within the AAAS section on medical sciences for identification of new genes and development of diagnosis and treatment of Fanconi anemia an inherited disease characterized by skeletal anomalies bone marrow failure and susceptibility to tumors and leukemias among other symptoms Auerbach discovered a cellular marker for the syndrome through patients hypersensitivity to a DNA damaging agent thereby facilitating prenatal and postnatal diagnosis Insights from this research have led to the use of umbilical cord blood transplantation as an alternative to bone marrow transplantation in the treatment of Fanconi anemia and other blood disorders Cori Bargmann Torsten N Wiesel Professor and head of the Laboratory of Neural Circuits and Behavior is a new fellow within the section on neuroscience chosen for contributions to the field of behavioral neuroscience Bargmann s research resulted in the identification of the first molecular odorant receptor genes in the model organism C elegans as well as the genetically regulated mechanism by which the C elegans roundworm engages in social or solitary feeding Her research into signaling pathways confirmed that artificial activation of individual sensory neurons each of which is primarily dedicated to a single behavioral task such as attraction or repulsion can generate their encoded behaviors in response to novel stimuli Bargmann also is an investigator at the Howard Hughes Medical Institute Nathaniel Heintz the James and Marilyn Simons Professor and head of the Laboratory of Molecular Biology was elected within the section on neuroscience for contributions to molecular neuroscience The Heintz laboratory has identified a variety of genes expressed in the mammalian central nervous system responsible for its development function and dysfunction The lab also developed a large scale screen method involving the modification of bacterial artificial chromosomes to allow efficient analysis of patterns of gene expression subcellular localization of

    Original URL path: http://newswire.rockefeller.edu/2006/11/28/three-rockefeller-scientists-elected-aaas-fellows/ (2016-02-13)
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