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  • 1
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    Inhibition of histone methyltransferase DOT1L silences ER{alpha} gene and blocks proliferation of antiestrogen-resistant breast cancer cells (2019)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2019
    Description: 〈p〉Breast cancer (BC) resistance to endocrine therapy results from constitutively active or aberrant estrogen receptor α (ERα) signaling, and ways to block ERα pathway in these tumors are sought after. We identified the H3K79 methyltransferase DOT1L as a novel cofactor of ERα in BC cell chromatin, where the two proteins colocalize to regulate estrogen target gene transcription. DOT1L blockade reduces proliferation of hormone-responsive BC cells in vivo and in vitro, consequent to cell cycle arrest and apoptotic cell death, with widespread effects on ER-dependent gene transcription, including ERα and FOXA1 gene silencing. Antiestrogen-resistant BC cells respond to DOT1L inhibition also in mouse xenografts, with reduction in ERα levels, H3K79 methylation, and tumor growth. These results indicate that DOT1L is an exploitable epigenetic target for treatment of endocrine therapy–resistant ERα-positive BCs.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Cortical 5-HT2A receptor signaling modulates anxiety-like behaviors in mice (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-07-29
    Description: Serotonin [5-hydroxytryptamine (5-HT)] neurotransmission in the central nervous system modulates depression and anxiety-related behaviors in humans and rodents, but the responsible downstream receptors remain poorly understood. We demonstrate that global disruption of 5-HT2A receptor (5HT2AR) signaling in mice reduces inhibition in conflict anxiety paradigms without affecting fear-conditioned and depression-related behaviors. Selective restoration of 5HT2AR signaling to the cortex normalized conflict anxiety behaviors. These findings indicate a specific role for cortical 5HT2AR function in the modulation of conflict anxiety, consistent with models of cortical, "top-down" influences on risk assessment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weisstaub, Noelia V -- Zhou, Mingming -- Lira, Alena -- Lambe, Evelyn -- Gonzalez-Maeso, Javier -- Hornung, Jean-Pierre -- Sibille, Etienne -- Underwood, Mark -- Itohara, Shigeyoshi -- Dauer, William T -- Ansorge, Mark S -- Morelli, Emanuela -- Mann, J John -- Toth, Miklos -- Aghajanian, George -- Sealfon, Stuart C -- Hen, Rene -- Gingrich, Jay A -- KO8 MH01711/MH/NIMH NIH HHS/ -- P01 DA12923/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 2006 Jul 28;313(5786):536-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Columbia University and the New York State Psychiatric Institute, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16873667" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anxiety/*physiopathology ; Cerebral Cortex/*metabolism ; Conditioning (Psychology) ; Conflict (Psychology) ; Depression/physiopathology ; Exploratory Behavior ; Fear ; Limbic System/metabolism ; Mice ; Mice, Knockout ; Patch-Clamp Techniques ; Periaqueductal Gray/metabolism ; Prosencephalon/metabolism ; Receptor, Serotonin, 5-HT2A/genetics/*metabolism ; Receptor, Serotonin, 5-HT2C/metabolism ; Receptors, Neurotransmitter/metabolism ; Risk-Taking ; Serotonin/physiology ; *Signal Transduction ; Synaptic Transmission
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Computational approaches to developmental patterning (2012)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2012-04-14
    Description: Computational approaches are breaking new ground in understanding how embryos form. Here, we discuss recent studies that couple precise measurements in the embryo with appropriately matched modeling and computational methods to investigate classic embryonic patterning strategies. We include signaling gradients, activator-inhibitor systems, and coupled oscillators, as well as emerging paradigms such as tissue deformation. Parallel progress in theory and experiment will play an increasingly central role in deciphering developmental patterning.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morelli, Luis G -- Uriu, Koichiro -- Ares, Saul -- Oates, Andrew C -- New York, N.Y. -- Science. 2012 Apr 13;336(6078):187-91. doi: 10.1126/science.1215478.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22499940" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Body Patterning ; Computational Biology ; *Computer Simulation ; Drosophila/embryology ; Embryo, Nonmammalian/cytology/metabolism ; Embryonic Development ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; *Models, Biological ; Signal Transduction ; Zebrafish/embryology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    Modulation of phospholipid signaling by GLABRA2 in root-hair pattern formation (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-05-31
    Description: The root-hair pattern of Arabidopsis is determined through a regulatory circuit composed of transcription factor genes. The homeobox gene GLABRA2 (GL2) has been considered a key component, acting farthest downstream in this regulation. GL2 modified to include a transactivating function caused epidermal cells to develop ectopic root hairs or root hair-like structures. With this system, the phospholipase Dzeta1 gene (AtPLDzeta1) was identified as a direct target of GL2. Inducible expression of AtPLDzeta1 promoted ectopic root-hair initiation. We conclude that GL2 exerts its regulatory effect on root-hair development through modulation of phospholipid signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ohashi, Yohei -- Oka, Atsuhiro -- Rodrigues-Pousada, Renato -- Possenti, Marco -- Ruberti, Ida -- Morelli, Giorgio -- Aoyama, Takashi -- New York, N.Y. -- Science. 2003 May 30;300(5624):1427-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12775839" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/*genetics/growth & development/*metabolism ; Arabidopsis Proteins/chemistry/*genetics/*metabolism ; Dexamethasone/pharmacology ; Gene Expression Regulation, Plant ; Genes, Plant ; Homeodomain Proteins/chemistry/genetics/*metabolism ; Morphogenesis ; Phospholipase D/*genetics/metabolism ; Phospholipids/*metabolism ; Plant Epidermis/cytology/metabolism ; Plant Roots/cytology/*growth & development/metabolism ; Plants, Genetically Modified ; Promoter Regions, Genetic ; *Signal Transduction
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    Discovery of powerful gamma-ray flares from the Crab Nebula (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-01-08
    Description: The well-known Crab Nebula is at the center of the SN1054 supernova remnant. It consists of a rotationally powered pulsar interacting with a surrounding nebula through a relativistic particle wind. The emissions originating from the pulsar and nebula have been considered to be essentially stable. Here, we report the detection of strong gamma-ray (100 mega-electron volts to 10 giga-electron volts) flares observed by the AGILE satellite in September 2010 and October 2007. In both cases, the total gamma-ray flux increased by a factor of three compared with the non-flaring flux. The flare luminosity and short time scale favor an origin near the pulsar, and we discuss Chandra Observatory x-ray and Hubble Space Telescope optical follow-up observations of the nebula. Our observations challenge standard models of nebular emission and require power-law acceleration by shock-driven plasma wave turbulence within an approximately 1-day time scale.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tavani, M -- Bulgarelli, A -- Vittorini, V -- Pellizzoni, A -- Striani, E -- Caraveo, P -- Weisskopf, M C -- Tennant, A -- Pucella, G -- Trois, A -- Costa, E -- Evangelista, Y -- Pittori, C -- Verrecchia, F -- Del Monte, E -- Campana, R -- Pilia, M -- De Luca, A -- Donnarumma, I -- Horns, D -- Ferrigno, C -- Heinke, C O -- Trifoglio, M -- Gianotti, F -- Vercellone, S -- Argan, A -- Barbiellini, G -- Cattaneo, P W -- Chen, A W -- Contessi, T -- D'Ammando, F -- DePris, G -- Di Cocco, G -- Di Persio, G -- Feroci, M -- Ferrari, A -- Galli, M -- Giuliani, A -- Giusti, M -- Labanti, C -- Lapshov, I -- Lazzarotto, F -- Lipari, P -- Longo, F -- Fuschino, F -- Marisaldi, M -- Mereghetti, S -- Morelli, E -- Moretti, E -- Morselli, A -- Pacciani, L -- Perotti, F -- Piano, G -- Picozza, P -- Prest, M -- Rapisarda, M -- Rappoldi, A -- Rubini, A -- Sabatini, S -- Soffitta, P -- Vallazza, E -- Zambra, A -- Zanello, D -- Lucarelli, F -- Santolamazza, P -- Giommi, P -- Salotti, L -- Bignami, G F -- New York, N.Y. -- Science. 2011 Feb 11;331(6018):736-9. doi: 10.1126/science.1200083. Epub 2011 Jan 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Istituto Nazionale di Astrofisica-Istituto di Astrofisica Spaziale e Fisica Cosmica (INAF-IASF) Roma, via del Fosso del Cavaliere 100, 00133 Roma, Italy. pi.agile@iasf-roma.inaf.it〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21212318" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    Low-pass DNA sequencing of 1200 Sardinians reconstructs European Y-chromosome phylogeny (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-08-03
    Description: Genetic variation within the male-specific portion of the Y chromosome (MSY) can clarify the origins of contemporary populations, but previous studies were hampered by partial genetic information. Population sequencing of 1204 Sardinian males identified 11,763 MSY single-nucleotide polymorphisms, 6751 of which have not previously been observed. We constructed a MSY phylogenetic tree containing all main haplogroups found in Europe, along with many Sardinian-specific lineage clusters within each haplogroup. The tree was calibrated with archaeological data from the initial expansion of the Sardinian population ~7700 years ago. The ages of nodes highlight different genetic strata in Sardinia and reveal the presumptive timing of coalescence with other human populations. We calculate a putative age for coalescence of ~180,000 to 200,000 years ago, which is consistent with previous mitochondrial DNA-based estimates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Francalacci, Paolo -- Morelli, Laura -- Angius, Andrea -- Berutti, Riccardo -- Reinier, Frederic -- Atzeni, Rossano -- Pilu, Rosella -- Busonero, Fabio -- Maschio, Andrea -- Zara, Ilenia -- Sanna, Daria -- Useli, Antonella -- Urru, Maria Francesca -- Marcelli, Marco -- Cusano, Roberto -- Oppo, Manuela -- Zoledziewska, Magdalena -- Pitzalis, Maristella -- Deidda, Francesca -- Porcu, Eleonora -- Poddie, Fausto -- Kang, Hyun Min -- Lyons, Robert -- Tarrier, Brendan -- Gresham, Jennifer Bragg -- Li, Bingshan -- Tofanelli, Sergio -- Alonso, Santos -- Dei, Mariano -- Lai, Sandra -- Mulas, Antonella -- Whalen, Michael B -- Uzzau, Sergio -- Jones, Chris -- Schlessinger, David -- Abecasis, Goncalo R -- Sanna, Serena -- Sidore, Carlo -- Cucca, Francesco -- HG005552/HG/NHGRI NIH HHS/ -- HG005581/HG/NHGRI NIH HHS/ -- HG006513/HG/NHGRI NIH HHS/ -- HG007022/HG/NHGRI NIH HHS/ -- N01-AG-1-2109/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2013 Aug 2;341(6145):565-9. doi: 10.1126/science.1237947.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dipartimento di Scienze della Natura e del Territorio, Universita di Sassari, Sassari, Italy. pfrancalacci@uniss.it〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23908240" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Chromosomes, Human, Y/*classification/*genetics ; European Continental Ancestry Group/*genetics ; *Evolution, Molecular ; Haplotypes ; Humans ; Italy ; Male ; Phylogeny ; Polymorphism, Single Nucleotide
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
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  • 7
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    Genetic oscillations. A Doppler effect in embryonic pattern formation (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-07-12
    Description: During embryonic development, temporal and spatial cues are coordinated to generate a segmented body axis. In sequentially segmenting animals, the rhythm of segmentation is reported to be controlled by the time scale of genetic oscillations that periodically trigger new segment formation. However, we present real-time measurements of genetic oscillations in zebrafish embryos showing that their time scale is not sufficient to explain the temporal period of segmentation. A second time scale, the rate of tissue shortening, contributes to the period of segmentation through a Doppler effect. This contribution is modulated by a gradual change in the oscillation profile across the tissue. We conclude that the rhythm of segmentation is an emergent property controlled by the time scale of genetic oscillations, the change of oscillation profile, and tissue shortening.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Soroldoni, Daniele -- Jorg, David J -- Morelli, Luis G -- Richmond, David L -- Schindelin, Johannes -- Julicher, Frank -- Oates, Andrew C -- 098025/Wellcome Trust/United Kingdom -- MC_UP_1202/3/Medical Research Council/United Kingdom -- WT098025MA/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 Jul 11;345(6193):222-5. doi: 10.1126/science.1253089.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstr 108, 01307 Dresden, Germany. Medical Research Council (MRC)-National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK. Department of Cell and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, UK. ; Max Planck Institute for the Physics of Complex Systems, Nothnitzer Strasse 38, 01187 Dresden, Germany. ; Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstr 108, 01307 Dresden, Germany. Departamento de Fisica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and Instituto de Fisica de Buenos Aires, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Pabellon 1, Ciudad Universitaria, 1428 Buenos Aires, Argentina. ; Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstr 108, 01307 Dresden, Germany. ; Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstr 108, 01307 Dresden, Germany. Laboratory for Optical and Computational Instrumentation, University of Wisconsin at Madison, 271 Animal Sciences, 1675 Observatory Drive, Madison, WI 53706, USA. ; Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstr 108, 01307 Dresden, Germany. Medical Research Council (MRC)-National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK. Department of Cell and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, UK. aoates@nimr.mrc.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25013078" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Body Patterning/*genetics ; *Doppler Effect ; Embryo, Nonmammalian/physiology ; *Periodicity ; Zebrafish/embryology/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    ATAT1-enriched vesicles promote microtubule acetylation via axonal transport (2019)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2019
    Description: 〈p〉Microtubules are polymerized dimers of α- and β-tubulin that underlie a broad range of cellular activities. Acetylation of α-tubulin by the acetyltransferase ATAT1 modulates microtubule dynamics and functions in neurons. However, it remains unclear how this enzyme acetylates microtubules over long distances in axons. Here, we show that loss of ATAT1 impairs axonal transport in neurons in vivo, and cell-free motility assays confirm a requirement of α-tubulin acetylation for proper bidirectional vesicular transport. Moreover, we demonstrate that the main cellular pool of ATAT1 is transported at the cytosolic side of neuronal vesicles that are moving along axons. Together, our data suggest that axonal transport of ATAT1-enriched vesicles is the predominant driver of α-tubulin acetylation in axons.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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