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  • 1
    Publication Date: 2008-07-04
    Description: Herpesviruses are characterized by their ability to maintain life-long latent infections in their animal hosts. However, the mechanisms that allow establishment and maintenance of the latent state remain poorly understood. Herpes simplex virus 1 (HSV-1) establishes latency in neurons of sensory ganglia, where the only abundant viral gene product is a non-coding RNA, the latency associated transcript (LAT). Here we show that LAT functions as a primary microRNA (miRNA) precursor that encodes four distinct miRNAs in HSV-1 infected cells. One of these miRNAs, miR-H2-3p, is transcribed in an antisense orientation to ICP0-a viral immediate-early transcriptional activator that is important for productive HSV-1 replication and thought to have a role in reactivation from latency. We show that miR-H2-3p is able to reduce ICP0 protein expression, but does not significantly affect ICP0 messenger RNA levels. We also identified a fifth HSV-1 miRNA in latently infected trigeminal ganglia, miR-H6, which derives from a previously unknown transcript distinct from LAT. miR-H6 shows extended seed complementarity to the mRNA encoding a second HSV-1 transcription factor, ICP4, and inhibits expression of ICP4, which is required for expression of most HSV-1 genes during productive infection. These results may explain the reported ability of LAT to promote latency. Thus, HSV-1 expresses at least two primary miRNA precursors in latently infected neurons that may facilitate the establishment and maintenance of viral latency by post-transcriptionally regulating viral gene expression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666538/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666538/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Umbach, Jennifer Lin -- Kramer, Martha F -- Jurak, Igor -- Karnowski, Heather W -- Coen, Donald M -- Cullen, Bryan R -- R01 AI067968/AI/NIAID NIH HHS/ -- R01 AI067968-02/AI/NIAID NIH HHS/ -- R01 AI067968-03/AI/NIAID NIH HHS/ -- T32 CA009111/CA/NCI NIH HHS/ -- England -- Nature. 2008 Aug 7;454(7205):780-3. doi: 10.1038/nature07103. Epub 2008 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Microbiology and Center for Virology, Duke University Medical Center, Durham, North Carolina 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18596690" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Line ; Down-Regulation ; *Gene Expression Regulation, Viral ; Genome, Viral/genetics ; Herpesvirus 1, Human/*genetics/physiology ; Humans ; Immediate-Early Proteins/biosynthesis/genetics ; Male ; Mice ; MicroRNAs/*genetics/*metabolism ; RNA Processing, Post-Transcriptional ; RNA, Messenger/genetics/metabolism ; RNA, Viral/*genetics/*metabolism ; Ubiquitin-Protein Ligases/biosynthesis/genetics ; Virus Latency/*genetics/physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 1991-05-10
    Description: Malignant gliomas are the most common malignant brain tumors and are almost always fatal. A thymidine kinase-negative mutant of herpes simplex virus-1 (dlsptk) that is attenuated for neurovirulence was tested as a possible treatment for gliomas. In cell culture, dlsptk killed two long-term human glioma lines and three short-term human glioma cell populations. In nude mice with implanted subcutaneous and subrenal U87 human gliomas, intraneoplastic inoculation of dlsptk caused growth inhibition. In nude mice with intracranial U87 gliomas, intraneoplastic inoculation of dlsptk prolonged survival. Genetically engineered viruses such as dlsptk merit further evaluation as novel antineoplastic agents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Martuza, R L -- Malick, A -- Markert, J M -- Ruffner, K L -- Coen, D M -- NS24279/NS/NINDS NIH HHS/ -- R01-AI26126/AI/NIAID NIH HHS/ -- SO7RRO5381/RR/NCRR NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1991 May 10;252(5007):854-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Neurogenetics Laboratory, Harvard Medical School, Massachusetts General Hospital-East, Charlestown 02129.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1851332" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antiviral Agents/pharmacology ; Brain Neoplasms/*therapy ; Cells, Cultured ; Dose-Response Relationship, Drug ; Foscarnet ; Glioma/*therapy ; Mice ; Mice, Nude ; Mutagenesis ; Phosphonoacetic Acid/analogs & derivatives/pharmacology ; Simplexvirus/genetics/*immunology ; Thymidine Kinase/genetics ; Vidarabine/pharmacology ; Viral Vaccines/*therapeutic use
    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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  • 3
    Publication Date: 2007-05-26
    Description: To understand the constraints on biological diversity, we analyzed how selection and development interact to control the evolution of inflorescences, the branching structures that bear flowers. We show that a single developmental model accounts for the restricted range of inflorescence types observed in nature and that this model is supported by molecular genetic studies. The model predicts associations between inflorescence architecture, climate, and life history, which we validated empirically. Paths, or evolutionary wormholes, link different architectures in a multidimensional fitness space, but the rate of evolution along these paths is constrained by genetic and environmental factors, which explains why some evolutionary transitions are rare between closely related plant taxa.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prusinkiewicz, Przemyslaw -- Erasmus, Yvette -- Lane, Brendan -- Harder, Lawrence D -- Coen, Enrico -- New York, N.Y. -- Science. 2007 Jun 8;316(5830):1452-6. Epub 2007 May 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computer Science, University of Calgary, 2500 University Drive N.W. Calgary, Alberta T2N 1N4, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17525303" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/*anatomy & histology/genetics/*growth & development ; Arabidopsis Proteins/genetics/physiology ; *Biological Evolution ; Climate ; Computer Simulation ; Flowers/*anatomy & histology/genetics/*growth & development ; Gene Expression ; Genes, Plant ; Mathematics ; Meristem/growth & development ; *Models, Biological ; Selection, Genetic ; Transcription Factors/genetics/physiology
    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
    Publication Date: 2005-02-12
    Description: Most protein phosphatases have little intrinsic substrate specificity, making selective pharmacological inhibition of specific dephosphorylation reactions a challenging problem. In a screen for small molecules that protect cells from endoplasmic reticulum (ER) stress, we identified salubrinal, a selective inhibitor of cellular complexes that dephosphorylate eukaryotic translation initiation factor 2 subunit alpha (eIF2alpha). Salubrinal also blocks eIF2alpha dephosphorylation mediated by a herpes simplex virus protein and inhibits viral replication. These results suggest that selective chemical inhibitors of eIF2alpha dephosphorylation may be useful in diseases involving ER stress or viral infection. More broadly, salubrinal demonstrates the feasibility of selective pharmacological targeting of cellular dephosphorylation events.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boyce, Michael -- Bryant, Kevin F -- Jousse, Celine -- Long, Kai -- Harding, Heather P -- Scheuner, Donalyn -- Kaufman, Randal J -- Ma, Dawei -- Coen, Donald M -- Ron, David -- Yuan, Junying -- AI19838/AI/NIAID NIH HHS/ -- AI26077/AI/NIAID NIH HHS/ -- DDK42394/DK/NIDDK NIH HHS/ -- DK47119/DK/NIDDK NIH HHS/ -- ES08681/ES/NIEHS NIH HHS/ -- GM64703/GM/NIGMS NIH HHS/ -- NS35138/NS/NINDS NIH HHS/ -- R37-AG012859/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2005 Feb 11;307(5711):935-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15705855" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Differentiation ; Apoptosis/*drug effects ; Cell Cycle Proteins ; Cell Line ; Cinnamates/*pharmacology/toxicity ; *Cytoprotection ; Dose-Response Relationship, Drug ; Endoplasmic Reticulum/*metabolism ; Enzyme Inhibitors/pharmacology ; Eukaryotic Initiation Factor-2/*metabolism ; Genes, Reporter ; Herpesvirus 1, Human/drug effects/physiology ; Keratitis, Herpetic/drug therapy/virology ; Male ; Mice ; Oxazoles/pharmacology/toxicity ; PC12 Cells ; Phosphoprotein Phosphatases/metabolism ; Phosphorylation ; Protein Folding ; Protein Kinases/metabolism ; Protein Phosphatase 1 ; Proteins/metabolism ; Rats ; Thiourea/*analogs & derivatives/*pharmacology/toxicity ; Tunicamycin/pharmacology ; Viral Proteins/metabolism ; Virus Replication/drug effects
    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
    Publication Date: 2014-03-07
    Description: The generation of acoustic communication signals is widespread across the animal kingdom, and males of many species, including Drosophilidae, produce patterned courtship songs to increase their chance of success with a female. For some animals, song structure can vary considerably from one rendition to the next; neural noise within pattern generating circuits is widely assumed to be the primary source of such variability, and statistical models that incorporate neural noise are successful at reproducing the full variation present in natural songs. In direct contrast, here we demonstrate that much of the pattern variability in Drosophila courtship song can be explained by taking into account the dynamic sensory experience of the male. In particular, using a quantitative behavioural assay combined with computational modelling, we find that males use fast modulations in visual and self-motion signals to pattern their songs, a relationship that we show is evolutionarily conserved. Using neural circuit manipulations, we also identify the pathways involved in song patterning choices and show that females are sensitive to song features. Our data not only demonstrate that Drosophila song production is not a fixed action pattern, but establish Drosophila as a valuable new model for studies of rapid decision-making under both social and naturalistic conditions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coen, Philip -- Clemens, Jan -- Weinstein, Andrew J -- Pacheco, Diego A -- Deng, Yi -- Murthy, Mala -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Mar 13;507(7491):233-7. doi: 10.1038/nature13131. Epub 2014 Mar 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08544, USA [2] Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA. ; 1] Department of Physics, Princeton University, Princeton, New Jersey 08544, USA [2] Department of Biophysics, University of Washington School of Medicine, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24598544" target="_blank"〉PubMed〈/a〉
    Keywords: *Animal Communication ; Animals ; *Courtship ; Cues ; Decision Making/physiology ; Drosophila melanogaster/anatomy & histology/*physiology ; Female ; Male ; Neural Pathways ; Sexual Behavior, Animal/physiology ; *Vibration ; Wings, Animal/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2012-03-16
    Description: The posterior parietal cortex (PPC) has an important role in many cognitive behaviours; however, the neural circuit dynamics underlying PPC function are not well understood. Here we optically imaged the spatial and temporal activity patterns of neuronal populations in mice performing a PPC-dependent task that combined a perceptual decision and memory-guided navigation in a virtual environment. Individual neurons had transient activation staggered relative to one another in time, forming a sequence of neuronal activation spanning the entire length of a task trial. Distinct sequences of neurons were triggered on trials with opposite behavioural choices and defined divergent, choice-specific trajectories through a state space of neuronal population activity. Cells participating in the different sequences and at distinct time points in the task were anatomically intermixed over microcircuit length scales (〈100 micrometres). During working memory decision tasks, the PPC may therefore perform computations through sequence-based circuit dynamics, rather than long-lived stable states, implemented using anatomically intermingled microcircuits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321074/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321074/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harvey, Christopher D -- Coen, Philip -- Tank, David W -- R01 MH083686/MH/NIMH NIH HHS/ -- R01 MH083686-05/MH/NIMH NIH HHS/ -- R01-MH083686/MH/NIMH NIH HHS/ -- RC1 NS068148/NS/NINDS NIH HHS/ -- RC1 NS068148-02/NS/NINDS NIH HHS/ -- RC1-NS068148/NS/NINDS NIH HHS/ -- England -- Nature. 2012 Mar 14;484(7392):62-8. doi: 10.1038/nature10918.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08544, USA. christopher_harvey@hms.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22419153" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/physiology ; Animals ; Decision Making/*physiology ; Male ; Maze Learning/*physiology ; Memory/*physiology ; Mice ; Mice, Inbred C57BL ; Models, Neurological ; Parietal Lobe/cytology/*physiology ; Photic Stimulation ; *User-Computer Interface
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2006-08-19
    Description: To understand evolutionary paths connecting diverse biological forms, we defined a three-dimensional genotypic space separating two flower color morphs of Antirrhinum. A hybrid zone between morphs showed a steep cline specifically at genes controlling flower color differences, indicating that these loci are under selection. Antirrhinum species with diverse floral phenotypes formed a U-shaped cloud within the genotypic space. We propose that this cloud defines an evolutionary path that allows flower color to evolve while circumventing less-adaptive regions. Hybridization between morphs located in different arms of the U-shaped path yields low-fitness genotypes, accounting for the observed steep clines at hybrid zones.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Whibley, Annabel C -- Langlade, Nicolas B -- Andalo, Christophe -- Hanna, Andrew I -- Bangham, Andrew -- Thebaud, Christophe -- Coen, Enrico -- New York, N.Y. -- Science. 2006 Aug 18;313(5789):963-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, John Innes Centre, Colney Lane, Norwich NR4 7UH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16917061" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Biological ; Alleles ; Antirrhinum/classification/*genetics ; Base Sequence ; *Biological Evolution ; Crosses, Genetic ; Flowers/*genetics ; Gene Flow ; Gene Frequency ; Genes, Plant ; *Genetic Speciation ; Genotype ; Haplotypes ; Hybridization, Genetic ; Models, Genetic ; Molecular Sequence Data ; Phenotype ; Phylogeny ; Pigmentation/*genetics ; Pigments, Biological/genetics ; Principal Component Analysis ; Selection, Genetic
    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
    Publication Date: 2012-03-03
    Description: A major challenge in biology is to understand how buds comprising a few cells can give rise to complex plant and animal appendages like leaves or limbs. We address this problem through a combination of time-lapse imaging, clonal analysis, and computational modeling. We arrive at a model that shows how leaf shape can arise through feedback between early patterns of oriented growth and tissue deformation. Experimental tests through partial leaf ablation support this model and allow reevaluation of previous experimental studies. Our model allows a range of observed leaf shapes to be generated and predicts observed clone patterns in different species. Thus, our experimentally validated model may underlie the development and evolution of diverse organ shapes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kuchen, Erika E -- Fox, Samantha -- de Reuille, Pierre Barbier -- Kennaway, Richard -- Bensmihen, Sandra -- Avondo, Jerome -- Calder, Grant M -- Southam, Paul -- Robinson, Sarah -- Bangham, Andrew -- Coen, Enrico -- Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2012 Mar 2;335(6072):1092-6. doi: 10.1126/science.1214678.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉John Innes Centre, Norwich Research Park, Norwich, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22383846" target="_blank"〉PubMed〈/a〉
    Keywords: Antirrhinum/anatomy & histology/genetics/growth & development ; Arabidopsis/anatomy & histology/genetics/growth & development ; Arabidopsis Proteins/genetics/metabolism ; Cell Polarity ; Computer Simulation ; Genes, Plant ; *Models, Biological ; *Morphogenesis ; Plant Leaves/*anatomy & histology/cytology/*growth & development ; Time-Lapse Imaging
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1982-12-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dover, G A -- Strachan, T -- Coen, E S -- Brown, S D -- New York, N.Y. -- Science. 1982 Dec 10;218(4577):1069.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7146894" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; DNA/*genetics ; Genes ; Humans
    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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  • 10
    Publication Date: 1986-10-03
    Description: Viral infection of mammalian cells entails the regulated induction of viral gene expression. The induction of many viral genes, including the herpes simplex virus gene encoding thymidine kinase (tk), depends on viral regulatory proteins that act in trans. Because recognition of the tk promoter by cellular transcription factors is well understood, its trans induction by viral regulatory proteins may serve as a useful model for the regulation of eukaryotic gene expression. A comprehensive set of mutations was therefore introduced into the chromosome of herpes simplex virus at the tk promoter to directly analyze the effects of promoter mutations on tk transcription. The promoter domains required for efficient tk expression under conditions of trans induction corresponded to those important for recognition by cellular transcription factors. Thus, trans induction of tk expression may be catalyzed initially by the interaction of viral regulatory proteins with cellular transcription factors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coen, D M -- Weinheimer, S P -- McKnight, S L -- New York, N.Y. -- Science. 1986 Oct 3;234(4772):53-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3018926" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Gene Expression Regulation ; Genes, Viral ; Mutation ; *Promoter Regions, Genetic ; RNA, Messenger/genetics ; Simplexvirus/genetics/growth & development ; Transcription, Genetic ; *Virus Activation ; Xenopus
    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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