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  • 1
    ISSN: 1432-1432
    Keywords: Cellular slime molds ; Animals ; Fungi ; Plantae ; Maximum-likelihood method ; Evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The phylogenetic position of Dictyostelium inferred from 18S rRNA data contradicts that from protein data. Protein trees always show the close affinity of Dictyostelium with animals, fungi, and plants, whereas in 18S rRNA trees the branching of Dictyostelium is placed at a position before the massive radiation of protist groups including the divergence of the three kingdoms. To settle this controversial issue and to determine the correct position of Dictyostelium, we inferred the phylogenetic relationship among Dictyostelium and the three kingdoms Animalia, Fungi, and Plantae by a maximum-likelihood method using 19 different protein data sets. It was shown at the significance level of 1 SE that the branching of Dictyostelium antedates the divergence of Animalia and Fungi, and Plantae is an outgroup of the Animalia-Fungi-Dictyostelium clade.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular evolution 42 (1996), S. 183-193 
    ISSN: 1432-1432
    Keywords: Small-subunit ribosomal RNA ; Phylogeny ; Animals ; Fungi ; Plants ; Alveolates ; Heterokonts ; Stramenopiles
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The evolutionary relationships of four eukaryotic kingdoms—Animalia, Plantae, Fungi, and Protista—remain unclear. In particular, statistical support for the closeness of animals to fungi rather than to plants is lacking, and a preferred branching order of these and other eukaryotic lineages is still controversial even though molecular sequences from diverse eukaryotic taxa have been analyzed. We report a statistical analysis of 214 sequences of nuclear small-subunit ribosomal RNA (srRNA) gene undertaken to clarify these evolutionary relationships. We have considered the variability of substitution rates and the nonindependence of nucleotide substitution across sites in the srRNA gene in testing alternative hypotheses regarding the branching patterns of eukaryote phylogeny. We find that the rates of evolution among sites in the srRNA sequences vary substantially and are approximately gamma distributed with size and shape parameter equal to 0.76. Our results suggest that (1) the animals and true fungi are indeed closer to each other than to any other “crown” group in the eukaryote tree, (2) red algae are the closest relatives of animals, true fungi, and green plants, and (3) the heterokonts and alveolates probably evolved prior to the divergence of red algae and animal-fungus-green-plant lineages. Furthermore, our analyses indicate that the branching order of the eukaryotic lineages that diverged prior to the evolution of alveolates may be generally difficult to resolve with the srRNA sequence data.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Machine vision and applications 8 (1995), S. 187-193 
    ISSN: 1432-1769
    Keywords: Tracking ; Segmentation ; Pigs ; Animals ; Computer vision
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract An algorithm was developed for the segmentation and tracking of piglets and tested on a 200-image sequence of 10 piglets moving on a straw background. The image-capture rate was 1 image/140 ms. The segmentation method was a combination of image differencing with respect to a median background and a Laplacian operator. The features tracked were blob edges in the segmented image. During tracking, the piglets were modelled as ellipses initialised on the blobs. Each piglet was tracked by searching for blob edges in an elliptical window about the piglet's position, which was predicted from its previous two positions.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1573-322X
    Keywords: Animals ; Asia ; consciousness ; Australia ; Hong Kong ; India ; Israel ; Japan ; New Zealand ; The Philippines ; Russia ; Singapore ; Thailand
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Philosophy
    Notes: Abstract The interactions between humans, animals and the environment have shaped human values and ethics, not only the genes that we are made of. The animal rights movement challenges human beings to reconsider interactions between humans and other animals, and maybe connected to the environmental movement that begs us to recognize the fact that there are symbiotic relationships between humans and all other organisms. The first part of this paper looks at types of bioethics, the implications of autonomy and the value of being alive. Then the level of consciousness of these relationships are explored in survey results from Asia and the Pacific, especially in the 1993 International Bioethics Survey conducted in Australia, Hong Kong, India, Israel, Japan, New Zealand, The Philippines, Russia, Singapore and Thailand. Very few mentioned animal consciousness in the survey, but there were more biocentric comments in Australia and Japan; and more comments with the idea of harmony including humans in Thailand. Comparisons between questions and surveys will also be made, in an attempt to describe what people imagine animal consciousness to be, and whether this relates to human ethics of the relationships.
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  • 5
    ISSN: 1432-1009
    Keywords: Animals ; Indicators ; Air pollution ; Ecosystem responses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract With existing and proposed air-quality regulations, ecological disasters resulting from air emissions such as those observed at Copperhill, Tennessee, and Sudbury, Ontario, are unlikely. Current air-quality standards, however, may not protect ecosystems from subacute and chronic exposure to air emissions. The encouragement of the use of coal for energy production and the development of the fossil-fuel industries, including oil shales, tar sands, and coal liquification, point to an increase and spread of fossil-fuel emissions and the potential to influence a number of natural ecosystems. This paper reviews the reported responses of ecosystems to air-borne pollutants and discusses the use of animals as indicators of ecosystem responses to these pollutants. Animal species and populations can act as important indicators of biotic and abiotic responses of aquatic and terrestrial ecosystems. These responses can indicate long-term trends in ecosystem health and productivity, chemical cycling, genetics, and regulation. For short-term trends, fish and wildlife also serve as monitors of changes in community structure, signaling food-web contamination, as well as providing a measure of ecosystem vitality. Information is presented to show not only the importance of animals as indicators of ecosystem responses to air-quality degradation, but also their value as air-pollution indices, that is, as air-quality-related values (AQRV), required in current air-pollution regulation.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0878
    Keywords: Hypophysis ; Rostral pars distalis ; Mugil platanus ; Animals ; Prolactin hormone secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The rostral pars distalis (RPD) of the teleost Mugil platanus from animals pretreated with reserpine or 6-hydroxydopamine (6-HODA) were assayed for dopamine (DA) or noradrenaline (NA) or for prolactin hormone. Such determinations were coupled with electron microscopy. It was found that reserpine and 6-HODA produced a significant decrease in the content of DA, NA, and prolactin. Electron microscope studies revealed that prolactin cells became activated as judged by ultrastructural criteria. After 6-HODA treatment type “B” neurosecretory fibers entering the RPD became selectively destroyed. These observations lead us to suggest that prolactin secretion is under inhibitory control by type “B” neurosecretory fibers of adrenergic nature.
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  • 7
    ISSN: 0303-2647
    Keywords: Animals ; Cell nucleus ; Evolution ; Plants ; Protoctista ; Taxonomy
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 8
    Publication Date: 2014-03-05
    Description: Epithelial folding mediated by apical constriction converts flat epithelial sheets into multilayered, complex tissue structures and is used throughout development in most animals. Little is known, however, about how forces produced near the apical surface of the tissue are transmitted within individual cells to generate the global changes in cell shape that characterize tissue deformation. Here we apply particle tracking velocimetry in gastrulating Drosophila embryos to measure the movement of cytoplasm and plasma membrane during ventral furrow formation. We find that cytoplasmic redistribution during the lengthening phase of ventral furrow formation can be precisely described by viscous flows that quantitatively match the predictions of hydrodynamics. Cell membranes move with the ambient cytoplasm, with little resistance to, or driving force on, the flow. Strikingly, apical constriction produces similar flow patterns in mutant embryos that fail to form cells before gastrulation ('acellular' embryos), such that the global redistribution of cytoplasm mirrors the summed redistribution occurring in individual cells of wild-type embryos. Our results indicate that during the lengthening phase of ventral furrow formation, hydrodynamic behaviour of the cytoplasm provides the predominant mechanism transmitting apically generated forces deep into the tissue and that cell individualization is dispensable.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4111109/" 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/PMC4111109/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉He, Bing -- Doubrovinski, Konstantin -- Polyakov, Oleg -- Wieschaus, Eric -- 5R37HD15587/HD/NICHD NIH HHS/ -- P50 GM 071508/GM/NIGMS NIH HHS/ -- R01 HD015587/HD/NICHD NIH HHS/ -- R37 HD015587/HD/NICHD NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Apr 17;508(7496):392-6. doi: 10.1038/nature13070. Epub 2014 Mar 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA [2]. ; Department of Physics, Princeton University, Princeton, New Jersey 08544, USA. ; 1] Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA [2] Howard Hughes Medical Institute, Princeton University, Princeton, New Jersey 08544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24590071" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Membrane/metabolism ; *Cell Polarity ; *Cell Shape ; Cytoplasm/metabolism ; Drosophila melanogaster/*cytology/*embryology ; Female ; Gastrulation ; Hydrodynamics ; Male ; Mesoderm/cytology/metabolism ; *Morphogenesis ; Movement
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2014-04-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moss, Andrew -- Jensen, Eric -- Gusset, Markus -- England -- Nature. 2014 Apr 10;508(7495):186. doi: 10.1038/508186d.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Chester Zoo, UK. ; University of Warwick, Coventry, UK. ; World Association of Zoos and Aquariums, Gland, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24717506" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Animals, Zoo ; *Biodiversity ; Conservation of Natural Resources/*trends ; Ecology/*education
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2014-11-11
    Description: Autophagy is an evolutionarily conserved catabolic process that recycles nutrients upon starvation and maintains cellular energy homeostasis. Its acute regulation by nutrient-sensing signalling pathways is well described, but its longer-term transcriptional regulation is not. The nuclear receptors peroxisome proliferator-activated receptor-alpha (PPARalpha) and farnesoid X receptor (FXR) are activated in the fasted and fed liver, respectively. Here we show that both PPARalpha and FXR regulate hepatic autophagy in mice. Pharmacological activation of PPARalpha reverses the normal suppression of autophagy in the fed state, inducing autophagic lipid degradation, or lipophagy. This response is lost in PPARalpha knockout (Ppara(-/-), also known as Nr1c1(-/-)) mice, which are partially defective in the induction of autophagy by fasting. Pharmacological activation of the bile acid receptor FXR strongly suppresses the induction of autophagy in the fasting state, and this response is absent in FXR knockout (Fxr(-/-), also known as Nr1h4(-/-)) mice, which show a partial defect in suppression of hepatic autophagy in the fed state. PPARalpha and FXR compete for binding to shared sites in autophagic gene promoters, with opposite transcriptional outputs. These results reveal complementary, interlocking mechanisms for regulation of autophagy by nutrient status.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267857/" 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/PMC4267857/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Jae Man -- Wagner, Martin -- Xiao, Rui -- Kim, Kang Ho -- Feng, Dan -- Lazar, Mitchell A -- Moore, David D -- DK43806/DK/NIDDK NIH HHS/ -- P30 DK019525/DK/NIDDK NIH HHS/ -- P30DX56338-05A2/PHS HHS/ -- P39CA125123-04/CA/NCI NIH HHS/ -- R01 DK049780/DK/NIDDK NIH HHS/ -- R01 DK49780/DK/NIDDK NIH HHS/ -- R37 DK043806/DK/NIDDK NIH HHS/ -- S10RR027783-01A1/RR/NCRR NIH HHS/ -- U54HD-07495-39/HD/NICHD NIH HHS/ -- England -- Nature. 2014 Dec 4;516(7529):112-5. doi: 10.1038/nature13961. Epub 2014 Nov 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. ; Division of Endocrinology, Diabetes, and Metabolism and the Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19014, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25383539" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autophagy/genetics/*physiology ; Cell Line ; Cells, Cultured ; Fasting/physiology ; Gene Expression Regulation ; Hepatocytes/metabolism ; Liver/cytology/*metabolism/ultrastructure ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microtubule-Associated Proteins/genetics/metabolism ; PPAR alpha ; Receptors, Cytoplasmic and Nuclear/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 11
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    Nature Publishing Group (NPG)
    Publication Date: 2014-10-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- Callaway, Ewen -- England -- Nature. 2014 Oct 9;514(7521):153. doi: 10.1038/514153a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25297415" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Entorhinal Cortex/*cytology/physiology ; Hippocampus/*cytology/physiology ; Humans ; Models, Neurological ; *Nobel Prize ; Space Perception/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
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  • 12
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    Nature Publishing Group (NPG)
    Publication Date: 2014-11-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ledford, Heidi -- England -- Nature. 2014 Nov 13;515(7526):182-4. doi: 10.1038/515182a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25391943" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antidepressive Agents/pharmacology/therapeutic use ; Biomedical Research/economics/*statistics & numerical data/*trends ; Depression/*epidemiology/genetics/psychology/*therapy ; Depressive Disorder/epidemiology/genetics/psychology/therapy ; Disease Models, Animal ; Humans ; Mice ; *Neoplasms ; Neurosciences/*trends ; Stress, Psychological/epidemiology/etiology/therapy
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 13
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    Nature Publishing Group (NPG)
    Publication Date: 2014-06-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Enriquez, Jose Rafael Martinez -- England -- Nature. 2014 Jun 5;510(7503):35. doi: 10.1038/510035d.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Autonomous University of Mexico, Mexico City, Mexico.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24899294" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Drama/*history ; Literature, Modern/*history ; Science/*history ; Technology/*history
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
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  • 14
    Publication Date: 2014-11-21
    Description: The basic body plan and major physiological axes have been highly conserved during mammalian evolution, yet only a small fraction of the human genome sequence appears to be subject to evolutionary constraint. To quantify cis- versus trans-acting contributions to mammalian regulatory evolution, we performed genomic DNase I footprinting of the mouse genome across 25 cell and tissue types, collectively defining approximately 8.6 million transcription factor (TF) occupancy sites at nucleotide resolution. Here we show that mouse TF footprints conjointly encode a regulatory lexicon that is approximately 95% similar with that derived from human TF footprints. However, only approximately 20% of mouse TF footprints have human orthologues. Despite substantial turnover of the cis-regulatory landscape, nearly half of all pairwise regulatory interactions connecting mouse TF genes have been maintained in orthologous human cell types through evolutionary innovation of TF recognition sequences. Furthermore, the higher-level organization of mouse TF-to-TF connections into cellular network architectures is nearly identical with human. Our results indicate that evolutionary selection on mammalian gene regulation is targeted chiefly at the level of trans-regulatory circuitry, enabling and potentiating cis-regulatory plasticity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405208/" 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/PMC4405208/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stergachis, Andrew B -- Neph, Shane -- Sandstrom, Richard -- Haugen, Eric -- Reynolds, Alex P -- Zhang, Miaohua -- Byron, Rachel -- Canfield, Theresa -- Stelhing-Sun, Sandra -- Lee, Kristen -- Thurman, Robert E -- Vong, Shinny -- Bates, Daniel -- Neri, Fidencio -- Diegel, Morgan -- Giste, Erika -- Dunn, Douglas -- Vierstra, Jeff -- Hansen, R Scott -- Johnson, Audra K -- Sabo, Peter J -- Wilken, Matthew S -- Reh, Thomas A -- Treuting, Piper M -- Kaul, Rajinder -- Groudine, Mark -- Bender, M A -- Borenstein, Elhanan -- Stamatoyannopoulos, John A -- FDK095678A/PHS HHS/ -- R01 EY021482/EY/NEI NIH HHS/ -- R37 DK044746/DK/NIDDK NIH HHS/ -- R37DK44746/DK/NIDDK NIH HHS/ -- RC2 HG005654/HG/NHGRI NIH HHS/ -- RC2HG005654/HG/NHGRI NIH HHS/ -- T32 GM007266/GM/NIGMS NIH HHS/ -- U01ES01156/ES/NIEHS NIH HHS/ -- U54 HG007010/HG/NHGRI NIH HHS/ -- U54HG004592/HG/NHGRI NIH HHS/ -- U54HG007010/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 Nov 20;515(7527):365-70. doi: 10.1038/nature13972.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. ; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. ; 1] Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA [2] Department of Medicine, University of Washington, Seattle, Washington 98195, USA. ; Department of Biological Structure, University of Washington, Seattle, Washington 98195, USA. ; Department of Comparative Medicine, University of Washington, Seattle, Washington 98195, USA. ; 1] Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA [2] Division of Radiation Oncology, University of Washington, Seattle, Washington 98195, USA. ; 1] Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA [2] Department of Pediatrics, University of Washington, Seattle, Washington 98195, USA. ; 1] Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA [2] Department of Computer Science and Engineering, University of Washington, Seattle, Washington 98102, USA [3] Santa Fe Institute, Santa Fe, New Mexico 87501, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25409825" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conserved Sequence/*genetics ; DNA Footprinting ; *Evolution, Molecular ; Gene Expression Regulation, Developmental/genetics ; Gene Regulatory Networks/genetics ; Humans ; Mammals/*genetics ; Mice ; Regulatory Sequences, Nucleic Acid/*genetics ; Transcription Factors/*genetics/*metabolism
    Print ISSN: 0028-0836
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  • 15
    Publication Date: 2014-08-01
    Description: The translational control of oncoprotein expression is implicated in many cancers. Here we report an eIF4A RNA helicase-dependent mechanism of translational control that contributes to oncogenesis and underlies the anticancer effects of silvestrol and related compounds. For example, eIF4A promotes T-cell acute lymphoblastic leukaemia development in vivo and is required for leukaemia maintenance. Accordingly, inhibition of eIF4A with silvestrol has powerful therapeutic effects against murine and human leukaemic cells in vitro and in vivo. We use transcriptome-scale ribosome footprinting to identify the hallmarks of eIF4A-dependent transcripts. These include 5' untranslated region (UTR) sequences such as the 12-nucleotide guanine quartet (CGG)4 motif that can form RNA G-quadruplex structures. Notably, among the most eIF4A-dependent and silvestrol-sensitive transcripts are a number of oncogenes, superenhancer-associated transcription factors, and epigenetic regulators. Hence, the 5' UTRs of select cancer genes harbour a targetable requirement for the eIF4A RNA helicase.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492470/" 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/PMC4492470/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wolfe, Andrew L -- Singh, Kamini -- Zhong, Yi -- Drewe, Philipp -- Rajasekhar, Vinagolu K -- Sanghvi, Viraj R -- Mavrakis, Konstantinos J -- Jiang, Man -- Roderick, Justine E -- Van der Meulen, Joni -- Schatz, Jonathan H -- Rodrigo, Christina M -- Zhao, Chunying -- Rondou, Pieter -- de Stanchina, Elisa -- Teruya-Feldstein, Julie -- Kelliher, Michelle A -- Speleman, Frank -- Porco, John A Jr -- Pelletier, Jerry -- Ratsch, Gunnar -- Wendel, Hans-Guido -- GM-067041/GM/NIGMS NIH HHS/ -- GM-073855/GM/NIGMS NIH HHS/ -- MOP-10653/Canadian Institutes of Health Research/Canada -- P30 CA008748/CA/NCI NIH HHS/ -- R01 CA142798/CA/NCI NIH HHS/ -- R01-CA142798-01/CA/NCI NIH HHS/ -- England -- Nature. 2014 Sep 4;513(7516):65-70. doi: 10.1038/nature13485. Epub 2014 Jul 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA [2] Weill Cornell Graduate School of Medical Sciences, New York, New York 10065, USA [3]. ; 1] Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA [2]. ; Computational Biology Department, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. ; Stem Cell Center and Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. ; Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. ; 1] Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA [2] Novartis, Cambridge, Massachusetts 02139, USA (K.J.M.); The University of Arizona Cancer Center, Tucson, Arizona 85719, USA (J.H.S.). ; Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605 USA. ; 1] Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA [2] Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium. ; 1] Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA [2] Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA [3] Novartis, Cambridge, Massachusetts 02139, USA (K.J.M.); The University of Arizona Cancer Center, Tucson, Arizona 85719, USA (J.H.S.). ; Department of Chemistry, Center for Chemical Methodology and Library Development, Boston University, Boston, Massachusetts 02215, USA. ; Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium. ; Molecular Pharmacology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. ; Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. ; 1] Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada [2] Department of Oncology, McGill University, Montreal, Quebec H3G 1Y6, Canada [3] The Rosalind and Morris Goodman Cancer Research Center, McGill University, Montreal, Quebec H3G 1Y6, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079319" target="_blank"〉PubMed〈/a〉
    Keywords: 5' Untranslated Regions/*genetics ; Animals ; Antineoplastic Agents, Phytogenic/pharmacology/therapeutic use ; Base Sequence ; Cell Line, Tumor ; Epigenesis, Genetic ; Eukaryotic Initiation Factor-4A/*metabolism ; Female ; *G-Quadruplexes ; Humans ; Mice ; Mice, Inbred C57BL ; Nucleotide Motifs ; Oncogene Proteins/*biosynthesis/*genetics ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug ; therapy/genetics/*metabolism ; *Protein Biosynthesis/drug effects ; Ribosomes/metabolism ; Transcription Factors/metabolism ; Transcription, Genetic/drug effects/genetics ; Triterpenes/pharmacology
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  • 16
    Publication Date: 2014-02-18
    Description: The rapid turnover of the mammalian intestinal epithelium is supported by stem cells located around the base of the crypt. In addition to the Lgr5 marker, intestinal stem cells have been associated with other markers that are expressed heterogeneously within the crypt base region. Previous quantitative clonal fate analyses have led to the proposal that homeostasis occurs as the consequence of neutral competition between dividing stem cells. However, the short-term behaviour of individual Lgr5(+) cells positioned at different locations within the crypt base compartment has not been resolved. Here we establish the short-term dynamics of intestinal stem cells using the novel approach of continuous intravital imaging of Lgr5- Confetti mice. We find that Lgr5(+) cells in the upper part of the niche (termed 'border cells') can be passively displaced into the transit-amplifying domain, after the division of proximate cells, implying that the determination of stem-cell fate can be uncoupled from division. Through quantitative analysis of individual clonal lineages, we show that stem cells at the crypt base, termed 'central cells', experience a survival advantage over border stem cells. However, through the transfer of stem cells between the border and central regions, all Lgr5(+) cells are endowed with long-term self-renewal potential. These findings establish a novel paradigm for stem-cell maintenance in which a dynamically heterogeneous cell population is able to function long term as a single stem-cell pool.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964820/" 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/PMC3964820/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ritsma, Laila -- Ellenbroek, Saskia I J -- Zomer, Anoek -- Snippert, Hugo J -- de Sauvage, Frederic J -- Simons, Benjamin D -- Clevers, Hans -- van Rheenen, Jacco -- 092096/Wellcome Trust/United Kingdom -- 098357/Wellcome Trust/United Kingdom -- 098357/Z/12/Z/Wellcome Trust/United Kingdom -- England -- Nature. 2014 Mar 20;507(7492):362-5. doi: 10.1038/nature12972. Epub 2014 Feb 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Cancer Genomics Netherlands, Hubrecht Institute-KNAW and University Medical Centre Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands [2]. ; Cancer Genomics Netherlands, Hubrecht Institute-KNAW and University Medical Centre Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands. ; University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. ; Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; 1] Cavendish Laboratory, Department of Physics, J. J. Thomson Avenue, University of Cambridge, Cambridge CB3 0HE, UK [2] The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [3] The Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24531760" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division ; Cell Lineage ; Cell Survival ; Clone Cells/cytology ; Female ; *Homeostasis ; Intestinal Mucosa/*cytology ; Male ; Mice ; Models, Biological ; Molecular Imaging ; Receptors, G-Protein-Coupled/genetics/metabolism ; *Single-Cell Analysis ; Stem Cells/*cytology
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  • 17
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    Nature Publishing Group (NPG)
    Publication Date: 2014-01-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muller-Landau, Helene C -- England -- Nature. 2014 Feb 6;506(7486):44-5. doi: 10.1038/nature12851. Epub 2014 Jan 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Smithsonian Tropical Research Institute, Apartado Postal 0843-03092, Panama City, Panama.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24463509" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; Fungi/*physiology ; *Herbivory ; Insects/*physiology ; Trees/*microbiology/*physiology
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  • 18
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    Nature Publishing Group (NPG)
    Publication Date: 2014-10-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Check Hayden, Erika -- England -- Nature. 2014 Oct 30;514(7524):546. doi: 10.1038/514546a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25355339" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/*drug effects ; Animals ; Clinical Trials as Topic/*veterinary ; Dogs/*physiology ; Female ; Humans ; Longevity/*drug effects ; Male ; Mice ; Models, Animal ; Pets/*physiology ; Pilot Projects ; Sirolimus/administration & dosage/adverse effects/*pharmacology
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  • 19
    Publication Date: 2014-09-05
    Description: Receptor interacting protein kinase 1 (RIPK1) has an essential role in the signalling triggered by death receptors and pattern recognition receptors. RIPK1 is believed to function as a node driving NF-kappaB-mediated cell survival and inflammation as well as caspase-8 (CASP8)-dependent apoptotic or RIPK3/MLKL-dependent necroptotic cell death. The physiological relevance of this dual function has remained elusive because of the perinatal death of RIPK1 full knockout mice. To circumvent this problem, we generated RIPK1 conditional knockout mice, and show that mice lacking RIPK1 in intestinal epithelial cells (IECs) spontaneously develop severe intestinal inflammation associated with IEC apoptosis leading to early death. This early lethality was rescued by antibiotic treatment, MYD88 deficiency or tumour-necrosis factor (TNF) receptor 1 deficiency, demonstrating the importance of commensal bacteria and TNF in the IEC Ripk1 knockout phenotype. CASP8 deficiency, but not RIPK3 deficiency, rescued the inflammatory phenotype completely, indicating the indispensable role of RIPK1 in suppressing CASP8-dependent apoptosis but not RIPK3-dependent necroptosis in the intestine. RIPK1 kinase-dead knock-in mice did not exhibit any sign of inflammation, suggesting that RIPK1-mediated protection resides in its kinase-independent platform function. Depletion of RIPK1 in intestinal organoid cultures sensitized them to TNF-induced apoptosis, confirming the in vivo observations. Unexpectedly, TNF-mediated NF-kappaB activation remained intact in these organoids. Our results demonstrate that RIPK1 is essential for survival of IECs, ensuring epithelial homeostasis by protecting the epithelium from CASP8-mediated IEC apoptosis independently of its kinase activity and NF-kappaB activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takahashi, Nozomi -- Vereecke, Lars -- Bertrand, Mathieu J M -- Duprez, Linde -- Berger, Scott B -- Divert, Tatyana -- Goncalves, Amanda -- Sze, Mozes -- Gilbert, Barbara -- Kourula, Stephanie -- Goossens, Vera -- Lefebvre, Sylvie -- Gunther, Claudia -- Becker, Christoph -- Bertin, John -- Gough, Peter J -- Declercq, Wim -- van Loo, Geert -- Vandenabeele, Peter -- England -- Nature. 2014 Sep 4;513(7516):95-9. doi: 10.1038/nature13706.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] VIB Inflammation Research Center, Technologiepark 927, B-9052 Ghent, Belgium [2] Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, B-9052 Ghent, Belgium. ; Pattern Recognition Receptor Discovery Performance Unit, Immuno-inflammation Therapeutic Area, GlaxoSmithKline, Collegeville, Pennsylvania 19426, USA. ; 1] VIB Inflammation Research Center, Technologiepark 927, B-9052 Ghent, Belgium [2] Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, B-9052 Ghent, Belgium [3] VIB Bio Imaging Core Gent, Technologiepark 927, B-9052 Ghent, Belgium. ; Department of Medicine 1, Friedrich-Alexander-University, D-91054 Erlangen, Germany. ; 1] VIB Inflammation Research Center, Technologiepark 927, B-9052 Ghent, Belgium [2] Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, B-9052 Ghent, Belgium [3] Methusalem program, Ghent University, Technologiepark 927, B-9052 Ghent, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25186904" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/pharmacology ; *Apoptosis/drug effects ; Caspase 8/genetics/metabolism ; Cell Survival/drug effects ; Epithelial Cells/*cytology/drug effects/*metabolism/pathology ; Epithelium/drug effects/*metabolism/pathology ; Female ; Gene Deletion ; *Homeostasis/drug effects ; Inflammation/metabolism/pathology ; Intestines/*cytology/drug effects/*metabolism/pathology ; Male ; Mice ; Mice, Knockout ; Myeloid Differentiation Factor 88/deficiency ; NF-kappa B/metabolism ; Necrosis ; Organoids/cytology/drug effects/enzymology/metabolism ; Protein Kinases/metabolism ; Receptor-Interacting Protein Serine-Threonine ; Kinases/deficiency/genetics/*metabolism ; Receptors, Tumor Necrosis Factor, Type I/deficiency ; Survival Analysis ; Tumor Necrosis Factors/pharmacology
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  • 20
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    Nature Publishing Group (NPG)
    Publication Date: 2014-10-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Check Hayden, Erika -- England -- Nature. 2014 Oct 30;514(7524):554-7. doi: 10.1038/514554a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25355344" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Western/epidemiology ; Animals ; Chiroptera/virology ; Disease Outbreaks/*statistics & numerical data ; Disease Reservoirs/*virology ; Ebolavirus/*isolation & purification/*pathogenicity/physiology ; Global Health ; Hemorrhagic Fever, Ebola/*epidemiology/immunology/therapy/*virology ; Humans ; Immunity, Innate ; Primates/virology ; Survival Rate ; Swine/virology ; Virology
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  • 21
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    Nature Publishing Group (NPG)
    Publication Date: 2014-11-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carri, Maria Teresa -- England -- Nature. 2014 Nov 20;515(7527):343. doi: 10.1038/515343e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Rome 'Tor Vergata', Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25409816" target="_blank"〉PubMed〈/a〉
    Keywords: Amyotrophic Lateral Sclerosis/*economics ; Animals ; Biomedical Research/*economics ; Fund Raising/*methods ; Humans ; *Public Opinion
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  • 22
    Publication Date: 2014-08-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takeuchi, Tomonori -- Morris, Richard G M -- England -- Nature. 2014 Sep 18;513(7518):323-4. doi: 10.1038/nature13745. Epub 2014 Aug 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Cognitive and Neural Systems, University of Edinburgh, Edinburgh EH8 9JZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25162529" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Hippocampus/*physiology ; Male ; Memory/*physiology
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  • 23
    Publication Date: 2014-09-26
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476531/" 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/PMC4476531/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fieni, Francesca -- Johnson, Derrick E -- Hudmon, Andy -- Kirichok, Yuriy -- R01 NS078171/NS/NINDS NIH HHS/ -- England -- Nature. 2014 Sep 25;513(7519):E1-2. doi: 10.1038/nature13626.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of California San Francisco, San Francisco, California 94158, USA. ; Department of Biochemistry and Molecular Biology, Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25254480" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/*metabolism ; Female ; Mitochondria, Heart/*metabolism/*pathology ; Myocardium/*enzymology/*pathology ; *Stress, Physiological
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  • 24
    Publication Date: 2014-10-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rodell, Christopher B -- Burdick, Jason A -- England -- Nature. 2014 Oct 30;514(7524):574-5. doi: 10.1038/514574a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25355357" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Magnetics/*methods ; Nanotechnology/*methods ; Tissue Engineering/*methods
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  • 25
    Publication Date: 2014-04-18
    Description: Trisomy 21 is the most frequent genetic cause of cognitive impairment. To assess the perturbations of gene expression in trisomy 21, and to eliminate the noise of genomic variability, we studied the transcriptome of fetal fibroblasts from a pair of monozygotic twins discordant for trisomy 21. Here we show that the differential expression between the twins is organized in domains along all chromosomes that are either upregulated or downregulated. These gene expression dysregulation domains (GEDDs) can be defined by the expression level of their gene content, and are well conserved in induced pluripotent stem cells derived from the twins' fibroblasts. Comparison of the transcriptome of the Ts65Dn mouse model of Down's syndrome and normal littermate mouse fibroblasts also showed GEDDs along the mouse chromosomes that were syntenic in human. The GEDDs correlate with the lamina-associated (LADs) and replication domains of mammalian cells. The overall position of LADs was not altered in trisomic cells; however, the H3K4me3 profile of the trisomic fibroblasts was modified and accurately followed the GEDD pattern. These results indicate that the nuclear compartments of trisomic cells undergo modifications of the chromatin environment influencing the overall transcriptome, and that GEDDs may therefore contribute to some trisomy 21 phenotypes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Letourneau, Audrey -- Santoni, Federico A -- Bonilla, Ximena -- Sailani, M Reza -- Gonzalez, David -- Kind, Jop -- Chevalier, Claire -- Thurman, Robert -- Sandstrom, Richard S -- Hibaoui, Youssef -- Garieri, Marco -- Popadin, Konstantin -- Falconnet, Emilie -- Gagnebin, Maryline -- Gehrig, Corinne -- Vannier, Anne -- Guipponi, Michel -- Farinelli, Laurent -- Robyr, Daniel -- Migliavacca, Eugenia -- Borel, Christelle -- Deutsch, Samuel -- Feki, Anis -- Stamatoyannopoulos, John A -- Herault, Yann -- van Steensel, Bas -- Guigo, Roderic -- Antonarakis, Stylianos E -- U54HG007010/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 Apr 17;508(7496):345-50. doi: 10.1038/nature13200.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland [2]. ; Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland. ; Center for Genomic Regulation, University Pompeu Fabra, 08003 Barcelona, Spain. ; Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands. ; AneuPath 21, Institut de Genetique Biologie Moleculaire et Cellulaire, Translational medicine and Neuroscience program, IGBMC, ICS, PHENOMIN, CNRS, INSERM, Universite de Strasbourg, UMR7104, UMR964, 1 rue Laurent Fries, 67404 Illkirch, France. ; Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. ; Stem Cell Research Laboratory, Department of Obstetrics and Gynecology, Geneva University Hospitals, 1211 Geneva, Switzerland. ; FASTERIS SA, 1228 Plan-les-Ouates, Switzerland. ; 1] Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland [2] Swiss Institute of Bioinfomatics, 1211 Geneva, Switzerland. ; DOE Joint Genome Institute, Walnut Creek, California 94598, USA. ; 1] Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland [2] iGE3 Institute of Genetics and Genomics of Geneva, 1211 Geneva, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24740065" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Chromatin/chemistry/metabolism ; Chromosomes, Human, Pair 21/genetics ; Chromosomes, Mammalian/genetics ; DNA Replication Timing ; Down Syndrome/*genetics/pathology ; Female ; Fetus/cytology ; Fibroblasts ; Gene Expression Regulation/*genetics ; Genome/*genetics ; Histones/chemistry/metabolism ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Lysine/metabolism ; Male ; Methylation ; Mice ; Transcriptome/*genetics ; Twins, Monozygotic/genetics
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  • 26
    Publication Date: 2014-04-04
    Description: In the mammalian cerebral cortex, neural responses are highly variable during spontaneous activity and sensory stimulation. To explain this variability, the cortex of alert animals has been proposed to be in an asynchronous high-conductance state in which irregular spiking arises from the convergence of large numbers of uncorrelated excitatory and inhibitory inputs onto individual neurons. Signatures of this state are that a neuron's membrane potential (Vm) hovers just below spike threshold, and its aggregate synaptic input is nearly Gaussian, arising from many uncorrelated inputs. Alternatively, irregular spiking could arise from infrequent correlated input events that elicit large fluctuations in Vm (refs 5, 6). To distinguish between these hypotheses, we developed a technique to perform whole-cell Vm measurements from the cortex of behaving monkeys, focusing on primary visual cortex (V1) of monkeys performing a visual fixation task. Here we show that, contrary to the predictions of an asynchronous state, mean Vm during fixation was far from threshold (14 mV) and spiking was triggered by occasional large spontaneous fluctuations. Distributions of Vm values were skewed beyond that expected for a range of Gaussian input, but were consistent with synaptic input arising from infrequent correlated events. Furthermore, spontaneous fluctuations in Vm were correlated with the surrounding network activity, as reflected in simultaneously recorded nearby local field potential. Visual stimulation, however, led to responses more consistent with an asynchronous state: mean Vm approached threshold, fluctuations became more Gaussian, and correlations between single neurons and the surrounding network were disrupted. These observations show that sensory drive can shift a common cortical circuitry from a synchronous to an asynchronous state.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067243/" 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/PMC4067243/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tan, Andrew Y Y -- Chen, Yuzhi -- Scholl, Benjamin -- Seidemann, Eyal -- Priebe, Nicholas J -- EY-016454/EY/NEI NIH HHS/ -- EY-019288/EY/NEI NIH HHS/ -- EY-16752/EY/NEI NIH HHS/ -- R01 EY016454/EY/NEI NIH HHS/ -- R01 EY019288/EY/NEI NIH HHS/ -- T32 EY021462/EY/NEI NIH HHS/ -- England -- Nature. 2014 May 8;509(7499):226-9. doi: 10.1038/nature13159. Epub 2014 Mar 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Perceptual Systems, University of Texas, Austin, Texas 78712, USA [2] Department of Neuroscience, College of Natural Sciences, University of Texas, Austin, Texas 78712, USA [3]. ; 1] Center for Perceptual Systems, University of Texas, Austin, Texas 78712, USA [2] Department of Neuroscience, College of Natural Sciences, University of Texas, Austin, Texas 78712, USA [3] Department of Psychology, University of Texas, Austin, Texas 78712, USA [4]. ; 1] Center for Perceptual Systems, University of Texas, Austin, Texas 78712, USA [2] Department of Neuroscience, College of Natural Sciences, University of Texas, Austin, Texas 78712, USA [3] Department of Psychology, University of Texas, Austin, Texas 78712, USA. ; 1] Center for Perceptual Systems, University of Texas, Austin, Texas 78712, USA [2] Department of Neuroscience, College of Natural Sciences, University of Texas, Austin, Texas 78712, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695217" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Fixation, Ocular/*physiology ; Macaca mulatta ; Male ; *Models, Neurological ; Neurons/metabolism ; Photic Stimulation ; Synapses/metabolism ; Visual Cortex/cytology/*physiology
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  • 27
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    Nature Publishing Group (NPG)
    Publication Date: 2014-06-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ledford, Heidi -- England -- Nature. 2014 Jun 26;510(7506):454. doi: 10.1038/510454a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24965630" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Antineoplastic Agents/pharmacology/therapeutic use ; Benzamides/therapeutic use ; Clinical Trials as Topic ; DNA Repair/genetics ; *Drug Approval ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Humans ; Indoles/therapeutic use ; Mice ; Ovarian Neoplasms/drug therapy/genetics ; *Phthalazines/pharmacology/therapeutic use ; *Piperazines/pharmacology/therapeutic use ; Poly(ADP-ribose) Polymerase Inhibitors ; Poly(ADP-ribose) Polymerases/metabolism ; Survival Analysis ; Treatment Outcome ; United States ; United States Food and Drug Administration/*legislation & jurisprudence
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  • 28
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    Nature Publishing Group (NPG)
    Publication Date: 2014-04-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wood, Bernard -- England -- Nature. 2014 Apr 3;508(7494):31-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24707524" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Asia ; *Biological Evolution ; *Fossils ; History, 20th Century ; Hominidae/anatomy & histology/*classification ; Kenya ; Paleontology/*history ; Phylogeny ; Tanzania
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  • 29
    Publication Date: 2014-07-22
    Description: The relationship between synaptic excitation and inhibition (E/I ratio), two opposing forces in the mammalian cerebral cortex, affects many cortical functions such as feature selectivity and gain. Individual pyramidal cells show stable E/I ratios in time despite fluctuating cortical activity levels. This is because when excitation increases, inhibition increases proportionally through the increased recruitment of inhibitory neurons, a phenomenon referred to as excitation-inhibition balance. However, little is known about the distribution of E/I ratios across pyramidal cells. Through their highly divergent axons, inhibitory neurons indiscriminately contact most neighbouring pyramidal cells. Is inhibition homogeneously distributed or is it individually matched to the different amounts of excitation received by distinct pyramidal cells? Here we discover that pyramidal cells in layer 2/3 of mouse primary visual cortex each receive inhibition in a similar proportion to their excitation. As a consequence, E/I ratios are equalized across pyramidal cells. This matched inhibition is mediated by parvalbumin-expressing but not somatostatin-expressing inhibitory cells and results from the independent adjustment of synapses originating from individual parvalbumin-expressing cells targeting different pyramidal cells. Furthermore, this match is activity-dependent as it is disrupted by perturbing pyramidal cell activity. Thus, the equalization of E/I ratios across pyramidal cells reveals an unexpected degree of order in the spatial distribution of synaptic strengths and indicates that the relationship between the cortex's two opposing forces is stabilized not only in time but also in space.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117808/" 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/PMC4117808/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xue, Mingshan -- Atallah, Bassam V -- Scanziani, Massimo -- P30 NS047101/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jul 31;511(7511):596-600. doi: 10.1038/nature13321. Epub 2014 Jun 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Neurobiology Section, Division of Biological Sciences, Center for Neural Circuits and Behavior, University of California, San Diego, La Jolla, California 92093-0634, USA [2] Department of Neuroscience, University of California, San Diego, La Jolla, California 92093-0634, USA [3] Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA, and Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas 77030, USA. ; Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, Lisbon 1400-038, Portugal. ; 1] Neurobiology Section, Division of Biological Sciences, Center for Neural Circuits and Behavior, University of California, San Diego, La Jolla, California 92093-0634, USA [2] Department of Neuroscience, University of California, San Diego, La Jolla, California 92093-0634, USA [3] Howard Hughes Medical Institute, University of California, San Diego, La Jolla, California 92093-0634, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043046" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; HEK293 Cells ; Humans ; Male ; Mice ; Neural Inhibition/physiology ; Neurons/*physiology ; Pyramidal Cells/physiology ; Synapses/physiology ; Visual Cortex/*cytology/*physiology
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  • 30
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    Nature Publishing Group (NPG)
    Publication Date: 2014-09-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Check Hayden, Erika -- England -- Nature. 2014 Sep 25;513(7519):474-7. doi: 10.1038/513474a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25254458" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biomedical Research ; Chiroptera/virology ; Contact Tracing ; Ebolavirus/genetics/pathogenicity ; Equipment and Supplies, Hospital/statistics & numerical data ; Female ; Hemorrhagic Fever, Ebola/diagnosis/*epidemiology/transmission/virology ; *Hospitals ; Humans ; *Lassa Fever/diagnosis/epidemiology ; Male ; Sierra Leone/epidemiology
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  • 31
    Publication Date: 2014-02-21
    Description: Crohn's disease is a debilitating inflammatory bowel disease (IBD) that can involve the entire digestive tract. A single-nucleotide polymorphism (SNP) encoding a missense variant in the autophagy gene ATG16L1 (rs2241880, Thr300Ala) is strongly associated with the incidence of Crohn's disease. Numerous studies have demonstrated the effect of ATG16L1 deletion or deficiency; however, the molecular consequences of the Thr300Ala (T300A) variant remains unknown. Here we show that amino acids 296-299 constitute a caspase cleavage motif in ATG16L1 and that the T300A variant (T316A in mice) significantly increases ATG16L1 sensitization to caspase-3-mediated processing. We observed that death-receptor activation or starvation-induced metabolic stress in human and murine macrophages increased degradation of the T300A or T316A variants of ATG16L1, respectively, resulting in diminished autophagy. Knock-in mice harbouring the T316A variant showed defective clearance of the ileal pathogen Yersinia enterocolitica and an elevated inflammatory cytokine response. In turn, deletion of the caspase-3-encoding gene, Casp3, or elimination of the caspase cleavage site by site-directed mutagenesis rescued starvation-induced autophagy and pathogen clearance, respectively. These findings demonstrate that caspase 3 activation in the presence of a common risk allele leads to accelerated degradation of ATG16L1, placing cellular stress, apoptotic stimuli and impaired autophagy in a unified pathway that predisposes to Crohn's disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Murthy, Aditya -- Li, Yun -- Peng, Ivan -- Reichelt, Mike -- Katakam, Anand Kumar -- Noubade, Rajkumar -- Roose-Girma, Merone -- DeVoss, Jason -- Diehl, Lauri -- Graham, Robert R -- van Lookeren Campagne, Menno -- England -- Nature. 2014 Feb 27;506(7489):456-62. doi: 10.1038/nature13044. Epub 2014 Feb 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Pathology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Molecular Biology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; ITGR Human Genetics, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24553140" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Animals ; Autophagy/genetics ; Carrier Proteins/chemistry/*genetics/*metabolism ; Caspase 3/deficiency/genetics/*metabolism ; Cell Line ; Cells, Cultured ; Crohn Disease/*genetics/pathology ; Cytokines/immunology ; Enzyme Activation ; Female ; Food Deprivation ; Humans ; Macrophages/immunology/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mutagenesis, Site-Directed ; Polymorphism, Single Nucleotide/*genetics ; *Proteolysis ; Stress, Physiological ; Yersinia enterocolitica/immunology
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  • 32
    Publication Date: 2014-08-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reik, Wolf -- Kelsey, Gavin -- 095645/Wellcome Trust/United Kingdom -- MR/K011332/1/Medical Research Council/United Kingdom -- England -- Nature. 2014 Jul 31;511(7511):540-1. doi: 10.1038/nature13648. Epub 2014 Jul 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Epigenetics Programme, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK, and at the Centre for Trophoblast Research, University of Cambridge. [2] Wellcome Trust Sanger Institute, Cambridge. ; Epigenetics Programme, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK, and at the Centre for Trophoblast Research, University of Cambridge.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079550" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *DNA Methylation ; DNA Transposable Elements/physiology ; Embryo, Mammalian/metabolism ; *Epigenomics ; Genomic Imprinting ; Humans
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  • 33
    Publication Date: 2014-08-15
    Description: The study of cancer genes in mouse models has traditionally relied on genetically-engineered strains made via transgenesis or gene targeting in embryonic stem cells. Here we describe a new method of cancer model generation using the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) system in vivo in wild-type mice. We used hydrodynamic injection to deliver a CRISPR plasmid DNA expressing Cas9 and single guide RNAs (sgRNAs) to the liver that directly target the tumour suppressor genes Pten (ref. 5) and p53 (also known as TP53 and Trp53) (ref. 6), alone and in combination. CRISPR-mediated Pten mutation led to elevated Akt phosphorylation and lipid accumulation in hepatocytes, phenocopying the effects of deletion of the gene using Cre-LoxP technology. Simultaneous targeting of Pten and p53 induced liver tumours that mimicked those caused by Cre-loxP-mediated deletion of Pten and p53. DNA sequencing of liver and tumour tissue revealed insertion or deletion mutations of the tumour suppressor genes, including bi-allelic mutations of both Pten and p53 in tumours. Furthermore, co-injection of Cas9 plasmids harbouring sgRNAs targeting the beta-catenin gene and a single-stranded DNA oligonucleotide donor carrying activating point mutations led to the generation of hepatocytes with nuclear localization of beta-catenin. This study demonstrates the feasibility of direct mutation of tumour suppressor genes and oncogenes in the liver using the CRISPR/Cas system, which presents a new avenue for rapid development of liver cancer models and functional genomics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199937/" 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/PMC4199937/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xue, Wen -- Chen, Sidi -- Yin, Hao -- Tammela, Tuomas -- Papagiannakopoulos, Thales -- Joshi, Nikhil S -- Cai, Wenxin -- Yang, Gillian -- Bronson, Roderick -- Crowley, Denise G -- Zhang, Feng -- Anderson, Daniel G -- Sharp, Phillip A -- Jacks, Tyler -- 1K99CA169512/CA/NCI NIH HHS/ -- 2-P01-CA42063/CA/NCI NIH HHS/ -- 5-U54-CA151884-04/CA/NCI NIH HHS/ -- DP1 MH100706/MH/NIMH NIH HHS/ -- K99 CA169512/CA/NCI NIH HHS/ -- P30 CA014051/CA/NCI NIH HHS/ -- P30-CA14051/CA/NCI NIH HHS/ -- R00 CA169512/CA/NCI NIH HHS/ -- R01 DK097768/DK/NIDDK NIH HHS/ -- R01-CA115527/CA/NCI NIH HHS/ -- R01-CA132091/CA/NCI NIH HHS/ -- R01-CA133404/CA/NCI NIH HHS/ -- R01-EB000244/EB/NIBIB NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Oct 16;514(7522):380-4. doi: 10.1038/nature13589. Epub 2014 Aug 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [2]. ; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA. ; Tufts University and Harvard Medical School, Boston, Massachusetts 02115, USA. ; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA. ; 1] David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [2] Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [3] Harvard-MIT Division of Health Sciences &Technology, Cambridge, Massachusetts 02139, USA [4] Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA. ; 1] David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA. ; 1] David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [3] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119044" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; *CRISPR-Cas Systems ; Cell Transformation, Neoplastic/genetics ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; Female ; *Genes, Tumor Suppressor ; Genes, p53/genetics ; Genetic Engineering/*methods ; Hepatocytes/metabolism/pathology ; Lipid Metabolism ; Liver/cytology/*metabolism/pathology ; Liver Neoplasms/genetics/metabolism/pathology ; Mice ; Molecular Sequence Data ; Mutagenesis/*genetics ; Mutation/*genetics ; Oncogenes/*genetics ; PTEN Phosphohydrolase/genetics ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; beta Catenin/genetics
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  • 34
    Publication Date: 2014-07-11
    Description: N-methyl-d-aspartate (NMDA) receptors are Hebbian-like coincidence detectors, requiring binding of glycine and glutamate in combination with the relief of voltage-dependent magnesium block to open an ion conductive pore across the membrane bilayer. Despite the importance of the NMDA receptor in the development and function of the brain, a molecular structure of an intact receptor has remained elusive. Here we present X-ray crystal structures of the Xenopus laevis GluN1-GluN2B NMDA receptor with the allosteric inhibitor, Ro25-6981, partial agonists and the ion channel blocker, MK-801. Receptor subunits are arranged in a 1-2-1-2 fashion, demonstrating extensive interactions between the amino-terminal and ligand-binding domains. The transmembrane domains harbour a closed-blocked ion channel, a pyramidal central vestibule lined by residues implicated in binding ion channel blockers and magnesium, and a approximately twofold symmetric arrangement of ion channel pore loops. These structures provide new insights into the architecture, allosteric coupling and ion channel function of NMDA receptors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263351/" 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/PMC4263351/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Chia-Hsueh -- Lu, Wei -- Michel, Jennifer Carlisle -- Goehring, April -- Du, Juan -- Song, Xianqiang -- Gouaux, Eric -- R37 NS038631/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jul 10;511(7508):191-7. doi: 10.1038/nature13548. Epub 2014 Jun 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA [2]. ; 1] Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA [2] Howard Hughes Medical Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. ; Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25008524" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dizocilpine Maleate/chemistry ; Ion Channels/chemistry ; Ligands ; *Models, Molecular ; Phenols ; Piperidines/chemistry ; Protein Binding ; Protein Structure, Tertiary ; Protein Subunits/chemistry ; Receptors, N-Methyl-D-Aspartate/*chemistry ; Xenopus laevis/*physiology
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  • 35
    Publication Date: 2014-04-04
    Description: The formation of precise connections between retina and lateral geniculate nucleus (LGN) involves the activity-dependent elimination of some synapses, with strengthening and retention of others. Here we show that the major histocompatibility complex (MHC) class I molecule H2-D(b) is necessary and sufficient for synapse elimination in the retinogeniculate system. In mice lacking both H2-K(b) and H2-D(b) (K(b)D(b)(-/-)), despite intact retinal activity and basal synaptic transmission, the developmentally regulated decrease in functional convergence of retinal ganglion cell synaptic inputs to LGN neurons fails and eye-specific layers do not form. Neuronal expression of just H2-D(b) in K(b)D(b)(-/-) mice rescues both synapse elimination and eye-specific segregation despite a compromised immune system. When patterns of stimulation mimicking endogenous retinal waves are used to probe synaptic learning rules at retinogeniculate synapses, long-term potentiation (LTP) is intact but long-term depression (LTD) is impaired in K(b)D(b)(-/-) mice. This change is due to an increase in Ca(2+)-permeable AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. Restoring H2-D(b) to K(b)D(b)(-/-) neurons renders AMPA receptors Ca(2+) impermeable and rescues LTD. These observations reveal an MHC-class-I-mediated link between developmental synapse pruning and balanced synaptic learning rules enabling both LTD and LTP, and demonstrate a direct requirement for H2-D(b) in functional and structural synapse pruning in CNS neurons.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016165/" 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/PMC4016165/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Hanmi -- Brott, Barbara K -- Kirkby, Lowry A -- Adelson, Jaimie D -- Cheng, Sarah -- Feller, Marla B -- Datwani, Akash -- Shatz, Carla J -- EY02858/EY/NEI NIH HHS/ -- R01 EY002858/EY/NEI NIH HHS/ -- R01 EY013528/EY/NEI NIH HHS/ -- R01 EY13528/EY/NEI NIH HHS/ -- R01 MH071666/MH/NIMH NIH HHS/ -- T32 MH020016/MH/NIMH NIH HHS/ -- England -- Nature. 2014 May 8;509(7499):195-200. doi: 10.1038/nature13154. Epub 2014 Mar 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Biology and Neurobiology and Bio-X, James H. Clark Center, 318 Campus Drive, Stanford, California 94305, USA. ; Department of Molecular and Cell Biology & Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, USA. ; 1] Departments of Biology and Neurobiology and Bio-X, James H. Clark Center, 318 Campus Drive, Stanford, California 94305, USA [2] Sage Bionetworks, 1100 Fairview Avenue N., Seattle, Washington 98109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695230" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Geniculate Bodies/*cytology/*physiology ; H-2 Antigens/genetics/immunology/metabolism ; Histocompatibility Antigen H-2D/genetics/immunology/*metabolism ; Long-Term Potentiation/physiology ; Long-Term Synaptic Depression ; Mice ; *Neural Pathways ; Receptors, N-Methyl-D-Aspartate/metabolism ; Retina/*cytology/*physiology ; Retinal Ganglion Cells/cytology/physiology ; Synapses/*metabolism ; Synaptic Transmission
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  • 36
    Publication Date: 2014-02-04
    Description: The recognition events that mediate adaptive cellular immunity and regulate antibody responses depend on intercellular contacts between T cells and antigen-presenting cells (APCs). T-cell signalling is initiated at these contacts when surface-expressed T-cell receptors (TCRs) recognize peptide fragments (antigens) of pathogens bound to major histocompatibility complex molecules (pMHC) on APCs. This, along with engagement of adhesion receptors, leads to the formation of a specialized junction between T cells and APCs, known as the immunological synapse, which mediates efficient delivery of effector molecules and intercellular signals across the synaptic cleft. T-cell recognition of pMHC and the adhesion ligand intercellular adhesion molecule-1 (ICAM-1) on supported planar bilayers recapitulates the domain organization of the immunological synapse, which is characterized by central accumulation of TCRs, adjacent to a secretory domain, both surrounded by an adhesive ring. Although accumulation of TCRs at the immunological synapse centre correlates with T-cell function, this domain is itself largely devoid of TCR signalling activity, and is characterized by an unexplained immobilization of TCR-pMHC complexes relative to the highly dynamic immunological synapse periphery. Here we show that centrally accumulated TCRs are located on the surface of extracellular microvesicles that bud at the immunological synapse centre. Tumour susceptibility gene 101 (TSG101) sorts TCRs for inclusion in microvesicles, whereas vacuolar protein sorting 4 (VPS4) mediates scission of microvesicles from the T-cell plasma membrane. The human immunodeficiency virus polyprotein Gag co-opts this process for budding of virus-like particles. B cells bearing cognate pMHC receive TCRs from T cells and initiate intracellular signals in response to isolated synaptic microvesicles. We conclude that the immunological synapse orchestrates TCR sorting and release in extracellular microvesicles. These microvesicles deliver transcellular signals across antigen-dependent synapses by engaging cognate pMHC on APCs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3949170/" 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/PMC3949170/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Choudhuri, Kaushik -- Llodra, Jaime -- Roth, Eric W -- Tsai, Jones -- Gordo, Susana -- Wucherpfennig, Kai W -- Kam, Lance C -- Stokes, David L -- Dustin, Michael L -- 100262/Wellcome Trust/United Kingdom -- AI043542/AI/NIAID NIH HHS/ -- AI045757/AI/NIAID NIH HHS/ -- AI055037/AI/NIAID NIH HHS/ -- AI088377/AI/NIAID NIH HHS/ -- AI093884/AI/NIAID NIH HHS/ -- EY016586/EY/NEI NIH HHS/ -- K99 AI093884/AI/NIAID NIH HHS/ -- K99AI093884/AI/NIAID NIH HHS/ -- P30 CA016087/CA/NCI NIH HHS/ -- R01 AI043542/AI/NIAID NIH HHS/ -- R01 AI088377/AI/NIAID NIH HHS/ -- R21 AI055037/AI/NIAID NIH HHS/ -- R37 AI043542/AI/NIAID NIH HHS/ -- Wellcome Trust/United Kingdom -- England -- Nature. 2014 Mar 6;507(7490):118-23. doi: 10.1038/nature12951. Epub 2014 Feb 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Program in Molecular Pathogenesis, Helen L. and Martin S. Kimmel Center for Biology and Medicine of the Skirball Institute of Biomolecular Medicine, 540 First Avenue, New York, New York 10016, USA [2]. ; 1] Program in Structural Biology, Helen L. and Martin S. Kimmel Center for Biology and Medicine of the Skirball Institute of Biomolecular Medicine, 540 First Avenue, New York, New York 10016, USA [2]. ; Northwestern University Atomic and Nanoscale Characterization Experimental Center, Northwestern University, 2220 Campus Drive, Evanston, Illinois 60208, USA. ; Department of Biomedical Engineering, Columbia University, 500 W 120th Street, New York, New York 10027, USA. ; 1] Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA [2] Program in Immunology, Harvard Medical School, Boston, Massachusetts 02215, USA. ; 1] Program in Structural Biology, Helen L. and Martin S. Kimmel Center for Biology and Medicine of the Skirball Institute of Biomolecular Medicine, 540 First Avenue, New York, New York 10016, USA [2] New York Structural Biology Center, 89 Convent Avenue, New York, New York 10027, USA. ; 1] Department of Pathology, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA [2] Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, The University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7FY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24487619" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen-Presenting Cells/cytology/immunology/metabolism ; B-Lymphocytes/cytology/immunology/metabolism ; CD4-Positive T-Lymphocytes/immunology/metabolism/*secretion/virology ; *Cell Polarity ; DNA-Binding Proteins/metabolism ; Endosomal Sorting Complexes Required for Transport/metabolism ; Female ; HIV/metabolism ; Histocompatibility Antigens Class I/immunology/metabolism ; Humans ; Immunological Synapses/metabolism/*secretion/ultrastructure ; Intercellular Adhesion Molecule-1/metabolism ; Lymphocyte Activation ; Male ; Mice ; Protein Binding ; Protein Transport ; Receptors, Antigen, T-Cell/immunology/*metabolism/ultrastructure ; Secretory Vesicles/*metabolism/secretion ; Signal Transduction ; Transcription Factors/metabolism ; Vesicular Transport Proteins/metabolism ; Virus Release ; gag Gene Products, Human Immunodeficiency Virus/metabolism
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  • 37
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    Nature Publishing Group (NPG)
    Publication Date: 2014-11-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nogrady, Bianca -- England -- Nature. 2014 Nov 13;515(7526):S8-9. doi: 10.1038/515S8a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25390148" target="_blank"〉PubMed〈/a〉
    Keywords: Analgesics, Opioid/administration & dosage/therapeutic use ; Anemia, Sickle Cell/*complications/pathology/*physiopathology ; Animals ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism ; Child ; Erythrocytes/pathology ; Humans ; Mice ; Nerve Fibers/*drug effects/metabolism/*pathology ; Pain/*drug therapy/*etiology/metabolism/physiopathology ; Receptors, N-Methyl-D-Aspartate/metabolism ; TRPV Cation Channels/metabolism ; Temperature ; Trifluoperazine/therapeutic use
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  • 38
    Publication Date: 2014-03-29
    Description: Akt, also known as protein kinase B, plays key roles in cell proliferation, survival and metabolism. Akt hyperactivation contributes to many pathophysiological conditions, including human cancers, and is closely associated with poor prognosis and chemo- or radiotherapeutic resistance. Phosphorylation of Akt at S473 (ref. 5) and T308 (ref. 6) activates Akt. However, it remains unclear whether further mechanisms account for full Akt activation, and whether Akt hyperactivation is linked to misregulated cell cycle progression, another cancer hallmark. Here we report that Akt activity fluctuates across the cell cycle, mirroring cyclin A expression. Mechanistically, phosphorylation of S477 and T479 at the Akt extreme carboxy terminus by cyclin-dependent kinase 2 (Cdk2)/cyclin A or mTORC2, under distinct physiological conditions, promotes Akt activation through facilitating, or functionally compensating for, S473 phosphorylation. Furthermore, deletion of the cyclin A2 allele in the mouse olfactory bulb leads to reduced S477/T479 phosphorylation and elevated cellular apoptosis. Notably, cyclin A2-deletion-induced cellular apoptosis in mouse embryonic stem cells is partly rescued by S477D/T479E-Akt1, supporting a physiological role for cyclin A2 in governing Akt activation. Together, the results of our study show Akt S477/T479 phosphorylation to be an essential layer of the Akt activation mechanism to regulate its physiological functions, thereby providing a new mechanistic link between aberrant cell cycle progression and Akt hyperactivation in cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076493/" 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/PMC4076493/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Pengda -- Begley, Michael -- Michowski, Wojciech -- Inuzuka, Hiroyuki -- Ginzberg, Miriam -- Gao, Daming -- Tsou, Peiling -- Gan, Wenjian -- Papa, Antonella -- Kim, Byeong Mo -- Wan, Lixin -- Singh, Amrik -- Zhai, Bo -- Yuan, Min -- Wang, Zhiwei -- Gygi, Steven P -- Lee, Tae Ho -- Lu, Kun-Ping -- Toker, Alex -- Pandolfi, Pier Paolo -- Asara, John M -- Kirschner, Marc W -- Sicinski, Piotr -- Cantley, Lewis -- Wei, Wenyi -- 2P01CA120964/CA/NCI NIH HHS/ -- 5T32HL007893/HL/NHLBI NIH HHS/ -- CA177910/CA/NCI NIH HHS/ -- GM089763/GM/NIGMS NIH HHS/ -- GM094777/GM/NIGMS NIH HHS/ -- P01 CA120964/CA/NCI NIH HHS/ -- R01 CA132740/CA/NCI NIH HHS/ -- R01 CA167677/CA/NCI NIH HHS/ -- R01 CA177910/CA/NCI NIH HHS/ -- R01 GM041890/GM/NIGMS NIH HHS/ -- R01 GM089763/GM/NIGMS NIH HHS/ -- R01 GM094777/GM/NIGMS NIH HHS/ -- R01 HL111430/HL/NHLBI NIH HHS/ -- R01CA132740/CA/NCI NIH HHS/ -- S10 OD010612/OD/NIH HHS/ -- T32 HL007893/HL/NHLBI NIH HHS/ -- England -- Nature. 2014 Apr 24;508(7497):541-5. doi: 10.1038/nature13079. Epub 2014 Mar 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. ; 1] Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA [2] Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of Cancer Biology, Dana-Farber Cancer Institute and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA [2] Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA [3] Cancer Genetics Program and Division of Genetics, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA. ; Division of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. ; Cell Signaling Technology, Danvers, Massachusetts 01923, USA. ; Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. ; 1] Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA [2] The Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University, Suzhou 215123, China (Z.W.); Cancer Center at Weill Cornell Medical College and NewYork-Presbyterian Hospital, New York, New York 10065, USA (L.C.). ; Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA [2] Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA [3] The Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University, Suzhou 215123, China (Z.W.); Cancer Center at Weill Cornell Medical College and NewYork-Presbyterian Hospital, New York, New York 10065, USA (L.C.).〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670654" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/genetics ; Cell Cycle/*physiology ; Cell Proliferation ; Cyclin A2/metabolism ; Cyclin-Dependent Kinase 2/metabolism ; Embryonic Stem Cells/cytology/metabolism ; Enzyme Activation ; Male ; Mice ; Multiprotein Complexes/metabolism ; Neoplasms/enzymology/pathology ; Olfactory Bulb/cytology/enzymology/metabolism ; Oncogene Protein v-akt/chemistry/metabolism ; Phosphorylation ; Phosphoserine/metabolism ; Phosphothreonine/metabolism ; Proto-Oncogene Proteins c-akt/*chemistry/*metabolism ; TOR Serine-Threonine Kinases/metabolism
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  • 39
    Publication Date: 2014-03-14
    Description: Microfluidics, a technology characterized by the engineered manipulation of fluids at the submillimetre scale, has shown considerable promise for improving diagnostics and biology research. Certain properties of microfluidic technologies, such as rapid sample processing and the precise control of fluids in an assay, have made them attractive candidates to replace traditional experimental approaches. Here we analyse the progress made by lab-on-a-chip microtechnologies in recent years, and discuss the clinical and research areas in which they have made the greatest impact. We also suggest directions that biologists, engineers and clinicians can take to help this technology live up to its potential.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sackmann, Eric K -- Fulton, Anna L -- Beebe, David J -- England -- Nature. 2014 Mar 13;507(7491):181-9. doi: 10.1038/nature13118.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Materials Science Program, Department of Biomedical Engineering, Wisconsin Institutes for Medical Research, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, Wisconsin 53705-2275, USA. ; Wendt Commons Library, University of Wisconsin-Madison, 215 North Randall Avenue, Madison, Wisconsin 53706, USA. ; Department of Biomedical Engineering, Wisconsin Institutes for Medical Research, University of Wisconsin-Madison, 1111 Highland Avenue, Room 6009, Madison, Wisconsin 53705-2275, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24622198" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomedical Research/*methods/*trends ; Body Fluids/chemistry ; Cell Migration Assays ; Chemotaxis ; Diagnostic Tests, Routine ; Drug Discovery ; Humans ; *Microfluidic Analytical Techniques/instrumentation/methods/trends ; *Microfluidics/instrumentation/methods/statistics & numerical data/trends
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  • 40
    Publication Date: 2014-01-28
    Description: Citrullination is the post-translational conversion of an arginine residue within a protein to the non-coded amino acid citrulline. This modification leads to the loss of a positive charge and reduction in hydrogen-bonding ability. It is carried out by a small family of tissue-specific vertebrate enzymes called peptidylarginine deiminases (PADIs) and is associated with the development of diverse pathological states such as autoimmunity, cancer, neurodegenerative disorders, prion diseases and thrombosis. Nevertheless, the physiological functions of citrullination remain ill-defined, although citrullination of core histones has been linked to transcriptional regulation and the DNA damage response. PADI4 (also called PAD4 or PADV), the only PADI with a nuclear localization signal, was previously shown to act in myeloid cells where it mediates profound chromatin decondensation during the innate immune response to infection. Here we show that the expression and enzymatic activity of Padi4 are also induced under conditions of ground-state pluripotency and during reprogramming in mouse. Padi4 is part of the pluripotency transcriptional network, binding to regulatory elements of key stem-cell genes and activating their expression. Its inhibition lowers the percentage of pluripotent cells in the early mouse embryo and significantly reduces reprogramming efficiency. Using an unbiased proteomic approach we identify linker histone H1 variants, which are involved in the generation of compact chromatin, as novel PADI4 substrates. Citrullination of a single arginine residue within the DNA-binding site of H1 results in its displacement from chromatin and global chromatin decondensation. Together, these results uncover a role for citrullination in the regulation of pluripotency and provide new mechanistic insights into how citrullination regulates chromatin compaction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Christophorou, Maria A -- Castelo-Branco, Goncalo -- Halley-Stott, Richard P -- Oliveira, Clara Slade -- Loos, Remco -- Radzisheuskaya, Aliaksandra -- Mowen, Kerri A -- Bertone, Paul -- Silva, Jose C R -- Zernicka-Goetz, Magdalena -- Nielsen, Michael L -- Gurdon, John B -- Kouzarides, Tony -- 092096/Wellcome Trust/United Kingdom -- 101050/Wellcome Trust/United Kingdom -- 101861/Wellcome Trust/United Kingdom -- AI099728/AI/NIAID NIH HHS/ -- G1001690/Medical Research Council/United Kingdom -- Cancer Research UK/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2014 Mar 6;507(7490):104-8. doi: 10.1038/nature12942. Epub 2014 Jan 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [2]. ; 1] The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [2] Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden [3]. ; 1] The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [2] Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. ; 1] The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [2] EMBRAPA Dairy Cattle Research Center, Juiz de Fora, Brazil [3] Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. ; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK. ; 1] Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK [2] Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK. ; Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA. ; 1] European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK [2] Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK [3] Genome Biology and Developmental Biology Units, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. ; 1] The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [2] Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. ; Department of proteomics, The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health Sciences, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark. ; 1] The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [2] Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24463520" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arginine/chemistry/metabolism ; Binding Sites ; Cellular Reprogramming/genetics ; Chromatin/chemistry/*metabolism ; *Chromatin Assembly and Disassembly ; Citrulline/*metabolism ; DNA/metabolism ; Embryo, Mammalian/cytology/metabolism ; Gene Expression Regulation ; Histones/*chemistry/*metabolism ; Hydrolases/metabolism ; Mice ; Pluripotent Stem Cells/cytology/*metabolism ; Protein Binding ; *Protein Processing, Post-Translational ; Proteomics ; Substrate Specificity ; Transcription, Genetic
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  • 41
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    Nature Publishing Group (NPG)
    Publication Date: 2014-08-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fox, Douglas -- England -- Nature. 2014 Aug 21;512(7514):244-6. doi: 10.1038/512244a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25143097" target="_blank"〉PubMed〈/a〉
    Keywords: Ammonium Compounds/metabolism ; Animals ; Antarctic Regions ; Darkness ; *Ecosystem ; Hydrothermal Vents/microbiology ; *Ice Cover ; Lakes/*microbiology ; *Life ; Oceans and Seas ; Seawater/chemistry
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  • 42
    Publication Date: 2014-04-18
    Description: Reactive oxygen species (ROS) produced by phagocytes are essential for host defence against bacterial and fungal infections. Individuals with defective ROS production machinery develop chronic granulomatous disease. Conversely, excessive ROS can cause collateral tissue damage during inflammatory processes and therefore needs to be tightly regulated. Here we describe a protein, we termed negative regulator of ROS (NRROS), which limits ROS generation by phagocytes during inflammatory responses. NRROS expression in phagocytes can be repressed by inflammatory signals. NRROS-deficient phagocytes produce increased ROS upon inflammatory challenges, and mice lacking NRROS in their phagocytes show enhanced bactericidal activity against Escherichia coli and Listeria monocytogenes. Conversely, these mice develop severe experimental autoimmune encephalomyelitis owing to oxidative tissue damage in the central nervous system. Mechanistically, NRROS is localized to the endoplasmic reticulum, where it directly interacts with nascent NOX2 (also known as gp91(phox) and encoded by Cybb) monomer, one of the membrane-bound subunits of the NADPH oxidase complex, and facilitates the degradation of NOX2 through the endoplasmic-reticulum-associated degradation pathway. Thus, NRROS provides a hitherto undefined mechanism for regulating ROS production--one that enables phagocytes to produce higher amounts of ROS, if required to control invading pathogens, while minimizing unwanted collateral tissue damage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Noubade, Rajkumar -- Wong, Kit -- Ota, Naruhisa -- Rutz, Sascha -- Eidenschenk, Celine -- Valdez, Patricia A -- Ding, Jiabing -- Peng, Ivan -- Sebrell, Andrew -- Caplazi, Patrick -- DeVoss, Jason -- Soriano, Robert H -- Sai, Tao -- Lu, Rongze -- Modrusan, Zora -- Hackney, Jason -- Ouyang, Wenjun -- England -- Nature. 2014 May 8;509(7499):235-9. doi: 10.1038/nature13152. Epub 2014 Apr 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA [2] Flexus Biosciences, 75 Shoreway Road, Suite D, San Carlos, California 94070, USA (R.N.); American Society for Biochemistry and Molecular Biology, 11200 Rockville Pike, Suite 302, Rockville, Maryland 20852, USA (P.A.V.). ; Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Antibody Engineering, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Pathology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Bioinformatics, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24739962" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autoimmunity/genetics ; Bone Marrow Cells/cytology ; Central Nervous System/metabolism/pathology ; Encephalomyelitis, Autoimmune, Experimental/*immunology/*metabolism/pathology ; Endoplasmic Reticulum/enzymology/metabolism ; Escherichia coli/*immunology ; Female ; Inflammation/immunology/metabolism/pathology ; Listeria monocytogenes/*immunology ; Macrophages/cytology/enzymology/immunology/metabolism ; Male ; Mice ; NADPH Oxidase/metabolism ; Oxidation-Reduction ; Oxidative Stress ; Phagocytes/cytology/immunology/metabolism ; Proteins/genetics/*metabolism ; Reactive Oxygen Species/*antagonists & inhibitors/metabolism
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  • 43
    Publication Date: 2014-03-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Loehlin, David W -- Carroll, Sean B -- England -- Nature. 2014 Mar 13;507(7491):172-3. doi: 10.1038/nature13066. Epub 2014 Mar 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Laboratory of Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24598543" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Butterflies/*genetics/*physiology ; *DNA-Binding Proteins ; *Drosophila Proteins ; Female ; *Genes, Insect ; Male ; Molecular Mimicry/*genetics ; *Sex Characteristics
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  • 44
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    Nature Publishing Group (NPG)
    Publication Date: 2014-04-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tollefson, Jeff -- England -- Nature. 2014 Apr 17;508(7496):302-4. doi: 10.1038/508302a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24740049" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Birds ; Ecology ; *Electric Power Supplies/adverse effects/economics ; Electricity ; Internationality ; *Oceans and Seas ; *Water Movements ; Whale, Killer
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