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  • History, 20th Century  (77)
  • Mice, Inbred C57BL  (73)
  • Nature Publishing Group (NPG)  (150)
  • MDPI Publishing
  • 2010-2014  (150)
  • 2012  (150)
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  • 2010-2014  (150)
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  • 1
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    Myocardial infarction accelerates atherosclerosis (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-07-06
    Description: During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaques in the arterial wall and cause their rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. Here we show that the systemic response to ischaemic injury aggravates chronic atherosclerosis. After myocardial infarction or stroke, Apoe-/- mice developed larger atherosclerotic lesions with a more advanced morphology. This disease acceleration persisted over many weeks and was associated with markedly increased monocyte recruitment. Seeking the source of surplus monocytes in plaques, we found that myocardial infarction liberated haematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signalling. The progenitors then seeded the spleen, yielding a sustained boost in monocyte production. These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401326/" 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/PMC3401326/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dutta, Partha -- Courties, Gabriel -- Wei, Ying -- Leuschner, Florian -- Gorbatov, Rostic -- Robbins, Clinton S -- Iwamoto, Yoshiko -- Thompson, Brian -- Carlson, Alicia L -- Heidt, Timo -- Majmudar, Maulik D -- Lasitschka, Felix -- Etzrodt, Martin -- Waterman, Peter -- Waring, Michael T -- Chicoine, Adam T -- van der Laan, Anja M -- Niessen, Hans W M -- Piek, Jan J -- Rubin, Barry B -- Butany, Jagdish -- Stone, James R -- Katus, Hugo A -- Murphy, Sabina A -- Morrow, David A -- Sabatine, Marc S -- Vinegoni, Claudio -- Moskowitz, Michael A -- Pittet, Mikael J -- Libby, Peter -- Lin, Charles P -- Swirski, Filip K -- Weissleder, Ralph -- Nahrendorf, Matthias -- P50-CA086355/CA/NCI NIH HHS/ -- R01 AI084880/AI/NIAID NIH HHS/ -- R01 EB006432/EB/NIBIB NIH HHS/ -- R01 HL095612/HL/NHLBI NIH HHS/ -- R01 HL095629/HL/NHLBI NIH HHS/ -- R01 HL096576/HL/NHLBI NIH HHS/ -- R01-EB006432/EB/NIBIB NIH HHS/ -- R01-HL095629/HL/NHLBI NIH HHS/ -- R01-HL096576/HL/NHLBI NIH HHS/ -- T32 CA079443/CA/NCI NIH HHS/ -- T32-CA79443/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Jul 19;487(7407):325-9. doi: 10.1038/nature11260.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22763456" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apolipoproteins E/genetics ; Atherosclerosis/*etiology/*pathology ; Hematopoietic Stem Cells/cytology ; Inflammation/complications ; Mice ; Mice, Inbred C57BL ; Monocytes/cytology ; Myocardial Infarction/*complications/*pathology ; Spleen/cytology ; Stem Cells/cytology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Turing centenary: The dawn of computing (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-02-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dyson, George -- England -- Nature. 2012 Feb 22;482(7386):459-60. doi: 10.1038/482459a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gdyson@ias.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22358810" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Science Disciplines/history ; Computers/*history ; History, 17th Century ; History, 20th Century ; Logic ; London ; Mathematics/history ; Research Design ; United States ; World War II
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
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    David Sayre (1924-2012) (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-04-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kirz, Janos -- Miao, Jianwei -- England -- Nature. 2012 Apr 4;484(7392):38. doi: 10.1038/484038a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stony Brook University, New York, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22481349" target="_blank"〉PubMed〈/a〉
    Keywords: Biology/history ; Crystallography, X-Ray/*history ; Great Britain ; History, 20th Century ; Physics/history ; Spouses ; United States ; X-Rays
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
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    Turing centenary: Pattern formation (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-02-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reinitz, John -- England -- Nature. 2012 Feb 22;482(7386):464. doi: 10.1038/482464a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Statistics, University of Chicago, Chicago, Illinois 60637, USA. reinitz@galton.uchicago.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22358813" target="_blank"〉PubMed〈/a〉
    Keywords: Computer Simulation ; Developmental Biology/*history ; Diffusion ; History, 19th Century ; History, 20th Century ; Models, Biological ; Morphogenesis/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
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    IFITM3 restricts the morbidity and mortality associated with influenza (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-03-27
    Description: The 2009 H1N1 influenza pandemic showed the speed with which a novel respiratory virus can spread and the ability of a generally mild infection to induce severe morbidity and mortality in a subset of the population. Recent in vitro studies show that the interferon-inducible transmembrane (IFITM) protein family members potently restrict the replication of multiple pathogenic viruses. Both the magnitude and breadth of the IFITM proteins' in vitro effects suggest that they are critical for intrinsic resistance to such viruses, including influenza viruses. Using a knockout mouse model, we now test this hypothesis directly and find that IFITM3 is essential for defending the host against influenza A virus in vivo. Mice lacking Ifitm3 display fulminant viral pneumonia when challenged with a normally low-pathogenicity influenza virus, mirroring the destruction inflicted by the highly pathogenic 1918 'Spanish' influenza. Similar increased viral replication is seen in vitro, with protection rescued by the re-introduction of Ifitm3. To test the role of IFITM3 in human influenza virus infection, we assessed the IFITM3 alleles of individuals hospitalized with seasonal or pandemic influenza H1N1/09 viruses. We find that a statistically significant number of hospitalized subjects show enrichment for a minor IFITM3 allele (SNP rs12252-C) that alters a splice acceptor site, and functional assays show the minor CC genotype IFITM3 has reduced influenza virus restriction in vitro. Together these data reveal that the action of a single intrinsic immune effector, IFITM3, profoundly alters the course of influenza virus infection in mouse and humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648786/" 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/PMC3648786/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Everitt, Aaron R -- Clare, Simon -- Pertel, Thomas -- John, Sinu P -- Wash, Rachael S -- Smith, Sarah E -- Chin, Christopher R -- Feeley, Eric M -- Sims, Jennifer S -- Adams, David J -- Wise, Helen M -- Kane, Leanne -- Goulding, David -- Digard, Paul -- Anttila, Verneri -- Baillie, J Kenneth -- Walsh, Tim S -- Hume, David A -- Palotie, Aarno -- Xue, Yali -- Colonna, Vincenza -- Tyler-Smith, Chris -- Dunning, Jake -- Gordon, Stephen B -- GenISIS Investigators -- MOSAIC Investigators -- Smyth, Rosalind L -- Openshaw, Peter J -- Dougan, Gordon -- Brass, Abraham L -- Kellam, Paul -- 090382/Wellcome Trust/United Kingdom -- 090382/Z/09/Z/Wellcome Trust/United Kingdom -- 090385/Z/09/Z/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- 13031/Cancer Research UK/United Kingdom -- DHCS/04/G121/68/Department of Health/United Kingdom -- G0600371/Medical Research Council/United Kingdom -- G0600511/Medical Research Council/United Kingdom -- G0800767/Medical Research Council/United Kingdom -- G0800777/Medical Research Council/United Kingdom -- G0802752/Medical Research Council/United Kingdom -- G0901697/Medical Research Council/United Kingdom -- G1000758/Medical Research Council/United Kingdom -- MC_G1001212/Medical Research Council/United Kingdom -- MC_U122785833/Medical Research Council/United Kingdom -- P30 DK043351/DK/NIDDK NIH HHS/ -- R01 AI091786/AI/NIAID NIH HHS/ -- R01AI091786/AI/NIAID NIH HHS/ -- Chief Scientist Office/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2012 Mar 25;484(7395):519-23. doi: 10.1038/nature10921.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22446628" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Animals ; Cytokines/immunology ; England/epidemiology ; Gene Deletion ; Humans ; Influenza A Virus, H1N1 Subtype/classification/growth & development/pathogenicity ; Influenza A Virus, H3N2 Subtype/classification/growth & development/pathogenicity ; Influenza A virus/classification/growth & development/*pathogenicity ; Influenza B virus/classification/growth & development/pathogenicity ; Influenza, Human/complications/epidemiology/mortality/virology ; Leukocytes/immunology ; Lung/pathology/virology ; Membrane Proteins/chemistry/deficiency/genetics/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Molecular Sequence Data ; Orthomyxoviridae Infections/complications/*mortality/pathology ; Pneumonia, Viral/etiology/pathology/prevention & control ; Polymorphism, Single Nucleotide/genetics ; RNA-Binding Proteins/chemistry/genetics/*metabolism ; Scotland/epidemiology ; Virus Replication
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
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    Sustained translational repression by eIF2alpha-P mediates prion neurodegeneration (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-05-25
    Description: The mechanisms leading to neuronal death in neurodegenerative disease are poorly understood. Many of these disorders, including Alzheimer's, Parkinson's and prion diseases, are associated with the accumulation of misfolded disease-specific proteins. The unfolded protein response is a protective cellular mechanism triggered by rising levels of misfolded proteins. One arm of this pathway results in the transient shutdown of protein translation, through phosphorylation of the alpha-subunit of eukaryotic translation initiation factor, eIF2. Activation of the unfolded protein response and/or increased eIF2alpha-P levels are seen in patients with Alzheimer's, Parkinson's and prion diseases, but how this links to neurodegeneration is unknown. Here we show that accumulation of prion protein during prion replication causes persistent translational repression of global protein synthesis by eIF2alpha-P, associated with synaptic failure and neuronal loss in prion-diseased mice. Further, we show that promoting translational recovery in hippocampi of prion-infected mice is neuroprotective. Overexpression of GADD34, a specific eIF2alpha-P phosphatase, as well as reduction of levels of prion protein by lentivirally mediated RNA interference, reduced eIF2alpha-P levels. As a result, both approaches restored vital translation rates during prion disease, rescuing synaptic deficits and neuronal loss, thereby significantly increasing survival. In contrast, salubrinal, an inhibitor of eIF2alpha-P dephosphorylation, increased eIF2alpha-P levels, exacerbating neurotoxicity and significantly reducing survival in prion-diseased mice. Given the prevalence of protein misfolding and activation of the unfolded protein response in several neurodegenerative diseases, our results suggest that manipulation of common pathways such as translational control, rather than disease-specific approaches, may lead to new therapies preventing synaptic failure and neuronal loss across the spectrum of these disorders.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378208/" 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/PMC3378208/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moreno, Julie A -- Radford, Helois -- Peretti, Diego -- Steinert, Joern R -- Verity, Nicholas -- Martin, Maria Guerra -- Halliday, Mark -- Morgan, Jason -- Dinsdale, David -- Ortori, Catherine A -- Barrett, David A -- Tsaytler, Pavel -- Bertolotti, Anne -- Willis, Anne E -- Bushell, Martin -- Mallucci, Giovanna R -- MC_U105185860/Medical Research Council/United Kingdom -- MC_U123160654/Medical Research Council/United Kingdom -- MC_U132692719/Medical Research Council/United Kingdom -- MC_UP_A600_1023/Medical Research Council/United Kingdom -- MC_UP_A600_1024/Medical Research Council/United Kingdom -- U.1051.02.011.00001.01 (85860)/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2012 May 6;485(7399):507-11. doi: 10.1038/nature11058.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Toxicology Unit, Hodgkin Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22622579" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Death/drug effects ; Cinnamates/pharmacology ; Eukaryotic Initiation Factor-2/analysis/*chemistry/*metabolism ; Hippocampus/cytology/metabolism/pathology ; Kaplan-Meier Estimate ; Mice ; Mice, Inbred C57BL ; Neurodegenerative Diseases/etiology/*metabolism/pathology ; Neurons/drug effects/pathology ; Neuroprotective Agents ; Phosphoproteins/analysis/*metabolism ; Phosphorylation ; PrPSc Proteins/analysis/metabolism/toxicity ; Prion Diseases/pathology ; Prions/biosynthesis/genetics/*metabolism ; *Protein Biosynthesis/drug effects ; Protein Folding/drug effects ; Protein Phosphatase 1/genetics/metabolism ; Repressor Proteins/analysis/chemistry/*metabolism ; Synapses/drug effects/metabolism/pathology ; Synaptic Transmission/drug effects ; Thiourea/analogs & derivatives/pharmacology ; Unfolded Protein Response/physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
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    The split brain: a tale of two halves (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-03-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wolman, David -- England -- Nature. 2012 Mar 14;483(7389):260-3. doi: 10.1038/483260a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22422242" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Age Factors ; Animals ; Brain/*physiology/*physiopathology/surgery ; Cohort Studies ; Corpus Callosum/physiology/physiopathology/*surgery ; Epilepsy/history/surgery ; Female ; Functional Laterality/*physiology ; History, 20th Century ; History, 21st Century ; Humans ; Magnetic Resonance Imaging ; Male ; Morals ; Neurosciences/*history ; Seizures/history/surgery
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
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    Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-06-16
    Description: Autism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants. Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses, and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disability. Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics, further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant (Shank2(-/-)) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-D-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with D-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in Shank2(-/-) mice. Furthermore, treatment of Shank2(-/-) mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation, also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in Shank2(-/-) mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Won, Hyejung -- Lee, Hye-Ryeon -- Gee, Heon Yung -- Mah, Won -- Kim, Jae-Ick -- Lee, Jiseok -- Ha, Seungmin -- Chung, Changuk -- Jung, Eun Suk -- Cho, Yi Sul -- Park, Sae-Geun -- Lee, Jung-Soo -- Lee, Kyungmin -- Kim, Daesoo -- Bae, Yong Chul -- Kaang, Bong-Kiun -- Lee, Min Goo -- Kim, Eunjoon -- England -- Nature. 2012 Jun 13;486(7402):261-5. doi: 10.1038/nature11208.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, KAIST, Daejeon 305-701, Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22699620" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/*genetics ; Animals ; Antimetabolites/pharmacology ; *Autistic Disorder/genetics/metabolism ; Behavior, Animal/*drug effects/physiology ; Benzamides/*pharmacology ; Cycloserine/*pharmacology ; Disease Models, Animal ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins/*genetics ; Pyrazoles/*pharmacology ; Receptors, N-Methyl-D-Aspartate/*agonists/*metabolism
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  • 9
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    The aged niche disrupts muscle stem cell quiescence (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-10-02
    Description: The niche is a conserved regulator of stem cell quiescence and function. During ageing, stem cell function declines. To what extent and by what means age-related changes within the niche contribute to this phenomenon are unknown. Here we demonstrate that the aged muscle stem cell niche, the muscle fibre, expresses Fgf2 under homeostatic conditions, driving a subset of satellite cells to break quiescence and lose their self-renewing capacity. We show in mice that relatively dormant aged satellite cells robustly express sprouty 1 (Spry1), an inhibitor of fibroblast growth factor (FGF) signalling. Increasing FGF signalling in aged satellite cells under homeostatic conditions by removing Spry1 results in the loss of quiescence, satellite cell depletion and diminished regenerative capacity. Conversely, reducing niche-derived FGF activity through inhibition of Fgfr1 signalling or overexpression of Spry1 in satellite cells prevents their depletion. These experiments identify an age-dependent change in the stem cell niche that directly influences stem cell quiescence and function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605795/" 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/PMC3605795/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chakkalakal, Joe V -- Jones, Kieran M -- Basson, M Albert -- Brack, Andrew S -- 091475/Wellcome Trust/United Kingdom -- BB/F017626/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- R01 AR060868/AR/NIAMS NIH HHS/ -- R01 AR061002/AR/NIAMS NIH HHS/ -- WT091475/Wellcome Trust/United Kingdom -- England -- Nature. 2012 Oct 18;490(7420):355-60. doi: 10.1038/nature11438. Epub 2012 Sep 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center of Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23023126" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Aging/*physiology ; Animals ; Cell Aging ; Cell Count ; *Cell Cycle ; Cell Differentiation ; Cyclin-Dependent Kinase Inhibitor p27/metabolism ; Fibroblast Growth Factor 2/genetics/metabolism ; Flow Cytometry ; Homeostasis ; Membrane Proteins/metabolism ; Mice ; Mice, Inbred C57BL ; Muscle Cells/*cytology ; Muscle, Skeletal/cytology ; PAX7 Transcription Factor/metabolism ; Phosphoproteins/metabolism ; Satellite Cells, Skeletal Muscle/*cytology/metabolism/transplantation ; Signal Transduction ; Stem Cell Niche/*physiology ; Time Factors
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
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    Paul Mead Doty (1920-2011) (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-01-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rice, Stuart A -- Haselkorn, Robert -- England -- Nature. 2012 Jan 18;481(7381):266. doi: 10.1038/481266a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and the James Franck Institute, University of Chicago, Illinois 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22258598" target="_blank"〉PubMed〈/a〉
    Keywords: Biochemistry/*history ; DNA/chemistry ; History, 20th Century ; History, 21st Century ; Polymers/chemistry ; Proteins/chemistry ; United States
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 11
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    Increase in observed net carbon dioxide uptake by land and oceans during the past 50 years (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-08-04
    Description: One of the greatest sources of uncertainty for future climate predictions is the response of the global carbon cycle to climate change. Although approximately one-half of total CO(2) emissions is at present taken up by combined land and ocean carbon reservoirs, models predict a decline in future carbon uptake by these reservoirs, resulting in a positive carbon-climate feedback. Several recent studies suggest that rates of carbon uptake by the land and ocean have remained constant or declined in recent decades. Other work, however, has called into question the reported decline. Here we use global-scale atmospheric CO(2) measurements, CO(2) emission inventories and their full range of uncertainties to calculate changes in global CO(2) sources and sinks during the past 50 years. Our mass balance analysis shows that net global carbon uptake has increased significantly by about 0.05 billion tonnes of carbon per year and that global carbon uptake doubled, from 2.4 +/- 0.8 to 5.0 +/- 0.9 billion tonnes per year, between 1960 and 2010. Therefore, it is very unlikely that both land and ocean carbon sinks have decreased on a global scale. Since 1959, approximately 350 billion tonnes of carbon have been emitted by humans to the atmosphere, of which about 55 per cent has moved into the land and oceans. Thus, identifying the mechanisms and locations responsible for increasing global carbon uptake remains a critical challenge in constraining the modern global carbon budget and predicting future carbon-climate interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ballantyne, A P -- Alden, C B -- Miller, J B -- Tans, P P -- White, J W C -- England -- Nature. 2012 Aug 2;488(7409):70-2. doi: 10.1038/nature11299.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geology, University of Colorado, Boulder, Colorado 80309, USA. apballantyne@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22859203" target="_blank"〉PubMed〈/a〉
    Keywords: Atmosphere/*chemistry ; Carbon/analysis ; Carbon Dioxide/*analysis/history ; *Carbon Sequestration ; Climate Change/*statistics & numerical data ; History, 20th Century ; History, 21st Century ; Human Activities ; Models, Theoretical ; Oceans and Seas ; Seawater/*chemistry ; Time Factors ; Uncertainty
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    Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation (2012)
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    Publication Date: 2012-10-12
    Description: Adoptive cell transfer therapies (ACTs) with cytotoxic T cells that target melanocytic antigens can achieve remissions in patients with metastatic melanomas, but tumours frequently relapse. Hypotheses explaining the acquired resistance to ACTs include the selection of antigen-deficient tumour cell variants and the induction of T-cell tolerance. However, the lack of appropriate experimental melanoma models has so far impeded clear insights into the underlying mechanisms. Here we establish an effective ACT protocol in a genetically engineered mouse melanoma model that recapitulates tumour regression, remission and relapse as seen in patients. We report the unexpected observation that melanomas acquire ACT resistance through an inflammation-induced reversible loss of melanocytic antigens. In serial transplantation experiments, melanoma cells switch between a differentiated and a dedifferentiated phenotype in response to T-cell-driven inflammatory stimuli. We identified the proinflammatory cytokine tumour necrosis factor (TNF)-alpha as a crucial factor that directly caused reversible dedifferentiation of mouse and human melanoma cells. Tumour cells exposed to TNF-alpha were poorly recognized by T cells specific for melanocytic antigens, whereas recognition by T cells specific for non-melanocytic antigens was unaffected or even increased. Our results demonstrate that the phenotypic plasticity of melanoma cells in an inflammatory microenvironment contributes to tumour relapse after initially successful T-cell immunotherapy. On the basis of our work, we propose that future ACT protocols should simultaneously target melanocytic and non-melanocytic antigens to ensure broad recognition of both differentiated and dedifferentiated melanoma cells, and include strategies to sustain T-cell effector functions by blocking immune-inhibitory mechanisms in the tumour microenvironment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Landsberg, Jennifer -- Kohlmeyer, Judith -- Renn, Marcel -- Bald, Tobias -- Rogava, Meri -- Cron, Mira -- Fatho, Martina -- Lennerz, Volker -- Wolfel, Thomas -- Holzel, Michael -- Tuting, Thomas -- England -- Nature. 2012 Oct 18;490(7420):412-6. doi: 10.1038/nature11538. Epub 2012 Oct 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Experimental Dermatology, Department of Dermatology and Allergy, University of Bonn, D-53105 Bonn, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23051752" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Animals ; *Cell Dedifferentiation ; Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Disease Models, Animal ; Humans ; *Immunotherapy ; Inflammation/immunology/*pathology ; Melanoma/immunology/metabolism/*pathology/*therapy ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; T-Lymphocytes, Cytotoxic/*immunology/*transplantation ; Tumor Microenvironment/immunology ; Tumor Necrosis Factor-alpha/immunology/pharmacology ; gp100 Melanoma Antigen/metabolism
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    Nonlinear dendritic integration of sensory and motor input during an active sensing task (2012)
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    Publication Date: 2012-11-13
    Description: Active dendrites provide neurons with powerful processing capabilities. However, little is known about the role of neuronal dendrites in behaviourally related circuit computations. Here we report that a novel global dendritic nonlinearity is involved in the integration of sensory and motor information within layer 5 pyramidal neurons during an active sensing behaviour. Layer 5 pyramidal neurons possess elaborate dendritic arborizations that receive functionally distinct inputs, each targeted to spatially separate regions. At the cellular level, coincident input from these segregated pathways initiates regenerative dendritic electrical events that produce bursts of action potential output and circuits featuring this powerful dendritic nonlinearity can implement computations based on input correlation. To examine this in vivo we recorded dendritic activity in layer 5 pyramidal neurons in the barrel cortex using two-photon calcium imaging in mice performing an object-localization task. Large-amplitude, global calcium signals were observed throughout the apical tuft dendrites when active touch occurred at particular object locations or whisker angles. Such global calcium signals are produced by dendritic plateau potentials that require both vibrissal sensory input and primary motor cortex activity. These data provide direct evidence of nonlinear dendritic processing of correlated sensory and motor information in the mammalian neocortex during active sensation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Ning-long -- Harnett, Mark T -- Williams, Stephen R -- Huber, Daniel -- O'Connor, Daniel H -- Svoboda, Karel -- Magee, Jeffrey C -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Dec 13;492(7428):247-51. doi: 10.1038/nature11601. Epub 2012 Nov 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, Virginia 20147, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23143335" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/*physiology ; Calcium/metabolism ; Dendrites/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity/*physiology ; Patch-Clamp Techniques ; Pyramidal Cells/physiology ; Sensation/*physiology ; Signal Transduction
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    NOBEL 2012 Physiology or medicine: Mature cells can be rejuvenated (2012)
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    Publication Date: 2012-12-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rossant, Janet -- Mummery, Christine -- England -- Nature. 2012 Dec 6;492(7427):56. doi: 10.1038/492056a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23222608" target="_blank"〉PubMed〈/a〉
    Keywords: Adult Stem Cells/*cytology ; Animals ; *Cellular Reprogramming ; Cloning, Organism/*history ; History, 20th Century ; History, 21st Century ; Humans ; *Medicine ; *Nobel Prize ; *Nuclear Transfer Techniques ; *Physiology ; Rejuvenation ; Sheep
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    NOBEL 2012 Chemistry: Studies of a ubiquitous receptor family (2012)
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    Publication Date: 2012-12-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roth, Bryan L -- Marshall, Fiona H -- England -- Nature. 2012 Dec 6;492(7427):57. doi: 10.1038/492057a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23222609" target="_blank"〉PubMed〈/a〉
    Keywords: Biochemistry/history ; *Chemistry/history ; Drug Discovery/history ; High-Throughput Screening Assays/history ; History, 20th Century ; History, 21st Century ; Humans ; *Nobel Prize ; Receptors, G-Protein-Coupled/genetics/isolation & purification/*metabolism ; Structure-Activity Relationship
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    Atmospheric CO2 forces abrupt vegetation shifts locally, but not globally (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-07-06
    Description: It is possible that anthropogenic climate change will drive the Earth system into a qualitatively different state. Although different types of uncertainty limit our capacity to assess this risk, Earth system scientists are particularly concerned about tipping elements, large-scale components of the Earth system that can be switched into qualitatively different states by small perturbations. Despite growing evidence that tipping elements exist in the climate system, whether large-scale vegetation systems can tip into alternative states is poorly understood. Here we show that tropical grassland, savanna and forest ecosystems, areas large enough to have powerful impacts on the Earth system, are likely to shift to alternative states. Specifically, we show that increasing atmospheric CO2 concentration will force transitions to vegetation states characterized by higher biomass and/or woody-plant dominance. The timing of these critical transitions varies as a result of between-site variance in the rate of temperature increase, as well as a dependence on stochastic variation in fire severity and rainfall. We further show that the locations of bistable vegetation zones (zones where alternative vegetation states can exist) will shift as climate changes. We conclude that even though large-scale directional regime shifts in terrestrial ecosystems are likely, asynchrony in the timing of these shifts may serve to dampen, but not nullify, the shock that these changes may represent to the Earth system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Higgins, Steven I -- Scheiter, Simon -- England -- Nature. 2012 Aug 9;488(7410):209-12. doi: 10.1038/nature11238.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Physische Geographie, Goethe Universitat Frankfurt am Main, 60438 Frankfurt am Main, Germany. higgins@em.uni-frankfurt.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22763447" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Atmosphere/*chemistry ; Biomass ; Carbon/metabolism ; Carbon Dioxide/analysis/*metabolism ; Climate Change/*statistics & numerical data ; *Ecosystem ; Fires ; Geography ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Hot Temperature ; Models, Biological ; Photosynthesis/physiology ; Poaceae/growth & development/metabolism ; Probability ; Rain ; Stochastic Processes ; Time Factors ; Trees/*growth & development/metabolism ; Wood
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    Science in the developing world: Eritrea's shattered science (2012)
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    Publication Date: 2012-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barley, Shanta -- England -- Nature. 2012 Nov 1;491(7422):24-6. doi: 10.1038/491024a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23128207" target="_blank"〉PubMed〈/a〉
    Keywords: *Developed Countries ; Eritrea ; *Federal Government ; History, 20th Century ; History, 21st Century ; Hospitals/statistics & numerical data ; Human Rights/statistics & numerical data ; Humans ; *International Cooperation ; Medicine/*organization & administration ; Missouri ; Physicians/supply & distribution ; Public Health/statistics & numerical data ; Schools, Medical/history/manpower/organization & administration ; Science/manpower/*organization & administration
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    Resurrection of endogenous retroviruses in antibody-deficient mice (2012)
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    Publication Date: 2012-10-30
    Description: The mammalian host has developed a long-standing symbiotic relationship with a considerable number of microbial species. These include the microbiota on environmental surfaces, such as the respiratory and gastrointestinal tracts, and also endogenous retroviruses (ERVs), comprising a substantial fraction of the mammalian genome. The long-term consequences for the host of interactions with these microbial species can range from mutualism to parasitism and are not always completely understood. The potential effect of one microbial symbiont on another is even less clear. Here we study the control of ERVs in the commonly used C57BL/6 (B6) mouse strain, which lacks endogenous murine leukaemia viruses (MLVs) able to replicate in murine cells. We demonstrate the spontaneous emergence of fully infectious ecotropic MLV in B6 mice with a range of distinct immune deficiencies affecting antibody production. These recombinant retroviruses establish infection of immunodeficient mouse colonies, and ultimately result in retrovirus-induced lymphomas. Notably, ERV activation in immunodeficient mice is prevented in husbandry conditions associated with reduced or absent intestinal microbiota. Our results shed light onto a previously unappreciated role for immunity in the control of ERVs and provide a potential mechanistic link between immune activation by microbial triggers and a range of pathologies associated with ERVs, including cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511586/" 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/PMC3511586/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Young, George R -- Eksmond, Urszula -- Salcedo, Rosalba -- Alexopoulou, Lena -- Stoye, Jonathan P -- Kassiotis, George -- MC_U117512710/Medical Research Council/United Kingdom -- MC_U117581330/Medical Research Council/United Kingdom -- U.1175.02.005.00005(60891)/Medical Research Council/United Kingdom -- U.1175.02.006.00007(81330)/Medical Research Council/United Kingdom -- U117512710/Medical Research Council/United Kingdom -- U117581330/Medical Research Council/United Kingdom -- England -- Nature. 2012 Nov 29;491(7426):774-8. doi: 10.1038/nature11599. Epub 2012 Oct 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immunoregulation, MRC National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23103862" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Husbandry ; Animals ; Antibodies, Viral/*biosynthesis/immunology ; Cell Transformation, Viral ; Endogenous Retroviruses/genetics/growth & development/immunology/*physiology ; Female ; Immunocompromised Host/*immunology ; Leukemia/virology ; Leukemia Virus, Murine/genetics/growth & development/immunology/physiology ; Lymphoma/virology ; Male ; Mice ; Mice, Inbred C57BL ; Receptors, Antigen, T-Cell/deficiency/genetics ; Recombination, Genetic ; Viremia/immunology/virology ; *Virus Activation
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    PPAR-gamma is a major driver of the accumulation and phenotype of adipose tissue Treg cells (2012)
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    Publication Date: 2012-06-23
    Description: Obesity and type-2 diabetes have increased markedly over the past few decades, in parallel. One of the major links between these two disorders is chronic, low-grade inflammation. Prolonged nutrient excess promotes the accumulation and activation of leukocytes in visceral adipose tissue (VAT) and ultimately other tissues, leading to metabolic abnormalities such as insulin resistance, type-2 diabetes and fatty-liver disease. Although invasion of VAT by pro-inflammatory macrophages is considered to be a key event driving adipose-tissue inflammation and insulin resistance, little is known about the roles of other immune system cell types in these processes. A unique population of VAT-resident regulatory T (Treg) cells was recently implicated in control of the inflammatory state of adipose tissue and, thereby, insulin sensitivity. Here we identify peroxisome proliferator-activated receptor (PPAR)-gamma, the 'master regulator' of adipocyte differentiation, as a crucial molecular orchestrator of VAT Treg cell accumulation, phenotype and function. Unexpectedly, PPAR-gamma expression by VAT Treg cells was necessary for complete restoration of insulin sensitivity in obese mice by the thiazolidinedione drug pioglitazone. These findings suggest a previously unknown cellular mechanism for this important class of thiazolidinedione drugs, and provide proof-of-principle that discrete populations of Treg cells with unique functions can be precisely targeted to therapeutic ends.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387339/" 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/PMC3387339/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cipolletta, Daniela -- Feuerer, Markus -- Li, Amy -- Kamei, Nozomu -- Lee, Jongsoon -- Shoelson, Steven E -- Benoist, Christophe -- Mathis, Diane -- DK092541/DK/NIDDK NIH HHS/ -- DK51729/DK/NIDDK NIH HHS/ -- P30DK36836/DK/NIDDK NIH HHS/ -- R01 DK051729/DK/NIDDK NIH HHS/ -- R01 DK092541/DK/NIDDK NIH HHS/ -- R01 DK092541-02/DK/NIDDK NIH HHS/ -- R37 DK051729/DK/NIDDK NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Jun 28;486(7404):549-53. doi: 10.1038/nature11132.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722857" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/*cytology/immunology/pathology ; Animals ; Cell Differentiation ; Diabetes Mellitus, Type 2/drug therapy/metabolism/pathology ; Epididymis/cytology/immunology ; Forkhead Transcription Factors/metabolism ; Gene Expression ; Hypoglycemic Agents/pharmacology ; Inflammation/immunology/metabolism/pathology ; Insulin Resistance/physiology ; Lymphocyte Count ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Obesity/metabolism/pathology ; PPAR gamma/*metabolism ; Phenotype ; RNA, Messenger/genetics/metabolism ; T-Lymphocytes, Regulatory/*cytology/drug effects/*metabolism ; Thiazolidinediones/pharmacology ; Transcription, Genetic
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    Return to Rio: Second chance for the planet (2012)
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    Publication Date: 2012-06-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2012 Jun 6;486(7401):19. doi: 10.1038/486019a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22678261" target="_blank"〉PubMed〈/a〉
    Keywords: Biodiversity ; Brazil ; *Congresses as Topic/history ; *Conservation of Natural Resources/economics/history/legislation & ; jurisprudence/trends ; Developing Countries/economics ; *Environmental Policy/economics/history/legislation & jurisprudence/trends ; History, 20th Century ; History, 21st Century ; *International Cooperation/history/legislation & jurisprudence
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    Keith H. Campbell (1954-2012) (2012)
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    Publication Date: 2012-11-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Trounson, Alan -- England -- Nature. 2012 Nov 8;491(7423):193. doi: 10.1038/491193a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉California Institute for Regenerative Medicine, San Francisco, California 94107, USA. atrounson@cirm.ca.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23135461" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Awards and Prizes ; Cellular Reprogramming ; Cloning, Organism/*history ; Embryonic Stem Cells/physiology ; Female ; Great Britain ; History, 20th Century ; Induced Pluripotent Stem Cells/physiology ; Sheep ; Swine
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    Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice (2012)
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    Publication Date: 2012-07-06
    Description: Autism spectrum disorders (ASDs) are highly prevalent neurodevelopmental disorders, but the underlying pathogenesis remains poorly understood. Recent studies have implicated the cerebellum in these disorders, with post-mortem studies in ASD patients showing cerebellar Purkinje cell (PC) loss, and isolated cerebellar injury has been associated with a higher incidence of ASDs. However, the extent of cerebellar contribution to the pathogenesis of ASDs remains unclear. Tuberous sclerosis complex (TSC) is a genetic disorder with high rates of comorbid ASDs that result from mutation of either TSC1 or TSC2, whose protein products dimerize and negatively regulate mammalian target of rapamycin (mTOR) signalling. TSC is an intriguing model to investigate the cerebellar contribution to the underlying pathogenesis of ASDs, as recent studies in TSC patients demonstrate cerebellar pathology and correlate cerebellar pathology with increased ASD symptomatology. Functional imaging also shows that TSC patients with ASDs display hypermetabolism in deep cerebellar structures, compared to TSC patients without ASDs. However, the roles of Tsc1 and the sequelae of Tsc1 dysfunction in the cerebellum have not been investigated so far. Here we show that both heterozygous and homozygous loss of Tsc1 in mouse cerebellar PCs results in autistic-like behaviours, including abnormal social interaction, repetitive behaviour and vocalizations, in addition to decreased PC excitability. Treatment of mutant mice with the mTOR inhibitor, rapamycin, prevented the pathological and behavioural deficits. These findings demonstrate new roles for Tsc1 in PC function and define a molecular basis for a cerebellar contribution to cognitive disorders such as autism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615424/" 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/PMC3615424/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tsai, Peter T -- Hull, Court -- Chu, YunXiang -- Greene-Colozzi, Emily -- Sadowski, Abbey R -- Leech, Jarrett M -- Steinberg, Jason -- Crawley, Jacqueline N -- Regehr, Wade G -- Sahin, Mustafa -- K12 NS079414/NS/NINDS NIH HHS/ -- P30HD18655/HD/NICHD NIH HHS/ -- R01 NS032405/NS/NINDS NIH HHS/ -- R01NS032405/NS/NINDS NIH HHS/ -- R01NS58956/NS/NINDS NIH HHS/ -- T32 MH020017/MH/NIMH NIH HHS/ -- T32 NS007473/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2012 Aug 30;488(7413):647-51. doi: 10.1038/nature11310.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. peter.tsai@childrens.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22763451" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/complications/genetics/pathology/*physiopathology ; Behavior, Animal/drug effects ; Cell Count ; Cell Shape/drug effects ; Cerebellum/drug effects/pathology/*physiopathology ; Grooming/drug effects/physiology ; Heterozygote ; Maze Learning/drug effects/physiology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mutation/genetics ; Purkinje Cells/drug effects/*metabolism ; Rotarod Performance Test ; Sirolimus/pharmacology ; Synapses/metabolism ; TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism ; Tuberous Sclerosis/complications/genetics ; Tumor Suppressor Proteins/deficiency/*genetics/*metabolism ; Vocalization, Animal/drug effects/physiology
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    A FOXO3-IRF7 gene regulatory circuit limits inflammatory sequelae of antiviral responses (2012)
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    Publication Date: 2012-09-18
    Description: Antiviral responses must be tightly regulated to defend rapidly against infection while minimizing inflammatory damage. Type 1 interferons (IFN-I) are crucial mediators of antiviral responses and their transcription is regulated by a variety of transcription factors; principal among these is the family of interferon regulatory factors (IRFs). The IRF gene regulatory networks are complex and contain multiple feedback loops. The tools of systems biology are well suited to elucidate the complex interactions that give rise to precise coordination of the interferon response. Here we have used an unbiased systems approach to predict that a member of the forkhead family of transcription factors, FOXO3, is a negative regulator of a subset of antiviral genes. This prediction was validated using macrophages isolated from Foxo3-null mice. Genome-wide location analysis combined with gene deletion studies identified the Irf7 gene as a critical target of FOXO3. FOXO3 was identified as a negative regulator of Irf7 transcription and we have further demonstrated that FOXO3, IRF7 and IFN-I form a coherent feed-forward regulatory circuit. Our data suggest that the FOXO3-IRF7 regulatory circuit represents a novel mechanism for establishing the requisite set points in the interferon pathway that balances the beneficial effects and deleterious sequelae of the antiviral response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556990/" 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/PMC3556990/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Litvak, Vladimir -- Ratushny, Alexander V -- Lampano, Aaron E -- Schmitz, Frank -- Huang, Albert C -- Raman, Ayush -- Rust, Alistair G -- Bergthaler, Andreas -- Aitchison, John D -- Aderem, Alan -- HHSN272200700038C/AI/NIAID NIH HHS/ -- HHSN272200700038C/PHS HHS/ -- HHSN272200800058C/AI/NIAID NIH HHS/ -- HSN272200800058C/PHS HHS/ -- R01 AI025032/AI/NIAID NIH HHS/ -- R01 AI032972/AI/NIAID NIH HHS/ -- R01AI025032/AI/NIAID NIH HHS/ -- R01AI032972/AI/NIAID NIH HHS/ -- U19 AI100627/AI/NIAID NIH HHS/ -- U54 GM103511/GM/NIGMS NIH HHS/ -- U54 RR022220/RR/NCRR NIH HHS/ -- U54GM103511/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Oct 18;490(7420):421-5. doi: 10.1038/nature11428. Epub 2012 Sep 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Seattle Biomedical Research Institute, Seattle, Washington 98109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22982991" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Forkhead Transcription Factors/deficiency/genetics/*metabolism ; Gene Deletion ; Gene Expression Regulation/*immunology ; Inflammation/genetics/*immunology/*pathology ; Interferon Regulatory Factor-7/deficiency/genetics/*metabolism ; Interferon Type I/immunology ; Lung/immunology/pathology/virology ; Macrophages/immunology ; Mice ; Mice, Inbred C57BL ; Reproducibility of Results ; Vesiculovirus/*immunology
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    Novel Foxo1-dependent transcriptional programs control T(reg) cell function (2012)
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    Publication Date: 2012-11-09
    Description: Regulatory T (T(reg)) cells, characterized by expression of the transcription factor forkhead box P3 (Foxp3), maintain immune homeostasis by suppressing self-destructive immune responses. Foxp3 operates as a late-acting differentiation factor controlling T(reg) cell homeostasis and function, whereas the early T(reg)-cell-lineage commitment is regulated by the Akt kinase and the forkhead box O (Foxo) family of transcription factors. However, whether Foxo proteins act beyond the T(reg)-cell-commitment stage to control T(reg) cell homeostasis and function remains largely unexplored. Here we show that Foxo1 is a pivotal regulator of T(reg )cell function. T(reg) cells express high amounts of Foxo1 and display reduced T-cell-receptor-induced Akt activation, Foxo1 phosphorylation and Foxo1 nuclear exclusion. Mice with T(reg)-cell-specific deletion of Foxo1 develop a fatal inflammatory disorder similar in severity to that seen in Foxp3-deficient mice, but without the loss of T(reg) cells. Genome-wide analysis of Foxo1 binding sites reveals ~300 Foxo1-bound target genes, including the pro-inflammatory cytokine Ifng, that do not seem to be directly regulated by Foxp3. These findings show that the evolutionarily ancient Akt-Foxo1 signalling module controls a novel genetic program indispensable for T(reg) cell function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771531/" 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/PMC3771531/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ouyang, Weiming -- Liao, Will -- Luo, Chong T -- Yin, Na -- Huse, Morgan -- Kim, Myoungjoo V -- Peng, Min -- Chan, Pamela -- Ma, Qian -- Mo, Yifan -- Meijer, Dies -- Zhao, Keji -- Rudensky, Alexander Y -- Atwal, Gurinder -- Zhang, Michael Q -- Li, Ming O -- HG001696/HG/NHGRI NIH HHS/ -- R01 HG001696/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Nov 22;491(7425):554-9. doi: 10.1038/nature11581. Epub 2012 Nov 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23135404" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Cell Nucleus/metabolism/pathology ; Female ; Forkhead Transcription Factors/*metabolism ; Gene Expression Regulation/genetics ; Genome/genetics ; Immune Tolerance/genetics/immunology ; Interferon-gamma/deficiency/genetics ; Male ; Mice ; Mice, Inbred C57BL ; Proto-Oncogene Proteins c-akt/metabolism ; Receptors, Antigen, T-Cell/immunology/metabolism ; Signal Transduction ; T-Lymphocytes, Regulatory/*immunology/*metabolism/pathology ; *Transcription, Genetic
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    Aerosols implicated as a prime driver of twentieth-century North Atlantic climate variability (2012)
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    Publication Date: 2012-04-14
    Description: Systematic climate shifts have been linked to multidecadal variability in observed sea surface temperatures in the North Atlantic Ocean. These links are extensive, influencing a range of climate processes such as hurricane activity and African Sahel and Amazonian droughts. The variability is distinct from historical global-mean temperature changes and is commonly attributed to natural ocean oscillations. A number of studies have provided evidence that aerosols can influence long-term changes in sea surface temperatures, but climate models have so far failed to reproduce these interactions and the role of aerosols in decadal variability remains unclear. Here we use a state-of-the-art Earth system climate model to show that aerosol emissions and periods of volcanic activity explain 76 per cent of the simulated multidecadal variance in detrended 1860-2005 North Atlantic sea surface temperatures. After 1950, simulated variability is within observational estimates; our estimates for 1910-1940 capture twice the warming of previous generation models but do not explain the entire observed trend. Other processes, such as ocean circulation, may also have contributed to variability in the early twentieth century. Mechanistically, we find that inclusion of aerosol-cloud microphysical effects, which were included in few previous multimodel ensembles, dominates the magnitude (80 per cent) and the spatial pattern of the total surface aerosol forcing in the North Atlantic. Our findings suggest that anthropogenic aerosol emissions influenced a range of societally important historical climate events such as peaks in hurricane activity and Sahel drought. Decadal-scale model predictions of regional Atlantic climate will probably be improved by incorporating aerosol-cloud microphysical interactions and estimates of future concentrations of aerosols, emissions of which are directly addressable by policy actions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Booth, Ben B B -- Dunstone, Nick J -- Halloran, Paul R -- Andrews, Timothy -- Bellouin, Nicolas -- England -- Nature. 2012 Apr 4;484(7393):228-32. doi: 10.1038/nature10946.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Met Office Hadley Centre, FitzRoy Road, Exeter EX1 3PB, UK. ben.booth@metoffice.gov.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22498628" target="_blank"〉PubMed〈/a〉
    Keywords: *Aerosols ; Atlantic Ocean ; *Climate ; Droughts ; Global Warming/*statistics & numerical data ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Human Activities ; Radiation ; Seawater ; Temperature ; Volcanic Eruptions ; Water Movements
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    Nomenclature: English not Latin in botanical reports (2012)
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    Publication Date: 2012-12-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Udovicic, Frank -- England -- Nature. 2012 Dec 20;492(7429):356. doi: 10.1038/492356a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23257870" target="_blank"〉PubMed〈/a〉
    Keywords: *Botany ; History, 20th Century ; History, 21st Century ; International Cooperation ; *Language/history ; Research Report/*standards ; *Terminology as Topic ; Translations
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    Multi-isotope imaging mass spectrometry reveals slow protein turnover in hair-cell stereocilia (2012)
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    Publication Date: 2012-01-17
    Description: Hair cells of the inner ear are not normally replaced during an animal's life, and must continually renew components of their various organelles. Among these are the stereocilia, each with a core of several hundred actin filaments that arise from their apical surfaces and that bear the mechanotransduction apparatus at their tips. Actin turnover in stereocilia has previously been studied by transfecting neonatal rat hair cells in culture with a beta-actin-GFP fusion, and evidence was found that actin is replaced, from the top down, in 2-3 days. Overexpression of the actin-binding protein espin causes elongation of stereocilia within 12-24 hours, also suggesting rapid regulation of stereocilia lengths. Similarly, the mechanosensory 'tip links' are replaced in 5-10 hours after cleavage in chicken and mammalian hair cells. In contrast, turnover in chick stereocilia in vivo is much slower. It might be that only certain components of stereocilia turn over quickly, that rapid turnover occurs only in neonatal animals, only in culture, or only in response to a challenge like breakage or actin overexpression. Here we quantify protein turnover by feeding animals with a (15)N-labelled precursor amino acid and using multi-isotope imaging mass spectrometry to measure appearance of new protein. Surprisingly, in adult frogs and mice and in neonatal mice, in vivo and in vitro, the stereocilia were remarkably stable, incorporating newly synthesized protein at 〈10% per day. Only stereocilia tips had rapid turnover and no treadmilling was observed. Other methods confirmed this: in hair cells expressing beta-actin-GFP we bleached fiducial lines across hair bundles, but they did not move in 6 days. When we stopped expression of beta- or gamma-actin with tamoxifen-inducible recombination, neither actin isoform left the stereocilia, except at the tips. Thus, rapid turnover in stereocilia occurs only at the tips and not by a treadmilling process.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3267870/" 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/PMC3267870/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Duan-Sun -- Piazza, Valeria -- Perrin, Benjamin J -- Rzadzinska, Agnieszka K -- Poczatek, J Collin -- Wang, Mei -- Prosser, Haydn M -- Ervasti, James M -- Corey, David P -- Lechene, Claude P -- 2P41RR0112553-12/RR/NCRR NIH HHS/ -- F32DC009539/DC/NIDCD NIH HHS/ -- P41EB001974/EB/NIBIB NIH HHS/ -- P41RR14579/RR/NCRR NIH HHS/ -- R01 AR042423/AR/NIAMS NIH HHS/ -- R01 AR042423-08/AR/NIAMS NIH HHS/ -- R01 AR049899/AR/NIAMS NIH HHS/ -- R01 DC000033/DC/NIDCD NIH HHS/ -- R01 DC002281/DC/NIDCD NIH HHS/ -- R01AR049899/AR/NIAMS NIH HHS/ -- R01D K58762/PHS HHS/ -- R01DC00033/DC/NIDCD NIH HHS/ -- R01DC02281/DC/NIDCD NIH HHS/ -- R01DC03463/DC/NIDCD NIH HHS/ -- R01DC04179/DC/NIDCD NIH HHS/ -- R01EY12963/EY/NEI NIH HHS/ -- R01GM47214/GM/NIGMS NIH HHS/ -- R37DK39773/DK/NIDDK NIH HHS/ -- WT079643/Wellcome Trust/United Kingdom -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Jan 15;481(7382):520-4. doi: 10.1038/nature10745.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22246323" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/metabolism ; Animals ; Animals, Newborn ; Bleaching Agents ; Chickens ; Epithelium/drug effects/metabolism ; Fiducial Markers ; Hair Cells, Auditory, Inner/*cytology ; Homologous Recombination/drug effects ; Mass Spectrometry/*methods ; Mice ; Mice, Inbred C57BL ; Proteins/*metabolism ; Rana catesbeiana ; Stereocilia/*metabolism ; Tamoxifen/pharmacology
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    Justice for all (2012)
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    Publication Date: 2012-04-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2012 Apr 18;484(7394):287. doi: 10.1038/484287a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22517126" target="_blank"〉PubMed〈/a〉
    Keywords: *Federal Government ; Guatemala ; History, 20th Century ; *Human Experimentation/ethics/history/legislation & jurisprudence ; Humans ; *Morals ; Survivors ; United States
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    The translational landscape of mTOR signalling steers cancer initiation and metastasis (2012)
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    Publication Date: 2012-03-01
    Description: The mammalian target of rapamycin (mTOR) kinase is a master regulator of protein synthesis that couples nutrient sensing to cell growth and cancer. However, the downstream translationally regulated nodes of gene expression that may direct cancer development are poorly characterized. Using ribosome profiling, we uncover specialized translation of the prostate cancer genome by oncogenic mTOR signalling, revealing a remarkably specific repertoire of genes involved in cell proliferation, metabolism and invasion. We extend these findings by functionally characterizing a class of translationally controlled pro-invasion messenger RNAs that we show direct prostate cancer invasion and metastasis downstream of oncogenic mTOR signalling. Furthermore, we develop a clinically relevant ATP site inhibitor of mTOR, INK128, which reprograms this gene expression signature with therapeutic benefit for prostate cancer metastasis, for which there is presently no cure. Together, these findings extend our understanding of how the 'cancerous' translation machinery steers specific cancer cell behaviours, including metastasis, and may be therapeutically targeted.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663483/" 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/PMC3663483/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hsieh, Andrew C -- Liu, Yi -- Edlind, Merritt P -- Ingolia, Nicholas T -- Janes, Matthew R -- Sher, Annie -- Shi, Evan Y -- Stumpf, Craig R -- Christensen, Carly -- Bonham, Michael J -- Wang, Shunyou -- Ren, Pingda -- Martin, Michael -- Jessen, Katti -- Feldman, Morris E -- Weissman, Jonathan S -- Shokat, Kevan M -- Rommel, Christian -- Ruggero, Davide -- R01 CA140456/CA/NCI NIH HHS/ -- R01 CA154916/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Feb 22;485(7396):55-61. doi: 10.1038/nature10912.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Medicine and Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22367541" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Benzoxazoles/pharmacology ; Cell Line, Tumor ; Cell Movement/drug effects/genetics ; Eukaryotic Initiation Factor-4E/metabolism ; Eukaryotic Initiation Factors/metabolism ; Gene Expression Regulation, Neoplastic/drug effects/genetics ; Genome/genetics ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasm Invasiveness/genetics ; *Neoplasm Metastasis/drug therapy/genetics ; Phosphoproteins/metabolism ; Prostatic Neoplasms/drug therapy/genetics/*pathology ; *Protein Biosynthesis ; Pyrimidines/pharmacology ; RNA, Messenger/genetics/metabolism ; Repressor Proteins/metabolism ; *Signal Transduction ; TOR Serine-Threonine Kinases/antagonists & inhibitors/*metabolism
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    Automated design of ligands to polypharmacological profiles (2012)
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    Publication Date: 2012-12-14
    Description: The clinical efficacy and safety of a drug is determined by its activity profile across many proteins in the proteome. However, designing drugs with a specific multi-target profile is both complex and difficult. Therefore methods to design drugs rationally a priori against profiles of several proteins would have immense value in drug discovery. Here we describe a new approach for the automated design of ligands against profiles of multiple drug targets. The method is demonstrated by the evolution of an approved acetylcholinesterase inhibitor drug into brain-penetrable ligands with either specific polypharmacology or exquisite selectivity profiles for G-protein-coupled receptors. Overall, 800 ligand-target predictions of prospectively designed ligands were tested experimentally, of which 75% were confirmed to be correct. We also demonstrate target engagement in vivo. The approach can be a useful source of drug leads when multi-target profiles are required to achieve either selectivity over other drug targets or a desired polypharmacology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653568/" 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/PMC3653568/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Besnard, Jeremy -- Ruda, Gian Filippo -- Setola, Vincent -- Abecassis, Keren -- Rodriguiz, Ramona M -- Huang, Xi-Ping -- Norval, Suzanne -- Sassano, Maria F -- Shin, Antony I -- Webster, Lauren A -- Simeons, Frederick R C -- Stojanovski, Laste -- Prat, Annik -- Seidah, Nabil G -- Constam, Daniel B -- Bickerton, G Richard -- Read, Kevin D -- Wetsel, William C -- Gilbert, Ian H -- Roth, Bryan L -- Hopkins, Andrew L -- 083481/Wellcome Trust/United Kingdom -- BB/FOF/PF/15/09/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/J010510/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- MH082441/MH/NIMH NIH HHS/ -- R01 DA017204/DA/NIDA NIH HHS/ -- R01 MH061887/MH/NIMH NIH HHS/ -- U19 MH082441/MH/NIMH NIH HHS/ -- WT 083481/Wellcome Trust/United Kingdom -- England -- Nature. 2012 Dec 13;492(7428):215-20. doi: 10.1038/nature11691.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23235874" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Automation ; Drug Delivery Systems ; *Drug Design ; Female ; *Ligands ; Male ; Mice ; Mice, Inbred C57BL ; Models, Theoretical ; Pharmacological Phenomena ; Reproducibility of Results
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    Turing centenary: The incomputable reality (2012)
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    Publication Date: 2012-02-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cooper, Barry -- England -- Nature. 2012 Feb 22;482(7386):465. doi: 10.1038/482465a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Mathematics, University of Leeds, Leeds LS2 9JT, UK. pmt6sbc@leeds.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22358814" target="_blank"〉PubMed〈/a〉
    Keywords: *Algorithms ; Animals ; Artificial Intelligence ; Brain/physiology ; *Computer Simulation ; Computers/history ; History, 20th Century ; Humans ; Mathematics/history ; Morphogenesis ; Quantum Theory/history
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    Elinor Ostrom (1933-2012) (2012)
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    Publication Date: 2012-07-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Janssen, Marco A -- England -- Nature. 2012 Jul 11;487(7406):172. doi: 10.1038/487172a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Human Evolution and Social Change, Arizona State University, Tempe, Arizona 85287, USA. marco.janssen@asu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22785305" target="_blank"〉PubMed〈/a〉
    Keywords: California ; *Economics ; History, 20th Century ; Interdisciplinary Studies ; Interpersonal Relations ; Nobel Prize ; Social Control, Informal ; *Social Sciences
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    Novel role of PKR in inflammasome activation and HMGB1 release (2012)
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    Publication Date: 2012-07-18
    Description: The inflammasome regulates the release of caspase activation-dependent cytokines, including interleukin (IL)-1beta, IL-18 and high-mobility group box 1 (HMGB1). By studying HMGB1 release mechanisms, here we identify a role for double-stranded RNA-dependent protein kinase (PKR, also known as EIF2AK2) in inflammasome activation. Exposure of macrophages to inflammasome agonists induced PKR autophosphorylation. PKR inactivation by genetic deletion or pharmacological inhibition severely impaired inflammasome activation in response to double-stranded RNA, ATP, monosodium urate, adjuvant aluminium, rotenone, live Escherichia coli, anthrax lethal toxin, DNA transfection and Salmonella typhimurium infection. PKR deficiency significantly inhibited the secretion of IL-1beta, IL-18 and HMGB1 in E. coli-induced peritonitis. PKR physically interacts with several inflammasome components, including NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3), NLRP1, NLR family CARD domain-containing protein 4 (NLRC4), absent in melanoma 2 (AIM2), and broadly regulates inflammasome activation. PKR autophosphorylation in a cell-free system with recombinant NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC, also known as PYCARD) and pro-caspase-1 reconstitutes inflammasome activity. These results show a crucial role for PKR in inflammasome activation, and indicate that it should be possible to pharmacologically target this molecule to treat inflammation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4163918/" 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/PMC4163918/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lu, Ben -- Nakamura, Takahisa -- Inouye, Karen -- Li, Jianhua -- Tang, Yiting -- Lundback, Peter -- Valdes-Ferrer, Sergio I -- Olofsson, Peder S -- Kalb, Thomas -- Roth, Jesse -- Zou, Yongrui -- Erlandsson-Harris, Helena -- Yang, Huan -- Ting, Jenny P-Y -- Wang, Haichao -- Andersson, Ulf -- Antoine, Daniel J -- Chavan, Sangeeta S -- Hotamisligil, Gokhan S -- Tracey, Kevin J -- DK052539/DK/NIDDK NIH HHS/ -- G0700654/Medical Research Council/United Kingdom -- R01 DK052539/DK/NIDDK NIH HHS/ -- R01 GM057226/GM/NIGMS NIH HHS/ -- R01 GM062508/GM/NIGMS NIH HHS/ -- R01 GM62508/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Aug 30;488(7413):670-4. doi: 10.1038/nature11290.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, New York 11030, USA. blu@nshs.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22801494" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/metabolism ; Adenosine Triphosphate/pharmacology ; Animals ; Antigens, Bacterial/pharmacology ; Apoptosis Regulatory Proteins/metabolism ; Bacterial Toxins/pharmacology ; CARD Signaling Adaptor Proteins/metabolism ; Calcium-Binding Proteins/metabolism ; Carrier Proteins/metabolism ; Cell Line ; Cells, Cultured ; Crystallins/metabolism ; Escherichia coli/immunology/physiology ; Escherichia coli Infections/immunology/metabolism ; Female ; HMGB1 Protein/blood/*secretion ; Humans ; Inflammasomes/agonists/*metabolism ; Interleukin-18/blood ; Interleukin-1beta/blood ; Interleukin-6/analysis/blood ; Macrophages, Peritoneal/drug effects/metabolism ; Male ; Membrane Proteins/metabolism ; Mice ; Mice, Inbred C57BL ; Peritonitis/metabolism ; Phosphorylation ; RNA, Double-Stranded/immunology/pharmacology ; Rotenone/pharmacology ; Salmonella Infections/immunology/metabolism ; Salmonella typhimurium/immunology/physiology ; Transfection ; Uric Acid/pharmacology ; eIF-2 Kinase/antagonists & inhibitors/deficiency/genetics/*metabolism
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    Nobel work boosts drug development (2012)
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    Publication Date: 2012-10-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Van Noorden, Richard -- England -- Nature. 2012 Oct 18;490(7420):320. doi: 10.1038/490320a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23075956" target="_blank"〉PubMed〈/a〉
    Keywords: Arrestins/chemistry/history/metabolism ; Cell Communication ; *Drug Discovery/history ; History, 20th Century ; History, 21st Century ; *Nobel Prize ; Receptors, Adrenergic, beta-2/chemistry/history/metabolism ; Receptors, G-Protein-Coupled/antagonists & ; inhibitors/chemistry/history/*metabolism ; *Signal Transduction
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    APJ acts as a dual receptor in cardiac hypertrophy (2012)
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    Publication Date: 2012-07-20
    Description: Cardiac hypertrophy is initiated as an adaptive response to sustained overload but progresses pathologically as heart failure ensues. Here we report that genetic loss of APJ, a G-protein-coupled receptor, confers resistance to chronic pressure overload by markedly reducing myocardial hypertrophy and heart failure. In contrast, mice lacking apelin (the endogenous APJ ligand) remain sensitive, suggesting an apelin-independent function of APJ. Freshly isolated APJ-null cardiomyocytes exhibit an attenuated response to stretch, indicating that APJ is a mechanosensor. Activation of APJ by stretch increases cardiomyocyte cell size and induces molecular markers of hypertrophy. Whereas apelin stimulates APJ to activate Galphai and elicits a protective response, stretch signals in an APJ-dependent, G-protein-independent fashion to induce hypertrophy. Stretch-mediated hypertrophy is prevented by knockdown of beta-arrestins or by pharmacological doses of apelin acting through Galphai. Taken together, our data indicate that APJ is a bifunctional receptor for both mechanical stretch and the endogenous peptide apelin. By sensing the balance between these stimuli, APJ occupies a pivotal point linking sustained overload to cardiomyocyte hypertrophy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422434/" 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/PMC3422434/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scimia, Maria Cecilia -- Hurtado, Cecilia -- Ray, Saugata -- Metzler, Scott -- Wei, Ke -- Wang, Jianming -- Woods, Chris E -- Purcell, Nicole H -- Catalucci, Daniele -- Akasaka, Takeshi -- Bueno, Orlando F -- Vlasuk, George P -- Kaliman, Perla -- Bodmer, Rolf -- Smith, Layton H -- Ashley, Euan -- Mercola, Mark -- Brown, Joan Heller -- Ruiz-Lozano, Pilar -- NS05422/NS/NINDS NIH HHS/ -- P01 HL085577/HL/NHLBI NIH HHS/ -- R01 HL054732/HL/NHLBI NIH HHS/ -- R01 HL086879/HL/NHLBI NIH HHS/ -- R01HL054732/HL/NHLBI NIH HHS/ -- R01HL083463/HL/NHLBI NIH HHS/ -- R01HL086879/HL/NHLBI NIH HHS/ -- R01HL28143/HL/NHLBI NIH HHS/ -- R37 HL028143/HL/NHLBI NIH HHS/ -- R37HL059502/HL/NHLBI NIH HHS/ -- England -- Nature. 2012 Aug 16;488(7411):394-8. doi: 10.1038/nature11263.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22810587" target="_blank"〉PubMed〈/a〉
    Keywords: Adipokines ; Animals ; Aorta/pathology ; Arrestins/deficiency/genetics/metabolism ; Blood Pressure ; Cardiomegaly/*metabolism/pathology/physiopathology/prevention & control ; Female ; GTP-Binding Protein alpha Subunits, Gi-Go/metabolism ; Intercellular Signaling Peptides and ; Proteins/deficiency/genetics/metabolism/pharmacology ; Male ; Mechanoreceptors/metabolism ; Mechanotransduction, Cellular/drug effects/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myocytes, Cardiac/drug effects/pathology ; Receptors, G-Protein-Coupled/agonists/deficiency/genetics/*metabolism ; Signal Transduction/drug effects
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    Farish A. Jenkins Jr (1940-2012) (2012)
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    Publication Date: 2012-12-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shubin, Neil -- England -- Nature. 2012 Dec 6;492(7427):42. doi: 10.1038/492042a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Chicago, Chicago, Illinois 60637, USA. nshubin@uchicago.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23222601" target="_blank"〉PubMed〈/a〉
    Keywords: Anatomy/*history ; Animals ; Art ; Biological Evolution ; Expeditions/history ; Fossils ; History, 20th Century ; Mammals/anatomy & histology/physiology ; Movement ; Paleontology/*history ; United States
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    HVEM signalling at mucosal barriers provides host defence against pathogenic bacteria (2012)
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    Publication Date: 2012-07-18
    Description: The herpes virus entry mediator (HVEM), a member of the tumour-necrosis factor receptor family, has diverse functions, augmenting or inhibiting the immune response. HVEM was recently reported as a colitis risk locus in patients, and in a mouse model of colitis we demonstrated an anti-inflammatory role for HVEM, but its mechanism of action in the mucosal immune system was unknown. Here we report an important role for epithelial HVEM in innate mucosal defence against pathogenic bacteria. HVEM enhances immune responses by NF-kappaB-inducing kinase-dependent Stat3 activation, which promotes the epithelial expression of genes important for immunity. During intestinal Citrobacter rodentium infection, a mouse model for enteropathogenic Escherichia coli infection, Hvem-/- mice showed decreased Stat3 activation, impaired responses in the colon, higher bacterial burdens and increased mortality. We identified the immunoglobulin superfamily molecule CD160 (refs 7 and 8), expressed predominantly by innate-like intraepithelial lymphocytes, as the ligand engaging epithelial HVEM for host protection. Likewise, in pulmonary Streptococcus pneumoniae infection, HVEM is also required for host defence. Our results pinpoint HVEM as an important orchestrator of mucosal immunity, integrating signals from innate lymphocytes to induce optimal epithelial Stat3 activation, which indicates that targeting HVEM with agonists could improve host defence.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477500/" 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/PMC3477500/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shui, Jr-Wen -- Larange, Alexandre -- Kim, Gisen -- Vela, Jose Luis -- Zahner, Sonja -- Cheroutre, Hilde -- Kronenberg, Mitchell -- F32 AI083029/AI/NIAID NIH HHS/ -- F32 DK082249/DK/NIDDK NIH HHS/ -- F32-AI083029/AI/NIAID NIH HHS/ -- F32-DK082249/DK/NIDDK NIH HHS/ -- P01 DK046763/DK/NIDDK NIH HHS/ -- P01 DK46763/DK/NIDDK NIH HHS/ -- R01 AI050265/AI/NIAID NIH HHS/ -- R01 AI061516/AI/NIAID NIH HHS/ -- R01 AI064584/AI/NIAID NIH HHS/ -- R01-AI061516/AI/NIAID NIH HHS/ -- England -- Nature. 2012 Aug 9;488(7410):222-5. doi: 10.1038/nature11242.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22801499" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/immunology/metabolism ; Bacterial Load ; Cell Line ; Citrobacter rodentium/*immunology/*pathogenicity ; Disease Models, Animal ; Enterobacteriaceae Infections/immunology/microbiology ; Enteropathogenic Escherichia coli ; Epithelial Cells/immunology/metabolism ; Escherichia coli Infections ; GPI-Linked Proteins/immunology/metabolism ; Immunity, Mucosal/*immunology ; Intestines/immunology/microbiology ; Ligands ; Lung/immunology/microbiology ; Lymphocytes/immunology/metabolism ; Mice ; Mice, Inbred C57BL ; Mucous Membrane/*immunology/metabolism/*microbiology ; Pneumococcal Infections/immunology/microbiology ; Protein-Serine-Threonine Kinases/metabolism ; Receptors, Immunologic/immunology/metabolism ; Receptors, Tumor Necrosis Factor, Member ; 14/deficiency/genetics/immunology/*metabolism ; STAT3 Transcription Factor/metabolism ; *Signal Transduction ; Streptococcus pneumoniae/immunology ; Survival Rate
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    Retinal waves coordinate patterned activity throughout the developing visual system (2012)
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    Publication Date: 2012-10-13
    Description: The morphological and functional development of the vertebrate nervous system is initially governed by genetic factors and subsequently refined by neuronal activity. However, fundamental features of the nervous system emerge before sensory experience is possible. Thus, activity-dependent development occurring before the onset of experience must be driven by spontaneous activity, but the origin and nature of activity in vivo remains largely untested. Here we use optical methods to show in live neonatal mice that waves of spontaneous retinal activity are present and propagate throughout the entire visual system before eye opening. This patterned activity encompassed the visual field, relied on cholinergic neurotransmission, preferentially initiated in the binocular retina and exhibited spatiotemporal correlations between the two hemispheres. Retinal waves were the primary source of activity in the midbrain and primary visual cortex, but only modulated ongoing activity in secondary visual areas. Thus, spontaneous retinal activity is transmitted through the entire visual system and carries patterned information capable of guiding the activity-dependent development of complex intra- and inter-hemispheric circuits before the onset of vision.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962269/" 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/PMC3962269/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ackman, James B -- Burbridge, Timothy J -- Crair, Michael C -- P30 EY000785/EY/NEI NIH HHS/ -- R01 EY015788/EY/NEI NIH HHS/ -- R01 EY023105/EY/NEI NIH HHS/ -- T15LM070506/LM/NLM NIH HHS/ -- T32 EY017353/EY/NEI NIH HHS/ -- T32 EY022312/EY/NEI NIH HHS/ -- T32 NS007224/NS/NINDS NIH HHS/ -- T32NS007224/NS/NINDS NIH HHS/ -- England -- Nature. 2012 Oct 11;490(7419):219-25. doi: 10.1038/nature11529.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23060192" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Newborn ; Bicyclo Compounds, Heterocyclic/pharmacology ; Calcium/metabolism ; Gene Expression Regulation, Developmental/drug effects ; Mice ; Mice, Inbred C57BL ; Nicotinic Agonists/pharmacology ; Pyridines/pharmacology ; Retina/drug effects/growth & development ; Retinal Neurons/cytology/drug effects ; Visual Cortex/cytology/drug effects/*growth & development
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    Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth (2012)
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    Publication Date: 2012-10-05
    Description: Approximately 2% of colorectal cancer is linked to pre-existing inflammation known as colitis-associated cancer, but most develops in patients without underlying inflammatory bowel disease. Colorectal cancer often follows a genetic pathway whereby loss of the adenomatous polyposis coli (APC) tumour suppressor and activation of beta-catenin are followed by mutations in K-Ras, PIK3CA and TP53, as the tumour emerges and progresses. Curiously, however, 'inflammatory signature' genes characteristic of colitis-associated cancer are also upregulated in colorectal cancer. Further, like most solid tumours, colorectal cancer exhibits immune/inflammatory infiltrates, referred to as 'tumour-elicited inflammation'. Although infiltrating CD4(+) T(H)1 cells and CD8(+) cytotoxic T cells constitute a positive prognostic sign in colorectal cancer, myeloid cells and T-helper interleukin (IL)-17-producing (T(H)17) cells promote tumorigenesis, and a 'T(H)17 expression signature' in stage I/II colorectal cancer is associated with a drastic decrease in disease-free survival. Despite its pathogenic importance, the mechanisms responsible for the appearance of tumour-elicited inflammation are poorly understood. Many epithelial cancers develop proximally to microbial communities, which are physically separated from immune cells by an epithelial barrier. We investigated mechanisms responsible for tumour-elicited inflammation in a mouse model of colorectal tumorigenesis, which, like human colorectal cancer, exhibits upregulation of IL-23 and IL-17. Here we show that IL-23 signalling promotes tumour growth and progression, and development of a tumoural IL-17 response. IL-23 is mainly produced by tumour-associated myeloid cells that are likely to be activated by microbial products, which penetrate the tumours but not adjacent tissue. Both early and late colorectal neoplasms exhibit defective expression of several barrier proteins. We propose that barrier deterioration induced by colorectal-cancer-initiating genetic lesions results in adenoma invasion by microbial products that trigger tumour-elicited inflammation, which in turn drives tumour growth.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601659/" 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/PMC3601659/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grivennikov, Sergei I -- Wang, Kepeng -- Mucida, Daniel -- Stewart, C Andrew -- Schnabl, Bernd -- Jauch, Dominik -- Taniguchi, Koji -- Yu, Guann-Yi -- Osterreicher, Christoph H -- Hung, Kenneth E -- Datz, Christian -- Feng, Ying -- Fearon, Eric R -- Oukka, Mohamed -- Tessarollo, Lino -- Coppola, Vincenzo -- Yarovinsky, Felix -- Cheroutre, Hilde -- Eckmann, Lars -- Trinchieri, Giorgio -- Karin, Michael -- AI043477/AI/NIAID NIH HHS/ -- DK035108/DK/NIDDK NIH HHS/ -- DK080506/DK/NIDDK NIH HHS/ -- K08 DK081830/DK/NIDDK NIH HHS/ -- K99 DK088589/DK/NIDDK NIH HHS/ -- K99-DK088589/DK/NIDDK NIH HHS/ -- R01 AA020703/AA/NIAAA NIH HHS/ -- R01 AI043477/AI/NIAID NIH HHS/ -- R01 AI050265/AI/NIAID NIH HHS/ -- R01 CA082223/CA/NCI NIH HHS/ -- R01CA082223/CA/NCI NIH HHS/ -- England -- Nature. 2012 Nov 8;491(7423):254-8. doi: 10.1038/nature11465.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, California 92093-0723, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23034650" target="_blank"〉PubMed〈/a〉
    Keywords: Adenoma/genetics/immunology/*microbiology/*pathology ; Animals ; Bacteria/metabolism/pathogenicity ; Cell Division ; Cell Transformation, Neoplastic/*pathology ; Colitis/complications ; Colorectal Neoplasms/genetics/immunology/*microbiology/*pathology ; Disease Models, Animal ; Disease-Free Survival ; Genes, APC ; Humans ; Inflammation/genetics/immunology/microbiology/pathology ; Interleukin-17/genetics/*immunology ; Interleukin-23/deficiency/genetics/*immunology ; Mice ; Mice, Inbred C57BL ; Myeloid Cells/immunology/metabolism ; Myeloid Differentiation Factor 88/immunology/metabolism ; Signal Transduction ; Toll-Like Receptors/immunology/metabolism ; Tumor Microenvironment ; beta Catenin/metabolism
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    Turing centenary: Is the brain a good model for machine intelligence? (2012)
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    Publication Date: 2012-02-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brooks, Rodney -- Hassabis, Demis -- Bray, Dennis -- Shashua, Amnon -- England -- Nature. 2012 Feb 22;482(7386):462-3. doi: 10.1038/482462a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts Institute of Technology, USA〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22358812" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; *Artificial Intelligence ; Brain/cytology/*physiology ; Computers/history ; History, 20th Century ; Humans ; Intelligence/physiology ; *Models, Neurological ; Neurosciences/history/methods ; Time Factors
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    Quiet Texan to head science committee (2012)
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    Publication Date: 2012-12-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shen, Helen -- England -- Nature. 2012 Dec 6;492(7427):17. doi: 10.1038/492017a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23222583" target="_blank"〉PubMed〈/a〉
    Keywords: Climate Change ; *Federal Government ; History, 20th Century ; History, 21st Century ; Patents as Topic/legislation & jurisprudence ; Science/economics/*legislation & jurisprudence ; Texas ; United States ; United States Environmental Protection Agency
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    MEGF10 and MEGF11 mediate homotypic interactions required for mosaic spacing of retinal neurons (2012)
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    Publication Date: 2012-03-13
    Description: In many parts of the nervous system, neuronal somata display orderly spatial arrangements. In the retina, neurons of numerous individual subtypes form regular arrays called mosaics: they are less likely to be near neighbours of the same subtype than would occur by chance, resulting in 'exclusion zones' that separate them. Mosaic arrangements provide a mechanism to distribute each cell type evenly across the retina, ensuring that all parts of the visual field have access to a full set of processing elements. Remarkably, mosaics are independent of each other: although a neuron of one subtype is unlikely to be adjacent to another of the same subtype, there is no restriction on its spatial relationship to neighbouring neurons of other subtypes. This independence has led to the hypothesis that molecular cues expressed by specific subtypes pattern mosaics by mediating homotypic (within-subtype) short-range repulsive interactions. So far, however, no molecules have been identified that show such activity, so this hypothesis remains untested. Here we demonstrate in mouse that two related transmembrane proteins, MEGF10 and MEGF11, have critical roles in the formation of mosaics by two retinal interneuron subtypes, starburst amacrine cells and horizontal cells. MEGF10 and 11 and their invertebrate relatives Caenorhabditis elegans CED-1 and Drosophila Draper have hitherto been studied primarily as receptors necessary for engulfment of debris following apoptosis or axonal injury. Our results demonstrate that members of this gene family can also serve as subtype-specific ligands that pattern neuronal arrays.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310952/" 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/PMC3310952/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kay, Jeremy N -- Chu, Monica W -- Sanes, Joshua R -- EY022073/EY/NEI NIH HHS/ -- NS029169/NS/NINDS NIH HHS/ -- R01 EY022073/EY/NEI NIH HHS/ -- R01 NS029169/NS/NINDS NIH HHS/ -- R01 NS029169-20/NS/NINDS NIH HHS/ -- R01 NS029169-21/NS/NINDS NIH HHS/ -- R01 NS029169-22/NS/NINDS NIH HHS/ -- R37 NS029169/NS/NINDS NIH HHS/ -- England -- Nature. 2012 Mar 11;483(7390):465-9. doi: 10.1038/nature10877.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, 52 Oxford Street, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22407321" target="_blank"〉PubMed〈/a〉
    Keywords: Amacrine Cells/*cytology/metabolism ; Animals ; Cell Adhesion ; Gene Expression Regulation ; HEK293 Cells ; Humans ; Ligands ; Membrane Proteins/deficiency/genetics/*metabolism ; Mice ; Mice, Inbred C57BL ; Mutation ; Photoreceptor Cells, Vertebrate/metabolism ; Retinal Horizontal Cells/*cytology/metabolism
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    Long-term decline of global atmospheric ethane concentrations and implications for methane (2012)
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    Publication Date: 2012-08-24
    Description: After methane, ethane is the most abundant hydrocarbon in the remote atmosphere. It is a precursor to tropospheric ozone and it influences the atmosphere's oxidative capacity through its reaction with the hydroxyl radical, ethane's primary atmospheric sink. Here we present the longest continuous record of global atmospheric ethane levels. We show that global ethane emission rates decreased from 14.3 to 11.3 teragrams per year, or by 21 per cent, from 1984 to 2010. We attribute this to decreasing fugitive emissions from ethane's fossil fuel source--most probably decreased venting and flaring of natural gas in oil fields--rather than a decline in its other major sources, biofuel use and biomass burning. Ethane's major emission sources are shared with methane, and recent studies have disagreed on whether reduced fossil fuel or microbial emissions have caused methane's atmospheric growth rate to slow. Our findings suggest that reduced fugitive fossil fuel emissions account for at least 10-21 teragrams per year (30-70 per cent) of the decrease in methane's global emissions, significantly contributing to methane's slowing atmospheric growth rate since the mid-1980s.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simpson, Isobel J -- Sulbaek Andersen, Mads P -- Meinardi, Simone -- Bruhwiler, Lori -- Blake, Nicola J -- Helmig, Detlev -- Rowland, F Sherwood -- Blake, Donald R -- England -- Nature. 2012 Aug 23;488(7412):490-4. doi: 10.1038/nature11342.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of California-Irvine, Irvine, California 92697, USA. isimpson@uci.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22914166" target="_blank"〉PubMed〈/a〉
    Keywords: Atmosphere/*chemistry ; Biofuels/utilization ; Biomass ; Ethane/*analysis/*chemistry/history ; Greenhouse Effect ; History, 20th Century ; History, 21st Century ; Methane/*analysis/*chemistry/history ; Natural Gas/utilization ; Oil and Gas Fields ; Ozone/chemistry ; Wetlands
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    Computer modelling: Brain in a box (2012)
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    Publication Date: 2012-02-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Waldrop, M Mitchell -- England -- Nature. 2012 Feb 22;482(7386):456-8. doi: 10.1038/482456a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22358809" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*physiology ; Cognition/physiology ; *Computer Simulation ; European Union ; History, 20th Century ; History, 21st Century ; Humans ; Internationality ; *Models, Neurological ; Neurosciences/economics/history/trends ; Switzerland
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    An epigenetic silencing pathway controlling T helper 2 cell lineage commitment (2012)
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    Publication Date: 2012-07-06
    Description: During immune responses, naive CD4+ T cells differentiate into several T helper (TH) cell subsets under the control of lineage-specifying genes. These subsets (TH1, TH2 and TH17 cells and regulatory T cells) secrete distinct cytokines and are involved in protection against different types of infection. Epigenetic mechanisms are involved in the regulation of these developmental programs, and correlations have been drawn between the levels of particular epigenetic marks and the activity or silencing of specifying genes during differentiation. Nevertheless, the functional relevance of the epigenetic pathways involved in TH cell subset differentiation and commitment is still unclear. Here we explore the role of the SUV39H1-H3K9me3-HP1alpha silencing pathway in the control of TH2 lineage stability. This pathway involves the histone methylase SUV39H1, which participates in the trimethylation of histone H3 on lysine 9 (H3K9me3), a modification that provides binding sites for heterochromatin protein 1alpha (HP1alpha) and promotes transcriptional silencing. This pathway was initially associated with heterochromatin formation and maintenance but can also contribute to the regulation of euchromatic genes. We now propose that the SUV39H1-H3K9me3-HP1alpha pathway participates in maintaining the silencing of TH1 loci, ensuring TH2 lineage stability. In TH2 cells that are deficient in SUV39H1, the ratio between trimethylated and acetylated H3K9 is impaired, and the binding of HP1alpha at the promoters of silenced TH1 genes is reduced. Despite showing normal differentiation, both SUV39H1-deficient TH2 cells and HP1alpha-deficient TH2 cells, in contrast to wild-type cells, expressed TH1 genes when recultured under conditions that drive differentiation into TH1 cells. In a mouse model of TH2-driven allergic asthma, the chemical inhibition or loss of SUV39H1 skewed T-cell responses towards TH1 responses and decreased the lung pathology. These results establish a link between the SUV39H1-H3K9me3-HP1alpha pathway and the stability of TH2 cells, and they identify potential targets for therapeutic intervention in TH2-cell-mediated inflammatory diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Allan, Rhys S -- Zueva, Elina -- Cammas, Florence -- Schreiber, Heidi A -- Masson, Vanessa -- Belz, Gabrielle T -- Roche, Daniele -- Maison, Christele -- Quivy, Jean-Pierre -- Almouzni, Genevieve -- Amigorena, Sebastian -- England -- Nature. 2012 Jul 12;487(7406):249-53. doi: 10.1038/nature11173.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut Curie Research Center, 26 rue d'Ulm, 75248 Paris Cedex 05, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22763435" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Asthma/enzymology/immunology/pathology ; Cell Differentiation/genetics/immunology ; Cell Lineage/genetics/immunology ; Chromosomal Proteins, Non-Histone/metabolism ; Disease Models, Animal ; *Epigenesis, Genetic ; Female ; Gene Expression Regulation ; Gene Silencing ; Histones/metabolism ; Male ; Methyltransferases/deficiency/metabolism ; Mice ; Mice, Inbred C57BL ; Promoter Regions, Genetic ; Repressor Proteins/deficiency/metabolism ; Th1 Cells/metabolism ; Th2 Cells/*cytology/enzymology/*immunology
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    Visualization of splenic marginal zone B-cell shuttling and follicular B-cell egress (2012)
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    Publication Date: 2012-12-25
    Description: The splenic marginal zone is a unique microenvironment where resident immune cells are exposed to the open blood circulation. Even though it has an important role in responses against blood-borne antigens, lymphocyte migration in the marginal zone has not been intravitally visualized due to challenges associated with achieving adequate imaging depth in this abdominal organ. Here we develop a two-photon microscopy procedure to study marginal zone and follicular B-cell movement in the live mouse spleen. We show that marginal zone B cells are highly motile and exhibit long membrane extensions. Marginal zone B cells shuttle between the marginal zone and follicles with at least one-fifth of the cells exchanging between compartments per hour, a behaviour that explains their ability to deliver antigens rapidly from the open blood circulation to the secluded follicles. Follicular B cells also transit from follicles to the marginal zone, but unlike marginal zone B cells, they fail to undergo integrin-mediated adhesion, become caught in fluid flow and are carried into the red pulp. Follicular B-cell egress via the marginal zone is sphingosine-1-phosphate receptor-1 (S1PR1)-dependent. This study shows that marginal zone B cells migrate continually between marginal zone and follicles and establishes the marginal zone as a site of S1PR1-dependent B-cell exit from follicles. The results also show how adhesive differences of similar cells critically influence their behaviour in the same microenvironment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561487/" 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/PMC3561487/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arnon, Tal I -- Horton, Robert M -- Grigorova, Irina L -- Cyster, Jason G -- AI74847/AI/NIAID NIH HHS/ -- P30 DK063720/DK/NIDDK NIH HHS/ -- R01 AI074847/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Jan 31;493(7434):684-8. doi: 10.1038/nature11738. Epub 2012 Dec 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, California 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23263181" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/*cytology/drug effects/immunology ; Cell Adhesion/immunology ; Cell Movement/drug effects/immunology ; Dendritic Cells, Follicular/cytology/immunology ; Fingolimod Hydrochloride ; Immunosuppressive Agents/pharmacology ; Mice ; Mice, Inbred C57BL ; Microscopy, Confocal ; Propylene Glycols/pharmacology ; Sphingosine/analogs & derivatives/pharmacology ; Spleen/*cytology/immunology
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    Suppression of neuroinflammation by astrocytic dopamine D2 receptors via alphaB-crystallin (2012)
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    Publication Date: 2012-12-18
    Description: Chronic neuroinflammation is a common feature of the ageing brain and some neurodegenerative disorders. However, the molecular and cellular mechanisms underlying the regulation of innate immunity in the central nervous system remain elusive. Here we show that the astrocytic dopamine D2 receptor (DRD2) modulates innate immunity through alphaB-crystallin (CRYAB), which is known to suppress neuroinflammation. We demonstrate that knockout mice lacking Drd2 showed remarkable inflammatory response in multiple central nervous system regions and increased the vulnerability of nigral dopaminergic neurons to neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. Astrocytes null for Drd2 became hyper-responsive to immune stimuli with a marked reduction in the level of CRYAB. Preferential ablation of Drd2 in astrocytes robustly activated astrocytes in the substantia nigra. Gain- or loss-of-function studies showed that CRYAB is critical for DRD2-mediated modulation of innate immune response in astrocytes. Furthermore, treatment of wild-type mice with the selective DRD2 agonist quinpirole increased resistance of the nigral dopaminergic neurons to MPTP through partial suppression of inflammation. Our study indicates that astrocytic DRD2 activation normally suppresses neuroinflammation in the central nervous system through a CRYAB-dependent mechanism, and provides a new strategy for targeting the astrocyte-mediated innate immune response in the central nervous system during ageing and disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shao, Wei -- Zhang, Shu-zhen -- Tang, Mi -- Zhang, Xin-hua -- Zhou, Zheng -- Yin, Yan-qing -- Zhou, Qin-bo -- Huang, Yuan-yuan -- Liu, Ying-jun -- Wawrousek, Eric -- Chen, Teng -- Li, Sheng-bin -- Xu, Ming -- Zhou, Jiang-ning -- Hu, Gang -- Zhou, Jia-wei -- England -- Nature. 2013 Feb 7;494(7435):90-4. doi: 10.1038/nature11748. Epub 2012 Dec 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23242137" target="_blank"〉PubMed〈/a〉
    Keywords: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology ; Animals ; Astrocytes/drug effects/*immunology/*metabolism ; Dopaminergic Neurons/drug effects ; Immunity, Innate/drug effects ; Inflammation/chemically induced/genetics/*immunology/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Microglia/cytology/immunology ; Neuroprotective Agents/metabolism ; Quinpirole/pharmacology ; Receptors, Dopamine D2/agonists/deficiency/genetics/*metabolism ; Substantia Nigra/cytology/drug effects ; alpha-Crystallin B Chain/genetics/*metabolism
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    Inhibition dominates sensory responses in the awake cortex (2012)
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    Publication Date: 2012-11-23
    Description: The activity of the cerebral cortex is thought to depend on the precise relationship between synaptic excitation and inhibition. In the visual cortex, in particular, intracellular measurements have related response selectivity to coordinated increases in excitation and inhibition. These measurements, however, have all been made during anaesthesia, which strongly influences cortical state and therefore sensory processing. The synaptic activity that is evoked by visual stimulation during wakefulness is unknown. Here we measured visually evoked responses--and the underlying synaptic conductances--in the visual cortex of anaesthetized and awake mice. Under anaesthesia, responses could be elicited from a large region of visual space and were prolonged. During wakefulness, responses were more spatially selective and much briefer. Whole-cell patch-clamp recordings of synaptic conductances showed a difference in synaptic inhibition between the two conditions. Under anaesthesia, inhibition tracked excitation in amplitude and spatial selectivity. By contrast, during wakefulness, inhibition was much stronger than excitation and had extremely broad spatial selectivity. We conclude that during wakefulness, cortical responses to visual stimulation are dominated by synaptic inhibition, restricting the spatial spread and temporal persistence of neural activity. These results provide a direct glimpse of synaptic mechanisms that control sensory responses in the awake cortex.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3537822/" 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/PMC3537822/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haider, Bilal -- Hausser, Michael -- Carandini, Matteo -- 094077/Wellcome Trust/United Kingdom -- 095669/Wellcome Trust/United Kingdom -- G0800791/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2013 Jan 3;493(7430):97-100. doi: 10.1038/nature11665. Epub 2012 Nov 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK. b.haider@ucl.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23172139" target="_blank"〉PubMed〈/a〉
    Keywords: Anesthesia ; Animals ; Female ; Mice ; Mice, Inbred C57BL ; Models, Neurological ; Neural Inhibition/*physiology ; Patch-Clamp Techniques ; Photic Stimulation ; Synapses/metabolism ; Synaptic Transmission ; Time Factors ; Visual Cortex/*physiology ; Wakefulness/*physiology
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    Human cycles: History as science (2012)
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    Publication Date: 2012-08-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spinney, Laura -- England -- Nature. 2012 Aug 2;488(7409):24-6. doi: 10.1038/488024a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22859185" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Archives ; Conflict (Psychology) ; Databases, Factual ; Employment/statistics & numerical data/trends ; Epidemics/statistics & numerical data ; Food Chain ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; Humans ; *Models, Theoretical ; *Periodicity ; Politics ; Social Change/*history ; Statistics as Topic ; Violence/history/prevention & control/trends
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    Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists (2012)
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    Publication Date: 2012-03-31
    Description: Synchronizing rhythms of behaviour and metabolic processes is important for cardiovascular health and preventing metabolic diseases. The nuclear receptors REV-ERB-alpha and REV-ERB-beta have an integral role in regulating the expression of core clock proteins driving rhythms in activity and metabolism. Here we describe the identification of potent synthetic REV-ERB agonists with in vivo activity. Administration of synthetic REV-ERB ligands alters circadian behaviour and the circadian pattern of core clock gene expression in the hypothalami of mice. The circadian pattern of expression of an array of metabolic genes in the liver, skeletal muscle and adipose tissue was also altered, resulting in increased energy expenditure. Treatment of diet-induced obese mice with a REV-ERB agonist decreased obesity by reducing fat mass and markedly improving dyslipidaemia and hyperglycaemia. These results indicate that synthetic REV-ERB ligands that pharmacologically target the circadian rhythm may be beneficial in the treatment of sleep disorders as well as metabolic diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3343186/" 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/PMC3343186/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Solt, Laura A -- Wang, Yongjun -- Banerjee, Subhashis -- Hughes, Travis -- Kojetin, Douglas J -- Lundasen, Thomas -- Shin, Youseung -- Liu, Jin -- Cameron, Michael D -- Noel, Romain -- Yoo, Seung-Hee -- Takahashi, Joseph S -- Butler, Andrew A -- Kamenecka, Theodore M -- Burris, Thomas P -- DK080201/DK/NIDDK NIH HHS/ -- DK088499/DK/NIDDK NIH HHS/ -- DK089984/DK/NIDDK NIH HHS/ -- MH092769/MH/NIMH NIH HHS/ -- R01 DK073189/DK/NIDDK NIH HHS/ -- R01 DK080201/DK/NIDDK NIH HHS/ -- R01 DK080201-05/DK/NIDDK NIH HHS/ -- R01 MH092769/MH/NIMH NIH HHS/ -- R01 MH092769-02/MH/NIMH NIH HHS/ -- R01 MH093429/MH/NIMH NIH HHS/ -- R01 MH093429-01A1/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Mar 29;485(7396):62-8. doi: 10.1038/nature11030.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, Florida 33458, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22460951" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/drug effects/metabolism ; Animals ; Biological Clocks/drug effects/genetics/physiology ; Circadian Rhythm/*drug effects/genetics/*physiology ; Disease Models, Animal ; Energy Metabolism/*drug effects ; HEK293 Cells ; Humans ; Hypothalamus/drug effects/metabolism ; Liver/drug effects/metabolism ; Metabolome/drug effects ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Muscle, Skeletal/drug effects/metabolism ; Nuclear Receptor Subfamily 1, Group D, Member 1/*antagonists & ; inhibitors/metabolism ; Obesity/chemically induced/drug therapy/metabolism ; Pyrrolidines/*pharmacology ; Receptors, Cytoplasmic and Nuclear/*antagonists & inhibitors/metabolism ; Repressor Proteins/*antagonists & inhibitors/metabolism ; Thiophenes/*pharmacology
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    Nobel success: What makes a great lab? (2012)
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    Publication Date: 2012-10-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bynum, William -- England -- Nature. 2012 Oct 4;490(7418):31-2. doi: 10.1038/490031a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University College London, UK. w.bynum@ucl.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23038449" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chemistry/history ; Dogs ; England ; Genetics/history ; Germany ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Laboratories/*history/*standards/trends ; Molecular Biology/*history/standards ; New York ; *Nobel Prize ; Personality ; Physics/history ; Physiology/history ; Russia
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    Awards: Beit fellowships forge a Nobel link (2012)
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    Publication Date: 2012-10-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McMichael, Andrew -- Chantler, Cyril -- England -- Nature. 2012 Oct 25;490(7421):487. doi: 10.1038/490487c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23099395" target="_blank"〉PubMed〈/a〉
    Keywords: Awards and Prizes ; Biomedical Research/*history ; Fellowships and Scholarships/*history ; Great Britain ; History, 20th Century ; History, 21st Century ; *Nobel Prize
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    More extreme swings of the South Pacific convergence zone due to greenhouse warming (2012)
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    Publication Date: 2012-08-17
    Description: The South Pacific convergence zone (SPCZ) is the Southern Hemisphere's most expansive and persistent rain band, extending from the equatorial western Pacific Ocean southeastward towards French Polynesia. Owing to its strong rainfall gradient, a small displacement in the position of the SPCZ causes drastic changes to hydroclimatic conditions and the frequency of extreme weather events--such as droughts, floods and tropical cyclones--experienced by vulnerable island countries in the region. The SPCZ position varies from its climatological mean location with the El Nino/Southern Oscillation (ENSO), moving a few degrees northward during moderate El Nino events and southward during La Nina events. During strong El Nino events, however, the SPCZ undergoes an extreme swing--by up to ten degrees of latitude toward the Equator--and collapses to a more zonally oriented structure with commensurately severe weather impacts. Understanding changes in the characteristics of the SPCZ in a changing climate is therefore of broad scientific and socioeconomic interest. Here we present climate modelling evidence for a near doubling in the occurrences of zonal SPCZ events between the periods 1891-1990 and 1991-2090 in response to greenhouse warming, even in the absence of a consensus on how ENSO will change. We estimate the increase in zonal SPCZ events from an aggregation of the climate models in the Coupled Model Intercomparison Project phases 3 and 5 (CMIP3 and CMIP5) multi-model database that are able to simulate such events. The change is caused by a projected enhanced equatorial warming in the Pacific and may lead to more frequent occurrences of extreme events across the Pacific island nations most affected by zonal SPCZ events.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cai, Wenju -- Lengaigne, Matthieu -- Borlace, Simon -- Collins, Matthew -- Cowan, Tim -- McPhaden, Michael J -- Timmermann, Axel -- Power, Scott -- Brown, Josephine -- Menkes, Christophe -- Ngari, Arona -- Vincent, Emmanuel M -- Widlansky, Matthew J -- England -- Nature. 2012 Aug 16;488(7411):365-9. doi: 10.1038/nature11358.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CSIRO Marine and Atmospheric Research, Aspendale, Victoria 3195, Australia. wenju.cai@csiro.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22895343" target="_blank"〉PubMed〈/a〉
    Keywords: Databases, Factual ; El Nino-Southern Oscillation/history ; Global Warming/economics/history/*statistics & numerical data ; Greenhouse Effect/economics/history/*statistics & numerical data ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Models, Theoretical ; Pacific Ocean ; Rain ; Socioeconomic Factors
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    A biophysical signature of network affiliation and sensory processing in mitral cells (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-07-24
    Description: One defining characteristic of the mammalian brain is its neuronal diversity. For a given region, substructure, layer or even cell type, variability in neuronal morphology and connectivity persists. Although it is well known that such cellular properties vary considerably according to neuronal type, the substantial biophysical diversity of neurons of the same morphological class is typically averaged out and ignored. Here we show that the amplitude of hyperpolarization-evoked sag of membrane potential recorded in olfactory bulb mitral cells is an emergent, homotypic property of local networks and sensory information processing. Simultaneous whole-cell recordings from pairs of cells show that the amount of hyperpolarization-evoked sag potential and current (Ih) is stereotypic for mitral cells belonging to the same glomerular circuit. This is corroborated by a mosaic, glomerulus-based pattern of expression of the HCN2 (hyperpolarization-activated cyclic nucleotide-gated channel 2) subunit of the Ih channel. Furthermore, inter-glomerular differences in both membrane potential sag and HCN2 protein are diminished when sensory input to glomeruli is genetically and globally altered so that only one type of odorant receptor is universally expressed. Population diversity in this intrinsic property therefore reflects differential expression between local mitral cell networks processing distinct odour-related information.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442227/" 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/PMC3442227/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Angelo, Kamilla -- Rancz, Ede A -- Pimentel, Diogo -- Hundahl, Christian -- Hannibal, Jens -- Fleischmann, Alexander -- Pichler, Bruno -- Margrie, Troy W -- 085509/Wellcome Trust/United Kingdom -- MC_U117597156/Medical Research Council/United Kingdom -- MC_U1175975156/Medical Research Council/United Kingdom -- U.9500(97156)/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2012 Aug 16;488(7411):375-8. doi: 10.1038/nature11291.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22820253" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Gene Expression Profiling ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ; Ion Channels/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Models, Neurological ; Nerve Net/*physiology ; Olfactory Bulb/*cytology/*physiology ; Potassium Channels ; Receptors, Odorant/metabolism ; Smell/*physiology
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    Lunar science: Timely reminder to return to the Moon (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-10-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kring, David A -- Burns, Jack O -- Bussey, D Ben J -- England -- Nature. 2012 Oct 25;490(7421):487. doi: 10.1038/490487d.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23099396" target="_blank"〉PubMed〈/a〉
    Keywords: Astronauts/history/trends ; *Extraterrestrial Environment ; History, 20th Century ; History, 21st Century ; Mars ; Meteoroids ; Minor Planets ; *Moon ; Robotics ; Space Flight/instrumentation/*trends
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    James Crow (1916-2012) (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-01-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kondrashov, Alexey -- England -- Nature. 2012 Jan 25;481(7382):444. doi: 10.1038/481444a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, Michigan 48109, USA. kondrash@umich.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22281585" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Forensic Genetics/history ; Genetics, Population/*history ; History, 20th Century ; Humans ; Selection, Genetic ; United States
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    Targeting nuclear RNA for in vivo correction of myotonic dystrophy (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-08-04
    Description: Antisense oligonucleotides (ASOs) hold promise for gene-specific knockdown in diseases that involve RNA or protein gain-of-function effects. In the hereditary degenerative disease myotonic dystrophy type 1 (DM1), transcripts from the mutant allele contain an expanded CUG repeat and are retained in the nucleus. The mutant RNA exerts a toxic gain-of-function effect, making it an appropriate target for therapeutic ASOs. However, despite improvements in ASO chemistry and design, systemic use of ASOs is limited because uptake in many tissues, including skeletal and cardiac muscle, is not sufficient to silence target messenger RNAs. Here we show that nuclear-retained transcripts containing expanded CUG (CUG(exp)) repeats are unusually sensitive to antisense silencing. In a transgenic mouse model of DM1, systemic administration of ASOs caused a rapid knockdown of CUG(exp) RNA in skeletal muscle, correcting the physiological, histopathologic and transcriptomic features of the disease. The effect was sustained for up to 1 year after treatment was discontinued. Systemically administered ASOs were also effective for muscle knockdown of Malat1, a long non-coding RNA (lncRNA) that is retained in the nucleus. These results provide a general strategy to correct RNA gain-of-function effects and to modulate the expression of expanded repeats, lncRNAs and other transcripts with prolonged nuclear residence.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221572/" 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/PMC4221572/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wheeler, Thurman M -- Leger, Andrew J -- Pandey, Sanjay K -- MacLeod, A Robert -- Nakamori, Masayuki -- Cheng, Seng H -- Wentworth, Bruce M -- Bennett, C Frank -- Thornton, Charles A -- AR/NS48143/AR/NIAMS NIH HHS/ -- AR049077/AR/NIAMS NIH HHS/ -- K08 NS064293/NS/NINDS NIH HHS/ -- K08NS064293/NS/NINDS NIH HHS/ -- U01NS072323/NS/NINDS NIH HHS/ -- U54 NS048843/NS/NINDS NIH HHS/ -- U54NS48843/NS/NINDS NIH HHS/ -- England -- Nature. 2012 Aug 2;488(7409):111-5. doi: 10.1038/nature11362.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, University of Rochester, 601 Elmwood Avenue, Rochester, New York 14642, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22859208" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Base Sequence ; Cell Nucleus/drug effects/*genetics ; Disease Models, Animal ; Gene Knockdown Techniques ; *Gene Silencing ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred mdx ; Mice, Transgenic ; Muscle, Skeletal/drug effects/metabolism ; Myotonic Dystrophy/*genetics/pathology/physiopathology/*therapy ; Myotonin-Protein Kinase ; Oligonucleotides, Antisense/genetics/pharmacology/therapeutic use ; Protein-Serine-Threonine Kinases/genetics ; RNA/*antagonists & inhibitors/*genetics/metabolism ; RNA, Long Noncoding ; RNA, Messenger/antagonists & inhibitors/genetics/metabolism ; RNA, Untranslated/genetics ; Ribonuclease H/metabolism ; Transcriptome/drug effects/genetics ; Trinucleotide Repeat Expansion/genetics
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    Wylie Walker Vale Jr (1941-2012) (2012)
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    Publication Date: 2012-03-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Evans, Ronald -- England -- Nature. 2012 Mar 28;483(7391):542. doi: 10.1038/483542a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Salk Institute, La Jolla, California 92037, USA. evans@salk.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22460892" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Corticotropin-Releasing Hormone/chemistry/history/isolation & purification ; History, 20th Century ; History, 21st Century ; Humans ; Neuroendocrinology/*history ; Nobel Prize ; Thyrotropin-Releasing Hormone/history
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    LMB Cambridge: Bureaucracy bypass let research flourish (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-10-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wong, Min-Liang -- England -- Nature. 2012 Oct 25;490(7421):487. doi: 10.1038/490487e.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23099394" target="_blank"〉PubMed〈/a〉
    Keywords: England ; Financing, Organized ; History, 20th Century ; Laboratories/*history ; *Molecular Biology/history ; Research/economics/*organization & administration/*standards
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    An ultraviolet-radiation-independent pathway to melanoma carcinogenesis in the red hair/fair skin background (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-11-06
    Description: People with pale skin, red hair, freckles and an inability to tan--the 'red hair/fair skin' phenotype--are at highest risk of developing melanoma, compared to all other pigmentation types. Genetically, this phenotype is frequently the product of inactivating polymorphisms in the melanocortin 1 receptor (MC1R) gene. MC1R encodes a cyclic AMP-stimulating G-protein-coupled receptor that controls pigment production. Minimal receptor activity, as in red hair/fair skin polymorphisms, produces the red/yellow pheomelanin pigment, whereas increasing MC1R activity stimulates the production of black/brown eumelanin. Pheomelanin has weak shielding capacity against ultraviolet radiation relative to eumelanin, and has been shown to amplify ultraviolet-A-induced reactive oxygen species. Several observations, however, complicate the assumption that melanoma risk is completely ultraviolet-radiation-dependent. For example, unlike non-melanoma skin cancers, melanoma is not restricted to sun-exposed skin and ultraviolet radiation signature mutations are infrequently oncogenic drivers. Although linkage of melanoma risk to ultraviolet radiation exposure is beyond doubt, ultraviolet-radiation-independent events are likely to have a significant role. Here we introduce a conditional, melanocyte-targeted allele of the most common melanoma oncoprotein, BRAF(V600E), into mice carrying an inactivating mutation in the Mc1r gene (these mice have a phenotype analogous to red hair/fair skin humans). We observed a high incidence of invasive melanomas without providing additional gene aberrations or ultraviolet radiation exposure. To investigate the mechanism of ultraviolet-radiation-independent carcinogenesis, we introduced an albino allele, which ablates all pigment production on the Mc1r(e/e) background. Selective absence of pheomelanin synthesis was protective against melanoma development. In addition, normal Mc1r(e/e) mouse skin was found to have significantly greater oxidative DNA and lipid damage than albino-Mc1r(e/e) mouse skin. These data suggest that the pheomelanin pigment pathway produces ultraviolet-radiation-independent carcinogenic contributions to melanomagenesis by a mechanism of oxidative damage. Although protection from ultraviolet radiation remains important, additional strategies may be required for optimal melanoma prevention.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521494/" 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/PMC3521494/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mitra, Devarati -- Luo, Xi -- Morgan, Ann -- Wang, Jin -- Hoang, Mai P -- Lo, Jennifer -- Guerrero, Candace R -- Lennerz, Jochen K -- Mihm, Martin C -- Wargo, Jennifer A -- Robinson, Kathleen C -- Devi, Suprabha P -- Vanover, Jillian C -- D'Orazio, John A -- McMahon, Martin -- Bosenberg, Marcus W -- Haigis, Kevin M -- Haber, Daniel A -- Wang, Yinsheng -- Fisher, David E -- 5R01 AR043369-16/AR/NIAMS NIH HHS/ -- F30 ES020663-01/ES/NIEHS NIH HHS/ -- R01 AR043369/AR/NIAMS NIH HHS/ -- R01 CA101864/CA/NCI NIH HHS/ -- R01 CA129933/CA/NCI NIH HHS/ -- R01 CA131075/CA/NCI NIH HHS/ -- R01 CA176839/CA/NCI NIH HHS/ -- R01-CA101864/CA/NCI NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Nov 15;491(7424):449-53. doi: 10.1038/nature11624. Epub 2012 Oct 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23123854" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Gene Expression Regulation/drug effects ; Hair Color/*genetics ; Indoles/pharmacology ; Melanins/metabolism ; Melanoma/*genetics ; Mice ; Mice, Inbred C57BL ; Monophenol Monooxygenase/genetics ; Peroxidases/metabolism ; Protein Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins B-raf/genetics ; Receptor, Melanocortin, Type 1/genetics ; Skin Pigmentation/*genetics ; Sulfonamides/pharmacology ; Survival Analysis ; Tumor Cells, Cultured ; *Ultraviolet Rays
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    Phillip Vallentine Tobias (1925-2012) (2012)
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    Publication Date: 2012-07-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wood, Bernard -- England -- Nature. 2012 Jul 4;487(7405):40. doi: 10.1038/487040a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉George Washington University, Washington, DC 20052, USA. bernardawood@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22763546" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Fossils ; History, 20th Century ; *Hominidae/classification ; Paleontology/*history ; South Africa ; Tanzania
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    Legacy of a climate treaty: After Kyoto (2012)
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    Publication Date: 2012-11-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2012 Nov 29;491(7426):653. doi: 10.1038/491653a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23192125" target="_blank"〉PubMed〈/a〉
    Keywords: Carbon Footprint/economics/*legislation & jurisprudence/statistics & numerical ; data ; China ; Climate Change/*statistics & numerical data ; Developed Countries ; Developing Countries ; Environmental Policy/history/*legislation & jurisprudence/*trends ; Global Warming/history/legislation & jurisprudence/prevention & ; control/statistics & numerical data ; History, 20th Century ; History, 21st Century ; International Cooperation/*legislation & jurisprudence ; Japan
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    Generalized Levy walks and the role of chemokines in migration of effector CD8+ T cells (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-06-23
    Description: Chemokines have a central role in regulating processes essential to the immune function of T cells, such as their migration within lymphoid tissues and targeting of pathogens in sites of inflammation. Here we track T cells using multi-photon microscopy to demonstrate that the chemokine CXCL10 enhances the ability of CD8+ T cells to control the pathogen Toxoplasma gondii in the brains of chronically infected mice. This chemokine boosts T-cell function in two different ways: it maintains the effector T-cell population in the brain and speeds up the average migration speed without changing the nature of the walk statistics. Notably, these statistics are not Brownian; rather, CD8+ T-cell motility in the brain is well described by a generalized Levy walk. According to our model, this unexpected feature enables T cells to find rare targets with more than an order of magnitude more efficiency than Brownian random walkers. Thus, CD8+ T-cell behaviour is similar to Levy strategies reported in organisms ranging from mussels to marine predators and monkeys, and CXCL10 aids T cells in shortening the average time taken to find rare targets.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387349/" 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/PMC3387349/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harris, Tajie H -- Banigan, Edward J -- Christian, David A -- Konradt, Christoph -- Tait Wojno, Elia D -- Norose, Kazumi -- Wilson, Emma H -- John, Beena -- Weninger, Wolfgang -- Luster, Andrew D -- Liu, Andrea J -- Hunter, Christopher A -- AI-081478/AI/NIAID NIH HHS/ -- AI-090234/AI/NIAID NIH HHS/ -- AI-41158/AI/NIAID NIH HHS/ -- AI-42334/AI/NIAID NIH HHS/ -- CA-069212/CA/NCI NIH HHS/ -- EY-021314/EY/NEI NIH HHS/ -- F32 AI098374/AI/NIAID NIH HHS/ -- F32 AI098374-01/AI/NIAID NIH HHS/ -- R01 AI041158/AI/NIAID NIH HHS/ -- R01 AI041158-14/AI/NIAID NIH HHS/ -- R01 CA069212/CA/NCI NIH HHS/ -- R01 NS072298/NS/NINDS NIH HHS/ -- R21 EY021314/EY/NEI NIH HHS/ -- R21 EY021314-02/EY/NEI NIH HHS/ -- T32 AI007532/AI/NIAID NIH HHS/ -- T32 AI007532-15/AI/NIAID NIH HHS/ -- T32 AR007442/AR/NIAMS NIH HHS/ -- T32 AR007442-25/AR/NIAMS NIH HHS/ -- T32-AI-055400/AI/NIAID NIH HHS/ -- England -- Nature. 2012 Jun 28;486(7404):545-8. doi: 10.1038/nature11098.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 380 South University Avenue, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722867" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/immunology/microbiology ; CD8-Positive T-Lymphocytes/*cytology/*immunology ; *Cell Movement ; Chemokine CXCL10/antagonists & inhibitors/genetics/*immunology ; Female ; Ligands ; Male ; Mice ; Mice, Inbred C57BL ; Models, Immunological ; Receptors, CXCR3/genetics/metabolism ; Time Factors ; Toxoplasma/growth & development/immunology
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    Edward Donnall Thomas (1920-2012) (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-11-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Storb, Rainer -- England -- Nature. 2012 Nov 15;491(7424):334. doi: 10.1038/491334a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Fred Hutchinson Cancer Research Center, University of Washington, Seattle, USA. rstorb@fhcrc.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23151572" target="_blank"〉PubMed〈/a〉
    Keywords: *Allergy and Immunology ; Animals ; *Bone Marrow Transplantation/history ; History, 20th Century ; Humans ; United States
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    Input-specific control of reward and aversion in the ventral tegmental area (2012)
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    Details
    Publication Date: 2012-10-16
    Description: Ventral tegmental area (VTA) dopamine neurons have important roles in adaptive and pathological brain functions related to reward and motivation. However, it is unknown whether subpopulations of VTA dopamine neurons participate in distinct circuits that encode different motivational signatures, and whether inputs to the VTA differentially modulate such circuits. Here we show that, because of differences in synaptic connectivity, activation of inputs to the VTA from the laterodorsal tegmentum and the lateral habenula elicit reward and aversion in mice, respectively. Laterodorsal tegmentum neurons preferentially synapse on dopamine neurons projecting to the nucleus accumbens lateral shell, whereas lateral habenula neurons synapse primarily on dopamine neurons projecting to the medial prefrontal cortex as well as on GABAergic (gamma-aminobutyric-acid-containing) neurons in the rostromedial tegmental nucleus. These results establish that distinct VTA circuits generate reward and aversion, and thereby provide a new framework for understanding the circuit basis of adaptive and pathological motivated behaviours.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493743/" 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/PMC3493743/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lammel, Stephan -- Lim, Byung Kook -- Ran, Chen -- Huang, Kee Wui -- Betley, Michael J -- Tye, Kay M -- Deisseroth, Karl -- Malenka, Robert C -- NS069375/NS/NINDS NIH HHS/ -- P50 MH086403/MH/NIMH NIH HHS/ -- England -- Nature. 2012 Nov 8;491(7423):212-7. doi: 10.1038/nature11527. Epub 2012 Oct 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23064228" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Avoidance Learning/drug effects/*physiology ; Axons/metabolism ; Dopamine/metabolism ; Dopamine Antagonists/pharmacology ; Dopaminergic Neurons/metabolism ; GABAergic Neurons/metabolism ; Habenula/cytology/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Models, Neurological ; Neural Pathways/*physiology ; Receptors, Dopamine/metabolism ; *Reward ; Synapses/metabolism ; Ventral Tegmental Area/cytology/*physiology
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    Deciphering a neuronal circuit that mediates appetite (2012)
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    Publication Date: 2012-03-16
    Description: Hypothalamic neurons that co-express agouti-related protein (AgRP), neuropeptide Y and gamma-aminobutyric acid (GABA) are known to promote feeding and weight gain by integration of various nutritional, hormonal, and neuronal signals. Ablation of these neurons in mice leads to cessation of feeding that is accompanied by activation of Fos in most regions where they project. Previous experiments have indicated that the ensuing starvation is due to aberrant activation of the parabrachial nucleus (PBN) and it could be prevented by facilitating GABA(A) receptor signalling in the PBN within a critical adaptation period. We speculated that loss of GABA signalling from AgRP-expressing neurons (AgRP neurons) within the PBN results in unopposed excitation of the PBN, which in turn inhibits feeding. However, the source of the excitatory inputs to the PBN was unknown. Here we show that glutamatergic neurons in the nucleus tractus solitarius (NTS) and caudal serotonergic neurons control the excitability of PBN neurons and inhibit feeding. Blockade of serotonin (5-HT(3)) receptor signalling in the NTS by either the chronic administration of ondansetron or the genetic inactivation of Tph2 in caudal serotonergic neurons that project to the NTS protects against starvation when AgRP neurons are ablated. Likewise, genetic inactivation of glutamatergic signalling by the NTS onto N-methyl D-aspartate-type glutamate receptors in the PBN prevents starvation. We also show that suppressing glutamatergic output of the PBN reinstates normal appetite after AgRP neuron ablation, whereas it promotes weight gain without AgRP neuron ablation. Thus we identify the PBN as a hub that integrates signals from several brain regions to bidirectionally modulate feeding and body weight.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4000532/" 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/PMC4000532/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Qi -- Clark, Michael S -- Palmiter, Richard D -- DA024908/DA/NIDA NIH HHS/ -- R01 DA024908/DA/NIDA NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Mar 14;483(7391):594-7. doi: 10.1038/nature10899.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Biochemistry, University of Washington School of Medicine, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22419158" target="_blank"〉PubMed〈/a〉
    Keywords: Agouti-Related Protein/metabolism ; Animals ; Appetite/drug effects/*physiology ; Body Weight/drug effects ; Feeding Behavior/drug effects/physiology ; Female ; Glutamic Acid/metabolism ; Hypothalamus/*cytology/drug effects/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Neurons/drug effects/*physiology ; Ondansetron/pharmacology ; Receptors, GABA-A/metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; Serotonergic Neurons/drug effects/metabolism ; Solitary Nucleus/cytology ; Starvation/drug therapy/physiopathology/prevention & control ; Weight Gain/drug effects/physiology ; gamma-Aminobutyric Acid/metabolism
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    'Slings' enable neutrophil rolling at high shear (2012)
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    Publication Date: 2012-07-06
    Description: Most leukocytes can roll along the walls of venules at low shear stress (1 dyn cm-2), but neutrophils have the ability to roll at tenfold higher shear stress in microvessels in vivo. The mechanisms involved in this shear-resistant rolling are known to involve cell flattening and pulling of long membrane tethers at the rear. Here we show that these long tethers do not retract as postulated, but instead persist and appear as 'slings' at the front of rolling cells. We demonstrate slings in a model of acute inflammation in vivo and on P-selectin in vitro, where P-selectin-glycoprotein-ligand-1 (PSGL-1) is found in discrete sticky patches whereas LFA-1 is expressed over the entire length on slings. As neutrophils roll forward, slings wrap around the rolling cells and undergo a step-wise peeling from the P-selectin substrate enabled by the failure of PSGL-1 patches under hydrodynamic forces. The 'step-wise peeling of slings' is distinct from the 'pulling of tethers' reported previously. Each sling effectively lays out a cell-autonomous adhesive substrate in front of neutrophils rolling at high shear stress during inflammation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3433404/" 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/PMC3433404/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sundd, Prithu -- Gutierrez, Edgar -- Koltsova, Ekaterina K -- Kuwano, Yoshihiro -- Fukuda, Satoru -- Pospieszalska, Maria K -- Groisman, Alex -- Ley, Klaus -- EB02185/EB/NIBIB NIH HHS/ -- R01 EB002185/EB/NIBIB NIH HHS/ -- England -- Nature. 2012 Aug 16;488(7411):399-403. doi: 10.1038/nature11248.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22763437" target="_blank"〉PubMed〈/a〉
    Keywords: Adhesiveness ; Animals ; Antigens, CD/metabolism ; Cell Adhesion ; Cell Adhesion Molecules/metabolism ; E-Selectin/metabolism ; Inflammation/immunology/metabolism/pathology ; Intercellular Adhesion Molecule-1/metabolism ; *Leukocyte Rolling ; Lymphocyte Function-Associated Antigen-1/metabolism ; Membrane Glycoproteins/metabolism ; Mice ; Mice, Inbred C57BL ; Microvessels/metabolism ; Neutrophils/*cytology/immunology/*metabolism ; P-Selectin/metabolism ; *Shear Strength ; Th1 Cells/cytology/immunology ; Venules/metabolism
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    Opportunities and challenges for a sustainable energy future (2012)
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    Publication Date: 2012-08-17
    Description: Access to clean, affordable and reliable energy has been a cornerstone of the world's increasing prosperity and economic growth since the beginning of the industrial revolution. Our use of energy in the twenty-first century must also be sustainable. Solar and water-based energy generation, and engineering of microbes to produce biofuels are a few examples of the alternatives. This Perspective puts these opportunities into a larger context by relating them to a number of aspects in the transportation and electricity generation sectors. It also provides a snapshot of the current energy landscape and discusses several research and development opportunities and pathways that could lead to a prosperous, sustainable and secure energy future for the world.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chu, Steven -- Majumdar, Arun -- England -- Nature. 2012 Aug 16;488(7411):294-303. doi: 10.1038/nature11475.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉US Department of Energy, 1000 Independence Avenue SW, Washington DC 20585, USA. the.secretary@hq.doe.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22895334" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conservation of Energy Resources/statistics & numerical data/*trends ; Electricity ; Energy-Generating Resources/economics/history/statistics & numerical data ; Friction ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Horses/physiology ; Motor Vehicles ; Renewable Energy/economics/*statistics & numerical data ; Transportation/statistics & numerical data ; United States
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    Infection regulates pro-resolving mediators that lower antibiotic requirements (2012)
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    Publication Date: 2012-04-28
    Description: Underlying mechanisms for how bacterial infections contribute to active resolution of acute inflammation are unknown. Here, we performed exudate leukocyte trafficking and mediator-metabololipidomics of murine peritoneal Escherichia coli infections with temporal identification of pro-inflammatory (prostaglandins and leukotrienes) and specialized pro-resolving mediators (SPMs). In self-resolving E. coli exudates (10(5) colony forming units, c.f.u.), the dominant SPMs identified were resolvin (Rv) D5 and protectin D1 (PD1), which at 12 h were at significantly greater levels than in exudates from higher titre E. coli (10(7) c.f.u.)-challenged mice. Germ-free mice had endogenous RvD1 and PD1 levels higher than in conventional mice. RvD1 and RvD5 (nanograms per mouse) each reduced bacterial titres in blood and exudates, E. coli-induced hypothermia and increased survival, demonstrating the first actions of RvD5. With human polymorphonuclear neutrophils and macrophages, RvD1, RvD5 and PD1 each directly enhanced phagocytosis of E. coli, and RvD5 counter-regulated a panel of pro-inflammatory genes, including NF-kappaB and TNF-alpha. RvD5 activated the RvD1 receptor, GPR32, to enhance phagocytosis. With self-limited E. coli infections, RvD1 and the antibiotic ciprofloxacin accelerated resolution, each shortening resolution intervals (R(i)). Host-directed RvD1 actions enhanced ciprofloxacin's therapeutic actions. In 10(7) c.f.u. E. coli infections, SPMs (RvD1, RvD5, PD1) together with ciprofloxacin also heightened host antimicrobial responses. In skin infections, SPMs enhanced vancomycin clearance of Staphylococcus aureus. These results demonstrate that specific SPMs are temporally and differentially regulated during infections and that they are anti-phlogistic, enhance containment and lower antibiotic requirements for bacterial clearance.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3340015/" 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/PMC3340015/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chiang, Nan -- Fredman, Gabrielle -- Backhed, Fredrik -- Oh, Sungwhan F -- Vickery, Thad -- Schmidt, Birgitta A -- Serhan, Charles N -- P01 GM095467/GM/NIGMS NIH HHS/ -- P01 GM095467-01/GM/NIGMS NIH HHS/ -- P01 GM095467-02/GM/NIGMS NIH HHS/ -- P01GM095467/GM/NIGMS NIH HHS/ -- R01 GM038765/GM/NIGMS NIH HHS/ -- R01 GM038765-24/GM/NIGMS NIH HHS/ -- R01 GM038765-25/GM/NIGMS NIH HHS/ -- R01 GM038765-26/GM/NIGMS NIH HHS/ -- R01GM38765/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Apr 25;484(7395):524-8. doi: 10.1038/nature11042.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22538616" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/*pharmacology/therapeutic use ; Docosahexaenoic Acids/*metabolism ; Escherichia coli/*drug effects/immunology ; Escherichia coli Infections/drug therapy/*metabolism/microbiology ; Humans ; Hypothermia/prevention & control ; Macrophages/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Microbial Viability/drug effects ; Neutrophils/immunology ; Peritonitis/drug therapy/metabolism/microbiology ; Phagocytosis ; Skin Diseases/drug therapy/metabolism/microbiology ; Staphylococcal Infections/drug therapy/*metabolism/microbiology ; Staphylococcus aureus/drug effects/immunology ; Vancomycin/pharmacology/therapeutic use
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    Turing at 100: Legacy of a universal mind (2012)
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    Publication Date: 2012-02-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chouard, Tanguy -- England -- Nature. 2012 Feb 22;482(7386):455. doi: 10.1038/482455a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22358808" target="_blank"〉PubMed〈/a〉
    Keywords: Artificial Intelligence ; History, 20th Century ; Software/*history ; World War II
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    Pregnancy imprints regulatory memory that sustains anergy to fetal antigen (2012)
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    Publication Date: 2012-10-02
    Description: Pregnancy is an intricately orchestrated process where immune effector cells with fetal specificity are selectively silenced. This requires the sustained expansion of immune-suppressive maternal FOXP3(+) regulatory T cells (T(reg) cells), because even transient partial ablation triggers fetal-specific effector T-cell activation and pregnancy loss. In turn, many idiopathic pregnancy complications proposed to originate from disrupted fetal tolerance are associated with blunted maternal T(reg) expansion. Importantly, however, the antigen specificity and cellular origin of maternal T(reg) cells that accumulate during gestation remain incompletely defined. Here we show that pregnancy selectively stimulates the accumulation of maternal FOXP3(+) CD4 cells with fetal specificity using tetramer-based enrichment that allows the identification of rare endogenous T cells. Interestingly, after delivery, fetal-specific T(reg) cells persist at elevated levels, maintain tolerance to pre-existing fetal antigen, and rapidly re-accumulate during subsequent pregnancy. The accelerated expansion of T(reg) cells during secondary pregnancy was driven almost exclusively by proliferation of fetal-specific FOXP3(+) cells retained from prior pregnancy, whereas induced FOXP3 expression and proliferation of pre-existing FOXP3(+) cells each contribute to T(reg) expansion during primary pregnancy. Furthermore, fetal resorption in secondary compared with primary pregnancy becomes more resilient to partial maternal FOXP3(+) cell ablation. Thus, pregnancy imprints FOXP3(+) CD4 cells that sustain protective regulatory memory to fetal antigen. We anticipate that these findings will spark further investigation on maternal regulatory T-cell specificity that unlocks new strategies for improving pregnancy outcomes and novel approaches for therapeutically exploiting T(reg) cell memory.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465465/" 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/PMC3465465/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rowe, Jared H -- Ertelt, James M -- Xin, Lijun -- Way, Sing Sing -- F30 DK084674/DK/NIDDK NIH HHS/ -- F30DK084674/DK/NIDDK NIH HHS/ -- R01 AI087830/AI/NIAID NIH HHS/ -- R01 AI100934/AI/NIAID NIH HHS/ -- R01AI087830/AI/NIAID NIH HHS/ -- R01AI100934/AI/NIAID NIH HHS/ -- England -- Nature. 2012 Oct 4;490(7418):102-6. doi: 10.1038/nature11462. Epub 2012 Sep 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Minnesota School of Medicine, Department of Pediatrics, Minneapolis, Minnesota 55455, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23023128" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Animals ; Antigens/*immunology ; CD4-Positive T-Lymphocytes/cytology/immunology/metabolism/transplantation ; Clonal Anergy/*immunology ; Female ; Fetal Proteins/*immunology ; Fetus/immunology ; Forkhead Transcription Factors/metabolism ; Immunologic Memory/genetics/*immunology ; Interferon-gamma/immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Postpartum Period/immunology ; Pregnancy ; T-Lymphocytes, Regulatory/cytology/immunology/metabolism
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    The mystery of recent stratospheric temperature trends (2012)
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    Publication Date: 2012-11-30
    Description: A new data set of middle- and upper-stratospheric temperatures based on reprocessing of satellite radiances provides a view of stratospheric climate change during the period 1979-2005 that is strikingly different from that provided by earlier data sets. The new data call into question our understanding of observed stratospheric temperature trends and our ability to test simulations of the stratospheric response to emissions of greenhouse gases and ozone-depleting substances. Here we highlight the important issues raised by the new data and suggest how the climate science community can resolve them.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thompson, David W J -- Seidel, Dian J -- Randel, William J -- Zou, Cheng-Zhi -- Butler, Amy H -- Mears, Carl -- Osso, Albert -- Long, Craig -- Lin, Roger -- England -- Nature. 2012 Nov 29;491(7426):692-7. doi: 10.1038/nature11579.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Atmospheric Science, Colorado State University, Fort Collins, Colorado 80523, USA. davet@atmos.colostate.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23192146" target="_blank"〉PubMed〈/a〉
    Keywords: *Altitude ; *Atmosphere/analysis ; Climate ; Global Warming/history/statistics & numerical data ; History, 20th Century ; History, 21st Century ; Human Activities ; Models, Theoretical ; Spacecraft ; *Temperature ; Time Factors ; *Uncertainty
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    Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions (2012)
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    Publication Date: 2012-10-16
    Description: B cells regulate immune responses by producing antigen-specific antibodies. However, specific B-cell subsets can also negatively regulate T-cell immune responses, and have been termed regulatory B cells. Human and mouse regulatory B cells (B10 cells) with the ability to express the inhibitory cytokine interleukin-10 (IL-10) have been identified. Although rare, B10 cells are potent negative regulators of antigen-specific inflammation and T-cell-dependent autoimmune diseases in mice. How B10-cell IL-10 production and regulation of antigen-specific immune responses are controlled in vivo without inducing systemic immunosuppression is unknown. Using a mouse model for multiple sclerosis, here we show that B10-cell maturation into functional IL-10-secreting effector cells that inhibit in vivo autoimmune disease requires IL-21 and CD40-dependent cognate interactions with T cells. Moreover, the ex vivo provision of CD40 and IL-21 receptor signals can drive B10-cell development and expansion by four-million-fold, and generate B10 effector cells producing IL-10 that markedly inhibit disease symptoms when transferred into mice with established autoimmune disease. The ex vivo expansion and reinfusion of autologous B10 cells may provide a novel and effective in vivo treatment for severe autoimmune diseases that are resistant to current therapies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493692/" 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/PMC3493692/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yoshizaki, Ayumi -- Miyagaki, Tomomitsu -- DiLillo, David J -- Matsushita, Takashi -- Horikawa, Mayuka -- Kountikov, Evgueni I -- Spolski, Rosanne -- Poe, Jonathan C -- Leonard, Warren J -- Tedder, Thomas F -- AI057157/AI/NIAID NIH HHS/ -- AI56363/AI/NIAID NIH HHS/ -- U19 AI056363/AI/NIAID NIH HHS/ -- U54 AI057157/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2012 Nov 8;491(7423):264-8. doi: 10.1038/nature11501. Epub 2012 Oct 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23064231" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD19/genetics/metabolism ; Antigens, CD40/immunology/metabolism ; Antigens, CD5/metabolism ; Autoimmunity/*immunology ; B-Lymphocytes, Regulatory/cytology/*immunology/metabolism/secretion ; Cell Division ; Disease Models, Animal ; Encephalomyelitis, Autoimmune, Experimental/immunology/pathology ; Female ; Histocompatibility Antigens Class II/immunology ; Humans ; Interleukin-10/biosynthesis/immunology/secretion ; Interleukins/*immunology ; Mice ; Mice, Inbred C57BL ; Multiple Sclerosis/immunology/pathology ; Receptors, Interleukin-21/immunology/metabolism ; T-Lymphocytes/*immunology
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    Antibiotics in early life alter the murine colonic microbiome and adiposity (2012)
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    Publication Date: 2012-08-24
    Description: Antibiotics administered in low doses have been widely used as growth promoters in the agricultural industry since the 1950s, yet the mechanisms for this effect are unclear. Because antimicrobial agents of different classes and varying activity are effective across several vertebrate species, we proposed that such subtherapeutic administration alters the population structure of the gut microbiome as well as its metabolic capabilities. We generated a model of adiposity by giving subtherapeutic antibiotic therapy to young mice and evaluated changes in the composition and capabilities of the gut microbiome. Administration of subtherapeutic antibiotic therapy increased adiposity in young mice and increased hormone levels related to metabolism. We observed substantial taxonomic changes in the microbiome, changes in copies of key genes involved in the metabolism of carbohydrates to short-chain fatty acids, increases in colonic short-chain fatty acid levels, and alterations in the regulation of hepatic metabolism of lipids and cholesterol. In this model, we demonstrate the alteration of early-life murine metabolic homeostasis through antibiotic manipulation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553221/" 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/PMC3553221/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cho, Ilseung -- Yamanishi, Shingo -- Cox, Laura -- Methe, Barbara A -- Zavadil, Jiri -- Li, Kelvin -- Gao, Zhan -- Mahana, Douglas -- Raju, Kartik -- Teitler, Isabel -- Li, Huilin -- Alekseyenko, Alexander V -- Blaser, Martin J -- 1UL1-RR029893/RR/NCRR NIH HHS/ -- R01 DK090989/DK/NIDDK NIH HHS/ -- T-R01-DK090989/DK/NIDDK NIH HHS/ -- UL1 RR029893/RR/NCRR NIH HHS/ -- UL1 TR000038/TR/NCATS NIH HHS/ -- UL1-TR000038/TR/NCATS NIH HHS/ -- England -- Nature. 2012 Aug 30;488(7413):621-6. doi: 10.1038/nature11400.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22914093" target="_blank"〉PubMed〈/a〉
    Keywords: Adiposity/*drug effects/physiology ; Age Factors ; Animals ; Anti-Bacterial Agents/*administration & dosage/*pharmacology ; Body Composition/drug effects ; Body Weight/drug effects ; Bone Density/drug effects ; Bone Development/drug effects ; Cecum/drug effects/metabolism ; Cholesterol/metabolism ; Colon/*drug effects/*microbiology ; Fatty Acids, Volatile/metabolism ; Feces/microbiology ; Female ; Gastric Inhibitory Polypeptide/blood/metabolism ; Lipid Metabolism/drug effects ; Liver/drug effects/metabolism ; Male ; Metagenome/*drug effects ; Mice ; Mice, Inbred C57BL ; Polymerase Chain Reaction ; Weaning
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    366 days: Nature's 10 (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-12-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heuer, Rolf-Dieter -- Rosenzweig, Cynthia -- Steltzner, Adam -- Blanpain, Cedric -- Iorns, Elizabeth -- Wang, Jun -- Handelsman, Jo -- Gowers, Tim -- De Bernardinis, Bernardo -- Fouchier, Ron -- England -- Nature. 2012 Dec 20;492(7429):335-43. doi: 10.1038/492335a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23257862" target="_blank"〉PubMed〈/a〉
    Keywords: Access to Information ; Animals ; Bioterrorism/prevention & control ; Climate Change ; Disaster Planning/history ; Earthquakes/statistics & numerical data ; Forecasting ; Genomics ; History, 20th Century ; History, 21st Century ; Humans ; Influenza A Virus, H5N1 Subtype/genetics/pathogenicity ; Influenza, Human/transmission/virology ; Mars ; Neoplastic Stem Cells/cytology ; New York City ; Physics/history ; Publishing/economics ; Reproducibility of Results ; *Research/economics/standards/statistics & numerical data ; Security Measures ; Sexism/psychology/statistics & numerical data ; Space Flight/history/instrumentation
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    Antibiotics: Recover the lost art of drug discovery (2012)
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    Publication Date: 2012-05-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lewis, Kim -- England -- Nature. 2012 May 23;485(7399):439-40. doi: 10.1038/485439a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Northeastern University, Boston, Massachusetts 02115, USA. k.lewis@neu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22622552" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-Bacterial Agents/classification/*history ; Antibiotics, Antitubercular/history ; Daptomycin/history ; Drug Discovery/*history/methods/*trends ; Drug Resistance, Bacterial/drug effects ; History, 20th Century ; Prodrugs/chemical synthesis/pharmacology/therapeutic use
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    Resources: Stop squandering helium (2012)
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    Publication Date: 2012-06-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nuttall, William J -- Clarke, Richard H -- Glowacki, Bartek A -- England -- Nature. 2012 May 30;485(7400):573-5. doi: 10.1038/485573a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Technology Policy, Judge Business School, University of Cambridge, Cambridge CB2 1AG, UK. wjn21@cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22660302" target="_blank"〉PubMed〈/a〉
    Keywords: Commerce/economics ; Helium/economics/history/*isolation & purification/*supply & distribution ; History, 20th Century ; International Cooperation ; United States
    Print ISSN: 0028-0836
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    Earth summit: Rio report card (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-06-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tollefson, Jeff -- Gilbert, Natasha -- England -- Nature. 2012 Jun 6;486(7401):20-3. doi: 10.1038/486020a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22678262" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biodiversity ; Brazil ; Carbon Dioxide/analysis ; *Congresses as Topic/history/trends ; Conservation of Natural Resources/economics/history/*statistics & numerical data ; Desert Climate/adverse effects ; Developed Countries/economics/statistics & numerical data ; Developing Countries/economics/statistics & numerical data ; *Environmental Policy/economics/history/legislation & jurisprudence/trends ; Extinction, Biological ; History, 20th Century ; History, 21st Century ; *International Cooperation/history ; Ozone/history ; Politics ; Renewable Energy/economics/statistics & numerical data ; United Nations
    Print ISSN: 0028-0836
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    Back to Earth (2012)
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    Publication Date: 2012-06-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2012 Jun 6;486(7401):5. doi: 10.1038/486005a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22678243" target="_blank"〉PubMed〈/a〉
    Keywords: Conservation of Natural Resources/history/legislation & jurisprudence/statistics ; & numerical data ; Earth (Planet) ; Environmental Policy/history/*legislation & jurisprudence ; Forestry/history/statistics & numerical data ; History, 20th Century ; History, 21st Century ; *International Cooperation ; *Leadership ; Politics
    Print ISSN: 0028-0836
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    A war not yet won (2012)
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    Publication Date: 2012-06-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2012 May 30;485(7400):547-8. doi: 10.1038/485547b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22660278" target="_blank"〉PubMed〈/a〉
    Keywords: Child ; Disease Eradication/economics/history/*statistics & numerical data ; Global Health/economics/*statistics & numerical data ; History, 20th Century ; History, 21st Century ; Humans ; Poliomyelitis/economics/*epidemiology/history ; Poliovirus Vaccines/administration & dosage/economics ; Vaccination
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    Prions and chaperones: Outside the fold (2012)
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    Publication Date: 2012-02-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Trivedi, Bijal P -- England -- Nature. 2012 Feb 15;482(7385):294-6. doi: 10.1038/482294a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22337030" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/drug therapy/metabolism/prevention & control ; Amyloid beta-Peptides/metabolism ; Animals ; *Biological Evolution ; Clinical Trials as Topic ; Drosophila Proteins/deficiency/genetics/metabolism ; Drosophila melanogaster/genetics/metabolism ; Genetic Variation/genetics ; HSP90 Heat-Shock Proteins/antagonists & inhibitors/*metabolism ; Heat-Shock Proteins/deficiency/genetics/metabolism ; Heat-Shock Response/physiology ; History, 20th Century ; History, 21st Century ; Humans ; Models, Biological ; Neoplasms/drug therapy/metabolism ; Peptide Termination Factors/metabolism ; Prions/chemistry/*metabolism ; Protein Folding ; Saccharomyces cerevisiae/genetics/growth & development/metabolism ; Saccharomyces cerevisiae Proteins/metabolism
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    History: Science sociology began before Kuhn (2012)
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    Publication Date: 2012-05-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lehmann, Ulrich -- England -- Nature. 2012 May 9;485(7397):174. doi: 10.1038/485174e.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22575946" target="_blank"〉PubMed〈/a〉
    Keywords: History, 20th Century ; *Knowledge ; Literature, Modern/*history ; Philosophy/history ; Science/*history ; Sociology/*history
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    A passion for science without barriers. Interview by Adrianne Appel (2012)
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    Publication Date: 2012-01-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hopkins, Nancy -- England -- Nature. 2012 Jan 4;481(7379):13. doi: 10.1038/481013a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22222731" target="_blank"〉PubMed〈/a〉
    Keywords: Female ; History, 20th Century ; History, 21st Century ; Humans ; Male ; *Prejudice ; Research Personnel/history/psychology/*statistics & numerical data ; Science/*manpower/standards ; Sex Characteristics ; Women's Rights/*history
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    Neuron-type-specific signals for reward and punishment in the ventral tegmental area (2012)
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    Publication Date: 2012-01-20
    Description: Dopamine has a central role in motivation and reward. Dopaminergic neurons in the ventral tegmental area (VTA) signal the discrepancy between expected and actual rewards (that is, reward prediction error), but how they compute such signals is unknown. We recorded the activity of VTA neurons while mice associated different odour cues with appetitive and aversive outcomes. We found three types of neuron based on responses to odours and outcomes: approximately half of the neurons (type I, 52%) showed phasic excitation after reward-predicting odours and rewards in a manner consistent with reward prediction error coding; the other half of neurons showed persistent activity during the delay between odour and outcome that was modulated positively (type II, 31%) or negatively (type III, 18%) by the value of outcomes. Whereas the activity of type I neurons was sensitive to actual outcomes (that is, when the reward was delivered as expected compared to when it was unexpectedly omitted), the activity of type II and type III neurons was determined predominantly by reward-predicting odours. We 'tagged' dopaminergic and GABAergic neurons with the light-sensitive protein channelrhodopsin-2 and identified them based on their responses to optical stimulation while recording. All identified dopaminergic neurons were of type I and all GABAergic neurons were of type II. These results show that VTA GABAergic neurons signal expected reward, a key variable for dopaminergic neurons to calculate reward prediction error.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3271183/" 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/PMC3271183/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jeremiah Y -- Haesler, Sebastian -- Vong, Linh -- Lowell, Bradford B -- Uchida, Naoshige -- F32 DK078478/DK/NIDDK NIH HHS/ -- F32 DK078478-01/DK/NIDDK NIH HHS/ -- P30 DK046200/DK/NIDDK NIH HHS/ -- P30 DK046200-08/DK/NIDDK NIH HHS/ -- P30 DK057521/DK/NIDDK NIH HHS/ -- P30 DK057521-01/DK/NIDDK NIH HHS/ -- R01 DK075632/DK/NIDDK NIH HHS/ -- R01 DK075632-01/DK/NIDDK NIH HHS/ -- R01 DK075632-02/DK/NIDDK NIH HHS/ -- R01 DK075632-03/DK/NIDDK NIH HHS/ -- R01 DK075632-04/DK/NIDDK NIH HHS/ -- R01 DK075632-05/DK/NIDDK NIH HHS/ -- R01 DK075632-06/DK/NIDDK NIH HHS/ -- R01 DK075632-07/DK/NIDDK NIH HHS/ -- R01 DK089044/DK/NIDDK NIH HHS/ -- R01 DK089044-01/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Jan 18;482(7383):85-8. doi: 10.1038/nature10754.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22258508" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cues ; Dopamine/metabolism ; Dopaminergic Neurons/*metabolism ; GABAergic Neurons/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Odors/analysis ; Principal Component Analysis ; *Punishment ; *Reward ; Rhodopsin/metabolism ; Ventral Tegmental Area/*cytology/*physiology ; gamma-Aminobutyric Acid/metabolism
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    Louise Johnson (1940-2012) (2012)
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    Publication Date: 2012-10-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sansom, Mark -- England -- Nature. 2012 Oct 25;490(7421):488. doi: 10.1038/490488a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. mark.sansom@bioch.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23099399" target="_blank"〉PubMed〈/a〉
    Keywords: Biochemistry/history ; Biophysics/*history ; Crystallography, X-Ray/*history ; Glycogen Phosphorylase/chemistry/history ; Great Britain ; History, 20th Century ; History, 21st Century ; Muramidase/chemistry/history
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    Natural and anthropogenic variations in methane sources during the past two millennia (2012)
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    Publication Date: 2012-10-06
    Description: Methane is an important greenhouse gas that is emitted from multiple natural and anthropogenic sources. Atmospheric methane concentrations have varied on a number of timescales in the past, but what has caused these variations is not always well understood. The different sources and sinks of methane have specific isotopic signatures, and the isotopic composition of methane can therefore help to identify the environmental drivers of variations in atmospheric methane concentrations. Here we present high-resolution carbon isotope data (delta(13)C content) for methane from two ice cores from Greenland for the past two millennia. We find that the delta(13)C content underwent pronounced centennial-scale variations between 100 BC and AD 1600. With the help of two-box model calculations, we show that the centennial-scale variations in isotope ratios can be attributed to changes in pyrogenic and biogenic sources. We find correlations between these source changes and both natural climate variability--such as the Medieval Climate Anomaly and the Little Ice Age--and changes in human population and land use, such as the decline of the Roman empire and the Han dynasty, and the population expansion during the medieval period.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sapart, C J -- Monteil, G -- Prokopiou, M -- van de Wal, R S W -- Kaplan, J O -- Sperlich, P -- Krumhardt, K M -- van der Veen, C -- Houweling, S -- Krol, M C -- Blunier, T -- Sowers, T -- Martinerie, P -- Witrant, E -- Dahl-Jensen, D -- Rockmann, T -- England -- Nature. 2012 Oct 4;490(7418):85-8. doi: 10.1038/nature11461.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Marine and Atmospheric Research Utrecht, Utrecht University, Princetonplein 5, 3584CC Utrecht, The Netherlands. c.j.sapart@uu.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23038470" target="_blank"〉PubMed〈/a〉
    Keywords: Atmosphere/chemistry ; Biomass ; Carbon Isotopes ; Climate Change/history ; Fires/*history ; Greenland ; History, 15th Century ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, Ancient ; History, Medieval ; Holy Roman Empire ; Human Activities/*history ; Ice/analysis ; Methane/analysis/*history/*metabolism ; Population Dynamics ; Roman World/history
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    Hypocritical oaths (2012)
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    Publication Date: 2012-02-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2012 Feb 8;482(7384):132. doi: 10.1038/482132a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22318566" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Experimentation/ethics/statistics & numerical data ; Animals ; Embryonic Stem Cells ; Guatemala ; Hippocratic Oath ; History, 20th Century ; Human Experimentation/*ethics/*history ; Humans ; Informed Consent/ethics/history ; Pan troglodytes ; Patient Safety/history ; Placebos ; Sexually Transmitted Diseases/history ; United States
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    A tumour suppressor network relying on the polyamine-hypusine axis (2012)
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    Publication Date: 2012-06-23
    Description: Tumour suppressor genes encode a broad class of molecules whose mutational attenuation contributes to malignant progression. In the canonical situation, the tumour suppressor is completely inactivated through a two-hit process involving a point mutation in one allele and chromosomal deletion of the other. Here, to identify tumour suppressor genes in lymphoma, we screen a short hairpin RNA library targeting genes deleted in human lymphomas. We functionally identify those genes whose suppression promotes tumorigenesis in a mouse lymphoma model. Of the nine tumour suppressors we identified, eight correspond to genes occurring in three physically linked 'clusters', suggesting that the common occurrence of large chromosomal deletions in human tumours reflects selective pressure to attenuate multiple genes. Among the new tumour suppressors are adenosylmethionine decarboxylase 1 (AMD1) and eukaryotic translation initiation factor 5A (eIF5A), two genes associated with hypusine, a unique amino acid produced as a product of polyamine metabolism through a highly conserved pathway. Through a secondary screen surveying the impact of all polyamine enzymes on tumorigenesis, we establish the polyamine-hypusine axis as a new tumour suppressor network regulating apoptosis. Unexpectedly, heterozygous deletions encompassing AMD1 and eIF5A often occur together in human lymphomas and co-suppression of both genes promotes lymphomagenesis in mice. Thus, some tumour suppressor functions can be disabled through a two-step process targeting different genes acting in the same pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530829/" 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/PMC3530829/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scuoppo, Claudio -- Miething, Cornelius -- Lindqvist, Lisa -- Reyes, Jose -- Ruse, Cristian -- Appelmann, Iris -- Yoon, Seungtai -- Krasnitz, Alexander -- Teruya-Feldstein, Julie -- Pappin, Darryl -- Pelletier, Jerry -- Lowe, Scott W -- CA087497/CA/NCI NIH HHS/ -- CA148532/CA/NCI NIH HHS/ -- MOP-106530/Canadian Institutes of Health Research/Canada -- P01 CA013106/CA/NCI NIH HHS/ -- P01 CA087497/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Jul 12;487(7406):244-8. doi: 10.1038/nature11126.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Watson School of Biological Sciences, Cold Spring Harbor Laboratory, New York 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722845" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Tumor ; Disease Models, Animal ; Female ; Gene Deletion ; Gene Regulatory Networks ; Genetic Testing ; Humans ; Lymphoma, B-Cell/*genetics/physiopathology ; Lysine/*analogs & derivatives/chemistry ; Mice ; Mice, Inbred C57BL ; Polyamines/*chemistry ; RNA, Small Interfering/genetics/metabolism ; Reproducibility of Results ; Tumor Suppressor Proteins/*genetics
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    Dual-use research: Self-censorship is not enough (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-12-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, David -- Moreno, Jonathan -- England -- Nature. 2012 Dec 20;492(7429):345-7. doi: 10.1038/492345a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. dikaiser@mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23257863" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bioterrorism/prevention & control ; DNA, Recombinant/history ; Ferrets/virology ; Genetic Engineering/history/legislation & jurisprudence/standards ; History, 20th Century ; History, 21st Century ; Humans ; Influenza A Virus, H5N1 Subtype/*genetics/*pathogenicity ; Influenza, Human/epidemiology/*transmission/*virology ; Nuclear Warfare/history/legislation & jurisprudence ; Risk Assessment ; Security Measures/*history/*standards
    Print ISSN: 0028-0836
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    Rapid induction of inflammatory lipid mediators by the inflammasome in vivo (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-08-21
    Description: Detection of microbial products by host inflammasomes is an important mechanism of innate immune surveillance. Inflammasomes activate the caspase-1 (CASP1) protease, which processes the cytokines interleukin (IL)-1beta and IL-18, and initiates a lytic host cell death called pyroptosis. To identify novel CASP1 functions in vivo, we devised a strategy for cytosolic delivery of bacterial flagellin, a specific ligand for the NAIP5 (NLR family, apoptosis inhibitory protein 5)/NLRC4 (NLR family, CARD-domain-containing 4) inflammasome. Here we show that systemic inflammasome activation by flagellin leads to a loss of vascular fluid into the intestine and peritoneal cavity, resulting in rapid (less than 30 min) death in mice. This unexpected response depends on the inflammasome components NAIP5, NLRC4 and CASP1, but is independent of the production of IL-1beta or IL-18. Instead, inflammasome activation results, within minutes, in an 'eicosanoid storm'--a pathological release of signalling lipids, including prostaglandins and leukotrienes, that rapidly initiate inflammation and vascular fluid loss. Mice deficient in cyclooxygenase-1, a critical enzyme in prostaglandin biosynthesis, are resistant to these rapid pathological effects of systemic inflammasome activation by either flagellin or anthrax lethal toxin. Inflammasome-dependent biosynthesis of eicosanoids is mediated by the activation of cytosolic phospholipase A(2) in resident peritoneal macrophages, which are specifically primed for the production of eicosanoids by high expression of eicosanoid biosynthetic enzymes. Our results therefore identify eicosanoids as a previously unrecognized cell-type-specific signalling output of the inflammasome with marked physiological consequences in vivo.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465483/" 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/PMC3465483/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉von Moltke, Jakob -- Trinidad, Norver J -- Moayeri, Mahtab -- Kintzer, Alexander F -- Wang, Samantha B -- van Rooijen, Nico -- Brown, Charles R -- Krantz, Bryan A -- Leppla, Stephen H -- Gronert, Karsten -- Vance, Russell E -- AI063302/AI/NIAID NIH HHS/ -- AI075039/AI/NIAID NIH HHS/ -- AI080749/AI/NIAID NIH HHS/ -- EY016136/EY/NEI NIH HHS/ -- EY022208/EY/NEI NIH HHS/ -- R01 EY016136/EY/NEI NIH HHS/ -- R01 EY022208/EY/NEI NIH HHS/ -- England -- Nature. 2012 Oct 4;490(7418):107-11. doi: 10.1038/nature11351. Epub 2012 Aug 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, Division of Immunology and Pathogenesis, University of California at Berkeley, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22902502" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Bacterial/chemistry/genetics/metabolism ; Apoptosis Regulatory Proteins/deficiency/metabolism ; Bacterial Toxins/chemistry/genetics/metabolism ; Body Fluids/metabolism ; Body Temperature ; Calcium Signaling ; Calcium-Binding Proteins/deficiency/metabolism ; Capillary Permeability ; Caspase 1/deficiency/metabolism ; Cyclooxygenase 1/deficiency ; Cytosol/metabolism ; Death ; Eicosanoids/*biosynthesis/metabolism ; Female ; Flagellin/genetics/immunology/metabolism ; Fluid Shifts ; Hematocrit ; Immunity, Innate/immunology ; Inflammasomes/*metabolism ; Inflammation/immunology/metabolism/pathology ; Interleukin-18 ; Interleukin-1beta ; Intestines/metabolism ; Legionella pneumophila ; Macrophages, Peritoneal/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Neuronal Apoptosis-Inhibitory Protein/deficiency/metabolism ; Peritoneal Cavity ; Peritoneal Lavage ; Recombinant Fusion Proteins/genetics/metabolism ; Salmonella Infections/immunology ; Salmonella typhimurium/immunology ; Time Factors
    Print ISSN: 0028-0836
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    Radiation risks: Raiders of the lost archive (2012)
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    Publication Date: 2012-05-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2012 May 9;485(7397):162-3. doi: 10.1038/485162a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22575939" target="_blank"〉PubMed〈/a〉
    Keywords: Abnormalities, Radiation-Induced/epidemiology ; Animals ; Dogs ; *Dose-Response Relationship, Radiation ; Haplorhini ; History, 20th Century ; Humans ; International Cooperation ; Mice ; Nuclear Warfare ; *Radiation Injuries, Experimental/complications/history ; Radioactive Hazard Release ; Rats ; Swine ; *Tissue Banks/history/trends/utilization ; Tissue Preservation/*statistics & numerical data/trends
    Print ISSN: 0028-0836
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    Phylogeny: Rewriting evolution (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-06-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dolgin, Elie -- England -- Nature. 2012 Jun 27;486(7404):460-2. doi: 10.1038/486460a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22739294" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Developmental Biology/history ; *Evolution, Molecular ; History, 20th Century ; History, 21st Century ; Humans ; Invertebrates/genetics ; Mammals/genetics ; MicroRNAs/*analysis/*genetics ; *Phylogeny
    Print ISSN: 0028-0836
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    F. Sherwood Rowland (1927-2012) (2012)
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    Publication Date: 2012-04-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prather, Michael J -- Blake, Donald R -- England -- Nature. 2012 Apr 11;484(7393):168. doi: 10.1038/484168a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of California, Irvine, California, USA. mprather@uci.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22498618" target="_blank"〉PubMed〈/a〉
    Keywords: Chemistry/*history ; Chlorofluorocarbons/analysis/*chemistry ; Ecology/history ; Environmental Policy/history ; History, 20th Century ; History, 21st Century ; Nobel Prize ; Ozone/*analysis/*chemistry ; Petroleum Pollution ; United States
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    Human experiments: First, do harm (2012)
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    Publication Date: 2012-02-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walter, Matthew -- England -- Nature. 2012 Feb 8;482(7384):148-52. doi: 10.1038/482148a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22318585" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged, 80 and over ; Biomedical Research/ethics/history ; Child ; Female ; Gonorrhea/epidemiology/history ; Guatemala/epidemiology ; History, 20th Century ; History, 21st Century ; Human Experimentation/*ethics/*history/statistics & numerical data ; Humans ; Male ; Military Personnel/statistics & numerical data ; Military Science/ethics/history ; Sex Workers/statistics & numerical data ; Sexually Transmitted Diseases/epidemiology/*history/prevention & control ; Syphilis/epidemiology/history ; United States/epidemiology
    Print ISSN: 0028-0836
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    Targeting VEGF-B as a novel treatment for insulin resistance and type 2 diabetes (2012)
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    Publication Date: 2012-10-02
    Description: The prevalence of type 2 diabetes is rapidly increasing, with severe socioeconomic impacts. Excess lipid deposition in peripheral tissues impairs insulin sensitivity and glucose uptake, and has been proposed to contribute to the pathology of type 2 diabetes. However, few treatment options exist that directly target ectopic lipid accumulation. Recently it was found that vascular endothelial growth factor B (VEGF-B) controls endothelial uptake and transport of fatty acids in heart and skeletal muscle. Here we show that decreased VEGF-B signalling in rodent models of type 2 diabetes restores insulin sensitivity and improves glucose tolerance. Genetic deletion of Vegfb in diabetic db/db mice prevented ectopic lipid deposition, increased muscle glucose uptake and maintained normoglycaemia. Pharmacological inhibition of VEGF-B signalling by antibody administration to db/db mice enhanced glucose tolerance, preserved pancreatic islet architecture, improved beta-cell function and ameliorated dyslipidaemia, key elements of type 2 diabetes and the metabolic syndrome. The potential use of VEGF-B neutralization in type 2 diabetes was further elucidated in rats fed a high-fat diet, in which it normalized insulin sensitivity and increased glucose uptake in skeletal muscle and heart. Our results demonstrate that the vascular endothelium can function as an efficient barrier to excess muscle lipid uptake even under conditions of severe obesity and type 2 diabetes, and that this barrier can be maintained by inhibition of VEGF-B signalling. We propose VEGF-B antagonism as a novel pharmacological approach for type 2 diabetes, targeting the lipid-transport properties of the endothelium to improve muscle insulin sensitivity and glucose disposal.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hagberg, Carolina E -- Mehlem, Annika -- Falkevall, Annelie -- Muhl, Lars -- Fam, Barbara C -- Ortsater, Henrik -- Scotney, Pierre -- Nyqvist, Daniel -- Samen, Erik -- Lu, Li -- Stone-Elander, Sharon -- Proietto, Joseph -- Andrikopoulos, Sofianos -- Sjoholm, Ake -- Nash, Andrew -- Eriksson, Ulf -- England -- Nature. 2012 Oct 18;490(7420):426-30. doi: 10.1038/nature11464. Epub 2012 Sep 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Tissue Biology Group, Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23023133" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Diabetes Mellitus, Type 2/*drug therapy/*metabolism ; Diet, High-Fat ; Disease Models, Animal ; Dyslipidemias/drug therapy/metabolism ; Endothelium, Vascular/metabolism ; Female ; Glucose/metabolism ; Glucose Tolerance Test ; *Insulin Resistance ; Islets of Langerhans/anatomy & histology/cytology/pathology ; Lipid Metabolism ; Male ; Metabolic Syndrome X/drug therapy/metabolism ; Mice ; Mice, Inbred C57BL ; *Molecular Targeted Therapy ; Muscles/metabolism ; Obesity/metabolism/pathology ; Rats ; Rats, Wistar ; Signal Transduction/drug effects/immunology ; Vascular Endothelial Growth Factor B/*antagonists & ; inhibitors/deficiency/genetics/*metabolism
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    Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors (2012)
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    Publication Date: 2012-06-23
    Description: In the developing central nervous system (CNS), the control of synapse number and function is critical to the formation of neural circuits. We previously demonstrated that astrocyte-secreted factors powerfully induce the formation of functional excitatory synapses between CNS neurons. Astrocyte-secreted thrombospondins induce the formation of structural synapses, but these synapses are postsynaptically silent. Here we use biochemical fractionation of astrocyte-conditioned medium to identify glypican 4 (Gpc4) and glypican 6 (Gpc6) as astrocyte-secreted signals sufficient to induce functional synapses between purified retinal ganglion cell neurons, and show that depletion of these molecules from astrocyte-conditioned medium significantly reduces its ability to induce postsynaptic activity. Application of Gpc4 to purified neurons is sufficient to increase the frequency and amplitude of glutamatergic synaptic events. This is achieved by increasing the surface level and clustering, but not overall cellular protein level, of the GluA1 subunit of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) glutamate receptor (AMPAR). Gpc4 and Gpc6 are expressed by astrocytes in vivo in the developing CNS, with Gpc4 expression enriched in the hippocampus and Gpc6 enriched in the cerebellum. Finally, we demonstrate that Gpc4-deficient mice have defective synapse formation, with decreased amplitude of excitatory synaptic currents in the developing hippocampus and reduced recruitment of AMPARs to synapses. These data identify glypicans as a family of novel astrocyte-derived molecules that are necessary and sufficient to promote glutamate receptor clustering and receptivity and to induce the formation of postsynaptically functioning CNS synapses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383085/" 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/PMC3383085/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Allen, Nicola J -- Bennett, Mariko L -- Foo, Lynette C -- Wang, Gordon X -- Chakraborty, Chandrani -- Smith, Stephen J -- Barres, Ben A -- R01 DA015043/DA/NIDA NIH HHS/ -- R01 DA015043-09/DA/NIDA NIH HHS/ -- R01 NS075252/NS/NINDS NIH HHS/ -- R01 NS075252-01/NS/NINDS NIH HHS/ -- R01 NS077601/NS/NINDS NIH HHS/ -- R01 NS077601-01/NS/NINDS NIH HHS/ -- R01DA015043/DA/NIDA NIH HHS/ -- R01NS0725252/NS/NINDS NIH HHS/ -- R01NS077601/NS/NINDS NIH HHS/ -- England -- Nature. 2012 May 27;486(7403):410-4. doi: 10.1038/nature11059.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stanford University School of Medicine, Department of Neurobiology, 299 Campus Drive, Fairchild Science Building D231, Stanford, California 94305-5125, USA. nallen@salk.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722203" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Astrocytes/cytology/*metabolism/secretion ; Cerebellum/cytology/metabolism ; Culture Media, Conditioned/metabolism/pharmacology ; Excitatory Postsynaptic Potentials/*physiology ; Female ; Glypicans/deficiency/*metabolism/pharmacology ; Hippocampus/cytology/metabolism ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA/*metabolism ; Retinal Ganglion Cells/cytology/drug effects/metabolism ; Synapses/drug effects/*metabolism/pathology
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    China's dinosaur hunter: The ground breaker (2012)
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    Publication Date: 2012-09-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Kerri -- England -- Nature. 2012 Sep 6;489(7414):22-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22962704" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Beak ; Birds/anatomy & histology/*classification ; China ; Dinosaurs/anatomy & histology/*classification/physiology ; Expeditions ; Feathers/anatomy & histology/physiology ; *Fossils ; History, 20th Century ; History, 21st Century ; Museums ; Paleontology/*history/standards ; Peer Review, Research/standards ; *Phylogeny
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    Flickering gives early warning signals of a critical transition to a eutrophic lake state (2012)
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    Publication Date: 2012-11-20
    Description: There is a recognized need to anticipate tipping points, or critical transitions, in social-ecological systems. Studies of mathematical and experimental systems have shown that systems may 'wobble' before a critical transition. Such early warning signals may be due to the phenomenon of critical slowing down, which causes a system to recover slowly from small impacts, or to a flickering phenomenon, which causes a system to switch back and forth between alternative states in response to relatively large impacts. Such signals for transitions in social-ecological systems have rarely been observed, not the least because high-resolution time series are normally required. Here we combine empirical data from a lake-catchment system with a mathematical model and show that flickering can be detected from sparse data. We show how rising variance coupled to decreasing autocorrelation and skewness started 10-30 years before the transition to eutrophic lake conditions in both the empirical records and the model output, a finding that is consistent with flickering rather than critical slowing down. Our results suggest that if environmental regimes are sufficiently affected by large external impacts that flickering is induced, then early warning signals of transitions in modern social-ecological systems may be stronger, and hence easier to identify, than previously thought.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Rong -- Dearing, John A -- Langdon, Peter G -- Zhang, Enlou -- Yang, Xiangdong -- Dakos, Vasilis -- Scheffer, Marten -- 268732/European Research Council/International -- England -- Nature. 2012 Dec 20;492(7429):419-22. doi: 10.1038/nature11655. Epub 2012 Nov 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Palaeoecological Laboratory, Geography and Environment, University of Southampton, Southampton SO17 1BJ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23160492" target="_blank"〉PubMed〈/a〉
    Keywords: China ; Diatoms/isolation & purification ; *Eutrophication ; Forecasting/*methods ; Geologic Sediments/analysis/chemistry ; History, 19th Century ; History, 20th Century ; History, 21st Century ; *Lakes/chemistry ; Phosphorus/analysis ; Time Factors
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    NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-12-21
    Description: Alzheimer's disease is the world's most common dementing illness. Deposition of amyloid-beta peptide drives cerebral neuroinflammation by activating microglia. Indeed, amyloid-beta activation of the NLRP3 inflammasome in microglia is fundamental for interleukin-1beta maturation and subsequent inflammatory events. However, it remains unknown whether NLRP3 activation contributes to Alzheimer's disease in vivo. Here we demonstrate strongly enhanced active caspase-1 expression in human mild cognitive impairment and brains with Alzheimer's disease, suggesting a role for the inflammasome in this neurodegenerative disease. Nlrp3(-/-) or Casp1(-/-) mice carrying mutations associated with familial Alzheimer's disease were largely protected from loss of spatial memory and other sequelae associated with Alzheimer's disease, and demonstrated reduced brain caspase-1 and interleukin-1beta activation as well as enhanced amyloid-beta clearance. Furthermore, NLRP3 inflammasome deficiency skewed microglial cells to an M2 phenotype and resulted in the decreased deposition of amyloid-beta in the APP/PS1 model of Alzheimer's disease. These results show an important role for the NLRP3/caspase-1 axis in the pathogenesis of Alzheimer's disease, and suggest that NLRP3 inflammasome inhibition represents a new therapeutic intervention for the disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812809/" 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/PMC3812809/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heneka, Michael T -- Kummer, Markus P -- Stutz, Andrea -- Delekate, Andrea -- Schwartz, Stephanie -- Vieira-Saecker, Ana -- Griep, Angelika -- Axt, Daisy -- Remus, Anita -- Tzeng, Te-Chen -- Gelpi, Ellen -- Halle, Annett -- Korte, Martin -- Latz, Eicke -- Golenbock, Douglas T -- R01 AI083713/AI/NIAID NIH HHS/ -- R01 GM054060/GM/NIGMS NIH HHS/ -- R01 HL093262/HL/NHLBI NIH HHS/ -- U19 AI084048/AI/NIAID NIH HHS/ -- England -- Nature. 2013 Jan 31;493(7434):674-8. doi: 10.1038/nature11729. Epub 2012 Dec 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Clinical Neuroscience Unit, Department of Neurology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany. michael.Heneka@ukb.uni-bonn.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23254930" target="_blank"〉PubMed〈/a〉
    Keywords: Aged ; Aged, 80 and over ; Alzheimer Disease/enzymology/genetics/*pathology ; Amyloid beta-Peptides/metabolism ; Animals ; Behavior, Animal ; Brain/enzymology/*pathology ; Carrier Proteins/genetics/*metabolism ; Caspase 1/genetics/metabolism ; Gene Expression Regulation, Enzymologic ; Humans ; Inflammasomes/metabolism ; Interleukin-1beta/metabolism ; Memory ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mild Cognitive Impairment/enzymology/physiopathology ; Nitric Oxide Synthase Type II/metabolism ; Phagocytosis/genetics
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    Cancer: Solving an age-old problem (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-03-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dunn, Barbara -- England -- Nature. 2012 Feb 29;483(7387):S2-6. doi: 10.1038/483S2a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cancer Prevention, US National Cancer Institute, USA. dunnb@mail.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22378123" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Diet ; History, 18th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; Humans ; Male ; Molecular Targeted Therapy ; *Neoplasms/etiology/history/prevention & control/therapy ; Neoplastic Stem Cells/metabolism/pathology ; Porifera/cytology/genetics
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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