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  • 1
    Publication Date: 2018-05-07
    Description: Niphargus is a speciose amphipod genus found in groundwater habitats across Europe. Three Niphargus species living in the sulphidic Frasassi caves in Italy harbour sulphur-oxidizing Thiothrix bacterial ectosymbionts. These three species are distantly related, implying that the ability to form ectosymbioses with Thiothrix may be common among Niphargus. Therefore, Niphargus-Thiothrix associations may also be found in sulphidic aquifers other than Frasassi. In this study, we examined this possibility by analysing niphargids of the genera Niphargus and Pontoniphargus collected from the partly sulphidic aquifers of the Southern Dobrogea region of Romania, which are accessible through springs, wells and Movile Cave. Molecular and morphological analyses revealed seven niphargid species in this region. Five of these species occurred occasionally or exclusively in sulphidic locations, whereas the remaining two were restricted to nonsulphidic areas. Thiothrix were detected by PCR on all seven Dobrogean niphargid species and observed using microscopy to be predominantly attached to their hosts' appendages. 16S rRNA gene sequences of the Thiothrix epibionts fell into two main clades, one of which (herein named T4) occurred solely on niphargids collected in sulphidic locations. The other Thiothrix clade was present on niphargids from both sulphidic and nonsulphidic areas and indistinguishable from the T3 ectosymbiont clade previously identified on Frasassi-dwelling Niphargus. Although niphargids from Frasassi and Southern Dobrogea are not closely related, the patterns of their association with Thiothrix are remarkably alike. The finding of similar Niphargus-Thiothrix associations in aquifers located 1200 km apart suggests that they may be widespread in European groundwater ecosystems.
    Keywords: amphipods; ecology; sulphide; symbiosis; systematics; taxonomy ; Amphipoda ; Animals ; DNA, Bacterial ; Ecosystem ; Groundwater ; Molecular Sequence Data ; Phylogeny ; RNA, Ribosomal, 16S ; Romania ; Sequence Analysis, DNA ; Sulfur ; Symbiosis ; Thiothrix
    Language: English , English
    Type: article , publishedVersion
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  • 2
    Publication Date: 2016-03-17
    Description: The energetic burden of continuously concentrating solutes against gradients along the tubule may render the kidney especially vulnerable to ischaemia. Acute kidney injury (AKI) affects 3% of all hospitalized patients. Here we show that the mitochondrial biogenesis regulator, PGC1alpha, is a pivotal determinant of renal recovery from injury by regulating nicotinamide adenine dinucleotide (NAD) biosynthesis. Following renal ischaemia, Pgc1alpha(-/-) (also known as Ppargc1a(-/-)) mice develop local deficiency of the NAD precursor niacinamide (NAM, also known as nicotinamide), marked fat accumulation, and failure to re-establish normal function. Notably, exogenous NAM improves local NAD levels, fat accumulation, and renal function in post-ischaemic Pgc1alpha(-/-) mice. Inducible tubular transgenic mice (iNephPGC1alpha) recapitulate the effects of NAM supplementation, including more local NAD and less fat accumulation with better renal function after ischaemia. PGC1alpha coordinately upregulates the enzymes that synthesize NAD de novo from amino acids whereas PGC1alpha deficiency or AKI attenuates the de novo pathway. NAM enhances NAD via the enzyme NAMPT and augments production of the fat breakdown product beta-hydroxybutyrate, leading to increased production of prostaglandin PGE2 (ref. 5), a secreted autacoid that maintains renal function. NAM treatment reverses established ischaemic AKI and also prevented AKI in an unrelated toxic model. Inhibition of beta-hydroxybutyrate signalling or prostaglandin production similarly abolishes PGC1alpha-dependent renoprotection. Given the importance of mitochondrial health in ageing and the function of metabolically active organs, the results implicate NAM and NAD as key effectors for achieving PGC1alpha-dependent stress resistance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tran, Mei T -- Zsengeller, Zsuzsanna K -- Berg, Anders H -- Khankin, Eliyahu V -- Bhasin, Manoj K -- Kim, Wondong -- Clish, Clary B -- Stillman, Isaac E -- Karumanchi, S Ananth -- Rhee, Eugene P -- Parikh, Samir M -- K08-DK090142/DK/NIDDK NIH HHS/ -- K08-DK101560/DK/NIDDK NIH HHS/ -- P30-DK079337/DK/NIDDK NIH HHS/ -- R01 DK095072/DK/NIDDK NIH HHS/ -- R01-DK095072/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2016 Mar 24;531(7595):528-32. doi: 10.1038/nature17184. Epub 2016 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Nephrology and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA. ; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA. ; Division of Clinical Chemistry, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA. ; Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA. ; Bioinformatics and Systems Biology Core, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA. ; Nephrology and Endocrine Divisions, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. ; Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02139, USA. ; Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26982719" target="_blank"〉PubMed〈/a〉
    Keywords: 3-Hydroxybutyric Acid/metabolism ; Acute Kidney Injury/drug therapy/*metabolism ; Adipose Tissue/drug effects/metabolism ; Amino Acids/metabolism ; Animals ; Cytokines/metabolism ; Dinoprostone/biosynthesis/metabolism ; Humans ; Ischemia/drug therapy/metabolism ; Kidney/drug effects/*metabolism/physiology/physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; Mitochondria/metabolism ; NAD/*biosynthesis ; Niacinamide/deficiency/pharmacology/therapeutic use ; Nicotinamide Phosphoribosyltransferase/metabolism ; Oxidation-Reduction ; Signal Transduction/drug effects ; Stress, Physiological ; Transcription Factors/deficiency/*metabolism
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  • 3
    Publication Date: 2016-03-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bolkan, Scott -- Gordon, Joshua A -- England -- Nature. 2016 Apr 7;532(7597):45-6. doi: 10.1038/nature17311. Epub 2016 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Columbia University, New York, New York 10032, USA. ; Department of Psychiatry, Columbia University.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27007842" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Attention Deficit Disorder with Hyperactivity/*physiopathology/*psychology ; Female ; *Gene Deletion ; Humans ; Male ; Membrane Proteins/*deficiency/*genetics ; Thalamic Nuclei/*physiopathology
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  • 4
    Publication Date: 2016-03-05
    Description: Observing marine mammal (MM) populations continuously in time and space over the immense ocean areas they inhabit is challenging but essential for gathering an unambiguous record of their distribution, as well as understanding their behaviour and interaction with prey species. Here we use passive ocean acoustic waveguide remote sensing (POAWRS) in an important North Atlantic feeding ground to instantaneously detect, localize and classify MM vocalizations from diverse species over an approximately 100,000 km(2) region. More than eight species of vocal MMs are found to spatially converge on fish spawning areas containing massive densely populated herring shoals at night-time and diffuse herring distributions during daytime. We find the vocal MMs divide the enormous fish prey field into species-specific foraging areas with varying degrees of spatial overlap, maintained for at least two weeks of the herring spawning period. The recorded vocalization rates are diel (24 h)-dependent for all MM species, with some significantly more vocal at night and others more vocal during the day. The four key baleen whale species of the region: fin, humpback, blue and minke have vocalization rate trends that are highly correlated to trends in fish shoaling density and to each other over the diel cycle. These results reveal the temporospatial dynamics of combined multi-species MM foraging activities in the vicinity of an extensive fish prey field that forms a massive ecological hotspot, and would be unattainable with conventional methodologies. Understanding MM behaviour and distributions is essential for management of marine ecosystems and for accessing anthropogenic impacts on these protected marine species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Delin -- Garcia, Heriberto -- Huang, Wei -- Tran, Duong D -- Jain, Ankita D -- Yi, Dong Hoon -- Gong, Zheng -- Jech, J Michael -- Godo, Olav Rune -- Makris, Nicholas C -- Ratilal, Purnima -- England -- Nature. 2016 Mar 17;531(7594):366-70. doi: 10.1038/nature16960. Epub 2016 Mar 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Ocean Acoustics and Ecosystem Sensing, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, USA. ; Laboratory for Undersea Remote Sensing, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA. ; Northeast Fisheries Science Center, 166 Water Street, Woods Hole, Massachusetts 02543, USA. ; Institute of Marine Research, Post Office Box 1870, Nordnes, N-5817 Bergen, Norway.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26934221" target="_blank"〉PubMed〈/a〉
    Keywords: Acoustics ; Animals ; Aquatic Organisms/*physiology ; Atlantic Ocean ; Diet/veterinary ; Ecosystem ; *Feeding Behavior ; Fishes/*physiology ; Male ; Mammals/*physiology ; *Predatory Behavior ; Time Factors ; *Vocalization, Animal ; Whales/physiology
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2016-01-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Callaway, Ewen -- England -- Nature. 2016 Jan 14;529(7585):138-9. doi: 10.1038/529138a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26762436" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Western/epidemiology ; Animals ; Cats ; Chiroptera/*virology ; Disease Outbreaks/prevention & control/statistics & numerical data/veterinary ; Dogs ; Ebolavirus/*isolation & purification ; Hemorrhagic Fever, Ebola/*epidemiology/prevention & control/*veterinary/virology ; *Host Specificity ; Humans ; Livestock/virology ; Pets/virology ; Rodentia/virology ; Zoonoses/epidemiology/prevention & control/transmission/virology
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2016-02-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heuckeroth, Robert O -- England -- Nature. 2016 Mar 3;531(7592):44-5. doi: 10.1038/nature16877. Epub 2016 Feb 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Children's Hospital of Philadelphia Research Institute and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26863191" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Lineage ; *Cell- and Tissue-Based Therapy ; Drug Discovery/*methods ; Enteric Nervous System/*pathology ; Female ; Hirschsprung Disease/*drug therapy/*pathology ; Humans ; Male ; Neurons/*pathology
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  • 7
    Publication Date: 2016-03-17
    Description: Problematic fossils, extinct taxa of enigmatic morphology that cannot be assigned to a known major group, were once a major issue in palaeontology. A long-favoured solution to the 'problem of the problematica', particularly the 'weird wonders' of the Cambrian Burgess Shale, was to consider them representatives of extinct phyla. A combination of new evidence and modern approaches to phylogenetic analysis has now resolved the affinities of most of these forms. Perhaps the most notable exception is Tullimonstrum gregarium, popularly known as the Tully monster, a large soft-bodied organism from the late Carboniferous Mazon Creek biota (approximately 309-307 million years ago) of Illinois, USA, which was designated the official state fossil of Illinois in 1989. Its phylogenetic position has remained uncertain and it has been compared with nemerteans, polychaetes, gastropods, conodonts, and the stem arthropod Opabinia. Here we review the morphology of Tullimonstrum based on an analysis of more than 1,200 specimens. We find that the anterior proboscis ends in a buccal apparatus containing teeth, the eyes project laterally on a long rigid bar, and the elongate segmented body bears a caudal fin with dorsal and ventral lobes. We describe new evidence for a notochord, cartilaginous arcualia, gill pouches, articulations within the proboscis, and multiple tooth rows adjacent to the mouth. This combination of characters, supported by phylogenetic analysis, identifies Tullimonstrum as a vertebrate, and places it on the stem lineage to lampreys (Petromyzontida). In addition to increasing the known morphological disparity of extinct lampreys, a chordate affinity for T. gregarium resolves the nature of a soft-bodied fossil which has been debated for more than 50 years.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McCoy, Victoria E -- Saupe, Erin E -- Lamsdell, James C -- Tarhan, Lidya G -- McMahon, Sean -- Lidgard, Scott -- Mayer, Paul -- Whalen, Christopher D -- Soriano, Carmen -- Finney, Lydia -- Vogt, Stefan -- Clark, Elizabeth G -- Anderson, Ross P -- Petermann, Holger -- Locatelli, Emma R -- Briggs, Derek E G -- England -- Nature. 2016 Apr 28;532(7600):496-9. doi: 10.1038/nature16992. Epub 2016 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Geology and Geophysics, Yale University, 210 Whitney Avenue, New Haven, Connecticut 06511, USA. ; American Museum of Natural History, Central Park West at 79th Street, New York, New York 10024, USA. ; Field Museum of Natural History, 1400 S. Lake Shore Drive, Chicago, Illinois 60605, USA. ; X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Argonne, Illinois 60439, USA. ; Yale Peabody Museum of Natural History, 170 Whitney Avenue, New Haven, Connecticut 06511, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26982721" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Fins/anatomy & histology ; Animals ; Extinction, Biological ; Eye/anatomy & histology ; *Fossils ; Gastrointestinal Tract/anatomy & histology ; Illinois ; Lampreys/classification ; Notochord/anatomy & histology ; *Phylogeny ; Tooth/anatomy & histology ; Vertebrates/anatomy & histology/*classification
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  • 8
    Publication Date: 2016-01-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Betsholtz, Christer -- England -- Nature. 2016 Jan 14;529(7585):160-1. doi: 10.1038/nature16866. Epub 2016 Jan 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Genetics and Pathology at Uppsala University, and the Department of Medical Biochemistry and Biophysics at the Karolinska Institutet, Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26735011" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Endothelium, Vascular/*growth & development/*metabolism ; Female ; Forkhead Transcription Factors/*metabolism ; Humans ; Male
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  • 9
    Publication Date: 2016-03-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hollon, Nick G -- Phillips, Paul E M -- England -- Nature. 2016 Mar 31;531(7596):588-9. doi: 10.1038/nature17314. Epub 2016 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA. ; Department of Psychiatry &Behavioral Sciences and the Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27007851" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Decision Making ; Humans ; Male ; Neurons/*metabolism ; Nucleus Accumbens/*cytology/*metabolism ; Receptors, Dopamine D2/*metabolism ; *Risk Management
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  • 10
    Publication Date: 2016-05-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Callaway, Ewen -- England -- Nature. 2016 May 5;533(7601):20-1. doi: 10.1038/533020a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27147014" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Zoo/physiology ; Conservation of Natural Resources/economics/*methods ; *Extinction, Biological ; Female ; Fertilization in Vitro/economics/*veterinary ; Induced Pluripotent Stem Cells/*cytology ; Kenya ; Male ; Ovum/*cytology ; *Perissodactyla/physiology ; Reproduction/physiology ; Spermatozoa/*cytology
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  • 11
    Publication Date: 2016-04-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nowogrodzki, Anna -- England -- Nature. 2016 Mar 31;531(7596):561. doi: 10.1038/nature.2016.19599.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27029258" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Specimen Banks/*economics/trends ; Climate Change ; Financing, Government/*economics/trends ; Financing, Organized/economics ; Museums ; Research Support as Topic/*economics/trends ; Time Factors ; United States ; United States Government Agencies/economics/trends
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  • 12
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    Nature Publishing Group (NPG)
    Publication Date: 2016-01-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhattacharya, Shaoni -- England -- Nature. 2016 Jan 28;529(7587):452-5. doi: 10.1038/529452a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26819027" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Migration ; Animals ; Conservation of Natural Resources/*methods ; *Cooking ; Crime/legislation & jurisprudence/*prevention & control/*statistics & numerical ; data ; Cyprus ; Extinction, Biological ; Population Density ; *Songbirds/physiology
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  • 13
    Publication Date: 2016-04-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, Byron M -- England -- Nature. 2016 Apr 28;532(7600):449-50. doi: 10.1038/nature17886. Epub 2016 Apr 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Electrical and Computer Engineering and the Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27074510" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Brain Mapping ; Executive Function/*physiology ; Female ; Male ; Motor Cortex/*cytology/*physiology ; Movement/*physiology ; Neurons/*physiology
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  • 14
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hamilton, Garry -- England -- Nature. 2016 Mar 24;531(7595):432-4. doi: 10.1038/531432a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27008951" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Food Chain ; Marine Biology/trends ; Population Density ; Predatory Behavior ; Scyphozoa/*physiology
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 15
    Publication Date: 2016-02-26
    Description: The RAS/MAPK (mitogen-activated protein kinase) signalling pathway is frequently deregulated in non-small-cell lung cancer, often through KRAS activating mutations. A single endogenous mutant Kras allele is sufficient to promote lung tumour formation in mice but malignant progression requires additional genetic alterations. We recently showed that advanced lung tumours from Kras(G12D/+);p53-null mice frequently exhibit Kras(G12D) allelic enrichment (Kras(G12D)/Kras(wild-type) 〉 1) (ref. 7), implying that mutant Kras copy gains are positively selected during progression. Here we show, through a comprehensive analysis of mutant Kras homozygous and heterozygous mouse embryonic fibroblasts and lung cancer cells, that these genotypes are phenotypically distinct. In particular, Kras(G12D/G12D) cells exhibit a glycolytic switch coupled to increased channelling of glucose-derived metabolites into the tricarboxylic acid cycle and glutathione biosynthesis, resulting in enhanced glutathione-mediated detoxification. This metabolic rewiring is recapitulated in mutant KRAS homozygous non-small-cell lung cancer cells and in vivo, in spontaneous advanced murine lung tumours (which display a high frequency of Kras(G12D) copy gain), but not in the corresponding early tumours (Kras(G12D) heterozygous). Finally, we demonstrate that mutant Kras copy gain creates unique metabolic dependences that can be exploited to selectively target these aggressive mutant Kras tumours. Our data demonstrate that mutant Kras lung tumours are not a single disease but rather a heterogeneous group comprising two classes of tumours with distinct metabolic profiles, prognosis and therapeutic susceptibility, which can be discriminated on the basis of their relative mutant allelic content. We also provide the first, to our knowledge, in vivo evidence of metabolic rewiring during lung cancer malignant progression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4780242/" 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/PMC4780242/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kerr, Emma M -- Gaude, Edoardo -- Turrell, Frances K -- Frezza, Christian -- Martins, Carla P -- MC_UU_12022/4/Medical Research Council/United Kingdom -- MC_UU_12022/6/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2016 Mar 3;531(7592):110-3. doi: 10.1038/nature16967. Epub 2016 Feb 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Cancer Unit, University of Cambridge, Box 197, Cambridge Biomedical Campus, Cambridge CB2 0XZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26909577" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/metabolism/pathology ; Cell Line, Tumor ; Cell Transformation, Neoplastic/drug effects/genetics/metabolism/pathology ; Citric Acid Cycle ; DNA Copy Number Variations/*genetics ; Disease Progression ; Female ; Fibroblasts/metabolism ; Genes, ras/*genetics ; Genotype ; Glucose/*metabolism ; Glutathione/biosynthesis/metabolism ; *Glycolysis ; Lung Neoplasms/*drug therapy/genetics/*metabolism/pathology ; Male ; Mice ; Mutation/*genetics ; Oxidation-Reduction ; Phenotype ; Prognosis
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  • 16
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    Nature Publishing Group (NPG)
    Publication Date: 2016-01-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Popkin, Gabriel -- England -- Nature. 2016 Jan 7;529(7584):16-8. doi: 10.1038/529016a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26738578" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biophysical Phenomena ; Biophysics/*trends ; Birds/physiology ; Cytoskeleton/metabolism ; *Life ; Magnetic Phenomena ; *Models, Theoretical
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  • 17
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chi, Kelly Rae -- England -- Nature. 2016 Mar 3;531(7592):S16-7. doi: 10.1038/531S16a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26934521" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*anatomy & histology/*physiology ; Cognition/*physiology ; Computer Simulation ; Humans ; Models, Anatomic ; *Models, Neurological ; Neocortex/physiology ; Neurons/physiology ; Rats
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  • 18
    Publication Date: 2016-03-31
    Description: Brown and beige adipose tissues can dissipate chemical energy as heat through thermogenic respiration, which requires uncoupling protein 1 (UCP1). Thermogenesis from these adipocytes can combat obesity and diabetes, encouraging investigation of factors that control UCP1-dependent respiration in vivo. Here we show that acutely activated thermogenesis in brown adipose tissue is defined by a substantial increase in levels of mitochondrial reactive oxygen species (ROS). Remarkably, this process supports in vivo thermogenesis, as pharmacological depletion of mitochondrial ROS results in hypothermia upon cold exposure, and inhibits UCP1-dependent increases in whole-body energy expenditure. We further establish that thermogenic ROS alter the redox status of cysteine thiols in brown adipose tissue to drive increased respiration, and that Cys253 of UCP1 is a key target. UCP1 Cys253 is sulfenylated during thermogenesis, while mutation of this site desensitizes the purine-nucleotide-inhibited state of the carrier to adrenergic activation and uncoupling. These studies identify mitochondrial ROS induction in brown adipose tissue as a mechanism that supports UCP1-dependent thermogenesis and whole-body energy expenditure, which opens the way to improved therapeutic strategies for combating metabolic disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chouchani, Edward T -- Kazak, Lawrence -- Jedrychowski, Mark P -- Lu, Gina Z -- Erickson, Brian K -- Szpyt, John -- Pierce, Kerry A -- Laznik-Bogoslavski, Dina -- Vetrivelan, Ramalingam -- Clish, Clary B -- Robinson, Alan J -- Gygi, Steve P -- Spiegelman, Bruce M -- DK31405/DK/NIDDK NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2016 Apr 7;532(7597):112-6. doi: 10.1038/nature17399. Epub 2016 Mar 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA. ; Department of Neurology, Harvard Medical School, Boston, Massachusetts 02215, USA. ; MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27027295" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue, Brown/chemistry/cytology/metabolism ; Animals ; Cell Respiration ; Cysteine/*chemistry/genetics/metabolism ; *Energy Metabolism/drug effects ; Female ; Humans ; Ion Channels/*chemistry/deficiency/genetics/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mitochondria/drug effects/*metabolism ; Mitochondrial Proteins/*chemistry/deficiency/genetics/*metabolism ; Mutant Proteins/chemistry/genetics/metabolism ; Oxidation-Reduction ; Reactive Oxygen Species/*metabolism ; Sulfhydryl Compounds/metabolism ; *Thermogenesis/drug effects
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  • 19
    Publication Date: 2016-04-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chu, Derrick M -- Aagaard, Kjersti M -- England -- Nature. 2016 Apr 21;532(7599):316-7. doi: 10.1038/nature17887. Epub 2016 Apr 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA. ; Departments of Molecular and Human Genetics, Molecular and Cell Biology, and Molecular Physiology and Biophysics, Baylor College of Medicine.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27074514" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Child, Preschool ; Chronic Disease ; Clostridium symbiosum/isolation & purification/physiology ; Diet/adverse effects/methods ; Feces/microbiology ; Female ; Germ-Free Life ; Growth Disorders/*diet therapy/etiology/*microbiology ; Healthy Volunteers ; Humans ; Infant ; Intestines/drug effects/*microbiology ; Liver/metabolism ; Malawi ; Malnutrition/complications/*diet therapy/*microbiology ; Mice ; Microbiota/drug effects/genetics/*physiology ; Milk, Human/chemistry/microbiology ; Mothers ; Oligosaccharides/analysis/pharmacology/therapeutic use ; Ruminococcus/isolation & purification/physiology ; Somatomedins/biosynthesis ; Weight Gain/drug effects
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  • 20
    Publication Date: 2016-02-19
    Description: Sex differences in physiology and disease susceptibility are commonly attributed to developmental and/or hormonal factors, but there is increasing realization that cell-intrinsic mechanisms play important and persistent roles. Here we use the Drosophila melanogaster intestine to investigate the nature and importance of cellular sex in an adult somatic organ in vivo. We find that the adult intestinal epithelium is a cellular mosaic of different sex differentiation pathways, and displays extensive sex differences in expression of genes with roles in growth and metabolism. Cell-specific reversals of the sexual identity of adult intestinal stem cells uncovers the key role this identity has in controlling organ size, reproductive plasticity and response to genetically induced tumours. Unlike previous examples of sexually dimorphic somatic stem cell activity, the sex differences in intestinal stem cell behaviour arise from intrinsic mechanisms that control cell cycle duration and involve a new doublesex- and fruitless-independent branch of the sex differentiation pathway downstream of transformer. Together, our findings indicate that the plasticity of an adult somatic organ is reversibly controlled by its sexual identity, imparted by a new mechanism that may be active in more tissues than previously recognized.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hudry, Bruno -- Khadayate, Sanjay -- Miguel-Aliaga, Irene -- Medical Research Council/United Kingdom -- England -- Nature. 2016 Feb 18;530(7590):344-8. doi: 10.1038/nature16953.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Clinical Sciences Centre, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26887495" target="_blank"〉PubMed〈/a〉
    Keywords: Adult Stem Cells/*cytology ; Animals ; Cell Cycle ; Cell Proliferation ; Cell Transformation, Neoplastic ; Dosage Compensation, Genetic ; Drosophila Proteins/metabolism ; Drosophila melanogaster/*anatomy & histology/*cytology/genetics/growth & ; development ; Female ; Intestines/*cytology ; Male ; Nuclear Proteins/metabolism ; *Organ Size ; RNA-Binding Proteins/metabolism ; Reproduction ; Ribonucleoproteins/metabolism ; *Sex Characteristics ; Sex Differentiation/genetics
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  • 21
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cressey, Daniel -- England -- Nature. 2016 Mar 3;531(7592):128.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26949773" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Experimentation/*standards ; Animals ; Animals, Laboratory ; Bias (Epidemiology) ; Confidentiality ; Confounding Factors (Epidemiology) ; Feedback ; Guidelines as Topic ; *Internet ; Quality Control ; Random Allocation ; Reproducibility of Results ; *Research Design ; Sample Size ; *Software
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  • 22
    Publication Date: 2016-03-17
    Description: Microbial viruses can control host abundances via density-dependent lytic predator-prey dynamics. Less clear is how temperate viruses, which coexist and replicate with their host, influence microbial communities. Here we show that virus-like particles are relatively less abundant at high host densities. This suggests suppressed lysis where established models predict lytic dynamics are favoured. Meta-analysis of published viral and microbial densities showed that this trend was widespread in diverse ecosystems ranging from soil to freshwater to human lungs. Experimental manipulations showed viral densities more consistent with temperate than lytic life cycles at increasing microbial abundance. An analysis of 24 coral reef viromes showed a relative increase in the abundance of hallmark genes encoded by temperate viruses with increased microbial abundance. Based on these four lines of evidence, we propose the Piggyback-the-Winner model wherein temperate dynamics become increasingly important in ecosystems with high microbial densities; thus 'more microbes, fewer viruses'.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knowles, B -- Silveira, C B -- Bailey, B A -- Barott, K -- Cantu, V A -- Cobian-Guemes, A G -- Coutinho, F H -- Dinsdale, E A -- Felts, B -- Furby, K A -- George, E E -- Green, K T -- Gregoracci, G B -- Haas, A F -- Haggerty, J M -- Hester, E R -- Hisakawa, N -- Kelly, L W -- Lim, Y W -- Little, M -- Luque, A -- McDole-Somera, T -- McNair, K -- de Oliveira, L S -- Quistad, S D -- Robinett, N L -- Sala, E -- Salamon, P -- Sanchez, S E -- Sandin, S -- Silva, G G Z -- Smith, J -- Sullivan, C -- Thompson, C -- Vermeij, M J A -- Youle, M -- Young, C -- Zgliczynski, B -- Brainard, R -- Edwards, R A -- Nulton, J -- Thompson, F -- Rohwer, F -- England -- Nature. 2016 Mar 24;531(7595):466-70. doi: 10.1038/nature17193. Epub 2016 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, San Diego State University, 5500 Campanile Drive, San Diego, California 92182, USA. ; Biology Institute, Rio de Janeiro Federal University, Av. Carlos Chagas Filho 373, Rio de Janeiro, Rio de Janeiro 21941-599, Brazil. ; Department of Mathematics and Statistics, San Diego State University, 5500 Campanile Drive, San Diego, California 92182, USA. ; Hawaii Institute of Marine Biology, University of Hawaii at Manoa, 46-007 Lilipuna Road, Kaneohe, Hawaii 96744, USA. ; Computational Science Research Center, San Diego State University, 5500 Campanile Drive, San Diego, California 92182, USA. ; Rainbow Rock, Ocean View, Hawaii 96737, USA. ; Radboud University Medical Centre, Radboud Institute for Molecular Life Sciences, Centre for Molecular and Biomolecular Informatics, 6525HP Nijmegen, The Netherlands. ; Viral Information Institute, San Diego State University, 5500 Campanile Drive, San Diego, California 92182, USA. ; Scripps Institution of Oceanography, 8622 Kennel Way, La Jolla, California 92037, USA. ; Department of Biology, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA. ; Marine Sciences Department, Sao Paulo Federal University - Baixada Santista, Av. Alm. Saldanha da Gama, 89, Santos, Sao Paulo 11030-400, Brazil. ; National Geographic Society, 1145 17th St NW, Washington D.C. 20036, USA. ; CARMABI Foundation, Piscaderabaai z/n, Willemstad, Curacao, Netherlands Antilles. ; Aquatic Microbiology, Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, 1098XH Amsterdam, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26982729" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anthozoa/physiology/*virology ; Bacteriophages/pathogenicity/physiology ; Coral Reefs ; *Ecosystem ; Genes, Viral/genetics ; *Host-Pathogen Interactions ; Lysogeny ; Models, Biological ; Virulence/genetics ; Viruses/genetics/isolation & purification/*pathogenicity
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  • 23
    Publication Date: 2016-03-17
    Description: Lung metastasis is the lethal determinant in many cancers and a number of lines of evidence point to monocytes and macrophages having key roles in its development. Yet little is known about the immediate fate of incoming tumour cells as they colonize this tissue, and even less known about how they make first contact with the immune system. Primary tumours liberate circulating tumour cells (CTCs) into the blood and we have developed a stable intravital two-photon lung imaging model in mice for direct observation of the arrival of CTCs and subsequent host interaction. Here we show dynamic generation of tumour microparticles in shear flow in the capillaries within minutes of CTC entry. Rather than dispersing under flow, many of these microparticles remain attached to the lung vasculature or independently migrate along the inner walls of vessels. Using fluorescent lineage reporters and flow cytometry, we observed 'waves' of distinct myeloid cell subsets that load differentially and sequentially with this CTC-derived material. Many of these tumour-ingesting myeloid cells collectively accumulated in the lung interstitium along with the successful metastatic cells and, as previously understood, promote the development of successful metastases from surviving tumour cells. Although the numbers of these cells rise globally in the lung with metastatic exposure and ingesting myeloid cells undergo phenotypic changes associated with microparticle ingestion, a consistently sparse population of resident conventional dendritic cells, among the last cells to interact with CTCs, confer anti-metastatic protection. This work reveals that CTC fragmentation generates immune-interacting intermediates, and defines a competitive relationship between phagocyte populations for tumour loading during metastatic cell seeding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Headley, Mark B -- Bins, Adriaan -- Nip, Alyssa -- Roberts, Edward W -- Looney, Mark R -- Gerard, Audrey -- Krummel, Matthew F -- P01 HL024136/HL/NHLBI NIH HHS/ -- R21 CA167601/CA/NCI NIH HHS/ -- R21CA167601/CA/NCI NIH HHS/ -- U54 CA163123/CA/NCI NIH HHS/ -- England -- Nature. 2016 Mar 24;531(7595):513-7. doi: 10.1038/nature16985. Epub 2016 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, University of California, San Francisco, 513 Parnassus Ave, HSW512, San Francisco, California 94143-0511, USA. ; Department of Medical Oncology, Academic Medical Center Amsterdam, Meibergdreef, 91105AZ Amsterdam, The Netherlands. ; Departments of Medicine and Laboratory Medicine, University of California, San Francisco, 513 Parnassus Avenue, HSW512, California 94143-0511, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26982733" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Capillaries/pathology ; Cell Line, Tumor ; Cell Lineage ; *Cell Movement ; Dendritic Cells/cytology/immunology ; Female ; Genes, Reporter/genetics ; Humans ; Lung/blood supply/cytology/*immunology/*pathology ; Lung Neoplasms/*immunology/pathology/*secondary ; Male ; Melanoma, Experimental/immunology/pathology ; Mice ; Microscopy, Confocal ; Myeloid Cells/cytology ; Neoplasm Metastasis/*immunology/*pathology ; Neoplastic Cells, Circulating/pathology
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  • 24
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    Nature Publishing Group (NPG)
    Publication Date: 2016-05-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nagata, Shigekazu -- England -- Nature. 2016 May 18;533(7604):474-6. doi: 10.1038/nature18439.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Biochemistry and Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27225115" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caspases/*metabolism ; *Cell Differentiation ; Cytochrome c Group/*metabolism ; Drosophila melanogaster/*cytology ; Male ; Spermatozoa/*cytology/*metabolism
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  • 25
    Publication Date: 2016-04-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nardone, Roland M -- MacLeod, Roderick A F -- Capes-Davis, Amanda -- England -- Nature. 2016 Apr 21;532(7599):313.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27127813" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Tumor ; DNA Contamination ; Databases, Factual ; *Disease Models, Animal ; Guidelines as Topic ; Heterografts/*standards ; Humans ; National Cancer Institute (U.S.) ; Neoplasms/*pathology ; Quality Control ; Reproducibility of Results ; United States ; Xenograft Model Antitumor Assays/*standards
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  • 26
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    Nature Publishing Group (NPG)
    Publication Date: 2016-02-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 Feb 18;530(7590):254. doi: 10.1038/530254a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26887455" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Feed/*analysis ; *Animal Nutritional Physiological Phenomena ; Animals ; Animals, Laboratory/*physiology ; Diet/*veterinary ; Environment ; Japan ; Longevity/*physiology ; Mice ; Models, Animal ; Reproducibility of Results ; Research Design
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  • 27
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dance, Amber -- England -- Nature. 2016 Mar 3;531(7592):S2-3. doi: 10.1038/531S2a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26934523" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Amphetamines/adverse effects/pharmacology ; Animals ; Benzhydryl Compounds/pharmacology ; Biomedical Enhancement/ethics/*methods ; Caffeine/pharmacology ; Child ; Cognition/drug effects ; Dopamine/metabolism ; Healthy Volunteers ; Humans ; Intelligence/*drug effects ; Intelligence Tests ; Methylphenidate/adverse effects/pharmacology ; Neurotransmitter Agents/metabolism ; Nicotine/adverse effects/pharmacology ; Norepinephrine/metabolism ; Off-Label Use ; Performance-Enhancing Substances/adverse effects/*pharmacology ; Prefrontal Cortex/drug effects/physiology ; Rats ; Substance-Related Disorders/etiology ; Video Games/psychology
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  • 28
    Publication Date: 2016-04-29
    Description: Umbilical cord blood-derived haematopoietic stem cells (HSCs) are essential for many life-saving regenerative therapies. However, despite their advantages for transplantation, their clinical use is restricted because HSCs in cord blood are found only in small numbers. Small molecules that enhance haematopoietic stem and progenitor cell (HSPC) expansion in culture have been identified, but in many cases their mechanisms of action or the nature of the pathways they impinge on are poorly understood. A greater understanding of the molecular circuitry that underpins the self-renewal of human HSCs will facilitate the development of targeted strategies that expand HSCs for regenerative therapies. Whereas transcription factor networks have been shown to influence the self-renewal and lineage decisions of human HSCs, the post-transcriptional mechanisms that guide HSC fate have not been closely investigated. Here we show that overexpression of the RNA-binding protein Musashi-2 (MSI2) induces multiple pro-self-renewal phenotypes, including a 17-fold increase in short-term repopulating cells and a net 23-fold ex vivo expansion of long-term repopulating HSCs. By performing a global analysis of MSI2-RNA interactions, we show that MSI2 directly attenuates aryl hydrocarbon receptor (AHR) signalling through post-transcriptional downregulation of canonical AHR pathway components in cord blood HSPCs. Our study gives mechanistic insight into RNA networks controlled by RNA-binding proteins that underlie self-renewal and provides evidence that manipulating such networks ex vivo can enhance the regenerative potential of human HSCs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880456/" 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/PMC4880456/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rentas, Stefan -- Holzapfel, Nicholas T -- Belew, Muluken S -- Pratt, Gabriel A -- Voisin, Veronique -- Wilhelm, Brian T -- Bader, Gary D -- Yeo, Gene W -- Hope, Kristin J -- HG004659/HG/NHGRI NIH HHS/ -- MOP-126030/Canadian Institutes of Health Research/Canada -- NS075449/NS/NINDS NIH HHS/ -- England -- Nature. 2016 Apr 28;532(7600):508-11. doi: 10.1038/nature17665.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biomedical Sciences, Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Ontario L8S 4K1, Canada. ; Department of Cellular and Molecular Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92037, USA. ; Bioinformatics Graduate Program, University of California, San Diego, La Jolla, California 92037, USA. ; The Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada. ; Institute for Research in Immunology and Cancer, University of Montreal, Montreal, Quebec H3C 3J7, Canada. ; Department of Physiology, National University of Singapore and Molecular Engineering Laboratory, A*STAR, Singapore 138632, Singapore.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27121842" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Basic Helix-Loop-Helix Transcription Factors/genetics/*metabolism ; Cell Count ; *Cell Self Renewal/genetics ; Down-Regulation/genetics ; Female ; Fetal Blood/cytology ; Gene Knockdown Techniques ; Hematopoietic Stem Cells/*cytology/*metabolism ; Humans ; Male ; Mice ; Protein Binding ; RNA, Messenger/genetics/metabolism ; RNA-Binding Proteins/genetics/*metabolism ; Receptors, Aryl Hydrocarbon/genetics/*metabolism ; *Signal Transduction/genetics
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  • 29
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    Nature Publishing Group (NPG)
    Publication Date: 2016-02-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 Feb 11;530(7589):129-30. doi: 10.1038/530130a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26863944" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Disease Eradication/economics/*statistics & numerical data/*trends ; Dog Diseases/epidemiology/parasitology ; Dogs ; Dracunculiasis/*epidemiology/*parasitology/prevention & control/transmission ; *Dracunculus Nematode/isolation & purification ; Drinking Water/parasitology/standards ; Female ; Ghana/epidemiology ; Goals ; Malaria/epidemiology/parasitology/prevention & control/transmission ; Male ; Mosquito Control/methods ; Poliomyelitis/epidemiology ; Time Factors
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  • 30
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cyranoski, David -- England -- Nature. 2016 Apr 21;532(7599):300-2. doi: 10.1038/532300a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Nature from Shanghai, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27111614" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Husbandry ; Animal Welfare/economics/legislation & jurisprudence/standards ; Animals ; *Animals, Laboratory/genetics ; Biological Evolution ; Biomedical Research/economics/legislation & jurisprudence/*methods/*trends ; CRISPR-Cas Systems/genetics ; Callithrix ; China ; Cooperative Behavior ; Disease Models, Animal ; Genetic Engineering ; *Haplorhini/genetics ; Humans ; International Cooperation ; Japan ; Neurosciences/methods/trends ; Research Personnel/organization & administration
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  • 31
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    Nature Publishing Group (NPG)
    Publication Date: 2016-05-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 May 5;533(7601):8. doi: 10.1038/533008a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27146997" target="_blank"〉PubMed〈/a〉
    Keywords: Adiposity/physiology ; Animals ; Athletes ; Bicycling/physiology ; Brain/anatomy & histology/metabolism ; Dietary Fats/administration & dosage/metabolism ; Energy Metabolism/*physiology ; Heart Rate ; Hominidae/anatomy & histology/metabolism ; Humans ; Male
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  • 32
    Publication Date: 2016-04-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2016 Apr 28;532(7600):432-4. doi: 10.1038/532432a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27121823" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Austria ; Bacteria/genetics ; CRISPR-Cas Systems/*genetics ; France ; Genetic Engineering/*history ; Genetic Therapy/history ; Germany ; History, 20th Century ; History, 21st Century ; Microbiology/history ; New York City ; Patents as Topic ; Sweden
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  • 33
    Publication Date: 2016-03-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2016 Mar 17;531(7594):294-7. doi: 10.1038/531294a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26983522" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/*etiology/metabolism/pathology ; Amyloid/administration & dosage/adverse effects/chemistry/metabolism ; Amyloid beta-Peptides/administration & dosage/adverse ; effects/chemistry/metabolism ; Animals ; Creutzfeldt-Jakob Syndrome/epidemiology/etiology/metabolism/pathology ; Drug Contamination ; Great Britain/epidemiology ; Growth Hormone/administration & dosage ; Humans ; Mice ; *Models, Biological ; Parkinson Disease/etiology/metabolism/pathology ; Prions/administration & dosage/adverse effects/chemistry/metabolism ; alpha-Synuclein/administration & dosage/adverse effects/chemistry/metabolism ; tau Proteins/metabolism
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  • 34
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    Nature Publishing Group (NPG)
    Publication Date: 2016-01-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sohn, Emily -- England -- Nature. 2016 Jan 14;529(7585):243-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26771043" target="_blank"〉PubMed〈/a〉
    Keywords: Altitude ; Animals ; Animals, Wild ; *Caves ; *Disaster Planning ; *Diving ; *Expeditions ; *Mountaineering ; *Research ; *Research Personnel/psychology ; Safety ; Survival
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  • 35
    Publication Date: 2016-01-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sarewitz, Daniel -- England -- Nature. 2016 Jan 7;529(7584):6. doi: 10.1038/529006a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Consortium for Science, Policy and Outcomes at Arizona State University, and is based in Washington DC.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26738572" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cooperative Behavior ; Global Warming/*prevention & control ; Goals ; Humans ; International Cooperation ; Life Style ; Morals ; Paris ; *Policy Making ; Politics ; *Religion and Science
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  • 36
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ledford, Heidi -- England -- Nature. 2016 Apr 14;532(7598):162-4. doi: 10.1038/532162a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075078" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/administration & ; dosage/immunology/pharmacology/therapeutic use ; Antigens, CD40/antagonists & inhibitors ; Antineoplastic Combined Chemotherapy Protocols/administration & ; dosage/pharmacology/*therapeutic use ; CTLA-4 Antigen/antagonists & inhibitors/immunology ; Cancer Vaccines/administration & dosage/immunology/therapeutic use ; Child ; Clinical Trials as Topic ; Endpoint Determination ; Epigenesis, Genetic/drug effects ; Humans ; *Immunotherapy/trends ; Melanoma/drug therapy/immunology ; Mice ; Neoplasms/*drug therapy/*immunology/therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/mortality ; Survivors ; T-Lymphocytes/drug effects/immunology
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 Apr 21;532(7599):281. doi: 10.1038/532281a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27111602" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Welfare/legislation & jurisprudence ; Animals ; *Animals, Laboratory ; Biomedical Research/manpower/*trends ; CRISPR-Cas Systems/genetics ; China ; Cooperative Behavior ; Europe ; *Haplorhini/genetics ; Humans ; *Models, Animal
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  • 38
    Publication Date: 2016-03-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sims, David W -- Queiroz, Nuno -- England -- Nature. 2016 Mar 24;531(7595):448. doi: 10.1038/531448a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Marine Biological Association, Plymouth, UK. ; CIBIO/InBIO - University of Porto, Portugal.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27008956" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Fisheries/economics/*legislation & jurisprudence ; *Fishes ; Population Density
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  • 39
    Publication Date: 2016-02-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Florens, F B Vincent -- England -- Nature. 2016 Feb 4;530(7588):33. doi: 10.1038/530033a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Mauritius, Reduit, Mauritius.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26842049" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/legislation & jurisprudence ; Animal Culling/*legislation & jurisprudence ; Animals ; *Biodiversity ; *Chiroptera/physiology ; Conservation of Natural Resources/*legislation & jurisprudence ; Endangered Species/*legislation & jurisprudence ; Mauritius
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    Nature Publishing Group (NPG)
    Publication Date: 2016-05-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Savage, Neil -- England -- Nature. 2016 May 5;533(7601):S10-2. doi: 10.1038/533S10a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27144602" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Science Disciplines/economics ; Entrepreneurship/*economics/*organization & administration/statistics & numerical ; data/trends ; Europe ; Humans ; Inventions/economics/statistics & numerical data ; Investments/economics ; Laboratories/economics/organization & administration ; Licensure/economics ; Marketing/economics ; Patents as Topic ; Private Sector/economics/organization & administration/statistics & numerical ; data/trends ; Research/*economics/organization & administration ; Technology Transfer ; United States ; Universities/economics/organization & administration ; Vaccines/economics
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  • 41
    Publication Date: 2016-01-21
    Description: Haematopoietic stem cells (HSCs), which sustain production of all blood cell lineages, rely on glycolysis for ATP production, yet little attention has been paid to the role of mitochondria. Here we show in mice that the short isoform of a critical regulator of HSCs, Prdm16 (refs 4, 5), induces mitofusin 2 (Mfn2), a protein involved in mitochondrial fusion and in tethering of mitochondria to the endoplasmic reticulum. Overexpression and deletion studies, including single-cell transplantation assays, revealed that Mfn2 is specifically required for the maintenance of HSCs with extensive lymphoid potential, but not, or less so, for the maintenance of myeloid-dominant HSCs. Mfn2 increased buffering of intracellular Ca(2+), an effect mediated through its endoplasmic reticulum-mitochondria tethering activity, thereby negatively regulating nuclear translocation and transcriptional activity of nuclear factor of activated T cells (Nfat). Nfat inhibition rescued the effects of Mfn2 deletion in HSCs, demonstrating that negative regulation of Nfat is the prime downstream mechanism of Mfn2 in the maintenance of HSCs with extensive lymphoid potential. Mitochondria therefore have an important role in HSCs. These findings provide a mechanism underlying clonal heterogeneity among HSCs and may lead to the design of approaches to bias HSC differentiation into desired lineages after transplantation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Luchsinger, Larry L -- de Almeida, Mariana Justino -- Corrigan, David J -- Mumau, Melanie -- Snoeck, Hans-Willem -- 1S10OD020056-01/OD/NIH HHS/ -- 1S10RR027050-01/RR/NCRR NIH HHS/ -- F31 CA196045/CA/NCI NIH HHS/ -- R01 AG029262/AG/NIA NIH HHS/ -- R01 CA167286/CA/NCI NIH HHS/ -- England -- Nature. 2016 Jan 28;529(7587):528-31. doi: 10.1038/nature16500. Epub 2016 Jan 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York 10032, USA. ; Department of Medicine, Columbia University Medical Center, New York, New York 10032, USA. ; Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26789249" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Animals ; Calcium/metabolism ; Calcium Signaling ; Cell Differentiation ; Cell Lineage ; DNA-Binding Proteins/chemistry/metabolism ; Endoplasmic Reticulum/metabolism ; Female ; Fibroblasts ; GTP Phosphohydrolases/*metabolism ; Hematopoietic Stem Cells/*cytology/*metabolism ; Lymphocytes/*cytology/metabolism ; Male ; Mice ; Mitochondria/metabolism ; Mitochondrial Dynamics ; Myeloid Cells/cytology ; NFATC Transcription Factors/antagonists & inhibitors/metabolism ; Transcription Factors/chemistry/metabolism
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  • 42
    Publication Date: 2016-04-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arnold, Carrie -- England -- Nature. 2016 Apr 21;532(7599):292. doi: 10.1038/nature.2016.19755.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27111610" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibody Specificity/immunology ; Antivenins/*biosynthesis/economics/genetics/immunology ; Horses/immunology ; Humans ; Immunization, Passive ; Mice ; Snake Bites/immunology/mortality/*therapy ; Snake Venoms/*antagonists & inhibitors/genetics/immunology ; Synthetic Biology/*methods/*trends
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  • 43
    Publication Date: 2016-03-24
    Description: Targeted, temporally regulated neural modulation is invaluable in determining the physiological roles of specific neural populations or circuits. Here we describe a system for non-invasive, temporal activation or inhibition of neuronal activity in vivo and its use to study central nervous system control of glucose homeostasis and feeding in mice. We are able to induce neuronal activation remotely using radio waves or magnetic fields via Cre-dependent expression of a GFP-tagged ferritin fusion protein tethered to the cation-conducting transient receptor potential vanilloid 1 (TRPV1) by a camelid anti-GFP antibody (anti-GFP-TRPV1). Neuronal inhibition via the same stimuli is achieved by mutating the TRPV1 pore, rendering the channel chloride-permeable. These constructs were targeted to glucose-sensing neurons in the ventromedial hypothalamus in glucokinase-Cre mice, which express Cre in glucose-sensing neurons. Acute activation of glucose-sensing neurons in this region increases plasma glucose and glucagon, lowers insulin levels and stimulates feeding, while inhibition reduces blood glucose, raises insulin levels and suppresses feeding. These results suggest that pancreatic hormones function as an effector mechanism of central nervous system circuits controlling blood glucose and behaviour. The method we employ obviates the need for permanent implants and could potentially be applied to study other neural processes or used to regulate other, even dispersed, cell types.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stanley, Sarah A -- Kelly, Leah -- Latcha, Kaamashri N -- Schmidt, Sarah F -- Yu, Xiaofei -- Nectow, Alexander R -- Sauer, Jeremy -- Dyke, Jonathan P -- Dordick, Jonathan S -- Friedman, Jeffrey M -- GM067545/GM/NIGMS NIH HHS/ -- GM095654/GM/NIGMS NIH HHS/ -- MH105941/MH/NIMH NIH HHS/ -- U01 MH105941/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2016 Mar 31;531(7596):647-50. doi: 10.1038/nature17183. Epub 2016 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Genetics, Rockefeller University, New York, New York 10065, USA. ; Department of Chemical &Biological Engineering, Center for Biotechnology &Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, USA. ; Department of Radiology, Weill Cornell Medical College, New York, New York 10065, USA. ; Howard Hughes Medical Institute, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27007848" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Glucose/*metabolism ; Eating/*physiology ; Ferritins/genetics/metabolism ; Glucagon/blood ; Glucokinase/metabolism ; Homeostasis ; Hypoglycemia/metabolism ; Insulin/blood ; Integrases/metabolism ; *Magnetic Fields ; Mice ; Neural Inhibition ; Neurons/*physiology ; Pancreatic Hormones/metabolism ; *Radio Waves ; Recombinant Fusion Proteins/genetics/metabolism ; TRPV Cation Channels/genetics/metabolism ; Time Factors ; Ventromedial Hypothalamic Nucleus/*cytology/*physiology
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  • 44
    Publication Date: 2016-04-28
    Description: Despite the success of potent anti-retroviral drugs in controlling human immunodeficiency virus type 1 (HIV-1) infection, little progress has been made in generating an effective HIV-1 vaccine. Although passive transfer of anti-HIV-1 broadly neutralizing antibodies can protect mice or macaques against a single high-dose challenge with HIV or simian/human (SIV/HIV) chimaeric viruses (SHIVs) respectively, the long-term efficacy of a passive antibody transfer approach for HIV-1 has not been examined. Here we show, on the basis of the relatively long-term protection conferred by hepatitis A immune globulin, the efficacy of a single injection (20 mg kg(-1)) of four anti-HIV-1-neutralizing monoclonal antibodies (VRC01, VRC01-LS, 3BNC117, and 10-1074 (refs 9 - 12)) in blocking repeated weekly low-dose virus challenges of the clade B SHIVAD8. Compared with control animals, which required two to six challenges (median = 3) for infection, a single broadly neutralizing antibody infusion prevented virus acquisition for up to 23 weekly challenges. This effect depended on antibody potency and half-life. The highest levels of plasma-neutralizing activity and, correspondingly, the longest protection were found in monkeys administered the more potent antibodies 3BNC117 and 10-1074 (median = 13 and 12.5 weeks, respectively). VRC01, which showed lower plasma-neutralizing activity, protected for a shorter time (median = 8 weeks). The introduction of a mutation that extends antibody half-life into the crystallizable fragment (Fc) domain of VRC01 increased median protection from 8 to 14.5 weeks. If administered to populations at high risk of HIV-1 transmission, such an immunoprophylaxis regimen could have a major impact on virus transmission.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gautam, Rajeev -- Nishimura, Yoshiaki -- Pegu, Amarendra -- Nason, Martha C -- Klein, Florian -- Gazumyan, Anna -- Golijanin, Jovana -- Buckler-White, Alicia -- Sadjadpour, Reza -- Wang, Keyun -- Mankoff, Zachary -- Schmidt, Stephen D -- Lifson, Jeffrey D -- Mascola, John R -- Nussenzweig, Michel C -- Martin, Malcolm A -- AI-100148/AI/NIAID NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- UM1 AI100663-01/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2016 May 5;533(7601):105-9. doi: 10.1038/nature17677. Epub 2016 Apr 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA. ; Laboratory of Experimental Immunology, Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany. ; Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne, 50937 Cologne, Germany. ; AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA. ; Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27120156" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/administration & dosage/immunology ; Animals ; Antibodies, Monoclonal/administration & dosage/blood/genetics/immunology ; Antibodies, Neutralizing/administration & dosage/blood/genetics/immunology ; Female ; HIV Antibodies/*administration & dosage/blood/genetics/*immunology ; HIV Infections/immunology/prevention & control/transmission ; Half-Life ; Immunoglobulin Fc Fragments/chemistry/genetics/immunology ; Macaca mulatta/immunology/virology ; Male ; Mutation/genetics ; Protein Structure, Tertiary ; SAIDS Vaccines/administration & dosage/immunology ; Simian Acquired Immunodeficiency Syndrome/blood/*immunology/*prevention & control ; Simian Immunodeficiency Virus/*immunology ; Time Factors
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  • 45
    Publication Date: 2016-01-28
    Description: The process of ageing makes death increasingly likely, involving a random aspect that produces a wide distribution of lifespan even in homogeneous populations. The study of this stochastic behaviour may link molecular mechanisms to the ageing process that determines lifespan. Here, by collecting high-precision mortality statistics from large populations, we observe that interventions as diverse as changes in diet, temperature, exposure to oxidative stress, and disruption of genes including the heat shock factor hsf-1, the hypoxia-inducible factor hif-1, and the insulin/IGF-1 pathway components daf-2, age-1, and daf-16 all alter lifespan distributions by an apparent stretching or shrinking of time. To produce such temporal scaling, each intervention must alter to the same extent throughout adult life all physiological determinants of the risk of death. Organismic ageing in Caenorhabditis elegans therefore appears to involve aspects of physiology that respond in concert to a diverse set of interventions. In this way, temporal scaling identifies a novel state variable, r(t), that governs the risk of death and whose average decay dynamics involves a single effective rate constant of ageing, kr. Interventions that produce temporal scaling influence lifespan exclusively by altering kr. Such interventions, when applied transiently even in early adulthood, temporarily alter kr with an attendant transient increase or decrease in the rate of change in r and a permanent effect on remaining lifespan. The existence of an organismal ageing dynamics that is invariant across genetic and environmental contexts provides the basis for a new, quantitative framework for evaluating the manner and extent to which specific molecular processes contribute to the aspect of ageing that determines lifespan.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stroustrup, Nicholas -- Anthony, Winston E -- Nash, Zachary M -- Gowda, Vivek -- Gomez, Adam -- Lopez-Moyado, Isaac F -- Apfeld, Javier -- Fontana, Walter -- P40 OD010440/OD/NIH HHS/ -- R01 AG034994/AG/NIA NIH HHS/ -- England -- Nature. 2016 Feb 4;530(7588):103-7. doi: 10.1038/nature16550. Epub 2016 Jan 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26814965" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/genetics/*physiology ; Animals ; Caenorhabditis elegans/genetics/*physiology ; Caenorhabditis elegans Proteins/genetics ; Death ; Diet ; Forkhead Transcription Factors/genetics ; Kinetics ; Longevity/genetics/*physiology ; Oxidative Stress ; Phosphatidylinositol 3-Kinases/genetics ; Receptor, Insulin/genetics ; Risk ; Temperature ; Time Factors ; Transcription Factors/genetics
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  • 46