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  • 1
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    Micronucleus induction in the bone marrow of rats by pharmacological mechanisms. I: glucocorticoid receptor agonism (2013)
    Oxford University Press
    Details
    Publication Date: 2013-02-14
    Description: A novel selective glucocorticoid receptor (GR) agonist, AZD2906, was found to increase the incidence of micronucleated immature erythrocytes (MIE) in the bone marrow of rats given two oral doses at the maximum tolerated level. Because GR agonists as a class are considered not to be genotoxic and AZD2906 showed no activity in the standard in vitro tests or in vivo in a rat liver comet assay, investigative studies were performed to compare AZD2906 with a reference traditional GR agonist, prednisolone. Emphasis was placed on blood and bone marrow parameters in these studies because GR activation has been reported to induce erythropoiesis which, in turn, is known to increase MIE in the bone marrow. Both compounds induced almost identical, small increases in micronucleus frequency at all doses tested. Directly comparable changes in haematological and bone marrow parameters were also seen with significant decreases in lymphoid cells in both compartments and significant increases in numbers of circulating neutrophils. Although no evidence of increased erythropoiesis was seen as increased immature erythrocyte numbers either in the blood or in the bone marrow, histopathological examination showed focal areas in the bone marrow where the erythroid population was enriched in association with an atrophic myeloid lineage. This could have been due to direct stimulation of the erythroid lineage or a secondary effect of myelosuppression inducing a rebound increase in erythropoiesis into the vacant haematopoietic cell compartment. It was concluded that the increased MIE frequencies induced by both AZD2906 and prednisolone are a consequence of their pharmacological effects on the bone marrow, either by directly inducing erythropoiesis or by some other unknown effect on cellular function, and do not indicate potential genotoxicity. This conclusion is supported by the lack of carcinogenic risk in man demonstrated by decades of clinical use of prednisolone and other GR agonists.
    Print ISSN: 0267-8357
    Electronic ISSN: 1464-3804
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 2
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    A Prader-Willi locus lncRNA cloud modulates diurnal genes and energy expenditure (2013)
    Oxford University Press
    Details
    Publication Date: 2013-10-09
    Description: Prader–Willi syndrome (PWS), a genetic disorder of obesity, intellectual disability and sleep abnormalities, is caused by loss of non-coding RNAs on paternal chromosome 15q11-q13. The imprinted minimal PWS locus encompasses a long non-coding RNA (lncRNA) transcript processed into multiple SNORD116 small nucleolar RNAs and the spliced exons of the host gene, 116HG . However, both the molecular function and the disease relevance of the spliced lncRNA 116HG are unknown. Here, we show that 116HG forms a subnuclear RNA cloud that co-purifies with the transcriptional activator RBBP5 and active metabolic genes, remains tethered to the site of its transcription and increases in size in post-natal neurons and during sleep. Snord116del mice lacking 116HG exhibited increased energy expenditure corresponding to the dysregulation of diurnally expressed Mtor and circadian genes Clock , Cry1 and Per2 . These combined genomic and metabolic analyses demonstrate that 116HG regulates the diurnal energy expenditure of the brain. These novel molecular insights into the energy imbalance in PWS should lead to improved therapies and understanding of lncRNA roles in complex neurodevelopmental and metabolic disorders.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 3
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    Age, sex, density, winter weather, and population crashes in Soay sheep (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-05-26
    Description: Quantifying the impact of density, extrinsic climatic fluctuations, and demography on population fluctuations is a persistent challenge in ecology. We analyzed the effect of these processes on the irregular pattern of population crashes of Soay sheep on the St. Kilda archipelago, United Kingdom. Because the age and sex structure of the population fluctuates independently of population size, and because animals of different age and sex respond in different ways to density and weather, identical weather conditions can result in different dynamics in populations of equal size. In addition, the strength of density-dependent processes is a function of the distribution of weather events. Incorporating demographic heterogeneities into population models can influence dynamics and their response to climate change.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coulson, T -- Catchpole, E A -- Albon, S D -- Morgan, B J -- Pemberton, J M -- Clutton-Brock, T H -- Crawley, M J -- Grenfell, B T -- New York, N.Y. -- Science. 2001 May 25;292(5521):1528-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Zoology, Zoological Society of London, Regent's Park, London NW1 4RY, UK. tnc20@cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11375487" target="_blank"〉PubMed〈/a〉
    Keywords: *Aging ; Animals ; Female ; Hebrides ; Male ; Markov Chains ; Models, Statistical ; Nonlinear Dynamics ; Population Density ; Population Dynamics ; Reproduction ; Seasons ; *Sex Characteristics ; *Sheep/physiology ; Survival Analysis ; *Weather
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    Ecology. Seeking new recruits (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-03-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coulson, Tim -- Lindstrom, Jan -- Cotgreave, Peter -- New York, N.Y. -- Science. 2002 Mar 15;295(5562):2023-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11896258" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Birds/*physiology ; Conservation of Natural Resources ; Ecosystem ; Environment ; Logistic Models ; Longevity ; Population Density ; Population Dynamics ; Population Growth ; Stochastic Processes ; Survival Rate
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 5
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    Coupled dynamics of body mass and population growth in response to environmental change (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-07-24
    Description: Environmental change has altered the phenology, morphological traits and population dynamics of many species. However, the links underlying these joint responses remain largely unknown owing to a paucity of long-term data and the lack of an appropriate analytical framework. Here we investigate the link between phenotypic and demographic responses to environmental change using a new methodology and a long-term (1976-2008) data set from a hibernating mammal (the yellow-bellied marmot) inhabiting a dynamic subalpine habitat. We demonstrate how earlier emergence from hibernation and earlier weaning of young has led to a longer growing season and larger body masses before hibernation. The resulting shift in both the phenotype and the relationship between phenotype and fitness components led to a decline in adult mortality, which in turn triggered an abrupt increase in population size in recent years. Direct and trait-mediated effects of environmental change made comparable contributions to the observed marked increase in population growth. Our results help explain how a shift in phenology can cause simultaneous phenotypic and demographic changes, and highlight the need for a theory integrating ecological and evolutionary dynamics in stochastic environments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ozgul, Arpat -- Childs, Dylan Z -- Oli, Madan K -- Armitage, Kenneth B -- Blumstein, Daniel T -- Olson, Lucretia E -- Tuljapurkar, Shripad -- Coulson, Tim -- P01 AG022500/AG/NIA NIH HHS/ -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Jul 22;466(7305):482-5. doi: 10.1038/nature09210.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Life Sciences, Imperial College London, Ascot, Berkshire SL5 7PY, UK. a.ozgul@imperial.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20651690" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; Body Weight/*physiology ; Colorado ; Female ; *Global Warming ; Hibernation/*physiology ; Marmota/*anatomy & histology/growth & development/*physiology ; Phenotype ; Population Dynamics ; Reproduction/physiology ; Survival Rate ; Time Factors ; Weaning
    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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  • 6
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    Population biology: Case of the absent lemmings (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coulson, Tim -- Malo, Aurelio -- England -- Nature. 2008 Nov 6;456(7218):43-4. doi: 10.1038/456043a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18987726" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arvicolinae/*physiology ; *Ecosystem ; Female ; *Greenhouse Effect ; History, 20th Century ; History, 21st Century ; Norway ; Population Dynamics ; Seasons ; Snow ; Temperature
    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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  • 7
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    Sex-specific demography and generalization of the Trivers-Willard theory (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-09-22
    Description: The Trivers-Willard theory proposes that the sex ratio of offspring should vary with maternal condition when it has sex-specific influences on offspring fitness. In particular, mothers in good condition in polygynous and dimorphic species are predicted to produce an excess of sons, whereas mothers in poor condition should do the opposite. Despite the elegance of the theory, support for it has been limited. Here we extend and generalize the Trivers-Willard theory to explain the disparity between predictions and observations of offspring sex ratio. In polygynous species, males typically have higher mortality rates, different age-specific reproductive schedules and more risk-prone life history tactics than females; however, these differences are not currently incorporated into the Trivers-Willard theory. Using two-sex models parameterized with data from free-living mammal populations with contrasting levels of sex differences in demography, we demonstrate how sex differences in life history traits over the entire lifespan can lead to a wide range of sex allocation tactics, and show that correlations between maternal condition and offspring sex ratio alone are insufficient to conclude that mothers adaptively adjust offspring sex ratio.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schindler, Susanne -- Gaillard, Jean-Michel -- Gruning, Andre -- Neuhaus, Peter -- Traill, Lochran W -- Tuljapurkar, Shripad -- Coulson, Tim -- England -- Nature. 2015 Oct 8;526(7572):249-52. doi: 10.1038/nature14968. Epub 2015 Sep 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Oxford, Department of Zoology, Oxford OX1 3PS, UK. ; Laboratoire de Biometrie et Biologie Evolutive (UMR 5558), Universite Claude Bernard Lyon 1, 43 boulevard du 11 novembre 1918, 69622 Villeurbanne Cedex, France. ; Department of Computer Science, University of Surrey, Guildford GU2 7XH, UK. ; Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 1N4, Canada. ; School of Animal, Plant and Environmental Sciences, University of the Witwatersrand, Wits 2050, South Africa. ; Department of Biology, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26390152" target="_blank"〉PubMed〈/a〉
    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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  • 8
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    The evolutionary demography of ecological change: linking trait variation and population growth (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-03-17
    Description: Population dynamics and evolutionary change are linked by the fundamental biological processes of birth and death. This means that population growth may correlate with the strength of selection, whereas evolutionary change can leave an ecological signature. We decompose population growth in an age-structured population into contributions from variation in a quantitative trait. We report that the distribution of body sizes within a population of Soay sheep can markedly influence population dynamics, accounting for up to one-fifth of observed population growth. Our results suggest that there is substantial opportunity for evolutionary dynamics to leave an ecological signature and visa versa.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pelletier, Fanie -- Clutton-Brock, Tim -- Pemberton, Josephine -- Tuljapurkar, Shripad -- Coulson, Tim -- P01 AG 22500/AG/NIA NIH HHS/ -- P01 AG022500/AG/NIA NIH HHS/ -- P01 AG022500-04/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2007 Mar 16;315(5818):1571-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology and the Natural Environment Research Council (NERC) Centre for Population Biology, Imperial College London, Silwood Park, Ascot, Berkshire, SL5 7PY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17363672" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Birth Weight ; Body Size/genetics ; Body Weight/genetics ; Ecology ; Environment ; Female ; *Genetic Variation ; Hindlimb/anatomy & histology ; Male ; Mathematics ; Population Dynamics ; Population Growth ; *Quantitative Trait, Heritable ; Scotland ; *Selection, Genetic ; *Sheep/anatomy & histology/genetics/growth & development ; Weather
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
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    Why conservationists should heed Pokemon (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-04-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Balmford, Andrew -- Clegg, Lizzie -- Coulson, Tim -- Taylor, Jennie -- New York, N.Y. -- Science. 2002 Mar 29;295(5564):2367.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11924673" target="_blank"〉PubMed〈/a〉
    Keywords: Child ; Child, Preschool ; *Conservation of Natural Resources ; *Ecosystem ; Education ; Female ; Humans ; *Learning ; Male
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 10
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    Population biology: fur seals signal their own decline (2014)
    Nature Publishing Group (NPG)
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    Publication Date: 2014-07-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coulson, Tim -- Clegg, Sonya -- England -- Nature. 2014 Jul 24;511(7510):414-5. doi: 10.1038/511414a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology, University of Oxford, Oxford OX1 3PS, UK. ; 1] Department of Zoology, University of Oxford, Oxford OX1 3PS, UK. [2] Griffith School of Environment and Environmental Futures Research Institute, Griffith University, Gold Coast Campus, Queensland, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25056058" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Climate Change ; Female ; Fur Seals/*genetics ; *Heterozygote
    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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