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  • 1
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    Nicotine activation of alpha4* receptors: sufficient for reward, tolerance, and sensitization (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-11-06
    Description: The identity of nicotinic receptor subtypes sufficient to elicit both the acute and chronic effects of nicotine dependence is unknown. We engineered mutant mice with a4 nicotinic subunits containing a single point mutation, Leu9' --〉 Ala9' in the pore-forming M2 domain, rendering a4* receptors hypersensitive to nicotine. Selective activation of a4* nicotinic acetylcholine receptors with low doses of agonist recapitulates nicotine effects thought to be important in dependence, including reinforcement in response to acute nicotine administration, as well as tolerance and sensitization elicited by chronic nicotine administration. These data indicate that activation of a4* receptors is sufficient for nicotine-induced reward, tolerance, and sensitization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tapper, Andrew R -- McKinney, Sheri L -- Nashmi, Raad -- Schwarz, Johannes -- Deshpande, Purnima -- Labarca, Cesar -- Whiteaker, Paul -- Marks, Michael J -- Collins, Allan C -- Lester, Henry A -- DA-15663/DA/NIDA NIH HHS/ -- DA-3194/DA/NIDA NIH HHS/ -- MH-49716/MH/NIMH NIH HHS/ -- NS-11756/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2004 Nov 5;306(5698):1029-32.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15528443" target="_blank"〉PubMed〈/a〉
    Keywords: Alkaloids/metabolism ; Animals ; Azocines/metabolism ; Bicyclo Compounds, Heterocyclic/metabolism ; Brain/drug effects/metabolism ; Calcium/metabolism ; Cells, Cultured ; *Drug Tolerance ; Leucine ; Mice ; Mice, Inbred C57BL ; Motor Activity/drug effects ; Neurons/metabolism ; Nicotine/*pharmacology ; Point Mutation ; Pyridines/metabolism ; Quinolizines/metabolism ; Receptors, Nicotinic/genetics/*physiology ; *Reward ; Serine ; Tobacco Use Disorder/*metabolism ; Up-Regulation
    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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  • 2
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    The ubiquitin ligase parkin mediates resistance to intracellular pathogens (2013)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2013-09-06
    Description: Ubiquitin-mediated targeting of intracellular bacteria to the autophagy pathway is a key innate defence mechanism against invading microbes, including the important human pathogen Mycobacterium tuberculosis. However, the ubiquitin ligases responsible for catalysing ubiquitin chains that surround intracellular bacteria are poorly understood. The parkin protein is a ubiquitin ligase with a well-established role in mitophagy, and mutations in the parkin gene (PARK2) lead to increased susceptibility to Parkinson's disease. Surprisingly, genetic polymorphisms in the PARK2 regulatory region are also associated with increased susceptibility to intracellular bacterial pathogens in humans, including Mycobacterium leprae and Salmonella enterica serovar Typhi, but the function of parkin in immunity has remained unexplored. Here we show that parkin has a role in ubiquitin-mediated autophagy of M. tuberculosis. Both parkin-deficient mice and flies are sensitive to various intracellular bacterial infections, indicating parkin has a conserved role in metazoan innate defence. Moreover, our work reveals an unexpected functional link between mitophagy and infectious disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886920/" 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/PMC3886920/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Manzanillo, Paolo S -- Ayres, Janelle S -- Watson, Robert O -- Collins, Angela C -- Souza, Gianne -- Rae, Chris S -- Schneider, David S -- Nakamura, Ken -- Shiloh, Michael U -- Cox, Jeffery S -- P01 AI063302/AI/NIAID NIH HHS/ -- P30NS069496/NS/NINDS NIH HHS/ -- R01 AI081727/AI/NIAID NIH HHS/ -- R01 AI099439/AI/NIAID NIH HHS/ -- T32 AI060537/AI/NIAID NIH HHS/ -- England -- Nature. 2013 Sep 26;501(7468):512-6. doi: 10.1038/nature12566. Epub 2013 Sep 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology Program in Microbial Pathogenesis and Host Defense, University of California, San Francisco, San Francisco, California 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24005326" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autophagy/immunology ; Bone Marrow Cells/microbiology ; Drosophila melanogaster/genetics/*immunology/metabolism/*microbiology ; Female ; Immunity, Innate/*immunology ; Lysine/metabolism ; Macrophages/microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Mitochondria/metabolism/pathology ; Mitochondrial Degradation ; Models, Immunological ; Mycobacterium marinum/*immunology ; Mycobacterium tuberculosis/growth & development/*immunology/metabolism ; Polyubiquitin/chemistry/metabolism ; Salmonella typhimurium/*immunology ; Symbiosis/immunology ; Tuberculosis/enzymology/immunology/microbiology/pathology ; Ubiquitin/analysis/chemistry/metabolism ; Ubiquitin-Protein Ligases/chemistry/deficiency/*immunology/metabolism
    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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  • 3
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    A simple genetic basis for a complex psychological trait in laboratory mice (1995)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1995-09-08
    Description: Psychological traits are commonly inferred from covariation in sets of behavioral measures that otherwise appear to have little in common. Emotionality in mice is such a trait, defined here by covariation in activity and defecation in a novel environment and emergence into the open arms of an elevated plus maze. Behavioral and quantitative trait analyses were conducted on four measures obtained from 879 mice from an F2 intercross. Three loci, on murine chromosomes 1, 12, and 15, were mapped that influence emotionality. This trait, inferred from studies of strain, sex, and individual differences in rodents, may be related to human susceptibility to anxiety or neuroticism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Flint, J -- Corley, R -- DeFries, J C -- Fulker, D W -- Gray, J A -- Miller, S -- Collins, A C -- DA-00197/DA/NIDA NIH HHS/ -- DA-05131/DA/NIDA NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 1995 Sep 8;269(5229):1432-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7660127" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Behavior, Animal ; *Chromosome Mapping ; Defecation ; *Emotions ; Female ; Genes ; *Genetic Linkage ; Genetic Variation ; Lod Score ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Phenotype ; Regression Analysis
    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
    Electronic Resource
    Electronic Resource
    MECHANISMS THAT UNDERLIE SEX-LINKED AND GENOTYPICALLY DETERMINED DIFFERENCES IN THE DEPRESSANT ACTIONS OF ALCOHOL (1976)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 273 (1976), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1976.tb52893.x
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  • 5
    Electronic Resource
    Electronic Resource
    Biogeographic and Ecological Forces Responsible for Speciation in Ateles (2000)
    Springer
    International journal of primatology 21 (2000), S. 421-444 
    Details
    ISSN: 1573-8604
    Keywords: phylogenetics ; biogeography ; speciation ; Ateles ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We used the results of phylogenetic analyses of relationships among spider monkeys (Ateles) based on mitochondrial and nuclear DNA to investigate questions of their evolutionary origins and speciation mechanisms. We employed the concept of a local molecular clock to date nodes of interest (corresponding to hypothesized species and subspecies) in the various phylograms for comparison to hypothesized biogeographical events that might have affected speciation. We considered various mechanisms—Pleistocene refuge formation, riverine barriers, geological fluctuations, and ecological changes associated with these mechanisms—for their contribution to speciation in Ateles. Most speciation among the various species of Ateles occurred during the middle to late Pliocene, suggesting that Pleistocene refuge formation was not a key speciation mechanism. However, it is likely that the genetic structure of populations of Ateles was modified to some extent by refuge formation. Additionally, riverine barriers do not seem to interrupt gene flow significantly among Ateles. No river formed a barrier among species of Ateles, with the exception of the lower Amazon and possibly some of the black-water rivers draining the Guianan highlands. Large-scale geographic changes associated with the continued rise of the eastern and western cordilleras of the northern Andes and associated changes in habitat were the most important causes of speciation in Ateles. The various factors that modify genetic structure in Ateles are important to consider in order to protect endangered primate genera in the Neotropics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005487802312
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  • 6
    Electronic Resource
    Electronic Resource
    Phylogenetic Relationships of Spider Monkeys (Ateles) Based on Mitochondrial DNA Variation (2000)
    Springer
    International journal of primatology 21 (2000), S. 381-420 
    Details
    ISSN: 1573-8604
    Keywords: phylogenetics ; taxonomy ; systematic ; Ateles ; Cebidae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Our goal was to determine phylogenetic relationships among geographically and taxonomically distinct haplotypes of spider monkeys (Ateles) based on DNA sequence variation for the mitochondrial DNA control region and cytochrome c oxidase subunit II gene. We obtained samples from most previously recognized subspecies of Ateles, ranging from Central America throughout the Amazon Basin, to determine phylogenetic relationships among racially recognized groups. Comparison of DNA sequences using both parsimony analysis and genetic distance analysis produced phylogenetic relationships that were very similar for each genetic region. We analyzed the phylograms produced, along with associated bootstrap support, confidence probabilities, and genetic distances between taxonomic groups, to identify four monophyletic species of Ateles: Ateles paniscus, composed of haplotypes from the northeastern Amazon Basin; A. belzebuth in the southern Amazon Basin; A. hybridus, located primarily along the Magdalena River valley of Colombia; and A. geoffroyi, which includes two former species: A. geoffroyi and A. fusciceps. This arrangement is contradictory to long-held taxonomies of Ateles based on pelage variation and is similar to a recent analysis based on craniodental variation. Results of this investigation suggest patterns of gene flow, evolutionary relationships, and speciation patterns that are more plausible than previous pelage-based taxonomies, which required seemingly impossible patterns of gene flow. Conservation efforts aimed at protecting Ateles, one of the Neotropics most endangered genera, will also benefit from the findings presented in this paper.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005435718241
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  • 7
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    A method for fine mapping quantitative trait loci in outbred animal stocks (2000)
    National Academy of Sciences
    Details
    Publication Date: 2000-10-24
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 8
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    First Direct Observation of Runaway-Electron-Driven Whistler Waves in Tokamaks (2018)
    American Physical Society (APS)
    Details
    Publication Date: 2018-04-12
    Description: Author(s): D. A. Spong, W. W. Heidbrink, C. Paz-Soldan, X. D. Du, K. E. Thome, M. A. Van Zeeland, C. Collins, A. Lvovskiy, R. A. Moyer, M. E. Austin, D. P. Brennan, C. Liu, E. F. Jaeger, and C. Lau DIII-D experiments at low density ( n e ∼ 10 19     m − 3 ) have directly measured whistler waves in the 100–200 MHz range excited by multi-MeV runaway electrons. Whistler activity is correlated with runaway intensity (hard x-ray emission level), occurs in novel discrete frequency bands, and exhibits nonlinear... [Phys. Rev. Lett. 120, 155002] Published Wed Apr 11, 2018
    Keywords: Plasma and Beam Physics
    Print ISSN: 0031-9007
    Electronic ISSN: 1079-7114
    Topics: Physics
    Published by American Physical Society (APS)
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  • 9
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    Groundwater conceptual models: implications for evaluating diffuse pollution mitigation measures (2014)
    Geological Society of London
    Details
    Publication Date: 2014-02-26
    Description: The EU Water Framework Directive (WFD) identifies diffuse pollution as a long-term threat to water quality. Farming contributes significantly to this pollution. There is a clear need for mitigation measures and assessment of their efficacy. Accordingly, Demonstration Test Catchments (DTCs) have been established in England to test the effect of changes in agricultural practice on river water quality and ecology. However, the presence of groundwater in these hydrological systems implies a wide range of travel times for pollutants from source to receptor. Unless flow routes are better characterized, it will be difficult to gauge the success of control measures in the short term. Using 3D modelling and supplementary hydrochemical information, this study considers the hydrogeology of several sub-catchments in the Avon DTC, southern England. Data suggest that groundwater ages 〉25 years exist in parts of the catchments; clearly, observations like these must be used to judge the likely effectiveness of targeted control measures. The revealed hydrogeological complexity of the Avon catchment is unlikely to be unique, so the techniques described here should be applicable to other lowland river systems with moderate to high baseflow indices (〉0.5). To support the WFD, groundwater conceptual models should inform the design of effective measures for diffuse pollution mitigation.
    Print ISSN: 1470-9236
    Topics: Geosciences
    Published by Geological Society of London
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  • 10
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    The neuronal nicotinic receptor subunit genes (CHRNA6 and CHRNB3) are associated with subjective responses to tobacco (2007)
    Oxford University Press
    Details
    Publication Date: 2007-11-16
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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