2,415 research outputs found

    Genetic architecture of human obesity traits in the rhesus macaque

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    Objective: Whereas the metabolic consequences of obesity have been studied extensively in the rhesus macaque, corollary genetic studies of obesity are nonexistent. This study assessed genetic contributions to spontaneous adiposity in this species. Methods: Phenotypic variation by age class and sex for BMI, waist to height ratio, waist to thigh ratio, and waist circumference was assessed in 583 macaques. Total and sex-specific heritability for all traits was estimated, including waist to thigh ratio adjusted for BMI, as well as genotypic and phenotypic correlations. In addition, functional genetic variation at BDNF, FTO, LEP, LEPR, MC4R, PCSK1, POMC, and SIM1 was assessed in four animals with extreme spontaneous adiposity. Results: Trait heritability in the combined sample was low to moderate (0.14-0.32), whereas sex-specific heritability was more substantial (0.20-0.67). Heritability was greater in females for all traits except BMI. All traits were robustly correlated, with genetic correlations of 0.63 to 0.93 indicating substantial pleiotropy. Likely functional variants were discovered in the four macaques at all eight human obesity genes, including six missense mutations in BDNF, FTO, LEP, LEPR, and PCSK1 and, notably, one nonsense mutation in LEPR. Conclusions: A moderate polygenic contribution to adiposity in rhesus macaques was found, as well as mutations with potentially larger effects in multiple genes that influence obesity in humans

    Spectral Typing of Late Type Stellar Companions to Young Stars from Low Dispersion Near-Infrared Integral Field Unit Data

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    We used the Project 1640 near-infrared coronagraph and integral field spectrograph to observe 19 young solar type stars. Five of these stars are known binary stars and we detected the late-type secondaries and were able to measure their JH spectra with a resolution of R\sim30. The reduced, extracted, and calibrated spectra were compared to template spectra from the IRTF spectral library. With this comparison we test the accuracy and consistency of spectral type determination with the low-resolution near-infrared spectra from P1640. Additionally, we determine effective temperature and surface gravity of the companions by fitting synthetic spectra calculated with the PHOENIX model atmosphere code. We also present several new epochs of astrometry of each of the systems. Together these data increase our knowledge and understanding of the stellar make up of these systems. In addition to the astronomical results, the analysis presented helps validate the Project 1640 data reduction and spectral extraction processes and the utility of low-resolution, near-infrared spectra for characterizing late-type companions in multiple systems.Comment: Accepted to Astronomical Journal, 25 pages, 8 figure

    Direct Spectrum of the Benchmark T Dwarf HD 19467 B

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    HD 19467 B is presently the only directly imaged T dwarf companion known to induce a measurable Doppler acceleration around a solar-type star. We present spectroscopy measurements of this important benchmark object taken with the Project 1640 integral field unit at Palomar Observatory. Our high-contrast R ≈ 30 observations obtained simultaneously across the JH bands confirm the cold nature of the companion as reported from the discovery article and determine its spectral type for the first time. Fitting the measured spectral energy distribution to SpeX/IRTF T dwarf standards and synthetic spectra from BT-Settl atmospheric models, we find that HD 19467 B is a T5.5 ± 1 dwarf with effective temperature T_eff=978^(+20)_(-43) K. Our observations reveal significant methane absorption affirming its substellar nature. HD 19467 B shows promise to become the first T dwarf that simultaneously reveals its mass, age, and metallicity independent from the spectrum of light that it emits

    Communications Biophysics

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    Contains research objectives, summary of research and reports on four research projects.National Institutes of Health (Grant 5 P01 GM14940-05)National Institutes of Health (Grant 5 TOl GM01555-05)National Aeronautics and Space Administration (Grant NGL 22-009-304)B-D ElectrodyneBoston City Hospital Purchase Order 1065

    Imaging Cyclic AMP Changes in Pancreatic Islets of Transgenic Reporter Mice

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    Cyclic AMP (cAMP) and Ca2+ are two ubiquitous second messengers in transduction pathways downstream of receptors for hormones, neurotransmitters and local signals. The availability of fluorescent Ca2+ reporter dyes that are easily introduced into cells and tissues has facilitated analysis of the dynamics and spatial patterns for Ca2+ signaling pathways. A similar dissection of the role of cAMP has lagged because indicator dyes do not exist. Genetically encoded reporters for cAMP are available but they must be introduced by transient transfection in cell culture, which limits their utility. We report here that we have produced a strain of transgenic mice in which an enhanced cAMP reporter is integrated in the genome and can be expressed in any targeted tissue and with tetracycline induction. We have expressed the cAMP reporter in β-cells of pancreatic islets and conducted an analysis of intracellular cAMP levels in relation to glucose stimulation, Ca2+ levels, and membrane depolarization. Pancreatic function in transgenic mice was normal. In induced transgenic islets, glucose evoked an increase in cAMP in β-cells in a dose-dependent manner. The cAMP response is independent of (in fact, precedes) the Ca2+ influx that results from glucose stimulation of islets. Glucose-evoked cAMP responses are synchronous in cells throughout the islet and occur in 2 phases suggestive of the time course of insulin secretion. Insofar as cAMP in islets is known to potentiate insulin secretion, the novel transgenic mouse model will for the first time permit detailed analyses of cAMP signals in β-cells within islets, i.e. in their native physiological context. Reporter expression in other tissues (such as the heart) where cAMP plays a critical regulatory role, will permit novel biomedical approaches

    Observation of the decay BcJ/ψK+Kπ+B_c \rightarrow J/\psi K^+ K^- \pi^+

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    The decay BcJ/ψK+Kπ+B_c\rightarrow J/\psi K^+ K^- \pi^+ is observed for the first time, using proton-proton collisions collected with the LHCb detector corresponding to an integrated luminosity of 3fb1^{-1}. A signal yield of 78±1478\pm14 decays is reported with a significance of 6.2 standard deviations. The ratio of the branching fraction of \B_c \rightarrow J/\psi K^+ K^- \pi^+ decays to that of BcJ/ψπ+B_c \rightarrow J/\psi \pi^+ decays is measured to be 0.53±0.10±0.050.53\pm 0.10\pm0.05, where the first uncertainty is statistical and the second is systematic.Comment: 18 pages, 2 figure
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