Nuclear receptors and their coregulators in kidney

Nuclear receptors and their coregulators in kidney. Nuclear receptors are transcription factors that are essential in embryonic development, maintenance of differentiated cellular phenotypes, metabolism, and apoptosis. Dysfunction of nuclear receptor signaling leads to a wide spectra of proliferative, reproductive, and metabolic diseases, including cancers, infertility, obesity, and diabetes. In addition, many proteins have been identified as coregulators which can be recruited by DNA-binding nuclear receptors to affect transcriptional regulation. The cellular level of coregulators is crucial for nuclear receptor-mediated transcription and many coregulators have been shown to be targets for diverse intracellular signaling pathways and posttranslational modifications. This review provides a general overview of the roles and mechanism of action of nuclear receptors and their coregulators. Since progression of renal diseases is almost always associated with inflammatory processes and/or involve metabolic disorders of lipid and glucose, cell proliferation, hypertrophy, apoptosis, and hypertension, the importance of nuclear receptors and their coregulators in these contexts will be addressed

Inflammatory stress exacerbates ectopic lipid deposition in C57BL/6J mice

<p>Abstract</p> <p>Background</p> <p>Chronic systemic inflammation and abnormal free fatty acid metabolism are closely related to ectopic lipid deposition. In this study, we investigate if inflammation tissue-specifically disrupts lipogenesis and lipolysis in nonadipose tissues and adipose tissue, resulting in ectopic lipid deposition in C57BL/6J mice.</p> <p>Methods</p> <p>We used casein injection in C57BL/6J mice to induce a chronic systemic inflammatory stress in vivo. Serum was analyzed for free fatty acid and cytokines. Insulin sensitivities were evaluated by glucose and insulin tolerance tests. Liver, muscle, adipose tissues were taken for lipid analysis. Real-time polymerase chain reaction and western blotting were used to examine the gene and protein expression of molecules involved in adipogenesis and lipolysis in tissues.</p> <p>Results</p> <p>Casein injection elevated serum levels of IL-6 and SAA in mice, which are associated with increased lipid accumulation in liver and muscle, suggesting that chronic systemic inflammation induces ectopic lipid deposition in nonadipose tissues. The inflammatory stress upregulated mRNA and protein expression of sterol regulatory element binding protein 1, fatty acid synthase, and acetyl CoA carboxylase alpha, while inhibited these molecules expression in adipose. Interestingly, in the same experimental setting, inflammation increased triglyceride lipase and hormone-sensitive lipase expression in white adipose tissue. Inflammation also induced insulin resistance and increased serum free fatty acid levels in C57BL/6J mice.</p> <p>Conclusions</p> <p>Chronic systemic inflammation increased lipogenesis in nonadipose tissues and lipolysis in white adipose tissue, resulting in ectopic lipid deposition in nonadipose tissues. This disturbed free fatty acid homeostasis and caused insulin resistance in C57BL/6J mice.</p

Planet Occurrence within 0.25 AU of Solar-type Stars from Kepler

We report the distribution of planets as a function of planet radius (R_p), orbital period (P), and stellar effective temperature (Teff) for P < 50 day orbits around GK stars. These results are based on the 1,235 planets (formally "planet candidates") from the Kepler mission that include a nearly complete set of detected planets as small as 2 Earth radii (Re). For each of the 156,000 target stars we assess the detectability of planets as a function of R_p and P. We also correct for the geometric probability of transit, R*/a. We consider first stars within the "solar subset" having Teff = 4100-6100 K, logg = 4.0-4.9, and Kepler magnitude Kp < 15 mag. We include only those stars having noise low enough to permit detection of planets down to 2 Re. We count planets in small domains of R_p and P and divide by the included target stars to calculate planet occurrence in each domain. Occurrence of planets varies by more than three orders of magnitude and increases substantially down to the smallest radius (2 Re) and out to the longest orbital period (50 days, ~0.25 AU) in our study. For P < 50 days, the radius distribution is given by a power law, df/dlogR= k R^\alpha. This rapid increase in planet occurrence with decreasing planet size agrees with core-accretion, but disagrees with population synthesis models. We fit occurrence as a function of P to a power law model with an exponential cutoff below a critical period P_0. For smaller planets, P_0 has larger values, suggesting that the "parking distance" for migrating planets moves outward with decreasing planet size. We also measured planet occurrence over Teff = 3600-7100 K, spanning M0 to F2 dwarfs. The occurrence of 2-4 Re planets in the Kepler field increases with decreasing Teff, making these small planets seven times more abundant around cool stars than the hottest stars in our sample. [abridged]Comment: Submitted to ApJ, 22 pages, 10 figure

Weight Care Project: Health professionals' attitudes and ability to assess body weight status - Study protocol

<p>Abstract</p> <p>Background</p> <p>Health professionals working in primary care and public health have opportunities to address body weight status issues with their patients through face-to-face contact. The objectives of this all-Ireland project are: 1. to assess the attitudes, current practices/behaviours and knowledge of key health professional groups on body weight status; 2. to assess the health professional groups' ability to identify body weight status in both adults and children. The health professional groups are: (a) community related public health nurses; (b) school public health nurses; (c) GPs and practice nurses (primary care); and (d) occupational health nurses (workplace) from both Northern Ireland and the Republic of Ireland.</p> <p>Methods/Design</p> <p>This all-Ireland multi-disciplinary project follows a mixed methods approach using both quantitative and qualitative methodologies, and consists of four components:</p> <p>1. Literature review - to explore the role of health professionals in managing obesity through spontaneous intervention in a variety of health promotion settings.</p> <p>2. Telephone interviews and focus groups - to gain an in-depth insight into the views of health professionals in assessing body weight status.</p> <p>3. Survey (primarily online but also paper-based) - to determine the attitudes, current practices/behaviours and knowledge of health professionals in assessing body weight status.</p> <p>4. Online evaluation study - an online interactive programme will be developed to assess health professionals' ability to identify the body weight status of adults and children.</p> <p>Discussion</p> <p>This project will assess and report the attitudes, current practices/behaviours and knowledge of key health professional groups within Northern Ireland and the Republic of Ireland on body weight status, and their ability to identify body weight status in both adults and children. The results of this project will generate recommendations for clinical practice in managing obesity, which may inform policy guidelines.</p

Transit Timing Observations from Kepler: IV. Confirmation of 4 Multiple Planet Systems by Simple Physical Models

Eighty planetary systems of two or more planets are known to orbit stars other than the Sun. For most, the data can be sufficiently explained by non-interacting Keplerian orbits, so the dynamical interactions of these systems have not been observed. Here we present 4 sets of lightcurves from the Kepler spacecraft, which each show multiple planets transiting the same star. Departure of the timing of these transits from strict periodicity indicates the planets are perturbing each other: the observed timing variations match the forcing frequency of the other planet. This confirms that these objects are in the same system. Next we limit their masses to the planetary regime by requiring the system remain stable for astronomical timescales. Finally, we report dynamical fits to the transit times, yielding possible values for the planets' masses and eccentricities. As the timespan of timing data increases, dynamical fits may allow detailed constraints on the systems' architectures, even in cases for which high-precision Doppler follow-up is impractical.Comment: In the proofs process, corrections were made to tables -- most crucially, the timing data for Kepler-30b and the depths and radii of planets in Kepler-31 and 3

THE APOGEE SPECTROSCOPIC SURVEY OF KEPLER PLANET HOSTS: FEASIBILITY, EFFICIENCY, AND FIRST RESULTS

The Kepler mission has yielded a large number of planet candidates from among the Kepler Objects of Interest(KOIs), but spectroscopic follow-up of these relatively faint stars is a serious bottleneck in confirming and characterizing these systems. We present motivation and survey design for an ongoing project with the Sloan Digital Sky Survey III multiplexed Apache Point Observatory Galactic Evolution Experiment (APOGEE) near-infrared spectrograph to monitor hundreds of KOI host stars. We report some of our first results using representative targets from our sample, which include current planet candidates that we find to be false positives, as well as candidates listed as false positives that we do not find to be spectroscopic binaries. With this survey, KOI hosts are observed over ∼20 epochs at a radial velocity (RV) precision of 100–200ms−1. These observations can easily identify a majority of false positives caused by physically associated stellar or substellar binaries, and in many cases, fully characterize their orbits. We demonstrate that APOGEE is capable of achieving RV precision at the 100–200ms−1 level over long time baselines, and that APOGEE’s multiplexing capability makes it substantially more efficient at identifying false positives due to binaries than other single-object spectrographs working to confirm KOIs as planets. These APOGEE RVs enable ancillary science projects, such as studies of fundamental stellar astrophysics or intrinsically rare substellar companions. The coadded APOGEE spectra can be used to derive stellar properties (Teff, log g) and chemical abundances of over a dozen elements to probe correlations of planet properties with individual elemental abundances

The Physics of the B Factories

This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C

Transit timing observations from Kepler. IV. Confirmation of four multiple-planet systems by simple physical models

Eighty planetary systems of two or more planets are known to orbit stars other than the Sun. For most, the data can be sufficiently explained by non-interacting Keplerian orbits, so the dynamical interactions of these systems have not been observed. Here we present four sets of light curves from the Kepler spacecraft, each which of shows multiple planets transiting the same star. Departure of the timing of these transits from strict periodicity indicates that the planets are perturbing each other: the observed timing variations match the forcing frequency of the other planet. This confirms that these objects are in the same system. Next we limit their masses to the planetary regime by requiring the system remain stable for astronomical timescales. Finally, we report dynamical fits to the transit times, yielding possible values for the planets' masses and eccentricities. As the timespan of timing data increases, dynamical fits may allow detailed constraints on the systems' architectures, even in cases for which high-precision Doppler follow-up is impractical