Previous studies of body fat using tape measurement of body circumference and hand-held caliper skinfold measurements have suggested abnormal fat distribution in patients with diabetes mellitus. ...These methods, however, have high interobserver variability and cannot assess intra-abdominal fat independent of subcutaneous fat. We used computed tomography to evaluate body fat distribution in a group of 53 Japanese-American men of similar age and body mass index (weight divided by height squared). As determined by a 75-g oral glucose tolerance test, 29 subjects had type II diabetes and 24 were normal. Computed tomography cuts were obtained at three body levels to measure thorax, abdomen, and thigh subcutaneous fat area as well as intra-abdominal fat area. We found greater intra-abdominal fat in men with diabetes than in those without (123.74 vs. 95.54 cm2, P = 0.034) and a greater ratio of thorax to thigh subcutaneous fat (2.55 vs. 1.88, P = 0.016). These findings support the hypothesis that fat in different areas of the body differs metabolically. Computed tomography can be a useful tool for investigating whether abnormal body fat distribution is associated with the pathogenesis of abnormal glucose tolerance.
We present observations and timing analyses of 68 millisecond pulsars (MSPs) comprising the 15-year data set of the North American Nanohertz Observatory for Gravitational Waves (NANOGrav). NANOGrav ...is a pulsar timing array (PTA) experiment that is sensitive to low-frequency gravitational waves. This is NANOGrav's fifth public data release, including both "narrowband" and "wideband" time-of-arrival (TOA) measurements and corresponding pulsar timing models. We have added 21 MSPs and extended our timing baselines by three years, now spanning nearly 16 years for some of our sources. The data were collected using the Arecibo Observatory, the Green Bank Telescope, and the Very Large Array between frequencies of 327 MHz and 3 GHz, with most sources observed approximately monthly. A number of notable methodological and procedural changes were made compared to our previous data sets. These improve the overall quality of the TOA data set and are part of the transition to new pulsar timing and PTA analysis software packages. For the first time, our data products are accompanied by a full suite of software to reproduce data reduction, analysis, and results. Our timing models include a variety of newly detected astrometric and binary pulsar parameters, including several significant improvements to pulsar mass constraints. We find that the time series of 23 pulsars contain detectable levels of red noise, 10 of which are new measurements. In this data set, we find evidence for a stochastic gravitational-wave background.
There is an unmet need and urgency to find safe and effective anti-obesity interventions. Our recent study in mice fed on obesogenic diet found that treatment with the alcohol aversive drug ...disulfiram reduced feeding efficiency and led to a decrease in body weight and an increase in energy expenditure. The intervention with disulfiram improved glucose tolerance and insulin sensitivity, and mitigated metabolic dysfunctions in various organs through poorly defined mechanisms. Here, integrated analysis of transcriptomic and proteomic data from mouse and rat livers unveiled comparable signatures in response to disulfiram, revealing pathways associated with lipid and energy metabolism, redox, and detoxification. In cell culture, disulfiram was found to be a potent activator of autophagy, the malfunctioning of which has negative consequences on metabolic regulation. Thus, repurposing disulfiram may represent a potent strategy to combat obesity.
We report results from continued timing observations of PSR J0740+6620, a high-mass, 2.8-ms radio pulsar in orbit with a likely ultra-cool white dwarf companion. Our data set consists of combined ...pulse arrival-time measurements made with the 100-m Green Bank Telescope and the Canadian Hydrogen Intensity Mapping Experiment telescope. We explore the significance of timing-based phenomena arising from general-relativistic dynamics and variations in pulse dispersion. When using various statistical methods, we find that combining \(\sim 1.5\) years of additional, high-cadence timing data with previous measurements confirms and improves upon previous estimates of relativistic effects within the PSR J0740+6620 system, with the pulsar mass \(m_{\rm p} = 2.08^{+0.07}_{-0.07}\) M\(_\odot\) (68.3\% credibility) determined by the relativistic Shapiro time delay. For the first time, we measure secular variation in the orbital period and argue that this effect arises from apparent acceleration due to significant transverse motion. After incorporating contributions from Galactic differential rotation and off-plane acceleration in the Galactic potential, we obtain a model-dependent distance of \(d = 1.14^{+0.17}_{-0.15}\) kpc (68.3\% credibility). This improved distance confirms the ultra-cool nature of the white dwarf companion determined from recent optical observations. We discuss the prospects for future observations with next-generation facilities, which will likely improve the precision on \(m_{\rm p}\) for J0740+6620 by an order of magnitude within the next few years.
We readily produced recombinant pro-macrophage stimulating protein in a mammalian expression system, but it was only weakly active after proteolytic activation. Active macrophage stimulating protein ...is a disulfide-bonded heterodimer, but in our hands, the subunits of recombinant macrophage stimulating protein were mostly not disulfide bonded. Molecular modeling of the serine proteinase domain of macrophage stimulating protein based on homology to human trypsin suggested that macrophage stimulating protein, but not plasminogen or hepatocyte growth factor, has a Cys residue (672) in close proximity to the Cys residue (578) that forms the intersubunit disulfide link with the other subunit. We hypothesized that Cys672 might interfere with intersubunit disulfide formation by forming an intrasubunit disulfide with Cys578 and therefore mutated Cys672 to Ala. After kallikrein activation, the subunits of Cys672 → Ala macrophage stimulating protein were fully disulfide linked, and the mutant macrophage stimulating protein had 10–20-fold higher specific activity than the wild type recombinant macrophage stimulating protein.
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