Pericardial Fat and Myocardial Perfusion in Asymptomatic Adults from the Multi-Ethnic Study of Atherosclerosis

BACKGROUND:Pericardial fat has adverse effects on the surrounding vasculature. Previous studies suggest that pericardial fat may contribute to myocardial ischemia in symptomatic individuals. However, it is unknown if pericardial fat has similar effects in asymptomatic individuals. METHODS:We determined the association between pericardial fat and myocardial blood flow (MBF) in 214 adults with no prior history of cardiovascular disease from the Minnesota field center of the Multi-Ethnic Study of Atherosclerosis (43% female, 56% Caucasian, 44% Hispanic). Pericardial fat volume was measured by computed tomography. MBF was measured by MRI at rest and during adenosine-induced hyperemia. Myocardial perfusion reserve (PR) was calculated as the ratio of hyperemic to resting MBF. RESULTS:Gender-stratified analyses revealed significant differences between men and women including less pericardial fat (71.9±31.3 vs. 105.2±57.5 cm(3), p<0.0001) and higher resting MBF (1.12±0.23 vs. 0.93±0.19 ml/min/g, p<0.0001), hyperemic MBF (3.49±0.76 vs. 2.65±0.72 ml/min/g, p<0.0001), and PR (3.19±0.78 vs. 2.93±0.89, p = 0.03) in women. Correlations between pericardial fat and clinical and hemodynamic variables were stronger in women. In women only (p = 0.01 for gender interaction) higher pericardial fat was associated with higher resting MBF (p = 0.008). However, this association was attenuated after accounting for body mass index or rate-pressure product. There were no significant associations between pericardial fat and hyperemic MBF or PR after multivariate adjustment in either gender. In logistic regression analyses there was also no association between impaired coronary vasoreactivity, defined as having a PR <2.5, and pericardial fat in men (OR, 1.18; 95% CI, 0.82-1.70) or women (OR, 1.11; 95% CI, 0.68-1.82). CONCLUSIONS:Our data fail to support an independent association between pericardial fat and myocardial perfusion in adults without symptomatic cardiovascular disease. Nevertheless, these findings highlight potentially important differences between asymptomatic and symptomatic individuals with respect to the underlying subclinical disease burden

Bone-forming perivascular cells: Cellular heterogeneity and use for tissue repair

: Mesenchymal progenitor cells are broadly distributed across perivascular niches-an observation conserved between species. One common histologic zone with a high frequency of mesenchymal progenitor cells within mammalian tissues is the tunica adventitia, the outer layer of blood vessel walls populated by cells with a fibroblastic morphology. The diversity and functions of (re)generative cells present in this outermost perivascular niche are under intense investigation; we have reviewed herein our current knowledge of adventitial cell potential with a somewhat narrow focus on bone formation. Antigens of interest to functionally segregate adventicytes are discussed, including CD10, CD107a, aldehyde dehydrogenase isoforms, and CD140a, among others. Purified adventicytes (such as CD10+ , CD107alow , and CD140a+ cells) have stronger osteogenic potential and promote bone formation in vivo. Recent bone tissue engineering applications of adventitial cells are also presented. A better understanding of perivascular progenitor cell subsets may represent a beneficial advance for future efforts in tissue repair and bioengineering

A Compact Cold-Atom Interferometer with a High Data-Rate Grating Magneto-Optical Trap and a Photonic-Integrated-Circuit-Compatible Laser System

The extreme miniaturization of a cold-atom interferometer accelerometer requires the development of novel technologies and architectures for the interferometer subsystems. Here we describe several component technologies and a laser system architecture to enable a path to such miniaturization. We developed a custom, compact titanium vacuum package containing a microfabricated grating chip for a tetrahedral grating magneto-optical trap (GMOT) using a single cooling beam. In addition, we designed a multi-channel photonic-integrated-circuit-compatible laser system implemented with a single seed laser and single sideband modulators in a time-multiplexed manner, reducing the number of optical channels connected to the sensor head. In a compact sensor head containing the vacuum package, sub-Doppler cooling in the GMOT produces 15 uK temperatures, and the GMOT can operate at a 20 Hz data rate. We validated the atomic coherence with Ramsey interferometry using microwave spectroscopy, then demonstrated a light-pulse atom interferometer in a gravimeter configuration for a 10 Hz measurement data rate and T = 0 - 4.5 ms interrogation time, resulting in $\Delta$ g / g = 2.0e-6. This work represents a significant step towards deployable cold-atom inertial sensors under large amplitude motional dynamics.Comment: 21 pages, 10 figure

Decline in vaccine-type human papillomavirus prevalence in young men from a Midwest metropolitan area of the United States over the six years after vaccine introduction

Purpose: The aim of this study was to determine changes in human papillomavirus (HPV) prevalence among young men from a Midwest metropolitan area over the six years after vaccine introduction, including HPV prevalence in men overall, in vaccinated men to examine vaccine impact and in unvaccinated men to examine herd protection. An exploratory aim was to examine associations between number of vaccine doses and HPV prevalence. Methods: Men aged 14–26 years reporting male-female and/or male-male sexual contact were recruited from a primary care clinic, sexually transmitted disease clinic, and community setting during two waves of data collection: 2013–2014 (N = 400) and 2016–2017 (N = 347). Participants completed a questionnaire and were tested for penile, scrotal and anal HPV. Changes in prevalence of any (≥1 type) and vaccine-type HPV (HPV6, 11, 16, and/or 18) were examined using propensity score weighted logistic regression. Associations between number of doses and HPV infection were determined using chi-square tests and logistic regression. Results: The proportion of men with a history of ≥1 HPV vaccine doses increased from 23% to 44% (p < 0.001) from waves 1 to 2. After propensity score weighting, infection with ≥1 vaccine-type HPV significantly decreased among all men (29% to 20%; 31% decrease; odds ratio [OR] = 0.62, 95% confidence interval [CI] = 0.44–0.88) and unvaccinated men (32% to 21%; 36% decrease; OR = 0.56, 95%CI = 0.34–0.86); there was a non-significant decrease (21%) among vaccinated men. Associations between number of doses and HPV prevalence were not statistically significant. Conclusions: Prevalence of vaccine-type HPV decreased among all, vaccinated, and unvaccinated men six years after HPV vaccine recommendation, supporting vaccine impact and herd protection. Decreases in vaccine-type HPV in all men appear to be due to decreases in unvaccinated men, suggesting that the full impact of vaccination has yet to be realized. Continued monitoring and efforts to vaccinate men prior to sexual initiation are warranted

METTL15 introduces N4-methylcytidine into human mitochondrial 12S rRNA and is required for mitoribosome biogenesis.

Post-transcriptional RNA modifications, the epitranscriptome, play important roles in modulating the functions of RNA species. Modifications of rRNA are key for ribosome production and function. Identification and characterization of enzymes involved in epitranscriptome shaping is instrumental for the elucidation of the functional roles of specific RNA modifications. Ten modified sites have been thus far identified in the mammalian mitochondrial rRNA. Enzymes responsible for two of these modifications have not been characterized. Here, we identify METTL15, show that it is the main N4-methylcytidine (m4C) methyltransferase in human cells and demonstrate that it is responsible for the methylation of position C839 in mitochondrial 12S rRNA. We show that the lack of METTL15 results in a reduction of the mitochondrial de novo protein synthesis and decreased steady-state levels of protein components of the oxidative phosphorylation system. Without functional METTL15, the assembly of the mitochondrial ribosome is decreased, with the late assembly components being unable to be incorporated efficiently into the small subunit. We speculate that m4C839 is involved in the stabilization of 12S rRNA folding, therefore facilitating the assembly of the mitochondrial small ribosomal subunits. Taken together our data show that METTL15 is a novel protein necessary for efficient translation in human mitochondria.Medical Research Council, UK [MC_UU_00015/4]; EMBO [ALFT 701-2013 to L.V.H]; ‘Fundação para a Ciência e a Tecnologia’ [PD/BD/105750/2014 to P.R.-G.]

Heavy quarkonium: progress, puzzles, and opportunities

A golden age for heavy quarkonium physics dawned a decade ago, initiated by the confluence of exciting advances in quantum chromodynamics (QCD) and an explosion of related experimental activity. The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress. However, the broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles could only be partially anticipated. Since the release of the YR, the BESII program concluded only to give birth to BESIII; the $B$-factories and CLEO-c flourished; quarkonium production and polarization measurements at HERA and the Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the deconfinement regime. All these experiments leave legacies of quality, precision, and unsolved mysteries for quarkonium physics, and therefore beg for continuing investigations. The plethora of newly-found quarkonium-like states unleashed a flood of theoretical investigations into new forms of matter such as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b}, and b\bar{c} bound states have been shown to validate some theoretical approaches to QCD and highlight lack of quantitative success for others. The intriguing details of quarkonium suppression in heavy-ion collisions that have emerged from RHIC have elevated the importance of separating hot- and cold-nuclear-matter effects in quark-gluon plasma studies. This review systematically addresses all these matters and concludes by prioritizing directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K. Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D. Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A. Petrov, P. Robbe, A. Vair

DESI Survey Validation Data in the COSMOS/Hyper Suprime-Cam Field: Cool Gas Trace Main-sequence Star-forming Galaxies at the Cosmic Noon

We present the first result in exploring the gaseous halo and galaxy correlation using the Dark Energy Spectroscopic Instrument survey validation data in the Cosmic Evolution Survey (COSMOS) and Hyper Suprime-Cam field. We obtain multiphase gaseous halo properties in the circumgalactic medium by using 115 quasar spectra (signal-to-noise ratio > 3). We detect Mg ii absorption at redshift 0.6 < z < 2.5, C iv absorption at 1.6 < z < 3.6, and H i absorption associated with the Mg ii and C iv. By crossmatching the COSMOS2020 catalog, we identify the Mg ii and C iv host galaxies in 10 quasar fields at 0.9< z < 3.1. We find that within the impact parameter of 250 kpc, a tight correlation is seen between the strong Mg ii equivalent width and the host galaxy star formation rate. The covering fraction f c of the strong Mg ii selected galaxies, which is the ratio of the absorbing galaxy in a certain galaxy population, shows significant evolution in the main-sequence galaxies and marginal evolution in all the galaxy populations within 250 kpc at 0.9 < z < 2.2. The f c increase in the main-sequence galaxies likely suggests the coevolution of strong Mg ii absorbing gas and the main-sequence galaxies at the cosmic noon. Furthermore, Mg ii and C iv absorbing gas is detected out of the galaxy virial radius, tentatively indicating the feedback produced by the star formation and/or the environmental effects

Crystal engineering of HIV-1 reverse transcriptase for structure-based drug design

HIV-1 reverse transcriptase (RT) is a primary target for anti-AIDS drugs. Structures of HIV-1 RT, usually determined at ∼2.5–3.0 Å resolution, are important for understanding enzyme function and mechanisms of drug resistance in addition to being helpful in the design of RT inhibitors. Despite hundreds of attempts, it was not possible to obtain the structure of a complex of HIV-1 RT with TMC278, a nonnucleoside RT inhibitor (NNRTI) in advanced clinical trials. A systematic and iterative protein crystal engineering approach was developed to optimize RT for obtaining crystals in complexes with TMC278 and other NNRTIs that diffract X-rays to 1.8 Å resolution. Another form of engineered RT was optimized to produce a high-resolution apo-RT crystal form, reported here at 1.85 Å resolution, with a distinct RT conformation. Engineered RTs were mutagenized using a new, flexible and cost effective method called methylated overlap-extension ligation independent cloning. Our analysis suggests that reducing the solvent content, increasing lattice contacts, and stabilizing the internal low-energy conformations of RT are critical for the growth of crystals that diffract to high resolution. The new RTs enable rapid crystallization and yield high-resolution structures that are useful in designing/developing new anti-AIDS drugs