Placental opioid-enhancing factor (POEF): Generalizability of effects

A substance in amniotic fluid and placenta (POEF for Placental Opioid-Enhancing Factor) has been shown to enhance opiate- or opioid-mediated analgesia in rats. Recent studies have only touched on the generalizability of the phenomenon. The present studies further tested the generalizability of the POEF effect: they examined sex specificity of the mechanism, whether POEF activity exists in afterbirth material of species other than the rat; whether POEF activity exists in tissue other than afterbirth material; whether POEF activity could be demonstrated after injection rather than ingestion of afterbirth material; and whether POEF enhances all opioid-mediated phenomena. We found that (a) POEF is effective in male rats as well as in female rats; (b) POEF activity exists in human and dolphin afterbirth material; (c) ingestion of pregnant-rat liver does not produce enhancement of opioid-mediated analgesia; (d) POEF does not seem to be effective when amniotic fluid is injected either IPO or SC; and (e) POEF does not modify morphine-induced hyperthermia

The European Solar Telescope

The European Solar Telescope (EST) is a project aimed at studying the magnetic connectivity of the solar atmosphere, from the deep photosphere to the upper chromosphere. Its design combines the knowledge and expertise gathered by the European solar physics community during the construction and operation of state-of-the-art solar telescopes operating in visible and near-infrared wavelengths: the Swedish 1m Solar Telescope, the German Vacuum Tower Telescope and GREGOR, the French Télescope Héliographique pour l'Étude du Magnétisme et des Instabilités Solaires, and the Dutch Open Telescope. With its 4.2 m primary mirror and an open configuration, EST will become the most powerful European ground-based facility to study the Sun in the coming decades in the visible and near-infrared bands. EST uses the most innovative technological advances: the first adaptive secondary mirror ever used in a solar telescope, a complex multi-conjugate adaptive optics with deformable mirrors that form part of the optical design in a natural way, a polarimetrically compensated telescope design that eliminates the complex temporal variation and wavelength dependence of the telescope Mueller matrix, and an instrument suite containing several (etalon-based) tunable imaging spectropolarimeters and several integral field unit spectropolarimeters. This publication summarises some fundamental science questions that can be addressed with the telescope, together with a complete description of its major subsystems

A draft human pangenome reference

Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample

Genetic insights into resting heart rate and its role in cardiovascular disease.

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development