Ovulation suppression protects against chromosomal abnormalities in mouse eggs at advanced maternal age

The frequency of egg aneuploidy and trisomic pregnancies increases with maternal age. To what extent individual approaches can delay the "maternal age effect"is unclear because multiple causes contribute to chromosomal abnormalities in mammalian eggs. We propose that ovulation frequency determines the physiological aging of oocytes, a key aspect of which is the ability to accurately segregate chromosomes and produce euploid eggs. To test this hypothesis, ovulations were reduced using successive pregnancies, hormonal contraception, and a pre-pubertal knockout mouse model, and the effects on chromosome segregation and egg ploidy were examined. We show that each intervention reduces chromosomal abnormalities in eggs of aged mice, suggesting that ovulation reduction delays oocyte aging. The protective effect can be partly explained by retention of chromosomal Rec8-cohesin that maintains sister chromatid cohesion in meiosis. In addition, single-nucleus Hi-C (snHi-C) revealed deterioration in the 3D chromatin structure including an increase in extruded loop sizes in long-lived oocytes. Artificial cleavage of Rec8 is sufficient to increase extruded loop sizes, suggesting that cohesin complexes maintaining cohesion restrict loop extrusion. These findings suggest that ovulation suppression protects against Rec8 loss, thereby maintaining both sister chromatid cohesion and 3D chromatin structure and promoting production of euploid eggs. We conclude that the maternal age effect can be delayed in mice. An implication of this work is that long-term ovulation-suppressing conditions can potentially reduce the risk of aneuploid pregnancies at advanced maternal age

Polyimide hollow fiber membranes for CO2 separation from wet gas mixtures

Matrimid®5218 hollow fiber membranes were prepared using the dry-wet spinning process. The transport properties were measured with pure gases (H2, CO2, N2, CH4 and O2) and with a mixture (30% CO2 and 70% N2) in dry and wet conditions at 25 ºC, 50 ºC, 60 ºC and 75 ºC and up to 600 kPa. Interesting values of single gas selectivity up to 60 ºC (between 31 and 28 for CO2/N2 and between 33 and 30 for CO2/CH4) in dry condition were obtained. The separation factor measured for the mixture was 20% lower compared to the single gas selectivity, in the whole temperature range analyzed. In saturation conditions the data showed that water influences the performance of the membranes, inducing a reduction of the permeance of all gases. Moreover, the presence of water caused a decrease of single gas selectivity and separation factor, although not so significant, highlighting the very high water resistance of hollow fiber membrane modules

Genome-Wide SNP-genotyping array to study the evolution of the human pathogen Vibrio vulnificus Biotype 3

Vibrio vulnificus is an aquatic bacterium and an important human pathogen. Strains Of V. vulnificus are classified into three different biotypes. The newly emerged biotype 3 has been found to be clonal and restricted to Israel. In the family Vibrionaceae , horizontal gene transfer is the main mechanism responsible for the emergence of new pathogen groups. To better understand the evolution of the bacterium, and in particular to trace the evolution of biotype 3, we performed genome-wide SNP genotyping of 254 clinical and environmental V. vulnificus isolates with worldwide distribution recovered over a 30-year period, representing all phylogeny groups. A custom single-nucleotide polymorphism (SNP) array implemented on the Illumina GoldenGate platform was developed based on 570 SNPs randomly distributed throughout the genome. In general, the genotyping results divided the V. vulnificus species into three main phylogenetic lineages and an additional subgroup, clade B, consisting of environmental and clinical isolates from Israel. Data analysis suggested that 69% of biotype 3 SNPs are similar to SNPs from clade B, indicating that biotype 3 and clade B have a common ancestor. The rest of the biotype 3 SNPs were scattered along the biotype 3 genome, probably representing multiple chromosomal segments that may have been horizontally inserted into the clade B recipient core genome from other phylogroups or bacterial species sharing the same ecological niche. Results emphasize the continuous evolution of V. vulnificus and support the emergence of new pathogenic groups within this species as a recurrent phenomenon. Our findings contribute to a broader understanding of the evolution of this human pathogen

INFOGEST static in vitro simulation of gastrointestinal food digestion

peer-reviewedSupplementary information is available at http://dx.doi.org/10.1038/s41596-018-0119-1 or https://www.nature.com/articles/s41596-018-0119-1#Sec45.Developing a mechanistic understanding of the impact of food structure and composition on human health has increasingly involved simulating digestion in the upper gastrointestinal tract. These simulations have used a wide range of different conditions that often have very little physiological relevance, and this impedes the meaningful comparison of results. The standardized protocol presented here is based on an international consensus developed by the COST INFOGEST network. The method is designed to be used with standard laboratory equipment and requires limited experience to encourage a wide range of researchers to adopt it. It is a static digestion method that uses constant ratios of meal to digestive fluids and a constant pH for each step of digestion. This makes the method simple to use but not suitable for simulating digestion kinetics. Using this method, food samples are subjected to sequential oral, gastric and intestinal digestion while parameters such as electrolytes, enzymes, bile, dilution, pH and time of digestion are based on available physiological data. This amended and improved digestion method (INFOGEST 2.0) avoids challenges associated with the original method, such as the inclusion of the oral phase and the use of gastric lipase. The method can be used to assess the endpoints resulting from digestion of foods by analyzing the digestion products (e.g., peptides/amino acids, fatty acids, simple sugars) and evaluating the release of micronutrients from the food matrix. The whole protocol can be completed in ~7 d, including ~5 d required for the determination of enzyme activities.COST action FA1005 INFOGEST (http://www.cost-infogest.eu/ ) is acknowledged for providing funding for travel, meetings and conferences (2011-2015). The French National Institute for Agricultural Research (INRA, www.inra.fr) is acknowledged for their continuous support of the INFOGEST network by organising and co-funding the International Conference on Food Digestion and workgroup meeting

Is diet partly responsible for differences in COVID-19 death rates between and within countries?

Correction: Volume: 10 Issue: 1 Article Number: 44 DOI: 10.1186/s13601-020-00351-w Published: OCT 26 2020Reported COVID-19 deaths in Germany are relatively low as compared to many European countries. Among the several explanations proposed, an early and large testing of the population was put forward. Most current debates on COVID-19 focus on the differences among countries, but little attention has been given to regional differences and diet. The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. Among other factors that may be significant are the dietary habits. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit.Peer reviewe

First results on ProtoDUNE-SP liquid argon time projection chamber performance from a beam test at the CERN Neutrino Platform

The ProtoDUNE-SP detector is a single-phase liquid argon time projection chamber with an active volume of 7.2× 6.1× 7.0 m3. It is installed at the CERN Neutrino Platform in a specially-constructed beam that delivers charged pions, kaons, protons, muons and electrons with momenta in the range 0.3 GeV/c to 7 GeV/c. Beam line instrumentation provides accurate momentum measurements and particle identification. The ProtoDUNE-SP detector is a prototype for the first far detector module of the Deep Underground Neutrino Experiment, and it incorporates full-size components as designed for that module. This paper describes the beam line, the time projection chamber, the photon detectors, the cosmic-ray tagger, the signal processing and particle reconstruction. It presents the first results on ProtoDUNE-SP\u27s performance, including noise and gain measurements, dE/dx calibration for muons, protons, pions and electrons, drift electron lifetime measurements, and photon detector noise, signal sensitivity and time resolution measurements. The measured values meet or exceed the specifications for the DUNE far detector, in several cases by large margins. ProtoDUNE-SP\u27s successful operation starting in 2018 and its production of large samples of high-quality data demonstrate the effectiveness of the single-phase far detector design

The upgrade of the ALICE TPC with GEMs and continuous readout

The upgrade of the ALICE TPC will allow the experiment to cope with the high interaction rates foreseen for the forthcoming Run 3 and Run 4 at the CERN LHC. In this article, we describe the design of new readout chambers and front-end electronics, which are driven by the goals of the experiment. Gas Electron Multiplier (GEM) detectors arranged in stacks containing four GEMs each, and continuous readout electronics based on the SAMPA chip, an ALICE development, are replacing the previous elements. The construction of these new elements, together with their associated quality control procedures, is explained in detail. Finally, the readout chamber and front-end electronics cards replacement, together with the commissioning of the detector prior to installation in the experimental cavern, are presented. After a nine-year period of R&D, construction, and assembly, the upgrade of the TPC was completed in 2020.publishedVersio

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity