A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

The contribution of oxygen metabolism to the inflammatory response of murine RAW 264.7 macrophages

Makrofagi to jedne z najważniejszych komórek uczestniczących w pierwszej linii obrony organizmu przed patogenami, a przemiany biochemiczne zachodzące w tych komórkach mogą mieć znaczenie dla ich funkcji obronnych. Ponadto komórki te w określonym mikrośrodowisku mogą reprezentować dwa odmienne fenotypy, funkcjonować jako makrofagi aktywowane klasycznie (M1) lub aktywowane alternatywnie (M2). W makrofagach M1, po ich aktywacji, obserwujemy przejście metaboliczne w kierunku glikolizy tlenowej, którą można porównać do „efektu Warburga” występującego w komórkach nowotworowych. Celem pracy było określenie wpływu zahamowania syntazy ATP na przebieg procesu zapalnego indukowanego w linii komórkowej makrofagów mysich, poprzez oznaczenie poziomu tlenku azotu, ocenę żywotności oraz poziomu (całościowego) produkowanego białka. Badania przeprowadzono na linii komórkowej makrofagów mysich RAW 264.7, które traktowano oligomycyną (inhibitor syntazy ATP) w różnych stężeniach, dodatkowo część komórek stymulowano lipopolisacharydem (LPS) w stężeniu 10 μg/ml. Grupę kontrolną stanowiły komórki nietraktowane oligomycyną i niestymulowane LPS. Wpływ zahamowania syntazy ATP na poziom wydzielonego tlenku azotu określono przy użyciu metody Griess’a, a poziom (całościowego) białka za pomocą testu BCA. Ocenę żywotności przeprowadzono wykorzystując testy MTT oraz PrestoBlue. Uzyskane wyniki wskazują, że oligomycyna w najniższym wykorzystanym stężeniu powoduje obniżenie poziomu wydzielanego tlenku azotu. Nie wykazano natomiast zmian w aktywności dehydrogenaz mitochondrialnych (test MTT) w obecności oligomycyny, nie wpłynęła ona także na wydzielanie białek. Z kolei wyniki testu PrestoBlue wykazały wzrost żywotności komórek stymulowanych LPS. Przyszłe badania powinny być poszerzone o określenie poziomu wybranych, konkretnych białek pro- i przeciwzapalnych.Macrophages are one of the most important cell types participating in the body's first line of defense against pathogens, and biochemical processes taking place in these cells may have an impact on their defense functions. The cells display one of two major phenotypes depending of microenvironment, being either classically activated (M1) or alternatively activated (M2). In M1 macrophages, after activation, metabolic transition towards oxygen glycolysis occurs which can be compared to the "Warburg effect" in cancer cells. The aim of the study was to determine the effect of inhibition of ATP synthase on the course of the inflammatory process in murine macrophages by determining the level of nitric oxide, assessment of cell viability and the level (total) of proteins released by macrophages. The studies were carried out on the RAW 264.7 murine macrophage cell line which was treated with various concentrations of oligomycin (ATP synthase inhibitor). In addition, some of the cells were stimulated with lipopolysaccharide (LPS) at a concentration of 10 μg/ml. The control group consisted of cells untreated with oligomycin and non-stimulated with LPS. The effect of ATP synthase inhibition on the level of secreted nitric oxide was determined using the Griess test and the level of (total) protein was measured by the BCA test. Viability assessment was carried out using the MTT and PrestoBlue tests. The obtained results indicate that oligomycin in the lowest concentration used causes a decrease in the level of nitric oxide. Activity of mitochondrial dehydrogenases (the MTT test) showed no effect of oligomycin on cell viability, a similar effect was observed in the case of released proteins. The results of the PrestoBlue test showed an increase in the viability of cells stimulated with LPS when compared to non-stimulated with LPS. Future studies should concentrate on more detailed evaluation of proteins released by macrophages, namely exemplary pro- and anti-inflammatory proteins

Effect of a mixture of persistent environmental pollutants on the viability of human ovarian granulosa cells - HGrC1 line

Żywotność komórek ziarnistych, będących głównym komponentem pęcherzyków jajnikowych, to jeden z kluczowych parametrów zdrowia reprodukcyjnego kobiet. Na funkcjonowanie tych komórek mogą wpływać trwałe zanieczyszczenia organiczne, których obecność potwierdzono w płynie pęcherzykowym kobiet. Związki te oddziałując na takie procesy jak proliferacja i apoptoza, mogą mieć kluczowe znaczenie w rozwoju ziarniszczaka jajnika- jednego z najgroźniejszych nowotworów ginekologicznych. Celem pracy było określenie wpływu trwałych zanieczyszczeń organicznych środowiska na żywotność komórek ziarnistych. Badania przeprowadzono na linii komórkowej ludzkich komórek ziarnistych jajnika- HGrC1, które traktowano wybranymi trwałymi zanieczyszczeniami organicznymi (PFOA, PFOS, p,p’-DDE, HCB, PCB153) oraz ich mieszaninami. Wpływ badanych związków na apoptozę komórek ziarnistych określono za pomocą fluorymetrycznego pomiaru aktywności kaspazy-3 oraz oceny ekspresji genu kaspazy-3, z kolei wpływ na proliferację oceniono przy użyciu testu AlamarBlue. Badania wskazują, że wybrane trwałe zanieczyszczenia organiczne oraz ich mieszaniny, nie wpływają na proliferację komórek ziarnistych oraz aktywność kaspazy3. Wykazano natomiast zmianę ekspresji genu kaspazy-3 po 24h narażenia na mieszaninę związków, w stężeniu dziesięciokrotnie niższym od wykrytego w płynie pęcherzykowym. Wnioskujemy zatem, że długotrwałe narażenie na badane związki może skutkować zaburzeniem stosunku proliferacja/apoptoza w komórkach ziarnistych, co może być jedną z przyczyn prowadzących do zaburzeń w płodności.The viability of granulosa cells, the main component of ovarian follicles, is one of the key parameters of women's reproductive health. The function of these cells may be affected by persistent organic pollutants that have been confirmed in the follicular fluid of women. By affecting processes such as proliferation and apoptosis, these compounds may be crucial in the development of ovarian granulosa cell tumors - one of the most dangerous gynecological tumors. The aim of this study was to determine the effect of persistent environmental organic pollutants on granulosa cell viability. The study was performed on human ovarian granulosa cell line-HGrC1, which was treated with selected persistent organic pollutants (PFOA, PFOS, p,p'-DDE, HCB, PCB153) and their mixtures. The effect of the tested compounds on apoptosis of granulosa cells was determined by fluorometric measurement of caspase-3 activity and assessment of caspase-3 gene expression, whereas the effect on proliferation was evaluated using the AlamarBlue assay. Studies indicate that selected persistent organic pollutants and their mixtures, do not affect granulosa cell proliferation and caspase-3 activity. In contrast, the expression of the caspase-3 gene was altered after 24h of exposure to the mixture of compounds, at a concentration ten times lower than that detected in the follicular fluid. Thus, we conclude that long-term exposure to the tested compounds may result in a disruption of the proliferation/apoptosis ratio in granulosa cells, which may be one of the causes leading to fertility disorder

The Apelinergic System: Apelin, ELABELA, and APJ Action on Cell Apoptosis: Anti-Apoptotic or Pro-Apoptotic Effect?

The apelinergic system comprises two peptide ligands, apelin and ELABELA, and their cognate G-protein-coupled receptor, the apelin receptor APJ. Apelin is a peptide that was isolated from bovine stomach extracts; the distribution of the four main active forms, apelin-36, -17, -13, and pyr-apelin-13 differs between tissues. The mature form of ELABELA-32 can be transformed into forms called ELABELA-11 or -21. The biological function of the apelinergic system is multifaceted, and includes the regulation of angiogenesis, body fluid homeostasis, energy metabolism, and functioning of the cardiovascular, nervous, respiratory, digestive, and reproductive systems. This review summarises the mechanism of the apelinergic system in cell apoptosis. Depending on the cell/tissue, the apelinergic system modulates cell apoptosis by activating various signalling pathways, including phosphoinositide 3-kinase (PI3K), extracellular signal-regulated protein kinase (ERK1/2), protein kinase B (AKT), 5&rsquo;AMP-activated protein kinase(AMPK), and protein kinase A (PKA). Apoptosis is critically important during various developmental processes, and any dysfunction leads to pathological conditions such as cancer, autoimmune diseases, and developmental defects. The purpose of this review is to present data that suggest a significant role of the apelinergic system as a potential agent in various therapies

The Apelinergic System: Apelin, ELABELA, and APJ Action on Cell Apoptosis: Anti-Apoptotic or Pro-Apoptotic Effect?

The apelinergic system comprises two peptide ligands, apelin and ELABELA, and their cognate G-protein-coupled receptor, the apelin receptor APJ. Apelin is a peptide that was isolated from bovine stomach extracts; the distribution of the four main active forms, apelin-36, -17, -13, and pyr-apelin-13 differs between tissues. The mature form of ELABELA-32 can be transformed into forms called ELABELA-11 or -21. The biological function of the apelinergic system is multifaceted, and includes the regulation of angiogenesis, body fluid homeostasis, energy metabolism, and functioning of the cardiovascular, nervous, respiratory, digestive, and reproductive systems. This review summarises the mechanism of the apelinergic system in cell apoptosis. Depending on the cell/tissue, the apelinergic system modulates cell apoptosis by activating various signalling pathways, including phosphoinositide 3-kinase (PI3K), extracellular signal-regulated protein kinase (ERK1/2), protein kinase B (AKT), 5’AMP-activated protein kinase(AMPK), and protein kinase A (PKA). Apoptosis is critically important during various developmental processes, and any dysfunction leads to pathological conditions such as cancer, autoimmune diseases, and developmental defects. The purpose of this review is to present data that suggest a significant role of the apelinergic system as a potential agent in various therapies