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PAI1 was increased in plasma of women with early-onset preeclampsia, and PAI1-deficient EVTs were protected from the anti-migratory effects of palmitic acid. #link# Using first trimester placental explants, palmitic acid exposure decreased EVT invasion through Matrigel. Our findings reveal that palmitic acid induces an inflammatory response in EVTs and attenuates their migration through a mechanism involving PAI1. High levels of palmitic acid in pathophysiological situations like obesity may impair early placental development and predispose to placental dysfunction.Genetic recombination characterized by reciprocal exchange of genes on paired homologous chromosomes is the most prominent event in meiosis of almost all sexually reproductive organisms. It contributes to genome stability by ensuring the balanced segregation of paired homologs in meiosis, and it is also the major driving factor in generating genetic variation for natural and artificial selection. Meiotic recombination is subjected to the control of a highly stringent and complex regulating process and meiotic recombination frequency (MRF) may be affected by biological and abiotic factors such as sex, gene density, nucleotide content, and chemical/temperature treatments, having motivated tremendous researches for artificially manipulating MRF. Whether genome polyploidization would lead to a significant change in MRF has attracted both historical and recent research interests; however, tackling this fundamental question is methodologically challenging due to the lack of appropriate methods for tetrasomic genetic analysis, thus has led to controversial conclusions in the literature. This article presents a comprehensive and rigorous survey of genome duplication-mediated change in MRF using Saccharomyces cerevisiae as a eukaryotic model. It demonstrates that genome duplication can lead to consistently significant increase in MRF and rate of crossovers across all 16 chromosomes of S. cerevisiae, including both cold and hot spots of MRF. This ploidy-driven change in MRF is associated with weakened recombination interference, enhanced double-strand break density, and loosened chromatin histone occupation. link2 The study illuminates a significant evolutionary feature of genome duplication and opens an opportunity to accelerate response to artificial and natural selection through polyploidization.

In response to reported COVID-19 outbreaks among people experiencing homelessness (PEH) in other U.S. cities, we conducted multiple, proactive, facility-wide testing events for PEH living sheltered and unsheltered and homelessness service staff in Atlanta, Georgia. We describe SARS-CoV-2 prevalence and associated symptoms and review shelter infection prevention and control (IPC) policies.

PEH and staff were tested for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) during April 7-May 6, 2020. A subset of PEH and staff was screened for symptoms. Shelter assessments were conducted concurrently at a convenience sample of shelters using a standardized questionnaire.

Overall, 2,875 individuals at 24 shelters and nine unsheltered outreach events underwent SARS-CoV-2 testing and 2,860 (99.5%) had conclusive test results. SARS-CoV-2 prevalence was 2.1% (36/1,684) among PEH living sheltered, 0.5% (3/628) among PEH living unsheltered, and 1.3% (7/548) among staff. Reporting fever, cough, or shortness of breath in the last week during symptom screening was 14% sensitive and 89% specific for identifying COVID-19 cases compared with RT-PCR. Prevalence by shelter ranged 0%-27.6%. Repeat testing 3-4 weeks later at four shelters documented decreased SARS-CoV-2 prevalence (0%-3.9%). Nine of 24 shelters completed shelter assessments and implemented IPC measures as part of the COVID-19 response.

PEH living in shelters experienced higher SARS-CoV-2 prevalence compared with PEH living unsheltered. Facility-wide testing in congregate settings allowed for identification and isolation of COVID-19 cases and is an important strategy to interrupt SARS-CoV-2 transmission.

PEH living in shelters experienced higher SARS-CoV-2 prevalence compared with PEH living unsheltered. Facility-wide testing in congregate settings allowed for identification and isolation of COVID-19 cases and is an important strategy to interrupt SARS-CoV-2 transmission.

Low vaccine effectiveness against A(H3N2) influenza in seasons with little antigenic drift has been attributed to substitutions in hemagglutinin (HA) acquired during vaccine virus propagation in eggs. selleck chemical comparing recombinant HA vaccine (rHA) and cell-derived inactivated influenza vaccine (IIV) to egg-derived IIVs provide opportunities to assess how egg-adaptive substitutions influence HA immunogenicity.

Neutralization titers in pre- and post-immunization sera from 133 adults immunized with one of three types of influenza vaccines in a randomized, open-label trial during the 2018-2019 influenza season were measured against egg- and cell-derived A/Singapore/INFIMH-16-0019/2016-like and circulating A(H3N2) influenza viruses using HA-pseudoviruses.

All vaccines elicited neutralizing antibodies to all H3 vaccine antigens, but the rHA vaccine elicited the highest titers and seroconversion rates against all strains tested. Egg- and cell-derived IIVs elicited responses similar to each other. Pre-iponse rates, indicating that the cell-derived vaccine did not improve immunogenicity against the A(H3N2) viruses. The higher responses after rHA vaccination may be due to its higher HA content. All vaccines boosted titers to HA with egg-adaptive substitutions, suggesting boosting from past antigens or better exposure of HA epitopes. Studies comparing immunogenicity and effectiveness of different influenza vaccines across many seasons are needed.The comparative genomics of the transition of the opportunistic pathogen Pseudomonas aeruginosa from a free-living environmental strain to one that causes chronic infection in the airways of cystic fibrosis (CF) patients remain poorly studied. Chronic infections are thought to originate from colonization by a single strain sampled from a diverse, globally distributed population, followed by adaptive evolution to the novel, stressful conditions of the CF lung. However, we do not know whether certain clades are more likely to form chronic infections than others and we lack a comprehensive view of the suite of genes under positive selection in the CF lung. We analyzed whole-genome sequence data from 1,000 P. aeruginosa strains with diverse ecological provenances including the CF lung. CF isolates were distributed across the phylogeny, indicating little genetic predisposition for any one clade to cause chronic infection. Isolates from the CF niche experienced stronger positive selection on core genes than those derived from environmental or acute infection sources, consistent with recent adaptation to the lung environment. Genes with the greatest differential positive selection in the CF niche include those involved in core cellular processes such as metabolism, energy production, and stress response as well as those linked to patho-adaptive processes such as antibiotic resistance, cell wall and membrane modification, quorum sensing, biofilms, mucoidy, motility, and iron homeostasis. Many genes under CF-specific differential positive selection had regulatory functions, consistent with the idea that regulatory mutations play an important role in rapid adaptation to novel environments.Aqueous film-forming foams (AFFFs) are complex per- and polyfluoroalkyl substance (PFAS)-containing mixtures used extensively as fire suppressants. link3 AFFF-impacted groundwater and surface water have contaminated drinking water with PFASs in many communities, raising concerns about health effects from drinking water exposures. As individual PFASs have been identified as immune hazards, the immunotoxicity of complex PFAS mixtures is also a concern. Adult female and male C57BL/6 mice were given a commercial AFFF formulation for 10 days via gavage; administered dose was based on combined content of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) measured in the formulation (0, 1.88, 3.75, 7.5, or 10 mg PFOS+PFOA/kg body weight). A PFOA positive control of 7.5 mg/kg body weight was also given. Compared with the 0 mg/kg group, the following changes were noted Body weights of males exposed to 7.5 and 10 mg PFOS+PFOA/kg were reduced by 15%, on average; female body weights did not differ. Average relative liver weights were increased 50%-200% in males and 37.5%-193% in females and liver peroxisome proliferation was increased 2- to 12-fold in all doses of both sexes. Antigen-specific antibody production was suppressed, on average, by 13% in males and by 12.4% in females across all doses. Spleen cellularity and lymphocyte subpopulations did not differ by dose for either sex. Our data indicate that though this complex PFAS mixture contained fairly low PFOA content, it induced changes in C57BL/6 mice similar to changes induced by PFOA alone, likely due to the presence of PFOS and many other PFASs.Diagnosis, treatment, and management of invasive mould infections (IMI) are challenged by several risk factors, including local epidemiological characteristics, the emergence of fungal resistance and the innate resistance of emerging pathogens, the use of new immunosuppressants, as well as off-target effects of new oncological drugs. The presence of specific host genetic variants and the patient's immune system status may also influence the establishment of an IMI and the outcome of its therapy. Immunological components can thus be expected to play a pivotal role not only in the risk assessment and diagnosis, but also in the treatment of IMI. Cytokines could improve the reliability of an invasive aspergillosis diagnosis by serving as biomarkers as do serological and molecular assays, since they can be easily measured, and the turnaround time is short. The use of immunological markers in the assessment of treatment response could be helpful to reduce overtreatment in high risk patients and allow prompt escalattem to fight invasive mould infections and may be more important than the choice of the antifungal treatment. Individualized approaches for prevention and treatment of invasive mold infections are needed.

Previous diary work indicates that older people experience more intrusive and unwanted thoughts (i.e., cognitive interference) on days with stressors. We examined additional predictors of daily cognitive interference to enhance understanding of the psychological context surrounding this link. We specifically focused on factors related to subjective experiences of aging based on studies that have related higher stress and impairments in cognition such as executive control processes (working memory) to negative age stereotypes. Consistent with these findings, we generally expected stronger stress effects on cognitive interference when daily self-perceptions of aging (i.e., within-person fluctuations in awareness of age-related losses [AARC losses]) and general aging attitudes (i.e., individual differences in attitudes toward own aging [ATOA]) were more negative.

Participants (n = 91; ages 60 to 80) on Amazon's Mechanical Turk completed surveys on nine consecutive days, reporting on their ATOA (Day 1) as well as their stressors, AARC losses, and cognitive interference (Days 2 to 9).

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