202 research outputs found

    APRIL:TACI axis is dispensable for the immune response to rabies vaccination.

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    There is significant need to develop a single-dose rabies vaccine to replace the current multi-dose rabies vaccine regimen and eliminate the requirement for rabies immune globulin in post-exposure settings. To accomplish this goal, rabies virus (RABV)-based vaccines must rapidly activate B cells to secrete antibodies which neutralize pathogenic RABV before it enters the CNS. Increased understanding of how B cells effectively respond to RABV-based vaccines may improve efforts to simplify post-exposure prophylaxis (PEP) regimens. Several studies have successfully employed the TNF family cytokine a proliferation-inducing ligand (APRIL) as a vaccine adjuvant. APRIL binds to the receptors TACI and B cell maturation antigen (BCMA)-expressed by B cells in various stages of maturation-with high affinity. We discovered that RABV-infected primary murine B cells upregulate APRIL ex vivo. Cytokines present at the time of antigen exposure affect the outcome of vaccination by influencing T and B cell activation and GC formation. Therefore, we hypothesized that the presence of APRIL at the time of RABV-based vaccine antigen exposure would support the generation of protective antibodies against RABV glycoprotein (G). In an effort to improve the response to RABV vaccination, we constructed and characterized a live recombinant RABV-based vaccine vector which expresses murine APRIL (rRABV-APRIL). Immunogenicity testing in mice demonstrated that expressing APRIL from the RABV genome does not impact the primary antibody response against RABV G compared to RABV alone. In order to evaluate the necessity of APRIL for the response to rabies vaccination, we compared the responses of APRIL-deficient and wild-type mice to immunization with rRABV. APRIL deficiency does not affect the primary antibody response to vaccination. Furthermore, APRIL expression by the vaccine did not improve the generation of long-lived antibody-secreting plasma cells (PCs) as serum antibody levels were equivalent in response to rRABV-APRIL and the vector eight weeks after immunization. Moreover, APRIL is dispensable for the long-lived antibody-secreting PC response to rRABV vaccination as anti-RABV G IgG levels were similar in APRIL-deficient and wild-type mice six months after vaccination. Mice lacking the APRIL receptor TACI demonstrated primary anti-RABV G antibody responses similar to wild-type mice following immunization with the vaccine vector indicating that this response is independent of TACI-mediated signals. Collectively, our findings demonstrate that APRIL and associated TACI signaling is dispensable for the immune response to RABV-based vaccination

    Prevalence and correlates of reproductive coercion across ten sites: commonalities and divergence

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    Background Reproductive coercion (RC) is a type of abuse where a partner asserts control over a woman’s reproductive health trajectories. Recent research emphasizes that RC experiences may differ within and across low- and middle-income countries (LMICs), as compared to higher income contexts, given social pressures surrounding childbearing. To date, nationally representative surveys have lacked comprehensive measures for RC, leading to gaps in understanding its prevalence and risk factors. Across eight LMICs (10 sites), we aimed to (1) validate the RC Scale; (2) calculate prevalence of RC and specific behaviors; and (3) assess correlates of RC. Methods This analysis leverages cross-sectional Performance Monitoring for Action (PMA) data collected from November 2020 to May 2022. Analyses were limited to women in need of contraception (Burkina Faso n = 2767; Cîte d’Ivoire n = 1561; Kongo Central, Democratic Republic of Congo (DRC) n = 830; Kinshasa, DRC n = 846; Kenya n = 4588; Kano, Nigeria n = 535; Lagos, Nigeria n = 612; Niger n = 1525; Rajasthan, India n = 3017; Uganda n = 2020). Past-year RC was assessed via five items adapted from the original RC Scale and previously tested in LMICs. Confirmatory factor analysis examined fit statistics by site. Per-item and overall prevalence were calculated. Site-specific bivariate and multivariable logistic regression examined RC correlates across the socioecological framework. Results Confirmatory factor analysis confirmed goodness of fit across all sites, with moderate internal consistency (alpha range: 0.66 Cote d’Ivoire–0.89 Kinshasa, DRC/Lagos, Nigeria). Past-year reported prevalence of RC was highest in Kongo Central, DRC (20.3%) and lowest in Niger (3.1%). Prevalence of individual items varied substantially by geography. Polygyny was the most common RC risk factor across six sites (adjusted odds ratio (aOR) range: 1.59–10.76). Increased partner education levels were protective in Kenya and Kano, Nigeria (aOR range: 0.23–0.67). Other assessed correlates differed by site. Conclusions Understanding RC prevalence and behaviors is central to providing woman-centered reproductive care. RC was most strongly correlated with factors at the partner dyad level; future research is needed to unpack the relative contributions of relationship power dynamics versus cultural norms surrounding childbearing. Family plannin

    Quantifying sources of variability in infancy research using the infant-directed-speech preference

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    Psychological scientists have become increasingly concerned with issues related to methodology and replicability, and infancy researchers in particular face specific challenges related to replicability: For example, high-powered studies are difficult to conduct, testing conditions vary across labs, and different labs have access to different infant populations. Addressing these concerns, we report on a large-scale, multisite study aimed at (a) assessing the overall replicability of a single theoretically important phenomenon and (b) examining methodological, cultural, and developmental moderators. We focus on infants’ preference for infant-directed speech (IDS) over adult-directed speech (ADS). Stimuli of mothers speaking to their infants and to an adult in North American English were created using seminaturalistic laboratory-based audio recordings. Infants’ relative preference for IDS and ADS was assessed across 67 laboratories in North America, Europe, Australia, and Asia using the three common methods for measuring infants’ discrimination (head-turn preference, central fixation, and eye tracking). The overall meta-analytic effect size (Cohen’s d) was 0.35, 95% confidence interval = [0.29, 0.42], which was reliably above zero but smaller than the meta-analytic mean computed from previous literature (0.67). The IDS preference was significantly stronger in older children, in those children for whom the stimuli matched their native language and dialect, and in data from labs using the head-turn preference procedure. Together, these findings replicate the IDS preference but suggest that its magnitude is modulated by development, native-language experience, and testing procedure. (This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie SkƂodowska-Curie grant agreement No 798658.

    Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

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    Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∌38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

    The James Webb Space Telescope Mission

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    Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least 4m4m. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the 6.5m6.5m James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

    Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV