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Little is known about how specific individual viral lineages replicating systemically during acute Human Immunodeficiency Virus or Simian Immunodeficiency Virus (HIV/SIV) infection persist into chronic infection. In this study, we use molecularly barcoded SIV (SIVmac239M) to track distinct viral lineages for 12 weeks after intravenous (IV) or intrarectal (IR) challenge in macaques. Two Mafa-A1*063+ cynomolgus macaques (Macaca fascicularis, CM) were challenged IV, and two Mamu-A1*001+ rhesus macaques (Macaca mulatta, RM) were challenged IR with 200,000 Infectious Units (IU) of SIVmac239M. We sequenced the molecular barcode of SIVmac239M from all animals over the 12 weeks of the study to characterize the diversity and persistence of virus lineages. During the first three weeks post-infection, we found ~70-560 times more unique viral lineages circulating in the animals challenged IV compared to those challenged IR, which is consistent with the hypothesis that the challenge route is the primary driver restricting the transmission of individual viral lineages. We also characterized the sequences of T cell epitopes targeted during acute SIV infection, and found that the emergence of escape variants in acutely targeted epitopes can occur on multiple virus templates simultaneously, but that elimination of some of these templates is likely a consequence of additional host factors. These data imply that virus lineages present during acute infection can still be eliminated from the systemic virus population even after initial selection.

Despite complex presentation of adult hypertension and a concomitant obesity epidemic, little is known about overweight in relation to blood pressure among Caribbean children. We examined blood pressure in relation to body size in a cross-sectional study of 573 Barbadian children aged 9-10 years (2010-2011). The United States normative blood pressure percentiles were used to identify children with high (≥95th percentile) or high normal blood pressure (90th-95th percentile). The World Health Organization body mass index cut-off points were used to assess weight status.Thirty percent of children were overweight/obese. Percentage fat mass differed between girls (20.4%) and boys (17.72%) (p

We have addressed critical challenges in probiotic design to develop a commercially viable bacterial strain capable of removing the intestinal toxin, acetaldehyde. In this study, we report the engineering of the hag locus, a σD-dependent flagellin expression site, as a stable location for robust enzyme production. We demonstrate constitutive gene expression in relevant conditions driven by the endogenous hag promoter, following a deletion of the gene encoding a post-translational regulator of σD, FlgM, and a point mutation to abrogate the binding of the translational inhibitor CsrA. Reporter constructs demonstrate activity at the hag locus after germination, with a steady increase in heterologous expression throughout outgrowth and vegetative growth. To evaluate the chassis as a spore-based probiotic solution, we identified the physiologically relevant ethanol metabolic pathway and the subsequent accumulation of gut-derived acetaldehyde following alcohol consumption. We integrated a Cupriavidus necator aldehyde dehydrogenase gene (acoD) into the hag locus under the control of the flagellin promoter and observed a rapid reduction in acetaldehyde levels in gut-simulated conditions post-germination. This work demonstrates a promising approach for the development of genetically engineered spore-based probiotics., Competing Interests: CH, VR, BS, JO, and ZA are paid employees of ZBiotics Company and hold stock/stock options in ZBiotics Company. ZA is also a board member of ZBiotics Company. As such, employees of ZBiotics played a role in the study design, data collection and analysis, decision to publish, and preparation of the manuscript. Investors in ZBiotics Company provided financial support to the company and thus supported the salaries of CH, VR, BS, JO, and ZA but did not have any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Hassan-Casarez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The last two decades have witnessed a tremendous growth in probiotics and in the numbers of publications on their potential health benefits. Owing to their distinguishing beneficial effects and long history of safe use, species belonging to the Lactobacillus genus are among the most widely used probiotic species in human food and dietary supplements and are finding increased use in animal feed. Here, we isolated, identified, and evaluated the safety of two novel Limosilactobacillus reuteri (L. reuteri) isolates, ATCC PTA-126787 & ATCC PTA-126788. More specifically, we sequenced the genomes of these two L. reuteri strains using the PacBio sequencing platform. Using a combination of biochemical and genetic methods, we identified the two strains as belonging to L. reuteri species. Detailed in silico analyses showed that the two strains do not encode for any known genetic sequences of concern for human or animal health. In vitro assays confirmed that the strains are susceptible to clinically relevant antibiotics and do not produce potentially harmful by-products such as biogenic amines. In vitro bile and acid tolerance studies demonstrated that the two strains have similar survival profiles as the commercial L. reuteri probiotic strain DSM 17938. Most importantly, daily administration of the two probiotic strains to broiler chickens in drinking water for 26 days did not induce any adverse effect, clinical disease, or histopathological lesions, supporting the safety of the strains in an in vivo avian model. All together, these data provide in silico, in vitro and in vivo evidence of the safety of the two novel candidates for potential probiotic applications in humans as well as animals., Competing Interests: I have read the journal’s policy and want to declare the following conflicts of interest. The authors DG, SPM, NRT, VR, AV, DS, MP, AA, AK, EBH are employees of Elanco Animal Health, Inc. The author NL was an employee of Elanco Animal Health, Inc. at the time the work was done. Elanco Animal Health, Inc. is a company that develops, manufactures, and sells veterinary pharmaceuticals and nutritionals. This affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Consumption of fruit and vegetables is important for health, but is often lower than recommended and tends to be socio-economically patterned with lower consumption in more deprived groups. In 2008, the English Department of Health introduced the Change4Life convenience store programme. This aimed to increase retail access to fresh fruit and vegetables in deprived, urban areas by providing existing convenience stores with a range of support and branded point-of-sale materials and equipment., Methods: We undertook a mixed-methods study of the Change4Life convenience store programme in the North East of England around two years after initial implementation. Store mapping (n = 87; 100% stores) and systematic in-store observations (n = 74; 85% stores) provided information on intervention fidelity; the variety, purchase price and quality of fresh fruit and vegetables on sale; and purchase price compared to a major supermarket. Ten qualitative interviews with a purposive sample of retailers and other professionals explored experiences of the intervention and provided further insight on quantitative results., Results: Intervention stores were primarily located in socio-economically disadvantaged areas. Fidelity, in terms of presence of branded materials and equipment, was low and much was not being used as intended. Fresh fruit and vegetables on sale were of high quality and had a purchase price around 10% more than comparable products at a major supermarket. Interviewees were supportive of the health improvement aim of the intervention. Retailers were appreciative of part-funding for chill cabinets and free point-of-sale materials. The intervention suffered from: poor initial and on-going communication between the intervention delivery team and retailers; poor availability of replacement point-of-sale materials; and failure to cement intended links with health workers and community organisations., Conclusions: Overall, intervention fidelity was low and the intervention is unlikely to have had a substantial or long-term effect on customers' consumption of fruit and vegetables.