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In vivo base editing extends lifespan of a humanized mouse model of prion disease.
Nat Med
January 2025
Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Prion disease is a fatal neurodegenerative disease caused by the misfolding of prion protein (PrP) encoded by the PRNP gene. While there is currently no cure for the disease, depleting PrP in the brain is an established strategy to prevent or stall templated misfolding of PrP. Here we developed in vivo cytosine and adenine base strategies delivered by adeno-associated viruses to permanently modify the PRNP locus to achieve PrP knockdown in the mouse brain.
View Article and Find Full Text PDFHow Binding Site Flexibility Promotes RNA Scanning by TbRGG2 RRM: A Molecular Dynamics Simulation Study.
J Chem Inf Model
January 2025
Institute of Biophysics of the Czech Academy of Sciences, Kralovopolska 135, 612 00 Brno, Czech Republic.
RNA recognition motifs (RRMs) are a key class of proteins that primarily bind single-stranded RNAs. In this study, we applied standard atomistic molecular dynamics simulations to obtain insights into the intricate binding dynamics between uridine-rich RNAs and TbRGG2 RRM using the recently developed OL3-Stafix AMBER force field, which improves the description of single-stranded RNA molecules. Complementing structural experiments that unveil a primary binding mode with a single uridine bound, our simulations uncover two supplementary binding modes in which adjacent nucleotides encroach upon the binding pocket.
View Article and Find Full Text PDFInfluence of Saccharomyces cerevisiae CNCM I-1077 on the fecal pH, markers of gut permeability, fecal microbiota, and markers of systemic inflammation in sedentary horses fed a high-starch diet.
J Anim Sci
January 2025
Department of Animal Science, Texas A&M University and Texas A&M AgriLife Research, College Station, TX USA.
Thirty mature Quarter Horse geldings were used in a completely randomized 32-d study to test the hypotheses that supplemental live Saccharomyces cerevisiae CNCM I-1077 improves apparent digestion, stabilizes the fecal pH, reduces gut permeability, maintains microbial communities, and decreases inflammation in horses fed a high-starch diet. Horses were stratified by body weight, age, and body condition score (BCS) to one of two treatments: concentrate formulated with 2g starch • kg BW-1 • meal-1 (CON; n=15) or the same concentrate top-dressed with 25g/d Saccharomyces cerevisiae CNCM I-1077 (SC; n=15; 8×108 CFU). Horses were fed individually in stalls every 12h.
View Article and Find Full Text PDFCampylobacter spp. in chicken meat from traditional markets in Peru and its impact measured through a quantitative microbiological risk assessment.
Food Res Int
January 2025
Department of Animal and Public Health, School of Veterinary Medicine, Universidad Nacional Mayor de San Marcos, Av. Circunvalacion 2800, San Borja 15021, Lima 41, Peru; Tropical and Highlands Veterinary Research Institute, Universidad Nacional Mayor de San Marcos, Jr. 28 de Julio s/n, Jauja, 12150, Peru; Global Health Center, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martín de Porres 15102, Lima 41, Peru. Electronic address:
Campylobacter is a major cause of foodborne gastroenteritis worldwide, with the mishandling of contaminated chicken meat among the main pathways for human infection. Granted the disease burden due to this pathogen, systematic assessments of its potential impact are necessary. The aims of this study were to evaluate both presence and load of Campylobacter in chicken meat sold in traditional markets, assess risk factors related with the infrastructure and hygienic conditions of market stalls, and evaluate control strategies for campylobacteriosis in Peru through a quantitative microbiological risk assessment (QMRA), a data-driven, systematic approach to quantitatively assess risks by integrating empirical contamination levels, microbial behavior, and consumer exposure.
View Article and Find Full Text PDFDecoding fertility behaviour of married women in Zambia: A multipronged analysis of bio-demographic, socio-economic and intermediate factors.
PLOS Glob Public Health
January 2025
Demography and Population Studies Programme, Schools of Public Health and Social Sciences, University of Witwatersrand, Johannesburg, South Africa.
Despite national efforts and a decrease in total fertility rate, Zambia's fertility remains high compared to global and regional averages. While previous research has examined the influence of bio-demographic and socio-economic factors, it has neglected the role of overlooked intermediate variables such as age at first marriage, contraception use, and abortion. This study investigated the influence of these variables, while controlling for bio-demographic and socio-economic factors, on women's fertility behaviour in Zambia.
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