Biology subjects

Blake, D.

Publications and source records attributed to Blake, D..

6 recordsLinked to original sources

bioRxiv2025

Prevalence of Campylobacter and non-typhoidal Salmonella along broiler chicken production and distribution networks, Vietnam

Campylobacter and non-typhoidal Salmonella (NTS) are among the most common foodborne pathogens found in chickens at any production stage and cause gastroenteritis in humans. This study aimed to estimate the prevalence of Campylobacter spp. (C. coli and C. jejuni) and NTS in broiler production and distribution networks (PDN) using a Bayesian approach. A cross-sectional study was conducted in four provinces in northern Vietnam between March 2021 and March 2022. A total of 102 sites, including live bird markets, slaughter facilities (slaughterhouses and slaughter points), and their supplying farms, were randomly selected for sampling. Cecal and environmental samples were cultured for isolation of Campylobacter and NTS, with serotypes of NTS determined by targeted analysis of whole genome sequences. Bayesian models were developed to estimate the prevalence of Campylobacter at two levels (bird-level and site-level) and NTS at site-level. The selected best-fitted models indicated that C. jejuni prevalence was primarily influenced by site type, while C. coli was affected by both province and site types. For NTS, only site type was included. The highest overall prevalence of infected broilers was estimated on farms for C. coli (26.2% [95% High Density Interval (HDI): 19.0-36.0%]) and C. jejuni (19.9% [95%HDI 13.0-27.0%]). Slaughter points (97.6% [95%HDI 63.3-99.9%]) and wholesale markets (91.7% [95%HDI 28.2-99.9%]) had the highest probability of C. coli and C. jejuni contamination, respectively, but retail markets had the highest proportion of infected broilers at contaminated sites. NTS contamination was more frequent in markets and slaughter facilities (42.8% [95%HDI 30.8-57.1%]) than on farms (18.6% [95%HDI 9.5-30.1%]). Among 16 detected NTS serotypes, S. Infantis and S. Kentucky were the most common. These findings highlight the widespread contamination of broiler PDNs with Campylobacter and NTS in northern Vietnam, emphasizing the need for enhanced surveillance and control measures in PDNs to mitigate the risk of foodborne transmission. Author SummaryCampylobacter spp. and non-typhoidal Salmonella (NTS) are enteric pathogens that are key global pathogens causing diarrheal diseases. The Campylobacter species that are most frequently responsible for human diseases (campylobacteriosis) are Campylobacter jejuni (C. jejuni) and Campylobacter coli (C. coli). The severity of the salmonellosis depends on host factors and the serotype of NTS. Poultry and poultry products are recognized as major sources of NTS and Campylobacter infections in humans. In Vietnam, these pathogens have been detected in the broiler production and distribution networks (PDN). Factors that may increase the risk of transmission of those pathogens include low biosecurity practices, inadequate waste management, and high farm density. In this work, we estimated the prevalence of Campylobacter spp. (C. coli and C. jejuni) and NTS in PDN markets and slaughterhouses and farms supplying these facilities in four provinces in northern Vietnam. We estimated a high prevalence of Campylobacter contamination in slaughter points and wholesale markets and higher NTS contamination in slaughter facilities and markets than in farms. S. Infantis was one of the most frequently identified serovars. However, it was not reported as being frequently detected in humans in Vietnam. Therefore, serovar may vary depending on the source and region of contamination. Our results help us look at levels of infection/contamination with Campylobacter and NTS in the broiler PDNs, thus informing stakeholders to prevent and control campylobacteriosis and salmonellosis.

microbiology↗

bioRxiv2024

Spatial distribution of poultry farms using point pattern modelling: a method to address livestock environmental impacts and disease transmission risks

The distribution of farm locations and sizes is paramount to characterize patterns of disease spread. With some regions undergoing rapid intensification of livestock production, resulting in increased clustering of farms in peri-urban areas, measuring changes in the spatial distribution of farms is crucial to design effective interventions. However, those data are not available in many countries, their generation being resource-intensive. Here, we develop a farm distribution model (FDM), which allows the prediction of locations and sizes of poultry farms in countries with scarce data. The model combines (i) a Log-Gaussian Cox process model to simulate the farm distribution as a spatial Poisson point process, and (ii) a random forest model to simulate farm sizes (i.e. the number of animals per farm). Spatial predictors were used to calibrate the FDM on intensive broiler and layer farm distributions in Bangladesh, Gujarat (Indian state) and Thailand. The FDM yielded realistic farm distributions in terms of spatial clustering, farm locations and sizes, while providing insights on the factors influencing these distributions. Finally, we illustrate the relevance of modelling realistic farm distributions in the context of epidemic spread by simulating pathogen transmission on an array of spatial distributions of farms. We found that farm distributions generated from the FDM yielded spreading patterns consistent with simulations using observed data, while random point patterns underestimated the probability of large outbreaks. Indeed, spatial clustering increases vulnerability to epidemics, highlighting the need to account for it in epidemiological modelling studies. As the FDM maintains a realistic distribution of farm location and sizes, its use to inform mathematical models of disease transmission is particularly relevant for regions where these data are not available.

bioinformatics↗

bioRxiv2023

EPINEST, an agent-based model to simulate epidemic dynamics in large-scale poultry production and distribution networks

The rapid intensification of poultry production raises important concerns about the associated risks of zoonotic infections. Here, we introduce EPINEST (EPI-demic NEtwork Simulation in poultry Transportation systems): an agent-based modelling designed to simulate pathogen transmission within realistic poultry production and distribution networks. The modular structure of the model allows for easy parameterization to suit specific countries and system configurations. Moreover, the framework enables the replication of a wide range of eco-epidemiological scenarios by incorporating diverse pathogen life-history traits, modes of transmission and interactions between multiple strains and/or pathogens. EPINEST was developed in the context of an interdisciplinary multicentre study conducted in Bangladesh, India, Vietnam and Sri Lanka, and will facilitate the investigation of the spreading patterns of various health hazards such as avian influenza, Campylobacter, Salmonella and antimicrobial resistance in these countries. Furthermore, this modelling framework holds potential for broader application in veterinary epidemiology and One Health research, extending its relevance beyond poultry to encompass other livestock species and disease systems.

bioinformatics↗

bioRxiv2022

Alternative Splicing of Apoptosis Genes Promotes Human T Cell Survival

Alternative splicing occurs in the vast majority of human genes, giving rise to distinct mRNA and protein isoforms. We, and others, have previously identified hundreds of genes that change their isoform expression upon T cell activation via alternative splicing; however, how these changes link activation input with functional output remains largely unknown. Here we investigate how costimulation of T cells through the CD28 receptor impacts alternative splicing in T cells activated through the T cell receptor (CD3) and find that while CD28 signaling alone has minimal impact on splicing, it enhances the extent of change for up to 20% of TCR-induced alternative splicing events. Interestingly, a set of CD28-enhanced splicing events occur within genes encoding key components of the apoptotic signaling pathway; namely caspase-9, Bax and Bim. Using both CRISPR-edited cells and antisense oligos to force expression of specific isoforms, we show for all three of these genes that the isoform induced by CD3/CD28 costimulation promotes resistance to apoptosis, and that changes in all three genes together function combinatorially to further promote cell viability. Finally, we show that the JNK signaling pathway, induced downstream of CD3/CD28 costimulation, is required for each of these splicing events, further highlighting their co-regulation. Together these findings demonstrate that alternative splicing is a key mechanism by which costimulation of CD28 promotes viability of activated T cells.

molecular biology↗

bioRxiv2020

Nsr1, a nitrogen source-regulated microprotein, confers an alternative mechanism of G1/S transcriptional activation in budding yeast

Commitment to cell division at the end of G1 phase, termed Start in the budding yeast Saccharomyces cerevisiae, is strongly influenced by nutrient availability. To identify new dominant activators of Start that might operate under different nutrient conditions, we screened a genome-wide ORF overexpression library for genes that bypass a Start arrest caused by absence of the G1 cyclin Cln3 and the transcriptional activator Bck2. We recovered a hypothetical gene YLR053c, renamed NRS1 for Nitrogen-Responsive Start regulator 1, which encodes a poorly characterized 108 amino acid microprotein. Endogenous Nrs1 was nuclear-localized, restricted to poor nitrogen conditions, induced upon mTORCl inhibition, and cell cycle-regulated with a peak at Start. NRS1 interacted genetically with SWI4 and SWI6, which encode subunits of the main G1/S transcription factor complex SBF. Correspondingly, Nrs1 physically interacted with Swi4 and Swi6 and was localized to G1/S promoter DNA. Nrs1 exhibited inherent transactivation activity and fusion of Nrs1 to the SBF inhibitor Whi5 was sufficient to suppress other Start defects. Nrs1 appears to be a recently evolved microprotein that rewires the G1/S transcriptional machinery under poor nitrogeny conditions. Author SummarUnicellular microorganisms must adapt to ever-changing nutrient conditions and hence must adjust cell growth and proliferation to maximize fitness. In the budding yeast Saccharomyces cerevisiae, commitment to cell division, termed Start, is heavily influenced by nutrient availability. Our understanding of how Start is activated is based mainly on experiments carried out under rich nutrient conditions. To identify potential new Start regulators specific to poor nutrient environments, we screened for genes able to bypass a genetic Start arrest caused by loss of the G1 cyclin Cln3 and the transcriptional activator Bck2. This screen uncovered YLR053c, which we renamed NRS1 for Nitrogen-Responsive Start regulator. Sequence analysis across yeast species indicated that Nrs1 is a recently-evolved microprotein. We showed that NRS1 is nutrient- and cell cycle-regulated, and directly binds the main G1/S transcription factor complex SBF. We demonstrated that Nrs1 has an intrinsic trans-activation activity and provided genetic evidence to suggest that Nrs1 can bypass the requirement for normal Cln3-dependent activation of G1/S transcription. These results uncover a new mechanism of Start activation and illustrate how microproteins can rapidly emerge to rewire fundamental cellular processes.

cell biology↗

bioRxiv2019

Meta-Analysis of Transcriptomic Variation in T cell Populations Reveals Novel Signatures of Gene Expression and Splicing

Distinct T cell subtypes are typically defined by the expression of distinct gene repertoires. However, there is variability between studies regarding the markers used to define each T cell subtype. Moreover, previous analysis of gene expression in T cell subsets has largely focused on gene expression rather than alternative splicing. Here we take a meta-analysis approach, comparing eleven independent RNA-Seq studies of human Th1, Th2, Th17 and/or Treg cells to identify transcriptomic features that correlate consistently with subtype. We find that known master-regulators are consistently enriched in the appropriate subtype, however, cytokines and other genes often used as markers are more variable. Importantly, we also identify previously unknown transcriptomic markers that consistently differentiate between subsets, including a few Treg-specific splicing patterns. Together this work highlights the heterogeneity in gene expression between isolates of the same subtype, but also suggests additional markers that can be used to define functional groupings.

immunology↗