Brucella suis Seroprevalence and Associated Risk Factors in Dogs in Eastern Australia, 2016 to 2019

Brucella suis is a zoonotic disease of feral pigs that also affects pig hunting dogs, pig hunters, veterinarians and veterinary staff. In recent years the incidence of B. suis in the eastern Australian states of New South Wales (NSW) and Queensland (QLD) has increased. A cross-sectional study was conducted to document the seroprevalence, geographical extent and risk factors for B. suis in dogs at-risk of contracting the disease. Eligible dogs were those that were known to hunt or consume feral pig meat. Dogs were enrolled through private veterinary clinics and/or directly by District Veterinarians in six regions of NSW and QLD. Blood was collected by venepuncture and tested for B. suis antibodies using the Rose Bengal Test (RBT) followed by a Complement Fixation Test (CFT) if they returned a positive RBT. Owners were invited to complete a questionnaire on the dogs' signalment, husbandry including hunting practices and locations, and any clinical signs referable to brucellosis. Of the 317 dogs included in the prevalence survey, 21 were seropositive returning a survey-adjusted true seroprevalence of 9.3 (95% CI 0.45 to 18) B. suis positive dogs per 100 dogs at-risk. True seroprevalence ranged from 0 to 24 B. suis positive dogs per 100 across eastern Australia, with the highest prevalence in central west NSW and southern QLD. Adjusted for other factors, dogs that shared a household with other seropositive dogs and those that traveled away from their home regions to hunt were more likely to be seropositive. Clinical signs at presentation were not predictive of serostatus, with seropositive and seronegative dogs equally likely to present with signs consistent with brucellosis. The results obtained from this study show that B. suis exposure is relatively common in dogs that have contact with feral pigs, with one in 10 testing seropositive. Further studies are needed to understand the progression and risk of transmission from seropositive dogs

Chromosome contacts in activated T cells identify autoimmune disease candidate genes

BACKGROUND: Autoimmune disease-associated variants are preferentially found in regulatory regions in immune cells, particularly CD4+ T cells. Linking such regulatory regions to gene promoters in disease-relevant cell contexts facilitates identification of candidate disease genes. RESULTS: Within four hours, activation of CD4+ T cells invokes changes in histone modifications and enhancer RNA transcription that correspond to altered expression of the interacting genes identified by promoter capture Hi-C (PCHi-C). By integrating PCHi-C data with genetic associations for five autoimmune diseases we prioritised 245 candidate genes with a median distance from peak signal to prioritised gene of 153 kb. Just under half (108/245) prioritised genes related to activation-sensitive interactions. This included IL2RA, where allele-specific expression analyses were consistent with its interaction-mediated regulation, illustrating the utility of the approach. CONCLUSIONS: Our systematic experimental framework offers an alternative approach to candidate causal gene identification for variants with cell state-specific functional effects, with achievable sample sizes.This work was funded by the JDRF (9-2011-253), the Wellcome Trust (089989, 091157, 107881), the UK Medical Research Council (MR/L007150/1, MC_UP_1302/5), the UK Biotechnology and Biological Sciences Research Council (BB/J004480/1) and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. The research leading to these results has received funding from the European Union’s 7th Framework Programme (FP7/2007-2013) under grant agreement no. 241447 (NAIMIT). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (100140)

Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters

This is the final version of the article. It first appeared from Elsevier (Cell Press) via https://doi.org/10.1016/j.cell.2016.09.03

Los servicios en los esquemas de integración: algunas consideraciones y opciones para Centroamérica: versión provisional

Incluye Bibliografí

Australian bat lyssavirus

Background: Australian bat lyssavirus (ABLV) causes human illness that is indistinguishable from classical rabies. All Australian bats have the potential to carry and transmit ABLV, and potentially risky human exposures to bats are common. ABLV infection has resulted in three human deaths in Australia since 1996. Objective: The aim of this article is to equip general practitioners (GPs) to assist in the prevention and management of potential ABLV exposures in Australia, including complex clinical scenarios that are not fully addressed in current national guidelines. Discussion: Potential ABLV exposures are frequently encountered in general practice. GPs play a critical role in risk mitigation for groups such as veterinarians and wildlife carers, and in triggering urgent multidisciplinary responses to potential exposures. Timely notification of the public health unit following a potential exposure is crucial to ensure appropriate assessment and access to correct treatment. Complex exposure scenarios require careful consideration

Chromosome contacts in activated T cells identify autoimmune disease candidate genes

Abstract Background Autoimmune disease-associated variants are preferentially found in regulatory regions in immune cells, particularly CD4+ T cells. Linking such regulatory regions to gene promoters in disease-relevant cell contexts facilitates identification of candidate disease genes. Results Within 4 h, activation of CD4+ T cells invokes changes in histone modifications and enhancer RNA transcription that correspond to altered expression of the interacting genes identified by promoter capture Hi-C. By integrating promoter capture Hi-C data with genetic associations for five autoimmune diseases, we prioritised 245 candidate genes with a median distance from peak signal to prioritised gene of 153 kb. Just under half (108/245) prioritised genes related to activation-sensitive interactions. This included IL2RA, where allele-specific expression analyses were consistent with its interaction-mediated regulation, illustrating the utility of the approach. Conclusions Our systematic experimental framework offers an alternative approach to candidate causal gene identification for variants with cell state-specific functional effects, with achievable sample sizes

Additional file 2: Figures S1–S14. of Chromosome contacts in activated T cells identify autoimmune disease candidate genes

Figure S1. Comparison of longer and shorter CD4+ T cell activation timecourses. Figure S2. Summary distributions of interacting fragments. Figure S3. Validation of PCHi-C by ChIA-PET. Figure S4. Chromatin state profiles of interacting fragments. Figure S5. Relationship of gene expression to PIR number and mRNA half-life. Figure S6. Definition and quantification of regulatory RNAs. Figure S7. blockshifter calibration. Figure S8. MDN1 is prioritised for RA through ImmunoChip but not GWAS data. Figure S9. Gene prioritisation using COGS. Figure S10. Multiple genes on chromosome 1q32.1 (IL10, IL19, IL20, IL24, FCAMR/PIGR) are prioritised for T1D, CRO and UC. Figure S11. Histograms show the distribution of summed PIR length by gene in non-activated CD4+ T cells (top panel) and TAD length in naive CD4+ T cells. Figure S12. IRF8 and EMC8/COX4I1 on chromosome 16 are prioritised for RA and SLE. Figure S13. AHR on chromosome 7 is prioritised for RA in activated CD4+ T cells. Figure S14. Allelic imbalance in mRNA expression in individuals heterozygous for group A SNPs is confirmed with reporter SNP rs12244380 (IL2RA 3’ UTR). (PDF 4243 kb

Additional file 7: Table S6a. of Chromosome contacts in activated T cells identify autoimmune disease candidate genes

Results of ImmunoChip fine-mapping by GUESSFM. (GZ 2833 kb

Additional file 13: Table S8c. of Chromosome contacts in activated T cells identify autoimmune disease candidate genes

Whole-genome segmentation of non-activated and activated CD4 T cells into 15 states obtained from a CHROMHMM analysis using ChIP-seq data for non-activated CD4+ T cells. (GZ 1520 kb

Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters

SummaryLong-range interactions between regulatory elements and gene promoters play key roles in transcriptional regulation. The vast majority of interactions are uncharted, constituting a major missing link in understanding genome control. Here, we use promoter capture Hi-C to identify interacting regions of 31,253 promoters in 17 human primary hematopoietic cell types. We show that promoter interactions are highly cell type specific and enriched for links between active promoters and epigenetically marked enhancers. Promoter interactomes reflect lineage relationships of the hematopoietic tree, consistent with dynamic remodeling of nuclear architecture during differentiation. Interacting regions are enriched in genetic variants linked with altered expression of genes they contact, highlighting their functional role. We exploit this rich resource to connect non-coding disease variants to putative target promoters, prioritizing thousands of disease-candidate genes and implicating disease pathways. Our results demonstrate the power of primary cell promoter interactomes to reveal insights into genomic regulatory mechanisms underlying common diseases