Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
Project description:Brucella melitensis and Brucella canis differ by ~75 genes yet B. melitensis is highly virulent for humans while B. canis is considered rarely pathogenic. No identified bacterial factors or mechanisms account for this difference in virulence. To identify functional differences of these two bacteria, gene transcription was examined during infection of murine macrophages and compared to bacteria grown in broth. Our analysis identified transcriptional differences in macrophage infection between B. melitensis and B. canis genes involved in iron transport. Increased transcription of the TonB, enterobactin, and ferric anguibactin transport systems were observed in B. canis but not B. melitensis during infection of macrophages. Therefore, iron appears as an important requirement during the first 24h of infection by B. canis but not for B. melitensis and provides strategies for controlling these pathogens. Comparison of total bacterial RNA from Brucella canis infected murine macrophages to broth grown bacteria
Project description:Brucella melitensis and Brucella canis differ by ~75 genes yet B. melitensis is highly virulent for humans while B. canis is considered rarely pathogenic. No identified bacterial factors or mechanisms account for this difference in virulence. To identify functional differences of these two bacteria, gene transcription was examined during infection of murine macrophages and compared to bacteria grown in broth. Our analysis identified transcriptional differences in macrophage infection between B. melitensis and B. canis genes involved in iron transport. Increased transcription of the TonB, enterobactin, and ferric anguibactin transport systems were observed in B. canis but not B. melitensis during infection of macrophages. Therefore, iron appears as an important requirement during the first 24h of infection by B. canis but not for B. melitensis and provides strategies for controlling these pathogens. comparison of total bacterial RNA from Brucella canis infected murine macrophages and broth grown bacteria
Project description:Brucella melitensis and Brucella canis differ by ~75 genes yet B. melitensis is highly virulent for humans while B. canis is considered rarely pathogenic. No identified bacterial factors or mechanisms account for this difference in virulence. To identify functional differences of these two bacteria, gene transcription was examined during infection of murine macrophages and compared to bacteria grown in broth. Our analysis identified transcriptional differences in macrophage infection between B. melitensis and B. canis genes involved in iron transport. Increased transcription of the TonB, enterobactin, and ferric anguibactin transport systems were observed in B. canis but not B. melitensis during infection of macrophages. Therefore, iron appears as an important requirement during the first 24h of infection by B. canis but not for B. melitensis and provides strategies for controlling these pathogens. Comparison of total bacterial RNA from Brucella canis infected murine macrophages at 5 and 24h
Project description:Brucella melitensis and Brucella canis differ by ~75 genes yet B. melitensis is highly virulent for humans while B. canis is considered rarely pathogenic. No identified bacterial factors or mechanisms account for this difference in virulence. To identify functional differences of these two bacteria, gene transcription was examined during infection of murine macrophages and compared to bacteria grown in broth. Our analysis identified transcriptional differences in macrophage infection between B. melitensis and B. canis genes involved in iron transport. Increased transcription of the TonB, enterobactin, and ferric anguibactin transport systems were observed in B. canis but not B. melitensis during infection of macrophages. Therefore, iron appears as an important requirement during the first 24h of infection by B. canis but not for B. melitensis and provides strategies for controlling these pathogens. Comparison of total bacterial RNA from Brucella melitensis infected murine macrophages to broth grown bacteria
Project description:Rationale: Patients in the intensive care unit (ICU) are frequently exposed to unnecessary antibiotics. Markers of the host response to infection may aid pneumonia diagnosis and avoid antibiotic-induced complications. Objective: To assess the host response to suspected bacterial pneumonia through assessment of alveolar neutrophilia and transcriptomic profiling of alveolar macrophages. Methods: We determined the test characteristics of BAL neutrophilia for the diagnosis of bacterial pneumonia in 3 cohorts of mechanically ventilated patients. In one cohort, we also isolated alveolar macrophages from BAL fluid and used the transcriptome to identify signatures of bacterial pneumonia. Finally, we developed a humanized mouse model of Pseudomonas aeruginosa pneumonia to determine if pathogen-specific signatures can be identified in human alveolar macrophages. Measurements and Main Results: BAL neutrophilia was highly sensitive for bacterial pneumonia in both the retrospective (N = 851) and validation cohorts (N = 76 and N = 79) with a negative predictive value of over 90% when BAL neutrophil percentage was less than 50%. A transcriptional signature of bacterial pneumonia was present in both resident and recruited macrophages. Gene signatures from both cell types identified patients with bacterial pneumonia with test characteristics similar to BAL neutrophilia. Conclusions: A BAL neutrophil percentage of less than 50% is highly sensitive for bacterial pneumonia. Informative transcriptomic signatures can be generated from BAL fluid obtained during routine clinical care in the ICU. The identification of novel host response biomarkers is a promising approach to aid the diagnosis and treatment of pneumonia.
Project description:Translational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P. leucopus in aging studies. Notably, P. leucopus exhibits distinct body composition characteristics, emphasizing reduced muscle force exertion and a unique metabolism, particularly in fat mass. Cardiovascular assessments showed changes in arterial stiffness, challenging conventional assumptions and highlighting the need for a nuanced interpretation of aging-related phenotypes. Our study also highlights inherent challenges associated with maintaining and phenotyping P. leucopus cohorts. Behavioral considerations, including anxiety-induced responses during handling and phenotyping assessment, pose obstacles in acquiring meaningful data. Moreover, the unique anatomy of P. leucopus necessitates careful adaptation of protocols designed for Mus musculus. While showcasing potential benefits, further extensive analyses across broader age ranges and larger cohorts are necessary to establish the reliability of P. leucopus as a robust and translatable model for aging studies.
Project description:Ducks and wild aquatic birds are the natural reservoirs of avian influenza viruses. However, the host proteome response that causes disease in vivo during infection by the highly pathogenic avian influenza (HPAI) H5N1 virus is still not well understood. In the present study, we compared the proteome response in Muscovy duck lung tissue during 3 day of infection with either a highly virulent or an avirulent H5N1 virus. During infection, proteins involved in immune response of neutrophils and size of cells were increased markedly in the lung by the virulent strain, while the avirulent strain evoked a distinct response, characterized by an increase in proteins involved in cell movement, maturation of dendritic cells, adhesion of phagocytes, and immune response of macrophages.
Project description:BackgroundCopy number variation is an important dimension of genetic diversity and has implications in development and disease. As an important model organism, the mouse is a prime candidate for copy number variant (CNV) characterization, but this has yet to be completed for a large sample size. Here we report CNV analysis of publicly available, high-density microarray data files for 351 mouse tail samples, including 290 mice that had not been characterized for CNVs previously.ResultsWe found 9634 putative autosomal CNVs across the samples affecting 6.87% of the mouse reference genome. We find significant differences in the degree of CNV uniqueness (single sample occurrence) and the nature of CNV-gene overlap between wild-caught mice and classical laboratory strains. CNV-gene overlap was associated with lipid metabolism, pheromone response and olfaction compared to immunity, carbohydrate metabolism and amino-acid metabolism for wild-caught mice and classical laboratory strains, respectively. Using two subspecies of wild-caught Mus musculus, we identified putative CNVs unique to those subspecies and show this diversity is better captured by wild-derived laboratory strains than by the classical laboratory strains. A total of 9 genic copy number variable regions (CNVRs) were selected for experimental confirmation by droplet digital PCR (ddPCR).ConclusionThe analysis we present is a comprehensive, genome-wide analysis of CNVs in Mus musculus, which increases the number of known variants in the species and will accelerate the identification of novel variants in future studies.