Gut microbes contribute to variation in solid organ transplant outcomes in mice

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Microbiome 6 (2018): 96, doi:10.1186/s40168-018-0474-8.Solid organ transplant recipients show heterogeneity in the occurrence and timing of acute rejection episodes. Understanding the factors responsible for such variability in patient outcomes may lead to improved diagnostic and therapeutic approaches. Rejection kinetics of transplanted organs mainly depends on the extent of genetic disparities between donor and recipient, but a role for environmental factors is emerging. We have recently shown that major alterations of the microbiota following broad-spectrum antibiotics, or use of germ-free animals, promoted longer skin graft survival in mice. Here, we tested whether spontaneous differences in microbial colonization between genetically similar individuals can contribute to variability in graft rejection kinetics. We compared rejection kinetics of minor mismatched skin grafts in C57BL/6 mice from Jackson Laboratory (Jax) and Taconic Farms (Tac), genetically similar animals colonized by different commensal microbes. Female Tac mice rejected skin grafts from vendor-matched males more quickly than Jax mice. We observed prolonged graft survival in Tac mice when they were exposed to Jax mice microbiome through co-housing or fecal microbiota transplantation (FMT) by gastric gavage. In contrast, exposure to Tac mice did not change graft rejection kinetics in Jax mice, suggesting a dominant suppressive effect of Jax microbiota. High-throughput sequencing of 16S rRNA gene amplicons from Jax and Tac mice fecal samples confirmed a convergence of microbiota composition after cohousing or fecal transfer. Our analysis of amplicon data associated members of a single bacterial genus, Alistipes, with prolonged graft survival. Consistent with this finding, members of the genus Alistipes were absent in a separate Tac cohort, in which fecal transfer from Jax mice failed to prolong graft survival. These results demonstrate that differences in resident microbiome in healthy individuals may translate into distinct kinetics of graft rejection, and contribute to interpersonal variability in graft outcomes. The association between Alistipes and prolonged skin graft survival in mice suggests that members of this genus might affect host physiology, including at sites distal to the gastrointestinal tract. Overall, these findings allude to a potential therapeutic role for specific gut microbes to promote graft survival through the administration of probiotics, or FMT.This work was supported by NIH/NIAID R01 AI115716 to MLA

Evaluation of Employee Recruitment and Selection Processes in a Selected Organization

Import 22/07/2015Tato diplomová práce se zaměřuje na posouzení procesů získávání a výběru zaměstnanců ve vybrané organizaci, přesněji ve Věznici Mírov, která je organizační jednotkou vězeňské služby České republiky. Teoretická část vysvětluje pojmy řízení lidských zdrojů, personální činnosti, získávání zaměstnanců a jejich výběr. Praktická část diplomové práce se zaměřuje na představení Věznice Mírov. Sleduje získávání, výběr a následné přijímaní uchazečů o volné pracovní místo, konkrétně na civilní pracovní pozici speciálního pedagoga a služební místo strážný. Cílem práce je popsat a posoudit procesy získávání a výběru zaměstnanců do zvolené organizace v rámci pracovního a služebního poměru. Tyto posouzení jsou založeny na analýze současných procesů a dotazníkové šetření. Následně jsou navrhnuta doporučení na jejich zlepšení.This diploma thesis is focused on evaluation of employee recruitment and selection processes in a selected organization. The organization is Prison Mírov, it is the organizational part of Prison Service of the Czech Republic. Theoretical part explains terms in field of the human resources management, personal activities, employee recruitment and selecting employees. Practical part of diploma thesis is focused on the presentation of the Prison Mírov. It monitors attracting, selecting and hiring aspirants for free berth concretely civil job special educator and service job guard. Objective of this thesis is describe and review of processes attracting and selecting employees to the selected oranization in case of employment and civil service. These considerations are based on analysis of current processes and survey. Afterwards there are drafted recommendations for their improvement.115 - Katedra managementudobř

System-wide transcriptome damage and tissue identity loss in COVID-19 patients

The molecular mechanisms underlying the clinical manifestations of coronavirus disease 2019 (COVID-19), and what distinguishes them from common seasonal influenza virus and other lung injury states such as acute respiratory distress syndrome, remain poorly understood. To address these challenges, we combine transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues to define body-wide transcriptome changes in response to COVID-19. We then match these data with spatial protein and expression profiling across 357 tissue sections from 16 representative patient lung samples and identify tissue-compartment-specific damage wrought by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, evident as a function of varying viral loads during the clinical course of infection and tissue-type-specific expression states. Overall, our findings reveal a systemic disruption of canonical cellular and transcriptional pathways across all tissues, which can inform subsequent studies to combat the mortality of COVID-19 and to better understand the molecular dynamics of lethal SARS-CoV-2 and other respiratory infections., • Across all organs, fibroblast, and immune cell populations increase in COVID-19 patients • Organ-specific cell types and functional markers are lost in all COVID-19 tissue types • Lung compartment identity loss correlates with SARS-CoV-2 viral loads • COVID-19 uniquely disrupts co-occurrence cell type clusters (different from IAV/ARDS) , Park et al. report system-wide transcriptome damage and tissue identity loss wrought by SARS-CoV-2, influenza, and bacterial infection across multiple organs (heart, liver, lung, kidney, and lymph nodes) and provide a spatiotemporal landscape of COVID-19 in the lung

Accurate and complete genomes from metagenomes.

Genomes are an integral component of the biological information about an organism; thus, the more complete the genome, the more informative it is. Historically, bacterial and archaeal genomes were reconstructed from pure (monoclonal) cultures, and the first reported sequences were manually curated to completion. However, the bottleneck imposed by the requirement for isolates precluded genomic insights for the vast majority of microbial life. Shotgun sequencing of microbial communities, referred to initially as community genomics and subsequently as genome-resolved metagenomics, can circumvent this limitation by obtaining metagenome-assembled genomes (MAGs); but gaps, local assembly errors, chimeras, and contamination by fragments from other genomes limit the value of these genomes. Here, we discuss genome curation to improve and, in some cases, achieve complete (circularized, no gaps) MAGs (CMAGs). To date, few CMAGs have been generated, although notably some are from very complex systems such as soil and sediment. Through analysis of about 7000 published complete bacterial isolate genomes, we verify the value of cumulative GC skew in combination with other metrics to establish bacterial genome sequence accuracy. The analysis of cumulative GC skew identified potential misassemblies in some reference genomes of isolated bacteria and the repeat sequences that likely gave rise to them. We discuss methods that could be implemented in bioinformatic approaches for curation to ensure that metabolic and evolutionary analyses can be based on very high-quality genomes

Additional file 5: of Gut microbes contribute to variation in solid organ transplant outcomes in mice

Transfer efficiency of ASVs following cohousing or FMT. Tables identifying ASVs detected in the majority of mice from either Jax or Tac prior to cohousing or FMT and which of these ASVs were gained or lost by cohousing or FMT. (XLSX 233 kb

Additional file 4: of Gut microbes contribute to variation in solid organ transplant outcomes in mice

Alpha diversity of the fecal microbiota is not associated with prolonged skin transplant survival in Jax mice. Figure showing Shannon entropy and inverse Simpson index of fecal microbiota from female Jax and Tac skin transplant recipients A. before and after cohousing, and B. before and after FMT from male Jax or Tac mice. (PDF 788 kb

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A Wolbachia pangenome reconstructed through genome-resolved metagenomics from individual <em>Culex pipiens</em> ovaries reveals viral differentiation

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