Survey of small intestinal and systemic immune responses following murine Arcobacter butzleri infection

Background Arcobacter (A.) butzleri has been described as causative agent for sporadic cases of human gastroenteritis with abdominal pain and acute or prolonged watery diarrhea. In vitro studies revealed distinct adhesive, invasive and cytotoxic properties of A. butzleri. Information about the underlying immunopathological mechanisms of infection in vivo, however, are scarce. The aim of this study was to investigate the immunopathological properties of two different A. butzleri strains in a well-established murine infection model. Results Gnotobiotic IL-10 −/− mice, in which the intestinal microbiota was depleted by broad-spectrum antibiotic treatment, were perorally infected with two different A. butzleri strains isolated from a diseased patient (CCUG 30485) or fresh chicken meat (C1), respectively. Eventhough bacteria of either strain could stably colonize the intestinal tract at day 6 and day 16 postinfection (p.i.), mice did not exert infection induced symptoms such as diarrhea or wasting. In small intestines of infected mice, however, increased numbers of apoptotic cells could be detected at day 16, but not day 6 following infection with either strain. A strain-dependent influx of distinct immune cell populations such as T and B cells as well as of regulatory T cells could be observed upon A. butzleri infection which was accompanied by increased small intestinal concentrations of pro-inflammatory cytokines such as TNF, IFN-γ, MCP-1 and IL-6. Remarkably, inflammatory responses following A. butzleri infection were not restricted to the intestinal tract, given that the CCUG 30485 strain induced systemic immune responses as indicated by increased IFN-γ concentrations in spleens at day 6, but not day 16 following infection. Conclusion Upon peroral infection A. butzleri stably colonized the intestinal tract of gnotobiotic IL-10 −/− mice. The dynamics of distinct local and systemic inflammatory responses could be observed in a strain-dependent fashion pointing towards an immunopathogenic potential of A. butzleri in vivo. These results indicate that gnotobiotic IL-10 −/− mice are well suited to further investigate the molecular mechanisms underlying arcobacteriosis in vivo

Arcobacter butzleri Induce Colonic, Extra-Intestinal and Systemic Inflammatory Responses in Gnotobiotic IL-10 Deficient Mice in a Strain-Dependent Manner

BACKGROUND: The immunopathological impact of human Arcobacter (A.) infections is under current debate. Episodes of gastroenteritis with abdominal pain and acute or prolonged watery diarrhea were reported for A. butzleri infected patients. Whereas adhesive, invasive and cytotoxic capacities have been described for A. butzleri in vitro, only limited information is available about the immunopathogenic potential and mechanisms of infection in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Gnotobiotic IL-10-/- mice were generated by broad-spectrum antibiotic treatment and perorally infected with the A. butzleri strains CCUG 30485 and C1 shown to be invasive in cell culture assays. Bacterial colonization capacities, clinical conditions, intestinal, extra-intestinal and systemic immune responses were monitored at day six and 16 postinfection (p.i.). Despite stable intestinal A. butzleri colonization at high loads, gnotobiotic IL-10-/- mice were virtually unaffected and did not display any overt symptoms at either time point. Notably, A. butzleri infection induced apoptosis of colonic epithelial cells which was paralleled by increased abundance of proliferating cells. Furthermore A. butzleri infection caused a significant increase of distinct immune cell populations such as T and B cells, regulatory T cells, macrophages and monocytes in the colon which was accompanied by elevated colonic TNF, IFN-γ, nitric oxide (NO), IL-6, IL-12p70 and MCP-1 concentrations. Strikingly, A. butzleri induced extra-intestinal and systemic immune responses as indicated by higher NO concentrations in kidney and increased TNF, IFN-γ, IL-12p70 and IL-6 levels in serum samples of infected as compared to naive mice. Overall, inflammatory responses could be observed earlier in the course of infection by the CCUG 30485 as compared to the C1 strain. CONCLUSION/SIGNIFICANCE: Peroral A. butzleri infection induced not only intestinal but also extra-intestinal and systemic immune responses in gnotobiotic IL-10-/- mice in a strain-dependent manner. These findings point towards an immunopathogenic potential of A. butzleri in vertebrate hosts

Управление производственным процессом на предприятии

В выпускной квалификационной работе будет рассмотрена оптимизация производственного процесса на деревообрабатывающем предприятии в рамках управления производственным процессом.In the final qualifying work will consider the optimization of the production process at the woodworking enterprise in the management of the production process

Партисипаторность как механизм успешной реализации проекта туристско-рекреационного кластера "Северск" в рамках концепции "ИНО ТОМСК 2020"

Общественность выступает потребителем туристских услуг, не вовлеченным в процессы реализации. В итоге, усилия и затраты государства приобретают низкую эффективность. Местное население, уже изначально, ограничено и дистанционно к системе предоставления туристских услуг. Накапливаются нереализованные социальные ожидания населения, что может привести к риску социальной нестабильности. Запустились процессы переосмысления образа жизни в городе, благодаря городским территориальным сообществам. Повысились требования людей к качеству городской среды. Население стало отстаивать право на доступное и качественное жилье, на удобные дворы и улицы, на хорошие парки и скверы.The public acts as a consumer of social services, not involved in the implementation processes. As a result, the efforts and costs of the state acquire low efficiency. The local population, already initially, is limited and remotely to the system of providing social services. Unrealized social expectations of the population accumulate, which can lead to the risk of social instability. The processes of rethinking the way of life in the city were launched, thanks to the urban territorial communities. People's demands for the quality of the urban environment have increased. The population began to uphold the right to affordable and quality housing, to comfortable yards and streets, to good parkand public gardens. The notion of "comfortable city" has become a trend in different regions

Технологические решения для строительства эксплуатационной наклонно-направленной скважины глубиной 2680 метров Катыльгинском нефтяном месторождении (Томская область)

Цель работы – рассмотреть амбарное и безамбарное бурение, сравнить, описать преимущества. В процессе исследования проводились разбор и исследование процесса бурения по безамбарной и амбарной технологии. В результате исследования были выявлены преимущества использования безамбарной технологии.The purpose of the work is to examine the barn and bezambar drilling, compare, describe the advantages. In the course of the study, the drilling process was analyzed and studied in the case of bezambar and granary technology. As a result of the research, the advantages of using the zero-bar technology were revealed

MHCII-independent CD4(+) T cells protect injured CNS neurons via IL-4

A body of experimental evidence suggests that T cells mediate neuroprotection following CNS injury; however, the antigen specificity of these T cells and how they mediate neuroprotection are unknown. Here, we have provided evidence that T cell-mediated neuroprotection after CNS injury can occur independently of major histocompatibility class II (MHCII) signaling to T cell receptors (TCRs). Using two murine models of CNS injury, we determined that damage-associated molecular mediators that originate from injured CNS tissue induce a population of neuroprotective, IL-4-producing T cells in an antigen-independent fashion. Compared with wild-type mice, IL-4-deficient animals had decreased functional recovery following CNS injury; however, transfer of CD4+ T cells from wild-type mice, but not from IL-4-deficient mice, enhanced neuronal survival. Using a culture-based system, we determined that T cell-derived IL-4 protects and induces recovery of injured neurons by activation of neuronal IL-4 receptors, which potentiated neurotrophin signaling via the AKT and MAPK pathways. Together, these findings demonstrate that damage-associated molecules from the injured CNS induce a neuroprotective T cell response that is independent of MHCII/TCR interactions and is MyD88 dependent. Moreover, our results indicate that IL-4 mediates neuroprotection and recovery of the injured CNS and suggest that strategies to enhance IL-4-producing CD4+ T cells have potential to attenuate axonal damage in the course of CNS injury in trauma, inflammation, or neurodegeneration

Popular Branchings and Their Dual Certificates

Let G be a digraph where every node has preferences over its incoming edges. The preferences of a node extend naturally to preferences over branchings, i.e., directed forests; a branching B is popular if B does not lose a head-to-head election (where nodes cast votes) against any branching. Such popular branchings have a natural application in liquid democracy. The popular branching problem is to decide if G admits a popular branching or not. We give a characterization of popular branchings in terms of dual certificates and use this characterization to design an efficient combinatorial algorithm for the popular branching problem. When preferences are weak rankings, we use our characterization to formulate the popular branching polytope in the original space and also show that our algorithm can be modified to compute a branching with least unpopularity margin. When preferences are strict rankings, we show that “approximately popular” branchings always exist.TU Berlin, Open-Access-Mittel – 202