85 research outputs found

    Traumatic brain injury increases levels of miR-21 in extracellular vesicles: implications for neuroinflammation

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    Traumatic brain injury (TBI) is an important health concern and effective treatment strategies remain elusive. Understanding the complex multicellular response to TBI may provide new avenues for intervention. In the context of TBI, cell–cell communication is critical. One relatively unexplored form of cell–cell communication in TBI is extracellular vesicles (EVs). These membrane‐bound vesicles can carry many different types of cargo between cells. Recently, miRNA in EVs have been shown to mediate neuroinflammation and neuronal injury. To explore the role of EV‐associated miRNA in TBI, we isolated EVs from the brain of injured mice and controls, purified RNA from brain EVs, and performed miRNA sequencing. We found that the expression of miR‐212 decreased, while miR‐21, miR‐146, miR‐7a, and miR‐7b were significantly increased with injury, with miR‐21 showing the largest change between conditions. The expression of miR‐21 in the brain was primarily localized to neurons near the lesion site. Interestingly, adjacent to these miR‐21‐expressing neurons were activated microglia. The concurrent increase in miR‐21 in EVs with the elevation of miR‐21 in neurons, suggests that miR‐21 is secreted from neurons as potential EV cargo. Thus, this study reveals a new potential mechanism of cell–cell communication not previously described in TBI

    Re-shaping models of E.coli population dynamics in livestock faeces: Increased bacterial risk to humans?

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    Dung-pats excreted directly on pasture from grazing animals can contribute a significant burden of faecal microbes to agricultural land. The aim of this study was to use a combined field and modelling approach to determine the importance of Escherichia coli growth in dung-pats when predicting faecal bacteria accumulation on grazed grassland. To do this an empirical model was developed to predict the dynamics of an E. coli reservoir within 1 ha plots each grazed by four beef steers for six months. Published first-order die-off coefficients were used within the model to describe the expected decline of E. coli in dung-pats. Modelled estimates using first-order kinetics led to an underestimation of the observed E. coli land reservoir, when using site-specific die-off coefficients. A simultaneous experiment determined the die-off profiles of E. coli within fresh faeces of beef cattle under field relevant conditions and suggested that faecal bacteria may experience growth and re-growth in the period post defecation when exposed to a complex interaction of environmental drivers such as variable temperature, UV radiation and moisture levels. This growth phase in dung-pats is not accounted for in models based on first-order die-off coefficients. When the model was amended to incorporate the growth of E. coli, equivalent to that observed in the field study, the prediction of the E. coli reservoir was improved with respect to the observed data and produced a previously unquantified step-change improvement in model predictions of the accumulation of these faecal bacteria on grasslands. Results from this study suggest that the use of first-order kinetic equations for determining land-based reservoirs of faecal bacteria should be approached with caution and greater emphasis placed on accounting for actual survival patterns observed under field relevant conditions

    Abundance and Distribution of Enteric Bacteria and Viruses in Coastal and Estuarine Sediments—a Review

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    The long term survival of fecal indicator organisms (FIOs) and human pathogenic microorganisms in sediments is important from a water quality, human health and ecological perspective. Typically, both bacteria and viruses strongly associate with particulate matter present in freshwater, estuarine and marine environments. This association tends to be stronger in finer textured sediments and is strongly influenced by the type and quantity of clay minerals and organic matter present. Binding to particle surfaces promotes the persistence of bacteria in the environment by offering physical and chemical protection from biotic and abiotic stresses. How bacterial and viral viability and pathogenicity is influenced by surface attachment requires further study. Typically, long-term association with surfaces including sediments induces bacteria to enter a viable-but-non-culturable (VBNC) state. Inherent methodological challenges of quantifying VBNC bacteria may lead to the frequent under-reporting of their abundance in sediments. The implications of this in a quantitative risk assessment context remain unclear. Similarly, sediments can harbor significant amounts of enteric viruses, however, the factors regulating their persistence remains poorly understood. Quantification of viruses in sediment remains problematic due to our poor ability to recover intact viral particles from sediment surfaces (typically <10%), our inability to distinguish between infective and damaged (non-infective) viral particles, aggregation of viral particles, and inhibition during qPCR. This suggests that the true viral titre in sediments may be being vastly underestimated. In turn, this is limiting our ability to understand the fate and transport of viruses in sediments. Model systems (e.g., human cell culture) are also lacking for some key viruses, preventing our ability to evaluate the infectivity of viruses recovered from sediments (e.g., norovirus). The release of particle-bound bacteria and viruses into the water column during sediment resuspension also represents a risk to water quality. In conclusion, our poor process level understanding of viral/bacterial-sediment interactions combined with methodological challenges is limiting the accurate source apportionment and quantitative microbial risk assessment for pathogenic organisms associated with sediments in aquatic environments

    Skeletal Adaptation to Intramedullary Pressure-Induced Interstitial Fluid Flow Is Enhanced in Mice Subjected to Targeted Osteocyte Ablation

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    Interstitial fluid flow (IFF) is a potent regulatory signal in bone. During mechanical loading, IFF is generated through two distinct mechanisms that result in spatially distinct flow profiles: poroelastic interactions within the lacunar-canalicular system, and intramedullary pressurization. While the former generates IFF primarily within the lacunar-canalicular network, the latter generates significant flow at the endosteal surface as well as within the tissue. This gives rise to the intriguing possibility that loading-induced IFF may differentially activate osteocytes or surface-residing cells depending on the generating mechanism, and that sensation of IFF generated via intramedullary pressurization may be mediated by a non-osteocytic bone cell population. To begin to explore this possibility, we used the Dmp1-HBEGF inducible osteocyte ablation mouse model and a microfluidic system for modulating intramedullary pressure (ImP) to assess whether structural adaptation to ImP-driven IFF is altered by partial osteocyte depletion. Canalicular convective velocities during pressurization were estimated through the use of fluorescence recovery after photobleaching and computational modeling. Following osteocyte ablation, transgenic mice exhibited severe losses in bone structure and altered responses to hindlimb suspension in a compartment-specific manner. In pressure-loaded limbs, transgenic mice displayed similar or significantly enhanced structural adaptation to Imp-driven IFF, particularly in the trabecular compartment, despite up to ∼50% of trabecular lacunae being uninhabited following ablation. Interestingly, regression analysis revealed relative gains in bone structure in pressure-loaded limbs were correlated with reductions in bone structure in unpressurized control limbs, suggesting that adaptation to ImP-driven IFF was potentiated by increases in osteoclastic activity and/or reductions in osteoblastic activity incurred independently of pressure loading. Collectively, these studies indicate that structural adaptation to ImP-driven IFF can proceed unimpeded following a significant depletion in osteocytes, consistent with the potential existence of a non-osteocytic bone cell population that senses ImP-driven IFF independently and potentially parallel to osteocytic sensation of poroelasticity-derived IFF

    Vancouver, British Columbia: Host City for SRM 2006

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    The Rangelands archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform March 202

    Defoliation Response of Bluebunch Wheatgrass and Crested Wheatgrass: Why We Cannot Graze These Two Species in the Same Manner

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    The Rangelands archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform March 202
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