March1-dependent modulation of donor MHC II on CD103+ dendritic cells mitigates alloimmunity.

In transplantation, donor dendritic cells (do-DCs) initiate the alloimmune response either by direct interaction with host T cells or by transferring intact donor MHC to host DCs. However, how do-DCs can be targeted for improving allograft survival is still unclear. Here we show CD103+ DCs are the major do-DC subset involved in the acute rejection of murine skin transplants. In the absence of CD103+ do-DCs, less donor MHC-II is carried to host lymph nodes, fewer allogenic T cells are primed and allograft survival is prolonged. Incubation of skin grafts with the anti-inflammatory mycobacterial protein DnaK reduces donor MHC-II on CD103+DCs and prolongs graft survival. This effect is mediated through IL-10-induced March1, which ubiquitinates and decreases MHC-II levels. Importantly, in vitro pre-treatment of human DCs with DnaK reduces their ability to prime alloreactive T cells. Our findings demonstrate a novel therapeutic approach to dampen alloimmunity by targeting donor MHC-II on CD103+DCs

Comparative Analysis between Hydrous Ethanol and Gasoline C Pricing in Brazilian Retail Market

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miR-155 in the progression of lung fibrosis in systemic sclerosis

Background\ud MicroRNA (miRNA) control key elements of mRNA stability and likely contribute to the dysregulated lung gene expression observed in systemic sclerosis associated interstitial lung disease (SSc-ILD). We analyzed the miRNA gene expression of tissue and cells from patients with SSc-ILD. A chronic lung fibrotic murine model was used.\ud \ud Methods\ud RNA was isolated from lung tissue of 12 patients with SSc-ILD and 5 controls. High-resolution computed tomography (HRCT) was performed at baseline and 2–3 years after treatment. Lung fibroblasts and peripheral blood mononuclear cells (PBMC) were isolated from healthy controls and patients with SSc-ILD. miRNA and mRNA were analyzed by microarray, quantitative polymerase chain reaction, and/or Nanostring; pathway analysis was performed by DNA Intelligent Analysis (DIANA)-miRPath v2.0 software. Wild-type and miR-155 deficient (miR-155ko) mice were exposed to bleomycin.\ud \ud Results\ud Lung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (q < 0.25). DIANA-miRPath revealed 57 Kyoto Encyclopedia of Genes and Genomes pathways related to the most dysregulated miRNA. miR-155 and miR-143 were strongly correlated with progression of the HRCT score. Lung fibroblasts only mildly expressed miR-155/miR-21 after several stimuli. miR-155 PBMC expression strongly correlated with lung function tests in SSc-ILD. miR-155ko mice developed milder lung fibrosis, survived longer, and weaker lung induction of several genes after bleomycin exposure compared to wild-type mice.\ud \ud Conclusions\ud miRNA are dysregulated in the lungs and PBMC of patients with SSc-ILD. Based on mRNA-miRNA interaction analysis and pathway tools, miRNA may play a role in the progression of the disease. Our findings suggest that targeting miR-155 might provide a novel therapeutic strategy for SSc-ILD

Linking plant phenology to conservation biology

Phenology has achieved a prominent position in current scenarios of global change research given its role inmonitoring and predicting the timing of recurrent life cycle events. However, the implications of phenology to environmental conservation and management remain poorly explored. Here,we present the first explicit appraisal of howphenology-amultidisciplinary science encompassing biometeorology, ecology, and evolutionary biology- can make a key contribution to contemporary conservation biology. We focus on shifts in plant phenology induced by global change, their impacts on species diversity and plant-animal interactions in the tropics, and how conservation efforts could be enhanced in relation to plant resource organization. We identify the effects of phenological changes and mismatches in the maintenance and conservation of mutualistic interactions, and examine how phenological research can contribute to evaluate, manage and mitigate the consequences of land-use change and other natural and anthropogenic disturbances, such as fire, exotic and invasive species. Wealso identify cutting-edge tools that can improve the spatial and temporal coverage of phenological monitoring, from satellites to drones and digital cameras. We highlight the role of historical information in recovering long-term phenological time series, and track climate-related shifts in tropical systems. Finally, we propose a set of measures to boost the contribution of phenology to conservation science.Weadvocate the inclusion of phenology into predictive models integrating evolutionary history to identify species groups that are either resilient or sensitive to future climate-change scenarios, and understand how phenological m ismatches can affect community dynamics, ecosystem services, and conservation over time

Coefficient shifts in geographical ecology: an empirical evaluation of spatial and non-spatial regression

Copyright © 2009 The Authors. Copyright © ECOGRAPHY 2009.A major focus of geographical ecology and macro ecology is to understand the causes of spatially structured ecological patterns. However, achieving this understanding can be complicated when using multiple regressions, because the relative importance of explanatory variables, as measured by regression coefficients, can shift depending on whether spatially explicit or non-spatial modelling is used. However, the extent to which coefficients may shift and why shifts occur are unclear. Here, we analyze the relationship between environmental predictors and the geographical distribution of species richness, body size, range size and abundance in 97 multi-factorial data sets. Our goal was to compare standardized partial regression coefficients of non-spatial ordinary least squares regressions (i.e. models fitted using ordinary least squares without taking autocorrelation into account; “OLS models” hereafter) and eight spatial methods to evaluate the frequency of coefficient shifts and identify characteristics of data that might predict when shifts are likely. We generated three metrics of coefficient shifts and eight characteristics of the data sets as predictors of shifts. Typical of ecological data, spatial autocorrelation in the residuals of OLS models was found in most data sets. The spatial models varied in the extent to which they minimized residual spatial autocorrelation. Patterns of coefficient shifts also varied among methods and datasets, although the magnitudes of shifts tended to be small in all cases. We were unable to identify strong predictors of shifts, including the levels of autocorrelation in either explanatory variables or model residuals. Thus, changes in coefficients between spatial and non-spatial methods depend on the method used and are largely idiosyncratic, making it difficult to predict when or why shifts occur. We conclude that the ecological importance of regression coefficients cannot be evaluated with confidence irrespective of whether spatially explicit modelling is used or not. Researchers may have little choice but to be more explicit about the uncertainty of models and more cautious in their interpretation

Lutzomyia longipalpis Saliva Induces Heme Oxygenase-1 Expression at Bite Sites

Sand flies bite mammalian hosts to obtain a blood meal, driving changes in the host inflammatory response that support the establishment of Leishmania infection. This effect is partially attributed to components of sand fly saliva, which are able to recruit and activate leukocytes. Our group has shown that heme oxygenase-1 (HO-1) favors Leishmania survival in infected cells by reducing inflammatory responses. Here, we show that exposure to sand fly bites is associated with induction of HO-1 in vivo. Histopathological analyses of skin specimens from human volunteers experimentally exposed to sand fly bites revealed that HO-1 and Nrf2 are produced at bite sites in the skin. These results were recapitulated in mice ears injected with a salivary gland sonicate (SGS) or exposed to sand fly bites, indicating that vector saliva may be a key factor in triggering HO-1 expression. Resident skin macrophages were the main source HO-1 at 24–48 h after bites. Additionally, assays in vivo after bites and in vitro after stimulation with saliva both demonstrated that HO-1 production by macrophages was Nrf2-dependent. Collectively, our data demonstrates that vector saliva induces early HO-1 production at the bite sites, representing a major event associated with establishment of naturally-transmitted Leishmania infections

Erratum to: The study of cardiovascular risk in adolescents – ERICA: rationale, design and sample characteristics of a national survey examining cardiovascular risk factor profile in Brazilian adolescents

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