T Cell LFA-1 Engagement Induces HuR-Dependent Cytokine mRNA Stabilization through a Vav-1, Rac1/2, p38MAPK and MKK3 Signaling Cascade

Engagement of the β2 integrin, lymphocyte function-associated antigen-1 (LFA-1), results in stabilization of T cell mRNA transcripts containing AU-rich elements (AREs) by inducing rapid nuclear-to-cytosolic translocation of the RNA-stabilizing protein, HuR. However, little is known regarding integrin-induced signaling cascades that affect mRNA catabolism. This study examines the role of the GTPases, Rac 1 and Rac 2, and their downstream effectors, in the LFA-1-induced effects on mRNA.Engagement of LFA-1 to its ligand, ICAM-1, in human peripheral T cells resulted in rapid activation of Rac1 and Rac2. siRNA-mediated knockdown of either Rac1 or Rac2 prevented LFA-1-stimulated stabilization of the labile transcripts encoding IFN-γ and TNF-α, and integrin mediated IFN-γ mRNA stabilization was absent in T cells obtained from Rac2 gene-deleted mice. LFA-1 engagement-induced translocation of HuR and stabilization of TNF- α mRNA was lost in Jurkat cells deficient in the Rac guanine nucleotide exchange factor Vav-1 (J.Vav1). The transfection of J.Vav1 cells with constitutively active Rac1 or Rac2 stabilized a labile β-globin reporter mRNA, in a HuR-dependent manner. Furthermore, LFA-1-mediated mRNA stabilization and HuR translocation in mouse splenic T cells was dependent on the phosphorylation of the mitogen-activated protein kinase kinase, MKK3, and its target MAP kinase p38MAPK, and lost in T cells obtained from MKK3 gene-deleted mice.Collectively, these results demonstrate that LFA-1-induced stabilization of ARE-containing mRNAs in T cells is dependent on HuR, and occurs through the Vav-1, Rac1/2, MKK3 and p38MAPK signaling cascade. This pathway constitutes a molecular switch that enhances immune and pro-inflammatory gene expression in T cells undergoing adhesion at sites of activation and effector function

Climatic and geographic predictors of life history variation in Eastern Massasauga (Sistrurus catenatus): A range-wide synthesis

Elucidating how life history traits vary geographically is important to understanding variation in population dynamics. Because many aspects of ectotherm life history are climate-dependent, geographic variation in climate is expected to have a large impact on population dynamics through effects on annual survival, body size, growth rate, age at first reproduction, size-fecundity relationship, and reproductive frequency. The Eastern Massasauga (Sistrurus catenatus) is a small, imperiled North American rattlesnake with a distribution centered on the Great Lakes region, where lake effects strongly influence local conditions. To address Eastern Massasauga life history data gaps, we compiled data from 47 study sites representing 38 counties across the range. We used multimodel inference and general linear models with geographic coordinates and annual climate normals as explanatory variables to clarify patterns of variation in life history traits. We found strong evidence for geographic variation in six of nine life history variables. Adult female snout-vent length and neonate mass increased with increasing mean annual precipitation. Litter size decreased with increasing mean temperature, and the size-fecundity relationship and growth prior to first hibernation both increased with increasing latitude. The proportion of gravid females also increased with increasing latitude, but this relationship may be the result of geographically varying detection bias. Our results provide insights into ectotherm life history variation and fill critical data gaps, which will inform Eastern Massasauga conservation efforts by improving biological realism for models of population viability and climate change

SNAPSHOT USA 2019 : a coordinated national camera trap survey of the United States

This article is protected by copyright. All rights reserved.With the accelerating pace of global change, it is imperative that we obtain rapid inventories of the status and distribution of wildlife for ecological inferences and conservation planning. To address this challenge, we launched the SNAPSHOT USA project, a collaborative survey of terrestrial wildlife populations using camera traps across the United States. For our first annual survey, we compiled data across all 50 states during a 14-week period (17 August - 24 November of 2019). We sampled wildlife at 1509 camera trap sites from 110 camera trap arrays covering 12 different ecoregions across four development zones. This effort resulted in 166,036 unique detections of 83 species of mammals and 17 species of birds. All images were processed through the Smithsonian's eMammal camera trap data repository and included an expert review phase to ensure taxonomic accuracy of data, resulting in each picture being reviewed at least twice. The results represent a timely and standardized camera trap survey of the USA. All of the 2019 survey data are made available herein. We are currently repeating surveys in fall 2020, opening up the opportunity to other institutions and cooperators to expand coverage of all the urban-wild gradients and ecophysiographic regions of the country. Future data will be available as the database is updated at eMammal.si.edu/snapshot-usa, as well as future data paper submissions. These data will be useful for local and macroecological research including the examination of community assembly, effects of environmental and anthropogenic landscape variables, effects of fragmentation and extinction debt dynamics, as well as species-specific population dynamics and conservation action plans. There are no copyright restrictions; please cite this paper when using the data for publication.Publisher PDFPeer reviewe

279 - Xanes Studies on UV-Irradiated Interstellar Ice Analogs: A Comparison to STARDUST Samples

We present C-, N-, and O-XANES (X-ray Absorption Near-Edge Spectroscopy) results of organic residues produced in the laboratory from the UV irradiation of astrophysical ice analogs containing H20, CO, CH30H, NH31 in order to mimic processes that may occur in cold icy bodies of the outer Solar System, particularly in comets, Such analyses showed that laboratory-formed organic residues mainly consist of a solid phase and an oily phase. C-XANES analysis of the solid phase suggests a rich distribution of organic functionalities, among which carbonyl groups, C=C bonds, and alcohols are present. Results from N-XANES indicate the possible presence of amide, amine, and nitrile groups, The O-XANES spectra confirmed the a-bearing groups, These results are compared with the XANES spectra obtained from STARDUST cometary samples

Role of autophagy genetic variants for the risk of Candida infections

Candida albicans can cause candidemia in neutropenic and critically ill patients, and oropharyngeal candidiasis in HIV-positive patients with low CD4(+) counts. However, not all patients at risk develop Candida infections, and the genetic background of the patient might play a role in the susceptibility to infection. Autophagy mediates pathogen clearance and modulation of inflammation. The aim of this study was to assess the effect of genetic variation in the ATG16L1 and IRGM autophagy genes on the susceptibility to candidemia and oropharyngeal candidiasis. We assessed whether genetic variation in the ATG16L1 and IRGM genes influences susceptibility to candidemia in a cohort of candidemia patients of both African and European origin. In addition, we assessed the effect of these polymorphisms for the susceptibility to oropharyngeal candidiasis in an HIV-positive cohort from Tanzania. Functional studies have been performed to assess the effect of the ATG16L1 and IRGM genetic variants on cytokine production both in vitro and in vivo. The results indicate that ATG16L1 variants modulate production of TNFα, but not other cytokines, while no effects were seen in the presence of IRGM polymorphisms. In addition, no significant associations between the SNPs in the ATG16L1 and IRGM genetic variants and the incidence of candidemia or oropharyngeal candidiasis were identified. In conclusion, despite moderate effects on the modulation of proinflammatory cytokine production, genetic variation in the autophagy genes ATG16L1 and IRGM has a minor impact on the susceptibility to both mucosal and systemic Candida infections

Ælfric of Eynsham and Two<i>Post-Mortem</i>Visions

This essay discusses what is possibly the earliest translation from theVitas Patrumcorpus into a Western European vernacular, i.e. the Old English version of two visions of departing souls from theVerba Seniorumby Ælfric of Eynsham. Contrary to received notions, Ælfric favoured the narratives of the Desert Fathers as sources for paradigms of clerical celibacy and continence, two of the values that he was most anxious to teach and on which he took a strongly reformist stance. The two case studies presented aim to shed new light on the diffusion and appreciation of the Desert Fathers tales in Benedictine Reform England, in that they will show that, not unlike many anonymous homilists, Ælfric too drew on them as eschatological sources to conjure up two dramaticpost-mortemscenes

Relationship between latitude (untransformed) and age-zero annual growth as explained by the top-ranked model using AIC_c (Table 3).

<p>The shaded area represents the smoothed 95% CI using t-based approximations. County and district abbreviations are as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172011#pone.0172011.g001" target="_blank">Fig 1</a>.</p

Sources for Eastern Massasauga life history information including locality and study years.

<p>Sources for Eastern Massasauga life history information including locality and study years.</p