GEF-H1 Mediated Control of NOD1 Dependent NF-κB Activation by Shigella Effectors

Shigella flexneri has evolved the ability to modify host cell function with intracellular active effectors to overcome the intestinal barrier. The detection of these microbial effectors and the initiation of innate immune responses are critical for rapid mucosal defense activation. The guanine nucleotide exchange factor H1 (GEF-H1) mediates RhoA activation required for cell invasion by the enteroinvasive pathogen Shigella flexneri. Surprisingly, GEF-H1 is requisite for NF-κB activation in response to Shigella infection. GEF-H1 interacts with NOD1 and is required for RIP2 dependent NF-κB activation by H-Ala-D-γGlu-DAP (γTriDAP). GEF-H1 is essential for NF-κB activation by the Shigella effectors IpgB2 and OspB, which were found to signal in a NOD1 and RhoA Kinase (ROCK) dependent manner. Our results demonstrate that GEF-H1 is a critical component of cellular defenses forming an intracellular sensing system with NOD1 for the detection of microbial effectors during cell invasion by pathogens

Wolbachia Mediate Variation of Host Immunocompetence

BACKGROUND: After decades during which endosymbionts were considered as silent in their hosts, in particular concerning the immune system, recent studies have revealed the contrary. In the present paper, we addressed the effect of Wolbachia, the most prevalent endosymbiont in arthropods, on host immunocompetence. To this end, we chose the A. vulgare-Wolbachia symbiosis as a model system because it leads to compare consequences of two Wolbachia strains (wVulC and wVulM) on hosts from the same population. Moreover, A. vulgare is the only host-species in which Wolbachia have been directly observed within haemocytes which are responsible for both humoral and cellular immune responses. METHODOLOGY/PRINCIPAL FINDINGS: We sampled gravid females from the same population that were either asymbiotic, infected with wVulC, or infected with wVulM. The offspring from these females were tested and it was revealed that individuals harbouring wVulC exhibited: (i) lower haemocyte densities, (ii) more intense septicaemia in their haemolymph and (iii) a reduced lifespan as compared to individuals habouring wVulM or asymbiotic ones. Therefore, individuals in this population of A. vulgare appeared to suffer more from wVulC than from wVulM. Symbiotic titer and location in the haemocytes did not differ for the two Wolbachia strains showing that these two parameters were not responsible for differences observed in their extended phenotypes in A. vulgare. CONCLUSION/SIGNIFICANCE: The two Wolbachia strains infecting A. vulgare in the same population induced variation in immunocompetence and survival of their hosts. Such variation should highly influence the dynamics of this host-symbiont system. We propose in accordance with previous population genetic works, that wVulM is a local strain that has attenuated its virulence through a long term adaptation process towards local A. vulgare genotypes whereas wVulC, which is a widespread and invasive strain, is not locally adapted

Urban air pollution and emergency room admissions for respiratory symptoms: a case-crossover study in Palermo, Italy

<p>Abstract</p> <p>Background</p> <p>Air pollution from vehicular traffic has been associated with respiratory diseases. In Palermo, the largest metropolitan area in Sicily, urban air pollution is mainly addressed to traffic-related pollution because of lack of industrial settlements, and the presence of a temperate climate that contribute to the limited use of domestic heating plants. This study aimed to investigate the association between traffic-related air pollution and emergency room admissions for acute respiratory symptoms.</p> <p>Methods</p> <p>From January 2004 through December 2007, air pollutant concentrations and emergency room visits were collected for a case-crossover study conducted in Palermo, Sicily. Risk estimates of short-term exposures to particulate matter and gaseous ambient pollutants including carbon monoxide, nitrogen dioxide, and sulfur dioxide were calculated by using a conditional logistic regression analysis.</p> <p>Results</p> <p>Emergency departments provided data on 48,519 visits for respiratory symptoms. Adjusted case-crossover analyses revealed stronger effects in the warm season for the most part of the pollutants considered, with a positive association for PM₁₀(odds ratio = 1.039, 95% confidence interval: 1.020 - 1.059), SO₂(OR = 1.068, 95% CI: 1.014 - 1.126), nitrogen dioxide (NO₂: OR = 1.043, 95% CI: 1.021 - 1.065), and CO (OR = 1.128, 95% CI: 1.074 - 1.184), especially among females (according to an increase of 10 μg/m³in PM₁₀, NO₂, SO₂, and 1 mg/m³in CO exposure). A positive association was observed either in warm or in cold season only for PM₁₀.</p> <p>Conclusions</p> <p>Our findings suggest that, in our setting, exposure to ambient levels of air pollution is an important determinant of emergency room (ER) visits for acute respiratory symptoms, particularly during the warm season. ER admittance may be considered a good proxy to evaluate the adverse effects of air pollution on respiratory health.</p

Aldo Keto Reductase 1B7 and Prostaglandin F2α Are Regulators of Adrenal Endocrine Functions

Prostaglandin F2α (PGF2α), represses ovarian steroidogenesis and initiates parturition in mammals but its impact on adrenal gland is unknown. Prostaglandins biosynthesis depends on the sequential action of upstream cyclooxygenases (COX) and terminal synthases but no PGF2α synthases (PGFS) were functionally identified in mammalian cells. In vitro, the most efficient mammalian PGFS belong to aldo-keto reductase 1B (AKR1B) family. The adrenal gland is a major site of AKR1B expression in both human (AKR1B1) and mouse (AKR1B3, AKR1B7). Thus, we examined the PGF2α biosynthetic pathway and its functional impact on both cortical and medullary zones. Both compartments produced PGF2α but expressed different biosynthetic isozymes. In chromaffin cells, PGF2α secretion appeared constitutive and correlated to continuous expression of COX1 and AKR1B3. In steroidogenic cells, PGF2α secretion was stimulated by adrenocorticotropic hormone (ACTH) and correlated to ACTH-responsiveness of both COX2 and AKR1B7/B1. The pivotal role of AKR1B7 in ACTH-induced PGF2α release and functional coupling with COX2 was demonstrated using over- and down-expression in cell lines. PGF2α receptor was only detected in chromaffin cells, making medulla the primary target of PGF2α action. By comparing PGF2α-responsiveness of isolated cells and whole adrenal cultures, we demonstrated that PGF2α repressed glucocorticoid secretion by an indirect mechanism involving a decrease in catecholamine release which in turn decreased adrenal steroidogenesis. PGF2α may be regarded as a negative autocrine/paracrine regulator within a novel intra-adrenal feedback loop. The coordinated cell-specific regulation of COX2 and AKR1B7 ensures the generation of this stress-induced corticostatic signal

Functional MRI and Diffusion Tensor Imaging of Brain Reorganization After Experimental Stroke

The potential of the adult brain to reorganize after ischemic injury is critical for functional recovery and provides a significant target for therapeutic strategies to promote brain repair. Despite the accumulating evidence of brain plasticity, the interaction and significance of morphological and physiological modifications in post-stroke brain tissue remain mostly unclear. Neuroimaging techniques such as functional MRI (fMRI) and diffusion tensor imaging (DTI) enable in vivo assessment of the spatial and temporal pattern of functional and structural changes inside and outside ischemic lesion areas. This can contribute to the elucidation of critical aspects in post-stroke brain remodeling. Task/stimulus-related fMRI, resting-state fMRI, or pharmacological MRI enables direct or indirect measurement of neuronal activation, functional connectivity, or neurotransmitter system responses, respectively. DTI allows estimation of the structural integrity and connectivity of white matter tracts. Together, these MRI methods provide an unprecedented means to (a) measure longitudinal changes in tissue structure and function close by and remote from ischemic lesion areas, (b) evaluate the organizational profile of neural networks after stroke, and (c) identify degenerative and restorative processes that affect post-stroke functional outcome. Besides, the availability of MRI in clinical institutions as well as research laboratories provides an optimal basis for translational research on stroke recovery. This review gives an overview of the current status and perspectives of fMRI and DTI applications to study brain reorganization in experimental stroke models

Investigations into a putative role for the novel BRASSIKIN pseudokinases in compatible pollen-stigma interactions in Arabidopsis thaliana.

BACKGROUND: In the Brassicaceae, the early stages of compatible pollen-stigma interactions are tightly controlled with early checkpoints regulating pollen adhesion, hydration and germination, and pollen tube entry into the stigmatic surface. However, the early signalling events in the stigma which trigger these compatible interactions remain unknown. RESULTS: A set of stigma-expressed pseudokinase genes, termed BRASSIKINs (BKNs), were identified and found to be present in only core Brassicaceae genomes. In Arabidopsis thaliana Col-0, BKN1 displayed stigma-specific expression while the BKN2 gene was expressed in other tissues as well. CRISPR deletion mutations were generated for the two tandemly linked BKNs, and very mild hydration defects were observed for wild-type Col-0 pollen when placed on the bkn1/2 mutant stigmas. In further analyses, the predominant transcript for the stigma-specific BKN1 was found to have a premature stop codon in the Col-0 ecotype, but a survey of the 1001 Arabidopsis genomes uncovered three ecotypes that encoded a full-length BKN1 protein. Furthermore, phylogenetic analyses identified intact BKN1 orthologues in the closely related outcrossing Arabidopsis species, A. lyrata and A. halleri. Finally, the BKN pseudokinases were found to be plasma-membrane localized through the dual lipid modification of myristoylation and palmitoylation, and this localization would be consistent with a role in signaling complexes. CONCLUSION: In this study, we have characterized the novel Brassicaceae-specific family of BKN pseudokinase genes, and examined the function of BKN1 and BKN2 in the context of pollen-stigma interactions in A. thaliana Col-0. Additionally, premature stop codons were identified in the predicted stigma specific BKN1 gene in a number of the 1001 A. thaliana ecotype genomes, and this was in contrast to the out-crossing Arabidopsis species which carried intact copies of BKN1. Thus, understanding the function of BKN1 in other Brassicaceae species will be a key direction for future studies