Knocking at the brain’s door: intravital two-photon imaging of autoreactive T cell interactions with CNS structures

Since the first applications of two-photon microscopy in immunology 10 years ago, the number of studies using this advanced technology has increased dramatically. The two-photon microscope allows long-term visualization of cell motility in the living tissue with minimal phototoxicity. Using this technique, we examined brain autoantigen-specific T cell behavior in experimental autoimmune encephalitomyelitis, the animal model of human multiple sclerosis. Even before disease symptoms appear, the autoreactive T cells arrive at their target organ. There they crawl along the intraluminal surface of central nervous system (CNS) blood vessels before they extravasate. In the perivascular environment, the T cells meet phagocytes that present autoantigens. This contact activates the T cells to penetrate deep into the CNS parenchyma, where the infiltrated T cells again can find antigen, be further activated, and produce cytokines, resulting in massive immune cell recruitment and clinical disease

Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action

In the present study, upon showing sexual dimorphism in dimethyl fumarate (DMF) efficacy to moderate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats, cellular and molecular substrate of this dimorphism was explored. In rats of both sexes, DMF administration from the day of immunization attenuated EAE severity, but this effect was more prominent in males leading to loss of the sexual dimorphism observed in vehicle-administered controls. Consistently, in male rats, DMF was more efficient in diminishing the number of CD4+ T lymphocytes infiltrating spinal cord (SC) and their reactivation, the number of IL-17+ T lymphocytes and particularly cellularity of their highly pathogenic IFN-gamma+GM-CSF+IL-17+ subset. This was linked with changes in SC CD11b+CD45+TCR alpha beta- microglia/proinflammatory monocyte progeny, substantiated in a more prominent increase in the frequency of anti-inflammatory phygocyting CD163+ cells and the cells expressing high surface levels of immunoregulatory CD83 molecule (associated with apoptotic cells phagocytosis and implicated in downregulation of CD4+ T lymphocyte reactivation) among CD11b+CD45+TCR alpha beta- cells in male rat SC. These changes were associated with greater increase in the nuclear factor (erythroid-derived 2)-like 2 expression in male rats administered with DMF. In accordance with the previous findings, DMF diminished reactive nitrogen and oxygen species generation and consistently, SC level of advanced oxidation protein products, to the greater extent in male rats. Overall, our study indicates sex-specificity in the sensitivity of DMF cellular and molecular targets and encourages sex-based clinical research to define significance of sex for action of therapeutic agents moderating autoimmune neuroinflammation-/oxidative stress-related nervous tissue damage

Hydrological and Agricultural Impacts of Climate Change in the Vu Gia-Thu Bon River Basin in Central Vietnam

This paper summarizes some of the climate (change) impact modeling activities conducted in the Land useandClimate Changeinteractionsin Central Vietnam (LUCCi)project. The study area is the Vu Gia-Thu Bon (VGTB) river basin in Central Vietnam, which is characterized by recurrent floods during the rainy season, but also water shortages during the dry season. The impact modeling activities, such as the validation of the models are hindered by the scarcity of hydrometeorological data and an unfavorable distribution of the observation network, i.e., station data is available only for the lowlands. In total, two different process-based and distributed hydrological models are applied in concert with climate change and land use projections. Based on that, the magnitudes and return periods of extreme flows are estimated. The modeling results suggest increases of extreme high flows due to climate change. A multi-objective agro-economical model was developed for a typical irrigation scheme in the region in order to optimize the area for cropping, irrigation-techniques and schedules. The model results suggest the irrigation technique Alternate Wetting and Drying, which has the potential to increase the benefits for the farmers and help to mitigate greenhouse gases at the same time. In addition, the regional-scale crop model GLAM is applied for groundnut under rainfed conditions, which is capable to identify regions suitable for cropping in the future. The paper further synthesizes recommendations for local stakeholders in Central Vietnam.<br/

Environmental controls and facies architecture of a jurassic carbonate episode La Manga Formation), Mendoza Province, Neuquén Basin

La Manga Formation is a vast carbonate system developed in the Neuquén Basin. The age is based in ammonite faunas, ranging from Early Callovian (Bodenbenderi-Proximum Zone) to Middle Oxfordian (Cordatum Standard Zone to Transversarium Standard Zone, and probably to the lower part of the Bifurcatus Standard Zone). A stratigraphical and sedimentological analysis, in the outcrops exposed in the south of Mendoza province, enabled the recognition of five facies associations of a carbonate ramp corresponding to (1) distal outer ramp, (2) proximal outer to distal middle ramp, (3) proximal middle ramp, (4) inner ramp deposits (shoreface, shoal, patch reef, shallow subtidal lagoon and tidal flat) and (5) paleokarstic facies. These facies correspond to homoclinal to distally steepened carbonate ramp. The facies associations are included into three third-order depositional sequences (DS-1, DS-2, DS-3) represented by transgressive and highstand systems tracts with sequence boundaries of regional character. Different controlling factors can be recognised in the deposition of this unit. The abrupt changes of facies, as well as paleokarst and epikarst discontinuity surfaces in the successions provide important evidence in terms of depositional environment and vertical evolution of the carbonate ramp. Facies patterns are variable across the outcrop area and vertically through time because of a combination of ramp morphology, siliciclastic supply, sea level changes and tectonic effects. In the southern sections, siliciclastic influx influenced the deposition of proximal middle ramp facies later overlain by scleractinian patch reefs which grew up throughout progressive stages from aggradational to progradational facies in response to climate controls and nutrient levels influence. In northern outcrops, tectonic controls affected the ramp topography and influenced the development of distal deep marine facies. Shallow subtidal and peritidal cycles indicate a combination of allocyclic and autocyclic processes controlling accommodation space and sediment accumulation.Fil: Palma, Ricardo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; ArgentinaFil: Bressan, Graciela Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; ArgentinaFil: Riccardi, Alberto Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: López Gómez, José. Universidad Complutense de Madrid; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Martín Chivelet, Javier. Consejo Superior de Investigaciones Científicas; España. Universidad Complutense de Madrid; Españ