Different immunological mechanisms govern protection from experimental stroke in young and older mice with recombinant TCR ligand therapy

Stroke is a leading cause of death and disability in the United States. The lack of clinical success in stroke therapies can be attributed, in part, to inadequate basic research on aging rodents. The current study demonstrates that recombinant TCR ligand therapy uses different immunological mechanisms to protect young and older mice from experimental stroke. In young mice, RTL1000 therapy inhibited splenocyte efflux while reducing frequency of T cells and macrophages in the spleen. Older mice treated with RTL1000 exhibited a significant reduction in inflammatory cells in the brain and inhibition of splenic atrophy. Our data suggest age specific differences in immune response to stroke that allow unique targeting of stroke immunotherapies

Protostellar accretion traced with chemistry. High resolution C18O and continuum observations towards deeply embedded protostars in Perseus

Context: Understanding how accretion proceeds is a key question of star formation, with important implications for both the physical and chemical evolution of young stellar objects. In particular, very little is known about the accretion variability in the earliest stages of star formation. Aims: To characterise protostellar accretion histories towards individual sources by utilising sublimation and freeze-out chemistry of CO. Methods: A sample of 24 embedded protostars are observed with the Submillimeter Array (SMA) in context of the large program "Mass Assembly of Stellar Systems and their Evolution with the SMA" (MASSES). The size of the C$^{18}$O emitting region, where CO has sublimated into the gas-phase, is measured towards each source and compared to the expected size of the region given the current luminosity. The SMA observations also include 1.3 mm continuum data, which are used to investigate whether a link can be established between accretion bursts and massive circumstellar disks. Results: Depending on the adopted sublimation temperature of the CO ice, between 20% and 50% of the sources in the sample show extended C$^{18}$O emission indicating that the gas was warm enough in the past that CO sublimated and is currently in the process of refreezing; something which we attribute to a recent accretion burst. Given the fraction of sources with extended C$^{18}$O emission, we estimate an average interval between bursts of 20000-50000 yr, which is consistent with previous estimates. No clear link can be established between the presence of circumstellar disks and accretion bursts, however the three closest known binaries in the sample (projected separations <20 AU) all show evidence of a past accretion burst, indicating that close binary interactions may also play a role in inducing accretion variability.Comment: Accepted for publication in A&A, 21 pages, 13 figure

Targeting immune co-stimulatory effects of PD-L1 and PD-L2 might represent an effective therapeutic strategy in stroke

Stroke outcome is worsened by the infiltration of inflammatory immune cells into ischemic brains. Our recent study demonstrated that PD-L1- and to a lesser extent PD-L2-deficient mice had smaller brain infarcts and fewer brain-infiltrating cells vs. wild-type (WT) mice, suggesting a pathogenic role for PD-ligands in experimental stroke. We sought to ascertain PD-L1 and PD-L2-expressing cell types that affect T-cell activation, post-stroke in the context of other known co-stimulatory molecules. Thus, cells from male WT and PD-L-deficient mice undergoing 60 min of middle cerebral artery occlusion (MCAO) followed by 96 h of reperfusion were treated with neutralizing antibodies to study co-stimulatory and co-inhibitory interactions between CD80, cytotoxic T-lymphocyte antigen-4 (CTLA-4), PD-1, and PD-Ls that regulate CD8(+) and CD4(+) T-cell activation. We found that antibody neutralization of PD-1 and CTLA-4 signaling post-MCAO resulted in higher proliferation in WT CD8(+) and CD4(+) T-cells, confirming an inhibitory role of PD-1 and CTLA-4 on T-cell activation. Also, CD80/CD28 interactions played a prominent regulatory role for the CD8(+) T-cells and the PD-1/PD-L2 interactions were dominant in controlling the CD4(+) T-cell responses in WT mice after stroke. A suppressive phenotype in PD-L1-deficient mice was attributed to CD80/CTLA-4 and PD-1/PD-L2 interactions. PD-L2 was crucial in modulating CD4(+) T-cell responses, whereas PD-L1 regulated both CD8(+) and CD4(+) T-cells. To establish the contribution of PD-L1 and PD-L2 on regulatory B-cells (Bregs), infarct volumes were evaluated in male PD-L1- and PD-L2-deficient mice receiving IL-10(+) B-cells 4h post-MCAO. PD-L2- but not PD-L1-deficient recipients of IL-10(+) B-cells had markedly reduced infarct volumes, indicating a regulatory role of PD-L2 on Bregs. These results imply that PD-L1 and PD-L2 differentially control induction of T- and Breg-cell responses after MCAO, thus suggesting that selective targeting of PD-L1 and PD-L2 might represent a valuable therapeutic strategy in stroke

Etudes glaciaires, géographiques et botaniques dans le massif des Grandes Rousses - Alpes françaises

Article publié dans Etudes Glaciologiques : Tirol autrichien Massif des grandes Rousses. Ministère de l'Agriculture-Direction de l'Hydraulique- Services d'Etudes des grandes forces hydrauliques ( Région des Alpes) - Grenoble 1909 - pp 33-112Ce travail de 1905 repose sur un aperçu géomorphologique, phytogéographique et des mesures glaciologiques du massif des Grandes Rousses dans les Alpes françaises

A retrospective analysis of geriatric trauma patients: venous lactate is a better predictor of mortality than traditional vital signs

BACKGROUND: Traditional vital signs (TVS), including systolic blood pressure (SBP), heart rate (HR) and their composite, the shock index, may be poor prognostic indicators in geriatric trauma patients. The purpose of this study is to determine whether lactate predicts mortality better than TVS. METHODS: We studied a large cohort of trauma patients age ≥ 65 years admitted to a level 1 trauma center from 2009-01-01 - 2011-12-31. We defined abnormal TVS as hypotension (SBP < 90 mm Hg) and/or tachycardia (HR > 120 beats/min), an elevated shock index as HR/SBP ≥ 1, an elevated venous lactate as ≥ 2.5 mM, and occult hypoperfusion as elevated lactate with normal TVS. The association between these variables and in-hospital mortality was compared using Chi-square tests and multivariate logistic regression. RESULTS: There were 1987 geriatric trauma patients included, with an overall mortality of 4.23% and an incidence of occult hypoperfusion of 20.03%. After adjustment for GCS, ISS, and advanced age, venous lactate significantly predicted mortality (OR: 2.62, p < 0.001), whereas abnormal TVS (OR: 1.71, p = 0.21) and SI ≥ 1 (OR: 1.18, p = 0.78) did not. Mortality was significantly greater in patients with occult hypoperfusion compared to patients with no sign of circulatory hemodynamic instability (10.67% versus 3.67%, p < 0.001), which continued after adjustment (OR: 2.12, p = 0.01). CONCLUSIONS: Our findings demonstrate that occult hypoperfusion was exceedingly common in geriatric trauma patients, and was associated with a two-fold increased odds of mortality. Venous lactate should be measured for all geriatric trauma patients to improve the identification of hemodynamic instability and optimize resuscitative efforts