MHCII-independent CD4(+) T cells protect injured CNS neurons via IL-4

A body of experimental evidence suggests that T cells mediate neuroprotection following CNS injury; however, the antigen specificity of these T cells and how they mediate neuroprotection are unknown. Here, we have provided evidence that T cell-mediated neuroprotection after CNS injury can occur independently of major histocompatibility class II (MHCII) signaling to T cell receptors (TCRs). Using two murine models of CNS injury, we determined that damage-associated molecular mediators that originate from injured CNS tissue induce a population of neuroprotective, IL-4-producing T cells in an antigen-independent fashion. Compared with wild-type mice, IL-4-deficient animals had decreased functional recovery following CNS injury; however, transfer of CD4+ T cells from wild-type mice, but not from IL-4-deficient mice, enhanced neuronal survival. Using a culture-based system, we determined that T cell-derived IL-4 protects and induces recovery of injured neurons by activation of neuronal IL-4 receptors, which potentiated neurotrophin signaling via the AKT and MAPK pathways. Together, these findings demonstrate that damage-associated molecules from the injured CNS induce a neuroprotective T cell response that is independent of MHCII/TCR interactions and is MyD88 dependent. Moreover, our results indicate that IL-4 mediates neuroprotection and recovery of the injured CNS and suggest that strategies to enhance IL-4-producing CD4+ T cells have potential to attenuate axonal damage in the course of CNS injury in trauma, inflammation, or neurodegeneration

Up, close and personal: the new Front National visual strategy under Marine Le Pen

Extensive analyses of Marine Le Pen’s media interventions as leader of the French Front National have revealed mostly rhetorical differences from her father’s discourse. In particular, despite Marine Le Pen’s professed openness toward women and their policy concerns, and despite her professed intention to transform the FN into party suitable for government, there has been little progress in these directions. However, the FN’s visual discourse has been all but ignored by the scholarly analysis, despite the fact that campaign visuals encode significant social and political information. This paper finds that the FN candidates’ visual presentation has undergone major transformations from the 2007 to the 2012 legislative elections. Specifically FN candidates in 2012 are more likely to visually portray themselves like mainstream party candidates. Compared to the 2007 elections, women candidates, in particular, were more likely to visually promote their personal qualities in 2012, in some respects more than 2012 men candidates

A noncanonical role for the engulfment gene ELMO1 in neutrophils that promotes inflammatory arthritis

Rheumatoid arthritis is characterized by progressive joint inflammation and affects similar to 1% of the human population. We noted single-nucleotide polymorphisms (SNPs) in the apoptotic cell-engulfment genes ELMO1, DOCK2, and RAC1 linked to rheumatoid arthritis. As ELMO1 promotes cytoskeletal reorganization during engulfment, we hypothesized that ELMO1 loss would worsen inflammatory arthritis. Surprisingly, Elmo1-deficient mice showed reduced joint inflammation in acute and chronic arthritis models. Genetic and cell-biology studies revealed that ELMO1 associates with receptors linked to neutrophil function in arthritis and regulates activation and early neutrophil recruitment to the joints, without general inhibition of inflammatory responses. Further, neutrophils from the peripheral blood of human donors that carry the SNP in ELMO1 associated with arthritis display increased migratory capacity, whereas ELMO1 knockdown reduces human neutrophil migration to chemokines linked to arthritis. These data identify 'noncanonical' roles for ELMO1 as an important cytoplasmic regulator of specific neutrophil receptors and promoter of arthritis

Association of intravenous thrombolysis and pre-interventional reperfusion: a post hoc analysis of the SWIFT DIRECT trial.

BACKGROUND A potential benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is pre-interventional reperfusion. Currently, there are few data on the occurrence of pre-interventional reperfusion in patients randomized to IVT or no IVT before MT. METHODS SWIFT DIRECT (Solitaire With the Intention For Thrombectomy Plus Intravenous t-PA vs DIRECT Solitaire Stent-retriever Thrombectomy in Acute Anterior Circulation Stroke) was a randomized controlled trial including acute ischemic stroke IVT eligible patients being directly admitted to a comprehensive stroke center, with allocation to IVT with MT versus MT alone. The primary endpoint of this analysis was the occurrence of pre-interventional reperfusion, defined as a pre-interventional expanded Thrombolysis in Cerebral Infarction score of ≥2a. The effect of IVT and potential treatment effect heterogeneity were analyzed using logistic regression analyses. RESULTS Of 396 patients, pre-interventional reperfusion occurred in 20 (10.0%) patients randomized to IVT with MT, and in 7 (3.6%) patients randomized to MT alone. Receiving IVT favored the occurrence of pre-interventional reperfusion (adjusted OR 2.91, 95% CI 1.23 to 6.87). There was no IVT treatment effect heterogeneity on the occurrence of pre-interventional reperfusion with different strata of Randomization-to-Groin-Puncture time (p for interaction=0.33), although the effect tended to be stronger in patients with a Randomization-to-Groin-Puncture time >28 min (adjusted OR 4.65, 95% CI 1.16 to 18.68). There were no significant differences in rates of functional outcomes between patients with and without pre-interventional reperfusion. CONCLUSION Even for patients with proximal large vessel occlusions and direct access to MT, IVT resulted in an absolute increase of 6% in rates of pre-interventional reperfusion. The influence of time strata on the occurrence of pre-interventional reperfusion should be studied further in an individual patient data meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER clinicaltrials.gov NCT03192332

Slc20a2, Encoding the Phosphate Transporter PiT2, Is an Important Genetic Determinant of Bone Quality and Strength.

Osteoporosis is characterized by low bone mineral density (BMD) and fragility fracture and affects over 200 million people worldwide. Bone quality describes the material properties that contribute to strength independently of BMD, and its quantitative analysis is a major priority in osteoporosis research. Tissue mineralization is a fundamental process requiring calcium and phosphate transporters. Here we identify impaired bone quality and strength in Slc20a2-/- mice lacking the phosphate transporter SLC20A2. Juveniles had abnormal endochondral and intramembranous ossification, decreased mineral accrual, and short stature. Adults exhibited only small reductions in bone mass and mineralization but a profound impairment of bone strength. Bone quality was severely impaired in Slc20a2-/- mice: yield load (-2.3 SD), maximum load (-1.7 SD), and stiffness (-2.7 SD) were all below values predicted from their bone mineral content as determined in a cohort of 320 wild-type controls. These studies identify Slc20a2 as a physiological regulator of tissue mineralization and highlight its critical role in the determination of bone quality and strength. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc

Subcritical multiplicative chaos for regularized counting statistics from random matrix theory

For an N×N random unitary matrix U_N, we consider the random field defined by counting the number of eigenvalues of U_N in a mesoscopic arc of the unit circle, regularized at an N-dependent scale Ɛ_N>0. We prove that the renormalized exponential of this field converges as N → ∞ to a Gaussian multiplicative chaos measure in the whole subcritical phase. In addition, we show that the moments of the total mass converge to a Selberg-like integral and by taking a further limit as the size of the arc diverges, we establish part of the conjectures in [55]. By an analogous construction, we prove that the multiplicative chaos measure coming from the sine process has the same distribution, which strongly suggests that this limiting object should be universal. The proofs are based on the asymptotic analysis of certain Toeplitz or Fredholm determinants using the Borodin-Okounkov formula or a Riemann-Hilbert problem for integrable operators. Our approach to the L¹-phase is based on a generalization of the construction in Berestycki [5] to random fields which are only asymptotically Gaussian. In particular, our method could have applications to other random fields coming from either random matrix theory or a different context

Superconductivity mediated by charge fluctuations in layered molecular crystals

We consider the competition between superconducting, charge ordered, and metallic phases in layered molecular crystals with the theta and beta" structures. Applying slave-boson theory to the relevant extended Hubbard model, we show that the superconductivity is mediated by charge fluctuations and the Cooper pairs have d(xy) symmetry. This is in contrast to the kappa-(BEDT-TTF)(2)X family, for which theoretical calculations give superconductivity mediated by spin fluctuations and with d(x)2(-y)2 symmetry. We predict several materials that should become superconducting under pressure

Vertical stratification of the air microbiome in the lower troposphere

The troposphere constitutes the final frontier of global ecosystem research due to technical challenges arising from its size, low biomass, and gaseous state. Using a vertical testing array comprising a meteorological tower and a research aircraft, we conducted synchronized measurements of meteorological parameters and airborne biomass (n = 480) in the vertical air column up to 3,500 m. The taxonomic analysis of metagenomic data revealed differing patterns of airborne microbial community composition with respect to time of day and height above ground. The temporal and spatial resolution of our study demonstrated that the diel cycle of airborne microorganisms is a ground-based phenomenon that is entirely absent at heights >1,000 m. In an integrated analysis combining meteorological and biological data, we demonstrate that atmospheric turbulence, identified by potential temperature and high-frequency three-component wind measurements, is the key driver of bioaerosol dynamics in the lower troposphere. Multivariate regression analysis shows that at least 50% of identified airborne microbial taxa (n = ∼10,000) are associated with either ground or height, allowing for an understanding of dispersal patterns of microbial taxa in the vertical air column. Due to the interconnectedness of atmospheric turbulence and temperature, the dynamics of microbial dispersal are likely to be impacted by rising global temperatures, thereby also affecting ecosystems on the planetary surface

GlobCurrent : Multisensor synergy for surface current estimation

The GlobCurrent project (http://www.globcurrent.org) aims to: (i) advance the quantitative estimation of ocean surface currents from satellite sensor synergy; and (ii) demonstrate impact in user-led scientific, operational and commercial applications that, in turn, will improve and strengthen the uptake of satellite measurements. It is often demonstrated that sharp gradients in the sea surface temperature (SST) and current fields and the ocean surface chlorophyll-a distribution are spatially correlated with the sea surface roughness anomaly fields at small spatial scales, in the sub-mesocale (1-10 km) to the mesoscale (30-80 km). At the larger mesoscale range (>50 km), information derived from radar altimeters often depict the presence of coherent structures and eddies. The variability often appears largest in regions where the intense surface current regimes (>100 - 200 km) are found. These 2dimensional structures manifested in the satellite observations represent evidence of the upper ocean (~100-200 m) dynamics. Whereas the quasi geostrophic assumption is valid for the upper ocean dynamics at the larger scale (>100 km), possible triggering mechanisms for the expressions at the mesoscale-to-submesoscale may include spiraling tracers of inertial motion and the interaction of the wind-driven Ekman layer with the quasi-geostrophic current field. This latter, in turn, produces bands of downwelling (convergence) and upwelling (divergence) near fronts. A regular utilization of the sensor synergy approach with the combination of Sentinel-3, Sentinel-2 and Sentinel-1 together with other satellite missions will provide a highly valuable data set for further research and development to better relate the 2-dimensional surface expressions and the upper ocean dynamics