A zone of preferential ion heating extends tens of solar radii from Sun

The extreme temperatures and non-thermal nature of the solar corona and solar wind arise from an unidentified physical mechanism that preferentially heats certain ion species relative to others. Spectroscopic indicators of unequal temperatures commence within a fraction of a solar radius above the surface of the Sun, but the outer reach of this mechanism has yet to be determined. Here we present an empirical procedure for combining interplanetary solar wind measurements and a modeled energy equation including Coulomb relaxation to solve for the typical outer boundary of this zone of preferential heating. Applied to two decades of observations by the Wind spacecraft, our results are consistent with preferential heating being active in a zone extending from the transition region in the lower corona to an outer boundary 20-40 solar radii from the Sun, producing a steady state super-mass-proportional $\alpha$-to-proton temperature ratio of $5.2-5.3$. Preferential ion heating continues far beyond the transition region and is important for the evolution of both the outer corona and the solar wind. The outer boundary of this zone is well below the orbits of spacecraft at 1 AU and even closer missions such as Helios and MESSENGER, meaning it is likely that no existing mission has directly observed intense preferential heating, just residual signatures. We predict that {Parker Solar Probe} will be the first spacecraft with a perihelia sufficiently close to the Sun to pass through the outer boundary, enter the zone of preferential heating, and directly observe the physical mechanism in action.Comment: 11 pages, 7 figures, accepted for publication in the Astrophysical Journal on 1 August 201

Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation

Sleep deprivation reduces the dextran radial distribution and 125I-apoE inflow from CSF into brain. A-B) Representative images of cascade blue dextran (CB) in mice on normal sleep cycle (A) and in mice during sleep deprivation (SD) (B). Cascade blue dextran (10 kDa) was injected into cisterna magna and the mice perfusion fixed (PFA) at 15 min. The vasculature was outline by lectin (green). Scale bars 100 μm (A-B). C) 125I-ApoE2 (yellow column), 125I-apoE3 (red column) and 125I-apoE4 (orange column) inflow into brain from the CSF were reduced in SD mice. D) 14C-inulin inflow into brain from the CSF was reduced with SD and not affected by apoE isoforms. 125I-ApoE (10 nM) and 14C-inulin were intracisternally injected and the brain analyzed for radioactivity. Values are mean ± SEM. N = 6 mice per group. (EPS 15099 kb

Phase transition enhanced thermoelectric figure-of-merit in copper chalcogenides

While thermoelectric materials can be used for solid state cooling, waste heat recovery, and solar electricity generation, low values of the thermoelectric figure of merit, zT, have led to an efficiency too low for widespread use. Thermoelectric effects are characterized by the Seebeck coefficient or thermopower, which is related to the entropy associated with charge transport. For example, coupling spin entropy with the presence of charge carriers has enabled the enhancement of zT in cobalt oxides. We demonstrate that the coupling of a continuous phase transition to carrier transport in Cu 2Se over a broad (360–410 K) temperature range results in a dramatic peak in thermopower, an increase in phonon and electron scattering, and a corresponding doubling of zT (to 0.7 at 406 K), and a similar but larger increase over a wider temperature range in the zT of Cu 1.97 Ag .03Se (almost 1.0 at 400 K). The use of structural entropy for enhanced thermopower could lead to new engineering approaches for thermoelectric materials with high zT and new green applications for thermoelectrics

Autism gene Ube3a and seizures impair sociability by repressing VTA Cbln1

Summary Maternally inherited 15q11-13 chromosomal triplications cause a frequent and highly penetrant autism linked to increased gene dosages of UBE3A, which both possesses ubiquitin-ligase and transcriptional co-regulatory functions. Here, using in vivo mouse genetics, we show that increasing UBE3A in the nucleus down-regulates glutamatergic synapse organizer cerebellin-1 (Cbln1) that is needed for sociability in mice. Epileptic seizures also repress Cbln1 and are found to expose sociability impairments in mice with asymptomatic increases of UBE3A. This Ube3a-seizure synergy maps to glutamate neurons of the midbrain ventral tegmental area (VTA) where Cbln1 deletions impair sociability and weaken glutamatergic transmission. We provide preclinical evidence that viral-vector-based chemogenetic activations of, or Cbln1 restorations in VTA glutamatergic neurons rescues sociability deficits induced by Ube3a and/or seizures. Our results suggest a gene × seizure interaction in VTA glutamatergic neurons that impairs sociability by downregulating Cbln1, a key node in the expanding protein interaction network of autism genes

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

The SPHERE XAO system: design and performance

International audienc

Loss of T cell and B cell quiescence precedes the onset of microbial flora-dependent wasting disease and intestinal inflammation in Gimap5-deficient mice

Homeostatic control of the immune system involves mechanisms that ensure the self-tolerance, survival and quiescence of hematopoietic-derived cells. In this study, we demonstrate that the GTPase of immunity associated protein (Gimap)5 regulates these processes in lymphocytes and hematopoietic progenitor cells. As a consequence of a recessive N-ethyl-N-nitrosourea–induced germline mutation in the P-loop of Gimap5, lymphopenia, hepatic extramedullary hematopoiesis, weight loss, and intestinal inflammation occur in homozygous mutant mice. Irradiated fetal liver chimeric mice reconstituted with Gimap5-deficient cells lose weight and become lymphopenic, demonstrating a hematopoietic cell-intrinsic function for Gimap5. Although Gimap5-deficient CD4(+) T cells and B cells appear to undergo normal development, they fail to proliferate upon Ag-receptor stimulation although NF-κB, MAP kinase and Akt activation occur normally. In addition, in Gimap5-deficient mice, CD4(+) T cells adopt a CD44(high) CD62L(low) CD69(low) phenotype and show reduced IL-7rα expression, and T-dependent and T-independent B cell responses are abrogated. Thus, Gimap5-deficiency affects a noncanonical signaling pathway required for Ag-receptor–induced proliferation and lymphocyte quiescence. Antibiotic-treatment or the adoptive transfer of Rag-sufficient splenocytes ameliorates intestinal inflammation and weight loss, suggesting that immune responses triggered by microbial flora causes the morbidity in Gimap5-deficient mice. These data establish Gimap5 as a key regulator of hematopoietic integrity and lymphocyte homeostasis

Loss of T cell and B cell quiescence precedes the onset of microbial flora-dependent wasting disease and intestinal inflammation in Gimap5-deficient mice

Homeostatic control of the immune system involves mechanisms that ensure the self-tolerance, survival and quiescence of hematopoietic-derived cells. In this study, we demonstrate that the GTPase of immunity associated protein (Gimap)5 regulates these processes in lymphocytes and hematopoietic progenitor cells. As a consequence of a recessive N-ethyl-N-nitrosourea-induced germline mutation in the P-loop of Gimap5, lymphopenia, hepatic extramedullary hematopoiesis, weight loss, and intestinal inflammation occur in homozygous mutant mice. Irradiated fetal liver chimeric mice reconstituted with Gimap5-deficient cells lose weight and become lymphopenic, demonstrating a hematopoietic cell-intrinsic function for Gimap5. Although Gimap5-deficient CD4(+) T cells and B cells appear to undergo normal development, they fail to proliferate upon Ag-receptor stimulation although NF-kappaB, MAP kinase and Akt activation occur normally. In addition, in Gimap5-deficient mice, CD4(+) T cells adopt a CD44(high)CD62L(low)CD69(low) phenotype and show reduced IL-7ralpha expression, and T-dependent and T-independent B cell responses are abrogated. Thus, Gimap5-deficiency affects a noncanonical signaling pathway required for Ag-receptor-induced proliferation and lymphocyte quiescence. Antibiotic-treatment or the adoptive transfer of Rag-sufficient splenocytes ameliorates intestinal inflammation and weight loss, suggesting that immune responses triggered by microbial flora causes the morbidity in Gimap5-deficient mice. These data establish Gimap5 as a key regulator of hematopoietic integrity and lymphocyte homeostasis