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Sensory processing atypicalities are a common feature in Autism Spectrum Disorders (ASD) and have previously been linked to a range of behaviours in individuals with ASD and atypical neurological development. More recently research has demonstrated a relationship between autistic traits in the neurotypical (NT) population and increased levels of atypical sensory behaviours. The aim of the present study is to extend previous research by examining specific patterns across aspects of autistic traits and sensory behaviours within both ASD and NT populations. The present study recruited 580 NT adults and 42 high-functioning ASD adults with a confirmed diagnosis to investigate the relationship between specific aspects of autistic traits and sensory processing using the subscales of the autism spectrum quotient (AQ) and adult/adolescent sensory profile (AASP). Results showed a significant relationship between all subscales except for attention to detail and imagination on the AQ and provided the first evidence that the strength and pattern of this relationship is identical between NT and ASD adults. These data also provided support for the broader autism phenotype, uncovering a clear progression of sensory atypicalities in line with an increase in autistic traits, regardless of diagnostic status, which has potential implications for the spectrum approach to ASD and how sensory behaviours across the whole of the neurotypical population are conceptualised.

We review the current status of knowledge concerning the early phases of star formation during cosmic dawn. This includes the first generations of stars forming in the lowest mass dark matter halos in which cooling and condensation of gas with primordial composition is possible at very high redshift ( z > 20 ), namely metal-free Population III stars, and the first generation of massive black holes forming at such early epochs, the so-called black hole seeds. The formation of black hole seeds as end states of the collapse of Population III stars, or via direct collapse scenarios, is discussed. In particular, special emphasis is given to the physics of supermassive stars as potential precursors of direct collapse black holes, in light of recent results of stellar evolution models, and of numerical simulations of the early stages of galaxy formation. Furthermore, we discuss the role of the cosmic radiation produced by the early generation of stars and black holes at high redshift in the process of reionization.

يتناول هذا الكتاب موضوع \"الملابس المملوكية\" والذي قام بتأليفه (ل. أ. ماير) في حوالي (269) صفحة من القطع المتوسط موضوع (الملابس في عصر المملوكي) ؛ ويعتبر عصر المماليك 648-923 هـ (1250-1517 م) من أزهى عصور تاريخنا القومي. وما زالت آثاره المادية من فنون وصناعات تزخر بها المتاحف العالمية وعلى رأسها متحف الفن الإسلامي بالقاهرة. وفيه نستعرض المحتويات التالية من الكتاب : الخليفة، السلطان، الأرستقراطية العسكرية، أسلحة ودروع، رجال الدين، خلع التشریف، المسيحيون واليهود والسامرة، النساء، ملحق رقم-1-(القماش) ملحق رقم-2-(خاص بمراجع عن استقبال سفير البندقية)، المراجع، قائمة اللوحات، الفهارس.

Black holes arrived early Previously published models of supermassive black hole formation have struggled to explain the fact that — according to observations of distant quasars — supermassive black holes were already in place less than a billion years after the Big Bang. A new series of numerical simulations suggests that the conditions for direct collapse into a supermassive black hole can arise naturally on this time scale from mergers between massive protogalaxies. Multi-scale gas inflows give rise to an unstable, massive nuclear gas disk that expands to form a sub-parsec scale gas cloud in only 100,000 years. The cloud undergoes gravitational collapse, which leads to the formation of a massive black hole. Observations of distant quasars indicate that billion-solar-mass supermassive black holes existed less than a billion years after the Big Bang, but models have struggled to explain this. These authors report simulations showing that mergers between massive protogalaxies produce the conditions for collapse into supermassive black holes. Merger-driven gas inflows give rise to a nuclear gas disk that funnels gas to a sub-parsec-scale cloud. Gravitational collapse of this cloud leads to the formation of a massive black hole. Observations of distant quasars indicate that supermassive black holes of billions of solar masses already existed less than a billion years after the Big Bang 1 . Models in which the ‘seeds’ of such black holes form by the collapse of primordial metal-free stars 2 , 3 cannot explain the rapid appearance of these supermassive black holes because gas accretion is not sufficiently efficient 4 , 5 , 6 . Alternatively, these black holes may form by direct collapse of gas within isolated protogalaxies 7 , 8 , but current models require idealized conditions, such as metal-free gas, to prevent cooling and star formation from consuming the gas reservoir 9 , 10 , 11 . Here we report simulations showing that mergers between massive protogalaxies naturally produce the conditions for direct collapse into a supermassive black hole with no need to suppress cooling and star formation. Merger-driven gas inflows give rise to an unstable, massive nuclear gas disk of a few billion solar masses, which funnels more than 10 8 solar masses of gas to a sub-parsec-scale gas cloud in only 100,000 years. The cloud undergoes gravitational collapse, which eventually leads to the formation of a massive black hole. The black hole can subsequently grow to a billion solar masses on timescales of about 10 8 years by accreting gas from the surrounding disk.

Glycinergic synapses play a central role in motor control and pain processing in the central nervous system. Glycine receptors (GlyRs) are key players in mediating fast inhibitory neurotransmission at these synapses. While previous high-resolution structures have provided insights into the molecular architecture of GlyR, several mechanistic questions pertaining to channel function are still unanswered. Here, we present Cryo-EM structures of the full-length GlyR protein complex reconstituted into lipid nanodiscs that are captured in the unliganded (closed), glycine-bound (open and desensitized), and allosteric modulator-bound conformations. A comparison of these states reveals global conformational changes underlying GlyR channel gating and modulation. The functional state assignments were validated by molecular dynamics simulations, and the observed permeation events are in agreement with the anion selectivity and conductance of GlyR. These studies provide the structural basis for gating, ion selectivity, and single-channel conductance properties of GlyR in a lipid environment. Glycinergic synapses play a central role in motor control and pain processing in the central nervous system. Here, authors present cryo-EM structures of the full-length glycine receptors (GlyRs) reconstituted into lipid nanodiscs in the unliganded, glycine-bound and allosteric modulator-bound conformations and reveal global conformational changes underlying GlyR channel gating and modulation.

Bacteria interact with each other in nature and often compete for limited nutrient and space resources. However, it is largely unknown whether and how bacteria also interact with human fungal pathogens naturally found in the environment. Here, we identified a soil bacterium, Bacillus safensis , which potently blocked several key Cryptococcus neoformans virulence factors, including formation of the antioxidant pigment melanin and production of the antiphagocytic polysaccharide capsule. The bacterium also inhibited de novo cryptococcal biofilm formation but had only modest inhibitory effects on already formed biofilms or planktonic cell growth. The inhibition of fungal melanization was dependent on direct cell contact and live bacteria. B. safensis also had anti-virulence factor activity against another major human-associated fungal pathogen, Candida albicans . Specifically, dual-species interaction studies revealed that the bacterium strongly inhibited C. albicans filamentation and biofilm formation. In particular, B. safensis physically attached to and degraded candidal filaments. Through genetic and phenotypic analyses, we demonstrated that bacterial chitinase activity against fungal cell wall chitin is a factor contributing to the antipathogen effect of B. safensis . IMPORTANCE Pathogenic fungi are estimated to contribute to as many human deaths as tuberculosis or malaria. Two of the most common fungal pathogens, Cryptococcus neoformans and Candida albicans , account for up to 1.4 million infections per year with very high mortality rates. Few antifungal drugs are available for treatment, and development of novel therapies is complicated by the need for pathogen-specific targets. Therefore, there is an urgent need to identify novel drug targets and new drugs. Pathogens use virulence factors during infection, and it has recently been proposed that targeting these factors instead of the pathogen itself may represent a new approach to develop antimicrobials. Here, we identified a soil bacterium that specifically blocked virulence factor production and biofilm formation by C. neoformans and C. albicans . We demonstrate that the bacterial antipathogen mechanism is based in part on targeting the fungal cell wall, a structure not found in human cells. Pathogenic fungi are estimated to contribute to as many human deaths as tuberculosis or malaria. Two of the most common fungal pathogens, Cryptococcus neoformans and Candida albicans , account for up to 1.4 million infections per year with very high mortality rates. Few antifungal drugs are available for treatment, and development of novel therapies is complicated by the need for pathogen-specific targets. Therefore, there is an urgent need to identify novel drug targets and new drugs. Pathogens use virulence factors during infection, and it has recently been proposed that targeting these factors instead of the pathogen itself may represent a new approach to develop antimicrobials. Here, we identified a soil bacterium that specifically blocked virulence factor production and biofilm formation by C. neoformans and C. albicans . We demonstrate that the bacterial antipathogen mechanism is based in part on targeting the fungal cell wall, a structure not found in human cells.

The immune-pathology in Crohn’s disease is linked to dysregulated CD4+ T cell responses biased towards pathogenic TH17 cells. However, the role of CD8+ T cells able to produce IL-17 (Tc17 cells) remains unclear. Here we characterize the peripheral blood and intestinal tissue of Crohn’s disease patients (n = 61) with flow and mass cytometry and reveal a strong increase of Tc17 cells in active disease, mainly due to induction of conventional T cells. Mass cytometry shows that Tc17 cells express a distinct immune signature (CD6 high , CD39, CD69, PD-1, CD27 low ) which was validated in an independent patient cohort. This signature stratifies patients into groups with distinct flare-free survival associated with differential CD6 expression. Targeting of CD6 in vitro reduces IL-17, IFN-γ and TNF production. These results identify a distinct Tc17 cell population in Crohn’s disease with proinflammatory features linked to disease activity. The Tc17 signature informs clinical outcomes and may guide personalized treatment decisions. The T cell compartment in patients with Crohn's disease is dysregulated. Here the authors use cytometric profiling to reveal an enrichment of distinct Tc17 cells during active Crohn's disease and may suggest CD6 as a potential target for therapeutic studies.