Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces

TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al

Autism Symptoms and Internalizing Psychopathology in Girls and Boys with Autism Spectrum Disorders

Findings regarding phenotypic differences between boys and girls with ASD are mixed. We compared autism and internalizing symptoms in a sample of 8-18 year-old girls (n = 20) and boys (n = 20) with ASD and typically developing (TYP) girls (n = 19) and boys (n = 17). Girls with ASD were more impaired than TYP girls but did not differ from boys with ASD in autism symptoms. In adolescence, girls with ASD had higher internalizing symptoms than boys with ASD and TYP girls, and higher symptoms of depression than TYP girls. Girls ages 8-18 with ASD resemble boys with ASD and not TYP girls, and appear to be at increased risk for affective symptoms in the teen years

Observations of Lyα\alpha Emitters at High Redshift

In this series of lectures, I review our observational understanding of high-$z$ Ly$\alpha$ emitters (LAEs) and relevant scientific topics. Since the discovery of LAEs in the late 1990s, more than ten (one) thousand(s) of LAEs have been identified photometrically (spectroscopically) at $z\sim 0$ to $z\sim 10$. These large samples of LAEs are useful to address two major astrophysical issues, galaxy formation and cosmic reionization. Statistical studies have revealed the general picture of LAEs' physical properties: young stellar populations, remarkable luminosity function evolutions, compact morphologies, highly ionized inter-stellar media (ISM) with low metal/dust contents, low masses of dark-matter halos. Typical LAEs represent low-mass high-$z$ galaxies, high-$z$ analogs of dwarf galaxies, some of which are thought to be candidates of population III galaxies. These observational studies have also pinpointed rare bright Ly$\alpha$ sources extended over $\sim 10-100$ kpc, dubbed Ly$\alpha$ blobs, whose physical origins are under debate. LAEs are used as probes of cosmic reionization history through the Ly$\alpha$ damping wing absorption given by the neutral hydrogen of the inter-galactic medium (IGM), which complement the cosmic microwave background radiation and 21cm observations. The low-mass and highly-ionized population of LAEs can be major sources of cosmic reionization. The budget of ionizing photons for cosmic reionization has been constrained, although there remain large observational uncertainties in the parameters. Beyond galaxy formation and cosmic reionization, several new usages of LAEs for science frontiers have been suggested such as the distribution of {\sc Hi} gas in the circum-galactic medium and filaments of large-scale structures. On-going programs and future telescope projects, such as JWST, ELTs, and SKA, will push the horizons of the science frontiers.Comment: Lecture notes for `Lyman-alpha as an Astrophysical and Cosmological Tool', Saas-Fee Advanced Course 46. Verhamme, A., North, P., Cantalupo, S., & Atek, H. (eds.) --- 147 pages, 103 figures. Abstract abridged. Link to the lecture program including the video recording and ppt files : https://obswww.unige.ch/Courses/saas-fee-2016/program.cg

Effects of psychological and psychosocial interventions on sport performance:a meta-analysis

Background: Psychologists are increasingly supporting the quest for performance enhancement in sport and there is a need to evaluate the evidence base underpinning their work. Objectives: To synthesize the most rigorous available research that has evaluated psychological, social, and psychosocial interventions with sport performers on variables relating to their athletic performance, and to address some of the perplexing issues in the sport psychology intervention literature (e.g., do interventions have a lasting effect on sport performance?). Methods: Randomized controlled trials were identified through electronic databases, hand-searching volumes of pertinent journals, scrutinizing reference lists of previous reviews, and contacting experts in the evaluation of interventions in this field. Included studies were required to evaluate the effects of psychological, social, or psychosocial interventions on sport performance in athletes when compared to a no-treatment or placebo-controlled treatment comparison group. A random effects meta-analysis calculating the standardized mean difference (Hedges’ g), meta-regressions, and trim and fill analyses were conducted. Data were analyzed at post-test and follow-up (ranging from 1 to 4 weeks after the intervention finished) assessments. Results: Psychological and psychosocial interventions were shown to enhance sport performance at post-test (k = 35, n = 997, Hedges’ g = 0.57, 95 % CI = 0.22–0.92) and follow-up assessments (k = 8, n = 189, Hedges’ g = 1.16, 95 % CI = 0.25–2.08); no social interventions were included or evaluated. Larger effects were found for psychosocial interventions and there was some evidence that effects were greatest in coach-delivered interventions and in samples with a greater proportion of male participants. Conclusions: Psychological and psychosocial interventions have a moderate positive effect on sport performance, and this effect may last at least a month following the end of the intervention. Future research would benefit from following guidelines for intervention reporting

Risk factors, management, and outcomes of hemolysis, elevated liver enzymes, and low platelets syndrome and elevated liver enzymes, low platelets syndrome.

OBJECTIVE: To describe the risk factors, management and outcomes of hemolysis, elevated liver enzymes, and low platelets (HELLP) and elevated liver enzymes, low platelets (ELLP) syndrome in the United Kingdom. METHODS: A case-control study was conducted using the U.K. Obstetric Surveillance System between June 2011 and May 2012, including 129 women diagnosed with HELLP, 81 diagnosed with ELLP, and 476 control women. RESULTS: Women with HELLP were more likely than those in the control group to be 35+ years old (33% compared with 22%, adjusted odds ratio [OR] 1.85, 95% confidence interval [CI] 1.12-3.06), nulliparous (67% compared with 43%, adjusted OR 4.16, 95% CI 2.48-6.98), have had a previous gestational hypertensive disorder (9% compared with 7%, adjusted OR 3.47, 95% CI 1.49-8.09), and have a multiple pregnancy (7% compared with 2%, adjusted OR 4.51, 95% CI 1.45-14.06). Women with ELLP were more likely than those in the control group to be nulliparous (79% compared with 43%, adjusted OR 8.35, 95% CI 3.88-17.95), and have had a previous gestational hypertensive disorder (7% compared with 7%, adjusted OR 4.66, 95% CI 1.37-15.89). Of the women diagnosed antenatally with HELLP or ELLP, 51% (71/138) had planned management of immediate delivery, 43% (60/138) had delivery planned within 48 hours, and 5% (7/138) had planned expectant (conservative) management. No differences were found between women who had delivery planned within 48 hours and those who had planned immediate delivery in terms of the proportion who received blood products (37% compared with 33%, P=.681); were admitted to the intensive care unit (57% compared with 61%, P=.652); experienced severe morbidity (10% compared with 4%, P=.300); or had a neonate with major complications (6% compared with 11%, P=.342). CONCLUSION: A short delay in the delivery of women diagnosed antenatally with HELLP or ELLP syndrome may be considered. However, the rarity of the condition limits study power

Response Inhibition, Peer Preference and Victimization, and Self-Harm: Longitudinal Associations in Young Adult Women with and without ADHD

Self-harm (suicidal ideation and attempts; non-suicidal self-injuries behavior) peaks in adolescence and early-adulthood, with rates higher for women than men. Young women with childhood psychiatric diagnoses appear to be at particular risk, yet more remains to be learned about the key predictors or mediators of self-harm outcomes. Our aims were to examine, with respect to self-harm-related outcomes in early adulthood, the predictive validity of childhood response inhibition, a cardinal trait of attention-deficit hyperactivity disorder (ADHD), as well as the potential mediating effects of social preference and peer victimization, ascertained in early adolescence. Participants were an ethnically and socioeconomically diverse sample of 228 girls with and without ADHD, an enriched sample for deficits in response inhibition. Childhood response inhibition (RI) predicted young-adult suicide ideation (SI), suicide attempts (SA), and non-suicidal self-injury (NSSI), over and above full-scale IQ, mother's education, household income, and age. Importantly, teacher-rated social preference in adolescence was a partial mediator of the RI-SI/SA linkages; self-reported peer victimization in adolescence emerged as a significant partial mediator of the RI-NSSI linkage. We discuss implications for conceptual models of self-harm and for needed clinical services designed to detect and reduce self-harm