The GB Virus C (GBV-C) NS3 Serine Protease Inhibits HIV-1 Replication in a CD4+ T Lymphocyte Cell Line without Decreasing HIV Receptor Expression

Introduction: Persistent infection with GBV-C (GB Virus C), a non-pathogenic virus related to hepatitis C virus (HCV), prolongs survival in HIV infection. Two GBV-C proteins, NS5A and E2, have been shown previously to inhibit HIV replication in vitro. We investigated whether the GBV-C NS3 serine protease affects HIV replication. Results: GBV-C NS3 protease expressed in a human CD4+ T lymphocyte cell line significantly inhibited HIV replication. Addition of NS4A or NS4A/4B coding sequence to GBV-C NS3 increased the effect on HIV replication. Inhibition of HI

Behavioural and functional evidence revealing the role of RBFOX1 variation in multiple psychiatric disorders and traits

Common variation in the gene encoding the neuron-specific RNA splicing factor RNA Binding Fox-1 Homolog 1 (RBFOX1) has been identified as a risk factor for several psychiatric conditions, and rare genetic variants have been found causal for autism spectrum disorder (ASD). Here, we explored the genetic landscape of RBFOX1 more deeply, integrating evidence from existing and new human studies as well as studies in Rbfox1 knockout mice. Mining existing data from large-scale studies of human common genetic variants, we confirmed gene-based and genome-wide association of RBFOX1 with risk tolerance, major depressive disorder and schizophrenia. Data on six mental disorders revealed copy number losses and gains to be more frequent in ASD cases than in controls. Consistently, RBFOX1 expression appeared decreased in post-mortem frontal and temporal cortices of individuals with ASD and prefrontal cortex of individuals with schizophrenia. Brain-functional MRI studies demonstrated that carriers of a common RBFOX1 variant, rs6500744, displayed increased neural reactivity to emotional stimuli, reduced prefrontal processing during cognitive control, and enhanced fear expression after fear conditioning, going along with increased avoidance behaviour. Investigating Rbfox1 neuron-specific knockout mice allowed us to further specify the role of this gene in behaviour. The model was characterised by pronounced hyperactivity, stereotyped behaviour, impairments in fear acquisition and extinction, reduced social interest, and lack of aggression; it provides excellent construct and face validity as an animal model of ASD. In conclusion, convergent translational evidence shows that common variants in RBFOX1 are associated with a broad spectrum of psychiatric traits and disorders, while rare genetic variation seems to expose to early-onset neurodevelopmental psychiatric disorders with and without developmental delay like ASD, in particular. Studying the pleiotropic nature of RBFOX1 can profoundly enhance our understanding of mental disorder vulnerability

The translational genetics of ADHD and related phenotypes in model organisms

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder resulting from the interaction between genetic and environmental risk factors. It is well known that ADHD co-occurs frequently with other psychiatric disorders due, in part, to shared genetics factors. Although many studies have contributed to delineate the genetic landscape of psychiatric disorders, their specific molecular underpinnings are still not fully understood. The use of animal models can help us to understand the role of specific genes and environmental stimuli-induced epigenetic modifications in the pathogenesis of ADHD and its comorbidities. The aim of this review is to provide an overview on the functional work performed in rodents, zebrafish and fruit fly and highlight the generated insights into the biology of ADHD, with a special focus on genetics and epigenetics. We also describe the behavioral tests that are available to study ADHD-relevant phenotypes and comorbid traits in these models. Furthermore, we have searched for new models to study ADHD and its comorbidities, which can be useful to test potential pharmacological treatments

Alferes Gamboa e a Sociedade Comemorativa da Independência do Império, 1869-1889

As festas da Independência brasileira promovidas pela Sociedade Comemorativa da Independência do Império no Rio de Janeiro revelam um significativo engajamento popular com o Estado imperial. O controle dessas celebrações pelo 'povo' da capital do Brasil aos poucos chegou a preocupar tanto membros da elite - perturbados diante do controle dos símbolos nacionais como a estátua equestre de d. Pedro I por patriotas populares - como republicanos que rejeitavam a monarquia, pois os patriotas populares demonstraram um monarquismo preocupante. Depois da morte do fundador e principal líder da Sociedade, em 1886, um grupo de homens estreitamente associado ao governo conservador tomou o seu controle e tentou impor celebrações convenientes e disciplinadas

Performance of the 2 MeV microwave gun for the SSRL 150 MeV linac

As described in a previous article, the preinjector linac for SSRL's 3 GeV synchrotron is fed by a 2 MeV, 1.5 A, low-emittance microwave gun, consisting of a thermionic cathode mounted in the first cell of a 1-1/2-cell S-band cavity. In this article, we report on the successful operation of the low-emittance gun, the longitudinally-bunching alpha-magnet, and the three-microbunch FET-pulsed beam-chopper. Simulations predict a normalized rms emittance at the gun exit of less than 10 {pi}{center dot}m{sub e}c{center dot}{mu}m; chromatic effects in transport optics increase this to approximately 30 {pi}{center dot}m{sub e}c{center dot}{mu}m. The gun was specifically designed to have a longitudinal phase-space suited to magnetic compression, as a result of which we predict that peak currents in excess of 300 A in a 1 ps bunch are feasible with the existing alpha-magnet. Results of simulations and experiments will be presented and compared. 13 refs., 9 figs