Prevalence of Hepatitis E Virus in Swine Fed on Kitchen Residue

The aim of this study was to investigate the prevalence of swine hepatitis E virus (HEV) in pigs fed different feedstuffs (kitchen residue or mixed feeds) and genetic identification of HEV isolated in Hebei province, China. Serum and fecal samples were collected from adult swine. Anti-HEV antibody was evaluated by double sandwich antigen enzyme immunoassay. HEV RNA was extracted from fecal samples and amplified by nested RT-PCR. The reaction products were sequenced, and the sequence analyzed. Virus-like particles were distinguishable by negative staining in the electron microscope. Histopathological observation and immunohistochemical localization were used in the animal models. Overall, the anti-HEV positive percentage of serum samples from pigs fed on kitchen residue was 87.10% (27/31), and 53.06% (130/245) from pigs fed on complete feed. The HEV RNA positivity rate of fecal samples from pigs fed on kitchen residue was 61.54% (8/13), but zero for pigs fed on complete feed. Sequence analysis of these eight samples and comparison with the published sequence showed that there were eight groups that belonged to genotype 4 d and the nucleotide identity was 95.6–99.3%. swHE11 is most closely related to strain CCC220, and the other seven HEV isolates were most closely related to strains swGX40, SwCH189 and V0008ORF3, which are isolates from human and pigs. Histopathological observation showed that there was liver damage in the experimental group, and immunohistochemistry indicated that the HEV antigens were strongly positive at 7 days after infection. The results demonstrated that the prevalence of HEV in pigs fed on kitchen residue was higher than in those fed on complete feed (P<0.05)

Anti-PD-1 increases the clonality and activity of tumor infiltrating antigen specific T cells induced by a potent immune therapy consisting of vaccine and metronomic cyclophosphamide

BACKGROUND: Future cancer immunotherapies will combine multiple treatments to generate functional immune responses to cancer antigens through synergistic, multi-modal mechanisms. In this study we explored the combination of three distinct immunotherapies: a class I restricted peptide-based cancer vaccine, metronomic cyclophosphamide (mCPA) and anti-PD-1 treatment in a murine tumor model expressing HPV16 E7 (C3). METHODS: Mice were implanted with C3 tumors subcutaneously. Tumor bearing mice were treated with mCPA (20 mg/kg/day PO) for seven continuous days on alternating weeks, vaccinated with HPV16 E7(49-57) peptide antigen formulated in the DepoVax (DPX) adjuvanting platform every second week, and administered anti-PD-1 (200 μg/dose IP) after each vaccination. Efficacy was measured by following tumor growth and survival. Immunogenicity was measured by IFN-γ ELISpot of spleen, vaccine draining lymph nodes and tumor draining lymph nodes. Tumor infiltration was measured by flow cytometry for CD8α(+) peptide-specific T cells and RT-qPCR for cytotoxic proteins. The clonality of tumor infiltrating T cells was measured by TCRβ sequencing using genomic DNA. RESULTS: Untreated C3 tumors had low expression of PD-L1 in vivo and anti-PD-1 therapy alone provided no protection from tumor growth. Treatment with DPX/mCPA could delay tumor growth, and tri-therapy with DPX/mCPA/anti-PD-1 provided long-term control of tumors. We found that treatment with DPX/mCPA/anti-PD-1 enhanced systemic antigen-specific immune responses detected in the spleen as determined by IFN-γ ELISpot compared to those in the DPX/mCPA group, but immune responses in tumor-draining lymph nodes were not increased. Although no increases in antigen-specific CD8α(+) TILs could be detected, there was a trend for increased expression of cytotoxic genes within the tumor microenvironment as well as an increase in clonality in mice treated with DPX/mCPA/anti-PD-1 compared to those with anti-PD-1 alone or DPX/mCPA. Using a library of antigen-specific CD8α(+) T cell clones, we found that antigen-specific clones were more frequently expanded in the DPX/mCPA/anti-PD-1 treated group. CONCLUSIONS: These results demonstrate how the efficacy of anti-PD-1 may be improved by combination with a potent and targeted T cell activating immune therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40425-016-0169-2) contains supplementary material, which is available to authorized users

Anxiety disorders in children with Williams syndrome, their mothers, and their siblings: Implications for the etiology of anxiety disorders

This study examines the prevalence of anxiety disorders in children with Williams syndrome (WS), their sibling closest in age, and their mothers as well as the predictors of anxiety in these groups. The prevalence of anxiety disorders was assessed and compared to that in the general population. Children with WS had a significantly higher prevalence of specific phobia, generalized anxiety disorder (GAD), and separation anxiety in comparison to children in the general population. While mothers had a higher prevalence of GAD than population controls, the excess was accounted for by mothers who had onset after the birth of their WS child. The siblings had rates similar to the general population. This pattern of findings suggests the presence of a gene in the WS region whose deletion predisposes to anxiety disorders. It is also worthwhile to investigate relations between genes deleted in WS and genes previously implicated in anxiety disorders

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201

Minimum information about an uncultivated virus genome (MIUVIG)

This is the final version. Available on open access from Nature Research via the DOI in this recordNOTE: the full list of funders and grants is in the acknowledgements section of the articleWe present an extension of the Minimum Information about any (x) Sequence (MIxS) standard for reporting sequences of uncultivated virus genomes. Minimum Information about an Uncultivated Virus Genome (MIUViG) standards were developed within the Genomic Standards Consortium framework and include virus origin, genome quality, genome annotation, taxonomic classification, biogeographic distribution and in silico host prediction. Community-wide adoption of MIUViG standards, which complement the Minimum Information about a Single Amplified Genome (MISAG) and Metagenome-Assembled Genome (MIMAG) standards for uncultivated bacteria and archaea, will improve the reporting of uncultivated virus genomes in public databases. In turn, this should enable more robust comparative studies and a systematic exploration of the global virosphere.Simons Foundation InternationalNatural Environment Research Council (NERC

Aggression in Low Functioning Children and Adolescents with Autistic Disorder

BACKGROUND: Parents, caregivers and mental health professionals have often reported violence and aggression in children or adolescents with autistic disorder. However, most of these observations derived from anecdotal reports, and studies on frequency and characterization of aggression in autism remain limited. Our objective was to better characterize and understand the different types of aggressive behaviors displayed by a large group of individuals with autism in different observational situations. METHODOLOGY/FINDINGS: The study was conducted on 74 children and adolescents with autism and 115 typically developing control individuals matched for sex, age and pubertal stage. Other-Injurious Behaviors (OIB) were assessed in three observational situations (parents at home, two caregivers at day-care, a nurse and a child psychiatrist during blood drawing) using validated scales. The frequency of OIB was significantly higher in individuals with autism compared to typically developing control individuals during the blood drawing (23% vs. 0%, P<0 .01). The parents observed significantly less OIB in their children than caregivers (34% vs. 58%, P<0.05). In addition, the most frequent concurrent behaviors occurring just before the appearance of OIB in individuals with autism were anxiety-related behaviors and excitation according to the parental as well as the caregiver observation. CONCLUSIONS/SIGNIFICANCE: The results suggest that in a stressful situation, such as the blood drawing, individuals with autism release their stress through behaviors such as OIB, whereas typically developing individuals regulate and express their stress through cognitive skills such as mental coping strategies, symbolization skills with representation and anticipation of the stressful situation, social interaction and verbal or non-verbal communication. The findings underline also the key role of the environment in assessing OIB and developing therapeutic perspectives, with an individual who modulates his/her behavior according to the environment, and an environment that perceives this behavior and reacts to it with different tolerance thresholds according to the observers

Antibiotic Selection Pressure and Macrolide Resistance in Nasopharyngeal Streptococcus pneumoniae: A Cluster-Randomized Clinical Trial

Jeremy Keenan and colleagues report that during a cluster-randomized clinical trial in Ethiopia, nasopharyngeal pneumococcal resistance to macrolides was significantly higher in communities randomized to receive azithromycin compared with untreated control communities