The chemical signatures underlying host plant discrimination by aphids

The diversity of phytophagous insects is largely attributable to speciation involving shifts between host plants. These shifts are mediated by the close interaction between insects and plant metabolites. However, there has been limited progress in understanding the chemical signatures that underlie host preferences. We use the pea aphid (Acyrthosiphon pisum) to address this problem. Host-associated races of pea aphid discriminate between plant species in race-specific ways. We combined metabolomic profiling of multiple plant species with behavioural tests on two A. pisum races, to identify metabolites that explain variation in either acceptance or discrimination. Candidate compounds were identified using tandem mass spectrometry. Our results reveal a small number of compounds that explain a large proportion of variation in the differential acceptability of plants to A. pisum races. Two of these were identified as L-phenylalanine and L-tyrosine but it may be that metabolically-related compounds directly influence insect behaviour. The compounds implicated in differential acceptability were not related to the set correlated with general acceptability of plants to aphids, regardless of host race. Small changes in response to common metabolites may underlie host shifts. This study opens new opportunities for understanding the mechanistic basis of host discrimination and host shifts in insects

A randomized controlled trial on the effectiveness of strength training on clinical and muscle cellular outcomes in patients with prostate cancer during androgen deprivation therapy: rationale and design

Background Studies indicate that strength training has beneficial effects on clinical health outcomes in prostate cancer patients during androgen deprivation therapy. However, randomized controlled trials are needed to scientifically determine the effectiveness of strength training on the muscle cell level. Furthermore, close examination of the feasibility of a high-load strength training program is warranted. The Physical Exercise and Prostate Cancer (PEPC) trial is designed to determine the effectiveness of strength training on clinical and muscle cellular outcomes in non-metastatic prostate cancer patients after high-dose radiotherapy and during ongoing androgen deprivation therapy. Methods/design Patients receiving androgen deprivation therapy for 9-36 months combined with external high-dose radiotherapy for locally advanced prostate cancer are randomized to an exercise intervention group that receives a 16 week high-load strength training program or a control group that is encouraged to maintain their habitual activity level. In both arms, androgen deprivation therapy is continued until the end of the intervention period. Clinical outcomes are body composition (lean body mass, bone mineral density and fat mass) measured by Dual-energy X-ray Absorptiometry, serological outcomes, physical functioning (muscle strength and cardio-respiratory fitness) assessed with physical tests and psycho-social functioning (mental health, fatigue and health-related quality of life) assessed by questionnaires. Muscle cellular outcomes are a) muscle fiber size b) regulators of muscle fiber size (number of myonuclei per muscle fiber, number of satellite cells per muscle fiber, number of satellite cells and myonuclei positive for androgen receptors and proteins involved in muscle protein degradation and muscle hypertrophy) and c) regulators of muscle fiber function such as proteins involved in cellular stress and mitochondrial function. Muscle cellular outcomes are measured on muscle cross sections and muscle homogenate from muscle biopsies obtained from muscle vastus lateralis. Discussion The findings from the PEPC trial will provide new knowledge on the effects of high-load strength training on clinical and muscle cellular outcomes in prostate cancer patients during androgen deprivation therapy. Trial registration ClinicalTrials.gov: NCT0065822

IFITM3 restricts the morbidity and mortality associated with influenza

The 2009 H1N1 influenza pandemic showed the speed with which a novel respiratory virus can spread and the ability of a generally mild infection to induce severe morbidity and mortality in a subset of the population. Recent in vitro studies show that the interferon-inducible transmembrane (IFITM) protein family members potently restrict the replication of multiple pathogenic viruses1, 2, 3, 4, 5, 6, 7. Both the magnitude and breadth of the IFITM proteins’ in vitro effects suggest that they are critical for intrinsic resistance to such viruses, including influenza viruses. Using a knockout mouse model8, we now test this hypothesis directly and find that IFITM3 is essential for defending the host against influenza A virus in vivo. Mice lacking Ifitm3 display fulminant viral pneumonia when challenged with a normally low-pathogenicity influenza virus, mirroring the destruction inflicted by the highly pathogenic 1918 ‘Spanish’ influenza9, 10. Similar increased viral replication is seen in vitro, with protection rescued by the re-introduction of Ifitm3. To test the role of IFITM3 in human influenza virus infection, we assessed the IFITM3 alleles of individuals hospitalized with seasonal or pandemic influenza H1N1/09 viruses. We find that a statistically significant number of hospitalized subjects show enrichment for a minor IFITM3 allele (SNP rs12252-C) that alters a splice acceptor site, and functional assays show the minor CC genotype IFITM3 has reduced influenza virus restriction in vitro. Together these data reveal that the action of a single intrinsic immune effector, IFITM3, profoundly alters the course of influenza virus infection in mouse and human

PARV4 prevalence, phylogeny, immunology and coinfection with HIV, HBV and HCV in a multicentre African cohort.

<h4>Background</h4> <p>The seroprevalence of human parvovirus-4 (PARV4) varies considerably by region. In sub-Saharan Africa, seroprevalence is high in the general population, but little is known about the transmission routes or the prevalence of coinfection with blood-borne viruses, HBV, HCV and HIV.</p> <h4>Methods</h4> <p>To further explore the characteristics of PARV4 in this setting, with a particular focus on the prevalence and significance of coinfection, we screened a cohort of 695 individuals recruited from Durban and Kimberley (South Africa) and Gaborone (Botswana) for PARV4 IgG and DNA, as well as documenting HIV, HBV and HCV status.</p> <h4>Results</h4> <p>Within these cohorts, 69% of subjects were HIV-positive. We identified no cases of HCV by PCR, but 7.4% were positive for HBsAg. PARV4 IgG was positive in 42%; seroprevalence was higher in adults (69%) compared to children (21%) (p<0.0001) and in HIV-positive (52%) compared to HIV-negative individuals (24%) (p<0.0001), but there was no association with HBsAg status. We developed an on-line tool to allow visualization of coinfection data (https://purl.oclc.org/coinfection-viz). We identified five subjects who were PCR-positive for PARV4 genotype-3. Ex vivo CD8+ T cell responses spanned the entire PARV4 proteome and we propose a novel HLA-B*57:03-restricted epitope within the NS protein. </p> <h4>Conclusions</h4> <p>This characterisation of PARV4 infection provides enhanced insights into the epidemiology of infection and co-infection in African cohorts, and provides the foundations for planning further focused studies to elucidate transmission pathways, immune responses, and the clinical significance of this organism.</p