A real-time PCR method for quantification of the total and major variant strains of the Deformed wing virus

Funding: ELB was supported by a Biotechnology and Biological Sciences Research Council (BBSRC) EASTBIO Doctoral Training Partnership (http://www.bbsrc.ac.uk) [grant number BB/J01446X/1] and an Eastern Association Regional Studentship (EARS) and The Morley Agricultural Foundation awarded to ASB. CRC was supported by a KTN BBSRC CASE studentship (BB/M503526/1) (http://www.bbsrc.ac.uk), part-funded by the Scottish Beekeeping Association (https://www.scottishbeekeepers.org.uk/) and the Animal Health - Disease Prevention, Scottish Government awarded to ASB CRC. This project received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 613960 (SMARTBEES) (http://www.smartbees-fp7.eu/) awarded to ASB. The funders had no role in study design, data collection and analysis decision to publish, or preparation of the manuscript. Acknowledgments The authors wish to thank Mr W. Thrale, Mr Z. Blackmore, Mr J. Quinlan, and Mr J. Palombo for sample collection from the South East of England and Margie Ramsey for Beinn Eighe National Nature Reserve sample collection.Peer reviewedPublisher PD

High rates of infection by blood parasites during the nestling phase in UK Columbids with notes on ecological associations

Studies of blood parasite infection in nestling birds rarely find a high prevalence of infection. This is likely due to a combination of short nestling periods (limiting the age at which nestlings can be sampled) and long parasite prepatent periods before gametocytes can be detected in peripheral blood. Here we examine rates of blood parasite infection in nestlings from three Columbid species in the UK. We use this system to address two key hypotheses in the epidemiology of avian haemoparasites: first, that nestlings in open nests have a higher prevalence of infection; and second, that nestlings sampled at 14 days old have a higher apparent infection rate than those sampled at 7 days old. Open-nesting individuals had a 54% infection rate compared with 25% for box-nesters, probably due to an increased exposure of open-nesting species to dipteran vectors. Nestlings sampled at 14 days had a 68% infection rate compared with 32% in nestlings sampled at 7 days, suggesting that rates of infection in the nest are high. Further work should examine nestlings post-fledging to identify rates of successful parasite infection (as opposed to abortive development within a dead-end host) as well as impacts on host post-fledging survival and behaviour

UCP2 Regulates the Glucagon Response to Fasting and Starvation

Glucagon is important for maintaining euglycemia during fasting/starvation, and abnormal glucagon secretion is associated with type 1 and type 2 diabetes; however, the mechanisms of hypoglycemia-induced glucagon secretion are poorly understood. We previously demonstrated that global deletion of mitochondrial uncoupling protein 2 (UCP2−/−) in mice impaired glucagon secretion from isolated islets. Therefore, UCP2 may contribute to the regulation of hypoglycemia-induced glucagon secretion, which is supported by our current finding that UCP2 expression is increased in nutrient-deprived murine and human islets. Further to this, we created α-cell–specific UCP2 knockout (UCP2AKO) mice, which we used to demonstrate that blood glucose recovery in response to hypoglycemia is impaired owing to attenuated glucagon secretion. UCP2-deleted α-cells have higher levels of intracellular reactive oxygen species (ROS) due to enhanced mitochondrial coupling, which translated into defective stimulus/secretion coupling. The effects of UCP2 deletion were mimicked by the UCP2 inhibitor genipin on both murine and human islets and also by application of exogenous ROS, confirming that changes in oxidative status and electrical activity directly reduce glucagon secretion. Therefore, α-cell UCP2 deletion perturbs the fasting/hypoglycemic glucagon response and shows that UCP2 is necessary for normal α-cell glucose sensing and the maintenance of euglycemia

Evidence that the C-terminal PB2-binding region of the influenza A virus PB1 protein is a discrete alpha-helical domain

AbstractThe influenza A virus RNA-dependent RNA polymerase is a heterotrimer composed of PB1, PB2 and PA subunits and essential for viral replication. However, little detailed structural information is available for this important enzyme. We show by circular dichroism spectroscopy that polypeptides from the C-terminus of PB1 that are capable of binding efficiently to PB2 fold into stable α-helical structures. Structure prediction analysis of this region of PB1 indicates that it likely consists of a three-helical bundle. Deletion of any of the helices abrogated transcriptional function. Thus, PB1 contains a C-terminal α-helical PB2-binding domain that is essential for nucleotide polymerization activity

Examining the Psychopathology of Incarcerated Male Firesetters using the Millon Clinical Multiaxial Inventory-III

Research to date has been equivocal on the relationship between firesetting and psychopathology, and has been impeded by studies lacking adequate control samples. The present study examined psychopathology in a sample of incarcerated adult male firesetters (n = 112) and prison controls (n = 113) using the Millon Clinical Multiaxial Inventory-III. Firesetters demonstrated multiple elevated scores on personality and clinical syndrome scales. Logistic regression showed that the borderline personality scale was the strongest personality scale discriminator between firesetters and controls. Major depression and drug dependence were the strongest clinical syndrome scale predictors. However, both clinical syndrome scale predictors appeared to be mediated by borderline personality scores indicating that firesetters are best characterized by responding indicative of borderline personality traits rather than other psychopathological deficits. The results suggest that, relative to other offenders, firesetters face challenges with impulse control, affect regulation, stability of interpersonal relationships, and self-image

FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells

Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types