Squirrelpox virus: assessing prevalence, transmission and environmental degradation

Red squirrels (Sciurus vulgaris) declined in Great Britain and Ireland during the last century, due to habitat loss and the introduction of grey squirrels (Sciurus carolinensis), which competitively exclude the red squirrel and act as a reservoir for squirrelpox virus (SQPV). The disease is generally fatal to red squirrels and their ecological replacement by grey squirrels is up to 25 times faster where the virus is present. We aimed to determine: (1) the seropositivity and prevalence of SQPV DNA in the invasive and native species at a regional scale; (2) possible SQPV transmission routes; and, (3) virus degradation rates under differing environmental conditions. Grey (n = 208) and red (n = 40) squirrel blood and tissues were sampled. Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qPCR) techniques established seropositivity and viral DNA presence, respectively. Overall 8% of squirrels sampled (both species combined) had evidence of SQPV DNA in their tissues and 22% were in possession of antibodies. SQPV prevalence in sampled red squirrels was 2.5%. Viral loads were typically low in grey squirrels by comparison to red squirrels. There was a trend for a greater number of positive samples in spring and summer than in winter. Possible transmission routes were identified through the presence of viral DNA in faeces (red squirrels only), urine and ectoparasites (both species). Virus degradation analyses suggested that, after 30 days of exposure to six combinations of environments, there were more intact virus particles in scabs kept in warm (25°C) and dry conditions than in cooler (5 and 15°C) or wet conditions. We conclude that SQPV is present at low prevalence in invasive grey squirrel populations with a lower prevalence in native red squirrels. Virus transmission could occur through urine especially during warm dry summer conditions but, more notably, via ectoparasites, which are shared by both species

A Double Sigma Model for Double Field Theory

We define a sigma model with doubled target space and calculate its background field equations. These coincide with generalised metric equation of motion of double field theory, thus the double field theory is the effective field theory for the sigma model.Comment: 26 pages, v1: 37 pages, v2: references added, v3: updated to match published version - background and detail of calculations substantially condensed, motivation expanded, refs added, results unchange

Impaired decisional impulsivity in pathological videogamers

Abstract Background Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort. Methods Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice), and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task). We used stringent diagnostic criteria highlighting functional impairment. Results In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time. Conclusions We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours

Although compulsive sexual behaviour (CSB) has been conceptualized as a "behavioural" addiction and common or overlapping neural circuits may govern the processing of natural and drug rewards, little is known regarding the responses to sexually explicit materials in individuals with and without CSB. Here, the processing of cues of varying sexual content was assessed in individuals with and without CSB, focusing on neural regions identified in prior studies of drug-cue reactivity. 19 CSB subjects and 19 healthy volunteers were assessed using functional MRI comparing sexually explicit videos with non-sexual exciting videos. Ratings of sexual desire and liking were obtained. Relative to healthy volunteers, CSB subjects had greater desire but similar liking scores in response to the sexually explicit videos. Exposure to sexually explicit cues in CSB compared to non-CSB subjects was associated with activation of the dorsal anterior cingulate, ventral striatum and amygdala. Functional connectivity of the dorsal anterior cingulate-ventral striatum-amygdala network was associated with subjective sexual desire (but not liking) to a greater degree in CSB relative to non-CSB subjects. The dissociation between desire or wanting and liking is consistent with theories of incentive motivation underlying CSB as in drug addictions. Neural differences in the processing of sexual-cue reactivity were identified in CSB subjects in regions previously implicated in drug-cue reactivity studies. The greater engagement of corticostriatal limbic circuitry in CSB following exposure to sexual cues suggests neural mechanisms underlying CSB and potential biological targets for interventions

Subanesthetic ketamine treatment promotes abnormal interactions between neural subsystems and alters the properties of functional brain networks

Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia

13,915 reasons for equity in sexual offences legislation: A national school-based survey in South Africa

<p>Abstract</p> <p>Objective</p> <p>Prior to 2007, forced sex with male children in South Africa did not count as rape but as "indecent assault", a much less serious offence. This study sought to document prevalence of male sexual violence among school-going youth.</p> <p>Design</p> <p>A facilitated self-administered questionnaire in nine of the 11 official languages in a stratified (province/metro/urban/rural) last stage random national sample.</p> <p>Setting</p> <p>Teams visited 5162 classes in 1191 schools, in October and November 2002.</p> <p>Participants</p> <p>A total of 269,705 learners aged 10–19 years in grades 6–11. Of these, 126,696 were male.</p> <p>Main outcome measures</p> <p>Schoolchildren answered questions about exposure in the last year to insults, beating, unwanted touching and forced sex. They indicated the sex of the perpetrator, and whether this was a family member, a fellow schoolchild, a teacher or another adult. Respondents also gave the age when they first suffered forced sex and when they first had consensual sex.</p> <p>Results</p> <p>Some 9% (weighted value based on 13915/127097) of male respondents aged 11–19 years reported forced sex in the last year. Of those aged 18 years at the time of the survey, 44% (weighted value of 5385/11450) said they had been forced to have sex in their lives and 50% reported consensual sex. Perpetrators were most frequently an adult not from their own family, followed closely in frequency by other schoolchildren. Some 32% said the perpetrator was male, 41% said she was female and 27% said they had been forced to have sex by both male and female perpetrators. Male abuse of schoolboys was more common in rural areas while female perpetration was more an urban phenomenon.</p> <p>Conclusion</p> <p>This study uncovers endemic sexual abuse of male children that was suspected but hitherto only poorly documented. Legal recognition of the criminality of rape of male children is a first step. The next steps include serious investment in supporting male victims of abuse, and in prevention of all childhood sexual abuse.</p

Human rhinovirus infection of epithelial cells modulates airway smooth muscle migration

Rationale: Airway remodeling, a characteristic feature of asthma, begins in early life. Recurrent human rhinovirus (HRV) infections are a potential inciting stimulus for remodeling. One component of airway remodeling is an increase in airway smooth muscle cell mass with a greater proximity of the airway smooth muscle cells (ASMC) to the airway epithelium. We asked whether human bronchial epithelial cells infected with HRV produced mediators that are chemotactic for ASMC. Methods: ASMC migration was investigated using the modified Boyden Chamber and the xCELLigence Real-Time Cell Analyzer. Multiplex bead analysis was used to measure HRV-induced epithelial chemokine release. The chemotactic effects of CCL5, CXCL8 and CXCL10 were also examined. Results: Supernatants from HRV-infected epithelial cells caused ASMC chemotaxis. Pre-treatment of ASMC with pertussis toxin abrogated chemotaxis, as did treatment with formoterol, forskolin, or 8-bromo-cAMP. CCL5, CXCL8, and CXCL10 were most up-regulated chemokines produced by HRV-infected airway epithelial cells. When recombinant CCL5, CXCL8 and CXCL10 were used at levels found in epithelial supernatants they induced ASMC chemotaxis similar to that seen with epithelial cell supernatants. When examined individually, CCL5 was the most effective chemokine in causing ASMC migration and treatment of supernatant from HRV-infected epithelial cells with anti-CCL5 antibodies significantly attenuated ASMC migration. Conclusion: These findings suggest that HRV-induced CCL5 can induce ASMC chemotaxis, and thus may contribute to the pathogenesis of airway remodeling in asthmatic patients