An early block in the replication of the atypical bluetongue virus serotype 26 in culicoides cells is determined by its capsid proteins

Arboviruses such as bluetongue virus (BTV) replicate in arthropod vectors involved in their transmission between susceptible vertebrate-hosts. The “classical” BTV strains infect and replicate effectively in cells of their insect-vectors (Culicoides biting-midges), as well as in those of their mammalian-hosts (ruminants). However, in the last decade, some “atypical” BTV strains, belonging to additional serotypes (e.g., BTV-26), have been found to replicate efficiently only in mammalian cells, while their replication is severely restricted in Culicoides cells. Importantly, there is evidence that these atypical BTV are transmitted by direct-contact between their mammalian hosts. Here, the viral determinants and mechanisms restricting viral replication in Culicoides were investigated using a classical BTV-1, an “atypical” BTV-26 and a BTV-1/BTV-26 reassortant virus, derived by reverse genetics. Viruses containing the capsid of BTV-26 showed a reduced ability to attach to Culicoides cells, blocking early steps of the replication cycle, while attachment and replication in mammalian cells was not restricted. The replication of BTV-26 was also severely reduced in other arthropod cells, derived from mosquitoes or ticks. The data presented identifies mechanisms and potential barriers to infection and transmission by the newly emerged “atypical” BTV strains in Culicoides.</p

Identifying factors associated with sedentary time after stroke. Secondary analysis of pooled data from nine primary studies.

<p><b>Background</b>: High levels of sedentary time increases the risk of cardiovascular disease, including recurrent stroke.</p> <p><b>Objective</b>: This study aimed to identify factors associated with high sedentary time in community-dwelling people with stroke.</p> <p><b>Methods</b>: For this data pooling study, authors of published and ongoing trials that collected sedentary time data, using the activPAL monitor, in community-dwelling people with stroke were invited to contribute their raw data. The data was reprocessed, algorithms were created to identify sleep-wake time and determine the percentage of waking hours spent sedentary. We explored demographic and stroke-related factors associated with total sedentary time and time in uninterrupted sedentary bouts using unique, both univariable and multivariable, regression analyses.</p> <p><b>Results</b>: The 274 included participants were from Australia, Canada, and the United Kingdom, and spent, on average, 69% (SD 12.4) of their waking hours sedentary. Of the demographic and stroke-related factors, slower walking speeds were significantly and independently associated with a higher percentage of waking hours spent sedentary (p = 0.001) and uninterrupted sedentary bouts of <i>>30</i> and <i>>60 min</i> (p = 0.001 and p = 0.004, respectively). Regression models explained 11–19% of the variance in total sedentary time and time in prolonged sedentary bouts.</p> <p><b>Conclusion</b>: We found that variability in sedentary time of people with stroke was largely unaccounted for by demographic and stroke-related variables. Behavioral and environmental factors are likely to play an important role in sedentary behavior after stroke. Further work is required to develop and test effective interventions to address sedentary behavior after stroke.</p

Selection of porcine intestinal isolates as probiotics for pathogen reduction in pigs

Putative lactobacilli were isolated from the porcine small intestine and assessed in vitro for potential probiotic traits. Viability of all isolates tested was unaffected at porcine bile concentrations of 0.3 % (w/v), with some tolerating up to 3.5 % (w/v) bile. Randomly amplified polymorphic DNA (RAPD) and/or pulsed field gel electrophoresis (PFGE) were used to genetically fingerprint the porcine isolates. Some of these cultures demonstrated antagonistic activity against pathogens Escherichia coli O157:H45 and Salmonella typhimurium DT104 when assayed on agar plates and in co-culture. For example, no Salmonella were detected after 8 h of associative culture with one intestinal isolate,L. salivarius B-24. However, when co-cultured under constant pH conditions, no inhibition was observed, indicating that acid may be one of the mechanisms involved in the antimicrobial activity of this strain. Assessment of these strains is on-going with a view to the development of probiotic feed additives which could potentially reduce pathogen carriage in pigs

An Early Block in the Replication of the Atypical Bluetongue Virus Serotype 26 in Culicoides Cells Is Determined by Its Capsid Proteins

Arboviruses such as bluetongue virus (BTV) replicate in arthropod vectors involved in their transmission between susceptible vertebrate-hosts. The “classical” BTV strains infect and replicate effectively in cells of their insect-vectors (Culicoides biting-midges), as well as in those of their mammalian-hosts (ruminants). However, in the last decade, some “atypical” BTV strains, belonging to additional serotypes (e.g., BTV-26), have been found to replicate efficiently only in mammalian cells, while their replication is severely restricted in Culicoides cells. Importantly, there is evidence that these atypical BTV are transmitted by direct-contact between their mammalian hosts. Here, the viral determinants and mechanisms restricting viral replication in Culicoides were investigated using a classical BTV-1, an “atypical” BTV-26 and a BTV-1/BTV-26 reassortant virus, derived by reverse genetics. Viruses containing the capsid of BTV-26 showed a reduced ability to attach to Culicoides cells, blocking early steps of the replication cycle, while attachment and replication in mammalian cells was not restricted. The replication of BTV-26 was also severely reduced in other arthropod cells, derived from mosquitoes or ticks. The data presented identifies mechanisms and potential barriers to infection and transmission by the newly emerged “atypical” BTV strains in Culicoides

Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment

Peer reviewedPublisher PD

Distribution and Phylogeny of EFL and EF-1α in Euglenozoa Suggest Ancestral Co-Occurrence Followed by Differential Loss

BACKGROUND: The eukaryotic elongation factor EF-1alpha (also known as EF1A) catalyzes aminoacyl-tRNA binding by the ribosome during translation. Homologs of this essential protein occur in all domains of life, and it was previously thought to be ubiquitous in eukaryotes. Recently, however, a number of eukaryotes were found to lack EF-1alpha and instead encode a related protein called EFL (for EF-Like). EFL-encoding organisms are scattered widely across the tree of eukaryotes, and all have close relatives that encode EF-1alpha. This intriguingly complex distribution has been attributed to multiple lateral transfers because EFL's near mutual exclusivity with EF-1alpha makes an extended period of co-occurrence seem unlikely. However, differential loss may play a role in EFL evolution, and this possibility has been less widely discussed. METHODOLOGY/PRINCIPAL FINDINGS: We have undertaken an EST- and PCR-based survey to determine the distribution of these two proteins in a previously under-sampled group, the Euglenozoa. EF-1alpha was found to be widespread and monophyletic, suggesting it is ancestral in this group. EFL was found in some species belonging to each of the three euglenozoan lineages, diplonemids, kinetoplastids, and euglenids. CONCLUSIONS/SIGNIFICANCE: Interestingly, the kinetoplastid EFL sequences are specifically related despite the fact that the lineages in which they are found are not sisters to one another, suggesting that EFL and EF-1alpha co-occurred in an early ancestor of kinetoplastids. This represents the strongest phylogenetic evidence to date that differential loss has contributed to the complex distribution of EFL and EF-1alpha

Differences in risk factors for three types of stroke: UK prospective study and meta-analyses

OBJECTIVE: To compare associations of behavioral and related factors for incident subarachnoid hemorrhage and intracerebral hemorrhage and ischemic stroke. METHODS: A total of 712,433 Million Women Study participants without prior stroke, heart disease, or cancer reported behavioral and related factors at baseline (1999-2007) and were followed up by record linkage to national hospital admission and death databases. Cox regression yielded adjusted relative risks (RRs) by type of stroke. Heterogeneity was assessed with χ2 tests. When appropriate, meta-analyses were done of published prospective studies. RESULTS: After 12.9 (SD 2.6) years of follow-up, 8,128 women had an incident ischemic stroke, 2,032 had intracerebral hemorrhage, and 1,536 had subarachnoid hemorrhage. In women with diabetes mellitus, the risk of ischemic stroke was substantially increased (RR 2.01, 95% confidence interval [CI] 1.84-2.20), risk of intracerebral hemorrhage was increased slightly (RR 1.31, 95% CI 1.04-1.65), but risk of subarachnoid hemorrhage was reduced (RR 0.43, 95% CI 0.26-0.69) (heterogeneity by stroke type, p < 0.0001). Stroke incidence was greater in women who rated their health as poor/fair compared to those who rated their health as excellent/good (RR 1.36, 95% CI 1.30-1.42). Among 565,850 women who rated their heath as excellent/good, current smokers were at an increased risk of all 3 stroke types, (although greater for subarachnoid hemorrhage [≥15 cigarettes/d vs never smoker, RR 4.75, 95% CI 4.12-5.47] than for intracerebral hemorrhage [RR 2.30, 95% CI 1.94-2.72] or ischemic stroke [RR 2.50, 95% CI 2.29-2.72]; heterogeneity p < 0.0001). Obesity was associated with an increased risk of ischemic stroke and a decreased risk of hemorrhagic stroke (heterogeneity p < 0.0001). Meta-analyses confirmed the associations and the heterogeneity across the 3 types of stroke. CONCLUSION: Classic risk factors for stroke have considerably different effects on the 3 main pathologic types of stroke

Dissemination and implementation of suicide prevention training in one Scottish region

<p>Abstract</p> <p>Background</p> <p>As part of a national co-ordinated and multifaceted response to the excess suicide rate, the <it>Choose Life </it>initiative, the Highland Choose Life Group launched an ambitious programme of training for National Health Service (NHS), Council and voluntary organisation staff. In this study of the dissemination and implementation of STORM (Skills-based Training On Risk Management), we set out to explore not only the outcomes of training, but key factors involved in the processes of diffusion, dissemination and implementation of the educational intervention.</p> <p>Methods</p> <p>Participants attending STORM training in Highland Region provided by 12 trained facilitators during the period March 2004 to February 2005 were recruited. Quantitative data collection from participants took place at three time points; immediately before training, immediately post-training and six months after training. Semi-structured telephone interviews were carried out with the training facilitators and with a sample of course participants 6 months after they had been trained. We have utilized the conceptual model described by Greenhalgh and colleagues in a Framework analysis of the data, for considering the determinants of diffusion, dissemination and implementation of interventions in health service delivery and organization.</p> <p>Results</p> <p>Some 203 individuals completed a series of questionnaire measures immediately pre (time 1) and immediately post (time 2) training and there were significant improvements in attitudes and confidence of participants. Key factors in the diffusion, dissemination and implementation process were the presence of a champion or local opinion leader who supported and directed the intervention, local adaptation of the materials, commissioning of a group of facilitators who were provided with financial and administrative support, dedicated time to provide the training and regular peer-support.</p> <p>Conclusion</p> <p>Features that contributed to the success of STORM were <it>related to both the context </it>(the multi-dimensional support provided from the host organisation and the favourable policy environment) <it>and the intervention </it>(openness to local adaptation, clinical relevance and utility), and the dynamic interaction between context and the intervention.</p

Diet breadth, coexistence and rarity in bumblebees

Factors that determine the relative abundance of bumblebee species remain poorly understood, rendering management of rare and declining species difficult. Studies of bumblebee communities in the Americas suggest that there are strong competitive interactions between species with similar length tongues, and that this competition determines the relative abundance of species. In contrast, in Europe it is common to observe several short-tongued species coexisting with little or no evidence for competition shaping community structure. In this study we examine patterns of abundance and distribution in one of the most diverse bumblebee communities in Europe, found in the mountains of southern Poland. We quantify forage use when collecting nectar and pollen for 23 bumblebee species, and examine patterns of co-occurrence and niche overlap to determine whether there is evidence for inter-specific competition. We also test whether rarity can be explained by diet breadth. Up to 16 species were found coexisting within single sites, with species richness peaking in mountain pasture at ~1000m altitude. Results concur with previous studies indicating that the majority of pollen collected by bumblebees is from Fabaceae, but that some bee species (e.g. B. ruderatus) are much more heavily dependent on Fabaceae than others (e.g. B. lucorum). Those species that forage primarily on Fabaceae tended to have long tongues. In common with studies in the UK, diet breadth was correlated with abundance: rarer species tended to visit fewer flower species, after correcting for differences in sample size. No evidence was found for similarity in tongue length or dietary overlap influencing the likelihood of co-occurrence of species. However, the most abundant species (which co-occurred at most sites) occupied distinct dietary niche space. While species with tongues of similar length tended, overall, to have higher dietary niche overlap, among the group of abundant short-tongued species that commonly co-occurred there was marked dietary differentiation which may explain their coexistence