No evidence for infection of UK prostate cancer patients with XMRV, BK virus, Trichomonas vaginalis or human papilloma viruses.

The prevalence of specific infections in UK prostate cancer patients was investigated. Serum from 84 patients and 62 controls was tested for neutralisation of xenotropic murine leukaemia virus-related virus (XMRV) Envelope. No reactivity was found in the patient samples. In addition, a further 100 prostate DNA samples were tested for XMRV, BK virus, Trichomonas vaginalis and human papilloma viruses by nucleic acid detection techniques. Despite demonstrating DNA integrity and assay sensitivity, we failed to detect the presence of any of these agents in DNA samples, bar one sample that was weakly positive for HPV16. Therefore we conclude that these infections are absent in this typical cohort of men with prostate cancer

Design of a combinatorial DNA microarray for protein-DNA interaction studies

BACKGROUND: Discovery of precise specificity of transcription factors is an important step on the way to understanding the complex mechanisms of gene regulation in eukaryotes. Recently, double-stranded protein-binding microarrays were developed as a potentially scalable approach to tackle transcription factor binding site identification. RESULTS: Here we present an algorithmic approach to experimental design of a microarray that allows for testing full specificity of a transcription factor binding to all possible DNA binding sites of a given length, with optimally efficient use of the array. This design is universal, works for any factor that binds a sequence motif and is not species-specific. Furthermore, simulation results show that data produced with the designed arrays is easier to analyze and would result in more precise identification of binding sites. CONCLUSION: In this study, we present a design of a double stranded DNA microarray for protein-DNA interaction studies and show that our algorithm allows optimally efficient use of the arrays for this purpose. We believe such a design will prove useful for transcription factor binding site identification and other biological problems

Anaerobe-enriched gut microbiota predicts pro-inflammatory responses in pulmonary tuberculosis

BACKGROUND: The relationship between tuberculosis (TB), one of the leading infectious causes of death worldwide, and the microbiome, which is critical for health, is poorly understood. METHODS: To identify potential microbiome-host interactions, profiling of the oral, sputum and stool microbiota [n = 58 cases, n = 47 culture-negative symptomatic controls (SCs)] and whole blood transcriptome were done in pre-treatment presumptive pulmonary TB patients. This was a cross-sectional study. Microbiota were also characterised in close contacts of cases (CCCs, n = 73) and close contacts of SCs (CCSCs, n = 82) without active TB. FINDINGS: Cases and SCs each had similar α- and β-diversities in oral washes and sputum, however, β-diversity differed in stool (PERMANOVA p = 0•035). Cases were enriched with anaerobes in oral washes, sputum (Paludibacter, Lautropia in both) and stool (Erysipelotrichaceae, Blautia, Anaerostipes) and their stools enriched in microbial genes annotated as amino acid and carbohydrate metabolic pathways. In pairwise comparisons with their CCCs, cases had Megasphaera-enriched oral and sputum microbiota and Bifidobacterium-, Roseburia-, and Dorea-depleted stools. Compared to their CCSCs, SCs had reduced α-diversities and many differential taxa per specimen type. Cases differed transcriptionally from SCs in peripheral blood (PERMANOVA p = 0•001). A co-occurrence network analysis showed stool taxa, Erysipelotrichaceae and Blautia, to negatively co-correlate with enriched "death receptor" and "EIF2 signalling" pathways whereas Anaerostipes positively correlated with enriched "interferon signalling", "Nur77 signalling" and "inflammasome" pathways; all of which are host pathways associated with disease severity. In contrast, none of the taxa enriched in SCs correlated with host pathways. INTERPRETATION: TB-specific microbial relationships were identified in oral washes, induced sputum, and stool from cases before the confounding effects of antibiotics. Specific anaerobes in cases' stool predict upregulation of pro-inflammatory immunological pathways, supporting the gut microbiota's role in TB. FUNDING: European & Developing Countries Clinical Trials Partnership, South African-Medical Research Council, National Institute of Allergy and Infectious Diseases

Muscle fiber conduction velocity is more affected after eccentric than concentric exercise

It has been shown that mean muscle fiber conduction velocity (CV) can be acutely impaired after eccentric exercise. However, it is not known whether this applies to other exercise modes. Therefore, the purpose of this experiment was to compare the effects of eccentric and concentric exercises on CV, and amplitude and frequency content of surface electromyography (sEMG) signals up to 24 h post-exercise. Multichannel sEMG signals were recorded from biceps brachii muscle of the exercised arm during isometric maximal voluntary contraction (MVC) and electrically evoked contractions induced by motor-point stimulation before, immediately after and 2 h after maximal eccentric (ECC group, N = 12) and concentric (CON group, N = 12) elbow flexor exercises. Isometric MVC decreased in CON by 21.7 ± 12.0% (± SD, p < 0.01) and by 30.0 ± 17.7% (p < 0.001) in ECC immediately post-exercise when compared to baseline. At 2 h post-exercise, ECC showed a reduction in isometric MVC by 24.7 ± 13.7% (p < 0.01) when compared to baseline, while no significant reduction (by 8.0 ± 17.0%, ns) was observed in CON. Similarly, reduction in CV was observed only in ECC both during the isometric MVC (from baseline of 4.16 ± 0.3 to 3.43 ± 0.4 m/s, p < 0.001) and the electrically evoked contractions (from baseline of 4.33 ± 0.4 to 3.82 ± 0.3 m/s, p < 0.001). In conclusion, eccentric exercise can induce a greater and more prolonged reduction in muscle force production capability and CV than concentric exercis

Self-reported tobacco smoking practices among medical students and their perceptions towards training about tobacco smoking in medical curricula: A cross-sectional, questionnaire survey in Malaysia, India, Pakistan, Nepal, and Bangladesh

<p>Abstract</p> <p>Background</p> <p>Tobacco smoking issues in developing countries are usually taught non-systematically as and when the topic arose. The World Health Organisation and Global Health Professional Student Survey (GHPSS) have suggested introducing a separate integrated tobacco module into medical school curricula. Our aim was to assess medical students' tobacco smoking habits, their practices towards patients' smoking habits and attitude towards teaching about smoking in medical schools.</p> <p>Methods</p> <p>A cross-sectional questionnaire survey was carried out among final year undergraduate medical students in Malaysia, India, Nepal, Pakistan, and Bangladesh. An anonymous, self-administered questionnaire included items on demographic information, students' current practices about patients' tobacco smoking habits, their perception towards tobacco education in medical schools on a five point Likert scale. Questions about tobacco smoking habits were adapted from GHPSS questionnaire. An <it>'ever smoker' </it>was defined as one who had smoked during lifetime, even if had tried a few puffs once or twice. 'Current smoker' was defined as those who had smoked tobacco product on one or more days in the preceding month of the survey. Descriptive statistics were calculated.</p> <p>Results</p> <p>Overall response rate was 81.6% (922/1130). Median age was 22 years while 50.7% were males and 48.2% were females. The overall prevalence of 'ever smokers' and 'current smokers' was 31.7% and 13.1% respectively. A majority (> 80%) of students asked the patients about their smoking habits during clinical postings/clerkships. Only a third of them did counselling, and assessed the patients' willingness to quit. Majority of the students agreed about doctors' role in tobacco control as being role models, competence in smoking cessation methods, counseling, and the need for training about tobacco cessation in medical schools. About 50% agreed that current curriculum teaches about tobacco smoking but not systematically and should be included as a separate module. Majority of the students indicated that topics about health effects, nicotine addiction and its treatment, counselling, prevention of relapse were important or very important in training about tobacco smoking.</p> <p>Conclusion</p> <p>Medical educators should consider revising medical curricula to improve training about tobacco smoking cessation in medical schools. Our results should be supported by surveys from other medical schools in developing countries of Asia.</p

Phylogenetic relationships of cone snails endemic to Cabo Verde based on mitochondrial genomes

Background: Due to their great species and ecological diversity as well as their capacity to produce hundreds of different toxins, cone snails are of interest to evolutionary biologists, pharmacologists and amateur naturalists alike. Taxonomic identification of cone snails still relies mostly on the shape, color, and banding patterns of the shell. However, these phenotypic traits are prone to homoplasy. Therefore, the consistent use of genetic data for species delimitation and phylogenetic inference in this apparently hyperdiverse group is largely wanting. Here, we reconstruct the phylogeny of the cones endemic to Cabo Verde archipelago, a well-known radiation of the group, using mitochondrial (mt) genomes. Results: The reconstructed phylogeny grouped the analyzed species into two main clades, one including Kalloconus from West Africa sister to Trovaoconus from Cabo Verde and the other with a paraphyletic Lautoconus due to the sister group relationship of Africonus from Cabo Verde and Lautoconus ventricosus from Mediterranean Sea and neighboring Atlantic Ocean to the exclusion of Lautoconus endemic to Senegal (plus Lautoconus guanche from Mauritania, Morocco, and Canary Islands). Within Trovaoconus, up to three main lineages could be distinguished. The clade of Africonus included four main lineages (named I to IV), each further subdivided into two monophyletic groups. The reconstructed phylogeny allowed inferring the evolution of the radula in the studied lineages as well as biogeographic patterns. The number of cone species endemic to Cabo Verde was revised under the light of sequence divergence data and the inferred phylogenetic relationships. Conclusions: The sequence divergence between continental members of the genus Kalloconus and island endemics ascribed to the genus Trovaoconus is low, prompting for synonymization of the latter. The genus Lautoconus is paraphyletic. Lautoconus ventricosus is the closest living sister group of genus Africonus. Diversification of Africonus was in allopatry due to the direct development nature of their larvae and mainly triggered by eustatic sea level changes during the Miocene-Pliocene. Our study confirms the diversity of cone endemic to Cabo Verde but significantly reduces the number of valid species. Applying a sequence divergence threshold, the number of valid species within the sampled Africonus is reduced to half.Spanish Ministry of Science and Innovation [CGL2013-45211-C2-2-P, CGL2016-75255-C2-1-P, BES-2011-051469, BES-2014-069575, Doctorado Nacional-567]info:eu-repo/semantics/publishedVersio

The Cyprinodon variegatus genome reveals gene expression changes underlying differences in skull morphology among closely related species

Genes in durophage intersection set at 15 dpf. This is a comma separated table of the genes in the 15 dpf durophage intersection set. Given are edgeR results for each pairwise comparison. Columns indicating whether a gene is included in the intersection set at a threshold of 1.5 or 2 fold are provided. (CSV 13 kb

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself