The genome sequence of <i>Trypanosoma brucei gambiense</i>, causative agent of chronic Human African Trypanosomiasis

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; &lt;i&gt;Trypanosoma brucei gambiense&lt;/i&gt; is the causative agent of chronic Human African Trypanosomiasis or sleeping sickness, a disease endemic across often poor and rural areas of Western and Central Africa. We have previously published the genome sequence of a &lt;i&gt;T. b. brucei&lt;/i&gt; isolate, and have now employed a comparative genomics approach to understand the scale of genomic variation between &lt;i&gt;T. b. gambiense&lt;/i&gt; and the reference genome. We sought to identify features that were uniquely associated with &lt;i&gt;T. b. gambiense&lt;/i&gt; and its ability to infect humans.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and findings:&lt;/b&gt; An improved high-quality draft genome sequence for the group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; DAL 972 isolate was produced using a whole-genome shotgun strategy. Comparison with &lt;i&gt;T. b. brucei&lt;/i&gt; showed that sequence identity averages 99.2% in coding regions, and gene order is largely collinear. However, variation associated with segmental duplications and tandem gene arrays suggests some reduction of functional repertoire in &lt;i&gt;T. b. gambiense&lt;/i&gt; DAL 972. A comparison of the variant surface glycoproteins (VSG) in &lt;i&gt;T. b. brucei&lt;/i&gt; with all &lt;i&gt;T. b. gambiense&lt;/i&gt; sequence reads showed that the essential structural repertoire of VSG domains is conserved across &lt;i&gt;T. brucei&lt;/i&gt;.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; This study provides the first estimate of intraspecific genomic variation within &lt;i&gt;T. brucei&lt;/i&gt;, and so has important consequences for future population genomics studies. We have shown that the &lt;i&gt;T. b. gambiense&lt;/i&gt; genome corresponds closely with the reference, which should therefore be an effective scaffold for any &lt;i&gt;T. brucei&lt;/i&gt; genome sequence data. As VSG repertoire is also well conserved, it may be feasible to describe the total diversity of variant antigens. While we describe several as yet uncharacterized gene families with predicted cell surface roles that were expanded in number in &lt;i&gt;T. b. brucei&lt;/i&gt;, no &lt;i&gt;T. b. gambiense&lt;/i&gt;-specific gene was identified outside of the subtelomeres that could explain the ability to infect humans.&lt;/p&gt

Effectiveness of a single-session early psychological intervention for children after road traffic accidents: a randomised controlled trial

BACKGROUND: Road traffic accidents (RTAs) are the leading health threat to children in Europe, resulting in 355,000 injuries annually. Because children can suffer significant and long-term mental health problems following RTAs, there is considerable interest in the development of early psychological interventions. To date, the research in this field is scarce, and currently no evidence-based recommendations can be made. METHODS: To evaluate the effectiveness of a single-session early psychological intervention, 99 children age 7-16 were randomly assigned to an intervention or control group. The manualised intervention was provided to the child and at least one parent around 10 days after the child's involvement in an RTA. It included reconstruction of the accident using drawings and accident-related toys, and psychoeducation. All of the children were interviewed at 10 days, 2 months and 6 months after the accident. Parents filled in questionnaires. Standardised instruments were used to assess acute stress disorder (ASD), posttraumatic stress disorder (PTSD), depressive symptoms and behavioural problems. RESULTS: The children of the two study groups showed no significant differences concerning posttraumatic symptoms and other outcome variables at 2 or at 6 months. Interestingly, analyses showed a significant intervention x age-group effect, indicating that for preadolescent children the intervention was effective in decreasing depressive symptoms and behavioural problems. CONCLUSIONS: This study is the first to show a beneficial effect of a single-session early psychological intervention after RTA in preadolescent children. Therefore, an age-specific approach in an early stage after RTAs may be a promising way for further research. Younger children can benefit from the intervention evaluated here. However, these results have to be interpreted with caution, because of small subgroup sizes. Future studies are needed to examine specific approaches for children and adolescents. Also, the intervention evaluated here needs to be studied in other groups of traumatised children. TRIAL REGISTRATION: Clinical Trial Registry: ClinicalTrials.gov: NCT00296842

Predation by Bears Drives Senescence in Natural Populations of Salmon

Classic evolutionary theory predicts that populations experiencing higher rates of environmentally caused (“extrinsic”) mortality should senesce more rapidly, but this theory usually neglects plausible relationships between an individual's senescent condition and its susceptibility to extrinsic mortality. We tested for the evolutionary importance of this condition dependence by comparing senescence rates among natural populations of sockeye salmon (Oncorhynchus nerka) subject to varying degrees of predation by brown bears (Ursus arctos). We related senescence rates in six populations to (1) the overall rate of extrinsic mortality, and (2) the degree of condition dependence in this mortality. Senescence rates were determined by modeling the mortality of individually-tagged breeding salmon at each site. The overall rate of extrinsic mortality was estimated as the long-term average of the annual percentage of salmon killed by bears. The degree of condition dependence was estimated as the extent to which bears killed salmon that exhibited varying degrees of senescence. We found that the degree of condition dependence in extrinsic mortality was very important in driving senescence: populations where bears selectively killed fish showing advanced senescence were those that senesced least rapidly. The overall rate of extrinsic mortality also contributed to among-population variation in senescence-but to a lesser extent. Condition-dependent susceptibility to extrinsic mortality should be incorporated more often into theoretical models and should be explicitly tested in natural populations

Assessing smoking status in disadvantaged populations: is computer administered self report an accurate and acceptable measure?

Background: Self report of smoking status is potentially unreliable in certain situations and in high-risk populations. This study aimed to determine the accuracy and acceptability of computer administered self-report of smoking status among a low socioeconomic (SES) population. Methods: Clients attending a community service organisation for welfare support were invited to complete a cross-sectional touch screen computer health survey. Following survey completion, participants were invited to provide a breath sample to measure exposure to tobacco smoke in expired air. Sensitivity, specificity, positive predictive value and negative predictive value were calculated. Results: Three hundred and eighty three participants completed the health survey, and 330 (86%) provided a breath sample. Of participants included in the validation analysis, 59% reported being a daily or occasional smoker. Sensitivity was 94.4% and specificity 92.8%. The positive and negative predictive values were 94.9% and 92.0% respectively. The majority of participants reported that the touch screen survey was both enjoyable (79%) and easy (88%) to complete. Conclusions: Computer administered self report is both acceptable and accurate as a method of assessing smoking status among low SES smokers in a community setting. Routine collection of health information using touch-screen computer has the potential to identify smokers and increase provision of support and referral in the community setting

Phylogenetic Beta Diversity Metrics, Trait Evolution and Inferring the Functional Beta Diversity of Communities

The beta diversity of communities along gradients has fascinated ecologists for decades. Traditionally such studies have focused on the species composition of communities, but researchers are becoming increasingly interested in analyzing the phylogenetic composition in the hope of achieving mechanistic insights into community structure. To date many metrics of phylogenetic beta diversity have been published, but few empirical studies have been published. Further inferences made from such phylogenetic studies critically rely on the pattern of trait evolution. The present work provides a study of the phylogenetic dissimilarity of 96 tree communities in India. The work compares and contrasts eight metrics of phylogenetic dissimilarity, considers the role of phylogenetic signal in trait data and shows that environmental distance rather than spatial distance is the best correlate of phylogenetic dissimilarity in the study system

Quantum adiabatic machine learning

We develop an approach to machine learning and anomaly detection via quantum adiabatic evolution. In the training phase we identify an optimal set of weak classifiers, to form a single strong classifier. In the testing phase we adiabatically evolve one or more strong classifiers on a superposition of inputs in order to find certain anomalous elements in the classification space. Both the training and testing phases are executed via quantum adiabatic evolution. We apply and illustrate this approach in detail to the problem of software verification and validation.Comment: 21 pages, 9 figure

A Simple but Highly Effective Approach to Evaluate the Prognostic Performance of Gene Expression Signatures

BACKGROUND: Highly parallel analysis of gene expression has recently been used to identify gene sets or 'signatures' to improve patient diagnosis and risk stratification. Once a signature is generated, traditional statistical testing is used to evaluate its prognostic performance. However, due to the dimensionality of microarrays, this can lead to false interpretation of these signatures. PRINCIPAL FINDINGS: A method was developed to test batches of a user-specified number of randomly chosen signatures in patient microarray datasets. The percentage of random generated signatures yielding prognostic value was assessed using ROC analysis by calculating the area under the curve (AUC) in six public available cancer patient microarray datasets. We found that a signature consisting of randomly selected genes has an average 10% chance of reaching significance when assessed in a single dataset, but can range from 1% to ∼40% depending on the dataset in question. Increasing the number of validation datasets markedly reduces this number. CONCLUSIONS: We have shown that the use of an arbitrary cut-off value for evaluation of signature significance is not suitable for this type of research, but should be defined for each dataset separately. Our method can be used to establish and evaluate signature performance of any derived gene signature in a dataset by comparing its performance to thousands of randomly generated signatures. It will be of most interest for cases where few data are available and testing in multiple datasets is limited

ETS Transcription Factors Control Transcription of EZH2 and Epigenetic Silencing of the Tumor Suppressor Gene Nkx3.1 in Prostate Cancer

ETS transcription factors regulate important signaling pathways involved in cell differentiation and development in many tissues and have emerged as important players in prostate cancer. However, the biological impact of ETS factors in prostate tumorigenesis is still debated.We performed an analysis of the ETS gene family using microarray data and real-time PCR in normal and tumor tissues along with functional studies in normal and cancer cell lines to understand the impact in prostate tumorigenesis and identify key targets of these transcription factors. We found frequent dysregulation of ETS genes with oncogenic (i.e., ERG and ESE1) and tumor suppressor (i.e., ESE3) properties in prostate tumors compared to normal prostate. Tumor subgroups (i.e., ERG(high), ESE1(high), ESE3(low) and NoETS tumors) were identified on the basis of their ETS expression status and showed distinct transcriptional and biological features. ERG(high) and ESE3(low) tumors had the most robust gene signatures with both distinct and overlapping features. Integrating genomic data with functional studies in multiple cell lines, we demonstrated that ERG and ESE3 controlled in opposite direction transcription of the Polycomb Group protein EZH2, a key gene in development, differentiation, stem cell biology and tumorigenesis. We further demonstrated that the prostate-specific tumor suppressor gene Nkx3.1 was controlled by ERG and ESE3 both directly and through induction of EZH2.These findings provide new insights into the role of the ETS transcriptional network in prostate tumorigenesis and uncover previously unrecognized links between aberrant expression of ETS factors, deregulation of epigenetic effectors and silencing of tumor suppressor genes. The link between aberrant ETS activity and epigenetic gene silencing may be relevant for the clinical management of prostate cancer and design of new therapeutic strategies

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente