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Considering the public opinion, managing an intolerable risk through risk mitigation by remediation alone is likely insufficient in many cases. A viable strategy would offer a range of social support options that enable individual decision-making and the protection of risk groups.The actin cytoskeleton plays a central role in establishing cell polarity and shape during embryonic morphogenesis. Daam1, a member of the Formin family of actin cytoskeleton regulators, is a Dvl2-binding protein that functions in the Wnt/Planar Cell Polarity (PCP) pathway. To examine the role of the Daam proteins in mammalian development, we generated Daam-deficient mice by gene targeting and found that Daam1, but not Daam2, is necessary for fetal survival. Embryonic development of Daam1 mutants was delayed most likely due to functional defects in the labyrinthine layer of the placenta. Examination of Daam2 and Daam1/2 double mutants revealed that Daam1 and Daam2 are functionally redundant during placental development. Of note, neural tube closure defects (NTD), which are observed in several mammalian PCP mutants, are not observed in Wnt5a or Daam1 single mutants, but arise in Daam1;Wnt5a double mutants. These findings demonstrate a unique function for Daam genes in placental development and are consistent with a role for Daam1 in the Wnt/PCP pathway in mammals.Non-melanoma skin cancer (NMSC) has a high and increasing incidence all over the world. Solar radiation is the main aetiology for humans. Although most research into photocarcinogenesis uses UVB as a source of radiation, UVA is also carcinogenic in long term. Pomegranate (PGE) and cocoa (CE) extracts have been used for medicinal purposes for time immemorial. Recently, it has been claimed that some of their properties may be an effective preventative measure against photocarcinogenesis and photoaging, but to date in vivo models have not been tested using RUVA, the objective of the present work. A lower incidence of lesions was observed in SKH-1 mice treated with PGE (p less then 0.001), and lower incidence of invasive squamous carcinoma in both treatment groups (p less then 0.001 for PGE and p less then 0.05 for CE); the PGE group also showed a lower level of cell proliferation than the control group (p less then 0.001). Significantly greater p53 alteration was observed in the control group than the treatment groups (p less then 0.001 for PGE and p = 0.05 for CE). No significant differences were found in relation to TIMP-1 and MMP-9. Taken together, the results suggest that oral feeding of PGE and CE to SKH-1 mice affords substantial protection against the adverse effects of RUVA, especially PGE.BACKGROUND Energy drinks (ED) are caffeine- and sugar-rich beverages with other ingredients that are marketed for their energy-boosting and performance-enhancing effects. The consumption of these drinks, with and without alcohol, is dramatically increasing worldwide, despite the reported side effects and potential harms to consumers. Few studies, to date, have explored the perceptions and experiences of young adults towards these beverages. OBJECTIVE The present study aimed to explore the consumption patterns and correlates of ED consumption, as well as the perceptions and experiences of university students in Lebanon towards these beverages. METHODS A sequential explanatory mixed-methods approach was adopted. Data collection was conducted in two private universities in Beirut, Lebanon. A self-administered 36-item quantitative survey was first used to explore the prevalence and correlates of ED consumption among a convenience sample of university students (n = 226). The survey included questions related to sosales and marketing of these beverages, especially among young consumers.We examined seventy million well-characterized human mutations, and their impact on G+C-compositional dynamics, in order to understand the formation and maintenance of major genomic nucleotide sequence patterns. Among novel mutations, those that change a strong (S) base pair GC/CG to a weak (W) pair AT/TA occur at nearly twice the frequency of the opposite mutations. Such imbalance puts strong downward pressure on overall GC-content. However, along protracted paths to fixation, S→W mutations are much less likely to propagate than W→S mutations. The magnitude of relative propagation disadvantages for S→W mutations is inexplicable by any currently-accepted model. This fact forced us to re-examine the quantitative features of Biased Gene Conversion (BGC) theory. Revised parameters of BGC that, per average individual, convert 7-14 W base pairs into S pairs, would account for the S-content turnover differences between new and old mutations, and make BGC an instrumental force for nucleotide dynamics and evolution. om mutational degradation or fail to degrade such inhomogeneities in specific chromosomal regions.Benchmarking RNA-seq differential expression analysis methods using spike-in and simulated RNA-seq data has often yielded inconsistent results. The spike-in data, which were generated from the same bulk RNA sample, only represent technical variability, making the test results less reliable. We compared the performance of 12 differential expression analysis methods for RNA-seq data, including recent variants in widely used software packages, using both RNA spike-in and simulation data for negative binomial (NB) model. Performance of edgeR, DESeq2, and ROTS was particularly different between the two benchmark tests. Then, each method was tested under most extensive simulation conditions especially demonstrating the large impacts of proportion, dispersion, and balance of differentially expressed (DE) genes. DESeq2, a robust version of edgeR (edgeR.rb), voom with TMM normalization (voom.tmm) and sample weights (voom.sw) showed an overall good performance regardless of presence of outliers and proportion of DE genes. The performance of RNA-seq DE gene analysis methods substantially depended on the benchmark used. Based on the simulation results, suitable methods were suggested under various test conditions.Terpenes are the largest class of natural products with extensive structural diversity and are widely used as pharmaceuticals, herbicides, flavourings, fragrances, and biofuels. While they have mostly been isolated from plants and fungi, the availability and analysis of bacterial genome sequence data indicates that bacteria also possess many putative terpene synthase genes. In this study, we further explore this potential for terpene synthase activity in bacteria. Twenty two potential class I terpene synthase genes (TSs) were selected to represent the full sequence diversity of bacterial synthase candidates and recombinantly expressed in E. coli. Terpene synthase activity was detected for 15 of these enzymes, and included mono-, sesqui- and diterpene synthase activities. A number of confirmed sesquiterpene synthases also exhibited promiscuous monoterpene synthase activity, suggesting that bacteria are potentially a richer source of monoterpene synthase activity then previously assumed. Several terpenoid products not previously detected in bacteria were identified, including aromandendrene, acora-3,7(14)-diene and longiborneol. Overall, we have identified promiscuous terpene synthases in bacteria and demonstrated that terpene synthases with substrate promiscuity are widely distributed in nature, forming a rich resource for engineering terpene biosynthetic pathways for biotechnology.Approximately one fourth of the Earth's Northern Hemisphere is underlain by permafrost, earth materials (soil, organic matter, or bedrock), that has been continuously frozen for at least two consecutive years. Numerous studies point to evidence of accelerated climate warming in the Arctic and sub-Arctic where permafrost is located. Changes to permafrost biochemical processes may critically impact ecosystem processes at the landscape scale. Here, we sought to understand how the permafrost metabolome responds to thaw and how this response differs based on location (i.e. chronosequence of permafrost formation constituting diverse permafrost types). We analyzed metabolites from microbial cells originating from Alaskan permafrost. Overall, permafrost thaw induced a shift in microbial metabolic processes. Of note were the dissimilarities in biochemical structure between frozen and thawed samples. The thawed permafrost metabolomes from different locations were highly similar. In the intact permafrost, several metabolites with antagonist properties were identified, illustrating the competitive survival strategy required to survive a frozen state. Interestingly, the intensity of these antagonistic metabolites decreased with warmer temperature, indicating a shift in ecological strategies in thawed permafrost. These findings illustrate the impact of change in temperature and spatial variability as permafrost undergoes thaw, knowledge that will become crucial for predicting permafrost biogeochemical dynamics as the Arctic and Antarctic landscapes continue to warm.OBJECTIVE The World Health Organization created the Severe Acute Respiratory Infection (SARI) criteria in 2011 to monitor influenza (flu)-related hospitalization. [https://www.selleckchem.com/products/imidazole-ketone-erastin.html Imidazole ketone erastin concentration] Many studies have since used the SARI case definition as inclusion criteria for surveillance studies. We sought to determine the sensitivity, specificity, positive predictive value, and negative predictive value of the SARI criteria for detecting ten different respiratory viruses in a Middle Eastern pediatric cohort. MATERIALS AND METHODS The data for this study comes from a prospective acute respiratory surveillance study of hospitalized children less then 2 years in Amman, Jordan from March 16, 2010 to March 31, 2013. Participants were recruited if they had a fever and/or respiratory symptoms. Nasal and throat swabs were obtained and tested by real-time RT-PCR for eleven viruses. Subjects meeting SARI criteria were determined post-hoc. Sensitivity, specificity, positive predictive value, and negative predictive value of the SARI case definition for detecting ten different viruses were calculated and results were stratified by age. RESULTS Of the 3,175 patients enrolled, 3,164 were eligible for this study, with a median age of 3.5 months, 60.4% male, and 82% virus-positive (44% RSV and 3.8% flu). The sensitivity and specificity of the SARI criteria for detecting virus-positive patients were 44% and 77.9%, respectively. Sensitivity of SARI criteria for any virus was lowest in children less then 3 months at 22.4%. Removing fever as a criterion improved the sensitivity by 65.3% for detecting RSV in children less then 3 months; whereas when cough was removed, the sensitivity improved by 45.5% for detecting flu in same age group. CONCLUSIONS The SARI criteria have poor sensitivity for detecting RSV, flu, and other respiratory viruses-particularly in children less then 3 months. Researchers and policy makers should use caution if using the criteria to estimate burden of disease in children.BACKGROUND Post-traumatic stress disorder (PTSD) is a severe and disabling condition that may lead to functional impairment and reduced productivity. Psychological interventions have been shown to be effective in its management. The objective of this study was to assess the cost-effectiveness of a range of interventions for adults with PTSD. METHODS A decision-analytic model was constructed to compare costs and quality-adjusted life-years (QALYs) of 10 interventions and no treatment for adults with PTSD, from the perspective of the National Health Service and personal social services in England. Effectiveness data were derived from a systematic review and network meta-analysis. Other model input parameters were based on published sources, supplemented by expert opinion. RESULTS Eye movement desensitisation and reprocessing (EMDR) appeared to be the most cost-effective intervention for adults with PTSD (with a probability of 0.34 amongst the 11 evaluated options at a cost-effectiveness threshold of £20,000/QALY), followed by combined somatic/cognitive therapies, self-help with support, psychoeducation, selective serotonin reuptake inhibitors (SSRIs), trauma-focused cognitive behavioural therapy (TF-CBT), self-help without support, non-TF-CBT and combined TF-CBT/SSRIs.