Codon usage bias and the evolution of influenza A viruses. Codon Usage Biases of Influenza Virus

<p>Abstract</p> <p>Background</p> <p>The influenza A virus is an important infectious cause of morbidity and mortality in humans and was responsible for 3 pandemics in the 20^thcentury. As the replication of the influenza virus is based on its host's machinery, codon usage of its viral genes might be subject to host selection pressures, especially after interspecies transmission. A better understanding of viral evolution and host adaptive responses might help control this disease.</p> <p>Results</p> <p>Relative Synonymous Codon Usage (RSCU) values of the genes from segment 1 to segment 6 of avian and human influenza viruses, including pandemic H1N1, were studied via Correspondence Analysis (CA). The codon usage patterns of seasonal human influenza viruses were distinct among their subtypes and different from those of avian viruses. Newly isolated viruses could be added to the CA results, creating a tool to investigate the host origin and evolution of viral genes. It was found that the 1918 pandemic H1N1 virus contained genes with mammalian-like viral codon usage patterns, indicating that the introduction of this virus to humans was not through <it>in toto </it>transfer of an avian influenza virus.</p> <p>Many human viral genes had directional changes in codon usage over time of viral isolation, indicating the effect of host selection pressures. These changes reduced the overall GC content and the usage of G at the third codon position in the viral genome. Limited evidence of translational selection pressure was found in a few viral genes.</p> <p>Conclusions</p> <p>Codon usage patterns from CA allowed identification of host origin and evolutionary trends in influenza viruses, providing an alternative method and a tool to understand the evolution of influenza viruses. Human influenza viruses are subject to selection pressure on codon usage which might assist in understanding the characteristics of newly emerging viruses.</p

Developing an online learning community for mental health professionals and service users: a discursive analysis

<p>Abstract</p> <p>Background</p> <p>There is increasing interest in online collaborative learning tools in health education, to reduce costs, and to offer alternative communication opportunities. Patients and students often have extensive experience of using the Internet for health information and support, and many health organisations are increasingly trying out online tools, while many healthcare professionals are unused to, and have reservations about, online interaction.</p> <p>Methods</p> <p>We ran three week-long collaborative learning courses, in which 19 mental health professionals (MHPs) and 12 mental health service users (MHSUs) participated. Data were analysed using a discursive approach to consider the ways in which participants interacted, and how this contributed to the goal of online learning about using Internet technologies for mental health practice.</p> <p>Results</p> <p>MHSUs and MHPs were able to discuss issues together, listening to the views of the other stakeholders. Discussions on synchronous format encouraged participation by service users while the MHPs showed a preference for an asynchronous format with longer, reasoned postings. Although participants regularly drew on their MHP or MHSU status in discussions, and participants typically drew on either a medical expert discourse or a "lived experience" discourse, there was a blurred boundary as participants shifted between these positions.</p> <p>Conclusions</p> <p>The anonymous format was successful in that it produced a "co-constructed asymmetry" which permitted the MHPs and MHSUs to discuss issues online, listening to the views of other stakeholders. Although anonymity was essential for this course to 'work' at all, the recourse to expert or lay discourses demonstrates that it did not eliminate the hierarchies between teacher and learner, or MHP and MHSU. The mix of synchronous and asynchronous formats helped MHSUs to contribute. Moderators might best facilitate service user experience by responding within an experiential discourse rather than an academic one.</p

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Publisher Correction: Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

This corrects the article DOI: 10.1038/ncomms5999

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc

Novel insight into the genetic basis of high-altitude pulmonary hypertension in Kyrgyz highlanders

The Central Asian Kyrgyz highland population provides a unique opportunity to address genetic diversity and understand the genetic mechanisms underlying high-altitude pulmonary hypertension (HAPH). Although a significant fraction of the population is unaffected, there are susceptible individuals who display HAPH in the absence of any lung, cardiac or hematologic disease. We report herein the analysis of the whole-genome sequencing of healthy individuals compared with HAPH patients and other controls (total n = 33). Genome scans reveal selection signals in various regions, encompassing multiple genes from the first whole-genome sequences focusing on HAPH. We show here evidence of three candidate genes MTMR4, TMOD3 and VCAM1 that are functionally associated with well-known molecular and pathophysiological processes and which likely lead to HAPH in this population. These processes are (a) dysfunctional BMP signaling, (b) disrupted tissue repair processes and (c) abnormal endothelial cell function. Whole-genome sequence of well-characterized patients and controls and using multiple statistical tools uncovered novel candidate genes that belong to pathways central to the pathogenesis of HAPH. These studies on high-altitude human populations are pertinent to the understanding of sea level diseases involving hypoxia as a main element of their pathophysiology