Detection of a MicroRNA Signal in an In Vivo Expression Set of mRNAs

Background. microRNAs (miRNAs) are approximately 21 nucleotide non-coding transcripts capable of regulating gene expression. The most widely studied mechanism of regulation involves binding of a miRNA to the target mRNA. As a result, translation of the target mRNA is inhibited and the mRNA may be destabilized. The inhibitory effects of miRNAs have been linked to diverse cellular processes including malignant proliferation, apoptosis, development, differentiation, and metabolic processes. We asked whether endogenous fluctuations in a set of mRNA and miRNA profiles contain correlated changes that are statistically distinguishable from the many other fluctuations in the data set. Methodology/Principal Findings. RNA was extracted from 12 human primary brain tumor biopsies. These samples were used to determine genome-wide mRN

LEARN: A multi-centre, cross-sectional evaluation of Urology teaching in UK medical schools

OBJECTIVE: To evaluate the status of UK undergraduate urology teaching against the British Association of Urological Surgeons (BAUS) Undergraduate Syllabus for Urology. Secondary objectives included evaluating the type and quantity of teaching provided, the reported performance rate of General Medical Council (GMC)-mandated urological procedures, and the proportion of undergraduates considering urology as a career. MATERIALS AND METHODS: LEARN was a national multicentre cross-sectional study. Year 2 to Year 5 medical students and FY1 doctors were invited to complete a survey between 3rd October and 20th December 2020, retrospectively assessing the urology teaching received to date. Results are reported according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). RESULTS: 7,063/8,346 (84.6%) responses from all 39 UK medical schools were included; 1,127/7,063 (16.0%) were from Foundation Year (FY) 1 doctors, who reported that the most frequently taught topics in undergraduate training were on urinary tract infection (96.5%), acute kidney injury (95.9%) and haematuria (94.4%). The most infrequently taught topics were male urinary incontinence (59.4%), male infertility (52.4%) and erectile dysfunction (43.8%). Male and female catheterisation on patients as undergraduates was performed by 92.1% and 73.0% of FY1 doctors respectively, and 16.9% had considered a career in urology. Theory based teaching was mainly prevalent in the early years of medical school, with clinical skills teaching, and clinical placements in the later years of medical school. 20.1% of FY1 doctors reported no undergraduate clinical attachment in urology. CONCLUSION: LEARN is the largest ever evaluation of undergraduate urology teaching. In the UK, teaching seemed satisfactory as evaluated by the BAUS undergraduate syllabus. However, many students report having no clinical attachments in Urology and some newly qualified doctors report never having inserted a catheter, which is a GMC mandated requirement. We recommend a greater emphasis on undergraduate clinical exposure to urology and stricter adherence to GMC mandated procedures

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Afterword: three letters

The essays consider issues of affect and emotion in terms of three early English letters - by Chaucer, the Paston family, and Henry VIII - in order to consider issues of the personal and the literary. It also comments on the volume of essays as a whole, and consider the field of the history of emotions and affect studies

Genera Palmarum - The Evolution and Classification of the Palms

Since the publication of the first edition of Genera Palmarum in 1987, there has been an explosion of interest in this quintessentially tropical flowering plant family. Palms tend to attract attention, perhaps because of their recognisable rather simple growth form, their ecological and economic importance, or indeed simply because of their association with the exotic. The numerous biological intrigues within the family explain the abundance of palm research across the world, as demonstrated by the vast body of palm literature published since 1987 that is listed in the bibliography of this book. Genera Palmarum Edition 1 provided the basic taxonomic framework on which such palm studies could be based. Over the same period, worldwide interest in the cultivation of palms has also increased dramatically, and the range of species now available to the amateur grower is truly astonishing. In the past twenty years, there have been major advances in our understanding of the palm family. New exploration, particularly in Madagascar and the West Pacific, has uncovered remarkable new genera, even at the very moment that the manuscript of this new edition was completed in April 2007. Moreover, several genera that were known only from fragmentary type material have been rediscovered. Exploration throughout the tropics has provided new observations that have allowed detailed reassessment of genera. At the same time a vast new range of phylogenetically informative characters has become available, principally through analysis of DNA. Despite some challenging properties inherent within palm genomes, a substantial body of literature has been amassed since the publication of the first molecular phylogenetic study of palms in 1995. More than any other source, these molecular characters have allowed us to gain a thorough understanding of palm phylogenetics and to obtain sometimes dramatic new insights into both relationships and morphology. The first edition of Genera Palmarum, which was based on painstaking comparison across the family, provided a hypothesis of relationships that has now been comprehensively tested using the most up-to-date tools and methods. The new classification that we present here provides confirmation of some of the groupings recognised in the first edition, but has also revealed substantial differences and at times quite surprising discrepancies when compared with previous classifications. This new edition of Genera Palmarum is more than just a revision of the first edition. In almost every respect, it is an entirely new book. The taxonomic core of the book, namely the generic descriptions have been extensively rewritten, restructured and augmented. All other content, the notes associated with each genus, the introductory chapters and so on, have been written de novo. We have amassed the most extensive and complete selection of palm images ever published, thanks to the generosity of many contributors; only a few of these featured in the first edition. Even the illustrations have been revised, with some errors corrected and new genera illustrated by Lucy T. Smith in the characteristic style of Marion Ruff Sheehan. The team for this new Genera Palmarum came together for the first time at a meeting held at the Montgomery Botanical Center on 17 January 2003, the details of the phylogenetic classification were thrashed out at a week long summit held in the L.H. Bailey Hortorium in early June 2004. Responsibilities for each part of the book were shared out among the authors as follows. JD took on the revision of the taxonomy, descriptions and keys. He also contributed many of the notes and introductory chapters (Natural History and Conservation and the introduction to the Classification of Palms) and supplementary materials, such as the geographical listings and the literature cited. NWU supported JD closely in this commitment, and took the lead on the rewriting of Chapter 1, The Structure of Palms, with collaboration from JD and WJB. MMH contributed all chapters, notes and descriptive information on pollen and fossils. WJB wrote the introductory chapters on Chromosomes and Cytogenetics, Phylogeny and Evolution (with CBA-L) and Biogeography. CBA-L, WJB and CEL together prepared all the phylogenetic notes for the taxonomic accounts. CEL provided the Chemistry chapter and new illustrations for the glossary, which he revised with the other co-authors. JD took on the role of collating the manuscript and co-ordinating with Kew Publishing and co-authors. This new Genera Palmarum will, we hope, provide a robust framework for the studies of the palm family for many years to come. There are still areas of uncertainty, but we believe that the higher-level classification of subfamilies, tribes and subtribes is largely robust and unlikely to require substantial change. Uncertainties in inter-generic relationships and generic circumscription remain, and the field of species-level phylogenetics remains wide open. We hope that our work has the same invigorating affect that the first edition of Genera Palmarum appeared to have and look forward to reflecting, in another two decades, on the triumphs of a new generation of palm biologists