Project description:Since it was launched in 2006, PLOS ONE has published over fifty articles illustrating the many facets of the emerging field of synthetic biology. This article reviews these publications by organizing them into broad categories focused on DNA synthesis and assembly techniques, the development of libraries of biological parts, the use of synthetic biology in protein engineering applications, and the engineering of gene regulatory networks and metabolic pathways. Finally, we review articles that describe enabling technologies such as software and modeling, along with new instrumentation. In order to increase the visibility of this body of work, the papers have been assembled into the PLOS ONE Synthetic Biology Collection (www.ploscollections.org/synbio). Many of the innovative features of the PLOS ONE web site will help make this collection a resource that will support a lively dialogue between readers and authors of PLOS ONE synthetic biology papers. The content of the collection will be updated periodically by including relevant articles as they are published by the journal. Thus, we hope that this collection will continue to meet the publishing needs of the synthetic biology community.
Project description:The burden that Parkinson's disease (PD) exacts on the population continues to increase year after year. Though refinement of symptomatic treatments continues at a reasonable pace, no accepted therapies are available to slow or prevent disease progression. The leucine-rich repeat kinase 2 (LRRK2) gene was identified in PD genetic studies and offers new hope for novel therapeutic approaches. The evidence linking LRRK2 kinase activity to PD susceptibility is presented, as well as seminal discoveries relevant to the prosecution of LRRK2 kinase inhibition. Finally, suggestions are made for predictive preclinical modeling and successful first-in-human trials.
Project description:BackgroundThere is little research on the long-term outcomes of open carpal tunnel release. The purpose of this retrospective study was to determine the functional and symptomatic outcomes of patients at a minimum of ten years postoperatively.MethodsTwo hundred and eleven patients underwent open carpal tunnel release from 1996 to 2000 performed by the same hand fellowship-trained surgeon. Follow-up with validated self-administered questionnaire instruments was conducted an average of thirteen years after surgery. The principal outcomes included the Levine-Katz symptom and function scores, ranging from 1 point (best) to 5 points (worst), and satisfaction with the results of surgery. The patients self-reported current comorbidities.ResultsAfter a mean follow-up of thirteen years (range, eleven to seventeen years), 92% (194) of 211 patients were located. They included 140 who were still living and fifty-four who had died. Seventy-two percent (113) of the 157 located, surviving patients responded to the questionnaire. The mean Levine-Katz symptom score (and standard deviation) was 1.3 ± 0.5 points, and 13% of patients had a poor symptom score (≥2 points). The mean Levine-Katz function score was 1.6 ± 0.8 points, and 26% had a poor function score (≥2 points). The most common symptom-related complaint was weakness in the hand, followed by diurnal pain, numbness, and tingling. The least common symptoms were nocturnal pain and tenderness at the incision. Eighty-eight percent of the patients were either completely satisfied or very satisfied with the surgery. Seventy-four percent reported their symptoms to be completely resolved. Thirty-three percent of men were classified as having poor function compared with 23% of women. Two (1.8%) of 113 patients underwent repeat surgery.ConclusionsAt an average of thirteen years after open carpal tunnel release, the majority of patients are satisfied and free of symptoms of carpal tunnel syndrome.
Project description:Open peer review (OPR), as with other elements of open science and open research, is on the rise. It aims to bring greater transparency and participation to formal and informal peer review processes. But what is meant by `open peer review', and what advantages and disadvantages does it have over standard forms of review? How do authors or reviewers approach OPR? And what pitfalls and opportunities should you look out for? Here, we propose ten considerations for OPR, drawing on discussions with authors, reviewers, editors, publishers and librarians, and provide a pragmatic, hands-on introduction to these issues. We cover basic principles and summarise best practices, indicating how to use OPR to achieve best value and mutual benefits for all stakeholders and the wider research community.
Project description:It is now becoming generally accepted that a significant amount of human genetic variation is due to structural changes of the genome rather than to base-pair changes in the DNA. As for base-pair changes, knowledge of gene and genome function has been informed by structural alterations that convey clinical phenotypes. Genomic disorders are a class of human conditions that result from structural changes of the human genome that convey traits or susceptibility to traits. The path to the delineation of genomic disorders is intertwined with the evolving technologies that have enabled the resolution of human genome analyses to continue increasing. Similarly, the ability to perform high-resolution human genome analysis has fueled the current and future clinical implementation of such discoveries in the evolving field of genome medicine.
Project description:AoB PLANTS is a not-for-profit, open access, plant science journal and one of three peer-reviewed journals owned and managed by the Annals of Botany Company. This article explains events and thinking that led to the starting of AoB PLANTS and how the unique features of the Journal came to be formalized prior to its launch in September 2009. The article also describes how the Journal's management developed over the first 10 years and summarizes the Journal's achievements in a decade where open access journals have proliferated despite subscription journals continuing to dominate the publishing of peer-reviewed botanical science.
Project description:AoB PLANTS is a not-for-profit, open access, plant science journal and one of three peer-reviewed journals owned and managed by the Annals of Botany Company. This article explains events and thinking that led to the starting of AoB PLANTS and how the unique features of the Journal came to be formalized prior to its launch in September 2009. The article also describes how the Journal's management developed over the first 10 years and summarizes the Journal's achievements in a decade where open access journals have proliferated despite subscription journals continuing to dominate the publishing of peer-reviewed botanical science.
Project description:The February 2012 issues of GENETICS and G3: Genes, Genomes, Genetics present a collection of articles reporting recent advances from the international Collaborative Cross (CC) project. The goal of the CC project is to develop a new resource that will enhance quantitative trait locus (QTL) and systems genetic analyses in mice. The CC consists of hundreds of independently bred, octo-parental recombinant inbred lines (Figure 1). The work reported in these issues represents progress toward completion of the CC, proof-of-principle experiments using incipient inbred CC mice, and new research areas and complementary resources facilitated by the CC project.
Project description:The two thrombopoietin receptor agonists (TPO-RA), eltrombopag and romiplostim, were licensed in the US for treatment of immune thrombocytopenia (ITP) in 2008 and, since then, their use has progressively increased around the world; they are currently used in more than 100 countries. The six largest randomized controlled trials conducted in ITP have used one of these two agents. All studies have demonstrated a platelet response rate between 50-90%, depending on the criteria used, with good safety and tolerability. TPO-RA were shown to be effective in reducing bleeding and the need for concomitant or rescue medication. Many other investigations of their mechanism of effect, prospective and retrospective trials, and studies focusing on toxicity have been performed widening our knowledge of these two agents. Initial concerns on issues such as myelofibrosis have not been confirmed. Only a small number of patients develop moderate-severe reticulin fibrosis and/or collagen fibrosis; however, these are usually reversed after discontinuation of TPO-RA. Studies indicate, however, that TPO-RA may increase the risk of venous thromboembolism. Both TPO-RA are currently approved in patients with chronic ITP aged >1-year who are refractory to at least one other treatment. Eltrombopag has acquired two additional indications: severe aplastic anemia refractory to first-line treatment and hepatitis C patients undergoing treatment with interferon-ribavirin. Despite these wide-ranging studies, important questions still need to be answered. This summary review on TPO-RA will summarize what is known regarding efficacy in ITP, evaluate safety concerns in more depth, and focus on the questions that remain.
Project description:The horse reference genome from the Thoroughbred mare Twilight has been available for a decade and, together with advances in genomics technologies, has led to unparalleled developments in equine genomics. At the core of this progress is the continuing improvement of the quality, contiguity and completeness of the reference genome, and its functional annotation. Recent achievements include the release of the next version of the reference genome (EquCab3.0) and generation of a reference sequence for the Y chromosome. Horse satellite-free centromeres provide unique models for mammalian centromere research. Despite extremely low genetic diversity of the Y chromosome, it has been possible to trace patrilines of breeds and pedigrees and show that Y variation was lost in the past approximately 2300 years owing to selective breeding. The high-quality reference genome has led to the development of three different SNP arrays and WGSs of almost 2000 modern individual horses. The collection of WGS of hundreds of ancient horses is unique and not available for any other domestic species. These tools and resources have led to global population studies dissecting the natural history of the species and genetic makeup and ancestry of modern breeds. Most importantly, the available tools and resources, together with the discovery of functional elements, are dissecting molecular causes of a growing number of Mendelian and complex traits. The improved understanding of molecular underpinnings of various traits continues to benefit the health and performance of the horse whereas also serving as a model for complex disease across species.