Evidence for a nuclear compartment of transcription and splicing located at chromosome domain boundaries

The nuclear topography of splicing snRNPs, mRNA transcripts and chromosome domains in various mammalian cell types are described. The visualization of splicing snRNPs, defined by the Sm antigen, and coiled bodies, revealed distinctly different distribution patterns in these cell types. Heat shock experiments confirmed that the distribution patterns also depend on physiological parameters. Using a combination of fluorescencein situ hybridization and immunodetection protocols, individual chromosome domains were visualized simultaneously with the Sm antigen or the transcript of an integrated human papilloma virus genome. Three-dimensional analysis of fluorescence-stained target regions was performed by confocal laser scanning microscopy. RNA transcripts and components of the splicing machinery were found to be generally excluded from the interior of the territories occupied by the individual chromosomes. Based on these findings we present a model for the functional compartmentalization of the cell nucleus. According to this model the space between chromosome domains, including the surface areas of these domains, defines a three-dimensional network-like compartment, termed the interchromosome domain (ICD) compartment, in which transcription and splicing of mRNA occurs

Diversity and linkage disequilibrium analysis within a selected set of cultivated tomatoes

Within the Dutch genomics initiative the “Centre for Biosystems Genomics” (CBSG) a major research effort is directed at the identification and unraveling of processes and mechanisms affecting fruit quality in tomato. The basis of this fruit quality program was a diverse set of 94 cultivated tomato cultivars, representing a wide spectrum of phenotypes for quality related traits. This paper describes a diversity study performed on these cultivars, using information of 882 AFLP markers, of which 304 markers had a known map position. The AFLP markers were scored as much as possible in a co-dominant fashion. We investigated genome distribution and coverage for the mapped markers and conclude that it proved difficult to arrive at a dense and uniformly distributed coverage of the genome with markers. Mapped markers and unmapped markers were used to investigate population structure. A clear substructure was observed which seemed to coincide with a grouping based on fruit size. Finally, we studied amount and decay of linkage disequilibrium (LD) along the chromosomes. LD was observed over considerable (genetic) distances. We discuss the feasibility of marker-trait association studies and conclude that the amount of genetic variation in our set of cultivars is limited, but that there exists scope for association studies

Magnetic Coupling in the Quiet Solar Atmosphere

Three kinds of magnetic couplings in the quiet solar atmosphere are highlighted and discussed, all fundamentally connected to the Lorentz force. First the coupling of the convecting and overshooting fluid in the surface layers of the Sun with the magnetic field. Here, the plasma motion provides the dominant force, which shapes the magnetic field and drives the surface dynamo. Progress in the understanding of the horizontal magnetic field is summarized and discussed. Second, the coupling between acoustic waves and the magnetic field, in particular the phenomenon of wave conversion and wave refraction. It is described how measurements of wave travel times in the atmosphere can provide information about the topography of the wave conversion zone, i.e., the surface of equal Alfv\'en and sound speed. In quiet regions, this surface separates a highly dynamic magnetic field with fast moving magnetosonic waves and shocks around and above it from the more slowly evolving field of high-beta plasma below it. Third, the magnetic field also couples to the radiation field, which leads to radiative flux channeling and increased anisotropy in the radiation field. It is shown how faculae can be understood in terms of this effect. The article starts with an introduction to the magnetic field of the quiet Sun in the light of new results from the Hinode space observatory and with a brief survey of measurements of the turbulent magnetic field with the help of the Hanle effect.Comment: To appear in "Magnetic Coupling between the Interior and the Atmosphere of the Sun", eds. S.S. Hasan and R.J. Rutten, Astrophysics and Space Science Proceedings, Springer-Verlag, Heidelberg, Berlin, 200

Variation in antibiotic prescription rates in febrile children presenting to emergency departments across Europe (MOFICHE) : A multicentre observational study

Funding Information: This project has received funding from the European Union?s Horizon 2020 research and innovation programme under grant agreement No. 668303. The Research was supported by the National Institute for Health Research Biomedical Research Centres at Imperial College London, Newcastle Hospitals NHS Foundation Trust and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. For the remaining authors no sources of funding were declared. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We acknowledge all research nurses for their help in collecting data, and Anda Nagle (Riga) and the Institute of Microbiology at University Medical Centre Ljubljana for their help in collecting data on antimicrobial resistance. Members of the PERFORM consortium are listed in S11 Text. Publisher Copyright: Copyright: © 2020 Hagedoorn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background The prescription rate of antibiotics is high for febrile children visiting the emergency department (ED), contributing to antimicrobial resistance. Large studies at European EDs covering diversity in antibiotic and broad-spectrum prescriptions in all febrile children are lacking. A better understanding of variability in antibiotic prescriptions in EDs and its relation with viral or bacterial disease is essential for the development and implementation of interventions to optimise antibiotic use. As part of the PERFORM (Personalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union) project, the MOFICHE (Management and Outcome of Fever in Children in Europe) study aims to investigate variation and appropriateness of antibiotic prescription in febrile children visiting EDs in Europe. Methods and findings Between January 2017 and April 2018, data were prospectively collected on febrile children aged 0–18 years presenting to 12 EDs in 8 European countries (Austria, Germany, Greece, Latvia, the Netherlands [n = 3], Spain, Slovenia, United Kingdom [n = 3]). These EDs were based in university hospitals (n = 9) or large teaching hospitals (n = 3). Main outcomes were (1) antibiotic prescription rate; (2) the proportion of antibiotics that were broad-spectrum antibiotics; (3) the proportion of antibiotics of appropriate indication (presumed bacterial), inappropriate indication (presumed viral), or inconclusive indication (unknown bacterial/viral or other); (4) the proportion of oral antibiotics of inappropriate duration; and (5) the proportion of antibiotics that were guideline-concordant in uncomplicated urinary and upper and lower respiratory tract infections (RTIs). We determined variation of antibiotic prescription and broad-spectrum prescription by calculating standardised prescription rates using multilevel logistic regression and adjusted for general characteristics (e.g., age, sex, comorbidity, referral), disease severity (e.g., triage level, fever duration, presence of alarming signs), use and result of diagnostics, and focus and cause of infection. In this analysis of 35,650 children (median age 2.8 years, 55% male), overall antibiotic prescription rate was 31.9% (range across EDs: 22.4%–41.6%), and among those prescriptions, the broad-spectrum antibiotic prescription rate was 52.1% (range across EDs: 33.0%–90.3%). After standardisation, differences in antibiotic prescriptions ranged from 0.8 to 1.4, and the ratio between broad-spectrum and narrow-spectrum prescriptions ranged from 0.7 to 1.8 across EDs. Standardised antibiotic prescription rates varied for presumed bacterial infections (0.9 to 1.1), presumed viral infections (0.1 to 3.3), and infections of unknown cause (0.1 to 1.8). In all febrile children, antibiotic prescriptions were appropriate in 65.0% of prescriptions, inappropriate in 12.5% (range across EDs: 0.6%–29.3%), and inconclusive in 22.5% (range across EDs: 0.4%–60.8%). Prescriptions were of inappropriate duration in 20% of oral prescriptions (range across EDs: 4.4%–59.0%). Oral prescriptions were not concordant with the local guideline in 22.3% (range across EDs: 11.8%–47.3%) of prescriptions in uncomplicated RTIs and in 45.1% (range across EDs: 11.1%–100%) of prescriptions in uncomplicated urinary tract infections. A limitation of our study is that the included EDs are not representative of all febrile children attending EDs in that country. Conclusions In this study, we observed wide variation between European EDs in prescriptions of antibiotics and broad-spectrum antibiotics in febrile children. Overall, one-third of prescriptions were inappropriate or inconclusive, with marked variation between EDs. Until better diagnostics are available to accurately differentiate between bacterial and viral aetiologies, implementation of antimicrobial stewardship guidelines across Europe is necessary to limit antimicrobial resistance.publishersversionPeer reviewe

A qualitative analysis of relatives', health professionals' and service users' views on the involvement in care of relatives in Bipolar Disorder

Background: Relatives of people with bipolar disorder report that services do not meet their own needs, despite clinical recommendations for the development of care plans for relatives, provision of information regarding their statutory entitlements, and formal involvement in decision making meetings. Further, there is now conclusive evidence highlighting the benefits of relatives' involvement in improving outcomes for service users, relatives, and the health system as a whole. This qualitative study explored the views of relatives of people with bipolar disorder, service users and healthcare professionals regarding the barriers and the facilitators to relatives' involvement in care. Methods: Thirty five people were interviewed (12 relatives, 11 service users and 12 healthcare professionals). Audio recordings were transcribed verbatim and common themes in participants' narratives emerged using framework analysis. Results: Participants' accounts confirmed the existence of opportunities for relatives to be involved. These, however, were limited and not always accessible. There were three factors identified that influenced accessibility namely: pre-existing worldviews, the quality of relationships and of communication between those involved, and specific structural impediments. Discussion: These themes are understood as intertwined and dependent on one another. People's thoughts, beliefs, attitudes, cultural identifications and worldviews often underlie the ways by which they communicate and the quality of their relationship. These, however, need to be conceptualised within operational frameworks and policy agendas in health settings that often limit bipolar relatives' accessibility to opportunities for being more formally involved. Conclusions: Involving relatives leads to clear benefits for relatives, service users, healthcare professionals, and the health system as a whole. Successful involvement of relatives, however, depends on a complex network of processes and interactions among all those involved and requires strategic planning from policy makers, operational plans and allocation of resources