45 research outputs found

    RanGAP1*SUMO1 is phosphorylated at the onset of mitosis and remains associated with RanBP2 upon NPC disassembly

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    The RanGTPase activating protein RanGAP1 has essential functions in both nucleocytoplasmic transport and mitosis. In interphase, a significant fraction of vertebrate SUMO1-modified RanGAP1 forms a stable complex with the nucleoporin RanBP2/Nup358 at nuclear pore complexes. RanBP2 not only acts in the RanGTPase cycle but also is a SUMO1 E3 ligase. Here, we show that RanGAP1 is phosphorylated on residues T409, S428, and S442. Phosphorylation occurs before nuclear envelope breakdown and is maintained throughout mitosis. Nocodazole arrest leads to quantitative phosphorylation. The M-phase kinase cyclin B/Cdk1 phosphorylates RanGAP1 efficiently in vitro, and T409 phosphorylation correlates with nuclear accumulation of cyclin B1 in vivo. We find that phosphorylated RanGAP1 remains associated with RanBP2/Nup358 and the SUMO E2–conjugating enzyme Ubc9 in mitosis, hence mitotic phosphorylation may have functional consequences for the RanGTPase cycle and/or for RanBP2-dependent sumoylation

    A simple proposal for the publication of journal citation distributions

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    Although the Journal Impact Factor (JIF) is widely acknowledged to be a poor indicator of the quality of individual papers, it is used routinely to evaluate research and researchers. Here, we present a simple method for generating the citation distributions that underlie JIFs. Application of this straightforward protocol reveals the full extent of the skew of these distributions and the variation in citations received by published papers that is characteristic of all scientific journals. Although there are differences among journals across the spectrum of JIFs, the citation distributions overlap extensively, demonstrating that the citation performance of individual papers cannot be inferred from the JIF. We propose that this methodology be adopted by all journals as a move to greater transparency, one that should help to refocus attention on individual pieces of work and counter the inappropriate usage of JIFs during the process of research assessment

    Standardising and Harmonising Research Data Policy in Scholarly Publishing

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    To address the complexities researchers face during publication, and the potential community-wide benefits of wider adoption of clear data policies, the publisher Springer Nature has developed a standardised, common framework for the research data policies of all its journals. An expert working group was convened to audit and identify common features of research data policies of the journals published by Springer Nature, where policies were present. The group then consulted with approximately 30 editors, covering all research disciplines within the organisation. The group also consulted with academic editors, librarians and funders, which informed development of the framework and the creation of supporting resources. Four types of data policy were defined in recognition that some journals and research communities are more ready than others to adopt strong data policies. As of January 2017 more than 700 journals have adopted a standard policy and this number is growing weekly. To potentially enable standardisation and harmonisation of data policy across funders, institutions, repositories, societies and other publishers, the policy framework was made available under a Creative Commons license. However, the framework requires wider debate with these stakeholders and an Interest Group within the Research Data Alliance (RDA) has been formed to initiate this process

    The profile and treatment outcomes of the older (aged 60 years and above) tuberculosis patients in Tamilnadu, South India

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    Background: With changing demographic patterns in the context of a high tuberculosis (TB) burden country, like India, there is very little information on the clinical and demographic factors associated with poor treatment outcome in the sub-group of older TB patients. The study aimed to assess the proportion of older TB patients (60 years of age and more), to compare the type of TB and treatment outcomes between older TB patients and other TB patients (less than 60 years of age) and to describe the demographic and clinical characteristics of older TB patients and assess any associations with TB treatment outcomes. Methods: A retrospective cohort study involving a review of records from April to June 2011 in the 12 selected districts of Tamilnadu, India. Demographic, clinical and WHO defined disease classifications and treatment outcomes of all TB patients aged 60 years and above were extracted from TB registers maintained routinely by Revised National TB Control Program (RNTCP). Results: Older TB patients accounted for 14% of all TB patients, of whom 47% were new sputum positive. They had 38% higher risk of unfavourable treatment outcomes as compared to all other TB patients (Relative risk (RR)-1.4, 95% CI 1.2–1.6). Among older TB patients, the risk for unfavourable treatment outcomes was higher for those aged 70 years and more (RR 1.5, 95% CI 1.2–1.9), males (RR 1.5, 95% CI 1.0–2.1), re-treatment patients (RR 2.5, 95% CI 1.9–3.2) and those who received community-based Direct Observed Treatment (RR 1.4, 95% CI 1.1–1.9). Conclusion: Treatment outcomes were poor in older TB patients warranting special attention to this group – including routine assessment and recording of co-morbidities, a dedicated recording, reporting and monitoring of outcomes for this age-group and collaboration with National programme of non-communicable diseases for comprehensive management of co-morbidities

    Outbreak of Parasitic Dinoflagellate Piscinoodinium sp. Infection in an Endangered Fish from India: Arulius Barb (Dawkinsia arulius)

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    Freshwater velvet disease is caused by the dinoflagellate parasite, Piscinoodinium sp. This parasite has been reported in tropical and subtropical fishes, and it can cause devastating losses. Moreover, Piscinoodinium sp. is identified as one of the least studied finfish parasites, and the available molecular information about this parasite is meager. Recently, Piscinoodinium sp. was responsible for the 100% cumulative mortality of the captive-bred F1 generation of Arulius barb (Dawkinsia arulius), an endangered freshwater fish native to India. The trophont stages of the parasite were observed in the skin and gills of the affected fish. The total DNA was extracted from the trophonts collected from the affected Arulius barb and the partial nucleotide sequence of the rDNA complex region (2334 bp) was amplified using PCR. The amplified PCR product exhibited a high sequence identity (97.61%) with Piscinoodinium sp. In the phylogenetic analysis of the SSU rDNA, Piscinoodinium sp. emerged as a separate clade from other dinoflagellate species. This is the first report of the infection of Piscinoodinium sp. in Arulius barb and the molecular information generated from this study can serve as a baseline to study the diversity of the parasite in India. Furthermore, the impact of this parasite among wild fish stock is not known, and this parasite needs further research focus to generate more molecular information and to understand the host–pathogen interaction

    Software Citation Checklist for Developers

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    This document provides a minimal, generic checklist that developers of software (either open or closed source) used in research can use to ensure they are following good practice around software citation. This will help developers get credit for the software they create, and improve transparency, reproducibility, and reuse

    Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015

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    Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, life expectancy from birth increased from 61.7 years (95% uncertainty interval 61.4-61.9) in 1980 to 71.8 years (71.5-72.2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11.3 years (3.7-17.4), to 62.6 years (56.5-70.2). Total deaths increased by 4.1% (2.6-5.6) from 2005 to 2015, rising to 55.8 million (54.9 million to 56.6 million) in 2015, but age-standardised death rates fell by 17.0% (15.8-18.1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14.1% (12.6-16.0) to 39.8 million (39.2 million to 40.5 million) in 2015, whereas age-standardised rates decreased by 13.1% (11.9-14.3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42.1%, 39.1-44.6), malaria (43.1%, 34.7-51.8), neonatal preterm birth complications (29.8%, 24.8-34.9), and maternal disorders (29.1%, 19.3-37.1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death. Interpretation At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems. Copyright (C) The Author(s). Published by Elsevier Ltd.Peer reviewe
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