64 research outputs found

    hUBC9 associates with MEKK1 and type I TNF-α receptor and stimulates NFκB activity

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    AbstracthUBC9, an E2 ubiquitin conjugating enzyme, was identified by yeast two-hybrid screening and coprecipitation studies to interact with MEKK1 and the type I TNF-α receptor, respectively. Because both of these proteins regulate NFκB activity, the role of hUBC9 in modulating NFκB activity was investigated. Overexpression of hUBC9 in HeLa cells stimulated the activity of NFκB as determined by NFκB reporter and IL-6 secretion assays. hUBC9 also synergized with MEKK1 to activate NFκB reporter activity. Thus, hUBC9 modulates NFκB activity which, at least in part, can be attributed to its interaction with MEKK1 and the type I TNF-α receptor

    Seasonal Occurrence, Horizontal Movements, and Habitat Use Patterns of Whale Sharks (\u3ci\u3eRhincodon typus\u3c/i\u3e) in the Gulf of Mexico

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    In the northern Gulf of Mexico (GOM), whale sharks (Rhincodon typus) form large aggregations at continental shelf-edge banks during summer; however, knowledge of movements once they leave aggregation sites is limited. Here we report on the seasonal occurrence of whale sharks in the northern GOM based on over 800 whale shark sightings from 1989 to 2016, as well as the movements of 42 whale sharks tagged with satellite-linked and popup satellite archival transmitting tags from 2008 to 2015. Sightings data were most numerous during summer and fall often with aggregations of individuals reported along the continental shelf break. Most sharks (66%) were tagged during this time at Ewing Bank, a known aggregation site off the coast of Louisiana. Whale shark track duration ranged from three to 366 days and all tagged individuals, which ranged from 4.5 to 12.0 m in total length, remained within the GOM. Sightings data revealed that whale sharks occurred primarily in continental shelf and shelf-edge waters (81%) whereas tag data revealed the sharks primarily inhabited continental slope and open ocean waters (91%) of the GOM. Much of their time spent in open ocean waters was associated with the edge of the Loop Current and associated mesoscale eddies. During cooler months, there was a net movement southward, corresponding with the time of reduced sighting reports. Several sharks migrated to the southwest GOM during fall and winter, suggesting this region could be important overwintering habitat and possibly represents another seasonal aggregation site. The three long-term tracked whale sharks exhibited interannual site fidelity, returning one year later to the vicinity where they were originally tagged. The increased habitat use of north central GOM waters by whale sharks as summer foraging grounds and potential interannual site fidelity to Ewing Bank demonstrate the importance of this region for this species

    Population Connectivity of Pelagic Megafauna in the Cuba-Mexico-United States Triangle

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    The timing and extent of international crossings by billfishes, tunas, and sharks in the Cuba-Mexico-United States (U.S.) triangle was investigated using electronic tagging data from eight species that resulted in \u3e22,000 tracking days. Transnational movements of these highly mobile marine predators were pronounced with varying levels of bi- or tri-national population connectivity displayed by each species. Billfishes and tunas moved throughout the Gulf of Mexico and all species investigated (blue marlin, white marlin, Atlantic bluefin tuna, yellowfin tuna) frequently crossed international boundaries and entered the territorial waters of Cuba and/or Mexico. Certain sharks (tiger shark, scalloped hammerhead) displayed prolonged periods of residency in U.S. waters with more limited displacements, while whale sharks and to a lesser degree shortfin mako moved through multiple jurisdictions. The spatial extent of associated movements was generally associated with their differential use of coastal and open ocean pelagic ecosystems. Species with the majority of daily positions in oceanic waters off the continental shelf showed the greatest tendency for transnational movements and typically traveled farther from initial tagging locations. Several species converged on a common seasonal movement pattern between territorial waters of the U.S. (summer) and Mexico (winter)

    LIMPRINT: the UK experience - subjective control of swelling in patients attending specialist lymphedema services

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    Background and study design: This study was undertaken as part of the UK LIMPRINT international study to determine the number of people with chronic oedema and its impact on health services. Overall 7436 with chronic oedema (CO) were recruited in the main UK study from a range of health settings. Methods and results: Subjective control of arm and leg chronic oedema (CO) was defined for patients attending three Lymphoedema services in the UK. Of the total available in the UK dataset 5165 (69.4%)/ 7436(100%) of participants were included. Reasons for exclusions included the following: lack of information (1669), having both arm and leg swelling (272), lack of description of control (5) and professional inability to decide whether CO was controlled (325). Arm swelling occurred in 953 (18.5%), with leg CO in 4212 (81.5%). Poor control was found in 1430 (27.7%) and good control in 3735 (72.3%). Control of arm swelling was worse in men and control increased overall in those aged over 45 years. In contrast control of CO worsened in those with leg CO with increasing age and multiple co-morbidities. Obesity and cellulitis, particularly an episode in the last year were associated with poor control. Independent risk factors for arm CO were obesity, neurological disease and cellulitis in the last year and for leg CO: obesity, poor mobility, heart disease, presence of a wound, cellulitis in the last year and duration of swelling. Conclusion: Control of CO within specialised centres is complex due to sociodemographic and clinical comorbidities

    Precision Medicine in Diabetes: A Consensus Report From the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

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    The convergence of advances in medical science, human biology, data science, and technology has enabled the generation of new insights into the phenotype known as "diabetes." Increased knowledge of this condition has emerged from populations around the world, illuminating the differences in how diabetes presents, its variable prevalence, and how best practice in treatment varies between populations. In parallel, focus has been placed on the development of tools for the application of precision medicine to numerous conditions. This Consensus Report presents the American Diabetes Association (ADA) Precision Medicine in Diabetes Initiative in partnership with the European Association for the Study of Diabetes (EASD), including its mission, the current state of the field, and prospects for the future. Expert opinions are presented on areas of precision diagnostics and precision therapeutics (including prevention and treatment), and key barriers to and opportunities for implementation of precision diabetes medicine, with better care and outcomes around the globe, are highlighted. Cases where precision diagnosis is already feasible and effective (i.e., monogenic forms of diabetes) are presented, while the major hurdles to the global implementation of precision diagnosis of complex forms of diabetes are discussed. The situation is similar for precision therapeutics, in which the appropriate therapy will often change over time owing to the manner in which diabetes evolves within individual patients. This Consensus Report describes a foundation for precision diabetes medicine, while highlighting what remains to be done to realize its potential. This, combined with a subsequent, detailed evidence-based review (due 2022), will provide a roadmap for precision medicine in diabetes that helps improve the quality of life for all those with diabetes.This article is freely available via Open Access. Click on the publisher URL to access it via the publisher's site.R01 HD094150/HD/NICHD NIH HHS/United States DP3 DK111906/DK/NIDDK NIH HHS/United States U01 DK105535/DK/NIDDK NIH HHS/United States R01 DK104942/DK/NIDDK NIH HHS/United States U54 DK118612/DK/NIDDK NIH HHS/United States R21 AI142483/AI/NIAID NIH HHS/United States R01 DK122586/DK/NIDDK NIH HHS/United States P30 DK026687/DK/NIDDK NIH HHS/United States WT_/Wellcome Trust/United Kingdom R01 DK052431/DK/NIDDK NIH HHS/United States UL1 TR001873/TR/NCATS NIH HHS/United States R01 DK104351/DK/NIDDK NIH HHS/United Statesaccepted version, submitted versio

    Proceedings of Patient Reported Outcome Measure’s (PROMs) Conference Oxford 2017: Advances in Patient Reported Outcomes Research

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    A33-Effects of Out-of-Pocket (OOP) Payments and Financial Distress on Quality of Life (QoL) of People with Parkinson’s (PwP) and their Carer

    Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

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    Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

    The trans-ancestral genomic architecture of glycemic traits

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    Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

    Large expert-curated database for benchmarking document similarity detection in biomedical literature search

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    Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe
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