Institution
University of Dundee
Education•Dundee, United Kingdom•
About: University of Dundee is a education organization based out in Dundee, United Kingdom. It is known for research contribution in the topics: Population & Protein kinase A. The organization has 19258 authors who have published 39640 publications receiving 1919433 citations. The organization is also known as: Universitas Dundensis & Dundee University.
Papers published on a yearly basis
Papers
More filters
••
Aarhus University1, French Institute of Health and Medical Research2, Washington University in St. Louis3, Tufts Medical Center4, University of Rochester5, Queen's University6, Helsinki University Central Hospital7, Oslo University Hospital8, Karolinska Institutet9, Aarhus University Hospital10, University of the Witwatersrand11, Churchill Hospital12, Johns Hopkins University13, Chelsea and Westminster Hospital NHS Foundation Trust14, Imperial College London15, California Pacific Medical Center16, University of Edinburgh17, Florey Institute of Neuroscience and Mental Health18, University of Sydney19, Greenwich Hospital20, University of Dundee21, University of California, San Diego22
TL;DR: The results support a revision of the NeuPSIG recommendations for the pharmacotherapy of neuropathic pain and allow a strong recommendation for use and proposal as first-line treatment in neuropathicPain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin.
Abstract: Summary Background New drug treatments, clinical trials, and standards of quality for assessment of evidence justify an update of evidence-based recommendations for the pharmacological treatment of neuropathic pain. Using the Grading of Recommendations Assessment, Development, and E valuation (GRADE), we revised the Special Interest Group on Neuropathic Pain (NeuPSIG) recommendations for the pharmacotherapy of neuropathic pain based on the results of a systematic review and meta-analysis. Methods Between April, 2013, and January, 2014, NeuPSIG of the International Association for the Study of Pain did a systematic review and meta-analysis of randomised, double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January , 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies. We used number needed to treat (NNT) for 50% pain relief as a primary measure and assessed publication bias; NNT was calculated with the fi xed-eff ects Mantel-Haenszel method. Findings 229 studies were included in the meta-analysis. Analysis of publication bias suggested a 10% overstatement of treatment eff ects. Studies published in peer-reviewed journals reported greater eff ects than did unpublished studies (r² 9·3%, p=0·009). T rial outcomes were generally modest: in particular, combined NNTs were 6·4 (95% CI 5·2–8·4) for serotonin-noradrenaline reuptake inhibitors, mainly including duloxetine (nine of 14 studies); 7·7 (6·5–9·4) for pregabalin; 7·2 (5·9–9·21) for gabapentin, including gabapentin extended release and enacarbil; and 10·6 (7·4–19·0) for capsaicin high-concentration patches. NNTs were lower for tricyclic antidepressants, strong opioids, tramadol, and botulinum toxin A, and undetermined for lidocaine patches. Based on GRADE, fi nal quality of evidence was moderate or high for all treatments apart from lidocaine patches; tolerability and safety, and values and preferences were higher for topical drugs; and cost was lower for tricyclic antidepressants and tramadol. These fi ndings permitted a strong recommendation for use and proposal as fi rst-line treatment in neuropathic pain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin; a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin high-concentration patches, and tramadol; and a weak recommendation for use and proposal as third line for strong opioids and botulinum toxin A. Topical agents and botulinum toxin A are recommended for peripheral neuropathic pain only. Interpretation Our results support a revision of the NeuPSIG recommendations for the pharmacotherapy of neuropathic pain. Inadequate response to drug treatments constitutes a substantial unmet need in patients with neuropathic pain. Modest effi cacy, large placebo responses, heterogeneous diagnostic criteria, and poor phenotypic profi ling probably account for moderate trial outcomes and should be taken into account in future studies. Funding NeuPSIG of the International Association for the Study of Pain.
2,512 citations
••
Stephen Sawcer1, Garrett Hellenthal2, Matti Pirinen2, Chris C. A. Spencer2 +262 more•Institutions (67)
TL;DR: In this article, a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, they have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci.
Abstract: Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
2,511 citations
••
University of Kiel1, Cedars-Sinai Medical Center2, Wellcome Trust Sanger Institute3, University of Pennsylvania4, QIMR Berghofer Medical Research Institute5, Peninsula College of Medicine and Dentistry6, University of Edinburgh7, University of Cambridge8, University of Otago9, University of Washington10, University of Groningen11, University of Liège12, Harvard University13, Casa Sollievo della Sofferenza14, King's College London15, University of Chicago16, Yale University17, Johns Hopkins University18, Ludwig Maximilian University of Munich19, Charité20, McGill University21, Lille University of Science and Technology22, Cincinnati Children's Hospital Medical Center23, Ghent University24, Torbay Hospital25, Mater Health Services26, Université libre de Bruxelles27, RWTH Aachen University28, University of Utah29, Örebro University30, Leiden University31, University of Paris32, Technion – Israel Institute of Technology33, University of Western Australia34, Tel Aviv University35, University of Dundee36, University of Manchester37, University of Pittsburgh38, Royal Hospital for Sick Children39, Katholieke Universiteit Leuven40, Guy's and St Thomas' NHS Foundation Trust41, University of Bern42, University of Toronto43, University of Amsterdam44, Karolinska Institutet45, University of Zurich46, Université de Montréal47, Emory University48, Newcastle University49
TL;DR: A meta-analysis of six Crohn's disease genome-wide association studies and a series of in silico analyses highlighted particular genes within these loci implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP.
Abstract: We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
2,482 citations
••
TL;DR: This work proposes the first unified hierarchical classification system, designed on the basis of the transposition mechanism, sequence similarities and structural relationships, that can be easily applied by non-experts.
Abstract: Our knowledge of the structure and composition of genomes is rapidly progressing in pace with their sequencing. The emerging data show that a significant portion of eukaryotic genomes is composed of transposable elements (TEs). Given the abundance and diversity of TEs and the speed at which large quantities of sequence data are emerging, identification and annotation of TEs presents a significant challenge. Here we propose the first unified hierarchical classification system, designed on the basis of the transposition mechanism, sequence similarities and structural relationships, that can be easily applied by non-experts. The system and nomenclature is kept up to date at the WikiPoson web site.
2,425 citations
••
TL;DR: Four major serine/threonine-specific protein phosphatase catalytic subunits are present in the cytoplasm of animal cells and have broad and overlapping specificities in vitro, and account for virtually all measurable activity in tissue extracts toward a variety of phosphoproteins that regulate metabolism, muscle contractility, and other processes.
Abstract: Four major serine/threonine-specific protein phosphatase catalytic subunits are present in the cytoplasm of animal cells. Three of these enzymes, PP-1, PP-2A, and PP-2B, are members of the same gene family, while PP-2C appears to be distinct. PP-1, PP-2A, and PP-2B are complexed to other subunits in vivo, whereas PP-2C has only been isolated as a monomeric protein. PP-1, PP-2A, and PP-2C have broad and overlapping specificities in vitro, and account for virtually all measurable activity in tissue extracts toward a variety of phosphoproteins that regulate metabolism, muscle contractility, and other processes. Their precise functions in vivo are unknown, although important clues to the physiological roles of PP-1 and PP-2A are provided by the effects of okadaic acid and by the subcellular localization of PP-1. The active forms of PP-1 are largely particulate, and their association with subcellular structures is mediated by "targetting subunits" that direct PP-1 to particular locations, enhance its activity toward certain substrates, and confer important regulatory properties upon it. This concept is best established for the glycogen-bound enzymes in skeletal muscle and liver (PP-1G) and the myofibrillar form (PP-1M) in skeletal muscle. The activities of PP-1 and PP-2B are controlled by the second messengers cyclic AMP and calcium. The activity of PP-2B is dependent on calcium and calmodulin, while PP-1 is controlled in a variety of ways that depend on the form of the enzyme and the tissue. PP-1 can be inhibited by cyclic AMP in a variety of cells through the A-kinase-catalyzed phosphorylation of inhibitor-1 and its isoforms. Phosphorylation of the glycogen-binding subunit of PP-1G by A-kinase promotes translocation of the catalytic subunit from glycogen particles to cytosol in skeletal muscle, inhibiting the dephosphorylation of glycogen-metabolizing enzymes. Allosteric inhibition of hepatic PP-1G by phosphorylase a occurs in response to signals that elevate cyclic AMP or calcium, and prevents the activation of glycogen synthase in liver. PP-1 can also be activated indirectly by calcium through the ability of PP-2B to dephosphorylate inhibitor-1. This control mechanism may operate in dopaminoceptive neurones of the brain and other cells. The inactive cytosolic form of PP-1 (PP-1I) can be activated in vitro through the glycogen synthase kinase-3-catalyzed phosphorylation of its inhibitory subunit (inhibitor-2), but the physiological significance is unclear.(ABSTRACT TRUNCATED AT 400 WORDS)
2,368 citations
Authors
Showing all 19404 results
Name | H-index | Papers | Citations |
---|---|---|---|
Matthias Mann | 221 | 887 | 230213 |
Mark I. McCarthy | 200 | 1028 | 187898 |
Stefan Schreiber | 178 | 1233 | 138528 |
Kenneth C. Anderson | 178 | 1138 | 126072 |
Masayuki Yamamoto | 171 | 1576 | 123028 |
Salvador Moncada | 164 | 495 | 138030 |
Jorge E. Cortes | 163 | 2784 | 124154 |
Andrew P. McMahon | 162 | 415 | 90650 |
Philip Cohen | 154 | 555 | 110856 |
Dirk Inzé | 149 | 647 | 74468 |
Andrew T. Hattersley | 146 | 768 | 106949 |
Antonio Lanzavecchia | 145 | 408 | 100065 |
Kim Nasmyth | 142 | 294 | 59231 |
David Price | 138 | 1687 | 93535 |
Dario R. Alessi | 136 | 354 | 74753 |