scispace - formally typeset
Search or ask a question
Institution

University of Dundee

EducationDundee, 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
More filters
Journal ArticleDOI
TL;DR: Computational and experimental characterisation of the general screening library revealed that the selected compounds showed a broad range of lead‐like space, showed a high degree of structural integrity and purity, and demonstrated appropriate solubility for the purposes of biochemical screening.
Abstract: To enable the establishment of a drug discovery operation for neglected diseases, out of 2.3 million commercially available compounds 222 552 compounds were selected for an in silico library, 57 438 for a diverse general screening library, and 1 697 compounds for a focused kinase set. Compiling these libraries required a robust strategy for compound selection. Rules for unwanted groups were defined and selection criteria to enrich for lead-like compounds which facilitate straightforward structure–activity relationship exploration were established. Further, a literature and patent review was undertaken to extract key recognition elements of kinase inhibitors (“core fragments”) to assemble a focused library for hit discovery for kinases. Computational and experimental characterisation of the general screening library revealed that the selected compounds 1) span a broad range of lead-like space, 2) show a high degree of structural integrity and purity, and 3) demonstrate appropriate solubility for the purposes of biochemical screening. The implications of this study for compound selection, especially in an academic environment with limited resources, are considered.

372 citations

Journal ArticleDOI
TL;DR: The data suggest that Keap1 is a specialized sensor that quantifies stress by monitoring the intracellular concentrations of NO, Zn2+, and alkenals, which collectively serve as second messengers that may signify danger and/or damage.
Abstract: Recognition and repair of cellular damage is crucial if organisms are to survive harmful environmental conditions. In mammals, the Keap1 protein orchestrates this response, but how it perceives adverse circumstances is not fully understood. Herein, we implicate NO, Zn2+, and alkenals, endogenously occurring chemicals whose concentrations increase during stress, in this process. By combining molecular modeling with phylogenetic, chemical, and functional analyses, we show that Keap1 directly recognizes NO, Zn2+, and alkenals through three distinct sensors. The C288 alkenal sensor is of ancient origin, having evolved in a common ancestor of bilaterans. The Zn2+ sensor minimally comprises H225, C226, and C613. The most recent sensor, the NO sensor, emerged coincident with an expansion of the NOS gene family in vertebrates. It comprises a cluster of basic amino acids (H129, K131, R135, K150, and H154) that facilitate S-nitrosation of C151. Taken together, our data suggest that Keap1 is a specialized sensor that quantifies stress by monitoring the intracellular concentrations of NO, Zn2+, and alkenals, which collectively serve as second messengers that may signify danger and/or damage.

372 citations

Journal ArticleDOI
TL;DR: Two recent reports have identified DNA (cytosine-5)methyltransferase and the DNA repair endonuclease XPG as binding to PCNA, and all seem to occur through a conserved motif that is likely to contact the same site on PCNA.
Abstract: Proliferating cell nuclear antigen (PCNA) has recently been identified as a target for the binding of several proteins. The cell cycle regulatory protein, p21, and the replication endonuclease, Fen1, have already been described as competing for PCNA binding. Two recent reports have identified DNA (cytosine-5)methyltransferase (MCMT) and the DNA repair endonuclease XPG as binding to PCNA.1,2 The remarkable thing about these interactions is that they all seem to occur through a conserved motif that is likely to contact the same site on PCNA. This has fascinating implications for a regulatory network linking these diverse protein functions. BioEssays20:195–199, 1998. © 1998 John Wiley & Sons, Inc.

371 citations

Journal ArticleDOI
TL;DR: In this article, the authors describe the emergence of new team/process-oriented roles for so-called hybrid accountants in the manufacturing division of a multinational pharmaceuticals organisation, and highlight institutional contradictions that create potential openings for change, and discuss the praxis that underpin when, how and why role(s) change is carved out.
Abstract: Recent years have witnessed a flurry of commentaries, mainly in the professional accounting literature, on new business-oriented roles for management accountants. Often premised on the generalisation of survey data, such work undoubtedly provides useful publicity to the underlying trends. However, to date, empirical research into the dynamics of role(s) change in actual organisations is scarce. This paper describes the emergence of new team/process-oriented roles for so-called ‘hybrid’ accountants in the manufacturing division of a multinational pharmaceuticals organisation. Adopting institutional theory, the following provides insight into role(s) change, as processes that encompass both institutional embeddedness and transformational agency. We highlight institutional contradictions that create potential openings for change, and discuss the praxis that underpin when, how and why role(s) change is carved out.

371 citations

Journal ArticleDOI
Kyle J. Gaulton1, Kyle J. Gaulton2, Teresa Ferreira2, Yeji Lee3  +258 moreInstitutions (73)
TL;DR: This paper performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry, and identified 49 distinct association signals at these loci including five mapping in or near KCNQ1.
Abstract: We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.

370 citations


Authors

Showing all 19404 results

NameH-indexPapersCitations
Matthias Mann221887230213
Mark I. McCarthy2001028187898
Stefan Schreiber1781233138528
Kenneth C. Anderson1781138126072
Masayuki Yamamoto1711576123028
Salvador Moncada164495138030
Jorge E. Cortes1632784124154
Andrew P. McMahon16241590650
Philip Cohen154555110856
Dirk Inzé14964774468
Andrew T. Hattersley146768106949
Antonio Lanzavecchia145408100065
Kim Nasmyth14229459231
David Price138168793535
Dario R. Alessi13635474753
Network Information
Related Institutions (5)
University of Edinburgh
151.6K papers, 6.6M citations

95% related

University College London
210.6K papers, 9.8M citations

95% related

University of Manchester
168K papers, 6.4M citations

94% related

Imperial College London
209.1K papers, 9.3M citations

94% related

University of Cambridge
282.2K papers, 14.4M citations

93% related

Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202361
2022205
20211,653
20201,520
20191,473
20181,524