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: The bacterial species diversity of three colonic tissue samples from elderly people was investigated by sequence analysis of randomly cloned eubacterial 16S rDNA, providing the first molecular information on the microbial diversity present in human colonic samples.

379 citations

Journal ArticleDOI
Sandosh Padmanabhan1, Olle Melander2, Toby Johnson3, Anna Maria Di Blasio, Wai K. Lee1, Davide Gentilini, Claire E. Hastie1, Cristina Menni4, Cristina Menni1, Maria Cristina Monti5, Christian Delles1, Stewart Laing1, Barbara Corso5, Gerjan Navis6, Arjan J. Kwakernaak6, Pim van der Harst6, Murielle Bochud7, Marc Maillard7, Michel Burnier7, Thomas Hedner8, Sverre E. Kjeldsen9, Björn Wahlstrand8, Marketa Sjögren2, Cristiano Fava10, Cristiano Fava2, Martina Montagnana10, Martina Montagnana2, Elisa Danese2, Elisa Danese10, Ole Torffvit, Bo Hedblad2, Harold Snieder6, John M. C. Connell11, Morris Brown12, Nilesh J. Samani13, Martin Farrall14, Giancarlo Cesana4, Giuseppe Mancia4, Stefano Signorini, Guido Grassi4, Susana Eyheramendy15, H.-Erich Wichmann16, Maris Laan17, David P. Strachan18, Peter S. Sever19, Denis C. Shields20, Alice Stanton21, Peter Vollenweider7, Alexander Teumer22, Henry Völzke22, Rainer Rettig22, Christopher Newton-Cheh23, Christopher Newton-Cheh24, Pankaj Arora23, Pankaj Arora24, Feng Zhang25, Nicole Soranzo25, Nicole Soranzo26, Tim D. Spector25, Gavin Lucas, Sekar Kathiresan23, Sekar Kathiresan24, David S. Siscovick27, Jian'an Luan, Ruth J. F. Loos, Nicholas J. Wareham, Brenda W.J.H. Penninx28, Brenda W.J.H. Penninx6, Brenda W.J.H. Penninx29, Ilja M. Nolte6, Martin W. McBride1, William H. Miller1, Stuart A. Nicklin1, Andrew H. Baker1, Delyth Graham1, Robert A. McDonald1, Jill P. Pell1, Naveed Sattar1, Paul Welsh1, Patricia B. Munroe3, Mark J. Caulfield3, Alberto Zanchetti30, Anna F. Dominiczak1 
TL;DR: The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.
Abstract: Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 59 region of Uromodulin (UMOD; rs13333226, combined P value of 3.6x10(-11)). The minor G allele is associated with a lower risk of hypertension (OR [95% CI]: 0.87 [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.

378 citations

Journal ArticleDOI
TL;DR: Data indicate that a novel action of leptin in the CNS is to facilitate hippocampal synaptic plasticity via enhanced NMDA receptor-mediated Ca(2+) influx.
Abstract: The obese gene product leptin is an important signaling protein that regulates food intake and body weight via activation of the hypothalamic leptin receptor (Ob-Rb; Jacob et al., 1997). However, there is growing evidence that Ob-Rb is also expressed in CNS regions, not directly associated with energy homeostasis (Mercer et al., 1996; Hakansson et al., 1998). In the hippocampus, an area of the brain involved in learning and memory, we have found that leptin facilitates the induction of synaptic plasticity. Leptin converts short-term potentiation of synaptic transmission induced by primed burst stimulation of the Schaffer collateral commissural pathway into long-term potentiation. The mechanism underlying this effect involves facilitation of NMDA receptor function because leptin rapidly enhances NMDA-induced increases in intracellular Ca(2+) levels ([Ca(2+)](i)) and facilitates NMDA, but not AMPA, receptor-mediated synaptic transmission. The signaling mechanism underlying these effects involves activation of phosphoinositide 3-kinase, mitogen-activated protein kinase, and Src tyrosine kinases. These data indicate that a novel action of leptin in the CNS is to facilitate hippocampal synaptic plasticity via enhanced NMDA receptor-mediated Ca(2+) influx. Impairment of this process may contribute to the cognitive deficits associated with diabetes mellitus.

378 citations

Journal ArticleDOI
TL;DR: While phosphorylation of eIF2 serves to impair general protein synthesis, it causes upregulation of the translation of certain specific mRNAs that encode transcription factors which can exert effects on gene expression at multiple levels.

378 citations

Journal ArticleDOI
TL;DR: Results indicate that PtdIns(3,4,5)P3 plays several roles in the PDK1-induced activation of P KBalpha, and binds to the PH domain of PKB, altering its conformation so that it can be activated by PDK 1.
Abstract: 3-Phosphoinositide-dependent protein kinase-1 (PDK1) interacts stereoselectively with the d-enantiomer of PtdIns(3,4,5)P3 (KD 1.6 nM) and PtdIns(3,4)P2 (KD 5.2 nM), but binds with lower affinity to PtdIns3P or PtdIns(4,5)P2. The binding of PtdIns(3,4,5)P3 to PDK1 was greatly decreased by making specific mutations in the pleckstrin homology (PH) domain of PDK1 or by deleting it. The same mutations also greatly decreased the rate at which PDK1 activated protein kinase Balpha (PKBalpha) in vitro in the presence of lipid vesicles containing PtdIns(3,4,5)P3, but did not affect the rate at which PDK1 activated a PKBalpha mutant lacking the PH domain in the absence of PtdIns(3,4,5)P3. When overexpressed in 293 or PAE cells, PDK1 was located at the plasma membrane and in the cytosol, but was excluded from the nucleus. Mutations that disrupted the interaction of PtdIns(3,4,5)P3 or PtdIns(4,5)P2 with PDK1 abolished the association of PDK1 with the plasma membrane. Growth-factor stimulation promoted the translocation of transfected PKBalpha to the plasma membrane, but had no effect on the subcellular distribution of PDK1 as judged by immunoelectron microscopy of fixed cells. This conclusion was also supported by confocal microscopy of green fluorescent protein-PDK1 in live cells. These results, together with previous observations, indicate that PtdIns(3,4,5)P3 plays several roles in the PDK1-induced activation of PKBalpha. First, it binds to the PH domain of PKB, altering its conformation so that it can be activated by PDK1. Secondly, interaction with PtdIns(3,4,5)P3 recruits PKB to the plasma membrane with which PDK1 is localized constitutively by virtue of its much stronger interaction with PtdIns(3,4,5)P3 or PtdIns(4,5)P2. Thirdly, the interaction of PDK1 with PtdIns(3,4,5)P3 facilitates the rate at which it can activate PKB.

378 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