Institution
University of Aberdeen
Education•Aberdeen, United Kingdom•
About: University of Aberdeen is a education organization based out in Aberdeen, United Kingdom. It is known for research contribution in the topics: Population & Health care. The organization has 21174 authors who have published 49962 publications receiving 2105479 citations. The organization is also known as: Aberdeen University.
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TL;DR: The potency of a wider range of nitrogen-containing bisphosphonates, including the highly potent, heterocycle-containing zoledronic acid and minodronate, is examined, finding a clear correlation between the ability to inhibit farnesyl diphosphate synthase in vitro, and to inhibit protein prenylation in cell-free extracts and in purified osteoclasts in vitro and in vivo.
Abstract: It has long been known that small changes to the structure of the R(2) side chain of nitrogen-containing bisphosphonates can dramatically affect their potency for inhibiting bone resorption in vitro and in vivo, although the reason for these differences in antiresorptive potency have not been explained at the level of a pharmacological target. Recently, several nitrogen-containing bisphosphonates were found to inhibit osteoclast-mediated bone resorption in vitro by inhibiting farnesyl diphosphate synthase, thereby preventing protein prenylation in osteoclasts. In this study, we examined the potency of a wider range of nitrogen-containing bisphosphonates, including the highly potent, heterocycle-containing zoledronic acid and minodronate (YM-529). We found a clear correlation between the ability to inhibit farnesyl diphosphate synthase in vitro, to inhibit protein prenylation in cell-free extracts and in purified osteoclasts in vitro, and to inhibit bone resorption in vivo. The activity of recombinant human farnesyl diphosphate synthase was inhibited at concentrations > or = 1 nM zoledronic acid or minodronate, the order of potency (zoledronic acid approximately equal to minodronate > risedronate > ibandronate > incadronate > alendronate > pamidronate) closely matching the order of antiresorptive potency. Furthermore, minor changes to the structure of the R(2) side chain of heterocycle-containing bisphosphonates, giving rise to less potent inhibitors of bone resorption in vivo, also caused a reduction in potency up to approximately 300-fold for inhibition of farnesyl diphosphate synthase in vitro. These data indicate that farnesyl diphosphate synthase is the major pharmacological target of these drugs in vivo, and that small changes to the structure of the R(2) side chain alter antiresorptive potency by affecting the ability to inhibit farnesyl diphosphate synthase.
849 citations
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University of Plymouth1, Marine Biological Association of the United Kingdom2, University of Porto3, University of Aberdeen4, Joint Institute for Marine and Atmospheric Research5, Inter-American Tropical Tuna Commission6, ETH Zurich7, University College Cork8, Queen's University Belfast9, Swansea University10
TL;DR: Maximum-likelihood methods are used to test for Lévy patterns in relation to environmental gradients in the largest animal movement data set assembled for this purpose and results are consistent with the LÉvy-flight foraging hypothesis, supporting the contention that organism search strategies naturally evolved in such a way that they exploit optimal Lé Ivy patterns.
Abstract: An optimal search theory, the so-called Levy-flight foraging hypothesis1, predicts that predators should adopt search strategies known as Levy flights where prey is sparse and distributed unpredictably, but that Brownian movement is sufficiently efficient for locating abundant prey2, 3, 4. Empirical studies have generated controversy because the accuracy of statistical methods that have been used to identify Levy behaviour has recently been questioned5, 6. Consequently, whether foragers exhibit Levy flights in the wild remains unclear. Crucially, moreover, it has not been tested whether observed movement patterns across natural landscapes having different expected resource distributions conform to the theory’s central predictions. Here we use maximum-likelihood methods to test for Levy patterns in relation to environmental gradients in the largest animal movement data set assembled for this purpose. Strong support was found for Levy search patterns across 14 species of open-ocean predatory fish (sharks, tuna, billfish and ocean sunfish), with some individuals switching between Levy and Brownian movement as they traversed different habitat types. We tested the spatial occurrence of these two principal patterns and found Levy behaviour to be associated with less productive waters (sparser prey) and Brownian movements to be associated with productive shelf or convergence-front habitats (abundant prey). These results are consistent with the Levy-flight foraging hypothesis1, 7, supporting the contention8, 9 that organism search strategies naturally evolved in such a way that they exploit optimal Levy patterns.
848 citations
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Hacettepe University1, Boston Children's Hospital2, Katholieke Universiteit Leuven3, University of Bologna4, Radboud University Nijmegen5, University of Aberdeen6, Claude Bernard University Lyon 17, European Respiratory Society8, Cardiff University9, University Hospital of Lausanne10, University of Queensland11, Ghent University12, University of Paris13, Istituto Giannina Gaslini14, Post Graduate Institute of Medical Education and Research15, Carlos III Health Institute16, National and Kapodistrian University of Athens17, University of Rennes18, University Hospital Heidelberg19, University College London20, Goethe University Frankfurt21, Catholic University of the Sacred Heart22, McGill University23
TL;DR: Treatment duration for aspergillosis is strongly recommended based on clinical improvement, degree of immunosuppression and response on imaging, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended.
848 citations
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Delft University of Technology1, UNESCO-IHE Institute for Water Education2, Vienna University of Technology3, University of Saskatchewan4, University of Illinois at Urbana–Champaign5, Swedish Meteorological and Hydrological Institute6, National Center for Atmospheric Research7, Karlsruhe Institute of Technology8, University of Bristol9, Russian Academy of Sciences10, University of Arizona11, Rhodes University12, University of Bologna13, University of Aberdeen14, Agrocampus Ouest15
TL;DR: The Prediction in Ungauged Basins (PUB) initiative of the International Association of Hydrological Sciences (IAHS) launched in 2003 and concluded by the PUB Symposium 2012 held in Delft (23-25 October 2012), set out to shift the scientific culture of hydrology towards improved scientific understanding of hydrological processes, as well as associated uncertainties and the development of models with increasing realism and predictive power as discussed by the authors.
Abstract: The Prediction in Ungauged Basins (PUB) initiative of the International Association of Hydrological Sciences (IAHS), launched in 2003 and concluded by the PUB Symposium 2012 held in Delft (23–25 October 2012), set out to shift the scientific culture of hydrology towards improved scientific understanding of hydrological processes, as well as associated uncertainties and the development of models with increasing realism and predictive power. This paper reviews the work that has been done under the six science themes of the PUB Decade and outlines the challenges ahead for the hydrological sciences community.Editor D. KoutsoyiannisCitation Hrachowitz, M., Savenije, H.H.G., Bloschl, G., McDonnell, J.J., Sivapalan, M., Pomeroy, J.W., Arheimer, B., Blume, T., Clark, M.P., Ehret, U., Fenicia, F., Freer, J.E., Gelfan, A., Gupta, H.V., Hughes, D.A., Hut, R.W., Montanari, A., Pande, S., Tetzlaff, D., Troch, P.A., Uhlenbrook, S., Wagener, T., Winsemius, H.C., Woods, R.A., Zehe, E., and Cudennec, C., 2013. A d...
848 citations
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TL;DR: This review brings the reader up to date with both pure and applied research in the field and provides a detailed overview of present thinking into the mode of action of azadirachtin.
844 citations
Authors
Showing all 21424 results
Name | H-index | Papers | Citations |
---|---|---|---|
Paul M. Thompson | 183 | 2271 | 146736 |
Feng Zhang | 172 | 1278 | 181865 |
Ian J. Deary | 166 | 1795 | 114161 |
Peter A. R. Ade | 162 | 1387 | 138051 |
David W. Johnson | 160 | 2714 | 140778 |
Pete Smith | 156 | 2464 | 138819 |
Naveed Sattar | 155 | 1326 | 116368 |
John R. Hodges | 149 | 812 | 82709 |
Ruth J. F. Loos | 142 | 647 | 92485 |
Alan J. Silman | 141 | 708 | 92864 |
Michael J. Keating | 140 | 1169 | 76353 |
David Price | 138 | 1687 | 93535 |
John D. Scott | 135 | 625 | 83878 |
Aarno Palotie | 129 | 711 | 89975 |
Rajat Gupta | 126 | 1240 | 72881 |