Institution
University of Hawaii at Manoa
Education•Honolulu, Hawaii, United States•
About: University of Hawaii at Manoa is a education organization based out in Honolulu, Hawaii, United States. It is known for research contribution in the topics: Population & Sea surface temperature. The organization has 13693 authors who have published 25161 publications receiving 1023924 citations.
Papers published on a yearly basis
Papers
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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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TL;DR: In this paper, a 350-amino acid protein (NUDT9) and a homologous domain near the carboxy terminus of the LTRPC2/TrpC7 putative cation channel both function as specific ADPR pyrophosphatases.
Abstract: Free ADP-ribose (ADPR), a product of NAD hydrolysis and a breakdown product of the calcium-release second messenger cyclic ADPR (cADPR), has no defined role as an intracellular signalling molecule in vertebrate systems. Here we show that a 350-amino-acid protein (designated NUDT9) and a homologous domain (NUDT9 homology domain) near the carboxy terminus of the LTRPC2/TrpC7 putative cation channel both function as specific ADPR pyrophosphatases. Whole-cell and single-channel analysis of HEK-293 cells expressing LTRPC2 show that LTRPC2 functions as a calcium-permeable cation channel that is specifically gated by free ADPR. The expression of native LTRPC2 transcripts is detectable in many tissues including the U937 monocyte cell line, in which ADPR induces large cation currents (designated IADPR) that closely match those mediated by recombinant LTRPC2. These results indicate that intracellular ADPR regulates calcium entry into cells that express LTRPC2.
847 citations
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Centers for Disease Control and Prevention1, Mario Negri Institute for Pharmacological Research2, University of Texas Health Science Center at Houston3, Northern Illinois University4, Children's Memorial Hospital5, Mayo Clinic6, Fudan University7, Columbia University8, Boston University9, RTI International10, University of Arizona11, University of Hawaii at Manoa12, University of Bari13, University College London14, Wellcome Trust15, University of California, San Francisco16, Mississippi University for Women17, University of Limoges18, UCL Institute of Neurology19, Medical University of South Carolina20, National Institutes of Health21, Karolinska Institutet22, University of Calgary23
TL;DR: The purpose of this document is to promote consistency in definitions and methods in an effort to enhance future population‐based epidemiologic studies, facilitate comparison between populations, and encourage the collection of data useful for the promotion of public health.
Abstract: Worldwide, about 65 million people are estimated to have epilepsy. Epidemiologic studies are necessary to define the full public health burden of epilepsy; to set public health and health care priorities; to provide information needed for prevention, early detection, and treatment; to identify education and service needs; and to promote effective health care and support programs for people with epilepsy. However, different definitions and epidemiologic methods complicate the tasks of these studies and their interpretations and comparisons. The purpose of this document is to promote consistency in definitions and methods in an effort to enhance future population-based epidemiologic studies, facilitate comparison between populations, and encourage the collection of data useful for the promotion of public health. We discuss: (1) conceptual and operational definitions of epilepsy, (2) data resources and recommended data elements, and (3) methods and analyses appropriate for epidemiologic studies or the surveillance of epilepsy. Variations in these are considered, taking into account differing resource availability and needs among countries and differing purposes among studies.
844 citations
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TL;DR: This article found that multinational ownership, multinational customers, and exports to developed countries increase self-regulation of environmental performance, and suggested that globalization might also have positive environmental effects because global ties increase selfregulation pressures on firms in low-regulation countries.
Abstract: Critics assert that globalization is detrimental to the environment because it encourages location of polluting industries in countries with low environmental regulations. We suggest that globalization might also have positive environmental effects because global ties increase self-regulation pressures on firms in low-regulation countries. Using survey data from firms in China we find that multinational ownership, multinational customers, and exports to developed countries increase self-regulation of environmental performance.
841 citations
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Lamont–Doherty Earth Observatory1, University of Bristol2, Wesleyan University3, Yale University4, National Oceanography Centre, Southampton5, Utrecht University6, University of Hawaii at Manoa7, Pennsylvania State University8, University of Southern California9, Museum für Naturkunde10, University of North Carolina at Chapel Hill11, University of California, Santa Cruz12, Cardiff University13, Institute of Arctic and Alpine Research14, University of South Florida St. Petersburg15, VU University Amsterdam16, Autonomous University of Barcelona17, Claremont McKenna College18
TL;DR: This paper reviewed events exhibiting evidence for elevated atmospheric CO2, global warming, and ocean acidification over the past ~300 million years of Earth's history, some with contemporaneous extinction or evolutionary turnover among marine calcifiers.
Abstract: Ocean acidification may have severe consequences for marine ecosystems; however, assessing its future impact is difficult because laboratory experiments and field observations are limited by their reduced ecologic complexity and sample period, respectively. In contrast, the geological record contains long-term evidence for a variety of global environmental perturbations, including ocean acidification plus their associated biotic responses. We review events exhibiting evidence for elevated atmospheric CO2, global warming, and ocean acidification over the past ~300 million years of Earth’s history, some with contemporaneous extinction or evolutionary turnover among marine calcifiers. Although similarities exist, no past event perfectly parallels future projections in terms of disrupting the balance of ocean carbonate chemistry—a consequence of the unprecedented rapidity of CO2 release currently taking place.
838 citations
Authors
Showing all 13867 results
Name | H-index | Papers | Citations |
---|---|---|---|
Pulickel M. Ajayan | 176 | 1223 | 136241 |
Steven N. Blair | 165 | 879 | 132929 |
Qiang Zhang | 161 | 1137 | 100950 |
Jack M. Guralnik | 148 | 453 | 83701 |
Thomas J. Smith | 140 | 1775 | 113919 |
James A. Richardson | 136 | 363 | 75778 |
Donna Neuberg | 135 | 810 | 72653 |
Jian Zhou | 128 | 3007 | 91402 |
Eric F. Bell | 128 | 631 | 72542 |
Jorge Luis Rodriguez | 128 | 834 | 73567 |
Bin Wang | 126 | 2226 | 74364 |
Nicholas J. Schork | 125 | 587 | 62131 |
Matthew Jones | 125 | 1161 | 96909 |
Anthony F. Jorm | 124 | 798 | 67120 |
Adam G. Riess | 118 | 363 | 117310 |