Institution
Johns Hopkins University School of Medicine
Healthcare•Baltimore, Maryland, United States•
About: Johns Hopkins University School of Medicine is a healthcare organization based out in Baltimore, Maryland, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 44277 authors who have published 79222 publications receiving 4788882 citations.
Topics: Population, Medicine, Cancer, Transplantation, Gene
Papers published on a yearly basis
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TL;DR: The characteristic inward rectification of Orai is mediated by an interaction between the polybasic STIM1 and a Pro-rich region in the N terminus of Obrai1 and the essential properties of ORAi1 function can be rationalized by interactions with discrete regions ofSTIM1.
Abstract: Influx of Ca(2+) through store-operated Ca(2+) channels (SOCs) is a central component of receptor-evoked Ca(2+) signals. Orai channels are SOCs that are gated by STIM1, a Ca(2+) sensor located in the ER but how it gates and regulates the Orai channels is unknown. Here, we report the molecular basis for gating of Orais by STIM1. All Orai channels are fully activated by the conserved STIM1 amino acid fragment 344-442, which we termed SOAR (the STIM1 Orai activating region). SOAR acts in combination with STIM1 (450-485) to regulate the strength of interaction with Orai1. Activation of Orai1 by SOAR recapitulates all the kinetic properties of Orai1 activation by STIM1. However, mutations of STIM1 within SOAR prevent activation of Orai1 but not co-clustering of STIM1 and Orai1 in response to Ca(2+) store depletion, indicating that STIM1-Orai1 co-clustering is not sufficient for Orai1 activation. An intact carboxy terminus alpha-helicial region of Orai is required for activation by SOAR. Deleting most of the Orai1 amino terminus impaired Orai1 activation by STIM1, but Orai1(Delta1-73) interacted with and was fully activated by SOAR. Accordingly, the characteristic inward rectification of Orai is mediated by an interaction between the polybasic STIM1 (672-685) and a Pro-rich region in the N terminus of Orai1. Hence, the essential properties of Orai1 function can be rationalized by interactions with discrete regions of STIM1.
616 citations
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TL;DR: It is proposed that localized activation, transmitted by the recruitment of cytosolic proteins, may be a general mechanism for gradient sensing by G protein-linked chemotactic systems including those involvingChemotactic cytokines in leukocytes.
615 citations
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TL;DR: Application of the simple thermoregulatory principle of increasing and decreasing body surface area/body mass in hot and cold climates, respectively, may explain the major systematic differences in body form between living and fossil hominids inhabiting tropical and higher latitude regions of the world.
Abstract: Hominids—both living and past—exhibit considerable variation in body size and shape. Both theoretical considerations and empirical observations indicate that some of this variation may be attributable to climatic adaptation. Application of the simple thermoregulatory principle of increasing and decreasing body surface area/body mass in hot and cold climates, respectively, may explain the major systematic differences in body form between living and fossil hominids inhabiting tropical and higher latitude regions of the world. Consideration of potential climatic influences on morphology has important ramifications for reconstructing body form and behavior of past hominids, interpreting geographic and temporal variability and migrational events, explaining the origins and perfection of hominid bipedalism, and better understanding changes in brain size and encephalization during hominid evolution. © 1994 Wiley-Liss, Inc.
615 citations
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TL;DR: The Health Belief Model as mentioned in this paper relates psychological theories of decision making (which attempt to explain action in a choice situation) to an individual's decision about alternative health behaviors, and it has been attributed the origins of that tradition of behavior motivation theory underlying the health belief model to Lewinian 2 theory of goal setting in the level-of-aspiration situation.
Abstract: The Health Belief Model relates psychological theories of decision making (which attempt to explain action in a choice situation) to an individual’s decision about alternative health behaviors. Rosenstock 1 has attributed the origins of that tradition of behavior motivation theory underlying the Health Belief Model to Lewinian 2 theory of goal setting in the level-of-aspiration situation (a special case of the latter’s general field theory). Lewin and associates hypothesized that behavior depends mainly upon two variables: (1) the value placed by an individual on a particular outcome and (2) the individual’s estimate of the likelihood that a given action will result in that outcome.
615 citations
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TL;DR: It has been proposed that immunologically induced histamine release is an active, enzymatically mediated process which occurs as a multistep response of viable cells to a specific antigenic stimulus.
Abstract: Human leukocytes, isolated from the blood of ragweed-sensitive donors, release histamine upon reaction with a purified protein antigen derived from this pollen. The release process has been studied with washed cells suspended in a defined, serum-free medium. Physiologic levels of pH, ionic strength, and temperature, as well as both calcium and magnesium, are required for optimal cellular reactivity. The level of cellular sensitivity of approximately 200 ragweed-sensitive donors has been ascertained, and the kinetics of the release process studied. The rate of histamine release is a function of antigen concentration, but even with a large excess of this reagent it is impossible to abolish a lag phase. Chelation of the divalent cations or a decrease in the reaction temperature may be utilized to stop the reaction. These measures are effective both before and after the initiation of histamine release. Diminished cellular reactivity (desensitization) has been achieved by several procedures. These have in common the addition of antigen to cells in an environment deficient in but a single respect, followed by a restoration of optimal conditions. The significance of these data has been discussed and it has been proposed that immunologically induced histamine release is an active, enzymatically mediated process which occurs as a multistep response of viable cells to a specific antigenic stimulus.
614 citations
Authors
Showing all 44754 results
Name | H-index | Papers | Citations |
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Robert Langer | 281 | 2324 | 326306 |
Bert Vogelstein | 247 | 757 | 332094 |
Solomon H. Snyder | 232 | 1222 | 200444 |
Steven A. Rosenberg | 218 | 1204 | 199262 |
Kenneth W. Kinzler | 215 | 640 | 243944 |
Hagop M. Kantarjian | 204 | 3708 | 210208 |
Mark P. Mattson | 200 | 980 | 138033 |
Stuart H. Orkin | 186 | 715 | 112182 |
Paul G. Richardson | 183 | 1533 | 155912 |
Aaron R. Folsom | 181 | 1118 | 134044 |
Gonçalo R. Abecasis | 179 | 595 | 230323 |
Jie Zhang | 178 | 4857 | 221720 |
Daniel R. Weinberger | 177 | 879 | 128450 |
David Baker | 173 | 1226 | 109377 |
Eliezer Masliah | 170 | 982 | 127818 |