Institution
Howard Hughes Medical Institute
Nonprofit•Chevy Chase, Maryland, United States•
About: Howard Hughes Medical Institute is a nonprofit organization based out in Chevy Chase, Maryland, United States. It is known for research contribution in the topics: Gene & RNA. The organization has 20371 authors who have published 34677 publications receiving 5247143 citations. The organization is also known as: HHMI & hhmi.org.
Topics: Gene, RNA, Population, Cellular differentiation, Transcription factor
Papers published on a yearly basis
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TL;DR: This work has cloned, expressed, analysed electrical properties, and determined the crystal structure of a K+ channel (MthK) from Methanobacterium thermoautotrophicum in the Ca2+-bound, opened state.
Abstract: Ion channels exhibit two essential biophysical properties; that is, selective ion conduction, and the ability to gate-open in response to an appropriate stimulus. Two general categories of ion channel gating are defined by the initiating stimulus: ligand binding (neurotransmitter- or second-messenger-gated channels) or membrane voltage (voltage-gated channels). Here we present the structural basis of ligand gating in a K(+) channel that opens in response to intracellular Ca(2+). We have cloned, expressed, analysed electrical properties, and determined the crystal structure of a K(+) channel (MthK) from Methanobacterium thermoautotrophicum in the Ca(2+)-bound, opened state. Eight RCK domains (regulators of K(+) conductance) form a gating ring at the intracellular membrane surface. The gating ring uses the free energy of Ca(2+) binding in a simple manner to perform mechanical work to open the pore.
1,337 citations
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TL;DR: Calcium signaling activates the phosphatase calcineurin and induces movement of NFATc proteins into the nucleus, where they cooperate with other proteins to form complexes on DNA.
1,335 citations
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TL;DR: The results support a role for the striated muscle dystrophin-glycoprotein complex in linking the actin- based cytoskeleton with the extracellular matrix and suggest that dystophin and dystroglycan may play substantially different functional roles in nonmuscle tissues.
Abstract: The dystrophin-glycoprotein complex was tested for interaction with several components of the extracellular matrix as well as actin. The 156-kD dystrophin-associated glycoprotein (156-kD dystroglycan) specifically bound laminin in a calcium-dependent manner and was inhibited by NaCl (IC50 = 250 mM) but was not affected by 1,000-fold (wt/wt) excesses of lactose, IKVAV, or YIGSR peptides. Laminin binding was inhibited by heparin (IC50 = 100 micrograms/ml), suggesting that one of the heparin-binding domains of laminin is involved in binding dystroglycan while negatively charged oligosaccharide moieties on dystroglycan were found to be necessary for its laminin-binding activity. No interaction between any component of the dystrophin-glycoprotein complex and fibronectin, collagen I, collagen IV, entactin, or heparan sulfate proteoglycan was detected by 125I-protein overlay and/or extracellular matrix protein-Sepharose precipitation. In addition, laminin-Sepharose quantitatively precipitated purified dystrophin-glycoprotein complex, demonstrating that the laminin-binding site is accessible when dystroglycan is associated with the complex. Dystroglycan of nonmuscle tissues also bound laminin. However, the other proteins of the striated muscle dystrophin-glycoprotein complex appear to be absent, antigenically dissimilar or less tightly associated with dystroglycan in nonmuscle tissues. Finally, we show that the dystrophin-glycoprotein complex cosediments with F-actin but does not bind calcium or calmodulin. Our results support a role for the striated muscle dystrophin-glycoprotein complex in linking the actin-based cytoskeleton with the extracellular matrix. Furthermore, our results suggest that dystrophin and dystroglycan may play substantially different functional roles in nonmuscle tissues.
1,333 citations
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University of Adelaide1, Harvard University2, Broad Institute3, Howard Hughes Medical Institute4, University of Mainz5, Max Planck Society6, University of Tübingen7, Hungarian Academy of Sciences8, Stockholm University9, Facultad de Filosofía y Letras10, The Heritage Foundation11, University of Basel12, Autonomous University of Barcelona13, University of Valladolid14, Hartwick College15
TL;DR: In this paper, the authors generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost 400,000 polymorphisms.
Abstract: We generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost 400,000 polymorphisms. Enrichment of these positions decreases the sequencing required for genome-wide ancient DNA analysis by a median of around 250-fold, allowing us to study an order of magnitude more individuals than previous studies and to obtain new insights about the past. We show that the populations of Western and Far Eastern Europe followed opposite trajectories between 8,000-5,000 years ago. At the beginning of the Neolithic period in Europe, ∼8,000-7,000 years ago, closely related groups of early farmers appeared in Germany, Hungary and Spain, different from indigenous hunter-gatherers, whereas Russia was inhabited by a distinctive population of hunter-gatherers with high affinity to a ∼24,000-year-old Siberian. By ∼6,000-5,000 years ago, farmers throughout much of Europe had more hunter-gatherer ancestry than their predecessors, but in Russia, the Yamnaya steppe herders of this time were descended not only from the preceding eastern European hunter-gatherers, but also from a population of Near Eastern ancestry. Western and Eastern Europe came into contact ∼4,500 years ago, as the Late Neolithic Corded Ware people from Germany traced ∼75% of their ancestry to the Yamnaya, documenting a massive migration into the heartland of Europe from its eastern periphery. This steppe ancestry persisted in all sampled central Europeans until at least ∼3,000 years ago, and is ubiquitous in present-day Europeans. These results provide support for a steppe origin of at least some of the Indo-European languages of Europe.
1,332 citations
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TL;DR: It is argued that the requirement for two signals to initiate the adaptive immune response may reflect the evolutionary history of host defences.
1,332 citations
Authors
Showing all 20486 results
Name | H-index | Papers | Citations |
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Bert Vogelstein | 247 | 757 | 332094 |
Richard A. Flavell | 231 | 1328 | 205119 |
Steven A. Rosenberg | 218 | 1204 | 199262 |
Kenneth W. Kinzler | 215 | 640 | 243944 |
Robert J. Lefkowitz | 214 | 860 | 147995 |
Rob Knight | 201 | 1061 | 253207 |
Irving L. Weissman | 201 | 1141 | 172504 |
Ronald M. Evans | 199 | 708 | 166722 |
Francis S. Collins | 196 | 743 | 250787 |
Craig B. Thompson | 195 | 557 | 173172 |
Thomas C. Südhof | 191 | 653 | 118007 |
Joan Massagué | 189 | 408 | 149951 |
Stuart H. Orkin | 186 | 715 | 112182 |
John P. A. Ioannidis | 185 | 1311 | 193612 |
Eric R. Kandel | 184 | 603 | 113560 |