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51.
Houlden H Johnson J Gardner-Thorpe C Lashley T Hernandez D Worth P Singleton AB Hilton DA Holton J Revesz T Davis MB Giunti P Giunti P Wood NW 《Nature genetics》2007,39(12):1434-1436
The microtubule-associated protein tau (encoded by MAPT) and several tau kinases have been implicated in neurodegeneration, but only MAPT has a proven role in disease. We identified mutations in the gene encoding tau tubulin kinase 2 (TTBK2) as the cause of spinocerebellar ataxia type 11. Affected brain tissue showed substantial cerebellar degeneration and tau deposition. These data suggest that TTBK2 is important in the tau cascade and in spinocerebellar degeneration. 相似文献
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Two defining functional features of ion channels are ion selectivity and channel gating. Ion selectivity is generally considered an immutable property of the open channel structure, whereas gating involves transitions between open and closed channel states, typically without changes in ion selectivity. In store-operated Ca(2+) release-activated Ca(2+) (CRAC) channels, the molecular mechanism of channel gating by the CRAC channel activator, stromal interaction molecule 1 (STIM1), remains unknown. CRAC channels are distinguished by a very high Ca(2+) selectivity and are instrumental in generating sustained intracellular calcium concentration elevations that are necessary for gene expression and effector function in many eukaryotic cells. Here we probe the central features of the STIM1 gating mechanism in the human CRAC channel protein, ORAI1, and identify V102, a residue located in the extracellular region of the pore, as a candidate for the channel gate. Mutations at V102 produce constitutively active CRAC channels that are open even in the absence of STIM1. Unexpectedly, although STIM1-free V102 mutant channels are not Ca(2+)-selective, their Ca(2+) selectivity is dose-dependently boosted by interactions with STIM1. Similar enhancement of Ca(2+) selectivity is also seen in wild-type ORAI1 channels by increasing the number of STIM1 activation domains that are directly tethered to ORAI1 channels, or by increasing the relative expression of full-length STIM1. Thus, exquisite Ca(2+) selectivity is not an intrinsic property of CRAC channels but rather a tuneable feature that is bestowed on otherwise non-selective ORAI1 channels by STIM1. Our results demonstrate that STIM1-mediated gating of CRAC channels occurs through an unusual mechanism in which permeation and gating are closely coupled. 相似文献
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Mary Jo Nye 《Annals of science》2013,70(5):585-590
The influential French chemist Marcelin Berthelot spoke against the use of Dalton's atomic theory and Avogadro's hypothesis in the second half of the nineteenth century. This paper argues that Berthelot conceded that atomism might be acceptable as a system of conventions, but he feared the power of such conventions in constructing a realistic picture of atoms which was not warranted empirically. Equally, Berthelot's anti-atomism was a last-ditch effort to assert the place of chemistry within the tradition of natural history and to deny the possible reduction of chemical science to the laws of nineteenth-century physics. 相似文献
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FengPing Wang ShuLin Lu Beth N. Orcutt Wei Xie Ying Chen Xiang Xiao Katrina J. Edwards 《科学通报(英文版)》2013,58(4-5):456-467
The discovery of the marine “deep biosphere”—microorganisms living deep below the seafloor—is one of the most significant and exciting discoveries since the ocean drilling program began more than 40 years ago. Study of the deep biosphere has become a research frontier and a hot spot both for geological and biological sciences. Here, we introduce the history of the discovery of the deep biosphere, and then we describe the types of environments for life below the seafloor, the energy sources for the living creatures, the diversity of organisms within the deep biosphere, and the new tools and technologies used in this research field. We will highlight several recently completed Integrated Ocean Drilling Program Expeditions, which targeted the subseafloor deep biosphere within the crust and sediments. Finally, future research directions and challenges of deep biosphere investigation towards uncovering the roles of subsurface microorganisms will be briefly addressed. 相似文献
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Zusammenfassung Sieben inaktive Begleit-Corticosteroide, die vonReichstein und anderen aus der Nebennierenrinde isoliert worden sind, enthalten ein Asymmetriezentrum in C20. Es sind bisher sind noch keine Schlußfolgerungen bezüglich der Konfiguration der natürlichen Substanzen in diesem Zentrum relativ zum Rest des Moleküls gezogen worden.In der vorliegenden Abhandlung wird darauf hingewiesen, daß die Konfiguration an Hand der Betrachtung des Hinderniseffekts, welcher wahrscheinlich den sterischen Lauf der Reaktionen, die zur Partialsynthese der Verbindungen dieser Gruppe angewendet werden, reguliert, mit ziemlicher Sicherheit abgeleitet werden kann. Auf diese Weise sind die Konfigurationen aller sieben natürlichen Steroide festgesetzt und mit den Bezeichnungen der vorgeschlagenen Nomenklatur für die Beschreibung der Konfiguration in C20 relativ zu der in C17 unter Bezugnahme auf ein zyklisches Zwischenprodukt von festgesetzter geometrischer Orientierung ausgedrückt worden.Die Konfiguration in C20 einiger synthetischer 20-Oxy-Verbindungen der 17-Isoallopregnan- und 17-Iso-5-pregnen-Reihe sind durch Vergleich mit den entsprechenden 17-Normal-Verbindungen mit Hilfe der Methode des Molekularrotationsunterschiedes nachBarton abgeleitet worden. Im Falle zweier epimerischer 17-Isoallopregnan-3,17,20-triole sind die optischen Eigenschaften nicht entscheidend und zwei Serien von experimentellen Tatsachen scheinen sich zu widersprechen.Experimentelles Beweismaterial, das erst nach der Fertigstellung dieser Abhandlung beigebracht worden war, zeigt, daß eine der Literaturangaben unrichtig ist, wie in der «Note added to proof» erwähnt worden ist.In der Abhandlung ist eine Reihe von Vorschlägen für die Standardisierung der Nomenklatur der Steroide eingeschlossen. 相似文献
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Mary Anne Rogers 《西北部美国博物学家》2011,51(2)
Geographic and nongeographic variation in morphology was examined in Thomomys townsendii . A univariate analysis of external and cranial characters from a large population sample (66 adults; fusion of cranial sutures used as aging criteria) was used to assess variation among three adult age classes and between sexes. Only minor variation is apparent among age classes; however, sexual dimorphism is pronounced. Univariate and multivariate techniques were used to analyze external and cranial measurements and pelage characters for adults throughout the species range. These analyses show little to support the seven subspecific designations recognized by Davis (1937). The general pattern is one of homogeneity throughout the range of Thomomys townsendii . With the possible exception of T. t. nevadensis samples, current subspecies are not defined as morphological units. In fact, differentiation is found among populations within some subspecies. The most apparent pattern seen in these analyses is the divergence between the Humboldt River (including Honey Lake Valley samples) and Snake River systems. These results will be considered with those of a companion paper on the genetic variation in this species to more adequately assess the patterns of differentiation in Thomomys townsendii . 相似文献
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We report the first records of the western gray squirrel ( Sciurus griseus ) from Modoc County and eastern Lassen County in northeastern California. Specimens from Modoc County represent the first records of the species from the Great Basin geographic province. We conclude that these records represent a range expansion based upon previous fieldwork that did not report the species in the region. 相似文献