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991.
Mutations in SEPT9 cause hereditary neuralgic amyotrophy 总被引:7,自引:0,他引:7
Kuhlenbäumer G Hannibal MC Nelis E Schirmacher A Verpoorten N Meuleman J Watts GD De Vriendt E Young P Stögbauer F Halfter H Irobi J Goossens D Del-Favero J Betz BG Hor H Kurlemann G Bird TD Airaksinen E Mononen T Serradell AP Prats JM Van Broeckhoven C De Jonghe P Timmerman V Ringelstein EB Chance PF 《Nature genetics》2005,37(10):1044-1046
Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant recurrent neuropathy affecting the brachial plexus. HNA is triggered by environmental factors such as infection or parturition. We report three mutations in the gene septin 9 (SEPT9) in six families with HNA linked to chromosome 17q25. HNA is the first monogenetic disease caused by mutations in a gene of the septin family. Septins are implicated in formation of the cytoskeleton, cell division and tumorigenesis. 相似文献
992.
Remobilization of southern African desert dune systems by twenty-first century global warming 总被引:3,自引:0,他引:3
Although desert dunes cover 5 per cent of the global land surface and 30 per cent of Africa, the potential impacts of twenty-first century global warming on desert dune systems are not well understood. The inactive Sahel and southern African dune systems, which developed in multiple arid phases since the last interglacial period, are used today by pastoral and agricultural systems that could be disrupted if climate change alters twenty-first century dune dynamics. Empirical data and model simulations have established that the interplay between dune surface erodibility (determined by vegetation cover and moisture availability) and atmospheric erosivity (determined by wind energy) is critical for dunefield dynamics. This relationship between erodibility and erosivity is susceptible to climate-change impacts. Here we use simulations with three global climate models and a range of emission scenarios to assess the potential future activity of three Kalahari dunefields. We determine monthly values of dune activity by modifying and improving an established dune mobility index so that it can account for global climate model data outputs. We find that, regardless of the emission scenario used, significantly enhanced dune activity is simulated in the southern dunefield by 2039, and in the eastern and northern dunefields by 2069. By 2099 all dunefields are highly dynamic, from northern South Africa to Angola and Zambia. Our results suggest that dunefields are likely to be reactivated (the sand will become significantly exposed and move) as a consequence of twenty-first century climate warming. 相似文献
993.
994.
Mathematical models have become a necessary tool for organizing the rapidly increasing amounts of large-scale data on biochemical pathways and for advanced evaluation of their structure and regulation. Most of these models have addressed specific pathways using either stoichiometric or flux-balance analysis, or fully kinetic Michaelis-Menten representations, metabolic control analysis, or biochemical systems theory. So far, the predictions of kinetic models have rarely been tested using direct experimentation. Here, we validate experimentally a biochemical systems theoretical model of sphingolipid metabolism in yeast. Simulations of metabolic fluxes, enzyme deletion and the effects of inositol (a key regulator of phospholipid metabolism) led to predictions that show significant concordance with experimental results generated post hoc. The model also allowed the simulation of the effects of acute perturbations in fatty-acid precursors of sphingolipids, a situation that is not amenable to direct experimentation. The results demonstrate that modelling now allows testable predictions as well as the design and evaluation of hypothetical 'thought experiments' that may generate new metabolomic approaches. 相似文献
995.
Lister AM Edwards CJ Nock DA Bunce M van Pijlen IA Bradley DG Thomas MG Barnes I 《Nature》2005,438(7069):850-853
The giant deer, or 'Irish elk', has featured extensively in debates on adaptation, sexual selection, and extinction. Its huge antlers--the largest of any deer species, living or extinct--formed a focus of much past work. Yet the phylogenetic position of the giant deer has remained an enigma. On the basis of its flattened antlers, the species was previously regarded as closely related to the living fallow deer. Recent morphological studies, however, have challenged that view and placed the giant deer closer to the living red deer or wapiti. Here we present a new phylogenetic analysis encompassing morphological and DNA sequence evidence, and find that both sets of data independently support a sister-group relationship of giant and fallow deer. Our results include the successful extraction and sequencing of DNA from this extinct species, and highlight the value of a joint molecular and morphological approach. 相似文献
996.
LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription 总被引:4,自引:0,他引:4
Metzger E Wissmann M Yin N Müller JM Schneider R Peters AH Günther T Buettner R Schüle R 《Nature》2005,437(7057):436-439
997.
Yip CK Kimbrough TG Felise HB Vuckovic M Thomas NA Pfuetzner RA Frey EA Finlay BB Miller SI Strynadka NC 《Nature》2005,435(7042):702-707
Type III secretion systems (TTSSs) are multi-protein macromolecular 'machines' that have a central function in the virulence of many Gram-negative pathogens by directly mediating the secretion and translocation of bacterial proteins (termed effectors) into the cytoplasm of eukaryotic cells. Most of the 20 unique structural components constituting this secretion apparatus are highly conserved among animal and plant pathogens and are also evolutionarily related to proteins in the flagellar-specific export system. Recent electron microscopy experiments have revealed the gross 'needle-shaped' morphology of the TTSS, yet a detailed understanding of the structural characteristics and organization of these protein components within the bacterial membranes is lacking. Here we report the 1.8-A crystal structure of EscJ from enteropathogenic Escherichia coli (EPEC), a member of the YscJ/PrgK family whose oligomerization represents one of the earliest events in TTSS assembly. Crystal packing analysis and molecular modelling indicate that EscJ could form a large 24-subunit 'ring' superstructure with extensive grooves, ridges and electrostatic features. Electron microscopy, labelling and mass spectrometry studies on the orthologous Salmonella typhimurium PrgK within the context of the assembled TTSS support the stoichiometry, membrane association and surface accessibility of the modelled ring. We propose that the YscJ/PrgK protein family functions as an essential molecular platform for TTSS assembly. 相似文献
998.
The birth of stars involves not only accretion but also, counter-intuitively, the expulsion of matter in the form of highly supersonic outflows. Although this phenomenon has been seen in young stars, a fundamental question is whether it also occurs among newborn brown dwarfs: these are the so-called 'failed stars', with masses between stars and planets, that never manage to reach temperatures high enough for normal hydrogen fusion to occur. Recently, evidence for accretion in young brown dwarfs has mounted, and their spectra show lines that are suggestive of outflows. Here we report spectro-astrometric data that spatially resolve an outflow from a brown dwarf. The outflow's characteristics appear similar to, but on a smaller scale than, outflows from normal young stars. This result suggests that the outflow mechanism is universal, and perhaps relevant even to the formation of planets. 相似文献
999.
1000.
I examine the thesis that Otto Neurath anticipated the programme of naturalised epistemology already at the time of the Vienna Circle and consider the relation between Neurath's proposals and those of two contemporary theorists whose research programmes he would thus have broadly anticipated. The thesis is confirmed by reference to Neurath's own writings. The connection between Neurath's programme and the programmes of his two successors considered here, however, is found to be highly indirect in one case and nonexistent in the other — despite their undeniable overlap. 相似文献