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991.
Reineke J Tenzer S Rupnik M Koschinski A Hasselmayer O Schrattenholz A Schild H von Eichel-Streiber C 《Nature》2007,446(7134):415-419
Clostridium difficile, the causative agent of nosocomial antibiotic-associated diarrhoea and pseudomembranous colitis, possesses two main virulence factors: the large clostridial cytotoxins A and B. It has been proposed that toxin B is cleaved by a cytosolic factor of the eukaryotic target cell during its cellular uptake. Here we report that cleavage of not only toxin B, but also all other large clostridial cytotoxins, is an autocatalytic process dependent on host cytosolic inositolphosphate cofactors. A covalent inhibitor of aspartate proteases, 1,2-epoxy-3-(p-nitrophenoxy)propane, completely blocked toxin B function on cultured cells and was used to identify its catalytically active protease site. To our knowledge this is the first report on a bacterial toxin that uses eukaryotic signals for induced autoproteolysis to deliver its toxic domain into the cytosol of target cells. On the basis of our data, we present an integrated model for the uptake and inositolphosphate-induced activation of toxin B. 相似文献
992.
Tomasko MG Archinal B Becker T Bézard B Bushroe M Combes M Cook D Coustenis A de Bergh C Dafoe LE Doose L Douté S Eibl A Engel S Gliem F Grieger B Holso K Howington-Kraus E Karkoschka E Keller HU Kirk R Kramm R Küppers M Lanagan P Lellouch E Lemmon M Lunine J McFarlane E Moores J Prout GM Rizk B Rosiek M Rueffer P Schröder SE Schmitt B See C Smith P Soderblom L Thomas N West R 《Nature》2005,438(7069):765-778
The irreversible conversion of methane into higher hydrocarbons in Titan's stratosphere implies a surface or subsurface methane reservoir. Recent measurements from the cameras aboard the Cassini orbiter fail to see a global reservoir, but the methane and smog in Titan's atmosphere impedes the search for hydrocarbons on the surface. Here we report spectra and high-resolution images obtained by the Huygens Probe Descent Imager/Spectral Radiometer instrument in Titan's atmosphere. Although these images do not show liquid hydrocarbon pools on the surface, they do reveal the traces of once flowing liquid. Surprisingly like Earth, the brighter highland regions show complex systems draining into flat, dark lowlands. Images taken after landing are of a dry riverbed. The infrared reflectance spectrum measured for the surface is unlike any other in the Solar System; there is a red slope in the optical range that is consistent with an organic material such as tholins, and absorption from water ice is seen. However, a blue slope in the near-infrared suggests another, unknown constituent. The number density of haze particles increases by a factor of just a few from an altitude of 150 km to the surface, with no clear space below the tropopause. The methane relative humidity near the surface is 50 per cent. 相似文献
993.
Unprecedented Arctic ozone loss in 2011 总被引:7,自引:0,他引:7
Manney GL Santee ML Rex M Livesey NJ Pitts MC Veefkind P Nash ER Wohltmann I Lehmann R Froidevaux L Poole LR Schoeberl MR Haffner DP Davies J Dorokhov V Gernandt H Johnson B Kivi R Kyrö E Larsen N Levelt PF Makshtas A McElroy CT Nakajima H Parrondo MC Tarasick DW von der Gathen P Walker KA Zinoviev NS 《Nature》2011,478(7370):469-475
Chemical ozone destruction occurs over both polar regions in local winter-spring. In the Antarctic, essentially complete removal of lower-stratospheric ozone currently results in an ozone hole every year, whereas in the Arctic, ozone loss is highly variable and has until now been much more limited. Here we demonstrate that chemical ozone destruction over the Arctic in early 2011 was--for the first time in the observational record--comparable to that in the Antarctic ozone hole. Unusually long-lasting cold conditions in the Arctic lower stratosphere led to persistent enhancement in ozone-destroying forms of chlorine and to unprecedented ozone loss, which exceeded 80 per cent over 18-20 kilometres altitude. Our results show that Arctic ozone holes are possible even with temperatures much milder than those in the Antarctic. We cannot at present predict when such severe Arctic ozone depletion may be matched or exceeded. 相似文献
994.
Lindblad-Toh K Garber M Zuk O Lin MF Parker BJ Washietl S Kheradpour P Ernst J Jordan G Mauceli E Ward LD Lowe CB Holloway AK Clamp M Gnerre S Alföldi J Beal K Chang J Clawson H Cuff J Di Palma F Fitzgerald S Flicek P Guttman M Hubisz MJ Jaffe DB Jungreis I Kent WJ Kostka D Lara M Martins AL Massingham T Moltke I Raney BJ Rasmussen MD Robinson J Stark A Vilella AJ Wen J Xie X Zody MC;Broad Institute Sequencing Platform Whole Genome Assembly Team Baldwin J Bloom T Chin CW Heiman D Nicol R 《Nature》2011,478(7370):476-482
The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ~4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ~60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease. 相似文献
995.
Mortlock DJ Warren SJ Venemans BP Patel M Hewett PC McMahon RG Simpson C Theuns T Gonzáles-Solares EA Adamson A Dye S Hambly NC Hirst P Irwin MJ Kuiper E Lawrence A Röttgering HJ 《Nature》2011,474(7353):616-619
The intergalactic medium was not completely reionized until approximately a billion years after the Big Bang, as revealed by observations of quasars with redshifts of less than 6.5. It has been difficult to probe to higher redshifts, however, because quasars have historically been identified in optical surveys, which are insensitive to sources at redshifts exceeding 6.5. Here we report observations of a quasar (ULAS?J112001.48+064124.3) at a redshift of 7.085, which is 0.77 billion years after the Big Bang. ULAS?J1120+0641 has a luminosity of 6.3 × 10(13)L(⊙) and hosts a black hole with a mass of 2 × 10(9)M(⊙) (where L(⊙) and M(⊙) are the luminosity and mass of the Sun). The measured radius of the ionized near zone around ULAS?J1120+0641 is 1.9?megaparsecs, a factor of three smaller than is typical for quasars at redshifts between 6.0 and 6.4. The near-zone transmission profile is consistent with a Lyα damping wing, suggesting that the neutral fraction of the intergalactic medium in front of ULAS?J1120+0641 exceeded 0.1. 相似文献
996.
Stadler MB Murr R Burger L Ivanek R Lienert F Schöler A van Nimwegen E Wirbelauer C Oakeley EJ Gaidatzis D Tiwari VK Schübeler D 《Nature》2011,480(7378):490-495
997.
Standfuss J Edwards PC D'Antona A Fransen M Xie G Oprian DD Schertler GF 《Nature》2011,471(7340):656-660
G-protein-coupled receptors (GPCRs) comprise the largest family of membrane proteins in the human genome and mediate cellular responses to an extensive array of hormones, neurotransmitters and sensory stimuli. Although some crystal structures have been determined for GPCRs, most are for modified forms, showing little basal activity, and are bound to inverse agonists or antagonists. Consequently, these structures correspond to receptors in their inactive states. The visual pigment rhodopsin is the only GPCR for which structures exist that are thought to be in the active state. However, these structures are for the apoprotein, or opsin, form that does not contain the agonist all-trans retinal. Here we present a crystal structure at a resolution of 3 ? for the constitutively active rhodopsin mutant Glu 113 Gln in complex with a peptide derived from the carboxy terminus of the α-subunit of the G protein transducin. The protein is in an active conformation that retains retinal in the binding pocket after photoactivation. Comparison with the structure of ground-state rhodopsin suggests how translocation of the retinal β-ionone ring leads to a rotation of transmembrane helix 6, which is the critical conformational change on activation. A key feature of this conformational change is a reorganization of water-mediated hydrogen-bond networks between the retinal-binding pocket and three of the most conserved GPCR sequence motifs. We thus show how an agonist ligand can activate its GPCR. 相似文献
998.
The quasi-biennial oscillation (QBO) and semi-annual oscillation (SAO) characteristics of O3, NO2, and NO3 from 2002 to 2008 were analyzed using Global Ozone Monitoring by Occultation of Stars (GOMOS) satellite observations. From
investigations of the vertical and latitudinal structures of interannual anomalies for O3 and the vertical velocity of the
residual circulation (w-star), we conclude that dynamic transport is the principal factor controlling the QBO pattern of O3. Under the influence of vertical transport, the QBO signals of O3 originate in the middle stratosphere and propagate downward along with the w-star anomalies over the equator. The residual
circulation has a significant role in tropical regions, regardless of altitude, while in extratropical regions, dynamic effects
are important in some years in the lower stratosphere. In the middle stratosphere, dynamic transport is most efficient in
the Southern Hemisphere. We also analyzed NO2 anomalies and found that their QBO pattern was deep and stationary in the middle and upper stratosphere over the equator.
This was due to the large depth over which w-star was anomalous. The latitudinal structure of NO2 was asymmetric in extratropical areas in the middle stratosphere, but in the upper layers, the QBO pattern and dynamic influences
were only observed in tropical zones. The interannual anomalies of NO3 had an apparent SAO pattern in the tropical upper stratosphere because of different dynamic and chemical effects in different
SAO phases. Chemical reactions may also have contributed to the QBO-type distribution of NO2 and the SAO-type distribution of NO3. 相似文献
999.
Ohne Zusammenfassung 相似文献
1000.