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91.
92.
Zeolites crystallize in a variety of three-dimensional structures in which oxygen atoms are shared between tetrahedra containing silicon and/or aluminium, thus yielding negatively charged tetrahedral frameworks that enclose cavities and pores of molecular dimensions occupied by charge-balancing metal cations and water molecules. Cation migration in the pores and changes in water content associated with concomitant relaxation of the framework have been observed in numerous variable-temperature studies, whereas the effects of hydrostatic pressure on the structure and properties of zeolites are less well explored. The zeolite sodium aluminosilicate natrolite was recently shown to undergo a volume expansion at pressures above 1.2 GPa as a result of reversible pressure-induced hydration; in contrast, a synthetic analogue, potassium gallosilicate natrolite, exhibited irreversible pressure-induced hydration with retention of the high-pressure phase at ambient conditions. Here we report the structure of the high-pressure recovered phase and contrast it with the high-pressure phase of the sodium aluminosilicate natrolite. Our findings show that the irreversible hydration behaviour is associated with a pronounced rearrangement of the non-framework metal ions, thus emphasizing that they can clearly have an important role in mediating the overall properties of zeolites. 相似文献
93.
Summary The alpha-adrenergic agonist phenylephrine (up to 1 mM) did not affect basal and NaF-stimulated adenylate cyclase activities of human fat cell ghosts, but caused a dose-dependent inhibition of cAMP formation in the presence of catecholamines. 相似文献
94.
Cichon S Buervenich S Kirov G Akula N Dimitrova A Green E Schumacher J Klopp N Becker T Ohlraun S Schulze TG Tullius M Gross MM Jones L Krastev S Nikolov I Hamshere M Jones I Czerski PM Leszczynska-Rodziewicz A Kapelski P Bogaert AV Illig T Hauser J Maier W Berrettini W Byerley W Coryell W Gershon ES Kelsoe JR McInnis MG Murphy DL Nurnberger JI Reich T Scheftner W O'Donovan MC Propping P Owen MJ Rietschel M Nöthen MM McMahon FJ Craddock N 《Nature genetics》2004,36(8):783-4; author reply 784-5
95.
Trifunovic A Wredenberg A Falkenberg M Spelbrink JN Rovio AT Bruder CE Bohlooly-Y M Gidlöf S Oldfors A Wibom R Törnell J Jacobs HT Larsson NG 《Nature》2004,429(6990):417-423
Point mutations and deletions of mitochondrial DNA (mtDNA) accumulate in a variety of tissues during ageing in humans, monkeys and rodents. These mutations are unevenly distributed and can accumulate clonally in certain cells, causing a mosaic pattern of respiratory chain deficiency in tissues such as heart, skeletal muscle and brain. In terms of the ageing process, their possible causative effects have been intensely debated because of their low abundance and purely correlative connection with ageing. We have now addressed this question experimentally by creating homozygous knock-in mice that express a proof-reading-deficient version of PolgA, the nucleus-encoded catalytic subunit of mtDNA polymerase. Here we show that the knock-in mice develop an mtDNA mutator phenotype with a threefold to fivefold increase in the levels of point mutations, as well as increased amounts of deleted mtDNA. This increase in somatic mtDNA mutations is associated with reduced lifespan and premature onset of ageing-related phenotypes such as weight loss, reduced subcutaneous fat, alopecia (hair loss), kyphosis (curvature of the spine), osteoporosis, anaemia, reduced fertility and heart enlargement. Our results thus provide a causative link between mtDNA mutations and ageing phenotypes in mammals. 相似文献
96.
Insight into steroid scaffold formation from the structure of human oxidosqualene cyclase 总被引:1,自引:0,他引:1
Thoma R Schulz-Gasch T D'Arcy B Benz J Aebi J Dehmlow H Hennig M Stihle M Ruf A 《Nature》2004,432(7013):118-122
In higher organisms the formation of the steroid scaffold is catalysed exclusively by the membrane-bound oxidosqualene cyclase (OSC; lanosterol synthase). In a highly selective cyclization reaction OSC forms lanosterol with seven chiral centres starting from the linear substrate 2,3-oxidosqualene. Valuable data on the mechanism of the complex cyclization cascade have been collected during the past 50 years using suicide inhibitors, mutagenesis studies and homology modelling. Nevertheless it is still not fully understood how the enzyme catalyses the reaction. Because of the decisive role of OSC in cholesterol biosynthesis it represents a target for the discovery of novel anticholesteraemic drugs that could complement the widely used statins. Here we present two crystal structures of the human membrane protein OSC: the target protein with an inhibitor that showed cholesterol lowering in vivo opens the way for the structure-based design of new OSC inhibitors. The complex with the reaction product lanosterol gives a clear picture of the way in which the enzyme achieves product specificity in this highly exothermic cyclization reaction. 相似文献
97.
Martensitic transformations are diffusionless, solid-to-solid phase transitions, and have been observed in metals, alloys, ceramics and proteins. They are characterized by a rapid change of crystal structure, accompanied by the development of a rich microstructure. Martensitic transformations can be irreversible, as seen in steels upon quenching, or they can be reversible, such as those observed in shape-memory alloys. In the latter case, the microstructures formed on cooling are easily manipulated by loads and disappear upon reheating. Here, using mathematical theory and numerical simulation, we explain these sharp differences in behaviour on the basis of the change in crystal symmetry during the transition. We find that a necessary condition for reversibility is that the symmetry groups of the parent and product phases be included in a common finite symmetry group. In these cases, the energy barrier to lattice-invariant shear is generically higher than that pertaining to the phase change and, consequently, transformations of this type can occur with virtually no plasticity. Irreversibility is inevitable in all other martensitic transformations, where the energy barrier to plastic deformation (via lattice-invariant shears, as in twinning or slip) is no higher than the barrier to the phase change itself. Various experimental observations confirm the importance of the symmetry of the stable states in determining the macroscopic reversibility of martensitic transformations. 相似文献
98.
99.
Dauwerse JG Dixon J Seland S Ruivenkamp CA van Haeringen A Hoefsloot LH Peters DJ Boers AC Daumer-Haas C Maiwald R Zweier C Kerr B Cobo AM Toral JF Hoogeboom AJ Lohmann DR Hehr U Dixon MJ Breuning MH Wieczorek D 《Nature genetics》2011,43(1):20-22
We identified a deletion of a gene encoding a subunit of RNA polymerases I and III, POLR1D, in an individual with Treacher Collins syndrome (TCS). Subsequently, we detected 20 additional heterozygous mutations of POLR1D in 252 individuals with TCS. Furthermore, we discovered mutations in both alleles of POLR1C in three individuals with TCS. These findings identify two additional genes involved in TCS, confirm the genetic heterogeneity of TCS and support the hypothesis that TCS is a ribosomopathy. 相似文献
100.
Suhre K Wallaschofski H Raffler J Friedrich N Haring R Michael K Wasner C Krebs A Kronenberg F Chang D Meisinger C Wichmann HE Hoffmann W Völzke H Völker U Teumer A Biffar R Kocher T Felix SB Illig T Kroemer HK Gieger C Römisch-Margl W Nauck M 《Nature genetics》2011,43(6):565-569
We present a genome-wide association study of metabolic traits in human urine, designed to investigate the detoxification capacity of the human body. Using NMR spectroscopy, we tested for associations between 59 metabolites in urine from 862 male participants in the population-based SHIP study. We replicated the results using 1,039 additional samples of the same study, including a 5-year follow-up, and 992 samples from the independent KORA study. We report five loci with joint P values of association from 3.2 × 10(-19) to 2.1 × 10(-182). Variants at three of these loci have previously been linked with important clinical outcomes: SLC7A9 is a risk locus for chronic kidney disease, NAT2 for coronary artery disease and genotype-dependent response to drug toxicity, and SLC6A20 for iminoglycinuria. Moreover, we identify rs37369 in AGXT2 as the genetic basis of hyper-β-aminoisobutyric aciduria. 相似文献