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排序方式: 共有67条查询结果,搜索用时 15 毫秒
1.
Alcaïs A Alter A Antoni G Orlova M Nguyen VT Singh M Vanderborght PR Katoch K Mira MT Vu HT Ngyuen TH Nguyen NB Moraes M Mehra N Schurr E Abel L 《Nature genetics》2007,39(4):517-522
Host genetics has an important role in leprosy, and variants in the shared promoter region of PARK2 and PACRG were the first major susceptibility factors identified by positional cloning. Here we report the linkage disequilibrium mapping of the second linkage peak of our previous genome-wide scan, located close to the HLA complex. In both a Vietnamese familial sample and an Indian case-control sample, the low-producing lymphotoxin-alpha (LTA)+80 A allele was significantly associated with an increase in leprosy risk (P = 0.007 and P = 0.01, respectively). Analysis of an additional case-control sample from Brazil and an additional familial sample from Vietnam showed that the LTA+80 effect was much stronger in young individuals. In the combined sample of 298 Vietnamese familial trios, the odds ratio of leprosy for LTA+80 AA/AC versus CC subjects was 2.11 (P = 0.000024), which increased to 5.63 (P = 0.0000004) in the subsample of 121 trios of affected individuals diagnosed before 16 years of age. In addition to identifying LTA as a major gene associated with early-onset leprosy, our study highlights the critical role of case- and population-specific factors in the dissection of susceptibility variants in complex diseases. 相似文献
2.
Zusammenfassung Der Seitenkettenabbau von C21-Steroiden zu Androgenen in Rattentesteshomogenat erwies sich abhängig von der Konzentration der Vorstufen und konnte durch gewisse Pyridinderivate präferentiell blockiert werden. 相似文献
3.
The fossil record preserves numerous natural experiments that can shed light on the response of ecological communities to environmental change. However, directly observing the community dynamics of extinct organisms is not possible. As an alternative, neutral ecological models suggest that species abundance distributions reflect dynamical processes like migration, competition, recruitment, and extinction. Live-dead comparisons suggest that such distributions can be faithfully preserved in the rock record. Here we use a maximum-likelihood approach to show that brachiopod (lamp shell) abundance distributions from four temporally distinct ecological landscapes from the Glass Mountains, Texas (of the Permian period), exhibit significant differences. Further, all four are better fitted by zero-sum multinomial distributions, characteristic of Hubbell's neutral model, than by log-normal distributions, as predicted by the traditional ecological null hypothesis. Using the neutral model as a guide, we suggest that sea level fluctuations spanning about 10 Myr altered the degrees of isolation and exchange among local communities within these ecological landscapes. Neither these long-term environmental changes nor higher-frequency sea level fluctuations resulted in wholesale extinction or major innovation within evolutionary lineages. 相似文献
4.
Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome 总被引:6,自引:0,他引:6
Windpassinger C Auer-Grumbach M Irobi J Patel H Petek E Hörl G Malli R Reed JA Dierick I Verpoorten N Warner TT Proukakis C Van den Bergh P Verellen C Van Maldergem L Merlini L De Jonghe P Timmerman V Crosby AH Wagner K 《Nature genetics》2004,36(3):271-276
Distal hereditary motor neuropathy (dHMN) or distal spinal muscular atrophy (OMIM #182960) is a heterogeneous group of disorders characterized by an almost exclusive degeneration of motor nerve fibers, predominantly in the distal part of the limbs. Silver syndrome (OMIM #270685) is a rare form of hereditary spastic paraparesis mapped to chromosome 11q12-q14 (SPG17) in which spasticity of the legs is accompanied by amyotrophy of the hands and occasionally also the lower limbs. Silver syndrome and most forms of dHMN are autosomal dominantly inherited with incomplete penetrance and a broad variability in clinical expression. A genome-wide scan in an Austrian family with dHMN-V (ref. 4) showed linkage to the locus SPG17, which was confirmed in 16 additional families with a phenotype characteristic of dHMN or Silver syndrome. After refining the critical region to 1 Mb, we sequenced the gene Berardinelli-Seip congenital lipodystrophy (BSCL2) and identified two heterozygous missense mutations resulting in the amino acid substitutions N88S and S90L. Null mutations in BSCL2, which encodes the protein seipin, were previously shown to be associated with autosomal recessive Berardinelli-Seip congenital lipodystrophy (OMIM #269700). We show that seipin is an integral membrane protein of the endoplasmic reticulum (ER). The amino acid substitutions N88S and S90L affect glycosylation of seipin and result in aggregate formation leading to neurodegeneration. 相似文献
5.
Increasing dominance of large lianas in Amazonian forests 总被引:1,自引:0,他引:1
Phillips OL Vásquez Martínez R Arroyo L Baker TR Killeen T Lewis SL Malhi Y Monteagudo Mendoza A Neill D Núñez Vargas P Alexiades M Cerón C Di Fiore A Erwin T Jardim A Palacios W Saldias M Vinceti B 《Nature》2002,418(6899):770-774
Ecological orthodoxy suggests that old-growth forests should be close to dynamic equilibrium, but this view has been challenged by recent findings that neotropical forests are accumulating carbon and biomass, possibly in response to the increasing atmospheric concentrations of carbon dioxide. However, it is unclear whether the recent increase in tree biomass has been accompanied by a shift in community composition. Such changes could reduce or enhance the carbon storage potential of old-growth forests in the long term. Here we show that non-fragmented Amazon forests are experiencing a concerted increase in the density, basal area and mean size of woody climbing plants (lianas). Over the last two decades of the twentieth century the dominance of large lianas relative to trees has increased by 1.7-4.6% a year. Lianas enhance tree mortality and suppress tree growth, so their rapid increase implies that the tropical terrestrial carbon sink may shut down sooner than current models suggest. Predictions of future tropical carbon fluxes will need to account for the changing composition and dynamics of supposedly undisturbed forests. 相似文献
6.
RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-beta 总被引:18,自引:0,他引:18
Takayanagi H Kim S Matsuo K Suzuki H Suzuki T Sato K Yokochi T Oda H Nakamura K Ida N Wagner EF Taniguchi T 《Nature》2002,416(6882):744-749
7.
Intracellularly injected tetanus toxin inhibits exocytosis in bovine adrenal chromaffin cells 总被引:19,自引:0,他引:19
The clostridial neurotoxins tetanus and botulinum toxin type A are known to block transmitter release from nerve terminals, probably by interfering with some essential process controlling exocytosis after the entry of Ca2+ ions. Although exocytosis occurs in many secretory cells, these toxins show a high specificity for neurones and the secretory response of cultured bovine adrenal medullary cells is not inhibited by exposure to medium containing tetanus or botulinum toxin type A (although it is by botulinum toxin type D). Here we report that when tetanus toxin and botulinum neurotoxin type A are injected intracellularly into chromaffin cells they strongly inhibit secretion, as revealed by the measurement of cell capacitance. These results indicate that these toxins are normally ineffective in chromaffin cells because they are not bound and internalized, so do not reach their site of action. Furthermore, we have localized the secretion-blocking effects of the toxin to a fragment comprising the light chain covalently linked to part of the heavy chain, suggesting that this part of the molecule contains the active site. 相似文献
8.
Delay in vesicle fusion revealed by electrochemical monitoring of single secretory events in adrenal chromaffin cells. 总被引:48,自引:0,他引:48
In synapses, a rise in presynaptic intracellular calcium leads to secretory vesicle fusion in less than a millisecond, as indicated by the short delay from excitation to postsynaptic signal. In nonsynaptic secretory cells, studies at high time resolution have been limited by the lack of a detector as fast and sensitive as the postsynaptic membrane. Electrochemical methods may be sensitive enough to detect catecholamines released from single vesicles. Here, we show that under voltage-clamp conditions, stochastically occurring signals can be recorded from adrenal chromaffin cells using a carbon-fibre electrode as an electrochemical detector. These signals obey statistics characteristic for quantal release; however, in contrast to neuronal transmitter release, secretion occurs with a significant delay after short step depolarizations. Furthermore, we identify a pedestal or 'foot' at the onset of unitary events which may represent the slow leak of catecholamine molecules out of a narrow 'fusion pore' before the pore dilates for complete exocytosis. 相似文献
9.
Summary Within a new series of 3- and 4-monosubstituted pyridin derivatives, some have been found to modify qualitatively and quantitatively the adrenocortical function in vitro as preferential inhibitors of aldosterone or cortisol and as stimulators of corticosterone and cortisol respectively.
Mitteilung IV «Über die adrenale Steroidbiosynthese in vitro». 相似文献
Mitteilung IV «Über die adrenale Steroidbiosynthese in vitro». 相似文献
10.
Summary Cortexone labeled in the 21-position with C14 yielded radioactive Aldosterone through incubation with beef adrenal homogenate. Its activity, due entirely to the 21 carbon atom, showed that about 48% of the Aldosterone had arisen from a direct conversion of cortexone without intermediate degradation. The low yield by weight in this conversion suggests, however, that cortexone is not the only natural precursor for Aldosterone in the adrenal.The radioactivity of the corticosterone obtained showed that about 84% of it originated from added cortexone. Lack of radioactivity of the hydrocortisone confirmed that it does not essentially result from cortexone.
134. Mitteilung über Steroide. Auszugsweise vorgetragen am 3. August 1955 anlässlich des 3. Internat. Kongresses für Biochemie in Brüssel. 133. Mitteilung sieheE. Vischer, Ch. Meystre undA. Wettstein, Helv. chim. Acta38, 1502 (1955). 相似文献
134. Mitteilung über Steroide. Auszugsweise vorgetragen am 3. August 1955 anlässlich des 3. Internat. Kongresses für Biochemie in Brüssel. 133. Mitteilung sieheE. Vischer, Ch. Meystre undA. Wettstein, Helv. chim. Acta38, 1502 (1955). 相似文献