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Many receptors and allosteric proteins function through binding of a molecule to induce a conformational change, which then influences a remote active site. In synthetic systems, comparable intramolecular information transfer can be effected by using the shape of one part of a molecule to control the stereoselectivity of reactions occurring some distance away. However, the need for direct communication with the reaction site usually limits such remote stereocontrol to distances of not more than about five bond lengths. Cyclic structures overcome this problem by allowing the controlling centre and the reaction site to approach each other, but the information transfer spans only short absolute distances. Truly remote stereocontrol can, however, be achieved with rigid compounds containing amide groups: the conformation of the amides can be controlled by stereogenic centres and responds to that of neighbouring amide groups and in turn influences stereoselective reactions. This strategy has allowed remote stereocontrol spanning 8 (ref. 11) or 9 (ref. 12) bonds. Here we demonstrate stereocontrol over a reaction taking place more than 20 bond lengths from the controlling centre, corresponding to a linear distance of over 2.5 nm. This transmission of information, achieved by conformational changes relayed through the molecule, provides a chemical model of allostery and might serve as a molecular mechanism for communicating and processing information. 相似文献
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Kao WH Klag MJ Meoni LA Reich D Berthier-Schaad Y Li M Coresh J Patterson N Tandon A Powe NR Fink NE Sadler JH Weir MR Abboud HE Adler SG Divers J Iyengar SK Freedman BI Kimmel PL Knowler WC Kohn OF Kramp K Leehey DJ Nicholas SB Pahl MV Schelling JR Sedor JR Thornley-Brown D Winkler CA Smith MW Parekh RS;Family Investigation of Nephropathy Diabetes Research Group 《Nature genetics》2008,40(10):1185-1192
As end-stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans, we hypothesized that susceptibility alleles for ESRD have a higher frequency in the West African than the European gene pool. We carried out a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and found a highly significant association between excess African ancestry and nondiabetic ESRD (lod score = 5.70) but not diabetic ESRD (lod = 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% CI = 0.39-0.63) compared to African ancestry. Multiple common SNPs (allele frequencies ranging from 0.2 to 0.6) in the gene encoding nonmuscle myosin heavy chain type II isoform A (MYH9) were associated with two to four times greater risk of nondiabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans. 相似文献
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Gribouval O Gonzales M Neuhaus T Aziza J Bieth E Laurent N Bouton JM Feuillet F Makni S Ben Amar H Laube G Delezoide AL Bouvier R Dijoud F Ollagnon-Roman E Roume J Joubert M Antignac C Gubler MC 《Nature genetics》2005,37(9):964-968
Autosomal recessive renal tubular dysgenesis is a severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (Potter phenotype). Absence or paucity of differentiated proximal tubules is the histopathological hallmark of the disease and may be associated with skull ossification defects. We studied 11 individuals with renal tubular dysgenesis, belonging to nine families, and found that they had homozygous or compound heterozygous mutations in the genes encoding renin, angiotensinogen, angiotensin converting enzyme or angiotensin II receptor type 1. We propose that renal lesions and early anuria result from chronic low perfusion pressure of the fetal kidney, a consequence of renin-angiotensin system inactivity. This is the first identification to our knowledge of a renal mendelian disorder linked to genetic defects in the renin-angiotensin system, highlighting the crucial role of the renin-angiotensin system in human kidney development. 相似文献
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Madeleine Lamborot A. Espinoza E. Alvarez 《Cellular and molecular life sciences : CMLS》1979,35(5):593-595
Summary Most of 12 taxa karyotypes retain 6 pairs of metacentric macrochromosomes (primitive), but show reduced numbers of microchromosomes (2n=34, 32 and 30). Others whow increased diploid numbers due to macrochromosomal fissions (up to 4 fissions, 2n=40). One shows a fission polymorphism.We thank Dr. W.P. Hall for his many suggestions and comments; and L. Alvarez, E. Barrientos, I. Campos, M. Fernandez and F.N. Manzur for generous assistance. This study was aided by the Project del Servicio de Desarrollo Científico de la Universidad de Chile, No. B259-783. 相似文献
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Barbara E. C. Banks Jill R. Carstairs Madeleine Ennis f. L. Pearce C. A. Vernon 《Cellular and molecular life sciences : CMLS》1978,34(10):1371-1372
Summary The effects in vivo and in vitro of the antiserum to mouse nerve growth factor (NGF) are independent of the presence of complement. These results are consistent with the view that the antiserum acts by neutralizing endogenous NGF.Acknowledgments. Financial support from the Whitehall Foundation, New York, The Wellcome Foundation, U.K. (to J.R.C.) and the Science Research Council (Studentship to M.E.) is gratefully acknowledged. We thank Professor J.H. Humphrey, National Institute for Medical, Research, Mill Hill, London, for discussion and determination of plasma C3 levels. 相似文献
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Explosive volcanic eruptions are driven by exsolution of H2O-rich vapour from silicic magma. Eruption dynamics involve a complex interplay between nucleation and growth of vapour bubbles and crystallization, generating highly nonlinear variation in the physical properties of magma as it ascends beneath a volcano. This makes explosive volcanism difficult to model and, ultimately, to predict. A key unknown is the temperature variation in magma rising through the sub-volcanic system, as it loses gas and crystallizes en route. Thermodynamic modelling of magma that degasses, but does not crystallize, indicates that both cooling and heating are possible. Hitherto it has not been possible to evaluate such alternatives because of the difficulty of tracking temperature variations in moving magma several kilometres below the surface. Here we extend recent work on glassy melt inclusions trapped in plagioclase crystals to develop a method for tracking pressure-temperature-crystallinity paths in magma beneath two active andesite volcanoes. We use dissolved H2O in melt inclusions to constrain the pressure of H2O at the time an inclusion became sealed, incompatible trace element concentrations to calculate the corresponding magma crystallinity and plagioclase-melt geothermometry to determine the temperature. These data are allied to ilmenite-magnetite geothermometry to show that the temperature of ascending magma increases by up to 100 degrees C, owing to the release of latent heat of crystallization. This heating can account for several common textural features of andesitic magmas, which might otherwise be erroneously attributed to pre-eruptive magma mixing. 相似文献
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K. B. Ruf E. V. YoungLai J. H. Kitchen Madeleine Vuillet 《Cellular and molecular life sciences : CMLS》1976,32(5):661-663
Summary Precocious sexual maturation was induced in immature female rats by 2 types of unilateral hypothalamic lesions. Stainless steel electrodes produced smaller tissue defects but proved more efficient than platinum electrodes.Supported by Swiss National Science Foundation grant No. 3.016.73.Supported by Canadian Medical Research Council grant No. MT 4192.Supported by a contribution from the Roche Research Foundation for Scientific Exchange and Biomedical Collaboration with Switzerland 相似文献
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R. Walter Madeleine A. Kirchberger V. J. Hruby 《Cellular and molecular life sciences : CMLS》1972,28(8):959-960
Zusammenfassung Adenylat-Cyclase in plasmamembranreichen Präparationen des Epitheliums von der Harnblase der Kröte wird durch Arginine-Vasopressin aktiviert. Diese Aktivierung wird durch mehre Oxytocinanaloge, die alle eine Substitution des Glutaminrestes in Position 4 des Hormones durch Leucin oder Isoleucin gemeinsam haben, kompetitiv gehemmt. Der stärkste Antagonist der Serie ist [2,4-diisoleucin]-Oxytocin und die antagonistische Aktivität nimmt in der Reihenfolge [4-Leucin]-, [2-Isoleucin-4-leucin]-, [2,4-Dileucin]- und [2-Phenylalanin-4-leucin]-Oxytocin ab. Die Resultate werden an Hand der Oxytocinkonformation diskutiert.
Supported by United States Public Health Service grants No. AM-13567 (RW), by the Life Sciences Foundation, Inc., and by the National Science Foundation No. GB-30716X (VJH).
Neurohypophyseal hormone analogs are denoted in accordance with the IUPAC-IUB [Tentative Rules (Biochemistry6, 362, 1967)]. 相似文献
Supported by United States Public Health Service grants No. AM-13567 (RW), by the Life Sciences Foundation, Inc., and by the National Science Foundation No. GB-30716X (VJH).
Neurohypophyseal hormone analogs are denoted in accordance with the IUPAC-IUB [Tentative Rules (Biochemistry6, 362, 1967)]. 相似文献