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81.
Thompson DA Li Y McHenry CL Carlson TJ Ding X Sieving PA Apfelstedt-Sylla E Gal A 《Nature genetics》2001,28(2):123-124
The chromophore of the visual pigments, 11-cis retinal, is derived from vitamin A (all-trans retinol) through a series of reactions that take place in retinal pigment epithelium (RPE); (ref. 1). The first of these reactions is catalyzed by lecithin retinol acyltransferase (LRAT); (ref. 2). We screened 267 retinal dystrophy patients for mutations in LRAT and identified disease-associated mutations (S175R and 396delAA) in three individuals with severe, early-onset disease. We showed that the S175R mutant has no acyltransferase activity in transfected COS-7 cells. Our findings highlight the importance of genetic defects in vitamin A metabolism as causes of retinal dystrophies and extend prospects for retinoid replacement therapy in this group of diseases. 相似文献
82.
根据古里雅冰芯中NO^-3浓度可以揭示太阳活动变化的事实,研究了长期以来存在争议的Maunder极小期(1645~1715年)的太阳活动状况,结果不仅证实这一时期太阳活动极小期的存在,而且也证实这一时期内太阳活动周期是正常的,即存在11a左右的黑子周期。研究还发现,太阳活动可能存在36a左右的周期,这一结果对于日地关系研究具有重要的意义。 相似文献
83.
Ninglian Wang Tandong Yao Dahe Qin L. G. Thompson E. Mosley-Thompson J. Cole-Dai M. E. Davis P. -N. Lin 《科学通报(英文版)》1999,44(17):1616-1616
A36Cl peak was found in the predicted section of Guliya ice core, from the Qinghai-Tibetan Plateau, at about 37 kaBP. This cannot
be interpreted by means of changes in the accumulation rate, but by the enhanced cosmogenic isotope production rate in the
atmosphere. Compared with the records of10Be and36Cl in the other regions, the peaks of the cosmogenic isotopes are global and can be considered as time marks. An intriguing
fact is that the peaks coincided with cold periods. 相似文献
84.
85.
86.
Telomere reduction in human colorectal carcinoma and with ageing 总被引:98,自引:0,他引:98
We have hypothesized that end-to-end chromosome fusions observed in some tumours could play a part in genetic instability associated with tumorigenesis and that fusion may result from the loss of the long stretches of G-rich repeats found at the ends of all linear chromosomes. We therefore asked whether there is telomere loss or reduction in common tumours. Here we show that in most of the colorectal carcinomas that we analysed, there is a reduction in the length of telomere repeat arrays relative to the normal colonic mucosa from the same patient. We speculate on the consequences of this loss for tumorigenesis. We also show that the telomere arrays are much smaller in colonic mucosa and blood than in fetal tissue and sperm, and that there is a reduction in average telomere length with age in blood and colon mucosa. We propose that the telomerase is inactive in somatic tissues, and that telomere length is an indicator of the number of cell divisions that it has taken to form a particular tissue and possibly to generate tumours. 相似文献
87.
W Thompson 《Nature》1983,302(5909):614-616
The synaptic connections among the cells of the vertebrate nervous system undergo extensive rearrangements early in development. During their initial growth, neurones apparently form synaptic connections with an excessive number of targets, later retracting a portion of these synapses in establishing the adult neural circuits. Because of the profound effects which experience has upon the developing nervous system, a question of considerable interest has been the role which the functional use of these developing synapses might play in determining the final pattern of connectivity. At the neuromuscular junction the early changes in synaptic connections are well documented, and here questions about the importance of function can be relatively easily addressed. Mammalian skeletal muscle fibres experience a perinatal period of synapse elimination so that all but one of several synapses formed on each muscle fibre are lost. This synapse elimination is sensitive to alterations of neuromuscular use or activity. Reduction of muscle use by tenotomy or by paralysis of the muscle with drugs blocking nerve impulse conduction or neuromuscular transmission delays or even prevents synapse loss, while increased use produced by stimulation of the muscle nerve apparently accelerates the rate at which synapses are lost. I report here a further examination of the role of neuromuscular activity in synapse elimination. I show that chronic neuromuscular stimulation accelerates synapse elimination but that this acceleration is dependent on the temporal pattern in which the stimuli are presented: brief stimulus trains containing 100 Hz bursts of stimuli produce this acceleration whereas the same number of stimuli presented continuously at 1 Hz do not. Furthermore, the 100 Hz activity pattern which is effective in altering synapse elimination also alters two other muscle properties: the sensitivity of the muscle fibers to acetylcholine and the 'speed' of muscle contractions. These findings suggest that the ability of muscle fibres to maintain more than one nerve terminal, like other muscle properties, is sensitive to the pattern of muscle use rather than just the total amount of use. 相似文献
88.
Targetted correction of a mutant HPRT gene in mouse embryonic stem cells 总被引:11,自引:0,他引:11
T Doetschman R G Gregg N Maeda M L Hooper D W Melton S Thompson O Smithies 《Nature》1987,330(6148):576-578
Two recent developments suggest a route to predetermined alterations in mammalian germlines. These are, first, the characterization of mouse embryonic stem (ES) cells that can still enter the germline after genetic manipulation in culture and second, the demonstration that homologous recombination between a native target chromosomal gene and exogenous DAN can be used in culture to modify specifically the target locus. We here use gene targetting functionally to correct the mutant hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene in the ES cell line which has previously been isolated and used to produce an HPRT-deficient mouse. This modification of a chosen gene in pluripotent ES cells demonstrates the feasibility of this route to manipulating mammalian genomes in predetermined ways. 相似文献
89.
90.
Summary Red blood cell nuclei from avian anaemic blood have been fractionated by rate sedimentation on discontinous sucrose gradients into fractions which can be distinguished both by their RNA synthesizing ability and by their morphology as revealed by electron microscopy.Acknowledgment. We wish to thank H. Gitay for the electron micrographs. This work was supported by grants from the University of Cape Town Research Committee and the Council for Scientific and Industrial Research. 相似文献