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311.
The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum 总被引:4,自引:0,他引:4
Howard HC Mount DB Rochefort D Byun N Dupré N Lu J Fan X Song L Rivière JB Prévost C Horst J Simonati A Lemcke B Welch R England R Zhan FQ Mercado A Siesser WB George AL McDonald MP Bouchard JP Mathieu J Delpire E Rouleau GA 《Nature genetics》2002,32(3):384-392
Peripheral neuropathy associated with agenesis of the corpus callosum (ACCPN) is a severe sensorimotor neuropathy associated with mental retardation, dysmorphic features and complete or partial agenesis of the corpus callosum. ACCPN is transmitted in an autosomal recessive fashion and is found at a high frequency in the province of Quebec, Canada. ACCPN has been previously mapped to chromosome 15q. The gene SLC12A6 (solute carrier family 12, member 6), which encodes the K+-Cl- transporter KCC3 and maps within the ACCPN candidate region, was screened for mutations in individuals with ACCPN. Four distinct protein-truncating mutations were found: two in the French Canadian population and two in non-French Canadian families. The functional consequence of the predominant French Canadian mutation (2436delG, Thr813fsX813) was examined by heterologous expression of wildtype and mutant KCC3 in Xenopus laevis oocytes; the truncated mutant is appropriately glycosylated and expressed at the cellular membrane, where it is non-functional. Mice generated with a targeted deletion of Slc12a6 have a locomotor deficit, peripheral neuropathy and a sensorimotor gating deficit, similar to the human disease. Our findings identify mutations in SLC12A6 as the genetic lesion underlying ACCPN and suggest a critical role for SLC12A6 in the development and maintenance of the nervous system. 相似文献
312.
The delivery of extraterrestrial organic molecules to Earth by meteorites may have been important for the origin and early evolution of life. Indigenous amino acids have been found in meteorites-over 70 in the Murchison meteorite alone. Although it has been generally accepted that the meteoritic amino acids formed in liquid water on a parent body, the water in the Murchison meteorite is depleted in deuterium relative to the indigenous organic acids. Moreover, the meteoritical evidence for an excess of laevo-rotatory amino acids is hard to understand in the context of liquid-water reactions on meteorite parent bodies. Here we report a laboratory demonstration that glycine, alanine and serine naturally form from ultraviolet photolysis of the analogues of icy interstellar grains. Such amino acids would naturally have a deuterium excess similar to that seen in interstellar molecular clouds, and the formation process could also result in enantiomeric excesses if the incident radiation is circularly polarized. These results suggest that at least some meteoritic amino acids are the result of interstellar photochemistry, rather than formation in liquid water on an early Solar System body. 相似文献
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316.
Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. 总被引:40,自引:0,他引:40
R K Sunahara H C Guan B F O'Dowd P Seeman L G Laurier G Ng S R George J Torchia H H Van Tol H B Niznik 《Nature》1991,350(6319):614-619
Dopamine receptors belong to a superfamily of receptors that exert their biological effects through guanine nucleotide-binding (G) proteins. Two main dopamine receptor subtypes have been identified, D1 and D2, which differ in their pharmacological and biochemical characteristics. D1 stimulates adenylyl cyclase activity, whereas D2 inhibits it. Both receptors are primary targets for drugs used to treat many psychomotor diseases, including Parkinson's disease and schizophrenia. Whereas the dopamine D1 receptor has been cloned, biochemical and behavioural data indicate that dopamine D1-like receptors exist which either are not linked to adenylyl cyclase or display different pharmacological activities. We report here the cloning of a gene encoding a 477-amino-acid protein with strong homology to the cloned D1 receptor. The receptor, called D5, binds drugs with a pharmacological profile similar to that of the cloned D1 receptor, but displays a 10-fold higher affinity for the endogenous agonist, dopamine. As with D1, the dopamine D5 receptor stimulates adenylyl cyclase activity. Northern blot and in situ hybridization analyses reveal that the receptor is neuron-specific, localized primarily within limbic regions of the brain; no messenger RNA was detected in kidney, liver, heart or parathyroid gland. The existence of a dopamine D1-like receptor with these characteristics had not been predicted and may represent an alternative pathway for dopamine-mediated events and regulation of D2 receptor activity. 相似文献
317.
In this paper we make an empirical investigation of the relationship between the consistency, coherence and validity of probability judgements in a real-world forecasting context. Our results indicate that these measures of the adequacy of an individual's probability assessments are not closely related as we anticipated. Twenty-nine of our thirty-six subjects were better calibrated in point probabilities than in odds and our subjects were, in general more coherent using point probabilities than odds forecasts. Contrary to our expectations we found very little difference in forecasting response and performance between simple and compound holistic forecasts. This result is evidence against the ‘divide-and-conquer’ rationale underlying most applications of normative decision theory. In addition, our recompositions of marginal and conditional assessments into compound forecasts were no better calibrated or resolved than their holistic counterparts. These findings convey two implications for forecasting. First, untrained judgemental forecasters should use point probabilities in preference to odds. Second, judgemental forecasts of complex compound probabilities may be as well assessed holistically as they are using methods of decomposition and recomposition. In addition, our study provides a paradigm for further studies of the relationship between consistency, coherence and validity in judgemental probability forecasting. 相似文献
318.
力反馈是机器人控制技术中一种重要的反馈。位于机器人手臂和夹持器之间的腕部力传感器是最重要的力传感器。对力传感器进行标定就是找出其标定矩阵。作者提出了求标定矩阵的方法,并指出Shimino和美国机器人技术公司——RTI的标定方法是错误的。专门设计的实验表明,用作者提出的方法所得的标定矩阵进行计算,测定载荷与实际施加的载荷是相接近的,而RTI公司的结果与施加载荷相差甚大。作者还提出了一种简化的6×6标定矩阵,用其计算的结果也与实际施加载荷接近。 相似文献
319.
R. Martinez B. Rietberg J. Skyler J. R. Oster G. O. Perez 《Cellular and molecular life sciences : CMLS》1991,47(3):270-272
Summary The effect of hyperkalemia on insulin secretion remains undefined. We evaluated portal and peripheral insulin levels in anesthetized dogs after infusions of KCl. The mean maximal increase in peripheral plasma potassium at infusion rates of 0.2 mEq/kg/h was 0.68±0.20 mEq/l. There were no significant increases in either portal or peripheral insulin levels. In contrast, in six dogs whose plasma potassium concentration increased in each case by more than 2.0 mEq/l (infusion rate of 0.5 mEq/kg/h), portal insulin levels increased fivefold (p<0.05). We conclude that only marked increases in plasma potassium concentration stimulate pancreatic insulin secretion. 相似文献
320.
't Hooft G Susskind L Witten E Fukugita M Randall L Smolin L Stachel J Rovelli C Ellis G Weinberg S Penrose R 《Nature》2005,433(7023):257-259