大鼠胎儿期噪声暴露对成年后听觉目标探索行为的影响

环境噪声被认为是影响健康的重要因素之一,但有关胎儿期环境噪声对成年后听觉行为的影响缺少系统的研究。本研究对胎儿噪声暴露组、成年噪声暴露组和正常对照组大鼠在出生后第11周开始进行为期17d的听觉目标探索训练,观察其在水迷宫中寻找听觉目标的行为差异。以大鼠寻找平台的时间、成功率、运动轨迹为指标对其听觉目标探索行为进行比较。结果发现,噪声暴露可导致大鼠在水迷宫中的听觉目标探索行为的缺陷,在胎儿期噪声暴露比成年期噪声暴露对动物探索听觉目标的行为影响更大。该结果提示,孕期进行适当的噪声防护以保证优生优育是非常必要的。     

Crystal structure of a NO-forming nitrite reductase mutant: an analog of a transition state in enzymatic reaction

I257E was obtained by site directed mutagenesis of nitrite reductase from Achromobacter cycloclastes. The mutant has no enzyme activity. Its crystal structure determined at 1.65A resolution shows that the side-chain carboxyl group of the mutated residue, Glu257, coordinates with the type 2 copper in the mutant and blocks the contact between the type 2 copper and its solvent channel, indicating that the accessibility of the type 2 copper is essential for maintaining the activity of nitrite reductase. The carboxylate is an analog of the substrate, nitrite, but the distances between the type 2 copper and the two oxygen atoms of the side-chain carboxyl group are reversed in comparison to the binding of nitrite to the native enzyme. In the mutant, both the type 2 copper and the N epsilon atom on the imidazole ring of its coordinated residue His135 move in the substrate binding direction relative to the native enzyme. In addition, an EPR study showed that the type 2 copper in the mutant is in a reduced state. We propose that mutant I257E is in a state corresponding to a transition state in the enzymatic reaction.     

Large-scale cortical functional organization and speech perception across the lifespan

Aging is accompanied by substantial changes in brain function, including functional reorganization of large-scale brain networks. Such differences in network architecture have been reported both at rest and during cognitive task performance, but an open question is whether these age-related differences show task-dependent effects or represent only task-independent changes attributable to a common factor (i.e., underlying physiological decline). To address this question, we used graph theoretic analysis to construct weighted cortical functional networks from hemodynamic (functional MRI) responses in 12 younger and 12 older adults during a speech perception task performed in both quiet and noisy listening conditions. Functional networks were constructed for each subject and listening condition based on inter-regional correlations of the fMRI signal among 66 cortical regions, and network measures of global and local efficiency were computed. Across listening conditions, older adult networks showed significantly decreased global (but not local) efficiency relative to younger adults after normalizing measures to surrogate random networks. Although listening condition produced no main effects on whole-cortex network organization, a significant age group x listening condition interaction was observed. Additionally, an exploratory analysis of regional effects uncovered age-related declines in both global and local efficiency concentrated exclusively in auditory areas (bilateral superior and middle temporal cortex), further suggestive of specificity to the speech perception tasks. Global efficiency also correlated positively with mean cortical thickness across all subjects, establishing gross cortical atrophy as a task-independent contributor to age-related differences in functional organization. Together, our findings provide evidence of age-related disruptions in cortical functional network organization during speech perception tasks, and suggest that although task-independent effects such as cortical atrophy clearly underlie age-related changes in cortical functional organization, age-related differences also demonstrate sensitivity to task domains.     

高磷血症维持性血液透析患者的临床分析

目的:比较不同血磷水平的维持性血液透析的尿毒症患者的临床表现和实验室指标,探讨其临床意义。方法:选择上海交通大学医学院附属新华医院(崇明)肾内科28例高血磷(SP>1.6mmol/L)的维持性血液透析患者为病例组,30例血磷正常(SP≤1.6mmol/L)维持性血液透析患者为对照组,比较两组患者的原发病组成,年龄,性别,透析龄,皮肤瘙痒发生率,腰背痛发生率,血钙,血碳酸氢根,血红蛋白,红细胞压积,血碱性磷酸酶,肾功能,血浆白蛋白水平及左心室肥厚发生率。结果:病例组与对照组在原发病组成,年龄(43.2±9.8岁vs 40.5±12.2岁),男女性别比例(16/12 vs.17/13),透析龄(32.56±6.71月vs.35.43±5.82月)等方面无显著性差异(P>0.05),有可比性,在血红蛋白(83.22±6.71g/L vs 103.36±5.84g/L),红细胞压积(24.83±1.92%vs.30.76±1.52%),血钙(1.71±0.16mmol/L vs.2.23±0.21 mmol/L),血碳酸氢根(14.2±3.1mmol/L vs 20.6±4.9 mmol/L),血碱性磷酸酶(124.26±16.33U/L vs.61.47±14.91 U/L),皮肤瘙痒发生率(22/28 vs.7/30),腰背痛发生率(19/28 vs.6/30),左心室肥厚发生率(20/28 vs 12/30),有显著性差异(P<0.05),肌酐(956±142mmol/L vs.923±156 mmol/L),尿素氮(23.1±6.3mmol/L vs.24.8±8.9mmol/L),血浆白蛋白(30.5±3.8g/L vs.31.2±2.9g/L),无显著性差异(P>0.05)。结论:伴有高磷血症的维持性血液透析患者与血磷正常的患者相比,血碱性磷酸酶,皮肤瘙痒发生率,腰背痛发生率及左心室肥厚发生率较高,而血钙,血碳酸氢根,血红蛋白及红细胞压积较低,有一定差异。     

Crystal structure of C-terminal desundecapeptide nitrite reductase from Achromobacter cycloclastes

Monoclinic crystal structure of C-terminal desundecapeptide nitrite reductase (NiRc-11) from Achromobacter cycloclastes was determined at 2.6A. NiRc-11 exists as a loose trimer in the crystal. Deletion of 11 residues eliminates all intersubunit hydrogen bonds mediated by the C-terminal tail. The rigid irregular coil 105-112, which constitutes part of the sidewall of the active site pocket, undergoes conformational changes and becomes highly flexible in NiRc-11. Correspondingly, the linker segments between the two copper sites 95-100 and 135-136 are partly relaxed in conformation, which leads to disrupted active site microenvironments responsible for the activity loss and spectral change of NiRc-11. Comparison with the native structure revealed a bulky residue Met331 fastened by hydrogen bonding, which may play a direct role in keeping the right copper site geometry by protruding its side chain against the irregular coil 105-112. Sequence alignment showed that the bulky residue is conserved at position 331, indicating an equal importance of C-terminal segment in other copper-containing nitrite reductases.     

pH-profile crystal structure studies of C-terminal despentapeptide nitrite reductase from Achromobacter cycloclastes

Crystal structures of C-terminal despentapeptide nitrite reductase (NiRc-5) from Achromobacter cycloclastes were determined from 1.9 to 2.3A at pH 5.0, 5.4, and 6.2. NiRc-5, that has lost about 30% activity, is found to possess quite similar trimeric structures as the native enzyme. Electron density and copper content measurements indicate that the activity loss is not caused by the release of type 2 copper (T2Cu). pH-profile structural comparisons with native enzyme reveal that the T2Cu active center in NiRc-5 is perturbed, accounting for the partial loss of enzyme activity. This perturbation likely results from the less constrained conformations of two catalytic residues, Asp98 and His255. Hydrogen bonding analysis shows that the deletion of five residues causes a loss of more than half the intersubunit hydrogen bonds mediated by C-terminal tail. This study shows that the C-terminal tail plays an important role in controlling the conformations around the T2Cu site at the subunit interface, and helps keep the optimum microenvironment of active center for the full enzyme activity of AcNiR.     

VicRK(YycFG)双组分调节系统

细菌双组分调节系统,或称之为双组分信号转导系统,是细菌感应外界多变环境,维持自身存活和生长繁衍的重要感应系统.在这些调节系统中,最早发现于枯草芽孢杆菌的VicRK(YycFG)系统因与细胞存活密切相关而倍受关注.该系统存在于少数低G+C含量的革兰氏阳性菌中,包括金黄色葡萄球菌和肺炎链球菌等致病菌,高度保守.许多证据显示,VicRK(YycFG)具有调控细胞壁合成与代谢、胞膜完整、细胞分裂、脂类代谢、多糖合成与被膜形成以及细菌毒力等多种功能,参与细胞的生长、分裂与感染.该系统异常可导致细菌生活力严重下降,甚至死亡,因而成为防治该类病原菌的重要靶标.