Trak1 mutation disrupts GABA(A) receptor homeostasis in hypertonic mice

Hypertonia, which results from motor pathway defects in the central nervous system (CNS), is observed in numerous neurological conditions, including cerebral palsy, stroke, spinal cord injury, stiff-person syndrome, spastic paraplegia, dystonia and Parkinson disease. Mice with mutation in the hypertonic (hyrt) gene exhibit severe hypertonia as their primary symptom. Here we show that hyrt mutant mice have much lower levels of gamma-aminobutyric acid type A (GABA(A)) receptors in their CNS, particularly the lower motor neurons, than do wild-type mice, indicating that the hypertonicity of the mutants is likely to be caused by deficits in GABA-mediated motor neuron inhibition. We cloned the responsible gene, trafficking protein, kinesin binding 1 (Trak1), and showed that its protein product interacts with GABA(A) receptors. Our data implicate Trak1 as a crucial regulator of GABA(A) receptor homeostasis and underscore the importance of hyrt mice as a model for studying the molecular etiology of hypertonia associated with human neurological diseases.     

Institutional experience of PTH evaluation on fine-needle washing after aspiration biopsy to locate hyperfunctioning parathyroid tissue

Assaying parathyroid hormone (PTH) in the washing liquid after fine-needle aspiration biopsy (FNAB) seems to be a valid approach to locate parathyroid tissue. PTH-FNAB was evaluated in 47 patients with a clinical picture of primary hyperparathyroidism (PHP) and ultrasonography (US) suggestive of parathyroid lesion. The patients were subdivided into two groups on the basis of the absence or presence of US thyroid alterations. The result of PTH-FNAB was compared with those of cytology, scintigraphy and, in 24 patients, surgical outcome. PTH-FNAB samples with a value higher than that recorded in the serum and higher than our institutional cut-off were deemed to be probable samples of parathyroid tissue. Cytology proved diagnostic for benign thyroid lesions, non-diagnostic for thyroid lesions, hyperplastic parathyroid tissue, undetermined or malignant thyroid lesions and other lesions in 45%, 30%, 17%, 4%, and 4% of cases, respectively. In 47% of cases, PTH-FNAB indicated that the sample had been taken in parathyroid tissue. In patients without US alterations, the diagnostic accuracy of PTH-FNAB was greater than that of scintigraphy. After surgery, comparison between the results of PTH-FNAB and scintigraphy, in terms of positive predictive value (PPV), revealed the superiority of PTH-FNAB; PPV was 94% for FNAB and 71% for scintigraphy, while sensitivity was 83% and 69%, respectively. PTH-FNAB evaluation after FNAB appears to be more diagnostic than cytology and scintigraphy. Of all the procedures used, PTH-FNAB appears to be the method of choice when the target is US suggestive and reachable. PTH-FNAB appears to be a useful method of guiding surgical intervention.     

动态贝叶斯网络在复杂系统中建模方法的研究

提出了用动态贝叶斯网络(DBN)对复杂系统进行建模的有效方法。基本思路是将扩展后的隐变量引入了DBN的演化过程中来建立马尔可夫模型,并给出了引入扩展后的隐变量的DBN结构学习算法框架。进而,利用贝叶斯概率统计方法对后续时间片的充分统计因子进行了估计,并通过当前已存在的充分统计因子和估计的充分统计因子对基于时间变化的转移概率进行了学习。原理性分析和仿真实验结果也验证了该方法的有效性。     

Microsatellites are preferentially associated with nonrepetitive DNA in plant genomes.

Microsatellites are a ubiquitous class of simple repetitive DNA sequence. An excess of such repetitive tracts has been described in all eukaryotes analyzed and is thought to result from the mutational effects of replication slippage. Large-scale genomic and EST sequencing provides the opportunity to evaluate the abundance and relative distribution of microsatellites between transcribed and nontranscribed regions and the relationship of these features to haploid genome size. Although this has been studied in microbial and animal genomes, information in plants is limited. We assessed microsatellite frequency in plant species with a 50-fold range in genome size that is mostly attributable to the recent amplification of repetitive DNA. Among species, the overall frequency of microsatellites was inversely related to genome size and to the proportion of repetitive DNA but remained constant in the transcribed portion of the genome. This indicates that most microsatellites reside in regions pre-dating the recent genome expansion in many plants. The microsatellite frequency was higher in transcribed regions, especially in the untranslated portions, than in genomic DNA. Contrary to previous reports suggesting a preferential mechanism for the origin of microsatellites from repetitive DNA in both animals and plants, our findings show a significant association with the low-copy fraction of plant genomes.     

高等院校成人教育管理略论

成人教育的发展对提高全民素质 ,促进社会进步有重要的作用。高等学校的成人教育如何更好的为社会主义经济文化建设服务 ,关键是教育质量 ,加强成人教育质量的管理是提高成人教育质量的关键。     

Assessing the impact of population stratification on genetic association studies

Population stratification refers to differences in allele frequencies between cases and controls due to systematic differences in ancestry rather than association of genes with disease. It has been proposed that false positive associations due to stratification can be controlled by genotyping a few dozen unlinked genetic markers. To assess stratification empirically, we analyzed data from 11 case-control and case-cohort association studies. We did not detect statistically significant evidence for stratification but did observe that assessments based on a few dozen markers lack power to rule out moderate levels of stratification that could cause false positive associations in studies designed to detect modest genetic risk factors. After increasing the number of markers and samples in a case-cohort study (the design most immune to stratification), we found that stratification was in fact present. Our results suggest that modest amounts of stratification can exist even in well designed studies.     

The nature and transport mechanism of hydrated hydroxide ions in aqueous solution

Compared to other ions, protons (H(+)) and hydroxide ions (OH(-)) exhibit anomalously high mobilities in aqueous solutions. On a qualitative level, this behaviour has long been explained by 'structural diffusion' the continuous interconversion between hydration complexes driven by fluctuations in the solvation shell of the hydrated ions. Detailed investigations have led to a clear understanding of the proton transport mechanism at the molecular level. In contrast, hydroxide ion mobility in basic solutions has received far less attention, even though bases and base catalysis play important roles in many organic and biochemical reactions and in the chemical industry. The reason for this may be attributed to the century-old notion that a hydrated OH(-) can be regarded as a water molecule missing a proton, and that the transport mechanism of such a 'proton hole' can be inferred from that of an excess proton by simply reversing hydrogen bond polarities. However, recent studies have identified OH(-) hydration complexes that bear little structural similarity to proton hydration complexes. Here we report the solution structures and transport mechanisms of hydrated hydroxide, which we obtained from first-principles computer simulations that explicitly treat quantum and thermal fluctuations of all nuclei. We find that the transport mechanism, which differs significantly from the proton hole picture, involves an interplay between the previously identified hydration complexes and is strongly influenced by nuclear quantum effects.     

抛物线的斜线插补生成算法

根据斜线插补算法的基本原理导出抛物线的生成算法。其结构以形式简单，实用性强的递推公式得出。     

兰州地区某工程垃圾地基土处理方法研究

对兰州地区某工程垃圾地基土进行了表层开挖、灰土紧密和换填夯实的综合技术处理.利用原位现场静载荷试验,研究了垃圾土处理前后的变形性能、承载力和变形机理,为工程基础选型提供了依据.     

技术社会的解释学分析

随着技术在社会生活中作用的日益凸现,许多学科和理论都开始关注技术社会。从学理上来说,对概念的解释和理解是研究的前提。在解释学看来,对技术社会的理解有三种方式:一是把技术社会理解为社会发展的技术统治阶段,这个时期技术成为统治和控制社会的力量;二是把技术社会理解为以技术为交往媒介和中心的交往共同体;三是把技术社会理解为以技术作为职业或工作核心的人员构成的社会。