The role of Self-Defined Race/Ethnicity in Population Structure Control

Population-based association studies are powerful tools for the genetic mapping of complex diseases. However, this method is sensitive to potential confounding by population structure. While statistical methods that use genetic markers to detect and control for population structure have been the focus of current literature, the utility of self-defined race/ethnicity in controlling for population structure has been controversial. In this study of 1334 individuals, who self-identified as either African American, European American or Hispanic, we demonstrated that when the true underlying genetic structure and the self-defined racial/ethnic groups were roughly in agreement with each other, the self-defined race/ethnicity information was useful in the control of population structure.     

Effect of divalent cations on structure-function relationships of the antitumor protein α-sarcin

α-Sarcin binds one Zn(II) cation per protein molecule, with a K_d value of 0.9 mM, determined by equilibrium dialysis experiments. Ca(II), Mg(II), and Mn(II) do not bind to α-sarcin. Cd(II) and Co(II) also behave as Zn(II). The binding produces local modifications on the protein conformation affecting the microenvironment of tryptophan residues. The three cations modify the fluorescence emission of the protein. The near-u. v. circular dichroism spectrum of the protein is also altered. The binding of Zn(II) and related cations does not modify the secondary structure of the protein. The ribonucleolytic activity of a-sarcin is inhibited upon Zn(II) binding, but no alteration of the ability of the protein to aggregate phospholipid vesicles has been observed.     

Sperm chromatin integrity in young men with no experiences of infertility and men from idiopathic infertility couples

Damage to the genetic component of spermatozoa seems to play the main role in a majority of cases where current approaches fail to reveal the specific cause of male infertility. In this study, we compared semen quality in men assigned to two defined groups: men from couples with unexplained infertility – idiopathic infertility (A) and young men with no experiences of infertility (B). All samples were examined by standard ejaculate analysis and sperm chromatin structure assay (SCSA). Sperm chromatin damage was significantly higher in men from group A than in those from group B. Similar results were obtained by comparison of men from group A (all men were normozoospermic) with normozoospermic men from group B. According to these results, we can suppose that chromatin disorders may be the causal factor of subfertility or infertility in some of these men. No evidence for a strong association between chromatin disorders and standard parameters of ejaculates was found. We failed to confirm a relationship between smoking and sperm quality in men from any of the investigated groups. SCSA is a method that facilitates the identification of infertile men who otherwise show normal semen variables.     

蛙皮素对PC-3细胞骨架及细胞内游离Ca~(2+)的影响

目的:观察蛙皮素(BBS)对前列腺癌PC-3细胞骨架形态及细胞内游离Ca2+([Ca2+]i)浓度的影响。方法:①利用免疫荧光法(IH),结合激光扫描共聚焦显微镜(LSCM)检测10-5mol/L浓度BBS处理的PC-3细胞角蛋白(CK)的表达,以反映其对细胞骨架形态的影响;②应用Fluo-3/AM荧光标记技术和LSCM检测不同浓度BBS(10-9、10-7、10-5mol/L)处理的PC-3细胞[Ca2+]i浓度。结果:①10-5mol/L浓度的BBS可促进PC-3细胞CK表达及伪足形成;②BBS可提高PC-3细胞[Ca2+]i浓度,并具有浓度依赖性。结论:实验证明一定浓度的BBS可明显提高PC-3细胞[Ca2+]i浓度及CK表达,进而影响PC-3细胞骨架形态。本研究为探索BBS应用于肿瘤研究以及BBS作用后细胞内信息传递途径提供了基础。     

Working‐correlation‐structure identification in generalized estimating equations

Selecting an appropriate working correlation structure is pertinent to clustered data analysis using generalized estimating equations (GEE) because an inappropriate choice will lead to inefficient parameter estimation. We investigate the well‐known criterion of QIC for selecting a working correlation structure, and have found that performance of the QIC is deteriorated by a term that is theoretically independent of the correlation structures but has to be estimated with an error. This leads us to propose a correlation information criterion (CIC) that substantially improves the QIC performance. Extensive simulation studies indicate that the CIC has remarkable improvement in selecting the correct correlation structures. We also illustrate our findings using a data set from the Madras Longitudinal Schizophrenia Study. Copyright © 2008 John Wiley & Sons, Ltd.     

一种识别蛋白质的保守氨基酸残基的新方法

保守氨基酸残基在生物进化过程中具有较强的稳定性,一般不会发生太大的变化;生物信息学认为：氨基酸序列决定蛋白质结构,蛋白质结构决定蛋白质功能。因此,作者基于氨基酸的生化特性、几何特性和动态特性描述了一个新颖的算法去发现蛋白酶家族中的保守氨基酸残基,而保守氨基酸残基将对蛋白质的结构和功能的研究具有重要的意义。     

Ultrastructure of aberrant serotonin-immunoreactive fibers in the caudate putamen complex of the aged rat

Degeneration of neurons in the central nervous system is associated with morphological changes. Previous observations made at the light microscopical level indicated degeneration of serotonin-immunoreactive (IR) fibers in the aged rat brain. In this study, a comparison at the ultrastructural level was made between serotonin-IR normal thin and aberrant swollen varicose fibers in the caudate-putamen complex of the aged rat. Ultrastructural features such as the size and content of the thin varicose fibers resembled those in the caudate-putamen complex of the young rat as reported by others. The aberrant profiles were swollen, reaching a size of 6 microns. Their vesicles varied in size and were no longer uniformly round. Moreover, distorted mitochondria and membrane-filled vacuolelike structures were a common feature of the aberrant profiles. These changes are indicative of a degenerative process and give further evidence that, whereas many serotonergic fibers are preserved at high age, other serotonergic fibers are degenerating in the caudate-putamen complex of the aged rat.     

Ridge number density: A new parameter for in vivo bone structure analysis

An advanced analysis of the mechanical properties of bone should include information about the microarchitecture of cancellous bone in addition to its density. It has recently been shown that high-resolution quantitative computed tomography and magnetic resonance imaging have the potential to assess such information in a noninvasive way in patients. Both techniques, however, lack sufficient spatial resolution to image the individual trabeculae with true precision. In this work, a new parameter, Ridge number density (RND), is introduced. RND is a measure for the trabecular number, which can be extracted directly from high-resolution three-dimensional (3D) images of patients. We applied the RND technique to a test group of nine healthy, postmenopausal women measured repetitively with a high-resolution 3D peripheral quantitative computed tomography (3D-pQCT) system with 165 × 165 × 165 μm³ voxel size. Simultaneously with the RND determination, the trabecular bone density (TBD) was also assessed in the same volume of interest. The examination site was the distal radius. The intersubject variability of the measured test group was 10.5% for RND and 26.3% for TBD. The root mean square error between first and second examinations (midterm reproducibility) was 1.6% and 1.1%, respectively. RND is determined independently from TBD and pertains to the structure of the cancellous bone. As such, it might add crucial information in cases where bone mass or bone density measurements alone give ambigous results.     

N-ω-Carbethoxypentyl-4-quinolones: A New Class of Leukotriene Biosynthesis Inhibitors

6-[(4-Quinolinyl)oxy]hexanoic acids and the corresponding esters were designed and synthesized as inhibitors of the production of arachidonic acid metabolites. The inhibitory activities were assayed in vitro by evaluation of serum leukotriene B₄ and thromboxane B₂ production. While all 6-[(4-quinolinyl)oxy]hexanoic acids and their esters proved to be inactive, the N-alkyl-4-quinolones, obtained as by-products in their synthesis, were found to be a new class of leukotriene biosynthesis inhibitors.     

The growth of the second underpotentially deposited silver layer on Pt(100)

The electrodeposition of Ag on Pt(100)-(1 × 1) in perchlorate electrolyte was studied by means of time-resolved in situ scanning tunnelling microscopy (STM) and cyclic voltammetry. One monolayer of Ag is deposited underpotentially (upd) ca. 500 mV positive of the Ag⁺/Ag equilibrium potential. Several millivolts positive of the equilibrium potential, a second well defined upd layer forms. Its growth was observed to proceed via island formation and coalescence. This process occurs in two separate stages that manifest themselves in voltammetric peaks as well as in the STM images.