BLOC-2, AP-3, and AP-1 proteins function in concert with Rab38 and Rab32 proteins to mediate protein trafficking to lysosome-related organelles

Lysosome-related organelles (LROs) are synthesized in specialized cell types where they largely coexist with conventional lysosomes. Most of the known cellular transport machinery involved in biogenesis are ubiquitously expressed and shared between lysosomes and LROs. Examples of common components are the adaptor protein complex-3 (AP-3) and biogenesis of lysosome-related organelle complex (BLOC)-2. These protein complexes control sorting and transport of newly synthesized integral membrane proteins from early endosomes to both lysosomes and LROs such as the melanosome. However, it is unknown what factors cooperate with the ubiquitous transport machinery to mediate transport to LROs in specialized cells. Focusing on the melanosome, we show that the ubiquitous machinery interacts with cell type-specific Rab proteins, Rab38 and Rab32, to facilitate transport to the maturing organelle. BLOC-2, AP-3, and AP-1 coimmunoprecipitated with Rab38 and Rab32 from MNT-1 melanocytic cell extracts. BLOC-2, AP-3, AP-1, and clathrin partially colocalized with Rab38 and Rab32 by confocal immunofluorescence microscopy in MNT-1 cells. Rab38- and Rab32-deficient MNT-1 cells displayed abnormal trafficking and steady state levels of known cargoes of the BLOC-2, AP-3, and AP-1 pathways, the melanin-synthesizing enzymes tyrosinase and tyrosinase-related protein-1. These observations support the idea that Rab38 and Rab32 are the specific factors that direct the ubiquitous machinery to mediate transport from early endosomes to maturing LROs. Additionally, analysis of tyrosinase-related protein-2 and total melanin production indicates that Rab32 has unique functions that cannot be carried out by Rab38 in melanosome biogenesis.     

超声图像处理中Snake模型研究

Snake模型是一种基于高层信息的有效目标轮廓提取算法,其优点是作用过程及最后结果的目标轮廓是一条完整的曲线,从而引起广泛的关注。鉴于医学超声图像的信噪比较低,用经典的边缘提取算法无法得到较好的结果,因此人们将Snake模型进行了各种各样的改进,并且越来越多地将它运用到医学超声图像处理中来。本文对乳腺超声图像进行阈值分割、形态滤波等一系列预处理后,将改进的Snake模型对乳腺超声图像进行肿瘤的边缘提取,得到了比较好的结果。     

The distribution of Athetis lepigone and prediction of its potential distribution based on GARP and MaxEnt

Athetis lepigone (Möschler) is a new agronomic pest which has caused serious damages to summer maize in China. In order to effectively monitor it, it is necessary to carry‐out a worldwide investigation on its potential geographical distribution. In this study, we give two ecological niche models, Genetic Algorithm for Rule‐set Production and Maximum Entropy (MaxEnt), to predict the potential geographical distribution of A. lepigone. The results indicate that the suitable areas for A. lepigone are mainly in China (Beijing, Tianjin, central and southern Hebei, northern Jiangsu, Shandong, most of Henan, northern Anhui, central and southern Shanxi, central and southern Shaanxi, small parts of north‐west in Hubei, eastern Gansu, parts of Ningxia, western of Xinjiang and Dandong, and Liaoning) and other Asian countries (South Korea, North Korea and Japan). Parts of Europe (south‐western Russia, Ukraine, Moldova, Romania, Hungary, Bulgaria, Slovenia, and Croatia, Bosnia and Herzegovina, Serbia, parts of Austria, western Poland, the Czech Republic, Germany, northern Italy, Denmark, western Lithuania, Latvia, Estonia, southern Finland and Sweden) are also highly suitable for A. lepigone. In addition, in the states of the USA including Michigan, New York, Chicago, Missouri, Ohio, Illinois and Indiana are also favourable for its occurrence although till now no reports about of this species has been recorded. A jackknife test in MaxEnt showed that the mean temperature of the driest quarter was the most important environmental variable affecting the distribution of this pest.     

基于遗传算法预测2D三向的蛋白质结构

本文基于范德华力势能预测2D三向的蛋白质结构。首先,将蛋白质结构预测这一生物问题转化为数学问题,并建立基于范德华力势能函数的数学模型。其次,使用遗传算法对数学模型进行求解,为了提高蛋白质结构预测效率,我们在标准遗传算法的基础上引入了调整算子这一概念,改进了遗传算法。最后,进行数值模拟实验。实验的结果表明范德华力势能函数模型是可行的,同时,和规范遗传算法相比,改进后的遗传算法能够较大幅度提高算法的搜索效率,并且遗传算法在蛋白质结构预测问题上有巨大潜力。     

Uteroglobin, an apically secreted protein of the uterine epithelium, is secreted non-polarized from MDCK cells and mainly basolaterally from Caco-2 cell

A complete cDNA encoding rabbit Uteroglobin was constructed and expressed in MDCK and Caco-2 cells. The MDCK cells secrete Uteroglobin in approximately equal amounts to the apical and the basolateral side, whereas the Caco-2 cells secrete Uteroglobin mainly to the basolateral side. Both MDCK and Caco-2 cells thus secrete Uteroglobin in a non-sorted manner. It has, however, previously been shown that Uteroglobin is secreted exclusively at the apical membrane in primary cell culture of endometrial epithelial cells [S.K. Mani et al. (1991) Endocrinology 128, 1563-1573]. This suggests that either the endometrial epithelium has an apical default pathway or recognises a sorting signal not recognised by MDCK cells and Caco-2 cells. Our data thus show that a soluble molecule can be secreted at the apical, the basolateral or both membranes depending on the cell type.     

Can morphogenesis be understood in terms of physical rules?

Because the morphogenesis of biological systems is not fully understood, researches from various points of view are necessary. The present author has recently made computer simulations with his colleagues to construct branching systems of human organs, such as the lung airway and the liver blood vessels. In the simulations certain rules are assumed to govern bifurcating processes of the systems. These rules are expressed in terms of physical and geometrical concepts, such as minimum energy consumption and uniform filling of branches in the space of organs. Results of computer simulation are quite similar to real structures. However, actual mechanisms of morphogenesis, i.e. effects of genes or proteins, are not considered in these studies. In this article, the present work is discussed in relation to the concept of biological pattern formation by Meinhardt and a recent study by Miura and Shiota on lung growth.     

Data mining the protein data bank: automatic detection and assignment of carbohydrate structures

Knowledge of the 3D structure of glycans is a prerequisite for a complete understanding of the biological processes glycoproteins are involved in. However, due to a lack of standardised nomenclature, carbohydrate compounds are difficult to locate within the Protein Data Bank (PDB). Using an algorithm that detects carbohydrate structures only requiring element types and atom coordinates, we were able to detect 1663 entries containing a total of 5647 carbohydrate chains. The majority of chains are found to be N-glycosidically bound. Noncovalently bound ligands are also frequent, while O-glycans form a minority. About 30% of all carbohydrate containing PDB entries comprise one or several errors. The automatic assignment of carbohydrate structures in PDB entries will improve the cross-linking of glycobiology resources with genomic and proteomic data collections, which will be an important issue of the upcoming glycomics projects. By aiding in detection of erroneous annotations and structures, the algorithm might also help to increase database quality.     

基于乒乓算法的复杂疾病标志物识别

目的:生物标志物是标识系统、器官、组织等改变或可能发生改变的生化指标,具有非常广泛的临床应用。本文希望从高通量数据出发,提出一种新的研究复杂疾病标志物的方法。方法:以"组学"数据为研究对象,利用乒乓算法构建lnc RNA-mRNA交互网络,通过随机游走算法计算选出复杂疾病的生物标志物,并将其与t检验结果比较。结果:将本文方法运用于食管癌标志物的识别,得出与食管癌发生和发展过程相关的14个lnc RNA(CCAT1、MEG3、Snhg1、MALAT1、HOTAIR、UCA1、PVT1、CASC9、LOC100130476、TUG1、BC200、POU6F2-AS2、TP73-AS1和ZEB1-AS1)和12个mRNA(SPARC、CMTM7、Sph K1、NANOG、LOXL2、HMGCS2、FZD7、PTOV1、CADM1、CTHRC1、MGMT和RECK)。对比显示,识别出t检验未识别出的4个lnc RNA(BC200、POU6F2-AS2、TP73-AS1和ZEB1-AS1)和3个mRNA(CADM1、Sph K1和RECK)。结论:该方法能够更有效的预测复杂疾病相关的标志物。     

Polygenic risk for schizophrenia and neurocognitive performance in patients with schizophrenia

Both neurocognitive deficits and schizophrenia are highly heritable. Genetic overlap between neurocognitive deficits and schizophrenia has been observed in both the general population and in the clinical samples. This study aimed to examine if the polygenic architecture of susceptibility to schizophrenia modified neurocognitive performance in schizophrenia patients. Schizophrenia polygenic risk scores (PRSs) were first derived from the Psychiatric Genomics Consortium (PGC) on schizophrenia, and then the scores were calculated in our independent sample of 1130 schizophrenia trios, who had PsychChip data and were part of the Schizophrenia Families from Taiwan project. Pseudocontrols generated from the nontransmitted parental alleles of the parents in these trios were compared with alleles in schizophrenia patients in assessing the replicability of PGC‐derived susceptibility variants. Schizophrenia PRS at the P‐value threshold (PT) of 0.1 explained 0.2% in the variance of disease status in this Han‐Taiwanese samples, and the score itself had a P‐value 0.05 for the association test with the disorder. Each patient underwent neurocognitive evaluation on sustained attention using the continuous performance test and executive function using the Wisconsin Card Sorting Test. We applied a structural equation model to construct the neurocognitive latent variable estimated from multiple measured indices in these 2 tests, and then tested the association between the PRS and the neurocognitive latent variable. Higher schizophrenia PRS generated at the PT of 0.1 was significantly associated with poorer neurocognitive performance with explained variance 0.5%. Our findings indicated that schizophrenia susceptibility variants modify the neurocognitive performance in schizophrenia patients.     

混合分布理论及应用

本文介绍了混合分布的历史及其一般理论．在阐述混合分布理论在医学、农业、渔业、地理学等方面的应用以及在统计学其它有关分支中的应用的基础上,还详细讨论了这一理论可能在遗传分析中的作用,并提出一些值得进一步研究的问题．