Equivalence of regression curves sharing common parameters

In clinical trials, the comparison of two different populations is a common problem. Nonlinear (parametric) regression models are commonly used to describe the relationship between covariates, such as concentration or dose, and a response variable in the two groups. In some situations, it is reasonable to assume some model parameters to be the same, for instance, the placebo effect or the maximum treatment effect. In this paper, we develop a (parametric) bootstrap test to establish the similarity of two regression curves sharing some common parameters. We show by theoretical arguments and by means of a simulation study that the new test controls its significance level and achieves a reasonable power. Moreover, it is demonstrated that under the assumption of common parameters, a considerably more powerful test can be constructed compared with the test that does not use this assumption. Finally, we illustrate the potential applications of the new methodology by a clinical trial example.     

Biosynthesis and function of chondroitin sulfate

Background

Chondroitin sulfate proteoglycans (CSPGs) are principal pericellular and extracellular components that form regulatory milieu involving numerous biological and pathophysiological phenomena. Diverse functions of CSPGs can be mainly attributed to structural variability of their polysaccharide moieties, chondroitin sulfate glycosaminoglycans (CS-GAG). Comprehensive understanding of the regulatory mechanisms for CS biosynthesis and its catabolic processes is required in order to understand those functions.

Scope of review

Here, we focus on recent advances in the study of enzymatic regulatory pathways for CS biosynthesis including successive modification/degradation, distinct CS functions, and disease phenotypes that have been revealed by perturbation of the respective enzymes in vitro and in vivo.

Major conclusions

Fine-tuned machineries for CS production/degradation are crucial for the functional expression of CS chains in developmental and pathophysiological processes.

General significance

Control of enzymes responsible for CS biosynthesis/catabolism is a potential target for therapeutic intervention for the CS-associated disorders.     

Phenotype and Micro-array characterization of duplication 11q22.1-q25 and review of the literature

Partial duplication of 11q is related to several malformations like growth retardation, intellectual disability, hypoplasia of corpus callosum, short nose, palate defects, cardiac, urinary tract abnormalities and neural tube defects. We have studied the clinical and molecular characteristics of a patient with severe intellectual disabilities, dysmorphic features, congenital inguinal hernia and congenital cerebral malformation which is referred to as cytogenetic exploration. We have used FISH and array CGH analysis for a better understanding of the double chromosomic aberration involving a 7p microdeletion along with a partial duplication of 11q due to adjacent segregation of a paternal reciprocal translocation t(7;11)(p22;q21) revealed after banding analysis. The patient's karyotype formula was: 46,XY,der(7)t(7;11)(p22;q21)pat. FISH study confirmed these rearrangement and array CGH technique showed precisely the loss of at least 140 Kb on chromosome7p22.3pter and 33.4 Mb on chromosome11q22.1q25. Dysmorphic features, severe intellectual disability and brain malformations could result from the 11q22.1q25 trisomy. Our study provides an additional case for better understanding and delineating the partial duplication 11q.     

Conservation of inter-residue interactions and prediction of folding rates of domain repeats

Domains are the main structural and functional units of larger proteins. They tend to be contiguous in primary structure and can fold and function independently. It has been observed that 10–20% of all encoded proteins contain duplicated domains and the average pairwise sequence identity between them is usually low. In the present study, we have analyzed the structural similarity between domain repeats of proteins with known structures available in the Protein Data Bank using structure-based inter-residue interaction measures such as the number of long-range contacts, surrounding hydrophobicity, and pairwise interaction energy. We used RADAR program for detecting the repeats in a protein sequence which were further validated using Pfam domain assignments. The sequence identity between the repeats in domains ranges from 20 to 40% and their secondary structural elements are well conserved. The number of long-range contacts, surrounding hydrophobicity calculations and pairwise interaction energy of the domain repeats clearly reveal the conservation of 3-D structure environment in the repeats of domains. The proportions of mainchain–mainchain hydrogen bonds and hydrophobic interactions are also highly conserved between the repeats. The present study has suggested that the computation of these structure-based parameters will give better clues about the tertiary environment of the repeats in domains. The folding rates of individual domains in the repeats predicted using the long-range order parameter indicate that the predicted folding rates correlate well with most of the experimentally observed folding rates for the analyzed independently folded domains.     

Identification of fragments targeting an alternative pocket on HIV-1 gp41 by NMR screening and similarity searching

The HIV-1 envelope glycoprotein gp41 fusion intermediate is a promising drug target for inhibiting viral entry. However, drug development has been impeded by challenges inherent in mediating the underlying protein–protein interaction. Here we report on the identification of fragments that bind to a C-terminal sub-pocket adjacent to the well-known hydrophobic pocket on the NHR coiled coil. Using a specifically designed assay and ligand-based NMR screening of a fragment library, we identified a thioenylaminopyrazole compound with a dissociation constant of ～500 μM. Interaction with the C-terminal sub-pocket was confirmed by paramagnetic relaxation enhancement NMR experiments, which also yielded the binding mode. Shape-based similarity searching detected additional phenylpyrazole and phenyltriazole fragments within the library, enriching the hit rate over random screening, and revealing molecular features required for activity. Discovery of the novel scaffolds and binding mechanism suggests avenues for extending the interaction surface and improving the potency of a hydrophobic pocket binding inhibitor.     

辽宁老秃顶子自然保护区植物区系多样性

通过野外实地调查,利用植物区系谱、多样性指数、相关分析和聚类模型等方法,对辽宁老秃顶子植物区系多样性进行量化分析,揭示山地生物多样性特点、规律以及与周边植被生态的关系。结果表明:(1)辽宁老秃顶子自然保护区种子植物种类组成丰富,共有野生种子植物123科429属1 006种,且优势科现象明显,单种属和少种属占比率较高,表现出一定古老残遗性。（2）老秃顶子自然保护区植物种的区系分布型多样,区系组成复杂,来源较广泛,具有一定古老性,但植物特有现象不明显,以温带性质分布种为主,符合暖温带北部的华北植物区系特点。(3)老秃顶子山与相邻9个山地比较,植物区系Shannon-Wiener指数差异明显(1.736～2.259),其中庐山和徂徕山的Shannon-Wiener指数较高,而白石砬子和长白山的较低;10个山地的Simpson指数差异不显著(0.711 4～0.871 5)。(4)相关性分析显示,10个不同山地植物区系之间的相似程度显著,相关系数达0.617～0.995;聚类分析显示,老秃顶子山与千山、凤凰山的植物区系关系较近。本研究结果支持老秃顶子山、千山和凤凰山共同划归华北植物区系的观点,认为把老秃顶子山保护区植物区系划归于华北山地植物亚地区较为合理。     

Visualization of Gluten and Starch Distributions in Dough by Fluorescence Fingerprint Imaging

A novel method combining imaging techniques and fluorescence fingerprint (FF) data measurement was developed to visualize the distributions of gluten and starch in dough without any preprocessing. Fluorescence images of thin sections of gluten, starch, and dough were acquired under 63 different combinations of excitation and emission wavelengths, resulting in a set of data consisting of the FF data for each pixel. Cosine similarity values between the FF of each pixel in the dough and those of gluten and starch were calculated. Each pixel was colored according to the cosine similarity value to obtain a pseudo-color image showing the distributions of gluten and starch. The dough sample was then fluorescently stained for gluten and starch. The stained image showed patterns similar to the pseudo-color FF image, validating the effectiveness of the FF imaging method. The method proved to be a powerful visualization tool, applicable in fields other than food technology.     

A decade of seasonal dynamics and co-occurrences within freshwater bacterioplankton communities from eutrophic Lake Mendota,WI, USA

With an unprecedented decade-long time series from a temperate eutrophic lake, we analyzed bacterial and environmental co-occurrence networks to gain insight into seasonal dynamics at the community level. We found that (1) bacterial co-occurrence networks were non-random, (2) season explained the network complexity and (3) co-occurrence network complexity was negatively correlated with the underlying community diversity across different seasons. Network complexity was not related to the variance of associated environmental factors. Temperature and productivity may drive changes in diversity across seasons in temperate aquatic systems, much as they control diversity across latitude. While the implications of bacterioplankton network structure on ecosystem function are still largely unknown, network analysis, in conjunction with traditional multivariate techniques, continues to increase our understanding of bacterioplankton temporal dynamics.     

山西省重点保护野生植物资源及区系特征研究

以《国家重点保护野生植物名录(第一批)》和《山西省重点保护野生植物名录(第一批)》为依据,建立山西省重点保护野生植物名录。共记录57种保护植物,隶属于38科45属（其中国家Ⅰ级保护2种,国家Ⅱ级保护6种,省级保护49种）。分析结果得出,山西省重点保护野生植物在全省的分布不集中,零散分布于全省61个县区境内,且绝大多数物种的分布范围很狭窄。山西省重点保护野生植物区系具有复杂多样、起源古老、孑遗植物和单种属多等特点,科、属植物区系成分以温带分布型占优势,同时也有较明显的热带性质,过渡性特征比较明显,有其独特的地理优势和保护价值。本研究旨在对山西省重点保护野生植物资源现状及区系特征进行初步研究,从而为野生植物资源的保护和合理有效地利用提供科学的理论依据与参考。     

基于SSR标记的陆地棉早熟相关种质遗传多样性分析

丰富的遗传变异对于提高作物的环境适应性和遗传改良进度至关重要。为了解我国早熟陆地棉种质资源遗传多样性,本研究利用136对SSR引物对186份陆地棉材料(96份早熟陆地棉材料和90份中、晚熟陆地棉材料)进行了遗传多样性分析,共检测到等位基因变异355个,平均2.61个。在早熟棉材料中,有134对多态性SSR引物扩增出341个条带,平均2.54个;中、晚熟材料中有133对多态性SSR引物,扩增出345个条带,平均2.59个。早熟棉材料的位点多态性信息含量(PIC)、有效等位基因数(Ne)、基因型多样性(H')分别为0.684、3.994和1.361;中、晚熟棉材料的PIC、Ne、H'分别为0.668、3.852和1.343。早熟棉材料和中、晚熟棉材料的Jaccard相似性系数分别在0.349~0.935和0.270~0.907之间,平均为0.635、0.666。遗传相似性系数总体平均值接近,但早熟棉变化范围较中、晚熟棉小。用类平均法(UPGMA)进行聚类可将186份材料分成2个类群。总体上来看,供试材料遗传相似性系数较高,说明我国陆地棉早熟相关种质遗传基础狭窄。本研究结果为早熟棉育种亲本选配,早熟棉种质创新提供依据。