Study on TFF1 and PALB2 gene variants associated with gastric carcinoma risk in the Chinese Han population

ObjectiveGastric carcinoma (GC) has received extensive attention due to its complex pathogenesis. Studies have shown that the expression of Trefoil factor 1 (TFF1) and Partner and localiser of BRCA2 (PALB2) genes promotes the occurrence of GC. Therefore, we investigated whether TFF1 and PALB2 gene polymorphisms are associated with GC risk in the Chinese Han population.MethodsA total of 509 GC cases and 505 controls were recruited, and single nucleotide polymorphisms (SNPs) of TFF1 and PALB2 in these subjects were genotyped. The association between each candidate polymorphism and GC risk was assessed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). The visualization of gene-gene interactions and functional enrichment analysis were then performed using Cytoscape software and the R package “cluster profile”.ResultsThe TFF1 rs2156310 polymorphism significantly reduced the predisposition to GC in people under 60 years of age (AA vs. AG - GG, OR = 0.58, 95% CI = 0.35–0.97, p = 0.036). The gender-stratified analysis found that PALB2 rs513313 was significantly associated with the risk of GC in males (CT vs. TT, OR = 1.51, 95% CI = 1.06–2.15, p = 0.022). Besides, PALB2 rs249954 significantly reduced the susceptibility to GC in females (AA vs GG, OR = 0.42, 95% CI = 0.19–0.94, p = 0.034).ConclusionOur results revealed that TFF1 and PALB2 gene polymorphisms were correlated with the genetic susceptibility to GC, providing certain data support for researchers to further study the mechanism of GC.     

Comparison of mechanistic and hybrid modeling approaches for characterization of a CHO cultivation process: Requirements,pitfalls and solution paths

Despite the advantages of mathematical bioprocess modeling, successful model implementation already starts with experimental planning and accordingly can fail at this early stage. For this study, two different modeling approaches (mechanistic and hybrid) based on a four-dimensional antibody-producing CHO fed-batch process are compared. Overall, 33 experiments are performed in the fractional factorial four-dimensional design space and separated into four different complex data partitions subsequently used for model comparison and evaluation. The mechanistic model demonstrates the advantage of prior knowledge (i.e., known equations) to get informative value relatively independently of the utilized data partition. The hybrid approach displayes a higher data dependency but simultaneously yielded a higher accuracy on all data partitions. Furthermore, our results demonstrate that independent of the chosen modeling framework, a smart selection of only four initial experiments can already yield a very good representation of a full design space independent of the chosen modeling structure. Academic and industry researchers are recommended to pay more attention to experimental planning to maximize the process understanding obtained from mathematical modeling.     

中国菌物分类学和多样性研究的历史与现状概况

我国菌物分类学研究始于20世纪初,经过百余年的不断探索和发展,取得了丰硕的成果,并逐渐走进世界前列。本研究通过对世界菌物名称信息库Fungal Names进行数据统计,对发现自中国的菌物新物种和中国学者发表菌物新分类单元等数据开展分析,从中揭示中国菌物分类学的历史和发展趋势。过去,一共有2 214位中国学者参与发表了15 626个菌物新分类单元,包括 3个新纲、27个新目及亚目、117个新科及亚科、769个新属及亚属、11 100个新种、322个新种下单元和3 288个新组合。在全球已知的菌物物种中,自中国发现的新物种有10 233种,隶属于 3界13门44纲174目572科2 379属,占全球已知物种多样性的6.84%,居世界第二位。地理分布上,我国西南地区(云南、四川、贵州、西藏)和低纬度的热带、亚热带地区(中国台湾、广东)发现的新物种最多。根据每年发现的新分类单元数量趋势和命名作者的构成,可将中国菌物分类学的发展历史分为五个阶段：外人在华采菌及研究(1750s-1929)、中国菌物分类学起步(1930-1949)、新中国菌物分类学早期发展(1950-1977)、全国性菌物标本采集与研究(1978-2010)、走进世界前列(2011至今)。本研究对每个发展时期的分类学概况和重要历史事件进行了总结和回顾,通过上述综述性研究,有助于系统地了解中国菌物分类学不同阶段的发展趋势和研究概况,为学科当下和未来的发展提供参考。     

A genome-wide perspective on the diversity and selection signatures in indigenous goats using 53 K single nucleotide polymorphism array

Tibetan goats, Taihang goats, Jining grey goats, and Meigu goats are the representative indigenous goats in China, found in Qinghai-Tibet Plateau, Western pastoral area, Northern and Southern agricultural regions. Very few studies have conducted a comprehensive analysis of the genomic diversity and selection of these breeds. We genotyped 96 unrelated individuals, using goat 53 K Illumina BeadChip array, of the following goat breeds: Tibetan (TG), Taihang (THG), Jining grey (JGG), and Meigu (MGG). A total of 45 951 single nucleotide polymorphisms were filtered to estimate the genetic diversity and selection signatures. All breeds had a high proportion (over 95%) of polymorphic loci. The observed and excepted heterozygosity ranged from 0.338 (MGG) to 0.402 (JGG) and 0.339 (MGG) to 0.395 (JGG), respectively. Clustering analysis displayed a genetically distinct lineage for each breed, and their Fst were greater than 0.25, indicating that they had a higher genetic differentiation between groups. Furthermore, effective population size reduced in all four populations, indicating a loss of genetic diversity. In addition, runs of homozygosity were mainly distributed in 5–10 Mb. Lastly, we identified signature genes, which were closely related to high-altitude adaptation (ADIRF) and prolificity (CNTROB, SMC3, and PTEN). This study provides a valuable resource for future studies on genome-wide perspectives on the diversity and selection signatures of Chinese indigenous goats.     

Glutamine repeats and inherited neurodegenerative diseases: molecular aspects

Several dominantly inherited, late onset, neurodegenerative diseases are due to expansion of CAG repeats, leading to expansion of glutamine repeats in the affected proteins. These proteins are of very different sizes and, with one exception, show no sequence homology to known proteins or to each other; their functions are unknown. In some, the glutamine repeat starts near the N-terminus, in another near the middle and in another near the C-terminus, but regardless of these differences, no disease has been observed in individuals with fewer than 37 repeats, and absence of disease has never been found in those with more than 41 repeats. Protein constructs with more than 41 repeats are toxic to E. coli and to CHO cells in culture, and they elicit ataxia in transgenic mice. These observations argue in favour of a distinct change of structure associated with elongation beyond 37–41 glutamine repeats. The review describes experiments designed to find out what these structures might be and how they could influence the properties of the proteins of which they form part. Poly- -glutamines form pleated sheets of β-strands held together by hydrogen bonds between their amides. Incorporation of glutamine repeats into a small protein of known structure made it associate irreversibly into oligomers. That association took place during the folding of the protein molecules and led to their becoming firmly interlocked by either strand- or domain-swapping. Thermodynamic considerations suggest that elongation of glutamine repeats beyond a certain length may lead to a phase change from random coils to hydrogen-bonded hairpins. Possible mechanisms of expansion of CAG repeats are discussed in the light of looped DNA model structures.     

Tachykinin NK-1 receptor probed with constrained analogues of substance P

The action of rotameric probes introduced either in position 7 or 8 in the sequence of substance P (SP) was investigated, i.e. -tetrahydroisoquinoleic acid (Tic), -fluorenylglycine (Flg), -diphenylalanine (Dip), the diastereoisomers of -1-indanylglycine (Ing) and -benz[ƒ]indanylglycine (Bfi), the Z- and E-isomers of dehydrophenylalanine and dehydronaphthylalanine (Δ^ZPhe, Δ^EPhe, Δ^ZNal, Δ^ENal) and (Dmp). The aim of this study was the topographical characterization of the binding subsites of human NK-1 receptor expressed in CHO cells, especially the S₇ and S₈ subsites, corresponding to residues Phe⁷ and Phe⁸ of substance P. According to the binding potencies of these substituted-SP analogues, the S₇ binding subsite is smaller than the S₈ subsite: the S₇ subsite accepts only one aromatic nucleus, while the S₈ can accommodate three coplanar nuclei altogether. These findings are compatible with the idea that the S₈ binding subsite may reside in the extracellular loops of the hNK-1 receptor. NK-1 agonists bind to human NK-1 receptor and activate the production of both inositol phosphates and cyclic AMP. As already quoted for septide, [pGlu⁶, Pro⁹]SP(6–11), discrepancies are observed between affinity (K_i) and activity (EC₅₀) values for IPs production. While a weak correlation between K_i and EC₅₀ values for IPs production could be found (r = 0.70), an excellent correlation could be demonstrated between their affinities (K_i) and their potencies (EC₅₀) for cAMP production (r = 0.97). The high potency (EC₅₀) observed for ‘septide-like’ molecules on PI hydrolysis, compared to their affinity is not an artefact related to the high level of NK-1 receptors expressed on CHO cells since a good correlation was found between EC₅₀ values obtained for PI hydrolysis and those measured for spasmogenic activity in guinea pig ileum bioassay (r = 0.94).

According to the binding potencies of constrained analogues of phenylalanine, the S₇ binding subsite of human NK-1 receptor is small, whereas the S₈, which can accommodate three coplanar nuclei, might probably reside in the extracellular loop. The discrepancies observed between affinity (K_i) and activity (EC₅₀) values for IPs production are not an artefact of CHO cells since a good correlation was found between EC₅₀ for PI hydrolysis and those measured in guinea pig ileum bioassay.     

具有竞争指针的短时记忆神经网络模型

在我们以前提出的短时记忆神经网络模型基础上［３］,我们在新模型中引入突触竞争机制,提出了一个新的短时记忆神经网络模型。模型仍由两个神经网络所组成;其一为与长时记忆共有的信息内容表达网络,另一个为指针神经元环路。由于表达区神经元与指针神经元间的突触权重的竞争,使得模型可以表现出由干扰引起的短时记忆的遗忘。相应于自由回忆序列位置效应和汉字组块两个心理学实验,对模型做了计算机仿真。仿真结果显示模型的行为与两个心理实验定量地符合得很好。由此表明现在的模型更合适于作为短时记忆的模型。     

Genetic variation at storage protein-coding loci of common wheat (cv ‘Chinese Spring’) induced by nitrosoethylurea and by the cultivation of immature embryos in vitro

Electrophoretic patterns of seed storage proteins, the high-molecular-weight glutenins and gliadins, were studied in 468 plants of the common wheat cultivar Chinese Spring regenerated from callus culture of immature embryos, in 115 plants grown from seeds treated with nitrosoethylurea and in 260 control plants. From 5 to 21 single grains were analysed from each plant. In these three groups, the frequency of inherited mutations causing the loss of all proteins controlled by a locus (null-mutations, probably caused by a chromosomal deficiency) was 0.69%, 2.07%, and 0.05% per locus (the differences were statistically significant), respectively, while that of mutations causing the loss of a single protein band was 0.11%, 0.33%, and 0.05%, respectively. The loss of all of the gliadins controlled by Gli-B1 or GH-B2 (mutations were probably caused by a deletion of satellites of the corresponding chromosomes), was significantly higher than the loss of gliadins controlled by genomes A and D. Gene mutations altering the electrophoretic mobility of a single protein band in the pattern were found only in the second group of plants (0.44%). Therefore, chemical mutagenesis which produced not only more mutations than cultivation of immature wheat embryos in vitro, but also a higher ratio of mutations that altered DNA sequences, can be considered as an easier and comparatively more promising way for obtaining new improved variants of loci controlling biochemical characteristics in wheat. Somaclonal variation, on the other hand, was probably mainly caused by chromosomal abnormalities and could therefore hardly be considered as a useful tool in wheat breeding.     

红头豆芫菁成虫芫菁素含量的研究

芫菁素在红头豆芫菁体内主要贮存在雄虫的生殖腺和卵内。与野生群体两性芫菁素的平均含量相比较,刚交配过的雄虫失去体内７０％的芫菁素,其雌配偶体内芫菁素含量相应升高４３％。红头豆芫菁可用作中药材。经１１０℃烘干后的雄虫,用酸水解后提取的芫菁素含量比直接提取的含量增高４倍。