Deciphering the biosynthesis pathway of the antitumor thiocoraline from a marine actinomycete and its expression in two streptomyces species

Thiocoraline is a thiodepsipeptide antitumor compound produced by two actinomycetes Micromonospora sp. ACM2-092 and Micromonospora sp. ML1, isolated from two marine invertebrates (a soft coral and a mollusc) found of the Indian Ocean coast of Mozambique. By using oligoprimers derived from nonribosomal peptide synthetase (NRPS) consensus sequences, six PCR fragments containing putative NRPS adenylation domains were amplified from the chromosome of Micromonospora sp. ML1. Insertional inactivation of each adenylation domain showed that two of them generated nonproducing mutants, thereby indicating that these domains were involved in thiocoraline biosynthesis. Sequencing of a 64.6 kbp DNA region revealed the presence of 36 complete open reading frames (ORFs) and two incomplete ones. Heterologous expression of a region of about 53 kbp, containing 26 of the ORFs, in Streptomyces albus and S. lividans led to the production of thiocoraline in these streptomycetes. Surprisingly, the identified gene cluster contains more NRPS modules than expected on the basis of the number of amino acids of thiocoraline. TioR and TioS would most probably constitute the NRPS involved in the biosynthesis of the thiocoraline backbone, according to the colinearity of the respective modules. It is proposed that two other NRPSs, TioY and TioZ, could be responsible for the biosynthesis of a small peptide molecule which could be involved in regulation of the biosynthesis of thicoraline in Micromonospora sp. ML1. In addition, a pathway is proposed for the biosynthesis of the unusual starter unit, 3-hydroxy-quinaldic acid.     

基于遗传中心法则的零件逐步求精创新设计

针对零件创新设计中功能分解标准各异,运算耗时随零件复杂度成指数递增以及设计局限性强等难点。在生物遗传学中心法则和基因互补配对原则的启发下,探索一种结合矢量运算、矢量组合和约束函数的面向全过程全反馈闭环逐步求精零件创新设计方法。由于采用零件特征基因编码和零件特征融合算法,简化了功能分解的依据并提高零件运算速度。文章阐述了实现的具体框架和创新设计算例,并在CATIA5R8平台验证该方法是可行。     

痛泻要方对肠易激综合征大鼠血浆及肠黏膜CGRP影响的实验研究

目的：探讨肠易激综合征（irritable bowel syndrome）的发病机制以及痛泻要方煎剂治疗肠易激综合征内脏高敏感性模型大鼠的机制。方法：选用清洁级新生sD大鼠,采用结肠慢性刺激法加夹尾刺激法造模。造模成功后,将实验动物分组为空白对照组（A组）、模型对照组（B组）、中药低剂量组（C组）、中药中剂量组（D组）、中药高剂量组（E组）、西药奥替溴铵（F组）。A组和B组以生理盐水按4ml／100g（40g／kg／d）灌胃,C、D、E、F组分别以低剂量痛泻要方煎剂组按0．4ml／100g（4g／kg／d）、中剂量痛泻要方煎剂组按1．2ml／100g（12g／kg／d）、高剂量痛泻要方煎剂组按4ml／100g（40g／kg／d）灌胃、西药奥替溴铵组按4ml／100g（150g,kg／d）灌胃,每天两次,连续30天。结果：痛泻要方高剂量组能显著增加血浆和结肠组织CCRP含量,痛泻要方低剂量组、中剂量组与西药组均不能。结论：痛泻要方可能是通过增加模型大鼠血浆和结肠组织CGRP含量来实现的。     

基于视觉-行为-情感的产品族设计基因

为进一步探索产品族设计中关于体现品牌特征和用户情感的问题,提出基于视觉-行为-情感的产品族设计基因研究方法.在分析品牌识别的硅性因素和隐性因素基础上,提出情感设计基因、行为设计基因和视觉设计基因的概念,构建了基于视觉-行为-情感的产品族设计基因的层次模型,讨论了产品族设计基因的构造方法和循环模型,探讨了产品族设计基因、信息建模、品牌风格基冈的构建,以及产品族设计基囚与品牌风格基因的映射、评价与优化等研究方法与关键技术.以家用绣花机外形设计为例,构建了产品族设计基因,以及与晶牌风格感性意象的映射,开发了计算机辅助家用绣花机设计系统软件,包括设计DNA装配模块、设计评价模块和设计知识库模块.该系统可以实现家用绣花机造型设计的快速生成与设计评价,验证了基于视觉-行为-情感的产品族设计基因理沦体系.     

DRD2和5-HTR2A基因多态性及其交互作用对奥氮平治疗精神分裂症疗效的影响

目的：探讨多巴胺D2受体（dopamine D2 receptor, DRD2）和5-羟色胺2A受体（5-hydroxytryptamine 2A receptor, 5-HTR2A）基因多态性及其交互作用与奥氮平治疗精神分裂症疗效的关系。方法：纳入147例接受单一奥氮平治疗的精神分裂症住院患者为研究对象,采用阳性与阴性症状量表（PANSS）评定药物疗效,按PANSS减分率≥50%和<50%,分为有效组和无效组。采用多重高温连接酶检测反应技术（iMLDR）检测DRD2（rs1799978、rs1800497）和5-HTR2A（rs6311、rs6313）基因多态性;采用多因素Logistic回归分析各基因型和奥氮平疗效的关联性,采用多因子降维法（MDR）分析基因-基因的交互作用。结果：有效组和无效组rs1799978、rs6313位点基因型和等位基因频率分布差异均有统计学意义（P<0.05）,而两组rs1800497、rs6311位点基因型和等位基因频率分布差异均无统计学意义（P>0.05）;rs1799978位点GA和GG型患者奥氮平疗效较野生AA型好,其比值比（OR）及95%CI分别为5.101（1.118～23.267）、6.051（2.454～14.925）;rs6313位点CT和CC型患者奥氮平疗效较野生TT型好,其OR及95%CI分别为2.623（1.054～6.528）、3.412（1.180～9.869）;rs1799978、rs1800497和rs6313位点间存在交互作用,其交互模型为最优基因-基因交互作用模型（P<0.05）,该模型检验样本准确度为0.727 3,交叉验证一致性为10/10。结论：DRD2（rs1799978）和5-HTR2A（rs6313）基因多态性可能与奥氮平治疗精神分裂症疗效相关,DRD2（rs1799978、rs1800497）和5-HTR2A（rs6313）对奥氮平疗效的影响存在交互作用。     

What function for human lithostathine?: structural investigations by three-dimensional structure modeling and high-resolution NMR spectroscopy

Human lithostathine is a 144-residue protein, expressed in variousorgans and pathologies. Several biological functions have beenproposed for this protein. Among others, inhibition of nucleationand growth of CaCO₃ crystals in the pancreas and bacterial aggregationhas retained attention, because lithostathine presents highsequence similarities with calcium-dependent (or C-type) lectins.To study its structure-function relationship and compare itwith that of C-type lectins, we have built a model for lithostathine.This model is derived from the only two C-type lectins of knownstructures: rat mannose binding protein and human E-selectin.An original strategy, inspired by that proposed by Havel andSnow, was designed for model building. We have undertaken NMRstudies on the natural protein. Although complete structuredetermination has not yet been achieved, the NMR studies didconfirm the main characteristics of the model. From analysisof the proposed model, we concluded that lithostathine is notexpected to present sugar- or calcium-binding properties. Therefore,the mechanisms of bacterial aggregation and inhibition of CaCO₃nucleation and growth have not yet been elucidated.     

Form gene clustering method about pan-ethnic-group products based on emotional semantic

The use of pan-ethnic-group products form knowledge primarily depends on a designer’s subjective experience without user participation. The majority of studies primarily focus on the detection of the perceptual demands of consumers from the target product category. A pan-ethnic-group products form gene clustering method based on emotional semantic is constructed. Consumers’ perceptual images of the pan-ethnic-group products are obtained by means of product form gene extraction and coding and computer aided product form clustering technology. A case of form gene clustering about the typical pan-ethnic-group products is investigated which indicates that the method is feasible. This paper opens up a new direction for the future development of product form design which improves the agility of product design process in the era of Industry 4.0.