Identification of the hot spot residues for pyridine derivative inhibitor CCT251455 and ATP substrate binding on monopolar spindle 1 (MPS1) kinase by molecular dynamic simulation

Protein kinase monopolar spindle 1 plays an important role in spindle assembly checkpoint at the onset of mitosis. Over expression of MPS1 correlated with a wide range of human tumors makes it an attractive target for finding an effective and specific inhibitor. In this work, we performed molecular dynamics simulations of protein MPS1 itself as well as protein bound systems with the inhibitor and natural substrate based on crystal structures. The reported orally bioavailable 1 h-pyrrolo [3,2-c] pyridine inhibitors of MPS1 maintained stable binding in the catalytic site, while natural substrate ATP could not stay. Comparative study of stability and flexibility of three systems reveals position shifting of β-sheet region within the catalytic site, which indicates inhibition mechanism was through stabilizing the β-sheet region. Binding free energies calculated with MM-GB/PBSA method shows different binding affinity for inhibitor and ATP. Finally, interactions between protein and inhibitor during molecular dynamic simulations were measured and counted. Residue Gly605 and Leu654 were suggested as important hot spots for stable binding of inhibitor by molecular dynamic simulation. Our results reveal an important position shifting within catalytic site for non-inhibited proteins. Together with hot spots found by molecular dynamic simulation, the results provide important information of inhibition mechanism and will be referenced for designing novel inhibitors.     

Plant Hormone Metabolome and Transcriptome Analysis of Dwarf and Wild-type Banana

Journal of Plant Growth Regulation - Gibberellin (GA), auxin (IAA) and brassinosteroid (BR) are indispensable in the process of plant growth and development. Currently, research on the regulatory...     

“岗课赛证”四位一体“动物微生物”课程教学改革探索与实践

为适应当前职业教育政策,积极推进高水平职业院校“岗课赛证”综合育人课程建设,“动物微生物”课程教学团队进行“岗课赛证”四位一体课程教学改革,以岗位能力培养为核心,以职业标准和技能大赛为引导制定课程标准,编写特色教材,通过任务驱动法、项目式教学法和引“赛场”入课堂教学方法提高课堂教学效果,打造优质教育教学资源,加强课程师资力量建设,实现岗位、课程、大赛、证书的互为融通,把学生培养为企业需要的高素质技能型人才,全面提升教学质量。     

秦岭野生大熊猫牙齿的形态机能

大熊猫(Ailuropoda melanoleuca)是国家一级保护动物,被誉为国宝.牙齿作为大熊猫消化器官之一,相对于其他动物而言,大熊猫牙齿有其自身的构造特点.以往学者和专家对大熊猫牙齿形态的研究侧重于为大熊猫的种群分类寻找根据(Dvadi,1869; Milne-Edwards,1870;王将克,1974),更多关注牙齿在大熊猫进化、演变过程中的意义(王令红等,1982;黄万波,1993).研究的齿位大多局限于臼齿(张鹤宇和刘理,1959),所得结果或数据并不详细和全面.此外,还有一些学者对大熊猫牙齿釉质的超微组织结构进行研究(赵资奎等,1984 ).     

耐盐绒毛白蜡特异性SCAR分子标记的鉴定

该研究以耐盐型和盐敏感型绒毛白蜡及其F1代为材料,采用混合品系分析法进行RAPD分析。结果显示:在随机选取的150个10碱基随机引物中,仅有引物S20在耐盐基因池和盐敏感基因池间扩增出特异而可重复的592bp的多态性片段,命名为S20-592。获得的RAPD标记S20-592经克隆、测序、重新设计一对特异性引物转化成更稳定的SCAR标记。通过F1代个体验证,耐盐型个体均能扩增出此差异条带而盐敏感型个体中不能扩增出此差异条带,证明该SCAR标记的特异引物可用于耐盐绒毛白蜡物种的快速分子鉴定。     

遗传改良对杉木针叶和种实性状的影响

为揭示遗传改良对主要造林用材树种叶和种实性状的影响,阐明性状的变异趋势,该研究以杉木第4轮育种的精选树(改良群体)、四省五地的表型优树与古树(未改良群体)为对象,调查了218个无性系的针叶和种实性状指标,采用方差分析和多重对比方法研究遗传改良对杉木及不同类型杉木的表型差异,并通过相关性分析探究遗传改良对杉木针叶和球果部分表型性状的影响,以及利用主成分分析和聚类分析进行了分类。结果表明:(1)未改良群体的针叶长、针叶宽和出籽率分别比改良群体小13.28%、10.81%和33.90%,其他性状表现为未改良群体大于改良群体,差异在10.90%～27.03%之间。未改良群体球果长、球果宽和出籽率的变异系数,分别比改良群体大9.14%、12.73%和15.38%。(2)球果长、球果宽、苞鳞长和苞鳞宽4个性状,在未改良群体中仅有球果长和球果宽(0.931)、苞鳞长和苞鳞宽(0.622)之间呈极显著正相关,经遗传改良后,该4个性状两两之间均呈显著或极显著正相关。(3)四川雅安(SCYA)的球果长和球果宽的性状比改良群体大48.83%和53.26%,安徽黄山(AHHS)的百粒重比改良群体大16.92%。(4)遗传改良导致松张型球果的杉木比例降低,紧包型和反翘型球果的杉木比例增加。综上认为,杉木的遗传改良导致球果大小下降,改变了不同针叶和球果类型的比例,同时会改变针叶性状和种实性状的相关性,将为杉木种质资源评价和未来多目标育种提供依据。     

Lifespan extension by dietary intervention in a mouse model of Cockayne Syndrome uncouples early postnatal development from segmental progeria

Cockayne syndrome (CS) is a rare autosomal recessive segmental progeria characterized by growth failure, lipodystrophy, neurological abnormalities, and photosensitivity, but without skin cancer predisposition. Cockayne syndrome life expectancy ranges from 5 to 16 years for the two most severe forms (types II and I, respectively). Mouse models of CS have thus far been of limited value due to either very mild phenotypes, or premature death during postnatal development prior to weaning. The cause of death in severe CS models is unknown, but has been attributed to extremely rapid aging. Here, we found that providing mutant pups with soft food from as late as postnatal day 14 allowed survival past weaning with high penetrance independent of dietary macronutrient balance in a novel CS model (Csa^?/? | Xpa^?/?). Survival past weaning revealed a number of CS‐like symptoms including small size, progressive loss of adiposity, and neurological symptoms, with a maximum lifespan of 19 weeks. Our results caution against interpretation of death before weaning as premature aging, and at the same time provide a valuable new tool for understanding mechanisms of progressive CS‐related progeroid symptoms including lipodystrophy and neurodysfunction.