MTDLs Design on AChE （Acetylcholinesterase） and β-Secretase （BACE-1）： 3D-QSAR and Molecular Docking Studies

To find promising new multitargeted AD （Alzheimer＇s disease） inhibitors, the 3D-QSAR （three-dimensional quantitative structure-activity relationship） model for 32 AD inhibitors was established by using the CoMFA （comparative molecular field analysis） and CoMSIA （comparative molecular similarity index analysis） methods. Results showed that the CoMFA and CoMSIA models were constructed successfully with a good cross-validated coefficient （q2） and a non-cross-validated coefficient （R2）, and the binding modes obtained by molecular docking were in agreement with the 3D-QSAR results, which suggests that the present 3D-QSAR model has good predictive capability to guide the design and structural modification of novel multitargeted AD inhibitors. Meanwhile, we found that one side of inhibitory molecule should be small group so that it would be conductive to enter the gorge to interact with the catalytic active sites of AChE （acetylcholinesterase）, and the other side of inhibitory molecule should be large group so that it would be favorable for interaction with the peripheral anionic site of ACHE. Furthermore, based on the 3D-QSAR model and the binding modes of AChE and [3-secretase （BACE-1）, the designed molecules could both act on dual binding sites of AChE （catalytic and peripheral sites） and dual targets （ACHE and BACE-1）. We hope that our results could provide hints for the design of new multitargeted AD derivatives with more potency and selective activity.

IPv6协议一致性测试描述语言设计与实现

IPv6协议一致性测试是检验IPv6协议实现是否正确的重要方法。为弥补我国在该领域研究水平的不足,文中提出了一种模块化测试描述模型,设计了模块化测试描述语言(Modular Test Description Language,MTDL),并开发了基于该模型和语言的IPv6协议一致性测试系统。在对IPv6协议标准深入分析的基础上设计了一套测试集,用自主开发的测试系统在Linux系统平台上对IPv6协议进行了测试,得到了预期结果,验证了MTDL语言的正确性和有效性。

MULTI-TILLERING DWARF1, a new allele of BRITTLE CULM 12, affects plant height and tiller in rice

Plant height and tillering are crucial factors determining rice plant architecture and influencing rice grain production. In this study, rnulti-tillering dwarf1 （mtdl）, a stable multi-tiller and dwarf mutant, was screened from the ethylmethane sulfonate-treated japonica rice variety Wuyunging7. Compared with the wild type, mtdl mutant exhibited pleiotropic phenotypes, including dwarf- ism, more tillers, brittle culms and delayed heading date. By employing map-based cloning strategy, the gene MTD1 was finally mapped to an approximately 66-kb region on the short arm of chromosome 9. Sequencing results showed that the gene LOCOsO9g02650 （BC12） in mtdl mutant had a single nucleotide substitution （G to A）, which gen- erated a premature translation stop. Over-expressing MTD1/BC12 coding sequ（nce rescued all the phenotypes of mtdl mutants including plant height and tillers, which confirms that BC12 is the mutated gene in mtdl mutant. Quantitative reverse tran,-eription-PCR analysis showed that MTDI/BCI2 could negatively regulate the expression of MONOCULM 1, IDEAL PLANT ARCHITECTURE1 and Tillering and Dwarf 1, and control rice tillering. Remark- ably, a-amylase activity analysis and gibberellic acid （GA） treatment showed that the dwarf phenotype of mtdl mutant was dependent on GA biosynthesis pathway. These results facilitated to further uncover the molecular mechanism of the growth and development in rice.