Hydroxyethylamine-based inhibitors of BACE1: P1–P3 macrocyclization can improve potency,selectivity, and cell activity

We describe a systematic study of how macrocyclization in the P₁–P₃ region of hydroxyethylamine-based inhibitors of β-site amyloid precursor protein (APP)-cleaving enzyme (BACE1) modulates in vitro activity. This study reveals that in a number of instances macrocyclization of bis-terminal dienes leads to improved potency toward BACE1 and selectivity against cathepsin D (CatD), as well as greater amyloid β-peptide (Aβ)-lowering activity in HEK293T cells stably expressing APP_SW. However, for several closely related analogs the benefits of macrocyclization are attenuated by the effects of other structural features in different regions of the molecules. X-ray crystal structures of three of these novel macrocyclic inhibitors bound to BACE1 revealed their binding conformations and interactions with the enzyme.     

Highly sensitive determination of the methylated p16 gene in cancer patients by microchip electrophoresis

The p16 tumor suppressor gene is inactivated by promoter region hypermethylation in many types of tumor. Recent studies showed that aberrant methylation of the p16 gene is an early event in many tumors, especially in lung cancer, and may constitute a new biomarker for early detection and monitoring of prevention trials. We detected tumor-associated aberrant hypermethylation of the p16 gene in plasma and tissue DNA from 153 specimens using a modified semi-nested methylation-specific PCR (MSP) combining plastic microchip electrophoresis or slab gel electrophoresis, respectively. Specimens were from 79 lung cancer patients, 15 abdominal tumor patients, 30 positive controls and 30 negative controls. The results showed that the positive rate obtained by microchip electrophoresis was more than 26.6% higher and the same specificity was kept when compared with slab gel electrophoresis. The microchip electrophoresis can rapidly and accurately analyze the PCR products of methylated DNA and obviously improve the positive rate of diagnosis of cancer patients when compared with gel electrophoresis. This method with the high assay sensitivity might be used for detection of methylation of p16 gene and even to facilitate early diagnosis of cancer patients.     

A comprehensive gene network for fine tuning floral development in poplar

Herbaceous model species, especially Arabidopsis has provided a wealth of information about the genes involved in floral induction and development of inflorescences and flowers. While the genus Populus is an important model system for the molecular biology of woody plant. These two genuses differ in many ways. This study was designed to improve understanding of flower development in poplar at a system level, as its regulatory pathway to a large extent remains poorly known, owing to the presently limited mutant pool. To address this issue, a poplar GeneChip was employed to detect genes expressed during the whole floral developmental process. Using the expressed floral genes, a systematic gene network was constructed with the aid of functional association with Arabidopsis. The results suggested that autonomous, gibberellin, vernalization, photoperiod, ethylene, brassinosteroid, stress-induced and floral suppression pathways are involved in poplar flowering. Modularity analysis revealed several pathways in common with Arabidopsis, such as autonomous, gibberellin, vernalization and photoperiod pathways. In addition, brassinosteroid, stress-induced and floral suppression pathways were implicated as additional novel pathways. Notably, a difference in vernalization between Arabidopsis and poplar was revealed. Autonomous, gibberellin, vernalization, photoperiod, ethylene, brassinosteroid, stress-induced and floral suppression pathways integrated into a systematic gene network in floral development of poplar. Compared to Arabidopsis, brassinosteroid, stress-induced and floral suppression pathways are additional in poplar, and FLC is absent in vernalization pathway in poplar. Preliminary conclusions drawn here provide a basis for both identification of key genes and elucidation of molecular mechanisms involved in poplar floral development.     

用RAPD技术鉴定小麦属间不对称体细胞杂种

用随机引物扩增多态DNA(RAPD)技术对三种不同组合:小麦(Triticum aestivum)( )簇毛麦(Haynaldia villosa);小麦( )羊草(Leymus chinensis)和小麦( )高冰草(Agropyron elongatum)的属间不对称杂种进行分子鉴定,不同杂种植株的基因组经随机引物扩增后,均出现双亲的多态特异产物,证实它们含有双亲的基因组。将引物OPJ-12扩增的高冰草多态特异产物(分子量为0.77bp的DNA片段)分离纯化并标记作探针,用Southern杂交证明了小麦( )高冰草杂种经OPJ-12扩增的0.77kbp特异片段与高冰草这一片段具有同源性。本文结果证明,RAPD技术可作为小麦属间不对称体细胞杂种的一种快速、简便、有效的分子鉴定方法。     

花香的生物合成、调控及基因工程研究进展

花香能提高观赏植物的审美特性,并且在植物的繁衍中起着重要作用。近年来,随着分子生物学的发展,花香分子水平的研究呈现加速发展的趋势,已成为当前的一大研究热点。该文主要论述了花香的生物合成途径及关键酶基因、分子水平的调控和共调控探索、花香基因工程策略,以期为花香性状改良提供参考。     

菲菊头蝠冬眠期的精子储存

菲菊头蝠是分布于亚热带和热带的翼手目种类,在中国大陆南部和海南岛有广泛分布。为探讨热带菲菊头蝠是否具有冬眠期(12 月至翌年2 月)储精现象及生殖腺组织结构的变化,对海南岛的菲菊头蝠成年雄蝠和成年雌蝠生殖系统在冬眠期间的变化进行了石蜡切片观察。结果显示:成年雄蝠在冬眠期间附睾内储存大量精子,推测其储存时间超过2 个月;冬眠期间曲细精管横截面积、精子细胞数量和间质细胞数量在冬眠期逐月显著性减少,精原细胞和精母细胞的数量在12 月与翌年1 月间均无显著性变化,而在冬眠末期的2 月显著增多。在雌蝠子宫和卵巢内均未发现精子储存现象,但卵巢内具有初级卵泡和次级卵泡,雄蝠在冬眠期间曲细精管逐月萎缩,但生精上皮精母细胞的数量在冬眠末期明显上升。     

昆虫体内储存蛋白的研究进展

储存蛋白是昆虫体内普遍存在的一种特异性血淋巴蛋白 ,通常在幼虫的脂肪体内合成 ,释放进入血淋巴中。化蛹时 ,又被脂肪体选择性吸收 ,作为氨基酸的贮存库对成虫变态发育和雌性卵发育起着重要的作用。该文介绍了昆虫体内储存蛋白的特性、功能、及调节机制。     

文昌鱼profilin同源基因的胚胎发育表达图式

本研究利用胚胎整体原位杂交技术结合系列组织学切片技术,以及Northern blot 分析,对进化上处于特殊地位的模式动物文昌鱼profilin 基因不同发育时期的表达图式进行了系统研究,揭示了该基因的动态表达图式与肌肉分化的过程一致,文昌鱼profilin 基因可能与胚胎早期肌肉的发育相关。同时,通过Southern blot 检测对青岛文昌鱼profilin 基因可能存在的同源体进行了探讨,试图为弄清文昌鱼肌肉发育分化的分子机制提供资料。