An epi-allelic series of p53 hypomorphs created by stable RNAi produces distinct tumor phenotypes in vivo

The application of RNA interference (RNAi) to mammalian systems has the potential to revolutionize genetics and produce novel therapies. Here we investigate whether RNAi applied to a well-characterized gene can stably suppress gene expression in hematopoietic stem cells and produce detectable phenotypes in mice. Deletion of the Trp53 tumor suppressor gene greatly accelerates Myc-induced lymphomagenesis, resulting in highly disseminated disease. To determine whether RNAi suppression of Trp53 could produce a similar phenotype, we introduced several Trp53 short hairpin RNAs (shRNAs) into hematopoietic stem cells derived from E(mu)-Myc transgenic mice, and monitored tumor onset and overall pathology in lethally irradiated recipients. Different Trp53 shRNAs produced distinct phenotypes in vivo, ranging from benign lymphoid hyperplasias to highly disseminated lymphomas that paralleled Trp53-/- lymphomagenesis in the E(mu)-Myc mouse. In all cases, the severity and type of disease correlated with the extent to which specific shRNAs inhibited p53 activity. Therefore, RNAi can stably suppress gene expression in stem cells and reconstituted organs derived from those cells. In addition, intrinsic differences between individual shRNA expression vectors targeting the same gene can be used to create an 'epi-allelic series' for dissecting gene function in vivo.     

Ru2 and Ru encode mouse orthologs of the genes mutated in human Hermansky-Pudlak syndrome types 5 and 6

Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous disease involving abnormalities of melanosomes, platelet dense granules and lysosomes. Here we have used positional candidate and transgenic rescue approaches to identify the genes mutated in ruby-eye 2 and ruby-eye mice (ru2 and ru, respectively), two 'mimic' mouse models of HPS. We also show that these genes are orthologs of the genes mutated in individuals with HPS types 5 and 6, respectively, and that their protein products directly interact. Both genes are previously unknown and are found only in higher eukaryotes, and together represent a new class of genes that have evolved in higher organisms to govern the synthesis of highly specialized lysosome-related organelles.     

A gravitationally lensed quasar with quadruple images separated by 14.62 arcseconds

Gravitational lensing is a powerful tool for the study of the distribution of dark matter in the Universe. The cold-dark-matter model of the formation of large-scale structures (that is, clusters of galaxies and even larger assemblies) predicts the existence of quasars gravitationally lensed by concentrations of dark matter so massive that the quasar images would be split by over 7 arcsec. Numerous searches for large-separation lensed quasars have, however, been unsuccessful. All of the roughly 70 lensed quasars known, including the first lensed quasar discovered, have smaller separations that can be explained in terms of galaxy-scale concentrations of baryonic matter. Although gravitationally lensed galaxies with large separations are known, quasars are more useful cosmological probes because of the simplicity of the resulting lens systems. Here we report the discovery of a lensed quasar, SDSS J1004 + 4112, which has a maximum separation between the components of 14.62 arcsec. Such a large separation means that the lensing object must be dominated by dark matter. Our results are fully consistent with theoretical expectations based on the cold-dark-matter model.     

CUL-4 ubiquitin ligase maintains genome stability by restraining DNA-replication licensing

To maintain genome stability, DNA replication is strictly regulated to occur only once per cell cycle. In eukaryotes, the presence of 'licensing proteins' at replication origins during the G1 cell-cycle phase allows the formation of the pre-replicative complex. The removal of licensing proteins from chromatin during the S phase ensures that origins fire only once per cell cycle. Here we show that the CUL-4 ubiquitin ligase temporally restricts DNA-replication licensing in Caenorhabditis elegans. Inactivation of CUL-4 causes massive DNA re-replication, producing cells with up to 100C DNA content. The C. elegans orthologue of the replication-licensing factor Cdt1 (refs 2, 3) is required for DNA replication. C. elegans CDT-1 is present in G1-phase nuclei but disappears as cells enter S phase. In cells lacking CUL-4, CDT-1 levels fail to decrease during S phase and instead remain constant in the re-replicating cells. Removal of one genomic copy of cdt-1 suppresses the cul-4 re-replication phenotype. We propose that CUL-4 prevents aberrant re-initiation of DNA replication, at least in part, by facilitating the degradation of CDT-1.     

杨树不同杂交组合苗期性状遗传变异

对T120×S3107等8个杂交组合及各组合内无性系间的苗高、胸径、分枝情况等性状变异进行了研究。结果表明,组合间和无性系间在各性状上存在着显著的变异,苗高、胸径、侧枝的广义遗传力分别为77.75%,52.64%,56.96%。各杂交组合苗高和胸径平均值均超过对照T120和I 69。I 69×S3244,I 69×I 63组合的苗高和胸径性状表现都较好。因此,从这批材料中选出优良无性系是有可能的。     

上海餐饮服务业排污收费的影响因子及其调控

选取上海中心城区餐饮服务业发达的静安区为实证研究样区,分析2000年不同季节580户餐饮服务业的1000多个排污收费数据,结果表明:①废水COD_cr和石油类累积等标污染负荷比超过95%,是最突出污染因子;主要污染源是排水量1000吨/月以上的企业,污染负荷比60%以上.污染物浓度与排水量显著负相关.②废水排污收费总额与污染负荷高度线形相关.收费单价与单位水量污染负荷正相关,与三次曲线拟合模型最吻合.③废水总平均排污收费单价0.26元/吨,明显低于上海市区11个污水处理厂平均运营成本0.53元/吨。在数据分析基础上,从实施"排污即收费,超标就罚款",推进总量与浓度控制相结合等角度进一步探讨了加强沙锅南海餐饮服务业排污收费调控管理的途径,为餐饮服务业排污收费的定价标准和监管模式提供客观依据.     

基于TCP/IP的多用户通信的实现技术

在基于TCP／IP的C／S架构下,针对多用户登录和客户端间多用户通信中的若干问题,提出了一些解决方案、算法与实现,并用Visual C^ 给出了一个相应的应用实例。     

REE geochemistry of suspended sediments from the rivers around the Yellow Sea and provenance indicators

Rare earth element (REE) compositions of the suspended sediments from the rivers around the Yellow Sea were different in that Korean river sediments (Han, Keum and Yeongsan Rivers) yield stronger fractionations than Chinese river sediments (Changjiang, Huanghe and Yalujiang), shown by obvious enrichments of LREE (light rare earth element) relative to UCC (upper continental crust).Variations of source rock compositions in the drainage basins are responsible for the differences of REE compositions between the river sediments. REE fractionation parameters including (La/Yb)ucc and (Gd/Yb)ucc as well as the ratios of La/Sc and Th/Sc can be treated as proper proxies for identifying the Chinese river sediments from those Korean river matters, and furthermore, for studying the provenances and paleoenvironmental changes of the marginal seas of China.     

Change in the sedimentary environment of Wanquan River Estuary,Hainan Island,China

Pb geochronology and sediment core profiles of organic carbon, total sulfur and organic carbon isotope (d 13C) values were used to reconstruct the local environ-mental history of the Shamei Lagoon, located in the Wan-quan River Estuary, eastern Hainan Island, China. Totalsulfur and d 13C values decreased upwards in the top 30 cm of a sediment core that spanned the last 200 years of deposi-tion. Total sulfur concentration and d 13C values respectively decreased upward from 1.92% to 0.36%, and -20.63?to -23.64? The C/S ratio in the 19th century and earlier was relatively stable in the range of 0.47—0.80, and there was a positive correlation between organic carbon and total sulfur. Since around 1900 AD, the C/S ratio increased rapidly to a maximum of 3.94, but no simple correlation was found be-tween organic carbon and total sulfur during this more re-cent period. These results indicated that before 1800 AD, the lagoon had a fully marine character, and the location of to-day抯 Wanquan River Estuary was an open embayment.From 1800 to 1900, the salinity of Shamei Lagoon decreased noticeably. The amount of seawater which could enter thelagoon decreased gradually as the Yudai spit grew. Today,seawater scarcely affects the lagoon; it is essentially a fresh-water basin.