Differential effects of oncogenic K-Ras and N-Ras on proliferation, differentiation and tumor progression in the colon

Kras is commonly mutated in colon cancers, but mutations in Nras are rare. We have used genetically engineered mice to determine whether and how these related oncogenes regulate homeostasis and tumorigenesis in the colon. Expression of K-Ras(G12D) in the colonic epithelium stimulated hyperproliferation in a Mek-dependent manner. N-Ras(G12D) did not alter the growth properties of the epithelium, but was able to confer resistance to apoptosis. In the context of an Apc-mutant colonic tumor, activation of K-Ras led to defects in terminal differentiation and expansion of putative stem cells within the tumor epithelium. This K-Ras tumor phenotype was associated with attenuated signaling through the MAPK pathway, and human colon cancer cells expressing mutant K-Ras were hypersensitive to inhibition of Raf, but not Mek. These studies demonstrate clear phenotypic differences between mutant Kras and Nras, and suggest that the oncogenic phenotype of mutant K-Ras might be mediated by noncanonical signaling through Ras effector pathways.     

氯代苯并三唑类紫外线吸收剂的合成

通过重氮化,偶合,还原和烷基化反应合成了７个氯代苯并三唑类紫外线吸收剂,在烷基化反应中使用了相转移催化剂三乙基苄基氯化铵。合成的紫外线吸收剂经红外,核磁共振,质谱等确证了结构。测定吸收波长发现引入氯原子使其摩尔消光系数增大,最大吸收波长向长波方向移动。     

锥阀稳态液动力及阀芯表面压力分布数值模拟

基于Fluent流场仿真软件,对锥阀外流和内流情况下阀芯所受稳态液动力及阀芯表面压力分布进行了数值模拟和分析。结果表明,稳态液动力随着阀口压差的增大而增加;当阀口压差大于2.5MPa时,阀芯表面出现负压,阀口处发生气蚀;当阀口开度为1mm时,稳态液动力最大;在其他条件相同的情况下,锥阀内流时的液动力小于锥阀外流时的液动力。     

The cystic fibrosis transmembrane conductance regulator (CFTR) and its stability

The cystic fibrosis transmembrane conductance regulator (CFTR) is responsible for the disease cystic fibrosis (CF). It is a membrane protein belonging to the ABC transporter family functioning as a chloride/anion channel in epithelial cells around the body. There are over 1500 mutations that have been characterised as CF-causing; the most common of these, accounting for ~70 % of CF cases, is the deletion of a phenylalanine at position 508. This leads to instability of the nascent protein and the modified structure is recognised and then degraded by the ER quality control mechanism. However, even pharmacologically ‘rescued’ F508del CFTR displays instability at the cell’s surface, losing its channel function rapidly and it is rapidly removed from the plasma membrane for lysosomal degradation. This review will, therefore, explore the link between stability and structure/function relationships of membrane proteins and CFTR in particular and how approaches to study CFTR structure depend on its stability. We will also review the application of a fluorescence labelling method for the assessment of the thermostability and the tertiary structure of CFTR.     

Putting a brake on synaptic vesicle endocytosis

In chemical synapses, action potentials evoke synaptic vesicle fusion with the presynaptic membrane at the active zone to release neurotransmitter. Synaptic vesicle endocytosis (SVE) then follows exocytosis to recapture vesicle proteins and lipid components for recycling and the maintenance of membrane homeostasis. Therefore, SVE plays an essential role during neurotransmission and is one of the most precisely regulated biological processes. Four modes of SVE have been characterized and both positive and negative regulators have been identified. However, our understanding of SVE regulation remains unclear, especially the identity of negative regulators and their mechanisms of action. Here, we review the current knowledge of proteins that function as inhibitors of SVE and their modes of action in different forms of endocytosis. We also propose possible physiological roles of such negative regulation. We believe that a better understanding of SVE regulation, especially the inhibitory mechanisms, will shed light on neurotransmission in health and disease.     

Nine new species of the subgenus Stegana (Oxyphortica) from the Oriental region,with morphological and molecular evidence based on Chinese species (Diptera: Drosophilidae)

Nine new species of the subgenus Stegana (Oxyphortica) have been discovered from the Oriental Region: S. (O.) chuanjiangi Zhang and Chen, sp. nov., S (O.) dainuo Wang and Chen, sp. nov., S. (O.) dawa Zhang and Chen, sp. nov., S. (O.) laohlie Zhang and Chen, sp. nov., S. (O.) luchun Wang and Chen, sp. nov., S. (O.) mengwan Wang and Chen, sp. nov., S. (O.) triodonta Cheng and Chen, sp. nov. from southern China; S. (O.) dehiscens Cheng and Chen, sp. nov. and S. (O.) spinosa Cheng and Chen, sp. nov. from eastern Malaysia. One newly recorded species from China: S. (O.) maichouensis Sidorenko is re-described. The DNA sequences of the mitochondrial COI gene with BOLD Process ID and GenBank accession numbers are provided for the above seven new species and five known species from China: S. (O.) acutipenis Xu, Gao and Chen, S. (O.) adentata Toda and Peng, S. (O.) hirtipenis Xu, Gao and Chen, S. (O.) latipenis Xu, Gao and Chen, and S. (O.) maichouensis Sidorenko. Intra- and interspecific pairwise K-2P distances among these species are summarized and the phylogenetic relationships are reconstructed based on the neighbour-joining (NJ) analyses.

www.zoobank.org/urn:lsid:zoobank.org:pub:2FA403F6-5535-40A4-9FD0-ADB9913EDE83.     

Genome-wide association studies of 14 agronomic traits in rice landraces

Uncovering the genetic basis of agronomic traits in crop landraces that have adapted to various agro-climatic conditions is important to world food security. Here we have identified ～ 3.6 million SNPs by sequencing 517 rice landraces and constructed a high-density haplotype map of the rice genome using a novel data-imputation method. We performed genome-wide association studies (GWAS) for 14 agronomic traits in the population of Oryza sativa indica subspecies. The loci identified through GWAS explained ～ 36% of the phenotypic variance, on average. The peak signals at six loci were tied closely to previously identified genes. This study provides a fundamental resource for rice genetics research and breeding, and demonstrates that an approach integrating second-generation genome sequencing and GWAS can be used as a powerful complementary strategy to classical biparental cross-mapping for dissecting complex traits in rice.     

Chromosome boundary elements and regulation of heterochromatin spreading

Chromatin is generally classified as euchromatin or heterochromatin, each with distinct histone modifications, compaction levels, and gene expression patterns. Although the proper formation of heterochromatin is essential for maintaining genome integrity and regulating gene expression, heterochromatin can also spread into neighboring regions in a sequence-independent manner, leading to the inactivation of genes. Because the distance of heterochromatin spreading is stochastic, the formation of boundaries, which block the spreading of heterochromatin, is critical for maintaining stable gene expression patterns. Here we review the current understanding of the mechanisms underlying heterochromatin spreading and boundary formation.