High expression of NEK2 promotes lung cancer progression and drug resistance and is regulated by mutant EGFR

Molecular and Cellular Biochemistry - An increasing amount of research showed that endothelial cells (ECs) play crucial role in vascular disorders such as atherosclerosis (AS). LncRNA OIP5-AS1 and...     

基于遥感和GIS的巢湖流域生态功能分区研究

生态功能分区是区域自然资源科学管理及可持续发展利用的基础。基于生态功能分区原则,考虑流域——子流域完整性进行巢湖流域生态功能分区。在综合分析巢湖流域生态环境基本特征的基础上,确定生态功能分区原则、依据、方法及命名,基于遥感与GIS在数据采集方面及多层面叠加功能的优势,通过遥感数据对研究区土地利用信息的提取以及利用DEM空间分析进行子流域划分等技术手段,探讨了遥感和GIS技术支持下的研究区子流域生态功能划分方法,形成了巢湖流域生态功能分区方案,将全流域分为5个生态功能区和12个生态功能亚区,并阐明了不同生态功能区的生态保护重点与经济社会发展约束。对于新调整行政区划的巢湖流域生态环境综合治理具有重要的现实意义,可为流域产业布局、生态防灾减灾、环境保护与建设规划等提供科学依据。     

Interacting genetic loci on chromosomes 20 and 10 influence extreme human obesity

Obesity is a multigenic trait that has a substantial genetic component. Animal models confirm a role for gene-gene interactions, and human studies suggest that as much as one-third of the heritable variance may be due to nonadditive gene effects. To evaluate potential epistatic interactions among five regions, on chromosomes 7, 10, and 20, that have previously been linked to obesity phenotypes, we conducted pairwise correlation analyses based on alleles shared identical by descent (IBD) for independent obese affected sibling pairs (ASPs), and we determined family-specific nonparametric linkage (NPL) scores in 244 families. The correlation analyses were also conducted separately, by race, through use of race-specific allele frequencies. Conditional analyses for a qualitative trait (body mass index [BMI] >/=27) and hierarchical models for quantitative traits were used to further refine evidence of gene interaction. Both the ASP-specific IBD-sharing probability and the family-specific NPL score revealed that there were strong positive correlations between 10q (88-97 cM) and 20q (65-83 cM), through single-point and multipoint analyses with three obesity thresholds (BMI >/=27, >/=30, and >/=35) across African American and European American samples. Conditional analyses for BMI >/=27 found that the LOD score at 20q rises from 1.53 in the baseline analysis to 2.80 (empirical P=.012) when families were weighted by evidence for linkage at 10q (D10S1646) through use of zero-one weights (weight(0-1)) and to 3.32 (empirical P<.001) when proportional weights (weight(prop)) were used. For percentage fat mass, variance-component analysis based on a two-locus epistatic model yielded significant evidence for interaction between 20q (75 cM) and the chromosome 10 centromere (LOD = 1.74; P=.024), compared with a two-locus additive model (LOD = 0.90). The results from multiple methods and correlated phenotypes are consistent in suggesting that epistatic interactions between loci in these regions play a role in extreme human obesity.     

β-Ionone-induced apoptosis in human osteosarcoma (U2os) cells occurs via a p53-dependent signaling pathway

β-Ionone is a constituent of vegetables and fruits, and can induce apoptosis in some types of malignant cells. However, the mechanism of apoptosis in osteosarcoma (U2os) cells is currently unclear. In this study, we determined whether β-ionone can induce apoptosis in U2os cells in vitro and which signal pathway(s) is involved. We found that β-ionone inhibited cell proliferation in U2os cells in a concentration- and time-dependent manner and caused cell cycle arrest at the G1-S phase. TUNEL assay, DNA ladder and assessment of Caspase 3 activity showed that apoptosis was the determinant in the effects of β-ionone. Furthermore, Expression of the p53 protein increased in a concentration-dependent and time-dependent manner according to immunocytochemistry and immunoblotting after β-ionone treatment. In addition, β-ionone upregulated Bax protein and downregulated Bcl2 protein which led to Bax translocation and cytochrome c release, subsequently activated Caspase 3, thus resulting in apoptosis. In summary, these data suggested that β-ionone induced apoptosis in a concentration-dependent manner in U2os cells via a p53-dependent mitochondrial pathway.     

The isolation of the <Emphasis Type="Italic">IGT</Emphasis> family genes in <Emphasis Type="Italic">Malus × domestica</Emphasis> and their expressions in four idiotype apple cultivars

IGT family genes share the highly conserved motif GφL-(A/T) IGT in domain II and play an essential role in plant form. The tree architecture of apple (Malus ×?domestica Borkh.) affects fruit quality and yield. However, little information is available regarding IGT family genes in apple. Apple cultivars of four ideotypes (columnar, tip bearer, spur, and standard) were selected to characterize IGT family genes. Four IGT family members named MdoTAC1a, MdoTAC1b, MdoLAZY1, and MdoLAZY2 were found in the apple genome, sharing four conserved domains. In addition, MdoLAZY1 and MdoLAZY2 contain a fifth domain (EAR motif) at the C-terminus. There was no difference in the coding sequences of each gene in the four cultivars, but several mutated sites were found in their promoters. The four genes displayed lower expression levels in all tested tissues and organs of the columnar cultivar than in the other three cultivars, while expression levels of MdoTAC1a and MdoTAC1b in shoot tips and vegetative buds were highest in the standard cultivar, followed by spur, tip bearing, and columnar cultivars in decreasing order. These results indicate that IGT gene promoters are of great importance in the development of apple tree architecture and lay a theoretical basis for developing gene-specific markers for marker-assisted selection in breeding programs.     

Rapid endocytosis of interleukin-15 by cerebral endothelia

Interleukin (IL)-15 receptors are present in the cerebral endothelia composing the blood-brain barrier where they show robust up-regulation by neuroinflammation. To determine how IL15 receptor subunits participate in the endocytosis and intracellular trafficking of IL15, we performed confocal microscopic imaging and radioactive tracer uptake assays in primary brain microvessel endothelial cells and related cell lines transfected with modulatory molecules. By immunostaining and co-localization studies with organelle markers, we showed that IL15 was rapidly endocytosed via lipid rafts and was directed to diverse intracellular pathways. During the course of intracellular trafficking, Alexa dye-conjugated IL15 was partially co-localized with both the specific receptor IL15Rα and the co-receptor IL2Rγ. However, deletion of one of the receptor subunits had only a minor effect in slowing IL15 uptake when primary brain microvessel endothelial cells from the receptor knockout mice were compared with those from wildtype mice. IL15 was trafficked to early, recycling, and late endosomes, to the Golgi, and to lysosomes. The diffuse distribution suggests that IL15 activates multiple endothelial signaling events.     

Genetic loci for blood lipid levels identified by linkage and association analyses in Caribbean Hispanics

To identify genetic loci influencing blood lipid levels in Caribbean Hispanics, we first conducted a genome-wide linkage scan in 1,211 subjects from 100 Dominican families on five lipid quantitative traits: total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), and LDL-C/HDL-C ratio. We then investigated the association between blood lipid levels and 21,361 single nucleotide polymorphisms (SNP) under the 1-logarithm of odds (LOD) unit down regions of linkage peaks in an independent community-based subcohort (N = 814, 42% Dominican) from the Northern Manhattan Study (NOMAS). We found significant linkage evidence for LDL-C/HDL-C on 7p12 (multipoint LOD = 3.91) and for TC on 16q23 (LOD = 3.35). In addition, we identified suggestive linkage evidence of LOD > 2.0 on 15q23 for TG, 16q23 for LDL-C, 19q12 for TC and LDL-C, and 20p12 for LDL-C. In the association analysis of the linkage peaks, we found that seven SNPs near FLJ45974 were associated with LDL-C/HDL-C with a nominal P < 3.5 × 10(-5), in addition to associations (P < 0.0001) for other lipid traits with SNPs in or near CDH13, SUMF2, TLE3, FAH, ARNT2, TSHZ3, ZNF343, RPL7AL2, and TMC3. Further studies are warranted to perform in-depth investigations of functional genetic variants in these regions.     

Cerebral microvascular IL15 is a novel mediator of TNF action

The blood-brain barrier is a gatekeeper and modulatory interface for the CNS. Cerebral endothelial cells are the major component of the blood-brain barrier, and they modify inflammatory signals from the circulation to the CNS by production and secretion of secondary substances. The inflammatory mediators induced by tumor necrosis factor α (TNF) were determined by microarray analysis of RBE4 cerebral endothelial cells, at 0, 6, 12, or 24 h after TNF treatment. Interleukin (IL)-15 and its receptors were among the most robustly up-regulated genes. This was confirmed by real-time RT-PCR and western blotting. The three subunits of the IL15 receptor complex (IL15Rα, IL2Rβ, and IL2Rγ) showed differential regulation by TNF in their time course and amplitude of increased expression. Consistent with increased expression of the specific high affinity receptor IL15Rα, TNF increased cellular uptake of ¹²⁵I-IL15 and enhanced the fluorescent intensity of Alexa568-IL15 in RBE4 cells. TNF treatment in mice also increased the level of expression of IL15 receptors in enriched cerebral microvessels. We conclude that the cerebral microvascular IL15 system is a novel inflammatory mediator that transduces the actions of TNF.     

Octadecylated silica monolith capillary column with integrated nanoelectrospray ionization emitter for highly efficient proteome analysis

An improved strategy for the preparation of octadecylated silica monolith capillary column with high homogeneity was proposed. Column performance was evaluated by nanoscale HPLC. The design for constructing an integrated nanoelectrospray emitter on the octadecylated silica monolith capillary column was first introduced. In comparison with the separated configuration where the emitter is connected to monolithic capillary column by the aid of a zero dead volume union, the integrated capillary column has the inherent advantage of the minimized extracolumn volume thus providing improved separation quality. The performance of the integrated monolithic capillary column was evaluated by separation of BSA tryptic digest, and peak capacity of 313 with a 30-cm column was obtained. The high separation performance allowed highly confident identification of 662 distinct proteins through assignment of 1933 unique peptides by analysis of tryptic digest of 0.5 mug of Saccharomyces cerevisiae proteins. The higher separation efficiency by a 60-cm monolithic capillary column increased the proteome coverage with identification of 1323 proteins through assignment of 5501 unique peptides over 400-min gradient elution.