ALBERT

Description: IL-27 is a multifunctional cytokine that has both pro-inflammatory and anti-inflammatory functions. Although IL-27 has been shown to potently inhibit lung fibrosis, the detailed mechanism of IL-27 in this proc...

Description: Background: Asian corn borer (ACB), Ostrinia furnacalis (Guenée), is the major insect pest of maize in China and countries of East and Southeast Asia, the Pacific and Australasia. ACB can develop strong resistance to the transgenic Bt maize expressing Cry1Ab, the most widely commercialized Bt maize worldwide. However, the molecular basis for the resistance mechanisms of ACB to Cry1Ab remained unclear. Two biological replicates of the transcriptome of Bt susceptible (ACB-BtS) and Cry1Ab resistant (ACB-AbR) strains of ACB were sequenced using Solexa/Illumina RNA-Seq technology to identify Cry1Ab resistance-relevant genes. Results: The numbers of unigenes for two biological replications were 63,032 and 53,710 for ACB-BtS and 57,770 and 54,468 for ACB-AbR. There were 35,723 annotated unigenes from ACB reads found by BLAST searching NCBI non-redundant, NCBI non-redundant nucleotide, Swiss-prot protein, Kyoto Encyclopedia of Genes and Genomes, Cluster of Orthologous Groups of proteins, and Gene Ontology databases. Based on the NOISeq method, 3,793 unigenes were judged to be differentially expressed between ACB-BtS and ACB-AbR. Cry1Ab resistance appeared to be associated with change in the transcription level of enzymes involved in growth regulation, detoxification and metabolic/catabolic process. Among previously described Bt toxin receptors, the differentially expressed unigenes associated with aminopeptidase N and chymotrypsin/trypsin were up-regulated in ACB-AbR. Whereas, other putative Cry receptors, cadherin-like protein, alkaline phosphatase, glycolipid, actin, V-type proton ATPase vatalytic, heat shock protein, were under-transcripted. Finally, GPI-anchor biosynthesis was found to be involved in the significantly enriched pathway, and all genes mapped to the pathway were substantially down-regulated in ACB-AbR. Conclusion: To our knowledge, this is the first comparative transcriptome study to discover candidate genes involved in ACB Bt resistance. This study identified differentially expressed unigenes related to general Bt resistance in ACB. The assembled, annotated transcriptomes provides a valuable genomic resource for further understanding of the molecular basis of ACB Bt resistance mechanisms.

Description: Background: Somatic Copy Number Alterations (CNAs) in human genomes are present in almost all human cancers. Systematic efforts to characterize such structural variants must effectively distinguish significant consensus events from random background aberrations. Here we introduce Significant Aberration in Cancer (SAIC), a new method for characterizing and assessing the statistical significance of recurrent CNA units. Three main features of SAIC include: (1) exploiting the intrinsic correlation among consecutive probes to assign a score to each CNA unit instead of single probes; (2) performing permutations on CNA units that preserve correlations inherent in the copy number data; and (3) iteratively detecting Significant Copy Number Aberrations (SCAs) and estimating an unbiased null distribution by applying an SCA-exclusive permutation scheme. Results: We test and compare the performance of SAIC against four peer methods (GISTIC, STAC, KC-SMART, CMDS) on a large number of simulation datasets. Experimental results show that SAIC outperforms peer methods in terms of larger area under the Receiver Operating Characteristics curve and increased detection power. We then apply SAIC to analyze structural genomic aberrations acquired in four real cancer genome-wide copy number data sets (ovarian cancer, metastatic prostate cancer, lung adenocarcinoma, glioblastoma). When compared with previously reported results, SAIC successfully identifies most SCAs known to be of biological significance and associated with oncogenes (e.g., KRAS, CCNE1, and MYC) or tumor suppressor genes (e.g., CDKN2A/B). Furthermore, SAIC identifies a number of novel SCAs in these copy number data that encompass tumor related genes and may warrant further studies. Conclusions: Supported by a well-grounded theoretical framework, SAIC has been developed and used to identify SCAs in various cancer copy number data sets, providing useful information to study the landscape of cancer genomes. Open-source and platform-independent SAIC software is implemented using C++, together with R scripts for data formatting and Perl scripts for user interfacing, and it is easy to install and efficient to use. The source code and documentation are freely available at http://www.cbil.ece.vt.edu/software.htm.

Description: Background: Both transcriptional factor Ets-1 and integrin alphavbeta6 play an important role in the development and progression of cancer. The aim of our study was to investigate the expression of Integrin alphavbeta6 and Ets-1, two proteins' correlation and their clinical significance in colorectal cancerous tissues. Results: The specimens were arranged into microarray using the immunohistochemistry method to investigate the expression of integrin alphavbeta6 and transcriptional factor Ets-1 in these tissues. Among the 158 tissue specimens, 36.07% were positive for alphavbeta6 expression, and 57.59% were positive for Ets-1 expression. There were obvious statistical differences existed regarding differentiation, N stage, M stage and TNM stage between alphavbeta6 and Ets-1 positively and negatively expressing tumors. The correlation analysis confirmed the expression of alphavbeta6 and Ets-1 were positively correlated in colorectal cancer. The Kaplan-Meier survival analysis showed that patients who were both alphavbeta6 and Ets-1 positive relapsed earlier than those who were both alphavbeta6 and Ets-1 negative; and the former group had much shorter survival time than the latter. And Cox model indicated that alphavbeta6 and Ets-1 were the independent prognostic factors (RR = 2.175, P = 0.012 and RR = 3.903, P 〈 0.001). Conclusions: The expression of alphavbeta6 and Ets-1 were positively correlated, and their expression degrees were associated with the differentiation, N stage, M stage and TNM stage of the tumors. Hence, the combination of alphavbeta6 and Ets-1 can be used as a prognostic marker in colorectal cancer, especially for the early stage.

Description: Background: Reduced beta2-glycoprotein I (beta2-GPI) is a free thiol-containing form of beta2-GPI that displays a powerful effect in protecting endothelial cells from oxidative stress-induced cell death. The present study aims to investigate the effect of beta2-GPI or reduced beta2-GPI on ox-LDL-induced foam cell formation and on cell apoptosis and to determine the possible mechanisms. Methods: The RAW264.7 macrophage cell line was selected as the experimental material. Oil red O staining and cholesterol measurement were used to detect cholesterol accumulation qualitatively and quantitatively, respectively. Flow cytometry was used to detect cell apoptosis. Real-time quantitative PCR was used to detect the mRNA expression of the main proteins that are associated with the transport of cholesterol, such as CD36, SRB1, ABCA1 and ABCG1. Western blot analysis was used to detect the protein expression of certain apoptosis-related proteins, such as caspase-9, caspase-3, p38 MAPK/p-p38 MAPK and JNK/p-JNK. Results: Beta2-GPI or reduced beta2-GPI decreased ox-LDL-induced cholesterol accumulation (96.45 +/- 8.51 mug/mg protein vs. 114.35 +/- 10.38 mug/mg protein, p 〈 0.05;74.44 +/- 5.27 mug/mg protein vs. 114.35 +/- 10.38 mug/mg protein, p 〈 0.01) and cell apoptosis (30.00 +/- 5.10% vs. 38.70 +/- 7.76%, p 〈 0.05; 20.66 +/- 2.50% vs. 38.70 +/- 7.76%, p 〈 0.01), and there are significant differences between beta2-GPI and reduced beta2-GPI (p 〈 0.05). Reduced beta2-GPI decreased the ox-LDL-induced expression of CD36 mRNA and ABCA1 mRNA (p 〈 0.05), as well as CD36, cleaved caspase-9, cleaved caspase-3, p-p38 MAPK and p-JNK proteins (p 〈 0.05 or p 〈 0.01). Beta2-GPI did not significantly decrease the expression of ABCA1 mRNA and the p-p38 MAPK protein. Conclusions: Both beta2-GPI and reduced beta2-GPI inhibit ox-LDL-induced foam cell formation and cell apoptosis, and the latter exhibits a stronger inhibition effect. Both of these glycoproteins reduce the lipid intake of macrophages by downregulating CD36 as well as protein expression. Reduced beta2-GPI inhibits cell apoptosis by reducing the ox-LDL-induced phosphorylation of p38 MAPK and JNK, and the amount of cleaved caspase-3 and caspase-9. Beta2-GPI does not inhibit the ox-LDL-induced phosphorylation of p38 MAPK.

Description: Background: The WRKY transcription factor is an important member of the stress-related transcription factors, which mediate diverse abiotic stresses in many plants. However, up until now, the number of WRKY members, and the regulatory mechanisms involved in abiotic stress responses in Pak-choi (Brassica campestris ssp. chinensis), remained unknown. Results: We isolated and identified 56 full-length WRKY cDNAs from a Pak-choi stress-induced cDNA library. The 56 putative BcWRKY proteins were divided into three groups based on structural and phylogenetic analyses. A subcellular localization prediction indicated that the putative BcWRKY proteins were enriched in the nuclear region. Experiments involving BcWRKY25 and BcWRKY40 confirmed the prediction. A total of 22 BcWRKYs were differentially expressed in response to at least one stress condition (abscisic acid, cold, salinity, heat, or osmosis) tested on Pak-choi leaves, and a co-expression analysis indicated stress-inducible BcWRKYs co-regulated multiple abiotic stresses. BcWRKY33, BcWRKY40, BcWRKY53, and BcWRKY70 acted as key regulators and played dominant roles within co-regulatory networks of stress-inducible BcWRKYs. Conclusions: We first isolated and characterized the 56 stress-inducible WRKY transcription factor family members. A total of 22 stress-inducible BcWRKYs found in leaves can co-regulate multiple environmental stresses by integrating the potential mutual interactions of WRKYs in Pak-choi. This information will be valuable when exploring the molecular mechanisms of WRKYs in response to abiotic stresses in plants.

Description: Background: Variants in Methylenetetrahydrofolate reductase (MTHFR) gene may result in a lowered catalytic activity and associate with subsequent elevated serum homocysteine (Hcy) concentration, abnormal DNA synthesis and methylation, cardiovascular risk, and unhealthy aging. Several investigations on the relationship of MTHFR C677T polymorphism with serum lipid profile and longevity have been conducted in some populations, but findings remain mixed. Herein, we sought to look at the association between MTHFR C677T and lipid profile in a longevous cohort in Bama, a well-known home of longevity in China. Methods: Genotyping of MTHFR C677T was undertaken in 516 long-lived inhabitants (aged 90 and older, long-lived group, LG) and 493 healthy controls (aged 60-75, non-long-lived group, non-LG) recruited from Bama area. Correlation between MTHFR genotypes and lipids was then evaluated. Results: T allele and TT genotype were significantly more prevalent in LG (P = 0.001 and 0.002, respectively), especially in females, than in non-LG. No difference in the tested lipid measures among MTHFR C677T genotypes was observed in LG, non-LG and total population (P 〉 0.05 for each). However, female but not male T carriers exhibited higher TC and LDL-C levels than did T noncarriers in the total population and in LG after stratification by sex (P 〈 0.05 for each). These differences did not however remain through further subdivision by hyperlipidemia and normolipidemia. Conclusion: The higher prevalence of MTHFR 677 T genotypes and its modest unfavorable impact on lipids in Bama long-lived individuals may imply an existence of other protective genotypes which require further determination.

Description: Nicotine is known to differentially regulate cortical interneuron and pyramidal neuron activities in the neocortex, while the underlying molecular mechanisms have not been well studied. In this study, RNA-sequ...

Description: Background: The T790M mutation of epithelial growth factor receptor (EGFR) is a major cause of the acquired resistance to EGFR tyrosine kinase inhibitor (EGFR-TKIs) treatment for lung cancer patients. The Hippo pathway effector, TAZ, has emerged as a key player in organ growth and tumorigenesis, including lung cancer. Results: In this study, we have discovered high TAZ expression in non-small cell lung cancer (NSCLC) cells harboring dual mutation and TAZ depletion sensitized their response to EGFR-TKIs. Mechanistically, knockdown of TAZ in T790M-induced resistant cells leaded to reduced anchorage-independent growth in vitro, tumor formation and resistance to gefitinib in vivo, correlated with epithelial-mesenchymal transition (EMT) and suppressed migration and invasion. Furthermore, we confirmed CTGF and AXL, novel EMT markers and potential therapeutic targets for overcoming EGFR inhibitor resistance, as directly transcriptional targets of TAZ. Conclusions: Taken together, this study suggests that expression of TAZ is an intrinsic mechanism of T790M-induced resistance in response to EGFR-TKIs. Combinational targeting on both EGFR and TAZ may enhance the efficacy of EGFR-TKIs in acquired resistance of NSCLC.