Association between variants of EXT2 and type 2 diabetes: a replication and meta-analysis

Recent publications have found an association between variants of exostosin 2 (EXT2) gene and the risk of type 2 diabetes in some population but not in others. In an attempt to address these inconsistencies, we investigated EXT2 variants in two independent cohorts, and conducted a literature-based meta-analysis. Through regression model, we assessed the relationship between the EXT2 single nucleotide polymorphisms (SNPs) (rs3740878, rs11037909 and rs1113132) and the risk of type 2 diabetes in Han Chinese population, including a total of 2,533 cases and 2,643 controls. We combined our data with that from previously published studies and performed a meta-analysis to evaluate the effect size of the gene. Consistent with some studies, we found marginal association for the rs3740878 (OR = 1.07, 95 % CI = 0.99, 1.16, p = 0.09), rs11037909 (OR = 1.07, 95 % CI = 0.99, 1.16, p = 0.08), and rs1113132 (OR = 1.08, 95 % CI = 1.00, 1.17, p = 0.06) in our 2 cohorts. Meta-analysis, comprising 9,224 type 2 diabetes and 10,484 controls, revealed that three SNPs (rs3740878, rs11037909 and rs1113132) in EXT2 were significantly associated with type 2 diabetes (ORs range from 1.06 to 1.07, p = 0.038, p = 0.008 and p = 0.005, respectively). Variation in the EXT2 locus appears to be associated with a small increase in the risk of type 2 diabetes. However, well-designed prospective studies with larger sample size and more ethnic groups are needed to further validate the results.     

How the Sequence of a Gene Specifies Structural Symmetry in Proteins

Internal symmetry is commonly observed in the majority of fundamental protein folds. Meanwhile, sufficient evidence suggests that nascent polypeptide chains of proteins have the potential to start the co-translational folding process and this process allows mRNA to contain additional information on protein structure. In this paper, we study the relationship between gene sequences and protein structures from the viewpoint of symmetry to explore how gene sequences code for structural symmetry in proteins. We found that, for a set of two-fold symmetric proteins from left-handed beta-helix fold, intragenic symmetry always exists in their corresponding gene sequences. Meanwhile, codon usage bias and local mRNA structure might be involved in modulating translation speed for the formation of structural symmetry: a major decrease of local codon usage bias in the middle of the codon sequence can be identified as a common feature; and major or consecutive decreases in local mRNA folding energy near the boundaries of the symmetric substructures can also be observed. The results suggest that gene duplication and fusion may be an evolutionarily conserved process for this protein fold. In addition, the usage of rare codons and the formation of higher order of secondary structure near the boundaries of symmetric substructures might have coevolved as conserved mechanisms to slow down translation elongation and to facilitate effective folding of symmetric substructures. These findings provide valuable insights into our understanding of the mechanisms of translation and its evolution, as well as the design of proteins via symmetric modules.     

Identification of miRs-143 and -145 that is associated with bone metastasis of prostate cancer and involved in the regulation of EMT

The principal problem arising from prostate cancer (PCa) is its propensity to metastasize to bone. MicroRNAs (miRNAs) play a crucial role in many tumor metastases. The importance of miRNAs in bone metastasis of PCa has not been elucidated to date. We investigated whether the expression of certain miRNAs was associated with bone metastasis of PCa. We examined the miRNA expression profiles of 6 primary and 7 bone metastatic PCa samples by miRNA microarray analysis. The expression of 5 miRNAs significantly decreased in bone metastasis compared with primary PCa, including miRs-508-5p, -145, -143, -33a and -100. We further examined other samples of 16 primary PCa and 13 bone metastases using real-time PCR analysis. The expressions of miRs-143 and -145 were verified to down-regulate significantly in metastasis samples. By investigating relationship of the levels of miRs-143 and -145 with clinicopathological features of PCa patients, we found down-regulations of miRs-143 and -145 were negatively correlated to bone metastasis, the Gleason score and level of free PSA in primary PCa. Over-expression miR-143 and -145 by retrovirus transfection reduced the ability of migration and invasion in vitro, and tumor development and bone invasion in vivo of PC-3 cells, a human PCa cell line originated from a bone metastatic PCa specimen. Their upregulation also increased E-cadherin expression and reduced fibronectin expression of PC-3 cells which revealed a less invasive morphologic phenotype. These findings indicate that miRs-143 and -145 are associated with bone metastasis of PCa and suggest that they may play important roles in the bone metastasis and be involved in the regulation of EMT Both of them may also be clinically used as novel biomarkers in discriminating different stages of human PCa and predicting bone metastasis.     

Graphene‐Tailored Thermodynamics and Kinetics to Fabricate Metal Borohydride Nanoparticles with High Purity and Enhanced Reversibility

Due to their ultrahigh theoretical capacity, metal borohydrides are considered to be one of the most promising candidate hydrogen storage materials. Their application still suffers, however, from high operating temperature, sluggish kinetics, and poor reversibility. Designing nanostructures is an effective way of addressing these issues, but seeking suitable approaches remains a big challenge. Here, a space‐confined solid‐gas reaction to synthesize Mg(BH₄)₂ nanoparticles supported on grapheme is reported, which serves as the structural support for the dispersed Mg(BH₄)₂ nanoparticles. More notably, density functional theory calculations reveal that graphene could weaken both the Mg? H bonds of MgH₂ and B? B bonds of B₂H₆, which could thermodynamically and kinetically facilitate the chemical transformation to synthesize Mg(BH₄)₂ with high purity. Because of the synergistic effects of both the significant reduction in particle size and the catalytic effect of graphene, an onset dehydrogenation temperature of ≈154 °C is observed for Mg(BH₄)₂ nanoparticles, and a complete dehydrogenation could be achieved at a temperature as low as 225 °C, with the formation of MgB₂ as the by‐product. This work provides a new perspective to tailoring the thermodynamics and kinetics of chemical reactions toward the favorable synthesis of functional inorganic materials.     

脉冲电场对水结构影响的研究

本文研究了脉冲电场对水的导电率、ｐＨ值、折射率、透光率影响。结果表明,１．０×１０５ｖ／ｍ脉冲电场处理去离子水、蒸馏水５、３０ｍｉｎ后,电导率、折射率增加;透光率、ｐＨ值降低。电处理水具有“记忆”效应。对自来水作相同处理后,除电导率没测到变化外,其它指标也有变化。研究发现,电场处理水引起其结构改变,电场强度起决定作用,其次是处理时间。本文还探讨了作用机理。     

Meta-analysis of the association between five single nucleotide polymorphisms in the <Emphasis Type="Italic">BDNF</Emphasis> gene and allergic inflammation susceptibility

The association between five single nucleotide polymorphisms (SNPs) in brain-derived neurotrophic factor (BDNF) gene (rs6265, rs10767664, rs12273539, rs962369 and rs11030101) and allergic inflammatory disease susceptibility has been extensively reported, while the conclusions were inconclusive. The present study was designed to qualitatively and quantitatively evaluate the relationship between the BDNF polymorphisms and allergic disease risks. A comprehensive literature search of the shared public electronic databases was conducted before September 1, 2016. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using review manager 5.3. Eleven eligible studies (a total of 5217, 6432, 6432, 6432, 4216 subjects focused on rs6265, rs10767664, rs12273539, rs962369 and rs11030101, respectively) were finally contained. Significant genetic association of rs6265 variant and susceptibility of allergic inflammation was observed under allele contrast, recessive and over-dominant model in the overall analysis. Besides, stratified analysis by ethnicity found that the close relationship between rs6265 polymorphism and increased allergic disease risk of Caucasian was observed under recessive and over-dominant model, as well as under allele contrast, recessive, homozygous and over-dominant model in the Asian. Additionally, subgroup analysis based on the disease types showed the obvious relation of rs6265 and asthma risk in several hereditary model. Moreover, strong association between rs10767664 polymorphism and extraordinary risk of allergic disease was also detected in four genetic models. However, no association was discovered with rs962369, rs12273539 and rs11030101. The present meta-analysis suggested that the SNPs (rs10767664 and rs6265) in the BDNF gene is potentially associated with increased allergic disease susceptibility.     

Study of the tolerance of Hippochaete ramosissimum to Cu stress

We investigated the tolerance of Hippochaete ramosissimum and the changes in physiological metabolism following exposure to copper using pot experiments and analyzing plant physiology and biochemistry. The results showed that Cu tolerance in Hippochaete ramosissimum varied significantly between different populations; the tolerance of plants living in Cu polluted areas for extended periods of time exceeded that of plants living in unpolluted areas. SOD and POD activities in highly Cu tolerant plants increased noticeably following exposure to Cu. This indicates that maintaining and increasing the two kinds of protective enzyme activities are the primary foundations of plant tolerance. However, no change in CAT activity was demonstrated following Cu exposure. In summary, there existed considerable differences in physiological metabolism between different populations of Hippochaete ramosissimum following exposure to Cu.