Association of Mitochondrial DNA Polymerase γ Gene <i>POLG1</i> Polymorphisms with Parkinsonism in Chinese Populations

Background: Mitochondrial DNA polymerase gamma (POLG1) mutations were associated with levodopa-responsive Parkinsonism. POLG1 gene contains a number of common nonsynonymous SNPs and intronic regulatory SNPs which may have functional consequences. It is of great interest to discover polymorphisms variants associated with Parkinson's disease (PD), both in isolation and in combination with specific SNPs.Materials and Methods: We conducted a case-control study and genotyped twenty SNPs and poly-Q polymorphisms of POLG1 gene including in 344 Chinese sporadic PD patients and 154 healthy controls. All the polymorphisms of POLG1 we found in this study were sequenced by PCR products with dye terminator methods using an ABI-3100 sequencer. Hardy-Weinberg equilibrium and linkage disequilibrium (LD) for association between twenty POLG1 SNPs and PD were calculated using the program Haploview.Principal Results: We provided evidence for strong association of four intronic SNPs of the POLG1 gene (new report: c.2070-12T>A and rs2307439: c.2070-64G>A in intron 11, P = 0.00011, OR = 1.727; rs2302084: c.3105-11T>C and rs2246900: c.3105-36A>G in intron 19, P = 0.00031, OR = 1.648) with PD. However, we did not identify any significant association between ten exonic SNPs of POLG1 and PD. Linkage disequilibrium analysis indicated that c.2070-12T>A and c.2070-64G>A could be parsed into one block as Haplotype 1 as well as c.3105-11T>C and c.3105-36A>G in Haplotype 2. In addition, case and control study on association of POLG1 CAG repeat (poly-Q) alleles with PD showed a significant association (P = 0.03, OR = 2.16) of the non-10/11Q variants with PD. Although intronic SNPs associated with PD didn't influence POLG1 mRNA alternative splicing, there was a strong association of c.2070-12T>A and c.2070-64G>A with decreased POLG1 mRNA level and protein levels.Conclusions: Our findings indicate that POLG1 may play a role in the pathogenesis of PD in Chinese populations.</p

The Complex Symmetry Gravitational Theory as a New Alternative of Dark Energy

We propose that complex symmetry gravitational theory (CSGT) explain the accelerating expansion of universe. In this paper universe is taken as the double complex symmetric space. Cosmological solution is obtained within CSGT. The conditions of the accelerating expansion of universe are discussed within CSGT. Moreover, the range of equation of state of matter $\omega_\epsilon$ is given in the hyperbolic imaginary space.Comment: Latex 9 pages, submitted to International Journal of Theoretical Physic

Population phylogenomic analysis of mitochondrial DNA in wild boars and domestic pigs revealed multiple domestication events in East Asia

A fine-grained mitochondrial DNA phylogenomic analysis was conducted in domestic pigs and wild boars, revealing that pig domestication in East Asia occurred in the Mekong and the middle and downstream regions of the Yangtze river

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

Integrating random walk and binary regression to identify novel miRNA-disease association

Abstract Background In the last few decades, cumulative experimental researches have witnessed and verified the important roles of microRNAs (miRNAs) in the development of human complex diseases. Benefitting from the rapid growth both in the availability of miRNA-related data and the development of various analysis methodologies, up until recently, some computational models have been developed to predict human disease related miRNAs, efficiently and quickly. Results In this work, we proposed a computational model of Random Walk and Binary Regression-based MiRNA-Disease Association prediction (RWBRMDA). RWBRMDA extracted features for each miRNA from random walk with restart on the integrated miRNA similarity network for binary logistic regression to predict potential miRNA-disease associations. RWBRMDA obtained AUC of 0.8076 in the leave-one-out cross validation. Additionally, we carried out three different patterns of case studies on four human complex diseases. Specifically, Esophageal cancer and Prostate cancer were conducted as one kind of case study based on known miRNA-disease associations in HMDD v2.0 database. Out of the top 50 predicted miRNAs, 94 and 90% were respectively confirmed by recent experimental reports. To simulate new disease without known related miRNAs, the information of known Breast cancer related miRNAs was removed. As a result, 98% of the top 50 predicted miRNAs for Breast cancer were confirmed. Lymphoma, the verified ratio of which was 88%, was used to assess the prediction robustness of RWBRMDA based on the association records in HMDD v1.0 database. Conclusions We anticipated that RWBRMDA could benefit the future experimental investigations about the relation between human disease and miRNAs by generating promising and testable top-ranked miRNAs, and significantly reducing the effort and cost of identification works

MKRMDA: multiple kernel learning-based Kronecker regularized least squares for MiRNA–disease association prediction

Abstract Background Recently, as the research of microRNA (miRNA) continues, there are plenty of experimental evidences indicating that miRNA could be associated with various human complex diseases development and progression. Hence, it is necessary and urgent to pay more attentions to the relevant study of predicting diseases associated miRNAs, which may be helpful for effective prevention, diagnosis and treatment of human diseases. Especially, constructing computational methods to predict potential miRNA–disease associations is worthy of more studies because of the feasibility and effectivity. Methods In this work, we developed a novel computational model of multiple kernels learning-based Kronecker regularized least squares for MiRNA–disease association prediction (MKRMDA), which could reveal potential miRNA–disease associations by automatically optimizing the combination of multiple kernels for disease and miRNA. Results MKRMDA obtained AUCs of 0.9040 and 0.8446 in global and local leave-one-out cross validation, respectively. Meanwhile, MKRMDA achieved average AUCs of 0.8894 ± 0.0015 in fivefold cross validation. Furthermore, we conducted three different kinds of case studies on some important human cancers for further performance evaluation. In the case studies of colonic cancer, esophageal cancer and lymphoma based on known miRNA–disease associations in HMDDv2.0 database, 76, 94 and 88% of the corresponding top 50 predicted miRNAs were confirmed by experimental reports, respectively. In another two kinds of case studies for new diseases without any known associated miRNAs and diseases only with known associations in HMDDv1.0 database, the verified ratios of two different cancers were 88 and 94%, respectively. Conclusions All the results mentioned above adequately showed the reliable prediction ability of MKRMDA. We anticipated that MKRMDA could serve to facilitate further developments in the field and the follow-up investigations by biomedical researchers

Development in plasma surface diffusion techniques of Ti-6Al-4V alloy: a review

Ti-6Al-4V alloy has been widely used as an important structural material in aerospace, automotive, and chemical and biomedical industries due to its high specific strength and excellent corrosion resistance. However, the poor tribological properties and low resistance to high temperature oxidation limit extensive applications of the alloy. Plasma surface diffusion treatments, including plasma carbonizing, plasma nitriding, and plasma alloying treatments, contribute to improve wear resistance and the anti-oxidation property of the alloy by introducing other elements into the surface of the alloy to form hard surface layers under low pressure conditions. In this review article, the developments in microstructure and properties of the layers generated by the three techniques were reviewed systematically. In particular, the development in the phase determination of the plasma-nitrided layer was analyzed. New approaches in accelerating the diffusion of atoms and optimizing process were analyzed in detail

Genetic Diversity of Main Inbred Indica Rice Varieties Applied in Guangdong Province as Revealed by Molecular Marker

Genetic diversity of 299 inbred indica rice varieties, including 33 introduced varieties, applied in Guangdong Province of China were assessed using 20 ILP (intron length polymorphism) and 34 SSR (simple sequence repeat) markers. Totally, 154 loci were screened for the 299 varieties, with the average number of alleles (Na), rare alleles (Nr), and polymorphism information content (PIC) scored at 3.4, 0.7 and 0.32, respectively. The Nei's genetic distance (GD) was estimated ranging from 0 to 0.7529 with an average of 0.4797. There was no significant difference of Na, Nr, PIC or GDs between the introduced and local varieties. Neighbor-joining (NJ) analysis showed that the 299 varieties failed into three main distinct groups, and the 33 introduced varieties were distributed over all the groups or subgroups. Model-based cluster analysis demonstrated that only 73 (24.4%) of the 299 varieties and 7 (21.2%) of the 33 introduced varieties could be distinctly classified into the three groups. Analysis of molecular variance showed that within the groups divided by NJ analysis, the genetic variations revealed by ILP, SSR and these two combined were 7.7%, 5.6% and 6.6%, and within the groups divided by region (Guangdong local and the introduced varieties), the genetic variables were 2.1%, 4.6%, 5.4%, respectively. These results suggested that the genetic diversity of the 299 inbred rice varieties in Guangdong Province was low, simultaneously relationship among varieties was poor and close in all kind of groups. Hence, it is very necessary to extend the genetic diversity during the breeding and selection practical procedure

Function characterization and expression regulation of two different-sized 3 ' untranslated region-containing interferon genes from clone F of gibel carp Carassius auratus gibelio

Fish interferon (IFN)-mediated antiviral innate immunity is the first line of defense against virus invasion. In the present study, we identify two fish IFN genes (here tentatively named IFNa and IFNc) with different-sized 3&#39; UTRs from clone F strain of gibel carp Carassius auratus gibelio. Carp IFNa has a relatively short 3&#39;UTR without AU-rich elements (AREs) but IFNc has a long one with 9 AREs. Functionally, carp IFNa and IFNc display significantly antiviral potential to viral infection, likely through induction of downstream IFN-stimulated genes (ISGs). Both carp IFN genes are induced by viral infection, poly(I:C) treatment and IRF3/7, which are ascribed to the IFN-sensitive response elements (ISRE) within their promoters. Carp IFN genes are also induced by each other and by themselves, indicating existence of a positive feedback loop in fish IFN-mediated antiviral immune response. Comparative analyses of 3&#39;UTR-mediated expression regulation at mRNA and protein levels show that the ARE-containing 3&#39;UTR of carp IFNc rather than the short 3&#39;UTR of carp IFNa promotes mRNA decay but instead results in high-level protein expression, indicating that 3&#39;UTR of fish IFN mRNAs might be a potential factor for regulation of IFN-mediated antiviral immune response. Considering a fact that a given protein function is largely related to its protein level, these results suggest that both promoter and 3&#39;UTR contribute to the transcription and translation of fish IFN genes, thus shaping their eventually antiviral potential.</p