Polymorphism of a widely used building block for halogen‐bonded assemblies: 1,3,5‐trifluoro‐2,4,6‐triiodobenzene

After reporting the structure of a new polymorph of 1,3,5‐trifluoro‐2,4,6‐triiodobenzene (denoted BzF3I3 ), C₆F₃I₃, (I), which crystallized in the space group P 2₁/c , we perform a comparative analysis with the already reported P 2₁/n polymorph, (II) [Reddy et al. (2006). Chem. Eur. J. 12 , 2222–2234]. In polymorph (II), type‐II I…I halogen bonds and I…π interactions connect molecules in such a way that a three‐dimensional structure is formed; however, the way in which molecules are connected in polymorph (I), through type‐II I…I halogen bonds and π–π interactions, gives rise to an exfoldable lamellar structure, which looks less tightly bound than that of (II). In agreement with this structural observation, both the melting point and the melting enthalpy of (I) are lower than those of (II).     

IRAP: An efficient retrotransposon-based electrophoretic technique for studying genetic variability among geographical isolates of Schistosoma japonicum

In the present study, a inter-retrotransposon-amplified polymorphism (IRAP) technique, based on retrotransposons, was used to examine genetic variability among Schistosoma japonicum isolates from different provinces in mainland China. Of the 15 primers screened, 5 produced highly reproducible IRAP patterns. Using these primers, 54 discernible DNA fragments were generated with 40 (74.07%) being polymorphic, indicating considerable genetic variation among the examined S. japonicum isolates. The primer LTR-11 was found to be able to differentiate male and female parasites, producing one constant specific band for female S. japonicum isolates. The percentages of polymorphic bands (PPB) among all parasites, among isolates from mountainous provinces and among those from the lake/marshland areas were 74.07, 48.15, and 66.67%, respectively. UPGMA analysis revealed that the IRAP profiles could group S. japonicum isolates in mainland China into two clades (mountainous and lake/marshland types), and samples from the same geographical origins clustered together. These results demonstrated that the IRAP technique is suitable for studying genetic diversity and population structures, and also provides an effective technique for studying sex differentiation of S. japonicum.     

Label-free molecular beacon system based on DNAs containing abasic sites and fluorescent ligands that bind abasic sites

A new class of label-free molecular beacon (MB) system based on DNA strands that contain abasic (AP) sites (AP-DNA) and adopt stem-loop structures, in combination with fluorescent ligands that bind these AP sites, has been developed. Unlike a conventional MB, which requires covalent labeling of the MB with a fluorophore and a quencher, the developed system (APMB) does not require covalent attachment of signal transduction units. Detailed sensing functions of a series of APMB systems were examined with the aid of the fluorescent ligand named ATMND to provide insight into the design strategy for APMB systems. The effects of the stem length and the position of the AP site in the stem moiety on the fluorescence response of the APMB system were examined. Genotyping of a G/C SNP of PCR amplification products was successfully demonstrated with the APMB system and blue-fluorescent ATMND as a ligand. The APMB system was further extended to a system that utilized green-fluorescent lumiflavin.     

Detection of single nucleotide polymorphisms by a gold nanowire-on-film SERS sensor coupled with S1 nuclease treatment

Single nucleotide polymorphisms (SNPs) can serve as important biomarkers for genetic diseases, for which accurate detection of SNPs is essential for early diagnosis. We have developed a novel SNP sensor by combining a Au nanowire-on-film surface-enhanced Raman scattering (SERS) platform with S1 nuclease reaction. The combined sensor system provides reproducible SERS signals only in the presence of perfectly matched target DNAs, to probe DNAs as a result of single-stranded DNA-specific degradation by S1 nuclease. Furthermore, point mutations in DNA causing Wilson disease and Avellino corneal dystrophy were successfully identified by this sensor, thereby indicating its practical ability to diagnose genetic diseases.     

Common variants at the promoter region of the APOM confer a risk of rheumatoid arthritis

Although the genetic component in the etiology of rheumatoid arthritis (RA) has been consistently suggested, many novel genetic loci remain to uncover. To identify RA risk loci, we performed a genome-wide association study (GWAS) with 100 RA cases and 600 controls using Affymetrix SNP array 5.0. The candidate risk locus (APOM gene) was re-sequenced to discover novel promoter and coding variants in a group of the subjects. Replication was performed with the independent case-control set comprising of 578 RAs and 711 controls. Through GWAS, we identified a novel SNP associated with RA at the APOM gene in the MHC class III region on 6p21.33 (rs805297, odds ratio (OR) = 2.28, P = 5.20 × 10-7). Three more polymorphisms were identified at the promoter region of the APOM by the re-sequencing. For the replication, we genotyped the four SNP loci in the independent case-control set. The association of rs805297 identified by GWAS was successfully replicated (OR = 1.40, P = 6.65 × 10-5). The association became more significant in the combined analysis of discovery and replication sets (OR = 1.56, P = 2.73 × 10-10). The individuals with the rs805297 risk allele (A) at the promoter region showed a significantly lower level of APOM expression compared with those with the protective allele (C) homozygote. In the logistic regressions by the phenotype status, the homozygote risk genotype (A/A) consistently showed higher ORs than the heterozygote one (A/C) for the phenotype-positive RAs. These results indicate that APOM promoter polymorphisms are significantly associated with the susceptibility to RA.     

Polymorphisms in genes involved in innate immunity and susceptibility to benzene-induced hematotoxicity

Benzene, a recognized hematotoxicant and carcinogen, can damage the human immune system. We studied the association between single nucleotide polymorphisms (SNPs) in genes involved in innate immunity and benzene hematotoxicity in a cross-sectional study of workers exposed to benzene (250 workers and 140 controls). A total of 1,236 tag SNPs in 149 gene regions of six pathways were included in the analysis. Six gene regions were significant for their association with white blood cell (WBC) counts (MBP, VCAM1, ALOX5, MPO, RAC2, and CRP) based on gene-region (P<0.05) and SNP analyses (FDR<0.05). VCAM1 rs3176867, ALOX5 rs7099684, and MPO rs2071409 were the three most significant SNPs. They showed similar effects on WBC subtypes, especially granulocytes, lymphocytes, and monocytes. A 3-SNP block in ALOXE3 (rs7215658, rs9892383, and rs3027208) showed a global association (omnibus P = 0.0008) with WBCs even though the three SNPs were not significant individually. Our study suggests that polymorphisms in innate immunity genes may play a role in benzene-induced hematotoxicity; however, independent replication is necessary.     

Association of Paraoxonase 1 (PON1) polymorphisms with osteoporotic fracture risk in postmenopausal Korean women

There is increasing evidence of a biochemical link between lipid oxidation and bone metabolism. Paraoxonase 1 (PON1) prevents the oxidation of low-density lipoprotein (LDL) and metabolizes biologically active phospholipids in oxidized LDLs. Here, we performed association analyses of genetic variation in PON1 to ascertain its contribution to osteoporotic fractures (OFs) and bone mineral density (BMD). We directly sequenced the PON1 gene in 24 Korean individuals and identified 26 sequence variants. A large population of Korean postmenopausal women (n=1,329) was then genotyped for eight selected PON1 polymorphisms. BMD at the lumbar spine and femoral neck was measured using dual-energy X-ray absorptiometry. Lateral thoracolumbar (T4-L4) radiographs were obtained for vertebral fracture assessment, and the occurrence of non-vertebral fractures (i.e., wrist, hip, forearm, humerus, rib, and pelvis) was examined using self-reported data. Multivariate analyses showed that none of the polymorphisms was associated with BMD at either site. However, +5989A>G and +26080T>C polymorphisms were significantly associated with non-vertebral and vertebral fractures, respectively, after adjustment for covariates. Specifically, the minor allele of +5989A>G exerted a highly protective effect against non-vertebral fractures (OR=0.59, P=0.036), whereas the minor allele of +26080T>C was associated with increased susceptibility to vertebral fractures (OR=1.73, P=0.020). When the risk for any OFs (i.e., vertebral or non-vertebral) was considered, the statistical significance of both polymorphisms persisted (P=0.002-0.010). These results suggest that PON1 polymorphisms could be one of useful genetic markers for OF risk in postmenopausal women.     

Polymorphism of 4-Fluorophenylpyruvic Acid Studied by X-Ray Crystallography and Vibrational Spectroscopy

Two polymorphic forms (I and II) of 4-fluorophenylpyruvic acid (F-PPA) were obtained by crystallization from different solvents, showing a melting point at 163.2 and 171.0 °C. Crystal structures of polymorphs I and II were determined by X-ray crystallography. IR and Raman spectra of the two polymorphs were measured and the spectral characteristics were compared with those of phenylpyruvic acid. the two polymorphs show similar molecular and crystal structures to each other, except for the molecular geometries of the enol and the carboxylic acid moieties. Distinct IR spectral differences which result from the crystal field splitting were observed between the two polymorphs.     

中国普通野生稻线粒体DNA的限制性片段长度多态性

用BamHI／H454、BamHI／pQT2-7-1、EcoRI／B376和EcoRI／pQT12四种酶／探针组合对85份普通野生稻、亚洲栽培稻和橹稻进行了线粒体DNA的限制性片段长度多态性的分析．共检测到16条多态性带，15种表型，组合成14种线粒体DNA变异类型．其中抽稻和粳稻的线粒体DNA已分化，培稻偏粳型，大部分普通野生稻属（或偏）拉型，但江西的东乡普通野生稻类型比较独特．中国普遍野生稻的线粒体DNA与地理分布相关，湖南的江永、茶陵和江西的东乡等不同的群体以地理位置相聚，随地理梯度遗传分化由少到多．