Secretoglobin 1A member 1 (SCGB1A1) + 38A/G polymorphism is associated with asthma risk: A meta-analysis

Background

Epidemiological studies have evaluated the association between Secretoglobin 1A member 1 (SCGB1A1) + 38A/G polymorphism and asthma, but the results remain inconclusive. The aim of this study was to perform a meta-analysis to investigate a more authentic association between SCGB1A1 + 38A/G polymorphism and asthma.

Methods

Published literature from PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Embase databases were searched for eligible publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random or fixed-effect model according the between-study heterogeneity.

Results

A total of 19 case-control studies in 18 articles were included in the meta-analysis, including 3191 cases and 5182 controls. We found that SCGB1A1 + 38A/G polymorphism was associated with a significantly increased risk of asthma risk when all studies were pooled in a dominant model (OR = 1.29; 95% CI 1.08–1.54; P = 0.005). The cumulative meta-analysis and sensitivity analysis further strengthened the stability of the result. Furthermore, publication bias was not detected.

Conclusions

This study suggested that SCGB1A1 + 38A/G polymorphism was a risk factor for asthma. Further large and well-designed studies are needed to confirm this association.     

A genetic variant in the promoter of APE1 gene (− 656 T > G) is associated with breast cancer risk and progression in a Chinese population

Background/aims

APE1 is an important DNA repair protein in the base excision repair pathway. Genetic variations in APE1 have been suggested to influence individuals' susceptibility to human malignancies. The present study was aimed to investigate the associations between two functional polymorphisms in APE1 (− 656 T > G and 1349 T>G) and breast cancer risk.

Methods

We genotyped the two polymorphisms in a case-control study of 500 breast cancer patients and 799 age-matched cancer-free controls using the TaqMan method. Unconditional logistic regression adjusted for potential confounding factors was used to assess the associations.

Results

We found that the variant genotypes of the − 656 T>G were significantly associated with decreased breast cancer risk, compared with the wild genotype [TG/GG vs. TT: adjusted odds ratio (OR) = 0.71, 95% confidence interval (CI) = 0.56–0.91], and the protective effect of this polymorphism was more predominant among the subgroups of younger subjects (< 52 years) (OR = 0.65, 95% CI = 0.46–0.92). Besides, we found that the variant genotypes were associated with less frequent lymph node metastasis (P = 0.020, OR = 0.64, 95% CI = 0.44–0.94). We did not observe any significant association between the 1349 T>G polymorphism and breast cancer risk.

Conclusion

Our results suggest that the APE1 − 656 T>G but not the 1349 T>G polymorphism may influence the susceptibility and progression of breast cancer in the Chinese population. Large population-based prospective studies are required to validate these findings.     

The structural definition of adducts of stoichiometry AgX:dppf (1:1)(n), X = simple anion, dppf = bis(diphenylphosphino)ferrocene

Single crystal X-ray structural characterizations are recorded for an array of adducts of the form AgX:dppf (1:1)_(n), X = simple (pseudo-)halide or oxy-anion, ‘dppf’ = bis(diphenyl phosphino)ferrocene, for adducts X = Cl (new phase), Br, I, SCN, OCN, CN, NO₃ (new phase), O₂CCH₃, n = 2, the form being dimeric [(dppf-P,P′)Ag(μ-X)₂Ag(P,P′-dppf)], for X = I, SCN, [Ag(μ-X)₂(P-dppf-P′)₂Ag′]; for X = O₂CCF₃, n = ∞, the form is an extended polymer: ?Ag(O · CO · CF₃)(P-dppf-P′)Ag′(O?. A dichloromethane solvate phase of CuI:dppf (1:1)₂ (also centrosymmetric) is also recorded. Synthetic procedures for all adducts have been reported. All compounds have been characterized both in solution (¹H, ¹³C, ³¹P NMR, ESI MS) and in the solid state (IR). The topology of the structures in the solid state was found to depend on the nature of the counterion.     

Molecular characterization of calreticulin from Anopheles stephensi midgut cells and functional assay of the recombinant calreticulin with Plasmodium berghei ookinetes

Transmission blocking vaccines (TBVs) that target the antigens on the midgut epithelium of Anopheles mosquitoes are among the promising tools for the elimination of the malaria parasite. Characterization and analysis of effective antigens is the first step to design TBVs. Calreticulin (CRT), a lectin-like protein, from Anopheles albimanus midgut, has shown antigenic features, suggesting a promising and novel TBV target. CRT is a highly conserved protein with similar features in vertebrates and invertebrates including anopheline. We cloned the full-length crt gene from malaria vector, Anopheles stephensi (AsCrt) and explored the interaction of recombinant AsCrt protein, expressed in a prokaryotic system (pGEX-6p-1), with surface proteins of Plasmodium berghei ookinetes by immunofluorescence assay. The cellular localization of AsCrt was determined using the baculovirus expression system. Sequence analysis of the whole cDNA of AsCrt revealed that AsCrt contains an ORF of 1221 bp. The amino acid sequence of AsCrt protein obtained in this study showed 64% homology with similar protein in human. The AsCrt shares the most common features of CRTs from other species. This gene encodes a 406 amino-acid protein with a molecular mass of 46 kDa, which contains a predicted 16 amino-acid signal peptides, conserved cysteine residues, a proline-rich region, and highly acidic C-terminal domain with endoplasmic reticulum retrieval sequence HDEL. The production of GST-AsCrt recombinant protein was confirmed by Western blot analysis using an antibody against the GST protein. The FITC-labeled GST-AsCrt exhibited a significant interaction with P. berghei ookinete surface proteins. Purified recombinant GST-AsCrt, labeled with FITC, displayed specific binding to the surface of P. berghei ookinetes in comparison with control. Moreover, the expression of AsCrt in baculovirus expression system indicated that AsCrt was localized on the surface of Sf9 cells. Our results suggest that AsCrt could be utilized as a potential target for future studies in TBV area for malaria control.     

Dye-sensitized photocurrents and adsorption properties of merocyanine dye at atomically flat rutile (1 1 0) and (1 0 0) TiO2 surfaces

The crystal-face dependence of the dye-sensitized photocurrents and the adsorption properties of benzothiazole merocyanine (Mc[18,1]) dye molecules were investigated, using atomically flat (1 0 0) and (1 1 0) TiO₂ single crystal surfaces. From the estimation of the amount of the transferred charge from the TiO₂ surface to CO groups of dye molecules based on NEXAFS data, it was revealed that the interaction of the adsorbed molecules and the (1 1 0) surface was much stronger than that for the (1 0 0) surface. On the other hand, the absorbed photon to current conversion efficiency (APCE) value was almost the same for both surfaces. We suggested a possible explanation as follows: the energy difference between the LUMO of Mc[18,1] and the conduction band of TiO₂ was large enough to give a nearly 100% quantum efficiency of electron transfer from photoexcited dye to TiO₂, which made the difference in the interaction between dye molecules and TiO₂ not apparent. The incident photon to current conversion efficiency (IPCE) for the (1 0 0) surface was much larger than that for the (1 1 0) surface, which was explained by the fact that the amount of the adsorbed dye molecules on the (1 0 0) surface was larger than on the (1 1 0) surface, probably due to the larger surface density of five-coordinated Ti sites in the former surface.     

The − 974C>A (rs3087459) gene polymorphism in the endothelin gene (EDN1) is associated with risk of developing acute coronary syndrome in Mexican patients

Endothelial dysfunction plays an essential role in the development and progression of atherosclerotic lesions. Endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) are considered important molecules in the endothelial dysfunction process. The aim of the present study was to evaluate the role of eNOS and ET-1 (EDN1) gene polymorphisms as susceptibility markers for acute coronary syndrome (ACS). Six polymorphisms (rs1799983, rs2070744, rs1800783, rs3087459, rs1800541, and rs5369) of eNOS and EDN1 genes were analyzed by 5′ exonuclease TaqMan genotyping assays in a group of 452 patients with ACS and 283 healthy controls. The results showed increased frequencies of the A allele of the END1-914 C>A (rs3087459) polymorphism in ACS patients when compared to controls (OR = 1.56, Pc = 0.01). Under an additive model, the “AA” genotype was associated with an increased risk of developing ACS, adjusted for gender, hypertension, dyslipidemia, alcohol consumption, smoking, and diabetes (OR = 1.56, p = 0.045). Linkage disequilibrium analysis showed one EDN1 haplotype (AT) with increased frequency in ACS patients when compared to healthy controls (OR = 1.65, Pc = 0.0015). The “AT” haplotype was associated with the risk of developing ACS after adjusting for cardiovascular risk factors using multiple logistic analysis. In this case, the adjusted OR was 1.73 for the AT haplotype (Pc = 0.0018). In summary, resulting data suggest that the END1-914 C>A gene polymorphism could be involved in the risk of developing ACS in Mexican individuals.     

Cloning,characterization, hypoxia and heat shock response of hypoxia inducible factor-1 (HIF-1) from the small abalone Haliotis diversicolor

In this study, hypoxia inducible factor-1α (HIF-1α) and hypoxia inducible factor-1β (HIF-1β) from small abalone Haliotis diversicolor were cloned. The cDNA of H. diversicolor HIF-1α (HdHIF-1α) is 2833 bp encoding a protein of 711aa and H. diversicolor HIF-1β (HdHIF-1β) is 1919 bp encoding a protein of 590aa. Similar to other species' HIF-1, HdHIF-1 has one basic helix–loop–helix (bHLH) domain and two Per-Arnt-Sim (PAS) domains, and HdHIF-1α has a oxygen-dependent degradation domain (ODDD) with two proline hydroxylation motifs and a C-terminal transactivation domain (C-TAD) with an asparagine hydroxylation motif. Under normoxic conditions, HdHIF-1α and HdHIF-1β mRNAs were constitutively present in all examined tissues. Under hypoxia (2.0 mg/L DO at 25 °C) stress, HdHIF-1α expression was up-regulated in gills at 4 h, 24 h and 96 h, and in hemocytes at 24 h and 96 h, while HdHIF-1β remained relatively constant. Under thermal stress (31 °C), HdHIF-1α expression was significantly increased in gills at 4 h, and hemocytes at 0 h and 4 h, while HdHIF-1β expression still remained relatively constant. These results suggested that HIF-1α may play an important role in adaption to poor environment in H. diversicolor.     

Syntheses and structures of adducts of stoichiometry MX:dpex (2:1)(n), M = Cu, Ag, X = (pseudo-) halogen, dppx = Ph2E(CH2)xEPh2, E = P, As

Single crystal X-ray studies have defined the structures of a number of adducts of the form MX:dpex (2:1), M = univalent coinage metal (Cu, Ag), X = (pseudo-)halide, dpex = bis(diphenylpnicogeno)alkane, Ph₂E(CH₂)_xEPh₂, E = P, As, of diverse types, some novel. The adducts of AgCl,Br:dppm and AgNCO:dpem (x = 1) are tetranuclear as is the AgNO₃:dppp (x = 3) array, all derivative of the familiar ‘step’ structure while the combination CuCN:dppm yields a two-dimensional web of twenty-membered macro/metallacycles. Synthetic procedures for all adducts have been reported. All compounds have been characterized both in solution (¹H, ¹³C, ³¹P NMR, ESI MS) and in the solid state (IR).     

Coexistence of major and minor tautomers of 1-methylcytosine (1-MeC) in a single metal complex, trans-Pt(1-MeC-N3)(1-MeC-N4)X2 (X = Cl, I): metal migration N3 → N4 at acidic pH

Two complexes of composition trans-Pt(1-MeC-N3)(1-MeC-N4)I₂ · 2H₂O (4) and trans-Pt(1-MeC-N3)(1-MeC-N4)Cl₂ (5) are described and characterized by X-ray analysis, which simultaneously contain the preferred aminooxo tautomer I and the rare iminooxo tautomer II of 1-methylcytosine (1-MeC) bonded to the heavy metal, via N3 and N4, respectively. Formation of 4 originates from [Pt(1-MeC-N3)₃I]I (2), which likewise has been characterized by X-ray crystal structure analysis. A feasible way of formation of 4, which involves a metal migration process from N3 to N4 occurring at moderately acidic pH, is proposed. It appears to be yet another mechanism of metal migration, different from previously established cases which are redox-assisted and hydroxide-promoted, respectively.     

Infantile-onset ascending hereditary spastic paraplegia with bulbar involvement due to the novel ALS2 mutation c.2761C > T

Recessive mutations in the alsin gene cause three clinically distinct motor neuron diseases: juvenile amyotrophic lateral sclerosis (ALS2), juvenile primary lateral sclerosis (JPLS) and infantile-onset ascending hereditary spastic paraplegia (IAHSP). A total of 23 different ALS2 mutations have been described for the three disorders so far. Most of these mutations result in a frameshift leading to a premature truncation of the alsin protein. We report the novel ALS2 truncating mutation c.2761C > T; p.R921X detected by homozygosity mapping and sequencing in two infants affected by IAHSP with bulbar involvement. The mutation c.2761C > T resides in the pleckstrin domain, a characteristic segment of guanine nucleotide exchange factors of the Rho GTPase family, which is involved in the overall neuronal development or maintenance. This study highlights the importance of using homozygosity mapping combined with candidate gene analysis to identify the underlying genetic defect as in this Saudi consanguineous family.     

Interferon induced with helicase C domain 1 (IFIH1): Trends on helicase domain and type 1 diabetes onset

The Interferon-induced with helicase C domain 1 (IFIH1) gene has been hypothesized as involved in the viral etiology of type 1 diabetes (T1D) and other autoimmune disorders, since it is implicated in viral recognition. In our study we analyzed IFIH1 rs6432714 and rs10930046 SNPs in T1D patients stratified for the presence of celiac disease and autoimmune thyroid disease. No association with susceptibility to develop the diseases was found. The rs6432714, a tag-SNP that represents part of helicase domain of IF1H1 protein showed a trend of association only with T1D development (P > 0.025 after Bonferroni adjustment) in log-additive model (OR = 1.45, P = 0.0365, power = 0.99), indicating that helicase domain of IFIH1 protein could be associated with the susceptibility to T1D.     

Comparative genomic analysis shows that Streptococcus suis meningitis isolate SC070731 contains a unique 105 K genomic island

Streptococcus suis (SS) is an important swine pathogen worldwide that occasionally causes serious infections in humans. SS infection may result in meningitis in pigs and humans. The pathogenic mechanisms of SS are poorly understood. Here, we provide the complete genome sequence of S. suis serotype 2 (SS2) strain SC070731 isolated from a pig with meningitis. The chromosome is 2,138,568 bp in length. There are 1933 predicted protein coding sequences and 96.7% (57/59) of the known virulence-associated genes are present in the genome. Strain SC070731 showed similar virulence with SS2 virulent strains HA9801 and ZY05719, but was more virulent than SS2 virulent strain P1/7 in the zebrafish infection model. Comparative genomic analysis revealed a unique 105 K genomic island in strain SC070731 that is absent in seven other sequenced SS2 strains. Further analysis of the 105 K genomic island indicated that it contained a complete nisin locus similar to the nisin U locus in S. uberis strain 42, a prophage similar to S. oralis phage PH10 and several antibiotic resistance genes. Several proteins in the 105 K genomic island, including nisin and RelBE toxin–antitoxin system, contribute to the bacterial fitness and virulence in other pathogenic bacteria. Further investigation of newly identified gene products, including four putative new virulence-associated surface proteins, will improve our understanding of SS pathogenesis.     

Molecular cloning and tissue distribution of the phosphotyrosine interaction domain containing 1 (PID1) gene in Tianfu goat

Phosphotyrosine interaction domain containing 1 (PID1) is an important mediator in the development of obesity-related insulin resistance in humans and animals. For a better understanding of the structure and function of the PID1 gene and to study its effect in caprine, the cDNA of the PID1 gene from the abdominal muscle of Tianfu goat was cloned and sequenced. The structure of PID1 was analyzed using bioinformatics tools. The results showed that the full sequence of the caprine PID1 cDNA was 896 bp long and contained a 654 bp long coding region that encoded a 217 amino acid sequence. Fifteen phosphorylation sites were predicted in the translated PID1 protein. The protein had a phosphotyrosine-binding domain between Arg⁵³ and Ile¹⁹⁹. A phylogenic tree based on the PID1 proteins from other species revealed that the caprine protein was closely related to cattle PID1. Fluorescence quantitative PCR analyses revealed that PID1 was expressed in the heart, liver, spleen, lung, kidney, leg muscle, abdominal muscle and longissimus dorsi muscle of goats. In particular, high expression levels of PID1 were detected in liver and abdominal muscle, and low expression levels were seen in lung. Furthermore, the PID1 mRNA expression levels in the longissimus dorsi muscles increased gradually with the age of the goats (P < 0.05). Western blotting results detected the PID1 protein in six of the tissues in which PID1 was shown to be expressed; the two exceptions were liver and spleen.     

n − 3, but not n − 6 lipid particle uptake requires cell surface anchoring

Omega-3 (n − 3) fatty acids are emerging as bioactive agents protective against cardiovascular disease. However, their cellular delivery pathways are poorly defined. Here we questioned whether the uptake of n − 3 triglyceride-rich particles (TGRP) is mediated by cell surface proteoglycans (PG) using LDL receptor (LDLR)+/+ and LDLR−/− cell models. LDLR+/+ but not LDLR−/− cells showed higher n − 6 over n − 3 TGRP uptake. Removal of cell surface proteins and receptors by pronase markedly enhanced the uptake of n − 3 but not n − 6 TGRP. Lactoferrin blockage of apoE-mediated pathways decreased the uptake of n − 6 TGRP by up to 85% (p < 0.05) but had insignificant effect on n − 3 TGRP uptake. PG removal by sodium chlorate in LDLR+/+ cells substantially reduced n − 3 TGRP uptake but had little effect on n − 6 TGRP uptake. Thus, while n − 6 TGRP uptake is preferentially mediated by LDLR-dependent pathways, the uptake of n − 3 TGRP depends more on PG and non-LDLR cell surface anchoring.     

Structures and excitation energies of ozone-water clusters O3(H2O)n (n = 1-4)

Hybrid density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations have been carried out for ozone-water clusters O₃(H₂O)_n (n = 1-4) in order to obtain hydration effects on the absorption spectrum of ozone. The first water molecule in n = 1 is bound to the ozone molecule by an oxygen orientation form in which the oxygen atom of H₂O orients the central oxygen atom of O₃. In n = 2, the water dimer is bound to O₃ and then the cyclic structure is formed as the most stable structure. For n = 3 (or n = 4), the cyclic water trimer (or tetramer) is bound by a hydrogen bond to the ozone molecule. The TD-DFT calculations of O₃(H₂O)_n (n = 0-4) show that the first and second excitation energies of O₃ are blue-shifted by the interaction with the water clusters. The magnitude of the spectral shift is largest in n = 2, and the shifts of the excitation energies are +0.07 eV for S₁ and +0.13 eV for S₂ states. In addition to the spectral shifts (S₁ and S₂ states), it is suggested that a charge-transfer band is appeared as a low-lying excited state above the S₁ and S₂ states. The origin of the spectrum shifts was discussed on the basis of theoretical results.