Decavanadate, decaniobate, tungstate and molybdate interactions with sarcoplasmic reticulum Ca2+-ATPase: quercetin prevents cysteine oxidation by vanadate but does not reverse ATPase inhibition

Recently we demonstrated that the decavanadate (V10) ion is a stronger Ca2+-ATPase inhibitor than other oxometalates, such as the isoelectronic and isostructural decaniobate ion, and the tungstate and molybdate monomer ions, and that it binds to this protein with a 1 : 1 stoichiometry. The V10 interaction is not affected by any of the protein conformations that occur during the process of calcium translocation (i.e. E1, E1P, E2 and E2P) (Fraqueza et al., J. Inorg. Biochem., 2012). In the present study, we further explore this subject, and we can now show that the decaniobate ion, [Nb10 = Nb10O28]6−, is a useful tool in deducing the interaction and the non-competitive Ca2+-ATPase inhibition by the decavanadate ion [V10 = V10O28]6−. Moreover, decavanadate and vanadate induce protein cysteine oxidation whereas no effects were detected for the decaniobate, tungstate or molybdate ions. The presence of the antioxidant quercetin prevents cysteine oxidation, but not ATPase inhibition, by vanadate or decavanadate. Definitive V(IV) EPR spectra were observed for decavanadate in the presence of sarcoplasmic reticulum Ca2+- ATPase, indicating a vanadate reduction at some stage of the protein interaction. Raman spectroscopy clearly shows that the protein conformation changes that are induced by V10, Nb10 and vanadate are different from the ones induced by molybdate and tungstate monomer ions. Here, Mo and W cause changes similar to those by phosphate, yielding changes similar to the E1P protein conformation. The putative reduction of vanadium(V) to vanadium(IV) and the non-competitive binding of the V10 and Nb10 decametalates may explain the differences in the Raman spectra compared to those seen in the presence of molybdate or tungstate. Putting it all together, we suggest that the ability of V10 to inhibit the Ca2+- ATPase may be at least in part due to the process of vanadate reduction and associated protein cysteine oxidation. These results contribute to the understanding and application of these families of mono- and polyoxometalates as effective modulators of many biological processes, particularly those associated with calcium homeostasis.MA thanks CCMAR; LAEBC and MPMM thank QFM-UC for financial support. CAO is grateful for a QEII fellowship and Discovery Project grant (DP110105530) from the Australian Research Council. WHC acknowledges support from the U.S. Department of Energy Office of Basic Energy Science via grant DE-FG02-05ER15693, the National Science Foundation via EAR-0814242 and an NSF CCI grant through the Center for Sustainable Materials Chemistry, number CHE-1102637

Characterization of decavanadate and decaniobate solutions by Raman spectroscopy

The decaniobate ion, (Nb10 = [Nb10O28]6−) being isoelectronic and isostructural with the decavanadate ion (V10 = [V10O28]6−), but chemically and electrochemically more inert, has been useful in advancing the understanding of V10 toxicology and pharmacological activities. In the present study, the solution chemistry of Nb10 and V10 between pH 4 and 12 is studied by Raman spectroscopy. The Raman spectra of V10 show that this vanadate species dominates up to pH 6.45 whereas it remains detectable until pH 8.59, which is an important range for biochemistry. Similarly, Nb10 is present between pH 5.49 and 9.90 and this species remains detectable in solution up to pH 10.80. V10 dissociates at most pH values into smaller tetrahedral vanadate oligomers such as V1 and V2, whereas Nb10 dissociates into Nb6 under mildly (10 > pH > 7.6) or highly alkaline conditions. Solutions of V10 and Nb10 are both kinetically stable under basic pH conditions for at least two weeks and at moderate temperature. The Raman method provides a means of establishing speciation in the difficult niobate system and these findings have important consequences for toxicology activities and pharmacological applications of vanadate and niobate polyoxometalates

Correlates of absolute and excessive weight gain during pregnancy

OBJECTIVE: Factors associated with weight gain during pregnancy that may be linked to maternal overweight and obesity were examined. METHODS: In this observational study, 144 women reported on demographics, (prepregnancy) body weight, and lifestyles in self-reported questionnaires at 30 weeks gestation. Body weight at the end of pregnancy (self-reported at 6 weeks postpartum) was used to determine total gestational weight gain. Multivariate prediction models were developed to identify factors associated with total gestational weight gain and excessive gestational weight gain (i.e., higher weight gain than recommended by the Institute of Medicine). RESULTS: Women gained 14.4 (+/-5.0) kg during pregnancy. Obese women gained almost 4 kg less than normal weight women. Pregnant women judging themselves to be less physically active or women who reported increased food intakes during pregnancy gained significantly more weight. Over one third of women (38%) gained more weight than recommended. Being overweight, judging yourself to be less physically active than others, and a perceived elevated food intake during pregnancy were significantly associated with excessive weight gain (odds ratio [OR] = 6.33, 95% confidence interval [CI]: 2.01-19.32; OR = 3.96, 95% CI: 1.55l, 10.15; and OR = 3.14, 95% CI: 1.18, 8.36, respectively). A higher age at menarche and hours of sleep reduced the odds for excessive weight gain (OR = 0.75, 95% CI: 0.57, 0.99; and OR = 0.35, 95% CI: 0.57, 0.93, respectively). CONCLUSIONS: Mean hours of sleep, perceived physical activity, and measures of food intake at 30 weeks gestation were identified as modifiable behavioral correlates for excessive gestational weight gain. Strategies to optimize gestational weight gain need to be explored, with a focus on the identified factors

Trade in the Shadow of Power : Japanese Industrial Exports in the Interwar years

During the interwar years, Japanese industrialisation accelerated alongside the expansion of industrial exports to regional markets. Trade blocs in the interwar years were used as an instrument of imperial power to foster exports and as a substitute for productivity to encourage industrial production. The historiography on Japanese industrialisation in the interwar years describes heavy industries' interests in obtaining access to wider markets to increase economies of scale and reduce unit costs. However, this literature provides no quantitative evidence that proves the success of those mechanisms in expanding exports. In this paper we scrutinise how Japan—a relatively poor country—used colonial as well as informal power interventions to expand regional markets for its exports, especially for the most intensive human capital sector of the industrializing economy

CELSR2 is a candidate susceptibility gene in idiopathic scoliosis

A Swedish pedigree with an autosomal dominant inheritance of idiopathic scoliosis was initially studied by genetic linkage analysis, prioritising genomic regions for further analysis. This revealed a locus on chromosome 1 with a putative risk haplotype shared by all affected individuals. Two affected individuals were subsequently exome-sequenced, identifying a rare, non-synonymous variant in the CELSR2 gene. This variant is rs141489111, a c. G6859A change in exon 21 (NM_001408), leading to a predicted p. V2287I (NP_001399.1) change. This variant was found in all affected members of the pedigree, but showed reduced penetrance. Analysis of tagging variants in CELSR1-3 in a set of 1739 Swedish-Danish scoliosis cases and 1812 controls revealed significant association (p = 0.0001) to rs2281894, a common synonymous variant in CELSR2. This association was not replicated in case-control cohorts from Japan and the US. No association was found to variants in CELSR1 or CELSR3. Our findings suggest a rare variant in CELSR2 as causative for idiopathic scoliosis in a family with dominant segregation and further highlight common variation in CELSR2 in general susceptibility to idiopathic scoliosis in the Swedish-Danish population. Both variants are located in the highly conserved GAIN protein domain, which is necessary for the auto-proteolysis of CELSR2, suggesting its functional importance.Peer reviewe

Functional Inequalities Involving Numerical Differentiation Formulas of Order Two

We write expressions connected with numerical differentiation formulas of order 2 in the form of Stieltjes integral, then we use Ohlin lemma and Levin–Stechkin theorem to study inequalities connected with these expressions. In particular, we present a new proof of the inequality f(x+y2)≤1(y-x)2∫xy∫xyf(s+t2)dsdt≤1y-x∫xyf(t)dtsatisfied by every convex function f:R→R and we obtain extensions of this inequality. Then we deal with non-symmetric inequalities of a similar form

OGRDB: a reference database of inferred immune receptor genes

The immune rejection of allografts is mediated by T cells via two distinct pathways: the direct and the indirect pathways. Direct alloresponse to intact donor MHC molecules is ensured by T cells which are polyclonal and directed toward a variety of antigens. This response is highly sensitive to treatment by immunosuppressive drugs including Cyclosporin A. Indirect alloresponse is oligoclonal and involves a few dominant antigen peptides on donor MHC. In contrast to its direct counterpart, indirect allorecognition is thought to be poorly sensitive to blockade by cyclosporin A. It is likely that indirect and direct types of alloresponses play different roles in the physiology of the rejection process. T cell responses occurring via direct allorecognition play a critical role during the early phase of acute graft rejection by sensitizing the host to graft antigens. Alternatively, once such sensitization has taken place, indirect type of alloresponse may become predominant and presumably represent the driving force in the actual destruction of transplanted tissues. In addition, we and others have provided strong circumstantial evidence indicating that secondary T cell responses via indirect allorecognition spread to new determinants on donor MHC and tissue-specific antigens. This phenomenon is likely to play an important role in late and chronic rejection, a major obstacle to long-term graft acceptance in clinical transplantation. Finally, a series of studies have demonstrated that early, pre-transplant treatment with tolerogenic donor-derived MHC peptides can protect the graft from rejection in rodents. Although the mechanisms involved in MHC-peptide-induced tolerance are ill defined, this strategy represents a promising approach for ensuring long-lasting graft acceptance in the absence of widespread immunosuppression. It is now crucial to further explore the mechanims involved in immunogenicity and tolerogenicity of MHC peptides and to initiate clinical studies to evaluate the efficacy of blocking indirect alloresponses in transplanted patients