Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium

Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest P value 3.87?×?10(-12) for SNP rs634990 in Caucasians, and 9.65?×?10(-4) for rs8032019 in Asians. The overall meta-analysis provided P value 9.20?×?10(-23) for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95?% CI 1.64, 2.16, P?相似文献   

Hypothyroid States Mitigate the Diabetes-Induced Reduction of Calbindin D-28k, Calretinin, and Parvalbumin Immunoreactivity in Type 2 Diabetic Rats

In this study, we investigated the differences in calbindin D-28k (CB), calretinin, (CR) and parvalbumin (PV) immunoreactivity in the hippocampus of Zucker diabetic fatty (ZDF) rats and Zucker lean control (ZLC) rats. In addition, we observed the effects of hypothyroidism on the levels of immunoreactivity of these proteins in ZDF rats. For this study, 7-week-old ZDF rats were used, and methimazole treatment was continued for 5 weeks to induce hypothyroidism. The animals were sacrificed at 12 weeks of age. ZDF rats showed increased blood glucose levels compared to those in ZLC rats. Methimazole intervention significantly reduced total and free T3 levels, and it ameliorated the increase of blood glucose levels in ZDF rats. In ZLC rats, CB, CR, and PV immunoreactivity was detected in regions of the hippocampus proper. In vehicle-treated ZDF rats, CB, CR, and PV immunoreactivity was significantly decreased in the hippocampus. However, in the methimazole-treated rats, CB, CR, and PV immunoreactivity was significantly increased compared to that in the vehicle-treated rats. These results suggest that hypothyroidism ameliorated the diabetes-induced reduction of CB, CR, and PV immunoreactivity in the hippocampus.     

Assembly and maintenance of nodes of ranvier rely on distinct sources of proteins and targeting mechanisms

We have investigated the source(s) and targeting of components to PNS nodes of Ranvier. We show adhesion molecules are freely diffusible within the axon membrane and accumulate at forming nodes from local sources, whereas ion channels and cytoskeletal components are largely immobile and require transport to the node. We further characterize targeting of NF186, an adhesion molecule that pioneers node formation. NF186 redistributes to nascent nodes from a mobile, surface pool. Its initial accumulation and clearance from the internode require extracellular interactions, whereas targeting to mature nodes, i.e., those flanked by paranodal junctions, requires intracellular interactions. After incorporation into the node, NF186 is immobile, stable, and promotes node integrity. Thus, nodes assemble from two sources: adhesion molecules, which initiate assembly, accumulate by diffusion trapping via interactions with Schwann cells, whereas ion channels and cytoskeletal components accumulate via subsequent transport. In mature nodes, components turnover slowly and are replenished via transport. VIDEO ABSTRACT:     

Molecular and catalytic properties of 2,4'-dihydroxyacetophenone dioxygenase from Burkholderia sp. AZ11

The gene dad encoding 2,4'-dihydroxyacetophenone (DHAP) dioxygenase was cloned from Burkholderia sp. AZ11. The initiation codon GTG was converted to ATG for high-level expression of the enzyme in Escherichia coli. The enzyme was moderately thermostable, and the recombinant enzyme was briefly purified. The enzyme (M(r)=90 kDa) was a homotetramer with a subunit M(r) of 23 kDa. It contained 1.69 mol of non-heme iron, and had a dark gray color. On anaerobic incubation of it with DHAP, the absorption at around 400 nm increased due to the formation of an enzyme-DHAP complex. Multiple sequence alignment suggested that His77, His79, His115, and Glu96 in the cupin fold were possible metal ligands. The apparent K(m) for DHAP and the apparent V(max) were estimated to be 1.60 μM and 6.28 μmol/min/mg respectively. 2-Hydroxyacetophenone was a poor substrate. CuCl(2) and HgCl(2) strongly inhibited the enzyme, while FeSO(4) weakly activated it.     

1H NMR-based metabolite profiling of diet-induced obesity in a mouse mode

High-fat diets (HFD) and high-carbohydrate diets (HCD)- induced obesity through different pathways, but the metabolic differences between these diets are not fully understood. Therefore, we applied proton nuclear magnetic resonance ((1)H NMR)-based metabolomics to compare the metabolic patterns between C57BL/6 mice fed HCD and those fed HFD. Principal component analysis derived from (1)H NMR spectra of urine showed a clear separation between the HCD and HFD groups. Based on the changes in urinary metabolites, the slow rate of weight gain in mice fed the HCD related to activation of the tricarboxylic acid cycle (resulting in increased levels of citrate and succinate in HCD mice), while the HFD affected nicotinamide metabolism (increased levels of 1-methylnicotineamide, nicotinamide-N-oxide in HFD mice), which leads to systemic oxidative stress. In addition, perturbation of gut microflora metabolism was also related to different metabolic patterns of those two diets. These findings demonstrate that (1)H NMR-based metabolomics can identify diet-dependent perturbations in biological pathways.     

Systemic PPARγ Deletion Impairs Circadian Rhythms of Behavior and Metabolism

Compelling evidence from both human and animal studies suggests a physiological link between the circadian rhythm and metabolism but the underlying mechanism is still incompletely understood. We examined the role of PPARγ, a key regulator of energy metabolism, in the control of physiological and behavioral rhythms by analyzing two strains of whole-body PPARγ null mouse models. Systemic inactivation of PPARγ was generated constitutively by using Mox2-Cre mice (MoxCre/flox) or inducibly by using the tamoxifen system (EsrCre/flox/TM). Circadian variations in oxygen consumption, CO(2) production, food and water intake, locomotor activity, and cardiovascular parameters were all remarkably suppressed in MoxCre/flox mice. A similar phenotype was observed in EsrCre/flox/TM mice, accompanied by impaired rhythmicity of the canonical clock genes in adipose tissues and liver but not skeletal muscles or the kidney. PPARγ inactivation in isolated preadipocytes following exposure to tamoxifen led to a similar blockade of the rhythmicity of the clock gene expression. Together, these results support an essential role of PPARγ in the coordinated control of circadian clocks and metabolic pathways.     

New liquid chromatography method combining thermo-responsive material and inductive heating via alternating magnetic field

In this study, we examined the feasibility of a novel liquid chromatography technique that combines temperature-responsive polymeric materials with inductive heating via an alternating magnetic field (AMF). We considered the following components of the technique: (i) the preparation of composite materials of magnetite and silica, (ii) their heating behavior under the AMF, (iii) the conjugation of temperature-responsive polymers for the packing materials, and (iv) the elution profiles of the model compounds in the AMF. The results showed that we could influence the elution of the model compounds by AMF induction heating generated by the surrounding coil.     

Micromechanical evaluation of mineralized multilayers

The biomechanical stability of osseointegrated implants is of particular importance, especially the stability which is achieved from structural manipulation at the interface between the implant surface and the bone tissues. Nanoscale β-tricalcium phosphate-immobilized titanium was prepared by discharge into a physiological buffered saline solution. Compared with hydroxyapatite, it has been shown to be effective in generating a bone-like chemical structure on the surface by cooperative interaction between osteoblastic cells and the β-tricalcium phosphate. The present study, after cell cultivation, investigates the nanostructures and biomechanical property differences of a mineralized layer formed on two samples of nano-calcium phosphate-immobilized titanium. A scanning probe microscope study revealed that the mineralized tissue formed on the β-tricalcium phosphate samples after 1 week of cell culture showed significantly higher roughness, compared with hydroxyapatite samples. Nanoindentation micromechanical evaluation of the in vitro generated multilayered structures exhibited thicker bone-like mineralized layers on the β-tricalcium phosphate samples. A successful modification of titanium implants through the cooperative interaction between osteoblastic cells and nano β-tricalcium phosphate is anticipated.     

Propionate sensor using coenzyme-A transferase and acyl-CoA oxidase

We developed an amperometric propionate sensor using comprised of two recombinant enzymes, propionate coenzyme A CoA transferase from Clostridium propionicum and short-chain acyl-CoA oxidase from Arabidopsis thaliana. Response current increased linearly with increase in propionate concentration from 10 microM to 100 microM. The detection limit was 10 microM propionate.