APOA5 genotype influences the association between 25-hydroxyvitamin D and high density lipoprotein cholesterol

OBJECTIVE: Circulating levels of 25-hydroxyvitamin D (25OHD) are positively associated with high density lipoprotein (HDL) cholesterol. We sought to replicate a previously reported interaction between APOA5 genotype and vitamin D, and to examine whether HDL-associated genetic loci modify the association between serum 25OHD and HDL cholesterol. METHODS: We examined whether 42 single nucleotide polymorphisms (SNPs) modify the association between serum 25OHD and HDL cholesterol in the 1958 British Birth cohort (aged 45 years, n = 4978). RESULTS: We identified a borderline interaction between the SNP rs12272004 (near the APOA5) and serum 25OHD on HDL cholesterol (P(interaction) = 0.05). The interaction was particularly prominent among the samples collected during winter (P(interaction) = 0.001). None of the other loci showed an interaction with serum 25OHD concentrations on HDL cholesterol. CONCLUSIONS: Our study in 4978 British Whites provides further support that APOA5 genotype modifies the association between vitamin D metabolites and HDL cholesterol.

The Met Office Unified Model Global Atmosphere 3.0/3.1 and JULES Global Land 3.0/3.1 configurations

We describe Global Atmosphere 3.0 (GA3.0): a configuration of the Met Office Unified Model (MetUM) developed for use across climate research and weather prediction activities. GA3.0 has been formulated by converging the development paths of the Met Office's weather and climate global atmospheric model components such that wherever possible, atmospheric processes are modelled or parametrized seamlessly across spatial resolutions and timescales. This unified development process will provide the Met Office and its collaborators with regular releases of a configuration that has been evaluated, and can hence be applied, over a variety of modelling régimes. We also describe Global Land 3.0 (GL3.0): a configuration of the JULES community land surface model developed for use with GA3.0.

Calcium-mediated binding of DNA to 1,2-distearoyl-sn-glycero-3-phosphocholine-containing mixed lipid monolayers

The calcium-mediated interaction of DNA with monolayers of the non-toxic, zwitterionic phospholipid, 1,2-distearoyl-sn-glycero-3-phosphocholine when mixed with 50 mol% of a second lipid, either the zwitteronic 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine or neutral cholesterol was investigated using a combination of surface pressure-area isotherms, Brewster angle microscopy, external reflectance Fourier transform infrared spectroscopy and specular neutron reflectivity in combination with contrast variation. When calcium and DNA were both present in the aqueous subphase, changes were observed in the compression isotherms as well as the surface morphologies of the mixed lipid monolayers. In the presence of calcium and DNA, specular neutron reflectivity showed that directly underneath the head groups of the lipids comprising the monolayers, DNA occupied a layer comprising approximately 13 and 18% v/v DNA for the 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine and cholesterol-containing monolayers, respectively. The volume of the corresponding layer for 1,2-distearoyl-sn-glycero-3-phosphocholine only containing monolayers was ∼15% v/v DNA. Furthermore regardless of the presence and nature of the second lipid and the surface pressure of the monolayer, the specular neutron reflectivity experiments showed that the DNA-containing layer was 20–27 Å thick, suggesting the presence of a well-hydrated layer of double-stranded DNA. External reflectance Fourier transform infrared studies confirmed the presence of double stranded DNA, and indicated that the strands are in the B-form conformation. The results shed light on the interaction between lipids and nucleic acid cargo as well as the role of a second lipid in lipid-based carriers for drug delivery.

Stromal-derived factor-1 alpha (CXCL12) levels increase in periodontal disease

Background: The CXC chemokine receptor 4 (CXCR4) and its ligand, stromal cell-derived factor-1 (SDF-1 alpha or CXC chemokine ligand 12) are involved in the trafficking of leukocytes into and out of extravascular tissues. The purpose of this study was to determine whether SDF-1 alpha secreted by host cells plays a role in recruiting inflammatory cells into the periodontia during local inflammation. Methods: SDF-1 alpha levels were determined by enzyme-linked immunosorbent assay in gingival crevicular fluid (GCF) of 24 individuals with periodontitis versus healthy individuals in tissue biopsies and in a preclinical rat model of Porphyromonas gingivalis lipopolysaccharide-induced experimental bone loss. Neutrophil chemotaxis assays were also used to evaluate whether SDF-1 alpha plays a role in the recruitment of host cells at periodontal lesions. Results: Subjects with periodontal disease had higher levels of SDF-1 alpha in their GCF compared to healthy subjects. Subjects with periodontal disease who underwent mechanical therapy demonstrated decreased levels of SDF-1 alpha. Immunohistologic staining showed that SDF-1 alpha and CXCR4 levels were elevated in samples obtained from periodontally compromised individuals. Similar results were observed in the rodent model. Neutrophil migration was enhanced in the presence of SDF-1 alpha, mimicking immune cell migration in periodontal lesions. Conclusions: SDF-1 alpha may be involved in the immune defense pathway activated during periodontal disease. Upon the development of diseased tissues, SDF-1 alpha levels increase and may recruit host defensive cells into sites of inflammation. These studies suggest that SDF-1 alpha may be a useful biomarker for the identification of periodontal disease progression.

Na+-glucose transporter-2 messenger ribonucleic acid expression in kidney of diabetic rats correlates with glycemic levels: Involvement of hepatocyte nuclear factor-1 alpha expression and activity

Mutations in Na+-glucose transporters (SGLT)-2 and hepatocyte nuclear factor (HNF)-1 alpha genes have been related to renal glycosuria and maturity-onset diabetes of the young 3, respectively. However, the expression of these genes have not been investigated in type 1 and type 2 diabetes. Here in kidney of diabetic rats, we tested the hypotheses that SGLT2 mRNA expression is altered; HNF-1 alpha is involved in this regulation; and glycemic homeostasis is a related mechanism. The in vivo binding of HNF-1 alpha into the SGLT2 promoter region in renal cortex was confirmed by chromatin immunoprecipitation assay. SGLT2 and HNF-1 alpha mRNA expression (by Northern and RT-PCR analysis) and HNF-1 binding activity of nuclear proteins (by EMSA) were investigated in diabetic rats and treated or not with insulin or phlorizin (an inhibitor of SGLT2). Results showed that diabetes increases SGLT2 and HNF-1 alpha mRNA expression (similar to 50%) and binding of nuclear proteins to a HNF-1 consensus motif (similar to 100%). Six days of insulin or phlorizin treatment restores these parameters to nondiabetic-rat levels. Moreover, both treatments similarly reduced glycemia, despite the differences in plasma insulin and urinary glucose concentrations, highlighting the plasma glucose levels as involved in the observed modulations. This study shows that SGLT2 mRNA expression and HNF-1 alpha expression and activity correlate positively in kidney of diabetic rats. It also shows that diabetes-induced changes are reversed by lowering glycemia, independently of insulinemia. Our demonstration that HNF-1 alpha binds DNA that encodes SGLT2 supports the hypothesis that HNF-1 alpha, as a modulator of SGLT2 expression, may be involved in diabetic kidney disease.

NEUREGULINS 1-ALPHA AND 1-BETA ON THE REGENERATION THE PERIPHERAL NERVES

Objective: To evaluate the effect of the neuregulins 1-alpha and 1-beta on the regeneration the sciatic nerves of male adult C57BL/6J mice, using the tubulization technique. Methods: Eighteen animals were used, divided into three groups. A polyethylene prosthesis was implanted in a 4.0 mm defect of the left sciatic nerve, as follows: group 1 containing only purified collagen (Vitrogen (R)); group 2, collagen with neuregulin 1-alpha; group 3, collagen with neuregulin 1-beta. The control group consisted of six segments of right sciatic nerves. After four weeks, the animals were sacrificed. A segment from the midpoint of the nerve regenerated inside the prostheses was extracted; histological sections were standardized, and slides were made up for histomorphometric analysis. Results: the results were statistically compared using the Tukey multiple comparisons test and The Student`s t test. The animals treated with neuregulins had greater numbers of myelinized axons, with a statistically significant difference in relation to the collagen-only group. There was no statistical difference between the neuregulin 1-alpha and 1-beta groups. Conclusion: The addition of neuregulins provided a significant increase in the number of myelinized fibers.

Pressure-induced electrical and structural anomalies in Pb(1-x)Ca(x)TiO(3) thin films grown at various oxygen pressures by chemical solution route

Lead calcium titanate (Pb(1-x)Ca(x)TiO(3) or PCT) thin films have been thermally treated under different oxygen pressures, 10, 40 and 80 bar, by using the so-called chemical solution deposition method. The structural, morphological, dielectric and ferroelectric properties were characterized by x-ray diffraction, FT-infrared and Raman spectroscopy, atomic force microscopy and polarization-electric-field hysteresis loop measurements. By annealing at a controlled pressure of around 10 and 40 bar, well-crystallized PCT thin films were successfully prepared. For the sample submitted to 80 bar, the x-ray diffraction, Fourier transformed-infrared and Raman data indicated deviation from the tetragonal symmetry. The most interesting feature in the Raman spectra is the occurrence of intense vibrational modes at frequencies of around 747 and 820 cm(-1), whose presence depends strongly on the amount of the pyrochlore phase. In addition, the Raman spectrum indicates the presence of symmetry-breaking disorder, which would be expected for an amorphous (disorder) and mixed pyrochlore-perovskite phase. During the high-pressure annealing process, the crystallinity and the grain size of the annealed film decreased. This process effectively suppressed both the dielectric and ferroelectric behaviour. Ferroelectric hysteresis loop measurements performed on these PCT films exhibited a clear decrease in the remanent polarization with increasing oxygen pressure.

Evidence for magnetic phase separation in La(0.86)Sr(0.14)Mn(1-x)Cu(x)O(3+delta) manganites from NMR and magnetic measurements

Polycrystalline La(0.86)Sr(0.14)Mn(1-x)Cu(x)O(3+delta) (x = 0, 0.05, 0.10, 0.15, 0.20) manganites were investigated by means of magnetic measurements and zero-field (139)La and (55)Mn nuclear magnetic resonance (NMR) spectroscopy. Magnetization versus temperature measurements revealed a paramagnetic to ferromagnetic transition in most samples, with lower Curie temperatures and broader transitions for samples with higher Cu contents. The details of the magnetization measurements suggested a phase-separated scenario, with ferromagnetic clusters embedded in an antiferromagnetic matrix, especially for the samples with large Cu contents (x = 0.15 and 0.20). Zero-field (139)La NMR measurements confirmed this finding, since the spectral features remained almost unchanged for all Cu-doped samples, whereas the bulk magnetization was drastically reduced with increasing Cu content. (55)Mn NMR spectra were again typical of ferromagnetic regions, with a broadening of the resonance line caused by the disorder introduced by the Cu doping. The results indicate a coexistence of different magnetic phases in the manganites studied, with the addition of Cu contributing to the weakening of the double-exchange interaction in most parts of the material.

Leakage current, ferroelectric and structural properties in Pb(1-x)Ba(x)TiO(3) thin films prepared by chemical route

Single-phase perovskite structure Pb(1-x)Ba(x)TiO(3) thin films (x = 0.30, 0.50 and 0.70) were deposited on Pt/Ti/SiO(2)/Si substrates by the spin-coating technique. The dielectric study reveals that the thin films undergo a diffuse type ferroelectric phase transition, which shows a broad peak. An increase of the diffusivity degree with the increasing Barium contents was observed, and it was associated to a grain decrease in the studied composition range. The temperature dependence of the phonon frequencies was used to characterize the phase transition temperatures. Raman modes persist above tetragonal to cubic phase transition temperature, although all optical modes should be Raman inactive. The origin of these modes was interpreted in terms of breakdown of the local cubic symmetry by chemical disorder. The absence of a well-defined transition temperature and the presence of broad bands in some interval temperature above FE-PE phase transition temperature Suggested a diffuse type phase transition. This result corroborates the dielectric constant versus temperature data, which showed a broad ferroelectric phase transition in these thin films. The leakage Current density of the PBT thin films was studied at different temperatures and the data follow the Schottky emission model. Through this analysis the Schottky barrier height values 0.75, 0.53 and 0.34 eV were obtained to the PBT70, PBT50 and PBT30 thin films, respectively. (C) 2008 Elsevier Ltd. All rights reserved.

An insight into the beginning stage of the aqueous ring opening metathesis polymerization of exo,exo-7-oxabicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic acid with Ru(III) compounds: the consumption of Ru(III) species in the presence of carboxylic acids monitored by ESR spectroscopy

The presence of paramagnetic species in the aqueous ring opening metathesis polymerizations of the exo,exo-7-oxabicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic acid monomer with RuCl(3) and K(2)[RuCl(5)H(2)O] compounds was studied using ESR techniques. It was observed that the intensities of the Ru(III) signals in the ESR spectra decrease on the time scale of the induction period so that the ROMP can take place. The intensity of the Ru(III) signal almost disappeared 50 min after reacting with K(2)[RuCl(5)H(2)O] and after 100 mm in the case of RuCl(3). Reactions of the cis-[Ru(NH(3))(4)(H(2)O)(2)](tfms)(3) and [Ru(NH(3))(5)H(2)O](tfms)(3) complexes with the monomer and different organic compounds representing the organic functions in the monomer (furan, norbornene, but-2-ene-1,4-diol and formic, acetic, oxalic and maleic acids) were also monitored by ESR and UV/vis spectra. It was deduced that the organic acids provide the disappearance of the Ru(III) signal. The proton NMR relaxation times of the residual water in D(2)O for reactions with oxalic acid suggested that the presence of paramagnetic ions in the solution decreases along with

Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the third national health and nutrition examination survey

OBJECTIVE— To determine the association between serum 25-hydroxyvitamin D (25OHD) and diabetes risk and whether it varies by ethnicity.
RESEARCH DESIGN AND METHODS— We performed an analysis of data from participants who attended the morning examination of the Third National Health and Nutrition Examination Survey (1988–1994), a cross-sectional survey of a nationally representative sample of the U.S. population. Serum levels of 25OHD, which reflect vitamin D status, were available from 6,228 people (2,766 non-Hispanic whites, 1,736 non-Hispanic blacks, and 1,726 Mexican Americans) aged ≥20 years with fasting and/or 2-h plasma glucose and serum insulin measurements.
RESULTS— Adjusting for sex, age, BMI, leisure activity, and quarter of year, ethnicityspecific odds ratios (ORs) for diabetes (fasting glucose ≥7.0 mmol/l) varied inversely across quartiles of 25OHD in a dose-dependent pattern (OR 0.25 [95% CI 0.11– 0.60] for non-Hispanic whites and 0.17 [0.08–0.37] for Mexican Americans) in the highest vitamin D quartile (25OHD ≥81.0 nmol/l) compared with the lowest 25OHD (≥43.9 nmol/l). This inverse association
was not observed in non-Hispanic blacks. Homeostasis model assessment of insulin resistance (loge) was inversely associated with serum 25OHD in Mexican Americans (P ≥ 0.0024) and non-Hispanic whites (P≥0.058) but not non-Hispanic blacks (P≥0.93), adjusting for confounders.
CONCLUSIONS— These results show an inverse association between vitamin D status and diabetes, possibly involving insulin resistance, in non-Hispanic whites and Mexican Americans. The lack of an inverse association in non-Hispanic blacks may reflect decreased sensitivity to vitamin D and/or related hormones such as the parathyroid hormone.

Vitamin D-fortified milk achieves the targeted serum 25-hydroxyvitamin D concentration without affecting that of parathyroid hormone in New Zealand toddlers

For young children, the level of vitamin D required to ensure that most achieve targeted serum 25-hydroxyvitamin D [25(OH)D] ≥50 nmol/L has not been studied. We aimed to investigate the effect of vitamin D-fortified milk on serum 25(OH)D and parathyroid hormone (PTH) concentrations and to examine the dose–response relationship between vitamin D intake from study milks and serum 25(OH)D concentrations in healthy toddlers aged 12–20 mo living in Dunedin, New Zealand (latitude 46°S). Data from a 20-wk, partially blinded, randomized trial that investigated the effect of providing red meat or fortified toddler milk on the iron, zinc, iodine, and vitamin D status in young New Zealand children (n = 181; mean age 17 mo) were used. Adherence to the intervention was assessed by 7-d weighed diaries at wk 2, 7, 11, 15, and 19. Serum 25(OH)D concentration was measured at baseline and wk 20. Mean vitamin D intake provided by fortified milk was 3.7 μg/d (range, 0–10.4 μg/d). After 20 wk, serum 25(OH)D concentrations but not PTH were significantly different in the milk groups. The prevalence of having a serum 25(OH)D <50 nmol/L remained relatively unchanged at 43% in the meat group, whereas it significantly decreased to between 11 and 15% in those consuming fortified study milk. In New Zealand, vitamin D intake in young children is minimal. Our findings indicate that habitual consumption of vitamin D-fortified milk providing a mean intake of nearly 4 μg/d was effective in achieving adequate year-round serum 25(OH)D for most children.

Low serum 25-hydroxyvitamin D is associated with increased risk of the development of the metabolic syndrome at five years : results from a national, population-based prospective study (the Australian Diabetes, Obesity and Lifestyle Study : AusDiab)

Context: Serum 25-hydroxyvitamin D [25(OH)D] concentration has been inversely associated with the prevalence of metabolic syndrome (MetS), but the relationship between 25(OH)D and incident MetS remains unclear.

Objective: We evaluated the prospective association between 25(OH)D, MetS, and its components in a large population-based cohort of adults aged 25 yr or older.

Design: We used baseline (1999–2000) and 5-yr follow-up data of the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab).

Participants: Of the 11,247 adults evaluated at baseline, 6,537 returned for follow-up. We studied those without MetS at baseline and with complete data (n = 4164; mean age 50 yr; 58% women; 92% Europids).

Outcome Measures: We report the associations between baseline 25(OH)D and 5-yr MetS incidence and its components, adjusted for age, sex, ethnicity, season, latitude, smoking, family history of type 2 diabetes, physical activity, education, kidney function, waist circumference (WC), and baseline MetS components.

Results: A total of 528 incident cases (12.7%) of MetS developed over 5 yr. Compared with those in the highest quintile of 25(OH)D (≥34 ng/ml), MetS risk was significantly higher in people with 25(OH)D in the first (<18 ng/ml) and second (18–23 ng/ml) quintiles; odds ratio (95% confidence interval) = 1.41 (1.02–1.95) and 1.74 (1.28–2.37), respectively. Serum 25(OH)D was inversely associated with 5-yr WC (P < 0.001), triglycerides (P < 0.01), fasting glucose (P < 0.01), and homeostasis model assessment for insulin resistance (P < 0.001) but not with 2-h plasma glucose (P = 0.29), high-density lipoprotein cholesterol (P = 0.70), or blood pressure (P = 0.46).

Conclusions: In Australian adults, lower 25(OH)D concentrations were associated with increased MetS risk and higher WC, serum triglyceride, fasting glucose, and insulin resistance at 5 yr. Vitamin D supplementation studies are required to establish whether the link between vitamin D deficiency and MetS is causal.

Serum 25-hydroxyvitamin D deficiency and the 5-year incidence of CKD

Low serum 25-hydroxyvitamin D (25[OH]D) levels have been associated with chronic kidney disease in cross-sectional studies. However, this association has not been studied prospectively in a large general population–based cohort.

This prospective cohort study shows that vitamin D deficiency is associated with a higher annual incidence of albuminuria and reduced eGFR and independently predicts the 5-year incidence of albuminuria. These associations warrant further exploration in long-term prospective clinical trials.

Association between serum concentration of 25-hydroxyvitamin D and the risk of hip arthroplasty for osteoarthritis: result from a prospective cohort study

OBJECTIVES: There is ongoing debate regarding the optimal serum concentrations of 25-hydroxy-vitamin D for musculoskeletal health, including osteoarthritis (OA). The aim of this prospective cohort study was to determine whether serum 25-hydroxy-vitamin D concentrations were associated with the risk of hip arthroplasty for OA. DESIGN: This study examined 9135 participants from the Australian Diabetes, Obesity and Lifestyle Study who had serum 25-hydroxy-vitamin D measured in 1999-2000 and were aged ≥40 years at the commencement of arthroplasty data collection. The incidence of hip arthroplasty for OA during 2002-2011 was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. RESULTS: Over an average 9.1 (standard deviation (SD) 2.7) years of follow-up, 201 hip arthroplasties for OA were identified (males n = 90; females n = 111). In males, a one-standard-deviation increase in 25-hydroxy-vitamin D was associated with a 25% increased incidence (HR 1.25, 95% CI 1.02-1.56), with a dose response relationship evident by quartiles of 25-hydroxy-vitamin D concentration (P for trend 0.04). These results were independent of age, body mass index (BMI), ethnicity, smoking status, physical activity, season of blood collection, latitude, hypertension and diabetes, area level disadvantage or after excluding those with extreme low 25-hydroxy-vitamin D concentrations. No significant association was observed in women (HR 1.10, 95% CI 0.87, 1.39). CONCLUSIONS: Increasing serum 25-hydroxy-vitamin D concentrations were associated with an increased risk of hip arthroplasty for OA in males, while no significant association was observed in females. The mechanism for the association warrants further investigation.