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Placental lipoprotein lipase (LPL) is crucial for placental lipid transfer. Impaired LPLgene expression and activity were reported in pregnancies complicated by gestational diabetes mellitus (GDM) and intra-uterine growth restriction. We hypothesized that placental LPLDNA methylation is altered by maternal metabolic status and could contribute to fetal programming. The objective of this study was thus to assess whether placental LPLDNA methylation is associated with GDM and both maternal and newborn lipid profiles. Placenta biopsies were sampled at delivery from 126 women including 27 women with GDM diagnosed following a post 75 g-oral glucose tolerance test (OGTT) between weeks 24 and 28 of gestation. Placental LPLDNA methylation and expression levels were determined using bisulfite pyrosequencing and quantitative real-time PCR, respectively. DNA methylation levels within LPLproximal promoter region (CpG1) and intron 1 CpG island (CpGs 2 and 3) were lower in placenta of women with GDM. DNA methylation levels at LPL-CpG1 and CpG3 were also negatively correlated with maternal glucose (2-h post OGTT; r=–0.22; P=0.02) and HDL-cholesterol levels (third trimester of pregnancy; r=–0.20; p=0.03), respectively. Moreover, we report correlation between LPL-CpG2 DNA methylation and cord blood lipid profile. DNA methylation levels within intron 1 CpG island explained up to 26% (r?–0.51; P<0.001) of placental LPLmRNA expression variance. Overall, we showed that maternal metabolic profile is associated with placental LPLDNA methylation dysregulation. Our results suggest that site-specific LPLepipolymorphisms in the placenta are possibly functional and could potentially be involved in determining the future metabolic health of the newborn.

An oxygen transport model derived for limiting current density operation was employed to explore its use for hydrogen transport. Limiting current data obtained from a variety of fuel cell designs (alkaline, proton exchange membrane, sulphuric acid) demonstrated the model's validity and allowed determination of the hydrogen mass transport coefficient, a key cell performance parameter. Under specific operating conditions, the proposed model is consistent with the continuous stirred tank reactor and the logarithmic mean concentration difference models. The proposed model is preferable because it is more general and derived from a specific physical mechanism. Experimental precautions needed to ensure well‐defined limiting currents without the presence of artefacts were reemphasized and expanded. Model use for predictive purposes is also briefly discussed.

Aging is a complex process modulated by multiple interactions between environmental and genetic factors. Myotonic dystrophy (DM 1) is an autosomal dominant disorder caused by an unstable (CTG)n repeat expansion in the DM1 protein kinase (DMPK) gene. The affected male patients' life expectancy at birth (53.2 years) is more than two decades below that observed in most occidental populations. The DMPK gene expression is pleiotropic and includes the premature expression of several agerelated signs, symptoms and metabolic disturbances including hormonal dysfunctions, progressive decrease in muscular mass, presenile cataracts, alopecia, reduced alertness, insulin resistance, dyslipidemia, erectile dysfunction and hypogonadism. The aim of this study was to analyze the relationship between aging covariates and the severity of DM1 expression in 136 DM1 male subjects. DM1 clinical expression was assessed on a validated neuromuscular disability rating scale and was correlated with plasma total testosterone (rs = -0.31, p < 0.001), luteinizing hormone (LH) (rs = 0.52, p < 0.001) and follicle stimulating hormone (FSH) (rs = 0.54, p < 0.001) levels. Following LH releasing hormone stimulation, FSH and LH concentrations increased as a function of DM1 severity (p < 0.05). Muscular disability in DM1 was also positively associated with fasting plasma insulin and triglyceride concentrations (p < 0.05). The association of plasma apolipoprotein B and low-density lipoprotein cholesterol levels with DM1 was not linear across their distribution and tended to reflect cell membrane damage progression. These results suggest that DM1, a simple M endelian trait, can represent a valuable model to illustrate the complex relationships between variables associated with male aging.

The effects of acute allergen exposure on bronchoalveolar lavage cells and mediators and mucosal inflammatory cells were evaluated in 10 subjects with atopic asthma who underwent lavage and biopsy 24 hours after segmental endobronchial allergen challenge. Increased numbers of bronchoalveolar lavage eosinophils were retrieved from the allergen-challenged sites compared with the saline-challenged sites (mean 21.4 vs 1.5 x 10^3 cells/ml; p < 0.02). Numbers of neutrophils and proportions of CD4^+, CD8^+, CD25^+, and HLA-DR^+ T cells were similar at the saline- and allergen-challenged sites. In contrast to the bronchoalveolar lavage findings, eosinophil numbers were not increased in the bronchial submucosa or epithelium. There was also no significant difference in neutrophils, mast cells, CD3^+, CD4^+, or CD8^+ T cells in the submucosa after allergen challenge, but the number of activated (CD25^+) T lymphocytes in the mucosa did increase after allergen challenge. Allergen challenge did not induce any significant change in endothelial expression of P-selectin, E-selectin, intercellular adhesion molecule-1, or vascular cell adhesion molecule-1. CD11a^+ and very late antigen-4^+ cell numbers were similar in the saline- and allergen-challenged sites. This study suggests that in patients with very mild asthma, local allergen challenge induces persistent bronchoalveolar lavage eosinophilia, but the recruitment process seems to have diminished or ceased by 24 hours. (J ALLERGY CLIN IMMUNOL 1996;98:133-43.)

Sixteen borosilicate glasses containing up to 20% zirconium oxide and 10% simulated fission products or lanthanum oxide were prepared by fusion at 1150 to 1350°C. Their leaching rates in distilled water at 100°C as measured in a Soxhlet extractor varied from 0.9 to 10.9 × 10−6g/m2· s. The results were analysed by multiple linear regression analysis. Some of the glasses studied may constitute a suitable matrix for the disposal of radioactive waste.

The two dimensional conformational spaces available for acetoxymethyl groups in carbohydrates are reported. The studies were performed on two molecules differing in their C-4 configurations, i.e. glucoand galacto. The acetoxymethyl group was assigned a mean geometry derived from the computation of 19 equivalent groups as found in pertinent acetylated carbohydrates. The internal energy calculations were performed by including the partitioned contributions arising from the non-bonded energies, electrostatic interactions, and torsion energy. An instability rating of 3 kcal/mol was assigned to conformations involving periinteractions, i.e., trans–gaucheand gauche–gaucheforms in glucoand galactocarbohydrates, respectively. The results which are best described in term of topology show that several conformations corresponding to the transand gauchestates of the C—O single bond are preferred. However, significant shifts from perfect staggering are observed. The predicted regions of low energy are found to be in good agreement with experimental data from crystal structures of acetylated carbohydrates.

The effects of 6-dimethylaminopurine (6-DMAP) (a putative phosphorylation inhibitor) on the state of assembly of microtubules and intermediate filaments have been studied during the first cell cycle of the sea urchin Strongylocentrotus droebachiensis. Changes in the spatial organization of cytoskeletal structures were studied by indirect immunofluorescence with anti-tubulin and anti-IFa antibodies. The rates and patterns of protein phosphorylation in control and treated eggs were also investigated. The transfer of fertilized eggs to 600 microM 6-DMAP within 4 min following insemination inhibits pronuclear migration and syngamy. This also prevents male pronuclear decondensation, while chromatin condensation and nuclear envelope breakdown do not occur in the female pronucleus. Immunolabeling with anti-tubulin antibodies reveals the presence of cortical microtubules as early as 15 min after fertilization in both control and treated eggs. However, no sperm astral microtubules could be detected in the treated eggs. At later stages, from syngamy (40 min) up to nuclear envelope breakdown (90 min), 6-DMAP affects neither cortical microtubule organization nor the state of chromatin condensation but it precludes nuclear envelope breakdown and entry into mitosis. Treatment of the fertilized eggs after nuclear envelope breakdown induces permanent chromosome decondensation and premature disappearance of the mitotic apparatus. This last event involves disruption of the spatial organization of both microtubules and putative intermediate filaments. Quantitative measurements of protein phosphorylation show that 6-DMAP efficiently and reversibly inhibits 32P incorporation into proteins. Qualitative analysis of the autoradiograms of 32P-labeled proteins separated by SDS-PAGE reveals that a major protein band, migrating with an apparent molecular weight of 31 × 10(3)Mr, is specifically dephosphorylated in eggs treated with 6-DMAP. This study suggests that protein phosphorylation is required for sperm aster microtubule growth and migration, but not for cortical microtubule polymerization. It also strengthens the hypothesis that, in sea urchin eggs, putative intermediate filaments are tightly associated with spindle microtubules. Finally, it confirms that inhibiting protein phosphorylation before nuclear envelope breakdown reversibly prevents the entry into mitosis.