Trends in Child Overweight Rates and Energy Intake in France From 1999 to 2007: Relationships With Socioeconomic Status

Our objectives were (i) to assess the current prevalence of childhood overweight (including obesity) (OWOB) in France and its relationship with comprehensive socioeconomic status (SES) indicators and (ii) to examine trends in OWOB prevalence and changes in energy intake (EI) and sedentary behavior (SED) based on the previous INCA 1 (Individuelle Nationale des Consommations Alimentaires) data (1998–1999). A representative sample of children aged 3–14 (n = 1,030) was taken from the 2006–2007 cross‐sectional INCA 2 food consumption survey. Weight and height were measured. The prevalence of OWOB was estimated according to the IOTF (International Obesity Task Force) definition. Average daily EI was evaluated using a 7‐day food record. SED (screen time) and SES were reported by answering questionnaires. SES indicators included the occupation and level of education of the head of the household (HH), and variables describing household wealth. Composite indices of SES were computed by correspondence analysis, and relationships with OWOB were explored by logistic regression analysis. In total, 14.5% (95% CI: 12.1–17.0) of the children were OWOB. All SES indicators were inversely correlated to OWOB. Average EI was equal to 1,739 kcal/day. Daily, children spent 113.5 min watching television, and 38.5 min playing video games or using a computer. Compared to the INCA 1 study, OWOB prevalence was not significantly different, EI was lower, and SED was higher. These trends were the same across all occupational categories of heads of household. Although overall rates of childhood OWOB are currently stabilizing, no change was observed in the strong inverse socioeconomic gradient of OWOB between the two studies.     

Mathematical modeling of pulmonary tuberculosis therapy: Insights from a prototype model with rifampin

There is a critical need for improved and shorter tuberculosis (TB) treatment. Current in vitro models of TB, while valuable, are poor predictors of the antibacterial effect of drugs in vivo. Mathematical models may be useful to overcome the limitations of traditional approaches in TB research. The objective of this study was to set up a prototype mathematical model of TB treatment by rifampin, based on pharmacokinetic, pharmacodynamic and disease submodels.The full mathematical model can simulate the time-course of tuberculous disease from the first day of infection to the last day of therapy. Therapeutic simulations were performed with the full model to study the antibacterial effect of various dosage regimens of rifampin in lungs.The model reproduced some qualitative and quantitative properties of the bactericidal activity of rifampin observed in clinical data. The kill curves simulated with the model showed a typical biphasic decline in the number of extracellular bacteria consistent with observations in TB patients. Simulations performed with more simple pharmacokinetic/pharmacodynamic models indicated a possible role of a protected intracellular bacterial compartment in such a biphasic decline.This modeling effort strongly suggests that current dosage regimens of RIF may be further optimized. In addition, it suggests a new hypothesis for bacterial persistence during TB treatment.     

A novel cholesterol‐insensitive mode of membrane binding promotes cytolysin‐mediated translocation by Streptolysin O

Cytolysin‐mediated translocation (CMT), performed by Streptococcus pyogenes, utilizes the cholesterol‐dependent cytolysin Streptolysin O (SLO) to translocate the NAD⁺‐glycohydrolase (SPN) into the host cell during infection. SLO is required for CMT and can accomplish this activity without pore formation, but the details of SLO's interaction with the membrane preceding SPN translocation are unknown. Analysis of binding domain mutants of SLO and binding domain swaps between SLO and homologous cholesterol‐dependent cytolysins revealed that membrane binding by SLO is necessary but not sufficient for CMT, demonstrating a specific requirement for SLO in this process. Despite being the only known receptor for SLO, this membrane interaction does not require cholesterol. Depletion of cholesterol from host membranes and mutation of SLO's cholesterol recognition motif abolished pore formation but did not inhibit membrane binding or CMT. Surprisingly, SLO requires the coexpression and membrane localization of SPN to achieve cholesterol‐insensitive membrane binding; in the absence of SPN, SLO's binding is characteristically cholesterol‐dependent. SPN's membrane localization also requires SLO, suggesting a co‐dependent, cholesterol‐insensitive mechanism of membrane binding occurs, resulting in SPN translocation.     

Balancing the costs of carbon gain and water transport: testing a new theoretical framework for plant functional ecology

A novel framework is presented for the analysis of ecophysiological field measurements and modelling. The hypothesis ‘leaves minimise the summed unit costs of transpiration and carboxylation’ predicts leaf‐internal/ambient CO₂ ratios (c_i/c_a) and slopes of maximum carboxylation rate (V_cmax) or leaf nitrogen (N_area) vs. stomatal conductance. Analysis of data on woody species from contrasting climates (cold‐hot, dry‐wet) yielded steeper slopes and lower mean c_i/c_a ratios at the dry or cold sites than at the wet or hot sites. High atmospheric vapour pressure deficit implies low c_i/c_a in dry climates. High water viscosity (more costly transport) and low photorespiration (less costly photosynthesis) imply low c_i/c_a in cold climates. Observed site‐mean c_i/c_a shifts are predicted quantitatively for temperature contrasts (by photorespiration plus viscosity effects) and approximately for aridity contrasts. The theory explains the dependency of c_i/c_a ratios on temperature and vapour pressure deficit, and observed relationships of leaf δ¹³C and N_area to aridity.     

S-Palmitoylation and S-Oleoylation of Rabbit and Pig Sarcolipin

Sarcolipin (SLN) is a regulatory peptide present in sarcoplasmic reticulum (SR) from skeletal muscle of animals. We find that native rabbit SLN is modified by a fatty acid anchor on Cys-9 with a palmitic acid in about 60% and, surprisingly, an oleic acid in the remaining 40%. SLN used for co-crystallization with SERCA1a (Winther, A. M., Bublitz, M., Karlsen, J. L., Moller, J. V., Hansen, J. B., Nissen, P., and Buch-Pedersen, M. J. (2013) Nature 495, 265–2691; Ref. 1) is also palmitoylated/oleoylated, but is not visible in crystal structures, probably due to disorder. Treatment with 1 m hydroxylamine for 1 h removes the fatty acids from a majority of the SLN pool. This treatment did not modify the SERCA1a affinity for Ca²⁺ but increased the Ca²⁺-dependent ATPase activity of SR membranes indicating that the S-acylation of SLN or of other proteins is required for this effect on SERCA1a. Pig SLN is also fully palmitoylated/oleoylated on its Cys-9 residue, but in a reverse ratio of about 40/60. An alignment of 67 SLN sequences from the protein databases shows that 19 of them contain a cysteine and the rest a phenylalanine at position 9. Based on a cladogram, we postulate that the mutation from phenylalanine to cysteine in some species is the result of an evolutionary convergence. We suggest that, besides phosphorylation, S-acylation/deacylation also regulates SLN activity.     

Effects of electrical stimulation and choline availability on the release and contents of acetylcholine and choline in superfused slices from rat striatum

The presence of 5 or 20 microM choline in the eserinized medium superfusing striatal slices enhanced the spontaneous release of acetylcholine (ACh) at both concentrations and, at 20 microM, the release of transmitter evoked by electrical field stimulation. Neither the electrical stimulation nor the addition of choline altered choline acetyltransferase activity. These results show that ACh release is dependent on the availability of extracellular choline. The rate of choline efflux was 7 times higher than the rate of ACh release, was not affected by stimulation, and was increased by 40% when hemicholinium-3 (HC-3), an inhibition of choline uptake, was present. The muscarinic antagonist atropine (1 microM) increased the evoked release of ACh into both the choline-free medium and that containing 20 microM choline. An adenosine receptor antagonist, 1,3-diethyl-8-phenyl xanthine (10 microM), failed to affect ACh release or the enhancement of release produced by atropine. In medium containing HC-3, stimulation of the slices elicited ACh release for the first 20 min of the 30 min stimulation period (15 Hz); thereafter, although stimulation was continued, the rate of release decreased to that associated with spontaneous release. Tissue ACh contents were not modified by the addition of choline or atropine to the medium, but were depressed by HC-3. Neither atropine nor HC-3 altered tissue choline content. The total amount of ACh + choline released during an experiment was 5-15 times higher than the decrease in tissue levels of these two compounds during the same period of time.(ABSTRACT TRUNCATED AT 250 WORDS)     

Monomeric state and Ca2+ transport by sarcoplasmic reticulum Ca2(+)-ATPase, reconstituted with an excess of phospholipid

The structural basis for Ca2+ transport was examined in vesicles reconstituted with an excess of phospholipid by a cholate dialysis procedure. Unincorporated protein and vesicles with a relatively high protein content were removed by sucrose density centrifugation (3-12%), leaving a fraction of lipid-rich vesicles (lipid to protein weight ratio 800-900:1) with a high coupling ratio (1.0) and transport capacity (25 mumol/mg protein, after Ca-phosphate loading). Freeze-fracture analysis showed that the reconstituted vesicles had a remarkably narrow size distribution (diameter 794 +/- 77 A (S.D.], suitable for stereological analysis. Intramembranous particles were dispersed and occurred with a low frequency in the fractured shells, also before sucrose fractionation. It was calculated that the number of intramembranous particles corresponded to the number of Ca2(+)-ATPase polypeptide/vesicle. A ratio of unity between particles and polypeptide chains was also obtained from the density of particle distribution on flat surfaces of fused vesicles, prepared by sucrose fractionation. The size of the particles formed a broad distribution, having a peak value around 60-67 A, both in the reconstituted preparation and sarcoplasmic reticulum vesicles. No evidence for protein-protein interactions was found in chemical cross-linking experiments. It is concluded that the intramembranous particles in the reconstituted preparations are referable to monomeric Ca2(+)-ATPase which is capable of transporting Ca2+ inside the vesicles. The implications of the observations for the associational state of Ca2(+)-ATPase at high protein concentration are considered in relation to previous ultrastructural investigations of membranous Ca2(+)-ATPase in native and two-dimensional-crystalline forms.