Association of maternal iodine status with child IQ: a meta-analysis of individual-participant data

Dataset, supplement to the article (to be added later

The use of lower or higher than recommended doses of folic acid supplements during pregnancy is associated with child attentional dysfunction at 4–5 years of age in the inma project

We assessed the association between the use of lower-and higher-than-recommended doses of folic acid supplements (FAs) during pregnancy and attentional function in boys and girls at age of 4–5. We analyzed data from 1329 mother-child pairs from the mother-child cohort INfancia y Medio Ambiente Project (INMA) study. Information on FAs use during pregnancy was collected in personal interviews at weeks 12 and 30, and categorized in <400, 400–999 (recommended dose), and ≥1000 µg/day. Child attentional function was assessed by Conners’ Kiddie Continuous Performance Test. Multivariable regression analyses were used to estimate incidence rate ratios (IRR) and beta coefficients with 95% confidence intervals (CI). Compared to recommended FAs doses, the periconceptional use of <400 and ≥1000 µg/day was associated with higher risk of omission errors—IRR = 1.14 (95% CI: 1.01; 1.29) and IRR = 1.16 (95% CI: 1.02; 1.33), respectively. The use of FAs < 400 µg/day and ≥1000 µg/day was significantly associated with deficits of attentional function only in boys. FAs use < 400 µg/day was associated with higher omission errors with IRR = 1.22 and increased hit reaction time (HRT) β = 34.36, and FAs use ≥ 1000 µg/day was associated with increased HRT β = 33.18 and HRT standard error β = 3.31. The periconceptional use of FAs below or above the recommended doses is associated with deficits of attentional function in children at age of 4–5, particularly in boys

Stratification strength and light climate explain variation in chlorophyll a at the continental scale in a European multilake survey in a heatwave summer

To determine the drivers of phytoplankton biomass, we collected standardized morphometric, physical, and biological data in 230 lakes across the Mediterranean, Continental, and Boreal climatic zones of the European continent. Multilinear regression models tested on this snapshot of mostly eutrophic lakes (median total phosphorus [TP] = 0.06 and total nitrogen [TN] = 0.7 mg L−1), and its subsets (2 depth types and 3 climatic zones), show that light climate and stratification strength were the most significant explanatory variables for chlorophyll a (Chl a) variance. TN was a significant predictor for phytoplankton biomass for shallow and continental lakes, while TP never appeared as an explanatory variable, suggesting that under high TP, light, which partially controls stratification strength, becomes limiting for phytoplankton development. Mediterranean lakes were the warmest yet most weakly stratified and had significantly less Chl a than Boreal lakes, where the temperature anomaly from the long-term average, during a summer heatwave was the highest (+4°C) and showed a significant, exponential relationship with stratification strength. This European survey represents a summer snapshot of phytoplankton biomass and its drivers, and lends support that light and stratification metrics, which are both affected by climate change, are better predictors for phytoplankton biomass in nutrient-rich lakes than nutrient concentrations and surface temperature

Characterisation Of A Gain-of-function Mutant Of Poly(adp-ribose) Polymerase

In order to examine the stucture-function relationship of the poly (ADP-ribose) polymerase (PARP) catalytic domain, potential active-site residues in the catalytic domain have previously been described. Here, we have used mutagenesis with hydroxylamine to generate a random library of PARP mutants. The identification, overproduction in insect cells, purification and characterization of a gain-of-function mutant (L713F) is described. We show that the k(cat) of this mutant is increased over nine times compared to the wild-type enzyme; the K(m) for NAD+ is unchanged. The size and the branching structure of the ADP-ribose polymers are similar in both the wild-type and the mutant enzyme. This mutation may have an allosteric effect on the catalytic site and could be useful in analyzing the consequences of poly ADP-ribose overproduction in vivo on cell survival following DNA damage.212231732

Crystallization And X-ray Crystallographic Analysis Of Recombinant Chicken Poly (adp-ribose) Polymerase Catalytic Domain Produced In Sf9 Insect Cells

Poly (ADP-ribose) polymerase (PARP) participates in the immediate response in mammalian cells exposed to DNA-damaging agents. Recombinant baculovirus harboring the cDNA of the chicken PARP catalytic domain (40 kDa) have been used to infect Spodoptera frugiperda (Sf9) insect cells. The recombinant polypeptide (30 mg per 1x109 cells) was purified to homogeneity by 3-aminobenzamide affinity chromatography. The enzymatic properties of the recombinant domain were similar to those of the native fragment. Crystals of the purified recombinant catalytic domain were grown by vapor diffusion. The crystals belong to space group P212121 with unit cell dimensions of a = 59.2 Å, b = 65.0 Å, c = 96.9 Å. They aresuitable for X-ray analysis and diffract to 2.0 Å.2441114116Althaus, F.R., Richter, C., ADP-ribosylation of proteins. Enzymology and biological significance (1987) Mol. Biol. Biochem. Biophys., 37, pp. 1-126De Murcia, G., Ménissier-de Murcia, J., Poly (ADP-ribose) polymerase: A molecular nick-sensor (1994) Trends Biochem. Sci., 19, pp. 172-176Giner, H., Simonin, F., De Murcia, G., Ménissier-de Murcia, J., Overproduction and large scale purification of the human poly (ADP-ribose) polymerase using a baculovirus expression system (1992) Gene, 114, pp. 279-283Ittel, M.E., Garnier, J.M., Jeltsh, J.M., Niedergang, C.P., Chicken poly (ADP-ribose) synthase (1991) Gene, 102, pp. 157-164Kabsch, W., Automatic indexing of rotation diffraction patterns (1988) J. Appl. Crystallogr., 21, pp. 67-71Kabsch, W., Evaluation of single crystal X-ray diffraction data from a position sensitive detector (1988) J. Appl. Crystallogr., 21, pp. 916-924Lautier, D., Lagueux, J., Thibodeau, J., Ménard, L., Poirier, G.G., Molecular and biochemical features of poly (ADP-ribose) metabolism (1993) Mol. Cell. Biochem., 122, pp. 171-193Luckow, V.A., Summers, M.D., Signals important for high level expression of foreign genes in Autographa california nuclear polyhedrosis virus expression vectors (1989) Virology, 170, pp. 31-39Matthews, B.W., Solvent content of protein crystals (1968) J. Mol. Biol., 33, pp. 491-497Matthews, B.W., X-ray structure of proteins (1977) The Proteins, 3, pp. 403-590. , (Neurath, H. & Hill, R. L., eds), Academic Press, New YorkMolinete, M., Vermeulen, W., Bürkle, A., Ménissier-de Murcia, J., Küpper, J., Hoeijmakers, J., De Murcia, G., Overproduction of the poly (ADP-ribose) polymerase DNA-binding domain blocks alkylation-induced DNA repair synthesis in mammalian cells (1993) EMBO J., 5, pp. 2109-2117Satoh, M.S., Poirier, G.G., Lindahl, T., NAD-dependent repair of damaged DNA by human cell extracts (1993) J. Biol. Chem., 268, pp. 5480-5487Simonin, F., Ménissier-de Murcia, J., Poch, O., Muller, S., Gradwohl, G., Molinete, M., Penning, C., De Murcia, G., Expression and site directed mutagenesis of the catalytic domain of human poly(ADP-ribose) polymerase in Escherichia coli (1990) J. Biol. Chem., 265, pp. 19249-19256Simonin, F., Poch, O., Delarue, M., De Murcia, G., Identification of potential active-site residues in the human poly (ADP-ribose) polymerase (1993) J. Biol. Chem., 268, pp. 8529-8535Simonin, F., Höfferer, L., Panzeter, P., Muller, S., De Murcia, G., Althaus, F., The carboxy-terminal domain of human poly (ADP-ribose) polymerase: Overproduction in Escherichia coli, large scale purification and characterization (1993) J. Biol. Chem., 268, pp. 13454-13461Suto, M.J., Suto, C.M., Inhibitors of poly (ADP-ribose) polymerase: Potential chemotherapeutic agents (1991) Drugs Fut., 18, pp. 723-73

A Novel Form of Ataxia Oculomotor Apraxia Characterized by Oxidative Stress and Aapoptosis Resistance

Several different autosomal recessive genetic disorders characterized by ataxia with oculomotor apraxia (AOA) have been identified with the unifying feature of defective DNA damage recognition and/or repair. We describe here the characterization of a novel form of AOA showing increased sensitivity to agents that cause single-strand breaks (SSBs) in DNA but having no gross defect in the repair of these breaks. Evidence for the presence of residual SSBs in DNA was provided by dramatically increased levels of poly (ADP-ribose)polymerase (PARP-1) auto-poly (ADP-ribosyl)ation, the detection of increased levels of reactive oxygen/nitrogen species (ROS/RNS) and oxidative damage to DNA in the patient cells. There was also evidence for oxidative damage to proteins and lipids. Although these cells were hypersensitive to DNA damaging agents, the mode of death was not by apoptosis. These cells were also resistant to TRAIL-induced death. Consistent with these observations, failure to observe a decrease in mitochondrial membrane potential, reduced cytochrome c release and defective apoptosis-inducing factor translocation to the nucleus was observed. Apoptosis resistance and PARP-1 hyperactivation were overcome by incubating the patient\u27s cells with antioxidants. These results provide evidence for a novel form of AOA characterized by sensitivity to DNA damaging agents, oxidative stress, PARP-1 hyperactivation but resistance to apoptosis

Differences in Emotion Regulation Considering Gender, Age, and Gambling Preferences in a Sample of Gambling Disorder Patients

Altres ajuts: This manuscript and research were supported by grants from the Instituto de Salud Carlos III (ISCIII) and cofounded by the FEDER funds/European Regional Development Fund (ERDF), a way to build Europe. CIBERobn and CIBERsam are initiatives of ISCIII. This work was also supported by the Delegación del Gobierno para el Plan Nacional sobre Drogas(2017I067).Introduction: Impairments in emotion regulation are understood to be a transdiagnostic risk factor of suffering from compulsive and addictive behaviors. The aim of this study was to investigate the role of emotion regulation deficits in gambling disorder and to analyze these differences taking gender, age, and gambling activity preferences into account. Methods: The sample included n = 484 patients seeking treatment for gambling disorder at a specialized outpatient service. Main outcomes were sociodemographic variables, emotion regulation, and gambling severity. Results: Differences between sexes were found in non-acceptance of emotions. Older patients obtained higher levels in non-acceptance of emotions, lack of emotion regulation strategies, emotional clarity, and global emotion regulation scores. No differences were found in emotion scores considering gambling preferences (non-strategic versus strategic). Path analysis showed that emotion regulation scores and age had a direct effect on gambling disorder severity, while emotion regulation and gambling preference were not mediational variables in the relationships of gender and age with gambling severity. Conclusions: Emotion regulation impairments differ in patients seeking treatment for gambling problems. Early prevention and intervention programs should incorporate the different dimensions of this process, taking into account clinical phenotypes