252 research outputs found
Sex-dependent Effects of Developmental Hypoxia on Cardiac Mitochondria from Adult Murine Offspring
The correlation potential in density functional theory at the GW-level: spherical atoms
As part of a project to obtain better optical response functions for nano
materials and other systems with strong excitonic effects we here calculate the
exchange-correlation (XC) potential of density-functional theory (DFT) at a
level of approximation which corresponds to the dynamically- screened-exchange
or GW approximation. In this process we have designed a new numerical method
based on cubic splines which appears to be superior to other techniques
previously applied to the "inverse engineering problem" of DFT, i.e., the
problem of finding an XC potential from a known particle density. The
potentials we obtain do not suffer from unphysical ripple and have, to within a
reasonable accuracy, the correct asymptotic tails outside localized systems.
The XC potential is an important ingredient in finding the particle-conserving
excitation energies in atoms and molecules and our potentials perform better in
this regard as compared to the LDA potential, potentials from GGA:s, and a DFT
potential based on MP2 theory.Comment: 13 pages, 9 figure
Transient Calcium and Dopamine Increase PKA Activity and DARPP-32 Phosphorylation
Reinforcement learning theorizes that strengthening of synaptic connections in medium spiny neurons of the striatum occurs when glutamatergic input (from cortex) and dopaminergic input (from substantia nigra) are received simultaneously. Subsequent to learning, medium spiny neurons with strengthened synapses are more likely to fire in response to cortical input alone. This synaptic plasticity is produced by phosphorylation of AMPA receptors, caused by phosphorylation of various signalling molecules. A key signalling molecule is the phosphoprotein DARPP-32, highly expressed in striatal medium spiny neurons. DARPP-32 is regulated by several neurotransmitters through a complex network of intracellular signalling pathways involving cAMP (increased through dopamine stimulation) and calcium (increased through glutamate stimulation). Since DARPP-32 controls several kinases and phosphatases involved in striatal synaptic plasticity, understanding the interactions between cAMP and calcium, in particular the effect of transient stimuli on DARPP-32 phosphorylation, has major implications for understanding reinforcement learning. We developed a computer model of the biochemical reaction pathways involved in the phosphorylation of DARPP-32 on Thr34 and Thr75. Ordinary differential equations describing the biochemical reactions were implemented in a single compartment model using the software XPPAUT. Reaction rate constants were obtained from the biochemical literature. The first set of simulations using sustained elevations of dopamine and calcium produced phosphorylation levels of DARPP-32 similar to that measured experimentally, thereby validating the model. The second set of simulations, using the validated model, showed that transient dopamine elevations increased the phosphorylation of Thr34 as expected, but transient calcium elevations also increased the phosphorylation of Thr34, contrary to what is believed. When transient calcium and dopamine stimuli were paired, PKA activation and Thr34 phosphorylation increased compared with dopamine alone. This result, which is robust to variation in model parameters, supports reinforcement learning theories in which activity-dependent long-term synaptic plasticity requires paired glutamate and dopamine inputs
The Dual Amylin- and Calcitonin-Receptor Agonist KBP-042 Increases Insulin Sensitivity and Induces Weight Loss in Rats with Obesity
Fish intake, erythrocyte n-3 fatty acid status and metabolic health in Danish adolescent girls and boys
Marinen-3 long-chain PUFA (n-3 LCPUFA) may have a beneficial effect on several aspects of the metabolic syndrome (dyslipidaemia, insulin resistance, hypertension and abdominal obesity). The metabolic syndrome is increasing in prevalence during adolescence, but only few studies have investigated the effects ofn-3 LCPUFA in adolescence. The present study examines associations between fish intake (assessed by a 7 d pre-coded food diary), erythrocyte (RBC) DHA status (analysed by GC) and metabolic syndrome measures (anthropometry, blood pressure and plasma lipids, insulin and glucose) in 109 17-year-old children from the Copenhagen Birth Cohort Study. Of the children, 8 % were overweight or obese and few showed signs of the metabolic syndrome, but all the metabolic syndrome variables were correlated. Median fish intake was 10·7 (interquartile range 3·6â21·2) g/d. Boys tended to have a higher fish intake (P = 0·052), but girls had significantly higher RBC levels of DHA (P = 0·001). Sex and fish intake explained 37 % of the variance in RBC-DHA (P < 0·001). After adjusting for confounders, high DHA status was found to be significantly correlated with higher systolic blood pressure (P = 0·014) and increased fasting insulin (P = 0·018), but no adverse association was observed with the mean metabolic syndromez-score. Overall, the present study showed the expected association between fish intake and RBC-DHA, which in contrast to our expectations tended to be associated with a poorer metabolic profile. Whether these results reflect the physiological function ofn-3 LCPUFA, lifestyle factors associated with fish intake in Denmark, or mere chance remains to be investigated.</jats:p
Fish oil supplementation from 9 to 18 months of age affects the insulin-like growth factor axis in a sex-specific manner in Danish infants
AbstractSeveral studies have investigated the effects of fish oil (FO) on infant growth, but little is known about the effects of FO and sex on insulin-like growth factor-1 (IGF-1), the main regulator of growth in childhood. We explored whether FOv. sunflower oil (SO) supplementation from 9 to 18 months of age affected IGF-1 and its binding protein-3 (IGFBP-3) and whether the potential effects were sex specific. Danish infants (n115) were randomly allocated to 5 ml/d FO (1·2 g/dn-3 long-chain PUFA (n-3 LCPUFA)) or SO. We measured growth, IGF-1, IGFBP-3 and erythrocyte EPA, a biomarker ofn-3 LCPUFA intake and status, at 9 and 18 months. Erythrocyte EPA increased strongly with FO compared with SO (P<0·001). There were no effects of FO compared with SO on IGF-1 in the total population, but a sexĂgroup interaction (P=0·02). Baseline-adjusted IGF-1 at 18 months was 11·1 ”g/l (95 % CI 0·4, 21·8;P=0·04) higher after FO compared with SO supplementation among boys only. The sexĂgroup interaction was borderline significant in the model of IGFBP-3 (P=0·09), with lower IGFBP-3 with FO compared with SO among girls only (P=0·03). The results were supported by sex-specific doseâresponse associations between changes in erythrocyte EPA and changes in IGF-1 and IGFBP-3 (bothP<0·03). Moreover, IGF-1 was sex specifically associated with BMI and length. In conclusion, FO compared with SO resulted in higher IGF-1 among boys and lower IGFBP-3 among girls. The potential long-term implications for growth and body composition should be investigated further.</jats:p
A study of associations between early DHA status and fatty acid desaturase (FADS) SNP and developmental outcomes in children of obese mothers
AbstractDHA from diet or endogenous synthesis has been proposed to affect infant development, however, results are inconclusive. In this study, we aim to verify previously observed fatty acid desaturase gene cluster (FADS) SNP-specific associations with erythrocyte DHA status in 9-month-old children and sex-specific association with developmental outcomes. The study was performed in 166 children (55 % boys) of obese mothers. Erythrocyte fatty acid composition was analysed in blood-samples obtained at 9 months of age, and developmental outcomes assessed by the Ages and Stages Questionnaire at 3 years. Erythrocyte DHA level ranged from 4·4 to 9·9 % of fatty acids, but did not show any association withFADSSNP or other potential determinants. Regression analysis showed associations between erythrocyte DHA and scores for personalâsocial skills (ÎČ1·8 (95 % CI 0·3, 3·3),P=0·019) and problem solving (ÎČ3·4 (95 % CI 1·2, 5·6),P=0·003). A tendency was observed for an association in opposite direction between minor alleles (G-variant) of rs1535 and rs174575 and personalâsocial skills (P=0·062 and 0·068, respectively), which became significant when the SNP were combined based on their previously observed effect on erythrocyte DHA at 9 months of age (ÎČ2·6 (95 % CI 0·01, 5·1),P=0·011). SexâSNP interaction was indicated for rs174575 genotype on fine motor scores (P=0·016), due to higher scores among minor allele carrying girls (P=0·043), whereas no effect was seen among boys. In conclusion, DHA-increasingFADSSNP and erythrocyte DHA status were consistently associated with improved personalâsocial skills in this small cohort of children of obese mothers irrespective of sex, but the sample was too small to verify potential sex-specific effects.</jats:p
Risk factors for respiratory work disability in a cohort of pulp mill workers exposed to irritant gases
<p>Abstract</p> <p>Background</p> <p>The association between chronic respiratory diseases and work disability has been demonstrated a number of times over the past 20 years, but still little is known about work disability in occupational cohorts of workers exposed to respiratory irritants. This study investigated job or task changes due to respiratory problems as an indicator of work disability in pulp mill workers occupationally exposed to irritants.</p> <p>Methods</p> <p>Data about respiratory symptoms and disease diagnoses, socio-demographic variables, occupational exposures, gassing episodes, and reported work changes due to respiratory problems were collected using a questionnaire answered by 3226 pulp mill workers. Information about work history and departments was obtained from personnel files. Incidence and hazard ratios for respiratory work disability were calculated with 95% confidence intervals (CI).</p> <p>Results</p> <p>The incidence of respiratory work disability among these pulp mill workers was 1.6/1000 person-years. The hazard ratios for respiratory work disability were increased for workers reporting gassings (HR 5.3, 95% CI 2.7-10.5) and for those reporting physician-diagnosed asthma, chronic bronchitis, and chronic rhinitis, when analyzed in the same model.</p> <p>Conclusions</p> <p>This cohort study of pulp mill workers found that irritant peak exposure during gassing episodes was a strong predictor of changing work due to respiratory problems, even after adjustment for asthma, chronic bronchitis, and chronic rhinitis.</p
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