Dynamical tunneling in molecules: Quantum routes to energy flow

Dynamical tunneling, introduced in the molecular context, is more than two decades old and refers to phenomena that are classically forbidden but allowed by quantum mechanics. On the other hand the phenomenon of intramolecular vibrational energy redistribution (IVR) has occupied a central place in the field of chemical physics for a much longer period of time. Although the two phenomena seem to be unrelated several studies indicate that dynamical tunneling, in terms of its mechanism and timescales, can have important implications for IVR. Examples include the observation of local mode doublets, clustering of rotational energy levels, and extremely narrow vibrational features in high resolution molecular spectra. Both the phenomena are strongly influenced by the nature of the underlying classical phase space. This work reviews the current state of understanding of dynamical tunneling from the phase space perspective and the consequences for intramolecular vibrational energy flow in polyatomic molecules.Comment: 37 pages and 23 figures (low resolution); Int. Rev. Phys. Chem. (Review to appear in Oct. 2007

Maternal Obesity, Overweight and Gestational Diabetes Affect the Offspring Neurodevelopment at 6 and 18 Months of Age – A Follow Up from the PREOBE Cohort

The study was registered at www.ClinicalTrials.gov, identifier:NCT01634464).Background: Brain development in fetal life and early infancy is critical to determine lifelong performance in various neuropsychological domains. Metabolic pathologies such as overweight, obesity, and gestational diabetes in pregnant women are prevalent and increasing risk factors that may adversely affect long-term brain development in their offspring.Objective: The objective of this research was to investigate the influence of maternal metabolic pathologies on the neurodevelopment of the offspring at 6 and 18 months of life.Design: This was a prospective case-control study of 331 mother- and child pairs from Granada, Spain. The mothers were included during pregnancy into four groups according to their pre-gestational body mass index and their gestational diabetes status; overweight (n:56), obese (n:64), gestational diabetic (n:79), and healthy normal weight controls (n:132). At 6 months and 18 months we assessed the children with the Bayley III scales of neurodevelopment.Results: At 6 months (n=215), we found significant group differences in cognition composite language, and expressive language. Post hoc test revealed unexpectedly higher scores in the obese group compared to the normal weight group and a similar trend in overweight and diabetic group. The effects on language remained significant after adjusting for confounders with an adjusted odds ratio for a value above median in composite language score of 3.3 (95% CI: 1.1, 10.0; p=0.035) for children of obese mothers. At 18 month (n=197), the offspring born to obese mothers had lost five points in language composite scores and the previous differences in language and cognition was replaced by a suggestive trend of lower gross motor scores in the overweight, obese, and diabetic groups.Conclusions: Infants of obese mothers had a temporary accelerated development of cognition and language, followed by a rapid deceleration until 18 months of age, particularly of language scores. This novel observation prompts further confirmative studies to explore possible placental and neurodevelopmental mechanisms involved.This study was funded by Spanish Ministry of Innovation and Science. Junta de Andalucía: Excellence Projects (P06-CTS-02341); Spanish Ministry of Education (Grant no. SB2010-0025); Spanish Ministry of Economy and Competitiveness (BFU2012-40254-C03-01); Further support was received by Abbott Laboratories, Granada, Spain

Genetically defined elevated homocysteine levels do not result in widespread changes of DNA methylation in leukocytes

BACKGROUND:DNA methylation is affected by the activities of the key enzymes and intermediate metabolites of the one-carbon pathway, one of which involves homocysteine. We investigated the effect of the well-known genetic variant associated with mildly elevated homocysteine: MTHFR 677C>T independently and in combination with other homocysteine-associated variants, on genome-wide leukocyte DNA-methylation. METHODS:Methylation levels were assessed using Illumina 450k arrays on 9,894 individuals of European ancestry from 12 cohort studies. Linear-mixed-models were used to study the association of additive MTHFR 677C>T and genetic-risk score (GRS) based on 18 homocysteine-associated SNPs, with genome-wide methylation. RESULTS:Meta-analysis revealed that the MTHFR 677C>T variant was associated with 35 CpG sites in cis, and the GRS showed association with 113 CpG sites near the homocysteine-associated variants. Genome-wide analysis revealed that the MTHFR 677C>T variant was associated with 1 trans-CpG (nearest gene ZNF184), while the GRS model showed association with 5 significant trans-CpGs annotated to nearest genes PTF1A, MRPL55, CTDSP2, CRYM and FKBP5. CONCLUSIONS:Our results do not show widespread changes in DNA-methylation across the genome, and therefore do not support the hypothesis that mildly elevated homocysteine is associated with widespread methylation changes in leukocytes

Angiogenic Activity of Sera from Pulmonary Tuberculosis Patients in Relation to IL-12p40 and TNFα Serum Levels

The role of angiogenesis in the pathogenesis of tuberculosis (TB) is not clear. The aim of this study was to examine the effect of sera from TB patients on angiogenesis induced by different subsets of normal human mononuclear cells (MNC) in relation to IL-12p40 and TNFα serum levels. Serum samples from 36 pulmonary TB patients and from 22 healthy volunteers were evaluated. To assess angiogenic reaction the leukocytes-induced angiogenesis test according to Sidky and Auerbach was performed. IL-12p40 and TNFα serum levels were evaluated by ELISA. Sera from TB patients significantly stimulated angiogenic activity of MNC compared to sera from healthy donors and PBS (p < 0.001). The number of microvessels formed after injection of lymphocytes preincubated with sera from TB patients was significantly lower compared to the number of microvessels created after injection of MNC preincubated with the same sera (p < 0.016). However, the number of microvessels created after the injection of lymphocytes preincubated with sera from healthy donors or with PBS alone was significantly higher (p < 0.017). The mean levels of IL-12p40 and TNFα were significantly elevated in sera from TB patients compared to healthy donors. We observed a correlation between angiogenic activity of sera from TB patients and IL-12p40 and TNFα serum levels (p < 0.01). Sera from TB patients constitute a source of mediators that participate in angiogenesis and prime monocytes for production of proangiogenic factors. The main proangiogenic effect of TB patients’ sera is mediated by macrophages/monocytes. TNFα and IL-12p40 may indirectly stimulate angiogenesis in TB

Cardiovascular and metabolic influences of fetal smoke exposure

Many epidemiological studies showed associations of low birth weight with cardiovascular disease, type 2 diabetes and obesity. The associations seem to be consistent and stronger among subjects with a postnatal catch up growth. It has been suggested that developmental changes in response to adverse fetal exposures might lead to changes in the fetal anatomy and physiology. These adaptations may be beneficial for short term, but may lead to common diseases in adulthood. Maternal smoking during pregnancy is one of the most important adverse fetal exposures in Western countries, and is known to be associated with a 150–200 g lower birth weight. An accumulating body of evidence suggests that maternal smoking during pregnancy might be involved in pathways leading to both low birth weight and common diseases, including cardiovascular disease, type 2 diabetes and obesity, in adulthood. In this review, we discuss epidemiological studies focused on the associations of maternal smoking with fetal growth and development and cardiovascular and metabolic disease in later life. We also discuss potential biological mechanisms, and challenges for future epidemiological studies

GM and KM immunoglobulin allotypes in the Galician population: new insights into the peopling of the Iberian Peninsula

<p>Abstract</p> <p>Background</p> <p>The current genetic structure of Iberian populations has presumably been affected by the complex orography of its territory, the different people and civilizations that settled there, its ancient and complex history, the diverse and persistent sociocultural patterns in its different regions, and also by the effects of the Iberian Peninsula representing a refugium area after the last glacial maximum. This paper presents the first data on <it>GM </it>and <it>KM </it>immunoglobulin allotypes in the Galician population and, thus, provides further insights into the extent of genetic diversity in populations settled in the geographic extremes of the Cantabrian region of northern Spain. Furthermore, the genetic relationships of Galicians with other European populations have been investigated.</p> <p>Results</p> <p>Galician population shows a genetic profile for <it>GM </it>haplotypes that is defined by the high presence of the European Mediterranean <it>GM</it>*<it>3 23 5* </it>haplotype, and the relatively high incidence of the African marker <it>GM*1,17 23' 5*</it>. Data based on comparisons between Galician and other Spanish populations (mainly from the north of the peninsula) reveal a poor correlation between geographic and genetic distances (<it>r </it>= 0.30, <it>P </it>= 0.105), a noticeable but variable genetic distances between Galician and Basque subpopulations, and a rather close genetic affinity between Galicia and Valencia, populations which are geographically separated by a long distance and have quite dissimilar cultures and histories. Interestingly, Galicia occupies a central position in the European genetic map, despite being geographically placed at one extreme of the European continent, while displaying a close genetic proximity to Portugal, a finding that is consistent with their shared histories over centuries.</p> <p>Conclusion</p> <p>These findings suggest that the population of Galicia is the result of a relatively balanced mixture of European populations or of the ancestral populations that gave rise to them. This would support the importance of the migratory movements that have taken place in Europe over the course of recent human history and their effects on the European genetic landscape.</p

Vitamin D levels and susceptibility to asthma, elevated immunoglobulin E levels, and atopic dermatitis: A Mendelian randomization study.

BACKGROUND: Low circulating vitamin D levels have been associated with risk of asthma, atopic dermatitis, and elevated total immunoglobulin E (IgE). These epidemiological associations, if true, would have public health importance, since vitamin D insufficiency is common and correctable. METHODS AND FINDINGS: We aimed to test whether genetically lowered vitamin D levels were associated with risk of asthma, atopic dermatitis, or elevated serum IgE levels, using Mendelian randomization (MR) methodology to control bias owing to confounding and reverse causation. The study employed data from the UK Biobank resource and from the SUNLIGHT, GABRIEL and EAGLE eczema consortia. Using four single-nucleotide polymorphisms (SNPs) strongly associated with 25-hydroxyvitamin D (25OHD) levels in 33,996 individuals, we conducted MR studies to estimate the effect of lowered 25OHD on the risk of asthma (n = 146,761), childhood onset asthma (n = 15,008), atopic dermatitis (n = 40,835), and elevated IgE level (n = 12,853) and tested MR assumptions in sensitivity analyses. None of the four 25OHD-lowering alleles were associated with asthma, atopic dermatitis, or elevated IgE levels (p ≥ 0.2). The MR odds ratio per standard deviation decrease in log-transformed 25OHD was 1.03 (95% confidence interval [CI] 0.90-1.19, p = 0.63) for asthma, 0.95 (95% CI 0.69-1.31, p = 0.76) for childhood-onset asthma, and 1.12 (95% CI 0.92-1.37, p = 0.27) for atopic dermatitis, and the effect size on log-transformed IgE levels was -0.40 (95% CI -1.65 to 0.85, p = 0.54). These results persisted in sensitivity analyses assessing population stratification and pleiotropy and vitamin D synthesis and metabolism pathways. The main limitations of this study are that the findings do not exclude an association between the studied outcomes and 1,25-dihydoxyvitamin D, the active form of vitamin D, the study was underpowered to detect effects smaller than an OR of 1.33 for childhood asthma, and the analyses were restricted to white populations of European ancestry. This research has been conducted using the UK Biobank Resource and data from the SUNLIGHT, GABRIEL and EAGLE Eczema consortia. CONCLUSIONS: In this study, we found no evidence that genetically determined reduction in 25OHD levels conferred an increased risk of asthma, atopic dermatitis, or elevated total serum IgE, suggesting that efforts to increase vitamin D are unlikely to reduce risks of atopic disease

Comparative transcriptomic analysis reveals similarities and dissimilarities in saccharomyces cerevisiae wine strains response to nitrogen availability

Nitrogen levels in grape-juices are of major importance in winemaking ensuring adequate yeast growth and fermentation performance. Here we used a comparative transcriptome analysis to uncover wine yeasts responses to nitrogen availability during fermentation. Gene expression was assessed in three genetically and phenotypically divergent commercial wine strains (CEG, VL1 and QA23), under low (67 mg/L) and high nitrogen (670 mg/L) regimes, at three time points during fermentation (12h, 24h and 96h). Two-way ANOVA analysis of each fermentation condition led to the identification of genes whose expression was dependent on strain, fermentation stage and on the interaction of both factors. The high fermenter yeast strain QA23 was more clearly distinct from the other two strains, by differential expression of genes involved in flocculation, mitochondrial functions, energy generation and protein folding and stabilization. For all strains, higher transcriptional variability due to fermentation stage was seen in the high nitrogen fermentations. A positive correlation between maximum fermentation rate and the expression of genes involved in stress response was observed. The finding of common genes correlated with both fermentation activity and nitrogen up-take underlies the role of nitrogen on yeast fermentative fitness. The comparative analysis of genes differentially expressed between both fermentation conditions at 12h, where the main difference was the level of nitrogen available, showed the highest variability amongst strains revealing strain-specific responses. Nevertheless, we were able to identify a small set of genes whose expression profiles can quantitatively assess the common response of the yeast strains to varying nitrogen conditions. The use of three contrasting yeast strains in gene expression analysis prompts the identification of more reliable, accurate and reproducible biomarkers that will facilitate the diagnosis of deficiency of this nutrient in the grape-musts and the development of strategies to optimize yeast performance in industrial fermentations

Impaired Executive Function Mediates the Association between Maternal Pre-Pregnancy Body Mass Index and Child ADHD Symptoms

Increasing evidence suggests exposure to adverse conditions in intrauterine life may increase the risk of developing attention-deficit/hyperactivity disorder (ADHD) in childhood. High maternal pre-pregnancy body mass index (BMI) has been shown to predict child ADHD symptoms, however the neurocognitive processes underlying this relationship are not known. The aim of the present study was to test the hypothesis that this association is mediated by alterations in child executive function.A population-based cohort of 174 children (mean age = 7.3 ± 0.9 (SD) yrs, 55% girls) was evaluated for ADHD symptoms using the Child Behavior Checklist, and for neurocognitive function using the Go/No-go task. This cohort had been followed prospectively from early gestation and birth through infancy and childhood with serial measures of maternal and child prenatal and postnatal factors. Maternal pre-pregnancy BMI was a significant predictor of child ADHD symptoms (F((1,158)) = 4.80, p = 0.03) and of child performance on the Go/No-go task (F((1,157)) = 8.37, p = 0.004) after controlling for key potential confounding variables. A test of the mediation model revealed that the association between higher maternal pre-pregnancy BMI and child ADHD symptoms was mediated by impaired executive function (inefficient/less attentive processing; Sobel Test: t = 2.39 (± 0.002, SEM), p = 0.02).To the best of our knowledge this is the first study to report that maternal pre-pregnancy BMI-related alterations in child neurocognitive function may mediate its effects on ADHD risk. The finding is clinically significant and may extrapolate to an approximately 2.8-fold increase in the prevalence of ADHD among children of obese compared to those of non-obese mothers. These results add further evidence to the growing awareness that neurodevelopmental disorders such as ADHD may have their foundations very early in life