Obesity-Susceptibility Loci and Their Influence on Adiposity-Related Traits in Transition from Adolescence to Adulthood - The HUNT Study

Introduction

Obesity-susceptibility loci have been related to adiposity traits in adults and may affect body fat estimates in adolescence. There are indications that different sets of obesity-susceptibility loci influence level of and change in obesity-related traits from adolescence to adulthood.

Objectives

To investigate whether previously reported obesity-susceptible loci in adults influence adiposity traits in adolescence and change in BMI and waist circumference (WC) from adolescence into young adulthood. We also examined whether physical activity modifies the effects of these genetic loci on adiposity-related traits.

Methods

Nine obesity-susceptibility variants were genotyped in 1 643 adolescents (13–19 years old) from the HUNT study, Norway, who were followed-up into young adulthood. Lifestyle was assessed using questionnaires and anthropometric measurements were taken. The effects of genetic variants individually and combined in a genetic predisposition score (GPS) on obesity-related traits were studied cross-sectionally and longitudinally. A modifying effect of physical activity was tested.

Results

The GPS was significantly associated to BMI (B: 0.046 SD/allele [0.020, 0.073], p = 0.001) in adolescence and in young adulthood (B: 0.041 SD/allele [0.015, 0.067], p = 0.002) as it was to waist circumference (WC). The GPS was not associated to change in BMI (p = 0.762) or WC (p = 0.726). We found no significant interaction effect between the GPS and physical activity.

Conclusions

Our observations suggest that obesity-susceptibility loci established in adults affect BMI and WC already in adolescence. However, an association with change in adiposity-related traits from adolescence to adulthood could not be verified for these loci. Neither could an attenuating effect of physical activity on the association between the obesity-susceptibility genes and body fat estimates be revealed.     

Collectins: players of the innate immune system.

Collectins are a family of collagenous calcium-dependent defense lectins in animals. Their polypeptide chains consist of four regions: a cysteine-rich N-terminal domain, a collagen-like region, an alpha-helical coiled-coil neck domain and a C-terminal lectin or carbohydrate-recognition domain. These polypeptide chains form trimers that may assemble into larger oligomers. The best studied family members are the mannan-binding lectin, which is secreted into the blood by the liver, and the surfactant proteins A and D, which are secreted into the pulmonary alveolar and airway lining fluid. The collectins represent an important group of pattern recognition molecules, which bind to oligosaccharide structures and/or lipid moities on the surface of microorganisms. They bind preferentially to monosaccharide units of the mannose type, which present two vicinal hydroxyl groups in an equatorial position. High-affinity interactions between collectins and microorganisms depend, on the one hand, on the high density of the carbohydrate ligands on the microbial surface, and on the other, on the degree of oligomerization of the collectin. Apart from binding to microorganisms, the collectins can interact with receptors on host cells. Binding of collectins to microorganisms may facilitate microbial clearance through aggregation, complement activation, opsonization and activation of phagocytosis, and inhibition of microbial growth. In addition, the collectins can modulate inflammatory and allergic responses, affect apoptotic cell clearance and modulate the adaptive immune system.     

Skewed X-chromosome inactivation in female carriers of dyskeratosis congenita.

In this study, we report on a family with X-linked dyskeratosis congenita (DC). Linkage analysis with markers in the factor VIII gene at Xq28 yielded a LOD score of 2 at a recombination of 0. Clinical manifestations of DC, such as skin lesions following the Blaschko lines, were present in two obligate carrier females. Highly skewed X inactivation was observed in white blood cells, cultured skin fibroblasts, and buccal mucosa from female carriers of DC in this family. This suggests a critical role for the DC gene in bone marrow-cell and fibroblast-cell proliferation.     

Effects of pH,Salinity, Biomass Concentration,and Algal Organic Matter on Flocculant Efficiency of Synthetic Versus Natural Polymers for Harvesting Microalgae Biomass

This study investigated the effects of pH, salinity, biomass concentration, and algal organic matter (AOM) on the efficiency of four commercial cationic flocculants. The tannin-based biopolymers Tanfloc SG and SL and the polyacrylamide polymers Flopam FO 4800 SH and FO 4990 SH were tested for flocculation of two microalgae models, the freshwater Chlorella vulgaris and the marine Nannochloropsis oculata. Both biomass concentration and AOM presence affected all polymers evaluated, whereas salinity and pH affected only Flopam and Tanfloc, respectively. A restabilization effect due to overdosing was only observed for Flopam polymers and increasing Tanfloc dose resulted in improved efficiency. Flopam polymers showed a significant decrease in the maximum quantum yield of photosystem II as function of polymer dose for Chlorella, which supported the need for toxicological studies to assess the potential toxicity of Flopam. In overall, Tanfloc was not affected by salinity nor presented potential toxicity therefore being recommended for the flocculation of both freshwater and marine species.     

Contrasting dynamics of ciliate communities in sandy and silty sediments of an estuarine intertidal flat

During a 1-year study of the ciliate faunas of a silty and a sandy site on an intertidal flat in the Westerschelde estuary, a total number of 107 taxa were recorded belonging to at least 52 genera and 15 orders. Our results suggest that physical properties of the sediment were more important in regulating ciliate abundance, diversity and community composition than food availability, predation, temperature or oxygen concentration. Ciliate abundance and diversity were positively related to sediment grain size and the ciliate community of silty sediments was found to be a subset of that of sandy sediments. At the sandy site, where the sediment composition was stable, seasonal changes in the ciliate community were related to changes in food availability and/or temperature. At both the sandy and silty sites, a clear vertical gradient in the ciliate community was observed that appeared to be linked to gradients in food availability and oxygen concentration. These vertical gradients in ciliate community composition, however, were less steep than the measured oxygen gradients, probably due to the presence of oxic microniches in the anoxic zone.     

Network Analysis of Differential Expression for the Identification of Disease-Causing Genes

Genetic studies (in particular linkage and association studies) identify chromosomal regions involved in a disease or phenotype of interest, but those regions often contain many candidate genes, only a few of which can be followed-up for biological validation. Recently, computational methods to identify (prioritize) the most promising candidates within a region have been proposed, but they are usually not applicable to cases where little is known about the phenotype (no or few confirmed disease genes, fragmentary understanding of the biological cascades involved). We seek to overcome this limitation by replacing knowledge about the biological process by experimental data on differential gene expression between affected and healthy individuals. Considering the problem from the perspective of a gene/protein network, we assess a candidate gene by considering the level of differential expression in its neighborhood under the assumption that strong candidates will tend to be surrounded by differentially expressed neighbors. We define a notion of soft neighborhood where each gene is given a contributing weight, which decreases with the distance from the candidate gene on the protein network. To account for multiple paths between genes, we define the distance using the Laplacian exponential diffusion kernel. We score candidates by aggregating the differential expression of neighbors weighted as a function of distance. Through a randomization procedure, we rank candidates by p-values. We illustrate our approach on four monogenic diseases and successfully prioritize the known disease causing genes.     

Context dependency of infectious disease: the cyanobacterium Microcystis aeruginosa decreases white bacterial disease in Daphnia magna

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