Genetic polymorphisms in the hypothalamic pathway in relation to subsequent weight change--the DiOGenes study

BACKGROUND: Single nucleotide polymorphisms (SNPs) in genes encoding the components involved in the hypothalamic pathway may influence weight gain and dietary factors may modify their effects. AIM: We conducted a case-cohort study to investigate the associations of SNPs in candidate genes with weight change during an average of 6.8 years of follow-up and to examine the potential effect modification by glycemic index (GI) and protein intake. METHODS AND FINDINGS: Participants, aged 20-60 years at baseline, came from five European countries. Cases ('weight gainers') were selected from the total eligible cohort (n = 50,293) as those with the greatest unexplained annual weight gain (n = 5,584). A random subcohort (n = 6,566) was drawn with the intention to obtain an equal number of cases and noncases (n = 5,507). We genotyped 134 SNPs that captured all common genetic variation across the 15 candidate genes; 123 met the quality control criteria. Each SNP was tested for association with the risk of being a 'weight gainer' (logistic regression models) in the case-noncase data and with weight gain (linear regression models) in the random subcohort data. After accounting for multiple testing, none of the SNPs was significantly associated with weight change. Furthermore, we observed no significant effect modification by dietary factors, except for SNP rs7180849 in the neuromedin β gene (NMB). Carriers of the minor allele had a more pronounced weight gain at a higher GI (P = 2 x 10⁻⁷). CONCLUSIONS: We found no evidence of association between SNPs in the studied hypothalamic genes with weight change. The interaction between GI and NMB SNP rs7180849 needs further confirmation.

Impact of geographical region on urinary metabolomic and plasma fatty acid profiles in subjects with the metabolic syndrome across Europe: the LIPGENE study

The application of metabolomics in multi-centre studies is increasing. The aim of the present study was to assess the effects of geographical location on the metabolic profiles of individuals with the metabolic syndrome. Blood and urine samples were collected from 219 adults from seven European centres participating in the LIPGENE project (Diet, genomics and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis). Nutrient intakes, BMI, waist:hip ratio, blood pressure, and plasma glucose, insulin and blood lipid levels were assessed. Plasma fatty acid levels and urine were assessed using a metabolomic technique. The separation of three European geographical groups (NW, northwest; NE, northeast; SW, southwest) was identified using partial least-squares discriminant analysis models for urine (R 2 X: 0•33, Q 2: 0•39) and plasma fatty acid (R 2 X: 0•32, Q 2: 0•60) data. The NW group was characterised by higher levels of urinary hippurate and N-methylnicotinate. The NE group was characterised by higher levels of urinary creatine and citrate and plasma EPA (20 : 5 n-3). The SW group was characterised by higher levels of urinary trimethylamine oxide and lower levels of plasma EPA. The indicators of metabolic health appeared to be consistent across the groups. The SW group had higher intakes of total fat and MUFA compared with both the NW and NE groups (P≤ 0•001). The NE group had higher intakes of fibre and n-3 and n-6 fatty acids compared with both the NW and SW groups (all P< 0•001). It is likely that differences in dietary intakes contributed to the separation of the three groups. Evaluation of geographical factors including diet should be considered in the interpretation of metabolomic data from multi-centre studies.

Memory and burstiness in dynamic networks

A discrete-time random process is described, which can generate bursty sequences of events. A Bernoulli process, where the probability of an event occurring at time t is given by a fixed probability x, is modified to include a memory effect where the event probability is increased proportionally to the number of events that occurred within a given amount of time preceding t. For small values of x the interevent time distribution follows a power law with exponent −2−x. We consider a dynamic network where each node forms, and breaks connections according to this process. The value of x for each node depends on the fitness distribution, \rho(x), from which it is drawn; we find exact solutions for the expectation of the degree distribution for a variety of possible fitness distributions, and for both cases where the memory effect either is, or is not present. This work can potentially lead to methods to uncover hidden fitness distributions from fast changing, temporal network data, such as online social communications and fMRI scans.

Asymmetric oxidation of vinyl- and ethynyl terthiophene ligands in triruthenium complexes

A series of ruthenium(II) complexes [{RuCl(CO)(PMe3)3(–CHvCH–)}nX], 1a–1c (1a: n = 3, X = 3,3’’- dimethyl-2,2’:3’,2’’-terthiophene; 1b: n = 2, X = 2,2’-bithiophene; 1c: n = 2, X = 2,3-bis(3-methylthiophen- 2-yl)benzothiophene) and [{Cp*(dppe)2Ru(–CuC–)}3X], 1d (X = 3,3’’-dimethyl-2,2’:3’,2’’- terthiophene), were prepared and characterized by 1H, 13C and 31P NMR. Their redox, spectroscopic and bonding properties were studied with a range of spectro-electrochemical methods in combination with density functional theory calculations. The first two anodic steps observed for 1a and 1d are largely localized on the lateral frameworks of the molecular triangle, the direct conjugation between them being precluded due to the photostable open form of the dithienyl ethene moiety. The third anodic step is then mainly localized on the centerpiece of the triangular structure, affecting both bithiophene laterals. The experimental IR and UV-vis-NIR spectroelectrochemical data and, largely, also DFT calculations account for this explanation, being further supported by direct comparison with the anodic behavior of reference diruthenium complexes 1b and 1c.

Detection of SDHI insensitivity in a Zymoseptoria tritici field population associated with the SdhC-H152R and SdhD-R47W substitutions

BACKGROUND: Succinate dehydrogenase inhibitor fungicides are important in the management of Zymoseptoria tritici in wheat. New active ingredients from this group of fungicides have been introduced recently and are widely used. Because the fungicides act at a single enzyme site, resistance development in Z. tritici is classified as medium-to-high risk. RESULTS: Isolates from Irish experimental plots in 2015 were tested against the SDHI penthiopyrad during routine monitoring. The median of the population was approximately 2 x less sensitive than the median of the baseline population. Two of the 93 isolates were much less sensitive to penthiopyrad than least sensitive of the baseline isolates. These isolates were also insensitive to most of commercially available SDHIs. Analysis of the succinate dehydrogenase coding genes confirmed the presence of the substitutions SdhC-H152R and SdhD-R47W in the very insensitive isolates. CONCLUSION: This is the first report showing that the SdhC-H152R mutation detected in laboratory mutagenesis studies also exists in the field. The function and relevance of this mutation, combined with SdhD-R47W, still needs to be determined.

Quantitative structure of an acetate dye molecule analogue at the TiO2- acetic acid interface

The positions of atoms in and around acetate molecules at the rutile TiO2(110) interface with 0.1 M acetic acid have been determined with a precision of ±0.05 Å. Acetate is used as a surrogate for the carboxylate groups typically employed to anchor monocarboxylate dye molecules to TiO2 in dye-sensitised solar cells (DSSC). Structural analysis reveals small domains of ordered (2 x 1) acetate molecules, with substrate atoms closer to their bulk terminated positions compared to the clean UHV surface. Acetate is found in a bidentate bridge position, binding through both oxygen atoms to two five-fold titanium atoms such that the molecular plane is along the [001] azimuth. Density functional theory calculations provide adsorption geometries in excellent agreement with experiment. The availability of these structural data will improve the accuracy of charge transport models for DSSC.

The heterogeneity of wooded-agricultural landscape mosaics influences woodland bird community assemblages

Context Landscape heterogeneity (the composition and configuration of different landcover types) plays a key role in shaping woodland bird assemblages in wooded-agricultural mosaics. Understanding how species respond to landscape factors could contribute to preventing further decline of woodland bird populations. Objective To investigate how woodland birds with different species traits respond to landscape heterogeneity, and to identify whether specific landcover types are important for maintaining diverse populations in wooded-agricultural environments. Methods Birds were sampled from woodlands in 58 2 x 2 km tetrads across southern Britain. Landscape heterogeneity was quantified for each tetrad. Bird assemblage response was determined using redundancy analysis combined with variation partitioning and response trait analyses. Results For woodland bird assemblages, the independent explanatory importance of landscape composition and landscape configuration variables were closely interrelated. When considered simultaneously during variation partitioning, the community response was better represented by compositional variables. Different species responded to different landscape features and this could be explained by traits relating to woodland association, foraging strata and nest location. Ubiquitous, generalist species, many of which were hole-nesters or ground foragers, correlated positively with urban landcover while specialists of broadleaved woodland avoided landscapes containing urban areas. Species typical of coniferous woodland correlated with large conifer plantations. Conclusions At the 2 x 2 km scale, there was evidence that the availability of resources provided by proximate landcover types was highly important for shaping woodland bird assemblages. Further research to disentangle the effects of composition and configuration at different spatial scales is advocated.