Publications

Additional file 1: Table S1A-D. Characteristics of the participating studies in the main meta-analyses.

Introduction: Chronic inflammation plays a pathogenic role in cardiovascular disease (CVD) development. Dietary factors have been implicated in CVD etiology and may have an impact on chronic inflammation. Hypothesis: Proinflammatory diets are associated with higher CVD risk. Methods: We include74,544 women in the Nurses’ Health Study (from 1984 through 2012) and 43,904 men in the Health Professionals Follow-up Study (from 1986 through 2012), who were free of heart disease, stroke, and cancer at baseline. Dietary inflammatory potentials were assessed using an empirical dietary inflammatory pattern (EDIP) score that has been pre-defined by 18 food components based on their associations with circulating levels of systemic inflammation markers C-reactive protein, interleukin-6, and tumor necrosis factor-α receptor 2. Adjusted hazard ratios (HRs) and 95% confidence internals (CIs) for CVD were calculated using Cox regressions. Results: During 2,831,128 person-years of follow-up, we documented 13,249 incident CVD cases, including 8,178 coronary heart disease cases and 5,182 stroke cases. After adjusting for established risk factors and potential confounders including body-mass index and aspirin or other nonsteroidal anti-inflammatory medication use, a higher EDIP score was associated with an increased risk of CVD (in pooled analyses, HR [95% CI] comparing the highest to the lowest quintiles were 1.29 [1.22 to 1.37]; P trend <0.001), CHD (HR = 1.32[1.23 to 1.42]; P trend <0.001), and stroke (HR = 1.25 [1.14 to 1.37]; P trend <0.001). Associations were similar among subgroups of participants, including by age, sex, family history, BMI, physical activity, and alcohol intake; but were stronger among non/past-smoking than current smoking women ( P interaction <0.002). Conclusions: Findings from two large US prospective cohort studies suggest that inflammation may be a potential mechanism linking dietary patterns to CVD progression. Reducing the proinflammatory potentials of the diet may assist CVD prevention.

This paper uses the binding pocket of human carbonic anhydrase II (HCAII, EC 4.2.1.1) as a tool to examine the properties of Hofmeister anions that determine (i) where, and how strongly, they associate with concavities on the surfaces of proteins and (ii) how, upon binding, they alter the structure of water within those concavities. Results from X-ray crystallography and isothermal titration calorimetry show that most anions associate with the binding pocket of HCAII by forming inner-sphere ion pairs with the Zn(2+) cofactor. In these ion pairs, the free energy of anion-Zn(2+) association is inversely proportional to the free energetic cost of anion dehydration; this relationship is consistent with the mechanism of ion pair formation suggested by the "law of matching water affinities". Iodide and bromide anions also associate with a hydrophobic declivity in the wall of the binding pocket. Molecular dynamics simulations suggest that anions, upon associating with Zn(2+), trigger rearrangements of water that extend up to 8 Å away from their surfaces. These findings expand the range of interactions previously thought to occur between ions and proteins by suggesting that (i) weakly hydrated anions can bind complementarily shaped hydrophobic declivities, and that (ii) ion-induced rearrangements of water within protein concavities can (in contrast with similar rearrangements in bulk water) extend well beyond the first hydration shells of the ions that trigger them. This study paints a picture of Hofmeister anions as a set of structurally varied ligands that differ in size, shape, and affinity for water and, thus, in their ability to bind to—and to alter the charge and hydration structure of—polar, nonpolar, and topographically complex concavities on the surfaces of proteins.

This paper describes self-assembled monolayers (SAMs) on palladium that resist the nonspecific adsorption of proteins and the adhesion of mammalian cells. These SAMs form when thin films of palladium are exposed to solutions of alkanethiol with the general structure HS(CH2)m(OCH2CH2)nOH (m = 2, 11; n = 3, 6, 7). Ellipsometry and surface plasmon resonance spectroscopy (using a palladium-on-gold substrate) showed that these SAMs resist adsorption of all proteins present in bovine serum. Microislands of SAMs of octadecanethiol on palladium allowed patterned adhesion and growth of mammalian cells (in a "sea" of oligo(ethyleneglycol)-terminated SAM). The oligo(ethyleneglycol)-terminated SAM resisted the invasion of cells for over four weeks under standard conditions of cell culture; similar SAMs on gold remained patterned for only two weeks.

Background: The WNT signaling pathway is involved in a wide range of developmental events and maintenance of homeostasis in adult tissue, including lung development and health. WNT signaling genes have also been suggested to play a role in pathogenesis of lung diseases such as chronic obstructive pulmonary disease (COPD) and asthma. Aims and Objectives: The aim of this meta-analysis was to identify consistent disease markers for COPD, asthma, forced expiratory volume in one second (FEV1), and forced vital capacity (FVC) in nine genes of the WNT signaling cascade pathway (WNT10b, WIF1, WISP1, SFRP2, SFRP5, DKK1, Axin2, TCF7L2, and FZD3) using genome-wide association data from six European cohort studies. Methods: The six European cohort studies included are: B58C (UK), ECRHS (multicentre), EGEA (France), GINI / LISA (Germany), NFBC1966 (Finland), and SAPALDIA (Switzerland). We identified a total of 105 single nucleotide polymorphisms (SNPs) in the nine genes (including a region 2 kb in size up- and downstream the gene). Effect estimates were analyzed using a fixed or random effect pooled testing (depending on homogeneity) for association in the overall study population. Results and Conclusions: We identified weak genetic associations (p-values between 0.002 and 0.046) in our meta-analysis for COPD (Axin2), asthma (SFRP2, TCF7L2, WIF1, DKK1), FEV1 (SFRP2, TCF7L2, DKK1), and FVC (TCF7L2, WNT10b). Notably in TCF7L2 six different SNPs were identified (p-values between 0.002 and 0.046) in association with asthma, FEV1, and FVC. In literature, WNT signaling genes were linked to COPD (Axin2), asthma (TCF7L2, SFRP2), and decreased FEV1 and FVC (TCF7L2).

We report studies defining the diameter-dependent location of electrically active dopants in silicon (Si) and germanium (Ge) nanowires (NWs) prepared by nanocluster catalyzed vapor-liquid-solid (VLS) growth without measurable competing homogeneous decomposition and surface overcoating. The location of active dopants was assessed from electrical transport measurements before and after removal of controlled thicknesses of material from NW surfaces by low-temperature chemical oxidation and etching. These measurements show a well-defined transition from bulk-like to surface doping as the diameter is decreased <22-25 nm for n- and p-type Si NWs, although the surface dopant concentration is also enriched in the larger diameter Si NWs. Similar diameter-dependent results were also observed for n-type Ge NWs, suggesting that surface dopant segregation may be general for small diameter NWs synthesized by the VLS approach. Natural surface doping of small diameter semiconductor NWs is distinct from many top-down fabricated NWs, explains enhanced transport properties of these NWs and could yield robust properties in ultrasmall devices often dominated by random dopant fluctuations.

Forced Vital Capacity (FVC) is an important predictor of all-cause mortality in the absence of chronic respiratory conditions. Epidemiological evidence highlights the role of early life factors on adult FVC, pointing to environmental exposures and genes affecting lung development as risk factors for low FVC later in life. Although highly heritable, a small number of genes have been found associated with FVC, and we aimed at identifying further genetic variants by focusing on lung development genes.Per-allele effects of 24,728 SNPs in 403 genes involved in lung development were tested in 7,749 adults from three studies (NFBC1966, ECRHS, EGEA). The most significant SNP for the top 25 genes was followed-up in 46,103 adults (CHARGE and SpiroMeta consortia) and 5,062 children (ALSPAC). Associations were considered replicated if the replication p-value survived Bonferroni correction (p<0.002; 0.05/25), with a nominal p-value considered as suggestive evidence. For SNPs with evidence of replication, effects on the expression levels of nearby genes in lung tissue were tested in 1,111 lung samples (Lung eQTL consortium), with further functional investigation performed using public epigenomic profiling data (ENCODE).NCOR2-rs12708369 showed strong replication in children (p = 0.0002), with replication unavailable in adults due to low imputation quality. This intronic variant is in a strong transcriptional enhancer element in lung fibroblasts, but its eQTL effects could not be tested due to low imputation quality in the eQTL dataset. SERPINE2-rs6754561 replicated at nominal level in both adults (p = 0.036) and children (p = 0.045), while WNT16-rs2707469 replicated at nominal level only in adults (p = 0.026). The eQTL analyses showed association of WNT16-rs2707469 with expression levels of the nearby gene CPED1. We found no statistically significant eQTL effects for SERPINE2-rs6754561.We have identified a new gene, NCOR2, in the retinoic acid signalling pathway pointing to a role of vitamin A metabolism in the regulation of FVC. Our findings also support SERPINE2, a COPD gene with weak previous evidence of association with FVC, and suggest WNT16 as a further promising candidate.

This work examines the influence of ions in solution on electroosmosis inside a fused silica capillary using capillary electrophoresis; it thereby examines "shielding" at charged interfaces. Theories are reviewed that model ionic solutions as continuous dielectrics: the nonlinear form of the Poisson−Boltzmann equation gives rise to the simplified, more commonly used Debye−Hückel (DH) equation. Capillary electrophoresis (CE) is used to measure the rate of electroosmotic flow as a function of the concentration of different monovalent and divalent cations in aqueous solution. These data are used to test three specific predictions of DH theory: this theory does not describe these data adequately. The central reason behind the inadequacy of DH theory here is its inability to account for details at the level of individual ions other than by mean-field electrostatics: that is, chemical characteristics of ionsfor example, polarizability, hydrated size, energy of hydration, ability to coordinate other ions by chelationare not accounted for. A model (the "dissociation model") is described that treats the interactions between cations in solution and negatively charged groups on a surface in terms of discrete association equilibria with characteristic dissociation constants, Kdeff. CE is then used as a tool to measure values of Kdeff for different cations. These dissociation constants follow patterns that are consistent with ones that are familiar from studies in solution.