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A common functional polymorphism that results in a three- to four-fold difference in catechol-O-methyltransferase (COMT) enzyme activity has been related to psychiatric disorders such as ultra-ultra rapid cycling bipolar disorder, drug abuse and alcoholism (Lachman et al., 1996a; Karayiorgou et al., 1997; Vandenbergh et al., 1997; Papolos et al., 1998; Tiihonen et al., 1999). Several studies have also reported associations between the allele encoding the low enzyme activity COMT variant (L allele) and other-directed aggression (Strous et al., 1997; Lachman et al., 1998; Kotler et al., 1999) in schizophrenic and schizoaffective patients. The current study investigated whether the COMT L allele is also associated with suicide attempts in schizophrenic and schizoaffective patients. COMT genotypes were determined and history of suicide attempts was retrospectively investigated in a Finnish sample (n = 94) and a US sample (n = 54). Significant associations were observed between COMT genotype and suicide; specifically, history of violent suicide attempts. The COMT L allele was more frequent in subjects who had attempted suicide by violent means. These associations were significant in males but not females. These findings support a common neurobiological substrate for self- and other-directed aggression, and suggest that catecholaminergic alterations may contribute to these behaviors in schizophrenic and schizoaffective patients.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHeterogeneous, platinum-catalyzed hydrogenation of (diolefin)dialkylplatinum(II) complexes: kineticsTimothy M. Miller, Alan N. Izumi, Yen Shiang. Shih, and George M. WhitesidesCite this: J. Am. Chem. Soc. 1988, 110, 10, 3146–3156Publication Date (Print):May 1, 1988Publication History Published online1 May 2002Published inissue 1 May 1988https://pubs.acs.org/doi/10.1021/ja00218a024https://doi.org/10.1021/ja00218a024research-articleACS PublicationsRequest reuse permissionsArticle Views377Altmetric-Citations28LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Abstract Observational studies report that physical activity and metformin are associated with improved clinical outcome in patients with cancer. Inflammation is one biological mechanism hypothesized to mediate these associations. In this phase II, multicenter, 2 × 2 factorial trial, 139 patients with breast and colorectal cancer who completed standard therapy were randomized to one of four treatment groups for 12 weeks: exercise alone, metformin alone, exercise and metformin, or control. Inflammation outcomes included high-sensitivity C-reactive protein (hs-CRP), soluble tumor necrosis factor alpha receptor two (sTNFαR2), and IL6. The primary modeling strategy evaluated the trial product estimand that was quantified using a generalized linear mixed model. Compared with control, exercise alone reduced hs-CRP [−30.2%; 95% confidence interval (CI), −50.3, −1.0] and IL6 (−30.9%; 95% CI, −47.3, −9.5) but did not change sTNFαR2 (1.0%; 95% CI, −10.4, 13.9). Compared with control, metformin alone did not change hs-CRP (−13.9%; 95% CI, −40.0, 23.4), sTNFαR2 (−10.4%; 95% CI, −21.3, 2.0), or IL6 (−22.9%; 95% CI, −42.3, 2.0). Compared with control, exercise and metformin reduced sTNFαR2 (−13.1%; 95% CI, −22.9, −1.0) and IL6 (−38.7%; 95% CI, −52.3, −18.9) but did not change hs-CRP (−20.5%; 95% CI, −44.0, 12.7). The combination of exercise and metformin was not synergistic for hs-CRP, sTNFαR2, or IL6. In survivors of breast and colorectal cancer with low baseline physical activity and without type 2 diabetes, exercise and metformin reduced measures of inflammation that are associated with cancer recurrence and mortality.

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts – cis effects, and elsewhere in the genome – trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10−57), CCL4L1 (p = 3.9×10−21), IL18 (p = 6.8×10−13), LPA (p = 4.4×10−10), GGT1 (p = 1.5×10−7), SHBG (p = 3.1×10−7), CRP (p = 6.4×10−6) and IL1RN (p = 7.3×10−6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10−40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways.

Small (100−600 μm in width) hexagonal polymeric plates with faces patterned into hydrophobic and hydrophilic regions, and interacting through lateral capillary forces, were allowed to self-assemble at the perfluorodecalin/water interface. These plates were fabricated from photoresist and patterned by shadow evaporation of gold onto selected faces. The arrays that assembled from the 100 μm objects were similar in structure to those that assembled from millimeter-sized objects with analogous patterns of hydrophobic and hydrophilic faces, but with three important differences. (i) The contribution of buoyancy forces in establishing the level at which the 100 μm objects floated relative to the interface was small compared to the contribution of the vertical capillary forces. (ii) As a result, the designs of hydrophobic edges necessary to generate menisci useful in self-assembly were different for 100 μm objects than for millimeter-sized objects. (iii) The arrays that formed from the 100 μm objects had higher densities of defects than the arrays that formed from the millimeter-sized objects; these defects reflected the increase in the strength of the capillary forces (which favored assembly) relative to the shear forces (which disrupted assembly). This work adds two new elements to the study of mesoscale self-assembly: (i) It describes a new method of fabrication of plates with faces patterned into regions of different hydrophobicity that is applicable to small (perhaps <10 μm) objects, and (ii) it describes the self-assembly of 100 μm plates made by this method into ordered arrays. The work also established the contours of the menisci on the separate 100 μm and millimeter-sized plates. The scaling of the lateral and vertical capillary forces and buoyancy forces acting on millimeter-sized objects, relative to those acting on 100 μm objects, is described.

The liquid–metal eutectic of gallium and indium (EGaIn) is a useful electrode for making soft electrical contacts to self-assembled monolayers (SAMs). This electrode has, however, one feature whose effect on charge transport has been incompletely understood: a thin (approximately 0.7 nm) film—consisting primarily of Ga2O3—that covers its surface when in contact with air. SAMs that rectify current have been measured using this electrode in AgTS-SAM//Ga2O3/EGaIn (where AgTS = template-stripped Ag surface) junctions. This paper organizes evidence, both published and unpublished, showing that the molecular structure of the SAM (specifically, the presence of an accessible molecular orbital asymmetrically located within the SAM), not the difference between the electrodes or the characteristics of the Ga2O3 film, causes the observed rectification. By examining and ruling out potential mechanisms of rectification that rely either on the Ga2O3 film or on the asymmetry of the electrodes, this paper demonstrates that the structure of the SAM dominates charge transport through AgTS-SAM//Ga2O3/EGaIn junctions, and that the electrical characteristics of the Ga2O3 film have a negligible effect on these measurements.

No abstract is provided for this article.

Background Increased adiposity is linked with higher risk for cardiometabolic diseases. We aimed to determine to what extent elevated body mass index (BMI) within the normal weight range has causal effects on the detailed systemic metabolite profile in early adulthood. Methods and Findings We used Mendelian randomization to estimate causal effects of BMI on 82 metabolic measures in 12,664 adolescents and young adults from four population-based cohorts in Finland (mean age 26 y, range 16–39 y; 51% women; mean ± standard deviation BMI 24±4 kg/m2). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. In cross-sectional analyses, elevated BMI was adversely associated with cardiometabolic risk markers throughout the systemic metabolite profile, including lipoprotein subclasses, fatty acid composition, amino acids, inflammatory markers, and various hormones (p<0.0005 for 68 measures). Metabolite associations with BMI were generally stronger for men than for women (median 136%, interquartile range 125%–183%). A gene score for predisposition to elevated BMI, composed of 32 established genetic correlates, was used as the instrument to assess causality. Causal effects of elevated BMI closely matched observational estimates (correspondence 87%±3%; R2 = 0.89), suggesting causative influences of adiposity on the levels of numerous metabolites (p<0.0005 for 24 measures), including lipoprotein lipid subclasses and particle size, branched-chain and aromatic amino acids, and inflammation-related glycoprotein acetyls. Causal analyses of certain metabolites and potential sex differences warrant stronger statistical power. Metabolite changes associated with change in BMI during 6 y of follow-up were examined for 1,488 individuals. Change in BMI was accompanied by widespread metabolite changes, which had an association pattern similar to that of the cross-sectional observations, yet with greater metabolic effects (correspondence 160%±2%; R2 = 0.92). Conclusions Mendelian randomization indicates causal adverse effects of increased adiposity with multiple cardiometabolic risk markers across the metabolite profile in adolescents and young adults within the non-obese weight range. Consistent with the causal influences of adiposity, weight changes were paralleled by extensive metabolic changes, suggesting a broadly modifiable systemic metabolite profile in early adulthood. Please see later in the article for the Editors' Summary

This paper describes the use of patterned self-assembled monolayers (SAMs) in area-selective deposition of conducting polymers (polypyrrole and polyaniline) on insulating, hydroxyl-terminated surfaces such as Si/SiO2 and glass. Patterned SAMs of octadecylsiloxane were generated on the hydroxyl-terminated surfaces using microcontact printing; they defined and directed the deposition of conducting polymers. The rate of deposition on the hydrophobic surface is higher than that on the hydrophilic surface: immersion of a substrate patterned with a methyl-terminated SAM in an appropriate aqueous polymerization bath produced a "positive" pattern of the conducting polymer on the surface. The conducting polymer deposited on the hydrophobic region of a surface completely covered by the polymer could be readily removed by transferring it to adhesive tape to form a "positive" pattern on the tape, leaving a "negative" pattern on the surface of the substrate. The conducting polymer deposited on the hydrophobic surface had a more extended conformation, and thus a higher conductivity (approximately 3 orders of magnitude in difference), than that formed on the hydrophilic surface. The smallest features of conducting polymers generated using these procedures were ∼2 μm in lateral dimension. The edge roughness of these patterns was ∼0.5 μm. These patterned microstructures of conducting polymers were conductive; they have been used as electrodes in display devices based on polymer dispersed liquid crystals.

Abstract Background: Experimental studies found that the functionality of high density lipoprotein cholesterol (HDL-C) may be lost in the presence of diabetes mellitus (DM). We prospectively tested whether DM modified the association between HDL-C concentrations and cardiovascular disease (CVD). Methods: Included were 91,354 Chinese adults (8,244 participants with DM and 83,110 participants without DM) without use of lipid-lowering drugs and free of CVD or cancer at baseline (2006). The primary endpoint of interest was a composite of CVD (myocardial infarction, ischemic stroke and hemorrhagic stroke). Cumulative average HDL-C concentrations were calculated from all available HDL-C measures at baseline (2006) and during the follow-up period (2008, 2010, 2012 and 2014). Results: During a mean of 10.4 year of follow-up, there were 5,076 CVD events identified. Presence of DM significantly modified the association between HDL-C concentrations and CVD risk ( P interaction =0.003). The association between HDL-C concentrations and CVD followed a U-shaped curve in individuals without DM (P nonlinearity &lt;0.001). The adjusted hazard ratio (HR) of CVD was 1.25 (95% confidence interval (CI): 1.06-1.48) for HDL-C concentrations &lt;1.04 mmol/L and 1.80 (95% CI: 1.56-2.07) for HDL-C concentrations &gt;2.07 mmol/L, relative to the lowest risk group (HDL-C concentrations of 1.30-1.42mmol/L). In participants with DM, higher HDL-C concentrations were associated with a higher risk of CVD, in a dose-response manner (P nonlinearity =0.44; P trend &lt;0.001). The adjusted HR of CVD was 1.63 (95%CI: 1.20-2.20) for HDL-C concentrations &gt;2.07 mmol/L, relative to HDL-C concentrations of 1.30-1.42mmol/L. Conclusion: High HDL-C concentrations were paradoxically associated with increased risk of composite CVD outcomes in individuals with or without DM. However, low HDL-C concentrations failed to predict future CVD risk in individuals with DM.