Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts.

The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects.

Activation domains for controlling plant gene expression using designed transcription factors.

Targeted gene regulation via designed transcription factors has great potential for precise phenotypic modification and acceleration of novel crop trait development. To this end, designed transcriptional activators have been constructed by fusing transcriptional activation domains to DNA-binding proteins. In this study, a transcriptional activator from the herpes simplex virus, VP16, was used to identify plant regulatory proteins.

The CaaX specificities of Arabidopsis protein prenyltransferases explain era1 and ggb phenotypes.

Background: Protein prenylation is a common post-translational modification in metazoans, protozoans, fungi, and plants. This modification, which mediates protein-membrane and protein-protein interactions, is characterized by the covalent attachment of a fifteen-carbon farnesyl or twenty-carbon geranylgeranyl group to the cysteine residue of a carboxyl terminal CaaX motif. In Arabidopsis, era1 mutants lacking protein farnesyltransferase exhibit enlarged meristems, supernumerary floral organs, an enhanced response to abscisic acid (ABA), and drought tolerance.

Using trajectory analyses to refine phenotype for genetic association: conduct problems and the serotonin transporter (5HTTLPR).

Background: Conduct disorder is a serious, relatively common disorder of childhood and adolescence. Findings from genetic association studies searching for genetic determinants of the liability toward such behaviors have been inconsistent. One possible explanation for differential results is that most studies define phenotype from a single assessment; for many adolescents conduct problems decrease in severity over time, whereas for others such behaviors persist.

Farnesylcysteine lyase is involved in negative regulation of abscisic acid signaling in Arabidopsis.

The Arabidopsis FCLY gene encodes a specific farnesylcysteine (FC) lyase, which is responsible for the oxidative metabolism of FC to farnesal and cysteine. In addition, fcly mutants with quantitative decreases in FC lyase activity exhibit an enhanced response to ABA. However, the enzymological properties of the FCLY-encoded enzyme and its precise role in ABA signaling remain unclear.

Protein isoprenylation: the fat of the matter.

Protein isoprenylation refers to the covalent attachment of a 15-carbon farnesyl or 20-carbon geranylgeranyl moiety to a cysteine residue at or near the carboxyl terminus. This post-translational lipid modification, which mediates protein-membrane and protein-protein interactions, is necessary for normal control of abscisic acid and auxin signaling, meristem development, and other fundamental processes. Recent studies have also revealed roles for protein isoprenylation in cytokinin biosynthesis and innate immunity.

A discrete-time survival analysis of the relationship between truancy and the onset of marijuana use.

Objective: Despite truancy being a common behavior among teenagers, little research has assessed its deleterious effects. In this study, the effect of truancy on the initiation of marijuana use was examined.

Method: Using data from the Rochester Youth Development Study (a longitudinal sample of predominantly minority youth), discrete time survival analyses were estimated to assess the effect of truancy on the subsequent initiation of marijuana use.

Isoprenylcysteine methylation and demethylation regulate abscisic acid signaling in Arabidopsis.

Isoprenylated proteins bear an isoprenylcysteine methyl ester at the C terminus. Although isoprenylated proteins have been implicated in meristem development and negative regulation of abscisic acid (ABA) signaling, the functional role of the terminal methyl group has not been described. Here, we show that transgenic Arabidopsis thaliana plants overproducing isoprenylcysteine methyltransferase (ICMT) exhibit ABA insensitivity in stomatal closure and seed germination assays, establishing ICMT as a negative regulator of ABA signaling.

Genetic association of the CHRNA6 and CHRNB3 genes with tobacco dependence in a nationally representative sample.

Neuronal nicotinic acetylcholine receptors are activated by both endogenous acetylcholine and exogenous nicotine, making sequence variations in these receptors likely candidates for association with tobacco phenotypes. Previous studies have found evidence for significant association between single nucleotide polymorphisms (SNPs) in the genomic region containing the CHRNA6 and CHRNB3 genes and tobacco behaviors. In this study, we provide support for an association between these genes and tobacco dependence in the National Youth Survey Family Study wave 10, a nationally representative sample of households.

School-related risk and protective factors associated with truancy among urban youth placed at risk.

Truancy is a serious concern in the United States. Its negative effects are so pervasive that in 2003 the Office of Juvenile Justice and Delinquency Prevention named truancy prevention a national priority. Effective prevention of truancy requires a thorough understanding of the characteristics that describe truant youth as well as factors that may put them at risk for truancy.

Between- and within-family association test of the dopamine receptor D2 TaqIA polymorphism and alcohol abuse and dependence in a general population sample of adults.

Objective: Dopaminergic dysfunction has been hypothesized to play an important role in the etiology of alcohol-use disorders. A restriction fragment length polymorphism (RFLP) in the 3' untranslated region (3'UTR) of the DRD2 gene affects gene expression and has been implicated as a risk factor for alcohol dependence. This polymorphism (TaqIA) has been reported as positively associated with alcohol-use disorders in case-control samples, but these results have not been replicated in family-based association studies.

Arabidopsis thaliana plants possess a specific farnesylcysteine lyase that is involved in detoxification and recycling of farnesylcysteine.

In plants, prenylated proteins are involved in actin organization, calcium-mediated signal transduction, and many other biological processes. Arabidopsis thaliana mutants lacking functional protein prenyltransferase genes have also revealed roles for prenylated proteins in phytohormone signaling and meristem development. However, to date, the turnover of prenylated plant proteins and the fate of the prenylcysteine (PC) residue have not been described.

Truancy's effect on the onset of drug use among urban adolescents placed at risk.

Purpose: To examine the relationship between truancy and the onset of drug use.

Methods: Discrete time survival analysis was used to assess the effect of truancy on initiation of drug use after adjusting for several potential confounders from age 11 to 15 years, using data from the Denver Youth Survey, a longitudinal sample of youth who grew up in socially disorganized neighborhoods of Denver, CO.

Results: In this population, truancy was a significant predictor of initiation of alcohol, tobacco, and marijuana use.

Childhood maltreatment, subsequent antisocial behavior, and the role of monoamine oxidase A genotype.

Background: A functional promoter polymorphism in monoamine oxidase A (MAOA) has been implicated as a moderating factor in the relationship between childhood maltreatment and later adolescent and adult antisocial behavior. Despite wide interest in this hypothesis, results remain mixed from the few attempts at replication.

Methods: Regression-based analyses were conducted to test for a genotype-environment interaction using self-reported physical abuse and MAOA genotype to predict later antisocial behavior and arrests for violence by participants in the National Youth Survey Family Study.