Smoking Cessation Pharmacogenetics: Analysis of Varenicline and Bupropion in Placebo-Controlled Clinical Trials

Despite effective therapies for smoking cessation, most smokers find quitting difficult and most successful quitters relapse. Considerable evidence supports a genetic risk for nicotine dependence; however, less is known about the pharmacogenetics of smoking cessation. In the first pharmacogenetic investigation of the efficacy of varenicline and bupropion, we examined whether genes important in the pharmacodynamics and pharmacokinetics of these drugs and nicotine predict medication efficacy and adverse events. Subjects participated in randomized, double-blind, placebo-controlled smoking cessation clinical trials, comparing varenicline, a nicotinic acetylcholine receptor (nAChR) partial agonist, with bupropion, a norepinephrine/dopamine reuptake inhibitor, and placebo. Primary analysis included 1175 smokers of European ancestry, and 785 single nucleotide polymorphisms from 24 genes, representing 254 linkage disequilibrium (LD) bins (genes included nAChR subunits, additional varenicline-specific genes, and genes involved in nicotine or bupropion metabolism). For varenicline, continuous abstinence (weeks 9–12) was associated with multiple nAChR subunit genes (including CHRNB2, CHRNA5, and CHRNA4) (OR=1.76; 95% CI: 1.23–2.52) (p<0.005); for bupropion, abstinence was associated with CYP2B6 (OR=1.78; 95% CI: 1.27–2.50) (p<0.001). Incidence of nausea was associated with several nAChR subunit genes (OR=0.50; 95% CI: 0.36–0.70) (p<0.0001) and time to relapse after quitting was associated with HTR3B (HR=1.97; 95% CI: 1.45–2.68) (p<0.0001). These data provide evidence for multiple genetic loci contributing to smoking cessation and therapeutic response. Different loci are associated with varenicline vs bupropion response, suggesting that additional research may identify clinically useful markers to guide treatment decisions

The impact of firms’ social media initiatives on operational efficiency and innovativeness

Social media have been increasingly adopted for organizational purposes but their operational implications are not well understood. Firms’ social media initiatives might facilitate information flow and knowledge sharing within and across organizations, strengthening firm‐customer interaction, and improving internal and external collaboration. In this research we empirically examine the impact of social media initiatives on firms’ operational efficiency and innovativeness. Taking the resource‐based view of firms’ information capability, we consider firms’ social media initiatives as strategic resources for operational improvement. We posit that firms’ social media initiatives enhance dynamic knowledge‐sharing routines through an information‐rich social network, leading to both operational efficiency and innovativeness. Collecting secondary data in a longitudinal setting from multiple sources, we construct dynamic panel data (DPD) models. Based on system generalized method of moments (GMM) estimation, we show that firms’ social media initiatives improve operational efficiency and innovativeness. We identify the importance of an information‐rich social network to the creation of knowledge‐based advantage through firms’ social media initiatives, and discuss the theoretical and managerial implications from the perspective of operations management

Global mapping transcriptional start sites revealed both transcriptional and post-transcriptional regulation of cold adaptation in the methanogenic archaeon Methanolobus psychrophilus

Psychrophilic methanogenic Archaea contribute significantly to global methane emissions, but archaeal cold adaptation mechanisms remain poorly understood. Hinted by that mRNA architecture determined secondary structure respond to cold more promptly than proteins, differential RNA-seq was used in this work to examine the genome-wide transcription start sites (TSSs) of the psychrophilic methanogen Methanolobus psychrophilus R15 and its response to cold. Unlike most prokaryotic mRNAs with short 5′ untranslated regions (5′ UTR, median lengths of 20–40 nt), 51% mRNAs of this methanogen have large 5′ UTR (>50 nt). For 24% of the mRNAs, the 5′ UTR is >150 nt. This implies that post-transcriptional regulation may be significance in the psychrophile. Remarkably, 219 (14%) genes possessed multiple gene TSSs (gTSSs), and 84 genes exhibited temperature-regulated gTSS selection to express alternative 5′ UTR. Primer extension studies confirmed the temperature-dependent TSS selection and a stem-loop masking of ribosome binding sites was predicted from the longer 5′ UTRs, suggesting alternative 5′ UTRs-mediated translation regulation in the cold adaptation as well. In addition, 195 small RNAs (sRNAs) were detected, and Northern blots confirmed that many sRNAs were induced by cold. Thus, this study revealed an integrated transcriptional and post-transcriptional regulation for cold adaptation in a psychrophilic methanogen