Alterations in the Hippocampal Endocannabinoid System in Diet-Induced Obese Mice

The endocannabinoid (eCB) system plays central roles in the regulation of food intake and energy expenditure. Its alteration in activity contributes to the development and maintenance of obesity. Stimulation of the cannabinoid receptor type 1 (CB1receptor) increases feeding, enhances reward aspects of eating, and promotes lipogenesis, whereas its blockade decreases appetite, sustains weight loss, increases insulin sensitivity, and alleviates dysregulation of lipid metabolism. The hypothesis has been put forward that the eCB system is overactive in obesity. Hippocampal circuits are not directly involved in the neuronal control of food intake and appetite, but they play important roles in hed…

Back Cover: Promoter Activation in Δ hfq Mutants as an Efficient Tool for Specialized Metabolite Production Enabling Direct Bioactivity Testing (Angew. Chem. Int. Ed. 52/2019)

Telaprevir drug monitoring during antiviral therapy of hepatitis C graft infection after liver transplantation

Background & Aims Recurrence of hepatitis C virus (HCV) infection after orthotopical liver transplantation (OLT) is common and associated with reduced graft and patient survival. The protease inhibitor telaprevir may enhance virological response rates in patients after OLT in combination with pegylated interferon-alfa and ribavirin. Pharmacokinetic studies have shown significant drug–drug interactions between telaprevir and immunosuppression (IS), but telaprevir pharmacokinetics in OLT patients with IS are unknown. Aim of the present study was to analyse telaprevir plasma concentrations in patients with HCV genotype 1 infection after OLT in comparison to patients without OLT and IS. Methods…

Rücktitelbild: Promoter Activation in Δ hfq Mutants as an Efficient Tool for Specialized Metabolite Production Enabling Direct Bioactivity Testing (Angew. Chem. 52/2019)

Promoter Activation in Dhfq Mutants as an Efficient Tool for Specialized Metabolite Production Enabling Direct Bioactivity Testing

Abstract Natural products (NPs) from microorganisms have been important sources for discovering new therapeutic and chemical entities. While their corresponding biosynthetic gene clusters (BGCs) can be easily identified by gene‐sequence‐similarity‐based bioinformatics strategies, the actual access to these NPs for structure elucidation and bioactivity testing remains difficult. Deletion of the gene encoding the RNA chaperone, Hfq, results in strains losing the production of most NPs. By exchanging the native promoter of a desired BGC against an inducible promoter in Δhfq mutants, almost exclusive production of the corresponding NP from the targeted BGC in Photorhabdus, Xenorhabdus and Pseud…