Thiopeptides are a class of natural product antibiotics with diverse structures and functions. Their complex structures and biosynthesis have intrigued researchers since their discovery in 1948, but not a single thiopeptide has been approved for human use. This is mainly due to their poor solubility, challenging synthesis, and low bioavailability. This review summarizes the current research on the biosynthesis and biological activity of thiopeptide antibiotics since 2015. The focus of research since 2015 has been on uncovering biosynthetic routes, developing methods for total synthesis, and understanding the biological activity of thiopeptides. Overall, there is still much to learn about this family of molecules.Transcranial direct current stimulation (tDCS) is a safe, effective treatment for major depressive disorder (MDD). While antidepressant effects are heterogeneous, no studies have investigated trajectories of tDCS response. We characterized distinct improvement trajectories and associated baseline characteristics for patients treated with prefrontal tDCS, an active pharmacotherapy (escitalopram), and placebo. This is a secondary analysis of a randomized, non-inferiority, double-blinded trial (ELECT-TDCS, N = 245). Participants were diagnosed with an acute unipolar, nonpsychotic, depressive episode, and presented Hamilton Depression Rating Scale (17-items, HAM-D) scores ≥17. Latent trajectory modeling was used to identify HAM-D response trajectories over a 10-week treatment. Top-down (hypothesis-driven) and bottom-up (data-driven) methods were employed to explore potential predictive features using, respectively, conservatively corrected regression models and a cross-validated stability ranking procedure combined with elastic net regularization. Three trajectory classes that were distinct in response speed and intensity (rapid, slow, and no/minimal improvement) were identified for escitalopram, tDCS, and placebo. Differences in response and remission rates were significant early for all groups. Depression severity, use of benzodiazepines, and age were associated with no/minimal improvement. No significant differences in trajectory assignment were found in tDCS vs. placebo comparisons (38.3, 34, and 27.6%; vs. 23.3, 43.3, and 33.3% for rapid, slow, and no/minimal trajectories, respectively). Additional features are suggested in bottom-up analyses. Summarily, groups treated with tDCS, escitalopram, and placebo differed in trajectory class distributions and baseline predictors of response. Our results might be relevant for designing further studies.Understanding the neurobiological underpinnings of abstinence from drugs of abuse is critical to allow better recovery and ensure relapse prevention in addicted subjects. By comparing the long-term transcriptional consequences of morphine and cocaine exposure, we identified the metabotropic glutamate receptor subtype 4 (mGluR4) as a promising pharmacological target in morphine abstinence. We evaluated the behavioral and molecular effects of facilitating mGluR4 activity in abstinent mice. Transcriptional regulation of marker genes of medium spiny neurons (MSNs) allowed best discriminating between 4-week morphine and cocaine abstinence in the nucleus accumbens (NAc). Among these markers, Grm4, encoding mGluR4, displayed down-regulated expression in the caudate putamen and NAc of morphine, but not cocaine, abstinent mice. Chronic administration of the mGluR4 positive allosteric modulator (PAM) VU0155041 (2.5 and 5 mg/kg) rescued social behavior, normalized stereotypies and anxiety and blunted locomotor sensitization in morphine abstinent mice. This treatment improved social preference but increased stereotypies in cocaine abstinent mice. Finally, the beneficial behavioral effects of VU0155041 treatment in morphine abstinent mice were correlated with restored expression of key MSN and neural activity marker genes in the NAc. This study reports that chronic administration of the mGluR4 PAM VU0155041 relieves long-term deleterious consequences of morphine exposure.  https://www.selleckchem.com/products/mpp-dihydrochloride.html  It illustrates the neurobiological differences between opiate and psychostimulant abstinence and points to pharmacological repression of excessive activity of D2-MSNs in the NAc as a promising therapeutic lever in drug addiction.Experiments aiming to understand sensory-motor systems, cognition and behavior necessitate training animals to perform complex tasks. Traditional training protocols require lab personnel to move the animals between home cages and training chambers, to start and end training sessions, and in some cases, to hand-control each training trial. Human labor not only limits the amount of training per day, but also introduces several sources of variability and may increase animal stress. Here we present an automated training system for the 5-choice serial reaction time task (5CSRTT), a classic rodent task often used to test sensory detection, sustained attention and impulsivity. We found that full automation without human intervention allowed rapid, cost-efficient training, and decreased stress as measured by corticosterone levels. Training breaks introduced only a transient drop in performance, and mice readily generalized across training systems when transferred from automated to manual protocols. We further validated our automated training system with wireless optogenetics and pharmacology experiments, expanding the breadth of experimental needs our system may fulfill. Our automated 5CSRTT system can serve as a prototype for fully automated behavioral training, with methods and principles transferrable to a range of rodent tasks.Triple ionic-electronic conductors (TIECs) are materials that can simultaneously transport electronic species alongside two ionic species. The recent emergence of TIECs provides intriguing opportunities to maximize performance in a variety of electrochemical devices, including fuel cells, membrane reactors and electrolysis cells. However, the potential application of these nascent materials is limited by lack of fundamental knowledge of their transport properties and electrocatalytic activity. The goal of this Review is to summarize and analyse the current understanding of TIEC transport and electrochemistry in single-phase materials, including defect formation and conduction mechanisms. We particularly focus on the discovery criteria (for example, crystal structure and ion electronegativity), design principles (for example, cation and anion substitution chemistry) and operating conditions (for example, atmosphere) of materials that enable deliberate tuning of the conductivity of each charge carrier. Lastly, we identify important areas for further advances, including higher chemical stability, lower operating temperatures and discovery of n-type TIEC materials.