N-methyl-D-aspartate Receptors and Depression: Linking Psychopharmacology, Pathology and Physiology in a Unifying Hypothesis for the Epigenetic Code of Neural Plasticity.

Uncompetitive NMDAR (N-methyl-D-aspartate receptor) antagonists restore impaired neural plasticity, reverse depressive-like behavior in animal models, and relieve major depressive disorder (MDD) in humans. This review integrates recent findings from in silico, in vitro, in vivo, and human studies of uncompetitive NMDAR antagonists into the extensive body of knowledge on NMDARs and neural plasticity. Uncompetitive NMDAR antagonists are activity-dependent channel blockers that preferentially target hyperactive GluN2D subtypes because these subtypes are most sensitive to activation by low concentrations of extracellular glutamate and are more likely activated by certain pathological agonists and allosteric modulators.

Basic Affective Systems and Sex Differences in the Relationship between Anger and Fear.

Background: The possible interactions between anger and fear have not been widely explored in the psychological literature. Fear and anger are currently beginning to be studied by looking at their interrelationships, rather than seeing them as simply opposing emotions. Furthermore, there is a tendency to think that anger is more typical of men and fear of women.

Toxin-mediated depletion of NAD and NADP drives persister formation in a human pathogen.

Toxin-antitoxin (TA) systems are widespread in bacteria and implicated in genome stability, virulence, phage defense, and persistence. TA systems have diverse activities and cellular targets, but their physiological roles and regulatory mechanisms are often unclear. Here, we show that the NatR-NatT TA system, which is part of the core genome of the human pathogen Pseudomonas aeruginosa, generates drug-tolerant persisters by specifically depleting nicotinamide dinucleotides.

Epidemic control by social distancing and vaccination: Optimal strategies and remarks on the COVID-19 Italian response policy.

After the many failures in the control of the COVID-19 pandemic, identifying robust principles of epidemic control will be key in future preparedness. In this work, we propose an optimal control model of an age-of-infection transmission model under a two-phase control regime where social distancing is the only available control tool in the first phase, while the second phase also benefits from the arrival of vaccines. We analyzed the problem by an ad-hoc numerical algorithm under a strong hypothesis implying a high degree of prioritization to the protection of health from the epidemic attack, which we termed the "low attack rate" hypothesis.

Pharmacokinetics, Tolerability, and Safety of Esmethadone in Subjects with Chronic Kidney Disease or Hepatic Impairment.

Background And Objectives: Esmethadone (dextromethadone; d-methadone; S-methadone (+)-methadone; REL-1017) is a low potency N-methyl--aspartate (NMDA) receptor channel blocker that showed a rapid and sustained adjunctive antidepressant effects in patients with major depressive disorder with inadequate response to ongoing serotonergic antidepressant treatment. Previous studies indicated that esmethadone is partially excreted by the kidney (53.9% of the dose) and by the liver (39.