(S)-2-Mercaptohistidine:A First Selective Orthosteric GluK3 Antagonist

International audienceThe development of tool compounds for the ionotropic glutamate receptors (iGluRs) remains an important research objective, as these are essential for the study and understanding of the roles of these receptors in health and disease. Herein, we report on the pharmacological characterization of (S)-2-hydroxyhistidine (2a) and (S)-2-mercaptohistidine (2b) as mediators of glutamatergic neurotransmission. While 2a displayed negligible binding affinity or activity at all glutamate receptors and transporters investigated, 2b displayed selectivity for homomeric GluK3 with binding affinities in the low micromolar range (Ki = 6.42 ± 0.74 μM). The iGluR subtype selectivity ratio for 2b was calculated at ∼30-fold for GluK1/GluK3, GluA3/GluK3, and GluA4/GluK3 and >100-fold for GluK2/GluK3, GluA1/GluK3, and GluA2/GluK3. Unexpectedly, functional characterization of 2b revealed that the compound is an antagonist (Kb = 7.6 μM) at homomeric GluK3 receptors while exhibiting only weak agonist activity at GluA2 (EC50 = 3.25 ± 0.55 mM). The functional properties of 2b were explored further in electrophysiological recordings of mouse hippocampal neurons

The Importance of Trunk Muscle Strength for Balance, Functional Performance, and Fall Prevention in Seniors:A Systematic Review

<p>Background The aging process results in a number of functional (e.g., deficits in balance and strength/power performance), neural (e.g., loss of sensory/motor neurons), muscular (e.g., atrophy of type-II muscle fibers in particular), and bone-related (e.g., osteoporosis) deteriorations. Traditionally, balance and/or lower extremity resistance training were used to mitigate these age-related deficits. However, the effects of resistance training are limited and poorly translate into improvements in balance, functional tasks, activities of daily living, and fall rates. Thus, it is necessary to develop and design new intervention programs that are specifically tailored to counteract age-related weaknesses. Recent studies indicate that measures of trunk muscle strength (TMS) are associated with variables of static/dynamic balance, functional performance, and falls (i.e., occurrence, fear, rate, and/or risk of falls). Further, there is preliminary evidence in the literature that core strength training (CST) and Pilates exercise training (PET) have a positive influence on measures of strength, balance, functional performance, and falls in older adults.</p><p>Objective The objectives of this systematic literature review are: (a) to report potential associations between TMS/trunk muscle composition and balance, functional performance, and falls in old adults, and (b) to describe and discuss the effects of CST/PET on measures of TMS, balance, functional performance, and falls in seniors.</p><p>Data Sources A systematic approach was employed to capture all articles related to TMS/trunk muscle composition, balance, functional performance, and falls in seniors that were identified using the electronic databases PubMed and Web of Science (1972 to February 2013).</p><p>Study Selection A systematic approach was used to evaluate the 582 articles identified for initial review. Cross-sectional (i.e., relationship) or longitudinal (i.e., intervention) studies were included if they investigated TMS and an outcome-related measure of balance, functional performance, and/or falls. In total, 20 studies met the inclusionary criteria for review.</p><p>Study Appraisal and Synthesis Methods Longitudinal studies were evaluated using the Physiotherapy Evidence Database (PEDro) scale. Effect sizes (ES) were calculated whenever possible. For ease of discussion, the 20 articles were separated into three groups [i.e., cross-sectional (n = 6), CST (n = 9), PET (n = 5)].</p><p>Results The cross-sectional studies reported small-to-medium correlations between TMS/trunk muscle composition and balance, functional performance, and falls in older adults. Further, CST and/or PET proved to be feasible exercise programs for seniors with high-adherence rates. Age-related deficits in measures of TMS, balance, functional performance, and falls can be mitigated by CST (mean strength gain = 30 %, mean effect size = 0.99; mean balance/functional performance gain = 23 %, mean ES = 0.88) and by PET (mean strength gain = 12 %, mean ES = 0.52; mean balance/functional performance gain = 18 %, mean ES = 0.71).</p><p>Limitations Given that the mean PEDro quality score did not reach the predetermined cut-off of >= 6 for the intervention studies, there is a need for more high-quality studies to explicitly identify the relevance of CST and PET to the elderly population.</p><p>Conclusions Core strength training and/or PET can be used as an adjunct or even alternative to traditional balance and/or resistance training programs for old adults. Further, CST and PET are easy to administer in a group setting or in individual fall preventive or rehabilitative intervention programs because little equipment and space is needed to perform such exercises.</p>

Imidazol(in)ium Hydrogen Carbonates as a Genuine Source of N-Heterocyclic Carbenes (NHCs): Applications to the Facile Preparation of NHC Metal Complexes and to NHC-Organocatalyzed Molecular and Macromolecular Syntheses

Anion metathesis of imidazol(in)ium chlorides with KHCO3 afforded an easy one step access to air stable imidazol(in)ium hydrogen carbonates, denoted as [NHC(H)][HCO3]. In solution, these compounds were found to be in equilibrium with their corresponding imidazol(in)ium carboxylates, referred to as N-heterocyclic carbene (NHC)-CO2 adducts. The [NHC(H)][HCO3] salts were next shown to behave as masked NHCs, allowing for the NHC moiety to be readily transferred to both organic and organometallic substrates, without the need for dry and oxygen-free conditions. In addition, such [NHC(H)][HCO3] precursors were successfully investigated as precatalysts in two selected organocatalyzed reactions of molecular chemistry and polymer synthesis, namely, the benzoin condensation reaction and the ring-opening polymerization of D,L-lactide, respectively. The generation of NHCs from [NHC(H)][HCO3] precursors occurred via the formal loss of H2CO3 via a concerted low energy pathway, as substantiated by Density Functional Theory (DFT) calculations