Synthesis of monoalkylated calix[4]arenes via direct alkylation

A new one-step procedure for the synthesis of monoalkylated calix[4]arenes is presented. Reaction of calix[4]arene 1a or 1b with 1.2 equivalent of a weak base (K2CO3 in MeCN or CsF in DMF) and excess of alkylating agent affords the monoalkylated calix[4]arenes in moderate to good yield

Reliability of voluntary step execution behavior under single and dual task conditions

<p>Abstract</p> <p>Background</p> <p>The current study investigated the repeatability (test-retest reliability) of ground reaction force parameters recorded during a voluntary step execution under single (motor task) and dual task (motor and cognitive task) conditions for healthy adults and elderly individuals as well as the number of trials required to produce repeatable results.</p> <p>Methods</p> <p>Twenty-four healthy adults (21–63 years old) and 16 elderly adults (66–87 years) performed a voluntary rapid step execution following a tap on their heel while standing on a force platform under single and dual task conditions on three separate occasions. The first two tests were performed 30–60 minutes apart and the third test was performed a week later. Variables analyzed from the ground reaction force data included onset latency of step initiation (initiation phase), preparation and swing phases, foot-off and foot-contact times.</p> <p>Results</p> <p>Intraclass correlation coefficients (ICC(2,1)) were good to excellent across all parameters and test conditions for the pooled population and for elderly (0.74–0.92 and 0.62–0.88, respectively) except for the swing phase duration where lower values were seen (0.54–0.60 and 0.32–0.64 respectively). Values were similar under single and dual task conditions.</p> <p>Conclusion</p> <p>A voluntary step execution test, performed under single and dual task conditions especially foot-off and foot-contact times, is a reliable outcome measure that may be a useful tool to asses dynamic balance function for diagnostic purposes as well as clinical intervention trials.</p

The Human SLC1A5 (ASCT2) Amino Acid Transporter: From Function to Structure and Role in Cell Biology

SLC1A5, known as ASCT2, is a neutral amino acid transporter belonging to the SLC1 family and localized in the plasma membrane of several body districts. ASCT2 is an acronym standing for Alanine, Serine, Cysteine Transporter 2 even if the preferred substrate is the conditionally essential amino acid glutamine, with cysteine being a modulator and not a substrate. The studies around amino acid transport in cells and tissues began in the ‘60s by using radiolabeled compounds and competition assays. After identification of murine and human genes, the function of the coded protein has been studied in cell system and in proteoliposomes revealing that this transporter is a Na+ dependent antiporter of neutral amino acids, some of which are only inwardly transported and others are bi-directionally exchanged. The functional asymmetry merged with the kinetic asymmetry in line with the physiological role of amino acid pool harmonization. An intriguing function has been described for ASCT2 that is exploited as a receptor by a group of retroviruses to infect human cells. Interactions with scaffold proteins and post-translational modifications regulate ASCT2 stability, trafficking and transport activity. Two asparagine residues, namely N163 and N212, are the sites of glycosylation that is responsible for the definitive localization into the plasma membrane. ASCT2 expression increases in highly proliferative cells such as inflammatory and stem cells to fulfill the augmented glutamine demand. Interestingly, for the same reason, the expression of ASCT2 is greatly enhanced in many human cancers. This finding has generated interest in its candidacy as a pharmacological target for new anticancer drugs. The recently solved 3D structure of ASCT2 will aid in the rational design of such therapeutic compounds

Substrate-bound outward-open structure of a Na+-coupled sialic acid symporter reveals a new Na+ site

Many pathogenic bacteria utilise sialic acids as an energy source or use them as an external coating to evade immune detection. As such, bacteria that colonise sialylated environments deploy specific transporters to mediate import of scavenged sialic acids. Here, we report a substrate-bound 1.95 Å resolution structure and subsequent characterisation of SiaT, a sialic acid transporter from Proteus mirabilis. SiaT is a secondary active transporter of the sodium solute symporter (SSS) family, which use Na+ gradients to drive the uptake of extracellular substrates. SiaT adopts the LeuT-fold and is in an outward-open conformation in complex with the sialic acid N-acetylneuraminic acid and two Na+ ions. One Na+ binds to the conserved Na2 site, while the second Na+ binds to a new position, termed Na3, which is conserved in many SSS family members. Functional and molecular dynamics studies validate the substrate-binding site and demonstrate that both Na+ sites regulate N-acetylneuraminic acid transport