Synthesis of fluorosugar reagents for the construction of well-defined fluoroglycoproteins.

2-Deoxy-2-fluoroglycosyl iodides are privileged glycosyl donors for the stereoselective preparation of 1-Nu-β-fluorosugars, which are useful reagents for chemical site-selective protein glycosylation. Ready access to such β-fluorosugars enables the mild and efficient construction of well-defined fluoroglycoproteins.We thank the European Commission (Marie Curie CIG, O.B. and G.J.L.B.), MICINN, Spain (Juan de la Cierva Fellowship, O.B.), MINECO, Spain (CTQ2011-22872BQU) and Generalitat de Catalunya (M.S.) for generous financial support. We also thank Mr. Adrià Cardona-Benages (URV) for technical assis-tance. G.J.L.B. thanks the Royal Society (University Research Fellowship), Fundação para a Ciência a Tecnologia, Portugal (FCT Investigator), and the EPSRC for funding.This is the final version of the article. It first appeared from ACS via http://pubs.acs.org/doi/abs/10.1021/acs.orglett.5b01259

Mutations in fam20b and xylt1 Reveal That Cartilage Matrix Controls Timing of Endochondral Ossification by Inhibiting Chondrocyte Maturation

Differentiating cells interact with their extracellular environment over time. Chondrocytes embed themselves in a proteoglycan (PG)-rich matrix, then undergo a developmental transition, termed “maturation,” when they express ihh to induce bone in the overlying tissue, the perichondrium. Here, we ask whether PGs regulate interactions between chondrocytes and perichondrium, using zebrafish mutants to reveal that cartilage PGs inhibit chondrocyte maturation, which ultimately dictates the timing of perichondral bone development. In a mutagenesis screen, we isolated a class of mutants with decreased cartilage matrix and increased perichondral bone. Positional cloning identified lesions in two genes, fam20b and xylosyltransferase1 (xylt1), both of which encode PG synthesis enzymes. Mutants failed to produce wild-type levels of chondroitin sulfate PGs, which are normally abundant in cartilage matrix, and initiated perichondral bone formation earlier than their wild-type siblings. Primary chondrocyte defects might induce the bone phenotype secondarily, because mutant chondrocytes precociously initiated maturation, showing increased and early expression of such markers as runx2b, collagen type 10a1, and ihh co-orthologs, and ihha mutation suppressed early perichondral bone in PG mutants. Ultrastructural analyses demonstrated aberrant matrix organization and also early cellular features of chondrocyte hypertrophy in mutants. Refining previous in vitro reports, which demonstrated that fam20b and xylt1 were involved in PG synthesis, our in vivo analyses reveal that these genes function in cartilage matrix production and ultimately regulate the timing of skeletal development

Dictator Games: A Meta Study

Over the last 25 years, more than a hundred dictator game experiments have been published. This meta study summarizes the evidence. Exploiting the fact that most experiments had to fix parameters they did not intend to test, the meta study explores a rich set of control variables for multivariate analysis. It shows that Tobit models (assuming that dictators would even want to take money) and hurdle models (assuming that the decision to give a positive amount is separate from the choice of amount, conditional on giving) outperform mere meta-regression and OLS

Tissue distribution of radioiodinated FAUC113

Summary Aim: Disturbances of the D4 receptor subtype have been implicated in the genesis of a broad range of psychiatric disorders. In order to assess the suitability of a radioiodinated analogue of the D4-selective ligand FAUC 113 for tracer studies in vivo, we investigated the in-vivo stability, biodistribution and brain-uptake of 7-131I-FAUC 113 in Sprague-Dawley rats. Methods: Radiolabelling was carried out with high radiochemical yield and specific activity. After intravenous injection, blood and tissue samples, taken at designated time intervals, were collected for analysis. Analyses of metabolites were performed by radiohplc and radio-tlc. For in-vivo evaluation, sagittal cryo-sections of the rat brain were investigated by in-vitro and exvivo autoradiography on a μ-Imager system. Results: 7-131I-FAUC 113 was rapidly cleared from blood. Highest uptake was observed in kidney (0.603±0.047% ID/g, n=4) and liver (0.357±0.070% ID/g, n=4) at 10 min p.i.; 7-131I-FAUC 113 displayed rapid uptake (0.21-0.26% ID/g) and fast clearance in various brain regions consistent with the determined logP-value of 2.36±0.15 (n=4). In-vivo stability of 7-131I-FAUC 113 was confirmed in the frontal cortex (&gt;95%). Ex-vivo autoradiography revealed a frontal cortex-to-cerebellum ratio of 1.57±0.13 at 10 min p.i. (n=6). Coinjection with L-750667 could not suppress any putative specific binding of 7-131I-FAUC 113. In-vitro autoradiography using authentic 7-iodo-FAUC 113 or L-750667 failed to cause significant displacement of the radioligand. Conclusions: Radioiodinated FAUC 113 does not allow imaging of D4 receptors in the rat brain in vivo nor in vitro. Further work should aim at the development of selective dopamine D4 radioligands with improved tracer characteristics, such as receptor affinity and subtype selectivity, specific activity or blood-brainbarrier permeability.</jats:p