73 research outputs found
Measurement of Fibrosis Marker Xylosyltransferase I Activity by HPLC Electrospray Ionization Tandem Mass Spectrometry
18F-labelled triazolyl-linked argininamides targeting the neuropeptide Y Y1R for PET Imaging of mammary carcinoma
NeuropeptideYY(1) receptors (Y1R) have been found to be overexpressed in a number of different tumours, such as breast, ovarian or renal cell cancer. In mammary carcinoma the highY(1)R density together with its high incidence of 85% in primary human breast cancers and 100% in breast cancer derived lymph node metastases attracted special attention. Therefore, the aim of this study was the development of radioligandsforY(1)R imaging by positron emission tomography (PET) with a special emphasis on imaging agents with reduced lipophilicity to provide a PET ligand with improved biodistribution in comparison with previously published tracers targeting theY(1)R. Three new radioligands based on BIBP3226, bearing an F-18-fluoroethoxy linker (12), an F-18-PEG-linker (13) or an F-18-fluoroglycosyl moiety (11) were radiosynthesised in high radioactivity yields. The new radioligands displayedY(1)R affinities of 2.8 nM (12), 29 nM (13) and 208 nM (11) and were characterised in vitro regarding binding to human breast cancer MCF-7-Y1 cells and slices of tumour xenografts. In vivo, small animal PET studies were conducted in nude mice bearing MCF-7-Y1 tumours. The binding to tumours, solid tumour slices and tumour cells correlated well with theY(1)R affinities. Although 12 and 13 showed displaceable and specific binding toY(1)R in vitro and in vivo, the radioligands still need to be optimised to achieve higher tumour-to-background ratios forY(1)R imaging by PET.Yet the present study is another step towards an optimized PET radioligand for imaging ofY(1)R in vivo
Modelltheoretische Grundlagen wirtschaftspolitischer Kontroversen: eine computergestĂĽtzte Aufbereitung
Mainstream-Wirtschaftstheorie beherrscht den wirtschaftspolitischen Diskurs sowie die wissenschaftliche und Lehrbuch-Literatur. Die Verwendung digitaler Instrumente in der makroökonomischen Bildung hat erheblich zugenommen, erleichtert den Lernprozess und bietet eine praktische Darstellung der Makroökonomik, ihrer Instrumente und Ziele. In den verfügbaren makroökonomischen Simulatoren fehlt eine klare Diskussion der ökonomischen Theorie, die hinter der Konstruktion des Modells steht. Darüber hinaus spiegelt sich die Dominanz der neo-klassischen Theorie in der wirtschaftspolitischen Diskussion und Ausbildung wider. Das Projekt: Wir entwickeln eine digitale Lernplattform mit einem interaktiven Online-Lehrbuch, um Kontroversen auf den Grundlagen der makroökonomischen Theorie zu präsentieren und zu untersuchen Unser Ziel ist es, anhand des Simulators den Pluralismus in den Mittelpunkt makroökonomischer Bildung und politischer Diskussionen zu bringen
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
Macroeconomic effects of personal and functional income inequality: Theory and empirical evidence for the US and Germany
This paper presents a simple post-Kaleckian model of distribution and growth
that incorporates personal income inequality and interdependent social
norms. The model shows in an easily accessible manner that macroeconomic
effects of changes in personal and functional income distribution can
potentially reinforce or dampen each other. The resulting variety of demand
and growth regimes is due to different distributional effects on consumption
demand. Therefore, the second part of the paper investigates the empirical
relevance of the additional demand regimes by estimating aggregate
consumption functions with variables for personal and functional income
distribution for the United States and Germany. We find similar effects of
functional income distribution for both countries. However, for the US, we
find positive long-run effects of personal income inequality on consumption.
The effect is strongest for the top 10% income share and the Gini index and
less strong for the top 5% and 1% income shares. While this is evidence for
relative consumption patterns, it also supports the view that the “super
rich” are a relatively distant class for most people - questioning the
notion of expenditure cascades from the very top to the very bottom. In
contrast, for Germany we fail to find compelling evidence for effects of
personal income distribution
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