Zur Abhängigkeit der Bestimmung der „wahren Glucose“ von der Glas-Sorte der Reagenzgläser

Peer Reviewe

Variations in multiple sclerosis practice within Europe - Is it time for a new treatment guideline?

In the past 5 years, the combination of developments in diagnostic strategy and approval of new disease-modifying therapies has provided an opportunity to achieve dramatic improvements in patient outcomes in multiple sclerosis (MS). However, across Europe there are several factors that may prevent patients from receiving the best therapy at the appropriate time, and there is variation among countries in terms of which of these factors are most relevant. Here, we review current MS clinical practices in a number of countries in the European Union to identify differences regarding initiation of treatment in patients with clinically isolated syndrome or relapsing-remitting MS, and differences in the timing of treatment switch or escalation. While recognizing that policy is not static in any country, we believe that patients' interests would be better served if a European treatment guideline was developed. Such a guideline could both inform and be informed by national policies, facilitating the dissemination of best clinical practice internationally.info:eu-repo/semantics/publishedVersio

CRISPR-Mediated Protein Tagging with Nanoluciferase to Investigate Native Chemokine Receptor Function and Conformational Changes

© 2020 The Authors G protein-coupled receptors are a major class of membrane receptors that mediate physiological and pathophysiological cellular signaling. Many aspects of receptor activation and signaling can be investigated using genetically encoded luminescent fusion proteins. However, the use of these biosensors in live cell systems requires the exogenous expression of the tagged protein of interest. To maintain the normal cellular context here we use CRISPR/Cas9-mediated homology-directed repair to insert luminescent tags into the endogenous genome. Using NanoLuc and bioluminescence resonance energy transfer we demonstrate fluorescent ligand binding at genome-edited chemokine receptors. We also demonstrate that split-NanoLuc complementation can be used to investigate conformational changes and internalization of CXCR4 and that recruitment of β-arrestin2 to CXCR4 can be monitored when both proteins are natively expressed. These results show that genetically encoded luminescent biosensors can be used to investigate numerous aspects of receptor function at native expression levels

The Drosophila melanogaster Apaf-1 homologue ARK is required for most, but not all, programmed cell death

The Apaf-1 protein is essential for cytochrome c–mediated caspase-9 activation in the intrinsic mammalian pathway of apoptosis. Although Apaf-1 is the only known mammalian homologue of the Caenorhabditis elegans CED-4 protein, the deficiency of apaf-1 in cells or in mice results in a limited cell survival phenotype, suggesting that alternative mechanisms of caspase activation and apoptosis exist in mammals. In Drosophila melanogaster, the only Apaf-1/CED-4 homologue, ARK, is required for the activation of the caspase-9/CED-3–like caspase DRONC. Using specific mutants that are deficient for ark function, we demonstrate that ARK is essential for most programmed cell death (PCD) during D. melanogaster development, as well as for radiation-induced apoptosis. ark mutant embryos have extra cells, and tissues such as brain lobes and wing discs are enlarged. These tissues from ark mutant larvae lack detectable PCD. During metamorphosis, larval salivary gland removal was severely delayed in ark mutants. However, PCD occurred normally in the larval midgut, suggesting that ARK-independent cell death pathways also exist in D. melanogaster

Terminal Ligand and Packing Effects on Slow Relaxation in an Isostructural Set of [Dy(H2_{2}dapp)X2_{2}]+ Single Molecule Magnets**

Three new dysprosium complexes with a pentadentate ligand occupying five equatorial sites differ only in the nature of the axial ligands. These help tune the relaxation properties as judged by an analysis of the AC susceptibility data. More in depth analysis by using two recently suggested fitting equations lead to similar outcomes for all three systems. As a further contribution to the relaxation pathway involving the phonon bath it is concluded that a short nitrate-nitrate interaction between molecules helps dampen the spin phonon coupling. We report three structurally related single ion Dy compounds using the pentadentate ligand 2,6-bis((E)-1-(2-(pyridin-2-yl)-hydrazineylidene)ethyl)pyridine (H$_{2}$dapp) [Dy(H$_{2}$dapp)(NO$_{3}$)$_{2}$]NO$_{3}$ (1), [Dy(H$_{2}$dapp)(OAc)$_{2}$]Cl (2) and [Dy(H$_{2}$dapp)(NO$_{3}$)$_{2}$]Cl$_{0.92}$(NO$_{3}$)$_{0.08}$ (3). The (H$_{2}$dapp) occupies a helical twisted pentagonal equatorial arrangement with two anionic ligands in the axial positions. Further influence on the electronic and magnetic structure is provided by a closely associated counterion interacting with the central N−H group of the (H$_{2}$dapp). The slow relaxation of the magnetisation shows that the anionic acetates give the greatest slowing down of the magnetisation reversal. Further influence on the relaxation properties of compounds1 and 2 is the presence of short nitrate-nitrate intermolecular ligand contact opening further lattice relaxation pathways