FcγReceptors IIa on Cardiomyocytes and Their Potential Functional Relevance in Dilated Cardiomyopathy

ObjectivesThe purpose of this study was to investigate how cardiac autoantibodies might contribute to cardiac dysfunction in patients suffering from dilated cardiomyopathy (DCM).BackgroundIn the majority of DCM patients, it is possible to detect antibodies with negative inotropic effect on cardiomyocytes. The manner in which these antibodies impair cardiac function is poorly understood.MethodsImmunoglobulin (Ig)G was prepared from plasma of 11 DCM patients containing antibodies that induced a negative inotropic effect on cardiomyocytes. We analyzed the effects of antibodies/IgG fragments on calcium transients and on systolic cell shortening of adult rat cardiomyocytes and investigated the dependency of these effects on potential cardiomyocyte Fc receptors.ResultsIn contrast to control subjects, intact IgG from DCM patients reduced calcium transients and cell shortening of cardiomyocytes. The F(ab′)2fragments of these antibodies did not induce these effects but inhibited the functional effects of DCM-IgG of the respective patients’ IgG. These effects were also inhibited by Fc fragments of normal IgG. Reconstitution of the Fc part by incubation of cardiomyocytes with DCM-F(ab′)2fragments followed by goat-anti-human-F(ab′)-IgG again induced reduction of cell shortening and of calcium transients. In rat and human ventricular cardiomyocytes, Fcγreceptors IIa (CD32) were demonstrated by immunofluorescence.ConclusionsOur findings indicate that DCM-IgG-F(ab′)2bind to their cardiac antigen(s), but the Fc part might trigger the negative inotropic effects via the newly detected Fcγreceptor on cardiomyocytes. These results point to a novel potential mechanism for antibody-induced impairment of cardiac function in DCM patients

Prävention und Hilfe bei stoffgebundenen und stoffungebundenen Suchterkrankungen in Niedersachsen. Erster Forschungsbericht für das Niedersächsische Ministerium für Soziales, Gesundheit und Gleichstellung

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Colloidal Analysis of Particles Extracted from Microalloyed Steels

Different colloidal particle characterization methods are examined for their suitability to determine the particle size distribution of particles extracted from steels. Microalloyed steels are dissolved to extract niobium and titanium carbonitride particles that are important for the mechanical properties of these steels. Such particles have sizes ranging from several nanometers to hundreds of nanometers depending on the precipitation stage during the thermomechanically controlled rolling process. The size distribution of the particles is analyzed by dynamic light scattering (DLS), analytical ultracentrifugation (AUC), and hollow fiber flow field-flow fractionation (HF5) and compared to data obtained for reference particles as well as data from electron microscopy, the standard sizing technique used in metallurgy today. AUC and HF5 provide high-quality size distributions, average over large particle numbers that enables statistical analysis, and yield useful insights for alloy design; however, DLS fails due to a lack of resolution. Important aspects in the conversion and comparison of size distributions obtained for broadly distributed particle systems with different measurement principles and the role of surfactants used in sample preparation are discussed

Heidelberg-Studie 2000

Umfrage zum Leben und poltischen Problemen in Heidelberg. 1219 Telefoninterview

Mixed gas adsorption of carbon dioxide and methane on a series of isoreticular microporous metal-organic frameworks based on 2-substituted imidazolate-4-amide-5-imidates

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.In this work the adsorption of CO2 and CH4 on a series of isoreticular microporous metal–organic frameworks based on 2-substituted imidazolate-4-amide-5-imidates, IFP-1–IFP-6 (IFP = Imidazolate Framework Potsdam), is studied firstly by pure gas adsorption at 273 K. All experimental isotherms can be nicely described by using the Tòth isotherm model and show the preferred adsorption of CO2 over CH4. At low pressures the Tòth isotherm equation exhibits a Henry region, wherefore Henry's law constants for CO2 and CH4 uptake could be determined and ideal selectivity αCO2/CH4 has been calculated. Secondly, selectivities were calculated from mixture data by using nearly equimolar binary mixtures of both gases by a volumetric–chromatographic method to examine the IFPs. Results showed the reliability of the selectivity calculation. Values of αCO2/CH4 around 7.5 for IFP-5 indicate that this material shows much better selectivities than IFP-1, IFP-2, IFP-3, IFP-4 and IFP-6 with slightly lower selectivity αCO2/CH4 = 4–6. The preferred adsorption of CO2 over CH4 especially of IFP-5 and IFP-4 makes these materials suitable for gas separation application.DFG, SPP 1362, Poröse metallorganische Gerüstverbindunge

Differential phosphorylation of the N - terminal extension regulates phytochrome B signaling

Viczián, András. Institute of Plant Biology. Biological Research Centre. Szeged, Hungary.Ádám, Éva. Institute of Plant Biology. Biological Research Centre. Szeged, Hungary.Staudt, Anne Marie. University of Freiburg. Institute of Biology II. Freiburg, Germany.Lambert, Dorothee. University of Freiburg. Institute of Biology II. Freiburg, Germany.Klement, Eva. Biological Research Centre. Laboratory of Proteomics Research. Szeged, Hungary.Romero Montepaone, Sofia. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura (IFEVA). Buenos Aires, Argentina.Hiltbrunner, Andreas. University of Freiburg. Institute of Biology II. Freiburg, Germany.Casal, Jorge José. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura (IFEVA). Buenos Aires, Argentina.1635–1650Phytochrome B (phyB) is an excellent light quality and quantity sensor that can detect subtle changes in the light environment. The relative amounts of the biologically active photoreceptor (phyB Pfr) are determined by the light conditions and light independent thermal relaxation of Pfr into the inactive phyB Pr, termed thermal reversion. Little is known about the regulation of thermal reversion and how it affects plants’ light sensitivity. In this study we identified several serine/threonine residues on the N-terminal extension (NTE) of Arabidopsis thaliana phyB that are differentially phosphorylated in response to light and temperature, and examined transgenic plants expressing nonphosphorylatable and phosphomimic phyB mutants. The NTE of phyB is essential for thermal stability of the Pfr form, and phosphorylation of S86 particularly enhances the thermal reversion rate of the phyB Pfr–Pr heterodimer in vivo. We demonstrate that S86 phosphorylation is especially critical for phyB signaling compared with phosphorylation of the more N terminal residues. Interestingly, S86 phosphorylation is reduced in light, paralleled by a progressive Pfr stabilization under prolonged irradiation. By investigating other phytochromes (phyD and phyE) we provide evidence that acceleration of thermal reversion by phosphorylation represents a general mechanism for attenuating phytochrome signaling

Mechanisms and advancement of antifading agents for fluorescence microscopy and single-molecule spectroscopy

Modern fluorescence microscopy applications go along with increasing demands for the employed fluorescent dyes. In this work, we compared antifading formulae utilizing a recently developed reducing and oxidizing system (ROXS) with commercial antifading agents. To systematically test fluorophore performance in fluorescence imaging of biological samples, we carried out photobleaching experiments using fixed cells labeled with various commonly used organic dyes, such as Alexa 488, Alexa 594, Alexa 647, Cy3B, ATTO 550, and ATTO 647N. Quantitative evaluation of (i) photostability, (ii) brightness, and (iii) storage stability of fluorophores in samples mounted in different antifades (AFs) reveal optimal combinations of dyes and AFs. Based on these results we provide guidance on which AF should preferably be used with a specific dye. Finally, we studied the antifading mechanisms of the commercial AFs using single-molecule spectroscopy and reveal that these empirically selected AFs exhibit similar properties to ROXS AFs

Neurofascin (NF) 155-and NF186-Specific T Cell Response in a Patient Developing a Central Pontocerebellar Demyelination after 10 Years of CIDP

Background: Information and pathobiological understanding about central demyelinating manifestation in patients, who primarily suffer from chronic inflammatory demyelinating polyneuropathy (CIDP), are scarce. Methods: IFN-gamma-response as well as antibodies against the (para) nodal antigens neurofascin (NF) 155 and NF 186 had been tested by Elispot assay and ELISA before clinical manifestation and at follow-up. Case description and results: The patient described here developed a subacute brainstem syndrome more than 10 years after diagnosis of CIDP under low-dose maintenance treatment of intravenous immunoglobulins (IVIG). MRI revealed enhancing right-sided pontocerebellar lesion. CSF examination showed mild pleocytosis and elevated protein, and negative oligoclonal bands. Further diagnostics exclude differential diagnoses such as tuberculoma, sarcoidosis, or metastasis. Specific IFN-gamma response against NF155 and NF186 as measured by Elispot assay was elevated before clinical manifestation. NF155 and NF186 antibodies were negative. Escalation of IVIG treatment at 2 g/kg BW followed by 1.4 g/kg BW led to clinical remission albeit to a new asymptomatic central lesion. Follow-up NF155 and NF186-Elispot turned negative. Conclusion: The case reported here with a delayed central manifestation after an initially typical CIDP and NF155 and NF186 T cell responses does not resemble described cases of combined central and peripheral demyelination but may reflect a novel subtype within the great clinical heterogeneity of CIDP