Entwicklung und Anwendung eines NIRS-basierten Routineverfahrens zur Analyse der relativen und absoluten Fettsäurezusammensetzung in Rind- und Schweinefleisch sowie die Untersuchung von Kandidatengenen für den bovinen Fettstoffwechsel

Das Standardverfahren in der Fettsäureanalytik ist die Gaschromatographie. Dieses präzise Verfahren ist jedoch mit einem hohen Zeitaufwand verbunden. In der vorliegenden Arbeit sollte ein auf Nahinfrarotspektroskopie (NIRS) basierendes Hochdurchsatzverfahren entwickelt werden, das die Erfassung sowohl der relativen wie auch der absoluten Fettsäurezusammensetzung in Rind- und Schweinefleisch ermöglicht. Die umfangreiche Erhebung fettstoffwechselbezogener Parameter war ein wesentliches Erfordernis für das Fortschreiten des FUGATO-Projektes QuaLIPID, in dessen Rahmen die vorliegende Arbeit angefertigt wurde. Das Forschungsvorhaben QuaLIPID hatte zum Ziel, DNA-Varianten in Genen des Fettstoffwechsels bei Rind und Schwein zu identifizieren, die die Qualität tierischer Produkte maßgeblich beeinflussen. Dabei sollten Untersuchungen zur Assoziation von DNA-Variation und Merkmalen des Fettstoffwechsels in Rindern und Schweinen erfolgen, deren genetische Ausstattung eine Ausprägung von fettstoffwechselbezogenen Merkmalen im extrem niedrigen bzw. hohen Bereich begünstigt. Die Datengrundlage für die Identifizierung dieser Individuen sollte das NIRS-Verfahren liefern. Weiterhin leistete die vorliegende Arbeit einen Beitrag zur Evaluierung der Eignung von SNPs (single nucleotide polymorphisms) als Marker für Merkmale des Fettstoffwechsels beim Rind

Targeting cardiomyocyte ADAM10 ectodomain shedding promotes survival early after myocardial infarction

After myocardial infarction the innate immune response is pivotal in clearing of tissue debris as well as scar formation, but exaggerated cytokine and chemokine secretion with subsequent leukocyte infiltration also leads to further tissue damage. Here, we address the value of targeting a previously unknown a disintegrin and metalloprotease 10 (ADAM10)/CX3CL1 axis in the regulation of neutrophil recruitment early after MI. We show that myocardial ADAM10 is distinctly upregulated in myocardial biopsies from patients with ischemia-driven cardiomyopathy. Intriguingly, upon MI in mice, pharmacological ADAM10 inhibition as well as genetic cardiomycyte-specific ADAM10 deletion improves survival with markedly enhanced heart function and reduced scar size. Mechanistically, abolished ADAM10-mediated CX3CL1 ectodomain shedding leads to diminished IL-1β-dependent inflammation, reduced neutrophil bone marrow egress as well as myocardial tissue infiltration. Thus, our data shows a conceptual insight into how acute MI induces chemotactic signaling via ectodomain shedding in cardiomyocytes

Small intestinal mucosa expression of putative chaperone fls485

<p>Abstract</p> <p>Background</p> <p>Maturation of enterocytes along the small intestinal crypt-villus axis is associated with significant changes in gene expression profiles. <it>fls485 </it>coding a putative chaperone protein has been recently suggested as a gene involved in this process. The aim of the present study was to analyze <it>fls48</it>5 expression in human small intestinal mucosa.</p> <p>Methods</p> <p><it>fls485 </it>expression in purified normal or intestinal mucosa affected with celiac disease was investigated with a molecular approach including qRT-PCR, Western blotting, and expression strategies. Molecular data were corroborated with several <it>in situ </it>techniques and usage of newly synthesized mouse monoclonal antibodies.</p> <p>Results</p> <p>fls485 mRNA expression was preferentially found in enterocytes and chromaffine cells of human intestinal mucosa as well as in several cell lines including Rko, Lovo, and CaCo2 cells. Western blot analysis with our new anti-fls485 antibodies revealed at least two fls485 proteins. In a functional CaCo2 model, an increase in fls485 expression was paralleled by cellular maturation stage. Immunohistochemistry demonstrated fls485 as a cytosolic protein with a slightly increasing expression gradient along the crypt-villus axis which was impaired in celiac disease Marsh IIIa-c.</p> <p>Conclusions</p> <p>Expression and synthesis of fls485 are found in surface lining epithelia of normal human intestinal mucosa and deriving epithelial cell lines. An interdependence of enterocyte differentiation along the crypt-villus axis and fls485 chaperone activity might be possible.</p

Die Einführung der elektronischen Gesundheitskarte für Geflüchtete in den Bundesländern und Kommunen

Wenner J, Drüke F, Kämmerer S, Rolke K. Die Einführung der elektronischen Gesundheitskarte für Geflüchtete in den Bundesländern und Kommunen. Bielefeld University; 2018

CaM kinase II regulates cardiac hemoglobin expression through histone phosphorylation upon sympathetic activation

Sympathetic activation of beta-adrenoreceptors (beta-AR) represents a hallmark in the development of heart failure (HF). However, little is known about the underlying mechanisms of gene regulation. In human ventricular myocardium from patients with end-stage HF, we found high levels of phosphorylated histone 3 at serine-28 (H3S28p). H3S28p was increased by inhibition of the catecholamine-sensitive protein phosphatase 1 and decreased by beta-blocker pretreatment. By a series of in vitro and in vivo experiments, we show that the beta-AR downstream protein kinase CaM kinase II (CaMKII) directly binds and phosphorylates H3S28. Whereas, in CaMKII-deficient myocytes, acute catecholaminergic stimulation resulted in some degree of H3S28p, sustained catecholaminergic stimulation almost entirely failed to induce H3S28p. Genome-wide analysis of CaMKII-mediated H3S28p in response to chronic beta-AR stress by chromatin immunoprecipitation followed by massive genomic sequencing led to the identification of CaMKII-dependent H3S28p target genes. Forty percent of differentially H3S28p-enriched genomic regions were associated with differential, mostly increased expression of the nearest genes, pointing to CaMKII-dependent H3S28p as an activating histone mark. Remarkably, the adult hemoglobin genes showed an H3S28p enrichment close to their transcriptional start or end sites, which was associated with increased messenger RNA and protein expression. In summary, we demonstrate that chronic beta-AR activation leads to CaMKII-mediated H3S28p in cardiomyocytes. Thus, H3S28p-dependent changes may play an unexpected role for cardiac hemoglobin regulation in the context of sympathetic activation. These data also imply that CaMKII may be a yet unrecognized stress-responsive regulator of hematopoesis

Diminished PLK2 Induces Cardiac Fibrosis and Promotes Atrial Fibrillation.

[Figure: see text]