Methoden, Verfahren und Instrumente des Risikocontrollings und Risikomanagements in einer prozess- und faktororientierten Betrachtung unter besonderer Berücksichtigung der kennzahlenbasierten Insolvenzprophylaxe

nicht vorhande

DJ-1: A promising therapeutic candidate for ischemia-reperfusion injury.

DJ-1 is a multifaceted protein with pleiotropic functions that has been implicated in multiple diseases, ranging from neurodegeneration to cancer and ischemia-reperfusion injury. Ischemia is a complex pathological state arising when tissues and organs do not receive adequate levels of oxygen and nutrients. When the blood flow is restored, significant damage occurs over and above that of ischemia alone and is termed ischemia-reperfusion injury. Despite great efforts in the scientific community to ameliorate this pathology, its complex nature has rendered it challenging to obtain satisfactory treatments that translate to the clinic. In this review, we will describe the recent findings on the participation of the protein DJ-1 in the pathophysiology of ischemia-reperfusion injury, firstly introducing the features and functions of DJ-1 and, successively highlighting the therapeutic potential of the protein

Macrophage fumarate hydratase restrains mtRNA-mediated interferon production

Metabolic rewiring underlies the effector functions of macrophages1-3, but the mechanisms involved remain incompletely defined. Here, using unbiased metabolomics and stable isotope-assisted tracing, we show that an inflammatory aspartate-argininosuccinate shunt is induced following lipopolysaccharide stimulation. The shunt, supported by increased argininosuccinate synthase (ASS1) expression, also leads to increased cytosolic fumarate levels and fumarate-mediated protein succination. Pharmacological inhibition and genetic ablation of the tricarboxylic acid cycle enzyme fumarate hydratase (FH) further increases intracellular fumarate levels. Mitochondrial respiration is also suppressed and mitochondrial membrane potential increased. RNA sequencing and proteomics analyses demonstrate that there are strong inflammatory effects resulting from FH inhibition. Notably, acute FH inhibition suppresses interleukin-10 expression, which leads to increased tumour necrosis factor secretion, an effect recapitulated by fumarate esters. Moreover, FH inhibition, but not fumarate esters, increases interferon-β production through mechanisms that are driven by mitochondrial RNA (mtRNA) release and activation of the RNA sensors TLR7, RIG-I and MDA5. This effect is recapitulated endogenously when FH is suppressed following prolonged lipopolysaccharide stimulation. Furthermore, cells from patients with systemic lupus erythematosus also exhibit FH suppression, which indicates a potential pathogenic role for this process in human disease. We therefore identify a protective role for FH in maintaining appropriate macrophage cytokine and interferon responses

In-Cell Biochemistry Using NMR Spectroscopy

Biochemistry and structural biology are undergoing a dramatic revolution. Until now, mostly in vitro techniques have been used to study subtle and complex biological processes under conditions usually remote from those existing in the cell. We developed a novel in-cell methodology to post-translationally modify interactor proteins and identify the amino acids that comprise the interaction surface of a target protein when bound to the post-translationally modified interactors. Modifying the interactor proteins causes structural changes that manifest themselves on the interacting surface of the target protein and these changes are monitored using in-cell NMR. We show how Ubiquitin interacts with phosphorylated and non-phosphorylated components of the receptor tyrosine kinase (RTK) endocytic sorting machinery: STAM2 (Signal-transducing adaptor molecule), Hrs (Hepatocyte growth factor regulated substrate) and the STAM2-Hrs heterodimer. Ubiquitin binding mediates the processivity of a large network of interactions required for proper functioning of the RTK sorting machinery. The results are consistent with a weakening of the network of interactions when the interactor proteins are phosphorylated. The methodology can be applied to any stable target molecule and may be extended to include other post-translational modifications such as ubiquitination or sumoylation, thus providing a long-awaited leap to high resolution in cell biochemistry

Die Leipziger Neunundneunzig

DIE LEIPZIGER NEUNUNDNEUNZIG Die Leipziger Neunundneunzig ( - ) Einband ( - ) Titelseite ([1]) [Vorwort] (1) Georg Witkowski: Olle Kamellen (3) Richard Heinze: Lukian, wider den ungebildeten Büchersammler (14) Richard Schmidt: Von vergessenen Leipziger Büchern und Gärten (22) Ernst Schulz-Besser: Sprachkuriosa in der deutschen Literatur (32) Carl Ernst Poeschel: Romantische Typographie (39) Georg Steindorff: Tagebuchblatt aus Kairo (Dezember 1928) (42) Hermann Michel: Der Mops und der Mond (44) Gerhard Stumme: Meine Faustsammlung Erinnerungen und Ausblicke (55) Kurt Wiedenfeld: Wirtschaft und Kultur (67) Gustav Kirstein: Er sass und frass und hat ne Brille (75) Wilhelm Pinder: Zur Topographie des Humors (87) Hans Schulz: Max Klingers Bibliothek (96) Alfred Doren: Deutsches Leben in Florenz - Erinnerungen aus den neunziger Jahren (102) Otto Glauning: Schrift- und Buchwesen in der Kunst der Alten Meister (109) Max Förster: Die älteste Fassung von D. G. Rossettis Ballade "Sister Helen" (116) Erich Ebstein: Aus Leipzigs medizinischer Vergangenheit (140) Franz Adam Beyerlein: Der Dämon - Mit fünf Zeichnungen von Erich Gruner (145) Richard Graul: Leipziger Sammler der älteren Generation (160) Erich Brandenburg: Reinhard der Fuchs (167) Hugo Steiner-Prag: Penha Verde (178) Ludwig Volkmann: Der liebe Gott als Buchdrucker (188) Levin L. Schücking: Ein Besuch bei Swinburne (193) Ignaz Wiemeler: Handeinband und neue Sachlichkeit (200) Heinrich Uhlendahl: Etwas von der Kameliendame - Was nicht im Dumas steht (205) Fedor v. Zobeltitz: Ein Kommerslied für den Leipziger Bibliophilen-Abend (227) Anton Kippenberg: Der letzte Bibliophile (229) Inhalt (234) Mitglieder (236

Mouse models for cone degeneration

Loss of cone vision has devastating effects on everyday life. Even though much effort has been made to understand cone physiology and pathophysiology, no successful therapies are available for patients suffering from cone disorders. As complex retinal interactions cannot be studied in vitro, utilization of different animal models is inevitable. Due to recent advances in transgenesis, mice became the most popular animal model to study human diseases, also in ophthalmology. While there are similarities in retinal anatomy and pathophysiology between mice and humans, there are also differences, most importantly the lack of a cone-rich macula in mice. Instead, cones in mice are rare and distributed over the whole retina, which makes the analysis of cone pathophysiology very difficult in these animals. This hindrance is one of the reasons why our understanding of rod pathophysiological processes is much more advanced. Recently, however, the sparseness of cones was overcome by the generation of the Nrl (- / -) mouse that expresses only cone photoreceptors in the retina. This paper will give a brief overview of some of the known mouse models to study cone degeneration and discuss the current knowledge gained from the analysis of these models