Mitochondrial dysfunction in sepsis is associated with diminished intramitochondrial TFAM despite its increased cellular expression

Sepsis is characterized by a dysregulated immune response, metabolic derangements and bioenergetic failure. These alterations are closely associated with a profound and persisting mitochondrial dysfunction. This however occurs despite increased expression of the nuclear-encoded transcription factor A (TFAM) that normally supports mitochondrial biogenesis and functional recovery. Since this paradox may relate to an altered intracellular distribution of TFAM in sepsis, we tested the hypothesis that enhanced extramitochondrial TFAM expression does not translate into increased intramitochondrial TFAM abundance. Accordingly, we prospectively analyzed PBMCs both from septic patients (n = 10) and lipopolysaccharide stimulated PBMCs from healthy volunteers (n = 20). Extramitochondrial TFAM protein expression in sepsis patients was 1.8-fold greater compared to controls (p = 0.001), whereas intramitochondrial TFAM abundance was approximate 80% less (p < 0.001). This was accompanied by lower mitochondrial DNA copy numbers (p < 0.001), mtND1 expression (p < 0.001) and cellular ATP content (p < 0.001) in sepsis patients. These findings were mirrored in lipopolysaccharide stimulated PBMCs taken from healthy volunteers. Furthermore, TFAM-TFB2M protein interaction within the human mitochondrial core transcription initiation complex, was 74% lower in septic patients (p < 0.001). In conclusion, our findings, which demonstrate a diminished mitochondrial TFAM abundance in sepsis and endotoxemia, may help to explain the paradox of lacking bioenergetic recovery despite enhanced TFAM expression

FRESH bioprinting technology for tissue engineering - the influence of printing process and bioink composition on cell behavior and vascularization

The rapid and tailored biofabrication of natural materials is of high interest for the field of tissue engineering and regenerative medicine. Scaffolds require both high biocompatibility and tissue-dependent mechanical strength to function as basis for tissue-engineered implants. Thus, natural hydrogels such as fibrin are promising but their rapid biofabrication remains challenging. Printing of low viscosity and slow polymerizing solutions with good spatial resolution can be achieved by freeform reversible embedding of suspended hydrogels (FRESH) bioprinting of cell-laden natural hydrogels. In this study, fibrin and hyaluronic acid were used as single components as well as blended ink mixtures for the FRESH bioprinting. Rheometry revealed that single materials were less viscous than the blended bioink showing higher values for viscosity over a shear rate of 10–1000 s −1 . While fibrin showed viscosities between 0.1624 and 0.0017 Pa·s, the blended ink containing fibrin and hyaluronic acid were found to be in a range of 0.1–1 Pa·s. In 3D vascularization assays, formation of vascular structures within the printed constructs was investigated indicating that the printing process did not harm cells and allowed formation of vasculature comparable to moulded control samples. Best values for vascularization were achieved in bioinks consisting of 1.0% fibrin-0.5% hyaluronic acid. The vascular structure area and length were three times higher compared to other tested bioinks, and structure volume as well as number of branches revealed almost four times higher values. In this study, we combined the benefits of the FRESH printing technique with in vitro vascularization, showing that it is possible to achieve a mechanically stable small-scale hydrogel construct incorporating vascular network formation

Vernunftkritik und Aufkl\ue4rung: Studien zur Philosophie Kants und seines Jahrhunderts: Norbert Hinske zum siebzigsten Geburtstag

Mit dem vorliegenden Band m\uf6chten Freunde, Kollegen und Sch\ufcler das wissenschaftliche Werk Norbert Hinskes w\ufcrdigen, der am 24. Januar 2001 siebzig Jahre alt wird. Damit das Buch nicht eine lose Sammlung buntscheckiger Beitr\ue4ge ohne gemeinsames Vorzeichen w\ufcrde, hatten wir die Autoren gebeten, Themen aus der Philosophie der Aufkl\ue4rung zu bearbeiten; ansonsten war die Wahl des Sujets freigestellt. Schon allein aufgrund dieser Beschr\ue4nkung k\uf6nnen lange nicht alle, die ein Recht gehabt h\ue4tten, sich in dieser Form unter die Gratulanten zu mischen, hier vertreten sein. Die Konzentration auf einen Forschungsschwerpunkt hat jedoch den unbestreitbaren Vorteil, da f sie, bei aller Verschiedenheit der einzelnen Fragestellungen, dem Band thematische Einheit verleiht. Die Wahl fiel auf die Epoche der Aufkl\ue4rung -- wobei sich ein Schwerpunkt auf die Philosophie Kants von selbst ergab --, weil die Beitr\ue4ge einen Bezug zum Arbeitsgebiet des Jubilars haben sollten. Dazu z\ue4hlt zwar in besonderem Ma fe auch die Philosophie der Antike, an der Norbert Hinske nach wie vor ein sehr lebendiges Interesse hat, sein Name ist jedoch in ausgezeichneter Weise mit der Aufkl\ue4rungsforschung im allgemeinen und der Kantforschung im besonderen verbunden. Wir hoffen, da f das Buch Anregungen und Anst\uf6 fe zu weiteren Forschungen auf diesem Gebiet geben wird