Breaking bad: necroptosis in the pathogenesis of gastrointestinal diseases

A delicate balance between programmed cell death and proliferation of intestinal epithelial cells (IEC) exists in the gut to maintain homeostasis. Homeostatic cell death programs such as anoikis and apoptosis ensure the replacement of dead epithelia without overt immune activation. In infectious and chronic inflammatory diseases of the gut, this balance is invariably disturbed by increased levels of pathologic cell death. Pathological forms of cell death such as necroptosis trigger immune activation barrier dysfunction, and perpetuation of inflammation. A leaky and inflamed gut can thus become a cause of persistent low-grade inflammation and cell death in other organs of the gastrointestinal (GI) tract, such as the liver and the pancreas. In this review, we focus on the advances in the molecular and cellular understanding of programmed necrosis (necroptosis) in tissues of the GI tract. In this review, we will first introduce the reader to the basic molecular aspects of the necroptosis machinery and discuss the pathways leading to necroptosis in the GI system. We then highlight the clinical significance of the preclinical findings and finally evaluate the different therapeutic approaches that attempt to target necroptosis against various GI diseases. Finally, we review the recent advances in understanding the biological functions of the molecules involved in necroptosis and the potential side effects that may occur due to their systemic inhibition. This review is intended to introduce the reader to the core concepts of pathological necroptotic cell death, the signaling pathways involved, its immuno-pathological implications, and its relevance to GI diseases. Further advances in our ability to control the extent of pathological necroptosis will provide better therapeutic opportunities against currently intractable GI and other diseases

Donor-acceptor substituted polyenes : orientation in mono- and multilayers

Large molecules containing different chemical units whose interactions within the molecule result in new macroscopically observable effects, have become increasingly important.The organization of molecules of this type in ordered structures leads to functional molecular materials.Their use in molecular electronics requires that the units exhibit specific electronic properties. Recently, we reported on the intramolecular energy transfer through terminally substituted conjugated polyenes. An intramolecular electron transfer within donor-acceptor substituted polyenes can be achieved by introducing suitable terminal groups

Conformational snapshots of Tec kinases during signaling

The control of cellular signaling cascades is of utmost importance in regulating the immune response. Exquisitely precise protein-protein interactions and chemical modification of substrates by enzymatic catalysis are the fundamental components of the signals that alert immune cells to the presence of a foreign antigen. In particular, the phosphorylation events induced by protein kinase activity must be spatially and temporally regulated by specific interactions to maintain a normal and effective immune response. High resolution structures of many protein kinases along with supporting biochemical data are providing significant insight into the intricate regulatory mechanisms responsible for controlling cellular signaling. The Tec family kinases are immunologically important kinases for which regulatory details are beginning to emerge. This review focuses on bringing together structural insights gained over the years to develop an understanding of how domain interactions both within the Tec kinases and between the Tec kinases and other signaling molecules control immune cell function

Abschlussbericht des Forschungsprojekts "Broker für Dynamische Produktionsnetzwerke"

Der Broker für dynamische Produktionsnetzwerke (DPNB) ist ein vom Bundesministerium für Bildung und Forschung (BMBF) gefördertes und durch den Projektträger Karlsruhe (PTKA) betreutes Forschungsprojekt zwischen sieben Partnern aus Wissenschaft und Wirtschaft mit einer Laufzeit von Januar 2019 bis einschließlich Dezember 2021. Über den Einsatz von Cloud Manufacturing sowie Hard- und Software-Komponenten bei den teilnehmenden Unternehmen, sollen Kapazitätsanbieter mit Kapazitätsnachfrager verbunden werden. Handelbare Kapazitäten sind in diesem Falle Maschinen-, sowie Transport- und Montagekapazitäten, um Supply Chains anhand des Anwendungsfalls der Blechindustrie möglichst umfassend abzubilden. Der vorliegende Abschlussbericht fasst den Stand der Technik sowie die Erkenntnisse aus dem Projekt zusammen. Außerdem wird ein Überblick über die Projektstruktur sowie die Projektpartner gegeben

Macro- and Microphase Separation in Block Copolymer Supramolecular Assemblies Induced by Solvent Annealing

We fabricated block copolymer (BCP) supramolecules by hydrogen bonding various carboxyl- and phenol-containing azo compounds to the poly­(4-vinylpyridine) blocks of polystyrene-<i>block</i>-poly­(4-vinylpyridine) (PS-<i>b</i>-P4VP). Thin films of the BCP supramolecules were prepared by spin-coating. Optical microscopy showed that all films of BCP supramolecules are macroscopically homogeneous immediately after spin-casting. To induce phase separation, all films were exposed to 1,4-dioxane vapor at room temperature. This solvent annealing caused always microphase separation between PS and P4VP-azo phases and sometimes also macrophase separation, i.e., azo compounds crystallized out of BCP matrices. The problem of macrophase separation in the BCP supramolecules is observed already at low concentrations of carboxyl-containing azo compounds. But phenol-containing azo compounds do not macrophase separate up to a molar ratio of azo compounds to repeat units of P4VP as large as 0.5. We conclude that self-associated hydrogen bonds of carboxylic groups and π–π stacking of azo chromophores are driving forces for macrophase separation