University of Tübingen

About: University of Tübingen is a education organization based out in Tübingen, Germany. It is known for research contribution in the topics: Population & Immune system. The organization has 40555 authors who have published 84108 publications receiving 3015320 citations. The organization is also known as: Eberhard Karls University & Eberhard-Karls-Universität Tübingen.

Methylation determines fibroblast activation and fibrogenesis in the kidney

Abstract: Fibrogenesis is a pathological wound repair process that fails to cease, even when the initial insult has been removed. Fibroblasts are principal mediators of fibrosis, and fibroblasts from fibrotic tissues fail to return to their quiescent stage, including when cultured in vitro. In a search for underlying molecular mechanisms, we hypothesized that this perpetuation of fibrogenesis is caused by epigenetic modifications. We demonstrate here that hypermethylation of RASAL1, encoding an inhibitor of the Ras oncoprotein, is associated with the perpetuation of fibroblast activation and fibrogenesis in the kidney. RASAL1 hypermethylation is mediated by the methyltransferase Dnmt1 in renal fibrogenesis, and kidney fibrosis is ameliorated in Dnmt1(+/-) heterozygous mice. These studies demonstrate that epigenetic modifications may provide a molecular basis for perpetuated fibroblast activation and fibrogenesis in the kidney.

Genetic content of wild-type human cytomegalovirus

Abstract: The genetic content of wild-type human cytomegalovirus was investigated by sequencing the 235 645 bp genome of a low passage strain (Merlin). Substantial regions of the genome (genes RL1–UL11, UL105–UL112 and UL120–UL150) were also sequenced in several other strains, including two that had not been passaged in cell culture. Comparative analyses, which employed the published genome sequence of a high passage strain (AD169), indicated that Merlin accurately reflects the wild-type complement of 165 genes, containing no obvious mutations other than a single nucleotide substitution that truncates gene UL128. A sizeable subset of genes exhibits unusually high variation between strains, and comprises many, but not all, of those that encode proteins known or predicted to be secreted or membrane-associated. In contrast to unpassaged strains, all of the passaged strains analysed have visibly disabling mutations in one or both of two groups of genes that may influence cell tropism. One comprises UL128, UL130 and UL131A, which putatively encode secreted proteins, and the other contains RL5A, RL13 and UL9, which are members of the RL11 glycoprotein gene family. The case in support of a lack of protein-coding potential in the region between UL105 and UL111A was also strengthened.

Untersuchungen zur Synchronisierbarkeit einzelner Pigmentmangel-Mutanten von Chlorella

Abstract: Verschiedene Chlorella-Mutanten, die Chlorophyll a und b (Mutanten 10 und 11), je nach Kulturbedingungen nur Chlorophyll a oder Chlorophyll a und b (Mutante 41) oder nur Spuren von Chlorophyllen (Mutante 31) enthielten, wurden auf ihr Verhalten unter synchronisierenden Kulturbedingungen untersucht. Eine optimale Synchronisation war in einem Licht-Dunkel-Wechsel von 10 Licht- zu 14-Dunkelstunden zu erzielen. Die Synchronisationsscharfe war relativ gering. Unter keiner der angewendeten Kulturbedingungen lies sich eine Vollsynchronisation erzielen; der Synchronisationstyp war am besten mit einer Gruppen-synchronisation zu vergleichen, bei der laufend Zellen von der einen in die andere Gruppe uberwechseln. Unabhangig vom Vorhandensein von Chlorophyll a oder b und vom Ausmas organischer Zusatze zu den Nahrlosungen zeigten alle untersuchten Chlorella-Mutanten den gleichen Synchronisationstyp. Da die untersuchten Mutanten trotz verschiedener Pigmentzusammensetzung bis hin zum praktischen Chlorophyllverlust in gleicher Weise synchronisierbar sind, ist eine Beteiligung der Chlorophylle am “Zeitgeber-Mechanismus” als sehr unwahrscheinlich anzusehen.

2018 Update of the EULAR recommendations for the management of large vessel vasculitis.

Abstract: BACKGROUND Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations. METHODS Using EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations. RESULTS Three overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40-60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons. CONCLUSIONS We have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.

Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1

Abstract: Cytokines are multifunctional mediators that classically modulate immune activity by receptor-mediated pathways Macrophage migration inhibitory factor (MIF) is a cytokine that has a critical role in several inflammatory conditions but that also has endocrine and enzymatic functions The molecular targets of MIF action have so far remained unclear Here we show that MIF specifically interacts with an intracellular protein, Jab1, which is a coactivator of AP-1 transcription that also promotes degradation of the cyclin-dependent kinase inhibitor p27Kip1 (ref 10) MIF colocalizes with Jab1 in the cytosol, and both endogenous and exogenously added MIF following endocytosis bind Jab1 MIF inhibits Jab1- and stimulus-enhanced AP-1 activity, but does not interfere with the induction of the transcription factor NFkappaB Jab1 activates c-Jun amino-terminal kinase (JNK) activity and enhances endogenous phospho-c-Jun levels, and MIF inhibits these effects MIF also antagonizes Jab1-dependent cell-cycle regulation by increasing p27Kip1 expression through stabilization of p27Kip1 protein Consequently, Jab1-mediated rescue of fibroblasts from growth arrest is blocked by MIF Amino acids 50-65 and Cys 60 of MIF are important for Jab1 binding and modulation We conclude that MIF may act broadly to negatively regulate Jab1-controlled pathways and that the MIF-Jab1 interaction may provide a molecular basis for key activities of MIF