SUMOylation stabilizes sister kinetochore biorientation to allow timely anaphase

During mitosis, sister chromatids attach to microtubules from opposite poles, called biorientation. Sister chromatid cohesion resists microtubule forces, generating tension, which provides the signal that biorientation has occurred. How tension silences the surveillance pathways that prevent cell cycle progression and correct erroneous kinetochore–microtubule attachments remains unclear. Here we show that SUMOylation dampens error correction to allow stable sister kinetochore biorientation and timely anaphase onset. The Siz1/Siz2 SUMO ligases modify the pericentromere-localized shugoshin (Sgo1) protein before its tension-dependent release from chromatin. Sgo1 SUMOylation reduces its binding to protein phosphatase 2A (PP2A), and weakening of this interaction is important for stable biorientation. Unstable biorientation in SUMO-deficient cells is associated with persistence of the chromosome passenger complex (CPC) at centromeres, and SUMOylation of CPC subunit Bir1 also contributes to timely anaphase onset. We propose that SUMOylation acts in a combinatorial manner to facilitate dismantling of the error correction machinery within pericentromeres and thereby sharpen the metaphase–anaphase transition.     

Current Status of Human Papillomavirus-Related Head and Neck Cancer: From Viral Genome to Patient Care

Virologica Sinica - Human papillomavirus (HPV) infection identified as a definitive human carcinogen is increasingly being recognized for its role in carcinogenesis of human cancers. Up to...     

Expression levels of the metalloproteinase ADAM8 critically regulate proliferation,migration and malignant signalling events in hepatoma cells

Hepatocellular carcinoma (HCC) is one of the most common metastatic tumours. Tumour growth and metastasis depend on the induction of cell proliferation and migration by various mediators. Here, we report that the A Disintegrin and Metalloproteinase (ADAM) 8 is highly expressed in murine HCC tissues as well as in murine and human hepatoma cell lines Hepa1-6 and HepG2, respectively. To establish a dose-dependent role of different ADAM8 expression levels for HCC progression, ADAM8 expression was either reduced via shRNA- or siRNA-mediated knockdown or increased by using a retroviral overexpression vector. These two complementary approaches revealed that ADAM8 expression levels correlated positively with proliferation, clonogenicity, migration and matrix invasion and negatively with apoptosis of hepatoma cells. Furthermore, the analysis of pro-migratory and proliferative signalling pathways revealed that ADAM8 expression level was positively associated with expression of β1 integrin as well as with the activation of focal adhesion kinase (FAK), mitogen-activated protein kinase (MAPK), Src kinase and Rho A GTPase. Finally, up-regulation of promigatory signalling and cell migration was also seen with a proteolytically inactive ADAM8 mutant. These findings reveal that ADAM8 is critically up-regulated in hepatoma cells contributes to cell proliferation and survival and furthermore induces pro-migratory signalling pathways independently of its proteolytic activity. By this, ADAM8 can promote cell functions most relevant for HCC growth and metastasis.     

Characterization and phylogenomic analysis of Breznakiella homolactica gen. nov. sp. nov. indicate that termite gut treponemes evolved from non-acetogenic spirochetes in cockroaches

Spirochetes of the genus Treponema are surprisingly abundant in termite guts, where they play an important role in reductive acetogenesis. Although they occur in all termites investigated, their evolutionary origin is obscure. Here, we isolated the first representative of ‘termite gut treponemes’ from cockroaches, the closest relatives of termites. Phylogenomic analysis revealed that Breznakiella homolactica gen. nov. sp. nov. represents the most basal lineage of the highly diverse ‘termite cluster I', a deep-branching sister group of Treponemataceae (fam. ‘Termitinemataceae’) that was present already in the cockroach ancestor of termites and subsequently coevolved with its host. Breznakiella homolactica is obligately anaerobic and catalyses the homolactic fermentation of both hexoses and pentoses. Resting cells produced acetate in the presence of oxygen. Genome analysis revealed the presence of pyruvate oxidase and catalase, and a cryptic potential for the formation of acetate, ethanol, formate, CO₂ and H₂ - the fermentation products of termite gut isolates. Genes encoding key enzymes of reductive acetogenesis, however, are absent, confirming the hypothesis that the ancestral metabolism of the cluster was fermentative, and that the capacity for acetogenesis from H₂ plus CO₂ - the most intriguing property among termite gut treponemes - was acquired by lateral gene transfer.     

A muscle controlled finite-element model of laryngeal abduction and adduction

A three-dimensional finite-element model was developed to simulate the complex movement of the laryngeal cartilages during vocal fold abduction and adduction. The model consists of cricoid and arytenoid cartilages, as well as the intralaryngeal muscles and vocal folds. The active and passive properties of the muscles were idealised by one-dimensional elements based on the Hill theory. Its controlling input value is a time dependent stimulation rate. Optimisation loops have been carried out for the arrangement of the individual stimulation rates. Since in vivo measurements are not feasible, the developed biomechanical model shall be used to analyse the force distribution within the laryngeal muscles during phonatory manoeuvres. Simulations of abduction and adduction in different pitches of voice lead to realistic tensions of the vocal folds. The model is a first step to analyse motional vocal fold diseases and to predict the consequences of phonosurgical interventions.     

Laccase-catalyzed decolorization of the synthetic azo-dye diamond black PV 200 and of some structurally related derivatives

The kinetics of laccase-catalyzed transformation of the azo-dye Diamond Black PV 200 (CI Mordant Black 9) and various related synthesized derivatives were analyzed for dependence on pH and substrate structure. The reaction mixture of Diamond Black PV 200 was analyzed by HPLC/MS–MS and it was shown that upon laccase oxidation, reactive chinoid fragments of lower molecular weight were formed. These may further oligomerize as indicated by the appearance of a number of compounds with increased molecular weight. The pH optimum for the decolorization was pH 5 for Diamond Black PV 200 which did not change significantly when the substitution pattern of its basic structure was varied. Biodegradability, however, was strongly dependent on the structure of the dyes.