Search results for "HERA"

Phage Therapy in Gastrointestinal Diseases

2020

Gastrointestinal tract microbiota plays a key role in the regulation of the pathogenesis of several gastrointestinal diseases. In particular, the viral fraction, composed essentially of bacteriophages, influences homeostasis by exerting a selective pressure on the bacterial communities living in the tract. Gastrointestinal inflammatory diseases are mainly induced by bacteria, and have risen due to the emergence of antibiotic resistant strains. In the lack of effective treatments, phage therapy has been proposed as a clinical alternative to restore intestinal eubiosis, thanks to its immunomodulatory and bactericidal effect against bacterial pathogens, such as Clostridioides difficile in ulce…

Ribosome-Targeting Antibiotics Impair T Cell Effector Function and Ameliorate Autoimmunity by Blocking Mitochondrial Protein Synthesis

2019

Summary While antibiotics are intended to specifically target bacteria, most are known to affect host cell physiology. In addition, some antibiotic classes are reported as immunosuppressive for reasons that remain unclear. Here, we show that Linezolid, a ribosomal-targeting antibiotic (RAbo), effectively blocked the course of a T cell-mediated autoimmune disease. Linezolid and other RAbos were strong inhibitors of T helper-17 cell effector function in vitro, showing that this effect was independent of their antibiotic activity. Perturbing mitochondrial translation in differentiating T cells, either with RAbos or through the inhibition of mitochondrial elongation factor G1 (mEF-G1) progressi…

Biological insertion of computationally designed short transmembrane segments

2016

The great majority of helical membrane proteins are inserted co-translationally into the ER membrane through a continuous ribosome-translocon channel. The efficiency of membrane insertion depends on transmembrane (TM) helix amino acid composition, the helix length and the position of the amino acids within the helix. In this work, we conducted a computational analysis of the composition and location of amino acids in transmembrane helices found in membrane proteins of known structure to obtain an extensive set of designed polypeptide segments with naturally occurring amino acid distributions. Then, using an in vitro translation system in the presence of biological membranes, we experimental…

A Janus-Faced IM30 Ring Involved in Thylakoid Membrane Fusion Is Assembled from IM30 Tetramers.

2017

Summary Biogenesis and dynamics of thylakoid membranes likely involves membrane fusion events. Membrane attachment of the inner membrane-associated protein of 30 kDa (IM30) affects the structure of the lipid bilayer, finally resulting in membrane fusion. Yet, how IM30 triggers membrane fusion is largely unclear. IM30 monomers pre-assemble into stable tetrameric building blocks, which further align to form oligomeric ring structures, and differently sized IM30 rings bind to membranes. Based on a 3D reconstruction of IM30 rings, we locate the IM30 loop 2 region at the bottom of the ring and show intact membrane binding but missing fusogenic activity of loop 2 mutants. However, helix 7, which …

Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer.

2016

Abstract As a master regulator of chromatin function, the lysine methyltransferase EZH2 orchestrates transcriptional silencing of developmental gene networks. Overexpression of EZH2 is commonly observed in human epithelial cancers, such as non–small cell lung carcinoma (NSCLC), yet definitive demonstration of malignant transformation by deregulated EZH2 remains elusive. Here, we demonstrate the causal role of EZH2 overexpression in NSCLC with new genetically engineered mouse models of lung adenocarcinoma. Deregulated EZH2 silences normal developmental pathways, leading to epigenetic transformation independent of canonical growth factor pathway activation. As such, tumors feature a transcrip…

Interradicular Root Canals in Mandibular First Molars: A Literature Review and Ex Vivo Study

2019

Abstract Introduction Successful endodontic treatment vastly depends to a high degree on an accurate knowledge of root canal system morphology. It is a prerequisite to be aware of all possible reservoirs where bacteria and/or toxins can persist, compromising the surrounding tissues; such knowledge results in endodontic success. Methods The presence of interradicular canals and diverticula between the pulp chamber floor and the bifurcation area surface of 117 mandibular first molars was investigated. Access cavities were prepared, the teeth were embedded in plastic, and the pulp chambers were flooded with methylene blue and then centrifuged. An average of 4.2 (0.145 ± 0.03 mm thickness) slic…

Exosomal Chaperones and miRNAs in Gliomagenesis: State-of-Art and Theranostics Perspectives

2018

Gliomas have poor prognosis no matter the treatment applied, remaining an unmet clinical need. As background for a substantial change in this situation, this review will focus on the following points: (i) the steady progress in establishing the role of molecular chaperones in carcinogenesis; (ii) the recent advances in the knowledge of miRNAs in regulating gene expression, including genes involved in carcinogenesis and genes encoding chaperones; and (iii) the findings about exosomes and their cargo released by tumor cells. We would like to trigger a discussion about the involvement of exosomal chaperones and miRNAs in gliomagenesis. Chaperones may be either targets for therapy, due to their…

An Ex Vivo Study of Root Canal System Configuration and Morphology of 115 Maxillary First Premolars

2019

Abstract Introduction The aim of this study was to investigate the root canal system morphology of maxillary first premolars by means of micro–computed tomographic imaging in a Swiss-German population. Methods The root canal configuration (RCC) of 115 maxillary first premolars (Mx1Ps) were investigated by means of micro–computed tomographic imaging and 3-dimensional imaging. The RCC and the physiological foramina results are described by a 4-digit system code. Results Twelve different RCCs were observed in 30 single-rooted Mx1Ps; 2-2-2/2 (30.0%), 1-2-2/2 (13.3%), 1-2-1/2 (10%), and 2-2-1/2 (10.0%) were the most frequent ones. Seven different RCCs were observed in 2-rooted Mx1Ps (n = 81) in …

2016

Regulatory T cells (Treg) are essential for T cell homeostasis and maintenance of peripheral tolerance. They prevent activation of auto-reactive T effector cells (Teff) in the context of autoimmunity and allergy. Otherwise, Treg also inhibit effective immune responses against tumors. Besides a number of Treg-associated molecules such as Foxp3, CTLA-4 or GARP, known to play critical roles in Treg differentiation, activation and function, the involvement of additional regulatory elements is suggested. Herein, kinase activities seem to play an important role in Treg fine tuning. Nevertheless, our knowledge regarding the complex intracellular signaling pathways controlling phenotype and functio…

Stable radical anions generated from a porous perylenediimide metal-organic framework for boosting near-infrared photothermal conversion

2019

Radical anions of electron-deficient systems are widely used, but are easily reoxidized upon exposure to air. Therefore, the stabilization of radical anions under ambient conditions is of great significance, but still remains a scientific challenge. Herein, perylenediimide is employed to prepare a crystalline metal-organic framework for stabilizing radical anions without extensive chemical modification. The porous, three-dimensional framework of perylenediimide can trap electron donors such as amine vapors and produce radical anions in-situ through photo-induced electron transfer. The radical anions are protected against quenching by shielding effect in air and remain unobstructed in air fo…