Search results for " DAMAGE"
showing 10 items of 1139 documents
“Mitotic Slippage” and Extranuclear DNA in Cancer Chemoresistance: A Focus on Telomeres
2020
Mitotic slippage (MS), the incomplete mitosis that results in a doubled genome in interphase, is a typical response of TP53-mutant tumors resistant to genotoxic therapy. These polyploidized cells display premature senescence and sort the damaged DNA into the cytoplasm. In this study, we explored MS in the MDA-MB-231 cell line treated with doxorubicin (DOX). We found selective release into the cytoplasm of telomere fragments enriched in telomerase reverse transcriptase (hTERT), telomere capping protein TRF2, and DNA double-strand breaks marked by γH2AX, in association with ubiquitin-binding protein SQSTM1/p62. This occurs along with the alternative lengthening of telomeres (ALT) and DNA repa…
Multiple Sclerosis Therapy Consensus Group (MSTCG): position statement on disease-modifying therapies for multiple sclerosis (white paper)
2021
Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particular…
Evaluation of carotenoids and furosine content in air dried carrots and parsnips pre-treated with pulsed electric field (PEF)
2019
Carrot and parsnip slices were subjected to hot drying at 50, 60 and 70 °C with or without pulsed electric field (PEF) pre-treatment at 0.9 kV/cm and 1000 and 10,000 pulses. The effect of drying on processed samples was assessed by analysis of carotenoids, the furosine value, total phenols and the Whiteness Index (WI). PEF pre-treatment is effective in reducing drying times, but the degree of cellular breakdown makes the compounds more susceptible to chemical and enzymatic reactions. In our condition PEF pre-treatment increased the carotenoid degradation and promoted the Maillard reaction above all at the highest temperature of 70 °C. The assessment of carotenoid stability, together with th…
Detection of damage in civil engineering structures by PCA on enviromental vibration data
2018
The dynamic behavior of civil engineering structures are usually studied by means of ambient vibration observations and their performance is analyzed by Peak Picking and/or Operational Modal Analysis methods. This paper reports the first results of a statistical multivariate approach, specifically Principal Component Analysis, to detect a suspected structural damage on a sicilian highway bridge. Furthermore, the damage simulated in a simple structural model made it possible to understand the characteristics of the method consisting in comparing the observed data on an undamaged structure with those coming from a damaged one.
Nonlocal Elastic-Damage Models
2014
A theory of nonlocal isotropic damage for elastic quasi-brittle materials is presented under the assumption of isothermal conditions and small deformations. Key ingredients of this theory are a self-adjoint (regularization) operator which transforms a local field into a related nonlocal one while preserves uniform fields and a free energy which depends on the strain and (linearly) on the nonlocal damage variable, as well as on an (scalar) internal variable accounting for the damage hardening. The relevant thermodynamic restrictions on the constitutive equations are obtained by means of two alternative procedures, one based on the principle of virtual power and the other on the concept of “n…
Damage Indices and Photogrammetry for Decay Assessment of Stone-Built Cultural Heritage: The Case Study of the San Domenico Church Main Entrance Port…
2020
In recent decades, increasing attention is being paid to the multidisciplinary approach that allows the performance of both a preventive conservation and a more invasive restoration action. In this context, the present study aims to acquire information and data from field surveys undertaken in San Domenico Church, Southern Calabria, in order to provide a tool for the recording and the inventory of damage and decay phenomena, and assess their causes and scale. The subsequent calculation of damage indices also provided useful information in order to allow the prioritization of conservation and preservation responses.
Cytocidal effects of Escherichia coli hemolysin on human T lymphocytes.
1993
Escherichia coli hemolysin is the prototype of a large family of pore-forming toxins produced by gram-negative organisms. Besides its known cytotoxic activities against granulocytes, monocytes, endothelial cells, and renal epithelial cells, we now demonstrate that the toxin potently kills human T lymphocytes. Evidence based on different and independent approaches indicates that lymphocidal activity is due to formation of transmembrane pores. Additionally, cells prestimulated with phytohemagglutinin respond to low doses of E. coli hemolysin with DNA fragmentation similar to that observed in cells undergoing programmed cell death. Kinetic considerations lead us to conclude that DNA degradatio…
Molecular mechanisms of rosmarinic acid from Salvia miltiorrhiza in acute lymphoblastic leukemia cells
2015
Abstract Ethnopharmacological relevance Rosmarinic acid (RA), a major hydrosoluble bioactive compound found in the Chinese medicinal herb, Salvia miltiorrhiza Bunge, which has been used in traditional Chinese medicine to treat various diseases, including cancer. However, the mechanisms have not been fully elucidated. Aim of the study Guided by microarray hybridization and Ingenuity Pathway Analysis, we identified modes of action of rosmarinic acid (RA) isolated from S. miltiorrhiza on acute lymphoblastic leukemia cells. Materials and methods Microarray data were verified by independent methods: Real-time RT-PCR (mRNA expression), resazurin assay (cytotoxicity of RA towards parental CCRF-CEM…
Cell fate regulation upon DNA damage : p53 Serine 46 kinases pave the cell death road
2019
Mild and massive DNA damage are differentially integrated into the cellular signaling networks and, in consequence, provoke different cell fate decisions. After mild damage, the tumor suppressor p53 directs the cellular response to cell cycle arrest, DNA repair, and cell survival, whereas upon severe damage, p53 drives the cell death response. One posttranslational modification of p53, phosphorylation at Serine 46, selectively occurs after severe DNA damage and is envisioned as a marker of the cell death response. However, the molecular mechanism of action of the p53 Ser46 phospho-isomer, the molecular timing of this phosphorylation event, and its activating effects on apoptosis and ferropt…
DNA damage-induced cell death by apoptosis
2006
Following the induction of DNA damage, a prominent route of cell inactivation is apoptosis. During the last ten years, specific DNA lesions that trigger apoptosis have been identified. These include O6-methylguanine, base N-alkylations, bulky DNA adducts, DNA cross-links and DNA double-strand breaks (DSBs). Repair of these lesions are important in preventing apoptosis. An exception is O6-methylguanine-thymine lesions, which require mismatch repair for triggering apoptosis. Apoptosis induced by many chemical genotoxins is the consequence of blockage of DNA replication, which leads to collapse of replication forks and DSB formation. These DSBs are thought to be crucial downstream apoptosis-tr…