Search results for " Damage"
showing 10 items of 1139 documents
Destabilized green fluorescent protein detects rapid removal of transcription blocks after genotoxic exposure
2007
High stabilities of reporter proteins and their messenger RNAs (mRNAs) interfere with the detection of rapid transient changes in gene expression, such as transcriptional blocks posed by genotoxic DNA lesions. We have modified a green fluorescent protein (GFP) gene within the episomal pMARS vector by addition of a fragment encoding for mouse ornithine decarboxylase (ODC) proline-glutamate-serine-threonine-rich (PEST) sequence in order to target the protein to the proteasomes and achieved an unprecedentedly fast GFP turnover in permanently transfected human cells. As early as 1 h after inhibition of protein synthesis by cycloheximide, the number of fluorescent cells decreased more than 5-fo…
Transcription, apoptosis and p53: catch-22
2005
The tumor suppressor p53 is a transcription factor and is activated in response to DNA damage or oncogenic transformation through modification of its interaction with regulatory proteins. The transcription factor activity of p53 is thought to mediate its primary functions of cell-cycle arrest and apoptosis through the gene expression it regulates, and evidence to support this interpretation continues to accumulate. However, reports of transcription-independent activities of p53, especially in the induction of apoptosis, persist. In particular, recent studies suggest that cytosolic p53 directly interacts with members of the BCL-2 family of apoptosis regulators, thereby triggering mitochondri…
The repair of oxidized purines in the DNA of human lymphocytes requires an activation involving NF-YA-mediated upregulation of OGG1.
2014
8-Oxoguanine DNA glycosylase (OGG1), which initiates the repair of DNA purine modifications such as 8-oxo-7,8-dihydroguanine (8-oxoG), is often regarded as a house keeping protein ubiquitously active in mammalian cells. We have analysed the repair rates of oxidized purines generated by photosensitization in peripheral human lymphocytes and observed that the cells were virtually unable to remove these lesions (less than 10% removal within 24h). However, stimulation of the lymphocytes with phytohemagglutinin (PHA) strongly accelerated the repair so that ∼30% of the lesions were repaired within 4h. Within 24h following PHA stimulation and preceding the induction of cell proliferation, Western …
Protease-mediated processing of Argonaute proteins controls small RNA association
2020
SummarySmall RNA pathways defend the germlines of animals against selfish genetic elements and help to maintain genomic integrity. At the same time, their activity needs to be well-controlled to prevent silencing of ‘self’ genes. Here, we reveal a proteolytic mechanism that controls endogenous small interfering (22G) RNA activity in the Caenorhabditis elegans germline to protect genome integrity and maintain fertility. We find that WAGO-1 and WAGO-3 Argonaute (Ago) proteins are matured through proteolytic processing of their unusually proline-rich N-termini. In the absence of DPF-3, a P-granule-localized N-terminal dipeptidase orthologous to mammalian DPP8/9, processing fails, causing a cha…
A computational framework for coating fatigue analysis of wind turbine blades due to rain erosion
2021
Author's accepted manuscript The rain-induced fatigue damage in the wind turbine blade coating has attracted increasing attention owing to significant repair and maintenance costs. The present paper develops an improved computational framework for analyzing the wind turbine blade coating fatigue induced by rain erosion. The paper first presents an extended stochastic rain field simulation model that considers different raindrop shapes (spherical, flat, and spindle), raindrop sizes, impact angles, and impact speeds. The influence of these raindrop characteristics on the impact stress of the blade coating is investigated by a smoothed particle hydrodynamics approach. To address the expensive …
Pyrrolo[2,3-h]quinolinones: A new ring system with potent photoantiproliferative activity
2006
A new class of compounds, the pyrrolo[2,3-h]quinolin-2-ones, nitrogen isosters of the angular furocoumarin Angelicin, was synthesized with the aim of obtaining new photochemotherapeutic agents with increased antiproliferative activity and lower undesired toxic effects than the lead compound. Two synthetic pathways were approached to allow the isolation both of the dihydroderivatives 10-17 and of the aromatic ring system 23. Compounds 10-17 showed a remarkable phototoxicity and a great UVA dose dependence reaching IC(50) values at submicromolar level. Intracellular localization of these compounds has been evaluated by means of fluorescence microscopy using tetramethylrhodamine methyl ester a…
ESTIMATED AND EXPERIMENTAL FATIGUE LIVES OF 30CrNiMo8 STEEL UNDER IN-AND OUT-OF-PHASE COMBINED BENDING AND TORSION WITH VARIABLE AMPLITUDES
2007
Abstract— Calculated fatigue lives, based on three criteria for multiaxial random fatigue, were compared with lives obtained from tests on cylindrical specimens of 30CrNiMo8 steel subjected to in- and out-of-phase bending and torsion at variable amplitudes. In the chosen fatigue criteria the expected position of the fracture plane, determined from a variance method for the equivalent stress, were taken into account. The equivalent stress history was related to the rain flow method and fatigue damage was evaluated from the Palmgren–Miner hypothesis. It has been shown that the expected fatigue fracture planes agree with those determined by experiments. The most realistic estimations of fatigu…
Advance in Vascular Phenotype Assessment in Children and Adolescents
2010
Cardiovascular damage occurring in adults finds its roots in risk factors operating early in life. Among the factors influencing cardiovascular risk, blood pressure values represent an important measurable marker of the level of potential cardiovascular risk in children and adolescents. Indeed, there is growing evidence that mild blood pressure elevations are much more common than was thought in the past in a pediatric population. Furthermore, hypertension in childhood has gained ground in cardiovascular medicine thanks to the progress made in several areas of pathophysiological and clinical research.1 It is not uncommon for high blood pressure in the young to be accompanied by evidence of …
Ventilation, oxidative stress and risk of brain injury in preterm newborn
2020
AbstractPreterm infants have an increased risk of cognitive and behavioral deficits and cerebral palsy compared to term born babies. Especially before 32 weeks of gestation, infants may require respiratory support, but at the same time, ventilation is known to induce oxidative stress, increasing the risk of brain injury. Ventilation may cause brain damage through two pathways: localized cerebral inflammatory response and hemodynamic instability. During ventilation, the most important causes of pro-inflammatory cytokine release are oxygen toxicity, barotrauma and volutrauma. The purpose of this review was to analyze the mechanism of ventilation-induced lung injury (VILI) and the relationship…
Challenging Dogma: Thresholds for Genotoxic Carcinogens? The Case of Vinyl Acetate
2002
Although many questions remain unanswered, the general principle of the sequence of events leading to cancer after exposure to genotoxic carcinogens has become increasingly clear. This helps to understand the parameters that influence the shape of the dose-effect curve for carcinogenesis, including metabolic activation and inactivation of carcinogens, DNA repair, cell cycle control, apoptosis, and control by the immune system. A linear dose-response relationship with no observable threshold seems to be a conservative but adequate description for the carcinogenic activity of many genotoxic carcinogens, such as aflatoxin B1, the tobacco-specific nitrosoketone NNK, and probably N,N-diethylnit…