Search results for "Instability"

Coherent master equation for laser modelocking

2020

Modelocked lasers constitute the fundamental source of optically-coherent ultrashort-pulsed radiation, with huge impact in science and technology. Their modeling largely rests on the master equation (ME) approach introduced in 1975 by Hermann A. Haus. However, that description fails when the medium dynamics is fast and, ultimately, when light-matter quantum coherence is relevant. Here we set a rigorous and general ME framework, the coherent ME (CME), that overcomes both limitations. The CME predicts strong deviations from Haus ME, which we substantiate through an amplitude-modulated semiconductor laser experiment. Accounting for coherent effects, like the Risken-Nummedal-Graham-Haken multim…

The dual role of p53: DNA protection and antioxidant.

2011

The classical functions of p53 protein are those related to its role on DNA damage, cell growth arrest, senescence and apoptosis. For this reason it is called 'the guardian of the genome' and is considered one of the most important players in the development of cancer. However, more recently it has been show that p53 is not only involved in cancer, but also in ageing. p53 is stimulated by stress, which in turn results in the activation of a wide range of transcriptional targets. Low-intensity stress will activate p53 in a manner which results in antioxidant response, thus protecting against ageing because of its antioxidant function. On the contrary, high-intensity activation of p53 will re…

Fifteen years’ experience treating cells with inorganic arsenic, a molecule able to induce genetic / genomic instability and epigenetic changes even …

2016

Treating V79-Cl3 cells with 10 µM sodium arsenite (SA) for 24h we observed severe alterations in spindle morphology and aneuploidy; treating rat astrocytes with SA we detected HSP70 induction and DNA damage. We assumed that SA induced in dividing cells early genetic instability. Subsequently, we in vitro stabilized those V79-Cl3 cells dividing at the end of SA-treatment and maintained for long without SA (ASO cells). In ASO cells, we observed chromosomal rearrangements, increased spontaneous mutations, genome-wide DNA hypomethylation (GWDH), similarly to exposed cells. We inferred that a short-term SA exposure has long-term effects and that GWDH enhances the genetic instability. Consequentl…

Persistent genomic instability by arsenic exposure in V79 Chinese hamster cells

2006

Previously, we demonstrated that acute treatment with arsenic leads mammalian cells to exhibit persistent chromosomal instability and DNA hypomethylation, by performing investigations after about 2 months of subculturing. In order to evaluate quantitatively the continuing instability during the expanded growth, we carried out cytogenetic, morphologic and molecular analyses immediately after exposure and every week up to 112 cell generations. Briefly, V79 Chinese hamster cells were treated with 10 µM sodium arsenite (SA) for 24h; at the end of exposure, mitotic rounded-up cells were harvested by shake-off and allowed to grow in drug-free medium. The instability markers, micronucleated and mu…

Persistent dysregulation of DNA methylation in cells with arsenic-induced genomic instability

2009

The mechanisms by which arsenic-induced genomic instability is initiated and maintained are poorly understood. In previous studies long-term progression of chromosomal instability was typified by increasing aneuploidy in Chinese hamster V79 and human keratinocyte cells treated with arsenite for a 24 hr exposure period followed by growth in arsenic-free medium for 40-120 cell generations. In the current study the role of progressive DNA methylation changes was evaluated in long-term cell cultures after brief arsenite treatments as above. We have found altered genomic methylation patterns in cells that were briefly exposed to arsenic with evidence for widespread dysregulation of CpG methylati…

Identification of molecular markers involved in cellular response to aneuploidy in normal and tumor cells

2020

Long-term exposure to submicromolar arsenite induces bypass of the spindle assembly checkpoint in mammalian cells

2008

Mitosis is regulated by checkpoints that delay mitotic progression when chromosome segregation errors occur. Inaccuracy in checkpoint processes can lead to chromosome instability both in number and structure (CIN). Arsenic is reported to induce CIN by perturbing mitotic spindles and checkpoints, however, its carcinogenic mechanisms are poorly understood. We previously studied the long-term progression of chromosomal instability in V79 cells treated acutely with arsenite (10 M, 24 hr) followed by growth in arsenic-free medium for 120 cell generations, and found time-dependent increase of aneuploid cells. Here, we treated V79-derived G12 cells with sub-lethal doses (0.1-1.0 µM) of arsenite f…

DNA DEMETHYLATION CAUSED BY 5-AZA-2’-DEOXYCYTIDINE TREATMENT AFFECTS GENOME STABILITY BY INDUCING MITOTIC ALTERATIONS AND ANEUPLOIDY IN HCT-116 TUMOR…

2014

FANCD2 promotes mitotic rescue from transcription-mediated replication stress in SETX-deficient cancer cells

2022

AbstractReplication stress (RS) is a leading cause of genome instability and cancer development. A substantial source of endogenous RS originates from the encounter between the transcription and replication machineries operating on the same DNA template. This occurs predominantly under specific contexts, such as oncogene activation, metabolic stress, or a deficiency in proteins that specifically act to prevent or resolve those transcription-replication conflicts (TRCs). One such protein is Senataxin (SETX), an RNA:DNA helicase involved in resolution of TRCs and R-loops. Here we identify a synthetic lethal interaction between SETX and proteins of the Fanconi anemia (FA) pathway. Depletion of…

Hysteretic whirl stabilization in rotor-shaft-bearing systems on dry friction suspension

2009

SUMMARY. The undesired whirl of rotating machines can be reduced by elastic journal box suspension systems equipped with dry friction dampers. The critical speeds can be cut off by the adhesion of the friction surfaces and the whirl amplitude can be restrained throughout the remaining sliding range by a proper choice of the suspension-to-shaft stiffness ratio and of the support-to-rotor mass ratio. The dry friction forces counteract also efficiently the well known destabilising effect of the shaft hysteresis in the supercritical range. This lecture deals firstly with the natural precession speeds, investigates the steady response to unbalance and defines the ranges of adhesive or sliding co…