Search results for "ECK"
showing 10 items of 2091 documents
Repeated transfer of small RNA virus populations leading to balanced fitness with infrequent stochastic drift
1996
The population dynamics of RNA viruses have an important influence on fitness variation and, in consequence, on the adaptative potential and virulence of this ubiquitous group of pathogens. Earlier work with vesicular stomatitis virus showed that large population transfers were reproducibly associated with fitness increases, whereas repeated transfers from plaque to plaque (genetic bottlenecks) lead to losses in fitness. We demonstrate here that repeated five-plaque to five-plaque passage series yield long-term fitness stability, except for occasional stochastic fitness jumps. Repeated five-plaque passages regularly alternating with two consecutive large population transmissions did not cau…
CENPA overexpression promotes genome instability in pRb-depleted human cells
2009
Abstract Background Aneuploidy is a hallmark of most human cancers that arises as a consequence of chromosomal instability and it is frequently associated with centrosome amplification. Functional inactivation of the Retinoblastoma protein (pRb) has been indicated as a cause promoting chromosomal instability as well centrosome amplification. However, the underlying molecular mechanism still remains to be clarified. Results Here we show that pRb depletion both in wild type and p53 knockout HCT116 cells was associated with the presence of multipolar spindles, anaphase bridges, lagging chromosomes and micronuclei harbouring whole chromosomes. In addition aneuploidy caused by pRb acute loss was…
Bypass of cell cycle arrest induced by transient DNMT1 post-transcriptional silencing triggers aneuploidy in human cells
2012
Abstract Background Aneuploidy has been acknowledged as a major source of genomic instability in cancer, and it is often considered the result of chromosome segregation errors including those caused by defects in genes controlling the mitotic spindle assembly, centrosome duplication and cell-cycle checkpoints. Aneuploidy and chromosomal instability has been also correlated with epigenetic alteration, however the molecular basis of this correlation is poorly understood. Results To address the functional connection existing between epigenetic changes and aneuploidy, we used RNA-interference to silence the DNMT1 gene, encoding for a highly conserved member of the DNA methyl-transferases. DNMT1…
MAD2 depletion triggers premature cellular senescence in human primary fibroblasts by activating a P53 pathway preventing aneuploid cells propagation.
2012
The spindle assembly checkpoint (SAC) is a cellular surveillance mechanism that ensures faithful chromosome segregation during mitosis and its failure can result in aneuploidy. Previously, it was suggested that reduction of the MAD2 gene, encoding a major component of the SAC, induced aneuploidy in human tumor cells. However, tumor cell lines contain multiple mutations that might affect or exacerbate the cellular response to Mad2 depletion. Thus, the scenario resulting by Mad2 depletion in primary human cells could be different and more complex that the one depicted so far. We used primary human fibroblasts (IMR90) and epithelial breast cells (MCF10A) to gain further insight on the effects …
Checkpoint adaptation in recombination-deficient cells drives aneuploidy and resistance to genotoxic agents.
2020
Abstract Human cancers frequently harbour mutations in DNA repair genes, rendering the use of DNA damaging agents as an effective therapeutic intervention. As therapy-resistant cells often arise, it is important to better understand the molecular pathways that drive resistance in order to facilitate the eventual targeting of such processes. We employ recombination-defective diploid yeast as a model to demonstrate that, in response to genotoxic challenges, nearly all cells eventually undergo checkpoint adaptation, resulting in the generation of aneuploid cells with whole chromosome losses that have acquired resistance to the initial genotoxic challenge. We demonstrate that adaptation inhibit…
Physiological Mechanisms of Treatment Resistance
2009
It is generally accepted that tumor perfusion, microcirculation, characteristics of the interstitial space of tumors, oxygen (and nutrient) supply, tissue pH distribution and the bioenergetic status—factors that are usually closely linked and that define the so-called pathophysiological microenvironment—can markedly influence the therapeutic response of malignant tumors to sparsely ionizing radiation, chemotherapy, photodynamic therapy, hormonal therapy and immunotherapy. Besides more direct mechanisms involved in the development of acquired therapeutic resistance, there are in addition, obstacles in intratumor pharmacokinetics of antitumor agents due to delivery problems caused by an inade…
New archaeological discoveries through magnetic gradiometry: The early Celtic settlement on Mont Lassois, France
2006
The burial complex of the “Lady of Vix” was discovered and excavated in the 1950s at the foot of Mont Lassois (Figure 1), a mountain situated close to the town of Chatillion-sur-Seine in the Bourgogne region of France. The assemblage of the burial goods was rather extraordinary, including such items as an artfully crafted golden necklace with winged horses and a voluminous wine-mixing vessel, probably made in a Greek workshop, capable of holding 1100 liters. According to archaeological research, this member of the aristocracy must have lived during the period between 550 and 500 BCE. Several large-scale geophysical research projects were undertaken in the vicinity of the burial complex duri…
Predicting risk and outcomes for frail older adults: an umbrella review of frailty screening tools
2017
EXECUTIVE SUMMARY Background A scoping search identified systematic reviews on diagnostic accuracy and predictive ability of frailty measures in older adults. In most cases, research was confined to specific assessment measures related to a specific clinical model. Objectives To summarize the best available evidence from systematic reviews in relation to reliability, validity, diagnostic accuracy and predictive ability of frailty measures in older adults. Inclusion criteria Population Older adults aged 60 years or older recruited from community, primary care, long-term residential care and hospitals. Index test Available frailty measures in older adults. Reference test Cardiovascular Health…
Kihon Checklist to assess frailty in older adults: Some evidence on the internal consistency and validity of the Spanish version
2021
Aim The aim of this study was to assess the internal consistency, hypothesis testing and criterion-related validity of the Spanish versions of the Kihon Checklist (KCL) - the original 25-item and reduced 15-item versions - for screening frailty in community-dwelling older adults. Methods A cross-sectional study was carried out between March and September 2018 in Valencia province (Spain). A sample of 251 participants was recruited. Construct validity was assessed using four different frailty instruments, and alternative measures corresponding to the KCL domains (handgrip strength, gait speed, the Short Physical Performance Battery, skeletal muscle mass index, physical activity level, functi…
Dimensions underlying frailty indicators in the Kihon Checklist.
2019
Aim Frailty has become a current topic of debate in recent years among researchers as a key concept of clinical care in old age. One of the scales developed for its measurement is the Kihon Checklist (KCL). However, the dimensionality of the KCL has not been tested yet, and therefore the aim of the present study was to validate its dimensional structure. Methods This was a cross-sectional study carried out between March and September 2018 in Valencia province (Spain). Participation in the study was voluntary. A total of 251 participants were sampled. They answered sociodemographic and medical indicators, as well as five frailty scales, including the KCL. Results Five confirmatory models wit…