Search results for "BLAST"
showing 10 items of 2136 documents
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 …
High resistance to X-rays and therapeutic carbon ions in glioblastoma cells bearing dysfunctional ATM associates with intrinsic chromosomal instabili…
2014
To investigate chromosomal instability and radiation response mechanisms in glioblastoma cells.We undertook a comparative analysis of two patient-derived glioblastoma cell lines. Their resistance to low and high linear energy transfer (LET) radiation was assessed using clonogenic survival assay and their intrinsic chromosome instability status using fluorescence in situ hybridization. DNA damage was analyzed by pulsed-field gel electrophoresis and by γ-H2AX foci quantification. Expression of DNA damage response proteins was assessed by immunoblot.Increased radioresistance to X-rays as well as carbon ions was observed in glioblastoma cells exhibiting high levels of naturally occurring chromo…
Functional and genetic characterization of the non-lysosomal glucosylceramidase 2 as a modifier for Gaucher disease.
2013
Background: Gaucher disease (GD) is the most common inherited lysosomal storage disorder in humans, caused by mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GBA1). GD is clinically heterogeneous and although the type of GBA1 mutation plays a role in determining the type of GD, it does not explain the clinical variability seen among patients. Cumulative evidence from recent studies suggests that GBA2 could play a role in the pathogenesis of GD and potentially interacts with GBA1. Methods: We used a framework of functional and genetic approaches in order to further characterize a potential role of GBA2 in GD. Glucosylceramide (GlcCer) levels in spleen, liver and brain…
Yunis-Varón Syndrome Is Caused by Mutations in FIG4, Encoding a Phosphoinositide Phosphatase
2013
Yunis-Varón syndrome (YVS) is an autosomal-recessive disorder with cleidocranial dysplasia, digital anomalies, and severe neurological involvement. Enlarged vacuoles are found in neurons, muscle, and cartilage. By whole-exome sequencing, we identified frameshift and missense mutations of FIG4 in affected individuals from three unrelated families. FIG4 encodes a phosphoinositide phosphatase required for regulation of PI(3,5)P(2) levels, and thus endosomal trafficking and autophagy. In a functional assay, both missense substitutions failed to correct the vacuolar phenotype of Fig4-null mouse fibroblasts. Homozygous Fig4-null mice exhibit features of YVS, including neurodegeneration and enlarg…
Effects of mechanical stimulation on cell cycle duration in rat gingival fibroblast progenitor cells
2001
The aim of this investigation was to estimate cell cycle duration in rat gingival fibroblast progenitor cells in steady-state control and during sustained mechanical stimulation. Elastics (0.15 mm thick) were inserted between maxillary M1 and M2 of 8 wk-old male rats which were labelled with H3-TdR and killed in groups of 6-7 animals together with equal-sized groups of labelled control animals at intervals between 1-168 h. Autoradiographs of consecutive mesio-distal sections were used to determine grain counts for H3-TdR-labelled cells in the connective tissue of the gingival papilla between M2 and M3. Median cell cycle times (MCC) were estimated from plots of mean and median grain counts a…
Adult Neurogenesis in Reptiles
2011
Adult neurogenesis in reptiles is a well-documented phenomenon and exists in many telencephalic areas. The newly generated neurons originate along the walls of the lateral ventricles, mainly in the sulci. The putative neural progenitors are radial glial cells. These glial cells give rise to neuroblasts that migrate to their final destination. In general, the new neurons are born in the portion of the ventricular zone (VZ) adjacent to the telencephalic area where they will be recruited and migrate radially through the brain parenchyma along the processes of radial glial cells to their final destination, although migration to the olfactory bulbs (OB) is different. Specifically, it seems that …
Migrating neuroblasts of the rostral migratory stream are putative targets for the action of nitric oxide
2007
It has been demonstrated that the gaseous messenger nitric oxide influences cell proliferation and cell migration, and therefore affects adult neurogenesis in mammals. Here, we investigated the putative targets for this action in the rostral migratory stream of the rat. We used immunocytochemical detection of the beta1 subunit of the enzyme soluble guanylyl cyclase, which can be activated by nitric oxide. Our results under light and electron microscopy demonstrated that the migrating neuroblasts (type A cells) were beta1-immunopositive. The astrocytes (type B cells), immature precursors (type C cells) and ependymal cells (type E cells) were beta1-immunonegative. The neurochemical characteri…
Isolation and characterization of a 60-70-kD plasma membrane glycoprotein involved in the contact-dependent inhibition of growth
1990
Previous studies have shown that plasma membrane compounds are involved in the contact-dependent inhibition of growth of human diploid fibroblasts. The purification of the active plasma membrane glycoprotein is described in this report. The glycoprotein has an apparent molecular mass of 60-70 kD and, due to differential sialylation, isoelectric points between pH 5.5. and 6.2. Treatment with sialidase yielded one spot in two-dimensional gel electrophoresis with an isoelectric point of 6.3. After removal of the N-glycosidically linked oligosaccharide chains, the apparent molecular mass is reduced by approximately 22 kD. Treatment was diluted NaOH, which removes the O-glycosidically linked por…
Contact-dependent inhibition of growth of normal diploid human fibroblasts by plasma membrane glycoproteins.
1988
Homeostasis in vivo is maintained by a highly complex network of positive and negative signals. At the cellular level, this regulatory microenvironment can be divided, in a simplified fashion, into two major compartments: the humoral compartment, including compounds such as hormones, growth factors and nutrients, and the contact-environment compartment, including cell-cell and cell-matrix interactions. At least in cultures of diploid, non-transformed cells, cell-cell and cell-matrix interactions have been shown to be of major importance for the regulation of growth as well as of differentiation. Although until now the glycoprotein involved in the contact-dependent inhibition of growth has n…
Cohen syndrome is associated with major glycosylation defects
2014
International audience; Cohen syndrome (CS) is a rare autosomal recessive disorder with multisytemic clinical features due to mutations in the VPS13B gene, which has recently been described encoding a mandatory membrane protein involved in Golgi integrity. As the Golgi complex is the place where glycosylation of newly synthesized proteins occurs, we hypothesized that VPS13B deficiency, responsible of Golgi apparatus disturbance, could lead to glycosylation defects and/or mysfunction of this organelle, and thus be a cause of the main clinical manifestations of CS. The glycosylation status of CS serum proteins showed a very unusual pattern of glycosylation characterized by a significant accum…