Search results for "CELLULAR"
showing 10 items of 6449 documents
School achievement in adolescence and the risk of mental disorders in early adulthood: a Finnish nationwide register study
2023
AbstractSchool grades in adolescence have been linked to later psychiatric outcomes, but large-scale nationwide studies across the spectrum of mental disorders are scarce. In the present study, we examined the risk of a wide array of mental disorders in adulthood, as well as the risk of comorbidity, associated with school achievement in adolescence. We used population-based cohort data comprising all individuals born in Finland over the period 1980–2000 (N = 1,070,880) who were followed from age 15 or 16 until a diagnosis of mental disorder, emigration, death, or December 2017, whichever came first. Final grade average from comprehensive school was the exposure, and the first diagnosed ment…
Activation of the p38MAPK cascade is associated with upregulation of TNF alpha receptors in the spinal motor neurons of mouse models of familial ALS.
2005
Phosphorylated p38 mitogen-activated protein kinase (p38MAPK), but not activated c-jun-N-terminal kinase (JNK), increases in the motor neurons of transgenic mice overexpressing ALS-linked SOD1 mutants at different stages of the disease. This effect is associated with a selective increase of phosphorylated MKK3-6, MKK4 and ASK1 and a concomitant upregulation of the TNFalpha receptors (TNFR1 and TNFR2), but not IL1beta and Fas receptors. Activation of both p38 MAPK and JNK occurs in the activated microglial cells of SOD1 mutant mice at the advanced stage of the disease; however, this effect is not accompanied by the concomitant activation of the upstream kinases ASK1 and MKK3,4,6, while both …
Hepatocellular cancer cell lines, Hep-3B and Hep-G2 display the pleiotropic response to resveratrol and berberine
2022
Purpose Human carcinoma cells with different p53 status exposed to a combination of bioactive substances, resveratrol and berberine, revealed different responses in cell viability via p53-dependant apoptosis pathway activation. Materials and methods Using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, we investigated various and opposing effects in hepatocellular carcinoma cells, Hep-G2 and Hep-3B with different p53-status. Results Cells decreased in viability after treatment with dose-dependent concentrations of resveratrol and berberine. Hep-3B p53 mutants were more sensitive in comparison to the p53 wild type Hep-G2 cell line. A syne…
Epigenetic siRNA and Chemical Screens Identify SETD8 Inhibition as a Therapeutic Strategy for p53 Activation in High-Risk Neuroblastoma
2017
Given the paucity of druggable mutations in high-risk neuroblastoma (NB), we undertook chromatin-focused small interfering RNA and chemical screens to uncover epigenetic regulators critical for the differentiation block in high-risk NB. High-content Opera imaging identified 53 genes whose loss of expression led to a decrease in NB cell proliferation and 16 also induced differentiation. From these, the secondary chemical screen identified SETD8, the H4K20me1 methyltransferase, as a druggable NB target. Functional studies revealed that SETD8 ablation rescued the pro-apoptotic and cell-cycle arrest functions of p53 by decreasing p53K382me1, leading to activation of the p53 canonical pathway. I…
p73 deficiency results in impaired self renewal and premature neuronal differentiation of mouse neural progenitors independently of p53
2010
10 p.-5 fig.
Endoderm development requires centrioles to restrain p53-mediated apoptosis in the absence of ERK activity
2021
Centrioles comprise the heart of centrosomes, microtubule-organizing centers. To study the function of centrioles in lung and gut development, we genetically disrupted centrioles throughout the mouse endoderm. Surprisingly, removing centrioles from the endoderm did not disrupt intestinal growth or development but blocked lung branching. In the lung, acentriolar SOX2-expressing airway epithelial cells apoptosed. Loss of centrioles activated p53, and removing p53 restored survival of SOX2-expressing cells, lung branching, and mouse viability. To investigate how endodermal p53 activation specifically killed acentriolar SOX2-expressing cells, we assessed ERK, a prosurvival cue. ERK was active t…
Digital control circuitry for the p53 dynamics in cancer cell and apoptosis
2010
Abstract Experimental work and theoretical models deduce a “digital” response of the p53 transcription factor when genomic integrity is damaged. The mutual influence of p53 and its antagonist, the Mdm2 oncogene, is closed in a feedback. This paper proposes an aerospace-based architecture for translating the p53/Mdm2/DNA damage network into a digital circuitry in which the optimal control theory is applied for obtaining the requested dynamic evolutions of some considered cell species for repairing a DNA damage. The purpose of this paper is to demonstrate the usefulness of such digital circuitry design to detect and predict the cell species dynamics for shedding light on their inner and mutua…
Targeting HSP90 with the small molecule inhibitor AUY922 (luminespib) as a treatment strategy against hepatocellular carcinoma
2018
Hepatocellular carcinoma (HCC) is a highly malignant tumor that responds very poorly to existing therapies, most probably due to its extraordinary inter- and intra-tumor molecular heterogeneity. The modest therapeutic response to molecular targeted agents underlines the need for new therapeutic approaches for HCC. In our study, we took advantage of well-characterized human HCC cell lines, differing in transcriptomic subtypes, DNA mutation and amplification alterations, reflecting the heterogeneity of primary HCCs, to provide a preclinical evaluation of the specific heat shock protein 90 (HSP90) inhibitor AUY922 (luminespib). Indeed, HSP90 is highly expressed in different tumor types, but it…
Location-Awareness for Failure Management in Cellular Networks: An Integrated Approach
2021
Recent years have seen the proliferation of different techniques for outdoor and, especially, indoor positioning. Still being a field in development, localization is expected to be fully pervasive in the next few years. Although the development of such techniques is driven by the commercialization of location-based services (e.g., navigation), its application to support cellular management is considered to be a key approach for improving its resilience and performance. When different approaches have been defined for integrating location information into the failure management activities, they commonly ignore the increase in the dimensionality of the data as well as their integration into th…
A CNN Adaptive Model to Estimate PM10 Monitoring
2006
In this work we introduce a model for studying the distribution and control of atmospheric pollution from PM10. The model is based on the use of a cellular neural network (CNN) and more precisely on the integration of the mass-balance equation; at the same time it simulates the scenario regarding a planar grid describing the whole studied area (the city of Palermo) by means of a CNN and a set of Bayesian networks. The CNN allows us to define a grid system whose dynamic evolution is a redefinition of the diffusion equation that considers contributions coming from near cells for each element of the grid. Dynamics of each cell is influenced by meteorological effects and by parameters related t…