Search results for "DOMAIN"

SBEM multidomain analysis of plate bending and stretching problems

2010

A combined approach of SGBEM and conic quadratic optimization for limit analysis

2011

The static approach to evaluate the limit multiplier directly was rephrased using the Symmetric Galerkin Boundary Element Method (SGBEM) for multidomain type problems [1,2]. The present formulation couples SGBEM multidomain procedure with nonlinear optimization techniques, making use of the self-equilibrium stress equation [3-5]. This equation connects the stresses at the Gauss points of each substructure (bem-e) to plastic strains through a self-stress matrix computed in all the bem-elements of the discretized system. The analysis was performed by means of a conic quadratic optimization problem, in terms of discrete variables, and implemented using Karnak.sGbem code [6] coupled with MathLa…

Internal spring distribution for quasi brittle fracture via Symmetric Boundary Element Method

2009

Abstract In this paper the symmetric boundary element formulation is applied to the fracture mechanics problems for quasi brittle materials . The basic aim of the present work is the development and implementation of two discrete cohesive zone models using Symmetric Galerkin multi-zone Boundary Elements Method . The non-linearity at the process zone of the crack will be simulated through a discrete distribution of nodal springs whose generalized (or weighted) stiffnesses are obtainable by the cohesive forces and relative displacements modelling. This goal is reached coherently with the constitutive relation σ − Δ u that describes the interaction between mechanical and kinematical quantities…

Selective Inhibition of STAT3 with Respect to STAT1: Insights from Molecular Dynamics and Ensemble Docking Simulations

2016

STAT3 protein, which is known to be involved in cancer development, is a promising target for anticancer therapy. Successful inhibitors of STAT3 should not affect an activity of closely related protein STAT1, which makes their development challenging. The mechanisms of selectivity of several existing STAT3 inhibitors are not clear. In this work, we studied molecular mechanisms of selectivity of 13 experimentally tested STAT3 inhibitors by means of extensive molecular dynamics and ensemble docking simulations. It is shown that all studied inhibitors bind to the large part of the protein surface in an unspecific statistical manner. The binding to the dimerization interface of the SH2 domain, …

Parthenolide sensitizes hepatocellular carcinoma cells to trail by inducing the expression of death receptors through inhibition of STAT3 activation

2011

This article shows that HepG2, Hep3B, and SK-Hep1 cells, three lines of human hepatocellular carcinoma (HCC) cells, are resistant to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Parthenolide, a sesquiterpene lactone found in European feverfew, has been shown to exert both anti-inflammatory and anti-cancer activities. This article demonstrates that co-treatment with parthenolide and TRAIL-induced apoptosis with synergistic interactions in the three lines of HCC cells. In order to explain these effects we ascertained that parthenolide increased either at protein or mRNA level the total content of death receptors TRAIL-R1 and -R2 as well as their surfac…

Induction of tolerogenic lung CD4+ T cells by local treatment with a pSTAT-3 and pSTAT-5 inhibitor ameliorated experimental allergic asthma.

2010

Signal transducer and activator of transcription (STAT)-3 inhibitors play an important role in regulating immune responses. Galiellalactone (GL) is a fungal secondary metabolite known to interfere with the binding of phosphorylated signal transducer and activator of transcription (pSTAT)-3 as well of pSTAT-6 dimers to their target DNA in vitro. Intra nasal delivery of 50 μg GL into the lung of naive Balb/c mice induced FoxP3 expression locally and IL-10 production and IL-12p40 in RNA expression in the airways in vivo. In a murine model of allergic asthma, GL significantly suppressed the cardinal features of asthma, such as airway hyperresponsiveness, eosinophilia and mucus production, after…

Yeast karyopherins Kap123 and Kap95 are related to the function of the cell integrity pathway

2009

The characterization of mutant strains in the gene encoding karyopherin Kap123 has revealed several morphogenetic defects. Inactivation of KAP123 caused alterations in the actin cytoskeleton, resulting in hyperpolarization and resistance to the actin polymerization inhibitor latrunculin B. In fact, the level of actin filaments is increased in kap123 mutant cells. In addition to the defect in actin cytoskeleton, the kap123 mutant cells showed a weakened cell wall, cell lysis and a growth defect in either the presence of sodium dodecyl sulfate or at high temperatures, which is alleviated by osmotic stabilizers. These defects in cell integrity and the actin cytoskeleton suggested a relationshi…

Bromodomain factor 1 (Bdf1) protein interacts with histones

2001

AbstractUsing a yeast two-hybrid assay we detected an interaction between the N-terminal region of histone H4 (amino acids 1–59) and a fragment of the bromodomain factor 1 protein (Bdf1p) (amino acids 304–571) that includes one of the two bromodomains of this protein. No interaction was observed using fragments of histone H4 sequence smaller than the first 59 amino acids. Recombinant Bdf1p (rBdf1p) demonstrates binding affinity for histones H4 and H3 but not H2A and H2B in vitro. Moreover, rBdf1p is able to bind histones H3 and H4 having different degrees of acetylation. Finally, we have not detected histone acetyltransferase activity associated with Bdf1p.

The C-terminal region of the Hot1 transcription factor binds GGGACAAA-related sequences in the promoter of its target genes

2015

Response to hyperosmotic stress in the yeast Saccharomyces cerevisiae involves the participation of the general stress response mediated by Msn2/4 transcription factors and the HOG pathway. One of the transcription factors activated through this pathway is Hot1, which contributes to the control of the expression of several genes involved in glycerol synthesis and flux, or in other functions related to adaptation to adverse conditions. This work provides new data about the interaction mechanism of this transcription factor with DNA. By means of one-hybrid and electrophoretic mobility assays, we demonstrate that the C-terminal region, which corresponds to amino acids 610-719, is the DNA-bindi…

Lateral reorganization of plasma membrane is involved in the yeast resistance to severe dehydration

2010

International audience; In this study, we investigated the kinetic and the magnitude of dehydrations on yeast plasma membrane (PM) modifications because this parameter is crucial to cell survival. Functional (permeability) and structural (morphology, ultrastructure, and distribution of the protein Sur7-GFP contained in sterol-rich membrane microdomains) PM modifications were investigated by confocal and electron microscopy after progressive (non-lethal) and rapid (lethal) hyperosmotic perturbations. Rapid cell dehydration induced the formation of many PM invaginations followed by membrane internalization of low sterol content PM regions with time. Permeabilization of the plasma membrane occ…