Search results for " trip"

Decipher the mechanisms of protein conformational changes induced by nucleotide binding through free-energy landscape analysis: ATP binding to Hsp70.

2013

ATP regulates the function of many proteins in the cell by transducing its binding and hydrolysis energies into protein conformational changes by mechanisms which are challenging to identify at the atomic scale. Based on molecular dynamics (MD) simulations, a method is proposed to analyze the structural changes induced by ATP binding to a protein by computing the effective free-energy landscape (FEL) of a subset of its coordinates along its amino-acid sequence. The method is applied to characterize the mechanism by which the binding of ATP to the nucleotide-binding domain (NBD) of Hsp70 propagates a signal to its substrate-binding domain (SBD). Unbiased MD simulations were performed for Hsp…

"La fonte d'acqua dolce nella storia di Tripoli d'Occidente" di Ahmad Bey al-Na'ib al-Ansari: un esempio di storiografia arabo-ottomana di fine Ottoc…

2005

Neuronal Bioenergetics and Acute Mitochondrial Dysfunction: A Clue to Understanding the Central Nervous System Side Effects of Efavirenz

2014

Background. Neurological pathogenesis is associated with mitochondrial dysfunction and differences in neuronal/glial handling of oxygen and glucose. The main side effects attributed to efavirenz involve the CNS, but the underlying mechanisms are unclear. Methods. Human cell lines and rat primary cultures of neurons and astrocytes were treated with clinically relevant efavirenz concentration. Results. Efavirenz alters mitochondrial respiration, enhances reactive oxygen species generation, undermines mitochondrial membrane potential, and reduces adenosine triphosphate (ATP) levels in a concentration-dependent fashion in both neurons and glial cells. However, it activates adenosine monophospha…

Inhibition of Mitochondrial Function by Efavirenz Increases Lipid Content in Hepatic Cells

2010

Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) widely used in human immunodeficiency virus (HIV) infection therapy. It has been associated with hepatotoxic effects and alterations in lipid and body fat composition. Given the importance of the liver in lipid regulation, we have evaluated the effects of clinically used concentrations of EFV on the mitochondria and lipid metabolism of human hepatic cells in vitro. Mitochondrial function was rapidly undermined by EFV to an extent that varied with the concentration employed; in particular, respiration and intracellular adenosine triphosphate (ATP) levels were reduced whereas reactive oxygen species (ROS) production i…

Nuclear Translocation of Mismatch Repair Proteins MSH2 and MSH6 as a Response of Cells to Alkylating Agents

2000

Mammalian mismatch repair has been implicated in mismatch correction, the prevention of mutagenesis and cancer, and the induction of genotoxicity and apoptosis. Here, we show that treatment of cells specifically with agents inducing O(6)-methylguanine in DNA, such as N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N-nitrosourea, elevates the level of MSH2 and MSH6 and increases GT mismatch binding activity in the nucleus. This inducible response occurs immediately after alkylation, is long-lasting and dose-dependent, and results from translocation of the preformed MutSalpha complex (composed of MSH2 and MSH6) from the cytoplasm into the nucleus. It is not caused by an increase in MSH2 gen…

Regulation of ribonucleotide reductase in response to iron deficiency

2011

Ribonucleotide reductase (RNR) is an essential enzyme required for DNA synthesis and repair. Although iron is necessary for class Ia RNR activity, little is known about the mechanisms that control RNR in response to iron deficiency. In this work, we demonstrate that yeast cells control RNR function during iron deficiency by redistributing the Rnr2–Rnr4 small subunit from the nucleus to the cytoplasm. Our data support a Mec1/Rad53-independent mechanism in which the iron-regulated Cth1/Cth2 mRNA-binding proteins specifically interact with the WTM1 mRNA in response to iron scarcity, and promote its degradation. The resulting decrease in the nuclear-anchoring Wtm1 protein levels leads to the re…

Differential salinity-induced variations in the activity of H+-pumps and Na+/H+ antiporters that are involved in cytoplasm ion homeostasis as a funct…

2011

The characterisation of cellular responses to salinity in staple crops is necessary for the reliable identification of physiological markers of salinity tolerance. Under saline conditions, variations in proton gradients that are generated by membrane-bound H⁺ pumps are crucial for maintaining cytoplasm homeostasis. We examined short (15 h) and longer term effects (4 days) of NaCl stress on the H⁺ pumping activities that are associated with the plasma membrane (P-ATPase) and the tonoplast (V-ATPase and V-PPase) in rice (Oryza sativa L.) callus lines that displayed different levels of NaCl tolerance and were established from two japonica rice cultivars. The applied stress conditions were base…

Impaired Transporter Associated with Antigen Processing (TAP) Function Attributable to a Single Amino Acid Alteration in the Peptide TAP Subunit TAP1

2003

Abstract The heterodimeric peptide transporter TAP belongs to the ABC transporter family. Sequence comparisons with the P-glycoprotein and cystic fibrosis transmembrane conductance regulator and the functional properties of selective amino acids in these ABC transporters postulated that the glutamic acid at position 263 and the phenylalanine at position 265 of the TAP1 subunit could affect peptide transporter function. To define the role of both amino acids, TAP1 mutants containing a deletion or a substitution to alanine at position 263 or 265 were generated and stably expressed in murine and human TAP1−/− cells. The different TAP1 mutants were characterized in terms of expression and funct…

Impact des allocations en ressources sur l'efficacité des écoles primaires en Côte d'Ivoire

2011

The quality of primary education in Côte d'Ivoire has deteriorated sharply over the past three decades. This situation is the result of an approximate management of the education system, which is characterized by a lack of educational support, a misallocation of resources, a congestion of classrooms (42 students for a teacher in primary school) and a lack of skilled and well trained teachers. In addition, the military-political conflict in September 2002 did not allow to improve this situation; on the contrary, it has further deteriorated the situation. Thus, the aim of this thesis is first to analyze the influence of resource endowments on the effectiveness of primary schools in Cote d'Ivo…

Chromatin remodeling regulation by small molecules and metabolites.

2010

The eukaryotic genome is a highly organized nucleoprotein structure comprising of DNA, histones, non-histone proteins, and RNAs, referred to as chromatin. The chromatin exists as a dynamic entity, shuttling between the open and closed forms at specific nuclear regions and loci based on the requirement of the cell. This dynamicity is essential for the various DNA-templated phenomena like transcription, replication, and repair and is achieved through the activity of ATP-dependent chromatin remodeling complexes and covalent modifiers of chromatin. A growing body of data indicates that chromatin enzymatic activities are finely and specifically regulated by a variety of small molecules derived f…