Doxorubicin and the ERBB2 targeted therapy, trastuzumab, are routinely used in the treatment of HER2+ breast cancer. In mouse models, doxorubicin is known to cause cardiomyopathy and conditional cardiac knock out of Erbb2 results in dilated cardiomyopathy and increased sensitivity to doxorubicin-induced cell death. In humans, these drugs also result in cardiac phenotypes, but severity and rever...

Frataxin (FXN) is an α/β protein that plays an essential role in iron homeostasis. Apparently, the function of human FXN (hFXN) depends on the cooperative formation of crucial interactions between helix α1, helix α2, and the C-terminal region (CTR) of the protein. In this work we quantitatively explore these relationships using a purified recombinant fragment hFXN90-195. This variant shows the ...

Background Friedreich's ataxia (FA) is a rare autosomal recessive mitochondrial disease most commonly due to triplet repeat expansion guanine-adenine-adenine (GAA) in the FXN gene. Cardiac major cause of death, patients with reduced left ventricular ejection fraction (LVEF) having worse prognosis. Longitudinal strain (LS) appeared be better predictor outcome than LVEF different diseases. We com...

Friedreich's ataxia results from a deficiency in the mitochondrial protein frataxin, which carries single point mutations in some patients. In the present study, we analysed the consequences of different disease-related mutations in vitro on the stability and dynamics of human frataxin. Two of the mutations, G130V and D122Y, were investigated for the first time. Analysis by CD spectroscopy demo...

Direct coupling analysis (DCA) is a powerful statistical inference tool used to study protein evolution. It was introduced to predict protein folds and protein-protein interactions, and has also been applied to the prediction of entire interactomes. Here, we have used it to analyze three proteins of the iron-sulfur biogenesis machine, an essential metabolic pathway conserved in all organisms. W...

Friedreich's ataxia is caused by a deficit in frataxin, a small mitochondrial protein of unknown function that has been conserved during evolution. Previous studies have pointed out a role for frataxin in mitochondrial iron-sulfur (Fe-S) metabolism. Here, we have analyzed the incorporation of Fe-S clusters into yeast ferredoxin imported into isolated energized mitochondria from cells grown in t...

Reduced levels of frataxin, an essential protein of as yet unknown function, are responsible for causing the neurodegenerative pathology Friedreich's ataxia. Independent reports have linked frataxin to iron-sulphur cluster assembly through interactions with the two central components of this machinery: desulphurase Nfs1/IscS and the scaffold protein Isu/IscU. In this study, we use a combination...

Frataxin is a highly conserved nuclear-encoded mitochondrial protein whose deficiency is the primary cause of Friedreich's ataxia, an autosomal recessive neurodegenerative disease. The frataxin structure comprises a well-characterized globular domain that is present in all species and is preceded in eukaryotes by a non-conserved N-terminal tail that contains the mitochondrial import signal. Lit...

We consider a large class of arithmetical functions generated by Dirichlet series satisfying a functional equation with gamma factors. Our objective is to state some 12 results for the average order of these arithmetical functions. Our objective here is to state some B-theorems on the average order of a class of arithmetical functions. We indicate very briefly the class of arithmetical function...