On the stability of 2 \sqrt{2} x 2 \sqrt{2} oxygen ordered superstructures in YBa2Cu3O6+x

We have compared the ground-state energy of several observed or proposed " 2 \sqrt{2} x 2 \sqrt{2} oxygen (O) ordered superstructures " (from now on HS), with those of "chain superstructures" (CS) (in which the O atoms of the basal plane are ordered in chains), for different compositions x in YBa2Cu3O6+x. The model Hamiltonian contains i) the Madelung energy, ii) a term linear in the difference between Cu and O hole occupancies which controls charge transfer, and iii) covalency effects based on known results for $t-J$ models in one and two dimensions. The optimum distribution of charge is determined minimizing the total energy, and depends on two parameters which are determined from known results for x=1 and x=0.5. We obtain that on the O lean side, only CS are stable, while for x=7/8, a HS with regularly spaced O vacancies added to the x=1 structure is more stable than the corresponding CS for the same x. We find that the detailed positions of the atoms in the structure, and long-range Coulomb interactions, are crucial for the electronic structure, the mechanism of charge transfer, the stability of the different phases, and the possibility of phase separation.Comment: 24 text pages, Latex, one fig. included as ps file, to be publisheb in Phys. Rev.

Natural Antisense Transcripts: Molecular Mechanisms and Implications in Breast Cancers

Natural antisense transcripts are RNA sequences that can be transcribed from both DNA strands at the same locus but in the opposite direction from the gene transcript. Because strand-specific high-throughput sequencing of the antisense transcriptome has only been available for less than a decade, many natural antisense transcripts were first described as long non-coding RNAs. Although the precise biological roles of natural antisense transcripts are not known yet, an increasing number of studies report their implication in gene expression regulation. Their expression levels are altered in many physiological and pathological conditions, including breast cancers. Among the potential clinical utilities of the natural antisense transcripts, the non-coding|coding transcript pairs are of high interest for treatment. Indeed, these pairs can be targeted by antisense oligonucleotides to specifically tune the expression of the coding-gene. Here, we describe the current knowledge about natural antisense transcripts, their varying molecular mechanisms as gene expression regulators, and their potential as prognostic or predictive biomarkers in breast cancers

Rôle de la méthylation de l'ADN dans l'expression du locus INK4a-ARF-INK4b dans le cancer du sein

Breast cancer is a public health problem : one woman in 9 will suffer of it during her lifetime. The estrogen receptor expressing sub-type (ER+) is the most frequent, with 75 % of the cases. Those tumors frequently become resistant to hormonotherapy and spread as metastasis. In this case, chemotherapy needs to be administrated. The CDK4/6 inhibitors in combination with hormonotherapy appears as the new standard treatment for metastatic disease and allows to postpone the chemotherapy. Those drugs play the same role as the endogenous p16-p15 proteins, and it is expected that the patients who have lost their protein expression are also those who will present the best response to treatment. However, none of the currently tested biomarkers turns out to be predictive of treatment response. The INK locus, where p16/p14-p15 proteins are encoded, is often altered in cancers and is involved in cell cycle regulation. The p16/p14-p15 expression is negatively regulated by a non-coding RNA called ANRIL. My aim is to explore the molecular mechanisms linked to the non-coding RNA of the INK locus and involved in the expression regulation of the proteins p16/p14-p15, and to highlight potential biomarkers of the CDK4/6 inhibitors treatment response in ER+ breast cancer. To this end, I already collected In Vitro expression data by RT-qPCR in some cell lines with different expression patterns. DNA methylation are investigated thanks to a Deoxyazacytidine treatment, a DNA methylation inhibitor then by ImmunoPrecipitation of methylated DNA. So, the first links between the expression of the locus and its methylation can be done. In future, other treamtents, protein and RNA interactions will be studied to explain the potential links and molecular mechanisms.Role of the non-coding RNA on the p14, p15 and p16 proteins expression regulation in hormono-dependant breast cance

Identification of specific posttranslational O-mycoloylations mediating protein targeting to the mycomembrane

International audienc

Natural Antisense Transcripts: Molecular Mechanisms and Implications in Breast Cancers

peer reviewedNatural antisense transcripts are RNA sequences that can be transcribed from both DNA strands at the same locus but in the opposite direction from the gene transcript. Because strand-specific high-throughput sequencing of the antisense transcriptome has only been available for less than a decade, many natural antisense transcripts were first described as long non-coding RNAs. Although the precise biological roles of natural antisense transcripts are not known yet, an increasing number of studies report their implication in gene expression regulation. Their expression levels are altered in many physiological and pathological conditions, including breast cancers. Among the potential clinical utilities of the natural antisense transcripts, the non-coding|coding transcript pairs are of high interest for treatment. Indeed, these pairs can be targeted by antisense oligonucleotides to specifically tune the expression of the coding-gene. Here, we describe the current knowledge about natural antisense transcripts, their varying molecular mechanisms as gene expression regulators, and their potential as prognostic or predictive biomarkers in breast cancers

RNA-dependent sterol aspartylation in fungi

International audienceDiverting aminoacyl-transfer RNAs (tRNAs) from protein synthesis is a well-known process used by a wide range of bacteria to aminoacylate membrane constituents. By tRNA-dependently adding amino acids to glycerolipids, bacteria change their cell surface properties, which intensifies antimicrobial drug resistance, pathogenicity, and virulence. No equivalent aminoacylated lipids have been uncovered in any eukaryotic species thus far, suggesting that tRNA-dependent lipid remodeling is a process restricted to prokaryotes. We report here the discovery of ergosteryl-3β-O-l-aspartate (Erg-Asp), a conjugated sterol that is produced by the tRNA-dependent addition of aspartate to the 3β-OH group of ergosterol, the major sterol found in fungal membranes. In fact, Erg-Asp exists in the majority of "higher" fungi, including species of biotechnological interest, and, more importantly, in human pathogens like Aspergillus fumigatus We show that a bifunctional enzyme, ergosteryl-3β-O-l-aspartate synthase (ErdS), is responsible for Erg-Asp synthesis. ErdS corresponds to a unique fusion of an aspartyl-tRNA synthetase-that produces aspartyl-tRNAAsp (Asp-tRNAAsp)-and of a Domain of Unknown Function 2156, which actually transfers aspartate from Asp-tRNAAsp onto ergosterol. We also uncovered that removal of the Asp modifier from Erg-Asp is catalyzed by a second enzyme, ErdH, that is a genuine Erg-Asp hydrolase participating in the turnover of the conjugated sterol in vivo. Phylogenomics highlights that the entire Erg-Asp synthesis/degradation pathway is conserved across "higher" fungi. Given the central roles of sterols and conjugated sterols in fungi, we propose that this tRNA-dependent ergosterol modification and homeostasis system might have broader implications in membrane remodeling, trafficking, antimicrobial resistance, or pathogenicity