Downregulation of Homologous Recombination DNA Repair Genes by HDAC Inhibition in Prostate Cancer Is Mediated through the E2F1 Transcription Factor

Histone deacetylase inhibitors (HDACis) re-express silenced tumor suppressor genes and are currently undergoing clinical trials. Although HDACis have been known to induce gene expression, an equal number of genes are downregulated upon HDAC inhibition. The mechanism behind this downregulation remains unclear. Here we provide evidence that several DNA repair genes are downregulated by HDAC inhibition and provide a mechanism involving the E2F1 transcription factor in the process.Applying Analysis of Functional Annotation (AFA) on microarray data of prostate cancer cells treated with HDACis, we found a number of genes of the DNA damage response and repair pathways are downregulated by HDACis. AFA revealed enrichment of homologous recombination (HR) DNA repair genes of the BRCA1 pathway, as well as genes regulated by the E2F1 transcription factor. Prostate cancer cells demonstrated a decreased DNA repair capacity and an increased sensitization to chemical- and radio-DNA damaging agents upon HDAC inhibition. Recruitment of key HR repair proteins to the site of DNA damage, as well as HR repair capacity was compromised upon HDACi treatment. Based on our AFA data, we hypothesized that the E2F transcription factors may play a role in the downregulation of key repair genes upon HDAC inhibition in prostate cancer cells. ChIP analysis and luciferase assays reveal that the downregulation of key repair genes is mediated through decreased recruitment of the E2F1 transcription factor and not through active repression by repressive E2Fs.Our study indicates that several genes in the DNA repair pathway are affected upon HDAC inhibition. Downregulation of the repair genes is on account of a decrease in amount and promoter recruitment of the E2F1 transcription factor. Since HDAC inhibition affects several pathways that could potentially have an impact on DNA repair, compromised DNA repair upon HDAC inhibition could also be attributed to several other pathways besides the ones investigated in this study. However, our study does provide insights into the mechanism that governs downregulation of HR DNA repair genes upon HDAC inhibition, which can lead to rationale usage of HDACis in the clinics

The SuperCam Instrument Suite on the Mars 2020 Rover: Science Objectives and Mast-Unit Description

On the NASA 2020 rover mission to Jezero crater, the remote determination of the texture, mineralogy and chemistry of rocks is essential to quickly and thoroughly characterize an area and to optimize the selection of samples for return to Earth. As part of the Perseverance payload, SuperCam is a suite of five techniques that provide critical and complementary observations via Laser-Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman and Luminescence (TRR/L), visible and near-infrared spectroscopy (VISIR), high-resolution color imaging (RMI), and acoustic recording (MIC). SuperCam operates at remote distances, primarily 2-7 m, while providing data at sub-mm to mm scales. We report on SuperCam's science objectives in the context of the Mars 2020 mission goals and ways the different techniques can address these questions. The instrument is made up of three separate subsystems: the Mast Unit is designed and built in France; the Body Unit is provided by the United States; the calibration target holder is contributed by Spain, and the targets themselves by the entire science team. This publication focuses on the design, development, and tests of the Mast Unit; companion papers describe the other units. The goal of this work is to provide an understanding of the technical choices made, the constraints that were imposed, and ultimately the validated performance of the flight model as it leaves Earth, and it will serve as the foundation for Mars operations and future processing of the data.In France was provided by the Centre National d'Etudes Spatiales (CNES). Human resources were provided in part by the Centre National de la Recherche Scientifique (CNRS) and universities. Funding was provided in the US by NASA's Mars Exploration Program. Some funding of data analyses at Los Alamos National Laboratory (LANL) was provided by laboratory-directed research and development funds

The impact of regulatory requirements on the banking flows to emerging countries

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Le taux du crédit accordé aux entreprises françaises : coûts opératoires des banques et prime de risque de défaut

The lending rate to french firms : bank's operating costs and default risk premium This paper deals with the rending rate to French firms. According to previous models, lending rate determination was constrained by the costs of bank liabilities ; the first part examines whether it still holds. New firm liabilities (in the money market) give new short run constraints to some banks ; this assumption is also tested within the cointegration framework. In the second part, the difference between the lending rate and the money market rate is interpreted as a risk premium reflecting average default probability in the corporate sector. We find evidence consistent with a recent competitive behavior in the French banking System.Le taux du crédit accordé aux entreprises françaises : coûts opératoires des banques et prime de risque de défaut Cet article traite du taux d'intérêt débiteur pour les entreprises françaises. Selon les précédents modèles, le coût du crédit était déterminé sous la contrainte des coûts des ressources bancaires et la première partie examine si cela est toujours vrai. De nouvelles sources de financement pour les firmes (sur le marché monétaire) donnent de nouvelles contraintes de court terme aux banques ; cela est également testé dans le cadre de la cointégration. Dans la seconde partie, l'écart entre taux débiteur et taux du marché monétaire est interprété comme une prime de risque justifiée par la probabilité moyenne de faillite des entreprises. Le comportement concurrentiel récent est ainsi mis en évidence dans le cas français.Boutillier Michel, Dérangère Sabine. Le taux du crédit accordé aux entreprises françaises : coûts opératoires des banques et prime de risque de défaut. In: Revue économique, volume 43, n°2, 1992. pp. 363-382

The impact of regulatory requirements on the bank loans flows to emerging countries

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