Blood transcriptomics of drug-na\uefve sporadic Parkinson's disease patients

BACKGROUND: Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder that is clinically defined in terms of motor symptoms. These are preceded by prodromal non-motor manifestations that prove the systemic nature of the disease. Identifying genes and pathways altered in living patients provide new information on the diagnosis and pathogenesis of sporadic PD. METHODS: Changes in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls ("Discovery set") were analyzed by taking advantage of the Affymetrix platform. Patients were at the onset of motor symptoms and before initiating any pharmacological treatment. Data analysis was performed by applying Ranking-Principal Component Analysis, PUMA and Significance Analysis of Microarrays. Functional annotations were assigned using GO, DAVID, GSEA to unveil significant enriched biological processes in the differentially expressed genes. The expressions of selected genes were validated using RT-qPCR and samples from an independent cohort of 12 patients and controls ("Validation set"). RESULTS: Gene expression profiling of blood samples discriminates PD patients from healthy controls and identifies differentially expressed genes in blood. The majority of these are also present in dopaminergic neurons of the Substantia Nigra, the key site of neurodegeneration. Together with neuronal apoptosis, lymphocyte activation and mitochondrial dysfunction, already found in previous analysis of PD blood and post-mortem brains, we unveiled transcriptome changes enriched in biological terms related to epigenetic modifications including chromatin remodeling and methylation. Candidate transcripts as CBX5, TCF3, MAN1C1 and DOCK10 were validated by RT-qPCR. CONCLUSIONS: Our data support the use of blood transcriptomics to study neurodegenerative diseases. It identifies changes in crucial components of chromatin remodeling and methylation machineries as early events in sporadic PD suggesting epigenetics as target for therapeutic intervention

Epidemiology, diagnosis and management of superficial mycoses: ours three years retrospective analysis

Mycotic infections of the skin, hair and nails are disorder with high prevalence. Dermatophytes are the most frequently etiologic agents followed by yeasts and non-dermatophyte moulds. The geographic distribution is variable because of migration, lifestyle and socio-economics conditions. In this study, based on ours three years retrospective data analysis, we evaluate the epidemiology of etiologic agents, diagnosis and management of superficial mycoses. Our data and our experience suggest the importance of this microbiological diagnosis and the role of the Clinical Microbiologist to assess with Dermatologist and Primary Care Phyisician an appropriate diagnostic and therapeutic plan

Transposable element activation promotes neurodegeneration in a Drosophila model of Huntington's disease

: Huntington's disease (HD) is an autosomal dominant disorder with progressive motor dysfunction and cognitive decline. The disease is caused by a CAG repeat expansion in the IT15 gene, which elongates a polyglutamine stretch of the HD protein, Huntingtin. No therapeutic treatments are available, and new pharmacological targets are needed. Retrotransposons are transposable elements (TEs) that represent 40% and 30% of the human and Drosophila genomes and replicate through an RNA intermediate. Mounting evidence suggests that mammalian TEs are active during neurogenesis and may be involved in diseases of the nervous system. Here we show that TE expression and mobilization are increased in a Drosophila melanogaster HD model. By inhibiting TE mobilization with Reverse Transcriptase inhibitors, polyQ-dependent eye neurodegeneration and genome instability in larval brains are rescued and fly lifespan is increased. These results suggest that TE activation may be involved in polyQ-induced neurotoxicity and a potential pharmacological target

L'adoption lyonnaise des orphelins légitimes (1536-1793) : thèse pour le doctorat.... Tome 2 / présentée... par Paul Gonnet... ; Université de Paris, Faculté de droit

Contient une table des matièresAvec mode text

Additional file 7: of Blood transcriptomics of drug-naïve sporadic Parkinson’s disease patients

List of differentially expressed genes between PD patients and controls based on Significance Analysis of Microarrays (SAM). Significance Analysis of Microarrays was performed on normalized and filtered microarray data as described in the main text. The SAM test was run using 1000 permutations and a False Discovery Rate (FDR) of 10 %. Ratios are calculated as differences in gene expression between samples of PD patients and controls, with the top up-regulated genes first. (PDF 3122 kb

La maison rustique ou Manuel complet d'agriculture, d'économie rurale et domestique contenant la chimie agricole, la médecine vétérinaire... l'art de la cuisine,... la médecine et la chirurgie domestique.... Tome 1 / par M. C. D. P. S.

Contient une table des matièresAvec mode text