Detection of Changes in Nonlinear Dynamical Systems using Multiresolution Entropy

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Filaggrin Genotype Determines Functional and Molecular Alterations in Skin of Patients with Atopic Dermatitis and Ichthyosis Vulgaris

BACKGROUND: Several common genetic and environmental disease mechanisms are important for the pathophysiology behind atopic dermatitis (AD). Filaggrin (FLG) loss-of-function is of great significance for barrier impairment in AD and ichthyosis vulgaris (IV), which is commonly associated with AD. The molecular background is, however, complex and various clusters of genes are altered, including inflammatory and epidermal-differentiation genes. OBJECTIVE: The objective was to study whether the functional and molecular alterations in AD and IV skin depend directly on FLG loss-of-function, and whether FLG genotype determines the type of downstream molecular pathway affected. METHODS AND FINDINGS: Patients with AD/IV (n = 43) and controls (n = 15) were recruited from two Swedish outpatient clinics and a Swedish AD family material with known FLG genotype. They were clinically examined and their medical history recorded using a standardized questionnaire. Blood samples and punch biopsies were taken and trans-epidermal water loss (TEWL) and skin pH was assessed with standard techniques. In addition to FLG genotyping, the STS gene was analyzed to exclude X-linked recessive ichthyosis (XLI). Microarrays and quantitative real-time PCR were used to compare differences in gene expression depending on FLG genotype. Several different signalling pathways were altered depending on FLG genotype in patients suffering from AD or AD/IV. Disease severity, TEWL and pH follow FLG deficiency in the skin; and the number of altered genes and pathways are correlated to FLG mRNA expression. CONCLUSIONS: We emphasize further the role of FLG in skin-barrier integrity and the complex compensatory activation of signalling pathways. This involves inflammation, epidermal differentiation, lipid metabolism, cell signalling and adhesion in response to FLG-dependent skin-barrier dysfunction

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

THE POWER MUTH DISTRIBUTION∗

Muth introduced a probability distribution with application in reliability theory. We propose a new model from the Muth law. This paper studies its statistical properties, such as the computation of the moments, computer generation of pseudo-random data and the behavior of the failure rate function, among others. The estimation of parameters is carried out by the method of maximum likelihood and a Monte Carlo simulation study assesses the performance of this method. The practical usefulness of the new model is illustrated by means of two real data sets, showing that it may provide a better fit than other probability distributions

Detection of changes in nonlinear dynamical systems using multiresolution entropy

SIGLEAvailable at INIST (FR), Document Supply Service, under shelf-number : 14802 E, issue : a.1996 n.2812 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Detection of changes in nonlinear dynamical systems using multiresolution entropy

SIGLEAvailable at INIST (FR), Document Supply Service, under shelf-number : 14802 E, issue : a.1996 n.2812 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Distribución de los subtipos del VIH-1 en nueve países de américa del sur, 1995-2002

Objetivo Determinar la distribución de los subtipos del virus de la inmunodeficiencia humana (VIH-1) y las presencia de cepas recombinantes en Argentina, Bolivia, Colombia, Chile, Ecuador, Paraguay, Perú, Uruguay y Venezuela a través de estudios epidemiológicos y de genotipificación. Materiales y Métodos: Se incluyeron a los participantes de los protocolos realizados en los nueve paises, incluyendo poblaciones de trabajadoras sexuales (TS), hombres que tienen sexo con hombres (HSH), individuos VIH positivos, gestantes y paciente con tuberculosis (TB). Se utilizó la prueba de movilidad heteroduplex de envoltura (env HMA), ProRT, secuenciamiento completo o ambas para determinar los subtipos de VIH 1. Resultados: Se identificaron 3081 individuos positivos al VIH (de un total de 42 290 voluntarios), las prevalencias oscilaban entre menos de 1% a 29% según población estudiada, siendo mayor en los HSH. Un total de 1654 muestras (54%) fueron genotipificadas. Se encontró el subtipo B en 1380 (83%) muestras, el subtipo F en 218 (13%), así como los subtipos A y C en 0,1% y 0,4% respectivamente. Se hallaron subtipos recombinantes BF en 39 muestras (2%) y formas recombinantes CRF01_AE(0,1%), CRF17_BF(0,4%) y CRF02_AG(0,1%). En Venezuela, Colombia, Ecuador, Perú, Bolivia y Chile (paises andinos) predominó el subtipo B, mientras en Argentina, Uruguay y Paraguay hubo un alto porcentaje del subtipo F. Conclusiones: En la mayoría de países andinos la epidemia de VIH-1 se concentró en los HSH con un predominio del subtipo B. El subtipo F es más frecuente en las TS en Argentina y Uruguay. Esta información es útil para implementar planes de prevención y futuros ensayos de vacunas en esta región