Human Rights, Persons with Disabilities, ICF and the Convention on the Rights of Persons with Disabilities - Training Toolkit

No abstract available

Human Rights, Persons with Disabilities, ICF and the Convention on the Rights of Persons with Disabilities - Training Toolkit

No abstract available

Constitutive Expression of Pluripotency-Associated Genes in Mesodermal Progenitor Cells (MPCs)

Background: We recently characterized a progenitor of mesodermal lineage (MPCs) from the human bone marrow of adults or umbilical cord blood. These cells are progenitors able to differentiate toward mesenchymal, endothelial and cardiomyogenic lineages. Here we present an extensive molecular characterization of MPCs, from bone marrow samples, including 39 genes involved in stem cell machinery, differentiation and cell cycle regulation. Methodology/Principal Findings: MPCs are cytofluorimetrically characterized and quantitative RT-PCR was performed to evaluate the gene expression profile, comparing it with MSCs and hESCs lines. Immunofluorescence and dot-blot analysis confirm qRT-PCR data. MPCs exhibit an increased expression of OCT4, NANOG, SALL4, FBX15, SPP1 and to a lesser extent c-MYC and KLF4, but lack LIN28 and SOX2. MPCs highly express SOX15. Conclusions/Significance: MPCs express many pluripotency-associated genes and show a peculiar Oct-4 molecular circuit. Understanding this unique molecular mechanism could lead to identifying MPCs as feasible, long telomeres, target cells for reprogramming with no up-regulation of the p53 pathway. Furthermore MPCs are easily and inexpensively harvested fro

Mesodermal Progenitor Cells (MPCs) Differentiate into Mesenchymal Stromal Cells (MSCs) by Activation of Wnt5/Calmodulin Signalling Pathway

Mesenchymal Stromal Cells (MSCs) remain poorly characterized because of the absence of manifest physical, phenotypic, and functional properties in cultured cell populations. Despite considerable research on MSCs and their clinical application, the biology of these cells is not fully clarified and data on signalling activation during mesenchymal differentiation and proliferation are controversial. The role of Wnt pathways is still debated, partly due to culture heterogeneity and methodological inconsistencies. Recently, we described a new bone marrow cell population isolated from MSC cultures that we named Mesodermal Progenitor Cells (MPCs) for their mesenchymal and endothelial differentiation potential. An optimized culture method allowed the isolation from human adult bone marrow of a highly pure population of MPCs (more than 97%), that showed the distinctive SSEA-4+CD105+CD90(neg) phenotype and not expressing MSCA-1 antigen. Under these selective culture conditions the percentage of MSCs (SSEA-4(neg)CD105+CD90(bright) and MSCA-1+), in the primary cultures, resulted lower than 2%.We demonstrate that MPCs differentiate to MSCs through an SSEA-4+CD105+CD90(bright) early intermediate precursor. Differentiation paralleled the activation of Wnt5/Calmodulin signalling by autocrine/paracrine intense secretion of Wnt5a and Wnt5b (p<0.05 vs uncondictioned media), which was later silenced in late MSCs (SSEA-4(neg)). We found the inhibition of this pathway by calmidazolium chloride specifically blocked mesenchymal induction (ID₅₀ =  0.5 µM, p<0.01), while endothelial differentiation was unaffected.The present study describes two different putative progenitors (early and late MSCs) that, together with already described MPCs, could be co-isolated and expanded in different percentages depending on the culture conditions. These results suggest that some modifications to the widely accepted MSC nomenclature are required

Genetic, Phenotypic, and Interferon Biomarker Status in ADAR1-Related Neurological Disease

International audienceWe investigated the genetic, phenotypic, and interferon status of 46 patients from 37 families with neurological disease due to mutations in ADAR1. The clinicoradiological phenotype encompassed a spectrum of Aicardi–Goutières syndrome, isolated bilateral striatal necrosis, spastic paraparesis with normal neuroimaging, a progressive spastic dystonic motor disorder, and adult-onset psychological difficulties with intracranial calcification. Homozygous missense mutations were recorded in five families. We observed a p.Pro193Ala variant in the heterozygous state in 22 of 23 families with compound heterozygous mutations. We also ascertained 11 cases from nine families with a p.Gly1007Arg dominant-negative mutation, which occurred de novo in four patients, and was inherited in three families in association with marked phenotypic variability. In 50 of 52 samples from 34 patients, we identified a marked upregulation of type I interferon-stimulated gene transcripts in peripheral blood, with a median interferon score of 16.99 (interquartile range [IQR]: 10.64–25.71) compared with controls (median: 0.93, IQR: 0.57–1.30). Thus, mutations in ADAR1 are associated with a variety of clinically distinct neurological phenotypes presenting from early infancy to adulthood, inherited either as an autosomal recessive or dominant trait. Testing for an interferon signature in blood represents a useful biomarker in this context

Human rights, UN convention, and the International Classification of Functioning, Disability and Health: collecting data on persons with disabilities?

This article discusses the approaches to data collection embedded in the United Nations Convention on the Rights of People with Disabilities (CRPD) and the International Classification of Functioning, Disability and Health (ICF). It will start by briefly exploring different conceptualizations of disability (medical and social models, biopsychosocial, charity and human rights approaches) that impact on what is considered relevant data. The concept of disability has been widely explored by numerous authors in various fields, and the various models and approaches can co-exist. Historically, disability has evolved from being something intrinsic to the person and one-dimensional to reflecting an interaction between the individual and contextual factors. A movement toward the recognition of universal rights for all human beings has accompanied this change

Visuospatial attentive capabilities and saccadic inhibitory control in children with spastic cerebral palsy

Cerebral palsy (CP) is a non-progressive syndrome due to a pre- or perinatal brain injury. Although CP is defined as a movement disorder, it frequently involves attentional and executive impairments, as well as specific learning disabilities. Seven children (5 males and 2 females aged 9-16 years) with spastic CP (CPC) and 13 typically developing children (TDC) (6 males and 7 females aged 9-16 years) participated in the study. Six CPC suffered from right-sided hemiplegia, one was diplegic. Participants had normal IQ and normal or corrected-to-normal visual acuity. CPC did not show visual field defects within ± 10° of visual angle, had normal verbal comprehension and were able to sit independently. Eye movements were recorded by an infrared eye-tracking system (Tobii X120, Sweden), while subjects performed a visually-guided saccade task and a Posner cueing task. A square-shaped grey placeholder was displayed in each quadrant of the visual field at 7° of eccentricity from a central cross, on a black background of a pc screen placed at 80 cm in front of the subject. Participants had to make a saccade as fast as possible to a green target occurring inside one of the placeholders. In the cueing task, a non-informative cue (brief place-holder flash) unpredictably occurred 150 ms before the imperative target, either at the same (valid condition) or at a different (invalid condition) location. No differences in latency and amplitude were found between visually-guided saccades of both groups. By contrast, CPC had a great difficulty to suppress saccades towards task-irrelevant targets both during fixation and in the cuing task. Thus, the expectancy of a relevant target during central fixation elicited in 4 CPC saccades towards a place-holder in 20-60% of the trials (<15% in TDC). Furthermore, while TDC made inappropriate saccades to the cue in only 0-30% of the trials, 5 of 6 CPC did so in a much larger percentage of trials (up to 89%), with a remarkable preponderance for a specific quadrant or hemifield. Interestingly, we found no relationship between the hemifield of prevalent saccadic intrusions and the affected limbs by CP. In addition, in CPC we observed a significant correlation between the mean latency of visually-guided saccades and the percentage of trials in which saccades were erroneously made to the cue. Finally, by taking into account only the correct trials in the Posner task, in both groups saccade latencies were faster in the valid than in the invalid condition. This study shows that in CP, even in presence of a mild symptomatology, prefrontal inhibitory executive control is frequently impaired, in the absence of deficits in the low-level visuospatial attentive capabilities