0000000001315251
AUTHOR
Francisco García-garcía
Assessment of Targeted Next-Generation Sequencing as a Tool for the Diagnosis of Charcot-Marie-Tooth Disease and Hereditary Motor Neuropathy
Charcot-Marie-Tooth disease is characterized by broad genetic heterogeneity with >50 known disease-associated genes. Mutations in some of these genes can cause a pure motor form of hereditary motor neuropathy, the genetics of which are poorly characterized. We designed a panel comprising 56 genes associated with Charcot-Marie-Tooth disease/hereditary motor neuropathy. We validated this diagnostic tool by first testing 11 patients with pathological mutations. A cohort of 33 affected subjects was selected for this study. The DNAJB2 c.352+1G>A mutation was detected in two cases; novel changes and/or variants with low frequency (50 known disease-associated genes. Mutations in some of these gene…
Relation Between Genetic Factors and Frailty in Older Adults.
Frailty is a geriatric syndrome that identifies individuals at higher risk of disability, institutionalization, and death. We previously reported that frailty is related to oxidative stress and cognitive impairment-related biomarkers. The aim of this study was to determine whether frailty is associated with genetic variants.Longitudinal population-based cohort of 2488 community-dwelling people from Toledo, Spain, aged 65 years or older.We obtained blood samples from 78 individuals with frailty and 74 nonfrail individuals who were nonfrail (according to Fried criteria) from the Toledo Study of Healthy Ageing and extracted DNA using the Chemagic DNA blood kit.Sample genotyping was carried out…
Dysfunctional mitochondrial fission impairs cell reprogramming
We have recently shown that mitochondrial fission is induced early in reprogramming in a Drp1-dependent manner; however, the identity of the factors controlling Drp1 recruitment to mitochondria was unexplored. To investigate this, we used a panel of RNAi targeting factors involved in the regulation of mitochondrial dynamics and we observed that MiD51, Gdap1 and, to a lesser extent, Mff were found to play key roles in this process. Cells derived from Gdap1-null mice were used to further explore the role of this factor in cell reprogramming. Microarray data revealed a prominent down-regulation of cell cycle pathways in Gdap1-null cells early in reprogramming and cell cycle profiling uncovered…
Rilpivirine attenuates liver fibrosis through selective STAT1-mediated apoptosis in hepatic stellate cells
ObjectiveLiver fibrosis constitutes a major health problem worldwide due to its rapidly increasing prevalence and the lack of specific and effective treatments. Growing evidence suggests that signalling through cytokine-activated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways regulates liver fibrosis and regeneration. Rilpivirine (RPV) is a widely used anti-HIV drug not reported to produce hepatotoxicity. We aimed to describe the potential hepatoprotective effects of RPV in different models of chronic liver injury, focusing on JAK-STAT signalling regulation.DesignThe effects of RPV on hepatic steatosis, inflammation and fibrogenesis were studied in a nut…
Characterization of molecular mechanisms underlying the axonal Charcot–Marie–Tooth neuropathy caused by MORC2 mutations
Mutations in MORC2 lead to an axonal form of Charcot-Marie-Tooth (CMT) neuropathy type 2Z. To date, 31 families have been described with mutations in MORC2, indicating that this gene is frequently involved in axonal CMT cases. While the genetic data clearly establish the causative role of MORC2 in CMT2Z, the impact of its mutations on neuronal biology and their phenotypic consequences in patients remains to be clarified. We show that the full-length form of MORC2 is highly expressed in both embryonic and adult human neural tissues and that Morc2 expression is dynamically regulated in both the developing and the maturing murine nervous system. To determine the effect of the most common MORC2…
Uterine disorders affecting female fertility: what are the molecular functions altered in endometrium?
[EN]: Objective:To determine the molecular functions of genes exhibiting altered expression in the endometrium of women with uterine disorders affecting fertility. Design: Retrospective analysis integrating case and control data from multiple cohorts with endometrium gene expression in women with uterine disorders. Setting: Infertility research department affiliated with a university hospital. Patient(s): Two hundred and forty women, 121 of whom were controls, 119 of whom had endometrial adenocarcinoma (ADC), recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), or stage II–IV endometriosis. Intervention(s): None. Main Outcome Measure(s): Genomewide gene expression and alter…
Unveiling Sex-Based Differences in the Effects of Alcohol Abuse: A Comprehensive Functional Meta-Analysis of Transcriptomic Studies
AbstractThe abuse of alcohol, one of the most popular psychoactive substances, can cause several pathological and psychological consequences, including alcohol use disorder (AUD). An impaired ability to stop or control alcohol intake despite adverse health or social consequences characterize AUD. While AUDs predominantly occur in men, growing evidence suggests the existence of distinct cognitive and biological consequences of alcohol dependence in women. The molecular and physiological mechanisms participating in these differential effects remain unknown. Transcriptomic technology permits the detection of the biological mechanisms responsible for such sex-based differences, which supports t…
IL1β Induces Mesenchymal Stem Cells Migration and Leucocyte Chemotaxis Through NF-κB
Mesenchymal stem cells are often transplanted into inflammatory environments where they are able to survive and modulate host immune responses through a poorly understood mechanism. In this paper we analyzed the responses of MSC to IL-1β: a representative inflammatory mediator. Microarray analysis of MSC treated with IL-1β revealed that this cytokine activateds a set of genes related to biological processes such as cell survival, cell migration, cell adhesion, chemokine production, induction of angiogenesis and modulation of the immune response. Further more detailed analysis by real-time PCR and functional assays revealed that IL-1β mainly increaseds the production of chemokines such as CC…
The transcriptomics of an experimentally evolved plant-virus interaction
[EN] Models of plant-virus interaction assume that the ability of a virus to infect a host genotype depends on the matching between virulence and resistance genes. Recently, we evolved tobacco etch potyvirus (TEV) lineages on different ecotypes of Arabidopsis thaliana, and found that some ecotypes selected for specialist viruses whereas others selected for generalists. Here we sought to evaluate the transcriptomic basis of such relationships. We have characterized the transcriptomic responses of five ecotypes infected with the ancestral and evolved viruses. Genes and functional categories differentially expressed by plants infected with local TEV isolates were identified, showing heterogene…
Serum metabolomic profiling facilitates the non-invasive identification of metabolic biomarkers associated with the onset and progression of non-small cell lung cancer
Lung cancer (LC) is responsible for most cancer deaths. One of the main factors contributing to the lethality of this disease is the fact that a large proportion of patients are diagnosed at advanced stages when a clinical intervention is unlikely to succeed. In this study, we evaluated the potential of metabolomics by H-1-NMR to facilitate the identification of accurate and reliable biomarkers to support the early diagnosis and prognosis of non-small cell lung cancer (NSCLC). We found that the metabolic profile of NSCLC patients, compared with healthy individuals, is characterized by statistically significant changes in the concentration of 18 metabolites representing different amino acids…
Identificación de polimorfismos de un solo nucleótido relacionados con la fragilidad
Resumen Introduccion La busqueda de biomarcadores que permitan la deteccion y el posible tratamiento precoz de la fragilidad se ha convertido en uno de los objetivos primordiales de la comunidad cientifica geriatrica. El objetivo del presente estudio fue identificar polimorfismos de un solo nucleotido ([SNP] del ingles single nucleotide polymorphisms) relacionados con la fragilidad. Material y metodos El estudio se llevo a cabo en 152 sujetos de la cohorte del Estudio de Toledo (de 65 a 95 anos de edad), clasificados como fragiles (n = 78), y no fragiles (n = 74), segun los criterios de Fried. Tras la extraccion de sangre se aislo y amplifico el ADN para el analisis de SNP mediante la tecno…
Dysfunctional mitochondrial fission impairs cell reprogramming
We have recently shown that mitochondrial fission is induced early in reprogramming in a Drp1-dependent manner; however, the identity of the factors controlling Drp1 recruitment to mitochondria was unexplored. To investigate this, we used a panel of RNAi targeting factors involved in the regulation of mitochondrial dynamics and we observed that MiD51, Gdap1 and, to a lesser extent, Mff were found to play key roles in this process. Cells derived from Gdap1-null mice were used to further explore the role of this factor in cell reprogramming. Microarray data revealed a prominent down-regulation of cell cycle pathways in Gdap1-null cells early in reprogramming and cell cycle profiling uncovered…