298 research outputs found
El acceso a la información pública como transparencia gubernamental: análisis de la situación normativa del derecho de acceso a la información pública en la República Argentina
Fil: Conti, Lucio. Universidad Católica de Córdoba. Facultad de Ciencia Política y Relaciones Internacionales; Argentin
Mitochondrial Abnormalities in Down Syndrome: Pathogenesis, Effects and Therapeutic Approaches
Down syndrome (DS) consists of a complex phenotype with constant features, such as mental retardation and hypotonia, and variable features, including heart defects and susceptibility to Alzheimer’s disease, type 2 diabetes, obesity and immune disorders. Overexpression of genes mapping to chromosome 21 (Hsa21) is directly or indirectly responsible for pathogenesis of DS phenotypic features, as overexpressed Hsa21 genes dysregulate several other genes mapping to different chromosomes. Many of these genes are involved in mitochondrial function. Recent studies highlight a link between mitochondrial dysfunction, consistently observed in DS subjects, and DS phenotype. In this review, we first provide a basic overview of mitochondrial alterations in DS in terms of mitochondrial bioenergetics, biogenesis and morphology. We then discuss how mitochondrial malfunction may contribute to the pathogenesis of clinical manifestations and how specific Hsa21 genes may cause the disruption of mitochondrial phenotype. Finally, we focus on drugs, which affect mitochondrial function and network to propose possible therapeutic approaches aimed at improving and/or preventing various aspects of the DS phenotype. Our working hypothesis is that correcting the mitochondrial defect might improve the neurological phenotype and prevent DS-associated pathologies, thus providing a better quality of life for DS individuals and their families
DOF-binding sites additively contribute to guard cell-specificity of AtMYB60 promoter
<p>Abstract</p> <p>Background</p> <p>We previously demonstrated that the <it>Arabidopsis thaliana </it>AtMYB60 protein is an R2R3MYB transcription factor required for stomatal opening. <it>AtMYB60 </it>is specifically expressed in guard cells and down-regulated at the transcriptional levels by the phytohormone ABA.</p> <p>Results</p> <p>To investigate the molecular mechanisms governing <it>AtMYB60 </it>expression, its promoter was dissected through deletion and mutagenesis analyses. By studying different versions of <it>AtMYB60 </it>promoter::GUS reporter fusions in transgenic plants we were able to demonstrate a modular organization for the <it>AtMYB60 </it>promoter. Particularly we defined: a minimal promoter sufficient to confer guard cell-specific activity to the reporter gene; the distinct roles of different DOF-binding sites organised in a cluster in the minimal promoter in determining guard cell-specific expression; the promoter regions responsible for the enhancement of activity in guard cells; a promoter region responsible for the negative transcriptional regulation by ABA. Moreover from the analysis of single and multiple mutants we could rule out the involvement of a group of DOF proteins, known as CDFs, already characterised for their involvement in flowering time, in the regulation of <it>AtMYB60 </it>expression.</p> <p>Conclusions</p> <p>These findings shed light on the regulation of gene expression in guard cells and provide new promoter modules as useful tools for manipulating gene expression in guard cells, both for physiological studies and future biotechnological applications.</p
Overexpression of the Hsa21 Transcription Factor RUNX1 Modulates the Extracellular Matrix in Trisomy 21 Cells
Down syndrome is a neurodevelopmental disorder frequently characterized by other developmental defects, such as congenital heart disease. Analysis of gene expression profiles of hearts from trisomic fetuses have shown upregulation of extracellular matrix (ECM) genes. The aim of this work was to identify genes on chromosome 21 potentially responsible for the upregulation of ECM genes and to pinpoint any functional consequences of this upregulation. By gene set enrichment analysis of public data sets, we identified the transcription factor RUNX1, which maps to chromosome 21, as a possible candidate for regulation of ECM genes. We assessed that approximately 80% of ECM genes overexpressed in trisomic hearts have consensus sequences for RUNX1 in their promoters. We found that in human fetal fibroblasts with chromosome 21 trisomy there is increased expression of both RUNX1 and several ECM genes, whether located on chromosome 21 or not. SiRNA silencing of RUNX1 reduced the expression of 11 of the 14 ECM genes analyzed. In addition, collagen IV, an ECM protein secreted in high concentrations in the culture media of trisomic fibroblasts, was modulated by RUNX1 silencing. Attenuated expression of RUNX1 increased the migratory capacity of trisomic fibroblasts, which are characterized by a reduced migratory capacity compared to euploid controls
The grapevine guard cell-related VvMYB60 transcription factor is involved in the regulation of stomatal activity and is differentially expressed in response to ABA and osmotic stress
- Background: Under drought, plants accumulate the signaling hormone abscisic acid (ABA), which induces the rapid closure of stomatal pores to prevent water loss. This event is trigged by a series of signals produced inside guard cells which finally reduce their turgor. Many of these events are tightly regulated at the transcriptional level, including the control exerted by MYB proteins. In a previous study, while identifying the grapevine R2R3 MYB family, two closely related genes, VvMYB30 and VvMYB60 were found with high similarity to AtMYB60, an Arabidopsis guard cell-related drought responsive gene. - Results: Promoter-GUS transcriptional fusion assays showed that expression of VvMYB60 was restricted to stomatal guard cells and was attenuated in response to ABA. Unlike VvMYB30, VvMYB60 was able to complement the loss-of-function atmyb60-1 mutant, indicating that VvMYB60 is the only true ortholog of AtMYB60 in the grape genome. In addition, VvMYB60 was differentially regulated during development of grape organs and in response to ABA and drought-related stress conditions. - Conclusions: These results show that VvMYB60 modulates physiological responses in guard cells, leading to the possibility of engineering stomatal conductance in grapevine, reducing water loss and helping this species to tolerate drought under extreme climatic conditions
Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy
<p>Abstract</p> <p>Background</p> <p>The Down syndrome phenotype has been attributed to overexpression of chromosome 21 (Hsa21) genes. However, the expression profile of Hsa21 genes in trisomic human subjects as well as their effects on genes located on different chromosomes are largely unknown. Using oligonucleotide microarrays we compared the gene expression profiles of hearts of human fetuses with and without Hsa21 trisomy.</p> <p>Results</p> <p>Approximately half of the 15,000 genes examined (87 of the 168 genes on Hsa21) were expressed in the heart at 18–22 weeks of gestation. Hsa21 gene expression was globally upregulated 1.5 fold in trisomic samples. However, not all genes were equally dysregulated and 25 genes were not upregulated at all. Genes located on other chromosomes were also significantly dysregulated. Functional class scoring and gene set enrichment analyses of 473 genes, differentially expressed between trisomic and non-trisomic hearts, revealed downregulation of genes encoding mitochondrial enzymes and upregulation of genes encoding extracellular matrix proteins. There were no significant differences between trisomic fetuses with and without heart defects.</p> <p>Conclusion</p> <p>We conclude that dosage-dependent upregulation of Hsa21 genes causes dysregulation of the genes responsible for mitochondrial function and for the extracellular matrix organization in the fetal heart of trisomic subjects. These alterations might be harbingers of the heart defects associated with Hsa21 trisomy, which could be based on elusive mechanisms involving genetic variability, environmental factors and/or stochastic events.</p
Variegated silencing through epigenetic modifications of a large Xq region in a case of balanced X;2 translocation with Incontinentia Pigmenti-like phenotype
Molecular mechanisms underlying aberrant phenotypes in balanced X;autosome translocations are scarcely understood. We report the case of a de novo reciprocal balanced translocation X;2(q23;q33) presenting phenotypic alterations highly suggestive of Incontinentia Pigmenti (IP) syndrome, a genodermatosis with abnormal skin pigmentation and neurological failure, segregating as X-linked dominant disorder. Through molecular studies, we demonstrated that the altered phenotype could not be ascribed to chromosome microdeletions or to XIST-mediated inactivation of Xq24-qter. Interestingly, we found that the Xq24-qter region, which translocated downstream of the heterochromatic band 2q34, undergoes epigenetic silencing mediated by DNA methylation and histone alterations. Among the downregulated genes, we found the inhibitor of kappa light polypeptide gene enhancer in B cells, kinase gamma (IKBKG/NEMO), the causative gene of IP. We hypothesize that a mosaic functional nullisomy of the translocated genes, through a Position Effect Variegation-like heterochromatization, might be responsible for the proband's phenotypic anomalies. Partial silencing of IKBKG may be responsible for the skin anomalies observed, thereby mimicking the IP pathological condition. In addition to its clinical relevance, this paper addresses fundamental issues related to the chromatin status and nuclear localization of a human euchromatic region translocated proximally to heterochromatin. In conclusion, the study provides new insight into long-range gene silencing mechanisms and their direct impact in human disease
Pure 16q21q22.1 deletion in a complex rearrangement possibly caused by a chromothripsis event
Laboratory study of tissue repair of resin-based endodontic sealers in critical surgical defects
Filling materials should be restricted to the root canal space. However, sometimes it is impossible to control the apical extrusion, in this case, the fate of the filling material and the result of the treatment will depend on its physicochemical properties and biocompatibility. Objective: To evaluate the tissue response and bone repair capacity of endodontic sealers that were implanted in the calvaria of Wistar rats, forming the groups (n=16): AH Plus and Sealer Plus, compared to the clot group. Methodology: On days 30 and 60, the animals were euthanized, the calvaria was removed and processed for hematoxylin-eosin, immunohistochemistry for collagen type I, Picrosirus red and microtomographic analysis. Data were subjected to ANOVA and Tuckey tests (p<0.05). Results:At 30 days, all groups showed an intense inflammatory reaction (p>0.05). At 60 days, the AH Plus and Sealer Plus maintained an intense inflammatory infiltrate compared to the clot group (p<0.05). We observed immunopositive areas for type I collagen in all groups at 30 days and 60 days (p>0.05). We observed more red collagen fibers for the Sealer Plus compared to the clot group at 30 days (p<0.05). Considering the total fibers, the clot group at 30 days compared to 60 days after surgery showed an increase in the amount of matrix (p<0.05). There were no statistical differences between groups for green and yellow fibers (p>0.05). Regarding morphometric parameters, at 30 days, the newly formed bone volume and number of bone trabeculae were higher in the groups with sealers compared to the clot group (p<0.05). At 60 days, AH Plus and Sealer Plus showed greater bone neoformation compared to the clot group (p<0.05). Conclusions: Despite AH Plus and Sealer Plus induced an intense inflammatory reaction, they can be considered biocompatible materials, since they allowed bone repair
Particle profiling of EV‐lipoprotein mixtures by AFM nanomechanical imaging
The widely overlapping physicochemical properties of lipoproteins (LPs) and extracellular vesicles (EVs) represents one of the main obstacles for the isolation and characterization of these pervasive biogenic lipid nanoparticles. We herein present the application of an atomic force microscopy (AFM)-based quantitative morphometry assay to the rapid nanomechanical screening of mixed LPs and EVs samples. The method can determine the diameter and the mechanical stiffness of hundreds of individual nanometric objects within few hours. The obtained diameters are in quantitative accord with those measured via cryo-electron microscopy (cryo-EM); the assignment of specific nanomechanical readout to each object enables the simultaneous discrimination of co-isolated EVs and LPs even if they have overlapping size distributions. EVs and all classes of LPs are shown to be characterised by specific combinations of diameter and stiffness, thus making it possible to estimate their relative abundance in EV/LP mixed samples in terms of stoichiometric ratio, surface area and volume. As a side finding, we show how the mechanical behaviour of specific LP classes is correlated to distinctive structural features revealed by cryo-EM. The described approach is label-free, single-step and relatively quick to perform. Importantly, it can be used to analyse samples which prove very challenging to assess with several established techniques due to ensemble-averaging, low sensibility to small particles, or both, thus providing a very useful tool for quickly assessing the purity of EV/LP isolates including plasma- and serum-derived preparations
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