Visceral leishmaniasis (VL), caused by Leishmania spp protozoan parasites, can provoke overwhelming and protracted epidemics, with high casefatality rates. Despite extensive efforts towards the development of an effective prophylactic vaccine, no promising vaccine is available yet for humans. Multi-epitope peptide based vaccine development is manifesting as the new era of vaccination strategies against VL. Aim of the study was the design of chimeric peptides from immunogenic L. infantum proteins for encapsulation in PLGA nanoparticles (NPs) alone or in combination with MPLA adjuvant, or in PLGA NPs surface modified with an octapeptide mimicking TNF-alpha for DCs targeting, in order to construct a peptide-based nanovaccine. The in vitro evaluation of the above nanoformulations was performed in DCs isolated from HLA-A2.1 transgenic mice. Characterization of DCs transcriptional responses to these vaccine candidates via microarrays could improve our understanding of their mechanisms of action on DCs' functional differentiation and the type of adaptive immunity subsequently induced.
A Poly(Lactic-<i>co</i>-Glycolic) Acid Nanovaccine Based on Chimeric Peptides from Different <i>Leishmania infantum</i> Proteins Induces Dendritic Cells Maturation and Promotes Peptide-Specific IFNγ-Producing CD8<sup>+</sup> T Cells Essential for the Protection against Experimental Visceral Leishmaniasis.
Specimen part
View SamplesVisceral leishmaniasis (VL) caused by Leishmania donovani and L. infantum is a potentially fatal disease. To date there are no registered vaccines for disease prevention despite the fact that several vaccines are in preclinical development. Thus, new strategies are needed to improve vaccine efficacy based on a better understanding of the mechanisms mediating protective immunity and mechanisms of host immune responses subversion by immunopathogenic components of Leishmania. In the present study, determination of the immune mechanisms related to infection or protective immune responses against VL using an experimental nanovaccine as a vaccine model was conducted through microarray analysis.
Transcriptome Analysis Identifies Immune Markers Related to Visceral Leishmaniasis Establishment in the Experimental Model of BALB/c Mice.
No sample metadata fields
View SamplesParathyroid hormone (PTH) plays an essential role in regulating calcium and bone homeostasis in the adult, but whether PTH is required at all for regulating fetal-placental mineral homeostasis is uncertain. To address this we treated Pth-null mice in utero with 1 nmol PTH (1-84) or saline and examined placental calcium transfer 90 minutes later. It was found that placental calcium transfer increased in Pth-null fetuses treated with PTH as compared to Pth-null fetuses treated with saline. Subsequently, to determine the effect of PTH treatment on placental gene expression, in a separate experiment, 90 minutes after the fetal injections the placentas were removed for subsequent RNA extraction and microarray analysis.
Parathyroid hormone regulates fetal-placental mineral homeostasis.
Sex, Specimen part, Treatment
View SamplesThe circadian regulation of transcriptional processes has a broad impact on cell metabolism. Here, we compared the diurnal transcriptome of human skeletal muscle conducted on serial muscle biopsies in vivo with profiles of human skeletal myotubes synchronized in vitro. Extensive rhythmic transcription was observed in human skeletal muscle in comparison to in vitro cell culture. However, nearly half of the in vivo rhythmicity was lost at the mRNA accumulation level. siRNA-mediated clock disruption in primary myotubes significantly affected the expression of ~8% of all genes, with impact on glucose homeostasis and lipid metabolism. Genes involved in GLUT4 expression, translocation and recycling were negatively affected, whereas lipid metabolic genes were altered to promote activation of lipid utilization. Moreover, basal and insulin stimulated glucose uptake were significantly reduced upon CLOCK depletion. Altogether, our findings suggest an essential role for cell-autonomous circadian clocks in coordinating muscle glucose homeostasis and lipid metabolism in humans. Overall design: 100 samples from 2 donors. Together with GSE108539, part of the same study described above.
Transcriptomic analyses reveal rhythmic and CLOCK-driven pathways in human skeletal muscle.
Specimen part, Subject, Time
View SamplesIn fission yeast, the nuclear-localized Lsk1p-Lsc1p-Lsg1p cyclin dependent kinase complex is required for the reliable execution of cytokinesis and is also required for Ser-2 phosphorylation RNA pol II carboxy terminal domain.
Global gene expression analysis of fission yeast mutants impaired in Ser-2 phosphorylation of the RNA pol II carboxy terminal domain.
No sample metadata fields
View SamplesWe report high-throughput profiling of gene expression from whole zebrafish ventricles. We profile mRNA in uninjured ventricles and those undergoing regeneration 14 days after genetic ablation. This study provides a framework for understanding transcriptional changes during adult models of regeneration. Overall design: Examination of gene expression in cardiomyocytes under different states of proliferation.
Resolving Heart Regeneration by Replacement Histone Profiling.
No sample metadata fields
View SamplesWe used microarrays to identify transcripts regulated by dexamethasone in omental (Om) and abdominal subcutaneous (Abdsc) adipose tissues of severely obese females obtained during elective surgeries.
Depot Dependent Effects of Dexamethasone on Gene Expression in Human Omental and Abdominal Subcutaneous Adipose Tissues from Obese Women.
Specimen part, Disease stage, Treatment
View SamplesWhile histone deacetylase (HDAC) inhibitors are thought to regulate gene expression by post-translational modification of histone as well as non-histone proteins. While histone hyperacetylation has long been considered the paradigmatic mechanism of action, recent genome-wide profiles indicate more complex interactions with the epigenome. In particular, HDAC inhibitors also induce histone deacetylation at the promoters of highly active genes, resulting in gene suppression. This was linked to the loss of histone acetyltransferase (HAT) binding. To illustrate pre-clinical utility of the HDAC inhibitor SAHA as a therapeutic, we show reversal of diabetes-associated EP300 target genes in diabetic HAECs of primary origin. These results were confirmed using SAHA, C646 (EP300/CREBBP inhibitor) or EP300 siRNA. These findings suggest the inhibition of gene expression by SAHA is mediated by EP300 function and provide a rationale for clinical trials of safety and efficacy in patients with diabetes. Overall design: Human aortic endothelial cells from a diabetic and non-diabetic individual were stimulated with DMSO (control), SAHA (2 µM, HDAC inhibitor) or C646 (10 µM, EP300 inhibitor) for 12 hours, or EP300 siRNA or non-target siRNA (control) for 4 hours, followed by 48 hours in fresh media. Study performed in triplicate.
Systems approach to the pharmacological actions of HDAC inhibitors reveals EP300 activities and convergent mechanisms of regulation in diabetes.
No sample metadata fields
View SamplesAlveolar macrophages are the first line of defense against pathogens in the lungs of all mammalian species and therefore may constitute an appropriate therapeutic target cell in the treatment and prevention of opportunistic airway infections. Analysis of alveolar macrophages from several species has revealed a unique cellular phenotype and transcriptome, presumably linked to their distinct airway environment and function in host defense. The current study extends these findings to the horse.
Comparative transcriptome analysis of equine alveolar macrophages.
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MicroRNA-Offset RNA Alters Gene Expression and Cell Proliferation.
Specimen part, Treatment
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