Treatment of post-transplant patients with immunosuppressive drugs targeting the calcineurin-NFAT pathway, such as Cyclosporine A or Tacrolimus, are commonly associated with a higher incidence of opportunistic infections, such as Aspergillus fumigatus, which can lead to severe life-threating conditions. A component of the A. fumigatus cell wall, -glucan, is recognized by dendritic cells via the Dectin-1 receptor, triggering downstream signaling that leads to calcineurin-NFAT binding, NFAT translocation, and transcription of NFAT-regulated genes. Here, we address the question of whether calcineurin signaling in CD11c-expressing cells, such as DCs, has a specific role in the innate control of A. fumigatus. Impairment of calcineurin in CD11c-expressing cells (CD11ccrecnb1loxP) significantly increased susceptibility to systemic A. fumigatus infection and to intranasal infection in irradiated mice undergoing bone marrow transplant. Global expression profiling of bone marrow-derived DCs identified calcineurin-regulated processes in the immune response to infection, including expression of pentraxin-3, an important anti-fungal defense protein. These results suggest that calcineurin inhibition directly impairs important immunoprotective functions of myeloid cells, as shown by the higher susceptibility of CD11ccrecnbloxP mice in models of systemic and invasive pulmonary aspergillosis, including after allogeneic bone marrow transplantation. These findings are relevant to the clinical management of transplant patients with severe Aspergillus infections.
Impaired calcineurin signaling in myeloid cells results in downregulation of pentraxin-3 and increased susceptibility to aspergillosis.
Specimen part
View SamplesBackground: Exercise has a positive effect on overall health. This study was performed to get an overview of the effects of mixed exercise training on skeletal muscl
Identification of human exercise-induced myokines using secretome analysis.
Sex, Age, Race
View SamplesCockayne syndrome (CS) is an autossomal human disorder characterized by premature aging along with other symptoms. At the molecular level, CS is characterized by a deficiency in the Transcription-couple DNA repair pathway caused by a mutation mainly in ERCC6 gene and the absence of its functional protein. It has been shown that the presence of DNA damage and the lack of some functional proteins related to DNA repair constitute a barrier for somatic cell reprogramming. Recently, it was demonstrated that one protein involved in Genome Global Repair controls the expression of an important pluripotent gene, highligting its importance for cellular reprogramming.
Evidence for premature aging due to oxidative stress in iPSCs from Cockayne syndrome.
Specimen part, Disease, Cell line
View SamplesNatural grape-juice fermentations involve the sequential development of different yeast species which strongly influence the chemical and sensorial traits of the final product. In the present study,we aimed to examine the transcriptomic response of Saccharomyces cerevisiae to the presence of Hanseniaspora guilliermondii wine fermentation.
Genomic expression program of Saccharomyces cerevisiae along a mixed-culture wine fermentation with Hanseniaspora guilliermondii.
Treatment, Time
View SamplesWe treated logarithmically growing cultures of E.coli with a sub-lethal dose of an antimicrobial arylamide compound (PMX 10070) and Polymyxin B sulfate to measure transcriptional responses in an effort to understand mechanism of action
Antibacterial mechanism of action of arylamide foldamers.
No sample metadata fields
View SamplesThe NuRD complex is generally thought to repress transcription at both hyper- and hypomethylated regions in the genome. In addition, the complex is involved in the DNA damage response. Here, we show that ZMYND8 bridges NuRD to a number of putative DNA-binding zinc finger proteins. The ZMYND8 MYND domain directly interacts with PPPL? motifs in the NuRD subunit GATAD2A. Furthermore, GATAD2A and GATAD2B exclusively form homodimers and they thus define mutually exclusive NuRD subcomplexes. ZMYND8 and MBD3 share a large number of genome-wide binding sites, mostly active promoters and enhancers. Depletion of ZMYND8 does not affect NuRD occupancy genome-wide and expression of NuRD/ZMYND8 target genes in steady-state asynchronous cells. However, ZMYND8 facilitates immediate recruitment of GATAD2A/NuRD to induced sites of DNA damage. These results thus show that a specific substoichiometric interaction with a NuRD subunit paralogue provides unique functionality to a distinct NuRD subcomplex. Overall design: RNA-seq samples for HeLa FRT-TO mock, ZMYND8KO, and ZMYND8KO-rescue cells
ZMYND8 Co-localizes with NuRD on Target Genes and Regulates Poly(ADP-Ribose)-Dependent Recruitment of GATAD2A/NuRD to Sites of DNA Damage.
Subject
View SamplesBackground: Exercising is know to have an effect on exercising skeletal muscle, but unkown is the effect on non-exercising skeletal muscle. Gene expression changes in the non-exercising skeletal muscle would point to a signalling role of skeletal muscle
Pronounced effects of acute endurance exercise on gene expression in resting and exercising human skeletal muscle.
Sex, Age, Specimen part, Race, Subject, Time
View SamplesTo define and compare the genome-wide transcriptional signatures of Notch1+ cells in intestinal tumors and in normal ISCs we performed Affymetrix analyses of these two populations.
Lineage tracing of Notch1-expressing cells in intestinal tumours reveals a distinct population of cancer stem cells.
Specimen part
View SamplesLow concentrations of the dissolved leonardite humic acid HuminFeed (HF) prolonged the lifespan and enhanced the thermal stress resistance of the model organism Caenorhabditis elegans. Furthermore growth was impaired and reproduction delayed, effects which have also been identified in other polyphenolic monomers, including tannic acid, rosmarinic acid, and caffeic acid. Moreover, a chemical modification of HF (HF-HQ), which increases its phenolic/quinonoid moieties, magnified the biological impact on C. elegans. To gain a deep insight into the molecular basis of these effects, we performed global transcriptomics on young adult (3 d) and old adult (11 d) nematodes exposed to two concentrations of HF and young adults (3 d) exposed to two concentrations of HF-HQ.
The Nematode Caenorhabditis elegans, Stress and Aging: Identifying the Complex Interplay of Genetic Pathways Following the Treatment with Humic Substances.
Specimen part, Treatment
View SamplesRNA-Seq profiling of estrogen-receptor-positive MCF-7 cell lines with different perturbations of non-canonical WNT signaling . The MCF-7 cells were either transfected with an empty vector (pcDNA) or with a ROR2 overexpression construct, in parallel with or without stimulation with recombinant WNT5A. The objective was to find expression-responsive targets of these perturbations as potential drivers of increased cell invasiveness. Overall design: Four conditions of MCF-7 cells each in 3 replicates: 1. empty vector (pcDNA), 2. empty vector (pcDNA) with WNT5A stimulation, 3. ROR2 overexpression construct, 4. ROR2 overexpression construct with WNT5A stimulation
Ror2 Signaling and Its Relevance in Breast Cancer Progression.
No sample metadata fields
View Samples