Given the dearth of new antibiotics, host-directed therapies (HDTs) are especially desirable. Since IFN-gamma (IFN) plays a central role in host resistance to intracellular bacteria, including Mycobacterium tuberculosis, we searched for small molecules to augment the IFN response in macrophages. Using a novel screen we identified a compound belonging to the rocaglate family(CMLD009433) that synergize with a sub-threshold concentration of IFN to enhance macrophage activation.
Fine-tuning of macrophage activation using synthetic rocaglate derivatives.
Specimen part, Treatment
View SamplesNGS from RNA-seq of triple-negative breast cancer cell lines under standard growth conditions were obtained to identify transcriptional features associated with individual triple-negative breast cancer subtypes. All lines identified have been authenticated by short-tandem repeat sequencing and tested to be negative for mycoplasma.
Diverse, Biologically Relevant, and Targetable Gene Rearrangements in Triple-Negative Breast Cancer and Other Malignancies.
Sex, Specimen part, Disease, Cell line
View SamplesThe objective of this experiment was to determine global gene expression change in triple negative cell line upon knockdown of TGFBR3. Genotype specific differences in expression profiles have been evaluated using human HuGene1.0-ST affymetrix array. RNA was extracted from SUM159 controls and SUM159 TGFBR3KD cells cultured in 3-dimensional in vitro system.
Transforming growth factor beta receptor type III is a tumor promoter in mesenchymal-stem like triple negative breast cancer.
Cell line
View SamplesWe compared the gene expression profile from a group of children with T-cell acute lymphoblastic leukamia who remained in continuous complete remission (CCR) (n = 7) with that from a group who relapsed (n = 5), using Affymetrix HG-U133A arrays. Using the decision-tree based supervised learning algorithm Random Forest (RF), genes were ranked with respect to their ability to discriminate between patients who remained in CCR and those who relapsed. From the 300 top-ranked probe sets 9 genes were selected for further investigation and validation in an independent cohort of 25 T-ALL patients using quantitative real time polymerase chain reaction.
Identification of novel molecular prognostic markers for paediatric T-cell acute lymphoblastic leukaemia.
Sex, Age, Specimen part, Disease, Subject
View SamplesLateral root initiation was used as a model system to study the mechanisms behind auxin-induced cell division. Genome-wide transcriptional changes were monitored during the early steps of lateral root initiation. Inclusion of the dominant auxin signaling mutant solitary root1 (slr1) identified genes involved in lateral root initiation that act downstream of the AUX/IAA signaling pathway. Interestingly, key components of the cell cycle machinery were strongly defective in slr1, suggesting a direct link between AUX/IAA signaling and core cell cycle regulation. However, induction of the cell cycle in the mutant background by overexpression of the D-type cyclin (CYCD3;1) was able to trigger complete rounds of cell division in the pericycle that did not result in lateral root formation. Therefore, lateral root initiation can only take place when cell cycle activation is accompanied by cell fate respecification of pericycle cells. The microarray data also yielded evidence for the existence of both negative and positive feedback mechanisms that regulate auxin homeostasis and signal transduction in the pericycle, thereby fine-tuning the process of lateral root initiation.
Cell cycle progression in the pericycle is not sufficient for SOLITARY ROOT/IAA14-mediated lateral root initiation in Arabidopsis thaliana.
No sample metadata fields
View SamplesBackground: High density lipoprotein (HDL) protects the artery wall by removing cholesterol from lipid-laden macrophages. However, recent evidence suggests that it might also inhibit atherogenesis by combating inflammation. Methods and Results: To identify potential anti-inflammatory mechanisms, we challenged macrophages with lipopolysaccharide (LPS), an inflammatory microbial ligand for Toll-like receptor 4 (TLR4). HDL inhibited the expression of 33% (301 of 911) of the genes normally induced by LPS, microarray analysis revealed. One of its major targets was the type I interferon response pathway, a family of potent viral immunoregulators controlled by TLR4 and the TRAM/TRIF signaling pathway. Unexpectedly, HDLs ability to inhibit gene expression was independent of cellular cholesterol stores. Moreover, it was unaffected by downregulation of two ATP-binding cassette transporters, ABCA1 and ABCG1, that promote cholesterol efflux. To examine the pathways potential in vivo relevance, we used mice deficient in apolipoprotein (apo) A-I, HDLs major protein. After infection with Salmonella (a Gram-negative bacterium that expresses LPS), apoA-Ideficient mice had 6-fold higher plasma levels of interferon-beta-a key regulator of the type I interferon response than did wild-type mice. Conclusions: HDL inhibits a subset of LPS-stimulated macrophage genes that regulate the type I interferon response, and its action is independent of sterol metabolism. These findings raise the possibility that regulation of macrophage genes by HDL might link innate immunity and cardioprotection.
High-density lipoprotein suppresses the type I interferon response, a family of potent antiviral immunoregulators, in macrophages challenged with lipopolysaccharide.
Specimen part
View SamplesCD34+ positively isolated from healthy donors (stimulated by G-CSF) with magnetic beads (after blood leukapheresis)
NA-Seq: a discovery tool for the analysis of chromatin structure and dynamics during differentiation.
No sample metadata fields
View SamplesRNA-seq analysis of human 293 Tet-off cells depleted of PTBP1 and UPF1 alone and in tandem with specific siRNAs. Overall design: siRNA-based depletion of PTBP1, UPF1, and PTBP1/UPF1 together, with a validated non-silencing siRNA as a control.
Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway.
No sample metadata fields
View SamplesComprehensive analysis of gene expression in hematopoietic stem and progenitor cells from young and old mice.
Quiescent hematopoietic stem cells accumulate DNA damage during aging that is repaired upon entry into cell cycle.
Sex, Age, Specimen part, Time
View SamplesThe number of cells in an organ is a major factor for the determination of organ size. However, genetic basis of cell number determination is not well understood. Three grandifolia-D (gra-D) mutants of Arabidopsis thaliana developed huge leaves containing two- to three-fold increased number of cells of the wild type. Tiling array and microarray analysis of gra-D mutants suggested that genes found in a lower part of chromosome 4 were upregulated, suggesting the occurrence of segmental chromosomal duplications in the gra-D mutants. These region contain positive regulators of cell proliferation such as AINTEGUMENTA (ANT) and cyclin genes such as CYCD3;1.
Impact of segmental chromosomal duplications on leaf size in the grandifolia-D mutants of Arabidopsis thaliana.
Specimen part
View Samples