Malaria is a disease with diverse symptoms depending on host immune status and pathogenicity of Plasmodium parasites. The continuous parasite growth within a host suggests mechanisms of immune evasion and/or inhibition. To identify pathways commonly inhibited by malaria infection, we infected C67BL/6 mice with four Plasmodium yoelii strains causing different disease phenotypes and 24 progeny of a genetic cross. mRNAs from mouse spleens day 1 and/or day 4 post infection (p.i.) were hybridized to a mouse microarray to identify activated or inhibited pathways, upstream regulators, and linkages to parasite genetic loci. Strong interferon responses were observed after infection with N67 strain, whereas initial inhibition and later activation of hematopoiesis pathways were found after infection with 17XNL parasite. Inhibition of pathways such as Th1 activation, dendritic cell (DC) maturation, and NFAT immune regulation were observed in mice infected with all the parasite strains day 4 p.i., suggesting universally inhibited immune pathways. Treatment of infected mice with antibodies against T cell receptors OX40 or CD28 to activate malaria-inhibited pathways enhanced host survival. Controlled activation of these pathways may provide important strategies for better disease management and for developing an effective vaccine.
Detection of host pathways universally inhibited after Plasmodium yoelii infection for immune intervention.
Sex, Specimen part
View Sampleseffect of over-expression LIGHT on T cells for the liver gene expression
Lymphotoxin beta receptor-dependent control of lipid homeostasis.
No sample metadata fields
View SamplesThe metabolic enzyme diglyceride acyltransferase (DGAT) is responsible for the synthesis of triglycerides. Loss of its expression may sensitize cells to conditions of nutrient and oxygen that are commonly present in tumors. This study is designed to identify stress response pathways that may be induced following the shRNA-mediated knockdown of the two genes coding for the DGAT enzymes. In vitro growth conditions lacking serum and oxygen were used to mimic growth conditions commonly found in poorly perfused tumor domains
Triglycerides Promote Lipid Homeostasis during Hypoxic Stress by Balancing Fatty Acid Saturation.
Specimen part, Cell line, Treatment
View SamplesThe metabolic enzyme diglyceride acyltransferase (DGAT) is responsible for the synthesis of triglycerides. Loss of its expression may sensitize cells to conditions of nutrient and oxygen that are commonly present in tumors. This study is designed to identify stress response pathways that may be induced following the shRNA-mediated knockdown of the two genes coding for the DGAT enzymes.
Triglycerides Promote Lipid Homeostasis during Hypoxic Stress by Balancing Fatty Acid Saturation.
Specimen part, Treatment
View SamplesCD95 (also called FAS and APO-1) is a prototypical death receptor that
CD95 promotes tumour growth.
Sex, Age, Specimen part, Cell line
View SamplesWe aimed to identify microRNAs that are regulated by YAP in human mammary epithelial cells. Overall design: We utilized deep sequencing technology to identify microRNAs that are induced by YAP overexpression and repressed by YAP knockdown.
YAP mediates crosstalk between the Hippo and PI(3)K–TOR pathways by suppressing PTEN via miR-29.
Specimen part, Cell line, Subject
View SamplesWe have previously shown that rheumatoid factors (RF) produced by Fas-deficient autoimmune-prone mice typically bind autologous IgG2a with remarkably low affinity. Nevertheless, B cells representative of this RF population proliferate vigorously in response IgG2a/chromatin immune complexes through a mechanism dependent on the sequential engagement of the BCR and Toll-like receptor 9 (TLR9). To more precisely address the role of both receptors in this response, we analyzed the signaling pathways activated in AM14 B cells stimulated with these complexes. We found that the BCR not only serves to direct the chromatin complex to an internal compartment where it can engage TLR9 but also transmits a suboptimal signal that in combination with the signals emanating from TLR9 leads to NF?B activation and proliferation. Importantly, engagement of both receptors leads to the upregulation of a group of gene products, not induced by the BCR or TLR9 alone, that include IL-2. These data indicate that autoreactive B cells, stimulated by a combination of BCR and TLR9 ligands, acquire functional properties that may contribute to the activation of additional cells involved in the autoimmune disease process.
Functional outcome of B cell activation by chromatin immune complex engagement of the B cell receptor and TLR9.
No sample metadata fields
View SamplesCell proliferation is essential to rapid tissue growth and repair, but is inherently associated with considerable genome damage that cells must efficiently prevent or fix to prevent cell cycle arrest. Here, we implicate the transcription factor Gata6 in regulation of adult mouse hair follicle regeneration where it controls the renewal of the rapidly proliferating epithelial (matrix) progenitors and hence the extent of production of terminally differentiated lineages. We find that Gata6 protects against DNA damage associated with proliferation, thus preventing cell cycle arrest and apoptosis. Furthermore, we show that Gata6 stimulates the Eddarad/NF-kB pathway, important for DNA-damage repair and stress response in general, and for hair follicle growth in particular. Finally, we find Edaradd essential, downstream of Gata6 for cell survival and proliferation. Our data add to recent evidence in embryonic stem and neural progenitor cells, suggesting a model whereby developmentally regulated transcription factors protect from DNA damage associated with proliferation occurring at key stages of rapid tissue growth. Our data may aid in understanding why Gata6 is a frequent target of amplification in cancers. Overall design: Gene expression profiling by mRNA-seq to identify differentially expressed genes in wild type (WT) and Gata6 induced knockout (iKO) mouse epidermal keratinocytes
Gata6 promotes hair follicle progenitor cell renewal by genome maintenance during proliferation.
Treatment, Subject
View SamplesMetal oxide engineered nanoparticles, which are widely used in diverse applications, are known to impact terrestrial plants. These nanoparticles have a potential to induce changes in plant tissue transcriptomes, and thereby the productivity. Here we looked at how the two commonly used nanoparticles, nano-titania (TiO2) and nano-ceria (CeO2) can impact the underlying mechanisms associated plant growth at genome level.
Molecular and physiological responses to titanium dioxide and cerium oxide nanoparticles in Arabidopsis.
Age, Specimen part
View SamplesSeed germination of a terrestrial plant constitute dynamic changes in various physiological processes related to growth and development. These physiological processes can be affected by various abiotic and biotic stressors. Here we looked at how the two commonly used nanoparticles, nano-titania (TiO2) and nano-ceria (CeO2) can impact the underlying mechanisms associated with germination at genome level.
Phenotypic and genomic responses to titanium dioxide and cerium oxide nanoparticles in Arabidopsis germinants.
Age, Specimen part, Treatment
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