HTETOP cells, derived from the human fibrosarcoma cell line HT1080, express human topoisomearse II (TOP2A) exclusively from a tetracycline (TET)-regulated transgene, we used HTETOP cells to differentiate between TOP2A-dependent and independent apoptotic effects of doxorubicin and dexrazoxane.
Topoisomerase II{alpha}-dependent and -independent apoptotic effects of dexrazoxane and doxorubicin.
Cell line
View SamplesPregnane X receptor (PXR) is generally considered the most important sensor of natural and anthropogenic xenobiotics in vertebrates. In Xenopus, however, PXR plays a role in neural development and it is irresponsive to xenobiotics. We report a first broad-spectrum amphibian xenobiotic receptor, which is an ortholog of the mammalian constitutive androstane receptor (CAR). The low basal activity and pronounced responsiveness to activators such as drugs and steroids displayed by the Xenopus CAR resemble PXR, which both trace back to a common ancestor early in the divergence of land vertebrates. The constitutive activity of CAR emerged first in Sauropsida (reptiles and birds) and it is common to all fully terrestrial land vertebrates (Amniota). This activity can be mimicked by humanizing just two amino acids of the Xenopus CAR. These results demonstrate a remarkable plasticity of CAR which enabled its employment as Xenopus xenosensors. They open way to toxicogenomic and bioaugmentation studies in amphibians, a critically endangered taxon of land vertebrates. Taken together, we provide evidence for a much earlier origin of CAR, for its conservation in tetrapods which exceeds that of PXR, and for its remarkable functional plasticity which enabled its role as a PXR-like xenosensor in Amphibia.
Evolutionary history and functional characterization of the amphibian xenosensor CAR.
Sex, Specimen part, Treatment
View SamplesWe wanted to determine how type II versus type III Toxoplasma infection affect host gene expression
Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation.
Cell line
View SamplesWe wanted to determine how type I ROP16 affect host gene expression
Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation.
Specimen part
View SamplesWe wanted to determine how type II Toxoplasma GRA15 and type I ROP16 affect host gene expression. We infected bone marrow-derived macrophages (BMMs) from B6 mice with type II (Pru), type II +ROP16 I, type II gra15, or type II gra15 + ROP16I.
Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation.
Specimen part, Treatment
View SamplesWe provide a map of human ILC heterogeneity across multiple anatomical sites. Tissue-specific distinctions are particularly apparent for ILC1 populations, whose distribution was markedly altered in obesity or aging. Furthermore, the degree of ILC1 population hetero- geneity differed substantially in lymphoid versus mucosal sites. Together, these analyses comprise a comprehensive characterization of the spatial and temporal dynamics regulating the anatomical distri- bution, subset heterogeneity, and functional poten- tial of ILCs in non-diseased human tissues. Overall design: We present a quantitative analysis of ILC distribution and heterogeneity in lymphoid, mucosal, and metabolic tissues obtained from a diverse cohort of 44 previously non-diseased organ donors over a wide range of ages and body mass indexes (BMIs).
Spatial and Temporal Mapping of Human Innate Lymphoid Cells Reveals Elements of Tissue Specificity.
Specimen part, Subject
View SamplesExtramedullary hematopoiesis (EMH) refers to the differentiation of hematopoietic stem cells (HSCs) into effector cells that occurs in compartments outside of the bone marrow. Previous studies linked pattern recognition receptor (PRR)-expressing HSCs, EMH and immune responses to microbial stimuli. However, the factors that regulate EMH and whether EMH operates in broader immune contexts remain unknown. Here, we demonstrate a previously unrecognized role for thymic stromal lymphopoietin (TSLP) in promoting the population expansion of progenitor cells in the periphery and identify that TSLP-elicited progenitors differentiate into effector cells including macrophages, dendritic cells and granulocytes that contribute to TH2 cytokine responses. The frequency of circulating progenitor cells was also increased in allergic patients with a gain-of-function polymorphism in TSLP, suggesting the TSLP-EMH pathway may operate in human disease. These data identify that TSLP-induced EMH contributes to the development of allergic inflammation and indicate that EMH is a conserved mechanism of innate immunity.
Thymic stromal lymphopoietin-mediated extramedullary hematopoiesis promotes allergic inflammation.
Sex, Specimen part
View SamplesThe aim of this study was to explore what molecular and cellular processes predicate the conversion from insulitis to diabetes. The transcriptional profiles of CD45+ immune cells collected from pancreas of a cohort of age-matched female mice, which were scanned by MRI to determine the risk of diabetes development.
Early window of diabetes determinism in NOD mice, dependent on the complement receptor CRIg, identified by noninvasive imaging.
Sex, Age, Specimen part
View SamplesGene expression was compared between E18.5 E-cadherin conditional knockout (cKO) small intestine and E18.5 control mouse small intestine.
E-cadherin is required for intestinal morphogenesis in the mouse.
Specimen part
View SamplesWe studied the changes that occur in gene transcription during seasonal senescence in Populus trichocarpa pioneer leaves and fine roots. Plant senescence is a strictly regulated physiological process that allows relocating of valuable nutrients from senescent tissues before death. It might be induced by internal or external factors and among them, phytohormones play an undoubtedly significant role. Senescence was extensively studied in leaves, but the aging of other ephemeral organs, located underground, and its drivers are still poorly understood. We focused on collective results to fill in the knowledge gap about senescence of fine, absorptive roots and leaves in order to check if there are universal mechanisms involved during plant organ senescence. Transcriptional profiling was conducted with the use of microarrays to identify genes involved in developmental PCD. Samples were collected three times during a growth season. The first collection was considered as a control and was collected in early summer (July 7–15) when leaves and the root system were fully developed and functional. The second group of leaf and root samples were harvested in early autumn (October 1–7) when chlorophyll levels in leaves had decreased by approximately 40% and when fine roots had changed in color from white to brown. The third group of samples were harvested in the middle of autumn (November 2–9) when chlorophyll levels in leaves decreased by approximately 65% and fine roots were dark brown or black color. Our results reveal the important role of phytohormones in regulating the senescence of both studied organs. The transcriptomic analyses showed significant changes in gene expression that are associated with phytohormones, especially with ABA and jasmonates. We conclude that phytohormonal regulation of senescence in roots and leaves is organ-specific. In roots, phytohormones are involved indirectly in regulation of senescence by increasing tolerance for cold or resistance for pathogens, whereas such correlation was not observed in leaves.
Allies or Enemies: The Role of Reactive Oxygen Species in Developmental Processes of Black Cottonwood (<i>Populus trichocarpa</i>).
Specimen part
View Samples