Filter Results
29915 results
The integrin α11-overexpressing transgenic mouse strain was generated to further understand the function of α11, after generation of our integrin α11-KO strain. Analysis of the strain showed that integrin α11 was highly expressed in heart, which correlated with a fibrotic heart phenotype. To understand the molecular mechanisms underlying this phenotype, we then performed Microarray to investigate the differentially expressed genes between the WT and TG mice (α11-overexpressing mice) which may result from integrin α11 overexpression. The microarray was performed on RNA-isolates from the heart apex of 1-year-old WT (n=4) and α11-TG (n=6) mice. Total RNA isolation was performed using RNeasy Fibrous Tissue Mini Kit (Qiagen) in accordance with the manufacturer’s protocol. Quality of RNA samples was assessed using Agilent Bioanalyzer 2100. Microarray was carried out at the Norwegian Microarray Consortium/University of Bergen Microarray Core Facility at Haukeland University Hospital. Illumina Bead Array Technology was used, and the raw microarray data was quality examined in GenomeStudio. Differentially expressed genes were analysed using the Ingenuity Pathways Analysis (IPA) software (Ingenuity Systems, Redwood City, CA).
Data Types:
  • Tabular Data
  • Text
  • File Set
Glucocorticoids (GCs) and topoisomerase II inhibitors are used in the treatment of acute lymphoblastic leukaemia (ALL) due to their ability to induce cell death in lymphoid cells. GC-induced apoptosis is mediated by the glucocorticoid receptor (GR), whereas topoisomerase II inhibitors cause DNA damage and activate sensors of DNA damage including the tumour suppressor p53. In order to shed light on the role of the microenvironment in cell death and identify determinants of drug sensitivity we performed transcriptomic analysis in ALL cells treated with the synthetic glucocorticoid dexamethasone, and the topoisomerase II inhibitor etoposide combined with bone marrow-derived conditioned media (CM).
Data Types:
  • Tabular Data
  • Text
  • File Set
Neutrophils play a key role in the innate immunity and the first line of defense against invading pathogens. The aim of this work is to investigate the neutrophil responses and transcriptomic alteration in the porcine peripheral blood by employing Poly I:C to emulate viral infection. The pigs with the two-tailed critical value of neutrophilia post 4h with poly I:C stimulation from a Duroc-Erhualian F2 population.
Data Types:
  • Tabular Data
  • Text
  • File Set
Identification of pro- and anti-inflammatory pathways induced in M-CSF differentiated bone-marrow derived macrophages (BMDMs) after 3 h stimulation with two different TLR2 agonists, Helicobacter hepaticus polysacharide and Pam3CSK4 (75 ng/ml), using TSB (Tryptone Soya Broth) medium as a control
Data Types:
  • Tabular Data
  • Text
  • File Set
Primary human macrophages were cultured 1, 3 or 6 days with different stimuli. Macrophages are key cell types of the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer. Within this functional spectrum diverse and often opposing phenotypes are displayed which are dictated by environmental clues and depend on highly plastic transcriptional programs. Among these the ‘classical’ (M1) and ‘alternative’ (M2) macrophage polarization phenotypes are the best characterized. Understanding macrophage polarization in humans may reveal novel therapeutic intervention possibilities for chronic inflammation, wound healing and cancer. Systematic loss of function screening in human primary macrophages is limited due to lack of robust gene delivery methods and limited sample availability. To overcome these hurdles we developed cell-autonomous assays using the THP-1 cell line allowing genetic screens for human macrophage phenotypes. To confirm the relevance of the THP1-based system we performed microarray studies on THP1 cells and primary human cells subjected to various conditions.
Data Types:
  • Tabular Data
  • Text
  • File Set
Macrophages are key cell types of the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer. Within this functional spectrum diverse and often opposing phenotypes are displayed which are dictated by environmental clues and depend on highly plastic transcriptional programs. Among these the ‘classical’ (M1) and ‘alternative’ (M2) macrophage polarization phenotypes are the best characterized. Understanding macrophage polarization in humans may reveal novel therapeutic intervention possibilities for chronic inflammation, wound healing and cancer. Systematic loss of function screening in human primary macrophages is limited due to lack of robust gene delivery methods and limited sample availability. To overcome these hurdles we developed cell-autonomous assays using the THP-1 cell line allowing genetic screens for human macrophage phenotypes. To confirm the relevance of the THP1-based system we performed microarray studies on THP1 cells and primary human cells subjected to various conditions. THP1 cells were treated with PMA (phorbol 12-myristate 13-acetate) to derive macrophages which were then cultured 1, 3 or 6 days with different stimuli.
Data Types:
  • Tabular Data
  • Text
  • File Set
MicroRNAs expression profile was acquired in 99 frozen tissues corresponding to 14 Burkitt's lymphoma, 17 diffuse large B-cell lymphoma, 29 follicular lymphoma, 19 mantle cell lymphoma, 8 primary mediastinal B-cell lymphoma and 12 lymph nodes. Additionally, we performed microRNA expression profile of 14 Burkitts' lymphoma cell lines, 2 mantle cell lymphoma cell lines, 5 acute lymphoblastic leukemia cell preparations, 5 samples of mononucleosis cells, 4 Epstein Barr virus infected lymphoblastoid cell lines (EBV), 27 purified samples of B cells at different stage of development (13 GC-CD23-/CD39-, 11 GC-CD5- and 3 GC-CD5+), 4 peripheral blood CD19+ B cells, 4 purified samples of T cells (2 CD4+ and 2 CD8+) and 2 samples of bone marrow CD34+ cells. The data were used to discriminate among diverse pathological and nonpathological samples and to identify microRNAs expression differences between pathological samples and their nonpathological counterparts.
Data Types:
  • Tabular Data
  • Text
Gene expression analysis of the 18 microdissected human kidney tubules tissues.
Data Types:
  • Tabular Data
  • Text
Correct neural progenitor fate determination requires the coordination of extrinsic fate determinant signals with intrinsic responses. Post-translational modifications dynamically alter protein function and so are ideally situated to regulate development. Here we show that the deubiquitylaying enzyme, Usp9x modulates both intrinsic and extrinsic regulators of mouse neural progenitors. Nestin-cre mediated deletion of Usp9x from neural progenitors results in a transient disruption of cell adhesion and apical-basal polarity as well as the premature differentiation of intermediate neural progenitors. Ablation of Usp9x also significantly increased β-catenin protein levels, especially S33/S37/T41 phospho-β-catenin, and Wnt signalling. Usp9x was found to be part of the β-catenin destruction complex and loss of Usp9x affects destruction complex composition. Notch signalling was also increased in Usp9x ablated neural progenitors, coinciding with decreased Itch and Numb, and increased Notch intracellular domain protein levels. Usp9x co-localized and immunopreciptiated with Numb from neural progenitors suggesting it is required for Numb stabilisation. These data suggest Usp9x plays a role in coordinating intrinsic responses to extrinsic signals during neural development.
Data Types:
  • Tabular Data
  • Text
  • File Set
West Nile virus (WNV) and Chikungunya virus (CHIKV) are arboviruses that are constantly (re)-emerging and expanding their territory. Both viruses often cause a mild form of disease, but severe forms of the disease can consist of neurological symptoms, most often observed in young children and the elderly, which are poorly understood. To elucidate the mechanisms responsible for end-stage WNV and CHIKV neuroinvasive disease and pathogenesis, we used transcriptomics to compare the effector pathways in the brain during the early and late stage of disease in young mice. Mice were infected with WNV strain NY99 (accession AF196835.2, obtained from the Health Protection Agency, Porton Down, UK; P5 on Vero E6 cells) or CHIKV strain S27, accession AF369024). Nine-day old female C57/BL6 mice were inoculated intraperitoneally with either 10^5 TCID50/100 µL of WNV-NY99 (n=6) or 10^6.5 TCID50/100 µL of CHIKV-S27 (n=6), or mock-infected. Mice were sacrificed 2, 3 or 5 days post-innoculation depending on the virus. For transcriptomic analysis, cerebellum was separated from the brain and the right hemisphere was gently washed once in ice-cold PBS and stored in RNAlater® (Thermo Fisher Scientific, Bleiswijk, The Netherlands) until further processing. Total RNA was isolated from the brain samples using Trizol Reagentand the RNEasy Mini kit. RNA (200 ng) was labeled using the MessageAmp Premier RNA Amplification kit (Applied Biosystems) and hybridized to Affymetrix GeneChip® Mouse 4302 Arrays. Image analysis was performed using GeneChip Operating Software. Microarray Suite version 5.0 software (Affymetrix) was used to generate .dat and .cel files for each experiment. Using this approach, we find evidence for a strong inflammatory response was found in mice infected with WNV and CHIKV. The transcriptomics profile measured in mice with WNV and CHIKV neuroinvasive disease in our study showed strong overlap with the mRNA profile described in the literature for other viral neuroinvasive diseases.
Data Types:
  • Tabular Data
  • Text
6