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SRP186159
Bos taurus
20 Downloadable Samples
Illumina HiSeq 3000
Description
We report the effect of DKK1 treatment during culture on the length and transcriptome of embryos on day 15 of development, supporting the notion that changes early in development affect later stages of development. Overall design: Bovine embryos were produced in vitro and exposed to either 0 or 100 ng/ml DKK1 from day 5 to 7 of culture. Embryos were transferred on day 7 and recovered on day 15 for evaluation of length and transciptome
Publication Title
Dickkopf-related protein 1 is a progestomedin acting on the bovine embryo during the morula-to-blastocyst transition to program trophoblast elongation.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Ion Torrent Proton
Description
The neurobiological functions of a number of kinases expressed in the brain are unknown. Here, we report new findings on DCLK3 (Doublecortin-like kinase 3) which is preferentially expressed in neurons in the striatum and dentate gyrus. Its function has never been investigated. DCLK3 expression is markedly reduced in Huntington''s disease. Recent data obtained in studies related to cancer suggest DCLK3 could have anti-apoptotic effect. Thus, we hypothesized that early loss of DCLK3 in Huntington''s disease may render striatal neurons more susceptible to mutant huntingtin (mHtt). We discovered that DCLK3 silencing in the striatum of mice exacerbated the toxicity of an N-terminal fragment of mHtt. Conversely, overexpression of DCLK3 reduced neurodegeneration produced by mHtt. DCLK3 also produced beneficial effects on motor symptoms in a knock-in mouse model of Huntington''s disease. Using different mutants of DCLK3, we found that the kinase activity of the protein plays a key role in neuroprotection. To investigate the potential mechanisms underlying DCLK3 effects, we studied the transcriptional changes produced by the kinase domain in human striatal neurons in culture. Results show that DCLK3 regulates in a kinase-dependent manner the expression of many genes involved in transcription regulation and nucleosome/chromatin remodeling. Consistent with this, histological evaluation showed DCLK3 is present in the nucleus of striatal neurons and, protein-protein interaction experiments suggested that the kinase domain interacts with zinc finger proteins, including TADA3, a core component of SAGA complex. Our novel findings suggest that the presence of DCLK3 in striatal neurons may play a key role in transcription regulation and chromatin remodeling in these brain cells, and show that reduced expression of the kinase in Huntington's disease could render the striatum highly vulnerable to neurodegeneration. Examination of DCLK3 as neuroprotector against mutant huntingtin in vivo and in vitro models. Overall design: Examination of DCLK3 as neuroprotector against mutant huntingtin in vitro experiments.
Publication Title
The striatal kinase DCLK3 produces neuroprotection against mutant huntingtin.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Background & Aims: Ursodeoxycholic acid (UDCA) attenuates chemical and colitis-induced colon carcinogenesis in animal models. We investigated its mechanism of action on normal intestinal cells, in which carcinogenesis- or inflammation-related alterations do not interfere with the result. Methods: Alterations of gene expression were identified in Affymetrix arrays in isolated colon epithelium of mice fed with a diet containing 0.4% UDCA and were confirmed in the normal rat intestinal cell line IEC-6 by RT-PCR. The effect of the insulin receptor substrate 1 (Irs-1) expression and of ERK phosphorylation on proliferation was investigated in vitro by flow cytometry, western blotting, siRNA-mediated gene suppression or by pharmacological inhibition of the kinase activity. The ERK1-effect on Irs-1 transcription was tested in a reporter system. Results: UDCA-treatment in vivo suppressed potential pro-proliferatory genes including Irs-1 and reduced cell proliferation by more than 30%. In vitro it neutralised the proliferatory signals of IGF-1 and EGF and slowed down the cell cycle. Irs-1 transcription was suppressed due to high ERK1 activation. Both Irs-1 suppression and the persistent high ERK activation inhibited proliferation. Conversely, the decrease of phosphorylation of ERK1 (but not ERK2) or of its expression partially abrogated the inhibitory effects of UDCA. Conclusions: UDCA inhibits proliferation of intestinal epithelial cells by acting upon IGF-1 and EGF pathways and targeting ERK1 and, consequently, Irs-1. The inhibition of these pathways adds a new dimension to the physiological and therapeutic action of UDCA and, since both pathways are activated in inflammation and cancer, suggests new applications of UDCA in chemoprevention and chemotherapy.
Publication Title
UDCA slows down intestinal cell proliferation by inducing high and sustained ERK phosphorylation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
By using high-density DNA microarrays, we analyzed the gene-expression profile in a panel of germ cell tumour cell lines
Publication Title
Differentiation-Dependent Regulation of Human Endogenous Retrovirus K Sequences and Neighboring Genes in Germ Cell Tumor Cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Oxaliplatin (oxPt) resistance in colorectal cancers (CRC) is a major medical problem, and predictive markers are urgently needed. Recently, miR-625-3p was reported as a promising predictive marker. Here, we have used in vitro models to show that miR-625-3p functionally induces oxPt resistance in CRC cells, and have identified signalling networks affected by miR-625-3p. The p38 MAPK activator MAP2K6 was shown to be a direct target of miR-625-3p, and, accordingly, was downregulated in patients not responding to oxPt therapy. miR-625-3p resistance could be reversed in CRC cells by anti-miR-625-3p treatment and by ectopic expression of a miR-625-3p insensitive MAP2K6 variant. In addition, by reducing p38 MAPK signalling using either siRNA technology, chemical inhibitors to p38 or by ectopic expression of dominant negative MAP2K6 protein we induced resistance to oxPt. Transcriptome, proteome and phosphoproteome profiles revealed inactivation of MAP2K6-p38 signalling as one likely mechanism a possible driving force behind of oxPt resistance. Our study shows that miR-625-3p induces oxPt resistance by abrogating MAP2K6-p38 regulated apoptosis and cell cycle control networks, and corroborates the predictive power of miR-625-3p
Publication Title
miR-625-3p regulates oxaliplatin resistance by targeting MAP2K6-p38 signalling in human colorectal adenocarcinoma cells.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 96 Downloadable Samples
- Illumina mouse-6 v1.1 expression beadchip
Description
Analysis of tissues of DBA/2 mice fed a standard breeding diet (SBD) and high fat diet (HFD) revealed tissue specific roles in inflammation and disease, and altered communication between tissues. The tissues surveyed incuded adipose tissues (brown, inguinal, mesenteric, retro-peritoneal, subcutaneious and gonadal), muscle and liver.
Publication Title
High-fat diet leads to tissue-specific changes reflecting risk factors for diseases in DBA/2J mice.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Ion Torrent Proton
Description
Pentoxifylline attenuated hypertrophic scars by influencing the cell cycles Overall design: mRNA profiles of control hypertrophic scar fibroblasts and pentoxifylline treated cells were generated by deep sequencing, in triplicate, using Ion Proton.
Publication Title
The Akt/FoxO/p27<sup>Kip1</sup> axis contributes to the anti-proliferation of pentoxifylline in hypertrophic scars.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Bos taurus
- 18 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
The response to the presence of the ncpBVDV-infected PI or TI fetus is expected to provide information on the impact of the PI fetus on the immune response of the dam
Publication Title
Persistent fetal infection with bovine viral diarrhea virus differentially affects maternal blood cell signal transduction pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Sus scrofa
- 79 Downloadable Samples
- Illumina HiSeq 2500
Description
Boar taint (BT) is an offensive odour or taste observed in pork from a proportion of non-castrated male pigs. Surgical castration is effective in avoiding BT, but animal welfare issues have created an incentive for alternatives such as genomic selection. In order to find candidate biomarkers, gene expression profiles were analysed from tissues of non-castrated pigs grouped by their genetic merit of BT. Differential expression analysis revealed substantial changes with log-transformed fold changes of liver and testis from -3.39 to 2.96 and -7.51 to 3.53, respectively. Co-expression network analysis revealed one module with a correlation of -0.27 in liver and three modules with correlations of 0.31, -0.44 and -0.49 in testis. Differential expression and co-expression analysis revealed candidate biomarkers with varying biological functions: phase I (COQ3, COX6C, CYP2J2, CYP2B6, ACOX2) and phase II metabolism (GSTO1, GSR, FMO3) of skatole and androstenone in liver to steroidgenesis (HSD17B7, HSD17B8, CYP27A1), regulation of steroidgenesis (STARD10, CYB5R3) and GnRH signalling (MAPK3, MAP2K2, MAP3K2) in testis. Overrepresented pathways included “Ribosome”, “Protein export” and “Oxidative phosphorylation” in liver and “Steroid hormone biosynthesis” and “Gap junction” in testis. Future work should evaluate the biomarkers in large populations to ensure their usefulness in genomic selection programs. Overall design: Total RNA was extracted from liver and testis of 48 Danish Landrace pigs with low- medium and high genetic merit of boar taint and sequenced by Illumina HiSeq 2500.
Publication Title
Systems genomics study reveals expression quantitative trait loci, regulator genes and pathways associated with boar taint in pigs.
Sample Metadata Fields
Specimen part, Subject
View Samples- Arabidopsis thaliana
- 17 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Selected soil-borne rhizobacteria can trigger an induced systemic resistance (ISR) that is effective against a broad spectrum of pathogens. In Arabidopsis thaliana, the root-specific transcription factor MYB72 is required for the onset of ISR, but is also associated with plant survival under conditions of iron deficiency. Here we investigated the role of MYB72 in both processes. To identify MYB72 target genes, we analyzed the root transcriptomes of wild-type Col-0, mutant myb72, and complemented 35S:FLAG-MYB72/myb72 plants in response to ISR-inducing Pseudomonas fluorescens WCS417. Five WCS417-inducible genes were misregulated in myb72 and complemented in 35S:FLAG-MYB72/myb72. Amongst these, we uncovered -glucosidase BGLU42 as a novel component of the ISR signaling pathway. Overexpression of BGLU42 resulted in constitutive disease resistance, whereas bglu42 was defective in ISR. Furthermore, we found 195 genes to be constitutively upregulated in MYB72-overexpressing roots in the absence of WCS417. Many of these encode enzymes involved in the production of iron-mobilizing phenolic metabolites under conditions of iron deficiency. We provide evidence that BGLU42 is required for their release into the rhizosphere. Together, this work highlights a thus far unidentified link between the ability of beneficial rhizobacteria to stimulate systemic immunity and mechanisms induced by iron deficiency in host plants.
Publication Title
β-Glucosidase BGLU42 is a MYB72-dependent key regulator of rhizobacteria-induced systemic resistance and modulates iron deficiency responses in Arabidopsis roots.
Sample Metadata Fields
Specimen part
View Samples