Development and function of tissues and organs are powered by the activity of mitochondria. In humans, inherited genetic mutations that lead to progressive mitochondrial pathology often manifest during infancy and can lead to death, reflecting the indispensable nature of mitochondrial function and biogenesis. Here, we describe a zebrafish mutant for the gene mia40a, the life-essential homologue of the evolutionarily conserved Mia40 oxidoreductase which drives the biogenesis of cysteine-rich mitochondrial proteins. We report that mia40a mutant animals undergo progressive cellular respiration defects and develop enlarged mitochondria in skeletal muscles before their ultimate at the larval stage. We generated a rich transcriptomic and proteomic resource that allowed us to identify abnormalities in the development of endodermal organs, in particular the liver and pancreas. We identify the acinar cells of the exocrine pancreas to be severely affected by mutations in the MIA pathway. Our data contribute to a better understanding of the molecular, cellular and organismal effects of mitochondrial deficiency, important for the accurate diagnosis and future treatment strategies of these diseases. Overall design: Embryos obtained from an in-cross of heterozygous mia40awaw1/+ siblings were genotyped at 3 dpf. Pools of five mia40+/+ or mia40waw1/waw1 larvae, derived from the same clutch, were collected at indicated time-points for RNA extraction and transcriptomic profiling. Larvae used in 8 dpf experiments were subjected to external feeding from 5dpf before being collected for the analysis at 8dpf.
Loss of the Mia40a oxidoreductase leads to hepato-pancreatic insufficiency in zebrafish.
Specimen part, Subject
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Bifidobacteria can protect from enteropathogenic infection through production of acetate.
No sample metadata fields
View SamplesA huge number of microorganisms are colonized in human gut and the balance of their composition is closely related to human health. Recently, many probiotics such as bifidobacteria or lactobacilli have been introduced in our life as effective agents. However, we have not well understood their beneficial mechanisms including host-bacterial crosstalk. Accordingly, we took advantage of the protective mechanisms of probiotics against lethal infection of enterohemorrhagic Escherichia coli O157:H7 in murine gnotobiote model system
Bifidobacteria can protect from enteropathogenic infection through production of acetate.
No sample metadata fields
View SamplesA huge number of microorganisms are colonized in human gut and the balance of their composition is closely related to human health. Recently, many probiotics such as bifidobacteria or lactobacilli have been introduced in our life as effective agents. However, we have not well understood their beneficial mechanisms including host-bacterial crosstalk To analyze the differences of gene expression between BA- or BL-associated murine colonic epithelium, we performed comparative transcriptomic analysis.
Bifidobacteria can protect from enteropathogenic infection through production of acetate.
No sample metadata fields
View SamplesCidofovir is an acyclic nucleoside phosphonate with strong antiviral activity against a broad spectrum of DNA viruses. Although it has previously been shown that cidofovir exerts an antiproliferative effect on HPV positive cells by the induction of apoptosis, the exact mechanism of action remains to be unraveled. In order to study the activity of cidofovir against HPV, gene expression profiling was performed in cidofovir-treated and cidofovir-resistant HeLa, HaCaT, and PHK cells by means of microarrays (HG-U133 Plus 2, Affymetrix).
Cidofovir selectivity is based on the different response of normal and cancer cells to DNA damage.
Specimen part, Disease, Cell line
View SamplesReduced cancer incidence has been reported among type II diabetics treated with metformin. Metformin exhibits anti-proliferative and anti-neoplastic effects associated with inhibition of mTORC1, but the mechanisms are poorly understood. We provide the first genome-wide analysis of translational targets of canonical mTOR inhibitors (rapamycin and PP242) and metformin, revealing that metformin controls gene expression at the level of mRNA translation to an extent comparable to that of canonical mTOR inhibitors. Importantly, metformin's anti-proliferative activity can be explained by selective translational suppression of mRNAs encoding cell cycle regulators via the mTORC1/4E-BP pathway. Thus, metformin selectively inhibits mRNA translation of encoded proteins that promote neoplastic proliferation, motivating further studies of this compound and related biguanides in cancer prevention and treatment.
Distinct perturbation of the translatome by the antidiabetic drug metformin.
Cell line, Treatment
View SamplesMost cancer deaths are caused by metastases, which are the end-results of circulating tumor cells (CTC) that detach from the cancer primary and succeed to survive in distant organs. The aim of the present study was to develop a gene signature of CTC and to assess its prognostic relevance after surgery for pancreatic ductaladenocarcinoma (PDAC).
Pancreatic cancer circulating tumour cells express a cell motility gene signature that predicts survival after surgery.
Sex, Age, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells.
Specimen part
View SamplesTo elucidate the mechamisms of colonic Treg cell induction by microbial metabolite(s), chroloform-resistant bacteria (CRB)-associated mice was developed and given low-fiber diet (LFD) and high-fiber diet (HFD). The colonic epithelial cells were isolated and gene expression profiles were analyzed by GeneChip.
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells.
Sex, Age, Specimen part, Treatment
View SamplesCommensal bacteria shapes gut immune system. Colonization bacteria increase the frequency of regulatory T cells, however, the molecular mechanisms has not yet been unknown.
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells.
Specimen part
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