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showing 10 items of 3476 documents
Origin of the Metazoan Immune System: Identification of the Molecules and Their Functions in Sponges
2011
SYNOPSIS. During the evolutionary transition to Metazoa, cell-cell- as well as cell-matrix recognition molecules have been formed, which made a further step in evolution possible, the establishment of an immune system. Sponges [Porifera] represent the oldest still extant metazoan phylum and consequently testify to major features of the common metazoan ancestor, the Urmetazoa. Most studies with respect to evolution and phylogeny in sponges have been performed with the marine demosponges Suberites domuncula and Geodia cydonium. These animals possess effective defense systems against microbes and parasites which involve engulfment of bacteria into specific cells, but also signal transduction p…
2021
Myoglobin (MB) is an oxygen-binding protein usually found in cardiac myocytes and skeletal muscle fibers. It may function as a temporary storage and transport protein for O2 but could also have scavenging capacity for reactive oxygen and nitrogen species. In addition, MB has recently been identified as a hallmark in luminal breast cancer and was shown to be robustly induced under hypoxia. Cellular responses to hypoxia are regulated by the transcription factor hypoxia-inducible factor (HIF). For exploring the function of MB in breast cancer, we employed the human cell line MDA-MB-468. Cells were grown in monolayer or as 3D multicellular spheroids, which mimic the in vivo avascular tumor arch…
Role of the aryl hydrocarbon receptor (AhR) signaling pathway in exceptional longevity in humans
2018
Centenarians are the best example of successfully aging in humans. Thus, the characterization of the biological processes and pathways in this population is an excellent strategy to understand the lifespan extension. The aryl hydrocarbon receptor (AhR) is a ligand-activated-transcription factor historically known for regulating expression of several important drug-detoxifying proteins. But recently its role in the immune response and in cellular homeostasis has been recognized. Furthermore, AhR is activated in C. Elegans in extreme longevity due to a dietary restriction. We report here results of a whole transcriptome analysis of centenarians. The main biological process was the immune resp…
Characterisation of gd T cells infiltrating colorectal cancer
2021
We have read with great interest the paper by de Vries et al 1 reporting on the immune landscape of colorectal cancer (CRC) by high-dimensional mass cytometry, flow cytometry and single cell RNA sequencing. Among clusters of immune cells infiltrating CRC, authors have identified two populations of γδ T cells: one programmed cell death protein 1 (PD-1)+ population is almost exclusively found in DNA mismatch repair (MMR)-deficient (d) tumours, constitutes up to 8.4% of CD45+ cells and has an activated phenotype, and a PD-1− counterpart with a resting phenotype, which is also found in colorectal normal mucosa and MMR-proficient (p) tumours. Using deconvolution of transcriptomic datasets and si…
Study of the aryl hydrocarbon receptor mediated effects through in silico modeling and in vitro bioassays
2020
The aryl hydrocarbon receptor (AhR) is a cytoplasmatic sensor of diverse endogenous and exogenous substances. In a toxicological context, the former known as “dioxin receptor” has been investigated as a xenobiotic chemoreceptor and due to its roles in mediating carcinogenesis, endocrine disruption, among other immunological, hepatic, cardiovascular, and dermal toxicity mechanisms. The deep physiological implications of AhR in cellular proliferation, adhesion, division, differentiation, as well as in the reproductive, immunological and cardiovascular homeostasis have opened a new field of research in order to harness AhR’s pharmacological potential. Hence, AhR has become a therapeutic target…
Cancer Signaling Transcriptome Is Upregulated in Type 2 Diabetes Mellitus
2020
We aimed to explore the differences in the whole transcriptome of peripheral blood mononuclear cells between elderly individuals with and without type 2 diabetes (T2D). We conducted a microarray-based transcriptome analysis of 19 individuals with T2D and 15 without. Differentially expressed genes according to linear models were submitted to the Ingenuity Pathway Analysis system to conduct a functional enrichment analysis. We established that diseases, biological functions, and canonical signaling pathways were significantly associated with T2D patients when their logarithms of Benjamini&ndash
Higher plants possess two different types of ATX1-like copper chaperones.
2007
Abstract Copper (Cu) chaperones constitute a family of small Cu+-binding proteins required for Cu homeostasis in eukaryotes. The ATX1 family of Cu chaperones specifically delivers Cu to heavy metal P-type ATPases. The plant Arabidopsis thaliana expresses the ATX1-like Cu chaperone CCH, which exhibits a plant-specific carboxy-terminal domain (CTD) with unique structural properties. We show that CCH homologues from other higher plants contain CTDs with structural properties similar to Arabidopsis CCH. Furthermore, we identify a new ATX1-like Cu chaperone in Arabidopsis, AtATX1, which functionally complements yeast atx1Δ and sod1Δ associated phenotypes, and localizes to the cytosol of Arabidop…
Possible Editing of Alu Transcripts in Blood Cells of Sporadic Creutzfeldt–Jakob Disease (sCJD)
2011
Editing of RNA molecules gained major interest when coding mRNA was analyzed. A small, noncoding, Alu DNA element transcript that may act as regulatory RNA in cells was examined in this study. Alu DNA element transcription was determined in buffy coat from healthy humans and human sporadic Creutzfeldt-Jakob disease (sCJD) cases. In addition, non-sCJD controls, mostly dementia cases and Alzheimer's disease (AD) cases, were included. The Alu cDNA sequences were aligned to genomic Alu DNA elements by database search. A comparison of best aligned Alu DNA sequences with our RNA/cDNA clones revealed editing by deamination by ADAR (adenosine deaminase acting on RNA) and APOBEC (apolipoprotein B ed…
Multipotential nestin and Isl-1 positive mesenchymal stem cells isolated from human pancreatic islets.
2006
Mesenchymal cells in the developing pancreas express the neural stem cell marker nestin and the transcription factor islet-1 (Isl-1). Using defined culture conditions we isolated on a single cell basis nestin producing cells from human pancreatic islets. These cells were immortalized with lentiviral vectors coding for telomerase and mBmi. They are positive for Isl-1 and nestin and have the potential to adopt a pancreatic endocrine phenotype with expression of critical transcription factors including Ipf-1, Isl-1, Ngn-3, Pax4, Pax6, Nkx2.2, and Nkx6.1 as well as the islet hormones insulin, glucagon, and somatostatin. In addition, they can be differentiated into human albumin producing cells …
Inhibition of HSP27 blocks fibrosis development and EMT features by promoting Snail degradation
2013
Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by myofibroblast proliferation. Transition of epithelial/mesothelial cells into myofibroblasts [epithelial-to-mesenchymal transition (EMT)] occurs under the influence of transforming growth factor (TGF)-β1, with Snail being a major transcription factor. We study here the role of the heat-shock protein HSP27 in fibrogenesis and EMT. In vitro, we have up- and down-modulated HSP27 expression in mesothelial and epithelial cell lines and studied the expression of different EMT markers induced by TGF-β1. In vivo, we inhibited HSP27 with the antisense oligonucleotide OGX-427 (in phase II clinical trials as anticancer agent)…