Search results for " expression"
showing 10 items of 4731 documents
TPP2 mutation associated with sterile brain inflammation mimicking MS
2018
ObjectiveTo ascertain the genetic cause of a consanguineous family from Syria suffering from a sterile brain inflammation mimicking a mild nonprogressive form of MS.MethodsWe used homozygosity mapping and next-generation sequencing to detect the disease-causing gene in the affected siblings. In addition, we performed RNA and protein expression studies, enzymatic activity assays, immunohistochemistry, and targeted sequencing of further MS cases from Austria, Germany, Canada and Jordan.ResultsIn this study, we describe the identification of a homozygous missense mutation (c.82T>G, p.Cys28Gly) in the tripeptidyl peptidase II (TPP2) gene in all 3 affected siblings of the family. Sequencing o…
Lepidopteran species have a variety of defence strategies against bacterial infections
2017
The insect immune system has versatile ways of coping with microbial insults. Currently, innate immune priming has been described in several invertebrates, and the first insights into its mechanistic basis have been described. Here we studied infections with two different strains of Serratia marcescens bacteria in two different Lepidopteran hosts. The results reveal fundamental differences between the two hosts, a well-known model organism Galleria mellonella and a non-model species Arctia plantaginis. They differ in their strategies for resisting oral infections; priming their defences against a recurring sepsis; and upregulating immunity related genes as a response to the specific pathoge…
Role of MUC4 in idiopathic pulmonary fibrosis
2019
Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and irreversible form of fibrotic intersticial lung disease, characterized by uncontrolled fibroblast proliferative processes and alveolar type II epithelial dysfunction. MUC4, a multi-domain transmembrane glycoprotein, is often overexpressed in epithelial cancers, with consequences for the biological properties, involved in cellular processes related to IPF. However, the role of MUC4 in IPF has not beet studied yet. Objective: To analyze the implication of MUC4 in IPF Methods: Lung tissue from 14 healthy and 14 IPF patients was obtained. MUC4 expression was analyzed by western blot, RT-PCR and immunohistochemistry. T…
Genomic and transcriptomic profiling of resistant CEM/ADR-5000 and sensitive CCRF-CEM leukaemia cells for unravelling the full complexity of multi-fa…
2016
AbstractWe systematically characterised multifactorial multidrug resistance (MDR) in CEM/ADR5000 cells, a doxorubicin-resistant sub-line derived from drug-sensitive, parental CCRF-CEM cells developed in vitro. RNA sequencing and network analyses (Ingenuity Pathway Analysis) were performed. Chromosomal aberrations were identified by array-comparative genomic hybridisation (aCGH) and multicolour fluorescence in situ hybridisation (mFISH). Fifteen ATP-binding cassette transporters and numerous new genes were overexpressed in CEM/ADR5000 cells. The basic karyotype in CCRF-CEM cells consisted of 47, XX, der(5)t(5;14) (q35.33;q32.3), del(9) (p14.1), +20. CEM/ADR5000 cells acquired additional aber…
Cytotoxicity of sesquiterpene alkaloids from Nuphar plants toward sensitive and drug-resistant cell lines.
2018
Multi-drug resistance (MDR) is a critical problem in cancer chemotherapy. MDR causes the overexpression of ATP-binding cassette (ABC) transporters and mutations in tumor suppressor genes and oncogenes. To tackle this issue, in this study, we focused on Nuphar plants, which have been traditionally used as food. Sesquiterpene alkaloids (1–3) were isolated from N. japonicum and dimeric sesquiterpene thioalkaloids (4–10) were isolated from N. pumilum. P-glycoprotein-overexpressing CEM/ADR5000 cells were cross-resistant to 6,6′-dihydroxythiobinupharidine (10). Using in silico molecular docking, we calculated the binding energies and simulated the interactions of these compounds with the correspo…
Role of AxyZ Transcriptional Regulator in Overproduction of AxyXY-OprZ Multidrug Efflux System in Achromobacter Species Mutants Selected by Tobramycin
2017
ABSTRACT AxyXY-OprZ is an RND-type efflux system that confers innate aminoglycoside resistance to Achromobacter spp. We investigated here a putative TetR family transcriptional regulator encoded by the axyZ gene located upstream of axyXY-oprZ . An in-frame axyZ gene deletion assay led to increased MICs of antibiotic substrates of the efflux system, including aminoglycosides, cefepime, fluoroquinolones, tetracyclines, and erythromycin, indicating that the product of axyZ negatively regulates expression of axyXY-oprZ . Moreover, we identified an amino acid substitution at position 29 of AxyZ (V29G) in a clinical Achromobacter strain that occurred during the course of chronic respiratory tract…
Spheroids from adipose-derived stem cells exhibit an miRNA profile of highly undifferentiated cells
2017
Two-dimensional (2D) cell cultures have been extensively used to investigate stem cell biology, but new insights show that the 2D model may not properly represent the potential of the tissue of origin. Conversely, three-dimensional cultures exhibit protein expression patterns and intercellular junctions that are more representative of their in vivo condition. Multiclonal cells that grow in suspension are defined as "spheroids," and we have previously demonstrated that spheroids from adipose-derived stem cells (S-ASCs) displayed enhanced regenerative capability. With the current study, we further characterized S-ASCs to further understand the molecular mechanisms underlying their stemness pr…
Prox1 Is Required for Oligodendrocyte Cell Identity in Adult Neural Stem Cells of the Subventricular Zone
2016
Abstract Adult neural stem cells with the ability to generate neurons and glia cells are active throughout life in both the dentate gyrus (DG) and the subventricular zone (SVZ). Differentiation of adult neural stem cells is induced by cell fate determinants like the transcription factor Prox1. Evidence has been provided for a function of Prox1 as an inducer of neuronal differentiation within the DG. We now show that within the SVZ Prox1 induces differentiation into oligodendrocytes. Moreover, we find that loss of Prox1 expression in vivo reduces cell migration into the corpus callosum, where the few Prox1 deficient SVZ-derived remaining cells fail to differentiate into oligodendrocytes. Thu…
Mitochondrial dynamics and metabolism in induced pluripotency.
2020
Somatic cells can be reprogrammed to pluripotency by either ectopic expression of defined factors or exposure to chemical cocktails. During reprogramming, somatic cells undergo dramatic changes in a wide range of cellular processes, such as metabolism, mitochondrial morphology and function, cell signaling pathways or immortalization. Regulation of these processes during cell reprograming lead to the acquisition of a pluripotent state, which enables indefinite propagation by symmetrical self-renewal without losing the ability of reprogrammed cells to differentiate into all cell types of the adult. In this review, recent data from different laboratories showing how these processes are control…
Dynamic clonal remodelling in breast cancer metastases is associated with subtype conversion
2019
Background: Changes in the clinical subtype (CS) and intrinsic subtype (IS) between breast cancer (BC) metastases and corresponding primary tumours have been reported. However, their relationship with tumour genomic changes remains poorly characterised. Here, we analysed the association between genomic remodelling and subtype conversion in paired primary and metastatic BC samples. Methods: A total of 57 paired primary and metastatic tumours from GEICAM/2009-03 (ConvertHER, NCT01377363) study participants with centrally assessed CS (n = 57) and IS (n = 46) were analysed. Targeted capture and next-generation sequencing of 202 genes on formalin-fixed paraffin-embedded samples was performed. Th…