Search results for "Cause"

ΔNp63 drives metastasis in breast cancer cells via PI3K/CD44v6 axis

2016

P63 is a transcription factor belonging to the family of p53, essential for the development and differentiation of epithelia. In recent years, it has become clear that altered expression of the different isoforms of this gene can play an important role in carcinogenesis. The p63 gene encodes for two main isoforms known as TA and ΔN p63 with different functions. The role of these different isoforms in sustaining tumor progression and metastatic spreading however has not entirely been clarified. Here we show that breast cancer initiating cells express ΔNp63 isoform that supports a more mesenchymal phenotype associated with a higher tumorigenic and metastatic potential. On the contrary, the ma…

NOX2ko Mice Show Largely Increased Expression of a Mutated NOX2 mRNA Encoding an Inactive NOX2 Protein

2020

Background: The superoxide-generating enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2 or gp91phox, the phagocytic isoform) was reported as a major source of oxidative stress in various human diseases. Genetic deletion is widely used to study the impact of NOX2-derived reactive oxygen species (ROS) on disease development and progression in various animal models. Here, we investigate why NOX2 knockout mice show no NOX2 activity but express NOX2 mRNA and protein. Methods and Results: Oxidative burst (NOX2-dependent formation of ROS) was measured by L-012-based chemiluminescence and was largely absent in whole blood of NOX2 knockout mice. Protein expression was still de…

Small molecule inhibitors and stimulators of inducible nitric oxide synthase in cancer cells from natural origin (phytochemicals, marine compounds, a…

2019

Nitric oxide synthases (NOS) are a family of isoforms, which generate nitric oxide (NO). NO is one of the smallest molecules in nature and acts mainly as a potent vasodilator. It participates in various biological processes ranging from physiological to pathological conditions. Inducible NOS (iNOS, NOS2) is a calcium-independent and inducible isoform. Despite high iNOS expression in many tumors, the role of iNOS is still unclear and complex with both enhancing and prohibiting actions in tumorigenesis. Nature presents a broad variety of natural stimulators and inhibitors, which may either promote or inhibit iNOS response. In the present review, we give an overview of iNOS-modulating agents w…

2017

Coastal marine Vibrio cholerae populations usually exhibit high genetic diversity. To assess the genetic diversity of abundant V. cholerae non-O1/non-O139 populations in the Central European lake Neusiedler See, we performed a phylogenetic analysis based on recA, toxR, gyrB and pyrH loci sequenced for 472 strains. The strains were isolated from three ecologically different habitats in a lake that is a hot-spot of migrating birds and an important bathing water. We also analyzed 76 environmental and human V. cholerae non-O1/non-O139 isolates from Austria and other European countries and added sequences of seven genome-sequenced strains. Phylogenetic analysis showed that the lake supports a un…

Oral Monosodium Glutamate Administration Causes Early Onset of Alzheimer's Disease-Like Pathophysiology in APP/PS1 Mice.

2019

Glutamate excitotoxicity has long been related to Alzheimer's disease (AD) pathophysiology, and it has been shown to affect the major AD-related hallmarks, amyloid-β peptide (Aβ) accumulation and tau phosphorylation (p-tau). We investigated whether oral administration of monosodium glutamate (MSG) has effects in a murine model of AD, the double transgenic mice APP/PS1. We found that AD pathogenic factors appear earlier in APP/PS1 when supplemented with MSG, while wildtype mice were essentially not affected. Aβ and p-tau levels were increased in the hippocampus in young APP/PS1 animals upon MSG administration. This was correlated with increased Cdk5-p25 levels. Furthermore, in these mice, we…

Water: The First Archaic Mutagen of Evolution, the Adoptive Mother of Currently Nucleic Acids

2016

It would be intuitive to think that for the evolutionary onset of nucleic acids, and even before of their monomeric constituents, the water was crucial. Within the series of evolutions which start from the origin of the universe and still cannot, by definition, be considered concluded, certainly among the geothermal evolution end and the beginning of the chemical one, on Earth, the moment was favorable for the arrival of the first proto-nucleotides: from underground deposits of methanehydrate [1] and phosphate, with the support of all known pre-biotic physical-chemical conditions, were made the monomeric components of nucleic acids. The cradle of nucleic acids does not seem to have been so …

Nearly Complete Genome Sequences of Human Norovirus Belonging to Several Genotypes from Valencia, Spain

2019

Human noroviruses are responsible for most nonbacterial acute gastroenteritis cases. The GII.2, GII.4, and GII.17 genotypes of human noroviruses have recently arisen as the most frequent genotypes found in humans worldwide. We report here seven nearly complete genomes of these genotypes from patients with acute gastroenteritis in Valencia, Spain.

2021

Familial pancreatic cancer (FPC) is an established but rare inherited tumor syndrome that accounts for approximately 5% of pancreatic ductal adenocarcinoma (PDAC) cases. No major causative gene defect has yet been identified, but germline mutations in predisposition genes BRCA1/2, CDKN2A and PALB2 could be detected in 10–15% of analyzed families. Thus, the genetic basis of disease susceptibility in the majority of FPC families remains unknown. In an attempt to identify new candidate genes, we performed whole-genome sequencing on affected patients from 15 FPC families, without detecting BRCA1/2, CDKN2A or PALB2 mutations, using an Illumina based platform. Annotations from CADD, PolyPhen-2, S…

STAG1 mutations cause a novel cohesinopathy characterised by unspecific syndromic intellectual disability

2017

Item does not contain fulltext BACKGROUND: Cohesinopathies are rare neurodevelopmental disorders arising from a dysfunction in the cohesin pathway, which enables chromosome segregation and regulates gene transcription. So far, eight genes from this pathway have been reported in human disease. STAG1 belongs to the STAG subunit of the core cohesin complex, along with five other subunits. This work aimed to identify the phenotype ascribed to STAG1 mutations. METHODS: Among patients referred for intellectual disability (ID) in genetics departments worldwide, array-comparative genomic hybridisation (CGH), gene panel, whole-exome sequencing or whole-genome sequencing were performed following the …

Specific mosaicKRASmutations affecting codon 146 cause oculoectodermal syndrome and encephalocraniocutaneous lipomatosis

2016

Oculoectodermal syndrome (OES) and encephalocraniocutaneous lipomatosis (ECCL) are rare disorders that share many common features, such as epibulbar dermoids, aplasia cutis congenita, pigmentary changes following Blaschko lines, bony tumor-like lesions, and others. About 20 cases with OES and more than 50 patients with ECCL have been reported. Both diseases were proposed to represent mosaic disorders, but only very recently whole-genome sequencing has led to the identification of somatic KRAS mutations, p.Leu19Phe and p.Gly13Asp, in affected tissue from two individuals with OES. Here we report the results of molecular genetic studies in three patients with OES and one with ECCL. In all four…