Search results for "ROSAT"
showing 10 items of 520 documents
The Antioxidant Therapy: New Insights in the Treatment of Hypertension
2018
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play a key role in the regulation of the physiological and pathological signaling within the vasculature. In physiological conditions, a delicate balance between oxidants and antioxidants protects cells from the detrimental effects of ROS/RNS. Indeed, the imbalance between ROS/RNS production and antioxidant defense mechanisms leads to oxidative and nitrosative stress within the cell. These processes promote the vascular damage observed in chronic conditions, such as hypertension. The strong implication of ROS/RNS in the etiology of hypertension suggest that antioxidants could be effective in the treatment of this pathology. I…
Lack of association between screening interval and cancer stage in Lynch syndrome may be accounted for by over-diagnosis; a prospective Lynch syndrom…
2019
Background Recent epidemiological evidence shows that colorectal cancer (CRC) continues to occur in carriers of pathogenic mismatch repair (path_MMR) variants despite frequent colonoscopy surveillance in expert centres. This observation conflicts with the paradigm that removal of all visible polyps should prevent the vast majority of CRC in path_MMR carriers, provided the screening interval is sufficiently short and colonoscopic practice is optimal. Methods To inform the debate, we examined, in the Prospective Lynch Syndrome Database (PLSD), whether the time since last colonoscopy was associated with the pathological stage at which CRC was diagnosed during prospective surveillance. Path_MMR…
DNA methylation of shelf, shore and open sea CpG positions distinguish high microsatellite instability from low or stable microsatellite status colon…
2019
Aim: To investigate the genome-wide methylation of genetically characterized colorectal cancer stem cell (CR-CSC) lines. Materials & methods: Eight CR-CSC lines were isolated from primary colorectal cancer (CRC) tissues, cultured and characterized for aneuploidy, mutational status of CRC-related genes and microsatellite instability (MSI). Genome-wide DNA methylation was assessed by MethylationEPIC microarray. Results: We describe a distinctive methylation pattern that is maintained following in vivo passages in immune-compromised mice. We identified an epigenetic CR-CSC signature associated with MSI. We noticed that the preponderance of the differentially methylated positions do not re…
Contribution of allelic imbalance to colorectal cancer
2018
Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (AI) landscape in 1699 colorectal cancers, 256 of which have been whole-genome sequenced (WGSed). The imbalances pinpoint 38 genes as plausible AI targets based on previous knowledge. Unbiased CRISPR-Cas9 knockout and activation screens identified in total 79 genes within AI peaks regulating cell growth. Genetic and functional data implicate loss of TP53 as a sufficient driver of AI. The WGS highlights an influence of copy number aberrations on the rate of detected somatic point muta…
7-Keto-Cholesterol and Cholestan-3beta, 5alpha, 6beta-Triol Induce Eryptosis through Distinct Pathways Leading to NADPH Oxidase and Nitric Oxide Synt…
2019
Background/aims We showed that patho-physiological concentrations of either 7-keto-cholesterol (7-KC), or cholestane-3beta, 5alpha, 6beta-triol (TRIOL) caused the eryptotic death of human red blood cells (RBC), strictly dependent on the early production of reactive oxygen species (ROS). The goal of the current study was to assess the contribution of the erythrocyte ROS-generating enzymes, NADPH oxidase (RBC-NOX), nitric oxide synthase (RBC-NOS) and xanthine oxido-reductase (XOR) to the oxysterol-dependent eryptosis and pertinent activation pathways. Methods Phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, reactive oxygen/nitrogen species (RONS) and nitri…
Old meets new: Comparative examination of conventional and innovative RNA-based methods for body fluid identification of laundered seminal fluid stai…
2018
Abstract The knowledge about the type of the body fluid/tissue that contributed to a trace can provide contextual insight into crime scene reconstruction and connect a suspect or a victim to a crime scene. Especially in sexual assault cases, it is important to verify the presence of spermatozoa. Victims often tend to clean their underwear/bedding after a sexual assault. If they later decide to report the crime to the police, in our experience, investigators usually do not send laundered items for DNA examination, since they believe that analysis after washing is no longer promising. As not only the individualization of traces on laundered items could be important in court, but also the type…
An improved genome assembly uncovers prolific tandem repeats in Atlantic cod
2016
AbstractBackground: The first Atlantic cod (Gadus morhua) genome assembly published in 2011 was one of the early genome assemblies exclusively based on high-throughput 454 pyrosequencing. Since then, rapid advances in sequencing technologies have led to a multitude of assemblies generated for complex genomes, although many of these are of a fragmented nature with a significant fraction of bases in gaps. The development of long-read sequencing and improved software now enable the generation of more contiguous genome assemblies.Results: By combining data from Illumina, 454 and the longer PacBio sequencing technologies, as well as integrating the results of multiple assembly programs, we have …
The first high-density sequence characterized SNP-based linkage map of olive (Olea europaea L. subsp. europaea) developed using genotyping by sequenc…
2016
A number of linkage maps have been previously developed in olive; however, these are mostly composed of markers that have not been characterized at the sequence level, supplemented with smaller numbers of microsatellite markers. In this investigation, we sought to develop a saturated linkage mapping resource for olive composed entirely of sequence characterized markers. We employed genotyping by sequencing to develop a map of a F2 population derived from the selfing of the cultivar Koroneiki. The linkage map contained a total of 23 linkage groups comprised of 1,597 tagged SNP markers in 636 mapping bins spanning a genetic distance of 1189.7 cM. An additional 6,658 segregating SNPs were asso…
Exome-wide somatic mutation characterization of small bowel adenocarcinoma
2018
Small bowel adenocarcinoma (SBA) is an aggressive disease with limited treatment options. Despite previous studies, its molecular genetic background has remained somewhat elusive. To comprehensively characterize the mutational landscape of this tumor type, and to identify possible targets of treatment, we conducted the first large exome sequencing study on a population-based set of SBA samples from all three small bowel segments. Archival tissue from 106 primary tumors with appropriate clinical information were available for exome sequencing from a patient series consisting of a majority of confirmed SBA cases diagnosed in Finland between the years 2003–2011. Paired-end exome sequencing was…
Retrotransposon insertions can initiate colorectal cancer and are associated with poor survival
2019
Genomic instability pathways in colorectal cancer (CRC) have been extensively studied, but the role of retrotransposition in colorectal carcinogenesis remains poorly understood. Although retrotransposons are usually repressed, they become active in several human cancers, in particular those of the gastrointestinal tract. Here we characterize retrotransposon insertions in 202 colorectal tumor whole genomes and investigate their associations with molecular and clinical characteristics. We find highly variable retrotransposon activity among tumors and identify recurrent insertions in 15 known cancer genes. In approximately 1% of the cases we identify insertions in APC, likely to be tumor-initi…