Differential Expression of MicroRNAs in CD34+ Cells of 5q- Syndrome

<p>Abstract</p> <p>Background</p> <p>Myelodysplastic syndrome with isolated chromosome 5q deletion (5q- syndrome) is a clonal stem cell disorder characterized by ineffective hematopoiesis. MicroRNAs (miRNAs) are important regulators of hematopoiesis and their aberrant expression was detected in some clonal hematopoietic disorders. We thus analyzed miRNA expressions in bone marrow CD34+ cells of 5q- syndrome patients. Further, we studied gene expressions of <it>miR-143</it>, <it>miR-145</it>, <it>miR-378 </it>and <it>miR-146a </it>mapped within the 5q deletion.</p> <p>Results</p> <p>Using microarrays we identified 21 differently expressed miRNAs in 5q- patients compared to controls. Especially, <it>miR-34a </it>was markedly overexpressed in 5q- patients, suggesting its role in an increased apoptosis of bone marrow progenitors. Out of four miRNAs at del(5q), only <it>miR-378 </it>and <it>miR-146a </it>showed reduced gene expression in the patients. An integrative analysis of mRNA profiles and predicted putative targets defined potential downstream targets of the deregulated miRNAs. The list of targets included several genes that play an important role in the regulation of hematopoiesis (e.g. <it>KLF4</it>, <it>LEF1</it>, <it>SPI1</it>).</p> <p>Conclusions</p> <p>The study demonstrates global overexpression of miRNAs is associated with 5q- phenotype. Identification of hematopoiesis-relevant target genes indicates that the deregulated miRNAs may be involved in the pathogenesis of 5q- syndrome by a modulation of these targets. The expression data on miRNAs at del(5q) suggest the presence of mechanisms for compensation of a gene dosage.</p

In utero exposure to cigarette smoke and effects across generations:A conference of animals on asthma

Background: The prevalence of asthma and chronic obstructive pulmonary disease (COPD) has risen markedly over the last decades and is reaching epidemic proportions. However, underlying molecular mechanisms are not fully understood, hampering the urgently needed development of approaches to prevent these diseases. It is well established from epidemiological studies that prenatal exposure to cigarette smoke is one of the main risk factors for aberrant lung function development or reduced fetal growth, but also for the development of asthma and possibly COPD later in life. Of note, recent evidence suggests that the disease risk can be transferred across generations, that is, from grandparents to their grandchildren. While initial studies in mouse models on in utero smoke exposure have provided important mechanistic insights, there are still knowledge gaps that need to be filled. Objective: Thus, in this review, we summarize current knowledge on this topic derived from mouse models, while also introducing two other relevant animal models: the fruit fly Drosophila melanogaster and the zebrafish Danio rerio. Methods: This review is based on an intensive review of PubMed-listed transgenerational animal studies from 1902 to 2018 and focuses in detail on selected literature due to space limitations. Results: This review gives a comprehensive overview of mechanistic insights obtained in studies with the three species, while highlighting the remaining knowledge gaps. We will further discuss potential (dis)advantages of all three animal models. Conclusion/Clinical Relevance: Many studies have already addressed transgenerational inheritance of disease risk in mouse, zebrafish or fly models. We here propose a novel strategy for how these three model organisms can be synergistically combined to achieve a more detailed understanding of in utero cigarette smoke-induced transgenerational inheritance of disease risk

Zmeny masnych vyrobku a hotovych pokrmu s podilem masa behem skladovani

Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

The effect of water temperature on cooling during high pressure water descaling

Production of hot rolled steel plates is connected with high temperatures at which steel reacts with oxygen in the atmosphere and oxide layers (scales) are formed on the surface. Scales affect the surface quality of the product and must be eliminated before the product enters any further rolling operations. The scales are usually removed by high pressure flat jet water nozzles in a process called hydraulic descaling. One side effect of this form of descaling is intense cooling of the product, which runs counter to the purpose of descaling. One way to decrease this effect is to use water at higher temperatures. Laboratory experiments were performed in order to determine the degree of influence of water temperature on the intensity of cooling. Temperature measurements were used as an input for inverse algorithm calculations and heat transfer coefficient determinations. The variables were computed as a function of time and position. The results were compared and significant decrease in the cooling intensity was observed. The findings are discussed in detail