Abstract
MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression, and are frequently aberrantly expressed in cancer. We aimed to understand their role in the ...transformation of indolent follicular lymphoma (FL) into an aggressive diffuse large B cell lymphoma. This happens in ~3% of cases per year during the course of the disease, and is associated with median survival of only 2 years. The NGS revealed number of aberrations associated with transformed FL (tFL), including frequent high-level activity of MYC (amplifications, translocations, and mutations) or loss of DNA damage regulators (p53, CDKN2A/B). Firstly, we performed a miRNA profiling (TaqMan miRNA Arrays) in paired FL and tFL samples (N=8 pairs). This revealed a relatively small group of 5 miRNAs that are consistently differentially expressed in tFL (P<0.05, fold-change >1.5). Since the most frequently acquired aberration in tFL is the high-level activity of MYC we performed a correlation analysis of MYC levels and expression of these miRNAs in additional samples of FL, tFL, and CLL samples with/without MYC duplication (N=40 FL/tFL, N=39 CLL). This revealed that at least one of these miRNAs is significantly down-modulated (P<0.05) in cases with high-levels of MYC. The MYC-mediated repression of miRNA levels was also observed (P<0.05) in B cells from transgenic MYC over-expressing mice (MYC controlled by an Ig-alpha enhancer) in comparison to wild-type animals (samples obtained from young animals before occurrence of any malignancy). We have further shown that the levels of this miRNA affect B cell proliferation in vitro, and its low-levels associate with percentage of Ki67 positive cells in FL samples (P<0.005). Moreover, low levels of tFL-associated miRNA were present in FL cases with a shorter overall survival (P<0.01), and its expression directly affected BCR signalling (calcium flux assay after anti-IgM). We have shown that the expression of this miRNA is not only down-modulated by high-level MYC expression, but also by B cell adhesion to stromal cells in co-culture in vitro (HS-5 stromal cells). This suggests that its normal physiological function might be related to regulation of B cell functions in the context of immune niches, and this might play a role in FL progression and transformation. It remains to be elucidated what other molecular mechanisms ensure low-level expression of the studied miRNA in cases that do not harbor MYC over-expression, and what pool of target mRNAs is regulated by this miRNA in FL cells.This work was supported by: the Ministry of Health of the Czech Republic, grant nr. 16-29622A. All rights reserved. contact: marek.mraz@email.cz
Citation Format: Katerina Musilova, Gabriela Pavlasova, Vaclav Seda, Eva Vojackova, Katerina Cerna, Veronika Svobodova, Robert Pytlik, Vit Prochazka, Zuzana Prouzova, Sarka Pospisilova, Lenka Zlamalikova, Heidi Mocikova, Lenka Kruzova, Marie Jarosova, Andrew Evans, Clive Zent, Leos Kren, Marek Trneny, Jiri Mayer, Andrea Janikova, Marek Mraz. Differential expression of microRNAs in transformation of follicular lymphoma to diffuse large B cell lymphoma abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1479. doi:10.1158/1538-7445.AM2017-1479
Methotrexate (MTX) released from bone cement showed a useful local effect in animal models of bone tumours. However, local toxic reactions such as impaired wound healing were observed in areas ...surrounding the MTX-loaded implant. Therefore, we hypothesised that MTX released from bone cement would have harmful effects on human mesenchymal stem cells (MSC)—one of the basic components of bone marrow and tissue reparatory processes. Moreover, elution of MTX was calculated from implants prepared either with liquid or powdered MTX. During the 28-day incubation, the cement compounded with liquid MTX showed the highest elution rate of the drug. MTX released from pellets produced a significant decrease in proliferation of MSC as a consequence of a blockade of their cell cycle in the S/G2 phase. These findings indicate impairment of stem cell function in marginal areas surrounding the MTX-loaded cement and may help to explain problems with regeneration of tissues in these locations.
Study of Steel Wire Ropes Defects Lesnak, Michal; Prochazka, Jan; Hlavatý, Ivo ...
Applied Mechanics and Materials,
10/2014, Letnik:
683, Številka:
Research, Production and Use of Steel Ropes, Conveyors and Hoisting Machines
Journal Article
Recenzirano
This article deals with the study of defects in steel wire. In the study we model magnetic fields around rope genetated by magnetized part of rope. The work is based on the finite element program ...ANSYS. For the purposes of the experiments we consider one strand wire rope construction. We define different kinds of defects and faults. The shape of the magnetic induction lines of generated fields depends on the size of the defect, the depth of rope violation or the presence of other nearby defects. The location and number of disturbances have been chosen to achieve the most versatile outputs. All of these modifications were analyzed and the results displayed in the 3D colored.
The addiction to psychoactive drugs still remains among the relevant research topics. The research herein focuses on the study and analysis of the relations among the alexithymia, and personality ...styles. The analyses of such psychological constructs may represent valuable views beneficial for the progress in the up-to-date addictology. The article deals with a number of topics, such as, definition of alexithymia, the issue of addictology and personality aspects.. The applied statistical methods are descriptive statistics, factor analysis, non-parametric Spearman's correlation analysis and Mann-Whitney U Test. The reason for choosing the non-parametric statistics has been the conclusion of the normality test pointing at the fact that the acquired data had not complied with the normal distribution assumption. The data collection methods were questionnaires TAS-20 (Toronto Alexithymia Scale) to measure alexithymia, and PSSI (Personality Style and Disorder Inventory). The gross sample under research was represented by 55 probands, namely 14 women and 41 men. The data were collected in the Psychiatric Hospital of Marianna Oranžská in Bílá Voda. The obtained results enabled us to answer the postulated research questions, which were evaluated and the following conclusions were reached: In people addicted to alcohol alexithymia occurs in 41.83 %. In subjects addicted to psychoactive drugs with alexithymia there is a substantial difference in the personality styles of a schizoid, obsessive-compulsive, avoidant, negativistic, borderline, histrionic, and self-defeating type. We believe that in this field of research there is still a huge gap to be filled, and we hope that the research may help to do so by enriching the knowledge with concrete results.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Hosts have evolved a multiplicity of defensive responses against avian brood parasites. One of them is mobbing behaviour which often includes direct contact attacks. These aggressive strikes may not ...only distract the parasites but may also be fatal to them, as documented by cases of dead brood parasite females found near host nests. Here, we present the first video-recording of a great reed warbler (Acrocephalus arundinaceus) host whose vigorous nest defence appears to directly lead to the death of a female common cuckoo (Cuculus canorus). We suggest that the chance of parasite death probably rises with the presence of unfavourable factors, such as water below the nest. Our observation supports previous suggestions that hosts may pose a lethal danger to their parasites.
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