Kovarik, P D E*
Dotaz
Zobrazit nápovědu
- MeSH
- autoprotilátky krev MeSH
- dospělí MeSH
- ELISA MeSH
- fibrosarkom MeSH
- imunohistochemie MeSH
- lidé MeSH
- nádorový supresorový protein p53 imunologie MeSH
- nádory prsu imunologie krev patologie MeSH
- staging nádorů MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
To study the relationship between uniparental rDNA (encoding 18S, 5.8S and 26S ribosomal RNA) silencing (nucleolar dominance) and rRNA gene dosage, we studied a recently emerged (within the last 80 years) allotetraploid Tragopogon mirus (2n=24), formed from the diploid progenitors T. dubius (2n=12, D-genome donor) and T. porrifolius (2n=12, P-genome donor). Here, we used molecular, cytogenetic and genomic approaches to analyse rRNA gene activity in two sibling T. mirus plants (33A and 33B) with widely different rRNA gene dosages. Plant 33B had ~400 rRNA genes at the D-genome locus, which is typical for T. mirus, accounting for ~25% of total rDNA. We observed characteristic expression dominance of T. dubius-origin genes in all organs. Its sister plant 33A harboured a homozygous macrodeletion that reduced the number of T. dubius-origin genes to about 70 copies (~4% of total rDNA). It showed biparental rDNA expression in root, flower and callus, but not in leaf where D-genome rDNA dominance was maintained. There was upregulation of minor rDNA variants in some tissues. The RNA polymerase I promoters of reactivated T. porrifolius-origin rRNA genes showed reduced DNA methylation, mainly at symmetrical CG and CHG nucleotide motifs. We hypothesise that active, decondensed rDNA units are most likely to be deleted via recombination. The silenced homeologs could be used as a 'first reserve' to ameliorate mutational damage and contribute to evolutionary success of polyploids. Deletion and reactivation cycles may lead to bidirectional homogenisation of rRNA arrays in the long term.
- MeSH
- genová dávka * MeSH
- geny rRNA * MeSH
- metylace DNA MeSH
- molekulární evoluce MeSH
- molekulární sekvence - údaje MeSH
- organizátor jadérka MeSH
- polyploidie MeSH
- promotorové oblasti (genetika) MeSH
- RNA ribozomální 18S genetika MeSH
- RNA ribozomální 5.8S genetika MeSH
- RNA ribozomální genetika MeSH
- rostlinné geny * MeSH
- sekvenční analýza DNA MeSH
- sekvenční delece MeSH
- Tragopogon genetika MeSH
- umlčování genů * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
Uniparental silencing of 35S rRNA genes (rDNA), known as nucleolar dominance (ND), is common in interspecific hybrids. Allotetraploid Tragopogon mirus composed of Tragopogon dubius (d) and Tragopogon porrifolius (p) genomes shows highly variable ND. To examine the molecular basis of such variation, we studied the genetic and epigenetic features of rDNA homeologs in several lines derived from recently and independently formed natural populations. Inbred lines derived from T. mirus with a dominant d-rDNA homeolog transmitted this expression pattern over generations, which may explain why it is prevalent among natural populations. In contrast, lines derived from the p-rDNA dominant progenitor were meiotically unstable, frequently switching to co-dominance. Interpopulation crosses between progenitors displaying reciprocal ND resulted in d-rDNA dominance, indicating immediate suppression of p-homeologs in F1 hybrids. Original p-rDNA dominance was not restored in later generations, even in those segregants that inherited the corresponding parental rDNA genotype, thus indicating the generation of additional p-rDNA and d-rDNA epigenetic variants. Despite preserved intergenic spacer (IGS) structure, they showed altered cytosine methylation and chromatin condensation patterns, and a correlation between expression, hypomethylation of RNA Pol I promoters and chromatin decondensation was apparent. Reversion of such epigenetic variants occurred rarely, resulting in co-dominance maintained in individuals with distinct genotypes. Generally, interpopulation crosses may generate epialleles that are not present in natural populations, underlying epigenetic dynamics in young allopolyploids. We hypothesize that highly expressed variants with distinct IGS features may induce heritable epigenetic reprogramming of the partner rDNA arrays, harmonizing the expression of thousands of genes in allopolyploids.
- MeSH
- DNA rostlinná genetika MeSH
- epigenomika * MeSH
- fenotyp MeSH
- genom rostlinný genetika MeSH
- genotyp MeSH
- hybridizace genetická MeSH
- metylace DNA MeSH
- molekulární evoluce * MeSH
- polyploidie MeSH
- regulace genové exprese u rostlin * MeSH
- ribozomální DNA genetika MeSH
- Tragopogon genetika MeSH
- umlčování genů MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: The association between energy metabolism and prognosis in polytrauma patients has not yet been defined. The aim of this study was to describe energy metabolism and analyze the prognostic value of respiratory quotient (RQ) and nonprotein respiratory quotient (npRQ) in fasting polytrauma patients (fPP) and polytrauma patients with nutritional support (nsPP). METHODS: Twenty-two polytrauma patients (before and after parenteral nutrition administration) and 22 healthy controls (after overnight fasting) were examined on day 4 (median) after admission to the intensive care unit. To evaluate energy expenditure in nsPP and resting energy expenditure in fPP and controls with RQ and npRQ in all groups, we used indirect calorimetry. With regression analysis, the descriptive models of intensive care unit (ICU) length of stay (LOS) and mechanical ventilation time (VT) were derived. RESULTS: RQ and npRQ were significantly lower in fPP than in controls (P < 0.05 and P < 0.01, respectively) and in nsPP (P < 0.05). In nsPP, relationships between RQ or npRQ and the ICU LOS or mechanical VT were demonstrated (P < 0.0001, r = -0.78 for RQ and VT; P < 0.0001, r = -0.78 for npRQ and VT; P < 0.001, r = -0.69 for RQ and LOS; P < 0.001, r = -0.72 for npRQ and LOS). CONCLUSIONS: RQ and npRQ parameters measured by indirect calorimetry in polytrauma patients with parenteral nutrition on the fourth day of ICU stay related to clinical outcomes such as duration of mechanical ventilation and ICU LOS.
- MeSH
- bazální metabolismus MeSH
- časové faktory MeSH
- délka pobytu statistika a číselné údaje MeSH
- dospělí MeSH
- energetický metabolismus MeSH
- jednotky intenzivní péče MeSH
- lidé středního věku MeSH
- lidé MeSH
- nepřímá kalorimetrie metody statistika a číselné údaje MeSH
- omezení příjmu potravy MeSH
- parenterální výživa statistika a číselné údaje MeSH
- pilotní projekty MeSH
- polytrauma patofyziologie terapie MeSH
- prognóza MeSH
- prospektivní studie MeSH
- regresní analýza MeSH
- respirační funkční testy metody statistika a číselné údaje MeSH
- umělé dýchání statistika a číselné údaje MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
The affiliation number 1, "Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 65 Brno, Czech Republic" changed its zip code to 612 00 [...].
- Publikační typ
- tisková chyba MeSH
The aim was to determine the effect of fybrinolytic therapy by streptokinase on chemotherapy and radiation response in human colon cancer cells. The cells were treated with different concentrations of gemcitabine, cis-platine and streptokinase, at a single use or in combinations. Radiation was tested at a dose 0.5, 5 and 15 Gy in three different schedules. The chemotherapy showed higher cytotoxic effect in combination with streptokinase. On the other hand, the combination of chemotherapy with streptokinase and radiotherapy provide no improvement in sensitivity of cancer cells to treatment. The data suggest that fybrinolytic therapy could influence the effect of chemotherapy.
- MeSH
- buňky HT-29 MeSH
- časové faktory MeSH
- cisplatina farmakologie MeSH
- deoxycytidin analogy a deriváty farmakologie MeSH
- fibrinolytika farmakologie MeSH
- financování organizované MeSH
- lidé MeSH
- nádory tračníku MeSH
- proliferace buněk účinky léků účinky záření MeSH
- protinádorové látky farmakologie MeSH
- streptokinasa farmakologie MeSH
- synergismus léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
Background The lack of effective biomarkers for the screening and early detection of ovarian cancer (OC) is one of the most pressing problems in oncogynecology. Because epigenetic alterations occur early in the cancer development, they provide great potential to serve as such biomarkers. In our study, we investigated a potential of a four-gene methylation panel (including CDH13, HNF1B, PCDH17 and GATA4 genes) for the early detection of high-grade serous ovarian carcinoma (HGSOC). Methods For methylation detection we used methylation sensitive high-resolution melting analysis and real-time methylation specific analysis. We also investigated the relation between gene hypermethylation and gene relative expression using the 2-ΔΔCt method. Results The sensitivity of the examined panel reached 88.5%. We were able to detect methylation in 85.7% (12/14) of early stage tumors and in 89.4% (42/47) of late stage tumors. The total efficiency of the panel was 94.4% and negative predictive value reached 90.0%. The specificity and positive predictive value achieved 100% rates. Our results showed lower gene expression in the tumor samples in comparison to control samples. The more pronounced downregulation was measured in the group of samples with detected methylation. Conclusions In our study we designed the four-gene panel for HGSOC detection in ovarian tissue with 100% specificity and sensitivity of 88.5%. The next challenge is translation of the findings to the less invasive source for biomarker examination, such as plasma. Our results indicate that combination of examined genes deserve consideration for further testing in clinical molecular diagnosis of HGSOC.
- MeSH
- časná detekce nádoru MeSH
- lidé MeSH
- metylace DNA * MeSH
- nádorové biomarkery krev MeSH
- nádory vaječníků krev diagnóza genetika MeSH
- senzitivita a specificita MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
