Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.
- MeSH
- asistovaná reprodukce * MeSH
- genetické testování metody MeSH
- kongresy jako téma MeSH
- lékařská genetika metody MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Experiments were performed in C57BL/6J male mice to determine the effects of acetylcholinesterase (AChE) inhibitor pyridostigmine bromide (PB) and stress on cardiovascular function, structure, and apoptosis. Mice were studied for seven days under the following conditions: Controls (osmotic minipump with saline), PB (10 mg/kg/day, minipumps), shaker stress (45 stressors/day, minipump with saline) and PB+Stress combination. AChE activity was significantly reduced in all PB-treated mice. PB caused no changes in 24-h mean arterial pressure (MAP) or heart rate (HR). Stress increased 24-h MAP on day 1 and 24-h HR on day 7 in both Stress and PB+Stress groups. A significant reduction in the aortic wall thickness/diameter ratio (P <0.05 vs. control) and slightly reduced relative heart weight were observed in the PB group. These effects were blunted by simultaneous stress exposure. Immunochemistry was used to stain for Bax and Bcl-2 (apoptosis markers). There was a four-fold increase in Bax/Bcl-2 ratio in the heart of PB and PB+Stress treated mice while an attenuation was observed in aortic endothelium. Results suggest that a relatively short-term continuous PB exposure may have adverse effects on the heart and blood vessels, independently of changes in MAP and HR.
- MeSH
- acetylcholinesterasa krev metabolismus MeSH
- aorta účinky léků patologie patofyziologie MeSH
- apoptóza MeSH
- cholinesterasové inhibitory aplikace a dávkování toxicita MeSH
- fyziologický stres patologie patofyziologie MeSH
- kardiovaskulární systém účinky léků patofyziologie MeSH
- kortikosteron krev MeSH
- krevní tlak účinky léků MeSH
- myokard patologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- pyridostigmin-bromid aplikace a dávkování toxicita MeSH
- srdce účinky léků patofyziologie MeSH
- srdeční frekvence účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- MeSH
- acetylcholinesterasa účinky léků MeSH
- aorta účinky léků MeSH
- apoptóza účinky záření MeSH
- cholinesterasové inhibitory farmakologie MeSH
- finanční podpora výzkumu jako téma MeSH
- fyziologický stres genetika patofyziologie MeSH
- krevní tlak účinky záření MeSH
- myši inbrední C57BL MeSH
- pyridostigmin-bromid farmakologie MeSH
- srdce účinky léků MeSH
- srdeční frekvence účinky léků MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
An initiating role for RAS oncogene mutation in several epithelial cancers is supported by its high incidence in early-stage tumors and its ability to induce proliferation in the corresponding normal cells in vitro. Using retroviral transduction of thyroid epithelial cells as a model we ask here: (i) how mutant RAS can induce long-term proliferation in an epithelial cell in contrast to the premature senescence observed in fibroblasts; and (ii) what is the "clock" which eventually triggers spontaneous growth arrest even in epithelial clones generated by mutant RAS. The early response to RAS activation in thyroid epithelial cells showed two features not seen in fibroblasts: (i) a marked decrease in expression of the cyclin-dependent kinase inhibitor (CDKI) p27(kip1) and (ii) the absence of any induction of p21(waf1). When proliferation eventually ceased (after up to 20 population doublings) this occurred despite undiminished expression of mutant RAS and was tightly correlated with a return to the initial high level of p27(kip1) expression, together with the de novo appearance of p16(ink4a). Importantly, neither the CDKI changes nor the proliferative life span of RAS-induced epithelial clones was altered by induction of telomerase activity through forced expression of the catalytic subunit, hTERT, at levels sufficient to immortalize human fibroblasts. These data provide a basis for cell-type differences in sensitivity to RAS-induced proliferation which may explain the corresponding tumor-type specificity of RAS mutation. They also show for the first time in a primary human cell model that a telomere-independent mechanism can limit not only physiological but also oncogene-driven proliferation, pointing therefore to a tumour suppressor mechanism additional, or alternative, to the telomere clock.
- MeSH
- buněčné dělení genetika MeSH
- cykliny genetika metabolismus MeSH
- epitelové buňky fyziologie MeSH
- inhibitor p16 cyklin-dependentní kinasy genetika metabolismus MeSH
- inhibitor p21 cyklin-dependentní kinasy MeSH
- katalytická doména MeSH
- kultivované buňky MeSH
- lidé MeSH
- mikrofilamentové proteiny genetika metabolismus MeSH
- mutace MeSH
- onkogenní proteiny virové genetika MeSH
- ras proteiny * genetika MeSH
- štítná žláza * cytologie MeSH
- svalové proteiny * MeSH
- telomery * genetika metabolismus MeSH
- Check Tag
- lidé MeSH
