BACKGROUND: This study investigates the modulatory effect of stimulus sequence on neural responses to novel stimuli. A group of 34 healthy volunteers underwent event-related functional magnetic resonance imaging while performing a three-stimulus visual oddball task, involving randomly presented frequent stimuli and two types of infrequent stimuli - targets and distractors. NEW METHOD: We developed a modified categorization of rare stimuli that incorporated the type of preceding rare stimulus, and analyzed the event-related functional data according to this sequence categorization; specifically, we explored hemodynamic response modulation associated with increasing rare-to-rare stimulus interval. RESULTS: For two consecutive targets, a modulation of brain function was evident throughout posterior midline and lateral temporal cortex, while responses to targets preceded by distractors were modulated in a widely distributed fronto-parietal system. As for distractors that follow targets, brain function was modulated throughout a set of posterior brain structures. For two successive distractors, however, no significant modulation was observed, which is consistent with previous studies and our primary hypothesis. COMPARISON WITH EXISTING METHODS: The addition of the aforementioned technique extends the possibilities of conventional oddball task analysis, enabling researchers to explore the effects of the whole range of rare stimuli intervals. CONCLUSION: This methodology can be applied to study a wide range of associated cognitive mechanisms, such as decision making, expectancy and attention.
- MeSH
- dospělí MeSH
- kyslík krev MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- mapování mozku * MeSH
- mladý dospělý MeSH
- mozek krevní zásobení fyziologie MeSH
- neuropsychologické testy MeSH
- počítačové zpracování obrazu MeSH
- pozornost fyziologie MeSH
- světelná stimulace MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The terminal chromatin structures at the ends of eukaryotic chromosomes, the telomeres, are a focus of intensive research due to their importance for the maintenance of chromosome integrity. Their shortening due to incomplete replication functions as a molecular clock counting the number of cell divisions, and ultimately results in cell-cycle arrest and cellular senescence. Telomere shortening can be compensated by the nucleoprotein enzyme complex called telomerase, which is able to extend shortened telomeres. In humans, only embryonic and germ cells show telomerase activity that is sufficient for telomere length stability and cellular immortality. Unfortunately, telomerase is activated in cancer cells, which, thus, achieve unlimited growth and a malignant phenotype. Even if there were no any other links of telomere biology to other essential processes in the cell nucleus such as DNA repair, chromosome positioning, and nuclear architecture in mitosis and meiosis, the close connection of telomere biology to aging and cancer makes telomeres and techniques for their analysis important enough from the point of view of us, mortal and disease-prone people. In this chapter, we describe the most common types of analyses used in telomere biology: screening for typical and variant telomeric sequences, determination of telomere lengths, and measurement of telomerase activity.
- MeSH
- buněčný cyklus MeSH
- chromozomy ultrastruktura MeSH
- endodeoxyribonukleasy metabolismus MeSH
- fenotyp MeSH
- genetické techniky MeSH
- hybridizace in situ fluorescenční MeSH
- lidé MeSH
- molekulová hmotnost MeSH
- oprava DNA MeSH
- polymerázová řetězová reakce MeSH
- restrikční enzymy metabolismus MeSH
- sefarosa chemie MeSH
- stárnutí buněk MeSH
- telomerasa metabolismus MeSH
- telomery ultrastruktura MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Telomerase activity is closely connected to problems of cellular immortality, proliferative capacity, differentiation, cancer and aging. Correspondingly, techniques for its detection have been essential for progress in telomere biology and are of still increasing importance in molecular diagnostics and therapy of cancer. This article reviews the development of the telomere repeat amplification protocol (TRAP) and its various modifications as the most widespread assay to detect and measure telomerase activity. Alternative possibilities of telomerase activity detection are also discussed which make it possible to omit the PCR-mediated amplification of telomerase products. These approaches are based on recent advances in highly sensitive detection systems.
- MeSH
- biosenzitivní techniky MeSH
- financování organizované MeSH
- lidé MeSH
- nádorové biomarkery MeSH
- nádorové buňky kultivované enzymologie MeSH
- nádory diagnóza enzymologie genetika MeSH
- polymerázová řetězová reakce metody MeSH
- sekvence nukleotidů MeSH
- senzitivita a specificita MeSH
- telomerasa analýza metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
This paper examines telomeres from an evolutionary perspective. In the monocot plant order Asparagales two evolutionary switch-points in telomere sequence are known. The first occurred when the Arabidopsis-type telomere was replaced by a telomere based on a repeat motif more typical of vertebrates. The replacement is associated with telomerase activity, but the telomerase has low fidelity and this may have implications for the binding of telomeric proteins. At the second evolutionary switch-point, the telomere and its mode of synthesis are replaced by an unknown mechanism. Elsewhere in plants (Sessia, Vestia, Cestrum) and in arthropods, the telomere "typical" of the group is lost. Probably many other groups with "unusual" telomeres will be found. We question whether telomerase is indeed the original end-maintenance system and point to other candidate processes involving t-loops, t-circles, rolling circle replication and recombination. Possible evolutionary outcomes arising from the loss of telomerase activity in alternative lengthening of telomere (ALT) systems are discussed. We propose that elongation of minisatellite repeats using recombination/replication processes initially substitutes for the loss of telomerase function. Then in more established ALT groups, subtelomeric satellite repeats may replace the telomeric minisatellite repeat whilst maintaining the recombination/replication mechanisms for telomere elongation. Thereafter a retrotransposition-based end-maintenance system may become established. The influence of changing sequence motifs on the properties of the telomere cap is discussed. The DNA and protein components of telomeres should be regarded--as with any other chromosome elements--as evolving and co-evolving over time and responding to changes in the genome and to environmental stresses. We describe how telomere dysfunction, resulting in end-to-end chromosome fusions, can have a profound effect on chromosome evolution and perhaps even speciation.
- MeSH
- buněčné jádro fyziologie MeSH
- DNA rostlinná fyziologie MeSH
- finanční podpora výzkumu jako téma MeSH
- geneticky modifikované rostliny MeSH
- rostliny genetika MeSH
- techniky amplifikace nukleových kyselin metody MeSH
- techniky in vitro MeSH
- telomerasa metabolismus MeSH
- telomery fyziologie chemie MeSH
- MeSH
- finanční podpora výzkumu jako téma MeSH
- hybridizace in situ fluorescenční MeSH
- molekulární biologie MeSH
- nádory diagnostické užití terapie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- telomerasa fyziologie genetika terapeutické užití MeSH
- telomery fyziologie genetika MeSH
- Publikační typ
- přehledy MeSH
- srovnávací studie MeSH
- MeSH
- adenokarcinom genetika metabolismus MeSH
- finanční podpora výzkumu jako téma MeSH
- kolon embryologie metabolismus MeSH
- lidé MeSH
- nádorové proteiny genetika metabolismus MeSH
- nádory tračníku metabolismus patologie MeSH
- regulace genové exprese u nádorů účinky léků MeSH
- sestřih RNA MeSH
- telomerasa genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
