BACKGROUND: Telomeres are indispensable for genome stability maintenance. They are maintained by the telomere-associated protein complex, which include Ku proteins and a telomerase among others. Here, we investigated a role of Ku80 in Leishmania mexicana. Leishmania is a genus of parasitic protists of the family Trypanosomatidae causing a vector-born disease called leishmaniasis. METHODOLOGY/PRINCIPAL FINDINGS: We used the previously established CRISPR/Cas9 system to mediate ablation of Ku80- and Ku70-encoding genes in L. mexicana. Complete knock-outs of both genes were confirmed by Southern blotting, whole-genome Illumina sequencing, and RT-qPCR. Resulting telomeric phenotypes were subsequently investigated using Southern blotting detection of terminal restriction fragments. The genome integrity in the Ku80- deficient cells was further investigated by whole-genome sequencing. Our work revealed that telomeres in the ΔKu80 L. mexicana are elongated compared to those of the wild type. This is a surprising finding considering that in another model trypanosomatid, Trypanosoma brucei, they are shortened upon ablation of the same gene. A telomere elongation phenotype has been documented in other species and associated with a presence of telomerase-independent alternative telomere lengthening pathway. Our results also showed that Ku80 appears to be not involved in genome stability maintenance in L. mexicana. CONCLUSION/SIGNIFICANCE: Ablation of the Ku proteins in L. mexicana triggers telomere elongation, but does not have an adverse impact on genome integrity.
- MeSH
- antigen Ku genetika metabolismus MeSH
- genom protozoální MeSH
- Leishmania mexicana genetika metabolismus MeSH
- leishmanióza kožní parazitologie MeSH
- lidé MeSH
- nestabilita genomu * MeSH
- protozoální proteiny genetika metabolismus MeSH
- telomery genetika metabolismus MeSH
- Trypanosoma brucei brucei genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The aim of the present study was to investigate the reflection of psychoemotional stress in the body surface potential distribution as documented by isointegral maps of cardiac activation and recovery. In 72 young men (18.3+/- 7.3 y.) with no cardiovascular history body surface potential maps (BSPMs) at rest and during the test of mental arithmetic were recorded. The digitalized data for each point of the QRS, STT and QRST integral maps, for each subject in both situations, were processed and evaluated by methods of univariate as well as spatial mathematical and statistical modeling. The results showed during MA a significant decrease of repolarization integral values over the sternum and right precordium, which contributed to analogically localized decrements also in the QRST BSM. The decrease occurred in more than 2/3 of lead points. The most pronounced changes were observed in the right precordial area, where potentials decreased in more than in 70 % of subjects. In conclusion, the discriminative power of the difference STT and QRST integral maps was strong enough to distinguish the mental arithmetic induced changes in the superficial cardiac electric field. These adrenergic transient alterations in ventricular recovery may be of importance in subjects at risk for ventricular arrhythmias.
- MeSH
- elektrokardiografie MeSH
- lidé MeSH
- mapování potenciálů tělesného povrchu * MeSH
- převodní systém srdeční patofyziologie MeSH
- psychický stres patofyziologie MeSH
- srdeční komory patofyziologie MeSH
- statistické modely MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
