• MeSH
• antiflogistika nesteroidní farmakokinetika   farmakologie   terapeutické užití   MeSH
• antiflogistika farmakokinetika   farmakologie   terapeutické užití   MeSH
• bezpečnost MeSH
• inhibitory cyklooxygenasy 2 farmakokinetika   farmakologie   terapeutické užití   MeSH
• management farmakoterapie MeSH
• osteoartróza farmakoterapie   MeSH
• Publikační typ
• souborné dílo MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• farmakoterapie
• farmacie a farmakologie
• revmatologie

The aim of this prospective study was to assess the duration of culture-viable SARS-CoV-2 and to monitor the emergence of mutations in a cohort of 23 kidney transplant recipients (KTRs) from June 2022 to June 2023. Combined nares/oropharyngeal swabs were collected weekly starting as soon as possible after symptom onset. The time from symptom onset to a negative culture was 11 days (interquartile range, 8-14), while the time to negative reverse transcriptase quantitative polymerase chain reaction was 18 days (interquartile range, 15-30). Beyond the first swab, 21.7% had a positive culture, and 8.7% replicated viable virus for longer than 30 days. T cell depletion (rate ratio, 2.5; 95% confidence interval [95% CI], 1.9-3.3; P < .001) and time from transplantation (rate ratio, 0.93; 95% CI, 0.90-0.97; P = .006) were associated with the time of viable virus shedding. A cycle threshold value of 24.2 demonstrated a 91.3% negative predictive value of viability (95% credible interval [95% CrI], 76-100). The odds of viability decreased by 69% per week of infection (odds ratio, 0.31; 95% CrI, 0.12-0.76). Overall, ribonucleic acid sequencing did not show accelerated molecular evolution though mutation rate could be increased in molnupiravir-treated KTRs. In conclusion, viable SARS-CoV-2 is eliminated rapidly, the risk of virus evolution is low, and prolonged self-isolation is generally unnecessary for most KTRs.

• MeSH
• COVID-19 * virologie   epidemiologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• molekulární evoluce * MeSH
• mutace MeSH
• příjemce transplantátu * MeSH
• prospektivní studie MeSH
• SARS-CoV-2 * genetika   izolace a purifikace   fyziologie   MeSH
• senioři MeSH
• transplantace ledvin * MeSH
• vylučování virů * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

• Publikační typ
• abstrakty MeSH

Proteins encoded by antigen-processing genes (APGs) prepare antigens for presentation by the major histocompatibility complex class I (MHC I) molecules. Coevolution between APGs and MHC I genes has been proposed as the ancestral gnathostome condition. The hypothesis predicts a single highly expressed MHC I gene and tight linkage between APGs and MHC I. In addition, APGs should evolve under positive selection, a consequence of the adaptive evolution in MHC I. The presence of multiple highly expressed MHC I genes in some teleosts, birds, and urodeles appears incompatible with the coevolution hypothesis. Here, we use urodele amphibians to test two key expectations derived from the coevolution hypothesis: 1) the linkage between APGs and MHC I was studied in Lissotriton newts and 2) the evidence for adaptive evolution in APGs was assessed using 42 urodele species comprising 21 genera from seven families. We demonstrated that five APGs (PSMB8, PSMB9, TAP1, TAP2, and TAPBP) are tightly linked (<0.5 cM) to MHC I. Although all APGs showed some codons under episodic positive selection, we did not find a pervasive signal of positive selection expected under the coevolution hypothesis. Gene duplications, putative gene losses, and divergent allelic lineages detected in some APGs demonstrate considerable evolutionary dynamics of APGs in salamanders. Overall, our results indicate that if coevolution between APGs and MHC I occurred in urodeles, it would be more complex than envisaged in the original formulation of the hypothesis.

• MeSH
• duplikace genu MeSH
• genetická vazba MeSH
• geny MHC třídy I * MeSH
• molekulární evoluce * MeSH
• prezentace antigenu genetika   MeSH
• proteiny obojživelníků chemie   klasifikace   genetika   MeSH
• Urodela genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• genetika MeSH
• genom MeSH

• Konspekt
• Obecná genetika. Obecná cytogenetika. Evoluce
• NLK Obory
• genetika, lékařská genetika

In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including residues R346, K444, L452, N460, and F486. Here, we characterize the convergent evolution of Omicron subvariants and the properties of one recent lineage of concern, BQ.1.1. Our phylogenetic analysis suggests that these five substitutions are recurrently acquired, particularly in younger Omicron lineages. Epidemic dynamics modelling suggests that the five substitutions increase viral fitness, and a large proportion of the fitness variation within Omicron lineages can be explained by these substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 and BA.5 infection sera more efficiently, as demonstrated by neutralization assays. The pathogenicity of BQ.1.1 in hamsters is lower than that of BA.5. Our multiscale investigations illuminate the evolutionary rules governing the convergent evolution for known Omicron lineages as of 2022.

• MeSH
• biotest MeSH
• COVID-19 * MeSH
• fylogeneze MeSH
• křečci praví MeSH
• neutralizující protilátky MeSH
• protilátky virové MeSH
• SARS-CoV-2 genetika   MeSH
• substituce aminokyselin MeSH
• zvířata MeSH
• Check Tag
• křečci praví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Here, we present a study of the population genetic architecture and microevolution of the Egyptian fruit bat (Rousettus aegyptiacus) at the environmental margins in the Middle East using mitochondrial sequences and nuclear microsatellites. In contrast to the rather homogenous population structure typical of cave-dwelling bats in climax tropical ecosystems, a relatively pronounced isolation by distance and population diversification was observed. The evolution of this pattern could be ascribed to the complicated demographic history at higher latitudes related to the range margin fragmentation and complex geomorphology of the studied area. Lineages from East Africa and Arabia show divergent positions. Within the northwestern unit, the most marked pattern of the microsatellite data set is connected with insularity, as demonstrated by the separate status of populations from Saharan oases and Cyprus. These demes also exhibit a reduction in genetic variability, which is presumably connected with founder effects, drift and other potential factors related to island evolution as site-specific selection. Genetic clustering indicates a semipermeability of the desert barriers in the Sahara and Arabian Peninsula and a corridor role of the Nile Valley. The results emphasize the role of the island environment in restricting the gene flow in megabats, which is also corroborated by biogeographic patterns within the family, and suggests the possibility of nascent island speciation on Cyprus. Demographic analyses suggest that the colonization of the region was connected to the spread of agricultural plants; therefore, the peripatric processes described above might be because of or strengthened by anthropogenic changes in the environment.

• MeSH
• Bayesova věta MeSH
• Chiroptera genetika   MeSH
• genetická variace MeSH
• genotyp MeSH
• mikrosatelitní repetice MeSH
• mitochondriální DNA genetika   MeSH
• molekulární evoluce * MeSH
• molekulární sekvence - údaje MeSH
• ostrovy MeSH
• populační genetika * MeSH
• sekvenční analýza DNA MeSH
• shluková analýza MeSH
• tok genů MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• ostrovy MeSH
• Střední východ MeSH
• východní Afrika MeSH

• MeSH
• biologická evoluce MeSH
• viry MeSH
• Publikační typ
• souborné dílo MeSH

• Konspekt
• Virologie
• NLK Obory
• virologie
• biologie

Cancer development is a dynamic process during which the successive accumulation of mutations results in cells with increasingly malignant characteristics. Here, we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients receiving supportive care, with or without lenalidomide (follow-up 2.5-11 years). Whole-exome and targeted deep sequencing at multiple time points during the disease course reveals that both linear and branched evolutionary patterns occur with and without disease-modifying treatment. The application of disease-modifying therapy may create an evolutionary bottleneck after which more complex MDS, but also unrelated clones of haematopoietic cells, may emerge. In addition, subclones that acquired an additional mutation associated with treatment resistance (TP53) or disease progression (NRAS, KRAS) may be detected months before clinical changes become apparent. Monitoring the genetic landscape during the disease may help to guide treatment decisions.

• MeSH
• buňky kostní dřeně účinky léků   metabolismus   patologie   MeSH
• chemorezistence genetika   MeSH
• GTP-fosfohydrolasy genetika   metabolismus   MeSH
• inhibitory angiogeneze terapeutické užití   MeSH
• klonální evoluce účinky léků   MeSH
• lenalidomid MeSH
• lidé středního věku MeSH
• lidé MeSH
• management nemoci MeSH
• membránové proteiny genetika   metabolismus   MeSH
• monitorování fyziologických funkcí MeSH
• mutace MeSH
• myelodysplastické syndromy farmakoterapie   genetika   metabolismus   patologie   MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádorový supresorový protein p53 genetika   metabolismus   MeSH
• následné studie MeSH
• progrese nemoci MeSH
• protoonkogenní proteiny p21(ras) genetika   metabolismus   MeSH
• regulace genové exprese u nádorů * MeSH
• sekvenování exomu MeSH
• senioři MeSH
• thalidomid analogy a deriváty   terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Tragopogon mirus and T. miscellus are allotetraploids (2n = 24) that formed repeatedly during the past 80 years in eastern Washington and adjacent Idaho (USA) following the introduction of the diploids T. dubius, T. porrifolius, and T. pratensis (2n = 12) from Europe. In most natural populations of T. mirus and T. miscellus, there are far fewer 35S rRNA genes (rDNA) of T. dubius than there are of the other diploid parent (T. porrifolius or T. pratensis). We studied the inheritance of parental rDNA loci in allotetraploids resynthesized from diploid accessions. We investigate the dynamics and directionality of these rDNA losses, as well as the contribution of gene copy number variation in the parental diploids to rDNA variation in the derived tetraploids. RESULTS: Using Southern blot hybridization and fluorescent in situ hybridization (FISH), we analyzed copy numbers and distribution of these highly reiterated genes in seven lines of synthetic T. mirus (110 individuals) and four lines of synthetic T. miscellus (71 individuals). Variation among diploid parents accounted for most of the observed gene imbalances detected in F1 hybrids but cannot explain frequent deviations from repeat additivity seen in the allotetraploid lines. Polyploid lineages involving the same diploid parents differed in rDNA genotype, indicating that conditions immediately following genome doubling are crucial for rDNA changes. About 19% of the resynthesized allotetraploid individuals had equal rDNA contributions from the diploid parents, 74% were skewed towards either T. porrifolius or T. pratensis-type units, and only 7% had more rDNA copies of T. dubius-origin compared to the other two parents. Similar genotype frequencies were observed among natural populations. Despite directional reduction of units, the additivity of 35S rDNA locus number is maintained in 82% of the synthetic lines and in all natural allotetraploids. CONCLUSIONS: Uniparental reductions of homeologous rRNA gene copies occurred in both synthetic and natural populations of Tragopogon allopolyploids. The extent of these rDNA changes was generally higher in natural populations than in the synthetic lines. We hypothesize that locus-specific and chromosomal changes in early generations of allopolyploids may influence patterns of rDNA evolution in later generations.

• MeSH
• Asteraceae genetika   MeSH
• diploidie MeSH
• hybridizace genetická genetika   MeSH
• hybridizace in situ fluorescenční MeSH
• molekulární evoluce MeSH
• ribozomální DNA genetika   MeSH
• Southernův blotting MeSH
• tetraploidie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH