Raška, Pavel* Dotaz Zobrazit nápovědu
The essential role of MCM 2–7 proteins in the initiation of DNA replication in all eukaryotes is well known. Their role in replication elongation is supported by numerous studies, but there is still a knowledge gap in this respect. Even though biochemical studies have established an association of MCM proteins with replication forks, previous immunofluorescence studies in mammalian cells have suggested that MCM 2–7 proteins are displaced after replication initiation from sites of DNA replication. Therefore, we used a robust statistical method to more precisely analyse immunofluorescence localization of MCM 2 proteins with respect to the DNA replication foci. We show that despite the predominantly different localization of MCM 2 and replication signals, there is still a small but significant fraction of MCM 2 proteins that co-localize with DNA replication foci during most of S phase. The fluorescence localization of the MCM 2 proteins and DNA replication may thus reflect an active function of MCM 2 proteins associated with the replication foci and partially explain one facet of the “MCM paradox”.
- MeSH
- buněčné jádro metabolismus MeSH
- chromatin metabolismus MeSH
- financování organizované MeSH
- fluorescenční protilátková technika MeSH
- HeLa buňky MeSH
- jaderné proteiny metabolismus MeSH
- konfokální mikroskopie MeSH
- lidé MeSH
- neparametrická statistika MeSH
- počítačové zpracování obrazu metody MeSH
- proteiny buněčného cyklu metabolismus MeSH
- replikační počátek MeSH
- S fáze MeSH
- Check Tag
- lidé MeSH
Current research has identified extensive changes in land-use structure and land management of Central European rural landscapes due to shifting political and economic trajectories. These changes are exemplified by diverse processes of agricultural intensification, privatization and land fragmentation, land abandonment and overall changes in modes of production. The extensive record of these historically specific processes has posed a fundamental challenge for rural landscape conservation, which is addressed in this paper. First, we identify the key contradictions in rural landscape conservation, which include (i) conservation based on cultural versus environmental/ecological values, (ii) conservation based on spatial landscape patterns versus individual landscape features, and (iii) conservation based on the preservation of past landscapes versus conservation that also address the processes of change. Subsequently, we use a case study of an existing open-air museum in Zubrnice, northern Czechia, to analyze and discuss these dichotomies. In this regional case study, we first contextualize the land-use/land-cover change (LULC) reconstructed from old maps using a thorough archive (documentary proxies) and field research (survey of agrarian terraces, clearance cairns, and remnants of orchards) that enabled the construction of a narrative of specific landscape structures and features. Finally, we integrate the collected data with a novel methodological approach that allow for the spatial identification of the landscape segments that represent the narratives of historical change in modes of rural production and are therefore suitable for integration within the existing open-air museum to improve its conservation and education status.
- MeSH
- ekologie MeSH
- ekosystém MeSH
- lidé MeSH
- venkovské obyvatelstvo MeSH
- zachování přírodních zdrojů * MeSH
- zemědělství * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Electron tomographic reconstructions suffer from a number of artefacts arising from effects accompanying the processes of acquisition of a set of tilted projections of the specimen in a transmission electron microscope and from its subsequent computational handling. The most pronounced artefacts usually come from imprecise projection alignment, distortion of specimens during tomogram acquisition and from the presence of a region of missing data in the Fourier space, the "missing wedge". The ray artefacts caused by the presence of the missing wedge can be attenuated by the angular image filter, which attenuates the transition between the data and the missing wedge regions. In this work, we present an analysis of the influence of angular filtering on the resolution of averaged repetitive structural motives extracted from three-dimensional reconstructions of tomograms acquired in the single-axis tilting geometry.
- MeSH
- dítě MeSH
- draslík moč MeSH
- glykosurie MeSH
- hydrogenuhličitany krev MeSH
- hypokalemie komplikace MeSH
- koncentrace vodíkových iontů MeSH
- krev MeSH
- ledvinové kanálky patofyziologie MeSH
- lidé MeSH
- nemoci ledvin komplikace MeSH
- proteinurie MeSH
- renální aminoacidurie MeSH
- retinopathia pigmentosa komplikace MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- ženské pohlaví MeSH
The frequencies of adverse outcomes associated with male reproductive health, including infertility and testicular cancer, are increasing. These adverse trends are partially attributed to increased exposure to environmental agents such as endocrine-disrupting chemicals (EDCs). This study addresses effects on EDCs on adjacent prepubertal Sertoli TM4 cells, specifically on 1) testicular gap junctional intercellular communication (GJIC), one of the hallmarks of non-genotoxic carcinogenicity, 2) GJIC building blocks connexins (Cx), and 3) mitogen-activated protein kinases MAPKs. We selected eight representatives of EDCs: organochlorine chemicals such as pesticides dichlorodiphenyltrichloroethane, lindane, methoxychlor, and vinclozolin, industrial chemicals bisphenol A and 2,2',4,4',5,5'-hexachlorobiphenyl, and components of personal care products, triclocarban and triclosan. EDCs rapidly dysregulated GJIC in Sertoli TM4 cells mainly via MAPK p38 and/or Erk1/2 pathways by the intermediate hyper- or de-phosphorylation of Cx43 (Ser368, Ser282) and translocation of Cx43 from the plasma membrane, suggesting disturbed intracellular trafficking of Cx43 protein. Surprisingly, EDCs did not rapidly activate MAPK Erk1/2 or p38; on the contrary, TCC and TCS decreased their activity (phosphorylation). Our results indicate that EDCs might disrupt testicular homeostasis and development via testicular GJIC, junctional and non-junctional functions of Cx43 and MAPK-signaling pathways in Sertoli cells.
Humans are exposed to phthalates released from plastics, cosmetics, or food on a daily basis. Phthalates have low acute liver toxicity, but their chronic exposures could induce molecular and cellular effects linked to adverse health outcomes, such as liver tumor promotion or chronic liver diseases. The alternation of gap junctional intercellular communication (GJIC) and MAPK-Erk1/2 pathways in liver progenitor or oval cells can disrupt liver tissue homeostatic mechanisms and affect the development and severity of these adverse outcomes. Our study with 20 different phthalates revealed their structurally dependent effects on liver GJIC and MAPK-Erk1/2 signaling in rat liver WB-F344 cell line with characteristics of liver oval cells. The phthalates with a medium-length side chain (3-6 C) were the most potent dysregulators of GJIC and activators of MAPK-Erk1/2. The effects occurred rapidly, suggesting the activation of non-genomic (non-transcriptional) mechanisms directly by the parental compounds. Short-chain phthalates (1-2 C) did not dysregulate GJIC even after longer exposures and did not activate MAPK-Erk1/2. Longer chain (≥7 C) phthalates, such as DEHP or DINP, moderately activated MAPK-Erk1/2, but inhibited GJIC only after prolonged exposures (>12 h), suggesting that GJIC dysregulation occurs via genomic mechanisms, or (bio)transformation. Overall, medium-chain phthalates rapidly affected the key tissue homeostatic mechanisms in the liver oval cell population via non-genomic pathways, which might contribute to the development of chronic liver toxicity and diseases.
- MeSH
- buněčné linie MeSH
- játra cytologie účinky léků metabolismus MeSH
- krysa rodu rattus MeSH
- kyseliny ftalové aplikace a dávkování chemie toxicita MeSH
- MAP kinasový signální systém účinky léků MeSH
- mezerový spoj účinky léků MeSH
- mezibuněčná komunikace účinky léků MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
