Inbred mouse strains provide phenotypic homogeneity between individual mice. However, stochastic morphogenetic events combined with epigenetic changes due to exposure to environmental factors and ontogenic experience result in variability among mice with virtually identical genotypes, reducing the reproducibility of experimental mouse models. Here we used microscopic and cytometric techniques to identify individual patterns in gut-associated lymphoid tissue (GALT) that are induced by exposure to microbiota. By comparing germ-free (GF), conventional (CV) and gnotobiotic mice colonized with a defined minimal mouse microbiota (oMM12) MHC II-EGFP knock-in mice we quantified antigen-presenting cells (APCs) in the lamina propria, cryptopatches (CP), isolated lymphoid follicles (ILFs), Peyer's patches (PPs) and specific sections of the mesenteric lymphoid complex. We found that GF mice had a significantly larger outer intestinal surface area compared to CV and oMM12-colonized mice, which partially compensated for their lower density of the villi in the distal ileum. GF mice also contained fewer APCs than oMM12 mice in the Iamina propria of the villi and had a significantly smaller volume of the solitary intestinal lymphoid tissue (SILT). In both GF and oMM12 mice, PP follicles were significantly smaller compared to CV mice, although number was similar. Concomitantly, the number of pDCs in PPs was significantly lower in GF mice than in CV mice. Moreover, the cecal patch was dispersed into small units in GF mice whereas it was compact in CV mice. Taken together, we here provide further evidence that microbiota regulates SILT differentiation, the size and morphology of PPs, the cellular composition of mesenteric lymph nodes (MLNs) and the morphology of cecal patch. As such, microbiota directly affect not only the functional configuration of the immune system but also the differentiation of lymphoid structures. These findings highlight how standardized microbiota, such as oMM12, can promote reproducibility in animal studies by enabling microbiologically controlled experiments across laboratories.

• Klíčová slova
• Germ-free and gnotobiotic models, Gut-associated lymphoid tissue (GALT), Lymphoid tissue morphogenesis, MHCII-EGFP knock-in mice, Microbiota-induced immunity, Phenotypic plasticity,
• Publikační typ
• časopisecké články MeSH

Current standards in vascular reconstruction imply the use of autologous or synthetic material. Despite being standard, autologous grafts are limited by pathologies already affecting the patient and possible complications at the site of explantation, while synthetic grafts carry increased infection risks. Decellularized tissues have gained significant attention due to their potential for improving integration and functionality. The decellularization process removes cellular components while retaining the extracellular matrix, providing a scaffold that supports endothelial cell growth and minimizes immune rejection. Porcine decellularized vena cava is a promising candidate for vascular graft applications due to its structural similarity to human blood vessels and biocompatibility. In this study, we decellularized porcine vena cava with a combination of Triton X-100 and sodium dodecyl sulfate in four hours. We subsequently characterized the wall structure through histological stainings and proteomic analysis. Parameters such as wall thickness, intima-media layers thickness, collagen and elastin area fraction were quantified and compared. Moreover, decellularized veins were repopulated in vitro with human endothelial cells in static and dynamic conditions to verify the adhesion of human cells to the porcine scaffold and fully functionalize the lumen. An in-house-designed bioreactor was developed to seed endothelial cells on the lumen, mimicking the in vivo blood flow.

• Klíčová slova
• Bioreactor repopulation, Decellularization, Histological analysis, Porcine vena cava, Proteomics,
• MeSH
• bioreaktory MeSH
• decelularizovaná extracelulární matrix * chemie   MeSH
• endoteliální buňky pupečníkové žíly (lidské) cytologie   MeSH
• endoteliální buňky cytologie   MeSH
• extracelulární matrix chemie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• prasata MeSH
• tkáňové inženýrství metody   MeSH
• tkáňové podpůrné struktury * chemie   MeSH
• venae cavae * cytologie   chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• decelularizovaná extracelulární matrix * MeSH

Histones are positively charged proteins found in the chromatin of eukaryotic cells. They regulate gene expression and are required for the organization and packaging of DNA within the nucleus. Histones are extremely conserved, allowing for transcription, replication, and repair. This review delves into their complex structure and function in DNA assembly, their role in nucleosome assembly, and the higher-order chromatin structures they generate. We look at the five different types of histone proteins: H1, H2A, H2B, H3, H4, and their variations. These histones bind with DNA to produce nucleosomes, the basic units of chromatin that are essential for compacting DNA and controlling its accessibility. Their dynamic control of chromatin accessibility has important implications for genomic stability and cellular activities. We elucidate regulatory mechanisms in both normal and pathological situations by investigating their structural features, diverse interaction mechanisms, and chromatin impact. In addition, we discuss the functions of histone post-translational modifications (PTMs) and their significance in various disorders. These alterations, which include methylation, acetylation, phosphorylation, and ubiquitination, are crucial in regulating histone function and chromatin dynamics. We specifically describe and explore the role of changed histones in the evolution of cancer, neurological disorders, sepsis, autoimmune illnesses, and inflammatory conditions. This comprehensive review emphasizes histone's critical role in genomic integrity and their potential as therapeutic targets in various diseases.

• Klíčová slova
• Chromatin, Disease, Gene expression, Genomic stability, Histones, Nucleosomes, Post-translational modifications (PTMs),
• MeSH
• chromatin metabolismus   genetika   MeSH
• DNA * genetika   metabolismus   chemie   MeSH
• histony * metabolismus   genetika   chemie   MeSH
• lidé MeSH
• nádory * metabolismus   genetika   patologie   MeSH
• nukleozomy metabolismus   genetika   MeSH
• posttranslační úpravy proteinů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• chromatin MeSH
• DNA * MeSH
• histony * MeSH
• nukleozomy MeSH

BACKGROUND: Targeted alpha therapy (TAT) is an effective option for cancer treatment. To maximize its efficacy and minimize side effects, carriers must deliver radionuclides to target tissues. Most of the nuclides used in TAT decay via the alpha cascade, producing several radioactive daughter nuclei with sufficient energy to escape from the original carrier. Therefore, studying these daughter atoms is crucial in the search for new carriers. Nanoparticles have potential as carriers due to their structure, which can prevent the escape of daughter atoms and reduce radiation exposure to non-target tissues. This work focuses on determining the released activity of 221Fr and 213Bi resulting from the decay of 225Ac labelled TiO2 nanoparticles. RESULTS: Labelling of TiO2 nanoparticles has shown high sorption rates of 225Ac and its progeny, 221Fr and 213Bi, with over 92 % of activities sorbed on the nanoparticle surface for all measured radionuclides. However, in the quasi-dynamic in vitro system, the released activity of 221Fr and 213Bi is strongly dependent on the nanoparticles concentration, ranging from 15 % for a concentration of 1 mg/mL to approximately 50 % for a nanoparticle concentration of 10 μg/mL in saline solution. The released activities of 213Bi were lower, with a maximum value of around 20 % for concentrations of 0.05, 0.025, and 0.01 mg/mL. The leakage of 225Ac and its progeny was tested in various biological matrices. Minimal released activity was measured in saline at around 10 % after 48 h, while the maximum activity was measured in blood serum and plasma at 20 %. The amount of 225Ac released into the media was minimal (<3 %). The in vitro results were confirmed in a healthy mouse model. The difference in %ID/g was clearly visible immediately after dissection and again after 6 h when 213Bi reached equilibrium with 225Ac. CONCLUSION: The study verified the potential release of 225Ac progeny from the labelled TiO2 nanoparticles. Experiments were performed to determine the dependence of released activity on nanoparticle concentration and the biological environment. The results demonstrated the high stability of the prepared 225Ac@TiO2 NPs and the potential release of progeny over time. In vivo studies confirmed our hypothesis. The data obtained suggest that the daughter atoms can escape from the original carrier and follow their own biological pathways in the organism.

• Klíčová slova
• Actinium-225, Bismuth-213, Nanoparticles, Targeted alpha therapy, TiO(2),
• MeSH
• aktinium * chemie   MeSH
• izotopové značení MeSH
• myši MeSH
• nanočástice * chemie   MeSH
• radionuklidy * chemie   MeSH
• titan * chemie   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Actinium-225 MeSH Prohlížeč
• aktinium * MeSH
• radionuklidy * MeSH
• titan * MeSH
• titanium dioxide MeSH Prohlížeč

This manuscript investigates the phytochemical composition and biological potential of Chrozophora tinctoria extracts obtained with solvents of different polarities (ethyl acetate, ethanol, 70 % ethanol, and water). Comprehensive in vitro analyses revealed that ethanol and ethyl acetate extracts had the highest levels of phenolic and flavonoid compounds, which corresponded with strong antioxidant activity and significant inhibitory effects on key enzymes such as acetylcholinesterase, butyrylcholinesterase, α-amylase, α-glucosidase, and tyrosinase. Cytotoxicity tests on several human cell lines showed that the plant species tested did not exhibit cytotoxic activity. LC-MS-qTOF analysis identified bioactive components, with apigenin emerging as one of the most interesting compounds. An integrated in silico approach involving network pharmacology, molecular docking, and molecular dynamics simulations revealed strong and stable interactions between apigenin and therapeutic targets involved in neurodegenerative and metabolic processes. These findings could serve as an outline for future studies on the medicinal plant's potential.

• Klíčová slova
• Antioxidant, Chrozophora tinctoria, Enzyme inhibition, In silico analysis, Solvent polarity,
• MeSH
• antioxidancia farmakologie   izolace a purifikace   MeSH
• apigenin farmakologie   MeSH
• Bignoniaceae * chemie   MeSH
• chromatografie kapalinová MeSH
• fenoly farmakologie   izolace a purifikace   MeSH
• flavonoidy farmakologie   izolace a purifikace   MeSH
• fytonutrienty farmakologie   izolace a purifikace   MeSH
• inhibitory enzymů * farmakologie   izolace a purifikace   MeSH
• kapalinová chromatografie-hmotnostní spektrometrie MeSH
• lidé MeSH
• molekulární struktura MeSH
• rostlinné extrakty * chemie   farmakologie   MeSH
• simulace molekulární dynamiky MeSH
• simulace molekulového dockingu MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antioxidancia MeSH
• apigenin MeSH
• fenoly MeSH
• flavonoidy MeSH
• fytonutrienty MeSH
• inhibitory enzymů * MeSH
• rostlinné extrakty * MeSH

The centromere has a conserved function across eukaryotes; however, the associated DNA sequences exhibit remarkable diversity in both size and structure. In plants, some species possess well-defined centromeres dominated by tandem satellite repeats and centromeric retrotransposons, while others have centromeric regions composed almost entirely of retrotransposons. Using a combination of bioinformatic, molecular, and cytogenetic approaches, we analyzed the centromeric landscape of Humulus lupulus. We identified novel centromeric repeats and characterized two types of centromeric organization. Cytogenetic localization on metaphase chromosomes confirmed the genomic distribution of the major repeats and revealed unique centromeric organization specifically on chromosomes 2, 8, and Y. Two centromeric types are composed of the major repeats SaazCEN and SaazCRM1 (Ty3/Gypsy) which are further accompanied by chromosome-specific centromeric satellites, Saaz40, Saaz293, Saaz85, and HuluTR120. Chromosome 2 displays unbalanced segregation during mitosis and meiosis, implicating an important role for its centromere structure in segregation patterns. Moreover, chromosome 2-specific centromeric repeat Saaz293 is a new marker for studying aneuploidy in hops. Our findings provide new insights into chromosome segregation in hops and highlight the diversity and complexity of the centromere organization in H. lupulus.

• Klíčová slova
• Cannabaceae, asymmetric cell division, centromere, retrotransposons, sex chromosomes,
• MeSH
• centromera * genetika   MeSH
• chromozomy rostlin genetika   MeSH
• Humulus * genetika   MeSH
• meióza genetika   MeSH
• repetitivní sekvence nukleových kyselin * genetika   MeSH
• retroelementy * genetika   MeSH
• segregace chromozomů genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• retroelementy * MeSH

BACKGROUND: While teamwork is widely recognized as essential to safe and high-quality nursing care, its evaluation has been underexplored in Central and Eastern Europe. This study offers original insights by systematically assessing nursing teamwork in Slovak public hospitals. By identifying strengths and weaknesses in team dynamics through structured evaluation, it becomes possible to implement targeted, context-specific improvements that reflect the realities of the local healthcare system. OBJECTIVES: This study aimed to explore how registered nurses (RNs) perceive the level of teamwork in selected public hospitals in Slovakia and to identify key factors that influence these perceptions, addressing a significant gap in research within the Central and Eastern European healthcare context. DESIGN: The cross-sectional study. METHODS: The study included 346 RNs from four selected hospitals in the Slovak Republic. Data were collected using the Nursing Teamwork Survey (NTS) instrument between April 2022 and February 2023 and analyzed using descriptive and inferential statistics. RESULTS: Registered nurses perceived moderate teamwork during their last working shift. Perceived level of teamwork was significantly influenced by the unit type, the number of overtime hours in the past month, and the intention to leave the position. The results show significant associations between the perceived level of teamwork and overall job satisfaction, job satisfaction in the current position, satisfaction with teamwork, and overall patient safety level. Several variables were found to be significant predictors of teamwork among RNs (p ≤ 0.05). CONCLUSIONS: Effective teamwork among nurses is crucial for optimal patient outcomes. The study highlights the importance of enhancing teamwork in the Slovak healthcare setting and identifies factors influencing nurses' perceptions of teamwork. Addressing these factors can lead to a more positive teamwork environment and improved work satisfaction among nursing professionals. Targeted interventions based on identified predictors could be beneficial in achieving this goal.

• Klíčová slova
• Nursing Teamwork Survey, hospitals, registered nurses, teamwork,
• Publikační typ
• časopisecké články MeSH

The mechanistic target of rapamycin complex 1 (mTORC1) anchors a conserved signalling pathway that regulates growth in response to nutrient availability1-5. Amino acids activate mTORC1 through the Rag GTPases, which are regulated by GATOR, a supercomplex consisting of GATOR1, KICSTOR and the nutrient-sensing hub GATOR2 (refs. 6-9). GATOR2 forms an octagonal cage, with its distinct WD40 domain β-propellers interacting with GATOR1 and the leucine sensors Sestrin1 and Sestrin2 (SESN1 and SESN2) and the arginine sensor CASTOR1 (ref. 10). The mechanisms through which these sensors regulate GATOR2 and how they detach from it upon binding their cognate amino acids remain unknown. Here, using cryo-electron microscopy, we determined the structures of a stabilized GATOR2 bound to either Sestrin2 or CASTOR1. The sensors occupy distinct and non-overlapping binding sites, disruption of which selectively impairs the ability of mTORC1 to sense individual amino acids. We also resolved the apo (leucine-free) structure of Sestrin2 and characterized the amino acid-induced structural rearrangements within Sestrin2 and CASTOR1 that trigger their dissociation from GATOR2. Binding of either sensor restricts the dynamic WDR24 β-propeller of GATOR2, a domain essential for nutrient-dependent mTORC1 activation. These findings reveal the allosteric mechanisms that convey amino acid sufficiency to GATOR2 and the ensuing structural changes that lead to mTORC1 activation.

• Publikační typ
• časopisecké články MeSH

Precise control over the dynamic transformations that electrocatalysts undergo under operating conditions offers a powerful strategy for tailoring catalytic selectivity. Herein, the electrochemical modification of Cu2-xS-derived catalysts to generate selective active sites for the electroreduction of CO2 to formate is investigated. Through a combination of in situ and ex situ characterization techniques, it is demonstrated that electrochemical cycling induces sulfur leaching, resulting in the formation of reduced, amorphous copper structures that exhibit enhanced selectivity toward formate production. Compared to the pristine material, the electrochemically modified catalyst achieves a twofold improvement in Faradaic efficiency, reaching values as high as 75% for CO2-to-formate conversion. These findings not only establish a cost-effective and scalable platform for catalyst fabrication and activation, but also open new avenues for advancing sustainable CO2 conversion technologies toward industrial implementation.

• Klíčová slova
• CO2 reduction, copper sulfides, dynamic reconstructions, formate, in situ characterizations,
• Publikační typ
• časopisecké články MeSH

Few processes are as decisive as predation in shaping the structure and dynamics of ecological communities. For most predator species, however, the number of prey items killed by a predator in a day (predation rate) remains impossible to assess because direct observations are scarce or impossible to acquire. For such species, molecular gut content analyses are routinely used to test for the presence of a prey in the predator's gut. Specifically, our model uses a novel mechanistic representation of predation and digestion to integrate field data on prey detection and laboratory data on prey molecular signal decay in the predator's gut. Model fit provides an estimate of the slope and intercept of the digestion curve (molecular signal decay) and an estimate of the predation rate. In a case study targeting 25 carabid beetle species and 5 types of prey in agricultural fields (winter wheat), we use our model to estimate predation rates for each predator-prey pair. Based on predation rate estimates, we introduce a new biocontrol indicator at community scale and explore its potential for advanced agroecological research. We discuss the performance of our model on the basis of the scant information available in the literature and detail its conditions of application to highlight its advantages over existing predation models.

• Klíčová slova
• carabid beetle, hierarchical Bayesian model, molecular trophic ecology, pest regulation, predation rate,
• Publikační typ
• časopisecké články MeSH