This paper describes a compact video-ophthalmoscope (VO) designed for capturing retinal video sequences of the optic nerve head (ONH) under flicker light stimulation. The device uses an OLED display and a fiber optic-coupled LED light source, enabling high-frame-rate video at low illumination intensity (12 μW/cm2). Retinal responses were recorded in 10 healthy subjects during flicker light exposure with a pupil irradiance of 2 μW/cm2. Following 20 s of stimulation, all subjects displayed changes in retinal reflectance and pulsation attenuation, linked to blood flow and volume variations. These findings suggest that increased blood volume leads to decreased retinal reflectance. Temporal analysis confirmed the ability to capture flicker-induced retinal reflectance changes, indicating its potential for spatial and temporal analysis. Overall, this device offers a portable approach for investigating dynamic retinal responses to light stimuli, which can aid the diagnosis of retinal diseases like diabetic retinopathy, glaucoma, or neurodegenerative diseases affecting retinal blood circulation.

• MeSH
• audiovizuální záznam * přístrojové vybavení   MeSH
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• oftalmoskopy * MeSH
• retina * účinky záření   fyziologie   MeSH
• světelná stimulace * MeSH
• světlo * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články 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.

• MeSH
• chromatin metabolismus   genetika   chemie   MeSH
• DNA * metabolismus   chemie   MeSH
• genom MeSH
• histony * metabolismus   chemie   genetika   MeSH
• lidé MeSH
• nádory genetika   metabolismus   MeSH
• posttranslační úpravy proteinů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Collaterals improve recanalization in acute ischemic stroke patients treated with intravenous thrombolysis, but the mechanisms are poorly understood. To investigate it, an in vitro flow model of the middle cerebral artery was developed with or without collaterals. An occlusion was achieved using human blood clots. Recanalization time, thrombolysis (clot length decrease and red blood cell (RBC) release), pressure gradient across the clot and clot compaction were measured. Results showed that with or without collateral alteplase-treated RBC dominant clots showed recanalization time 98±23 min vs 130±35 min (difference 32 min, 95% CI -6-58 min), relative clot reduction 31.8±14.9% vs 30.3±13.2% (difference 1.5%, 95% CI 10.4-13.4%) and RBC release 0.30±0.07 vs 0.27±0.09 (difference 0.03, 95% CI 0.04-0.10). Similar results were observed with fibrin-dominant clots. In RBC dominant clots, the presence vs absence of collateral caused different pressure gradients across the clot 0.41±0.09 vs 0.70±0.09 mmHg (difference 0.29 mmHg, 95% CI -0.17-0.41 mmHg), and caused the reduction of initial clot compaction by 5%. These findings align with observations in patients, where collaterals shortened recanalization time. However, collaterals did not increase thrombolysis. Instead, they decreased the pressure gradient across the clot, resulting in less clot compaction and easier distal displacement of the clot.

• MeSH
• arteria cerebri media účinky léků   patofyziologie   diagnostické zobrazování   MeSH
• erytrocyty účinky léků   MeSH
• fibrinolytika terapeutické užití   farmakologie   MeSH
• ischemická cévní mozková příhoda * farmakoterapie   patofyziologie   MeSH
• kolaterální oběh * účinky léků   MeSH
• lidé MeSH
• tkáňový aktivátor plazminogenu terapeutické užití   farmakologie   MeSH
• trombolytická terapie metody   MeSH
• trombóza farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The diverse environmental distribution of Salmonella makes it a global source of human gastrointestinal infections. This study aimed to detect Salmonella spp. and explore their diversity and antimicrobial susceptibility patterns in clinical and environmental samples. Pre-enrichment, selective enrichment, and selective plating techniques were adopted for the Salmonella detection whereas the API 20E test and Vitek Compact 2 system were used to confirm the identity of isolates. Salmonella serovars were subjected to molecular confirmation by 16S rDNA gene sequencing. Disc diffusion method and Vitek 2 Compact system determined the antibiotic susceptibility of Salmonella serovars. Multiple antibiotic resistance index (MARI) was calculated to explore whether Salmonella serovars originate from areas with heavy antibiotic usage. Results depicted low Salmonella prevalence in clinical and environmental samples (3.5%). The main detected serovars included Salmonella Typhimurium, S. enteritidis, S. Infantis, S. Newlands, S. Heidelberg, S. Indian, S. Reading, and S. paratyphi C. All the detected Salmonella serovars (27) exhibited multidrug resistance to three or more antimicrobial classes. The study concludes that the overall Salmonella serovars prevalence was found to be low in environmental and clinical samples of Western Saudi Arabia (Makkah and Jeddah). However, antimicrobial susceptibility patterns of human and environmental Salmonella serovars revealed that all isolates exhibited multidrug-resistance (MDR) patterns to frequently used antibiotics, which might reflect antibiotic overuse in clinical and veterinary medicine. It would be suitable to apply and enforce rules and regulations from the One Health approach, which aim to prevent antibiotic resistance infections, enhance food safety, and improve human and animal health, given that all Salmonella spp. detected in this investigation were exhibiting MDR patterns.

• MeSH
• antibakteriální látky * farmakologie   MeSH
• DNA bakterií genetika   MeSH
• fylogeneze MeSH
• lidé MeSH
• mikrobiální testy citlivosti * MeSH
• mikrobiologie životního prostředí MeSH
• mnohočetná bakteriální léková rezistence * MeSH
• prevalence MeSH
• RNA ribozomální 16S * genetika   MeSH
• Salmonella enterica * účinky léků   genetika   izolace a purifikace   klasifikace   MeSH
• salmonelóza * mikrobiologie   epidemiologie   MeSH
• séroskupina * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Saudská Arábie MeSH

There is a lack of systematic research exploring cross-species variation in liver lobular geometry and zonation patterns of critical drug-metabolizing enzymes, a knowledge gap essential for translational studies. This study investigated the critical interplay between lobular geometry and key cytochrome P450 (CYP) zonation in four species: mouse, rat, pig, and human. We developed an automated pipeline based on whole slide images (WSI) of hematoxylin-eosin-stained liver sections and immunohistochemistry. This pipeline allows accurate quantification of both lobular geometry and zonation patterns of essential CYP proteins. Our analysis of CYP zonal expression shows that all CYP enzymes (besides CYP2D6 with panlobular expression) were observed in the pericentral region in all species, but with distinct differences. Comparison of normalized gradient intensity shows a high similarity between mice and humans, followed by rats. Specifically, CYP1A2 was expressed throughout the pericentral region in mice and humans, whereas it was restricted to a narrow pericentral rim in rats and showed a panlobular pattern in pigs. Similarly, CYP3A4 is present in the pericentral region, but its extent varies considerably in rats and appears panlobular in pigs. CYP2D6 zonal expression consistently shows a panlobular pattern in all species, although the intensity varies. CYP2E1 zonal expression covered the entire pericentral region with extension into the midzone in all four species, suggesting its potential for further cross-species analysis. Analysis of lobular geometry revealed an increase in lobular size with increasing species size, whereas lobular compactness was similar. Based on our results, zonated CYP expression in mice is most similar to humans. Therefore, mice appear to be the most appropriate species for drug metabolism studies unless larger species are required for other purposes, e.g., surgical reasons. CYP selection should be based on species, with CYP2E1 and CYP2D6 being the most preferable to compare four species. CYP1A2 could be considered as an additional CYP for rodent versus human comparisons, and CYP3A4 for mouse/human comparisons. In conclusion, our image analysis pipeline together with suggestions for species and CYP selection can serve to improve future cross-species and translational drug metabolism studies.

• Publikační typ
• časopisecké články MeSH

Background: Hydatidosis is a deadly parasitic disease that affects both humans and animals. It has received much attention due to widespread health and economic concerns. Materials and Methods: Thirty-three hydatid cysts from the slaughterhouse and butcher shops were analyzed, 17 from the lung and 16 from the liver. The specimens were collected from hydatid fluid and grown on nutritional agar and MacConkey agar using a sterile loop. A Vitek- 2 compact instrument was used to identify bacteria. The viability of the protoscoleces was also determined in these hydatid cysts. Results: The secondary infection rate with bacteria in hepatic and pulmonary hydatid cysts was 24 (72.7%) from a total of thirty-three samples. Several types of bacteria have been isolated from hepatic and pulmonary hydatid cysts. Aeromonas hydrophila had the highest infection rate in hepatic and pulmonary hydatid cysts reaching 20.83% while the lowest infection rate was 4.17% for Leuconostoc mesenteriodes, Lactococcus garvieae, Staphylococcus sciuri, and Staphylococcus hominis, Streptococcus uberis, Pseudomonas stutzer and Vibro vulnificus. Staphylococcus lentus and Lactococcus garvieae had the highest effect on the viability of protoscoleces in liver and lung, reaching 0%, and 13% respectively. Eleven of a total of 13 types of bacteria isolated from hydatid cysts in the liver and lung: were diagnosed for the first time and had not previously been recognized by earlier investigation. The rates of bacterial infection in hepatic and pulmonary hydatid cysts were 76.47% and 68.75%, respectively. Conclusion: The results of our current study indicate that the secondary infection rate with bacteria in hepatic and pulmonary hydatid cysts reached (72.7%), and different types of bacteria in hepatic and pulmonary hydatid cysts have a clear effect on the viability of protoscoleces.

• Klíčová slova
• protoskolex,
• MeSH
• Bacteria izolace a purifikace   klasifikace   patogenita   MeSH
• bakteriální infekce * mikrobiologie   parazitologie   patologie   MeSH
• Echinococcus mikrobiologie   růst a vývoj   MeSH
• echinokokóza mikrobiologie   MeSH
• klinické laboratorní techniky metody   přístrojové vybavení   MeSH
• mikrobiální viabilita MeSH
• ovce * mikrobiologie   parazitologie   MeSH
• statistika jako téma MeSH
• Publikační typ
• klinická studie MeSH

The group Anguimorpha represents one of the most unified squamate clades in terms of body plan, ecomorphology, ecophysiology and evolution. On the other hand, the anguimorphs vary between different habitats and ecological niches. Therefore, we focused on the group Anguimorpha to test a possible correlation between heart morphology and ecological niche with respect to phylogenetic position in Squamata with Sphenodon, Salvator, and Pogona as the outgroups. The chosen lepidosaurian species were investigated by microCT. Generally, all lepidosaurs had two well-developed atria with complete interatrial septum and one ventricle divided by ventricular septa to three different areas. The ventricles of all lepidosaurians had a compact layer and abundant trabeculae. The compact layer and trabeculae were developed in accordance with particular ecological niche of the species, the trabeculae in nocturnal animals with low metabolism, such as Sphenodon, Heloderma or Lanthanotus were more massive. On the other hand athletic animals, such as varanids or Salvator, had ventricle compartmentalization divided by three incomplete septa. A difference between varanids and Salvator was found in compact layer thickness: thicker in monitor lizards and possibly linked to their mammalian-like high blood pressure, and the level of ventricular septation. In summary: heart morphology varied among clades in connection with the ecological niche of particular species and it reflects the phylogenetic position in model clade Anguimorpha. In the absence of fossil evidence, this is the closest approach how to understand heart evolution and septation in clade with different cardiac compartmentalization levels.

• Publikační typ
• časopisecké články MeSH

Three-dimensional cell culture systems are increasingly used for biological and anticancer drug screening as they mimic the structure and microenvironment of tumors more closely than conventional two-dimensional cell models. In this study, the growth kinetics of colon adenocarcinoma-derived spheroids (HT-29 cell line) cultivated in liquid marble micro-bioreactors and nonadherent PDMS-coated well plates was investigated in detail and enabled precise control of the spheroid size by the seed cell density and cultivation time. The therapeutic effect of 5-fluorouracil and irinotecan hydrochloride in 2D monolayer cell culture and 3D tumor spheroids revealed an unexpected twist in their efficacy due to different ability to penetrate through 3D microtissue. For 5-fluorouracil, the inhibitory concentration IC50 after 48 h exposure increased from 11.3 μM for a 2D cell culture to 707.7 μM for a 3D spheroid. In the case of irinotecan, IC50 increased from 24.9 μM to 77.8 μM. Despite its higher molar weight, irinotecan appeared to penetrate the 3D spheroid structure more efficiently than 5-fluorouracil. While 5-fluorouracil mainly caused a suppression of spheroid growth from the outside, irinotecan affected the entire spheroid and caused its originally compact structure to disintegrate. The acquired results highlight the need to screen cancer chemotherapeutics on 3D tumor models, as contrasting results can be obtained compared to standard 2D cell cultures.

• MeSH
• adenokarcinom * MeSH
• buněčné sféroidy MeSH
• cytostatické látky * farmakologie   MeSH
• fluoruracil farmakologie   MeSH
• irinotekan farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádorové mikroprostředí MeSH
• nádory tračníku * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Tau is an intrinsically disordered microtubule-associated protein (MAP) implicated in neurodegenerative disease. On microtubules, tau molecules segregate into two kinetically distinct phases, consisting of either independently diffusing molecules or interacting molecules that form cohesive 'envelopes' around microtubules. Envelopes differentially regulate lattice accessibility for other MAPs, but the mechanism of envelope formation remains unclear. Here we find that tau envelopes form cooperatively, locally altering the spacing of tubulin dimers within the microtubule lattice. Envelope formation compacted the underlying lattice, whereas lattice extension induced tau envelope disassembly. Investigating other members of the tau family, we find that MAP2 similarly forms envelopes governed by lattice spacing, whereas MAP4 cannot. Envelopes differentially biased motor protein movement, suggesting that tau family members could spatially divide the microtubule surface into functionally distinct regions. We conclude that the interdependent allostery between lattice spacing and cooperative envelope formation provides the molecular basis for spatial regulation of microtubule-based processes by tau and MAP2.

• MeSH
• lidé MeSH
• mikrotubuly metabolismus   MeSH
• neurodegenerativní nemoci * metabolismus   MeSH
• proteiny asociované s mikrotubuly metabolismus   MeSH
• proteiny tau * metabolismus   MeSH
• proteiny metabolismus   MeSH
• tubulin metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Disordered proteins pose a major challenge to structural biology. A prominent example is the tumor suppressor p53, whose low expression levels and poor conformational stability hamper the development of cancer therapeutics. All these characteristics make it a prime example of "life on the edge of solubility." Here, we investigate whether these features can be modulated by fusing the protein to a highly soluble spider silk domain (NT∗). The chimeric protein displays highly efficient translation and is fully active in human cancer cells. Biophysical characterization reveals a compact conformation, with the disordered transactivation domain of p53 wrapped around the NT∗ domain. We conclude that interactions with NT∗ help to unblock translation of the proline-rich disordered region of p53. Expression of partially disordered cancer targets is similarly enhanced by NT∗. In summary, we demonstrate that inducing co-translational folding via a molecular "spindle and thread" mechanism unblocks protein translation in vitro.

• MeSH
• lidé MeSH
• nádorový supresorový protein p53 * metabolismus   MeSH
• nádory * MeSH
• proteinové domény MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH