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During development, tooth germs undergo various morphological changes resulting from interactions between the oral epithelium and ectomesenchyme. These processes are influenced by the extracellular matrix, the composition of which, along with cell adhesion and signaling, is regulated by metalloproteinases. Notably, these include matrix metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs), and a disintegrin and metalloproteinases with thrombospondin motifs (ADAMTSs). Our analysis of previously published scRNAseq datasets highlight that these metalloproteinases show dynamic expression patterns during tooth development, with expression in a wide range of cell types, suggesting multiple roles in tooth morphogenesis. To investigate this, Marimastat, a broad-spectrum inhibitor of MMPs, ADAMs, and ADAMTSs, was applied to ex vivo cultures of mouse molar tooth germs. The treated samples exhibited significant changes in tooth germ size and morphology, including an overall reduction in size and an inversion of the typical bell shape. The cervical loop failed to extend, and the central area of the inner enamel epithelium protruded. Marimastat treatment also disrupted proliferation, cell polarization, and organization compared with control tooth germs. In addition, a decrease in laminin expression was observed, leading to a disruption in continuity of the basement membrane at the epithelial-mesenchymal junction. Elevated hypoxia-inducible factor 1-alpha gene (Hif-1α) expression correlated with a disruption to blood vessel development around the tooth germs. These results reveal the crucial role of metalloproteinases in tooth growth, shape, cervical loop elongation, and the regulation of blood vessel formation during prenatal tooth development.NEW & NOTEWORTHY Inhibition of metalloproteinases during tooth development had a wide-ranging impact on molar growth affecting proliferation, cell migration, and vascularization, highlighting the diverse role of these proteins in controlling development.
- MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa metabolismus genetika MeSH
- inhibitory matrixových metaloproteinas farmakologie MeSH
- kyseliny hydroxamové farmakologie MeSH
- metaloproteasy metabolismus genetika MeSH
- moláry embryologie růst a vývoj metabolismus enzymologie MeSH
- morfogeneze MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- odontogeneze * MeSH
- proliferace buněk * MeSH
- vývojová regulace genové exprese MeSH
- zubní zárodek embryologie metabolismus enzymologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In the present work, we addressed the relationship between parental leave policies and social norms. Using a pre-registered, cross-national approach, we examined the relationship between parental leave policies and the perception of social norms for the gender division of childcare. In this study, 19,259 students (11,924 women) from 48 countries indicated the degree to which they believe childcare is (descriptive norm) and should be (prescriptive norm) equally divided among mothers and fathers. Policies were primarily operationalized as the existence of parental leave options in the respective country. The descriptive and prescriptive norms of equal division of childcare were stronger when parental leave was available in a country - also when controlling for potential confounding variables. Moreover, analyses of time since policy change suggested that policy change may initially affect prescriptive norms and then descriptive norms at a later point. However, due to the cross-sectional nature of the data, drawing causal inferences is difficult.
- MeSH
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- péče o dítě * MeSH
- průřezové studie MeSH
- rodičovská dovolená * MeSH
- sociální normy * MeSH
- srovnání kultur MeSH
- veřejná politika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Human migration is an increasingly common phenomenon and migrants are at risk of disadvantageous treatment. We reasoned that migrants may receive differential treatment by locals based on the closeness of their facial features to the host average. Residents of Türkiye, the country with the largest number of refugees currently, served as participants. Because many of these refugees are of Arabic origin, we created target facial stimuli varying along the axis connecting Turkish and Arabic morphological prototypes (excluding skin colour) computed using geometric morphometrics and available databases. Participants made judgements of two universal dimensions of social perception-warmth and competence-on these faces. We predicted that participants judging faces manipulated towards the Turkish average would provide higher warmth and competence ratings compared to judging the same faces manipulated towards the Arabic average. Bayesian statistical tools were employed to estimate parameter values in multilevel models with intercorrelated varying effects. The findings did not support the prediction and revealed raters (as well as target faces) to be an important source of variation in social judgements. In the absence of simple cues (e.g. skin colour, group labels), the effect of facial morphology on social judgements may be much more complex than previously assumed.
- MeSH
- Bayesova věta MeSH
- dospělí MeSH
- lidé MeSH
- mínění * MeSH
- mladiství MeSH
- mladý dospělý MeSH
- obličej anatomie a histologie MeSH
- rozpoznání obličeje fyziologie MeSH
- sociální percepce * MeSH
- stereotypizace * MeSH
- uprchlíci psychologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Turecko MeSH
Glioblastomas are aggressive brain tumors for which effective therapy is still lacking, resulting in dismal survival rates. These tumors display significant phenotypic plasticity, harboring diverse cell populations ranging from tumor core cells to dispersed, highly invasive cells. Neuron navigator 3 (NAV3), a microtubule-associated protein affecting microtubule growth and dynamics, is downregulated in various cancers, including glioblastoma, and has thus been considered a tumor suppressor. In this study, we challenge this designation and unveil distinct expression patterns of NAV3 across different invasion phenotypes. Using glioblastoma cell lines and patient-derived glioma stem-like cell cultures, we disclose an upregulation of NAV3 in invading glioblastoma cells, contrasting with its lower expression in cells residing in tumor spheroid cores. Furthermore, we establish an association between low and high NAV3 expression and the amoeboid and mesenchymal invasive phenotype, respectively, and demonstrate that overexpression of NAV3 directly stimulates glioblastoma invasive behavior in both 2D and 3D environments. Consistently, we observed increased NAV3 expression in cells migrating along blood vessels in mouse xenografts. Overall, our results shed light on the role of NAV3 in glioblastoma invasion, providing insights into this lethal aspect of glioblastoma behavior.
- MeSH
- fenotyp * MeSH
- glioblastom * patologie genetika metabolismus MeSH
- invazivní růst nádoru * genetika MeSH
- lidé MeSH
- membránové proteiny MeSH
- mikrotubuly metabolismus MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory mozku * patologie genetika metabolismus MeSH
- pohyb buněk genetika fyziologie MeSH
- proteiny nervové tkáně metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Cellular processes such as tissue regeneration, inflammation, and migration require the proteolysis of the extracellular matrix and the proteolytic activation of signaling molecules. A widely used and accessible technique for studying these processes is gelatin zymography, particularly for investigating matrix metalloproteinases (MMPs), though it is not limited to them. This method is favored for its simplicity, low cost, and robustness. Despite certain limitations, it remains a preferred approach for the initial investigation of complex samples.Here, we present a protocol applicable to various sample sources, including proteases from human cell lines and bacteria isolated from chronic wounds. We also explore changes in protease activity within exudates from human chronic wounds, a challenging analysis for more complex techniques. Additionally, we emphasize the potential to extend the basic protocol to study the conditions under which proteases are active.
Stálý zdravotně humanitární program České republiky MEDEVAC se zaměřuje na poskytování lékařské péče zranitelným skupinám obyvatelstva v regionech zasažených migrací, zatížených velkým množstvím uprchlíků nebo v místech, kde není dostupná specializovaná lékařská péče. Léčba je poskytována zdarma a výhradně civilistům, kteří se nacházejí ve vážném zdravotním stavu nebo kterým jejich zdravotní stav neumožňuje vést důstojný život. Program byl zahájen v roce 1993 v Bosně a Hercegovině, pokračoval v Kosovu a postupně byl rozšířen do řady dalších zemí. V současnosti je MEDEVAC programem Vlády ČR koordinovaným odborem azylové a migrační politiky Ministerstva vnitra ČR ve spolupráci s Ministerstvem zahraničních věcí ČR, Ministerstvem zdravotnictví ČR, Ministerstvem obrany ČR a Armádou ČR. Program MEDEVAC má zásadní vzdělávací význam. Účastníci si rozšiřují praktické zkušenosti se stavy typickými pro oblasti konfliktů a přírodních katastrof a seznamují se s organizačními zvláštnostmi péče v krizových oblastech. Zkušenosti získané v krizových oblastech jsou významným přínosem pro připravenost našeho zdravotnictví, zejména traumatologie a návazných oborů. Všeobecná fakultní nemocnice v Praze je zapojena od roku 2011 několika svými pracovišti – kromě I. chirurgické kliniky se na programu podílí i Oční klinika, Klinika rehabilitačního lékařství a Klinika gynekologie, porodnictví a neonatologie.
The MEDEVAC Permanent Medical Humanitarian Program of the Czech Republic focuses on providing medical care to vulnerable groups of the population in regions affected by migration, burdened by many refugees or in places where specialized medical care is not available. Treatment is provided free of charge and exclusively to civilians who are in a serious health condition or whose health condition does not allow them to lead a dignified life. The program started in 1993 in Bosnia and Herzegovina, continued in Kosovo and has gradually been extended to several other countries. At present, MEDEVAC is a program of the Government of the Czech Republic coordinated by the Department of Asylum and Migration Policy of the Ministry of the Interior of the Czech Republic in cooperation with the Ministry of Foreign Affairs, the Ministry of Health, the Ministry of Defense and the Army of the Czech Republic. The MEDEVAC program is of fundamental educational importance. Participants expand their practical experience with situations typical of conflict and natural disaster areas and become acquainted with the organizational specifics of care in crisis areas. The experience gained in crisis areas is a significant contribution to the preparedness of our health care system, especially traumatology and related fields. The General University Hospital in Prague has been involved in several of its departments since 2011, in addition to the First Surgical Clinic, the Department of Ophthalmology, the Department of Rehabilitation Medicine and the Department of Gynaecology, Obstetrics and Neonatology.
BACKGROUND: The nexus between fiscal unpredictability and environmental responsibility is a narrative of paramount significance. Therefore, this study aims to explore the impact of fiscal policy uncertainty on life expectancy and the mediating role of environmental taxation on this relationship, particularly from the perspective of China. EMPIRICAL METHODOLOGY: To confirm such notions, statistical data is collected using the National Bureau of Statistics of China. The final dataset has yearly data from thirty Chinese provinces. The ordinary least squares technique to measure direct impact and the MED-SEM approach for mediating impact are used. FINDINGS: The regression estimates show a negative and statistically significant impact of fiscal policy uncertainty on life expectancy. Moreover, environmental taxation has a positive and statistically significant partial mediating effect on the direct relationship. POLICY IMPLICATIONS: These results indicate that fiscal policy uncertainty can destabilize social security programs, housing support, and budgets, which consequently elevate poverty rates, adversely impact health, and possibly decline life expectancy. Moreover, when there is uncertainty in fiscal policy, governments can take advantage of this situation and introduce environmental taxes that provide the necessary funds to invest in the healthcare sector, encourage sustainable practices, and mitigate negative externalities. These results can significantly contribute to the public sector, environmental, and health economics fields and provide new research dimensions for academicians and policymakers.
BACKGROUND: Lipopolysaccharide (LPS)-induced inflammation of lung tissues triggers irreversible alterations in the lung parenchyma, leading to fibrosis and pulmonary dysfunction. While the molecular and cellular responses of immune and connective tissue cells in the lungs are well characterized, the specific epithelial response remains unclear due to the lack of representative cell models. Recently, we introduced human embryonic stem cell-derived expandable lung epithelial (ELEP) cells as a novel model for studying lung injury and regeneration. METHODS: ELEPs were derived from the CCTL 14 human embryonic stem cell line through activin A-mediated endoderm specification, followed by further induction toward pulmonary epithelium using FGF2 and EGF. ELEPs exhibit a high proliferation rate and express key structural and molecular markers of alveolar progenitors, such as NKX2-1. The effects of Escherichia coli LPS serotype O55:B5 on the phenotype and molecular signaling of ELEPs were analyzed using viability and migration assays, mRNA and protein levels were determined by qRT-PCR, western blotting, and immunofluorescent microscopy. RESULTS: We demonstrated that purified LPS induces features of a hybrid epithelial-to-mesenchymal transition in pluripotent stem cell-derived ELEPs, triggers the unfolded protein response, and upregulates intracellular β-catenin level through retention of E-cadherin within the endoplasmic reticulum. CONCLUSIONS: Human embryonic stem cell-derived ELEPs provide a biologically relevant, non-cancerous lung cell model to investigate molecular responses to inflammatory stimuli and address epithelial plasticity. This approach offers novel insights into the fine molecular processes underlying lung injury and repair.
- MeSH
- buněčné linie MeSH
- CD antigeny metabolismus MeSH
- endoplazmatické retikulum * metabolismus účinky léků MeSH
- epitelo-mezenchymální tranzice * účinky léků MeSH
- epitelové buňky * účinky léků metabolismus cytologie MeSH
- kadheriny * metabolismus MeSH
- lidé MeSH
- lidské embryonální kmenové buňky * cytologie MeSH
- lipopolysacharidy * farmakologie MeSH
- plíce * cytologie MeSH
- tyreoidální jaderný faktor 1 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Processes shaping the formation of the present-day population structure in highly urbanized Northern Europe are still poorly understood. Gaps remain in our understanding of when and how currently observable regional differences emerged and what impact city growth, migration, and disease pandemics during and after the Middle Ages had on these processes. RESULTS: We perform low-coverage sequencing of the genomes of 338 individuals spanning the eighth to the eighteenth centuries in the city of Sint-Truiden in Flanders, in the northern part of Belgium. The early/high medieval Sint-Truiden population was more heterogeneous, having received migrants from Scotland or Ireland, and displayed less genetic relatedness than observed today between individuals in present-day Flanders. We find differences in gene variants associated with high vitamin D blood levels between individuals with Gaulish or Germanic ancestry. Although we find evidence of a Yersinia pestis infection in 5 of the 58 late medieval burials, we were unable to detect a major population-scale impact of the second plague pandemic on genetic diversity or on the elevated differentiation of immunity genes. CONCLUSIONS: This study reveals that the genetic homogenization process in a medieval city population in the Low Countries was protracted for centuries. Over time, the Sint-Truiden population became more similar to the current population of the surrounding Limburg province, likely as a result of reduced long-distance migration after the high medieval period, and the continuous process of local admixture of Germanic and Gaulish ancestries which formed the genetic cline observable today in the Low Countries.
- MeSH
- dějiny středověku MeSH
- genetická variace MeSH
- genom lidský MeSH
- genomika MeSH
- lidé MeSH
- mor epidemiologie dějiny genetika MeSH
- populační genetika MeSH
- urbanizace * dějiny MeSH
- Check Tag
- dějiny středověku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- historické články MeSH
- Geografické názvy
- Belgie MeSH
