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- Schwarzer, M., et al.
(författare)
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Microbe-mediated intestinal NOD2 stimulation improves linear growth of undernourished infant mice
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 379:6634
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Tidskriftsartikel (refereegranskat)abstract
- The intestinal microbiota is known to influence postnatal growth. We previously found that a strain of Lactiplantibacillus plantarum (strain LpWJL) buffers the adverse effects of chronic undernutrition on the growth of juvenile germ-free mice. Here, we report that LpWJLsustains the postnatal growth of malnourished conventional animals and supports both insulin-like growth factor-1 (IGF-1) and insulin production and activity. We have identified cell walls isolated from LpWJL, as well as muramyl dipeptide and mifamurtide, as sufficient cues to stimulate animal growth despite undernutrition. Further, we found that NOD2 is necessary in intestinal epithelial cells for LpWJL-mediated IGF-1 production and for postnatal growth promotion in malnourished conventional animals. These findings indicate that, coupled with renutrition, bacteria cell walls or purified NOD2 ligands have the potential to alleviate stunting.
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- Brisuda, Antonín, et al.
(författare)
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Bladder cancer therapy using a conformationally fluid tumoricidal peptide complex
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Partially unfolded alpha-lactalbumin forms the oleic acid complex HAMLET, with potent tumoricidal activity. Here we define a peptide-based molecular approach for targeting and killing tumor cells, and evidence of its clinical potential (ClinicalTrials.gov NCT03560479). A 39-residue alpha-helical peptide from alpha-lactalbumin is shown to gain lethality for tumor cells by forming oleic acid complexes (alpha1-oleate). Nuclear magnetic resonance measurements and computational simulations reveal a lipid core surrounded by conformationally fluid, alpha-helical peptide motifs. In a single center, placebo controlled, double blinded Phase I/II interventional clinical trial of non-muscle invasive bladder cancer, all primary end points of safety and efficacy of alpha1-oleate treatment are reached, as evaluated in an interim analysis. Intra-vesical instillations of alpha1-oleate triggers massive shedding of tumor cells and the tumor size is reduced but no drug-related side effects are detected (primary endpoints). Shed cells contain alpha1-oleate, treated tumors show evidence of apoptosis and the expression of cancer-related genes is inhibited (secondary endpoints). The results are especially encouraging for bladder cancer, where therapeutic failures and high recurrence rates create a great, unmet medical need.
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- Sirovátka, T., et al.
(författare)
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Welfare State Agenda of Successful Populist Parties in Czechia and Slovakia
- 2022
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Ingår i: Problemy Polityki Spolecznej. - : Faculty of Political Science and International Studies, University of Warsaw. - 1640-1808 .- 2719-7328. ; 56:1, s. 23-45
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Tidskriftsartikel (refereegranskat)abstract
- Several studies suggest that the welfare state agenda, which has traditionally been a crucial issue for left-wing populist parties (LWP), has become important for all kinds of populist parties: centrist-populist (CP) as well as right-wing populist (RWP). In this paper, we examine the role of the welfare state agenda in the election programmes of the Czech and Slovak populist parties that either won the elections in 2017 in the Czech Republic and 2020 in Slovakia (this was the case for CP parties in both countries) or they won representation in Parliament in these elections (this was the case of RWP parties). The findings show that the welfare state agendas of CP and RWP parties regarding the pattern of welfare state objectives and deservingness criteria applied in their policy proposals do not differ so much in some respects. At the same time, the policy proposals of CP in the two countries diverge to some extent. Specific country political contexts such as the political opportunity structure and the manoeuvring of the populist parties may provide some explanation. Comparison with the other countries is a challenge for future research.
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- Tesarova, M, et al.
(författare)
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A quantitative analysis of 3D-cell distribution in regenerating muscle-skeletal system with synchrotron X-ray computed microtomography
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 14145-
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Tidskriftsartikel (refereegranskat)abstract
- One of the greatest enigmas of modern biology is how the geometry of muscular and skeletal structures are created and how their development is controlled during growth and regeneration. Scaling and shaping of vertebrate muscles and skeletal elements has always been enigmatic and required an advanced technical level in order to analyse the cell distribution in 3D. In this work, synchrotron X-ray computed microtomography (µCT) and chemical contrasting has been exploited for a quantitative analysis of the 3D-cell distribution in tissues of a developing salamander (Pleurodeles waltl) limb – a key model organism for vertebrate regeneration studies. We mapped the limb muscles, their size and shape as well as the number and density of cells within the extracellular matrix of the developing cartilage. By using tomographic approach, we explored the polarity of the cells in 3D, in relation to the structure of developing joints. We found that the polarity of chondrocytes correlates with the planes in joint surfaces and also changes along the length of the cartilaginous elements. Our approach generates data for the precise computer simulations of muscle-skeletal regeneration using cell dynamics models, which is necessary for the understanding how anisotropic growth results in the precise shapes of skeletal structures.
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