54 research outputs found

    Faddeev-Volkov solution of the Yang-Baxter Equation and Discrete Conformal Symmetry

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    The Faddeev-Volkov solution of the star-triangle relation is connected with the modular double of the quantum group U_q(sl_2). It defines an Ising-type lattice model with positive Boltzmann weights where the spin variables take continuous values on the real line. The free energy of the model is exactly calculated in the thermodynamic limit. The model describes quantum fluctuations of circle patterns and the associated discrete conformal transformations connected with the Thurston's discrete analogue of the Riemann mappings theorem. In particular, in the quasi-classical limit the model precisely describe the geometry of integrable circle patterns with prescribed intersection angles.Comment: 26 pages, 18 color figures, minor correction

    Diversity of respiratory parameters and metabolic adaptation to low oxygen tension in mesenchymal stromal cells

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    Objective Cell metabolism has been shown to play an active role in regulation of stemness and fate decision. In order to identify favorable culture conditions for mesenchymal stromal cells (MSCs) prior to transplantation, this study aimed to characterize the metabolic function of MSCs from different developmental stages in response to different oxygen tension during expansion. Materials and methods We cultured human fetal cardiac MSCs and human adult bone-marrow MSCs for a week under hypoxia (3% O2) and normoxia (20% O2). We performed mitochondrial characterization and assessed oxygen consumption- and extracellular acidification-rates (OCR and ECAR) in addition to oxygen-sensitive respiration and mitochondrial complex activities, using both the Seahorse and Oroboros systems. Results Adult and fetal MSCs displayed similar basal respiration and mitochondrial amount, however fetal MSCs had lower spare respiratory capacity and apparent coupling efficiency. Fetal MSCs expanded in either hypoxia or normoxia demonstrated similar acidification rates, while adult MSCs downregulated their aerobic glycolysis in normoxia. Acute decrease in oxygen tension caused a higher respiratory inhibition in adult compared to fetal MSCs. In both sources of MSCs, minor changes in complex activities in normoxic and hypoxic cultures were found. Conclusions In contrast to adult MSCs, fetal MSCs displayed similar respiration and aerobic glycolysis at different O2 culture concentrations during expansion. Adult MSCs adjusted their respiration to glycolytic activities, depending on the culture conditions thus displaying a more mature metabolic function. These findings are relevant for establishing optimal in vitro culturing conditions, with the aim to maximize engraftment and therapeutic outcome.CC BY-NC-ND 4.0Corresponding author: Department of Surgical Sciences, Uppsala University, 751 85, Uppsala, Sweden. E-mail address: [email protected] (K.-H. Grinnemo).Available online 3 February 2022, Version of Record 5 February 2022The project was funded by Karolinska Institute-Mayo Clinic Collaborative Grant 2013; The Swedish Research Council young investigator: 2013–3590; Stockholm county; The Swedish Research Council; The Family Erling-Persson Foundation; ERC-2018-AdG (834860 EYELETS); Uppsala county; Uppsala County Association against Heart and Lung Diseases; and Higher Education of the Russian Federation (agreement no. 075-15-2020-899).</p

    An integrative proteomics method identifies a regulator of translation during stem cell maintenance and differentiation

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    To characterize molecular changes during cell type transitions, the authors develop a method to simultaneously measure protein expression and thermal stability changes. They apply this approach to study differences between human pluripotent stem cells, their progenies, parental and allogeneic cells. Detailed characterization of cell type transitions is essential for cell biology in general and particularly for the development of stem cell-based therapies in regenerative medicine. To systematically study such transitions, we introduce a method that simultaneously measures protein expression and thermal stability changes in cells and provide the web-based visualization tool ProteoTracker. We apply our method to study differences between human pluripotent stem cells and several cell types including their parental cell line and differentiated progeny. We detect alterations of protein properties in numerous cellular pathways and components including ribosome biogenesis and demonstrate that modulation of ribosome maturation through SBDS protein can be helpful for manipulating cell stemness in vitro. Using our integrative proteomics approach and the web-based tool, we uncover a molecular basis for the uncoupling of robust transcription from parsimonious translation in stem cells and propose a method for maintaining pluripotency in vitro

    Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo

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    How individual components of the vascular basement membrane influence endothelial cell behaviour remains unclear. Here we show that laminin α4 (Lama4) regulates tip cell numbers and vascular density by inducing endothelial Dll4/Notch signalling in vivo. Lama4 deficiency leads to reduced Dll4 expression, excessive filopodia and tip cell formation in the mouse retina, phenocopying the effects of Dll4/Notch inhibition. Lama4-mediated Dll4 expression requires a combination of integrins in vitro and integrin β1 in vivo. We conclude that appropriate laminin/integrin-induced signalling is necessary to induce physiologically functional levels of Dll4 expression and regulate branching frequency during sprouting angiogenesis in vivo

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    Physical, Spatial, and Molecular Aspects of Extracellular Matrix of In Vivo Niches and Artificial Scaffolds Relevant to Stem Cells Research

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    Extracellular matrix can influence stem cell choices, such as self-renewal, quiescence, migration, proliferation, phenotype maintenance, differentiation, or apoptosis. Three aspects of extracellular matrix were extensively studied during the last decade: physical properties, spatial presentation of adhesive epitopes, and molecular complexity. Over 15 different parameters have been shown to influence stem cell choices. Physical aspects include stiffness (or elasticity), viscoelasticity, pore size, porosity, amplitude and frequency of static and dynamic deformations applied to the matrix. Spatial aspects include scaffold dimensionality (2D or 3D) and thickness; cell polarity; area, shape, and microscale topography of cell adhesion surface; epitope concentration, epitope clustering characteristics (number of epitopes per cluster, spacing between epitopes within cluster, spacing between separate clusters, cluster patterns, and level of disorder in epitope arrangement), and nanotopography. Biochemical characteristics of natural extracellular matrix molecules regard diversity and structural complexity of matrix molecules, affinity and specificity of epitope interaction with cell receptors, role of non-affinity domains, complexity of supramolecular organization, and co-signaling by growth factors or matrix epitopes. Synergy between several matrix aspects enables stem cells to retain their function in vivo and may be a key to generation of long-term, robust, and effective in vitro stem cell culture systems

    Isotopic resonance at 370 ppm deuterium negatively affects kinetics of luciferin oxidation by luciferase

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    Since 1930s, it has been known that some biochemical and biological processes exhibit abnormal kinetics at a deuterium concentration in the local environment of 250-600 ppm, which is 2-4 times higher that the normal concentration of 150 ppm D. We sought to test if the kinetics of firefly luciferase oxidizing luciferin, the reaction widely used as a read-out in various biochemical assays, is also affected by an elevated deuterium content. To this end, both luciferase and luciferin substrate solutions were prepared based on water with extra deuterium added to a concentration ranging from 150 ppm and up to 10,000 ppm (1%). Upon mixing the solutions, the luminescence intensity at different times was compared with that of the corresponding control solutions with 150 ppm D. A broad negative resonance was detected (p &lt; 10(-6)), with a approximate to 20% drop in luminescence at 370 ppm D. Given that, on average, about half of hydrogen atoms in proteins are not exchangeable in solution, this value corresponds to approximate to 260 ppm of deuterium in all enzyme's hydrogens, in a very good agreement with the prediction of the Isotopic resonance hypothesis

    New Properties of Drosophila Fab-7 Insulator

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    In the Abd-B 3′ cis-regulatory region, which is subdivided into a series of iab domains, boundary elements have previously been detected, including the Fab-7 element providing for the autonomous functioning of the iab-6 and iab-7 cis-regulatory domains. Here, it has been shown that a single copy of the 860-bp Fab-7 insulator effectively blocks the yellow and white enhancers. The eye and testis enhancers can stimulate the white promoter across the pair of Fab-7, which is indicative of a functional interaction between the insulators. Unexpectedly, Fab-7 has proved to lose the enhancer-blocking activity when placed near the white promoter. It seems likely that Fab-7 strengthens the relatively weak white promoter, which leads to the efficient enhancer–promoter interaction and insulator bypass
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