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81.
Sofía Campillo Lourdes Bohorquez Elena Gutirrez-Calabrs Diego García-Ayuso Vernica Miguel Mercedes Griera Yolanda Calle Sergio de Frutos Manuel Rodríguez-Puyol Diego Rodríguez-Puyol Laura Calleros 《Experimental & molecular medicine》2022,54(3):226
Cardiovascular disease is an important cause of death in patients with chronic kidney disease (CKD). Protein-bound uremic toxins, such as p-cresyl and indoxyl sulfate (IS), are poorly removed during hemodialysis, leading to vascular endothelial dysfunction and leukocyte extravasation. These processes can be related to dynamic adhesion structures called podosomes. Several studies have indicated the role of integrin-linked kinase (ILK) in the accumulation of integrin-associated proteins in podosomes. Here, we investigated the involvement of ILK and podosome formation in the adhesion and extravasation of monocytes under p-cresol (pc) and IS exposure. Incubation of THP-1 human monocyte cells with these toxins upregulated ILK kinase activity. Together, both toxins increased cell adhesion, podosome formation, extracellular matrix degradation, and migration of THP-1 cells, whereas ILK depletion with specific small interfering RNAs suppressed these processes. Interestingly, F-actin colocalized with cortactin in podosome cores, while ILK was colocalized in podosome rings under toxin stimulation. Podosome Wiskott-Aldrich syndrome protein (WASP)-interacting protein (WIP) and AKT protein depletion demonstrated that monocyte adhesion depends on podosome formation and that the ILK/AKT signaling pathway is involved in these processes. Ex vivo experiments showed that both toxins induced adhesion and podosome formation in leukocytes from wild-type mice, whereas these effects were not observed in leukocytes of conditional ILK-knockdown animals. In summary, under pc and IS stimulation, monocytes increase podosome formation and transmigratory capacity through an ILK/AKT signaling pathway-dependent mechanism, which could lead to vascular injury. Therefore, ILK could be a potential therapeutic target for the treatment of vascular damage associated with CKD.Subject terms: Experimental models of disease, Atherosclerosis, Mechanisms of disease, Integrins, End-stage renal disease 相似文献
82.
Germán Bianchini Mónica Denham Ana Cortés Tomàs Margalef Emilio Luque 《Journal of computational science》2010,1(4):229-237
Several Data-Driven Methods have been developed to try to solve the input parameters uncertainty when considering problems like Wildfires Prediction. In general, these methods operate over a large number of input parameters, and consider the most recent known behavior of wildfires. The purpose of the methods is to find the parameter set that best describes the real situation under consideration. Therefore, it is presumed that the same set of values could be used to predict the immediate future.However, because this kind of prediction is based on a single set of parameters, for those parameters that present a dynamic behavior (e.g. wind direction and speed), the new optimized values are not adequate to make a prediction.In this paper we propose an alternative method developed in a new branch of Data-Driven Prediction, which we called Multiple Overlapping Solution. This method combines statistical concepts and HPC (High Performance Computing) to obtain a higher quality prediction. 相似文献
83.
84.
Abderrahim Jourani Emilio Vilches 《Journal of Optimization Theory and Applications》2017,173(1):91-116
The existence and the convergence (up to a subsequence) of the Moreau-Yosida regularization for the state-dependent sweeping process with nonregular (subsmooth and positively alpha-far) sets are established. Then, by a reparametrization technique, the existence of solutions for bounded variation continuous state-dependent sweeping processes with nonregular (subsmooth and positively alpha-far) sets is proved. An application to vector hysteresis is discussed, where it is shown that the Play operator with positively alpha-far sets is well defined for bounded variation continuous inputs. 相似文献
85.
86.
Freezing the Dynamic Gap for Selectivity: Motion‐Based Design of Inhibitors of the Shikimate Kinase Enzyme
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Verónica Prado Dr. Emilio Lence Paul Thompson Prof. Alastair R. Hawkins Prof. Concepción González‐Bello 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(50):17988-18000
Shikimate kinase (SK), the fifth enzyme of the aromatic amino acid biosynthesis, is a recognized target for antibiotic drug discovery. The potential of the distinct dynamic apolar gap, which isolates the natural substrate from the solvent environment for catalysis, and the motion of Mycobacterium tuberculosis and Helicobacter pylori SK enzymes, which was observed by molecular dynamics simulations, was explored for inhibition selectivity. The results of the biochemical and computational studies reveal that the incorporation of bulky groups at position C5 of 5‐aminoshikimic acid and the natural substrate enhances the selectivity for the H. pylori enzyme due to key motion differences in the shikimic acid binding domain (mainly helix α5). These studies show that the less‐exploited motion‐based design approach not only is an alternative strategy for the development of competitive inhibitors, but could also be a way to achieve selectivity against a particular enzyme among its homologues. 相似文献
87.
Miscible blends of poly(ethylene oxide) with brush copolymers of poly(vinyl alcohol)‐graft‐poly(l‐lactide)
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Ainhoa Lejardi Jose‐Ramon Sarasua Agustin Etxeberria Emilio Meaurio 《Journal of Polymer Science.Polymer Physics》2016,54(13):1217-1226
Even though poly(ethylene oxide) (PEO) is immiscible with both poly(l ‐lactide) (PLLA) and poly(vinyl alcohol) (PVA), this article shows a working route to obtain miscible blends based on these polymers. The miscibility of these polymers has been analyzed using the solubility parameter approach to choose the proper ratios of the constituents of the blend. Then, PVA has been grafted with l ‐lactide (LLA) through ring‐opening polymerization to obtain a poly(vinyl alcohol)‐graft‐poly(l ‐lactide) (PVA‐g‐PLLA) brush copolymer with 82 mol % LLA according to 1H and 13C NMR spectroscopies. PEO has been blended with the PVA‐g‐PLLA brush copolymer and the miscibility of the system has been analyzed by DSC, FTIR, OM, and SEM. The particular architecture of the blends results in DSC traces lacking clearly distinguishable glass transitions that have been explained considering self‐concentration effects (Lodge and McLeish) and the associated concentration fluctuations. Fortunately, the FTIR analysis is conclusive regarding the miscibility and the specific interactions in these systems. Melting point depression analysis suggests that interactions of intermediate strength and PLOM and SEM reveal homogeneous morphologies for the PEO/PVA‐g‐PLLA blends. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 1217–1226 相似文献
88.
Teresa Bermúdez Antonio Martinón Emilio Negrín 《Integral Equations and Operator Theory》2010,68(3):301-312
We give a characterization of m-isometric operators on a separable Hilbert space. Moreover, we characterize the unilateral weighted shift operators which
are m-isometries. 相似文献
89.
M.?Bello HernándezEmail author B.?de la?Calle Ysern J.?J.?Guadalupe Hernández G.?Lopez Lagomasino 《Journal d'Analyse Mathématique》2002,86(1):1-23
We study the asymptotic properties of Stieltjes polynomials outside the support of the measure as well as the asymptotic behaviour of their zeros. These properties are used to estimate the rate of convergence of sequences of rational functions, whose poles are partially fixed, which approximate Markovtype functions. An estimate for the speed of convergence of the Gauss-Kronrod quadrature formula in the case of analytic functions is also given. 相似文献
90.
Morán E Blesa MC Medina ME Tornero JD Menéndez N Amador U 《Inorganic chemistry》2002,41(23):5961-5967
Different solid/liquid "exchange" reactions involving divalent cations, protons, or ammonium ions have been performed at low/moderate temperatures (between 80 and 500 degrees C) on alpha-NaFeO2 dipped in molten salts (or acid) media. Several ferrites have been obtained which are nonstoichiometric with partially inverse spinel structures. When sodium is replaced by divalent cations (Mg2+, Co2+, Ni2+, and Zn2+), the obtained ferrites are hyperstoichiometric (cation/oxygen ratio higher than 3/4) whereas proton or ammonium reactions result in hypostoichiometric materials (cation/oxygen lower than 3/4). All these ferrites present a platelet-like morphology and show ferrimagnetic, soft magnet behavior. 相似文献