Journal articles on the topic 'Activation barrier'
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1
Stepanov, A. V. "Activation process model: Einstein coefficients for activation barrier." Journal of Molecular Structure: THEOCHEM 805, no. 1-3 (March 2007): 87–90. http://dx.doi.org/10.1016/j.theochem.2006.10.021.
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Gessain, Grégoire, Yu-Huan Tsai, Laetitia Travier, Matteo Bonazzi, Solène Grayo, Pascale Cossart, Caroline Charlier, Olivier Disson, and Marc Lecuit. "PI3-kinase activation is critical for host barrier permissiveness to Listeria monocytogenes." Journal of Experimental Medicine 212, no. 2 (January 26, 2015): 165–83. http://dx.doi.org/10.1084/jem.20141406.
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Invasion of nonphagocytic cells, a critical property of Listeria monocytogenes (Lm) that enables it to cross host barriers, is mediated by the interaction of two bacterial surface proteins, InlA and InlB, with their respective receptors E-cadherin and c-Met. Although InlA–E-cadherin interaction is necessary and sufficient for Lm crossing of the intestinal barrier, both InlA and InlB are required for Lm crossing of the placental barrier. The mechanisms underlying these differences are unknown. Phosphoinositide 3-kinase (PI3-K) is involved in both InlA- and InlB-dependent pathways. Indeed, InlA-dependent entry requires PI3-K activity but does not activate it, whereas InlB–c-Met interaction activates PI3-K. We show that Lm intestinal target cells exhibit a constitutive PI3-K activity, rendering InlB dispensable for InlA-dependent Lm intestinal barrier crossing. In contrast, the placental barrier does not exhibit constitutive PI3-K activity, making InlB necessary for InlA-dependent Lm placental invasion. Here, we provide the molecular explanation for the respective contributions of InlA and InlB to Lm host barrier invasion, and reveal the critical role of InlB in rendering cells permissive to InlA-mediated invasion. This study shows that PI3-K activity is critical to host barrier permissiveness to microbes, and that pathogens exploit both similarities and differences of host barriers to disseminate.
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Bushuev, Mark B., Denis P. Pishchur, Elena B. Nikolaenkova, and Viktor P. Krivopalov. "Compensation effects and relation between the activation energy of spin transition and the hysteresis loop width for an iron(ii) complex." Physical Chemistry Chemical Physics 18, no. 25 (2016): 16690–99. http://dx.doi.org/10.1039/c6cp01892k.
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Wide thermal hysteresis loops for iron(ii) spin crossover complexes are associated with high activation barriers: the higher the activation barrier, the wider the hysteresis loop for a series of related spin crossover systems.
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Doering, Charles R., and Jonathan C. Gadoua. "Resonant activation over a fluctuating barrier." Physical Review Letters 69, no. 16 (October 19, 1992): 2318–21. http://dx.doi.org/10.1103/physrevlett.69.2318.
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de Jong, G. Theodoor, and F. Matthias Bickelhaupt. "Bond activation by group-11 transition-metal cations." Canadian Journal of Chemistry 87, no. 7 (July 2009): 806–17. http://dx.doi.org/10.1139/v09-009.
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We have computationally explored C–X bond activation by the group-11 transition-metal cations Cu+, Ag+, and Au+, and, for comparison, Pd, using relativistic density functional theory (DFT) at ZORA-BLYP/TZ2P. Oxidative insertion of the second-row transition-metal species Ag+ and Pd leads, for a given bond, to the highest overall reaction barriers. On the other hand, if we compare the different bonds oxidative insertion into the C–F bond is associated with (one of the) highest overall barriers whereas insertion into the C–Cl bond leads to the lowest overall barrier for any transition metal. The main trends in reactivity are rationalized using the activation strain model of chemical reactivity, which is an extension of the fragment approach to reaction profiles. In this model, the shape of the reaction profile ΔE(ζ) and the height of the overall reaction barrier ΔE≠ = ΔE(ζ=ζTS) are interpreted in terms of the strain energy ΔEstrain(ζ) associated with deforming the reactants along the reaction coordinate ζ plus the interaction energy ΔEint(ζ) between these deformed reactants: ΔE(ζ) = ΔEstrain(ζ) + ΔEint(ζ).
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Jiang, Heming, and Tian-Yu Sun. "The Activating Effect of Strong Acid for Pd-Catalyzed Directed C–H Activation by Concerted Metalation-Deprotonation Mechanism." Molecules 26, no. 13 (July 4, 2021): 4083. http://dx.doi.org/10.3390/molecules26134083.
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A computational study on the origin of the activating effect for Pd-catalyzed directed C–H activation by the concerted metalation-deprotonation (CMD) mechanism is conducted. DFT calculations indicate that strong acids can make Pd catalysts coordinate with directing groups (DGs) of the substrates more strongly and lower the C–H activation energy barrier. For the CMD mechanism, the electrophilicity of the Pd center and the basicity of the corresponding acid ligand for deprotonating the C–H bond are vital to the overall C–H activation energy barrier. Furthermore, this rule might disclose the role of some additives for C–H activation.
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Cheng, Chunyu, Yiming Zou, Jiahui Li, Amanda Jiamin Ong, Ronn Goei, Jingfeng Huang, Shuzhou Li, and Alfred Iing Yoong Tok. "Adsorption and Reaction Mechanisms of Direct Palladium Synthesis by ALD Using Pd(hfac)2 and Ozone on Si (100) Surface." Processes 9, no. 12 (December 13, 2021): 2246. http://dx.doi.org/10.3390/pr9122246.
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Palladium nanoparticles made by atomic layer deposition (ALD) normally involve formaldehyde or H2 as a reducing agent. Since formaldehyde is toxic and H2 is explosive, it is advantageous to remove this reducing step during the fabrication of palladium metal by ALD. In this work we have successfully used Pd(hfac)2 and ozone directly to prepare palladium nanoparticles, without the use of reducing or annealing agents. Density functional theory (DFT) was employed to explore the reaction mechanisms of palladium metal formation in this process. DFT results show that Pd(hfac)2 dissociatively chemisorbed to form Pd(hfac)* and hfac* on the Si (100) surface. Subsequently, an O atom of the ozone could cleave the C–C bond of Pd(hfac)* to form Pd* with a low activation barrier of 0.46 eV. An O atom of the ozone could also be inserted into the hfac* to form Pd(hfac-O)* with a lower activation barrier of 0.29 eV. With more ozone, the C–C bond of Pd(hfac-O)* could be broken to produce Pd* with an activation barrier of 0.42 eV. The ozone could also chemisorb on the Pd atom of Pd(hfac-O)* to form O3-Pd(hfac-O)*, which could separate into O-Pd(hfac-O)* with a high activation barrier of 0.83 eV. Besides, the activation barrier was 0.64 eV for Pd* that was directly oxidized to PdOx by ozone. Based on activation barriers from DFT calculations, it was possible to prepare palladium without reducing steps when ALD conditions were carefully controlled, especially the ozone parameters, as shown by our experimental results. The mechanisms of this approach could be used to prepare other noble metals by ALD without reducing/annealing agents.
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Winter, Michael C., Sandra S. Shasby, Dana R. Ries, and D. Michael Shasby. "PAR2 activation interrupts E-cadherin adhesion and compromises the airway epithelial barrier: protective effect of β-agonists." American Journal of Physiology-Lung Cellular and Molecular Physiology 291, no. 4 (October 2006): L628—L635. http://dx.doi.org/10.1152/ajplung.00046.2006.
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The airway epithelium is an important barrier between the environment and subepithelial tissues. The epithelium is also divided into functionally restricted apical and basolateral domains, and this restriction is dependent on the elements of the barrier. The protease-activated receptor-2 (PAR2) receptor is expressed in airway epithelium, and its activation initiates multiple effects including enhanced airway inflammation and reactivity. We hypothesized that activation of PAR2 would interrupt E-cadherin adhesion and compromise the airway epithelial barrier. The PAR2-activating peptide (PAR2-AP, SLIGRL) caused an immediate ∼50% decrease in the transepithelial resistance of primary human airway epithelium that persisted for 6–10 min. The decrease in resistance was accompanied by an increase in mannitol flux across the epithelium and occurred in cystic fibrosis transmembrane conductance receptor (CFTR) epithelium pretreated with amiloride to block Na and Cl conductances, confirming that the decrease in resistance represented an increase in paracellular conductance. In parallel experiments, activation of PAR2 interrupted the adhesion of E-cadherin-expressing L cells and of primary airway epithelial cells to an immobilized E-cadherin extracellular domain, confirming the hypothesis that activation of PAR2 interrupts E-cadherin adhesion. Selective interruption of E-cadherin adhesion with antibody to E-cadherin decreased the transepithelial resistance of primary airway epithelium by >80%. Pretreatment of airway epithelium or the E-cadherin-expressing L cells with the long-acting β-agonist salmeterol prevented PAR2 activation from interrupting E-cadherin adhesion and compromising the airway epithelial barrier. Activation of PAR2 interrupts E-cadherin adhesion and compromises the airway epithelial barrier.
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Stavenuiter, Fabian, and Laurent O. Mosnier. "Non-Canonical PAR3 Activation Induces Tie2-Dependent Endothelial Barrier Protective Effects." Blood 124, no. 21 (December 6, 2014): 2802. http://dx.doi.org/10.1182/blood.v124.21.2802.2802.
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Abstract Introduction: Endothelial barrier protective effects of activated protein C (APC) require the endothelial protein C receptor (EPCR), protease activated receptor 1 (PAR1), and PAR3. In contrast, PAR1 and PAR3 activation by thrombin results in barrier disruption. Non-canonical PAR1 and PAR3 activation by APC versus canonical activation by thrombin provide an explanation for the functional selectivity of these proteases. APC induces non-canonical PAR3 activation at Arg41 and synthetic peptides representing the tethered-ligand sequence of PAR3 after non-canonical cleavage (P3R) induce barrier protective effects in vitro and vascular integrity in vivo. However, signaling mechanisms employed by PAR3 remain undefined. To obtain better insights into the relation between coagulation proteases with endothelial barrier protective effects and canonical/non-canonical PAR1 and PAR3 activation, the PAR proteolysis analysis was extended to factor Xa (FXa). Similar to APC, FXa-mediates endothelial barrier protective effects that involve both PAR1 and EPCR. To date, however, no role for PAR3 in FXa-induced barrier integrity has been implicated. Results: In the presence of EPCR, FXa cleaved PAR1 at Arg41 similar to thrombin and not at Arg46 alike APC, whereas FXa cleaved PAR3 at the non-canonical Arg41 similar to APC but not at the canonical Lys38 corresponding to cleavage by thrombin. Surprisingly, changes in electric cell-substrate impedance sensing (ECIS) using the iCelligence system showed FXa induced an immediate drop in endothelial cell index (~60%) comparable to that induced by thrombin, indicating that FXa induced a loss of cell barrier function. Notwithstanding, after incubation of endothelial cells with FXa for 3 hours, FXa protected (~40%) against TRAP-induced loss of barrier function, similar to that induced by APC, confirming barrier protective effects of FXa. PAR1 blocking antibodies prevented the early FXa-mediated loss of barrier function, indicating that PAR1 cleavage at Arg41 was responsible for this.In contrast,a combinationofPAR1 and PAR2 blocking antibodies was needed to inhibit late (3h) FXa-mediated barrier protection. Blocking antibodies against PAR3 confirmed that canonical PAR3 activation enhanced PAR1-mediated barrier disruptive effects of thrombin (~15%). PAR3 blocking antibodies also significantly reduced the barrier protective effect of FXa (~15%), indicating a functional role for non-canonical PAR3 activation by FXa. Neither canonical (P3K) nor non-canonical (P3R) PAR3 tethered-ligand peptides directly induced significant phosphorylation of ERK1/2 or Akt in endothelial cells. The P3K however, but not the P3R peptide, enhanced TRAP induced ERK1/2 phosphorylation. No Akt phosphorylation was observed in endothelial cells treated with TRAP in the presence of either P3K or P3R. Interestingly, both APC and FXa but not thrombin induced prolonged activation of the endothelial cell specific Tie2 receptor, determined by phosphorylation of Y992 and S1119. Tie2 activation by FXa required PAR3 and EPCR with a partial contribution of PAR1 and PAR2. P3R induced potent activation of Tie2 achieving maximal activation at ~0.8 µM P3R, whereas P3K failed to do so. Additionally, neither (non-)canonical PAR1 nor PAR2 tethered-ligand peptides induced activation of Tie2. Activation of Tie2 by P3R was relatively fast and reached half-maximal activation in about 5 minutes. Blocking antibodies against Tie2 reduced FXa-mediated barrier protective effects by approximately 34%, whereas inhibition of Tie2 did not affect thrombin mediated barrier disruption. Immunohistochemistry indicated that Tie2 activation by FXa and P3R resulted in clustering of activated Tie2 at the cell borders. Accordingly, Tie2 activation by FXa and P3R resulted in changes in the cellular distribution of the tight-junction-associated protein zona occludens (ZO-1) in time. Conclusion: Here we identified a novel pathway for Tie2 activation by non-canonical PAR3 activation that promoted tight-junction formation and endothelial barrier protective effects. In contrast, canonical activation of PAR3 enhanced PAR1-mediated barrier disruptive effects by thrombin. These results exemplify the novel dimensions that non-canonical activation of PARs provides for the possible molecular mechanisms that are responsible for the functional selectivity of protease signaling. Disclosures No relevant conflicts of interest to declare.
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Carpenter, Chris. "Using Shale as a Barrier Simplifies Well Abandonment." Journal of Petroleum Technology 73, no. 01 (January 1, 2021): 62–63. http://dx.doi.org/10.2118/0121-0062-jpt.
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This article, written by JPT Technology Editor Chris Carpenter, contains highlights of paper SPE 199654, “Simplifying Well Abandonments Using Shale as a Barrier,” by Eric van Oort, SPE, and Maria Juenger, The University of Texas at Austin, and Munir Aldin, SPE, Metarock Laboratories, et al., prepared for the 2020 IADC/SPE International Drilling Conference and Exhibition, Galveston, Texas, 3-5 March. The paper has not been peer reviewed. The complete paper presents the results of an investigation into the creep behavior of North Sea shales and their ability to form effective annular barriers. The large-scale laboratory results show that Lark-Horda shales will form competent low-permeability annular barriers when left uncemented, as confirmed using pressure-pulse-decay measurements. Experimental conditions were found to influence the rate of barrier formation. Higher effective stress, higher temperature, and beneficial manipulation of annular fluid chemistry all have a significant effect. Introduction An alternative to traditional plug-and-abandonment techniques presented it-self more than a decade ago, with observations that formations such as mobile salts and shales could creep into uncemented annular spaces and form competent annular barriers that could be identified on sonic and ultrasonic bond logs and verified using pressure testing. Shale particularly has the necessary characteristics that several guidelines require of a good barrier, being largely impermeable, nonshrinking, ductile, and resistant to chemicals and substances, all of which help provide long-term integrity. Shales that appeared to be particularly well-suited to beneficial annular creep behavior were characterized by low strength and high ductility, high clay content with relatively high smectite content, low levels of quartz and carbonate cementation, relatively high porosity and low compressional wave velocity, and a tendency to yield wellbore instability problems while being drilled. Mechanisms other than creep were considered for the annular blockage behavior observed, but the mounting body of evidence indicates that the predominant mechanism is indeed creep (i.e., the viscoplastic behavior of argillaceous rocks). In the laboratory and field work published to date, stimulation of shale barriers through accelerated creep by pressure and temperature manipulation has received the most attention. The authors investigate barrier activation not only by temperature and pressure activation but also by chemical activation, because it offers practical advantages and reduces risks associated with temperature and pressure activation. Temperature has a significant effect on the viscoplastic behavior of shale, but heating a long shale section (with a minimum barrier length of 50 m) through casing with an effective downhole heater presents considerable practical challenges. Pressure reduction in the annulus through reduction of the hydrostatic head in the wellbore brings with it well-control concerns, particularly when no functional annular barrier is in place. By contrast, circulating a chemical solution in place in an annular space through casing perforations with a workstring and packer arrangement is relatively straightforward and is routine when practicing the perforate, wash, and cement technique in the field.
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Mizrahi, Inbal, Robijn Bruinsma, and Joseph Rudnick. "Packaging contests between viral RNA molecules and kinetic selectivity." PLOS Computational Biology 18, no. 4 (April 1, 2022): e1009913. http://dx.doi.org/10.1371/journal.pcbi.1009913.
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The paper presents a statistical-mechanics model for the kinetic selection of viral RNA molecules by packaging signals during the nucleation stage of the assembly of small RNA viruses. The effects of the RNA secondary structure and folding geometry of the packaging signals on the assembly activation energy barrier are encoded by a pair of characteristics: the wrapping number and the maximum ladder distance. Kinetic selection is found to be optimal when assembly takes place under conditions of supersaturation and also when the concentration ratio of capsid protein and viral RNA concentrations equals the stoichiometric ratio of assembled viral particles. As a function of the height of the activation energy barrier, there is a form of order-disorder transition such that for sufficiently low activation energy barriers, kinetic selectivity is erased by entropic effects associated with the number of assembly pathways.
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Capilla, Amalia, Dmitry Karachentsev, Rachel A. Patterson, Anita Hermann, Michelle T. Juarez, and William McGinnis. "Toll pathway is required for wound-induced expression of barrier repair genes in the Drosophila epidermis." Proceedings of the National Academy of Sciences 114, no. 13 (March 13, 2017): E2682—E2688. http://dx.doi.org/10.1073/pnas.1613917114.
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The epidermis serves as a protective barrier in animals. After epidermal injury, barrier repair requires activation of many wound response genes in epidermal cells surrounding wound sites. Two such genes in Drosophila encode the enzymes dopa decarboxylase (Ddc) and tyrosine hydroxylase (ple). In this paper we explore the involvement of the Toll/NF-κB pathway in the localized activation of wound repair genes around epidermal breaks. Robust activation of wound-induced transcription from ple and Ddc requires Toll pathway components ranging from the extracellular ligand Spätzle to the Dif transcription factor. Epistasis experiments indicate a requirement for Spätzle ligand downstream of hydrogen peroxide and protease function, both of which are known activators of wound-induced transcription. The localized activation of Toll a few cell diameters from wound edges is reminiscent of local activation of Toll in early embryonic ventral hypoderm, consistent with the hypothesis that the dorsal–ventral patterning function of Toll arose from the evolutionary cooption of a morphogen-responsive function in wound repair. Furthermore, the combinatorial activity of Toll and other signaling pathways in activating epidermal barrier repair genes can help explain why developmental activation of the Toll, ERK, or JNK pathways alone fail to activate wound repair loci.
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Černušák, Ivan, and Miroslav Urban. "Effect of electron correlation on SN2 activation barriers. Fourth-order MBPT calculations." Collection of Czechoslovak Chemical Communications 53, no. 10 (1988): 2239–49. http://dx.doi.org/10.1135/cccc19882239.
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The activation barriers for a series of model gas-phase nucleophilic displacement reactions have been calculated at the MBPT(4)/DZ + P + D level. Electron correlation significantly reduces the barrier height, in most cases by about 50%. The role of individual contributions up to the fourth order MBPT is analyzed in detail showing the vital importance of single and triple excitations.
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Schowen, R. L. "How an enzyme surmounts the activation energy barrier." Proceedings of the National Academy of Sciences 100, no. 21 (October 6, 2003): 11931–32. http://dx.doi.org/10.1073/pnas.2235806100.
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Li, Lisheng, Hua Wang, Jinyu Han, Xinli Zhu, and Qingfeng Ge. "Balancing the Activity and Selectivity of Propane Oxidative Dehydrogenation on NiOOH (001) and (010)." Transactions of Tianjin University 26, no. 5 (August 5, 2020): 341–51. http://dx.doi.org/10.1007/s12209-020-00267-3.
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Abstract Propane oxidative dehydrogenation (ODH) is an energy-efficient approach to produce propylene. However, ODH suffers from low propylene selectivity due to a relatively higher activation barrier for propylene formation compared with that for further oxidation. In this work, calculations based on density functional theory were performed to map out the reaction pathways of propane ODH on the surfaces (001) and (010) of nickel oxide hydroxide (NiOOH). Results show that propane is physisorbed on both surfaces and produces propylene through a two-step radical dehydrogenation process. The relatively low activation barriers of propane dehydrogenation on the NiOOH surfaces make the NiOOH-based catalysts promising for propane ODH. By contrast, the weak interaction between the allylic radical and the surface leads to a high activation barrier for further propylene oxidation. These results suggest that the catalysts based on NiOOH can be active and selective for the ODH of propane toward propylene.
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Hilfenhaus, Georg, Dai Phuong Nguyen, Jonathan Freshman, Divya Prajapati, Feiyang Ma, Dana Song, Safiyyah Ziyad, et al. "Vav3-induced cytoskeletal dynamics contribute to heterotypic properties of endothelial barriers." Journal of Cell Biology 217, no. 8 (June 1, 2018): 2813–30. http://dx.doi.org/10.1083/jcb.201706041.
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Through multiple cell–cell and cell–matrix interactions, epithelial and endothelial sheets form tight barriers. Modulators of the cytoskeleton contribute to barrier stability and act as rheostats of vascular permeability. In this study, we sought to identify cytoskeletal regulators that underlie barrier diversity across vessels. To achieve this, we correlated functional and structural barrier features to gene expression of endothelial cells (ECs) derived from different vascular beds. Within a subset of identified candidates, we found that the guanosine nucleotide exchange factor Vav3 was exclusively expressed by microvascular ECs and was closely associated with a high-resistance barrier phenotype. Ectopic expression of Vav3 in large artery and brain ECs significantly enhanced barrier resistance and cortical rearrangement of the actin cytoskeleton. Mechanistically, we found that the barrier effect of Vav3 is dependent on its Dbl homology domain and downstream activation of Rap1. Importantly, inactivation of Vav3 in vivo resulted in increased vascular leakage, highlighting its function as a key regulator of barrier stability.
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Akhmetova, A., J. Gamper, and L. Dalbergenova. "The problem of overcoming the language barrier when learning a foreign language in higher education institutions." Bulletin of the Karaganda University. Pedagogy series 100, no. 4 (December 28, 2020): 104–14. http://dx.doi.org/10.31489/2020ped4/104-114.
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This article is devoted to the study of the problem of overcoming language barriers that prevent students from successfully mastering a foreign language. The concept of «language barrier», its linguistic and psychological aspects are considered, and various approaches to its definition are analyzed. The article describes the main factors that affect the formation of the language barrier. Special attention is paid to the psychological aspects of the language barrier associated with internal fears, self-doubt, fear of making a mistake, which is one of the main causes of the language barrier. The paper explores possible ways to overcome language barriers when learning a foreign language, using modern methods and techniques in the classroom that contribute to the de-velopment of cognitive interest, activation of mental activity. The author highlights a personality-oriented ap-proach aimed at developing creative abilities and self-expression. The personality-oriented approach is the defining direction of research of methods of teaching a foreign language in this work. As an effective way to overcome the language barrier in teaching a foreign language, we propose a method of scenic interpretation of literary texts, which contributes to the activation of cognitive activity and the development of communica-tion skills. An experiment aimed at testing this method in 2nd-year students of Kokshetau state University is described. Sh. Ualikhanov, specialty: «Foreign language: two foreign languages», level A1, A2. The paper presents the results of an experiment that proves the effectiveness of using the method of scenic interpretation of literary texts in the study of a foreign language.
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Lu, Qing, Elizabeth O. Harrington, Heather Jackson, Nicole Morin, Christopher Shannon, and Sharon Rounds. "Transforming growth factor-β1-induced endothelial barrier dysfunction involves Smad2-dependent p38 activation and subsequent RhoA activation." Journal of Applied Physiology 101, no. 2 (August 2006): 375–84. http://dx.doi.org/10.1152/japplphysiol.01515.2005.
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Lung edema due to increased vascular permeability is a hallmark of acute lung injury and acute respiratory distress syndrome. Both p38 and RhoA signaling events are involved in transforming growth factor (TGF)-β1-increased endothelial permeability; however, the mechanism by which these pathways cooperate is not clear. In this study, we hypothesized that TGF-β1-induced changes in endothelial monolayer permeability and in p38 and RhoA activation are dependent on Smad2 signaling. We assessed the role of Smad2 in p38 activation and the role of p38 in RhoA activation by TGF-β1. We found that TGF-β1caused Smad2 phosphorylation between 0.5 and 1 h of exposure in endothelial cells. Knockdown of Smad2 protein prevented TGF-β1-induced p38 activation and endothelial barrier dysfunction. Furthermore, TGF-β1-enhanced RhoA activation was dependent on p38 activation. Inhibition of the RhoA-Rho kinase signaling pathway blunted TGF-β1-induced adherens junction disruption and focal adhesion complex formation. In addition, depletion of heat shock protein 27, a downstream signaling molecule of p38, did not prevent TGF-β1-induced endothelial barrier dysfunction. Finally, inhibition of de novo protein expression blunted TGF-β1-induced RhoA activation and endothelial barrier dysfunction. Our data indicate that TGF-β1induces endothelial barrier dysfunction involving Smad2-dependent p38 activation, resulting in RhoA activation by possible transcriptional regulation.
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LI, LAI-CAI, JUN-LING LIU, JING SHANG, XIN WANG, and NING-BEW WONG. "THEORETICAL INVESTIGATION ON THE ACTIVATION OF ETHANE VIA NICKEL ATOM CATALYSIS." Journal of Theoretical and Computational Chemistry 06, no. 02 (June 2007): 323–30. http://dx.doi.org/10.1142/s0219633607002976.
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The reaction mechanism of the activation of ethane by nickel atom has been investigated by density functional theory (DFT). The geometries and vibration frequencies of reactants, intermediates, transition states and products have been calculated at the B3LYP/6-311 + +G(d, p) level. Two main pathways, C – C bond activation and C – H bond activation, are identified. In former channel, the rate-limiting step is found to be hydrogen-transferring step with a high barrier of 227 kJ · mol-1. In the C – H bond activation pathway, the second hydrogen-transferring step is the rate-determining step of the whole reaction. The barrier of the step is 71 kJ · mol-1. Our results show that the studied reaction would undergo along C – H bond activation pathway to form the products H 2 molecule and Ni ⋯ethene complex. The present theoretical work indicates that Ni atom is more active than Ni + cation in activating ethane.
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BOATRIGHT, Kelly M., Cristina DEIS, Jean-Bernard DENAULT, Daniel P. SUTHERLIN, and Guy S. SALVESEN. "Activation of caspases-8 and -10 by FLIPL." Biochemical Journal 382, no. 2 (August 24, 2004): 651–57. http://dx.doi.org/10.1042/bj20040809.
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The first step in caspase activation is transition of the latent zymogen to an active form. For the initiator caspases, this occurs through dimerization of monomeric zymogens at an activating complex. Recent studies have suggested that FLIPL [FLICE-like inhibitory protein, long form; FLICE is FADD (Fas-associated death domain protein)-like interleukin-1β-converting enzyme], previously thought to act solely as an inhibitor of caspase-8 activation, can under certain circumstances function to enhance caspase activation. Using an in vitro induced-proximity assay, we demonstrate that activation of caspases-8 and -10 occurs independently of cleavage of either the caspase or FLIPL. FLIPL activates caspase-8 by forming heterodimeric enzyme molecules with substrate specificity and catalytic activity indistinguishable from those of caspase-8 homodimers. Significantly, the barrier for heterodimer formation is lower than that for homodimer formation, suggesting that FLIPL is a more potent activator of caspase-8 than is caspase-8 itself.
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DYBIEC, BARTŁOMIEJ, and EWA GUDOWSKA-NOWAK. "RESONANT ACTIVATION DRIVEN BY STRONGLY NON-GAUSSIAN NOISES." Fluctuation and Noise Letters 04, no. 02 (June 2004): L273—L285. http://dx.doi.org/10.1142/s0219477504001872.
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The constructive role of non-Gaussian random fluctuations is studied in the context of the passage over the dichotomously switching potential barrier. Our attention focuses on the interplay of the effects of independent sources of fluctuations: an additive stable noise representing non-equilibrium external random force acting on the system and a fluctuating barrier. In particular, the influence of the structure of stable noises on the mean escape time and on the phenomenon of resonant activation (RA) is investigated. By use of the numerical Monte Carlo method it is documented that the suitable choice of the barrier switching rate and random external fields may produce resonant phenomenon leading to the enhancement of the kinetics and the shortest, most efficient reaction time.
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Walsh, Jessica, Dan J. Tozer, Hasan Sari, Young T. Hong, Anna Drazyk, Guy Williams, N. Jon Shah, et al. "Microglial activation and blood–brain barrier permeability in cerebral small vessel disease." Brain 144, no. 5 (May 1, 2021): 1361–71. http://dx.doi.org/10.1093/brain/awab003.
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Abstract Cerebral small vessel disease (SVD) is a major cause of stroke and dementia. The underlying pathogenesis is poorly understood, but both neuroinflammation and increased blood–brain barrier permeability have been hypothesized to play a role, and preclinical studies suggest the two processes may be linked. We used PET magnetic resonance to simultaneously measure microglial activation using the translocator protein radioligand 11C-PK11195, and blood–brain barrier permeability using dynamic contrast enhanced MRI. A case control design was used with two disease groups with sporadic SVD (n = 20), monogenic SVD (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, CADASIL), and normal controls (n = 20) were studied. Hotspots of increased glial activation and blood–brain barrier permeability were identified as values greater than the 95th percentile of the distribution in controls. In sporadic SVD there was an increase in the volume of hotspots of both 11C-PK11195 binding (P = 0.003) and blood–brain barrier permeability (P = 0.007) in the normal appearing white matter, in addition to increased mean blood–brain barrier permeability (P < 0.001). In CADASIL no increase in blood–brain barrier permeability was detected; there was a non-significant trend to increased 11C-PK11195 binding (P = 0.073). Hotspots of 11C-PK11195 binding and blood–brain barrier permeability were not spatially related. A panel of 93 blood biomarkers relating to cardiovascular disease, inflammation and endothelial activation were measured in each participant; principal component analysis was performed and the first component related to blood–brain barrier permeability and microglial activation. Within the sporadic SVD group both hotspot and mean volume blood–brain barrier permeability values in the normal appearing white matter were associated with dimension 1 (β = 0.829, P = 0.017, and β = 0.976, P = 0.003, respectively). There was no association with 11C-PK11195 binding. No associations with blood markers were found in the CADASIL group. In conclusion, in sporadic SVD both microglial activation and increased blood–brain barrier permeability occur, but these are spatially distinct processes. No evidence of increased blood–brain barrier permeability was found in CADASIL.
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Jacobson, Jeffrey R., Steven M. Dudek, Patrick A. Singleton, Irina A. Kolosova, Alexander D. Verin, and Joe G. N. Garcia. "Endothelial cell barrier enhancement by ATP is mediated by the small GTPase Rac and cortactin." American Journal of Physiology-Lung Cellular and Molecular Physiology 291, no. 2 (August 2006): L289—L295. http://dx.doi.org/10.1152/ajplung.00343.2005.
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ATP is a physiologically relevant agonist released by various sources, including activated platelets, with complex effects mediated via activation of P2 purinergic receptors. ATP-induced endothelial cell (EC) production of prostacyclin and nitric oxide is recognized, and EC barrier enhancement evoked by ATP has been described. ATP effects on EC barrier function and vascular permeability, however, remain poorly characterized. Although the mechanisms involved are unclear, we previously identified activation of the small GTPase Rac and translocation of cortactin, an actin-binding protein, as key to EC barrier augmentation induced by simvastatin and sphingosine 1-phosphate and therefore examined the role of these molecules in ATP-induced EC barrier enhancement. ATP induced rapid, dose-dependent barrier enhancement in human pulmonary artery EC as measured by transendothelial electrical resistance, with a peak effect appreciable at 25 min (39% increase, 10 μM) and persisting at 2 h. These effects were associated with rearrangement of the EC actin cytoskeleton, early myosin light chain phosphorylation, and spatially defined (cell periphery) translocation of both Rac and cortactin. ATP (10 μM)-treated EC demonstrated a significant increase in Rac activation relative to controls, with a maximal effect (∼4-fold increase) at 10 min. Finally, ATP-induced barrier enhancement was markedly attenuated by reductions of either Rac or cortactin (small interfering RNA) relative to controls. Our results suggest for the first time that ATP-mediated barrier protection is associated with cytoskeletal activation and is dependent on both Rac activation and cortactin.
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Guillemot, Laurent, Diego Guerrera, Domenica Spadaro, Rocio Tapia, Lionel Jond, and Sandra Citi. "MgcRacGAP interacts with cingulin and paracingulin to regulate Rac1 activation and development of the tight junction barrier during epithelial junction assembly." Molecular Biology of the Cell 25, no. 13 (July 2014): 1995–2005. http://dx.doi.org/10.1091/mbc.e13-11-0680.
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The regulation of Rho-family GTPases is crucial to direct the formation of cell–cell junctions and tissue barriers. Cingulin (CGN) and paracingulin (CGNL1) control RhoA activation in epithelial cells by interacting with RhoA guanidine exchange factors. CGNL1 depletion also inhibits Rac1 activation during junction assembly. Here we show that, unexpectedly, Madin–Darby canine kidney epithelial cells depleted of both CGN and CGNL1 (double-KD cells) display normal Rac1 activation and tight junction (TJ) formation, despite decreased junctional recruitment of the Rac1 activator Tiam1. The expression of the Rac1 inhibitor MgcRacGAP is decreased in double-KD cells, and the barrier development and Rac1 activation phenotypes are rescued by exogenous expression of MgcRacGAP. MgcRacGAP colocalizes with CGN and CGNL1 at TJs and forms a complex and interacts directly in vitro with CGN and CGNL1. Depletion of either CGN or CGNL1 in epithelial cells results in decreased junctional localization of MgcRacGAP but not of ECT2, a centralspindlin-interacting Rho GEF. These results provide new insight into coordination of Rho-family GTPase activities at junctions, since apical accumulation of CGN and CGNL1 at TJs during junction maturation provides a mechanism to spatially restrict down-regulation of Rac1 activation through the recruitment of MgcRacGAP.
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Terakado, Masahiro, Yasuhiro Gon, Akiko Sekiyama, Ikuko Takeshita, Yutaka Kozu, Ken Matsumoto, Noriaki Takahashi, and Shu Hashimoto. "The Rac1/JNK pathway is critical for EGFR-dependent barrier formation in human airway epithelial cells." American Journal of Physiology-Lung Cellular and Molecular Physiology 300, no. 1 (January 2011): L56—L63. http://dx.doi.org/10.1152/ajplung.00159.2010.
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The airway epithelial barrier provides defenses against inhaled antigens and pathogens, and alterations of epithelial barrier function have been proposed to play a significant role in the pathogenesis of chronic airway diseases. Although the epidermal growth factor receptor (EGFR) plays roles in various physiological and pathological processes on the airway epithelium, the role of EGFR on barrier function in the airway remains largely unknown. In the present study, we assessed the effects of EGFR activation on paracellular permeability in airway epithelial cells (AECs). EGFR activation induced by the addition of EGF increased transepithelial electrical resistance (TER) in AECs. An EGFR-blocking antibody eradicated the development of TER, paracellular influx of dextran, and spatial organization of tight junction. Moreover, the effects of EGFR activation on paracellular permeability were eradicated by knockdown of occludin. To identify the EGFR signaling pathway that regulates permeability barrier development, we investigated the effects of several MAP kinase inhibitors on permeability barrier function. Pretreatment with a JNK-specific inhibitor, but not an ERK- or p38-specific inhibitor, attenuated the development of TER induced by EGFR activation. Rac1 is one of the upstream activators for JNK in EGFR signaling. Rac1 knockdown attenuated the phosphorylation of JNK activation and EGFR-mediated TER development. These results suggest that EGFR positively regulates permeability barrier development through the Rac1/JNK-dependent pathway.
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Aslam, Muhammad, Dursun Gündüz, Christian Troidl, Jacqueline Heger, Christian W. Hamm, and Rainer Schulz. "Purinergic Regulation of Endothelial Barrier Function." International Journal of Molecular Sciences 22, no. 3 (January 26, 2021): 1207. http://dx.doi.org/10.3390/ijms22031207.
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Increased vascular permeability is a hallmark of several cardiovascular anomalies, including ischaemia/reperfusion injury and inflammation. During both ischaemia/reperfusion and inflammation, massive amounts of various nucleotides, particularly adenosine 5′-triphosphate (ATP) and adenosine, are released that can induce a plethora of signalling pathways via activation of several purinergic receptors and may affect endothelial barrier properties. The nature of the effects on endothelial barrier function may depend on the prevalence and type of purinergic receptors activated in a particular tissue. In this review, we discuss the influence of the activation of various purinergic receptors and downstream signalling pathways on vascular permeability during pathological conditions.
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González-Medina, Alberto, Elena Hidalgo, and José Ayté. "Gcn5-mediated acetylation at MBF-regulated promoters induces the G1/S transcriptional wave." Nucleic Acids Research 47, no. 16 (July 1, 2019): 8439–51. http://dx.doi.org/10.1093/nar/gkz561.
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Abstract In fission yeast, MBF-dependent transcription is inactivated at the end of S phase through a negative feedback loop that involves the co-repressors, Yox1 and Nrm1. Although this repression system is well known, the molecular mechanisms involved in MBF activation remain largely unknown. Compacted chromatin constitutes a barrier to activators accessing promoters. Here, we show that chromatin regulation plays a key role in activating MBF-dependent transcription. Gcn5, a part of the SAGA complex, binds to MBF-regulated promoters through the MBF co-activator Rep2 in a cell cycle-dependent manner and in a reverse correlation to the binding of the MBF co-repressors, Nrm1 or Yox1. We propose that the co-repressors function as physical barriers to SAGA recruitment onto MBF promoters. We also show that Gcn5 acetylates specific lysine residues on histone H3 in a cell cycle-regulated manner. Furthermore, either in a gcn5 mutant or in a strain in which histone H3 is kept in an unacetylated form, MBF-dependent transcription is downregulated. In summary, Gcn5 is required for the full activation and correct timing of MBF-regulated gene transcription.
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Schlegel, Nicolas, and Jens Waschke. "VASP is involved in cAMP-mediated Rac 1 activation in microvascular endothelial cells." American Journal of Physiology-Cell Physiology 296, no. 3 (March 2009): C453—C462. http://dx.doi.org/10.1152/ajpcell.00360.2008.
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Accumulating evidence points to a significant role of vasodilator-stimulated phosphoprotein (VASP) in the maintenance of endothelial barrier functions. We have recently shown that impaired barrier functions in VASP-deficient microvascular myocardial endothelial cells (MyEnd VASP−/−) correlated with decreased Rac 1 activity. To further test the hypothesis that VASP is involved in regulation of Rac 1 activity, we studied cAMP-dependent Rac 1 activation. Both inhibition of Rac 1 activation by NSC-23766 and inhibition of PKA by PKI completely blunted the efficacy of forskolin/rolipram (F/R)-mediated cAMP increase to stabilize barrier functions as revealed by measurements of transendothelial resistance (TER). Because these results indicate that PKA/Rac 1 activation is important for barrier stabilization, we tested this signaling pathway in VASP−/− cells. We found that F/R and isoproterenol reduced permeability measured as FITC-dextran flux across VASP−/− monolayers, but not below baseline levels of wild-type cells (WT). Moreover, cAMP-mediated Rac 1 activation was reduced to ∼50% of WT levels, and both PKA inhibition by PKI and PKA anchoring via A kinase anchoring peptides (AKAPs) by HT31 almost completely abolished Rac 1 activation in VASP−/− and WT endothelium. Accordingly, HT31 significantly reduced F/R-mediated TER increase in WT cells and completely blocked the protective effect of cAMP on endothelial barrier properties. Together, our data underline the significant role of cAMP-mediated Rac 1 activation for endothelial barrier stabilization and demonstrate that both AKAP-mediated PKA anchoring and VASP are required for this process.
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Chetham, Paul M., Pavel Babál, James P. Bridges, Timothy M. Moore, and Troy Stevens. "Segmental regulation of pulmonary vascular permeability by store-operated Ca2+entry." American Journal of Physiology-Lung Cellular and Molecular Physiology 276, no. 1 (January 1, 1999): L41—L50. http://dx.doi.org/10.1152/ajplung.1999.276.1.l41.
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An intact endothelial cell barrier maintains normal gas exchange in the lung, and inflammatory conditions result in barrier disruption that produces life-threatening hypoxemia. Activation of store-operated Ca2+(SOC) entry increases the capillary filtration coefficient ( Kf,c) in the isolated rat lung; however, activation of SOC entry does not promote permeability in cultured rat pulmonary microvascular endothelial cells. Therefore, current studies tested whether activation of SOC entry increases macro- and/or microvascular permeability in the intact rat lung circulation. Activation of SOC entry by the administration of thapsigargin induced perivascular edema in pre- and postcapillary vessels, with apparent sparing of the microcirculation as evaluated by light microscopy. Scanning and transmission electron microscopy revealed that the leak was due to gaps in vessels ≥ 100 μm, consistent with the idea that activation of SOC entry influences macrovascular but not microvascular endothelial cell shape. In contrast, ischemia and reperfusion induced microvascular endothelial cell disruption independent of Ca2+entry, which similarly increased Kf,c. These data suggest that 1) activation of SOC entry is sufficient to promote macrovascular barrier disruption and 2) unique mechanisms regulate pulmonary micro- and macrovascular endothelial barrier functions.
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Guthrie, J. Peter. "Article." Canadian Journal of Chemistry 77, no. 5-6 (June 1, 1999): 934–42. http://dx.doi.org/10.1139/v99-109.
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Rate constants for hydration of carbon dioxide and ketene can be calculated by applying No Barrier Theory, which needs only equilibrium constants and distortion energies, the latter calculated using molecular orbital theory. The calculated free energies of activation are in satisfactory agreement with experiment: the rms error in free energy of activation is 2.38 kcal/mol. These compounds can also be described using Marcus Theory or Multidimensional Marcus Theory using the transferable intrinsic barrier appropriate to simple carbonyl compounds; in this case the rms error in free energy of activation is 2.19 kcal/mol. The two methods agree on preferred mechanistic path except for uncatalyzed hydration of ketene where Multidimensional Marcus Theory leads to a lower activation free energy for addition to the C=O, while No Barrier Theory leads to a lower free energy of activation for addition to the C=CH2. A rate constant for hydroxide ion catalyzed hydration of ketene can be calculated and is in accord with preliminary experimental results.Key words: ketene, carbon dioxide, hydration, Marcus Theory, No Barrier Theory.
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Birukova, Anna A., Xinyong Tian, Yufeng Tian, Katherine Higginbotham, and Konstantin G. Birukov. "Rap-afadin axis in control of Rho signaling and endothelial barrier recovery." Molecular Biology of the Cell 24, no. 17 (September 2013): 2678–88. http://dx.doi.org/10.1091/mbc.e13-02-0098.
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Activation of the Rho GTPase pathway determines endothelial cell (EC) hyperpermeability after injurious stimuli. To date, feedback mechanisms of Rho down-regulation critical for barrier restoration remain poorly understood. We tested a hypothesis that Rho down-regulation and barrier recovery of agonist-stimulated ECs is mediated by the Ras family GTPase Rap1. Thrombin-induced EC permeability driven by rapid activation of the Rho GTPase pathway was followed by Src kinase–dependent phosphorylation of the Rap1-specific guanine nucleotide exchange factor (GEF) C3G, activation of Rap1, and initiation of EC barrier recovery. Knockdown experiments showed that Rap1 activation was essential for down-regulation of Rho signaling and actin stress fiber dissolution. Rap1 activation also enhanced interaction between adherens junction (AJ) proteins VE-cadherin and p120-catenin and stimulated AJ reannealing mediated by the Rap1 effector afadin. This mechanism also included Rap1-dependent membrane translocation of the Rac1-specific GEF Tiam1 and activation of Rac1-dependent peripheral cytoskeletal dynamics, leading to resealing of intercellular gaps. These data demonstrate that activation of the Rap1-afadin axis is a physiological mechanism driving restoration of barrier integrity in agonist-stimulated EC monolayers via negative-feedback regulation of Rho signaling, stimulation of actin peripheral dynamics, and reestablishment of cell–cell adhesive complexes.
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Quadri, Sadiqa K., Mrinal Bhattacharjee, Kaushik Parthasarathi, Tatsuo Tanita, and Jahar Bhattacharya. "Endothelial Barrier Strengthening by Activation of Focal Adhesion Kinase." Journal of Biological Chemistry 278, no. 15 (January 28, 2003): 13342–49. http://dx.doi.org/10.1074/jbc.m209922200.
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Sumathi, K., and Asish K. Chandra. "Activation barrier for the .alpha.-cleavage process in thiones." Journal of Organic Chemistry 53, no. 6 (March 1988): 1239–43. http://dx.doi.org/10.1021/jo00241a022.
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Mesele, Oluwaseun O., and Ward H. Thompson. "Removing the barrier to the calculation of activation energies." Journal of Chemical Physics 145, no. 13 (October 6, 2016): 134107. http://dx.doi.org/10.1063/1.4964284.
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Cheng, Vincent K. W. "Isomerization activation barrier of a three atom dipolar cluster." Journal of Chemical Physics 108, no. 20 (May 22, 1998): 8456–60. http://dx.doi.org/10.1063/1.476273.
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Brenchley, Jason M., and Daniel C. Douek. "The mucosal barrier and immune activation in HIV pathogenesis." Current Opinion in HIV and AIDS 3, no. 3 (May 2008): 356–61. http://dx.doi.org/10.1097/coh.0b013e3282f9ae9c.
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Hamm-Alvarez, Sarah F., Allen Chang, Yanru Wang, Galina Jerdeva, H. Helen Lin, Kwang-Jin Kim, and David K. Ann. "Etk/Bmx activation modulates barrier function in epithelial cells." American Journal of Physiology-Cell Physiology 280, no. 6 (June 1, 2001): C1657—C1668. http://dx.doi.org/10.1152/ajpcell.2001.280.6.c1657.
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Etk/Bmx is a member of the Tec family of cytoplasmic non-receptor tyrosine kinases known to express in epithelial cells. We demonstrate herein that Etk activation in stably Etk-transfected epithelial Pa-4 cells resulted in a consistently increased transepithelial resistance (TER). After 24 h of hypoxic (1% O2) exposure, the TER and equivalent active ion transport rate ( I eq) were reduced to <5% of the normoxia control in Pa-4 cells, whereas both TER and I eqwere maintained at comparable and 60% levels, respectively, relative to their normoxic controls in cells with Etk activation. Moreover, Pa-4 cells exhibited an abundant actin stress fiber network with a diffuse distribution of β-catenin at the cell periphery. By contrast, Etk-activated cells displayed a redistribution of actin to an exclusively peripheral network, with a discrete band of β-catenin also concentrated at the cell periphery, and an altered occludin distribution profile. On the basis of these findings, we propose that Etk may be a novel regulator of epithelial junctions during physiological and pathophysiological conditions.
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Tong, Jing, Ying Wang, Bing Chang, Dai Zhang, Pengliang Liu, and Bingyuan Wang. "Activation of RhoA in Alcohol-Induced Intestinal Barrier Dysfunction." Inflammation 36, no. 3 (January 30, 2013): 750–58. http://dx.doi.org/10.1007/s10753-013-9601-7.
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Banan, A., L. Zhang, J. Z. Fields, A. Farhadi, D. A. Talmage, and A. Keshavarzian. "PKC-ζ prevents oxidant-induced iNOS upregulation and protects the microtubules and gut barrier integrity." American Journal of Physiology-Gastrointestinal and Liver Physiology 283, no. 4 (October 1, 2002): G909—G922. http://dx.doi.org/10.1152/ajpgi.00143.2002.
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Using intestinal (Caco-2) monolayers, we reported that inducible nitric oxide synthase (iNOS) activation is key to oxidant-induced barrier disruption and that EGF protects against this injury. PKC-ζ was required for protection. We thus hypothesized that PKC-ζ activation and iNOS inactivation are key in EGF protection. Wild-type (WT) Caco-2 cells were exposed to H2O2(0.5 mM) ± EGF or PKC modulators. Other cells were transfected to overexpress PKC-ζ or to inhibit it and then pretreated with EGF or a PKC activator (OAG) before oxidant. Relative to WT cells exposed to oxidant, pretreatment with EGF protected monolayers by 1) increasing PKC-ζ activity; 2) decreasing iNOS activity and protein, NO levels, oxidative stress, tubulin oxidation, and nitration); 3) increasing polymerized tubulin; 4) maintaining the cytoarchitecture of microtubules; and 5) enhancing barrier integrity. Relative to WT cells exposed to oxidant, transfected cells overexpressing PKC-ζ (+2.9-fold) were protected as indicated by decreases in all measures of iNOS-driven pathways and enhanced stability of microtubules and barrier function. Overexpression-induced inhibition of iNOS was OAG independent, but EGF potentiated this protection. Antisense inhibition of PKC-ζ (−95%) prevented all measures of EGF protection against iNOS upregulation. Thus EGF protects against oxidative disruption of the intestinal barrier by stabilizing the cytoskeleton in large part through the activation of PKC-ζ and downregulation of iNOS. Activation of PKC-ζ is by itself required for cellular protection against oxidative stress of iNOS. We have thus discovered novel biologic functions, suppression of the iNOS-driven reactions and cytoskeletal oxidation, among the atypical PKC isoforms.
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Nakayoshi, Tomoki, Shuichi Fukuyoshi, Koichi Kato, Eiji Kurimoto, and Akifumi Oda. "Computational Studies on Water-Catalyzed Mechanisms for Stereoinversion of Glutarimide Intermediates Formed from Glutamic Acid Residues in Aqueous Phase." International Journal of Molecular Sciences 20, no. 10 (May 15, 2019): 2410. http://dx.doi.org/10.3390/ijms20102410.
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Aspartic acid (Asp) residues are prone to non-enzymatic stereoinversion, and Asp-residue stereoinversion is believed to be mediated via a succinimide (SI) intermediate. The stereoinverted Asp residues are believed to cause several age-related diseases. However, in peptides and proteins, few studies have reported the stereoinversion of glutamic acid (Glu) residues whose structures are similar to that of Asp. We previously presumed that Glu-residue stereoinversion proceeds via a glutarimide (GI) intermediate and showed that the calculated activation barriers of SI- and GI-intermediate stereoinversion are almost equivalent in the gas phase. In this study, we investigated the stereoinversion pathways of the l-GI intermediate in the aqueous phase using B3LYP density functional methods. The calculated activation barrier of l-GI-intermediate stereoinversion in the aqueous phase was approximately 36 kcal·mol−1, which was much higher than that in the gas phase. Additionally, as this activation barrier exceeded that of Asp-residue stereoinversion, it is presumed that Glu-residue stereoinversion has a lower probability of proceeding under physiological conditions than Asp-residue stereoinversion.
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Schaefer, Ted, Craig S. Takeuchi, Guy M. Bernard, and Frank E. Hruska. "Theoretical and experimental barriers to internal rotation in 2,6-difluorobenzaldehyde and 2,4,6-trifluorobenzaldehyde. Relatively low barriers." Canadian Journal of Chemistry 73, no. 1 (January 1, 1995): 106–12. http://dx.doi.org/10.1139/v95-016.
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The free energies of activation at 110 K for rotation about the exocyclic C—C bonds in 2,6-difluorobenzaldehyde and 2,4,6-trifluorobenzaldehyde, in dimethyl ether solutions, are 18.8 ± 0.5 and 20.0 ± 0.5 kJ mol−1, respectively, as determined from 19F{1H} dynamic nuclear magnetic resonance measurements. For the parent compound ΔG≠ is 32.2 kJ mol−1 in the same solvent. These free energy barriers, the lowest available for benzaldehyde derivatives, are likely a result of steric and electrostatic repulsions between the C+—O− and C+—F− bonds. Computations of the spectroscopic barrier in the 2,6-difluoro compound at various levels of molecular orbital theory imply that the barrier is predominantly twofold, with a fourfold component of opposite sign, whose magnitude is about 10% of the twofold component. A correlation-gradient computation, MP2/6-31G*, finds a barrier height of 18.6 kJ mol−1 for this compound, lower by 3.0 kJ mol−1 than found with the 6-31G* basis and 2.9 kJ mol−1 with 6-31G**. Similar computations are compared for the parent compound and the 4-fluoro, 2,4,6-trifluoro, and 3,5-difluoro derivatives. Linear relationships exist between the computed spectroscopic barriers (ΔE values at absolute zero for the free molecules) and the free energy barriers for benzaldehyde and the four fluoro derivatives; the theoretical barriers utilize 6-31G** and correlation-gradient MP2/6-31G* procedures. For the 2,6-difluoro derivative, the computed frequencies of the torsional motions about the exocyclic C—C bond yield spectroscopic twofold barriers. These barriers are much lower than the computed energy differences between the planar and perpendicular conformers, perhaps because the negative fourfold components flatten the potential at its minimum. A rough estimate of the relationship between ΔG≠ and ΔE0 for the 2,6-difluorobenzaldehyde suggests that the solvent increases the internal barrier by only about 3 kJ mol−1. By way of contrast, the AM1 barriers, scaled by a factor of 1.9 (as previously recommended) range from 17.3 to 22.6 kJ mol−1, the ΔG≠ values from 18.8(5) to 34.4 kJ mol−1, and the MP2/6-31G* (correlation-gradient) barriers span 18.6 to 36.8 kJ mol−1 for benzaldehyde and the four fluorine derivatives. It seems likely that the internal barrier in benzaldehyde is considerably larger than that modeled on torsional frequencies. Keywords: Free energies of activation, internal rotational barriers in 2,6-difluoro- and 2,4,6-trifluorobenzaldehyde; molecular orbital computations, internal rotational barriers in 2,6-difluoro- and 2,4,6-trifluorobenzaldehyde; correlation gradient computations on internal barriers in benzaldehyde and four of its fluorine derivatives.
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Wahl-Jensen, Victoria M., Tatiana A. Afanasieva, Jochen Seebach, Ute Ströher, Heinz Feldmann, and Hans-Joachim Schnittler. "Effects of Ebola Virus Glycoproteins on Endothelial Cell Activation and Barrier Function." Journal of Virology 79, no. 16 (August 15, 2005): 10442–50. http://dx.doi.org/10.1128/jvi.79.16.10442-10450.2005.
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ABSTRACT Ebola virus causes severe hemorrhagic fever with high mortality rates in humans and nonhuman primates. Vascular instability and dysregulation are disease-decisive symptoms during severe infection. While the transmembrane glycoprotein GP1,2 has been shown to cause endothelial cell destruction, the role of the soluble glycoproteins in pathogenesis is largely unknown; however, they are hypothesized to be of biological relevance in terms of target cell activation and/or increase of endothelial permeability. Here we show that virus-like particles (VLPs) consisting of the Ebola virus matrix protein VP40 and GP1,2 were able to activate endothelial cells and induce a decrease in barrier function as determined by impedance spectroscopy and hydraulic conductivity measurements. In contrast, the soluble glycoproteins sGP and Δ-peptide did not activate endothelial cells or change the endothelial barrier function. The VLP-induced decrease in barrier function was further enhanced by the cytokine tumor necrosis factor alpha (TNF-α), which is known to induce a long-lasting decrease in endothelial cell barrier function and is hypothesized to play a key role in Ebola virus pathogenesis. Surprisingly, sGP, but not Δ-peptide, induced a recovery of endothelial barrier function following treatment with TNF-α. Our results demonstrate that Ebola virus GP1,2 in its particle-associated form mediates endothelial cell activation and a decrease in endothelial cell barrier function. Furthermore, sGP, the major soluble glycoprotein of Ebola virus, seems to possess an anti-inflammatory role by protecting the endothelial cell barrier function.
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Banan, A., L. J. Zhang, A. Farhadi, J. Z. Fields, M. Shaikh, and A. Keshavarzian. "PKC-β1 isoform activation is required for EGF-induced NF-κB inactivation and IκBα stabilization and protection of F-actin assembly and barrier function in enterocyte monolayers." American Journal of Physiology-Cell Physiology 286, no. 3 (March 2004): C723—C738. http://dx.doi.org/10.1152/ajpcell.00329.2003.
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Using monolayers of intestinal Caco-2 cells, we reported that activation of NF-κB is required for oxidative disruption and that EGF protects against this injury but the mechanism remains unclear. Activation of the PKC-β1 isoform is key to monolayer barrier integrity. We hypothesized that EGF-induced activation of PKC-β1 prevents oxidant-induced activation of NF-κB and the consequences of NF-κB activation, F-actin, and barrier dysfunction. We used wild-type (WT) and transfected cells. The latter were transfected with varying levels of cDNA to overexpress or underexpress PKC-β1. Cells were pretreated with EGF or PKC modulators ± oxidant. Pretreatment with EGF protected monolayers by increasing native PKC-β1 activity, decreasing IκBα phosphorylation/degradation, suppressing NF-κB activation (p50/p65 subunit nuclear translocation/activity), enhancing stable actin (increased F-actin-to-G-actin ratio), increasing stability of actin cytoskeleton, and reducing barrier hyperpermeability. Cells stably overexpressing PKC-β1 were protected by low, previously nonprotective doses of EGF or modulators. In these clones, we found enhanced IκBα stabilization, NF-κB inactivation, actin stability, and barrier function. Low doses of the modulators led to increases in PKC-β1 in the particulate fractions, indicating activation. Stably inhibiting endogenous PKC-β1 substantially prevented all measures of EGF's protection against NF-κB activation. We conclude that EGF-mediated protection against oxidant disruption of the intestinal barrier function requires PKC-β1 activation and NF-κB suppression. The molecular event underlying this unique effect of PKC-β1 involves inhibition of phosphorylation and increases in stabilization of IκBα. The ability to inhibit the dynamics of NF-κB/IκBα and F-actin disassembly is a novel mechanism not previously attributed to the classic subfamily of PKC isoforms.
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WACHTEL, Marco, Karl FREI, Elisabeth EHLER, Christian BAUER, Max GASSMANN, and Sergio M. GLOOR. "Extracellular signal-regulated protein kinase activation during reoxygenation is required to restore ischaemia-induced endothelial barrier failure." Biochemical Journal 367, no. 3 (November 1, 2002): 873–79. http://dx.doi.org/10.1042/bj20020746.
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During an ischaemic insult, oedema formation occurs as a consequence of increased vascular permeability. To study mechanisms leading to vascular barrier failure, endothelial cells were exposed to ischaemia (1% O2 in serum- and glucose-free medium) for 5h. In in vitro conditions, ischaemia increased paracellular permeability, disassembled actin stress fibres, displaced focal adhesion kinase (FAK) from focal adhesions and enhanced cytoskeletal association of occludin. Reoxygenation restored paracellular barrier function, actin organization and FAK distribution. The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) was rapidly activated after 30min, strongly inhibited after 5h of continuous ischaemia and reactivated 3 times more than control during reoxygenation. Inhibition of ERK activation during reoxygenation with U0126, an inhibitor of the ERK activator, MAPK/ERK kinase 1/2, prevented both barrier restoration and stress-fibre formation, but did not prevent recruitment of FAK to focal contacts. Under normoxic conditions, ERK inhibition led to barrier failure and disassembly of stress fibres only in the absence of serum. These results demonstrate that ERK activity is essential to rebuild a disrupted endothelial barrier after ischaemia and to maintain barrier function in cells exposed to non-ischaemic stress.
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Kubo, Akiharu, Keisuke Nagao, Mariko Yokouchi, Hiroyuki Sasaki, and Masayuki Amagai. "External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers." Journal of Experimental Medicine 206, no. 13 (December 7, 2009): 2937–46. http://dx.doi.org/10.1084/jem.20091527.
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Outermost barriers are critical for terrestrial animals to avoid desiccation and to protect their bodies from foreign insults. Mammalian skin consists of two sets of barriers: stratum corneum (SC) and tight junctions (TJs). How acquisition of external antigens (Ags) by epidermal Langerhans cells (LCs) occur despite these barriers has remained unknown. We show that activation-induced LCs elongate their dendrites to penetrate keratinocyte (KC) TJs and survey the extra-TJ environment located outside of the TJ barrier, just beneath the SC. Penetrated dendrites uptake Ags from the tip where Ags colocalize with langerin/Birbeck granules. TJs at KC–KC contacts allow penetration of LC dendrites by dynamically forming new claudin-dependent bicellular- and tricellulin-dependent tricellular TJs at LC–KC contacts, thereby maintaining TJ integrity during Ag uptake. Thus, covertly under keratinized SC barriers, LCs and KCs demonstrate remarkable cooperation that enables LCs to gain access to external Ags that have violated the SC barrier while concomitantly retaining TJ barriers to protect intra-TJ environment.
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Li, Feng, Neeraj Tiwari, James E. Rothman, and Frederic Pincet. "Kinetic barriers to SNAREpin assembly in the regulation of membrane docking/priming and fusion." Proceedings of the National Academy of Sciences 113, no. 38 (September 6, 2016): 10536–41. http://dx.doi.org/10.1073/pnas.1604000113.
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Neurotransmission is achieved by soluble NSF attachment protein receptor (SNARE)-driven fusion of readily releasable vesicles that are docked and primed at the presynaptic plasma membrane. After neurotransmission, the readily releasable pool of vesicles must be refilled in less than 100 ms for subsequent release. Here we show that the initial association of SNARE complexes, SNAREpins, is far too slow to support this rapid refilling owing to an inherently high activation energy barrier. Our data suggest that acceleration of this process, i.e., lowering of the barrier, is physiologically necessary and can be achieved by molecular factors. Furthermore, under zero force, a low second energy barrier transiently traps SNAREpins in a half-zippered state similar to the partial assembly that engages calcium-sensitive regulatory machinery. This result suggests that the barrier must be actively raised in vivo to generate a sufficient pause in the zippering process for the regulators to set in place. We show that the heights of the activation energy barriers can be selectively changed by molecular factors. Thus, it is possible to modify, both in vitro and in vivo, the lifespan of each metastable state. This controllability provides a simple model in which vesicle docking/priming, an intrinsically slow process, can be substantially accelerated. It also explains how the machinery that regulates vesicle fusion can be set in place while SNAREpins are trapped in a half-zippered state.
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Wang, Peiyi, Alexander D. Verin, Anna Birukova, Lydia I. Gilbert-McClain, Keri Jacobs, and Joe G. N. Garcia. "Mechanisms of sodium fluoride-induced endothelial cell barrier dysfunction: role of MLC phosphorylation." American Journal of Physiology-Lung Cellular and Molecular Physiology 281, no. 6 (December 1, 2001): L1472—L1483. http://dx.doi.org/10.1152/ajplung.2001.281.6.l1472.
Full textAbstract:
NaF, a potent G protein activator and Ser/Thr phosphatase inhibitor, significantly increased albumin permeability and decreased transcellular electrical resistance (TER), indicating endothelial cell (EC) barrier impairment. EC barrier dysfunction induced by NaF was accompanied by the development of actin stress fibers, intercellular gap formation, and significant time-dependent increases in myosin light chain (MLC) phosphorylation. However, despite rapid, albeit transient, activation of Ca2+/calmodulin-dependent MLC kinase (MLCK), the specific MLCK inhibitor ML-7 failed to affect NaF-induced MLC phosphorylation, actin cytoskeletal rearrangement, and reductions in TER, suggesting a limited role of MLCK in NaF-induced EC activation. In contrast, strategies to reduce Rho (C3 exoenzyme or toxin B) or to inhibit Rho-associated kinase (Y-27632 or dominant/negative RhoK) dramatically reduced MLC phosphorylation and actin stress fiber formation and significantly attenuated NaF-induced EC barrier dysfunction. Consistent with this role for RhoK activity, NaF selectively inhibited myosin-specific phosphatase activity, whereas the total Ser/Thr phosphatase activity remained unchanged. These data strongly suggest that MLC phosphorylation, mediated primarily by RhoK, and not MLCK, participates in NaF-induced EC actin cytoskeletal changes and barrier dysfunction.
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Moore, Timothy M., Natalie R. Norwood, Judy R. Creighton, Pavál Babal, George H. Brough, D. Michael Shasby, and Troy Stevens. "Receptor-dependent activation of store-operated calcium entry increases endothelial cell permeability." American Journal of Physiology-Lung Cellular and Molecular Physiology 279, no. 4 (October 1, 2000): L691—L698. http://dx.doi.org/10.1152/ajplung.2000.279.4.l691.
Full textAbstract:
The present study evaluated the necessity of store-operated Ca2+ entry in mediating thrombin-induced 20-kDa myosin light chain (MLC20) phosphorylation and increased permeability in bovine pulmonary artery endothelial cells (BPAECs). Thrombin (7 U/ml) and thapsigargin (1 μM) activated Ca2+ entry through a common pathway in confluent BPAECs. Similar increases in MLC20 phosphorylation were observed 5 min after thrombin and thapsigargin challenge, although thrombin produced a sustained increase in MLC20phosphorylation that was not observed in response to thapsigargin. Neither agonist increased MLC20 phosphorylation when Ca2+ influx was inhibited. Thrombin and thapsigargin induced inter-endothelial cell gap formation and increased FITC-dextran (molecular radii 23 Å) transfer across confluent BPAEC monolayers. Activation of store-operated Ca2+ entry was required for thapsigargin and thrombin receptor-activating peptide to increase permeability, demonstrating that activation of store-operated Ca2+ entry is coupled with MLC20phosphorylation and is associated with intercellular gap formation and increased barrier transport of macromolecules. Unlike thrombin receptor-activating peptide, thrombin increased permeability without activation of store-operated Ca2+ entry, suggesting that it partly disrupts the endothelial barrier through a proteolytic mechanism independent of Ca2+ signaling.
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Wu, Wan-Jung, Myunghoo Kim, Ming-Ting Tsai, Fatima Beatriz Saldana Morales, Daniel Fernando Zegarra Ruiz, Andrea Hill, Hyo Won Song, Kendra Norwood, and Gretchen Diehl. "Intestinal commensal bacteria promote gut barrier repair through non-canonical inflammasome pathway activation." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 83.7. http://dx.doi.org/10.4049/jimmunol.204.supp.83.7.
Full textAbstract:
Abstract The intestinal epithelial barrier critically separates exogenous microbes from our internal tissues. Signals from commensal microbes are known to support intestinal barrier integrity and repair. However, the role of specific microbes in maintaining the intestinal barrier is not well-defined. We hypothesize that signals from distinct commensal microbes play different roles in regulating the barrier. We find that mice develop severe colitis with decreased ability to repair the intestinal barrier after antibiotic depletion of intestinal microbes. We further isolated a mouse commensal E. coli that protects from increased colitis after antibiotic treatment. This protection depends on the presence of intestinal antigen presenting cells (APCs) that express the chemokine receptor CX3CR1. We screened a panel of human mucosal-associated E. coli and identified a subset that also protect from colitis in a CX3CR1+ APC dependent manner. All protective E. coli induce IL-1β secretion by activation of the non-canonical inflammasome pathway in CX3CR1+ APCs. In vivo protection is lost if IL-1β signaling is blocked with anti-IL-1β antibody. This E. coli induced IL-1β production activates type 3 innate lymphoid cells (ILC3) to produce IL-22 which drives epithelial proliferation and barrier repair. Collectively, we identified a novel mechanism by which a subset of mucosal-associated intestinal E. coli activate IL-1β production by APCs to protect the intestinal barrier from damage.
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Arifuzzaman, Mohammad, Yuvon R. Mobley, Hae Woong Choi, Pradeep Bist, Cristina A. Salinas, Zachary D. Brown, Swaine L. Chen, Herman F. Staats, and Soman N. Abraham. "MRGPR-mediated activation of local mast cells clears cutaneous bacterial infection and protects against reinfection." Science Advances 5, no. 1 (January 2019): eaav0216. http://dx.doi.org/10.1126/sciadv.aav0216.
Full textAbstract:
Mast cells (MCs) are strategically distributed at barrier sites and prestore various immunocyte-recruiting cytokines, making them ideal targets for selective activation to treat peripheral infections. Here, we report that topical treatment with mastoparan, a peptide MC activator (MCA), enhances clearance ofStaphylococcus aureusfrom infected mouse skins and accelerates healing of dermonecrotic lesions. Mastoparan functions by activating connective tissue MCs (CTMCs) via the MRGPRX2 (Mas-related G protein-coupled receptor member X2) receptor. Peripheral CTMC activation, in turn, enhances recruitment of bacteria-clearing neutrophils and wound-healing CD301b+dendritic cells. Consistent with MCs playing a master coordinating role, MC activation also augmented migration of various antigen-presenting dendritic cells to draining lymph nodes, leading to stronger protection against a second infection challenge. MCAs therefore orchestrate both the innate and adaptive immune arms, which could potentially be applied to combat peripheral infections by a broad range of pathogens.