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Essentials Dimeric high-affinity collagen receptor glycoprotein VI (GPVI) is present on resting platelets. Spatio-temporal organization of platelet GPVI-dimers was evaluated using advanced microscopy. Upon platelet adhesion to collagenous substrates, GPVI-dimers coalesce to form clusters. Clustering of GPVI-dimers may increase avidity and facilitate platelet activation. Summary: Background Platelet glycoprotein VI (GPVI) binding to subendothelial collagen exposed upon blood vessel injury initiates thrombus formation. Dimeric GPVI has high affinity for collagen, and occurs constitutively on resting platelets. Objective To identify higher-order oligomerization (clustering) of pre-existing GPVI dimers upon interaction with collagen as a mechanism to initiate GPVI-mediated signaling. Methods GPVI was located by use of fluorophore-conjugated GPVI dimer-specific Fab (antigen-binding fragment). The tested substrates include Horm collagen I fibers, soluble collagen III, GPVI-specific collagen peptides, and fibrinogen. GPVI dimer clusters on the platelet surface interacting with these substrates were visualized with complementary imaging techniques: total internal reflection fluorescence microscopy to monitor real-time interactions, and direct stochastic optical reconstruction microscopy (dSTORM), providing relative quantification of GPVI cluster size and density. Confocal microscopy was used to locate GPVI dimer clusters, glycoprotein Ib, integrin α2β1, and phosphotyrosine. Results Upon platelet adhesion to all collagenous substrates, GPVI dimers coalesced to form clusters; notably clusters formed along the fibers of Horm collagen. dSTORM revealed that GPVI density within clusters depended on the substrate, collagen III being the most effective. Clusters on fibrinogen-adhered platelets were much smaller and more numerous; whether these are pre-existing oligomers of GPVI dimers or fibrinogen-induced is not clear. Some GPVI dimer clusters colocalized with areas of phosphotyrosine, indicative of signaling activity. Integrin α2β1 was localized to collagen fibers close to GPVI dimer clusters. GPVI clustering depends on a dynamic actin cytoskeleton. Conclusions Platelet adhesion to collagen induces GPVI dimer clustering. GPVI clustering increases both avidity for collagen and the proximity of GPVI-associated signaling molecules, which may be crucial for the initiation and persistence of signaling.

Background: Platelet GPVI binding to subendothelial collagen exposed upon blood vessel injury initiates thrombus formation. Dimeric GPVI has high affinity for collagen and occurs constitutively on resting platelets. Objective: To identify higher order oligomerisation (clustering) of pre-existing GPVI-dimers upon interaction with collagen as a mechanism to initiate GPVI-mediated signalling. Methods: GPVI was located using fluorophore conjugated GPVI-dimer-specific Fab (antigen-binding fragment. Tested substrates include Horm collagen I fibres, soluble collagen III, GPVI-specific collagen peptides and fibrinogen. GPVI-dimer clusters on the platelet surface interacting with these substrates were visualised\ud using complementary imaging techniques: Total Internal Reflection Fluorescence Microscopy (TIRFM) to monitor real time interactions and direct Stochastic Optical Reconstruction Microscopy (dSTORM), providing relative quantification of GPVI cluster size and density. Confocal microscopy was used to locate GPVI-dimer clusters, GPIb, integrin α2β1, and phosphotyrosine. Results: Upon platelet adhesion to all collagenous substrates, GPVI-dimers coalesced to form clusters; notably clusters formed along the fibres of Horm collagen. dSTORM revealed that GPVI density within clusters depended on the substrate,\ud collagen III being most effective. Clusters on fibrinogen-adherred platelets were much smaller and more numerous; whether these are pre-existing oligomers of GPVI-dimers or\ud fibrinogen-induced is not conclusive. Some GPVI-dimer clusters colocalized with areas of phosphotyrosine, indicative of signalling activity. Integrin α2β1 localized to collagen fibres close to GPVI-dimer clusters. GPVI-clustering depends on a dynamic actin cytoskeleton.\ud Conclusions: Platelet adhesion to collagen induces GPVI-dimer clustering. GPVI-clustering increases both avidity for collagen and proximity of GPVI-associated signalling molecules, which may be crucial for initiation and persistence of signalling.

We prove the Hyers-Ulam stability of linear differential equations of first order,(t)y′(t) = y(t). Indeed, this paper deals with a generalization of a paper by Alsina and Ger [1] or of papers by Miura, Takahasi and Choda [2] and by Miura [3].

Cǎdariu and Radu applied the fixed point method to the investigation of Cauchy and Jensen functional equations. In this paper, we adopt the idea of Cǎdariu and Raduto prove the stability of a functional equation of the spiral of Theodorus, f(x + 1) = (1 + i/√x + 1) f(x).

Mammalian oocytes lack a centriole that acts as a microtubule organization center (MTOC) in most somatic cells. During oocyte maturation, MTOCs undergo remodeling processes, including decondensation, fragmentation, and self-organization. However, the underlying mechanisms of MTOC remodeling in mouse oocytes are not well understood. We showed that two pericentriolar proteins, Cep192 and Cep152, play crucial roles during MTOC remodeling in mouse oocytes. Cep192 is present in MTOCs at all stages of oocyte maturation, and its depletion induces ablation of MTOCs, delay in spindle formation, and abnormal chromosomal alignment in spindles. In the case of Cep152, its localization on MTOCs is limited at the germinal vesicle stage and then disappears from the MTOCs after the germinal vesicle breakdown stage. Cep152 exclusion from MTOCs is involved in the fragmentation of MTOCs, and it is regulated by cyclin-dependent kinase 1 activity. Our results demonstrate the different roles of Cep192 and Cep152 in MTOC remodeling and a novel regulatory mechanism during meiotic spindle formation in mouse oocytes.-Lee, I.-W., Jo, Y.-J., Jung, S.-M., Wang, H.-Y., Kim, N.-H., Namgoong, S. Distinct roles of Cep192 and Cep152 in acentriolar MTOCs and spindle formation during mouse oocyte maturation.

Employing organic redox mediators (ORMs) as mobile catalyst into the electrolyte system has been selected as an important strategy to lower the charging overpotentials in lithium-oxygen (Li-O2) batteries. Careful choice of molecular designs of ORMs can also tailor their redox potential and rate of electron-transfer to improve the catalytic efficiency. However, the stability of ORMs in Li–O2 cells was scarcely studied. In here, catalytic efficiency and stability of several important ORMs are assessed through in situ gas analysis and reactivity tests with singlet oxygen. Some well-known ORMs are detrimentally decomposed during the first cycle in Li–O2 cells, whereas nitroxyl-radical-based ORMs bear the most stable and efficient response. Analogous nitroxyl-radical derivatives further increase round-trip energy efficiency and electron-transfer kinetics. This study also emphasizes the evaluation of chemical stability of ORMs, which are mandatory for the long-term cyclability in Li–O2 cells. references W.-J. Kwak, H. Kim, H.-G. Jung, D. Aurbach, Y.-K. Sun, J. Electrochem. Soc. 2018, 165, A2274–A2293. W.-J. Kwak, H. Kim, Y. K. Petit, C. Leypold, T. T. Nguyen, N. Mahne, P. Redfern, L. A. Curtiss, H.-G. Jung, S. M. Borisov, S. A. Freunberger and Y.-K. Sun, Nat. Commun., 2019, 10, 1380.

Redox mediators have been studied passionately to improve energy efficiency and cycle life of lithium-oxygen batteries by facilitating decomposition of the discharge product (lithium peroxide) and, thus, reducing the side reactions at high potential during charging. Nevertheless, the cycling performance of lithium-oxygen batteries with redox mediators is still unsatisfactory; this problem must be verified and resolved for the successful application of redox mediators. In this study, we confirmed that widely used redox mediators cannot decompose by-products on the cathode, leading to passivation of the cathode surface despite the successful decomposition of lithium peroxide. By schematizing the routes for by-products formation, we described the processes by which by-products are accumulated on the cathode in the absence and presence of a redox mediator. Based on the intuitive verification of the unproven relationship between a redox mediator and by-products, we proposed a complementary strategy to overcome the limitations of redox mediator and prevent the accumulation of by-products, which is essential for improvement of lithium-oxygen batteries. References W.-J. Kwak, H. Kim, Y. K. Petit, C. Leypold, T. T. Nguyen, N. Mahne, P. Redfern, L. A. Curtiss, H.-G. Jung, S. M. Borisov, S. A. Freunberger and Y.-K. Sun, Nat. Commun., 2019, 10, 1380. W.-J. Kwak , R. Sharma , D. Sharon , C. Xia , H. Kim , L. R. Johnson , P. G. Bruce , L. F. Nazar , Y.-K. Sun , A. A. Frimer , M. Noked , S. A. Freunberger and D. Aurbach, Chem. Rev., 2020, just accepted. https://doi.org/10.1021/acs.chemrev.9b00609 M. M. Ottakam Thotiyl, S. A. Freunberger, Z. Peng and P. G. Bruce, J. Am. Chem. Soc., 2013, 135, 494.

Provided are a novel isoprene synthase derived from sweet potato and a method of preparing isoprene using the same, and more specifically, a novel isoprene synthase derived from sweet potato, a gene encoding the isoprene synthase, a host cell transformed with the gene, and a method of preparing isoprene using the same. The isoprene synthase of the present invention may have higher isoprene productivity as compared to isoprene synthases known in the related art to thereby be effectively used in isoprene biosynthesis and preparation of an isoprene polymer using the same.Patent family as of 30.12.2021AU2015297211 AA 20170309 AU20150297211 20150728 AU2015297211 BB 20201217 AU20150297211 20150728 KR102330593 B1 20211126 KR20150106009 20150727 KR20160013824 A 20160205 KR20150106009 20150727 US10287565 BB 20190514 US20150329343 20150728 US2017211056 AA 20170727 US20150329343 20150728 US2019203193 AA 20190704 US20190354321 20190315 WO16018036 A1 20160204 WO2015KR07851 20150728Link to currentpatent family on right

Предметом исследования являются элементы эстетики и поэтики предромантизма в творчестве С.С. Боброва, проводятся параллели с творческой манерой Юнга, М.В. Ломоносова, выявляются специфические особенности трактовки предромантической эстетики в лирике С.С. Боброва., The subject-matter of this research covers some elements of esthetics and poetics of pre-Romanticism in S. S. Bobrov`s poetry, parallels with Jung`s, M. V. Lomonosov`s creative manner are drawn, specific characteristic features of interpretation of pre-Romanticism esthetic in S. S. Bobrov`s poetry are brought to light.

Lithium (Li) metal is being intensively pursued as a negative electrode due to its high specific capacity. Yet, irreversible Li loss, dendrite formation of plated Li metal, and short circuiting, when being cycled as an electrode in battery cells presently impede its use. Furthermore, the flammability of liquid electrolytes poses a severe safety hazard. Replacement of organic liquids by solid electrolytes could pave the way for using Li metal, simultaneously improving specific energy and battery safety. Significant attention has been paid to ceramic electrolytes due to their high Li-ion conductivity at room temperature and robustness. Nevertheless, processing and manufacturing of the ceramics into sufficiently thin, highly dense, pinhole-free sheets, required for high specific energy and power devices, remains an active challenge. Additionally, the electrolyte must maintain contact with the solid electrodes while simultaneously inhibiting Li dendrites as well as be durable towards electrode volume changes and to external shock. Polymer electrolytes have been developed for a number of years. The advantages include good adhesion and contact to the electrodes. Still, their low conductivity at room temperature, especially in solid polymer electrolytes, along with their limited capability of suppressing Li dendrite formation, are persistent drawbacks.[i] To date, ceramic and polymer electrolytes remain a challenge. Hybrids with particulate ceramics embedded in polymer electrolytes have been investigated to improve the conductivity and mechanical properties. [ii] Our approach is to create continuously ordered hybrid electrolytes, which allows modification of the mechanical properties of the hybrid while retaining a high ionic conductivity through the ceramic phase. The ionic conductivity of the hybrid electrolyte is 1.5 x 10-4S/cm at 25 °C. The results of different ceramic-polymer compositions indicate that the mechanical properties of the hybrids can be adjusted by the presented approach. Electrochemical, mechanical, and microstructural characterizations of the hybrid will be reported. [i] G. M. Stone, S. A. Mullin, A. A. Teran, D. T. Hallinan Jr., A. M. Minor, A. Hexemer, N. P. Balsara, J. Electrochem. Soc., 2012, 159, A222–A227. [ii] Y.-C. Jung, S.-M. Lee, J.-H. Choi, S. S. Jang and D.-W. Kim, J. Electrochem. Soc., 2015, 162, A704–A710.

Carbon-based nanomaterials have been considered as promising candidates to mimic certain structure and function of native extracellular matrix materials for tissue engineering. Significant progress has been made in fabricating carbon nanoparticle-incorporated cell culture substrates, but limited studies have been reported on the development of three-dimensional (3D) tissue constructs using these nanomaterials. Here, we present a novel approach to engineer 3D multi-layered constructs using layer-by-layer (LbL) assembly of cells separated with self-assembled graphene oxide (GO)-based thin films. The GO-based structures are shown to serve as cell adhesive sheets that effectively facilitate the formation of multi-layer cell constructs with interlayer connectivity. By controlling the amount of GO deposited in forming the thin films, the thickness of the multi-layer tissue constructs could be tuned with high cell viability. Specifically, this approach could be useful for creating dense and tightly connected cardiac tissues through the co-culture of cardiomyocytes and other cell types. In this work, we demonstrated the fabrication of stand-alone multi-layer cardiac tissues with strong spontaneous beating behavior and programmable pumping properties. Therefore, this LbL-based cell construct fabrication approach, utilizing GO thin films formed directly on cell surfaces, has great potential in engineering 3D tissue structures with improved organization, electrophysiological function, and mechanical integrity.

Lithium metal is being intensively pursued as an anode due to its high specific capacity. However, dendrite formation, Li loss and short circuiting upon cell cycling presently impede its use. Furthermore, the flammability of liquid electrolytes poses a severe safety hazard. Replacement of organic liquids by solid electrolytes could pave the way for using lithium metal, simultaneously improving specific energy and battery safety. Efforts continue on ceramic electrolytes. Challenges include the formation and manufacture at scale of sufficiently thin, highly dense, pinhole-free sheets of ceramic electrolytes, required for high power devices. Such electrolytes must also maintain contact with the solid electrodes while inhibiting Li dendrites and be durable towards volume changes of the electrodes as well as to external shock. Polymer electrolytes have been developed for a number of years. They can exhibit good adhesion and contact to the electrodes, but typically have lower conductivity and limited capability of suppressing dendrite formation.[i] To date, ceramic and polymer electrolytes remain a challenge. Composites of particulate ceramics embedded within polymer electrolytes have been investigated to improve the conductivity and mechanical properties. [ii] Our approach is to create ordered composite electrolytes, which allows modification of the mechanical properties of the composite while retaining good overall ionic conductivity. The conductivity of the polymer-ceramic composite is 1.5E-4 S/cm at 25 °C. The results for different ceramic-polymer compositions indicate that the mechanical properties of the composite can be modified by the presented approach. Mechanical testing and the results of galvanostatic cycling will be reported. [i] G. M. Stone, S. A. Mullin, A. A. Teran, D. T. Hallinan Jr., A. M. Minor, A. Hexemer, N. P. Balsara, J. Electrochem. Soc., 2012, 159, A222–A227. [ii] Y.-C. Jung, S.-M. Lee, J.-H. Choi, S. S. Jang and D.-W. Kim, J. Electrochem. Soc., 2015, 162, A704–A710.

Four polymorphic variants of the platelet receptor for von Willebrand factor, glycoprotein Ib, have been described that differ in molecular weight on sodium dodecyl sulfate-polyacrylamide gels (Moroi, M., Jung, S. M., and Yoshida, N. (1984) Blood 64, 622-629). A recent report localized the polymorphic site to the heavily O-glycosylated region of the glycoprotein Ib alpha-chain known as the macroglycopeptide (Meyer, M., and Schellenberg, I. (1990) Thromb. Res. 58, 233-242). This region contains several tandem repeats of a mucin-like sequence, which appeared to be a likely site for polymorphic variation. We amplified genomic DNA corresponding to the macroglycopeptide from 206 individuals from four ethnic groups and identified three length variants based on the migration of the amplified DNA on denaturing polyacrylamide gels. DNA sequencing revealed that the three variants represented four alleles, two of which varied by only one base pair, a difference that did not result in an amino acid change. The three length variants differed in the number of tandem repeats of a 39-base pair sequence that results in perfect duplication of a 13-amino acid sequence that originated within a region flanked by Glu-396 and Thr-411. The smallest isoform contained one such sequence; the next largest, two repeats; and the largest, three repeats. The DNA sequence containing the tandem repeats was flanked by direct repeats typical of the target site duplications found flanking transposed DNA, suggesting a mechanism for acquisition of this region by the primordial glycoprotein Ib alpha precursor. The amino acid sequence of the repeated element that accounts for the polymorphism contained five sites for potential O-glycosylation, which together with the repeated amino acids would result in incremental differences in molecular weight of approximately 6,000 between the different isoforms. The addition of repeats to the macroglycopeptide is predicted to increase the length of this elongated glycosylated region and extend the distance between the ligand-binding domain of glycoprotein Ib and the platelet plasma membrane, an effect that would project the ligand-binding domain farther into the bloodstream. Such a change may alter the susceptibility of platelets to shear-induced activation, a process that requires an interaction between glycoprotein Ib and von Willebrand factor.

Macrophages display different phenotypes that can switch in response to their micro-environment. In our earlier study (Chiang, C. S., Liu, W. C. and Jung, S. M., 2005. Compartmental responses after thoracic irradiation of mice: strain differences. Int. J. Radiat. Oncol. Biol. Phys. 62:862) on radiation-induced cytokine expression in lung lavage samples, there was a suggestion that the procedures used to harvest lung macrophages affected the profiles they expressed. To further explore this issue, we examined gene expression by cell populations, mainly macrophages, isolated by lavage from lung and peritoneal cavity following either in vivo or in vitro stimulation with LPS, IFN-gamma or irradiation. We found that expression of mRNA for tumor necrosis factor-alpha, IL-1 alpha/beta and IL-6 varied several fold depending on whether the assay was performed on cells immediately after isolation or after in vitro manipulation. The relative level of inducible nitric oxide synthase (iNOS) to arginase I (Arg I), which is frequently used as index of the M1 versus M2 functional macrophage phenotype, also varied. LPS stimulation in vivo was able to change the profile from Arg I expression to one where the iNOS pathway became dominant, but was unable to do this in vitro. This contrasts with the ability of IFN-gamma to generate an iNOS-dominant pathway in vitro, but not in vivo. This study cautions that the expression of inflammatory cytokines and the iNOS to Arg I ratio, which is often used as an index of their functional capacity, varies with the experimental conditions.

Four polymorphic variants of the platelet receptor for von Willebrand factor, glycoprotein Ib, have been described that differ in molecular weight on sodium dodecyl sulfate-polyacrylamide gels (Moroi, M., Jung, S. M., and Yoshida, N. (1984) Blood 64, 622-629). A recent report localized the polymorphic site to the heavily O-glycosylated region of the glycoprotein Ib alpha-chain known as the macroglycopeptide (Meyer, M., and Schellenberg, I. (1990) Thromb. Res. 58, 233-242). This region contains several tandem repeats of a mucin-like sequence, which appeared to be a likely site for polymorphic variation. We amplified genomic DNA corresponding to the macroglycopeptide from 206 individuals from four ethnic groups and identified three length variants based on the migration of the amplified DNA on denaturing polyacrylamide gels. DNA sequencing revealed that the three variants represented four alleles, two of which varied by only one base pair, a difference that did not result in an amino acid change. The three length variants differed in the number of tandem repeats of a 39-base pair sequence that results in perfect duplication of a 13-amino acid sequence that originated within a region flanked by Glu-396 and Thr-411. The smallest isoform contained one such sequence; the next largest, two repeats; and the largest, three repeats. The DNA sequence containing the tandem repeats was flanked by direct repeats typical of the target site duplications found flanking transposed DNA, suggesting a mechanism for acquisition of this region by the primordial glycoprotein Ib alpha precursor. The amino acid sequence of the repeated element that accounts for the polymorphism contained five sites for potential O-glycosylation, which together with the repeated amino acids would result in incremental differences in molecular weight of approximately 6,000 between the different isoforms. The addition of repeats to the macroglycopeptide is predicted to increase the length of this elongated glycosylated region and extend the distance between the ligand-binding domain of glycoprotein Ib and the platelet plasma membrane, an effect that would project the ligand-binding domain farther into the bloodstream. Such a change may alter the susceptibility of platelets to shear-induced activation, a process that requires an interaction between glycoprotein Ib and von Willebrand factor.