53 research outputs found
MID2 can substitute for MID1 and control exocytosis of lytic granules in cytotoxic T cells
No full textWe have recently shown that the E3 ubiquitin ligase midline 1 (MID1) is upregulated in murine cytotoxic lymphocytes (CTL), where it controls exocytosis of lytic granules and the killing capacity. Accordingly, CTL from MID1 knock-out (MID1-/- ) mice have a 25-30% reduction in exocytosis of lytic granules and cytotoxicity compared to CTL from wild-type (WT) mice. We wondered why the MID1 gene knock-out did not affect exocytosis and cytotoxicity more severely and speculated whether MID2, a close homologue of MID1, might partially compensate for the loss of MID1 in MID1-/- CTL. Here, we showed that MID2, like MID1, is upregulated in activated murine T cells. Furthermore, MID1-/- CTL upregulated MID2 two-twenty-fold stronger than CTL from WT mice, suggesting that MID2 might compensate for MID1. In agreement, transfection of MID2 into MID1-/- CTL completely rescued exocytosis of lytic granules in MID1-/- CTL, and vice versa, knock-down of MID2 inhibited exocytosis of lytic granules in both WT and MID1-/- CTL, demonstrating that both MID1 and MID2 play a central role in the regulation of granule exocytosis and that functional redundancy exists between MID1 and MID2 in CTL
Midline 1 controls polarization and migration of murine cytotoxic T cells
No full textMidline 1 (MID1) is a microtubule-associated ubiquitin ligase that regulates protein phosphatase 2 A levels. Loss-of-function mutations in MID1 lead to the human X-linked Opitz G/BBB (OS) syndrome characterized by defective midline development during embryogenesis. We have recently shown that MID1 is strongly up-regulated in murine cytotoxic T lymphocytes (CTLs), and that it has a significant impact on exocytosis of lytic granules and the killing capacity of CTLs. The aims of the present study were to determine the localization of MID1 in migrating CTLs, and to investigate whether MID1 affects CTL polarization and migration. We found that MID1 mainly localizes to the uropod of migrating CTLs and that it has a substantial impact on CTL polarization and migration in vitro. Furthermore, analysis of contact hypersensitivity responses supported that MID1 controls effector functions of CTLs in hapten-challenged skin in vivo. These results provide significant new knowledge on the role of MID1 in CTL biology
Midline 1 directs lytic granule exocytosis and cytotoxicity of mouse killer T cells
No full textMidline 1 (MID1) is a microtubule-associated ubiquitin ligase that regulates protein phosphatase 2A activity. Loss-of-function mutations in MID1 lead to the X-linked Opitz G/BBB syndrome characterized by defective midline development during embryogenesis. Here, we show that MID1 is strongly upregulated in murine cytotoxic lymphocytes (CTLs), and that it controls TCR signaling, centrosome trafficking, and exocytosis of lytic granules. In accordance, we find that the killing capacity of MID1(-/-) CTLs is impaired. Transfection of MID1 into MID1(-/-) CTLs completely rescued lytic granule exocytosis, and vice versa, knockdown of MID1 inhibited exocytosis of lytic granules in WT CTLs, cementing a central role for MID1 in the regulation of granule exocytosis. Thus, MID1 orchestrates multiple events in CTL responses, adding a novel level of regulation to CTL activation and cytotoxicity
Author Correction:Vitamin D status and severity of COVID-19 (Scientific Reports, (2022), 12, 1, (19823), 10.1038/s41598-022-21513-9)
No full textSanne Grundvald Boelt was omitted from the author list in the original version of this Article. The Author Contributions section now reads: “A.A. contributed to the conception and idea of the work. N.M.N., A.S.C., L.B. and A.A. contributed to the design of the study. N.M.N., A.S.C., L.B. S.G.B contributed to the acquisition of data. N.M.N., A.H., L.B., S.G.B and T.G.J. contributed to the analyses of the data. All authors contributed to the interpretation of the data and the results in the manuscript. N.M.N. drafted the manuscript, made Fig. 1, T.G.J. made Fig. 2. All the authors revised the manuscript critically and has approved the final version.” The original Article has been corrected.</p
HIGH RESOLUTION ELECTRONIC SPECTOSCOPY OF THE FREE RADICAL
No full textAuthor Institution: Department of Chemistry, University of KentuckyJet-cooled laser excitation spectra of the bad system of the free radical will be presented. This study represents the first spectroscopic observation of this species, which may be important in the dry etching of integrated circuits using low pressure plasmas. High resolution spectra of several bands have been rotationally analyzed yielding precise molecular constants and structural data for the ground and electronically excited states. A few axis-switching transitions with have been assigned, consistent with a calculated axis-switching angle of . The electronic transition has and involves excitation of a non-boding electron localized on the terminal sulfur to a orbital delocalized over the S-S bond
The religio-political change in the reign of Augustus: the disappearance of public prodigies
No full textThe article explores the causes which led to the final disappearance of the Roman Republican practice of the expiation of public prodigies (ill-boding divinatory signs) in the beginning of the principate. After a short exposition of the system of Roman expiation of public prodigies, individual theories explaining their disappearance are explored in greater detail. These theories are dismissed as either erroneous or incomplete, e.g. these operating with the general decline of Roman republican religion, philosophical criticism of superstitious religious practices, abuse of prodigies in political controversies or for self-advertisement of important noblemen, loss of their importance after the political unification of Italy, etc. In conclusion, the author of this article formulates an alternative theory explaining the reasons behind their ultimate disappearance: they were so closely connected with the values of Roman political and religious elites and played such an important role in the process of building Roman national identity that they lost their rationale after the establishment of the principate, since from that time these values were invested into and this role played by Roman emperors and their families.The article explores the causes which led to the final disappearance of the Roman Republican practice of the expiation of public prodigies (ill-boding divinatory signs) in the beginning of the principate. After a short exposition of the system of Roman expiation of public prodigies, individual theories explaining their disappearance are explored in greater detail. These theories are dismissed as either erroneous or incomplete, e.g. these operating with the general decline of Roman republican religion, philosophical criticism of superstitious religious practices, abuse of prodigies in political controversies or for self-advertisement of important noblemen, loss of their importance after the political unification of Italy, etc. In conclusion, the author of this article formulates an alternative theory explaining the reasons behind their ultimate disappearance: they were so closely connected with the values of Roman political and religious elites and played such an important role in the process of building Roman national identity that they lost their rationale after the establishment of the principate, since from that time these values were invested into and this role played by Roman emperors and their families
Enhancement of osteogenesis on micro/nano-topographical carbon fiber-reinforced polyetheretherketone-nanohydroxyapatite biocomposite
No full textAs an FDA-approved implantable material, carbon fiber-reinforced polyetheretherketone (CFRPEEK) possesses excellent mechanical properties similar to those of human cortical bone and is a prime candidate to replace conventional metallic implants. The bioinertness and inferior osteogenic properties of CFRPEEK, however, limit its clinical application as orthopedic/dental implants. The present work aimed at developing a novel carbon fiber-reinforced polyetheretherketone-nanohydroxyapatite (PEEK/CF/n-HA) ternary biocomposite with micro/nano-topographical surface for the enhancement of the osteogenesis as a potential bioactive Material for bone grafting and bone tissue-engineering applications. The combined modification of oxygen plasma and sandblasting could improve the hydrophily and generate micro/nano-topographical structures on the surface of the CFRPEEK-based ternary biocomposite. The results clearly showcased that the micro-/nano-topographical PEEK/n-HA/CF ternary biocomposite demonstrated the outstanding ability to promote the proliferation and differentiation of MG-63 cells in vitro as well as to boost the osseointegration between implant and bone in vivo, thereby boding well application to bone tissue engineering. (C) 2014 Elsevier B.V. All rights reserved.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000348749200074&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Materials Science, BiomaterialsSCI(E)[email protected]; [email protected]
Molecular Dynamic Simulations of Diffusion and Phase Behaviors of Colloidal Particles in Two-Component Liquid Systems
No full textabstract: A comprehensive and systematic investigation on the diffusion and phase behaviors of nanoparticles and macromolecules in two component liquid-liquid systems via Molecule Dynamic (MD) simulations is presented in this dissertation.
The interface of biphasic liquid systems has attracted great attention because it offers a simple, flexible, and highly reproducible template for the assembly of a variety of nanoscale objects. However, certain important fundamental issues at the interface have not been fully explored, especially when the size of the object is comparable with the liquid molecules. In the first MD simulation system, the diffusion and self-assembly of nanoparticles with different size, shape and surface composition were studied in an oil/water system. It has been found that a highly symmetrical nanoparticle with uniform surface (e.g. buckyball) can lead to a better-defined solvation shell which makes the “effective radius” of the nanoparticle larger than its own radius, and thus, lead to slower transport (diffusion) of the nanoparticles across the oil-water interface. Poly(N-isopropylacrylamide) (PNIPAM) is a thermoresponsive polymer with a Lower Critical Solution Temperature (LCST) of 32°C in pure water. It is one of the most widely studied stimulus-responsive polymers which can be fabricated into various forms of smart materials. However, current understanding about the diffusive and phase behaviors of PNIPAM in ionic liquids/water system is very limited. Therefore, two biphasic water-ionic liquids (ILs) systems were created to investigate the interfacial behavior of PNIPAM in such unique liquid-liquid interface. It was found the phase preference of PNIPAM below/above its LCST is dependent on the nature of ionic liquids. This potentially allows us to manipulate the interfacial behavior of macromolecules by tuning the properties of ionic liquids and minimizing the need for expensive polymer functionalization. In addition, to seek a more comprehensive understanding of the effects of ionic liquids on the phase behavior of PNIPAM, PNIPAM was studied in two miscible ionic liquids/water systems. The thermodynamic origin causes the reduction of LCST of PNIPAM in imidazolium based ionic liquids/water system was found. Energy analysis, hydrogen boding calculation and detailed structural quantification were presented in this study to support the conclusions.Dissertation/ThesisDoctoral Dissertation Chemical Engineering 201
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