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1.	Lindh, Tova, et al. (författare) Expression of the Bacterial Enzyme IdeS Using a GFP Fusion in the Yeast Saccharomyces cerevisiae 2023. - 2nd Ingår i: Bacterial pathogenesis : Methods and protocols - Methods and protocols. - 1940-6029. - 9781071632437 ; , s. 131-146 Bokkapitel (refereegranskat)abstract Bacterial proteases are important enzymes used in several technical applications where controlled cleavage of proteins is needed. They are challenging enzymes to express recombinantly as parts of the proteome can be hydrolyzed by their activity. The eukaryotic model organism Saccharomyces cerevisiae is potentially a good expression host as it tolerates several stress conditions and is known to better express insoluble proteins compared to bacterial systems. In this chapter we describe how the protease IdeS from Streptococcus pyogenes can be expressed in S. cerevisiae. The expression of IdeS was followed by constructing a fused protein with GFP and measuring the fluorescence with flow cytometry. The protease presence was confirmed with a Western blot assay and activity was measured with an in vitro assay. To reduce potentially toxic effect on the host cell, the growth and production phases were separated by using the inducible promoter GAL1p to control recombinant gene expression. The protocol provided may be adopted for other bacterial proteases through minor modifications of the fused protein.
2.	Nordenfelt, Pontus, et al. (författare) Preface 2023. - 2nd Ingår i: Bacterial Pathogenesis - Methods and Protocols. - 1064-3745. - 9781493966738 ; 2674 Bokkapitel (övrigt vetenskapligt/konstnärligt)
3.	Albert, Heike, et al. (författare) In vivo enzymatic modulation of IgG glycosylation inhibits autoimmune disease in an IgG subclass-dependent manner 2008 Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 105:39, s. 15005-15009 Tidskriftsartikel (refereegranskat)abstract IgG antibodies are potent inducers of proinflammatory responses. During autoimmune diseases such as arthritis and systemic lupus erythematosus, IgG autoantibodies are responsible for the chronic inflammation and destruction of healthy tissues by cross-linking Fc receptors on innate immune effector cells. The sugar moiety attached to the asparagine-297 residue in the constant domain of the antibody is critical for the overall structure and function of the molecule. Removal of this sugar domain leads to the loss of the proinflammatory activity, suggesting that in vivo modulation of antibody glycosylation might be a strategy to interfere with autoimmune processes. In this work, we investigated whether removal of the majority of the IgG-associated sugar domain by endoglycosidase S (EndoS) from Streptococcus pyogenes is able to interfere with autoimmune inflammation. We demonstrate that EndoS injection efficiently removes the IgG-associated sugar domain in vivo and interferes with autoantibody-mediated proinflammatory processes in a variety of autoimmune models. Importantly, however, we observed a differential impact of EndoS-mediated sugar side chain hydrolysis on IgG activity depending on the individual IgG subclass.
4.	Allhorn, Maria, et al. (författare) EndoS from Streptococcus pyogenes is hydrolyzed by the cysteine proteinase SpeB and requires glutamic acid 235 and tryptophans for IgG glycan-hydrolyzing activity 2008 Ingår i: BMC Microbiology. - : Springer Science and Business Media LLC. - 1471-2180. ; 8:1 Tidskriftsartikel (refereegranskat)abstract ABSTRACT: BACKGROUND: The endoglycosidase EndoS and the cysteine proteinase SpeB from the human pathogen Streptococcus pyogenes are functionally related in that they both hydrolyze IgG leading to impairment of opsonizing antibodies and thus enhance bacterial survival in human blood. In this study, we further investigated the relationship between EndoS and SpeB by examining their in vitro temporal production and stability and activity of EndoS. Furthermore, theoretical structure modeling of EndoS combined with site-directed mutagenesis and chemical blocking of amino acids was used to identify amino acids required for the IgG glycan-hydrolyzing activity of EndoS. RESULTS: We could show that during growth in vitro S. pyogenes secretes the IgG glycan-hydrolyzing endoglycosidase EndoS prior to the cysteine proteinase SpeB. Upon maturation SpeB hydrolyzes EndoS that then loses its IgG glycan-hydrolyzing activity. Sequence analysis and structural homology modeling of EndoS provided a basis for further analysis of the prerequisites for IgG glycan-hydrolysis. Site-directed mutagenesis and chemical modification of amino acids revealed that glutamic acid 235 is an essential catalytic residue, and that tryptophan residues, but not the abundant lysine or the single cysteine residues, are important for EndoS activity. CONCLUSIONS: We present novel information about the amino acid requirements for IgG glycan-hydrolyzing activity of the immunomodulating enzyme EndoS. Furthermore, we show that the cysteine proteinase SpeB processes/degrades EndoS and thus emphasize the importance of the SpeB as a degrading/processing enzyme of proteins from the bacterium itself.
5.	Allhorn, Maria, et al. (författare) Enzymatically Generated Low Carbohydrate Antibodies as a Novel Treatment for Autoimmune Disease 2008 Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 18:11, s. 58-58 Konferensbidrag (refereegranskat)
6.	Allhorn, Maria, et al. (författare) Human IgG/FcgammaR Interactions Are Modulated by Streptococcal IgG Glycan Hydrolysis. 2008 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:1 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The human pathogen Streptococcus pyogenes produces an endoglycosidase, EndoS that hydrolyzes the chitobiose core of the asparagine-linked glycan on the heavy chain of human IgG. IgG-binding to Fc gamma receptors (FcgammaR) on leukocytes triggers effector functions including phagocytosis, oxidative burst and the release of inflammatory mediators. The interactions between FcgammaR and the Fc domain of IgG depend on the IgG glycosylation state. METHODOLOGY/PRINCIPAL FINDINGS: Here we show for the first time that EndoS hydrolyzes the heavy chain glycan of all four human IgG subclasses (IgG1-4), in purified form and in a plasma environment. An inactive form of EndoS, obtained by site-directed mutagenesis, binds IgG with high affinity, in contrast to wild type EndoS that only transiently interacts with IgG, as shown by Slot-blotting and surface plasmon resonance technology. Furthermore, EndoS hydrolysis of the IgG glycan influences the binding of IgG to immobilized soluble FcgammaR and to an erythroleukemic cell line, K562, expressing FcgammaRIIa. Incubation of whole blood with EndoS results in a dramatic decrease of IgG binding to activated monocytes as analyzed by flow cytometry. Moreover, the IgG bound to K562 cells dissociates when cells are treated with EndoS. Likewise, IgG bound to immobilized FcgammaRIIa and subsequently treated with EndoS, dissociates from the receptor as analyzed by surface plasmon resonance and Western blot. CONCLUSIONS/SIGNIFICANCE: We provide novel information about bacterial enzymatic modulation of the IgG/FcgammaR interaction that emphasizes the importance of glycosylation for antibody effector functions. Moreover, EndoS could be used as a biochemical tool for specific IgG N-glycan hydrolysis and IgG purification/detection, or as a potential immunosuppressing agent for treatment of antibody-mediated pathological processes.
7.	Allhorn, Maria, et al. (författare) Sugar-free antibodies--the bacterial solution to autoimmunity? 2009 Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923. ; 1173, s. 664-669 Tidskriftsartikel (refereegranskat)abstract The enzyme EndoS from Streptococcus pyogenes is an immunomodulatory molecule hydrolyzing the conserved glycans in the effector part of immunoglobulin G (IgG). EndoS is remarkably specific for IgG, and hydrolysis has profound effects on IgG effector functions. EndoS pretreatment of IgG, or direct administration to animals with experimental antibody-mediated autoimmune diseases, inhibits development of disease or cures animals from established disease. The properties of EndoS make it a unique experimental tool and an attractive alternative to current therapies of conditions involving pathogenic antibodies. This review describes the discovery of EndoS, the effects of EndoS on IgG effector functions in vitro and in vivo, the biotechnological potential of EndoS, and the outcomes of EndoS treatment in animal models of autoimmunity.
8.	Allhorn, Maria, et al. (författare) The IgG specific endoglycosidase EndoS inhibits both cellular and complement mediated autoimmune hemolysis. 2010 Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 115:24, s. 5080-5088 Tidskriftsartikel (refereegranskat)abstract EndoS from Streptococcus pyogenes is an immunomodulating enzyme that specifically hydrolyzes glycans from human IgG and thereby affects antibody effector functions. Autoimmune hemolytic anemia is caused by antibody mediated red blood cell (RBC) destruction and often resists treatment with corticosteroids that also cause frequent adverse effects. We show here that anti-RhD (anti-D) and rabbit anti-human-RBC antibodies (anti-RBC) mediated destruction of RBC, i.e. phagocytosis, complement activation and hemolysis in vitro and in vivo was inhibited by EndoS. Phagocytosis by monocytes in vitro was inhibited by pre-treatment of anti-D with EndoS before sensitization of RBC, and abrogated by direct addition of EndoS to blood containing sensitized RBC. The toxic effects of monocytes stimulated with anti-D-sensitized RBC, as measured by interleukin-8 secretion and oxygen metabolite production, was restrained by EndoS. Agglutination of RBC and complement mediated hemolysis in vitro in whole human blood caused by rabbit anti-RBC was inhibited by EndoS. Development of anemia in mice caused by a murine anti-RBC IgG2a monoclonal autoantibody, and complement activation and erythrophagocytosis by Kupffer cells in the liver, were reduced by EndoS. Our data indicate that EndoS is a potential therapeutic agent that might be evaluated as an alternative to current treatment regimens against antibody mediated destruction of RBC.
9.	Bacterial Pathogenesis : Methods and Protocols 2017. - 1 Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract This volume discusses various methods and protocols used for the experimentation of a wide range of bacterial species, such as Streptococcus pyogenes, Staphylococcus aureus, Streptococcus pneumonia, Listeria monocytogenes, and Mycobacterium marinum. Bacterial Pathogens: Methods and Protocols is divided into 6 parts: Part 1 describes different approaches to identifying and characterizing bacterial effector molecules; Part 2 deals with structural biology of bacterial pathogenesis and how to overcome folding and stability problems with recombinantly expressed proteins; Part 3 details methodology that identifies bacteria in complex communities and how genomes of bacterial pathogens have evolved; Part 4 reflects on the rapid development of advanced imaging techniques that address questions about molecular properties of individual live bacteria, ultrastructure of surfaces, and subcellular localization of bacterial proteins; Part 5 describes methods from in vitro and in vivo modeling of bacterial infections; and Part 6 explores how bacterial pathogens are the true experts of the immune system. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls.Cutting-edge and comprehensive, Bacterial Pathogens: Methods and Protocols is a valuable resource for anyone who is interested in this fascinating and evolving field.
10.	Bacterial Pathogenesis : Methods and Protocols 2023. - 2 Samlingsverk (redaktörskap) (refereegranskat)abstract This detailed volume presents a diverse set of methodological approaches designed to improve our understanding of bacterial infections from a wide range of bacterial species. Beginning with biofilms and subcellular compartments, the book explores transcriptional analysis, methods for studying plasmid dynamics, and tools for phylogenetic analysis of bacterial genomes, as well as bacterial effector proteins interfering with host systems, host response analysis, and in vivo and in vitro infection models. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step and readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and up-to-date, Bacterial Pathogenesis: Methods and Protocols, Second Edition is a vital resource for researchers in the area of infection biology, as well as but not limited to, those working in the fields of microbiology, immunology, structural biology, molecular biology, genetics, imaging, and computational study.
11.	Bacterial Sensing and Signaling 2009 Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract One of the keys to the development of novel anti-infective strategies. Over the last fifteen years it has become increasingly obvious that bacteria are not as simple and solitary as once believed. Rather, an accumulating body of work shows that bacteria are highly complicated and social organisms, constantly sensing their surroundings and altering both their environments and behaviors to ensure survival. Direct communication between bacteria turns out to be quite common, as are coordinated intra- and interspecies responses that include the formation of highly sophisticated microbial communities. In fact, threats to bacterial survival from assaults ranging from nutrient deprivation and oxygen depletion to the defenses of eukaryotic hosts are all managed through the integration of a dizzying array of complex sensory and communication systems with the appropriate bacterial behaviors. This volume provides an update of the current knowledge in the expanding field of bacterial sensing and signaling, highlighting its most important and interesting aspects. In twelve state-of-the-art articles, respected international experts address topics such as quorum sensing and secondary messengers, chemotaxis and magnetoaerotaxis, two-component phosphotransferase systems, bacterial virulence mechanisms, thermoregulation, and more. The final chapter represents a unique description of the tools available to manipulate many of the sensing and signaling systems described in this volume. Bacterial Sensing and Signaling is recommended reading for students, scientists and clinicians with interests in microbiology, immunology, ecology, biotechnology and a range of other disciplines.
12.	Bartsch, Yannic C, et al. (författare) IgG Fc sialylation is regulated during the germinal center reaction upon immunization with different adjuvants 2020 Ingår i: The Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 1097-6825 .- 0091-6749. ; 146:3, s. 652-666 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Effector functions of IgG antibodies (Abs) are regulated by their Fc N-glycosylation pattern. IgG Fc glycans that lack galactose and terminal sialic acid residues correlate with the severity of inflammatory (auto)immune disorders and have also been linked to the protection against viral infection and discussed in the context of vaccine-induced protection. In contrast, sialylated IgG Abs have shown immunosuppressive effects.OBJECTIVE: We sought to investigate IgG glycosylation programming during the germinal center (GC) reaction upon immunization of mice with a foreign protein antigen and different adjuvants.METHODS: Mice were analyzed for GC T, B cell and plasma cell responses as well as antigen-specific serum IgG subclass titers and Fc glycosylation patterns.RESULTS: Different adjuvants induce distinct IgG+ GC B cell responses with specific transcriptomes and expression levels of the α2,6-sialyltransferase responsible for IgG sialylation that correspond to distinct serum IgG Fc glycosylation patterns. Low IgG Fc sialylation programming in GC B cells was overall highly dependent on the T follicular helper (TFH) cell-inducing cytokine IL-6, especially induced by water-in-oil adjuvants and Mycobacterium tuberculosis (Mtb). Furthermore, low IgG Fc sialylation programming was dependent on adjuvants that induced IL-27R-dependent IFNγ+ TFH1 cells, IL-6/IL-23-dependent IL-17A+ TFH17 cells and high TFH/T follicular regulatory (TFR) cell ratios. The two latter were here dependent on Mtb and its cord factor.CONCLUSION: These findings on adjuvant-dependent GC responses and IgG glycosylation programming may aid the development of novel vaccination strategies to induce IgG Abs with both high affinity and defined Fc glycosylation patterns.
13.	Benkhoucha, Mahdia, et al. (författare) IgG glycan hydrolysis by EndoS inhibits experimental autoimmune encephalomyelitis 2012 Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 9:209 Tidskriftsartikel (refereegranskat)abstract Studies in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, have shown that B cells markedly influence the course of the disease, although whether their effects are protective or pathological is a matter of debate. EndoS hydrolysis of the IgG glycan has profound effects on IgG effector functions, such as complement activation and Fc receptor binding, suggesting that the enzyme could be used as an immunomodulatory therapeutic agent against IgG-mediated diseases. We demonstrate here that EndoS has a protective effect in myelin oligodendrocyte glycoprotein peptide amino acid 35-55 (MOG(35-55))-induced EAE, a chronic neuroinflammatory demyelinating disorder of the central nervous system (CNS) in which humoral immune responses are thought to play only a minor role. EndoS treatment in chronic MOG(35-55)-EAE did not impair encephalitogenic T cell priming and recruitment into the CNS of mice, consistent with a primary role of EndoS in controlling IgG effector functions. In contrast, reduced EAE severity coincided with poor serum complement activation and deposition within the spinal cord, suggesting that EndoS treatment impairs B cell effector function. These results identify EndoS as a potential therapeutic agent against antibody-mediated CNS autoimmune disorders.
14.	Bersellini Farinotti, Alex, et al. (författare) Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons 2019 Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 216:8, s. 1904-1924 Tidskriftsartikel (refereegranskat)abstract Rheumatoid arthritis-associated joint pain is frequently observed independent of disease activity, suggesting unidentified pain mechanisms. We demonstrate that antibodies binding to cartilage, specific for collagen type II (CII) or cartilage oligomeric matrix protein (COMP), elicit mechanical hypersensitivity in mice, uncoupled from visual, histological and molecular indications of inflammation. Cartilage antibody-induced pain-like behavior does not depend on complement activation or joint inflammation, but instead on tissue antigen recognition and local immune complex (IC) formation. smFISH and IHC suggest that neuronal Fcgr1 and Fcgr2b mRNA are transported to peripheral ends of primary afferents. CII-ICs directly activate cultured WT but not FcRγ chain-deficient DRG neurons. In line with this observation, CII-IC does not induce mechanical hypersensitivity in FcRγ chain-deficient mice. Furthermore, injection of CII antibodies does not generate pain-like behavior in FcRγ chain-deficient mice or mice lacking activating FcγRs in neurons. In summary, this study defines functional coupling between autoantibodies and pain transmission that may facilitate the development of new disease-relevant pain therapeutics.
15.	Bober, Marta, et al. (författare) Collagen VI Is a Subepithelial Adhesive Target for Human Respiratory Tract Pathogens 2010 Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 2:2, s. 160-166 Tidskriftsartikel (refereegranskat)abstract Bacterial engagement of specific host tissue structures can be a means of targeting a pathogen to a particular niche, establishing persistent infections and inducing invasion. In this context, primary adhesion is often the first crucial colonization step allowing pathogens to withstand the mechanical clearing mechanisms of the host. As a consequence, bacteria have evolved adhesins with the capacity to mediate interaction between microorganism and host. Here we describe Collagen VI as a novel target for adherence of Streptococcus pyogenes and Streptococcus pneumoniae. In upper and lower airways this Collagen was distributed in the lamina propria underneath the epithelial basement membrane. Both pathogens exhibited strong affinity to Collagen VI as shown by light and electron microscopy in combination with immunodetection and in vitro binding assays. For S. pyogenes this interaction was mediated by M1 protein. The presented data provide evidence for a previously unrecognized role for Collagen VI in host-pathogen interplay during respiratory tract infection. Copyright (C) 2009 S. Karger AG, Basel
16.	Bober, Marta, et al. (författare) The membrane bound LRR lipoprotein Slr, and the cell wall-anchored M1 protein from Streptococcus pyogenes both interact with type I collagen. 2011 Ingår i: PloS one. - : Public Library of Science. - 1932-6203. ; 6:5, s. e20345- Tidskriftsartikel (refereegranskat)abstract Streptococcus pyogenes is an important human pathogen and surface structures allow it to adhere to, colonize and invade the human host. Proteins containing leucine rich repeats (LRR) have been identified in mammals, viruses, archaea and several bacterial species. The LRRs are often involved in protein-protein interaction, are typically 20-30 amino acids long and the defining feature of the LRR motif is an 11-residue sequence LxxLxLxxNxL (x being any amino acid). The streptococcal leucine rich (Slr) protein is a hypothetical lipoprotein that has been shown to be involved in virulence, but at present no ligands for Slr have been identified. We could establish that Slr is a membrane attached horseshoe shaped lipoprotein by homology modeling, signal peptidase II inhibition, electron microscopy (of bacteria and purified protein) and immunoblotting. Based on our previous knowledge of LRR proteins we hypothesized that Slr could mediate binding to collagen. We could show by surface plasmon resonance that recombinant Slr and purified M1 protein bind with high affinity to collagen I. Isogenic slr mutant strain (MB1) and emm1 mutant strain (MC25) had reduced binding to collagen type I as shown by slot blot and surface plasmon resonance. Electron microscopy using gold labeled Slr showed multiple binding sites to collagen I, both to the monomeric and the fibrillar structure, and most binding occurred in the overlap region of the collagen I fibril. In conclusion, we show that Slr is an abundant membrane bound lipoprotein that is co-expressed on the surface with M1, and that both these proteins are involved in recruiting collagen type I to the bacterial surface. This underlines the importance of S. pyogenes interaction with extracellular matrix molecules, especially since both Slr and M1 have been shown to be virulence factors.
17.	Bratanis, Eleni, et al. (författare) BspK, a serine protease from the predatory bacterium Bdellovibrio bacteriovorus with utility for analysis of therapeutic antibodies 2017 Ingår i: Applied and Environmental Microbiology. - 0099-2240. ; 83:4 Tidskriftsartikel (refereegranskat)abstract The development of therapeutic and diagnostic antibodies is a rapidly growing field of research, being the fastest expanding group of products on the pharmaceutical market, and appropriate quality controls are crucial for their application. We have identified and characterized the serine protease termed BspK (Bdellovibrio serine protease K) from Bdellovibrio bacteriovorus and here show its activity on antibodies. Mutation of the serine residue at position 230 rendered the protease inactive. Further investigations of BspK enzymatic characteristics revealed autoproteolytic activity, resulting in numerous cleavage products. Two of the autoproteolytic cleavage sites in the BspK fusion protein were investigated in more detail and corresponded to cleavage after K28 and K210 in the N- and C-terminal parts of BspK, respectively. Further, BspK displayed stable enzymatic activity on IgG within the pH range of 6.0 to 9.5 and was inhibited in the presence of ZnCl2. BspK demonstrated preferential hydrolysis of human IgG1 compared to other immunoglobulins and isotypes, with hydrolysis of the heavy chain at position K226 generating two separate Fab fragments and an intact IgG Fc domain. Finally, we show that BspK preferentially cleaves its substrates C-terminally to lysines similar to the protease LysC. However, BspK displays a unique cleavage profile compared to several currently used proteases on the market.
18.	Chartier, Clement, et al. (författare) Analysis of Smokeless Spray Combustion in a Heavy-Duty Diesel Engine by Combined Simultaneous Optical Diagnostics 2009 Ingår i: SAE Technical Papers. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 0148-7191. ; 2009-01-1353 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract A heavy-duty diesel engine operating case producing no engine-out smoke was studied using combined simultaneous optical diagnostics. The case was close to a typical low-load modern diesel operating point without EGR. Parallels were drawn to the conceptual model by Dec and results from high-pressure combustion vessels. Optical results revealed that no soot was present in the upstream part of the jet cross-section. Soot was only observed in the recirculation zones close to the bowl perimeter. This indicated very slow soot formation and was explained by a significantly higher air entrainment rate than in Dec's study. The local fuel-air equivalence ratio, Φ, at the lift-off length was estimated to be 40% of the value in Dec's study. The lower Φ in the jet produced a different Φ-T history, explaining the soot results. The increased air entrainment rate was mainly due to smaller nozzle holes and increased TDC density. Furthermore, increased injection pressure was believed to reduce the residence time in the jet, thus reducing the soot formation. OH was detected at the periphery of the jet, upstream of the location where fuel started to react on the jet centerline. The OH region extended relatively far into the jet, further supporting the conclusion of a less fuel-rich jet in the current case. Partially oxidized fuel (POF) was found at the center of the jet, downstream of the lift-off position. This indicated that the temperature needed to start chemical reactions inside the jet had not been obtained at the lift-off position. The high-temperature reaction zone at the periphery thus added heat over a distance before POF was observed on the centerline.
19.	Cheung, Herman H., et al. (författare) Monitor – Biology 2004 Ingår i: Drug Discovery Today. - 1878-5832. ; 9:14, s. 621-622 Tidskriftsartikel (refereegranskat)abstract The hottest developments in the fields of cancer research, neuroscience, genomics and proteomics, anti-virals and more, with a pick of the key research papers in these areas.
20.	Cheung, Herman H., et al. (författare) Monitor – Biology 2004 Ingår i: Drug Discovery Today. - 1878-5832. ; 9:6, s. 287-290 Tidskriftsartikel (refereegranskat)abstract The hottest developments in the fields of cancer research, neuroscience, genomics and proteomics, anti-virals and more, with a pick of the key research papers in these areas.
21.	Collin, Mattias (författare) Antibody glycosylation as an immunological key in health and disease 2020 Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423. ; 30:4, s. 200-201 Tidskriftsartikel (refereegranskat)
22.	Collin, Mattias (författare) Antibody Glycosylation Predicts Relapse in Autoimmune Vasculitis 2017 Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 17, s. 15-15 Tidskriftsartikel (refereegranskat)
23.	Collin, Mattias (författare) Bacteria can help us cure autoimmune disease 2011 Ingår i: El Pais. ; 2011:Dec 16, s. 1-1 Tidskriftsartikel (populärvet., debatt m.m.)abstract The human immune system is very powerful, and if it is directed towards ourselves, it can lead to the very serious so-called autoimmune diseases
24.	Collin, Mattias (författare) Bacteria can help us cure autoimmune disease 2011 Ingår i: The Irish Times. ; 2011:Dec 21, s. 1-1 Tidskriftsartikel (populärvet., debatt m.m.)
25.	Collin, Mattias, et al. (författare) Bacterial Modulation of Fc Effector Functions 2013 Ingår i: Antibody Fc : Linking Adaptive and Innate Immunity - Linking Adaptive and Innate Immunity. - 9780123948021 ; , s. 317-332 Bokkapitel (refereegranskat)abstract Immunoglobulins (Igs, antibodies) are key players in adaptive immunity, and pathways mediated through the effector Fc portion of Ig are instrumental in controlling bacterial infections. Therefore, it is not very surprising that bacterial pathogens and commensals through co-evolution with their hosts have learned many tricks to interfere with Fc effector functions. In this chapter, we describe three principally different bacterial strategies to interfere with immunoglobulins: Specific Ig binding, specific or unspecific Ig protelolysis, and, finally, specific and unspecific hydrolysis of functionally important carbohydrates on the immunoglobulins. Elucidating these bacterial immune evasion mechanism evidences bacteria-host co-evolution and provides insight into fundamental aspects of human adaptive immunity and pathogenesis of infection.
26.	Collin, Mattias, et al. (författare) Biology 2004 Ingår i: Drug Discovery Today. - 1878-5832. ; 9:9, s. 420-422 Tidskriftsartikel (refereegranskat)abstract The hottest developments in the fields of cancer research, neuroscience, genomics and proteomics, anti-virals and more, with a pick of the key research papers in these areas.
27.	Collin, Mattias, et al. (författare) Biology 2004 Ingår i: Drug Discovery Today. - 1878-5832. ; 9:7, s. 338-340 Tidskriftsartikel (refereegranskat)abstract The hottest developments in the fields of cancer research, neuroscience, genomics and proteomics, anti-virals and more, with a pick of the key research papers in these areas.
28.	Collin, Mattias, et al. (författare) Constitutive expression of the antibacterial CXC chemokine GCP-2/CXCL6 by epithelial cells of the male reproductive tract. 2008 Ingår i: Journal of Reproductive Immunology. - : Elsevier BV. - 1872-7603 .- 0165-0378. ; 79, s. 37-43 Tidskriftsartikel (refereegranskat)abstract The reproductive tract is continuously challenged by potential pathogens present in the environment. Therefore, robust host defense mechanisms are essential both for the health of the individual and for fertilization. Antibiotic innate immunity peptides possess broad antimicrobial activity. Recently, we found that the CXC chemokine, granulocyte chemotactic protein (GCP)-2/CXCL6, possesses antibacterial activity. In the present study, we investigated, therefore, the presence of GCP-2/CXCL6 in the human male reproductive system. GCP-2/CXCL6 was detected at 19nM (mean; range: 5-47nM; n=14) in seminal plasma of fertile donors, i.e. at levels more than 100 times higher than those previously reported for the related chemokine IL-8/CXCL8. No GCP-2/CXCL6 could be detected in blood plasma of healthy donors, indicating local production in the male reproductive tract. In vasectomized donors, significantly lower levels of GCP-2/CXCL6 were found (mean: 3nM; range 2-7nM; n=7), demonstrating that the testis and epididymis contribute significantly to the GCP-2/CXCL6 content of seminal plasma. Strong expression of GCP-2/CXCL6 was found in the epithelium of the testis, epididymis and seminal vesicles, while the prostate epithelium showed weak expression, as determined by immunohistochemistry. A biological function is suggested, viz. at concentrations of the order of those found in seminal plasma, GCP-2/CXCL6 has antibacterial activity against the urogenital pathogen Neisseria gonorrhoeae. GCP-2/CXCL6 in seminal plasma may play roles in both host defense of the male urogenital tract and during fertilization.
29.	Collin, Mattias, et al. (författare) Contributions to Microbiology : Foreword 2009 Ingår i: Bacterial Sensing and Signaling. - Basel : KARGER. - 1662-291X .- 1420-9519. - 9783805591324 - 9783805591331 ; 16 Bokkapitel (övrigt vetenskapligt/konstnärligt)
30.	Collin, Mattias (författare) Don't forget about Streptococcus pyogenes! (comment on Microbes Infect. 5 (2003) 1329-1335) 2004 Ingår i: Microbes and Infection. - : Elsevier BV. - 1769-714X .- 1286-4579. ; 6:3, s. 336-336 Tidskriftsartikel (refereegranskat)
31.	Collin, Mattias, et al. (författare) Effect of SpeB and EndoS from Streptococcus pyogenes on human immunoglobulins 2001 Ingår i: Infection and Immunity. - 1098-5522. ; 69:11, s. 7187-7189 Tidskriftsartikel (refereegranskat)abstract Streptococcus pyogenes secretes a specific immunoglobulin G (IgG)-protease, SpeB, as well as the IgG glycan-hydrolyzing enzyme EndoS. Here we show that SpeB also degrades IgA, IgM, IgD, and IgE. We also show that EndoS only hydrolyzes the glycan moiety on native but not denatured IgG. Thus, SpeB has a broad immunoglobulin-degrading activity, while EndoS is highly specific for IgG.
32.	Collin, Mattias, et al. (författare) EndoS, a novel secreted protein from Streptococcus pyogenes with endoglycosidase activity on human IgG 2001 Ingår i: EMBO Journal. - : Wiley. - 1460-2075. ; 20:12, s. 3046-3055 Tidskriftsartikel (refereegranskat)abstract Streptococcus pyogenes is an important human pathogen that selectively interacts with proteins involved in the humoral defense system, such as immunoglobulins and complement factors. In this report we show that S.pyogenes has the ability to hydrolyze the chitobiose core of the asparagine-linked glycan on immuno globulin G (IgG) when bacteria are grown in the presence of human plasma. This activity is associated with the secretion of a novel 108 kDa protein denoted EndoS. EndoS has endoglycosidase activity on purified soluble IgG as well as IgG bound to the bacterial surface. EndoS is required for the activity on IgG, as an isogenic EndoS mutant could not hydrolyze the glycan on IgG. In addition, we show that the secreted streptococcal cysteine proteinase SpeB cleaves IgG in the hinge region in a papain-like manner. This is the first example of an endoglycosidase produced by a bacterial pathogen that selectively hydrolyzes human IgG, and reveals a novel mechanism which may contribute to S.pyogenes pathogenesis.
33.	Collin, Mattias, et al. (författare) EndoS and SpeB from Streptococcus pyogenes inhibit immunoglobulin-mediated opsonophagocytosis. 2002 Ingår i: Infection and Immunity. - 1098-5522. ; 70:12, s. 6646-6651 Tidskriftsartikel (refereegranskat)
34.	Collin, Mattias, et al. (författare) Extracellular enzymes with immunomodulating activities: variations on a theme in Streptococcus pyogenes 2003 Ingår i: Infection and Immunity. - 1098-5522. ; 71:6, s. 2983-2992 Forskningsöversikt (refereegranskat)
35.	Collin, Mattias (författare) From greasy bad guy to superficial savior! 2017 Ingår i: Forum for Nordic Dermato-Venerology. - 1402-2915. ; 22:1, s. 17-17 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
36.	Collin, Mattias, et al. (författare) Generation of a mature streptococcal cysteine proteinase is dependent on cell wall-anchored M1 protein 2000 Ingår i: Molecular Microbiology. - : Wiley. - 1365-2958 .- 0950-382X. ; 36:6, s. 1306-1318 Tidskriftsartikel (refereegranskat)abstract In the present study, we have generated a mutant strain of Streptococcus pyogenes, MC25, which lacks M protein on its surface, and we demonstrate that this strain is unable to generate a mature 28 kDa cysteine proteinase. Furthermore, we show that S. pyogenes bacteria of M1 serotype are dependent on cell wall-anchored M protein to cleave the secreted zymogen into a mature cysteine proteinase. We also show that MC25 secretes a 40 kDa zymogen, having a conformation different from that secreted by wild-type bacteria. We provide data showing that the cleavage site is not blocked but, presumably, the active site is. This suggests that M protein, when anchored to the cell wall, is involved in the unfolding of the zymogen and generation of a mature cysteine proteinase that can be activated under reducing conditions. Our data add new aspects to the interaction between two important virulence factors of S. pyogenes, the streptococcal cysteine proteinase and M protein.
37.	Collin, Mattias, et al. (författare) Identification of conditionally expressed genes in Streptococcus pyogenes using RNA fingerprinting 2001 Ingår i: FEMS Microbiology Letters. - 1574-6968. ; 196:2, s. 123-127 Tidskriftsartikel (refereegranskat)abstract RNA fingerprinting using arbitrarily primed reverse transcription-polymerase chain reaction was employed on isolated RNA from Streptococcus pyogenes bacteria in order to identify genes that were regulated in response to environmental changes. When S. pyogenes was cultured under glucose-rich growth conditions a number of transcriptionally up-regulated products were identified, cloned and sequenced. Using the Streptococcal Genome Sequencing Project database and similarity searches against the GenBank database the corresponding genes encoding enzyme IIB and IIC component of a putative phosphotransferase system were identified. Thus, we show that RNA fingerprinting could be a useful tool to identify unknown genes in S. pyogenes that are expressed under certain environmental conditions.
38.	Collin, Mattias, et al. (författare) IgG glycan hydrolysis by a bacterial enzyme as a therapy against autoimmune conditions. 2008 Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 105:11, s. 4265-4270 Tidskriftsartikel (refereegranskat)abstract EndoS from Streptococcus pyogenes efficiently hydrolyzes the functionally important and conserved N-linked glycan of IgG in human blood. Repeated i.v. administration of EndoS in rabbits completely hydrolyzes the glycans of the whole IgG pool, despite the generation of anti-EndoS antibodies. EndoS administration had no apparent effects on the health of the animals. EndoS hydrolysis of the IgG glycan has profound effects on IgG effector functions, such as complement activation and Fc receptor binding, suggesting that the enzyme could be used as an immunomodulatory therapeutic agent against IgG-mediated diseases. We demonstrate here that EndoS indeed has a protective effect in a mouse model of lethal IgG-driven immune (or idiopathic) thrombocytopenic purpura. EndoS pretreatment of pathogenic antibodies inhibits the development of disease, and the enzyme also rescues mice from already established disease when severe thrombocytopenia and s.c. bleeding have developed. These results identify EndoS as a potential therapeutic agent against diseases where pathogenic IgG antibodies are important and further emphasize antibody glycans as possible targets in future therapies against antibody-mediated autoimmune conditions.
39.	Collin, Mattias (författare) Kan man snacka bort representativ demokrati? 2007 Ingår i: Medicinska fakultetens personaltidning - närv. ; 2007:May, s. 12-12 Tidskriftsartikel (populärvet., debatt m.m.)abstract Universitet och högskolor är unika myndigheter i Sverige genom att ha en demokratisk styrning med stark representation från verksamheten. I universitetsstyrelsen finns visserligen mer politiskt tillsatta ledamöter och representanter för det omgivande samhället, men bara ett steg längre ned på fakultetsnivå, som vår egen fakultet, är verksamhets- representationen i det närmaste total. Vi bestämmer alltså i viss mån över oss själva!
40.	Collin, Mattias, et al. (författare) Monitor – Biology 2004 Ingår i: Drug Discovery Today. - 1878-5832. ; 9:24, s. 1082-1084 Tidskriftsartikel (refereegranskat)abstract The hottest developments in the fields of cancer research, neuroscience, genomics and proteomics, anti-virals and more, with a pick of the key research papers in these areas.
41.	Collin, Mattias, et al. (författare) Monitor – biology 2005 Ingår i: Drug Discovery Today. - 1878-5832. ; 10:15, s. 1073-1073 Tidskriftsartikel (refereegranskat)
42.	Collin, Mattias, et al. (författare) Monitor – biology 2005 Ingår i: Drug Discovery Today. - 1878-5832. ; 10:1, s. 75-77 Tidskriftsartikel (refereegranskat)
43.	Collin, Mattias, et al. (författare) Monitor – biology 2005 Ingår i: Drug Discovery Today. - 1878-5832. ; 10:7, s. 530-531 Tidskriftsartikel (refereegranskat)
44.	Collin, Mattias, et al. (författare) Monitor – Biology 2004 Ingår i: Drug Discovery Today. - 1878-5832. ; 9:12, s. 539-541 Tidskriftsartikel (refereegranskat)abstract An insight into the latest developments in drug discovery through brief synopses of recent publications, summarizing the chemistry, pharmacological significance and biological relevance of new molecules.
45.	Collin, Mattias, et al. (författare) Monitor – biology 2004 Ingår i: Drug Discovery Today. - 1878-5832. ; 9:19, s. 856-858 Tidskriftsartikel (refereegranskat)abstract The hottest developments in the fields of cancer research, neuroscience, genomics and proteomics, anti-virals and more, with a pick of the key research papers in these areas.
46.	Collin, Mattias, et al. (författare) Monitor – biology 2005 Ingår i: Drug Discovery Today. - 1878-5832. ; 10:17, s. 1201-1203 Tidskriftsartikel (refereegranskat)
47.	Collin, Mattias (författare) Streptococcus pyogenes secreted enzymes interacting with the human host 2001 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Streptococcus pyogenes is one of the most common bacteria infecting humans. One of the factors contributing to the disease-causing properties is the secreted streptococcal cysteine proteinase, SpeB, which degrades several host proteins in connective tissue and circulation. SpeB activity depends on the transformation from an inactive precursor, zymogen, into a mature proteinase. We show that the important cell wall-anchored M protein is involved in the unfolding and maturation of SpeB. An engineered strain lacking M protein secreted the SpeB zymogen in a conformational state that did not allow the maturation to proceed normally. Furthermore, we identified genes that were regulated by environmental changes using RNA fingerprinting. One of the identified glucose-induced genes encodes a phosphotransferase system that could be involved in the signaling leading to down-regulation of virulence genes in response to the nutritional status. Moreover, a novel secreted endoglycosidase, EndoS, has been identified. Purified EndoS removes the glycan from native human immunoglobulin G (IgG).This glycan is known to be important for IgG effector functions such as complement activation and binding to Fc receptors on phagocytic cells. Furthermore, it was discovered that SpeB cleaves the heavy chain of IgG resulting in distinct fragments separating the antigen-binding Fab portions from the effector-triggering Fc portion. SpeB also degrades the heavy chains of IgA, IgM, IgD and IgE. Finally, it was shown that both these enzymatic activities on human IgG have functional consequences with significantly impaired antibody-mediated killing of S. pyogenes in an ex vivo model.
48.	Collin, Mattias, et al. (författare) The carbohydrate switch between pathogenic and immunosuppressive antigen-specific antibodies. 2013 Ingår i: Experimental Dermatology. - : Wiley. - 0906-6705. ; 22:8, s. 511-514 Tidskriftsartikel (refereegranskat)abstract IgG antibodies have one conserved N-glycosylation site at Asn 297 in each of their constant heavy chain regions. These Fc glycans influence the overall structure and pro- or anti-inflammatory effector functions of IgG antibodies. The biantennary core glycan structure, consisting of four N-acetyl-glucosamine (GlcNAc) and three mannose residues, can be further decorated with fucose, a bisecting GlcNAc and terminal galactose or galactose plus sialic acid. Non-galactosylated (agalactosylated; G0) IgG antibodies have long been associated with pro-inflammatory effector functions in autoimmune patients with rheumatoid arthritis (RA). In contrast, it has been shown that sialylated IgGs are responsible for anti-inflammatory effects of intravenous immunoglobulin (IVIG; purified IgG from pooled human plasma), which is administered at high doses (2 g/kg) for the systemic treatment of autoimmune patients. It has become increasingly evident that pro-inflammatory immune responses, such as autoimmune reactions, primarily induce antigen-specific G0 IgGs, whereas tolerance induces immunosuppressive galactosylated and sialylated IgGs. Under physiological conditions, differentially glycosylated IgGs mediate their pro- or anti-inflammatory effector functions obviously as immune complexes (IC) in an antigen-specific manner. Therefore, antigen-specific galactosylated and sialylated IgGs may be a promising therapeutic tool for re-establishing tolerance against defined (self-) antigens in autoimmune or allergic patients. Here, we summarize these findings and outline our viewpoint on the development and function of differentially glycosylated antigen-specific IgG antibodies.
49.	Collin, Mattias, et al. (författare) Toward clinical use of the IgG specific enzymes IdeS and EndoS against antibody-mediated diseases 2017 Ingår i: Methods in Molecular Biology. - New York, NY : Springer New York. - 1064-3745. ; 1535, s. 339-351 Bokkapitel (refereegranskat)abstract The endoglycosidase EndoS and the protease IdeS from the human pathogen Streptococcus pyogenes are immunomodulating enzymes hydrolyzing human IgG. IdeS cleaves IgG in the lower hinge region, while EndoS hydrolyzes the conserved N-linked glycan in the Fc region. Both enzymes are remarkably specific for human IgG that after hydrolysis loses most of its effector functions, such as binding to leukocytes and complement activation, all contributing to bacterial evasion of adaptive immunity. However, taken out of their infectious context, we and others have shown that IdeS and EndoS can alleviate autoimmune disease in a number of animal models of antibody-mediated disorders. In this chapter, we will briefly describe the discovery and characterization of these unique enzymes, present the findings from a number of animal models of autoimmunity where the enzymes have been tested, and outline the ongoing clinical testing of IdeS. Furthermore, we will discuss the rationale for further development of IdeS and EndoS into novel pharmaceuticals against diseases where IgG antibodies contribute to the pathology, including, but not restricted to, chronic and acute autoimmunity, transplant rejection, and antidrug antibody reactions.
50.	Collin, Peter, et al. (författare) Undermatching butt welds in high strength steel 2009 Ingår i: Sustainable infrastructure. - Zürich : International Association for Bridge and Structural Engineering. - 9783857481215 ; , s. 280-281 Konferensbidrag (refereegranskat)

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