950 results
Search Results
2. The energy consumption and employment relationship: A clarification
- Author
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Dan, G
- Published
- 2020
3. COMPLEMENTARY FAIR DOMINATION IN GRAPHS.
- Author
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VENKATASUBRAMANIAN, SWAMINATHAN and SUNDARESWARAN, RAMAN
- Subjects
UNDIRECTED graphs ,DOMINATING set ,NEIGHBORS - Abstract
In a simple, finite undirected graph G, a dominating set D is a subset of the vertex set V(G) whose closed neighbourhood is V(G). Many types of domination have been studied. The studies are based either on the nature of domination or the type of dominating set or the type of the complement of the dominating set. Interaction between dominating set and its complement is also considered. Fair domination is the domination where every vertex in the complement of a dominating set has equal number of neighbours in the dominating set. In this paper, a dominating set whose vertices have equal number of neighbours in the complement is the subject of study. The parameter γ
cof (G) is introduced and studied. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
4. Immunological and molecular basics of the primary open angle glaucoma pathomechanism
- Author
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Andrzej Grąbczewski, Piotr Skopiński, A. Kubiak, Barbara J. Bałan, Katarzyna Samelska, Anna Zaleska-Żmijewska, and Jacek P. Szaflik
- Subjects
MAPK/ERK pathway ,Programmed cell death ,autophagy ,Open angle glaucoma ,genetic structures ,Immunology ,Excitotoxicity ,Glaucoma ,medicine.disease_cause ,Neuroprotection ,03 medical and health sciences ,0302 clinical medicine ,Immunology and Allergy ,Medicine ,oxidative stress ,complement ,Review Paper ,business.industry ,Autophagy ,apoptosis ,retinal ganglion cells (rgcs) ,medicine.disease ,eye diseases ,Complement system ,glaucoma ,sense organs ,business ,Neuroscience ,030215 immunology - Abstract
Glaucoma is a degenerative process of the optic nerve. Increased intraocular pressure is believed to be the main factor leading to the glaucomatous damage. The in vitro and in vivo animal glaucoma research models provide insight into the molecular changes in the retina in response to the injury factor. The damage is a complex process incorporating molecular and immunological changes. Such changes involve NFκB activity and complement activation. The processes affect the human antigen, JNK, MAPK, p53, MT2 and DBA/2J molecular pathways, activate the autophagy processes and compromise neuroprotective mechanisms. Activation and inhibition of immunological responses contribute to cell injury. The immunological mechanisms of glaucomatous degeneration include glial response, the complement, tumor necrosis factor α (TNF-α) pathways and toll-like receptors athways. Oxidative stress and excitotoxicity are factors contributing to cell death in glaucoma. The authors present an up-to-date review of the mechanisms involved and update on research focusing on a possible innovative glaucoma treatment.
- Published
- 2021
5. Generalized non-coprime graphs of groups
- Author
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Kathirvel, S. Anukumar, Cameron, Peter J., and Chelvam, T. Tamizh
- Published
- 2024
- Full Text
- View/download PDF
6. Summary of Research: Terminal Complement Inhibitor Ravulizumab in Generalized Myasthenia Gravis.
- Author
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Vu, Tuan, Meisel, Andreas, Mantegazza, Renato, Annane, Djillali, Katsuno, Masahisa, Aguzzi, Rasha, Enayetallah, Ahmed, Beasley, Kathleen N., Rampal, Nishi, and Howard Jr., James F.
- Subjects
COMPLEMENT inhibition ,ECULIZUMAB ,MYASTHENIA gravis ,RARE diseases - Abstract
This article provides a summary of a previously published paper: Terminal Complement Inhibitor Ravulizumab in Generalized Myasthenia Gravis. The paper reported the results of the CHAMPION-MG trial which investigated the drug ravulizumab in the rare disease, myasthenia gravis. 2xgQ8ocB58K7snciBh7N6W Terminal Complement Inhibitor Ravulizumab in Generalized Myasthenia Gravis (MP4 594600 KB) [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
7. C5aR1 is a master regulator in Colorectal Tumorigenesis via Immune modulation
- Author
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Xinyue Lv, Qingkai Wang, Wei Zhang, Long Zhang, Xuhui Zhou, Jianfeng Chen, Qun-Ying Lei, Xin Zhang, Weixing Dai, Qi Wang, Ling Li, Enjie Xu, Peipei Ding, Luying Li, Chaoqun Yang, Yuzhen Zhou, Danlei Zhou, Na Wang, Weiguo Hu, and Hongyu Gu
- Subjects
0301 basic medicine ,Male ,Chemokine ,Colorectal cancer ,Complement ,Azoxymethane ,Medicine (miscellaneous) ,CD8-Positive T-Lymphocytes ,medicine.disease_cause ,Peptides, Cyclic ,03 medical and health sciences ,chemistry.chemical_compound ,Gene Knockout Techniques ,Mice ,0302 clinical medicine ,Immune system ,medicine ,Animals ,colorectal tumorigenesis ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Receptor, Anaphylatoxin C5a ,Bone Marrow Transplantation ,Complement component 5 ,immune modulation ,biology ,business.industry ,Dextran Sulfate ,Complement C3 ,medicine.disease ,Colitis ,Complement system ,Gene Expression Regulation, Neoplastic ,Disease Models, Animal ,030104 developmental biology ,C5aR1 ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Carcinogenesis ,business ,Colorectal Neoplasms ,CD8 ,Research Paper - Abstract
Numerous factors have been claimed to play important roles in colorectal cancer (CRC) tumorigenesis, including myeloid-derived suppressor cells (MDSCs) and other immune cells, cytokines, and chemokines; however, the precise mechanisms of colorectal tumorigenesis remain elusive, and there is a lack of effective preventive treatments. Here, we investigated the role of complement system, a key regulator of immune surveillance and homeostasis, in colorectal tumorigenesis. Methods: The prototypical CRC model was induced by combined administration of azoxymethane (AOM)/ dextran sulfate sodium (DSS) in Wild-type (WT), C3-, C5-, C5ar1-, and C5ar2-deficient mice. Using flow cytometry, immunohistochemical staining and multiplex bead assay, we profiled the immune cells, cytokines and chemokines. Bone marrow transplantation was employed to determine the contribution of immune cells in colorectal tumorigenesis. Further, we used C5aR1 antagonist PMX205 to investigate the protective role in colorectal tumorigenesis. Results: Complement was extensively activated in inflamed tissues of AOM/DSS-induced murine CRC model, leading to multifaceted consequences. The deficiency of complement C5 or especially C5ar1, but not C3 almost completely prevented CRC tumorigenesis. C5a/C5aR1 signaling recruited MDSCs into the inflamed colorectum to impair CD8+ T cells, and modulated the production of critical cytokines and chemokines, thus initiating CRC. Moreover, the C5aR1 antagonist PMX205 strongly impeded colorectal tumorigenesis. Bone marrow transplantation further revealed that C5aR1 expression by immune cells was critical for colorectal tumorigenesis. Conclusion: Our study identifies C5a/C5aR1 signaling as a vital immunomodulatory program in CRC tumorigenesis and suggests a feasible preventive strategy.
- Published
- 2020
8. Microglia exacerbate white matter injury via complement C3/C3aR pathway after hypoperfusion
- Author
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Rubing Shi, Yuan Zhu, Liping Wang, Jiaji Pan, Zhijun Zhang, Kunlin Jin, Muyassar Mamtilahun, Yongting Wang, Ashwin Venkatesh, Guo-Yuan Yang, Xuanqiang Tu, Lin Yuan Zhang, and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Male ,Pathology ,medicine.medical_specialty ,Medicine (miscellaneous) ,microglia ,Inflammation ,Brain Ischemia ,Receptors, G-Protein-Coupled ,Rats, Sprague-Dawley ,03 medical and health sciences ,Myelin ,Mice ,0302 clinical medicine ,medicine ,Animals ,complement ,Complement Pathway, Classical ,Receptor ,Vascular dementia ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,chronic cerebral hypoperfusion ,Neuroinflammation ,Mice, Knockout ,Microglia ,business.industry ,Complement C3 ,medicine.disease ,White Matter ,Rats ,Mice, Inbred C57BL ,Perfusion ,030104 developmental biology ,medicine.anatomical_structure ,Brain Injuries ,Knockout mouse ,white matter injury ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Research Paper - Abstract
Microglial activation participates in white matter injury after cerebral hypoperfusion. However, the underlying mechanism is unclear. Here, we explore whether activated microglia aggravate white matter injury via complement C3-C3aR pathway after chronic cerebral hypoperfusion. Methods: Adult male Sprague-Dawley rats (n = 80) underwent bilateral common carotid artery occlusion for 7, 14, and 28 days. Cerebral vessel density and blood flow were examined by synchrotron radiation angiography and three-dimensional arterial spin labeling. Neurobehavioral assessments, CLARITY imaging, and immunohistochemistry were performed to evaluate activation of microglia and C3-C3aR pathway. Furthermore, C3aR knockout mice were used to establish the causal relationship of C3-C3aR signaling on microglia activation and white matter injury after hypoperfusion. Results: Cerebral vessel density and blood flow were reduced after hypoperfusion (p
- Published
- 2020
9. Leaky gut, circulating immune complexes, arthralgia, and arthritis in IBD: coincidence or inevitability?
- Author
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Xi-ya Jin, Dan-dan Li, Wei Quan, Yang Chao, and Bin Zhang
- Subjects
IMMUNE complexes ,INFLAMMATORY bowel diseases ,LYME disease ,ARTHRITIS ,INTESTINAL mucosa ,JOINT pain - Abstract
Most host-microbiota interactions occur within the intestinal barrier, which is essential for separating the intestinal epithelium from toxins, microorganisms, and antigens in the gut lumen. Gut inflammation allows pathogenic bacteria to enter the blood stream, forming immune complexes which may deposit on organs. Despite increased circulating immune complexes (CICs) in patients with inflammatory bowel disease (IBD) and discussions among IBD experts regarding their potential pathogenic role in extra-intestinal manifestations, this phenomenon is overlooked because definitive evidence demonstrating CICinduced extra-intestinal manifestations in IBD animal models is lacking. However, clinical observations of elevated CICs in newly diagnosed, untreated patients with IBD have reignited research into their potential pathogenic implications. Musculoskeletal symptoms are the most prevalent extra-intestinal IBD manifestations. CICs are pivotal in various arthritis forms, including reactive, rheumatoid, and Lyme arthritis and systemic lupus erythematosus. Research indicates that intestinal barrier restoration during the pre-phase of arthritis could inhibit arthritis development. In the absence of animal models supporting extra-intestinal IBD manifestations, this paper aims to comprehensively explore the relationship between CICs and arthritis onset via a multifaceted analysis to offer a fresh perspective for further investigation and provide novel insights into the interplay between CICs and arthritis development in IBD. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
10. IgG4 antibodies from patients with asymptomatic bancroftian filariasis inhibit the binding of IgG1 and IgG2 to C1q in a Fc-Fc-dependent mechanism
- Author
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Achim Hoerauf, Tomabu Adjobimey, and Ulrich Fabien Prodjinotho
- Subjects
Adult ,Male ,030231 tropical medicine ,Complement ,Immunology and Host-Parasite Interactions - Original Paper ,Asymptomatic ,Microfilaria ,030308 mycology & parasitology ,03 medical and health sciences ,Classical complement pathway ,Young Adult ,0302 clinical medicine ,Elephantiasis, Filarial ,Affinity chromatography ,parasitic diseases ,medicine ,Animals ,Humans ,Fc-Fc interactions ,Complement Pathway, Classical ,Microfilariae ,C1q ,IgG4 ,0303 health sciences ,General Veterinary ,biology ,Complement C1q ,General Medicine ,Middle Aged ,Acquired immune system ,ddc ,Complement system ,Immunoglobulin Fc Fragments ,Blot ,Infectious Diseases ,Insect Science ,Immunoglobulin G ,Immunology ,biology.protein ,Lymphatic filariasis ,Parasitology ,medicine.symptom ,Antibody ,Immune regulatory response - Abstract
A striking feature of lymphatic filariasis (LF) is the clinical heterogeneity among exposed individuals. While endemic normals (EN) remain free of infection despite constant exposure to the infective larvae, a small group of patients, generally microfilaria free (Mf-) develops severe pathology (CP) such as lymphedema or hydrocele. Another group of infected individuals remains asymptomatic while expressing large amounts of microfilariae (Mf+). This Mf+ group is characterized by an immune-suppressed profile with high levels of anti-inflammatory cytokines and elevated IgG4. This particular immunoglobulin is unable to activate the complement. The complement system plays a critical role in both innate and adaptive immunity. However, its importance and regulation during LF is not fully understood. Using affinity chromatography and solid-phase-enzyme-immunoassays, we investigated the ability of antibody isotypes from LF clinical groups to bind C1q, the first element of the complement’s classical pathway. The results indicate that while C1q is similarly expressed in all LF clinical groups, IgG1–2 in the plasma from Mf+ individuals presented significantly lower affinity to C1q compared to EN, Mf−, and CP. In addition, selective depletion of IgG4 significantly enhanced the affinity of IgG1–2 to C1q in Mf+ individuals. Strikingly, no effect was seen on the ability of IgG3 to bind C1q in the same conditions. More interestingly, papain-generated IgG4-Fc-portions interacted with Fc portions of IgG1–2 as revealed by far-western blot analysis. These data suggest that while being unable to bind C1q, IgG4 inhibits the first steps of the complement classical pathway by IgG1 or IgG2 via Fc-Fc interactions. Electronic supplementary material The online version of this article (10.1007/s00436-019-06451-2) contains supplementary material, which is available to authorized users.
- Published
- 2019
11. Autoimmune diseases - New insights into a troublesome field
- Author
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Thomas Lung, Michèle Nydegger, Martin Risch, Benjamin Sakem, Andreas Hemmerle, Urs E. Nydegger, and Lorenz Risch
- Subjects
Innate immunity ,2019-20 coronavirus outbreak ,Research paper ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunology ,Complement ,Biosimilar ,Disease ,RC581-607 ,Bioinformatics ,Review article ,Biosimilars I ,Immunology and Allergy ,Medicine ,Treatment strategy ,Monoclonal antibodies ,Immunologic diseases. Allergy ,business ,Cytokine ,Repurposing - Abstract
Recent updates in the diagnosis and management of chronic inflammatory conditions can be brought together to better understand autoimmune diseases (ADs). With organ-specific or organ-limited and systemic ADs, physicians often are faced with a dilemma when making a diagnosis and may feel a kind of embarrassment when a more distinct nosological entity cannot be found. ADs often overlap with other diseases and good diagnostic procedures for ADs only become evidence-based when refined histopathologic, immunopathologic, and general laboratory analyses are available. Immunofluorescence analyses, Western blotting, CUT & RUN technology allow localization of the site of autoantibody-reactivity on the relevant DNA sequence. The Polymerase chain reaction technology and CRISPR-Cas9, the new gene editor using pools of synthetic non-coding RNAs in screening experiments, are expected to lead to advances in the diagnosis of ADs. The current use of mRNA as a vaccine against COVID-19 has increased confidence in the use of mRNA or long non-coding RNAs in the treatment strategy for ADs. The integration of new knowledge about innate immunity, the complement system, vaccinology, and senescence into the care of patients with ADs expands the therapeutic arsenal of disease-modifying drugs and allows for the repurposing of anti-cytokine monoclonal/biosimilar antibodies, originally designed for chronic inflammatory diseases, for ADs. This review article brings together some of the most relevant ideas; a case report included in this review highlights the difficulty of distinguishing between ADs, chronic inflammation, and/or granular disease., Graphical abstract Image 1
- Published
- 2021
12. Spherical Linear Diophantine Fuzzy Graphs: Unleashing the Power of Fuzzy Logic for Uncertainty Modeling and Real-World Applications.
- Author
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Parimala, Mani and Jafari, Saeid
- Subjects
FUZZY graphs ,FUZZY logic ,FUZZY sets ,SOCIAL networks - Abstract
The theory of spherical linear Diophantine fuzzy sets (SLDFS) boasts several advantages over existing fuzzy set (FS) theories such as Picture fuzzy sets (PFS), spherical fuzzy sets (SFS), and T-spherical fuzzy sets (T-SFS). Notably, SLDFS offers a significantly larger portrayal space for acceptable triplets, enabling it to encompass a wider range of ambiguous and uncertain knowledge data sets. This paper delves into the regularity of spherical linear Diophantine fuzzy graphs (SLDFGs), establishing their fundamental concepts. We provide a geometrical interpretation of SLDFGs within a spherical context and define the operations of complement, union, and join, accompanied by illustrative examples. Additionally, we introduce the novel concept of a spherical linear Diophantine isomorphic fuzzy graph and showcase its application through a social network scenario. Furthermore, we explore how this amplified depiction space can be utilized for the study of various graph theoretical topics. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
13. The energy and edge energy of some Cayley graphs on the abelian group Zn4.
- Author
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Movahedi, Fateme
- Subjects
CAYLEY graphs ,ABELIAN groups ,EIGENVALUES ,GRAPH theory ,GROUP theory - Abstract
Let G = (V,E) be a simple graph such that λ
1 ,..., λn be the eigenvalues of G. The energy of graph G is denoted by E(G) and is defined as E(G) = Σi=1 n |λi |. The edge energy of G is the energy of line graph G. In this paper, we investigate the energy and edge energy for two Cayley graphs on the abelian group Zn 4 , namely, the Sudoku graph and the positional Sudoku graph. Also, we obtain graph energy and edge energy of the complement of these two graphs. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
14. Contribution of acute-phase reaction proteins to the diagnosis and treatment of 2019 novel coronavirus disease (COVID-19)
- Author
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Lu Li and Changzheng Chen
- Subjects
0301 basic medicine ,Male ,Epidemiology ,Gastroenterology ,Severity of Illness Index ,0302 clinical medicine ,complement ,030212 general & internal medicine ,Serum Amyloid A Protein ,biology ,Acute-phase protein ,Complement C4 ,Venous blood ,Complement C3 ,Middle Aged ,Prognosis ,Community-Acquired Infections ,Infectious Diseases ,Female ,medicine.symptom ,Acute phase reaction protein ,Coronavirus Infections ,Adult ,medicine.medical_specialty ,Pneumonia, Viral ,prealbumin ,Asymptomatic ,C-reactive protein ,03 medical and health sciences ,Young Adult ,Internal medicine ,Severity of illness ,medicine ,Humans ,Serum amyloid A ,Pandemics ,Aged ,Original Paper ,business.industry ,Case-control study ,COVID-19 ,serum amyloid A ,Pneumonia ,030104 developmental biology ,Case-Control Studies ,biology.protein ,business ,Acute-Phase Proteins - Abstract
The emergence of 2019 novel coronavirus disease (COVID-19) is currently a global concern. In this study, our goal was to explore the changing expression levels of acute-phase reaction proteins (APRPs) in the serum of COVID-19 patients and to elucidate the immunological characteristics of COVID-19. In the study design, we recruited 72 COVID-19 patients, including 22 cases of mild degree, 38 cases of moderate degree and 12 cases of severe degree. We also recruited 20 patients with community-acquired pneumonia (CAP) and 20 normal control subjects as a comparison. Fasting venous blood was taken to detect the content of complement 3 (C3), complement 4 (C4), C-reactive protein (CRP), serum amyloid A (SAA) and prealbumin (PA). When compared the COVID-19 group with the CAP and normal control groups, respectively, the mean value of CRP and SAA in the COVID-19 group (including mild, moderate and severe patients) had increased significantly (P < 0.01), whereas the mean values of C3, C4 and PA decreased (P < 0.01). For the asymptomatic or mild symptomatic patients with COVID-19, the actual aggravation of disease may be more advanced than the clinical appearances. Meanwhile, the statistical analyses indicated that the development of COVID-19 brought about a significant increase in the content of CRP and SAA (P < 0.01), and a decline in the content of C3, C4 and PA (P < 0.01). These findings suggested that the changes in the level of APRPs could be used as indicators to identify the degree and progression of COVID-19, and the significant changes might demonstrate the aggravation of disease. This study provided a new approach to improve the clinical management plan and prognosis of COVID-19.
- Published
- 2020
15. New biomarkers in SLE: from bench to bedside
- Author
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Paola Migliorini, Ilaria Puxeddu, Riccardo Capecchi, and Federico Pratesi
- Subjects
0301 basic medicine ,Chemokine ,biomarker ,chemokine ,complement ,cytokine ,systemic lupus ,medicine.medical_treatment ,Disease ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Pharmacology (medical) ,B-cell activating factor ,AcademicSubjects/MED00360 ,B cell ,030203 arthritis & rheumatology ,Kidney ,biology ,business.industry ,Complement system ,030104 developmental biology ,Cytokine ,medicine.anatomical_structure ,Supplement Papers ,Immunology ,biology.protein ,Biomarker (medicine) ,business ,Biomarkers - Abstract
Biomarkers may have a diagnostic or monitoring value, or may predict response to therapy or disease course. The aim of this review is to discuss new serum and urinary biomarkers recently proposed for the diagnosis and management of SLE patients. Novel sensitive and specific assays have been proposed to evaluate complement proteins, ‘old’ biomarkers that are still a cornerstone in the management of this disease. Chemokines and lectins have been evaluated as surrogate biomarkers of IFN signature. Other cytokines like the B cell activating factor (BAFF) family cytokines are directly related to perturbations of the B cell compartment as key pathogenetic mechanism of the disease. A large number of urine biomarkers have been proposed, either related to the migration and homing of leukocytes to the kidney or to the local regulation of inflammatory circuits and the survival of renal intrinsic cells. The combination of traditional disease-specific biomarkers and novel serum or urine biomarkers may represent the best choice to correctly classify, stage and treat patients with SLE.
- Published
- 2020
16. A human monoclonal antibody that specifically binds and inhibits the staphylococcal complement inhibitor protein SCIN
- Author
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Kok P. M. van Kessel, Girbe Buist, Herman Groen, Neeltje Kooi, Jan Maarten van Dijl, Goffe S. Elsinga, Hendrik P. J. Bonarius, Hedzer Hoekstra, Francisco Romero Pastrana, Microbes in Health and Disease (MHD), and Translational Immunology Groningen (TRIGR)
- Subjects
0301 basic medicine ,IMMUNE EVASION ,Complement C3-C5 Convertases ,medicine.disease_cause ,C3b ,Epitope ,Virulence factor ,Complement inhibitor ,Catalytic Domain ,complement ,PATHOGEN ,Pathogen ,biology ,Antibodies, Monoclonal ,Staphylococcal Infections ,Antibodies, Bacterial ,GENOME ,Editorial ,Infectious Diseases ,Staphylococcus aureus ,INFECTIONS ,Complement C3b ,EPIDERMOLYSIS-BULLOSA ,Rabbits ,immunotherapy ,Antibody ,Research Paper ,Protein Binding ,Monoclonal antibody ,Microbiology (medical) ,Virulence Factors ,medicine.drug_class ,AUREUS BACTEREMIA ,SCIN ,030106 microbiology ,Immunology ,Virulence ,Microbiology ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,medicine ,Journal Article ,Animals ,Humans ,lcsh:RC109-216 ,Fluorescent Dyes ,Antigens, Bacterial ,STRAINS ,complement pathway ,Complement Inactivating Agents ,030104 developmental biology ,Microscopy, Fluorescence ,biology.protein ,VIRULENCE ,passive immunization ,Parasitology ,RESISTANCE ,RESPONSES - Abstract
Staphylococcus aureus is a serious public health burden causing a wide variety of infections. Earlier detection of such infections could result in faster and more directed therapies that also prevent resistance development. Human monoclonal antibodies (humAbs) are promising tools for diagnosis and therapy owing to their relatively straightforward synthesis, long history of safe clinical use and high target specificity. Here we show that the humAb 6D4, which was obtained from a random screen of B-cells producing antibodies that bind to whole cells of S. aureus, targets the staphylococcal complement inhibitor (SCIN). The epitope recognized by 6D4 was localized to residues 26 to 36 in the N-terminus of SCIN, which overlap with the active site. Accordingly, 6D4 can inhibit SCIN activity as demonstrated through the analysis of C3b deposition on S. aureus cells and complement-induced lysis of rabbit erythrocytes. Importantly, while SCIN is generally regarded as a secreted virulence factor, 6D4 allowed detection of strongly increased SCIN binding to S. aureus cells upon exposure to human serum, relating to the known binding of SCIN to C3 convertases deposited on the staphylococcal cell surface. Lastly, we show that labeling of humAb 6D4 with a near-infrared fluorophore allows one-step detection of SCIN-producing S. aureus cells. Together, our findings show that the newly described humAb 6D4 specifically recognizes S. aureus SCIN, which can potentially be used for detection of human serum-incubated S. aureus strains expressing SCIN.
- Published
- 2018
17. Complement-associated loss of CA2 inhibitory synapses in the demyelinated hippocampus impairs memory
- Author
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Dennis S. W. Lee, Inge Huitinga, Sharon I. de Vries, Naomi Petersen, Jeroen J. G. Geurts, Stefan M. Gold, Jennifer L. Gommerman, M. Alfonso Malpede, Mohit Dubey, Valeria Ramaglia, GJ Schenk, Maarten H. P. Kole, Shanzeh M. Ahmed, Celbiologie, Sub Cell Biology, and Netherlands Institute for Neuroscience (NIN)
- Subjects
Male ,0301 basic medicine ,CA2 Region, Hippocampal ,Complement ,Clinical Neurology ,Hippocampal formation ,Inhibitory postsynaptic potential ,Hippocampus ,Pathology and Forensic Medicine ,Synapse ,Multiple sclerosis ,Cuprizone ,Mice ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,medicine ,Animals ,Humans ,Hippocampus (mythology) ,Aged ,Original Paper ,Microglia ,Chemistry ,Complement C1q ,Middle Aged ,medicine.disease ,Complement system ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Schaffer collateral ,Case-Control Studies ,Synapses ,Neurology (clinical) ,Demyelination ,Neuroscience ,030217 neurology & neurosurgery - Abstract
The complement system is implicated in synapse loss in the MS hippocampus, but the functional consequences of synapse loss remain poorly understood. Here, in post-mortem MS hippocampi with demyelination we find that deposits of the complement component C1q are enriched in the CA2 subfield, are linked to loss of inhibitory synapses and are significantly higher in MS patients with cognitive impairments compared to those with preserved cognitive functions. Using the cuprizone mouse model of demyelination, we corroborated that C1q deposits are highest within the demyelinated dorsal hippocampal CA2 pyramidal layer and co-localized with inhibitory synapses engulfed by microglia/macrophages. In agreement with the loss of inhibitory perisomatic synapses, we found that Schaffer collateral feedforward inhibition but not excitation was impaired in CA2 pyramidal neurons and accompanied by intrinsic changes and a reduced spike output. Finally, consistent with excitability deficits, we show that cuprizone-treated mice exhibit impaired encoding of social memories. Together, our findings identify CA2 as a critical circuit in demyelinated intrahippocampal lesions and memory dysfunctions in MS. Supplementary Information The online version contains supplementary material available at 10.1007/s00401-021-02338-8.
- Published
- 2021
18. Decreased expression levels of complement regulator CD55 contribute to the development of bullous pemphigoid
- Author
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Pei Qiao, Hui Fang, Shuai Shao, Jie Lei, Erle Dang, Hongjiang Qiao, Bing Li, Shengxian Shen, Jieyu Zhang, Yi-Xin Luo, and Gang Wang
- Subjects
0301 basic medicine ,bullous pemphigoid ,Regulator ,medicine.disease_cause ,Autoimmunity ,Pathogenesis ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,medicine ,complement ,skin and connective tissue diseases ,biology ,integumentary system ,ERK1/2 ,business.industry ,autoimmunity ,medicine.disease ,eye diseases ,Complement system ,HaCaT ,030104 developmental biology ,Oncology ,Immunology ,biology.protein ,Bullous pemphigoid ,Antibody ,CD55 ,business ,Research Paper - Abstract
Bullous pemphigoid is a common autoimmune blistering disease of the elderly associated with autoantibody-mediated complement activation, and complement dysregulation is critical for its pathogenesis. As a crucial regulator of the complement system, CD55 has been widely studied in autoimmune diseases. Here, we investigated the involvement of CD55 in bullous pemphigoid, as little is known regarding its role in this disease. We found that CD55 levels were significantly lower in the lesions of patients with bullous pemphigoid (n = 8) compared to those in skin samples from healthy controls (n = 6). Interestingly, CD55 depletion in HaCaT human keratinocytes enhanced autoantibody-mediated complement activation. Moreover, complement activation was blocked by exogenous recombinant CD55 protein in both skin sections and keratinocytes exposed to pathogenic antibodies from patients with bullous pemphigoid. Notably, a significant increase in the expression of TNF-α and IFN-γ, administration of which downregulated CD55 levels in HaCaT cells, was observed in the sera of patients with bullous pemphigoid (n = 38) compared to that in healthy controls (n = 19). We found that ERK1/2 is involved in both TNF-α- and IFN-γ-induced CD55 downregulation. Thus, CD55 deficiency is a crucial factor in bullous pemphigoid pathogenesis, suggesting that increasing CD55 levels may exert a therapeutic effect.
- Published
- 2017
19. Glutathione inhibits antibody and complement-mediated immunologic cell injury via multiple mechanisms
- Author
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Shan Gao, Jianglin Fan, Manabu Niimi, Xin Fang, Yanru Huang, Jian Yao, Honglan Piao, Xiling Zhang, and Zhen Zhang
- Subjects
0301 basic medicine ,Cell lysis ,MAP Kinase Signaling System ,Clinical Biochemistry ,Complement ,p38 ,Complement Membrane Attack Complex ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Immune system ,Antigen ,Mesangial cells ,Isoantibodies ,medicine ,Animals ,lcsh:QH301-705.5 ,Cell damage ,Complement Activation ,Antibody ,Cells, Cultured ,lcsh:R5-920 ,biology ,Kinase ,Organic Chemistry ,Glutathione ,Complement System Proteins ,medicine.disease ,Molecular biology ,Complement system ,Rats ,030104 developmental biology ,lcsh:Biology (General) ,chemistry ,Humoral immunity ,biology.protein ,Rabbits ,lcsh:Medicine (General) ,Research Paper ,Protein Binding - Abstract
Antioxidant glutathione (GSH) plays an important role in the regulation of immunity. However, little is known about its effects on humoral immunity, especially its action on effector molecules like antibody and complement. Given that these molecules contain abundant disulfide bonds, we speculated that GSH might influence the action of these proteins via its thiol function. Using a model of a glomerular mesangial cell (MC) lysis induced by antibodies plus complement, we addressed this hypothesis. Exposure of rat MCs to anti-Thy-1 antibody plus complement or anti-MC rabbit serum caused a complement-dependent cell lysis, which was completely blocked by GSH. Moreover, GSH potently prevented the antibody-mediated agglutination of red blood cells and aggregation of antibody-sensitized microspheres. Further analysis revealed that GSH inhibited antibody binding to antigens and promoted the conversion of the antibodies to its reduced forms. GSH also potently inhibited the formation and deposition of C5b-9 in MCs and suppressed both the classic and alternative complement activation pathway. Lastly, GSH attenuated P38 activation, an oxidative sensitive kinase that partially mediated the antibody- and complement-dependent MC lysis. Depletion of GSH via inhibiting gamma-glutamylcysteine synthetase or xCT transporter augmented P38 activation and sensitized MCs to the cell lysis. Collectively, our results indicate that GSH protects cells from immunological cell damage via mechanisms involving inhibition of antibody binding to the antigens, suppression of complement activation and augmentation of cellular defense mechanism. Our study provides novel mechanistic insights into the actions of GSH in the regulation of immune responses and suggests that GSH might be used to treat certain immune disorders., Grapiical abstract fx1, Highlights • Little information is available regarding the role of GSH on humoral immunity. • GSH inhibited antibody-triggered and complement-mediated immune responses. • GSH interfered with antibody binding to cell surface antigens via its thiol function. • GSH inhibited both the classic and alternative complement activation pathways. • GSH increased cell resistance to immunological injury via inhibition of P38.
- Published
- 2017
20. Blockade of the kallikrein-kinin system reduces endothelial complement activation in vascular inflammation
- Author
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Davalieva, Katarina, Makridakis, Manousos, Vlahou, Antonia, Frantzi, Maria, Boizard, Franck, Moussaoui, Nabila, Lescat, Ophélie, Fedou, Camille, Feuillet, Guylène, Casemayou, Audrey, Neau, Eric, Decatte, Luc, Raaijmakers, Anke, Vayssière, Christophe, Goua, Valérie, Lucas, Charlotte, Benachi, Alexandra, Delmas, Hélène Laurichesse, Allain-Launay, Emma, Boudailliez, Bernard, Simon, Elisabeth, Noel, Catherine, Floch, Corinne, Bourdat-Michel, Guylène, Weingertner, Anne-Sophie, Oury, Jean-François, Baudouin, Véronique, Bory, Jean-Paul, Pietrement, Christine, Fiorenza, Maryse, Kessler, Sylvie, Auriol, Françoise Conte, Marcorelles, Pascale, Collardeau-Frachon, Sophie, Magalhães, Pedro, Batut, Julie, Blader, Patrick, Saulnier Blache, Jean-Sebastien, Allegaert, Karel, Aubard, Yves, Basmaison, Odile, Benevent, Jean-Baptiste, Biquard, Florence, Champion, Gérard, Delbosc, Jean-Marie, Eckart, Philippe, Gaucherand, Pascal, Guigonis, Vincent, Hougas, Blandine, Martin, Alain, Martin, Sophie, Maupin-Hyvonnet, Mariannick, Merveille, Marina, Mousty, Eve, Nobili, François, Taque, Sophie, Latosinska, Agnieszka, Faguer, Stanislas, Beige, Joachim, van der Zanden, Loes, Levtchenko, Elena, Moulos, Panogiotis, Lounis, Nadia, Conte-Auriol, Françoise, Olsen, Henning, Hindryckx, An, De Catte, Luc, Vayssieres, Christophe, Sartor, Agnes, Groussolles, Marion, Plard, Christelle, Guerby, Paul, Connan, Laure, Morin, Mathieu, Simon, Elizabeth, Breaud, Jean, Saliou, Anne-Hélène, De Parscau, Loic, Jay, Nadine, Germouty, Isabelle, Le Bouar, Gwenaelle, Ryckewaert, Amelie, Manca-Pellissier, Marie-Christine, Merrot, Thierry, Laurichesse, Helene, Gallot, Denis, Bessenay, Lucie, Bidat, Laurent, Boize, Philippe, Winer, Norbert, Allain-Launey, Emma, Le Vaillant, Claudine, Prieur, Fabienne, Lavocat, Marie-Pierre, Coatleven, Frederic, Debromez, Eric, Harembat, Jérôme, Llanas, Brigitte, Favre, Romain, Moog, Raphael, Zaloszyc, Ariane, Massardier, Jérôme, DEMEDE, Delphine, Perrotin, Franck, Cloarec, Sylvie, Vequeau-Goua, Valérie, Descombes, Emmanuelle, Boulot, Pierre, Morin, Denis, Fuchs, Florent, Tenenbaum, Julie, Ville, Yves, Blanc, Thomas, Heidet, Laurence, Paris, Anne, Dobremez, Eric, Froute, Marie-Françoise, Gondry, Jean, Muszynski, Charles, Haraux, Elodie, Lobelle, Fabienne, Chevreau, Julien, Rosenblatt, Jonathan, Baudoin, Véronique, Deschenes, Georges, Guigue, Virginie, Amblard, Florence, Bourdat-Michel, Guylhène, Wühl, Elke, Schaefer, Franz, Elsässer, Michael, Persico, Nicola, Rossi, Federica, Manzoni, Gianantonio, De Marco, Erika, Montini, Giovanni, Capone, Valentina, Caforio, Leonardo, Zaccara, Antonio, Innocenzi, Michele, Bagolan, Pietro, Capozza, Nicola, Castagnetti, Marco, Mancini, Mariangela, Oepkes, Dick, van Scheltema, Phebe Adama, Feitz, Wout, Kortmann, Barbara, Schreuder, Michiel, Pawłowska, Barbara, Fortecka-Piestrzeniewicz, Katarzyna, Olejniczak, Dariusz, Ariceta, Gema, Arevalo, Silvia, RODO, Carlota, Fossum, Magdalena, Lindgren, Peter, Parvex, Paloma, Chehade, Hassib, He, Tianlin, Metzger, Jochen, Mullen, William, Mischak, Harald, Zürbig, Petra, Jankowski, Vera, Buffin-Meyer, Bénédicte, Tkaczyk, Marcin, Stańczyk, Małgorzata, Breuil, Benjamin, Siwy, Justyna, Szaflik, Krzysztof, Talar, Tomasz, Wojtera, Justyna, Krzeszowski, Waldemar, Decramer, Stéphane, Lopatko Fagerström, Ingrid, Ståhl, Anne-lie, Mossberg, Maria, Tati, Ramesh, Kristoffersson, Ann-Charlotte, Kahn, Robin, Bascands, Jean-Loup, Klein, Julie, Schanstra, Joost, Segelmark, Mårten, Karpman, Diana, Department of Pediatrics [Lund, Sweden] (Clinical Sciences), Lund University [Lund], Wallenberg Center for Molecular Medicine [Lund, Sweden], Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Nephrology [Lund, Sweden] (Clinical Sciences Lund), Department of Medical and Health Sciences [Lund, Sweden], Linköping University (LIU), The study was supported by The Swedish Research Council (K2015-99X-22877-01-6 and 2017-01920), The Knut and Alice Wallenberg Foundation (Wallenberg Clinical Scholar 2015.0320), The Torsten Söderberg Foundation, Skåne Centre of Excellence in Health, IngaBritt och Arne Lundberg's Research Foundation, Crown Princess Lovisa's Society for Child Care, Region Skåne and The Konung Gustaf V:s 80-årsfond (all to DK). Alfred Österlund Foundation (to LMFLL and RK). TheWallenberg Center forMolecular Medicine, The Swedish RheumatismAssociation, The Anna-Greta Crafoord Foundation, Greta and Johan Kock's Foundation, the Samariten Foundation, Fanny Ekdahl foundation, the Jerring foundation and the Thelma Zoegas Foundation (to RK). JPS and JK were partially funded by a grant from the 'Fondation pour la Recherche Médicale' (grant number DEQ20170336759). MS was funded by The Swedish Rheumatism Association and the Ingrid Asp Foundation., Schanstra, Joost, Macedonian Academy of Sciences and Arts [Skopje, North Macedonia] (MASA), Biomedical Research Foundation of the Academy of Athens (BRFAA), Mosaiques Diagnostics & Therapeutics (MOSAIQUES DIAGNOSTICS & THERAPEUTICS), Mosaiques Diagnostics & Therapeutics AG, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], KfH-Nierenzentrum und Klinikum St. Georg, Nephrologie, Leipzig, Radboud University Medical Center [Nijmegen], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), HybridStat Predictive Analytics [Athens, Greece], Centre d'investigation clinique de Toulouse (CIC 1436), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospitals Leuven [Leuven], Heidelberg University Hospital [Heidelberg], University of Milan, Mosaiques Diagnostics GmbH [Hanovre, Allemagne], Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany] (UKA), RWTH Aachen University, Polish Mother’s Memorial Hospital Research Institute [Lodz] (ICZMP), Mosaiques Diagnostics GmbH [Hannover, Germany], Mosaiques Diagnostics and Therapeutics AG [Hannover, Germany], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), and Université Fédérale Toulouse Midi-Pyrénées
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0301 basic medicine ,Male ,Research paper ,Mouse ,Kallikrein-Kinin System ,[SDV]Life Sciences [q-bio] ,Pharmacology ,Kidney ,Mice ,0302 clinical medicine ,Glomerular C3 deposition ,Cell-Derived Microparticles ,Complement Activation ,Cells, Cultured ,Chemistry ,General Medicine ,Kinin ,Middle Aged ,Receptor antagonist ,3. Good health ,[SDV] Life Sciences [q-bio] ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,medicine.symptom ,Endothelial microvesicles ,Complement C1 Inhibitor Protein ,Protein Binding ,Vasculitis ,Complement ,Radiology, Nuclear Medicine and Medical Imaging ,Adult ,Endothelium ,medicine.drug_class ,Inflammation ,Bradykinin ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Classical complement pathway ,medicine ,Animals ,Humans ,Aged ,Endothelial Cells ,Biological Transport ,Complement System Proteins ,Microvesicles ,Complement system ,Disease Models, Animal ,030104 developmental biology ,Immunoglobulin G ,Endothelium, Vascular ,Radiologi och bildbehandling - Abstract
Background: The complement and kallikrein-kinin systems (KKS) are activated during vascular inflammation. The aim of this study was to investigate if blockade of the KKS can affect complement activation on the endothelium during inflammation. Methods: Complement deposition on endothelial microvesicles was assayed in vasculitis patient plasma samples and controls. Plasma was perfused over glomerular endothelial cells and complement deposition assayed by flow cytometry. The effect of the kinin system was assessed using kinin receptor antagonists and C1-inhibitor. The in vivo effect was assessed in kidney sections from mice with nephrotoxic serum-induced glomerulonephritis treated with a kinin receptor antagonist. Findings: Vasculitis patient plasma had significantly more C3- and C9-positive endothelial microvesicles than controls. Perfusion of patient acute-phase plasma samples over glomerular endothelial cells induced the release of significantly more complement-positive microvesicles, in comparison to remission or control plasma. Complement activation on endothelial microvesicles was reduced by kinin B1- and B2-receptor antagonists or by C1-inhibitor (the main inhibitor of the classical pathway and the KKS). Likewise, perfusion of glomerular endothelial cells with C1-inhibitor-depleted plasma induced the release of complement-positive microvesicles, which was significantly reduced by kinin-receptor antagonists or C1-inhibitor. Mice with nephrotoxic serum-induced glomerulonephritis exhibited significantly reduced glomerular C3 deposition when treated with a B1-receptor antagonist. Interpretation: Excessive complement deposition on the endothelium will promote endothelial injury and the release of endothelial microvesicles. This study demonstrates that blockade of the KKS can reduce complement activation and thereby the inflammatory response on the endothelium. (C) 2019 The Authors. Published by Elsevier B.V. Funding Agencies|Swedish Research CouncilSwedish Research Council [K2015-99X-22877-01-6, 2017-01920]; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation [2015.0320]; Torsten Soderberg Foundation; Skane Centre of Excellence in Health; Crown Princess Lovisas Society for Child Care; Konung Gustaf V:s 80-arsfond; Alfred Osterlund Foundation; Wallenberg Center for Molecular Medicine; Swedish Rheumatism Association; Anna-Greta Crafoord Foundation; Greta and Johan Kocks Foundation; Samariten Foundation; Fanny Ekdahl foundation; Jerring foundation; Fondation pour la Recherche MedicaleFondation pour la Recherche Medicale [DEQ20170336759]; Ingrid Asp Foundation; IngaBritt och Arne Lundbergs Research Foundation; Region Skane; Thelma Zoegas Foundation
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- 2019
21. Higher-order structure and proteoforms of co-occurring C4b-binding protein assemblies in human serum
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Kadavá, Tereza, Hevler, Johannes F, Kalaidopoulou Nteak, Sofia, Yin, Victor C, Strasser, Juergen, Preiner, Johannes, and Heck, Albert JR
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- 2024
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22. Independent events and their complements.
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Crispim, Carolina Martins, Mizuno, Gabriel Perez, and Pizzinga, Adrian
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NUMERICAL calculations ,NUMERICAL analysis ,PROBABILITY theory ,MATHEMATICAL statistics ,MATHEMATICAL induction - Abstract
Take a family of independent events. If some of these events, or all of them, are replaced by their complements, then independence still holds. This fact, which is agreed upon by the members of the statistical/probability communities, is tremendously well known, is fairly intuitive and has always been frequently used for easing probability calculations and allowing important developments in probability theory. However, can this result be proven without advanced elements from probability theory, such as independent σ-fields and related results? This paper aims primarily to fill this possible gap. Two elementary proofs that require only introductory probability content are given in detail and compared with the 'technical' proof found in books on advanced probability theory. A discussion regarding how these proofs could be included in regular probability courses is also included in the survey. [ABSTRACT FROM AUTHOR]
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- 2021
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23. Complement Activation in Arterial and Venous Thrombosis is Mediated by Plasmin
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Bethany L. Walton, Kimberley Foley, Maria M. Aleman, Edward M. Conway, Jonathan H. Foley, Alisa S. Wolberg, Micaela Harrasser, Victor Lei, and Alice M. O'Byrne
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0301 basic medicine ,Plasmin ,medicine.medical_treatment ,PPACK, Phe-Pro-Arg-chloromethylketone ,Complement Pathway, Alternative ,lcsh:Medicine ,Complement C3-C5 Convertases ,030204 cardiovascular system & hematology ,tPA, tissue-type plasminogen activator ,0302 clinical medicine ,Leukocytes ,Fibrinolysin ,Complement Activation ,Complement component 5 ,IL-8, interleukin-8 ,TAT, thrombin antithrombin ,lcsh:R5-920 ,Fibrinolysis ,Thrombin ,Complement C5 ,Complement C4 ,hemic and immune systems ,General Medicine ,Complement C3 ,Complement C2 ,Complement C9 ,3. Good health ,Complement C6 ,Venous thrombosis ,Coagulation ,Complement C3b ,MAC, membrane attack complex ,lcsh:Medicine (General) ,FDP, fibrin degradation product ,medicine.drug ,Research Paper ,circulatory and respiratory physiology ,VWF, von Willebrand factor ,NETs, neutrophil extracellular traps ,Complement Activating Enzymes ,Complement ,chemical and pharmacologic phenomena ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,IVC, inferior vena cava ,medicine ,R751, arginine 751 ,Humans ,Thrombus ,MCP1-1, monocyte chemoattracant protein-1 ,business.industry ,lcsh:R ,FeCl3, ferric chloride ,Thrombosis ,medicine.disease ,Complement system ,030104 developmental biology ,VFKck, Val-Phe-Lys-chloromethylketone ,Immunology ,business ,Complement membrane attack complex ,PAR1, protease activated receptor 1 - Abstract
Thrombus formation leading to vaso-occlusive events is a major cause of death, and involves complex interactions between coagulation, fibrinolytic and innate immune systems. Leukocyte recruitment is a key step, mediated partly by chemotactic complement activation factors C3a and C5a. However, mechanisms mediating C3a/C5a generation during thrombosis have not been studied. In a murine venous thrombosis model, levels of thrombin–antithrombin complexes poorly correlated with C3a and C5a, excluding a central role for thrombin in C3a/C5a production. However, clot weight strongly correlated with C5a, suggesting processes triggered during thrombosis promote C5a generation. Since thrombosis elicits fibrinolysis, we hypothesized that plasmin activates C5 during thrombosis. In vitro, the catalytic efficiency of plasmin-mediated C5a generation greatly exceeded that of thrombin or factor Xa, but was similar to the recognized complement C5 convertases. Plasmin-activated C5 yielded a functional membrane attack complex (MAC). In an arterial thrombosis model, plasminogen activator administration increased C5a levels. Overall, these findings suggest plasmin bridges thrombosis and the immune response by liberating C5a and inducing MAC assembly. These new insights may lead to the development of strategies to limit thrombus formation and/or enhance resolution., Highlights • Thrombin is not a major direct contributor to C5a generation during venous thrombosis in mice. • Plasmin, a protease generated in response to thrombin generation and fibrin deposition, efficiently cleaves C5 to C5a. • In an arterial thrombosis model, administration of a plasminogen activator augments C5a plasma levels. • Plasmin participates in immunothrombosis, liberating chemotactic C5a and inducing assembly of the procoagulant C5b-9. Venous and arterial thrombosis are major causes of death and morbidity. Leukocytes are early and active participants in thrombus formation, recruited partly by complement factor C5a. We examined how C5a is generated in the setting of thrombosis. In venous thrombosis in mice, we show that thrombin, a key clot-promoting enzyme, is not a major contributor to C5a generation. Rather, plasmin, a fibrinolytic enzyme formed in response to thrombin generation and clot formation, efficiently generates C5a. The findings were validated in an arterial thrombosis model in mice. These insights may be valuable in developing therapeutic strategies to limit thrombus formation.
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- 2016
24. The expression of C1 inhibitor (C1INH) in macrophages is upregulated by retinal pigment epithelial cells - implication in subretinal immune privilege in the aging eye
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Heping Xu, Jiawu Zhao, Chang Luo, and Mei Chen
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0301 basic medicine ,Aging ,Complement ,Inflammation ,retinal pigment epithelial cells ,Retinal Pigment Epithelium ,03 medical and health sciences ,Complement inhibitor ,Mice ,0302 clinical medicine ,Immune privilege ,medicine ,Macrophage ,Animals ,complement ,Cells, Cultured ,Subretinal immune privilege ,Retinal pigment epithelium ,Chemistry ,Tumor Necrosis Factor-alpha ,Macrophages ,aging ,subretinal immune privilege ,Epithelial Cells ,Cell Biology ,Photoreceptor outer segment ,Coculture Techniques ,eye diseases ,Complement system ,Cell biology ,Up-Regulation ,Ageing ,030104 developmental biology ,medicine.anatomical_structure ,Retinal pigment epithelial cells ,030220 oncology & carcinogenesis ,Alternative complement pathway ,Cattle ,sense organs ,medicine.symptom ,Complement C1 Inhibitor Protein ,Research Paper ,Photoreceptor Cells, Vertebrate - Abstract
Age-related para-inflammation in the retina-choroidal interface is featured by low-levels of complement activation and subretinal macrophage accumulation. This study aimed to understand how complement expression in macrophages is regulated by retinal pigment epithelium (RPE). Bone marrow-derived macrophages (BMDMs) and RPE cells were cultured from 8-10 weeks old C57BL/6J mice. The BMDMs were co-cultured with normal RPE, or oxidized photoreceptor outer segment (oxPOS) or TNF-α pre-treated RPE, or apoptotic RPE, or RPE-choroid eyecups. Macrophages were then isolated and processed for real-time RT-PCR. The expression of complement inhibitor C1INH in BMDMs was significantly upregulated by RPE and RPE-choroid eyecups. The eyecups also upregulated CFH, CD59a, and Crry in BMDMs. oxPOS pre-treated RPE upregulated C1qb but down-regulated C3 expression in BMDMs. TNF-α pre-treated RPE enhanced C1INH and CFB expression. When BMDMs were treated with apoptotic RPE, the expression of C1qb, CFH, and CD59a was reduced, whereas the expression of C3, CFB and C1INH was increased. Our results suggest that RPE can modulate macrophages complement expression at the retina-choroidal interface even under aging or oxidative conditions. However, during inflammation, they may promote the alternative pathway of complement activation through down-regulating CFH and CD59a and upregulating CFB and C3.
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- 2018
25. Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome
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Johan Høgset Jansen, Camilla Schjalm, Ola Didrik Saugstad, Paal H.H. Lindenskov, Magnus Berglund, Rønnaug Solberg, Albert Castellheim, Terje Espevik, Per H. Nilsson, Tom Eirik Mollnes, Patrik Strömberg, Andreas Barratt-Due, Anub Mathew Thomas, Corinna Lau, and Runa Rørtveit
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0301 basic medicine ,Meconium ,Swine ,Complement ,Lipopolysaccharide Receptors ,Inflammation ,Pharmacology ,Systemic inflammation ,03 medical and health sciences ,Random Allocation ,0302 clinical medicine ,In vivo ,Toll-like receptor ,medicine ,Meconium aspiration syndrome ,Animals ,Humans ,Complement Activation ,C5 ,Innate immunity ,Original Paper ,biology ,business.industry ,VDP::Medical disciplines: 700::Clinical medical disciplines: 750 ,VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750 ,Complement C5 ,medicine.disease ,Complement system ,Meconium Aspiration Syndrome ,030104 developmental biology ,Animals, Newborn ,Myeloperoxidase ,Pediatrics, Perinatology and Child Health ,biology.protein ,Cytokines ,medicine.symptom ,business ,CD14 ,Ex vivo ,030215 immunology ,Developmental Biology - Abstract
Background: Meconium aspiration syndrome (MAS) is a severe lung condition affecting newborns and it can lead to a systemic inflammatory response. We previously documented complement activation and cytokine release in a piglet MAS model. Additionally, we showed ex vivo that meconium-induced inflammation was dependent on complement and Toll-like receptors. Objectives: To assess the efficacy of the combined inhibition of complement (C5) and CD14 on systemic inflammation induced in a forceful piglet MAS model. Methods: Thirty piglets were randomly allocated to a treatment group receiving the C5-inhibitor SOBI002 and anti-CD14 (n = 15) and a nontreated control group (n = 15). MAS was induced by intratracheal meconium instillation, and the piglets were observed for 5 h. Complement, cytokines, and myeloperoxidase (MPO) were measured by ELISA. Results: SOBI002 ablated C5 activity and the formation of the terminal complement complex in vivo. The combined inhibition attenuated the inflammasome cytokines IL-1β and IL-6 by 60 (p = 0.029) and 44% (p = 0.01), respectively, and also MPO activity in the bronchoalveolar fluid by 42% (p = 0.017). Ex vivo experiments in human blood revealed that the combined regimen attenuated meconium-induced MPO release by 64% (p = 0.008), but there was only a negligible effect with single inhibition, indicating a synergic cross-talk between the key molecules C5 and CD14. Conclusion: Combined inhibition of C5 and CD14 attenuates meconium-induced inflammation in vivo and this could become a future therapeutic regimen for MAS. © 2018 The Author(s) Published by S. Karger AG, Basel. This article is licensed under the Creative Commons AttributionNonCommercial-NoDerivatives 4.0 International License (CC BYNC-ND) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.
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- 2018
26. The complement of the complementary prism.
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Al-Addasi, Salah
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DIAMETER ,PRISMS - Abstract
In this paper we investigate some properties of the complement GG of the complementary prism of a graph G of order n. We show that GG is connected except for n = 1, with diameter 2 when n ≥ 3. Furthermore, we prove that for n = 3, the graph GG is Hamiltonian and self-centered, but it is never diametrical. Finally, we characterize GG that are self-complementary, divisor graphs, regular and Eulerian. [ABSTRACT FROM AUTHOR]
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- 2022
27. Novel Concepts in Picture Fuzzy Graphs With an Application.
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CHANG WAN, FEI DENG, SHITAO LI, KACPRZYK, JANUSZ, and RASHMANLOU, HOSSEIN
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FUZZY graphs ,ISOMORPHISM (Mathematics) ,SOCIAL institutions ,SOCIAL structure ,POLITICAL science ,PICTURES - Abstract
Vague graphs (VGs) play an important role in various fields such as computer science, psychology, medicine, political science, etc. and are used to effectively and efficiently find proper people in an organization or social institution. Therefore, in this paper, for the first time, we define the concept of a vague picture fuzzy graph (VPFG) and examine its properties. Likewise, the concepts of a complete-VPFG and a strong- VPFGs are introduced. First, we present several kinds of operations to the VPFGs and then give various products of the VPFGs. New terms such as the order and size, path, busy value, neighborhood degree, isomorphism, and complement of the VPFG are defined. Finally, an application of the VPFG to find the most effective person in a hospital is shown. [ABSTRACT FROM AUTHOR]
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- 2023
28. Mast Cells and Basophils in IgE-Independent Anaphylaxis.
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Pałgan, Krzysztof
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MAST cells ,ANAPHYLAXIS ,BASOPHILS ,ALLERGIES - Abstract
Anaphylaxis is a life-threatening or even fatal systemic hypersensitivity reaction. The incidence of anaphylaxis has risen at an alarming rate in the past decades in the majority of countries. Generally, the most common causes of severe or fatal anaphylaxis are medication, foods and Hymenoptera venoms. Anaphylactic reactions are characterized by the activation of mast cells and basophils and the release of mediators. These cells express a variety of receptors that enable them to respond to a wide range of stimulants. Most studies of anaphylaxis focus on IgE-dependent reactions. The mast cell has long been regarded as the main effector cell involved in IgE-mediated anaphylaxis. This paper reviews IgE-independent anaphylaxis, with special emphasis on mast cells, basophils, anaphylactic mediators, risk factors, triggers, and management. [ABSTRACT FROM AUTHOR]
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- 2023
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29. Results on soft graphs and soft multigraphs with application in controlling urban traffic flows.
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Baghernejad, M. and Borzooei, R. A.
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CITY traffic ,TRAFFIC flow ,TRAFFIC engineering ,MULTIGRAPH - Abstract
In this paper, first we introduce the notions of size, order, and degree of vertices and edges in a soft graph, and we give some examples for a better understanding of these concepts. Then, we define the fundamental concepts of the adjacency matrix of soft graphs, complement of soft graphs, and regularity based on the degree of vertices of soft graphs, and we investigate some related results. Moreover, we introduce the concept of soft multiset and soft multigraph and define the notions of union, intersection, complement, and sum, and then we investigate the relations among them. Finally, we give an application of soft graphs in controlling urban traffic flows. [ABSTRACT FROM AUTHOR]
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- 2023
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30. C5a Increases the Injury to Primary Neurons Elicited by Fibrillar Amyloid Beta
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Michael X. Hernandez, Eric Nguyen, Andrea J. Tenner, Pouya Namiranian, and Maria I. Fonseca
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0301 basic medicine ,Time Factors ,primary neurons ,Mice ,0302 clinical medicine ,complement ,Cells, Cultured ,Cerebral Cortex ,Mice, Knockout ,Neurons ,biology ,Microglia ,Chemistry ,Glutamate Decarboxylase ,General Neuroscience ,Neurodegeneration ,neurodegeneration ,amyloid ,medicine.anatomical_structure ,Cerebral cortex ,Microtubule-Associated Proteins ,medicine.medical_specialty ,C5a ,Amyloid ,Amyloid beta ,Central nervous system ,Complement C5a ,Peptides, Cyclic ,Proinflammatory cytokine ,lcsh:RC321-571 ,03 medical and health sciences ,Internal medicine ,medicine ,Animals ,Humans ,Receptor, Anaphylatoxin C5a ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Original Paper ,Amyloid beta-Peptides ,Dose-Response Relationship, Drug ,Antagonist ,medicine.disease ,Embryo, Mammalian ,Peptide Fragments ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,C5aR1 ,Gene Expression Regulation ,Vesicular Glutamate Transport Protein 1 ,biology.protein ,Neurology (clinical) ,030217 neurology & neurosurgery - Abstract
C5aR1, the proinflammatory receptor for C5a, is expressed in the central nervous system on microglia, endothelial cells, and neurons. Previous work demonstrated that the C5aR1 antagonist, PMX205, decreased amyloid pathology and suppressed cognitive deficits in two Alzheimer's Disease (AD) mouse models. However, the cellular mechanisms of this protection have not been definitively demonstrated. Here, primary cultured mouse neurons treated with exogenous C5a show reproducible loss of MAP-2 staining in a dose-dependent manner within 24 hr of treatment, indicative of injury to neurons. This injury is prevented by the C5aR1 antagonist PMX53, a close analog of PMX205. Furthermore, primary neurons derived from C5aR1 null mice exhibited no MAP-2 loss after exposure to the highest concentration of C5a tested. Primary mouse neurons treated with both 100 nM C5a and 5 µM fibrillar amyloid beta (fAβ), to model what occurs in the AD brain, showed increased MAP-2 loss relative to either C5a or fAβ alone. Blocking C5aR1 with PMX53 (100 nM) blocked the loss of MAP2 in these primary neurons to the level seen with fAβ alone. Similar experiments with primary neurons derived from C5aR1 null mice showed a loss of MAP-2 due to fAβ treatment. However, the addition of C5a to the cultures did not enhance the loss of MAP-2 and the addition of PMX53 to the cultures did not change the MAP-2 loss in response to fAβ. Thus, at least part of the beneficial effects of C5aR1 antagonist in AD mouse models may be due to protection of neurons from the toxic effects of C5a.
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- 2017
31. Multi-battle contests over complementary battlefields
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Stephenson, Daniel
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- 2024
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32. Control of complement-induced inflammatory responses to SARS-CoV-2 infection by anti-SARS-CoV-2 antibodies
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Bermejo-Jambrina, Marta, van der Donk, Lieve EH, van Hamme, John L, Wilflingseder, Doris, de Bree, Godelieve, Prins, Maria, de Jong, Menno, Nieuwkerk, Pythia, van Gils, Marit J, Kootstra, Neeltje A, and Geijtenbeek, Teunis BH
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- 2024
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33. Low pH impairs complement-dependent cytotoxicity against IgG-coated target cells
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Antonela Merlotti, Pehuén Pereyra Gerber, Ezequiel Dantas, Matias Ostrowski, Jorge Geffner, Augusto Varese, Juan Sabatté, and Fernando Erra Díaz
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0301 basic medicine ,ACIDOSIS ,CIENCIAS MÉDICAS Y DE LA SALUD ,medicine.drug_class ,PH ,Inmunología ,Monoclonal antibody ,Peripheral blood mononuclear cell ,COMPLEMENT ,03 medical and health sciences ,Immune system ,rituximab ,medicine ,cancer ,Humans ,complement ,RITUXIMAB ,Cytotoxicity ,business.industry ,pH ,Antibody-Dependent Cell Cytotoxicity ,purl.org/becyt/ford/3.1 [https] ,Complement System Proteins ,Hydrogen-Ion Concentration ,Virology ,Molecular biology ,Burkitt Lymphoma ,CANCER ,Complement-dependent cytotoxicity ,Complement system ,Medicina Básica ,030104 developmental biology ,Oncology ,Cell culture ,Immunoglobulin G ,Rituximab ,purl.org/becyt/ford/3 [https] ,acidosis ,business ,medicine.drug ,Research Paper - Abstract
Local acidosis is a common feature of allergic, vascular, autoimmune, and cancer diseases. However, few studies have addressed the effect of extracellular pH on the immune response. Here, we analyzed whether low pH could modulate complementdependent cytotoxicity (CDC) against IgG-coated cells. Using human serum as a complement source, we found that extracellular pH values of 5.5 and 6.0 strongly inhibit CDC against either B lymphoblast cell lines coated with the chimeric anti-CD20 mAb rituximab or PBMCs coated with the humanized anti-CD52 mAb alemtuzumab. Suppression of CDC by low pH was observed either in cells suspended in culture medium or in whole blood assays. Interestingly, not only CDC against IgG-coated cells, but also the activation of the complement system induced by the alternative and lectin pathways was prevented by low pH. Tumor-targeting mAbs represent one of the most successful tools for cancer therapy, however, the use of mAb monotherapy has only modest effects on solid tumors. Our present results suggest that severe acidosis, a hallmark of solid tumors, might impair complement-mediated tumor destruction directed by mAb. Fil: Dantas, Ezequiel Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Erra Diaz, Fernando Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Pereyra Gerber, Federico Pehuén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Merlotti Ippólito, Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Varese, Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Ostrowski, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Sabatte, Juan Atilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Geffner, Jorge Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
- Published
- 2016
34. BOUNDS ON THE GLOBAL DOUBLE ROMAN DOMINATION NUMBER IN GRAPHS.
- Author
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GUOLIANG HAO, SHOULIU WEI, SHEIKHOLESLAMI, SEYED MAHMOUD, and XIAODAN CHEN
- Subjects
- *
DOMINATING set - Abstract
Let G be a simple graph of order n and let γgdR(G) be the global double Roman domination number of G. In this paper, we give some upper bounds on the global double Roman domination number of G. In particular, we completely characterize the graph G with γgdR(G) = 2n-2 and γgdR(G) = 2n - 3. Our results answer a question posed by Shao et al. (2019). [ABSTRACT FROM AUTHOR]
- Published
- 2024
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35. Are software automation and teleworker substitutes? Preliminary evidence from Japan.
- Author
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Baldwin, Richard and Okubo, Toshihiro
- Subjects
AUTOMATION software ,COVID-19 pandemic ,SERVICE industries ,TELECOMMUTING ,ARTIFICIAL intelligence ,OFFICES - Abstract
Digital technology is reshaping workplaces by enabling spatial separation of offices, known as telework, or remote intelligence (RI) and by facilitating automation of service sector tasks via artificial intelligence (AI). This paper is the first attempt to empirically investigate whether AI and RI are complements or substitutes in the service sector. It uses a worker‐level panel of surveys collected from around 10,000 workers from pre‐COVID‐19 pandemic to late 2022. We find preliminary evidence that suggests that AI and RI are complements rather than substitutes. The evidence comes first from the positive correlation of investments in AI‐promoting and RI‐promoting software at the firm and worker level, and second from the positive correlation of workers' expectations regarding telework and software automation. The evidence is far from definitive but suggests that the complement‐substitution question is a fruitful line for future research. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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36. Dendritic spine loss in epileptogenic Type II focal cortical dysplasia: Role of enhanced classical complement pathway activation.
- Author
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Rossini, Laura, De Santis, Dalia, Cecchini, Erica, Cagnoli, Cinzia, Maderna, Emanuela, Cartelli, Daniele, Morgan, Bryan Paul, Torvell, Megan, Spreafico, Roberto, di Giacomo, Roberta, Tassi, Laura, de Curtis, Marco, and Garbelli, Rita
- Subjects
FOCAL cortical dysplasia ,DENDRITIC spines ,DYSPLASIA ,COMPLEMENT activation ,HIPPOCAMPAL sclerosis ,TEMPORAL lobe epilepsy ,PARTIAL epilepsy - Abstract
Dendritic spines are the postsynaptic sites for most excitatory glutamatergic synapses. We previously demonstrated a severe spine loss and synaptic reorganization in human neocortices presenting Type II focal cortical dysplasia (FCD), a developmental malformation and frequent cause of drug‐resistant focal epilepsy. We extend the findings, investigating the potential role of complement components C1q and C3 in synaptic pruning imbalance. Data from Type II FCD were compared with those obtained in focal epilepsies with different etiologies. Neocortical tissues were collected from 20 subjects, mainly adults with a mean age at surgery of 31 years, admitted to epilepsy surgery with a neuropathological diagnosis of: cryptogenic, temporal lobe epilepsy with hippocampal sclerosis, and Type IIa/b FCD. Dendritic spine density quantitation, evaluated in a previous paper using Golgi impregnation, was available in a subgroup. Immunohistochemistry, in situ hybridization, electron microscopy, and organotypic cultures were utilized to study complement/microglial activation patterns. FCD Type II samples presenting dendritic spine loss were characterized by an activation of the classical complement pathway and microglial reactivity. In the same samples, a close relationship between microglial cells and dendritic segments/synapses was found. These features were consistently observed in Type IIb FCD and in 1 of 3 Type IIa cases. In other patient groups and in perilesional areas outside the dysplasia, not presenting spine loss, these features were not observed. In vitro treatment with complement proteins of organotypic slices of cortical tissue with no sign of FCD induced a reduction in dendritic spine density. These data suggest that dysregulation of the complement system plays a role in microglia‐mediated spine loss. This mechanism, known to be involved in the removal of redundant synapses during development, is likely reactivated in Type II FCD, particularly in Type IIb; local treatment with anticomplement drugs could in principle modify the course of disease in these patients. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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37. A CD21 low phenotype, with no evidence of autoantibodies to complement proteins, is consistent with a poor prognosis in CLL
- Author
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Kevin J. Marchbank, Rachel Jones, Chris Pepper, Christopher Fegan, Rachael Watson, and Eva-Marie Nichols
- Subjects
Male ,Time Factors ,Chronic lymphocytic leukemia ,CD38 ,immune system diseases ,hemic and lymphatic diseases ,Medicine ,complement ,Aged, 80 and over ,B-Lymphocytes ,B cell ,Membrane Glycoproteins ,ZAP-70 Protein-Tyrosine Kinase ,ZAP70 ,breakpoint cluster region ,hemic and immune systems ,Middle Aged ,Prognosis ,medicine.anatomical_structure ,Phenotype ,Oncology ,Female ,IGHV@ ,CD79 Antigens ,Research Paper ,Adult ,Genes, Immunoglobulin Heavy Chain ,Down-Regulation ,Receptors, Antigen, B-Cell ,chemical and pharmacologic phenomena ,Biomarkers, Tumor ,Humans ,CD21 ,Phosphotyrosine ,Aged ,Autoantibodies ,business.industry ,Autoantibody ,Complement System Proteins ,poor prognosis ,medicine.disease ,ADP-ribosyl Cyclase 1 ,Leukemia, Lymphocytic, Chronic, B-Cell ,Survival Analysis ,Complement system ,Case-Control Studies ,Immunology ,Mutation ,Receptors, Complement 3d ,business ,CLL - Abstract
B-cell chronic lymphocytic leukemia (CLL) is characterized by differential BCR\ud signaling and autoimmune complications. Complement modulates B-cell function\ud via C3d and CD21 cross-linked to the B-cell receptor (BCR). We hypothesized that\ud CD21 contributes to BCR signaling and participates in the autoimmunity associated\ud with CLL. We analyzed CD21 expression on 106 CLL patient samples and matched\ud serum from 50 patients for the presence of soluble CD21 and autoantibodies to CR2,\ud CR1, MCP and FH. CD21 expression on CLL B-cells was significantly lower than that\ud expressed on B-cells from age-matched controls (P < 0.0001) and was inversely\ud correlated with soluble CD21 (r2 = –0.41). We found no evidence of autoantibody to\ud any complement regulator. Low CD21 expression correlated to prognostic subsets\ud of CLL patients, i.e. cases with unmutated IGHV genes (P = 0.0006), high CD38\ud (P = 0.02) and high ZAP70 expression (P = 0.0017). Low CD21 expression was\ud inversely correlated to the levels of phosphotyrosine induced in CLL cells following\ud BCR ligation with αIgM (r2=–0.21). Importantly, lower CD21 expression was also\ud predictive for reduced overall survival (P = 0.005; HR = 2.7). In conclusion, we\ud showed that reduced expression of CD21 on CLL B-cells appears functionally relevant\ud and was associated with poor clinical outcomes.
- Published
- 2015
38. Phenotypical Differences between Leishmania (Leishmania) amazonensis PH8 and LV79 Strains May Impact Survival in Mammal Host and in Phlebotomine Sand Flies.
- Author
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Tano, Fabia Tomie, Telleria, Erich Loza, Rêgo, Felipe Dutra, Coelho, Felipe Soares, de Rezende, Eloiza, Soares, Rodrigo Pedro, Traub-Cseko, Yara Maria, and Stolf, Beatriz Simonsen
- Subjects
SAND flies ,LEISHMANIA ,LUTZOMYIA ,AMASTIGOTES ,MAMMALS ,PARASITES ,MACROPHAGES - Abstract
We previously showed that L. (Leishmania) amazonensis promastigotes and amastigotes of the PH8 strain generated larger lesions in mice than LV79, and that lesion-derived amastigotes from the two strains differ in their proteomes. We recently reported that PH8 promastigotes are more phagocytized by macrophages. Promastigotes' membrane-enriched proteomes showed several differences, and samples of each strain clustered based on proteomes. In this paper, we show phenotypic differences between PH8 and LV79 promastigotes that may explain the higher virulence of PH8. We compared in vitro macrophage infections by day 4 (early) and day 6 (late stationary phase) cultures, resistance to complement, and LPG characteristics. PH8 promastigotes showed a higher infectivity and were more resistant to murine complement. LPG was different between the strains, which may influence the interaction with macrophages and survival to complement. We compared the infection of the permissive vector Lutzomyia longipalpis. PH8 was more abundant in the vector's gut 72 h after feeding, which is a moment where blood digestion is finished and the parasites are exposed to the gut environment. Our results indicate that PH8 promastigotes are more infective, more resistant to complement, and infect the permissive vector more efficiently. These data suggest that PH8 is probably better adapted to the sand fly and more prone to survive in the vertebrate host. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
39. CONNECTIVITY OF THE COMPLEMENT OF GENERALIZED TOTAL GRAPH OF FINITE FIELDS.
- Author
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Balamurugan, M., Kathirvel, S. Anukumar, and Chelvam, T. Tamizh
- Subjects
FINITE fields ,COMMUTATIVE rings ,UNDIRECTED graphs - Abstract
Let R be a commutative ring with identity, Z(R) be its zero-divisors, and H be a nonempty proper multiplicative prime subset of R: The generalized total graph of R is the simple undirected graph GT
H (R) with the vertex set R and two distinct vertices x and y are adjacent if and only if x+y ∈ H: In this paper, we investigate the vertex connectivity, edge connectivity and separation of GT(F) for the finite field F: In particular, we prove that k = k' = Δ for GT(F): [ABSTRACT FROM AUTHOR]- Published
- 2023
40. Syntactic Functions of Adjectives: A Comparative Approach with Examples from Albanian, English, German, French and Italian Languages.
- Author
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Beqiraj, Xhafer
- Subjects
- *
COMPARATIVE method , *ITALIAN language , *FRENCH language , *ENGLISH language , *INDO-European languages , *VALENCE (Chemistry) - Abstract
The present paper explores the attributive, epithetic and predicative functions of adjectives in the Albanian language, by considering the most relevant and contemporary theories such as the valency theory and the concepts of generative linguistics. Two reasons make this paper an important contribution to the domain of Linguistics: firstly, the syntactic functions of the adjectives in Albanian language have been analyzed insufficiently due to the fact that Albanian Linguistics is based on traditional theories and concepts. Therefore, many issues related to the syntactic functions of the adjectives remain unexplored. Secondly, as the paper focuses on the adjectives in Albanian language in terms of attributive, epithetic, and predicative functions, each function is illustrated with examples by comparing and contrasting them with other Indo-European languages. Therefore, this paper can be a reference to other non-Albanian researchers whose interest is either in understanding the syntactic issues of the Albanian language or attempting to compare and contrast it with other European languages. This paper is an extract from the doctoral dissertation, which I have reviewed and supplemented for the reader to have an insight into the syntactical system of the Albanian language with focus on adjectives, and to highlight the similarities and differences that exist between the Albanian language and other European languages. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
41. Innate and adaptive immune responses to SARS‐CoV‐2 in humans: relevance to acquired immunity and vaccine responses.
- Author
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Jordan, S. C.
- Subjects
VACCINE effectiveness ,SARS-CoV-2 ,IMMUNE response ,COVID-19 ,PSYCHONEUROIMMUNOLOGY - Abstract
Summary: The factors responsible for the spectrum of coronavirus 19 (COVID‐19) disease severity and the genesis and nature of protective immunity against COVID‐19 remain elusive. Multiple studies have investigated the immune responses to COVID‐19 in various populations, including those without evidence of COVID‐19 infection. Information regarding innate and adaptive immune responses to the novel severe respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has evolved rapidly. Data are accumulating defining disease phenotypes that aid in rational and informed development of new therapeutic approaches for the treatment of patients infected with SARS‐CoV‐2 and the development of novel vaccines. In this paper, data on important innate immune responses are summarized, including cytokines, specifically interleukin (IL)‐6 and complement, and potential treatments are explored. Adaptive immune responses and derivative therapeutics such as monoclonal antibodies directed at spike proteins are also examined. Finally, data on real‐time assessments of adaptive immune responses are explored, which include CD4+/CD8+ T cells, natural killer (NK) T cells, memory B cells and T follicular cells with specificities for COVID‐19 peptides in infected and normal individuals. Data of two novel vaccines have been released, both showing > 95% efficacy in preventing SARS‐CoV‐2 infection. Analysis of humoral and cellular responses to the vaccines will determine the robustness and durability of protection. In addition, long‐term assessment of SARS‐CoV‐2 memory B and T cell‐mediated immune responses in patients recovering from an infection or those with cross‐reactive immunological memory will help to define risk for future SARS‐CoV infections. Finally, patients recovering from SARS‐CoV‐2 infection may experience prolonged immune activation probably due to T cell exhaustion. This will be an important new frontier for study. This review summarizes published data on the relevant innate and adaptive immune responses to SARS‐CoV‐2. Data characterizing innate and adaptive immune responses have rapidly led to informed therapeutic interventions, including vaccine development and recognition of dysfunctional immune responses that are likely responsible for post‐COVID‐19 autoimmunity. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
42. Forgotten Index and Forgotten Coindex of Graphs.
- Author
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Malar, J. Senbaga and Meenakshi, A.
- Subjects
MOLECULAR connectivity index ,MOLECULAR structure ,CHEMICAL structure ,GRAPH connectivity - Abstract
Copyright of Baghdad Science Journal is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2024
- Full Text
- View/download PDF
43. The energy and edge energy of some Cayley graphs on the abelian group Zn4.
- Author
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Movahedi, Fateme
- Subjects
- *
CAYLEY graphs , *ABELIAN groups , *EIGENVALUES , *GRAPH theory , *GROUP theory - Abstract
Let G = (V,E) be a simple graph such that λ1,..., λn be the eigenvalues of G. The energy of graph G is denoted by E(G) and is defined as E(G) = Σi=1n |λi|. The edge energy of G is the energy of line graph G. In this paper, we investigate the energy and edge energy for two Cayley graphs on the abelian group Zn4, namely, the Sudoku graph and the positional Sudoku graph. Also, we obtain graph energy and edge energy of the complement of these two graphs. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
44. Energies of complements of unitary one-matching bi-Cayley graphs over commutative rings.
- Author
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Yang, Jinxing, Liu, Xiaogang, and Wang, Ligong
- Subjects
COMMUTATIVE rings ,CAYLEY graphs ,FINITE rings - Abstract
In this paper, we determine the energies of complements of unitary one-matching bi-Cayley graphs over finite commutative rings. We also determine the energies of some one-matching bi-gcd-graphs as well as the energies of complements of some one-matching bi-gcd-graphs, which are generalizations of unitary one-matching bi-Cayley graphs. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
45. Independent events and their complements. Part II.
- Author
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Mizuno, Gabriel Perez, Crispim, Carolina Martins, and Pizzinga, Adrian
- Subjects
CLASSROOM environment ,PROBABILITY theory ,COGNITIVE consistency ,ADULTS ,HIGHER education - Abstract
In a previous classroom note (Crispim et al., 2021), we addressed the proving (and the teaching) of a former and famous probability fact: if n random events are independent, then changing one, some, or all of them by the corresponding complements ends up again with independent events. Now, we explore the consequences. The first, for example, is the extension to when the number of events are infinite – which, indeed and perhaps surprisingly, stands as a corollary of the finite case. Also, and beyond covering only two events, we deal with the logical and intuitive consistency between independence and conditional probability. The theoretical content concludes with a proof that two seemingly different definitions of independent events found in the literature actually compare. Then, we finish the paper by discussing some classroom possibilities. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
46. Utilization of Nasal Mucus to Investigate the Pathophysiology of Chronic Rhinosinusitis.
- Author
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Parra-Ferro, Mauricio, Justice, Jeb M., Lobo, Brian C., Munger, Steven D., Schlosser, Rodney J., and Mulligan, Jennifer K.
- Subjects
NASAL polyps ,MUCUS ,PATHOLOGICAL physiology ,SINUSITIS ,GROWTH factors ,ALLERGIC rhinitis - Abstract
Background: Nasal mucus is proving to be a useful means by which to study the pathogenesis of chronic rhinosinusitis (CRS). Given the increase in publications examining nasal mucus and the lack of a review on this topic, we will focus on this noninvasive approach to studying CRS. Particular attention will be drawn towards inflammatory cytokines and biomarkers and their influence on disease severity. Methods: A literature review of papers published in English pertaining to nasal mucus was performed using the PubMed database. The search utilized combinations of the following keywords: sinusitis, polyps, sample collection, nasal mucus, or nasal secretion. Studies solely on acute or bacterial sinusitis, allergic rhinitis, or cystic fibrosis were not included. Results: A wide variety of materials and methods have been used to collect nasal mucus. Numerous assay types have been performed with the most common being ELISA, cytometric bead array, and proteomics. Most studies have focused on examining the levels of Th1/Th2 cytokines along with chemokines associated with type 2 immunity. Other factors identified include growth factors, senescence-associated proteins, complement, and antimicrobial defenses have also been identified. Nasal mucus cytokines have proven useful in cluster analysis and predicting postoperative improvement in Sino-nasal Outcome Test (SNOT-22) scores. One limitation of the use of nasal mucus is that some studies have suggested that nasal mucus does not always reflect the tissue microenvironment. Conclusions: Nasal mucus represents a critical tool by which to examine the sinonasal microenvironment in a noninvasive manner. Unlike studies of tissue, it can be utilized in both surgically and medically managed patients and avoids the trauma of biopsies. However, studies are still needed to determine the most effective method for nasal mucus collection. Studies should also take care to confirm that nasal mucus markers do, in fact, reflect the levels of the product studied in the tissue. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
47. A naturally hypersensitive porcine model may help understand the mechanism of COVID-19 mRNA vaccine-induced rare (pseudo) allergic reactions: complement activation as a possible contributing factor
- Author
-
Dézsi, László, Mészáros, Tamás, Kozma, Gergely, H-Velkei, Mária, Oláh, Csaba Zs., Szabó, Miklós, Patkó, Zsófia, Fülöp, Tamás, Hennies, Mark, Szebeni, Miklós, Barta, Bálint András, Merkely, Béla, Radovits, Tamás, and Szebeni, János
- Published
- 2022
- Full Text
- View/download PDF
48. ON ESSENTIALITY AND IRREDUCIBILITY IN A LATTICE.
- Author
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Sahoo, Tapatee, Panackal, Harikrishnan, Srinivas, Kedukodi Babushri, and Kuncham, Syam Prasad
- Subjects
ANALOGY ,ATOMS ,MATHEMATICAL connectedness - Abstract
We consider a bounded lattice (L, Λ, V) with the smallest element 0 and the greatest element 1. In this paper, we deal with the essentiality concepts associated with a lattice. For an arbitrary element ϑ of L, we define a ϑ-e-irreducible element in L, which is an analogy to the concept of the e-irreducible submodule in a module over a ring. It is well known that e-irreducible submodules have no proper essential extension. Indeed, we prove this remains true for elements in a bounded lattice. We establish a relation between the ϑ-complement and ϑ-e-irreducible element with suitable examples. We define the notion ϑ-socle and prove several properties when a lattice is compactly generated. Further, we construct a generalized complement graph of a distributive lattice and relate the properties such as connectedness, diameter, and cut vertices to atoms in a lattice. [ABSTRACT FROM AUTHOR]
- Published
- 2022
49. Autoantibodies against Complement Classical Pathway Components C1q, C1r, C1s and C1-Inh in Patients with Lupus Nephritis.
- Author
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Radanova, Maria, Vasilev, Vasil, Mihaylova, Galya, Kosturkova, Mariya, Kishore, Uday, and Roumenina, Lubka
- Subjects
AUTOANTIBODIES ,LUPUS nephritis ,ANTINUCLEAR factors ,SURFACE plasmon resonance ,G proteins - Abstract
Autoantibodies against the complement component C1q (anti-C1q) are among the main biomarkers in lupus nephritis (LN) known to contribute to renal injury. C1q, the recognition subcomponent of the complement classical pathway, forms a heterotetrameric complex with C1r and C1s, and can also associate a central complement regulator and C1 Inhibitor (C1-Inh). However, the frequency and the pathogenic relevance of anti-C1r, anti-C1s and anti-C1-Inh autoantibodies remain poorly studied in LN. In this paper, we screened for anti-C1q, anti-C1r, anti-C1s and anti-C1-Inh autoantibodies and evaluated their association with disease activity and severity in 74 LN patients followed up for 5 years with a total of 266 plasma samples collected. The presence of anti-C1q, anti-C1r, anti-C1s and anti-C1-Inh was assessed by ELISA. IgG was purified by Protein G from antigen-positive plasma and their binding to purified C1q, C1r and C1s was examined by surface plasmon resonance (SPR). The abilities of anti-C1q, anti-C1r and anti-C1s binding IgG on C1 complex formation were analyzed by ELISA. The screening of LN patients' plasma revealed 14.9% anti-C1q positivity; only 4.2%, 6.9% and 0% were found to be positive for anti-C1r, anti-C1s and anti-C1-Inh, respectively. Significant correlations were found between anti-C1q and anti-dsDNA, and anti-nuclear antibodies, C3 and C4, respectively. High levels of anti-C1q antibodies were significantly associated with renal histologic lesions and correlated with histological activity index. Patients with the most severe disease (A class according to BILAG Renal score) had higher levels of anti-C1q antibodies. Anti-C1r and anti-C1s antibodies did not correlate with the clinical characteristics of the LN patients, did not interfere with the C1 complex formation, and were not measurable via SPR. In conclusion, the presence of anti-C1q, but not anti-C1s or anti-C1r, autoantibodies contribute to the autoimmune pathology and the severity of LN. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
50. Role of complement, anti-complement therapeutics, and other targeted immunotherapies in myasthenia gravis.
- Author
-
Dalakas, Marinos C
- Subjects
MYASTHENIA gravis ,COMPLEMENT receptors ,THERAPEUTICS ,ANTIBODY formation ,IMMUNOTHERAPY - Abstract
Several patients with myasthenia gravis (MG) do not adequately respond to available drugs or exhibit poor tolerance, necessitating the need for new therapies. The paper discusses the rapidly evolving target-specific immunotherapies that promise long-standing remissions in the management of MG. It is specifically focused on the role of complement, anti-complement therapeutics, and the anti-FcRn and B cell monoclonals. Anti-AChR antibodies cause internalization of the receptors and activate complement leading to in situ MAC formation that damages the post-synaptic membrane of the neuromuscular junction. Inhibiting MAC formation by antibodies targeting key complements subcomponents is a reasonable therapeutic goal. Indeed, the anti-C5 monoclonal antibodies, Eculizumab, Ravulizumab, and Zilucoplan, have been successfully tested in MG with Eculizumab first and now Ravulizumab FDA-approved for refractory MG based on sustained long-term benefits. Among the biologics that inhibit FcRn, Efgartigimod caused rapid reduction of the circulating IgG in the lysosomes, and induced sustained clinical remission with good safety profile leading to FDA-approved indication. Anti-B cell agents, like Rituximab, can induce sustained long-term remissions, especially in IgG4 antibody-mediated Musk-MG, by targeting short-lived antibody-secreting plasmablasts. These biologics offer effective targeted immunotherapies with good tolerance promising to change the therapeutic algorithm in the chronic MG management. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
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