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Complement pathway

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https://www.readbyqxmd.com/read/28640789/complement-mediated-enhancement-of-monocyte-adhesion-to-endothelial-cells-by-hla-antibodies-and-blockade-by-a-specific-inhibitor-of-the-classical-complement-cascade-tnt003
#1
Nicole M Valenzuela, Kimberly A Thomas, Arend Mulder, Graham C Parry, Sandip Panicker, Elaine F Reed
BACKGROUND: Antibody-mediated rejection (AMR) of most solid organs is characterized by evidence of complement activation and/or intragraft macrophages (C4d + and CD68+ biopsies). We previously demonstrated that crosslinking of HLA I by antibodies triggered endothelial activation and monocyte adhesion. We hypothesized that activation of the classical complement pathway at the endothelial cell surface by HLA antibodies would enhance monocyte adhesion through soluble split product generation, in parallel with direct endothelial activation downstream of HLA signaling...
July 2017: Transplantation
https://www.readbyqxmd.com/read/28640690/a-new-layer-of-rrna-regulation-by-small-interference-rnas-and-the-nuclear-rnai-pathway
#2
Xufei Zhou, Xiangyang Chen, Yun Wang, Xuezhu Feng, Shouhong Guang
Ribosome biogenesis drives cell growth and proliferation, but mechanisms that modulate this process remain poorly understood. For a long time, small ribosomal RNA sequences have been widely treated as non-specific degradation products and neglected as garbage sequences. Recently, we identified a new class of antisense ribosomal siRNAs (risiRNAs) that downregulate pre-rRNA through the nuclear RNAi pathway in C. elegans. risiRNAs exhibit sequence characteristics similar to 22G RNA while complement to 18S and 26S rRNA...
June 22, 2017: RNA Biology
https://www.readbyqxmd.com/read/28637316/incorporating-comparative-genomics-into-the-design-test-learn-cycle-of-microbial-strain-engineering
#3
Maria Sardi, Audrey P Gasch
Engineering microbes with new properties is an important goal in industrial engineering, to establish biological factories for production of biofuels, commodity chemicals, and pharmaceutics. But engineering microbes to produce new compounds with high yield remains a major challenge toward economically viable production. Incorporating several modern approaches, including synthetic and systems biology, metabolic modeling, and regulatory rewiring have proven to significantly advance industrial strain engineering...
June 16, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28636684/balanced-work-function-as-a-driver-for-facile-hydrogen-evolution-reaction-comprehension-and-experimental-assessment-of-interfacial-catalytic-descriptor
#4
Aleksandar R Zeradjanin, Ashokanand Vimalanandan, George Polymeros, Angel A Topalov, Karl J J Mayrhofer, Michael Rohwerder
A major step in the development of (electro)catalysis would be the possibility to estimate accurately the energetics of adsorption processes related to reaction intermediates. Computational chemistry (e.g. using DFT) developed significantly in that direction and allowed the fast prediction of (electro)catalytic activity trends and improved the general understanding of adsorption at electrochemical interfaces. However, building a reliable and comprehensive picture of electrocatalytic reactions undoubtedly requires experimental assessment of adsorption energies...
June 21, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28636533/microrna-149-suppresses-hepatic-inflammatory-response-through-antagonizing-stat3-signaling-pathway
#5
Qiqi Zhang, Jia Su, Ziwei Wang, Hui Qi, Zeyong Ge, Zhijun Li, Wei-Dong Chen, Yan-Dong Wang
Chronic inflammation is increasingly recognized as an important component of tumorigenesis and metabolic diseases. The roles of microRNA149* (miRNA149*) in inflammation remain poorly understood. Here, we demonstrate that miR-149* is a suppressor of STAT3-mediated inflammation. MiR-149*-/- mice were generated with CRISPR/CAS9 technique. In a lipopolysaccharide (LPS)-induced inflammation model, miR-149*-/- mice show more severe liver injury and inflammation, compared with wild-type (WT) mice. MiR-149*-/- mice also displayed elevated messenger RNA (mRNA) levels of interleukin (IL)-6, inducible nitric oxide synthase (iNOS), complement C3 (C3) and IL-4 in response to LPS...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28635593/the-protein-slr1143-is-an-active-diguanylate-cyclase-in-synechocystis-sp-pcc-6803-and-interacts-with-the-photoreceptor-cph2
#6
Veronika Angerer, Philipp Schwenk, Thomas Wallner, Volkhard Kaever, Andreas Hiltbrunner, Annegret Wilde
Cyclic-di-GMP is an ubiquitous second messenger in bacteria. Several c-di-GMP receptor proteins have been identified to date, and downstream signalling pathways are often mediated through protein-protein interactions. The photoreceptor Cph2 from the cyanobacterium Synechocystis sp. PCC 6803 comprises three domains related to c-di-GMP metabolism: two GGDEF and one EAL domain. It has been shown that the C-terminal GGDEF domain acts as blue-light triggered c-di-GMP producer thereby inhibiting motility of the cells in blue light...
June 21, 2017: Microbiology
https://www.readbyqxmd.com/read/28634882/gingipain-of-porphyromonas-gingivalis-manipulates-m1-macrophage-polarization-through-c5a-pathway
#7
Yubo Hou, Haiyan Yu, Xinchan Liu, Gege Li, Jiahui Pan, Changyu Zheng, Weixian Yu
Gingipains secreted by Porphyromonas gingivalis (P. gingivalis, Pg) play an important role in maintaining macrophage infiltrating. And, this study is to evaluate effects of gingipain on M1 macrophage polarization after exposure to Porphyromonas gingivalis (P. gingivalis, Pg) and if these effects are through complement component 5a (C5a) pathway. Mouse RAW264.7 macrophages were exposed to gingipain extracts, Escherichia coli lipopolysaccharides (Ec-LPS), Pg-LPS with or without the C5aR antagonist: PMX-53 for 24 h...
June 20, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/28634480/fc-galactosylation-of-human-immunoglobulin-gamma-isotypes-improves-c1q-binding-and-enhances-complement-dependent-cytotoxicity
#8
Benjamin Peschke, Christian W Keller, Patrick Weber, Isaak Quast, Jan D Lünemann
Binding of the complement component C1q to the CH2 domain of antigen-bound immunoglobulin gamma (IgG) activates the classical complement pathway and depends on its close proximity to Fc fragments of neighboring antibodies. IgG subclasses contain a highly conserved asparagine 297 (N)-linked biantennary glycan within their CH2 domains, the core structure of which can be extended with terminal galactose and sialic acid residues. To investigate whether Fc-glycosylation regulates effector functions of human IgG subclasses, we cloned the antigen-binding region of the CD20-specific monoclonal antibody rituximab into IgG isotype expression vectors...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28634324/ficolins-do-not-alter-host-immune-responses-to-lipopolysaccharide-induced-inflammation-in-vivo
#9
Ninette Genster, Olga Østrup, Camilla Schjalm, Tom Eirik Mollnes, Jack B Cowland, Peter Garred
Ficolins are a family of pattern recognition molecules that are capable of activating the lectin pathway of complement. A limited number of reports have demonstrated a protective role of ficolins in animal models of infection. In addition, an immune modulatory role of ficolins has been suggested. Yet, the contribution of ficolins to inflammatory disease processes remains elusive. To address this, we investigated ficolin deficient mice during a lipopolysaccharide (LPS)-induced model of systemic inflammation...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28633524/charge-migration-in-eyring-walter-and-kimball-s-1944-model-of-the-electronically-excited-hydrogen-molecule-ion
#10
Dennis J Diestler, Gunter Hermann, Jörn Manz
In an elementary variational treatment of the electronic structure of H2+ Eyring, Walter and Kimball (EWK) serendipitously discovered charge migration (CM) in 1944. Using an analytic expression for the electronic probability density (EPD), they found that if the electron is initially localized on one of the protons (by taking the initial state to be a superposition of the ground and first-excited electronic energy eigenstates), then it oscillates adiabatically between fixed protons with a period T inversely proportional to the energy gap between the eigenstates...
June 21, 2017: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/28632884/components-of-the-alternative-complement-pathway-in-patients-with-psoriasis
#11
Betul Sereflican, Guler Bugdayci
INTRODUCTION: Psoriasis is a chronic inflammatory skin disease. Adipose tissue plays important roles in the events that regulate body metabolism. This study determined the levels of complement 3 ( C3), acylation-stimulating protein (ASP), and adipsin, which take part in the alternate complement pathway, and are synthesized in and secreted by adipose tissue. METHODS: Thirty-two patients with psoriasis were matched with 22 controls in terms of age, sex, body mass index, and lipid profiles...
June 2017: Acta Dermatovenerologica Alpina, Panonica, et Adriatica
https://www.readbyqxmd.com/read/28632844/complement-mediated-regulation-of-apolipoprotein-e-in-cultured-human-rpe-cells
#12
Ping Yang, Nikolai P Skiba, Grace M Tewkesbury, Victoria M Treboschi, Peter Baciu, Glenn J Jaffe
PURPOSE: Complement activation is implicated in the pathogenesis of age-related macular degeneration (AMD). Apolipoprotein E (ApoE) and complement activation products such as membrane attack complex (MAC) are present in eyes of individuals with AMD. Herein, we investigated the effect of complement activation on induction of ApoE accumulation in human retinal pigment epithelial (RPE) cells. METHODS: Cultured human RPE cells were primed with a complement-fixing antibody followed by treatment with C1q-depleted (C1q-Dep) human serum to elicit alternative pathway complement activation...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28631036/practical-recommendations-for-radium-223-treatment-of-metastatic-castration-resistant-prostate-cancer
#13
Yong Du, Ignasi Carrio, Giuseppe De Vincentis, Stefano Fanti, Harun Ilhan, Caroline Mommsen, Egbert Nitzsche, Francis Sundram, Wouter Vogel, Wim Oyen, Val Lewington
PURPOSE: Radium Ra 223 dichloride (radium-223, Xofigo®) is the first targeted alpha therapy for patients with castration-resistant prostate cancer and symptomatic bone metastases. Radium-223 provides a new treatment option for this setting, but also necessitates a new treatment management approach. We provide straightforward and practical recommendations for European nuclear medicine centres to optimize radium-223 service provision. METHODS: An independent research consultancy agency observed radium-223 procedures and conducted interviews with all key staff members involved in radium-223 treatment delivery in 11 nuclear medicine centres across six countries (Germany, Italy, the Netherlands, Spain, Switzerland and the UK) experienced in administering radium-223...
June 19, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28630873/an-integrative-developmental-genomics-and-systems-biology-approach-to-identify-an-in-vivo-sox-trio-mediated-gene-regulatory-network-in-murine-embryos
#14
Wenqing Jean Lee, Sumantra Chatterjee, Sook Peng Yap, Siew Lan Lim, Xing Xing, Petra Kraus, Wenjie Sun, Xiaoming Hu, V Sivakamasundari, Hsiao Yun Chan, Prasanna R Kolatkar, Shyam Prabhakar, Thomas Lufkin
Embryogenesis is an intricate process involving multiple genes and pathways. Some of the key transcription factors controlling specific cell types are the Sox trio, namely, Sox5, Sox6, and Sox9, which play crucial roles in organogenesis working in a concerted manner. Much however still needs to be learned about their combinatorial roles during this process. A developmental genomics and systems biology approach offers to complement the reductionist methodology of current developmental biology and provide a more comprehensive and integrated view of the interrelationships of complex regulatory networks that occur during organogenesis...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28630159/the-mystery-behind-membrane-insertion-a-review-of-the-complement-membrane-attack-complex
#15
REVIEW
Charles Bayly-Jones, Doryen Bubeck, Michelle A Dunstone
The membrane attack complex (MAC) is an important innate immune effector of the complement terminal pathway that forms cytotoxic pores on the surface of microbes. Despite many years of research, MAC structure and mechanism of action have remained elusive, relying heavily on modelling and inference from biochemical experiments. Recent advances in structural biology, specifically cryo-electron microscopy, have provided new insights into the molecular mechanism of MAC assembly. Its unique 'split-washer' shape, coupled with an irregular giant β-barrel architecture, enable an atypical mechanism of hole punching and represent a novel system for which to study pore formation...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28630141/temperature-responsive-mirnas-in-drosophila-orchestrate-adaptation-to-different-ambient-temperatures
#16
Isabel Fast, Charlotte Hewel, Laura Wester, Julia Schumacher, Daniel Gebert, Hans Zischler, Christian Berger, David Rosenkranz
The majority of Drosophila genes are expressed in a temperature-dependent manner, but the way in which small RNAs may contribute to this effect is completely unknown as we currently lack an idea of how small RNA transcriptomes change as a function of temperature. Applying high throughput sequencing techniques complemented by quantitative real-time PCR experiments, we demonstrate that altered ambient temperature induces drastic, but reversible changes in sequence composition and total abundance of both, miRNA- and piRNA populations...
June 19, 2017: RNA
https://www.readbyqxmd.com/read/28630122/eculizumab-blocks-vaccine-induced-opsonophagocytic-killing-of-meningococci-by-whole-blood-from-immunized-adults
#17
Monica Konar, Dan M Granoff
Eculizumab, a humanized anti-complement C5 monoclonal antibody for treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome, blocks the terminal complement pathway required for serum bactericidal activity (SBA). Because treated patients are at >1000-fold increased risk of meningococcal disease, vaccination is recommended, but whether vaccination can protect by opsonophagocytic activity in the absence of SBA is not known. Meningococci were added to anticoagulated blood from 12 healthy adults vaccinated with meningococcal serogroup B and serogroup A,C,W,Y vaccines...
June 19, 2017: Blood
https://www.readbyqxmd.com/read/28629435/eculizumab-treatment-stochastic-occurrence-of-c3-binding-to-individual-pnh-erythrocytes
#18
Michela Sica, Tommaso Rondelli, Patrizia Ricci, Maria De Angioletti, Antonio M Risitano, Rosario Notaro
BACKGROUND: C5 blockade by eculizumab prevents complement-mediated intravascular hemolysis in paroxysmal nocturnal hemoglobinuria (PNH). However, C3-bound PNH red blood cells (RBCs), arising in almost all treated patients, may undergo extravascular hemolysis reducing clinical benefits. Despite the uniform deficiency of CD55 and of CD59, there are always two distinct populations of PNH RBCs, with (C3+) and without (C3-) C3 binding. METHODS: To investigate this paradox, the phenomenon has been modeled in vitro by incubating RBCs from eculizumab untreated PNH patients with compatible sera containing eculizumab, and by assessing the C3 binding after activation of complement alternative pathway...
June 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28628799/a-novel-2-stage-approach-that-detects-complement-activation-in-patients-with-antiphospholipid-antibody-syndrome
#19
Jacob H Rand, Xiao-Xuan Wu, Lucia R Wolgast, Victor Lei, Edward M Conway
INTRODUCTION: The antiphospholipid syndrome (APS) is marked by autoantibodies that recognize anionic phospholipids in a cofactor-dependent manner. A role for complement has been implicated in the pathophysiology, however, elevations of complement activation markers have not been consistently demonstrated in clinical studies. We therefore designed a proof-of-principle study to determine whether complement activation might be detectable in APS by first exposing plasmas to phospholipid vesicles...
June 9, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28627616/distinct-cellular-phenotype-linked-to-defective-dna-interstrand-crosslink-repair-and-homologous-recombination
#20
Aleksandra M Gorniewska, Katarzyna Kluzek, Lidia Gackowska, Izabela Kubiszewska, Malgorzata Z Zdzienicka, Aneta Bialkowska
Repair of DNA interstrand crosslinks (ICLs) predominantly involves the Fanconi anemia (FA) pathway and homologous recombination (HR). The HR repair system eliminates DNA double strand breaks (DSBs) that emerge during ICLs removal. The current study presents a novel cell line, CL‑V8B, representing a new complementation group of Chinese hamster cell mutants hypersensitive to DNA crosslinking factors. CL‑V8B exhibits increased sensitivity to various DNA‑damaging agents, including compounds leading to DSBs formation (bleomycin and 6‑thioguanine), and is extremely sensitive to poly (ADP-ribose) polymerase inhibitor (>400‑fold), which is typical for HR‑defective cells...
June 15, 2017: Molecular Medicine Reports
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