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Complement pathway

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https://www.readbyqxmd.com/read/28109823/divergent-regulation-of-insulin-like-growth-factor-binding-protein-genes-in-cultured-atlantic-salmon-myotubes-under-different-models-of-catabolism-and-anabolism
#1
Daniel Garcia de la Serrana, Eduardo N Fuentes, Samuel A M Martin, Ian A Johnston, Daniel J Macqueen
Much attention has been given to insulin-like growth factor (Igf) pathways that regulate the balance of skeletal muscle protein synthesis and breakdown in response to a range of extrinsic and intrinsic signals. However, we have a less complete understanding of how the same signals modulate muscle mass upstream of such signalling, through a family of functionally-diverse Igf-binding proteins (Igfbps) that modify the availability of Igfs to the cell receptor Igf1r. We exposed cultured myotubes from Atlantic salmon (Salmo salar L...
January 18, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28109038/lectin-complement-pathway-molecules-are-decreased-in-patients-with-cirrhosis-and-constitute-the-risk-of-bacterial-infections
#2
Ildiko Foldi, Tamas Tornai, David Tornai, Nora Sipeki, Zsuzsanna Vitalis, Istvan Tornai, Tamas Dinya, Peter Antal-Szalmas, Maria Papp
BACKGROUND&AIMS: Lectin pathway molecules of the complement system are synthesized by hepatocytes and have pivotal role in innate host defense against infectious organisms. Ficolins(FCNs) act as soluble pattern recognition molecules, while mannan-binding lectin serine proteases(MASPs) do as effector molecules in elimination of pathogens. We aimed to study the significance of low level of these molecules in the development of cirrhosis-associated bacterial infections, which has not been elucidated so far...
January 20, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28108964/heme-oxygenase-1-defects-lead-to-reduced-chlorophyll-in-brassica-napus
#3
Lixia Zhu, Zonghui Yang, Xinhua Zeng, Jie Gao, Jie Liu, Bin Yi, Chaozhi Ma, Jinxiong Shen, Jinxing Tu, Tingdong Fu, Jing Wen
We previously described a Brassica napus chlorophyll-deficient mutant (ygl) with yellow-green seedling leaves and mapped the related gene, BnaC.YGL, to a 0.35 cM region. However, the molecular mechanisms involved in this chlorophyll defect are still unknown. In this study, the BnaC07.HO1 gene (equivalent to BnaC.YGL) was isolated by the candidate gene approach, and its function was confirmed by genetic complementation. Comparative sequencing analysis suggested that BnaC07.HO1 was lost in the mutant, while a long noncoding-RNA was inserted into the promoter of the homologous gene BnaA07...
January 20, 2017: Plant Molecular Biology
https://www.readbyqxmd.com/read/28107780/myb12-and-myb22-play-essential-roles-in-proanthocyanidin-and-flavonol-synthesis-in-red-fleshed-apple-malus-sieversii-f-niedzwetzkyana
#4
Nan Wang, Haifeng Xu, Shenghui Jiang, Zongying Zhang, Ninglin Lu, Huarong Qiu, Changzhi Qu, Yicheng Wang, Shujing Wu, Xuesen Chen
Flavonoids are major polyphenol compounds in plant secondary metabolism. Compared with cultivated apples, wild red-fleshed apples (Malus sieversii f. niedzwetzkyana) are excellent resources because of their high flavonoid content. In this work, R6R6, R6R1 and R1R1 genotypes were identified in an F1 segregating population of M. sieversii f. niedzwetzkyana. Significant differences in flavonoid compositions and contents were detected among the three genotypes by UPLC-ESI-TOF/MS analysis. Furthermore, two putative flavonoid-related genes encoding R2R3-MYB transcription factors, designated MYB12 and MYB22, were cloned and characterized...
January 20, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28105653/properdin-and-factor-h-production-by-human-dendritic-cells-modulates-their-t-cell-stimulatory-capacity-and-is-regulated-by-ifn-%C3%AE
#5
Karen O Dixon, Joseph O'Flynn, Ngaisah Klar-Mohamad, Mohamed R Daha, Cees van Kooten
Dendritic cells (DCs) and complement are both key members of the innate and adaptive immune response. Recent experimental mouse models have shown that production of alternative pathway (AP) components by DCs strongly affects their ability to activate and regulate T-cell responses. In this study we investigated the production and regulation of properdin (fP) and factor H (fH) both integral regulators of the AP, by DCs and tolerogenic DCs (tolDCs). Both fP and fH were produced by DCs, with significantly higher levels of both AP components produced by tolDCs...
January 20, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28104818/structure-and-activation-of-c1-the-complex-initiating-the-classical-pathway-of-the-complement-cascade
#6
Simon A Mortensen, Bjoern Sander, Rasmus K Jensen, Jan Skov Pedersen, Monika M Golas, Jens C Jensenius, Annette G Hansen, Steffen Thiel, Gregers R Andersen
The complement system is an important antimicrobial and inflammation-generating component of the innate immune system. The classical pathway of complement is activated upon binding of the 774-kDa C1 complex, consisting of the recognition molecule C1q and the tetrameric protease complex C1r2s2, to a variety of activators presenting specific molecular patterns such as IgG- and IgM-containing immune complexes. A canonical model entails a C1r2s2 with its serine protease domains tightly packed together in the center of C1 and an intricate intramolecular reaction mechanism for activation of C1r and C1s, induced upon C1 binding to the activator...
January 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28104134/eculizumab-and-belatacept-for-de-novo-atypical-hemolytic-uremic-syndrome-associated-with-cfhr3-cfhr1-deletion-in-a-kidney-transplant-recipient-a-case-report
#7
P Dedhia, A Govil, G Mogilishetty, R R Alloway, E S Woodle, B G Abu Jawdeh
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is associated with significant morbidity and mortality and occurs due to genetic or acquired abnormalities that result in the dysregulation of the alternative complement pathway. CASE REPORT: We report a case of post-living kidney transplantation de novo aHUS in a setting of heterozygous deletion in the complement factor H-related protein (CFHR)3-CFHR1 gene. The aHUS episode was possibly triggered by antibody-mediated rejection or tacrolimus...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28102344/predicting-drug-combination-index-and-simulating-the-network-regulation-dynamics-by-mathematical-modeling-of-drug-targeted-egfr-erk-signaling-pathway
#8
Lu Huang, Yuyang Jiang, Yuzong Chen
Synergistic drug combinations enable enhanced therapeutics. Their discovery typically involves the measurement and assessment of drug combination index (CI), which can be facilitated by the development and applications of in-silico CI predictive tools. In this work, we developed and tested the ability of a mathematical model of drug-targeted EGFR-ERK pathway in predicting CIs and in analyzing multiple synergistic drug combinations against observations. Our mathematical model was validated against the literature reported signaling, drug response dynamics, and EGFR-MEK drug combination effect...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101432/atypical-hemolytic-uremic-syndrome-in-first-trimester-pregnancy-successfully-treated-with-eculizumab
#9
Gabriela Andries, Michael Karass, Srikanth Yandrapalli, Katherine Linder, Delong Liu, John Nelson, Rahul Pawar, Savneek Chugh
BACKGROUND: Atypical hemolytic uremic syndrome is a rare disorder which is known to cause acute thrombotic microangiopathy during pregnancy with poor maternal and fetal outcomes. Atypical hemolytic uremic syndrome is caused mostly by dysregulation of alternative complement pathway secondary to genetic mutations. Most of the cases reported have been in the post-partum period. We report a rare case of a patient who presents with thrombotic microangiopathy in the first trimester of her eleventh pregnancy and was successfully treated with eculizumab...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28100627/inflammatory-biomarkers-predict-heart-failure-severity-and-prognosis-in-patients-with-heart-failure-with-preserved-ejection-fraction-a-holistic-proteomic-approach
#10
Camilla Hage, Erik Michaëlsson, Cecilia Linde, Erwan Donal, Jean-Claude Daubert, Li-Ming Gan, Lars H Lund
BACKGROUND: Underlying mechanisms in heart failure (HF) with preserved ejection fraction remain unknown. We investigated cardiovascular plasma biomarkers in HF with preserved ejection fraction and their correlation to diastolic dysfunction, functional class, pathophysiological processes, and prognosis. METHODS AND RESULTS: In 86 stable patients with HF and EF ≥45% in the Karolinska Rennes (KaRen) biomarker substudy, biomarkers were quantified by a multiplex immunoassay...
February 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28100419/redox-dysregulation-immuno-inflammatory-alterations-and-genetic-variants-of-bdnf-and-mmp-9-in-schizophrenia-pathophysiological-and-phenotypic-implications
#11
Fahmy T Ali, Eman M Abd El-Azeem, Marwa A Hamed, Mohamed A M Ali, Nour M Abd Al-Kader, Ekrami A Hassan
BACKGROUND: Although a clear mechanism underlying the pathophysiology of schizophrenia (SZ) remains elusive, oxidative stress, inflammatory syndrome and immune activation have become an attractive hypothesis for explaining the pathophysiology of SZ. Data from prior studies on the role of matrix metalloproteinase 9 (MMP-9) and brain-derived neurotrophic factor (BDNF) single nucleotide polymorphisms (SNPs) in SZ are contradictory. We aimed to investigate whether oxidative stress, inflammatory and immune activation markers as well as MMP-9 levels may be implicated in SZ pathogenesis...
January 15, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28099860/follicular-dendritic-cell-activation-by-tlr-ligands-promotes-autoreactive-b-cell-responses
#12
Abhishek Das, Balthasar A Heesters, Allison Bialas, Joseph O'Flynn, Ian R Rifkin, Jordi Ochando, Nanette Mittereder, Gianluca Carlesso, Ronald Herbst, Michael C Carroll
A hallmark of autoimmunity in murine models of lupus is the formation of germinal centers (GCs) in lymphoid tissues where self-reactive B cells expand and differentiate. In the host response to foreign antigens, follicular dendritic cells (FDCs) maintain GCs through the uptake and cycling of complement-opsonized immune complexes. Here, we examined whether FDCs retain self-antigens and the impact of this process in autoantibody secretion in lupus. We found that FDCs took up and retained self-immune complexes composed of ribonucleotide proteins, autoantibody, and complement...
January 17, 2017: Immunity
https://www.readbyqxmd.com/read/28098172/structural-diversity-of-anti-pancreatic-cancer-capsimycins-identified-in-mangrove-derived-streptomyces-xiamenensis-318-and-post-modification-via-a-novel-cytochrome-p450-monooxygenase
#13
He-Lin Yu, Shu-Heng Jiang, Xu-Liang Bu, Jia-Hua Wang, Jing-Yi Weng, Xiao-Mei Yang, Kun-Yan He, Zhi-Gang Zhang, Ping Ao, Jun Xu, Min-Juan Xu
Polycyclic tetramate macrolactams (PTMs) were identified as distinct secondary metabolites of the mangrove-derived Streptomyces xiamenensis 318. Together with three known compounds-ikarugamycin (1), capsimycin (2) and capsimycin B (3)-two new compounds, capsimycin C (4) with trans-diols and capsimycin D (5) with trans-configurations at C-13/C-14, have been identified. The absolute configurations of the tert/tert-diols moiety was determined in 4 by NMR spectroscopic analysis, CD spectral comparisons and semi-synthetic method...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097693/distinguishing-between-biochemical-and-cellular-function-are-there-peptide-signatures-for-cellular-function-of-proteins
#14
Shruti Jain, Kausik Bhattacharyya, Rachit Bakshi, Ankita Narang, Vani Brahmachari
The genome annotation and identification of gene function depends on conserved biochemical activity. However, in the cell, proteins with the same biochemical function can participate in different cellular pathways and cannot complement one another. Similarly, two proteins of very different biochemical functions are put in the same class of cellular function; for example, the classification of a gene as an oncogene or a tumour suppressor gene is not related to its biochemical function, but is related to its cellular function...
January 18, 2017: Proteins
https://www.readbyqxmd.com/read/28097447/mannose-binding-lectin-mbl-codon-54-rs1800450-polymorphism-predisposes-towards-medium-vessel-vasculitis-in-patients-with-systemic-lupus-erythematosus
#15
Vir Singh Negi, Panneer Devaraju, Durga Prasanna Misra, Vikramraj K Jain, Jignesh Babulal Usdadiya, Paul T Antony, Reena Gulati
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multiple etiological factors. Mannose-binding lectin (MBL) plays a key role in innate immunity by activating antibody-independent lectin complement pathway, opsonisation, phagocytosis, and immune complex (IC) clearance. Genetic polymorphisms in the promoter and coding regions of MBL gene affect the circulatory levels and biological activity of MBL. Defects in MBL can lead to defective opsonisation and, hence, hamper clearance of apoptotic debris, the persistence of which can drive autoantibody formation in lupus...
January 17, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28096309/anti-factor-b-and-anti-c3b-autoantibodies-in-c3-glomerulopathy-and-ig-associated-membranoproliferative-gn
#16
Maria Chiara Marinozzi, Lubka T Roumenina, Sophie Chauvet, Alexandre Hertig, Dominique Bertrand, Jérome Olagne, Marie Frimat, Tim Ulinski, Georges Deschênes, Stephane Burtey, Michel Delahousse, Bruno Moulin, Christophe Legendre, Véronique Frémeaux-Bacchi, Moglie Le Quintrec
In C3 glomerulopathy (C3G), the alternative pathway of complement is frequently overactivated by autoantibodies that stabilize the C3 convertase C3bBb. Anti-C3b and anti-factor B (anti-FB) IgG have been reported in three patients with C3G. We screened a cohort of 141 patients with C3G and Ig-associated membranoproliferative GN (Ig-MPGN) for anti-FB and anti-C3b autoantibodies using ELISA. We identified seven patients with anti-FB IgG, three patients with anti-C3b IgG, and five patients with anti-FB and anti-C3b IgG...
January 17, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28095100/association-of-combined-cigarette-smoking-and-arms2-loc387715-a69s-polymorphisms-with-age-related-macular-degeneration-a-meta-analysis
#17
Mohammad Hossein Jabbarpoor Bonyadi, Mehdi Yaseri, Mortaza Bonyadi, Masoud Soheilian, Homayoun Nikkhah
PURPOSE: The age-related maculopathy susceptibility2 (ARMS2)/LOC387715 A69S (rs10490924) polymorphism and cigarette smoking have been shown to have significant association with AMD. In this meta-analysis we used the results of available association studies of combined ARMS2/LOC387715 genotypes and cigarette smoking with AMD to estimate the possible synergistic or multiplicative effects. METHODS: Heterogeneity of studies was evaluated using the Cochran Q-test and the I-square index...
January 17, 2017: Ophthalmic Genetics
https://www.readbyqxmd.com/read/28093569/translational-evaluation-of-translocator-protein-as-a-marker-of-neuroinflammation-in-schizophrenia
#18
T Notter, J M Coughlin, T Gschwind, U Weber-Stadlbauer, Y Wang, M Kassiou, A C Vernon, D Benke, M G Pomper, A Sawa, U Meyer
Positron emission tomography (PET) imaging with radiotracers that target translocator protein 18 kDa (TSPO) has become a popular approach to assess putative neuroinflammatory processes and associated microglia activation in psychotic illnesses. It remains unclear, however, whether TSPO imaging can accurately capture low-grade inflammatory processes such as those present in schizophrenia and related disorders. Therefore, we evaluated the validity of TSPO as a disease-relevant marker of inflammation using a translational approach, which combined neurodevelopmental and neurodegenerative mouse models with PET imaging in patients with recent-onset schizophrenia and matched controls...
January 17, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28093457/functional-analysis-of-the-mammalian-rna-ligase-for-ire1-in-the-unfolded-protein-response
#19
Juthakorn Poothong, Witoon Tirasophon, Randal J Kaufman
The unfolded protein response (UPR) is a conserved signaling pathway activated upon the accumulation of unfolded proteins within the endoplasmic reticulum (ER), termed ER stress. Upon ER stress, HAC1 / XBP1 undergoes exon/intron specific excision by IRE1 to remove an intron and liberate the 5' and 3' exons. In yeast, the 5' and 3' HAC1 exons are subsequently ligated by tRNA ligase (Rlg1p) whereas XBP1 ligation in mammalian cells is catalyzed by a recently identified ligase, RtcB. In this study, the RNA ligase activity of the human RtcB involved in the unconventional splicing of XBP1 / HAC1 mRNA was explored in an rlg1-100 mutant yeast strain...
January 16, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28093242/the-zn-2-sensing-receptor-znr-gpr39-upregulates-colonocytic-cl-absorption-via-basolateral-kcc1-and-reduces-fluid-loss
#20
Laxmi Sunuwar, Hila Asraf, Mark Donowitz, Israel Sekler, Michal Hershfinkel
Administration of zinc, as a complement to oral rehydration solutions, effectively diminishes duration and severity of diarrhea, but it is not known whether it merely fulfills a nutritional deficiency, or if zinc has a direct role of regulating solute absorption. We show that Zn(2+) acts via a specific receptor, ZnR/GPR39, to reduce fluid loss. Intestinal fluid secretion triggered by cholera toxin (CTx) was lower in WT mice compared to ZnR/GPR39 KO. In the absence of dietary Zn(2+) we observed similar fluid accumulation in WT and ZnR/GPR39 KO mice, indicating that Zn(2+) and ZnR/GPR39 are both required for a beneficial effect of Zn(2+) in diarrhea...
January 13, 2017: Biochimica et Biophysica Acta
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