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Complement pathways

Alok K Shah, Gunter Hartel, Ian Brown, Clay Winterford, Renhua Na, Kim-Anh Lê Cao, Bradley A Spicer, Michelle A Dunstone, Wayne A Phillips, Reginald V Lord, Andrew P Barbour, David I Watson, Virendra Joshi, David C Whiteman, Michelle M Hill
Esophageal adenocarcinoma (EAC) is thought to develop from asymptomatic Barrett's esophagus (BE) with a low annual rate of conversion. Current endoscopy surveillance for BE patients is probably not cost-effective. Previously, we discovered serum glycoprotein biomarker candidates which could discriminate BE patients from EAC. Here, we aimed to validate candidate serum glycoprotein biomarkers in independent cohorts, and to develop a biomarker candidate panel for BE surveillance. Serum glycoprotein biomarker candidates were measured in 301 serum samples collected from Australia (4 states) and USA (1 clinic) using previously established lectin magnetic bead array (LeMBA) coupled multiple reaction monitoring mass spectrometry (MRM-MS) tier 3 assay...
August 10, 2018: Molecular & Cellular Proteomics: MCP
Huimin Zhang, Hongrui Jiang, Yongliang Fan, Zhi Chen, Mingxun Li, Yongjiang Mao, Niel A Karrow, Juan J Loor, Stephen Moore, Zhangping Yang
Mastitis is a highly prevalent disease in dairy cows that causes large economic losses. Streptococcus agalactiae is a common contagious pathogen, and a major cause of bovine mastitis. The immune response to intramammary infection with S. agalactiae in dairy cows is a very complex biological process. In order to understand the host immune response to S. agalactiae-induced mastitis, mammary gland of lactating Chinese Holstein cows was challenged with S. agalactiae via nipple tube perfusion. Visual inspection, analysis of milk somatic cell counts, histopathology and transmission electron microscopy of mammary tissue was performed to confirm S...
August 10, 2018: Journal of Agricultural and Food Chemistry
Pasquale Filannino, Maria De Angelis, Raffaella Di Cagno, Giorgia Gozzi, Ylenia Riciputi, Marco Gobbetti
Triplets of Lactobacullus plantarum strains were isolated from nine contrasting habitats. Without any passage through other culture media, isolation and cultivation were on model media that strictly reproduced the chemical and physical conditions and stressors of the habitats of origin. Here, we demonstrated how L. plantarum regulates and shapes its transcriptome in response to contrasting habitats. Firstly, multivariate clustering analysis of transcriptional data (RNA-Seq), complemented with metabolomics and phenomics, grouped the strains according to the habitats of origin...
August 9, 2018: Environmental Microbiology
Giuseppina Spartà, Ariana Gaspert, Thomas J Neuhaus, Marcus Weitz, Nilufar Mohebbi, Urs Odermatt, Peter F Zipfel, Carsten Bergmann, Guido F Laube
Background: Membranoproliferative glomerulonephritis (MPGN) with immune complexes and C3 glomerulopathy (C3G) in children are rare and have a variable outcome, with some patients progressing to end-stage renal disease (ESRD). Mutations in genes encoding regulatory proteins of the alternative complement pathway and of complement C3 (C3) have been identified as concausative factors. Methods: Three children with MPGN type I, four with C3G, i.e. three with C3 glomerulonephritis (C3GN) and one with dense deposit disease (DDD), were followed...
August 2018: Clinical Kidney Journal
Takuya Osada, Zachary C Hartman, Junping Wei, Gangjun Lei, Amy C Hobeika, William R Gwin, Marcio A Diniz, Neil Spector, Timothy M Clay, Wei Chen, Michael A Morse, H Kim Lyerly
BACKGROUND: Upregulation of human epidermal growth factor receptor 3 (HER3) is a major mechanism of acquired resistance to therapies targeting its heterodimerization partners epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), but also exposes HER3 as a target for immune attack. We generated an adenovirus encoding full length human HER3 (Ad-HER3) to serve as a cancer vaccine. Previously we reported the anti-tumor efficacy and function of the T cell response to this vaccine...
August 9, 2018: Breast Cancer Research: BCR
Ziran Xu, Xia He, Xu Shi, Yuhan Xia, Xiaomei Liu, Haitao Wu, Pengdong Li, Hongyu Zhang, Weisi Yin, Xiubo Du, Lisha Li, Yulin Li
BACKGROUND: Differentiation of human induced pluripotent stem cells (hiPSCs) into hepatocytes has important clinical significance in providing a new stem cell source for cell therapy of terminal liver disease. The differential gene expression analysis of hiPSCs, induced hepatocyte-like cells (HLCs), and primary human hepatocytes (PHHs) provides valuable information for optimization of an induction scheme and exploration of differentiation mechanisms. METHODS: Human hair follicle-derived iPSCs (hHF-iPSCs) were induced in vitro by mimicking the environment of a developing liver for 19 days...
August 9, 2018: Stem Cell Research & Therapy
Ashley Frazer-Abel
The approval in the US and Europe of Eculizumab in 2007 marked a change in complement therapeutics, and with it the landscape for complement testing in the clinical immunology laboratory changed. The change had begun even before that when C1-Inhibitor preparations were approved in the 1980s in Europe. There are now two classes of approved drugs that may impact the immunology laboratory, with two dozen more with novel modalities and potential indications that are in various stages of development. Every pathway and about every component of complement has been targeted by these drug development programs, and the modalities of the drugs in development are diverse...
August 6, 2018: Journal of Immunological Methods
Gabriela Canalli Kretzschmar, Luana Caroline Oliveira, Renato Mitsunori Nisihara, Thirumalaisamy P Velavan, Sérvio Túlio Stinghen, Ewalda R S Stahlke, Maria Luiza Petzl-Erler, Iara José T de Messias-Reason, Angelica Beate Winter Boldt
BACKGROUND: Pathophysiological mechanisms are still incompletely understood for leprosy, an urgent public health issue in Brazil. Complement receptor 1 (CR1) binds complement fragments C3b/C4b deposited on mycobacteria, mediating its entrance in macrophages. We investigated CR1 polymorphisms, gene expression and soluble CR1 levels in a case-control study with Brazilian leprosy patients, aiming to understand the role of this receptor in differential susceptibility to the disease. METHODOLOGY: Nine polymorphisms were haplotyped by multiplex PCR-SSP in 213 leprosy patients (47% multibacillary) and 297 controls...
August 9, 2018: PLoS Neglected Tropical Diseases
Li Zhang, Jin-Yang Liu, Huan Gu, Yanfang Du, Jian-Fang Zuo, Zhibin Zhang, Menglin Zhang, Pan Li, Jim M Dunwell, Yangrong Cao, Zuxin Zhang, Yuan-Ming Zhang
Although the legume-rhizobium symbiosis is a most important biological process, there is a limited knowledge about the protein interaction network between host and symbiont. Using interolog and domain-based approaches, we constructed an inter-species protein interactome containing 5,115 protein-protein interactions between 2,291 Glycine max and 290 Bradyrhizobium diazoefficiens USDA 110 proteins. The interactome was further validated by expression pattern analysis in nodules, GO term semantic similarity, co-expression analysis and luciferase complementation image assay...
August 9, 2018: Journal of Proteome Research
Tiannan Guo, Li Li, Qing Zhong, Niels J Rupp, Konstantina Charmpi, Christine E Wong, Ulrich Wagner, Jan H Rueschoff, Wolfram Jochum, Christian Daniel Fankhauser, Karim Saba, Cedric Poyet, Peter J Wild, Ruedi Aebersold, Andreas Beyer
It remains unclear to what extent tumor heterogeneity impacts on protein biomarker discovery. Here, we quantified proteome intra-tissue heterogeneity (ITH) based on a multi-region analysis of prostate tissues using pressure cycling technology and SWATH mass spectrometry. We quantified 6,873 proteins and analyzed the ITH of 3,700 proteins. The level of ITH varied depending on proteins and tissue types. Benign tissues exhibited more complex ITH patterns than malignant tissues. Spatial variability of ten prostate biomarkers was validated by immunohistochemistry in an independent cohort (n=83) using tissue microarrays...
May 29, 2018: Life science alliance
Margrit Hollborn, Charlotte Ackmann, Heidrun Kuhrt, Fabian Doktor, Leon Kohen, Peter Wiedemann, Andreas Bringmann
Purpose: Variants of complement factor genes, hypoxia and oxidative stress of the outer retina, and systemic hypertension affect the risk of age-related macular degeneration. Hypertension often results from the high intake of dietary salt that increases extracellular osmolarity. We determined the effects of extracellular hyperosmolarity, hypoxia, and oxidative stress on the expression of complement genes in cultured (dedifferentiated) human RPE cells and investigated the effects of C9 siRNA and C9 protein on RPE cells...
2018: Molecular Vision
Kathryn L Roche, Masatoshi Nukui, Benjamin A Krishna, Christine M O'Connor, Eain A Murphy
Infections with human cytomegalovirus (HCMV) are highly prevalent in the general population as the virus has evolved the capacity to undergo distinct replication strategies resulting in lytic, persistent, and latent infections. During the latent lifecycle, HCMV resides in subsets of cells within the hematopoietic cell compartment, including hematopoietic progenitor cells (HPCs) and peripheral blood monocytes. As only a small fraction of these cell types harbor viral genomes during natural latency, the identification and analysis of distinct changes mediated by viral infection are difficult to assess...
August 8, 2018: Journal of Virology
Yimeng Zeng, Alicia M Jones, Emily E Thomas, Barbara Nassif, Jonathan J Silberg, Laura Segatori
Monitoring the aggregation of proteins within the cellular environment is key to investigating the molecular mechanisms underlying the formation of off-pathway protein assemblies associated with the development of disease and testing therapeutic strategies to prevent the accumulation of non-native conformations. It remains challenging, however, to couple protein aggregation events underlying the cellular pathogenesis of a disease to genetic circuits and monitor their progression in a quantitative fashion using synthetic biology tools...
August 8, 2018: ACS Synthetic Biology
Anna E van Beek, Isatou Sarr, Simon Correa, Davis Nwakanma, Mieke C Brouwer, Diana Wouters, Fatou Secka, Suzanne T B Anderson, David J Conway, Michael Walther, Michael Levin, Taco W Kuijpers, Aubrey J Cunnington
Background: Plasmodium falciparum may evade complement-mediated host defense by hijacking complement Factor H (FH), a negative regulator of the alternative complement pathway. Plasma levels of FH vary between individuals and may therefore influence malaria susceptibility and severity. Methods: We measured convalescent FH plasma levels in 149 Gambian children who had recovered from uncomplicated or severe P. falciparum malaria and in 173 healthy control children...
July 2018: Open Forum Infectious Diseases
Susan A Maroney, Julie A Peterson, Wes Zwifelhofer, Nicholas D Martinez, Ke Yan, Rachel S Bercovitz, Ronald K Woods, Alan E Mast
BACKGROUND:  Neonates undergoing cardiopulmonary bypass (CPB) surgery to correct congenital heart defects often experience excessive bleeding. Exposure of blood to artificial materials during CPB may activate coagulation, complement and inflammatory pathways. In addition, the surgical stress placed on the haemostatic system may result in cross-activation of other plasma proteolytic cascades, which could further complicate physiological responses to the surgical procedure and post-operative recovery...
August 7, 2018: Thrombosis and Haemostasis
Yanhao Lai, Yossi Weizmann, Yuan Liu
Trinucleotide repeat (TNR) instability is associated with over 42 neurodegenerative diseases and cancer, for which the molecular mechanisms remain to be elucidated. We have shown that the DNA base excision repair (BER) pathway and its central component, DNA polymerase β (pol β), in particular, its polymerase activity plays an active role in regulating somatic TNR instability. Herein, we revealed a unique role of the pol β dRP lyase in preventing somatic TNR instability. We found that deficiency of pol β deoxyribose phosphate (dRP) lyase activity locked the pol β dRP lyase domain to a dRP group, and this 'tethered' pol β to its template forcing the polymerase to perform a processive DNA synthesis...
August 2, 2018: Nucleic Acids Research
Jason D Maarsingh, Shelley E Haydel
The PrrAB two-component system is conserved across all sequenced mycobacterial species and is essential for viability in Mycobacterium tuberculosis, thus making it a promising drug target. The prrAB operon was successfully deleted in nonpathogenic Mycobacterium smegmatis, and the ∆prrAB mutant strain exhibited clumping in ammonium-limited medium and significantly reduced growth during ammonium and hypoxic stress. To assess the influence of M. tuberculosis PrrA overexpression, we constructed a recombinant M...
August 7, 2018: Microbiology
Seline A Zwarthoff, Evelien T M Berends, Sanne Mol, Maartje Ruyken, Piet C Aerts, Mihály Józsi, Carla J C de Haas, Suzan H M Rooijakkers, Ronald D Gorham
Complement is essential for the protection against infections; however, dysregulation of complement activation can cause onset and progression of numerous inflammatory diseases. Convertase enzymes play a central role in complement activation and produce the key mediators of complement: C3 convertases cleave C3 to generate chemoattractant C3a and label target cells with C3b, which promotes phagocytosis; C5 convertases cleave C5 into chemoattractant C5a, and C5b, which drives formation of the membrane attack complex...
2018: Frontiers in Immunology
Ercan Bastu, Irem Demiral, Tuba Gunel, Ege Ulgen, Ece Gumusoglu, Mohammad Kazem Hosseini, Ugur Sezerman, Faruk Buyru, John Yeh
The aim of this prospective cohort study was to identify altered biologic processes in the endometrium that may be potential markers of receptive endometrium in patients with repeated implantation failure (RIF) as compared with fertile controls. The study was conducted in a university-affiliated in vitro fertilization (IVF) gynecology clinic and molecular biology and genetics laboratory. Healthy fertile controls (n = 24) and patients with RIF (n = 24) were recruited. Window of implantation gene profiling associated with RIF was performed...
August 6, 2018: Reproductive Sciences
Xiaoyi Li, Minghao Ma, Wanxuan Shao, Hengtao Wang, Ruixin Fan, Xiaohui Chen, Xigang Wang, Yaguang Zhan, Fansuo Zeng
As a photoreceptor specifically for UV-B light, UVR8 gene plays an important role in the photomorphogenesis and developmental growth of plants. In this research, we isolated the UVR8 gene from birch, named BpUVR8 (AHY02156). BpUVR8 overexpression rescued the uvr8 mutant phenotype using functional complementation assay of BpUVR8 in Arabidopsis uvr8 mutants, which showed that the function of UVR8 is conserved between Arabidopsis and birch. The expression analysis of BpUVR8 indicated that this gene is expressed in various tissues, but its expression levels in leaves are higher than in other organs...
September 2018: Plant Science: An International Journal of Experimental Plant Biology
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