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Molecular mimicry

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https://www.readbyqxmd.com/read/28411240/structural-basis-of-apoptosis-inhibition-by-the-fowlpox-virus-protein-fpv039
#1
Mohd Ishtiaq Anasir, Sofia Caria, Michael A Skinner, Marc Kvansakul
Programmed cell death or apoptosis of infected host cells is an important defense mechanism in response to viral infections. This process is regulated by pro-apoptotic and pro-survival members of the B-cell lymphoma 2 (Bcl-2) protein family. To counter premature death of a virus-infected cell, poxviruses use a range of different molecular strategies, including the mimicry of pro-survival Bcl-2 proteins. One such viral pro-survival protein is the fowlpox virus protein FPV039, which is a potent apoptosis inhibitor, but the precise molecular mechanism by which FPV039 inhibits apoptosis is unknown...
April 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28410377/plasma-from-patients-with-anti-glomerular-basement-membrane-disease-could-recognize-microbial-peptides
#2
Jian-Nan Li, Xiaoyu Jia, Yongqiang Wang, Can Xie, Taijiao Jiang, Zhao Cui, Ming-Hui Zhao
Infection has long been suspected as a trigger of autoimmune diseases, and molecular mimicry mechanism was hypothesized in this study. Microbe originated peptides were searched from the Uniprot database based on a previous defined critical amino acid motif within α3129-150, isoleucine137, tryptophan140, glycine142, phenylalanine 143 and phenylalanine 145. 23826 microbial peptides were identified using our searching strategy, among which seven were related with human infections. Circulating IgG and IgM antibodies against the seven microbial peptides were detected using ELISA in 76 patients with anti-GBM disease...
2017: PloS One
https://www.readbyqxmd.com/read/28397481/diagnosis-of-hepatitis-c-virus-infection-using-a-novel-mouse-monoclonal-antibody-to-detect-serum-hcv-e1-e2-antigens
#3
Iman Touni, Ashraf A Tabll, Shaimaa S Sobieh, Maha A Hewedy, Yasmine S El Abd, Sergei Viazov
BACKGROUND: Hepatitis C virus (HCV) is a major cause of liver disease worldwide and in Egypt. The aim of this study was to detect HCV E1/E2 antigens using a novel mouse monoclonal antibody (mAb) designated (7G9) as a diagnostic and alternative approach for HCV detection. METHODS: The detection of HCV-E1/E2 antigens in 138 patients positive for HCV infection tested by RT-PCR and 25 healthy individuals negative for HCV as control group was done by an optimized in-house ELISA and DotELISA (based on the molecular mimicry of E2 to immunoglobulins)...
April 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28394824/from-microbiome-to-infectome-in-autoimmunity
#4
Dimitrios P Bogdanos, Lazaros I Sakkas
PURPOSE OF REVIEW: The current review discusses the pros and cons of the microbiome studies conducted in search of the association between microbiota and autoimmunity. RECENT FINDINGS: We focus on the role of infectome and autoinfectome as a bridge to link the findings of microbiome studies with those emerging from investigations of the role of specific viruses and antiviral responses as triggers of autoimmunity (through various mechanisms such as molecular mimicry)...
April 7, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28379682/synthetic-random-copolymers-as-a-molecular-platform-to-mimic-host-defense-antimicrobial-peptides
#5
Haruko Takahashi, Gregory A Caputo, Satyavani Vemparala, Kenichi Kuroda
Synthetic polymers have been used as a molecular platform to develop host-defense antimicrobial peptide (AMP) mimetics which are effective in killing drug-resistant bacteria. In this topical review, we will discuss the AMP-mimetic design and chemical optimization strategies as well as the biological and biophysical implications of AMP mimicry by synthetic polymers. Traditionally, synthetic polymers have been used as a chemical means to replicate the chemical functionalities and physicochemical properties of AMPs (e...
April 17, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28359286/the-double-edged-sword-of-re-expression-of-genes-by-hypomethylating-agents-from-viral-mimicry-to-exploitation-as-priming-agents-for-targeted-immune-checkpoint-modulation
#6
REVIEW
Florian Wolff, Michael Leisch, Richard Greil, Angela Risch, Lisa Pleyer
Hypomethylating agents (HMAs) have been widely used over the last decade, approved for use in myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML). The proposed central mechanism of action of HMAs, is the reversal of aberrant methylation in tumor cells, thus reactivating CpG-island promoters and leading to (re)expression of tumor suppressor genes. Recent investigations into the mode of action of azacitidine (AZA) and decitabine (DAC) have revealed new molecular mechanisms that impinge on tumor immunity via induction of an interferon response, through activation of endogenous retroviral elements (ERVs) that are normally epigenetically silenced...
March 31, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28342734/integration-of-microbiome-and-epigenome-to-decipher-the-pathogenesis-of-autoimmune-diseases
#7
REVIEW
Beidi Chen, Luxi Sun, Xuan Zhang
The interaction between genetic predisposition and environmental factors are of great significance in the pathogenesis and development of autoimmune diseases (AIDs). The human mucosa is the most frequent site that interacts with the exterior environment, and commensal microbiota at the gut and other human mucosal cavities play a crucial role in the regulation of immune system. Growing evidence has shown that the compositional and functional changes of mucosal microbiota are closely related to AIDs. Gut dysbiosis not only influence the expression level of Toll-like receptors (TLRs) of antigen presenting cells, but also contribute to Th17/Treg imbalance...
March 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28284719/hypoxia-mediated-mechanisms-associated-with-antiangiogenic-treatment-resistance-in-glioblastomas
#8
REVIEW
Sean Mahase, Rachel N Rattenni, Pieter Wesseling, William Leenders, Clarissa Baldotto, Rajan Jain, David Zagzag
Glioblastomas (GBMs) are malignant tumors characterized by their vascularity and invasive capabilities. Antiangiogenic therapy (AAT) is a treatment option that targets GBM-associated vasculature to mitigate the growth of GBMs. However, AAT demonstrates transient effects, because many patients eventually develop resistance to this treatment. Several recent studies attempt to explain the molecular and biochemical basis of resistance to AAT in GBM patients. Experimental investigations suggest that the induction of extensive intratumoral hypoxia plays a key role in GBM escape from AAT...
March 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28245427/microbe-microbe-and-host-microbe-interactions-drive-microbiome-dysbiosis-and-inflammatory-processes
#9
Amy D Proal, Inge A Lindseth, Trevor G Marshall
An extensive microbiome comprised of bacteria, viruses, bacteriophages, and fungi is now understood to persist in nearly every human body site, including tissue and blood. The genomes of these microbes continually interact with the human genome in order to regulate host metabolism. Many components of this microbiome are capable of both commensal and pathogenic activity. They are additionally able to persist in both 'acute' and chronic forms. Inflammatory conditions historically studied separately (autoimmune, neurological and malignant) are now repeatedly tied to a common trend: imbalance or dysbiosis of these microbial ecosystems...
January 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28240004/gut-microbiota-and-pancreatic-diseases
#10
Marianna Signoretti, Roberta Roggiolani, Caterina Stornello, Gianfranco Delle Fave, Gabriele Capurso
Changes in diet, lifestyle and exposition to environmental risk factors account for the increased incidence of pancreatic disorders, including acute and chronic pancreatitis, and pancreatic cancer. The role of the microbiome in the development of pancreatic disorders is increasingly recognized. The translocation of gut bacteria and endotoxins following gut barrier failure is a key event contributing to the severity of acute pancreatitis, while small intestine bacterial overgrowth is common in patients with chronic pancreatitis and further worsens their symptoms and malnutrition...
February 24, 2017: Minerva Gastroenterologica e Dietologica
https://www.readbyqxmd.com/read/28237558/iminosugar-based-ceramide-mimicry-for-the-design-of-new-cert-start-domain-ligands
#11
Cécile Santos, Fabien Stauffert, Stéphanie Ballereau, Cécile Dehoux, Frédéric Rodriguez, Anne Bodlenner, Philippe Compain, Yves Génisson
The enigmatical dichotomy between the two CERT/GPBP protein isoforms, their vast panel of biological implications and the scarcity of known antagonist series call for new ligand chemotypes identification. We report the design of iminosugar-based ceramide mimics for the development of new START domain ligands potentially targeting either protein isoforms. Strategic choice of (i) an iminoxylitol core structure and (ii) the positioning of two dodecyl residues led to an extent of protein binding comparable to that of the natural cargo lipid ceramide or the archetypical inhibitor HPA-12...
February 14, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28224668/%C3%AF-hole-and-%C3%AF-hole-synthon-mimicry-in-third-generation-crystal-engineering-design-of-elastic-crystals
#12
Subhankar Saha, Gautam R Desiraju
Designing elastic crystals is a difficult task and is of relevance in potential applications from materials to biology. Here, multi-step crystal engineering based on σ-hole and π-hole synthon mimicry is performed to obtain binary organic molecular crystals with a high degree of flexibility. A structural model is proposed based only on σ-hole-oriented type-II halogen bonds with their characteristic orthogonal geometry. These σ-hole contacts are then partly replaced by chemically and geometrically similar π-hole synthons to obtain new crystals in the second step...
February 22, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28202777/nodding-syndrome-may-be-an-autoimmune-reaction-to-the-parasitic-worm-onchocerca-volvulus
#13
Tory P Johnson, Richa Tyagi, Paul R Lee, Myoung-Hwa Lee, Kory R Johnson, Jeffrey Kowalak, Abdel Elkahloun, Marie Medynets, Alina Hategan, Joseph Kubofcik, James Sejvar, Jeffrey Ratto, Sudhir Bunga, Issa Makumbi, Jane R Aceng, Thomas B Nutman, Scott F Dowell, Avindra Nath
Nodding syndrome is an epileptic disorder of unknown etiology that occurs in children in East Africa. There is an epidemiological association with Onchocerca volvulus, the parasitic worm that causes onchocerciasis (river blindness), but there is limited evidence that the parasite itself is neuroinvasive. We hypothesized that nodding syndrome may be an autoimmune-mediated disease. Using protein chip methodology, we detected autoantibodies to leiomodin-1 more abundantly in patients with nodding syndrome compared to unaffected controls from the same village...
February 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28182619/contribution-of-common-infections-to-cardiovascular-risk-in-hiv-positive-individuals
#14
Victoria Berquist, Jennifer F Hoy, Janine M Trevillyan
HIV-positive individuals are at increased risk for cardiovascular disease due to complex interactions between the increased incidence of traditional cardiovascular risk factors and HIV and antiretroviral-associated inflammation and dyslipidemia. Increasing evidence suggests that a number of important co-pathogens, including cytomegalovirus, hepatitis C virus, and periodontal disease, are likely to also be contributing. Mechanisms such as molecular mimicry and modification of lipids play a role; however, induction of systemic inflammation is the likely key pathogenic link by which this occurs...
February 9, 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28166054/elucidation-of-a-four-site-allosteric-network-in-fibroblast-growth-factor-receptor-tyrosine-kinases
#15
Huaibin Chen, William M Marsiglia, Min-Kyu Cho, Zhifeng Huang, Jingjing Deng, Steven P Blais, Weiming Gai, Shibani Bhattacharya, Thomas A Neubert, Nathaniel J Traaseth, Moosa Mohammadi
Receptor tyrosine kinase (RTK) signaling is tightly regulated by protein allostery within the intracellular tyrosine kinase domains. Yet the molecular determinants of allosteric connectivity in tyrosine kinase domain are incompletely understood. By means of structural (X-ray and NMR) and functional characterization of pathogenic gain-of-function mutations affecting the FGF receptor (FGFR) tyrosine kinase domain, we elucidated a long-distance allosteric network composed of four interconnected sites termed the 'molecular brake', 'DFG latch', 'A-loop plug', and 'αC tether'...
February 6, 2017: ELife
https://www.readbyqxmd.com/read/28165469/notch3-signaling-mediated-melanoma-endothelial-crosstalk-regulates-melanoma-stem-like-cell-homeostasis-and-niche-morphogenesis
#16
Mei-Yu Hsu, Moon Hee Yang, Caroline I Schnegg, Soonyean Hwang, Byungwoo Ryu, Rhoda M Alani
Melanoma is among the most virulent cancers, owing to its propensity to metastasize and its resistance to current therapies. The treatment failure is largely attributed to tumor heterogeneity, particularly subpopulations possessing stem cell-like properties, ie, melanoma stem-like cells (MSLCs). Evidence indicates that the MSLC phenotype is malleable and may be acquired by non-MSLCs through phenotypic switching upon appropriate stimuli, the so-called 'dynamic stemness'. Since the phenotypic characteristics and functional integrity of MSLCs depend on their vascular niche, using a two-dimensional (2D) melanoma-endothelium co-culture model, where the MSLC niche is recapitulated in vitro, we identified Notch3 signaling pathway as a micro-environmental cue governing MSLC phenotypic plasticity via pathway-specific gene expression arrays...
February 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28149332/the-immunomodulatory-anticancer-agent-rrx-001-induces-an-interferon-response-through-epigenetic-induction-of-viral-mimicry
#17
Hongjuan Zhao, Shoucheng Ning, Rosalie Nolley, Jan Scicinski, Bryan Oronsky, Susan J Knox, Donna M Peehl
BACKGROUND: RRx-001, a dinitroazetidine derivative, is a novel anticancer agent currently in phase II clinical trials. It mediates immunomodulatory effects either directly through polarization of tumor associated macrophages or indirectly through vascular normalization and increased T-lymphocyte infiltration. With multiple additional mechanisms of action including upregulation of oxidative stress, depletion of GSH and NADPH, anti-angiogenesis and epigenetic modulation, RRx-001 is being studied as a radio- and chemo-sensitizer to resensitize tumors to prior therapy and to prime tumors to respond to radiation, chemotherapy and immunotherapy in combination therapy studies...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28125580/molecular-mimicry-between-chikungunya-virus-and-host-components-a-possible-mechanism-for-the-arthritic-manifestations
#18
Vijayalakshmi Reddy, Anita Desai, Shankar Susarla Krishna, Ravi Vasanthapuram
BACKGROUND: Chikungunya virus (CHIKV), a reemerging pathogen causes a self limited illness characterized by fever, headache, myalgia and arthralgia. However, 10-20% affected individuals develop persistent arthralgia which contributes to considerable morbidity. The exact molecular mechanisms underlying these manifestations are not well understood. The present study investigated the possible occurrence of molecular mimicry between CHIKV E1 glycoprotein and host human components. METHODOLOGY: Bioinformatic tools were used to identify peptides of CHIKV E1 exhibiting similarity to host components...
January 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28111017/structural-mimicry-by-a-bacterial-f-box-effector-hijacks-the-host-ubiquitin-proteasome-system
#19
Kathy Wong, John D Perpich, Guennadi Kozlov, Miroslaw Cygler, Yousef Abu Kwaik, Kalle Gehring
Ankyrin B (AnkB/LegAU13) is a translocated F box effector essential for the intracellular replication of the pathogen Legionella pneumophila. AnkB co-opts a host ubiquitin ligase to decorate the pathogen-containing vacuole with K(48)-linked polyubiquitinated proteins and degrade host proteins as a source of energy. Here, we report that AnkB commandeers the host ubiquitin-proteasome system through mimicry of two eukaryotic protein domains. Using X-ray crystallography, we determined the 3D structure of AnkB in complex with Skp1, a component of the human SCF ubiquitination ligase...
February 7, 2017: Structure
https://www.readbyqxmd.com/read/28102519/nmdar-encephalitis-following-herpes-simplex-virus-encephalitis
#20
REVIEW
Jonathan Galli, Stacey L Clardy, Amanda L Piquet
PURPOSE OF REVIEW: Herpes simplex virus encephalitis (HSVE) is often associated with significant morbidity and mortality, and despite appropriate treatment with antivirals, worsening of neurological symptoms or relapse occurs in a subset of patients. Recent data suggests that many relapses are likely caused by a secondary immune response, with the N-methyl-D-aspartate receptor (NMDAR) antibody being the most commonly associated autoantibody. We provide a review of the relevant literature, examining the relationship between HSVE and development of autoimmunity...
January 2017: Current Infectious Disease Reports
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