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Molecular mimicry

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https://www.readbyqxmd.com/read/28284719/hypoxia-mediated-mechanisms-associated-with-antiangiogenic-treatment-resistance-in-glioblastomas
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28100677/paired-siglec-receptors-generate-opposite-inflammatory-responses-to-a-human-specific-pathogen
#14
Flavio Schwarz, Corinna S Landig, Shoib Siddiqui, Ismael Secundino, Joshua Olson, Nissi Varki, Victor Nizet, Ajit Varki
Paired immune receptors display near-identical extracellular ligand-binding regions but have intracellular sequences with opposing signaling functions. While inhibitory receptors dampen cellular activation by recognizing self-associated molecules, the functions of activating counterparts are less clear. Here, we studied the inhibitory receptor Siglec-11 that shows uniquely human expression in brain microglia and engages endogenous polysialic acid to suppress inflammation. We demonstrated that the human-specific pathogen Escherichia coli K1 uses its polysialic acid capsule as a molecular mimic to engage Siglec-11 and escape killing...
March 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28099001/conformational-dynamics-in-penicillin-binding-protein-2a-of-methicillin-resistant-staphylococcus-aureus-allosteric-communication-network-and-enablement-of-catalysis
#15
Kiran V Mahasenan, Rafael Molina, Renee Bouley, María T Batuecas, Jed F Fisher, Juan A Hermoso, Mayland Chang, Shahriar Mobashery
The mechanism of the β-lactam antibacterials is the functionally irreversible acylation of the enzymes that catalyze the cross-linking steps in the biosynthesis of their peptidoglycan cell wall. The Gram-positive pathogen Staphylococcus aureus uses one primary resistance mechanism. An enzyme, called penicillin-binding protein 2a (PBP2a), is brought into this biosynthetic pathway to complete the cross-linking. PBP2a effectively discriminates against the β-lactam antibiotics as potential inhibitors, and in favor of the peptidoglycan substrate...
February 8, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28098555/nematophagous-fungus-arthrobotrys-oligospora-mimics-olfactory-cues-of-sex-and-food-to-lure-its-nematode-prey
#16
Yen-Ping Hsueh, Matthew R Gronquist, Erich M Schwarz, Ravi David Nath, Ching-Han Lee, Shalha Gharib, Frank C Schroeder, Paul W Sternberg
To study the molecular basis for predator-prey coevolution, we investigated how Caenorhabditis elegans responds to the predatory fungus Arthrobotrys oligospora. C. elegans and other nematodes were attracted to volatile compounds produced by A. oligospora. Gas-chromatographic mass-spectral analyses of A. oligospora-derived volatile metabolites identified several odors mimicking food cues attractive to nematodes. One compound, methyl 3-methyl-2-butenoate (MMB) additionally triggered strong sex- and stage-specific attraction in several Caenorhabditis species...
January 18, 2017: ELife
https://www.readbyqxmd.com/read/28035914/antibody-mimicry-receptors-and-clinical-applications
#17
Alberto L Horenstein, Antonella Chillemi, Valeria Quarona, Andrea Zito, Valentina Mariani, Angelo C Faini, Fabio Morandi, Ilaria Schiavoni, Clara Maria Ausiello, Fabio Malavasi
This review focuses on the concept of antibodies acting as receptor agonists and antagonists, and on the potential relevance of this notion in applied medicine. Antibodies are composed of three functional units: two antigen-binding fragments (Fabs) that confer antigen specificity and one constant fragment (Fc) linking antibodies to immune effector functions. The proof-of-concept that large amounts of highly specific and homogeneous antibodies could be produced was provided in 1975 by César Milstein and Georges Köhler...
December 23, 2016: Human Antibodies
https://www.readbyqxmd.com/read/28009252/structural-basis-for-the-inhibition-of-recbcd-by-gam-and-its-synergistic-antibacterial-effect-with-quinolones
#18
Martin Wilkinson, Lucy Troman, Wan Ak Wan Nur Ismah, Yuriy Chaban, Matthew B Avison, Mark S Dillingham, Dale B Wigley
Our previous paper (Wilkinson et al, 2016) used high-resolution cryo-electron microscopy to solve the structure of the Escherichia coli RecBCD complex, which acts in both the repair of double-stranded DNA breaks and the degradation of bacteriophage DNA. To counteract the latter activity, bacteriophage λ encodes a small protein inhibitor called Gam that binds to RecBCD and inactivates the complex. Here, we show that Gam inhibits RecBCD by competing at the DNA-binding site. The interaction surface is extensive and involves molecular mimicry of the DNA substrate...
December 23, 2016: ELife
https://www.readbyqxmd.com/read/28002618/verteporfin-suppresses-cell-survival-angiogenesis-and-vasculogenic-mimicry-of-pdac-via-disrupting-the-yap-tead-complex
#19
Honglong Wei, Fuhai Wang, Yong Wang, Tao Li, Peng Xiu, Jingtao Zhong, Xueying Sun, Jie Li
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies. The Yes-associated protein-1 (YAP) plays a critical role in cell proliferation, apoptosis and angiogenesis. Verteporfin is a photosensitizer used in photodynamic therapy and also a small molecular inhibitor of the Hippo-YAP pathway. However, little is known whether verteporfin could inhibit YAP activity in PDAC cells. Our present results showed that verteporfin suppressed the proliferation of human PDAC PANC-1 and SW1990 cells by arresting cells at G1 phase, and inducing apoptosis in dose- and time-dependent manners...
December 21, 2016: Cancer Science
https://www.readbyqxmd.com/read/27999312/a-possible-role-of-intestinal-microbiota-in-the-pathogenesis-of-ankylosing-spondylitis
#20
REVIEW
Lianjun Yang, Liping Wang, Xin Wang, Cory J Xian, Hai Lu
Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily affecting the sacroiliac joints and the spine, for which the pathogenesis is thought to be a result of the combination of host genetic factors and environmental triggers. However, the precise factors that determine one's susceptibility to AS remain to be unraveled. With 100 trillion bacteria residing in the mammalian gut having established a symbiotic relation with their host influencing many aspects of host metabolism, physiology, and immunity, a growing body of evidence suggests that intestinal microbiota may play an important role in AS...
December 17, 2016: International Journal of Molecular Sciences
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