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Molecular mimicry

Giulia Gibiino, Loris Riccardo Lopetuso, Franco Scaldaferri, Gianenrico Rizzatti, Cecilia Binda, Antonio Gasbarrini
Bacteroidetes are the largest phylum of Gram-negative bacteria inhabiting our gastrointestinal tract and are considered the leading players of the healthy state and sophisticated homeostasis safeguarded by gut microbiota. Furthermore, specific roles have been attributed to some Bacteroidetes genera in the development of immune dysregulation, systemic disease such as metabolic syndrome and also neurological disorders. Glycoproteins secretion, short fatty acids imbalance, toxins production and molecular mimicry are only a part of the functions exerted by these commensals interacting with the host...
March 20, 2018: Digestive and Liver Disease
Guglielmo Lucchese, Benjamin Stahl
The present study seeks to determine potential associations between viral infections and neuropsychiatric diseases. To address this issue, we investigated the peptide commonalities between viruses that have been related to psychiatric and neurological disorders-such as rubella, human immunodeficiency virus, and herpesviruses-and human distal-less homeobox (DLX) proteins expressed in developing brain-namely, DLX1, DLX2, DLX5, and DLX6. Peptide matching analyses revealed a high degree of pentapeptide sharing...
2018: Frontiers in Neuroscience
Carlos M Baez-Cotto, Mahesh K Mahanthappa
Concentration-dependent supramolecular self-assembly of amphiphilic molecules in water furnishes a variety of nanostructured lyotropic liquid crystals (LLCs), which typically display high symmetry bicontinuous and discontinuous micellar morphologies. Aqueous dispersions of soft spherical micelles derived from small molecule amphiphile hydration typically pack into exemplary body-centered cubic and closest-packed LLCs. However, investigations of hydrated mixtures of the ionic surfactant tetramethylammonium decanoate loaded with 40 wt% n-decane (TMADec-40) revealed the formation of a high symmetry bicontinuous double diamond LLC, as well as cubic C15 and new hexagonal C14 Laves LLC phases that mirror the MgCu2 and MgZn2 intermetallic structure types, respectively...
April 3, 2018: ACS Nano
B Rodríguez-Iturbe, R J Johnson
The development of stress drives a host of biological responses that include the overproduction of a family of proteins named heat shock proteins (HSPs), because they were initially studied after heat exposure. HSPs are evolutionarily preserved proteins with a high degree of interspecies homology. HSPs are intracellular proteins that also have extracellular expression. The primary role of HSPs is to protect cell function by preventing irreversible protein damage and facilitating molecular traffic through intracellular pathways...
March 1, 2018: Physiology International
Yen-Hsiu Yeh, Ho-Fu Hsiao, Yen-Cheng Yeh, Tien-Wen Chen, Tsai-Kun Li
BACKGROUND: Tumor microenvironments (TMEs) activate various axes/pathways, predominantly inflammatory and hypoxic responses, impact tumorigenesis, metastasis and therapeutic resistance significantly. Although molecular pathways of individual TME are extensively studied, evidence showing interaction and crosstalk between hypoxia and inflammation remain unclear. Thus, we examined whether interferon (IFN) could modulate both inflammatory and hypoxic responses under normoxia and its relation with cancer development...
March 27, 2018: Journal of Experimental & Clinical Cancer Research: CR
Wangfeng Cai, Ying Ran, Yanni Li, Bangmao Wang, Lu Zhou
Autoimmune hepatitis (AIH) is a severe inflammatory liver disease. The underlying mechanisms remain unclear, but recent studies provided new perspectives on altered intestinal microbiome and permeability in AIH animal models and patients, highlighting gut-liver crosstalk in the pathogenesis of AIH. Transgenic AIH mice carrying HLA-DR3 showed reduced diversity and total load of gut microbiota. Germ-free mice are resistant to concanavalin A-induced liver injury, whereas enterogenouss antigens induce the activation of natural killer T cells participating in concanavalin A-induced liver injury, supporting the close relationship between microbiota and AIH...
December 2017: Best Practice & Research. Clinical Gastroenterology
Antonios Drakopoulos, Christina Tzitzoglaki, Kelly McGuire, Anja Hoffmann, Athina Konstantinidi, Dimitrios Kolokouris, Chunlong Ma, Kathrin Freudenberger, Johanna Hutterer, Günter Gauglitz, Jun Wang, Michaela Schmidtke, David D Busath, Antonios Kolocouris
Recently, the binding kinetics of a ligand-target interaction, such as the residence time of a small molecule on its protein target, are seen as increasingly important for drug efficacy. Here, we investigate these concepts to explain binding and proton blockage of rimantadine variants bearing progressively larger alkyl groups to influenza A virus M2 wild type (WT) and M2 S31N protein proton channel. We showed that resistance of M2 S31N to rimantadine analogues compared to M2 WT resulted from their higher k off rates compared to the k on rates according to electrophysiology (EP) measurements...
March 8, 2018: ACS Medicinal Chemistry Letters
Luis J Jara, Gabriela Medina, Miguel A Saavedra
PURPOSE OF REVIEW: To provide an update about the interactions between infections and autoimmune diseases (AIDs), from the molecular perspective to the clinical spectrum and the differentiation between infection and disease activity. RECENT FINDINGS: Any kind of infection may modify the innate and adaptive immune response through the following mechanisms: molecular mimicry, superantigens, epitope spreading and B-cell activation. The consequence is the overproduction of antibodies shared with those found in AIDs...
March 9, 2018: Current Opinion in Rheumatology
S D Sara Diani
Chronic diseases are defined diseases whose symptoms last for at least six months and tend to worsen over time. In Europe, they cause at least 86% of deaths. In this speculative unifying model I set a new hypothesis for the etiology of the majority of chronic diseases. The main aim is to put order and observe our organism in a systemic way, connecting pathologies we now see as disconnected phenomena, with the conceptual frameworks of complex systems and network medicine. Chronic diseases could be caused by a first unsolved acute infection...
April 2018: Medical Hypotheses
Kathryn A Patras, Victor Nizet
Group B Streptococcus (GBS) colonizes the gastrointestinal and vaginal epithelium of a significant percentage of healthy women, with potential for ascending intrauterine infection or transmission during parturition, creating a risk of serious disease in the vulnerable newborn. This review highlights new insights on the bacterial virulence determinants, host immune responses, and microbiome interactions that underpin GBS vaginal colonization, the proximal step in newborn infectious disease pathogenesis. From the pathogen perspective, the function GBS adhesins and biofilms, β-hemolysin/cytolysin toxin, immune resistance factors, sialic acid mimicry, and two-component transcriptional regulatory systems are reviewed...
2018: Frontiers in Pediatrics
Weili Liang, Shasha Song, Yintao Xu, Huiying Li, Huantao Liu
Breast cancer is a common malignant tumor in women. It has been suggested that a type of microcirculation pattern that does not rely on host microvascular endothelial cells known as vasculogenic mimicry (VM) may contribute to the poor effect of anti‑angiogenesis treatment on some patients with breast cancer. However, the formation and regulatory mechanism of VM in breast cancer are unclear and still require further investigation. The present study examined whether decreasing the expression of zinc finger E‑box binding homeobox (ZEB1) using siRNA can inhibit the formation of VM in Triple Negative Breast Cancer (TNBC), and its specific function and molecular mechanism...
March 5, 2018: Molecular Medicine Reports
Zahra Assur Sanghai, Linamarie Miller, Kelly R Molloy, Jonas Barandun, Mirjam Hunziker, Malik Chaker-Margot, Junjie Wang, Brian T Chait, Sebastian Klinge
Early co-transcriptional events of eukaryotic ribosome assembly result in the formation of precursors of the small (40S) and large (60S) ribosomal subunits1 . A multitude of transient assembly factors regulate and chaperone the systematic folding of pre-ribosomal RNA subdomains. However, due to limited structural information, the role of these factors during early nucleolar 60S assembly is not fully understood. Here we have determined cryo-EM reconstructions of the nucleolar pre-60S ribosomal subunit in different conformational states at resolutions up to 3...
March 5, 2018: Nature
Yahel Segal, Yehuda Shoenfeld
Since the early 1800s vaccines have saved numerous lives by preventing lethal infections. However, during the past two decades, there has been growing awareness of possible adverse events associated with vaccinations, cultivating heated debates and leading to significant fluctuations in vaccination rates. It is therefore pertinent for the scientific community to seriously address public concern of adverse effects of vaccines to regain public trust in these important medical interventions. Such adverse reactions to vaccines may be viewed as a result of the interaction between susceptibility of the vaccinated subject and various vaccine components...
March 5, 2018: Cellular & Molecular Immunology
Junqing Guo, Heng Cai, Xiaobai Liu, Jian Zheng, Yunhui Liu, Wei Gong, Jiajia Chen, Zhuo Xi, Yixue Xue
Glioma is recognized as a highly angiogenic malignant brain tumor. Vasculogenic mimicry (VM) greatly restricts the therapeutic effect of anti-angiogenic tumor therapy for glioma patients. However, the molecular mechanisms of VM formation in glioma remain unclear. Here, we demonstrated that LINC00339 was upregulated in glioma tissue as well as in glioma cell lines. The expression of LINC00339 in glioma tissues was positively correlated with glioma VM formation. Knockdown of LINC00339 inhibited glioma cell proliferation, migration, invasion, and tube formation, meanwhile downregulating the expression of VM-related molecular MMP-2 and MMP-14...
March 2, 2018: Molecular Therapy. Nucleic Acids
Sundus Erbas-Cakmak, Safacan Kolemen, Adam C Sedgwick, Thorfinnur Gunnlaugsson, Tony D James, Juyoung Yoon, Engin U Akkaya
The field of molecular logic gates originated 25 years ago, when A. P. de Silva published a seminal article in Nature. Stimulated by this ground breaking research, scientists were inspired to join the race to simulate the workings of the fundamental components of integrated circuits using molecules. The rules of this game of mimicry were flexible, and have evolved and morphed over the years. This tutorial review takes a look back on and provides an overview of the birth and growth of the field of molecular logics...
March 1, 2018: Chemical Society Reviews
Michal Motyka, Lucie Kampova, Ladislav Bocak
Multiple patterns and intraspecific polymorphism should not persist in mutualistic Müllerian systems due to purifying and frequency-dependent selection, but they are commonly identified in nature. We analysed molecular phylogeny and reconstructed dispersal history of 58 species of Dilophotes (Coleoptera: Lycidae) in Asia. Dilophotes colonized the Great Sundas and Malay Peninsula where they joined extensive mimetic communities of net-winged beetles. We identified the brightly bi-coloured males and females which adverged on five occasions to different autochthonous models...
February 27, 2018: Scientific Reports
Anastasiya Atanasova Chokoeva, Ilia Lozev, Irina Yungareva, Uwe Wollina, Torello Lotti, Georgi Konstantinov Maximov, Georgi Tchernev
It is well-established that drugs could be leading cause of occurrence of numerous diseases, including pemphigus, being either inducer or triggering factor of the autoimmunity. Despite medications, it should be kept in mind that chronic or acute infections are also capable of being a trigger in various types of cutaneous eruptions, including pemphigus. The rapidly obtained and uncompleted history for accompanied medication leads to general mistakes in the subsequent treatment approach, as the first step in such cases is discontinuation of the drug-inductor...
January 25, 2018: Open Access Macedonian Journal of Medical Sciences
Georgi Tchernev, Torello Lotti, Uwe Wollina, José Carlos Cardoso, Lyubomira Viktor Popova, Georgi Konstantinov Maximov, Ilia Lozev, Ivan Terziev
The pathogenesis, diagnosis and therapy of sarcoidosis as an autonomous disease are subjects of spirited discussions, which haven't found definitive conclusion yet. Distinguishing between sarcoidosis and sarcoid-like reactions (sarcoid - type granulomas) is not currently a medical "gold standard" and is not implemented in clinical practice. This leads to 1) misinterpretation of numerous available data; 2) difficulty in the interpretation of other unverified data, which is often followed by 3) inappropriate or inadequate therapeutic approach...
January 25, 2018: Open Access Macedonian Journal of Medical Sciences
Farzad Fatehi, Sergey N Kyrychko, Aleksandra Ross, Yuliya N Kyrychko, Konstantin B Blyuss
Among various possible causes of autoimmune disease, an important role is played by infections that can result in a breakdown of immune tolerance, primarily through the mechanism of "molecular mimicry". In this paper we propose and analyse a stochastic model of immune response to a viral infection and subsequent autoimmunity, with account for the populations of T cells with different activation thresholds, regulatory T cells, and cytokines. We show analytically and numerically how stochasticity can result in sustained oscillations around deterministically stable steady states, and we also investigate stochastic dynamics in the regime of bi-stability...
2018: Frontiers in Physiology
Alejandra Culebro, Miguel P Machado, João André Carriço, Mirko Rossi
Campylobacter jejuni and Campylobacter coli are the most common cause of bacterial gastroenteritis worldwide. Additionally, C. jejuni is the most common bacterial etiological agent in the autoimmune Guillain-Barré syndrome (GBS). Ganglioside mimicry by C. jejuni lipooligosaccharide (LOS) is the triggering factor of the disease. LOS-associated genes involved in the synthesis and transfer of sialic acid (glycosyltranferases belonging to family GT-42) are essential in C. jejuni to synthesize ganglioside-like LOS...
February 14, 2018: Scientific Reports
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