25 research outputs found

    Spatiotemporal dynamics of virus infection spreading in tissues

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    Virus spreading in tissues is determined by virus transport, virus multiplication in host cells and the virus-induced immune response. Cytotoxic T cells remove infected cells with a rate determined by the infection level. The intensity of the immune response has a bell-shaped dependence on the concentration of virus, i.e., it increases at low and decays at high infection levels. A combination of these effects and a time delay in the immune response determine the development of virus infection in tissues like spleen or lymph nodes. The mathematical model described in this work consists of reaction-diffusion equations with a delay. It shows that the different regimes of infection spreading like the establishment of a low level infection, a high level infection or a transition between both are determined by the initial virus load and by the intensity of the immune response. The dynamics of the model solutions include simple and composed waves, and periodic and aperiodic oscillations. The results of analytical and numerical studies of the model provide a systematic basis for a quantitative understanding and interpretation of the determinants of the infection process in target organs and tissues from the image-derived data as well as of the spatiotemporal mechanisms of viral disease pathogenesis, and have direct implications for a biopsy-based medical testing of the chronic infection processes caused by viruses, e.g. HIV, HCV and HBV. © 2016 Bocharov et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

    Understanding Ion Conductance on a Molecular Level: An All-Atom Modeling of the Bacterial Porin OmpF

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    AbstractAll-atom molecular dynamics simulations of the ion current through OmpF, the major porin in the outer membrane of Escherichia coli, were performed. Starting from the crystal structure, the all-atom modeling allows us to calculate a parameter-free ion conductance in semiquantitative agreement with experiment. Discrepancies between modeling and experiment occur, e.g., at salt concentrations above 1 M KCl or at high temperatures. At lower salt concentrations, the ions have separate pathways along the channel surface. The constriction zone in the channel contains, on one side, a series of positively charges (R42, R82, R132), and on the opposite side, two negatively charged residues (D113, E117). Mutations generated in the constriction zone by removing cationic residues enhance the otherwise small cation selectivity, whereas removing the anionic residues reverses the selectivity. Reduction of the negatively charged residues decreases the conductance by half, whereas cationic residues enhance the conductance. Experiments on mutants confirm the results of the molecular-level simulations

    The Course of Dyskeratosis Congenita Masked by Crohn’s Disease in a Primary School-Age Child: Case Report

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    Background. Dyskeratosis congenita (DC) is an extremely rare genetically determined syndrome associated with the formation of bone marrow depression and clinically manifested by abnormal pigmentation of the skin, onychodystrophy, cobble-stone tongue, damage to the gastrointestinal tract, lungs, etc. Pathology may occur under the guise of other, more common diseases, which leads to late verification of the diagnosis and affects the prognosis. Case report. The boy D., aged 7 years, was hospitalized with complaints of dysphagia, a change in the shape of nails, ulcerative lesions of the tongue, insufficient weight gain, thin stool. Laboratory: decrease in hemoglobin, pancytopenia, low concentration of IgG in blood serum. According to esophagogastroduodenoscopy— esophageal stenosis. Crohn’s disease was suspected, but the condition worsened against the background of anti-TNF therapy. According to the results of full-exome sequencing, a pathogenic variant c.1058C>T (chrX:154001427C>T; NM_001363.3; p.A353V) was detected in the DKC1 gene in a hemizygous state, on the basis of which DC was confirmed. Conclusion. Practitioners should be wary of DC, since its manifestations can often mimic other, more common pathological conditions, in particular inflammatory bowel diseases. The correct interpretation of the combination of clinical, laboratory and instrumental changes can help to get closer to the correct diagnosis even before receiving the results of a molecular genetic study and determine therapeutic tactics
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