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  • Result 11-20 of 5623
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11.
  • Moens, Lotte N. J., et al. (author)
  • HaloPlex Targeted Resequencing for Mutation Detection in Clinical Formalin-Fixed, Paraffin-Embedded Tumor Samples
  • 2015
  • In: Journal of Molecular Diagnostics. - : Elsevier BV. - 1525-1578 .- 1943-7811. ; 17:6, s. 729-739
  • Journal article (peer-reviewed)abstract
    • In recent years, the advent of massively parallel next-generation sequencing technologies has enabled substantial advances in the study of human diseases. Combined with targeted DNA enrichment methods, high sequence coverage can be obtained for different genes simultaneously at a reduced cost per sample, creating unique opportunities for clinical cancer diagnostics. However, the formalin-fixed, paraffin-embedded (FFPE) process of tissue samples, routinely used in pathology departments, results in DNA fragmentation and nucleotide modifications that introduce a number of technical challenges for downstream biomotecular analyses. We evaluated the HaloPlex target enrichment system for somatic mutation detection in 80 tissue fractions derived from 20 clinical cancer cases with paired tumor and normal tissue available in both FFPE and fresh-frozen format. Several modifications to the standard method were introduced, including a reduced target fragment Length and two strand capturing. We found that FFPE material can be used for HaloPlex-based target enrichment and next-generation sequencing, even when starting from small amounts of DNA. By specifically capturing both strands for each target fragment, we were able to reduce the number of false-positive errors caused by FFPE-induced artifacts and Lower the detection limit for somatic mutations. We believe that the HaloPlex method presented here will be broadly applicable as a tool for somatic mutation detection in clinical cancer settings.
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12.
  • Liu, Yawei, et al. (author)
  • Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE.
  • 2006
  • In: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 12:5, s. 518-525
  • Journal article (peer-reviewed)abstract
    • Neurons have been neglected as cells with a major immune-regulatory function because they do not express major histocompatibility complex class II. Our data show that neurons are highly immune regulatory, having a crucial role in governing T-cell response and central nervous system (CNS) inflammation. Neurons induce the proliferation of activated CD4+ T cells through B7-CD28 and transforming growth factor (TGF)-beta1–TGF-beta receptor signaling pathways, resulting in amplification of T-cell receptor signaling through phosphorylated ZAP-70, interleukin (IL)-2 and IL-9. The interaction between neurons and T cells results in the conversion of encephalitogenic T cells to CD25+TGF-beta1+CTLA-4+FoxP3+ T regulatory (Treg) cells that suppress encephalitogenic T cells and inhibit experimental autoimmune encephalomyelitis. Suppression is dependent on cytotoxic T lymphocyte antigen (CTLA)-4 but not TGF-beta1. Autocrine action of TGF-beta1, however, is important for the proliferative arrest of Treg cells. Blocking the B7 and TGF-beta pathways prevents the CNS-specific generation of Treg cells. These findings show that generation of neuron-dependent Treg cells in the CNS is instrumental in regulating CNS inflammation.
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13.
  • Mamontov, Eugen, 1955 (author)
  • Homeorhesis and evolutionary properties of living systems: From ordinary differential equations to the active-particle generalized kinetics theory
  • 2006
  • In: 10th Evolutionary Biology Meeting at Marseilles, 20-22 September 2006, Marseilles, France.
  • Conference paper (peer-reviewed)abstract
    • Advanced generalized-kinetic-theory (GKT) models for biological systems are developed for populations of active (or living) particles [1]-[5]. These particles are described with both the stochastic variables common in kinetic theory (such as time, the particle random location and velocity) and the stochastic variables related to the internal states of an active particle. Evolution of these states represents biological, ecological, or social properties of the particle behavior. Paper [6] analyzes a number of the well-known statistical-mechanics approaches and shows that the active-particle GKT (APGKT) is the only treatment capable of modelling living systems. Work [2] summarizes the significance of the notion of an active particle in kinetic models. This notion draws attention to the features distinguishing living matter from nonliving matter. They are discussed by many authors (e.g., [7]-[15], [1]-[3], [6], [16]-[18]). Work [11] considers a lot of differences between living and nonliving matters, and the limitations of the modelling approaches developed for nonliving matter. Work [6] mainly focuses on the comparison of a few theoretical mechanics treatments in terms of the key living-matter properties formulated in [15]. One of the necessary properties of the evolution of living systems is homeorhesis. It is, loosely speaking, a peculiar qualitative and quantitative insensitivity of a living system to the exogenous signals acting on it. The earlier notion, homeostasis, was introduced by W. B. Cannon in 1926 who discussed the phenomenon in detail later [7]. Homeorhesis introduced by C. H. Waddington [8, p. 32] generalizes homeostasis and is well known in biology [8], [9], [12]. It is an inherent part of mathematical models for oncogeny (e.g., [16]-[18], [6, Appendix]). Homeorhesis is also discussed in [3, Section 4] in connection with APGKT. Homeorhesis is documented in ecology (e.g., [11], [13, the left column on p. 675]) where it is one of the key notions of the strong Gaia theory, a version of the Gaia theory (e.g., [14, Chapter 8]). The strong Gaia theory “states that the planet with its life, a single living system, is regulated in certain aspects by that life” [14, p. 124]. The very origin of the name “Gaia” is related to homeorhesis or homeostasis [14, p. 118]. These notions are also used in psychology and sociology. If evolution of a system is not homeorhetic, the system can not be living. Work [6, Appendix] derives a preliminary mathematical formulation of homeorhesis in terms of the simplest dynamical systems, i.e. ordinary differential equations (ODEs). The present work complements, extended, and further specify the approach of [6, Appendix]. The work comprises the two main parts. The first part develops the sufficient conditions for ODE systems to describe homeorhesis, and suggests a fairly general structure of the ODE model. It regards homeorhesis as piecewise homeostasis. The model can be specified in different ways depending on specific systems and specific purposes of the analysis. An example of the specification is also noted (the PhasTraM nonlinear reaction-diffusion model for hyperplastic oncogeny [16]-[18]). The second part of the work discusses implementation of the above homeorhesis ODE model in terms of a special version [3] of APGKT (see above). The key feature of this version is that the components of a living population need not be discrete: the subdivision into the components is described with a general, continuous-discrete probability distribution (see also [6]). This enables certain properties of living matter noted in [15]. Moreover, the corresponding APGKT model presents a system of, firstly, a generalized kinetic equation for the conditional distribution function conditioned by the internal states of the population and, secondly, Ito's stochastic differential equations for these states. This treatement employs the results on nonstationary invariant diffusion stochastic processes [19]. The second part of the work also stresses that APGKT is substantially more important for the living-matter analysis than in the case of nonliving matter. One of the reasons is certain limitations in experimental sampling of the living-system modes presented with stochastic processes. A few directions for future research are suggested as well. REFERENCES: [1] Bellomo, N., Bellouquid, A. and Delitala, M., 2004, Mathematical topics on the modelling complex multicellular systems and tumor immune cells competition, Math. Models Methods Appl. Sci., 14, 1683-1733. [2] Bellomo, N., 2006, New hot Paper Comments, Essential Science Indicators, http://www.esi-topics.com/nhp/2006 /may- 06-NicolaBellomo.html. [3] Willander, M., Mamontov, E. and Chiragwandi, Z., 2004, Modelling living fluids with the subdivision into the components in terms of probability distributions, Math. Models Methods Appl. Sci. 14, 1495-1520. [4] Bellomo, N. and Maini, P.K., 2005, Preface and the Special Issue “Multiscale Cancer Modelling-A New Frontier in Applied Mathematics”, Math. Models Methods Appl. Sci., 15, iii-viii. [5] De Angelis, E. and Delitala, M., 2006, Modelling complex systems in applied sciences: Methods and tools of the mathematical kinetic theory for active particles. Mathl Comput. Modelling, 43, 1310-1328. [6] Mamontov, E., Psiuk-Maksymowicz, K. and Koptioug, A., 2006, Stochastic mechanics in the context of the properties of living systems, Mathl Comput. Modelling, Article in Press, 13 pp. [7] Cannon, W.B., 1932, The Wisdom of the Body (New York: Norton). [8] Waddington, C.H., 1957, The Strategy of the Genes. A Discussion of Some Aspects of Theoretical Biology (London, George Allen and Unwin). [9] Waddington, C.H., 1968, Towards a theoretical biology, Nature, 218, 525-527. [10] Cotnoir, P.-A., 1981, La compétence environnementale: Une affaire d’adaptation. Séminaire en écologie behaviorale, Univeristé du Québec, Montralé. Available online at: http://pac.cam.org/culture.doc . [11] O’Neill, R.V., DeAngelis, D.L., Waide, J.B. and Allen, T.F.H., 1986, A Hierarchical Concept of Ecosystems, Princeton: Princeton Univ. Press). [12] Sauvant, D., 1992, La modélisation systémique en nutrition, Reprod. Nutr. Dev., 32, 217-230. [13] Christensen, N.L., Bartuska, A.M., Brown, J.H., Carpenter, S., D'Antonio, C., Francis, R., Franklin, J.F., MacMahon, J.A., Noss, R.F., Parsons, D.J., Peterson, C.H., Turner, M.G. and Woodmansee, R.G., 1996, The Report of the Ecological Society of America Committee on the Scientific Basis for Ecosystem Management, Ecological Applications, 6, 665-691. Available online at: http://www.esa.org/pao/esaPositions/Papers/ReportOfSBEM.php. [14] Margulis, L., 1998, Symbiotic Planet. A New Look at Evolution (Amherst: Sciencewriters). [15] Hartwell, L.H., Hopfield, J.J., Leibler, S. and Murray, A.W., 1999, From molecular to modular cell biology, Nature, 402, C47-C52. [16] Mamontov, E., Koptioug, A.V. and Psiuk-Maksymowicz, K., 2006, The minimal, phase-transition model for the cell- number maintenance by the hyperplasia-extended homeorhesis, Acta Biotheoretica, 54, 44 pp., (no. 2, May-June, accepted). [17] Psiuk-Maksymowicz, K. and Mamontov, E., 2005, The time-slices method for rapid solving the Cauchy problem for nonlinear reaction-diffusion equations in the competition of homeorhesis with genotoxically activated hyperplasia, In: European Conference on Mathematical and Theoretical Biology - ECMTB05 (July 18-22, 2005) Book of Abstracts, Vol.1 (Dresden: Center for Information Services and High Performance Computing, Dresden Univ. Technol.), p. 429 (http://www.ecmtb05.org/). [18] Psiuk-Maksymowicz, K. and Mamontov, E., 2006, The homeorhesis-based modelling and fast numerical analysis for oncogenic hyperplasia under radiation therapy, submitted. [19] Mamontov, E., 2005, Nonstationary invariant distributions and the hydrodynamic-style generalization of the Kolmogorov-forward/Fokker-Planck equation, Appl. Math. Lett. 18 (9) 976-982.
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14.
  • Heyman, Lovisa (author)
  • Berries in Prevention of Metabolic Disease – focus on obesity, diabetes and gut microbiota
  • 2015
  • Doctoral thesis (other academic/artistic)abstract
    • The increasing prevalence of obesity is a worldwide health problem closely linked to diet and lifestyle factors. Obesity is associated with increased risk of several metabolic disorders including insulin resistance, nonalcoholic fatty liver disease and type 2 diabetes. Hence, there is a great need to identify dietary strategies for the prevention of obesity and related diseases. This thesis investigates the potential of different berries to mediate beneficial health effects in a mouse model of diet-induced obesity and prediabetes. We found that supplementation with lingonberries, blackcurrants and bilberries reduced body weight gain, insulin resistance, low-grade inflammation and hepatic lipid accumulation in C57BL/6J mice fed a high-fat diet. Supplementation with raspberries, crowberries, blackberries or prunes had no or small effects, whereas açai berries promoted development of obesity and fatty liver compared to the control group receiving high-fat diet without berries. Global hepatic gene expression analysis revealed that the phenotype in the lingonberry and bilberry groups was coupled to an anti-inflammatory effect, including downregulation of acute-phase proteins and inflammatory mediators. Mice receiving açai displayed an upregulation of steatosis markers and genes related to lipid synthesis, in line with the exacerbation of high-fat-induced fatty liver in these mice. The HELP-tagging assay was used to identify differentially methylated CpG sites in the lingonberry group compared to the high-fat control group. Lingonberries induced genome-wide and specific alterations of DNA methylation, however the significance of these findings remains to be established. Furthermore, different batches of lingonberries were found to have different capacity to prevent obesity. However lingonberries prevented low-grade inflammation, metabolic endotoxemia and modified the gut microbiota of high-fat fed mice, including increasing the Firmicutes/Bacteroidetes ratio. These findings were independent of effects on body weight gain and achieved regardless of the source of berries. The capacity of lingonberries to counteract negative outcomes of an unhealthy diet should be further evaluated in humans, including assessment of anti-inflammation and microbiota modulation. The generated knowledge about berries and their effects on metabolism may be useful in designing future dietary strategies aimed at preventing metabolic disease.
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15.
  • Rodríguez-Piñeiro, Ana María, et al. (author)
  • The colonic mucus protection depends on the microbiota
  • 2015
  • In: Gut microbes. - : Informa UK Limited. - 1949-0976 .- 1949-0984. ; 6:5, s. 326-30
  • Journal article (other academic/artistic)abstract
    • The intestinal mucus is a pivotal part of our intestinal protection. It provides slow diffusion of protective molecules, trapping of luminal material as bacteria and smooth transport in the small intestine. In colon it restricts bacterial access to the epithelium limiting the responses to the enormous bacterial load present at this location. The development of these systems depends on the microbiota composition as seen in our recent study comparing the mucus phenotype in 2 colonies kept in different husbandries within the same SPF animal facility. One colony had impenetrable colonic mucus while the other colony had more penetrable mucus. The mucus phenotypes were transmitted via the microbiota and clear differences in its composition could be detected. Candidates associated with the different colonies were identified but the observed mucus difference could not be assigned to a specific bacterium.
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16.
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17.
  • Fritz, Michael, 1981-, et al. (author)
  • Interferon-ɣ mediated signaling in the brain endothelium is critical for inflammation-induced aversion
  • 2018
  • In: Brain, behavior, and immunity. - Maryland Heights : Academic Press. - 0889-1591 .- 1090-2139. ; 67, s. 54-58
  • Journal article (peer-reviewed)abstract
    • Systemic inflammation elicits malaise and a negative affective state. The mechanism underpinning the aversive component of inflammation include cerebral prostaglandin synthesis and modulation of dopaminergic reward circuits, but the messengers that mediate the signaling between the peripheral inflammation and the brain have not been sufficiently characterized. Here we investigated the role of interferon-ɣ (IFN-ɣ) in the aversive response to systemic inflammation induced by a low dose (10μg/kg) of lipopolysaccharide (LPS) in mice. LPS induced IFN-ɣ expression in the blood and deletion of IFN-ɣ or its receptor prevented the development of conditioned place aversion to LPS. LPS induced expression of the chemokine Cxcl10 in the striatum of normal mice, but this induction was absent in mice lacking IFN-ɣ receptors or Myd88 in blood brain barrier endothelial cells. Furthermore, inflammation-induced aversion was blocked in mice lacking Cxcl10 or its receptor Cxcr3. Finally, mice with a selective deletion of the IFN-ɣ receptor in brain endothelial cells did not develop inflammation-induced aversion, demonstrating that the brain endothelium is the critical site of IFN-ɣ action. Collectively, these findings show that circulating IFN-ɣ that binds to receptors on brain endothelial cells and induces Cxcl10, is a central link in the signaling chain eliciting inflammation-induced aversion.
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18.
  • Schröder, Björn, et al. (author)
  • Intestinales Mikrobiom und Schleimhautbarriere bei chronisch entzündlichen Darmerkrankungen
  • 2021
  • In: Intestinales Mikrobiom und Innere Medizin. - : UNI-MED Verlag AG. - 9783837416053 ; , s. 46-55
  • Book chapter (other academic/artistic)abstract
    • Das intestinale Mikrobiom repräsentiert aktuell eines der Topthemen, die im Fokus der modernen Humanmedizin stehen. Doch erstaunlicherweise gab es bisher im deutschen Sprachraum keine handliche, aktuelle Übersicht zu diesem Thema. Daher werden in diesem Band zunächst Zusammensetzung und Dynamik des humanen intestinalen Mikrobioms erläutert, ehe in weiteren Kapiteln dann die wichtigsten Veränderungen und vor allem die Rolle des Mikrobioms bei zahlreichen Krankheiten wie chronisch entzündlichen Darmerkrankungen, Reizdarmsyndrom, Leber- und Gallenwegs- sowie Autoimmunerkrankungen diskutiert werden. Es folgen der Komplex Ernährung, Adipositas und Diabetes sowie Atherosklerose mit jeweils eigenen Kapiteln. Schließlich gibt es überraschende Beziehungen der Mikrobiota zur Malignomentstehung. Es folgt ein Abschnitt über Antibiotika und deren Rolle bei zum Teil dauerhaften Störungen der intestinalen Bakterien und Pilze. Am Ende des Buches wird am Beispiel von Mikrobiomtransfer ("Stuhltransplantation") und Probiotika auf die therapeutischen Konsequenzen eingegangen. Alle Kapitel sind auch für sich lesbar und verständlich.
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19.
  • Mamontov, Eugen, 1955, et al. (author)
  • Oncogenic hyperplasia caused by combination of various factors: A decision-support software for radionuclide therapy
  • 2007
  • In: Workshop "Mathematical Modelling and Analysis of Cancer Invasion of Tissues", Mar 26, 2007 - Mar 30, 2007, Dundee, Scotland.
  • Conference paper (peer-reviewed)abstract
    • The present work deals with the software based on the PhasTraM model [1] for oncogenic hyperplasia, the first stage of formation of any solid tumor. The work generalizes the related results of [2]-[6] and discusses application of the software for decision support in radionuclide therapy. The software capabilities to allow for combinations of various causes of oncogeny are emphasized. The causes comprise inflammation, immune dysfunction, and chronic psychological stress. The immune dysfunction is represented with hypogammaglobulenimia expressed in terms of the concentration of the immunoglobulin-G molecules. The level of chronic pychological stress is described with the concentration of the interleukin-6 molecules. The work considers how application of the software can support decisions on the specific radionuclide-therapy setting depending on the tissue-, organ-, and patient-specific data. This is illustrated by a number of numerical-simulation results, also the ones which include the effects of common and fractionation-based radionuclide-therapy modalities. A proper attention is paid to how specifically the input data can be prepared by prospective users of the software, i.e. the specialists who apply radionuclide therapy. The work also formulates a few directions for future research in connection with the features of the everyday work of the prospective users. REFERENCES: [1] E. Mamontov, K. Psiuk-Maksymowicz, A. Koptioug, 2006, Stochastic mechanics in the context of the properties of living systems, Mathl Comput. Modelling, 44(7-8) 595-607. [2] E. Mamontov, A. V. Koptioug, K. Psiuk-Maksymowicz, 2006, The minimal, phase-transition model for the cell-number maintenance by the hyperplasia-extended homeorhesis, Acta Biotheoretica, 54(2) 61-101. [3] K. Psiuk-Maksymowicz and E. Mamontov, 2006, The homeorhesis-based modelling and fast numerical analysis for oncogenic hyperplasia under radiotherapy, Mathl Comput. Modelling, Special Issue
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20.
  • Mamontov, Eugen, 1955, et al. (author)
  • The minimal, phase-transition model for the cell-number maintenance by the hyperplasia-extended homeorhesis
  • 2006
  • In: Acta Biotheoretica. - : Springer Science and Business Media LLC. - 0001-5342 .- 1572-8358. ; 54:2, s. 61-101
  • Journal article (peer-reviewed)abstract
    • Oncogenic hyperplasia is the first and inevitable stage of formation of a (solid) tumor. This stage is also the core of many other proliferative diseases. The present work proposes the first minimal model that combines homeorhesis with oncogenic hyperplasia where the latter is regarded as a genotoxically activated homeorhetic dysfunction. This dysfunction is specified as the transitions of the fluid of cells from a fluid, homeorhetic state to a solid, hyperplastic-tumor state, and back. The key part of the model is a nonlinear reaction-diffusion equation (RDE) where the biochemical-reaction rate is generalized to the one in the well-known Schlögl physical theory of the non-equilibrium phase transitions. A rigorous analysis of the stability and qualitative aspects of the model, where possible, are presented in detail. This is related to the spatially homogeneous case, i.e. when the above RDE is reduced to a nonlinear ordinary differential equation. The mentioned genotoxic activation is treated as a prevention of the quiescent G0-stage of the cell cycle implemented with the threshold mechanism that employs the critical concentration of the cellular fluid and the nonquiescent-cell-duplication time. The continuous tumor morphogeny is described by a time-space-dependent cellular-fluid concentration. There are no sharp boundaries (i.e. no concentration jumps exist) between the domains of the homeorhesis- and tumor-cell populations. No presumption on the shape of a tumor is used. To estimate a tumor in specific quantities, the model provides the time-dependent tumor locus, volume, and boundary that also points out the tumor shape and size. The above features are indispensable in the quantitative development of antiproliferative drugs or therapies and strategies to prevent oncogenic hyperplasia in cancer and other proliferative diseases. The work proposes an analytical-numerical method for solving the aforementioned RDE. A few topics for future research are suggested.
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