164 research outputs found
NS1 Specific CD8(+) T-Cells with Effector Function and TRBV11 Dominance in a Patient with Parvovirus B19 Associated Inflammatory Cardiomyopathy
Background: Parvovirus B19 (B19V) is the most commonly detected virus in endomyocardial biopsies (EMBs) from patients with inflammatory cardiomyopathy (DCMi). Despite the importance of T-cells in antiviral defense, little is known about the role of B19V specific T-cells in this entity.
Methodology and Principal Findings: An exceptionally high B19V viral load in EMBs (115,091 viral copies/mg nucleic acids), peripheral blood mononuclear cells (PBMCs) and serum was measured in a DCMi patient at initial presentation, suggesting B19V viremia. The B19V viral load in EMBs had decreased substantially 6 and 12 months afterwards, and was not traceable in PBMCs and the serum at these times. Using pools of overlapping peptides spanning the whole B19V proteome, strong CD8(+) T-cell responses were elicited to the 10-amico-acid peptides SALKLAIYKA (19.7% of all CD8(+) cells) and QSALKLAIYK (10%) and additional weaker responses to GLCPHCINVG (0.71%) and LLHTDFEQVM (0.06%). Real-time RT-PCR of IFN gamma secretion-assay-enriched T-cells responding to the peptides, SALKLAIYKA and GLCPHCINVG, revealed a disproportionately high T-cell receptor Vbeta (TRBV) 11 expression in this population. Furthermore, dominant expression of type-1 (IFN gamma, IL2, IL27 and Tbet) and of cytotoxic T-cell markers (Perforin and Granzyme B) was found, whereas gene expression indicating type-2 (IL4, GATA3) and regulatory T-cells (FoxP3) was low.
Conclusions: Our results indicate that B19V Ag-specific CD8(+) T-cells with effector function are involved in B19V associated DCMi. In particular, a dominant role of TRBV11 and type-1/CTL effector cells in the T-cell mediated antiviral immune response is suggested. The persistence of B19V in the endomyocardium is a likely antigen source for the maintenance of CD8(+) T-cell responses to the identified epitopes
Transport properties of copper phthalocyanine based organic electronic devices
Ambipolar charge carrier transport in Copper phthalocyanine (CuPc) is studied
experimentally in field-effect transistors and metal-insulator-semiconductor
diodes at various temperatures. The electronic structure and the transport
properties of CuPc attached to leads are calculated using density functional
theory and scattering theory at the non-equilibrium Green's function level. We
discuss, in particular, the electronic structure of CuPc molecules attached to
gold chains in different geometries to mimic the different experimental setups.
The combined experimental and theoretical analysis explains the dependence of
the mobilityand the transmission coefficient on the charge carrier type
(electrons or holes) and on the contact geometry. We demonstrate the
correspondence between our experimental results on thick films and our
theoretical studies of single molecule contacts. Preliminary results for
fluorinated CuPc are discussed.Comment: 18 pages, 16 figures; to be published in Eur. Phys. J. Special Topic
Molecular motors robustly drive active gels to a critically connected state
Living systems often exhibit internal driving: active, molecular processes
drive nonequilibrium phenomena such as metabolism or migration. Active gels
constitute a fascinating class of internally driven matter, where molecular
motors exert localized stresses inside polymer networks. There is evidence that
network crosslinking is required to allow motors to induce macroscopic
contraction. Yet a quantitative understanding of how network connectivity
enables contraction is lacking. Here we show experimentally that myosin motors
contract crosslinked actin polymer networks to clusters with a scale-free size
distribution. This critical behavior occurs over an unexpectedly broad range of
crosslink concentrations. To understand this robustness, we develop a
quantitative model of contractile networks that takes into account network
restructuring: motors reduce connectivity by forcing crosslinks to unbind.
Paradoxically, to coordinate global contractions, motor activity should be low.
Otherwise, motors drive initially well-connected networks to a critical state
where ruptures form across the entire network.Comment: Main text: 21 pages, 5 figures. Supplementary Information: 13 pages,
8 figure
Membranes by the Numbers
Many of the most important processes in cells take place on and across
membranes. With the rise of an impressive array of powerful quantitative
methods for characterizing these membranes, it is an opportune time to reflect
on the structure and function of membranes from the point of view of biological
numeracy. To that end, in this article, I review the quantitative parameters
that characterize the mechanical, electrical and transport properties of
membranes and carry out a number of corresponding order of magnitude estimates
that help us understand the values of those parameters.Comment: 27 pages, 12 figure
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Overview of mathematical approaches used to model bacterial chemotaxis I: the single cell
Mathematical modeling of bacterial chemotaxis systems has been influential and insightful in helping to understand experimental observations. We provide here a comprehensive overview of the range of mathematical approaches used for modeling, within a single bacterium, chemotactic processes caused by changes to external gradients in its environment. Specific areas of the bacterial system which have been studied and modeled are discussed in detail, including the modeling of adaptation in response to attractant gradients, the intracellular phosphorylation cascade, membrane receptor clustering, and spatial modeling of intracellular protein signal transduction. The importance of producing robust models that address adaptation, gain, and sensitivity are also discussed. This review highlights that while mathematical modeling has aided in understanding bacterial chemotaxis on the individual cell scale and guiding experimental design, no single model succeeds in robustly describing all of the basic elements of the cell. We conclude by discussing the importance of this and the future of modeling in this area
Conformational Spread in the Flagellar Motor Switch: A Model Study
The reliable response to weak biological signals requires that they be amplified with fidelity. In E. coli, the flagellar motors that control swimming can switch direction in response to very small changes in the concentration of the signaling protein CheY-P, but how this works is not well understood. A recently proposed allosteric model based on cooperative conformational spread in a ring of identical protomers seems promising as it is able to qualitatively reproduce switching, locked state behavior and Hill coefficient values measured for the rotary motor. In this paper we undertook a comprehensive simulation study to analyze the behavior of this model in detail and made predictions on three experimentally observable quantities: switch time distribution, locked state interval distribution, Hill coefficient of the switch response. We parameterized the model using experimental measurements, finding excellent agreement with published data on motor behavior. Analysis of the simulated switching dynamics revealed a mechanism for chemotactic ultrasensitivity, in which cooperativity is indispensable for realizing both coherent switching and effective amplification. These results showed how cells can combine elements of analog and digital control to produce switches that are simultaneously sensitive and reliable
Immunogenicity of recombinant hepatitis B vaccine: comparison of two different vaccination schedules
Distributed Fading Memory for Stimulus Properties in the Primary Visual Cortex
The brain has a one-back memory for visual stimuli. Neural responses to an image contain as much information about the current image as it does about another image presented immediately before
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