242 research outputs found
Polyfunctional T cell responses in children in early stages of chronic Trypanosoma cruzi infection contrast with monofunctional responses of long-term infected adults
Background: Adults with chronic Trypanosoma cruzi exhibit a poorly functional T cell compartment, characterized by monofunctional (IFN-γ-only secreting) parasite-specific T cells and increased levels of terminally differentiated T cells. It is possible that persistent infection and/or sustained exposure to parasites antigens may lead to a progressive loss of function of the immune T cells. Methodology/Principal Findings: To test this hypothesis, the quality and magnitude of T. cruzi-specific T cell responses were evaluated in T. cruzi-infected children and compared with long-term T. cruzi-infected adults with no evidence of heart failure. The phenotype of CD4+ T cells was also assessed in T. cruzi-infected children and uninfected controls. Simultaneous secretion of IFN-γ and IL-2 measured by ELISPOT assays in response to T. cruzi antigens was prevalent among T. cruzi-infected children. Flow cytometric analysis of co-expression profiles of CD4+ T cells with the ability to produce IFN-γ, TNF-α, or to express the co-stimulatory molecule CD154 in response to T. cruzi showed polyfunctional T cell responses in most T. cruzi-infected children. Monofunctional T cell responses and an absence of CD4+TNF-α+-secreting T cells were observed in T. cruzi-infected adults. A relatively high degree of activation and differentiation of CD4+ T cells was evident in T. cruzi-infected children. Conclusions/Significance: Our observations are compatible with our initial hypothesis that persistent T. cruzi infection promotes eventual exhaustion of immune system, which might contribute to disease progression in long-term infected subjects.Fil: Albareda, María Cecilia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: de Rissio, Ana María. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Tomas, Gonzalo. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Serjan, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Alvarez, María Gabriela. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Viotti, Rodolfo Jorge. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Fichera, Laura Edith. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Esteva, Mónica Inés. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Potente, Daniel Fernando. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Armenti, Alejandro. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Tarleton, Rick L.. University of Georgia; Estados UnidosFil: Laucella, Susana Adriana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
On domain walls in a Ginzburg-Landau non-linear S^2-sigma model
The domain wall solutions of a Ginzburg-Landau non-linear -sigma hybrid
model are unveiled. There are three types of basic topological walls and two
types of degenerate families of composite - one topological, the other
non-topological- walls. The domain wall solutions are identified as the finite
action trajectories (in infinite time) of a related mechanical system that is
Hamilton-Jacobi separable in sphero-conical coordinates. The physical and
mathematical features of these domain walls are thoroughly discussed.Comment: 26 pages, 18 figure
Elderly women with metabolic syndrome present higher cardiovascular risk and lower relative muscle strength
Discrete sources as the origin of the Galactic X-ray ridge emission
An unresolved X-ray glow (at energies above a few kiloelectronvolts) was
discovered about 25 years ago and found to be coincident with the Galactic disk
-the Galactic ridge X-ray emission. This emission has a spectrum characteristic
of a 1e8 K optically thin thermal plasma, with a prominent iron emission line
at 6.7 keV. The gravitational well of the Galactic disk, however, is far too
shallow to confine such a hot interstellar medium; instead, it would flow away
at a velocity of a few thousand kilometres per second, exceeding the speed of
sound in gas. To replenish the energy losses requires a source of 10^{43}
erg/s, exceeding by orders of magnitude all plausible energy sources in the
Milky Way. An alternative is that the hot plasma is bound to a multitude of
faint sources, which is supported by the recently observed similarities in the
X-ray and near-infrared surface brightness distributions (the latter traces the
Galactic stellar distribution). Here we report that at energies of 6-7 keV,
more than 80 per cent of the seemingly diffuse X-ray emission is resolved into
discrete sources, probably accreting white dwarfs and coronally active stars.Comment: 16 pages, 3 figures. Draft version of the paper that will appear in
Nature, Issue April 30, 200
Teste de envelhecimento acelerado em sementes de crambe (Crambe abyssinica Hochst), cultivar FMS Brilhante
Compensatory movements during functional activities in ambulatory children with Duchenne muscular dystrophy
Clinical and nutritional status in the late postoperative of pancreaticoduodenectomy: influence of pylorus preservation procedure
DOGS: Reaction-Driven de novo Design of Bioactive Compounds
We present a computational method for the reaction-based de novo design of drug-like molecules. The software DOGS (Design of Genuine Structures) features a ligand-based strategy for automated ‘in silico’ assembly of potentially novel bioactive compounds. The quality of the designed compounds is assessed by a graph kernel method measuring their similarity to known bioactive reference ligands in terms of structural and pharmacophoric features. We implemented a deterministic compound construction procedure that explicitly considers compound synthesizability, based on a compilation of 25'144 readily available synthetic building blocks and 58 established reaction principles. This enables the software to suggest a synthesis route for each designed compound. Two prospective case studies are presented together with details on the algorithm and its implementation. De novo designed ligand candidates for the human histamine H4 receptor and γ-secretase were synthesized as suggested by the software. The computational approach proved to be suitable for scaffold-hopping from known ligands to novel chemotypes, and for generating bioactive molecules with drug-like properties
Effects of a 10% carbamide peroxide bleaching agent on rat oral epithelium proliferation
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