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717 result(s) for "de Jesus, Miguel M."
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Microparticle traction force microscopy reveals subcellular force exertion patterns in immune cell–target interactions
Force exertion is an integral part of cellular behavior. Traction force microscopy (TFM) has been instrumental for studying such forces, providing spatial force measurements at subcellular resolution. However, the applications of classical TFM are restricted by the typical planar geometry. Here, we develop a particle-based force sensing strategy for studying cellular interactions. We establish a straightforward batch approach for synthesizing uniform, deformable and tuneable hydrogel particles, which can also be easily derivatized. The 3D shape of such particles can be resolved with superresolution (<50 nm) accuracy using conventional confocal microscopy. We introduce a reference-free computational method allowing inference of traction forces with high sensitivity directly from the particle shape. We illustrate the potential of this approach by revealing subcellular force patterns throughout phagocytic engulfment and force dynamics in the cytotoxic T-cell immunological synapse. This strategy can readily be adapted for studying cellular forces in a wide range of applications. Traction force microscopy is an effective method for measuring cellular forces but it is limited by planar geometry. Here the authors develop a facile method to produce deformable hydrogel particles and a reference-free computational method to resolve surface traction forces from particle shape deformation.
Autologous Adipose-Derived Mesenchymal Stromal Cells for the Treatment of Psoriasis Vulgaris and Psoriatic Arthritis: A Case Report
Psoriasis is a dermatologic disease of immune origins with no definitive cure. We report the Makati Medical Center experience of utilizing autologous mesenchymal stromal cells (MSCs) for one patient with psoriasis vulgaris (PV) and another with psoriatic arthritis (PA). Patients were educated and gave informed consent, according to the principles of the Declaration of Helsinki. The protocol was approved by the Cellular Transplantation Ethics Committee of the Makati Medical Center. Autologous MSCs were cultured from lipoaspirate and expanded in a clean room class 100 facility (Cellular Therapeutics Center, Makati Medical Center). MSCs were infused intravenously at a dose of 0.5–3.1 million cells/kg after complying with quality control parameters. Psoriasis area and severity index (PASI) evaluations were conducted by third-party dermatologists. The PA patient, who was previously unresponsive to standard treatment modalities, demonstrated a decrease in PASI (from 21.6 to 9.0, mild state after two infusions). No improvements were noted in joint pain until further treatment with etanercept and infliximab. The PV patient, who was previously dependent on methotrexate, showed a decrease in PASI from 24.0 to 8.3 after three infusions; this clinical improvement was sustained for 292 days (9.7 months) without methotrexate. The PV patient illustrated a marginal reduction in serum tumor necrosis factor-α (TNF-α), while significant (3.5- to 5-fold) decreases in reactive oxygen species (ROS) activity were noted. The ROS levels correlated with the clinical improvement of the PV patient. No serious adverse events were noted for either patient as a result of MSC infusions. This report demonstrates safe and tolerable transplantation of autologous MSCs for the treatment of psoriasis and warrants large clinical studies to investigate the long-term safety and efficacy of this approach.
β2 integrins impose a mechanical checkpoint on macrophage phagocytosis
Phagocytosis is an intensely physical process that depends on the mechanical properties of both the phagocytic cell and its chosen target. Here, we employed differentially deformable hydrogel microparticles to examine the role of cargo rigidity in the regulation of phagocytosis by macrophages. Whereas stiff cargos elicited canonical phagocytic cup formation and rapid engulfment, soft cargos induced an architecturally distinct response, characterized by filamentous actin protrusions at the center of the contact site, slower cup advancement, and frequent phagocytic stalling. Using phosphoproteomics, we identified β2 integrins as critical mediators of this mechanically regulated phagocytic switch. Macrophages lacking β2 integrins or their downstream effectors, Talin1 and Vinculin, exhibited specific defects in phagocytic cup architecture and selective suppression of stiff cargo uptake. We conclude that integrin signaling serves as a mechanical checkpoint during phagocytosis to pair cargo rigidity to the appropriate mode of engulfment. Phagocytosis is regulated by the mechanical properties of both the phagocyte and its cargo. Here, the authors show that macrophages employ β2 integrins to sense the rigidity of phagocytic cargo and then mount the appropriate form of engulfment.
Comparative performance of lateral flow immunochromatography, iELISA and Rose Bengal tests for the diagnosis of cattle, sheep, goat and swine brucellosis
Brucellosis is a world-wide extended zoonosis that causes a grave problem in developing economies. Animal vaccination and diagnosis are essential to control brucellosis, and the need for accurate but also simple and low-cost tests that can be implemented in low-infrastructure laboratories has been emphasized. We evaluated bovine, sheep, goat and swine lateral flow immunochromatography assay kits (LFA), the Rose Bengal test (RBT) and a well-validated protein G indirect ELISA (iELISA) using sera of Brucella culture-positive and unvaccinated brucellosis free livestock. Sera from cattle vaccinated with S19 and RB51 brucellosis vaccines were also tested. Finally, we compared RBT and LFA using sera of white Fulani cattle of unknown bacteriological status from a brucellosis endemic area of Nigeria. Although differences were not statistically significant, RBT showed the highest values for diagnostic sensitivity/specificity in cattle (LFA, 96.6/98.8; RBT, 98.9/100; and iELISA, 96.6/100) and the iELISA yielded highest values in sheep (LFA, 94.0/100; RBT, 92.0/100; iELISA, 100/100), goats (LFA, 95.7/96.2; RBT, 97.8/100; iELISA, 100/100) and pigs (LFA, 92.3/100; RBT, 92.3/100; iELISA, 100/100). Vaccine S19 administered subcutaneously interfered in all tests but conjunctival application minimized the problem. Although designed not to interfere in serodiagnosis, vaccine RB51 interfered in LFA and iELISA but not in the RBT. We found closely similar apparent prevalence results when testing the Nigerian Fulani cattle by RBT and LFA. Although both RBT and LFA (showing similar diagnostic performance) are suitable for small laboratories in resource-limited areas, RBT has the advantage that a single reagent is useful in all animal species. Considering these advantages, its low cost and that it is also useful for human brucellosis diagnosis, RBT might be a good choice for resource-limited laboratories.
Evaluation of particulate acellular vaccines against Brucella ovis infection in rams
The attenuated Brucella melitensis Rev 1 vaccine, used against brucellosis infection, interferes with serological diagnosis tests, may induce abortions in pregnant animals, and may infect humans. In order to overcome these drawbacks, we developed acellular vaccines based on a Brucella ovis antigenic complex (HS) containing outer membrane proteins and R-LPS entrapped in poly(anhydride) conventional and mannosylated nanoparticles (NP-HS and MAN-NP-HS) or in poly(ɛ-caprolactone) microparticles (HS-PEC) as antigen delivery systems and immunoadjuvants. Brucellosis free rams were vaccinated subcutaneously with a single dose of particles containing 3 mg of HS, and challenged 6 months thereafter. Protection was evaluated by clinical, bacteriological and serological examinations, in comparison with non-vaccinated control rams. HS-PEC vaccine induced protection (7 out of 13 animals were infected) equivalent to that induced by the reference Rev 1 vaccine (8/14). In contrast, animals immunized with NP-HS were not protected, showing similar results to that obtained in the control unvaccinated rams. Furthermore HS-PEC vaccine did not interfere against B. melitensis serodiagnostic tests. In summary, HS-PEC microparticles could be used as a safe and effective vaccine against brucellosis in rams.
A New Index of Democracy
The present paper analyses and revises the latest Democracy Index published by the Economist Intelligence Unit in the United Kingdom. We analyze the changes produced in the index from 2006 to 2011, as well as in the five basic factors that constitute the index: electoral process and pluralism; civil liberties; the functioning of government; political participation; and political culture. The analysis of these factors -measured by sixty variables- has made it possible to develop a new index, based on the data from 167 countries, and calculate a revised ranking. Countries have been classified into four types: democracies, flawed democracies, mixed systems, and authoritarian/totalitarian regimes. The new index permits a better understanding of the impact of the crisis through variables such as economic growth, human development, quality of life, corruption, and violence. Adapted from the source document.
Isomorfismo y serendipidad en la Sociología norteamerifcana
Isomorfismo y serendipidad en la Sociología norteamerifcana / coord. por Jesús Manuel de Miguel Rodríguez y Carmen Sánchez Jara
Brucella outer membrane complex-loaded microparticles as a vaccine against Brucella ovis in rams
Due to the important drawbacks of the Brucella melitensis Rev 1 vaccine, a safer vaccine based on an outer membrane complex from Brucella ovis encapsulated in poly-ɛ-caprolactone (PEC) microparticles (MP) was developed and tested in rams. Homogeneous batches of microparticles were prepared by a new double emulsion solvent evaporation method called “Total Recirculation One-Machine System” (TROMS). Such microparticles presented a mean diameter of 2 μm and displayed an antigen loading of about 13 μg HS per mg of microparticles. Subcutaneous vaccination of rams with 800 μg HS (hot saline antigenic extract of B. ovis) in PEC microparticles induced an adequate serological response against B. ovis antigens and conferred similar protection against challenge with B. ovis to that induced by the living attenuated B. melitensis Rev 1 reference vaccine. By contrast, lower doses (80 μg) of HS-PEC evoked reduced serological responses against B. ovis antigens and did not induce significant protection. The revaccination with 800 μg of HS-PEC increased the intensity and duration of the serological response against B. ovis antigens but did not improve the protection conferred by the single vaccination. Sample sera taken from any of the animals immunized with Rev 1 were seropositive in both Rose Bengal and the Complement Fixation tests (RBT, CFT) used for the diagnosis of smooth Brucella infections. By contrast, no positive reactors in both tests were recorded in the animals vaccinated with HS-PEC, being this a target objective of this study. HS-PEC microparticles can be used as a safe vaccine against brucellosis in rams, but further studies using higher doses of antigens are necessary to exploit their full potential for the prophylaxis of brucellosis in sheep.
Para una sociología de la fotografía
La Fotografía se inventa en 1839, la misma fecha en que Auguste Comte empieza a escribir sobre la nueva ciencia de la Sociología. El famoso Discours sur l'esprit positif se publica un lustro después. Es interesante recordar que ses \"discurso\" es en realidad un prólogo, largo (de unas 140 páginas), a su Tratado filosófico de astronomía popular. La visión del mundo a través del anteojo del teleobjetivo es, pues, iniciada por el nuevo espíritu positivo de la Sociología. Fotografía y Sociología son dos disciplinas hermanas, francesas por nacimiento, relacionadas desde su inicio. Ambas nacen en Europa, se exportan a América y se reimportan a finales del siglo XX desde Estados Unidos a Europa. Vienen entonces con ropajes y temas nuevos pero conservan un sabor antiguo. En esta migración de retorno, o en su naufragio, muchos europeos / as perdieron el interés por las ciencias sociales lo mismo que por la fotografía. En los años del presente fin du siècle se observa un renovado interés por la fotografía como instrumento de análisis social. La fotografía fija es una mezcla de arte y técnica (mecánica y química) que consiste en congelar un instante del tiempo. En este sentido, el análisis del \"momento decisivo\" se puede convertir en un instrumento excelente de análisis de la realidad social. A menudo se transforma también en una construcción de esa realidad social, distinta pero comparable a la que es capaz de producir un texto escrito. Idealmente, la combinación de texto escrito e imagen proyectada es el objetivo fundamental de la sociología en el siglo XXI.
Fotoperiodismo y etnografía: el caso de W. Eugene Smith y su proyecto sobre Deleitosa
Este artículo, basado tanto en trabajo de campo como en investigación documental, trata de un episodio fotográfico en la historia española todavía poco reconocido por investigadores españoles: la expedición en junio del 1950 del gran fotógrafo estadounidense W. Eugene Smith y sus dos ayudantes al pueblo cacereño de Deleitosa. El artículo describe los métodos de trabajo de Smith y su equipo; analiza el resultado de este trabajo, es decir, el famoso ensayo fotográfico «Spanish Village», publicado en la revista Life en 1951; mide el impacto social de Smith dentro y fuera de España; y compara la fotografía etnográfica con la periodística.