Hacia un nuevo Estado desarrollista: Desafíos para América Latina

La primera década del siglo xxi constituyó una coyuntura de transformaciones en el mapa político de América Latina. Después de una larga hegemonía de las fuerzas políticas de derecha y centro-derecha, las de izquierda y centro-izquierda —un conjunto muy heterogéneo— conquistaron los gobiernos de la región con un discurso crítico del modelo neoliberal, que subrayaba el papel del Estado como actor clave del proceso de desarrollo. En este escenario, la crisis de 2008 profundizó este debate, enfocando la relación del Estado con las élites y el capital extranjero, así como en su capacidad de articular una estrategia de desarrollo para construir sociedades más prósperas y justas. Este artículo revisita los dos paradigmas del papel del Estado en los procesos de desarrollo: el modelo neoliberal y el desarrollista, a la luz de enfoques teóricos de disciplinas como la ciencia política, la historia económica y la economía del desarrollo. Se concluye que el gran desafío de una nueva teoría y práctica del Estado en América Latina se encuentra en construir coaliciones desarrollistas amplias que permitan contrapesar los intereses centrífugos de las élites locales y las corporaciones trasnacionales

Estimating the Coronal Supra-Arcade Downflow Radio Emission: From Centimeter Through Submillimeter Wavelengths

Supra-arcade downflows (SADs) are infrequent, wiggly, and low-emission structures observed to descend through the solar corona, mostly in EUV and soft X-ray frequencies. Based on their physical characteristics, SADs have been interpreted as low-density bubbles and are related to magnetic reconnection processes during long-term erupting flares. In this work, we use numerical MHD simulations to compute flux density maps, which are convolved with telescope beams to synthesize images with the aim to assess the expected SAD emission in radio wavelengths. We assume that the emission is thermal bremsstrahlung from a fully ionized plasma and without any appreciable gyroresonance contribution since magnetic fields are of the order of 10 G. We find that SAD emission should be optically thin in the frequency range of [10–1,000] GHz, and the spatially integrated flux should be larger than 1 Jy. We conclude, therefore, that SADs consistently are less bright than the surrounding fan and that observing SADs in radio frequencies between [0.5–1,000] GHz is feasible with present instrumentation. The observing strategies are proposed, including the instruments that can be used. Moreover, since the emission is, for the most part, optically thin, the flux density is proportional to temperature, density, and line-of-sight depth and when combined with EUV and soft X-ray images may allow a better density and temperature determination of SADs.Fil: Zurbriggen, Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; Argentina. Universidade Presbiteriana Mackenzie; BrasilFil: Giménez de Castro, C. Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Costa, Andrea. Universidade Presbiteriana Mackenzie; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; ArgentinaFil: Cécere, Mariana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; Argentina. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba; ArgentinaFil: Selhorst, Caius L.. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Evidence of blood stage efficacy with a virosomal malaria vaccine in a Phase IIa clinical trial

Background Previous research indicates that a combination vaccine targeting different stages of the malaria life cycle is likely to provide the most effective malaria vaccine. This trial was the first to combine two existing vaccination strategies to produce a vaccine that induces immune responses to both the pre-erythrocytic and blood stages of the P. falciparum life cycle. Methods This was a Phase I/IIa study of a new combination malaria vaccine FFM ME-TRAP+PEV3A. PEV3A includes peptides from both the pre-erythrocytic circumsporozoite protein and the blood-stage antigen AMA-1. This study was conducted at the Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, UK. The participants were healthy, malaria naïve volunteers, from Oxford. The interventions were vaccination with PEV3A alone, or PEV3A+FFM ME-TRAP. The main outcome measure was protection from malaria in a sporozoite challenge model. Other outcomes included measures of parasite specific immune responses induced by either vaccine; and safety, assessed by collection of adverse event data. Results We observed evidence of blood stage immunity in PEV3A vaccinated volunteers, but no volunteers were completely protected from malaria. PEV3A induced high antibody titres, and antibodies bound parasites in immunofluorescence assays. Moreover, we observed boosting of the vaccine-induced immune response by sporozoite challenge. Immune responses induced by FFM ME-TRAP were unexpectedly low. The vaccines were safe, with comparable side effect profiles to previous trials. Although there was no sterile protection two major observations support an effect of the vaccine-induced response on blood stage parasites: (i) Lower rates of parasite growth were observed in volunteers vaccinated with PEV3A compared to unvaccinated controls (p = 0.012), and this was reflected in the PCR results from PEV3A vaccinated volunteers. These showed early control of parasitaemia by some volunteers in this group. One volunteer, who received PEV3A alone, was diagnosed very late, on day 20 compared to an average of 11.8 days in unvaccinated controls. (ii). Morphologically abnormal parasites were present in the blood of all (n = 24) PEV3A vaccinated volunteers, and in only 2/6 controls (p = 0.001). We describe evidence of vaccine-induced blood stage efficacy for the first time in a sporozoite challenge study

Multi-chromatic control of mammalian gene expression and signaling

The emergence and future of mammalian synthetic biology depends on technologies for orchestrating and custom tailoring complementary gene expression and signaling processes in a predictable manner. Here, we demonstrate for the first time multi-chromatic expression control in mammalian cells by differentially inducing up to three genes in a single cell culture in response to light of different wavelengths. To this end, we developed an ultraviolet B (UVB)-inducible expression system by designing a UVB-responsive split transcription factor based on the Arabidopsis thaliana UVB receptor UVR8 and the WD40 domain of COP1. The system allowed high (up to 800-fold) UVB-induced gene expression in human, monkey, hamster and mouse cells. Based on a quantitative model, we determined critical system parameters. By combining this UVB-responsive system with blue and red light-inducible gene control technology, we demonstrate multi-chromatic multi-gene control by differentially expressing three genes in a single cell culture in mammalian cells, and we apply this system for the multi-chromatic control of angiogenic signaling processes. This portfolio of optogenetic tools enables the design and implementation of synthetic biological networks showing unmatched spatiotemporal precision for future research and biomedical application

A Randomized Placebo-Controlled Phase Ia Malaria Vaccine Trial of Two Virosome-Formulated Synthetic Peptides in Healthy Adult Volunteers

BACKGROUND AND OBJECTIVES: Influenza virosomes represent an innovative human-compatible antigen delivery system that has already proven its suitability for subunit vaccine design. The aim of the study was to proof the concept that virosomes can also be used to elicit high titers of antibodies against synthetic peptides. The specific objective was to demonstrate the safety and immunogenicity of two virosome-formulated P. falciparum protein derived synthetic peptide antigens given in two different doses alone or in combination. METHODOLOGY/PRINCIPAL FINDINGS: The design was a single blind, randomized, placebo controlled, dose-escalating study involving 46 healthy Caucasian volunteers aged 18-45 years. Five groups of 8 subjects received virosomal formulations containing 10 microg or 50 microg of AMA 49-CPE, an apical membrane antigen-1 (AMA-1) derived synthetic phospatidylethanolamine (PE)-peptide conjugate or 10 ug or 50 ug of UK39, a circumsporozoite protein (CSP) derived synthetic PE-peptide conjugate or 50 ug of both antigens each. A control group of 6 subjects received unmodified virosomes. Virosomal formulations of the antigens (designated PEV301 and PEV302 for the AMA-1 and the CSP virosomal vaccine, respectively) or unmodified virosomes were injected i. m. on days 0, 60 and 180. In terms of safety, no serious or severe adverse events (AEs) related to the vaccine were observed. 11/46 study participants reported 16 vaccine related local AEs. Of these 16 events, all being pain, 4 occurred after the 1(st), 7 after the 2(nd) and 5 after the 3(rd) vaccination. 6 systemic AEs probably related to the study vaccine were reported after the 1(st) injection, 10 after the 2(nd) and 6 after the 3(rd). Generally, no difference in the distribution of the systemic AEs between either the doses applied (10 respectively 50 microg) or the synthetic antigen vaccines (PEV301 and PEV302) used for immunization was found. In terms of immunogenicity, both PEV301 and PEV302 elicited already after two injections a synthetic peptide-specific antibody response in all volunteers immunized with the appropriate dose. In the case of PEV301 the 50 microg antigen dose was associated with a higher mean antibody titer and seroconversion rate than the 10 microg dose. In contrast, for PEV302 mean titer and seroconversion rate were higher with the lower dose. Combined delivery of PEV301 and PEV302 did not interfere with the development of an antibody response to either of the two antigens. No relevant antibody responses against the two malaria antigens were observed in the control group receiving unmodified virosomes. CONCLUSIONS: The present study demonstrates that three immunizations with the virosomal malaria vaccine components PEV301 or/and PEV302 (containing 10 microg or 50 microg of antigen) are safe and well tolerated. At appropriate antigen doses seroconversion rates of 100% were achieved. Two injections may be sufficient for eliciting an appropriate immune response, at least in individuals with pre-existing anti-malarial immunity. These results justify further development of a final multi-stage virosomal vaccine formulation incorporating additional malaria antigens. TRIAL REGISTRATION: ClinicalTrials.gov NCT00400101

Canine distemper virus persistence in demyelinating encephalitis by swift intracellular cell-to-cell spread in astrocytes is controlled by the viral attachment protein

The mechanism of viral persistence, the driving force behind the chronic progression of inflammatory demyelination in canine distemper virus (CDV) infection, is associated with non-cytolytic viral cell-to-cell spread. Here, we studied the molecular mechanisms of viral spread of a recombinant fluorescent protein-expressing virulent CDV in primary canine astrocyte cultures. Time-lapse video microscopy documented that CDV spread was very efficient using cell processes contacting remote target cells. Strikingly, CDV transmission to remote cells could occur in less than 6 h, suggesting that a complete viral cycle with production of extracellular free particles was not essential in enabling CDV to spread in glial cells. Titration experiments and electron microscopy confirmed a very low CDV particle production despite higher titers of membrane-associated viruses. Interestingly, confocal laser microscopy and lentivirus transduction indicated expression and functionality of the viral fusion machinery, consisting of the viral fusion (F) and attachment (H) glycoproteins, at the cell surface. Importantly, using a single-cycle infectious recombinant H-knockout, H-complemented virus, we demonstrated that H, and thus potentially the viral fusion complex, was necessary to enable CDV spread. Furthermore, since we could not detect CD150/SLAM expression in brain cells, the presence of a yet non-identified glial receptor for CDV was suggested. Altogether, our findings indicate that persistence in CDV infection results from intracellular cell-to-cell transmission requiring the CDV-H protein. Viral transfer, happening selectively at the tip of astrocytic processes, may help the virus to cover long distances in the astroglial network, “outrunning” the host’s immune response in demyelinating plaques, thus continuously eliciting new lesions

La expresión de una flavodoxina cianobacteriana en plástidos de tomate incrementa el índice de cosecha y la tolerancia a estrés oxidativo

En un futuro no lejano, la humanidad deberá afrontar el aumento de la población junto al límite de la tierra cultivable, el estrés ambiental y el cambio climático, del cual ya somos parte. La Organización de las Naciones Unidas para la Alimentación y la Agricultura (FAO) estima que, para abastecer a la población mundial estimada en el año 2050, la producción de alimentos deberá crecer en torno a un 70%. Esta alta demanda exige el avance en la investigación de nuevas tecnologías que incrementen el índice de cosecha de los cultivos. En particular, el tomate (Solanum lycopersicum) es un fruto muy consumido a nivel mundial. Su importancia radica en su alto contenido de vitaminas al igual que antioxidantes. Debido a esto, en este proyecto nos propusimos generar plantas de tomate transgénicas que sobre-expresen la proteína cianobacteriana flavodoxina (Fld), y evaluar si éstas manifiestan mejoras agrícolas y tolerancia frente a estrés oxidativo, tal como fue demostrado en tabaco. Los resultados obtenidos demostraron una mejora en el índice de cosecha del cultivo. Las plantas que expresan Fld en cloroplastos tienen una menor expansión foliar, mayor cantidad de frutos, aunque de menor tamaño en comparación con la línea salvaje. Además, estas plantas demostraron una tolerancia aumentada frente a estrés oxidativo. Estos resultados generan interés en el estudio de la expresión de Fld en el desarrollo del fruto y cómo esta proteína afecta la expansión celularFil: Arce, Rocío C.. Universidad Nacional de RosarioFil: Mayta, Martín L.. Universidad Nacional de RosarioFil: Pagani, Constanza E.. Universidad Nacional de RosarioFil: Zurbriggen, Matías D.; . Universidad Nacional de RosarioFil: Valle, Estela M.. Universidad Nacional de RosarioFil: Zanor, María I.. Universidad Nacional de RosarioFil: Carrillo, Néstor. Universidad Nacional de Rosari

Phytochrome-Based Extracellular Matrix with Reversibly Tunable mechanical Properties

Interrogation and control of cellular fate and function using optogenetics is providing revolutionary insights into biology. Optogenetic control of cells is achieved by coupling genetically encoded photoreceptors to cellular effectors and enables unprecedented spatiotemporal control of signaling processes. Here, a fast and reversibly switchable photoreceptor is used to tune the mechanical properties of polymer materials in a fully reversible, wavelength‐specific, and dose‐ and space‐controlled manner. By integrating engineered cyanobacterial phytochrome 1 into a poly(ethylene glycol) matrix, hydrogel materials responsive to light in the cell‐compatible red/far‐red spectrum are synthesized. These materials are applied to study in human mesenchymal stem cells how different mechanosignaling pathways respond to changing mechanical environments and to control the migration of primary immune cells in 3D. This optogenetics‐inspired matrix allows fundamental questions of how cells react to dynamic mechanical environments to be addressed. Further, remote control of such matrices can create new opportunities for tissue engineering or provide a basis for optically stimulated drug depots