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Recent studies have shown that inflammatory diseases are becoming more frequent throughout the world. The causes of these disorders are multifactorial and include genetic, immunological, and environmental factors, and intestinal microbiota dysbiosis. The use of beneficial microorganisms has shown to be useful in the prevention and treatment of disorders such as colitis, mucositis, and even colon cancer by their immune-stimulating properties. It has also been shown that certain vitamins, especially riboflavin and folate derivatives, have proven to be helpful in the treatment of these diseases. The application of vitaminproducing lactic acid bacteria, especially strains that produce folate and riboflavin together with immune-stimulating strains, could be used as adjunct treatments in patients suffering from a wide range of inflammatory diseases since they could improve treatment efficiency and prevent undesirable side effects in addition to their nutrition values. In this review, the most up to date information on the current knowledge and uses of vitamin-producing lactic acid bacteria is discussed in order to stimulate further studies in this field. Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Levit, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Savoy, Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina

Vaginal lactobacilli (LAB) in probiotic formulas constitute a promising alternative for microbiome reconstitution and for the prevention and treatment of urogenital infections. A double-blind, randomised clinical trial was conducted to assess the safety of LAB-gelatine capsules vaginally administered to healthy sexually active women. Participants were randomised into three groups: intervention A: Lactobacillus reuteri CRL1324, L. gasseri CRL1263 and CRL1307; intervention B: L. rhamnosus CRL1332, L. gasseri CRL1256 and CRL1320; and intervention C: placebo. In a survey and clinical evaluation, participants received a blister with 7 capsules to be administered 1 per day. A second sampling and a new survey were conducted 3-10 days after completing application. Colposcopy was performed to assess adverse effects on vaginal-cervical mucosa. Vaginal swabs were taken for Gram staining to determine the Nugent score, and obtainment of viable-cell cultures to quantify cultivable lactic acid bacteria and pathogens. The main outcomes evaluated were overall satisfaction and secondary effects, including discomfort, urogenital infection, inflammatory response or other symptoms. No significant differences were found in Nugent score or in leukocyte numbers in vaginal samples either before or after the three interventions. However, a tendency to decrease in both the Nugent score and in leukocyte numbers was observed after interventions A and B, though not after C. A significant increase in cultivable lactobacilli was determined after LAB interventions. No severe adverse events were detected. LAB-containing capsules were well tolerated by subjects, so they could be proposed as an adequate alternative to restore vaginal lactobacilli in sexually active women. Fil: de Gregorio, Priscilla Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Maldonado, Natalia Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Vera Pingitore, Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Leccese Terraf, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Juárez Tomás, María Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: de Ruiz, C. Silva. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina Fil: Santos, V.. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina Fil: Wiese, B.. Medizinische Hochschule Hannover; Alemania Fil: Bru Chauve, Elena Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Paiz, M.C.. Hospital de Clínicas Nicolás Avellaneda; Argentina Fil: Reina, M.F.. Hospital de Clínicas Nicolás Avellaneda; Argentina Fil: Schujman, D.E.. Hospital de Clínicas Nicolás Avellaneda; Argentina Fil: Nader, Maria Elena Fatima. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina

El diagnóstico serológico de infecciones en curso es crítico para definir el tratamiento a emplear, prevenir problemas durante la gestación (ej. toxoplasmosis), controles en trasplantes, transfusiones de sangre y epidemiología. La respuesta de anticuerpos IgM es un parámetro relevante en este tipo de diagnóstico por su aparición temprana en suero durante las infecciones. Dicha respuesta puede ser medida por inmunoensayos de serología que utilizan superficies de captura con anticuerpos convencionales anti-IgM de alta especificidad. La primera meta de este proyecto consistió en desarrollar un reactivo anti-IgM genérico altamente estandarizado basado en nanobodies biotinilados capaces de inmovilizarse en forma orientada y generar superficies de alta eficiencia de captura. Para esto se siguió una metodología que permitió la obtención de nanobodies que demostraron buen desempeño para captura de IgM mediante su evaluación en inmunoensayos modelo de diagnóstico para los virus Dengue y Zika. Otra meta del proyecto consistió en desarrollar calibradores recombinantes para inmunoensayos serológicos. Los calibradores permiten discriminar entre sueros positivos y negativos, y típicamente se formulan utilizando sueros estándares caracterizados. Debido a que son finitos, cada vez que los sueros se agotan nuevos lotes deben ser generados y validados, elevando los costos de los kits diagnósticos. En este trabajo se desarrolló un calibrador constituido por una quimera nanobody-Fc. El componente Fc contiene los dominios constantes de IgM humana y es reconocido por el nanobody anti-IgM, y el componente nanobody es específico contra el antígeno del inmunoensayo serológico, en este caso se utilizó un nanobody anti-NS1 de Zika como modelo. La quimera fue producida con altos rendimientos a partir de cultivos de células de mamíferos y demostró ser funcional en los inmunoensayos. Tanto los nanobodies anti-IgM como el calibrador se presentan como valorables herramientas en el área diagnostico capaces de mejorar la estandarización de las pruebas de diagnóstico de infecciones agudas. Agencia Nacional de Investigación e Innovación

This article discusses dominant trends and countertrends in genetics and biotechnology for healthcare, based mainly on the theoretical approaches of Rose, Haraway, and Braidotti and their followers, which are reformulated for the context of development and directed towards a positive recreation of gender relations and sustainable development. The principal conceptual elements of these theories include: the rise of the biopolitical citizen, the development of biosocialities, and the construction of biopolitics focused on genetic responsibility and body ethics. O artigo discute tendências dominantes e contra tendências em genética e biotecnologia da saúde, seguindo principalmente as perspectivas teóricas de Rose, Haraway e Braidotti e seus seguidores, reformuladas para o contexto do desenvolvimento, e em direção a uma recriação positiva das relações de gênero e do desenvolvimento sustentável. Os elementos conceituais dessas teorias incluem: a ascensão do cidadão biopolítico, o desenvolvimento de biossocialidades e a construção da biopolítica focada na responsabilidade genética e na ética do corpo. O artigo discute tendências dominantes e contra tendências em genética e biotecnologia da saúde, seguindo principalmente as perspectivas teóricas de Rose, Haraway e Braidotti e seus seguidores, reformuladas para o contexto do desenvolvimento, e em direção a uma recriação positiva das relações de gênero e do desenvolvimento sustentável. Os elementos conceituais dessas teorias incluem: a ascensão do cidadão biopolítico, o desenvolvimento de biossocialidades e a construção da biopolítica focada na responsabilidade genética e na ética do corpo.

La Tuberculosis es la primera causa de muerte por un agente infeccioso en el mundo (desplazado provisoriamente por el COVID-19), provocando 1,7 millones de fallecidos anualmente. En Uruguay se observa un incremento de los casos desde 2006, con una incidencia en la población general de 30 casos en 100.000 habitantes. Esta incidencia puede aumentar más de 50 veces en determinadas poblaciones (personas privadas de libertad, personas HIV positivas, etc.). Conocer cuáles son las cepas de Mycobacterium tuberculosis que circulan en el país es una herramienta de gran importancia para identificar la aparición de brotes, detectar resistencia a fármacos y prevenir el aumento del número de casos de la enfermedad. A través del presente proyecto se generó una herramienta que permite la tipificación y análisis de resistencia de aislados de Mycobacterium tuberculosis mediante amplificación y secuenciación de regiones específicas de su genoma. Utilizando esta nueva herramienta, realizamos la tipificación y análisis de resistencia a fármacos anti-tuberculosis de 49 aislados del sistema penitenciario (SP) comparando con las cepas que circulan en la población general en los últimos años. A partir de dicho análisis no se detectaron casos de resistencia a los principales fármacos utilizados en el control de la enfermedad. Por otra parte, se encontró la presencia de una cepa particular representada de forma significativa en el SP con muy baja circulación a nivel comunitario (32% vs 1% de muestras del linaje X). Resulta interesante observar, que cerca del 36% de las cepas aisladas al ingreso al SP son precisamente de esta cepa, sin embargo en todo los casos se trata de personas con antecedentes que probablemente hayan adquirido la cepa en estadías anteriores en el SP. El sistema desarrollado permitirá realizar un seguimiento epidemiológico tanto en el SP como en la población general, así como determinar resistencia a fármacos anti-TB. Agencia Nacional de Investigación e Innovación

Las Infecciones del Tracto Urinario (ITU) son un problema frecuente. Escherichia coli es el principal agente etiológico, seguido por Staphylococcus saprophyticus, Klebsiella pneumoniae y Proteus mirabilis. La técnica de oro para el diagnóstico de ITU es el urocultivo, pero su resultado demora al menos 48h. La tira reactiva de orina (TRO) se utiliza como test rápido de tamizaje para ITU. La desventaja es su baja sensibilidad (41-64% para nitritos y 48-86% para leucocitos) y especificidad variable (82-98%), lo cual conduce en muchos casos a diagnósticos incorrectos y al uso inapropiado de antimicrobianos. El objetivo del estudio fue desarrollar un test inmunocromatográfico (TI) rápido para la detección de los uropatógenos más frecuentes en orina. A su vez, nos propusimos evaluar un formato comercial de TI para detectar E. coli en orina y evaluar su rendimiento en muestras clínicas de pacientes con sospecha de ITU. Se evaluaron y seleccionaron diferentes anticuerpos comerciales para la detección de los distintos uropatógenos mediante ELISA. Se desarrollaron los TI de producción propia para cada uropatógeno y se puso a punto el test comercial con formato universal utilizando el par de Ac anti E. coli seleccionado previamente. Para la validación del test se analizaron 161 muestras de orina de pacientes con sospecha de ITU y se comparó su resultado con el del urocultivo. Si bien se consiguió desarrollar un prototipo de TI que funcionó para la detección de los patógenos evaluados, su interpretación presentó dificultades visuales, por lo cual se procedió a utilizar el TI comercial que presentó mejor especificidad, valor predictivo positivo y precisión diagnóstica que la TRO. La combinación de ambas técnicas (TRO más TI) como método de tamizaje presenta una excelente sensibilidad (94%) y precisión diagnóstica (80%), representando una buena y rápida estrategia alternativa para los urocultivos. Agencia Nacional de Investigación e Innovación

An antibody-cytokine fusion protein, composed of the murine single-chain cytokine interleukin-12 (IL-12) genetically fused to a human IgG3 specific for the human tumor-associated antigen HER2/neu maintains antigen binding, cytokine bioactivity, and IL-12 heparin-binding activity. This latter property is responsible for the binding of the cytokine to glycosaminoglycans (GAGs) on the cell surface and the extracellular matrix and has been implicated in modulating IL-12 bioactivity. Previous studies indicate that the p40 subunit of human and murine IL-12 is responsible for the heparin-binding activity of this heterodimeric cytokine. In the present study we used bioinformatic analysis and site-directed mutagenesis to develop a version of the antibody-(IL-12) fusion protein without heparin-binding activity. This was accomplished by replacing the basic arginine (R) and lysine (K) residues in the cluster of amino acids 254–260 (RKKEKMK) of the murine IL-12 p40 subunit by the neutral non-polar amino acid alanine (A), generating an AAAEAMA mutant fusion protein. ELISA and flow cytometry demonstrated that the antibody fusion protein lacks heparin-binding activity but retains antigen binding. A Tcell proliferation assay showed IL-12 bioactivity in this construct. However, the IL-12 bioactivity is decreased compared to its non-mutated counterpart, which is consistent with an ancillary role of the heparin-binding site of IL-12 in modulating its activity. Thus, we have defined a cluster of amino acid residues with a crucial role in the heparin-binding activity of murine IL-12 in the context of an antibody-cytokine fusion protein. Fil: Luria Pérez, Rosendo. University of California at Los Angeles; Estados Unidos. Hospital de Niños de México "Federico Gómez"; México Fil: Candelaria, Pierre V.. University of California at Los Angeles; Estados Unidos Fil: Daniels Wells, Tracy R.. University of California at Los Angeles; Estados Unidos Fil: Rodríguez, José A.. University of California at Los Angeles; Estados Unidos Fil: Helguera, Gustavo Fernando. University of California at Los Angeles; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Penichet, Manuel L.. University of California at Los Angeles; Estados Unidos

Historically, the primary focus of studies of human white matter tracts has been on large tracts that connect anterior-toposterior cortical regions. These include the superior longitudinal fasciculus (SLF), the inferior longitudinal fasciculus (ILF), and the inferior fronto-occipital fasciculus (IFOF). Recently, more refined and well-understood tractography methods have facilitated the characterization of several tracts in the posterior of the human brain that connect dorsal-to-ventral cortical regions. These include the vertical occipital fasciculus (VOF), the posterior arcuate fasciculus (pArc), the temporo-parietal connection (TP-SPL), and the middle longitudinal fasciculus (MdLF). The addition of these dorso-ventral connective tracts to our standard picture of white matter architecture results in a more complicated pattern of white matter connectivity than previously considered. Dorso-ventral connective tracts may play a role in transferring information from superior horizontal tracts, such as the SLF, to inferior horizontal tracts, such as the IFOF and ILF. We present a full anatomical delineation of these major dorso-ventral connective white matter tracts (the VOF, pArc, TP-SPL, and MdLF). We show their spatial layout and cortical termination mappings in relation to the more established horizontal tracts (SLF, IFOF, ILF, and Arc) and consider standard values for quantitative features associated with the aforementioned tracts. We hope to facilitate further study on these tracts and their relations. To this end, we also share links to automated code that segments these tracts, thereby providing a standard approach to obtaining these tracts for subsequent analysis. We developed open source software to allow reproducible segmentation of the tracts: https ://githu b.com/brain life/Verti cal_Tract s. Finally, we make the segmentation method available as an open cloud service on the data and analyses sharing platform brainlife.io. Investigators will be able to access these services and upload their data to segment these tracts. Fil: Bullock, Daniel. Indiana University; Estados Unidos Fil: Takemura, Hiromasa. Center For Information And Neural Networks (cinet); Japón Fil: Caiafa, César Federico. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; Argentina Fil: Kitchell, Lindsey. Indiana University; Estados Unidos Fil: McPherson, Brent. Indiana University; Estados Unidos Fil: Caron, Bradley. Indiana University; Estados Unidos Fil: Pestilli, Franco. Indiana University; Estados Unidos

One of the most used formats in inmuno-polymerase chain reaction (IPCR) is known as "Universal" IPCR (signal-generating complexes is based on conjugates of biotinylated DNA, biotinylated IgG and avidin). In the present study, we evaluated the utility of using mono- and bi-biotinylated DNA probes, pre-self-assembled DNA-neutravidin complex, blocking step and glutaraldehyde pretreatment of standard PCR tubes to improve the analytical performance of the hTSH-IPCR assay. The use of pre-self-assembled mono-biotinylated DNA-neutravidin complex enhances both the sensitivity and the reproducibility of the hTSH-IPCR assay, even without blocking step: hTSH-IPCR assay showed an improved limit of detection (LOD: 0.01 μIU/ml), calibration sensitivity (SEN: 2.4) and analytic sensitivity (γ: 9 μIU/ml −1 ) in comparison with both a self-made ELISA and a commercial one. Fil: Abud, Julián Elías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina Fil: Santamaría, Clarisa Guillermina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina Fil: Oggero Eberhardt, Marcos Rafael. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina Fil: Rodriguez, Horacio Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina

Background: The 90-kDa heat-shock protein (Hsp90) from Nicotiana benthamiana (NbHsp90.3) is a promising adjuvant, especially for those vaccines that require a T cell-mediated immune response. Toxoplasma gondii SAG1 is considered one of the most important antigens for the development of effective subunit vaccines. Some epitopes located in the SAG1 C-terminus region have showed a strong humoral and cellular immune response. In the present study, we aimed to assess the efficacy of NbHsp90.3 as carrier/adjuvant of SAG1-derived peptide (SAG1HC) in a T. gondii infection murine model. Methods: In the present study, C57BL/6 mice were intraperitoneal. immunized with the NbHsp90.3-SAG1HC fusion protein (NbHsp90.3-SAG1HC group), mature SAG1 (SAG1m group), NbHsp90.3 (NbHsp90.3 group) or PBS buffer 1X (PBS group). The levels of IgG antibodies and the cytokine profile were determined by ELISA. Two weeks after the last immunization, all mice were orally challenged with 20 cysts of T. gondii Me49 strain and the number of brain cysts was determined. In addition, both humoral and cellular immune responses were also evaluated during the acute and chronic phase of T. gondii infection by ELISA.Results: The characterization of the immune response generated after vaccination with NbHsp90.3 as an adjuvant showed that rNbHsp90.3-SAG1HC-immunized mice produced antibodies that were able to recognize not only rSAG1m but also the native SAG1 present in the total lysate antigen extract (SAG1TLA) from T. gondii tachyzoites, while control groups did not. Furthermore, anti-rSAG1m IgG2a/2b antibodies were significantly induced. In addition, only the spleen cell cultures from NbHsp90.3-SAG1HC-immunized mice showed a significantly increased production of IFN-γ. During the chronic phase of T. gondii infection, the antibodies generated by the infection were unable to detect the recombinant protein, but they did react with TLA extract. In addition, splenocytes from all groups showed a high production of IFN-γ when stimulated with rGRA4, but only those from NbHsp90.3-SAG1HC group stimulated with rSAG1m showed high production of IFN-γ. Finally, NbHsp90.3-SAG1HC-immunized mice exhibited a significant reduction in the cyst load (56%) against T. gondii infection. Conclusions: We demonstrated that NbHsp90.3 enhances the humoral and cell-mediated immune response through a Th1 type cytokine production. Mice vaccinated with NbHsp90.3-SAG1HC exhibited a partial protection against T. gondii infection and it was correlated with the induction of memory immune response. For the first time, we developed and validated a vaccine formulation which, to our knowledge, for the first time includes the NbHsp90.3 protein covalently fused to a peptide from T. gondii SAG1 protein that contains T- and B-cell epitopes. Fil: Sánchez López, Edwin Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina Fil: Corigliano, Mariana Georgina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina Fil: Albarracín, Romina Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina Fil: Sander, Valeria Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina Fil: Legarralde, César Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina Fil: Bengoa Luoni, Sofia Ailin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina Fil: Clemente, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina

The prevention of microbial biofilm formation on a biomaterial surface is crucial in avoiding implants failures and the development of antibiotic resistant bacteria. It was reported that biodegradable Mg alloys may show antimicrobial effects due to the alkalinization of the corroding area. However, this issue is controversial and deserves a detailed study, since the processes occurring at the [biodegradable metal/biological medium] interface are complex and varied. Results showed that bacterial adhesion on AZ31 was lower than that of the titanium control and revealed that was dependent on surface composition, depicting some preferential sites for bacterial attachment (C-, P-, O-containing corrosion products) and others that are particularly avoided (active corrosion sites). As a key challenge, a strategy able to improve the performance of Mg alloys by both, reducing the formation of corrosion products and inhibiting bacterial adhesion was subsequently developed. A polymeric layer (polyTOH) was obtained by electropolymerization of thymol (TOH), a phytophenolic compound. The polyTOH can operate as a multifunctional film that improves the surface characteristics of the AZ31 Mg alloy by enhancing corrosion resistance (ions release was reduced to almost the half during the first days) and create an anti-adherent surface (bacterial attachment was 30-fold lower on polyTOH-AZ31 than on non-coated Mg alloy and 200-fold lower than Ti control and was constrained to specific regions). This anti-adherent property implies an additional advantage: enhancement of the efficacy of antibiotic treatments. Fil: Bertuola, Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina Fil: Miñan, Alejandro Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina Fil: Grillo, Claudia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina Fil: Salsa Cortizo, Maria Victoria. Universidad Nacional de La Plata. Facultad de Odontología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina Fil: Fernandez Lorenzo, Monica Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina. Universidad Nacional de La Plata. Facultad de Ingeniería; Argentina

Interferon lambda (IFN-λ) is an antiviral naturally produced in response to viral infections, with activity on cells of epithelial origin and located in the mucosal surfaces. This localized activity results in reduced toxicity compared to type I IFNs, whose receptors are ubiquitously expressed. IFN-λ has been effective in the therapy of respiratory viral infections, playing a crucial role in potentiating adaptive immune responses that initiate at mucosal surfaces. Human IFN-λ has polymorphisms that may cause differences in the interaction with the specific receptor in the human population. Interestingly, bovine IFN-λ3 has an in silico-predicted higher affinity for the human receptor than its human counterparts, with high identity with different human IFN-λ variants, making it a suitable antiviral therapeutic candidate for human health. Here, we demonstrate that a recombinant bovine IFN-λ (rbIFN-λ) produced in HEK-293 cells is effective in preventing SARS-CoV-2 infection of VERO cells, with an inhibitory concentration 50% (IC50) between 30 and 50 times lower than that of human type I IFN tested here (α2b and β1a). We also demonstrated the absence of toxicity of rbIFN-λ in human PBMCs and the lack of proinflammatory activity on these cells. Altogether, our results show that rbIFN-λ is as an effective antiviral potentially suitable for COVID-19 therapy. Among other potential applications, rbIFN-λ could be useful to preclude virus dispersion to the lungs and/or to reduce transmission from infected people. Moreover, and due to the non-specific activity of this IFN, it can be potentially effective against other respiratory viruses that may be circulating together with SARS-CoV-2. Fil: Cardoso, Nancy Patricia. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; Argentina Fil: Mansilla, Florencia Celeste. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; Argentina Fil: Benedetti, Estefanía. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina Fil: Turco, Cecilia Soledad. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; Argentina Fil: Barone, Lucas José. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; Argentina Fil: Iserte, Javier Alonso. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Soria, Ivana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; Argentina Fil: Baumeister, Elsa. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina Fil: Capozzo, Alejandra Victoria. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; Argentina

Deactivation of primed SARS-CoV-2 prior to cell entry constitutes an emergency brake in COVID-19 infection if vaccine-induced antibodies fail to block recognition of the human angiotensin-converting enzyme 2 (hACE2) receptor. The timing and locus for the therapeutic intervention are dictated by the cell entry mechanism and by the selective advantage of the dominant D614G mutation. Fil: Fernandez, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina

With the COVID-19 pandemic, the evolutionary fate of SARS-CoV-2 becomes a matter of utmost concern. Mutation D614G in the spike (S) protein has become dominant, and recent evidence suggests it yields a more stable phenotype with higher transmission efficacy. We carry out a structural analysis that provides mechanistic clues on the enhanced infectivity. The D614G substitution creates a sticky packing defect in subunit S1, promoting its association with subunit S2 as a means to stabilize the structure of S1 within the S1/S2 complex. The results raise the therapeutic possibility of immunologically targeting the epitope involved in stabilizing the G614 phenotype as a means of reducing the infection efficacy of SARS-CoV-2. This therapeutic modality would not a-priori interfere directly with current efforts toward the immunological targeting of the RBD epitope; hence, it could be exploited as a complementary treatment. Fil: Fernandez, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina

Silica and collagen are two of the most abundant substances in the Earth's geosphere and biosphere, respectively. Yet, their close association in nature has never been clearly demonstrated despite increasing evidence for the key role of silicon in mammalians. Foreseeing the therapeutic benefits of their association within composites or hybrids, a wide diversity of bio-inspired silica–collagen materials have been prepared over nearly 15 years. These works not only generated materials with a large range of structures and properties, from soft mineralized hydrogels to hard compact xerogels, but also provided more fundamental information about the interplay between polymer self-assembly processes and inorganic condensation mechanisms. Biological in vitro and in vivo evaluations suggest their bioactivity, cyto- and biocompatibility as well as controlled drug delivery properties. Hence they can now fully integrate the family of materials with high potential for the development of innovative biomedical devices. Fil: Heinemann, Sascha. Technische Universität Dresden; Alemania Fil: Coradin, Thibaud. Centre National de la Recherche Scientifique; Francia. Universite de Paris Vi; Francia Fil: Desimone, Martín Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina

The engineering of surfaces to control cell adhesion represents an active area of biomaterials research. Herein, we demonstrate that it is possible to tune the adhesion and proliferation of a human osteoblastic cell line (Saos-2) by tailoring the nanopore size of an oxide film coating. Fil: Bellino, Martin Gonzalo. Comisión Nacional de Energí­a Atómica. Gerencia del Area de Seguridad Nuclear y Ambiente. Gerencia de Quí­mica (CAC); Argentina Fil: Golbert, Sebastian. Comisión Nacional de Energí­a Atómica. Gerencia del Area de Seguridad Nuclear y Ambiente. Gerencia de Quí­mica (CAC); Argentina Fil: de Marzi, Mauricio Cesar. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina. Universidad Nacional de Lujan; Argentina Fil: Soler Illia, Galo Juan de Avila Arturo. Comisión Nacional de Energía Atómica. Gerencia del Area de Seguridad Nuclear y Ambiente. Gerencia de Quí­mica (CAC); Argentina Fil: Desimone, Martín Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco (i); Argentina

Silica–collagen type I nanocomposite hydrogels are evaluated as medicated dressings to prevent infection in chronic wounds. Two antibiotics, gentamicin and rifamycin, are encapsulated in a single step within plain silica nanoparticles. Their antimicrobial efficiency against Pseudomonas aeruginosa and Staphylococcus aureus is assessed. Gentamycin-loaded 500 nm particles can be immobilized at high silica dose in concentrated collagen hydrogels without modifying their fibrillar structure or impacting on their rheological behavior and increases their proteolytic stability. Gentamicin release from the nanocomposites is sustained over 7 days, offering an unparalleled prolonged antibacterial activity. Particle immobilization also decreases their cytotoxicity towards surface-seeded fibroblast cells. Rifamycin-loaded 100 nm particles significantly alter the collagen hydrogel structure at high silica doses. The thus-obtained nanocomposites show no antibacterial efficiency, due to strong adsorption of rifamycin on collagen fibers. The complex interplay of interactions between drugs, silica and collagen is a key factor regulating the properties of these composite hydrogels as antibiotic-delivering biological dressings and must be taken into account for future extension to other wound healing agents. Fil: Alvarez, Gisela Solange. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Hélary, Christophe. Universite Pierre et Marie Curie; Francia. Universite de Paris VI; Francia. Centre National de la Recherche Scientifique; Francia Fil: Mebert, Andrea Mathilde. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Wang, Xiaolin. Universite Pierre et Marie Curie; Francia. Universite de Paris VI; Francia. Centre National de la Recherche Scientifique; Francia Fil: Coradin, Thibaud. Universite Pierre et Marie Curie; Francia. Universite de Paris VI; Francia. Centre National de la Recherche Scientifique; Francia Fil: Desimone, Martín Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina

Introducción: La activación de las respuestas inmunes innata y adaptativa en la enfermedad celíaca, lleva a una alteración de la red local de citoquinas y desarrollo de inflamación y lesión intestinal. Los polimorfismos en el promotor del gen IL10 podrían jugar un papel en la determinación de la expresión fenotípica de la enfermedad celíaca, desbalanceando el equilibrio a favor de un aumento de la expresión de citoquinas proinflamatorias. Objetivo: analizar la contribución de polimorfismos de nucleótido simple en el gen IL10 en la susceptibilidad a la enfermedad celíaca. Materiales y métodos: se extrajo ADN de sangre entera de 40 pacientes con enfermedad celíaca y de 80 controles y se amplificó una región en el promotor del gen de IL10 que contiene los polimorfismos -1082 (rs1800896G/A), -819 (rs1800871C/T) y -592 (rs1800872C/A). Se secuenciaron amplicones de 695pb y, paracada polimorfismo, se estableció la presencia del alelo en homocigosis o heterocigosis. Se determinó el riesgo mediante el cálculo odds ratio (OR), considerando estadísticamente significativo un p < 0,05.Resultados: presentaron riesgo de desarrollar enfermedad celíaca los polimorfismos rs1800871T/C(OR = 2,22 [1,23 ? 4,01]; p = 0,0073) y rs1800872A/C (OR = 2,78 [1,27?6,09]; p = 0,009), con unmodelo dominante. El riesgo se asoció al sexo femenino (OR = 3,49, IC 95% [1,32 ? 9,19]; p = 0,009) y a concentraciones de a-tTG-IgA ≥ 100 U/ml (OR = 2,63, IC 95% [1,10 ? 6,28]; p = 0,03). Conclusiones: presentan riesgo de enfermedad celíaca los portadores del alelo menos frecuente T del rs1800871T/C y del alelo menos frecuente A del rs1800872A/C en el promotor del gen IL10, con un modelo dominante. El haplotipo que muestra asociación para el desarrollo de enfermedad celíaca es ATA. El análisis estratificado indica mayor riesgo de desarrollar la enfermedad en los portadores de los genotipos TC y TT del polimorfismo rs1800871T/C y de los genotipos AC y AA del polimorfismo rs1800872A/C asociados al sexo femenino y a las concentraciones de a-tTG-IgA ≥100 U/ml. Introduction: The activation of innate and adaptive immune responses in celiac disease leads to an alteration of the local cytokine network and the development of inflammation and intestinal injury. The polymorphisms in the IL10 gene promoter could play a role in determining the phenotypic expression of celiac disease, changing the balance towards an increase in the expression of proinflammatory cytokines. Objective: To analyze the contribution of simple nucleotide polymorphisms in the IL10 gene to the susceptibility to celiac disease. Materials and methods: We extracted DNA from whole blood of 40 patients with celiac disease and from 80 healthy individuals and then amplified a region in the IL10 gene promoter that contains the polymorphisms -1082 (rs1800896 G/A), -819 (rs1800871C/T) and -592 (rs1800872C/A). We sequenced 695-bp amplicons, and, for each polymorphism, established the presence of alleles in homozygosis or heterozygosis. We determined the risk by calculating the Odds Ratios (OR), considering a p

Recurrence rates in the laparoscopic repair of the hiatal hernia range from 12% to 59%. Limitation of reinforcement has been principally the risk of adverse events caused by synthetic materials. Biologic and resorbable synthetic materials are valid alternatives. This study compares the host response to all these materials after hiatal hernia repair. A total of 20 Landrace pigs, underwent laparoscopic primary hiatal hernia repair and reinforced with a polypropylene mesh (PROLENE: polypropylene [PP]), an absorbable synthetic scaffold (GOREBIO-A: polyglycolic acid [PGA]), a urinary bladder matrix scaffold, (Gentrix: urinary bladder matrix [UBM]), or without reinforcement, control group (C). Animals were survived for 3 months. Endpoints included gross morphology, biomechanical testing, and histology. Pigs in PP and PGA groups showed fibrosis at the repair site, with robust adhesions. In UBM and C groups, only mild adhesions were found. Load at failure (gr) and stiffness (gr/mm) of PP were higher than C group (PP:2103 ± 548.3 versus C:951.1 ± 372.7, P = 0.02; PP:643.3 ± 301 versus C:152.6 ± 142.7, P = 0.01). PGA and UBM values for both parameters were in between PP and C samples. However, stiffness in UBM was tended to be lower than PP group, and approached a significant difference (643.3 ± 301 versus 243 ± 122.1, P = 0.0536). In UBM group, the histology resembled native tissue. By contrast, PP and PGA groups showed mononuclear infiltrates, fibroencapsulation, necrosis, remnants of mesh, and disorganized tissue that was validated with a histologic score. In this setting, UBM scaffolds showed the most appropriate features for hiatal hernia repair, recovering the tissue properties that can help reduce the possibility of early failure and prevent complications associated with the implanted material. Fil: Amigo, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina Fil: Zubieta, Cecilia. Fundación Favaloro; Argentina Fil: Riganti, Juan Martin. Fundación Favaloro; Argentina Fil: Ramirez, Mauricio. Fundación Favaloro; Argentina Fil: Renda, Pedro. Fundación Favaloro; Argentina Fil: Lovera, Romina. Fundación Favaloro; Argentina Fil: Pascaner, Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina Fil: Vigliano, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina Fil: Craiem, Damian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina Fil: Young, D. Adam. No especifíca; Fil: Gilbert, Thomas W.. University of Pittsburgh; Estados Unidos Fil: Nieponice, Alejandro. University of Pittsburgh; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina

T cell epitope candidates are commonly identified using computational prediction tools in order to enable applications such as vaccine design, cancer neoantigen identification, development of diagnostics and removal of unwanted immune responses against protein therapeutics. Most T cell epitope prediction tools are based on machine learning algorithms trained on MHC binding or naturally processed MHC ligand elution data. The ability of currently available tools to predict T cell epitopes has not been comprehensively evaluated. In this study, we used a recently published dataset that systematically defined T cell epitopes recognized in vaccinia virus (VACV) infected C57BL/6 mice (expressing H-2Db and H-2Kb), considering both peptides predicted to bind MHC or experimentally eluted from infected cells, making this the most comprehensive dataset of T cell epitopes mapped in a complex pathogen. We evaluated the performance of all currently publicly available computational T cell epitope prediction tools to identify these major epitopes from all peptides encoded in the VACV proteome. We found that all methods were able to improve epitope identification above random, with the best performance achieved by neural network-based predictions trained on both MHC binding and MHC ligand elution data (NetMHCPan-4.0 and MHCFlurry). Impressively, these methods were able to capture more than half of the major epitopes in the top N = 277 predictions within the N = 767,788 predictions made for distinct peptides of relevant lengths that can theoretically be encoded in the VACV proteome. These performance metrics provide guidance for immunologists as to which prediction methods to use, and what success rates are possible for epitope predictions when considering a highly controlled system of administered immunizations to inbred mice. In addition, this benchmark was implemented in an open and easy to reproduce format, providing developers with a framework for future comparisons against new tools., Author summary Computational prediction tools are used to screen peptides to identify potential T cell epitope candidates. These tools, developed using machine learning methods, save time and resources in many immunological studies including vaccine discovery and cancer neoantigen identification. In addition to the already existing methods several epitope prediction tools are being developed these days but they lack a comprehensive and uniform evaluation to see which method performs best. In this study we did a comprehensive evaluation of publicly accessible MHC I restricted T cell epitope prediction tools using a recently published dataset of Vaccinia virus epitopes identified in the context of H-2Db and H-2Kb. We found that methods based on artificial neural network architecture and trained on both MHC binding and ligand elution data showed very high performance (NetMHCPan-4.0 and MHCFlurry). This benchmark analysis will help immunologists to choose the right prediction method for their desired work and will also serve as a framework for tool developers to evaluate new prediction methods.

Antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), are small and mostlypolycationic molecules that form part of the innate immune response. There are currently more than3000 experimentally reported AMPs. Particularly, in frogs, the temporin family, have beendiscovered as potential AMPs. The aim of this work is to review the latest publications about thisclass of peptides, discuss their properties and make an update of the last studies and new discoveriesin the field.More than 130 temporins have been identified in this family. The most studied temporins aretemporin A (TA), temporin B (TB) and temporin L (TL). These peptides showed antimicrobialactivity against Gram-negative, Gram-positive bacteria and fungi. Since the discovery of temporinsin 1996, several groups of research isolated different peptides from various species of frogs thatwere included as members of this family. Although antimicrobial activity of many temporins has not been analyzed yet, most of them showed antimicrobial and antifungal activities. Combination ofnanotechnology and AMPs as temporins in different antimicrobial treatments could be a promisingalternative for resistance pathogens. These studies demonstrate that, even with the advancement inscientific research on the composition and antimicrobial activity of temporins, further studies arenecessary to wholly understand their components and mechanisms of action. Fil: Romero, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Cardillo, Alejandra Beatriz. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología Industrial y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina Fil: Martínez Ceron, María Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología Industrial y Biotecnología; Argentina Fil: Camperi, Silvia Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología Industrial y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina Fil: Giudicessi, Silvana Laura. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología Industrial y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina

Florfenicol (FF) is a broad-spectrum antibiotic with the drawback of poor solubility in physiological media. Despite vehiculization of FF become an alternative, current devices usually showed low encapsulation efficiencies(EE) and uncontrolled fast release. In the present work, a novel drug delivery system based on alginate and Eudragit RS® (EuRS) for FF oral administration was developed. The strategy involved in situ crystallization of FF inside the matrix which allowed EE from 60 to 80%. Ionic gelation technique was used for pH-responsive beads preparation considering that alginate offers structural support for the hydrogel while hydrophobic EuRS delays the swelling of the system. Different formulations were analyzed by FTIR, DSC, XRD and SEM studies todemonstrate the presence of a blended polymeric matrix, the appearance of FF crystals and the role of EuRS in the FF release. A pH-dependent FF release was found when the drug and EuRS concentrations were modified.Approximately 40% and 20% of FF was released from alginate and alginate-EuRS beads at pH 7.4 in 1 h respectively,suggesting a modified release behavior. All formulations showed antimicrobial activity against Staphylococcus aureus and Escherichia coli. The blended formulation results a promising oral matrix adapted for the controlled release of FF along the intestine. Fil: Karp, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Turino, Ludmila Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Estenoz, Diana Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Castro, Guillermo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina Fil: Islan, German Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina

Three-dimensional bioprinting is a new technology that should be integrated into several areas, including medical technology. However, before designing and applying it on a large scale, several biophysical parameters and particularly printability need to be established. In the present work, general characteristics of the extrusion method, bioinks, and scaffolds are reviewed. Printability analysis of 3D bioprinting is also included., Centro de Investigación y Desarrollo en Fermentaciones Industriales

BioimpresorasAunque parezca increíble, estas impresoras pueden desarrollar tejidos artificiales, estructuras que ayudan a curar heridas o hacer impresiones con células en su interior que se adaptan a la necesidad de cada persona.En nuestro laboratorio de nanobiomateriales diseñamos una bioimpresora que es una ?máquina? que permite crear y fabricar objetos de base biológica y que pueden ser utilizados en el cuerpo humano.Para entender qué es una bioimpresora primero tenemos que entender cómo funcionauna impresora 3D:Las impresoras comunes (que son 2D) permiten imprimir una imagen digital o undibujo hecho con la computadora en una hoja de papel. Las impresoras 3D imprimen en varias capas, una arriba de la otra, como si fuera una torre de panqueques. Entonces, el resultado de la impresión es un objeto tridimensional, es decir, con tres dimensiones: altura, anchura y profundidad.La ?tinta? de una bioimpresora 3D es un gel que nos permite ?imprimir? una capa finita que seendurece rápido. Después, en una segunda ?pasada? deposita una nueva capa degel encima de la anterior, y así continúa creciendo la forma, capa a capa, hastaobtener una impresión tridimensional. Sobre la base de las impresoras 3D, en el laboratorio de nanobiomateriales se diseñó una bioimpresora que, en lugar deplástico derretido, usa un material que no necesita calor para derretirsey es además biocompatible, o sea que cuando está en contacto con alguna parte del cuerpo humano no genera rechazo ni reacciones perjudiciales. El materiales un biopolímero que gelifica: gelatina, celulosa, carrageninas y pectinas.¿Cómo funcionan?Primero dibujamos en la computadora la forma que queremos que tenga la bioimpresión. Luego ponemos el biomaterial dentro de una jeringa conectada a la bioimpresora y, por último, le indicamos que comience a imprimir. Veremos que la jeringa de la bioimpresora se irá moviendo en varias direcciones, depositando con su aguja el biomaterial, mientras va ?dibujando? la forma que diseñamos. La primera capa se deposita sobre la base plana, luego la bioimpresora subirá un poquito la jeringa para formar una nueva capa encima de la anterior y así hasta terminar de imprimir. ¿Y qué podemos hacer con la bioimpresora?Se pueden diseñar estructuras con células en su interior que se adaptan a cada necesidad e imprimir, por ejemplo:? estructuras que ayudan a curar heridas, cicatrizar y evitar infecciones(vendas o parches con antibióticos, cicatrizantes, etc.);? sustancias para uso en alimentos (colores, sabores, aromas y texturas)y cosmética (cremas y protectores solares);? tejidos artificiales (lo que se denomina ingeniería de tejidos) que se pueden usar para reemplazar tejidos dañados de nuestro cuerpo, y promover una sanaciónmucho más rápida y eficaz.Muchos de estos productos son muy utilizados sobre las heridas de personasdiabéticas que presentan un proceso de cicatrización muy dificultoso.Y por tratarse de componentes biodegradables y biocompatibles, la cantidad de aplicaciones que puede tener ¡solo dependen de nuestra imaginación! Fil: Katz, Sergio Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina Fil: Castro, Guillermo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina

Microfluidics is a very useful and promising technology that allowed engineering a huge variety of developments in several fields, such as biology, biomedical engineering, biotechnology, biochemistry, medicine and tissue engineering, among others. Moreover, when microfluidic is combined with hydrogel, the possibilities seem to be limitless. However, it is not found in the bibliography any report that shows the wide range of developments and application fields of this combination. In this review, the bibliography is explored by looking for these new systems that, combining microfluidics and hydrogels, substantially contribute to the state of the art. Seven large application fields are identified -from 649 papers reviewed-: 1) cell culture (out of the scope of this review), 2) biosensors, 3) gradient generator microdevices (GGMD), 4) active elements of hydrogel embedded into microfluidic devices, 5) separation devices, 6) models and 7) other uses. Most of these fields are presented and discussed in detail, the great benefits of the combination are highlighted and perspectives on future directions are exposed. Fil: Goy, Carla Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Departamento de Bioingeniería. Laboratorio de Medios e Interfases; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Departamento de Electricidad, Electrónica y Computación; Argentina Fil: Chaile, Roberto Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Departamento de Bioingeniería. Laboratorio de Medios e Interfases; Argentina Fil: Madrid, Rossana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Departamento de Bioingeniería. Laboratorio de Medios e Interfases; Argentina

Mesenchymal stem/stromal cells (MSCs) have been initially described decades ago as fibroblastic precursors that could be isolated from the bone marrow and establish cultures of fibroblastic cells. These fibroblastic cells were shown tosupport hematopoiesis in vitro, which is a characteristic of stromal cells, and, later, to give rise to mature mesenchymal cells such as bone, cartilage, and fat cells when cultured under appropriate conditions. The proposition that a mesenchymal stem cell exists in postnatal bone marrow and other tissues asblood vessel-associated cells provided further momentum to research on these cells, as well as divergences on how to call them. The impetus of using MSCs to replace cells lost in various types of conditions eventually decreased, as the therapeutic benefits provided by these cells were found to be mostly due to the secretion of paracrine signaling molecules,which can be carried by extracellular vesicles. In the meantime, MSCs were found to modulate the behavior of immunecells by means of secretion of molecules that could, in different scenarios, inhibit the activation of T cells that promote adaptive immune responses. Subsequently, the effects of MSCs on other cells of the immune system were alsodescribed. Today, a number of clinical trials using MSCs to treat conditions influenced by immune cells are under way. While preclinical data indicates that MSCs have important immunomodulatory properties, further studies are still in progress to increase the knowledge on the differences regarding the action of MSCs on immune cells according to their tissue of origin, on how MSCs exert their effects on the different types of immune cells, and on ways to improve the outcome of conditions influenced by immune cells when treated using MSCS. Fil: da Silva Meirelles, Lindolfo. Universidad Luterana; Brasil Fil: Bolontrade, Marcela Fabiana. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; Argentina Fil: Medeiros Markoski, Melissa. Universidad Federal de Ciencias de la Salud ; Brasil Fil: Dallagiovanna, Bruno. Carlos Chagas Institute - Fiocruz; Brasil Fil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina

The daily clinical practice frequently force physicians to make adecision of whether a patient is coursing an infectious disease at theacute or the chronic stage, since treatment may be different dependingon it. This is the case of toxoplasmosis, a worldwide disease caused bythe intracellular parasite Toxoplasma gondii. When a pregnant woman isinfected for the first time by T. gondii and is not treated, the parasite cancross the placenta and severely affect the fetus. In case of primary infection,the treatment protocol includes using antiparasitic drugs toprevent serious damages, including death of the unborn baby. However,antiparasitic chemicals have side effects that should be avoided, unlesstreatment is mandatory. That is why discrimination between long-termand primary T. gondii infection turns out to be critical in infectedpregnant women (Montoya and Remington, 2008).In this work we have used rP22a, an acute-phase recombinant protein werecently described (Costa et al., 2017), to assess anti-T. gondii IgG AI,calculated by two new easier approaches, one based on the area underthe avidity curve (AUAC) and the other one based on the E-P titrationmethod with minor variations. We compare our results with those obtainedwhen calculating the AI by the conventional methods abovementioned, and the performance to render a proper sample classificationas compared to that obtained having used a commercial kit asstandard. Fil: Garcia, Valeria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Peverengo, Luz María. Universidad Nacional del Litoral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Peretti, Leandro Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: González, Verónica Doris Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Gugliotta, Luis Marcelino. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Dalla Fontana, Maria L.. Laboratorio Central de la Provincia de Santa Fe; Argentina Fil: Marcipar, Iván Sergio. Universidad Nacional del Litoral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Lagier, Claudia Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina

Staphylococcus aureus is a worldwide pathogen that causes mastitis in dairy herds. Shortcomings in control programs have encouraged the development of vaccines against this pathogen. This study evaluated the vaccine candidate VacR, which included recombinant S. aureus protein clumping factor A (rClf), fibronectin binding protein A (rFnBP) and hemolysin beta (rBt), formulated with a novel immune-stimulating complex. Comparisons were made between healthy pregnant heifers that received either VacR (n = 8; VacR group) or phosphate buffered saline (PBS) plus adjuvant (control group) SC in the supramammary lymph node area on days 45 and 15 before the expected calving date. Blood and foremilk samples were collected from 7 to 60 days post-calving. After calving, heifers in the VacR group produced higher total IgG (IgGtotal) titers against each component, in both serum (rBt, 3.4 × 105; rClf, 3.1 × 105; rFnBP, 2.3 × 105) and milk (rBt, 2.6 × 104; rClf, 1.3 × 104; rFnBP, 1.1 × 104), than control heifers (P < 0.0001). There were increased concentrations of IgG1 and IgG2 in VacR group (P < 0.05), in both serum and milk. Humoral responses remained high throughout the period most susceptible to intramammary infections (P < 0.01). Antibodies produced against S. aureus rClf and rFnBP reduced bacterial adherence to fibronectin and fibrinogen by 73% and 67%, respectively (P < 0.001). Milk antibodies against these adhesins inhibited S. aureus invasion of a mammary epithelial cell line (MAC-T), resulting in 15.7% of bacteria internalized (P < 0.0001). There was an approximately 6-fold reduction in the hemolysis titer for the native hemolysin in the VacR group compared to the control group (P < 0.0001) and a significantly increase in the proportion of positive neutrophils (VacR, 29.7%; PBS, 13.1%) and the mean fluorescent index (VacR, 217.4; PBS, 152.6; P < 0.01) in the VacR group. The results suggest that VacR is a valuable vaccine candidate against S. aureus infections, and merits further field trials and experimental challenges. Fil: Pujato, Nazarena. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina Fil: Camussone, Cecilia María. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Rafaela; Argentina Fil: Renna, Maria Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina Fil: Perrig, Melina Soledad. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Morein Bror. Uppsala University; Suecia Fil: Calvinho, Luis Fernando. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Rafaela; Argentina Fil: Marcipar, Iván Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina

The aging female rat constitutes an interesting model of spontaneous and progressive age-related dopaminergic dysfunction as it allows assessing new therapeutic strategies for Parkinson's disease. Insulin-like growth factor I (IGF-I) is emerging as a powerful neuroprotective molecule, strongly induced in the central nervous system after different insults. We constructed a helper-dependent recombinant adenoviral vector (HDRAd-IGFI) harboring the gene for rat IGF-I. This was used to implement long-term IGF-I gene therapy in the hypothalamus of aged female rats, which display hypothalamic dopaminergic (DA) dysfunction and, as a consequence, chronic hyperprolactinemia. Rejuvenating long-term IGF-I gene therapy was implemented in young (3 months) and aged (24 months) female rats, which received a single intrahypothalamic injection of 4 × 109 viral particles of either HD-RAd-IGFI or HD-RAd-DsRed (control vector) and were sacrificed 119 days postinjection. In the young animals, neither vector modified serum prolactin (PRL) levels, but in the RAd-IGFI-injected aged rats a nearly full reversion of their hyperprolactinemic status was recorded. Morphometric analysis revealed a significant increase in the total number of tyrosine hydroxylase (TH)-positive cells in the hypothalamus of experimental compared with control aged animals (5874 ± 486 and 3390 ± 498, respectively). Our results indicate that IGF-I gene therapy in aged female rats is highly effective in rejuvenating the hypothalamic DA neuron groups. Fil: Schwerdt, José Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: López León, Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Cónsole, Gloria M. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina Fil: Brown, Oscar Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Morel, Gustavo Ramón. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Spinedi, Eduardo Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina Fil: Goya, Rodolfo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina

Neospora caninum, an intracellular protozoan parasite from the phylum Apicomplexa, is the etiologic agent of neosporosis, a disease considered as a major cause of reproductive loss in cattle and neuromuscular disease in dogs. Bovine neosporosis has a great economic impact in both meat and dairy industries, related to abortion, premature culling and reduced milk yields. Although many efforts have been made to restrain bovine neosporosis, there are still no efficacious control methods. Many vaccine-development studies focused in the apicomplexan proteins involved in the adhesion and invasion of the host cell. Among these proteins, profilins have recently emerged as potential vaccine antigens or even adjuvant candidates for several diseases caused by apicomplexan parasites. Profilins bind Toll-like receptors 11 and 12 initiating MyD88 signaling, that triggers IL-12 and IFN-γ production, which may promote protection against infection. Here we summarized the state-of-the-art of novel vaccine development based on apicomplexan profilins applied as antigens or adjuvants, and delved into recent advances on N. caninum vaccines using profilin in the mouse model and in cattle. Fil: Mansilla, Florencia Celeste. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Capozzo, Alejandra Victoria. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Background and Purpose: The multiple stent placement technique has largely improved the long-term outcomes of intracranial fusiform aneurysms, but the hemodynamic mechanisms remain unclear. In this study, we analyzed the hemodynamic changes caused by different stent-placement strategies in patient-specific models using the computational fluid dynamics technique, aiming to provide evidence for clinical decision-making. MATERIALS AND METHODS: Ten vertebral artery fusiform aneurysms were included, and their patient-specific computational fluid dynamics models were reconstructed. A fast virtual stent placement technique was used to simulate sequential multiple stent placements (from a single stent to triple stents) in the vertebral artery fusiform aneurysm models. Hemodynamic parameters, including wall shear stress, pressure, oscillatory shear index, relative residence time, and flow pattern, were calculated and compared among groups with different numbers of stents. RESULTS: Virtual stents were deployed in all 10 cases successfully, consistent with the real stent configuration. Wall shear stress decreased progressively by 7.2%, 20.6%, and 25.8% as the number of stents increased. Meanwhile, relative residence time and pressure increased on average by 11.3%, 15.4%, and 45.0% and by 15.7%, 21.5%, and 28.2%. The oscillatory shear index showed no stable variation trend. Flow patterns improved by weakening the intensity of the vortices and displacing the vortex center from the aneurysmal wall. CONCLUSIONS: Stent placement modifies hemodynamic patterns in vertebral artery fusiform aneurysms, which might favor thrombosis formation in the aneurysmal sac. This effect is amplified with the number of stents deployed. However, a potential risk of rupture or recanalization exists and should be considered when planning to use the multiple stent placement technique in vertebral artery fusiform aneurysms. Fil: Lv, N.. Second Military Medical University. Changhai Hospital; China Fil: Cao, W.. Second Military Medical University. Changhai Hospital; China Fil: Larrabide, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Karmonik, C.. Houston Methodist Research Institute; Estados Unidos Fil: Zhu, D.. Second Military Medical University. Changhai Hospital; China Fil: Liu, J.. Second Military Medical University. Changhai Hospital; China Fil: Huang, Q.. Second Military Medical University. Changhai Hospital; China Fil: Fang, Y.. Second Military Medical University. Changhai Hospital; China

If cultured in appropriate conditions, such as supplementing culture media with costly cytokines and growth factors, hematopoietic stem/progenitor cells (HSPCs) from different origins have shown to be an adequate source of erythroid cells. This requirement turns erythroid cells production into a complicated process to be scaled-up for future applications. The aim of our work was to genetically modify HSPCs with human erythropoietin (hEPO) sequence by lentiviral transgenesis in order for cells to secrete the hormone into the culture medium. Initially, we evaluated erythroid differentiation in colony forming units (CFU) assays and further analyzed cell expansion and erythroid differentiation throughout time in suspension cultures by flow cytometry and May-Grünwald-Giemsa staining. Additionally, we studied hEPO production and its isoforms profile. The different assessment approaches demonstrated erythroid differentiation, which was attributed to the hEPO secreted by the HSPCs. Our data demonstrate that it is possible to develop culture systems in which recombinant HSPCs are self-suppliers of hEPO. This feature makes our strategy attractive to be applied in biotechnological production processes of erythroid cells that are currently under development. Fil: Cappellino, Luisina Anabel. Universidad Nacional del Litoral; Argentina Fil: Kratje, Ricardo Bertoldo. Universidad Nacional del Litoral; Argentina Fil: Etcheverrigaray, Marina. Universidad Nacional del Litoral; Argentina Fil: Prieto, Claudio. Universidad Nacional del Litoral; Argentina

Brucellosis is a widespread zoonotic disease caused by Brucella spp. Brucella canis is the etiological agent of canine brucellosis, a disease that can lead to sterility in bitches and dogs causing important economic losses in breeding kennels. Early and accurate diagnosis of canine brucellosis is central to control the disease and lower the risk of transmission to humans. Here, we develop and validate enzyme and lateral flow immunoassays for improved serodiagnosis of canine brucellosis using as antigen the B. canis rough lipopolysaccharide (rLPS). The method used to obtain the rLPS allowed us to produce more homogeneous batches of the antigen that facilitated the standardization of the assays. To validate the assays, 284 serum samples obtained from naturally infected dogs and healthy animals were analyzed. For the B. canis-iELISA and B. canis-LFIA the diagnostic sensitivity was of 98.6%, and the specificity 99.5% and 100%, respectively. We propose the implementation of the B. canis-LFIA as a screening test in combination with the highly accurate laboratory g-iELISA. The B. canis-LFIA is a rapid, accurate and easy to use test, characteristics that make it ideal for the serological surveillance of canine brucellosis in the field or veterinary laboratories. Finally, a blind study including 1040 serum samples obtained from urban dogs showed a prevalence higher than 5% highlighting the need of new diagnostic tools for a more effective control of the disease in dogs and therefore to reduce the risk of transmission of this zoonotic pathogen to humans. Fil: Cortina, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina Fil: Novak, Analia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina Fil: Melli, Luciano Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina Fil: Elena, Sebastián. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; Argentina Fil: Corbera, Natalia Leonor. Provincia de Buenos Aires. Instituto Veterinario "Dr. Juan E. Romero"; Argentina Fil: Romero, Juan E.. Universidad Nacional de La Pampa. Facultad de Ciencias Veterinarias; Argentina Fil: Nicola, Ana M.. Ministerio de Agricultura, Ganadería, Pesca y Alimento. Servicio Nacional de Sanidad y Calidad Agroalimentaria; Argentina Fil: Ugalde, Juan Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina Fil: Comerci, Diego José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina. Comisión Nacional de Energía Atómica; Argentina Fil: Ciocchini, Andres Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina

Cystic echinococcosis is endemic in the Rio Negro province of Argentina and, for this, a control program using praziquantel in dogs was developed from 1980. The transmission rate to humans and sheep has decreased significantly, however transmission persists. In 2009 the vaccination of sheep with EG95 was incorporated in some areas of the province. The objective of the study was to evaluate the humoral responses to the vaccine EG95. Lambs received two vaccinations with the EG95 vaccine followed by a single booster injection when the animals were 1-1.5 years of age. Blood samples from 6 vaccinated groups and 4 no vaccinated sheep were obtained for determination of antibody titles against EG95 protein. Anti-EG95 responses were determined as described by Heath and Koolaard, 2012. Responses were evaluated from 331 animals. Median ELISA absorbance values in vaccinated group was 0.828, and in non-vaccinated groups was 0.218. EG95 antibody responses in sheep from different cohorts of non-immunized control groups and vaccinated groups reveal the sustained increase in response seen in animals following the third immunization. (p< 0.0001). Significant differences are also evidenced in ANOVA test (p< 0.001). An anti-EG95 antibody response was induced in all groups of immunized sheep, 4 times higher (0.828) than the mean observed in the control groups (0.218). Data described here indicate that following a third vaccination with the EG95 vaccine at 1 year of age the specific IgG responses detected in the serum of sheep increased to a level greater than that seen following the second immunization and that this response was maintained longitudinally over time, for at least 5 years. Fil: Larrieu, Edmundo Juan. Universidad Nacional de La Pampa. Facultad de Ciencias Veterinarias; Argentina. Universidad Nacional de Río Negro; Argentina Fil: Poggio, Thelma Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; Argentina Fil: Mujica, Guillermo. Provincia de Río Negro. Ministerio de Salud; Argentina Fil: Gauci, Charles G.. University of Melbourne; Australia Fil: Labanchi, Jose Luis. Provincia de Río Negro. Ministerio de Salud; Argentina Fil: Herrero, Eduardo. Provincia de Río Negro. Ministerio de Salud; Argentina Fil: Araya, Daniel. Provincia de Río Negro. Ministerio de Salud; Argentina Fil: Grizmado, Claudia. Provincia de Río Negro. Ministerio de Salud; Argentina Fil: Calabro, Arnoldo. Provincia de Río Negro. Ministerio de Salud; Argentina Fil: Talmon, Gabriel. Provincia de Río Negro. Ministerio de Salud; Argentina Fil: Crowley, Pablo Ernesto. Universidad Nacional de Río Negro; Argentina Fil: Santillán, Graciela. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbran". Departamento de Parasitología; Argentina Fil: Vizcaychipi, Katherina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbran". Departamento de Parasitología; Argentina Fil: Seleiman, Marcos. Provincia de Río Negro. Ministerio de Salud; Argentina Fil: Sepulveda, Luis. Provincia de Río Negro. Ministerio de Salud; Argentina Fil: Arezo, Marcos. Provincia de Río Negro. Ministerio de Salud; Argentina Fil: García Cachau, Mariela Alejandra. Universidad Nacional de La Pampa. Facultad de Ciencias Veterinarias; Argentina Fil: Lamberti, Roberto. Universidad Nacional de La Pampa. Facultad de Ciencias Veterinarias; Argentina Fil: Molina, Leonardo. Universidad Nacional de La Pampa. Facultad de Ciencias Veterinarias; Argentina Fil: Gino, Lilia Mabel. Universidad Nacional de La Pampa. Facultad de Ciencias Veterinarias; Argentina Fil: Donadeu, Meritxell. University of Melbourne; Australia Fil: Lightowlers, Marshall W.. University of Melbourne; Australia

Fluorescent semiconductor quantum dots (QDs) exhibit several unique properties that make them suitable candidates for biomolecular sensing, including high brightness, photostability, broad excitation, and narrow emission spectra. Assembling these QDs into robust and functionalizable nanosized clusters (QD-NSCs) can provide fluorescent probes that are several orders of magnitude brighter than individual QDs, thus allowing an even greater sensitivity of detection with simplified instrumentation. However, the formation of compact, antifouling, functionalizable, and stable QD-NSCs remains a challenging task, especially for a use at ultralow concentrations for single-molecule detection. Here, we describe the development of fluorescent QD-NSCs envisioned as a tool for fast and sensitive biomolecular recognition. First, QDs were assembled into very compact 100-150 nm diameter spherical aggregates; the final QD-NSCs were obtained by growing a cross-linked silica shell around these aggregates. Hydrolytic stability in several concentration and pH conditions is a key requirement for a potential and efficient single-molecule detection tool. However, the hydrolysis of Si-O-Si bonds leads to desorption of monosilane-based surface groups at very low silica concentrations or in a slightly basic medium. Thus, we designed a novel multidentate copolymer composed of multiple silane as well as zwitterionic monomers. Coating silica beads with this multidentate copolymer provided a robust surface chemistry that was demonstrated to be stable against hydrolysis, even at low concentrations. Copolymer-coated silica beads also showed low fouling properties and high colloidal stability in saline solutions. Furthermore, incorporation of additional azido-monomers enabled easy functionalization of QD-NSCs using copper-free bio-orthogonal cyclooctyne-azide click chemistry, as demonstrated by a biotin-streptavidin affinity test. Fil: Dembele, Fatimata. Universite Pierre et Marie Curie; Francia Fil: Tasso, Mariana Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina Fil: Trapiella Alfonso, Laura. Universite Pierre et Marie Curie; Francia Fil: Xu, Xiangzhen. Universite Pierre et Marie Curie; Francia Fil: Hanafi, Mohamed. Universite Pierre et Marie Curie; Francia Fil: Lequeux, Nicolas. Universite Pierre et Marie Curie; Francia Fil: Pons, Thomas. Universite Pierre et Marie Curie; Francia

Background: There is growing evidence that the serotonergic system, in particular serotonin 2A receptors, is involved in neuropsychiatric symptoms in Parkinson's disease (PD), including cognitive processing and visual hallucinations. However, the relationship between serotonin 2A receptor availability, visual hallucinations, and cognitive profile is unknown. The objective of this study was to investigate the level of serotonin 2A receptor availability in brain regions affected by visual hallucinations and to test the association with cognitive/behavioral changes in patients who have PD with visual hallucinations. Methods: Nondemented patients who had PD with (n = 11) and without (n = 8) visual hallucinations and age‐matched controls (n = 10) were recruited. All participants completed neuropsychological testing, which consisted of visuoperceptual, executive, memory, language, and frontal‐behavioral function. Positron emission tomography scans using [18F]setoperone, a serotonin 2A antagonist radioligand, were acquired in patients with PD, and a parametric binding potential map of [18F]setoperone was calculated with the simplified reference tissue model using the cerebellum as a reference. Results: Patients who had PD with visual hallucinations exhibited significantly lower scores on measures of executive and visuoperceptual functions compared with age‐matched controls. These changes were paralleled by decreased [18F]setoperone binding in the right insula, bilateral dorsolateral prefrontal cortex, right orbitofrontal cortex, right middle temporal gyrus, and right fusiform gyrus. The psychometric correlation analysis revealed significant relationships among tests associated with visuoperceptual function, memory and learning, and serotonin 2A binding in different prefrontal and ventral visual stream regions. There was also reduced serotonin 2A receptor binding in patients who had PD with depression. Conclusions: These findings support a complex interaction between serotonin 2A receptor function and cognitive processing in patients who have PD with visual hallucinations. Fil: Cho, Sang Soo. University of Toronto; Canadá Fil: Strafella, Antonio P.. University of Toronto; Canadá Fil: Duff Canning, Sarah. University of Toronto; Canadá Fil: Zurowski, Mateusz. University of Toronto; Canadá Fil: Vijverman, Anne Catherine. Onze‐Lieve‐Vrouw Hospital; Bélgica Fil: Bruno, Veronica Andrea. University of Toronto; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Aquino, Camila C.. University of Toronto; Canadá Fil: Criaud, Marion. University of Toronto; Canadá Fil: Rusjan, Pablo M.. University of Toronto; Canadá Fil: Houle, Sylvain. University of Toronto; Canadá Fil: Fox, Susan H.. University of Toronto; Canadá

Background: Natural speech analytics has seen some improvements over recent years, and this has opened a window for objective and quantitative diagnosis in psychiatry. Here, we used a machine learning algorithm applied to natural speech to ask whether language properties measured before psilocybin for treatment-resistant can predict for which patients it will be effective and for which it will not. Methods: A baseline autobiographical memory interview was conducted and transcribed. Patients with treatment-resistant depression received 2 doses of psilocybin, 10 mg and 25 mg, 7 days apart. Psychological support was provided before, during and after all dosing sessions. Quantitative speech measures were applied to the interview data from 17 patients and 18 untreated age-matched healthy control subjects. A machine learning algorithm was used to classify between controls and patients and predict treatment response. Results: Speech analytics and machine learning successfully differentiated depressed patients from healthy controls and identified treatment responders from non-responders with a significant level of 85% of accuracy (75% precision). Conclusions: Automatic natural language analysis was used to predict effective response to treatment with psilocybin, suggesting that these tools offer a highly cost-effective facility for screening individuals for treatment suitability and sensitivity. Limitations: The sample size was small and replication is required to strengthen inferences on these results. Fil: Carrillo, Facundo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación. Laboratorio de Inteligencia Artificial Aplicada; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Investigación en Ciencias de la Computación. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Investigación en Ciencias de la Computación; Argentina Fil: Sigman, Mariano. Universidad Torcuato Di Tella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Fernandez Slezak, Diego. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación. Laboratorio de Inteligencia Artificial Aplicada; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Investigación en Ciencias de la Computación. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Investigación en Ciencias de la Computación; Argentina Fil: Ashton, Philip. Imperial College London; Reino Unido Fil: Fitzgerald, Lily. Imperial College London; Reino Unido Fil: Stroud, Jack. Imperial College London; Reino Unido Fil: Nutt, David J.. Imperial College London; Reino Unido Fil: Carhart Harris, Robin L.. Imperial College London; Reino Unido

Listeriosis is a foodborne disease caused by Listeria monocytogenes. The aims of this work were to develop and validate an in-house real-time polymerase chain reaction (RT-PCR) for the detection of L. monocytogenes, and to determine its prevalence in raw ground beef samples from 53 butcheries that also sell ready-to-eat foods. One set of primers and one hydrolysis probe were designed for hly gene detection and then challenged with pure strains. The detection was successful for all L. monocytogenes strains analyzed and negative for all non-L. monocytogenes strains (detection limit, 10 colony forming unit [CFU]/mL). Inclusivity, exclusivity, and analytical accuracy were 100%. L. monocytogenes was detected in 41.5% of raw ground beef samples from the 53 butcheries analyzed. This RT-PCR may be a valuable method for rapid detection of L. monocytogenes in meat., Instituto de Genética Veterinaria, Facultad de Ciencias Veterinarias

Here, we described a detailed protocol to establish a newborn rat whole ovary culture, able to study direct effects (independent of hypothalamic-pituitary-gonadal axis) of Endocrine Disrupting Chemicals (EDC), such as Benzophenone 3 (BP-3). This method is useful to understand changes in follicle formation, primordial to primary transition and expression of regulatory molecules linked to these processes as also provides an alternative to animal models. Basic protocols described here are the following:BASIC PROTOCOL 1: RAT OVARIAN SURGERYBASIC PROTOCOL 2: WHOLE ORGAN/OVARIAN CULTUREBASIC PROTOCOL 3: RNA ISOLATION AND QUANTITATIVE REAL TIME-PCRBASIC PROTOCOL 4: HISTOLOGICAL PROCESSING AND STAINING Fil: Santamaría, Clarisa Guillermina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina Fil: Abud, Julián Elías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina Fil: Luque, Enrique Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina Fil: Kass, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina Fil: Rodriguez, Horacio Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina

Muscle-invasive bladder cancer (MIBC) is an aggressive form of urothelial bladder carcinoma (UBC) with poorer outcomes compared to the non-muscle invasive form (NMIBC). Higher recurrent rates and rapid progression after relapse in UBC is known to be linked with chronic inflammation. Here, the preclinical murine models of NMIBC (MB49) and MIBC (MB49-I) were used to assess the antitumor effects of DAB-1, an anti-inflammatory aminobenzoic acid derivative we have developed in order to target cancer-related inflammation. A subchronic toxicity study on cancer-free mice shown that DAB-1 treatment did not affect normal mouse development or normal function of vital organs. In mice bearing MB49-I tumors, whole body accumulation of the radioconjugate [ 131I]DAB-1 was higher than in control mice, the main sites of [131I]DAB-1 accumulation being the liver (34%), the intestines (21%), and the tumors (18%). In vivo molecular therapy of ectopic and orthotopic tumors indicated that treatment with DAB-1 efficiently inhibited tumor growth, metastasis formation, and mortality rate. The antitumor efficacy of DAB-1 was associated with strong decreased tumor cell proliferation and iNOS expression in tumor tissues and deactivation of macrophages from tumor-bearing mice. Mechanistic investigations revealed that DAB-1 efficiently inhibited i) TNFα/NFΚB and IL6/STAT3 signaling pathways activation; ii) TNFα-induced NO production by decreasing NFΚB transcriptional activation and functional iNOS expression; and iii) cellular proliferation with minimal or no effects on cell mortality or apoptosis. In conclusion, this study provides preclinical and biological/mechanistic data highlighting the potential of DAB-1 as a safe and efficient therapeutic agent for the treatment of patients with NMIBC and MIBC. Fil: Girouard, Julie. Université du Québec a Montreal; Canadá Fil: Belgorosky, Denise. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Hamelin Morrissette , Jovane. Université du Québec a Montreal; Canadá Fil: Boulanger, Valerie. Université du Québec a Montreal; Canadá Fil: D'Orio, Ernesto. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina Fil: Ramla, Djamel. Université du Québec a Montreal; Canadá Fil: Perron, Robert. Université du Québec a Montreal; Canadá Fil: Charpentier, Lucie. Université du Québec a Montreal; Canadá Fil: Van Themsche, Celine. Université du Québec a Montreal; Canadá Fil: Eijan, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina Fil: Bérubé, Gervais. Université du Québec a Montreal; Canadá Fil: Reyes Moreno, Carlos. Université du Québec a Montreal; Canadá

Inflammatory bowel diseases are chronic and relapsing-remitting disorders that affect the gastrointestinal tract. Previously, the administration of folate and riboflavin-producing lactic acid bacteria (LAB) or an immune-modulating strain showed beneficial effects as they were able to reduce the acute inflammation in mouse models. The aim of this work was to evaluate a mixture of vitamin-producing and immune-modulating LAB administering together with an anti-inflammatory drug during the remission period of a mouse model of recurrent colitis. BALB/c mice were intrarectally instilled with trinitrobenzene sulfonic acid (TNBS) and those who recovered from this acute challenge were given the LAB mixture, mesalazine, or the combination of both (mesalazine + LAB) during 21 days, followed by a second challenge with TNBS. Control mice instilled with ethanol (vehicle of TNBS) and receiving the different treatments were also evaluated in order to study the effect of chronic anti-inflammatory therapy. The combination of mesalazine and LAB mixture was the most effective to decrease the intestinal damage at macroscopic and histological levels and to reduce pro-inflammatory cytokines (IL-6 and TNF-α) in intestinal fluids. In animals instilled with ethanol, mesalazine produced a loss of body weight and intestinal damages with increased IL-6. These side effects were prevented by the co-administration of mesalazine and the LAB mixture. The LAB blend did not affect the primary anti-inflammatory treatment, was able to improve it, and also prevented the side effects of this therapy. Fil: Levit, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Savoy, Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina

The New World arenavirus Junin (JUNV) is the etiological agent of Argentine hemorrhagic fever (AHF). Previous studies of human macrophage infection by the Old-World arenaviruses Mopeia and Lassa showed that while the non-pathogenic Mopeia virus replicates and activates human macrophages, the pathogenic Lassa virus replicates but fails to activate human macrophages. Less is known in regard to the impact of New World arenavirus infection on the human macrophage immune response. Macrophage activation is critical for controlling infections but could also be usurped favoring immune evasion. Therefore, it is crucial to understand how the JUNV infection modulates macrophage plasticity to clarify its role in AHF pathogenesis. With this aim in mind, we compared infection with the attenuated Candid 1 (C#1) or the pathogenic P strains of the JUNV virus in human macrophage cultures. The results showed that both JUNV strains similarly replicated and induced morphological changes as early as 1 day post-infection. However, both strains differentially induced the expression of CD71, the receptor for cell entry, the activation and maturation molecules CD80, CD86, and HLA-DR and selectively modulated cytokine production. Higher levels of TNF-α, IL-10, and IL-12 were detected with C#1 strain, while the P strain induced only higher levels of IL-6. We also found that C#1 strain infection skewed macrophage polarization to M1, whereas the P strain shifted the response to an M2 phenotype. Interestingly, the MERTK receptor, that negatively regulates the immune response, was down-regulated by C#1 strain and up-regulated by P strain infection. Similarly, the target genes of MERTK activation, the cytokine suppressors SOCS1 and SOCS3, were also increased after P strain infection, in addition to IRF-1, that regulates type I IFN levels, which were higher with C#1 compared with P strain infection. Together, this differential activation/polarization pattern of macrophages elicited by P strain suggests a more evasive immune response and may have important implications in the pathogenesis of AHF and underpinning the development of new potential therapeutic strategies, Facultad de Ciencias Exactas, Instituto de Biotecnologia y Biologia Molecular, Centro de Investigación y Desarrollo en Fermentaciones Industriales

In rodents with acute myocardial infarction (AMI), high mobility group box 1 (HMGB1) injection has produced controversial results. Given the lack of data in large mammals, we searched the dose that would promote angiogenesis and expression of specific regenerative genes in sheep with AMI (protocol 1) and, subsequently, use this dose to study long-term effects on infarct size and left ventricular (LV) function (protocol 2). Protocol 1: Sheep with AMI received 250 μg (high-dose, n = 7), 25 μg (low-dose, n = 7) HMGB1, or PBS (placebo, n = 7) in 10 intramyocardial injections (0.2 ml each) in the peri-infarct area. Seven days later, only the high-HMGB1-dose group exhibited higher microvascular densities, Ki67-positive cardiomyocytes, and overexpression of VEGF, Ckit, Tbx20, Nkx2.5, and Gata4. Protocol 2: Sheep with AMI received HMGB1 250 μg (n = 6) or PBS (n = 6). At 60 days, HMGB1-treated sheep showed smaller infarcts (8.5 ± 2.11 vs. 12.2 ± 1.97% LV area, P < 0.05, ANOVA-Bonferroni) and higher microvascular density (capillaries, 1798 ± 252 vs. 1266 ± 250/mm2; arterioles, 18.3 ± 3.9 vs. 11.7 ± 2.2/mm2; both P < 0.01). Echocardiographic LV ejection fraction, circumferential shortening, and wall thickening increased from day 3 to 60 with HMGB1 (all P < 0.05). Conclusion: in ovine AMI, high-dose HMGB1 induces angio-arteriogenesis, reduces infarct size, and improves LV function at 2 months post-treatment. Fil: Bauza, Maria del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina Fil: Giménez, Carlos Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina Fil: Locatelli, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina Fil: De Lorenzi, Andrea. Fundación Favaloro; Argentina Fil: Hnatiuk, Anna. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina Fil: Capogrossi, Maurizio C.. Johns Hopkins Bayview Medical Center; Estados Unidos Fil: Crottogini, Alberto José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina Fil: Cuniberti, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina Fil: Olea, Fernanda Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina

Gold nanoparticles (AuNPs) have emerged as an interesting tool with high potential in the medical field and as a promising alternative against multidrug-resistant microorganisms. Green chemical synthesis of AuNPs conjugated with the flavonoid silybin (S) to generate a nano-system with dual antibacterial and antioxidant properties were performed. The S-AuNPs plasmon peak was found at 567 nm with narrow particle size distribution of around 58 nm. TEM and AFM images revealed the presence of spherical and homogeneous nanoparticles with an average diameter of 35 nm. Conjugation of silybin to the surface of AuNPs was confirmed by FTIR analysis. Antioxidant properties were found since the S-AuNPs were able to prevent the rapid oxidation of Brilliant Cresyl Blue, as reporter dye, in presence of sodium hypochlorite as strong oxidant. Also, S-AuNPs inactivated Gram-negative bacteria of nosocomial interest such as Pseudomonas aeruginosa and Escherichia coli. A minimum inhibitory concentration of 11.2 and 5.6 μg/ml was observed for each microbe respectively. Fluorescent live/dead assay confirmed that S-AuNPs can kill bacteria with significant cell damage only after 30 min of exposition. TEM images showed that S-AuNPs can strongly interact with bacteria surfaces leading to cell lysis. Also, S-AuNPs showed about half of cytotoxic concentration (CC50) compared within acyclovir (control) tested in Vero cells. Fil: Islan, German Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina Fil: Das, Suvadra. University of Calcutta; India. University of Engineering and Management; India Fil: Cacicedo, Maximiliano Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina Fil: Halder, Asim. University of Calcutta; India Fil: Mukherjee, Asmita. University Of Calcutta; India Fil: Cuestas, María Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina Fil: Roy, Partha. Adamas University; India Fil: Castro, Guillermo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina Fil: Mukherjee, Arup. Adamas University; India

Active packaging materials with antimicrobial properties have gained significant interest over the last decade. Furthermore, phages are potentially useful as antimicrobial agents in food. Phage stability assays were conducted in the whey protein concentrate (WPC) matrix over 5 weeks of storage. In addition, the phages incorporated in the WPC matrix were characterized by their release from films into an aqueous system and solid food, as well as by their antimicrobial activity against pathogenic E. coli in a liquid medium and in meat at refrigerated, room and abusive temperatures. The results demonstrate that phages are highly stable in WPC films within 5 weeks of storage. Moreover, WPC films can release a significant number of phages into an aqueous system and onto a meat surface at similar concentrations. Phage-added films produced a significant reduction in E. coli cells to non-detectable levels in antimicrobial assays. Similar results, such as a complete inactivation achieved for DH5α and O157:H7 STEC strains, were obtained when antimicrobial assays were performed on meat. As a conclusion, the six-phage cocktail added into WPC films was highly stable, effectively released from films and proved highly effective as a biocontrol tool, though not under all the conditions evaluated. Fil: Tomat, David Damian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Soazo, Marina del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Verdini, Roxana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Casabonne, Cecilia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Aquili, Virginia Daniela. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Balague, Claudia Elisabeht. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Quiberoni, Andrea del Lujan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; Argentina

Background: Skin and soft tissue infections involve microbial invasion of the skin and underlying soft tissues. To overcome this problem, nanocomposites were obtained using gelatin as a biopolymer scaffold and silver nanoparticles as a wide spectrum antimicrobial agent. Water and glycerol have been used as solvents for the gelatin hydrogel synthesis. This mixture led to a stable and homogeneous biomaterial with improved mechanical properties. Methods: Silver nanoparticles were characterized using SEM, EDS and TEM. Moreover, the AgNp/gelatin nanocomposite obtained using these nanoparticles was characterized using SEM and FTIR. Moreover, mechanical and swelling properties were studied. Results: The storage modulus was 3000 Pa for gelatin hydrogels and reached 5800 Pa for AgNp/gelatin nanocomposite. Silver nanoparticles have been studied as an alternative to antibiotics. Importantly, the rate of silver release was modulated as a function of the temperature of the nanocomposite. Thus, the silver release from the nanocomposites at 24 °C and 38 °C was analyzed by atomic absorption spectroscopy. The silver release reached 25% after 24 h at 24 °C, while a 75% release was achieved at 38°C in the same period, showing the material thermoresponsive behavior. AgNp/gelatin nanocomposite showed a deleterious effect over 99.99% of Pseudomonas aeruginosa and Staphylococcus aureus, leading to a material with antimicrobial properties. Conclusion: AgNp/gelatin nanocomposite with improved mechanical properties and silver nanoparticles as a source of silver ions has been synthesized. The properties of the nanocomposite with controlled silver delivery result in a more efficient topical pharmaceutical form for wound healing applications. Fil: Galdopórpora, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Morcillo, Marina Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Ibar, Angelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Pérez, Claudio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentina Fil: Tuttolomondo, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Desimone, Martín Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina

In an insightful article, Jacob Earl outlines the concept of innovative practice, addresses ethical problems and presents a permissive oversight proposal to deal with the ethical concerns identified. We agree to a large extent with Earl´s approach and, therefore, decided to develop his comprehensive analysis further. In particular, we want to extend it from national to global contexts. In this regard we argue that innovative practice in countries with poor regulation of the sale and marketing of new drugs carries a higher risk of crowding out research. In turn, this entails the potential harm to global public health caused by a significant reduction or exclusion of sound and socially valuable research. We think that analyzing innovative practices performed in a global landscape of poor regulation, like the one we find in many Latin American countries, can provide us with useful insights into Earl´s approach. Fil: Holzer, Felicitas Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Facultad Latinoamericana de Ciencias Sociales; Argentina Fil: Mastroleo, Ignacio Damian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto de Investigaciones Sociales de América Latina. - Facultad Latinoamericana de Ciencias Sociales. Instituto de Investigaciones Sociales de América Latina; Argentina

Extracellular vesicles (EVs) play key roles in cell biology and may provide new clinical diagnostics and therapies. However, it has proven difficult to develop protocols for their purification and characterization. One of the major barriers in the field has been a lack of convenient assays for their bioactivity. Developing assays has not been a trivial matter, because of the heterogeneity of EVs, the multiple activities they demonstrate, and the uncertainty about their modes of action. Therefore, it is likely that multiple assays for their activities are needed. One important assay will be for the anti-inflammatory activity observed in mice after administration of the small EVs commonly referred to as exosomes. We developed an assay for the anti-inflammatory activity of exosomes with a line of mouse macrophages. The assay makes it possible to rank different preparations of exosomes by their anti-inflammatory activity, and their ranking predicts their efficacy in suppressing LPS-stimulated inflammation in mice. The assay is convenient for comparing multiple samples and, therefore, should be useful in developing protocols for the purification and characterization of anti-inflammatory exosomes., Graphical Abstract

Several epidemiologic studies have revealed strong inverse associations between metformin use and risk of colorectal cancer development. Nevertheless, the underlying mechanisms are still uncertain. The Wnt/β-catenin pathway, which plays a central role in intestinal homeostasis and sporadic colorectal cancer development, is regulated by phosphorylation cascades that are dependent and independent of Wnt. Here we report that a noncanonical Ser552 phosphorylation in β-catenin, which promotes its nuclear accumulation and transcriptional activity, is blocked by metformin via AMPK-mediated PI3K/Akt signaling inhibition. Fil: Amable, Gastón Federico. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Martínez León, Eduardo Antonio. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Picco, María Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Di Siervi, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Davio, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina Fil: Rozengurt, Enrique. University of California at Los Angeles; Estados Unidos Fil: Rey, Osvaldo. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina