Fundación Instituto Leloir

About: Fundación Instituto Leloir is a facility organization based out in Buenos Aires, Argentina. It is known for research contribution in the topics: Dentate gyrus & Neurogenesis. The organization has 702 authors who have published 1052 publications receiving 39299 citations.

Community-level SARS-CoV-2 Seroprevalence Survey in urban slum dwellers of Buenos Aires City, Argentina: a participatory research.

Abstract: Background By July 1st, the incidence rate of RT-qPCR SARS-CoV-2 infection was 5.9% in Barrio Padre Mugica, one of the largest slums in Buenos Aires City. This study aimed to establish the seroprevalence of SARS-CoV-2 three months after the first case was reported. Methods Between June 10th and July 1st, a cross-sectional design was carried out on people over 14 years old, selected from a probabilistic sample of households. A finger prick sample was tested by ELISA to detect IgG-class antibodies against SARS-CoV-2. Multilevel model was applied to understand sector, household and individual conditions associated with seroconvert. Results Prevalence based on IgG was 53.4% (95%IC 52.8% to 54.1%). Among the IgG positive cases, 15% reported having compatible symptoms at some point in the past two months. There is evidence of within-household clustering effect (rho=0.52; 95% IC 0.36-0.67); living with a PCR-confirmed case doubled the chance of being SARS-CoV2 IgG positive (OR 2.13; 95% IC 1.17-3.85). The highest risk of infection was found in one of the most deprived areas of the slum, the “Bajo autopista” sector. Discussion High seroprevalence is shown, for each symptomatic RT-qPCR-confirmed diagnosis, 9 people were IgG positive, indicating a high rate of undetected (probable asymptomatic) infections. Given that transmission among family members is a leading driver of the disease’s spread, it is unsurprising that crowded housing situations in slums are directly associated with higher risk of infection and consequently high seroprevalence levels. This study contributes to the understanding of population immunity against SARS-CoV2, its relation to living conditions and viral spread, for future decision making.

Structural and Functional Analysis of Dengue Virus RNA

Abstract: Sequences and structures present at the 5' and 3' UTRs of RNA viruses play crucial roles in the initiation and regulation of translation, RNA synthesis and viral assembly. In dengue virus, as well as in other mosquito-borne flaviviruses, the presence of complementary sequences at the ends of the genome mediate long-range RNA-RNA interactions. Dengue virus RNA displays two pairs of complementary sequences (CS and UAR) required for genome circularization and viral viability. In order to study the molecular mechanism by which these RNA-RNA interactions participate in the viral life cycle, we developed a dengue virus replicon system. RNA transfection of the replicon in mosquito and mammalian cells allows discrimination between RNA elements involved in translation and RNA synthesis. We found that mutations within CS or UAR at the 5' or 3' ends of the RNA that interfere with base pairing did not significantly affect translation of the input RNA but seriously compromised or abolished RNA synthesis. Furthermore, a systematic mutational analysis of UAR sequences indicated that, beside the role in RNA cyclization, specific nucleotides within UAR are also important for efficient RNA synthesis.

IL-8, GRO and MCP-1 produced by hepatocellular carcinoma microenvironment determine the migratory capacity of human bone marrow-derived mesenchymal stromal cells without affecting tumor aggressiveness

Abstract: // Juan Bayo 1 , Alejandrina Real 1 , Esteban J. Fiore 1 , Mariana Malvicini 1 , Leonardo Sganga 6 , Marcela Bolontrade 2 , Oscar Andriani 3 , Carolina Bizama 4 , Cristobal Fresno 5 , Osvaldo Podhajcer 6 , Elmer Fernandez 5 , Manuel Gidekel 7, 8 , Guillermo D. Mazzolini 1, 3, * , Mariana G. Garcia 1, * 1 Gene Therapy Laboratory, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomedicas, CONICET, Universidad Austral, Buenos Aires, Argentina 2 Stem Cells Laboratory, IBYME, CONICET, Buenos Aires, Argentina 3 Liver Unit, Hospital Universitario Austral, Derqui-Pilar, Argentina 4 Universidad Catolica, Santiago, Chile 5 BioScience Data Mining Group, Catholic University of Cordoba, Cordoba, Argentina 6 Fundacion Instituto Leloir, CONICET, Buenos Aires, Argentina 7 Universidad de la Frontera, Temuco, Chile 8 Universidad Autonoma de Chile, Santiago, Chile * Both authors share credits for senior authorship Correspondence to: Guillermo D. Mazzolini, email: gmazzoli@austral.edu.ar Mariana G. Garcia, email: mggarcia@conicet.gov.ar Keywords: human mesenchymal stromal cells, tumor microenvironment, IL-8, human hepatocellular carcinoma, migration Received: October 29, 2015 Accepted: May 22, 2016 Published: June 25, 2016 ABSTRACT New therapies are needed for advanced hepatocellular carcinoma (HCC) and the use of mesenchymal stromal cells (MSCs) carrying therapeutic genes is a promising strategy. HCC produce cytokines recruiting MSCs to the tumor milieu and modifying its biological properties. Our aim was to study changes generated on human MSCs exposed to conditioned media (CM) derived from human HCC fresh samples and xenografts. All CM shared similar cytokines expression pattern including CXCL1-2-3/GRO, CCL2/MCP-1 and CXCL8/IL-8 being the latter with the highest concentration. Neutralizing and knockdown experiments of CCL2/MCP-1, CXCL8/IL-8, CXCR1 and CXCR2 reduced in vitro MSC migration of ≥20%. Simultaneous CXCR1 and CXCR2 neutralization resulted in 50% of MSC migration inhibition. MSC stimulated with CM (sMSC) from HuH7 or HC-PT-5 showed a 2-fold increase of migration towards the CM compared with unstimulated MSC (usMSC). Gene expression profile of sMSC showed ~500 genes differentially expressed compared with usMSC, being 46 genes related with cell migration and invasion. sMSC increased fibroblasts and endothelial cells chemotaxis. Finally, sMSC with HuH7 CM and then inoculated in HCC tumor bearing-mice did not modify tumor growth. In this work we characterized factors produced by HCC responsible for the changes in MSC chemotactic capacity with would have an impact on therapeutic use of MSCs for human HCC.

The two‐component systems PrrBA and NtrYX co‐ordinately regulate the adaptation of Brucella abortus to an oxygen‐limited environment

Abstract: Summary Brucella is the causative agent of the zoonotic disease brucellosis, which is endemic in many parts of the world. The success of Brucella as pathogen relies in its ability to adapt to the harsh environmental conditions found in mammalian hosts. One of its main adaptations is the induction of the expression of different genes involved in respiration at low oxygen tension. In this report we describe a regulatory network involved in this adaptation. We show that Brucella abortus PrrBA is a functional two-component signal transduction system that responds to the redox status and acts as a global regulator controlling the expression of the regulatory proteins NtrY, FnrN and NnrA, which are involved in the adaptation to survive at low oxygen tension. We also show that the two-component systems PrrBA and NtrYX co-ordinately regulate the expression of denitrification and high-affinity cytochrome oxidase genes. Strikingly, a double mutant strain in the prrB and ntrY genes is severely impaired in growth and virulence, while the ntrY and prrB single mutant strains are similar to wild-type B. abortus. The proposed regulatory network may contribute to understand the mechanisms used by Brucella for a successful adaptation to its replicative niche inside mammalian cells.