Specific Preferences in Lineage Choice and Phenotypic Plasticity of Glioma Stem Cells Under BMP4 and Noggin Influence

Although BMP4-induced differentiation of glioma stem cells (GSCs) is well recognized, details of the cellular responses triggered by this morphogen are still poorly defined. In this study, we established several GSC-enriched cell lines (GSC-ECLs) from high-grade gliomas. The expansion of these cells as adherent monolayers, and not as floating neurospheres, enabled a thorough study of the phenotypic changes that occurred during their differentiation. Herein, we evaluated GSC-ECLs' behavior toward differentiating conditions by depriving them of growth factors and/or by adding BMP4 at different concentrations. After analyzing cellular morphology, proliferation and lineage marker expression, we determined that GSC-ECLs have distinct preferences in lineage choice, where some of them showed an astrocyte fate commitment and others a neuronal one. We found that this election seems to be dictated by the expression pattern of BMP signaling components present in each GSC-ECL. Additionally, treatment of GSC-ECLs with the BMP antagonist, Noggin, also led to evident phenotypic changes. Interestingly, under certain conditions, some GSC-ECLs adopted an unexpected smooth muscle-like phenotype. As a whole, our findings illustrate the wide differentiation potential of GSCs, highlighting their molecular complexity and paving a way to facilitate personalized differentiating therapies.Fil: Videla Richardson, Guillermo Agustín. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Garcia, Carolina Paola. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Roisman, Alejandro. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Slavutsky, Irma Rosa. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Fernandez Espinosa, Damian Dario. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Romorini, Leonardo. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Miriuka, Santiago Gabriel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Arakaki, Naomi. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Martinetto, Horacio Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Scassa, Maria Elida. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Sevlever, Gustavo Emilio. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentin

Human embryonic stem cells display a pronounced sensitivity to the cyclin dependent kinase inhibitor Roscovitine

Background: The essentially unlimited expansion potential and the pluripotency of human embryonic stem cells (hESCs) make them attractive for cell-based therapeutic purposes. Although hESCs can indefinitely proliferate in culture, unlike transformed cancer cells, they are endowed with a cell-intrinsic property termed mitochondrial priming that renders them highly sensitive to apoptotic stimuli. Thus, all attempts to broaden the insights into hESCs apoptosis may be helpful for establishing pro-survival strategies valuable for its in vitro culture and further use in clinical applications. Cyclin-dependent kinases (CDKs), a family of serine/threonine protein kinases originally identified as regulators of the eukaryotic cell cycle, can also regulate transcription and differentiation. Moreover, there are compelling data suggesting that its activities are involved in certain apoptotic programs in different cell types. Currently, it is not completely determined whether CDKs regulate apoptotic processes in rapidly proliferating and apoptosisprone hESCs. In this study, to elucidate the effect of CDKs inhibition in hESCs we used Roscovitine (ROSC), a purine analogue that selectively inhibits the activities of these kinases. Results: Inhibition of CDKs by ROSC triggers programmed cell death in hESCs but not in proliferating somatic cells (human fibroblasts). The apoptotic process encompasses caspase-9 and -3 activation followed by PARP cleavage. ROSC treatment also leads to p53 stabilization, which coincides with site-specific phosphorylation at serine 46 and decreased levels of Mdm2. Additionally, we observed a transcriptional induction of p53AIP1, a repression of pro-survival factor Mcl1 and an up-regulation of pro-apoptotic BH3-only proteins NOXA and PUMA. Importantly, we found that the role of CDK2 inhibition appears to be at best accessory as an active CDK2 is not required to ensure hESCs survival. Conclusion: Our experimental data reveal that hESCs, contrary to fibroblasts, exhibit a pronounced sensitivity to ROSCFil: Videla Richardson, Guillermo. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Laboratorio de Investigaciones en Neurociencias Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Furmento, Verónica Alejandra. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Laboratorio de Investigaciones en Neurociencias Aplicadas; ArgentinaFil: Garcia, Carolina Paola. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Laboratorio de Investigaciones en Neurociencias Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Morris Hanon, Olivia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Laboratorio de Investigaciones en Neurociencias Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sevlever, Gustavo. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Laboratorio de Investigaciones en Neurociencias Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Romorini, Leonardo. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Laboratorio de Investigaciones en Neurociencias Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Scassa, Maria Elida. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Laboratorio de Investigaciones en Neurociencias Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Molecular findings of colombian patients with type VI mucopolysaccharidosis (Maroteaux-Lamy syndrome)

Q483-89Introduction: Maroteaux–Lamy syndrome, or mucopolysaccharidosis (MPS) type VI, is an autosomal recessive lysosomal storage disease caused by a deficient activity of the enzyme arylsulfatase B (ARSB), required to degrade dermatan sulfate. The onset and progression of the disease vary, producing a spectrum of clinical presentation. So far, 133 mutations have been reported. The aim of this study is to determine the mutations in the ARSB gene that are responsible for this disease in Colombian patients. Results: Fourteen patients with clinical manifestations and biochemical diagnosis of MPS VI were studied, including two siblings. The 8 exons of the gene were directly sequenced from patients' DNA, and 14 mutations were found. 57% of these mutations had not been previously reported (p.H111P, p.C121R, p.G446S, p.*534W, p.S334I, p.H147P, c.900TNG, and c.1531_1553del) and 43% had been previously reported (p.G144R, p.W322*, p.G302R, p.C447F, p.L128del, and c.1143-1GNC). Of the previously reported mutations, 80% have been associated with severe phenotypes and 20% with intermediate-severe phenotypes. Bioinformatic predictions indicate that the new mutations reported in this paper are also highly deleterious. Conclusions: Most of the Colombian patients in this study had private mutations

Epidemiologia: conceitos e aplicabilidade no Sistema Único de Saúde

A epidemiologia destaca-se como uma ferramenta básica e fundamental para o desenvolvimento do SUS, devido a sua aplicabilidade em toda a extensão deste sistema de saúde. Diante disso, é essencial que todos os profissionais e futuros profissionais envolvidos com o SUS sejam capazes de usar a epidemiologia como ferramenta de otimização e desenvolvimento. O livro "Epidemiologia: conceitos e aplicabilidade no Sistema Único de Saúde" traz de forma simples e objetiva conhecimentos básicos de epidemiologia que capacitarão o leitor a entender como a epidemiologia é praticada no SUS e como cada envolvido pode usá-la para fortalecer e consolidar esse sistema. Trata-se de uma grande oportunidade de explorar a aplicabilidade da epidemiologia no SUS como ferramenta de investigação e análise de fatores de risco e agravos, com vistas ao efetivo planejamento em saúde. Essa publicação é de grande valia para a proposta de educação permanente de profissionais e futuros profissionais do SUS

Effect of ω-3 and ω-9 fatty acid rich oils on lipoxygenases and cyclooxygenases enzymes and on the growth of a mammary adenocarcinoma model

Background Nutritional factors play a major role in cancer initiation and development. Dietary polyunsaturated fatty acids (PUFAs) have the ability to induce modifications in the activity of lipoxygenase (LOX) and cyclooxygenase (COX) enzymes that affect tumour growth. We studied the effect of two diets enriched in 6% Walnut and Peanut oils that are rich in ω-3 and ω9 PUFAs respectively on a murine mammary gland adenocarcinoma as compared with the control (C) that received commercial diet. Results Peanut oil enriched diet induced an increase in membrane arachidonic acid (AA) content and the cyclooxygenase enzyme derived 12-HHT (p < 0.05) and simultaneously showed decrease in 12-LOX, 15-LOX-2, 15-LOX-1 and PGE activities (p < 0.05) that corresponded to higher apoptosis and lower mitosis seen in this group (p < 0.05). Furthermore, Peanut oil group showed lower T-cell infiltration (p < 0.05), number of metastasis (p < 0.05) and tumour volume (p < 0.05) and longer survival rate compared to other groups. Conclusions The results of the present study showed that Peanut oil-enriched diet protects against mammary cancer development by modulating tumour membrane fatty acids composition and LOX and COX enzyme activities.Fil: Comba, Andrea. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Biología Celular; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Cátedra de Histología,embriología y Genética I; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Maestri, Damian. 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; ArgentinaFil: Berra, María Alejandra. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Biología Celular; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Cátedra de Histología,embriología y Genética I; ArgentinaFil: Garcia, Carolina Paola. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Biología Celular; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Cátedra de Histología,embriología y Genética I; ArgentinaFil: Das, Undurti N.. Jawaharlal Nehru Technological University; India. Undurti Narasimha Das; Estados Unidos. Krishna Institute of Medical Sciences; IndiaFil: Eynard, Aldo Renato. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Biología Celular; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Cátedra de Histología,embriología y Genética I; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Pasqualini, María Eugenia. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Biología Celular; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Cátedra de Histología,embriología y Genética I; Argentin

Propuesta estratégica de mejora en la implementación de los estándares mínimos del sistema de gestión de la seguridad y salud en el trabajo (SG-SST) en la empresa Prosegur para el primer semestre del 2019.

El documento consiste en un análisis de implementación y propuestas estratégicas sobre las acciones y el plan de mejora del Sistema de Gestión de la Seguridad y la Salud en el Trabajo (SG-SST) en la empresa Prosegur S.A para el primer semestre del 2019.The document consists of an analysis of implementation and strategic proposals on the actions and the improvement plan of the Safety and Health at Work Management System (SG-SST) in the company Prosegur S.A for the first semester of 2019

The reduction of methane production in the in vitro ruminal fermentation of different substrates is linked with the chemical composition of the essential oil

There is interest in identifying natural products capable of manipulating rumen microbial activity to develop new feed additives for ruminant nutrition as a strategy to reduce methane. Two trials were performed using the in vitro gas production technique to evaluate the interaction of substrate (n = 5) and additive (n = 6, increasing doses: 0, 0.3, 3, 30, and 300 µL/L of essential oils—EO—of Lippia turbinata or Tagetes minuta, and monensin at 1.87 mg/L). The two EO utilized were selected because they differ markedly in their chemical composition, especially in the proportion of oxygenated compounds. For both EO, the interaction between the substrate and additive was significant for all variables; however, the interaction behaved differently for the two EO. Within each substrate, the response was dose-dependent, without effects at a low level of EO and a negative outcome at the highest dose. The intermediate dose (30 µL/L) inhibited methane with a slight reduction on substrate digestibility, with L. turbinata being more effective than T. minuta. It is concluded that the effectiveness of the EO to reduce methane production depends on interactions between the substrate that is fermented and the additive dose that generates different characteristics within the incubation medium (e.g., pH); and thus, the chemical nature of the compounds of the EO modulates the magnitude of this response.Fil: Garcia, Florencia. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Colombatto, Dario. Universidad de Buenos Aires. Facultad de Agronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Brunetti, María Alejandra. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Cordoba. Estacion Experimental Agropecuaria Manfredi. Agencia de Extension Rural Cordoba.; ArgentinaFil: Martínez, María José. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Cordoba. Estacion Experimental Agropecuaria Manfredi. Agencia de Extension Rural Cordoba.; ArgentinaFil: Moreno, María Valeria. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Cordoba. Estacion Experimental Agropecuaria Manfredi. Agencia de Extension Rural Cordoba.; ArgentinaFil: Scorcione Turcato, María Carolina. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Cordoba. Estacion Experimental Agropecuaria Manfredi. Agencia de Extension Rural Cordoba.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Lucini, Enrique Iván. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; ArgentinaFil: Frossasco, Georgina Paola. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Cordoba. Estacion Experimental Agropecuaria Manfredi. Agencia de Extension Rural Cordoba.; ArgentinaFil: Martínez Ferrer, Jorge. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Cordoba. Estacion Experimental Agropecuaria Manfredi. Agencia de Extension Rural Cordoba.; Argentin

Molecular typing and differences in biofilm formation and antibiotic susceptibilities among Prototheca strains isolated in Italy and Brazil.

Bovine mastitis caused by Prototheca is a serious and complex problem that accounts for high economic losses in the dairy industry. The main objective of this study was to identify and characterize at genetic level different Prototheca strains and provide the most complete data about protothecal antibiotic resistance. The study involves 46 isolates from Italian (13 strains) and Brazilian (33 strains) mastitic milk. These strains were identified by multiplex PCR and single strand conformation polymorphism analysis and characterized by randomly amplified polymorphic DNA (RAPD)-PCR. Moreover, biofilm production and antibiotic susceptibility were evaluated. Forty-two strains resulted as Prototheca zopfii genotype 2, whereas 4 isolates could belong to a potential new Prototheca species. The RAPD-PCR, performed with 3 primers (M13, OPA-4, and OPA-18), showed a notable heterogeneity among isolates and grouped the strains according to the species and geographical origin. Biofilm production was species-dependent and P. zopfii genotype 2 strains were classified as strong biofilm producers. In vitro antibiotic susceptibility tests indicated that Prototheca strains were susceptible to antibacterial drugs belonging to aminoglycosides group; the highest activity against Prototheca strains was observed in the case of colistin sulfate, gentamicin, and netilmicin (100% of susceptible strains). It is interesting to note that all the Italian P. zopfii genotype 2 strains showed lower minimum inhibitory concentration values than the Brazilian ones. Nisin showed more efficacy than lysozyme and potassium sorbate, inhibiting 31% of the strains. Results obtained in this study confirmed that RAPD-PCR is a rapid, inexpensive, and highly discriminating tool for Prototheca strains characterization and could give a good scientific contribution for better understanding the protothecal mastitis in dairy herd

La imagen y la narrativa como herramientas para el abordaje psicosocial en escenarios de violencia. Departamento de Cundinamarca, Colombia y Valparaíso, Chile

El objetivo del presente trabajo es evaluar eventos psicosociales traumáticos originados por la violencia desde el enfoque narrativo y proponer recursos de afrontamiento psicosocial. La narración de los hechos traumáticos que transformaron el vivir de las víctimas permite preservar y transmitir sus experiencias, constituyéndose en una memoria viva y permitiendo ir tejiendo caminos como parte del abordaje terapéutico y psicosocial de la violencia sistemática y estructural que se ha padecido. A partir del análisis de dos relatos se abordan las subjetividades inmersas en contextos de violencia, el primer relato es el caso de Amparo víctima de violencia política por el conflicto armado y el segundo caso se refiere a la Masacre en El Salado, sector del Carmen del Bolívar, en Colombia. Este análisis busca resaltar los esfuerzos personales, familiares, colectivos y comunitarios para romper ciclos de violencia e injusticia, en el primer caso propone una entrevista a partir del análisis de los relatos, por medio de preguntas circulares, reflexivas y estratégicas. Por otra parte, presenta estrategias psicosociales en el caso de los pobladores del Salado. Se reconocen los repertorios de memorias como elementos simbólicos emergentes que revelan los sentidos y significados de las vivencias de sufrimiento, caminos de resiliencia, acciones que posibilitan denunciar los hechos y buscar caminos de reparación y justicia. Finalmente, se comparte un informe analítico y reflexivo de la experiencia sobre las imágenes y las narrativas que guían la comprensión, por medio de la exploración y profundización sobre acciones de memoria.The aim of this paper is to evaluate traumatic psychosocial events originated by violence from a narrative approach and to propose psychosocial coping resources. The narration of the traumatic events that transformed the lives of the victims allows the preservation and transmission of their experiences, constituting a living memory and making it possible to weave paths as part of the therapeutic and psychosocial approach to the systematic and structural violence they have suffered. From the analysis of two stories, the subjectivities immersed in contexts of violence are approached, the first story is the case of Amparo, victim of political violence due to the armed conflict and the second case refers to the Massacre in El Salado, sector of Carmen del Bolivar, in Colombia. This analysis seeks to highlight personal, family, collective and community efforts to break cycles of violence and injustice. In the first case, it proposes an interview based on the analysis of the stories, through circular, reflective and strategic questions. On the other hand, it presents psychosocial strategies in the case of the inhabitants of El Salado. The repertoires of memories are recognized as emerging symbolic elements that reveal the meanings and meanings of the experiences of suffering, paths of resilience, actions that make it possible to denounce the facts and seek paths of reparation and justice. Finally, an analytical and reflective report of the experience is shared on the images and narratives that guide the understanding, through the exploration and deepening of memory actions

Sexual risk among Colombian adolescents: knowledge, attitudes, normative beliefs, perceived control, intention, and sexual behavior

Background: Colombia has one of the highest rates of the human immunodeficiency virus (HIV) and pregnancies - both of which are influenced by lack of condom use -, among adolescent population in Latin America; however, the mechanisms underlying the inconsistent use of condoms in this population are poorly understood. This descriptive and cross-sectional study’s purpose was to examine sexual behavior and its precursors using the theory of planned behavior (TPB) and considering gender-based differences. Another objective was to study the mediating effect of intention in the relationship between behavior precursors and condom use based on the TPB. Methods: We recruited 1100 adolescents aged between 14 and 19 years old (M = 15.94, SD = 1.30, 54.4% female) from Bogotá and Barranquilla, two of the cities with highest adolescent birth rates among adolescents in Colombia. Sociodemographic variables, knowledge on HIV and other sexually transmitted infections (STIs), HIV/AIDS-related attitudes, including attitudes toward the use of condoms, normative beliefs, perceived behavioral control, behavioral intention, and sexual behavior were assessed using self-reports. All analyses were run using SPSS v25. The indirect effect of intention to explain the relationship between precursors and the use of condoms during sexual intercourse was estimated using the PROCESS v3 macro. Results: Descriptive analyses suggest a high risk of contracting sexually transmitted infections and unplanned pregnancies associated to inconsistent condom use, medium-low level of knowledge about sexual health, low normative beliefs regarding peers’ condom use, and a certain perceived difficulty for using condoms. Condoms are used 71% of the times they have sex, but only 22% of the participants use them consistently; girls use condoms more consistently than boys. Sexual risk characteristics differed significantly by gender. Mediation analyses indicated that condom use intention mediates the relationship between behavioral precursors and frequency of condom use, according to the TPB. Conclusions: Findings provide a better understanding of sexual risk and highlight important implications for the sexual and reproductive health of adolescents. There is a need of designing and implementing protocolized sexual health promotion programs in schools with the aim of reducing sexual risk behaviors in Colombian adolescents