Espacio y territorios: razón, pasión e imaginarios

En este caleidoscopio de acercamientos hacia lo espacial y territorial, las visiones se mueven desde aquellas románticas y existencialistas, pasando por aquellas objetivistas y positivistas, hasta las estructuralistas y postestructuralistas. Por el espacio y el territorio se interesan con enfoques diversos numerosas disciplinas, desde la psicología, la etología o la literatura, y las ciencias naturales como la biología o la ecología, hasta las ciencias sociales y políticas, como la geografía, la antropología, la economía y la sociología. Este interés multidisciplinario demuestra la importancia y la complejidad del tema espacial y territorial, y reclama la necesidad de su estudio y comprensión interdisciplinarios, como se intenta con esta publicación

I Congreso - Convergencias y divergencias. Hacia educaciones y desarrollo otros.

La presente colección, en su primera publicación, recoge la experiencia del I Congreso Internacional de Educación para el Desarrollo en Perspectiva Latinoamericana- EpDl “Convergencias y divergencias. Hacia educaciones y desarrollos otros.” organizado por el Centro de Educación para el Desarrollo-CED de UNIMINUTO, específicamente en relación con las ponencias, libros e iniciativas fotográficas presentadas en las seis líneas temáticas de este evento académico, a saber: (a) experiencias y prácticas pedagógicas; (b) acciones colectivas, movimientos y redes sociales; (c) perspectivas críticas al desarrollo; (d) producción de conocimiento; (e) diferencias, identidades y ciudadanía; (f) cuerpos, emociones y espiritualidades; a partir de éstas propuestas y en el marco de estas líneas, se reflexionó sobre las dinámicas y problemáticas derivadas del desarrollo hegemónico, así como sobre la posibilidad de diálogo entre saberes y conocimientos construidos de forma contextualizada, que permitan agenciar apuestas y proyectos alternativos disidentes en la búsqueda de “desarrollos y educaciones otras” desde América Latina

Relatioship between circulating levels of insulin-like growth factor-I and differential expression of genes related to lymphoid cell migration

A partir de investigaciones realizadas en los últimos años, se ha hecho evidente la comunicación bidireccional entre los sistemas inmune y endocrino. Existe un gran cuerpo de evidencia que sugiere que el eje conformado por la hormona de crecimiento (GH) y el factor de crecimiento similar a la insulina tipo I (IGF-I) tiene un papel importante en la funcionalidad del sistema inmune. Los efectos de estas hormonas sobre los diferentes tipos celulares y tejidos pueden darse por mecanismos endocrinos, autocrinos o paracrinos, pero esto es tema de constante investigación. Estudios recientes en modelos animales con silenciamiento específico del gen de IGF-I en hígado (Liver-specific Igf-I Deficient - LID), han mostrado parámetros normales de crecimiento, a pesar de la disminución en el IGF-I circulante (75%). Estos animales tienen, sin embargo, tamaños reducidos del bazo y timo y muestran alteraciones en la hemtaopoyesis y migración dirigida o quimiotaxis, indicativo del papel regulador del IGF-I circulante en la diferenciación y funcionalidad del sistema inmune. Se sabe que la nutrición es un regulador importante de los niveles séricos de IGF-I. Se ha demostrado que una dieta de bajo contenido de proteína (4%) conduce a una reducción en los niveles circulantes de IGF-I en un 75%, semejante a los observados en los animales LID, en comparación con una dieta de contenido normal de proteina. Lo anterior está acompañado de la expresión aumentada en bazo y timo de genes del eje hormonal (receptores y proteínas de unión), como mecanismo para compensar la baja biodisponibilidad de IGF-I circulante o del producido localmente. Sin embargo, son escasos los estudios adelantados con el fin de evaluar el significado funcional de los cambios observados en el eje GH/IGF-I en células del sistema inmune y su participación en el desarrollo de una respuesta inmune adecuada. El presente estudio se planteó con el objetivo de investigar si la disminución en el IGF-I circulante como consecuencia de la desnutrición tiene efectos a nivel de la regulación de la migración celular dirigida de células linfoides, parámetro funcional inmune esencial en la respuesta frente a un agente infeccioso. Como modelo experimental se emplearon ratones Balb/c macho de 4 semanas de edad que fueron alimentados con dietas normales (12% proteína) o restringidas (4% proteína). Cada grupo dietario fue distribuido en dos grupos, uno de los cuales recibió una inyección vía intravenosa de 100 UFC/g de peso corporal de Listeria monocytogenes (ATCC 19115). A los tres días post-infección los animales fueron sacrificados y muestras de suero, bazo y timo fueron rápidamente extraídas. Se llevaron a cabo ensayos para determinar los niveles de IGF-I circulante, análisis por citometría de flujo para evaluar la distribución de subpoblaciones linfoides positivas para el receptor de quimioquina CXCR4, además de ensayos de quimiotaxis celular y PCR en tiempo real para evaluar la capacidad migratoria de las células linfoides bajo las distintas condiciones. Adicionalmente, se obtuvieron los mapas proteómicos de bazo y timo de ratones en las condiciones experimentales del estudio, con el fin de identificar proteínas diferencialmente expresadas que puedan ser la base para iniciar la identificación de las vías moleculares responsables de los efectos observados. Los resultados mostraron que la infección con L. monocytogenes disminuye de forma significativa los niveles de IGF-I circulante, lo cual representa un hallazgo novedoso pues no ha sido descrito previamente que la infección regule los niveles de IGF-I en la circulación. Dado que uno de los órganos afectados por la listeriosis es el hígado, se puede presumir que la bacteria puede estar comprometiendo los mecanismos de síntesis o secreción del IGF-I hepático. En cuanto a la producción local de IGF-I, se encontró que el bazo conserva los niveles del péptido en condiciones de estrés nuticional, tal como ya había sido demostrado en un estudio anterior en nuestro laboratorio. Pero de manera interesante, en este trabajo se pudo demostrar que dicha capacidad homeostática del bazo se pierde en condiciones patológicas de infección, encontrando niveles significativamente, reducidos de IGF-I, presumiblemente por alteraciones en la etapa de traducción, ya que el nivel de expresión del mRNA no se afectó, incluso se encontró sobreexpresado en el bazo de ratones bien nutridos. Los ensayos funcionales de quimiotaxis demostraron que el IGF-I, al igual que la quimioquina CXCL12, es un inductor de la quimiotaxis de células linfoides, y de manera interesante, se observó un efecto aditivo en sus acciones, por un mecanismo aún por identificar. Si bien, IGF-I y CXCL12 son capaces de inducir la quimiotaxis celular en condiciones fisiológicas, los resultados mostraron que la deficiencia de proteína dietaria, aunque aparentemente no afecta la respuesta frente a los estímulos quimiotácticos, sí impone una reducción en la capacidad migratoria basal de células linfoides. El impacto negativo de la restricción nutricional se evidenció también a nivel de la quimiotaxis en condiciones patológicas, como se demostró en los ensayos de infección experimental con L. monocytogenes, donde se evidenció que el desarrollo de una respuesta quimiotáctica adecuada es dependiente del nivel de proteína dietaria. Dentro de los órganos estudiados, el timo resultó ser más sensible que el bazo al estrés nutricional. Los anteriores cambios funcionales en quimiotaxis podrian estar relacionados con los perfiles de expresión de genes involucrados en este proceso, principalmente con el sistema receptor de quimioquina/quimioquina. Dentro de los genes analizados, se encontró evidencia de que CCR1/CCL3 tiene un importante papel como inductor de la migración de linfocitos en respuesta a infección con L monocytogenes. Aunque se acepta que el receptor CXCR4 es el mediador clásico de los efectos de la quimioquina homeostática CXCL12, los resultados postulan un papel para el receptor CXCR7 en condiciones patológicas. Además, los resultados sugieren que los efectos estimulatorios de la migración del IGF-I en condiciones de desnutrición e infección, pueden involucrar además de su propio receptor, otros receptores, posiblemente de quimioquinas o integrinas, con los cuales ya se han descrito mecanismos de transactivación. Finalmente, con el fin de iniciar un análisis global de la expresión de proteínas asociadas a la respuesta inmune en bazo y timo, se llevó a cabo un análisis proteómico preliminar mediante dos aproximaciones metodológicas, encontrando perfiles de expresión diferencial por infección y desnutrición de acuerdo a cada órgano. Estos hallazgos apoyan la hipótesis del papel del IGF-I circulante en la regulación de la migración de células linfoides de manera específica de órgano y por lo tanto en la respuesta de defensa a infecciones entéricas con patógenos como L. monocytogenes. Estos resultados en conjunto muestran una relación molecular entre desnutrición, infección y niveles de IGF-I circulante con la migración de células linfoides que puede tener un papel importante en los mecanismos de defensa contra un agente infeccioso, comprometiendo procesos de desarrollo, diferenciación y respuesta inmune. / Abstract. From research conducted in recent years, it has become evident bidirectional communication between immune and endocrine systems. There is a large body of evidence suggesting that the axis formed by the growth hormone (GH) and insulin-like growth factor- I (IGF-I) has an important role in immune system functionality. The effects of these hormones on the different cell types and tissues can occur by endocrine, autocrine or paracrine mechanisms, but this is subject of ongoing research. Recent studies in animal models with specific gene silencing IGF-I in liver (Liver-specific IGF-I Deficient - LID), showed normal growth parameters, despite the decrease in circulating IGF-I (75%). These animals, however, reduced sizes of spleen and thymus and show alterations in hematopoiesis and directed migration or chemotaxis, indicating the regulatory role of circulating IGF-I on differentiation and function of the immune system. Nutrition is known to be an important regulator of serum IGF-I. It has been shown that a low-protein diet (4%) leads to a reduction in circulating levels of IGF-I by 75%, similar to those observed in LID animals, compared to a normal protein diet content. This is linked to the increased expression in spleen and thymus hormone axis genes (receptors and binding proteins) as a mechanism to compensate the low bioavailability or circulation of IGF-I. However, there are few studies conducted to assess the functional significance of observed changes in the GH / IGF-I in immune cells and their participation in the development of an adequate immune response. This study has the objective to investigate if the decreasing in circulating IGF-I as a result of malnutrition has effects at the level of regulation of directed cell migration of lymphoid cells, immune function essential parameter in the response to a infectious agent. As experimental model Balb/c male 4 weeks old mice were used. They were fed normal (12% protein) or restricted (4% protein) diets. Each dietary group was divided into two groups, one of which received an intravenous injection of 100 CFU/g of body weight of Listeria monocytogenes (ATCC 19115). Three days after infection, the animals were sacrificed. Serum, spleen and thymus samples were quickly taken. Tests were conducted to determine the levels of circulating IGF-I, analysis by flow cytometry where conducted to assess the distribution of positive lymphoid subpopulations for the chemokine receptor CXCR4, in addition to cellular chemotaxis and real-time PCR to assess the ability of migration of lymphoid cells under different conditions. Additionally, proteomic maps were obtained from spleen and thymus of mice in the experimental conditions of study to identify differentially expressed proteins that may be the basis to begin identifying the molecular pathways responsible for the observed effects. The results showed that infection with L. monocytogenes significantly decreases the levels of circulating IGF-I, which represents a novel finding since it has not been previously reported that infection regulates the levels of IGF-I in the circulation. Since one of the organs affected by listeriosis is the liver, it can be assumed that the bacteria may be compromising the mechanisms of synthesis and secretion of hepatic IGF-I. As for the local production of IGF-I, it was found that the spleen retains peptide levels under nutritional stress, as it has been demonstrated in a previous study in our laboratory. But interestingly, in this work it was possible to show that the homeostatic capacity of the spleen is lost in pathologic conditions of infection, finding significant levels of IGF-I reduced, presumably by alterations in the translation stage, since the mRNA level of expression was not affected, it was furthermore, over expressed in the spleens of well nourished mice. Functional chemotaxis tests showed that IGF-I, like the chemokine CXCL12, is an inducer of chemotaxis of lymphoid cells, and interestingly, it was observed an additive effect on their actions, by a yet unidentified mechanism. Although IGF-I and CXCL12 are able to induce cell chemotaxis in physiological conditions, the results showed that dietary protein deficiency, even apparently, does not affect the response to chemotactic stimuli, but it does impose a reduction in basal migratory capacity of lymphoid cells. The negative impact of nutritional restriction was also evident at the level of chemotaxis in pathological conditions, as demonstrated in tests of experimental infection with L. monocytogenes, which showed that the development of a proper chemotactic response depends on the level of dietary protein. Within the organs studied, the thymus was more sensitive than the spleen to nutritional stress. These previous functional changes in chemotaxis could be related to the profiles of gene expression involved in this process, mainly with the chemokine / chemokine receptor system. Among the analyzed genes, we found evidence that CCR1/CCL3 has an important role as an inducer of cell migration in response to infection with L. monocytogenes. Although it is accepted that the CXCR4 receptor mediates the effects of classic homeostatic chemokine CXCL12, the results postulate a rol for CXCR7 receptor in pathological conditios. Furthermore, the results suggest that the stimulatory effects of the migration of IGF-I in malnutrition and infection conditions, may involve in addition to its own receptor, other receptors, possibly chemokine or integrin, with which have been described transactivation mechanisms. Finally, in order to initiate a comprehensive analysis of protein expression associated with immune response in spleen and thymus, a preliminary proteomic analysis took place, using two methodological approaches, finding differential expression profiles of infection and malnutrition according to each organ. These findings support the hypothesis of the role of circulating IGF-I in regulating the specific migration of lymphoid cells in the organ and therefore in the defense response to enteric infections with pathogens such as L. monocytogenes. These results together show a molecular link between malnutrition, infection and levels of IGF-I circulating with migration of lymphoid cells that may have an important role in defense mechanisms against an infectious agent, compromising development processes, differentiation and immune response.Doctor en Ciencias-Química.Doctorad

Protein malnutrition promotes dysregulation of molecules involved in T cell migration in the thymus of mice infected with Leishmania infantum

Erratum: Protein malnutrition promotes dysregulation of molecules involved in T cell migration in the thymus of mice infected with Leishmania infantum Monica Losada-Barragán, Adriana Umaña-Pérez, Sergio Cuervo-Escobar, Luiz Ricardo Berbert, Renato Porrozzi, Fernanda N. Morgado, Daniella Areas Mendes-da-Cruz, Wilson Savino, Myriam Sánchez-Gómez & Patricia Cuervo Scientific Reports 7:45991; published online 11 April 2017; updated on 25 September 2017 In this Article, Figure 4 is incorrect. The correct Figure 4 appears below as Figure 1. The legend of Figure 4 was correct from the time of publication.Submitted by Sandra Infurna ([email protected]) on 2017-05-06T14:31:05Z No. of bitstreams: 1 fernanda_morgado_etal_IOC_2017.pdf: 1948820 bytes, checksum: 2f6cb145e6c680b0fd96fcf54446a3e2 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2017-05-06T14:50:06Z (GMT) No. of bitstreams: 1 fernanda_morgado_etal_IOC_2017.pdf: 1948820 bytes, checksum: 2f6cb145e6c680b0fd96fcf54446a3e2 (MD5)Made available in DSpace on 2017-05-06T14:50:06Z (GMT). No. of bitstreams: 1 fernanda_morgado_etal_IOC_2017.pdf: 1948820 bytes, checksum: 2f6cb145e6c680b0fd96fcf54446a3e2 (MD5) Previous issue date: 2017Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmaniose. Rio de Janeiro, RJ, Brasil.Universidad Nacional de Colombia. Sede Bogotá. Facultad de Ciencias. Departamento de Química. Grupo de Investigación en Hormonas. Bogotá, Colombia.Universidad Nacional de Colombia. Sede Bogotá. Facultad de Ciencias. Departamento de Química. Grupo de Investigación en Hormonas. Bogotá, Colombia.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmaniose. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmaniose. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.Universidad Nacional de Colombia. Sede Bogotá. Facultad de Ciencias. Departamento de Química. Grupo de Investigación en Hormonas. Bogotá, Colombia.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmaniose. Rio de Janeiro, RJ, Brasil.Protein malnutrition, the most deleterious cause of malnutrition in developing countries, has been considered a primary risk factor for the development of clinical visceral leishmaniasis (VL). Protein malnutrition and infection with Leishmania infantum leads to lymphoid tissue disorganization, including changes in cellularity and lymphocyte subpopulations in the thymus and spleen. Here we report that protein malnutrition modifies thymic chemotactic factors by diminishing the CCL5, CXCL12, IGF1, CXCL9 and CXCL10 protein levels in infected animals. Nevertheless, T cells preserve their migratory capability, as they were able to migrate ex vivo in response to chemotactic stimuli, indicating that malnutrition may compromise the thymic microenvironment and alter in vivo thymocyte migration. Decrease in chemotactic factors protein levels was accompanied by an early increase in the parasite load of the spleen. These results suggest that the precondition of malnutrition is affecting the cell-mediated immune response to L. infantum by altering T cell migration and interfering with the capacity of protein-deprived animals to control parasite spreading and proliferation. Our data provide evidence for a disturbance of T lymphocyte migration involving both central and peripheral T-cells, which likely contribute to the pathophysiology of VL that occurs in malnourished individuals

Preliminary study of ivermectin residues in bovine livers in the Bogota Savanna

The present study tended to determine the ivermectin residues in cattle livers using the competitive ELISA technique and correlate gender and age variables with residual presence. Also, it was described the histopathological findings in analyzed samples. A total of 90 livers of randomly selected cattle were sampled in a type II slaughterhouse located in the Bogota Savanna. The samples were analyzed for ivermectin residues using the competitive ELISA technique and a histopathological evaluation was performed using the H&E technique. Only the 22 % (20/90) of the analyzed samples presented ivermectin residues. Of the positive individuals, the majority came from Cogua 35 % (7/20), Zipaquira 30 % (6/20) and Sopo 20 % (4/20). The breeds with residues presence corresponded to Half-Blood 35 % (7/20), Zebu 25 % (5/20), Normande 20 % (4/20) and Jersey x Holstein 15 % (3/20). Eighty five, 85 % (17/20) of the individuals were older than 1.5 yr. In regard to the gender variable, the majority of animals were males 65 % (13/20). Of the evaluated animals 3 % (3/90) exceeded the maximum residue limit (> 100 ppb). No association was found between the presence of residues and the gender and age variables (P>0.05). The majority of histopathological changes were mild or moderate, with alterations in architecture and inflammatory changes standing out. It was found association between the presence of residue and variables microcirculatory alteration, inflammatory alteration and changes similar to the cell death (P<0.05). As a conclusion, the competitive ELISA test used in this study served as a screening method for the detection ivermectin residues in the analyzed samples

Proteomic profiling of splenic interstitial fluid of malnourished mice infected with Leishmania infantum reveals defects on cell proliferation and pro-inflammatory response

Protein malnutrition is a risk factor for developing visceral leishmaniasis. Because we previously demonstrated that protein malnutrition and infection with Leishmania infantum disrupts the splenic microarchitecture in BALB/c mice, alters T cell-subsets and increases splenic parasite load, we hypothesize that splenic microenvironment is precociously compromised in infected animals that suffered a preceding malnutrition. To evaluate this, we characterized the abundance of proteins secreted in the splenic interstitial fluid (IF) using an iTRAQ-based quantitative proteomics approach. In addition, local levels of pro-inflammatory and proliferation molecules were analyzed. Whereas well-nourished infected animals showed increased IL-1β and IL-2 levels, malnourished-infected mice displayed significant reduction of these cytokines. Remarkably, a two-weeks infection with L. infantum already modified protein abundance in the splenic IF of well-nourished mice, but malnourished animals failed to respond to infection in the same fashion. Malnutrition induced significant reduction of chemotactic and pro-inflammatory molecules as well as of proteins involved in nucleic acid and amino acid metabolism, indicating an impaired proliferative microenvironment. Accordingly, a significant decrease in Ki67 expression was observed, suggesting that splenocyte proliferation is compromised in malnourished animals. Together, our results show that malnutrition compromises the splenic microenvironment and alters the immune response to the parasite in malnourished individuals. Significance: Protein malnutrition is recognized as an important epidemiological risk factor for developing visceral leishmaniasis (VL). Locally secreted factors present in the interstitial fluid have important roles in initiating immune responses and in regulating fluid volume during inflammation. However, the regulation of secreted factors under pathological conditions such as malnutrition and infection are widely unknown. To analyze how protein malnutrition alters secreted proteins involved in the immune response to L. infantum infection we evaluated the proteomic profile of the interstitial fluid of the spleen in malnourished BALB/c mice infected with L. infantum. Our work revealed new elements that contribute to the understanding of the immunopathological events in the spleen of malnourished animals infected with L. infantum and opens new pathways for consideration of other aspects that could improve VL treatment in malnourished individuals

T-Cell Populations and Cytokine Expression Are Impaired in Thymus and Spleen of Protein Malnourished BALB/c Mice Infected with <i>Leishmania infantum</i>

<div><p>Visceral leishmaniasis (VL) is a parasitic infectious disease that causes significant morbidity and mortality in the tropical and subtropical regions of the world. Although infections with visceralizing <i>Leishmania</i> may be asymptomatic, factors such as undernutrition increase the likelihood of progressing to clinical disease. Protein malnutrition, the most deleterious cause of malnutrition in developing countries, has been considered as a primary risk factor for the development of clinical VL. However, data regarding the immunological basis of this association are scarce. With the aim to analyze the effects of protein malnutrition on <i>Leishmania infantum</i> infection, we used BALB/c mice subjected to control or low protein isocaloric diets. Each animal group was divided into two subgroups and one was infected with <i>L. infantum</i> resulting in four study groups: animals fed 14% protein diet (CP), animals fed 4% protein diet (LP), animals fed 14% protein diet and infected (CPi), and animals fed 4% protein diet and infected (LPi).The susceptibility to <i>L. infantum</i> infection and immune responses were assessed in terms of body and lymphoid organ weight, parasite load, lymphocyte subpopulations, and cytokine expression. LPi mice had a significant reduction of body and lymphoid organ weight and exhibited a severe decrease of lymphoid follicles in the spleen. Moreover, LPi animals showed a significant decrease in CD4⁺CD8⁺ T cells in the thymus, whereas there was an increase of CD4⁺ and CD8⁺ T cells percentages in the spleen. Notably, the cytokine mRNA levels in the thymus and spleen of protein malnourished-infected animals were altered compared to the CP mice. Protein malnutrition results in a drastic dysregulation of T cells and cytokine expression in the thymus and spleen of <i>L. infantum</i>-infected BALB/c mice, which may lead to defective regulation of the thymocyte population and an impaired splenic immune response, accelerating the events of a normal course of infection.</p></div

Protein malnutrition dysregulated cytokine expression in thymocytes and splenocytes of mice infected with <i>L. infantum</i>.

<p><i>IL-10, IL-12a, TGF-β, IL-4</i> and <i>IFNγ</i> mRNA expression levels were measured by qPCR in (<b>A</b>) thymocytes and (<b>B</b>) splenocytes of each experimental group. The values are expressed as normalized ratios between the target gene expression and the geometric median of the <i>ATP-5, GAPDH</i> and <i>CYC-1</i> genes. The values are expressed in pg/mL ± SEM. CP: animals fed 14% protein diet; LP: animals fed 4% protein diet, CPi: animals fed 14% protein diet and infected; LPi: animals fed 4% protein diet and infected. Two-way ANOVA analysis with Bonferroni pos-hoc test. Statistical differences due to diet: <b>a</b> (p<0.001), infection: <b>b</b> (p<0.05) and interaction between diet and infection: <b>c</b> (p<0.05).</p