85 research outputs found

    Monografía Corregimiento de Barrancominas y La Educación Contratada Departamento del Guainía

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    El presente trabajo de investigación hace parte de mi trabajo de grado y mediante la actual Monografía quiero destacar las características socio culturales especificas del corregimiento de Barrancominas en el departamento del Guainía y aportes de la etnoeducación que se imparte en este corregimiento a través de la educación contratada; mediante un trabajo de campo que recopila e interpreta las memorias y los acontecimientos que han ocurrido a lo largo de más de 48 años, en un estudio detallado que involucra a las fuentes vivas de la comunidad y pequeños documentos que reposan en los archivos de instituciones locales, entre otras. Dicha información se sustenta y se fundamenta por medio de fuentes bibliográficas, informes, revistas, mapas y fotografías que a través del enfoque cualitativo – etnográfico, le dan forma a un trabajo que termina haciendo un recuento de la educación en el medio rio Guaviare, más exactamente en la zona cinco que es administrada por la educación contratada del Guainía en cabeza del monseñor JOSELITO CARREÑO, Un dato importante sobre como la iglesia católica por muchos años ha brindado y administrado la educación en el corregimiento articulándose con las comunidades indígenas, y teniendo muy en cuenta sus costumbres, religión y cultura. El trabajo también nos muestra la gran diversidad de flora y fauna que posee esta parte de la región del departamento del Guainía. Al igual que la importancia de la ETNOEDUCACIÓN en el contexto de la diversidad cultural de nuestro departamento.This research work is part of my degree work and through the current Monograph I want to highlight the specific socio-cultural characteristics of the Barrancominas district in the department of Guainía and contributions of the ethnoeducation that is taught in this district through the contracted education ; through a field work that collects and interprets the memories and events that have occurred over more than 48 years, in a detailed study that involves the living sources of the community and small documents that rest in the archives of local institutions , among other. This information is supported and based on bibliographic sources, reports, journals, maps and photographs that, through the qualitative - ethnographic approach, shape a work that ends up accounting for education in the Guaviare river area, more exactly in zone five that is administered by the contracted education of the Guainía at the head of Monsignor JOSELITO CARREÑO, an important fact about how the Catholic church for many years has provided and administered education in the village articulating with the indigenous communities, and having very Consider your customs, religion and culture. The work also shows us the great diversity of flora and fauna that this part of the region of the department of Guainía possesses. Like the importance of ETNOEDUCATION in the context of the cultural diversity of our department

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    Este proyecto está direccionado a re proponer el modelo de Sistema de Gestión Integral de la Calidad para la firma constructora y de ingeniería Ingesandia S.A.S., el cual tiene como objetivo integrar los intereses de las partes interesadas de la organización, articulándolos con las expectativas y necesidades del cliente.

    Searching for glycosylated natural products in actinomycetes and identification of novel macrolactams and angucyclines

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    Many bioactive natural products are glycosylated compounds in which the sugar components usually participate in interaction and molecular recognition of the cellular target. Therefore, the presence of sugar moieties is important, in some cases essential, for bioactivity. Searching for novel glycosylated bioactive compounds is an important aim in the field of the research for natural products from actinomycetes. A great majority of these sugar moieties belong to the 6-deoxyhexoses and share two common biosynthetic steps catalyzed by a NDP-D-glucose synthase (GS) and a NDP-D-glucose 4,6-dehydratase (DH). Based on this fact, seventy one Streptomyces strains isolated from the integument of ants of the Tribe Attini were screened for the presence of biosynthetic gene clusters (BGCs) for glycosylated compounds. Total DNAs were analyzed by PCR amplification using oligo primers for GSs and DHs and also for a NDP-D-glucose-2,3-dehydratases. Amplicons were used in gene disruption experiments to generate non-producing mutants in the corresponding clusters. Eleven mutants were obtained and comparative dereplication analyses between the wild type strains and the corresponding mutants allowed in some cases the identification of the compound coded by the corresponding cluster (lobophorins, vicenistatin, chromomycins and benzanthrins) and that of two novel macrolactams (sipanmycin A and B). Several strains did not show UPLC differential peaks between the wild type strain and mutant profiles. However, after genome sequencing of these strains, the activation of the expression of two clusters was achieved by using nutritional and genetic approaches leading to the identification of compounds of the cervimycins family and two novel members of the warkmycins family. Our work defines a useful strategy for the identification new glycosylated compounds by a combination of genome mining, gene inactivation experiments and the activation of silent biosynthetic clusters in Streptomyces strains

    Protein Translation Inhibition is Involved in the Activity of the Pan-PIM Kinase Inhibitor PIM447 in Combination with Pomalidomide-Dexamethasone in Multiple Myeloma

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    Background: Proviral Insertion site for Moloney murine leukemia virus (PIM) kinases are overexpressed in hematologic malignancies, including multiple myeloma. Previous preclinical data from our group demonstrated the anti-myeloma effect of the pan-PIM kinase inhibitor PIM447. Methods: Based on those data, we evaluate here, by in vitro and in vivo studies, the activity of the triple combination of PIM447 + pomalidomide + dexamethasone (PIM-Pd) in multiple myeloma. Results: Our results show that the PIM-Pd combination exerts a potent anti-myeloma effect in vitro and in vivo, where it markedly delays tumor growth and prolongs survival of treated mice. Mechanism of action studies performed in vitro and on mice tumor samples suggest that the combination PIM-Pd inhibits protein translation processes through the convergent inhibition of c-Myc and mTORC1, which subsequently disrupts the function of eIF4E. Interestingly the MM pro-survival factor IRF4 is also downregulated after PIM-Pd treatment. As a whole, all these molecular changes would promote cell cycle arrest and deregulation of metabolic pathways, including glycolysis and lipid biosynthesis, leading to inhibition of myeloma cell proliferation. Conclusions: Altogether, our data support the clinical evaluation of the triple combination PIM-Pd for the treatment of patients with multiple myeloma.This work was supported by funding from Spanish FIS (PI15/00067, PI15/02156 and PI18/01600) and FEDER, AECC (GCB120981SAN), Junta de Castilla y León, Consejería de Sanidad (GRS 862/A/13 and BIO/SA05/14), Fundación Memoria de D. Samuel Solórzano Barruso of the University of Salamanca (FS/22-2015), Fundación Ramón Areces (FRA16/003), Sociedad Española de Hematología y Hemoterapia and Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León. E.M.O. was supported by an Inplant grant from IDIVAL. T.P. is supported by a grant from AECC (INVES18043PAÍN)

    Synergistic DNA-damaging effect in multiple myeloma with the combination of zalypsis, bor tezomib and dexamethasone

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    Despite new advances in multiple myeloma treatment and the consequent improvement in overall survival, most patients relapse or become refractory to treatment. This suggests that new molecules and combinations that may further inhibit important survival pathways for these tumor cells are needed. In this context, zalypsis is a novel compound, derived from marine organisms, with a powerful preclinical anti-myeloma effect based on the sensitivity of malignant plasma cells to DNA-damage induction; and it has already been tested in a phase I/II clinical trial in multiple myeloma. We hypothesized that the addition of this compound to the combination of bortezomib plus dexamethasone may improve efficacy with acceptable toxicity. The triple combination demonstrated strong synergy and higher efficacy compared with double combinations; not only in vitro, but also ex vivo and, especially, in in vivo experiments. The triple combination triggers cell death, mainly through a synergistic induction of DNA damage and a decrease in the nuclear localization of nuclear factor kappa B. Our findings support the clinical evaluation of this combination for relapsed and refractory myeloma patients.This work was in part funded by the Spanish ISCIII-FIS (PI 15/0067 and PI15/02156) and FEDER, the Spanish RTICC (RD12/0036/0058), "Asociación Española Contra el Cancer" (AECC, GCB120981SAN), the regional Council from “Castilla y León” (GRS 1175/A/15 and FIC335U14) and a research grant from Pharmamar SAU. MMS were also supported by the Network of Centers for Regenerative Medicine and Cellular Therapy from Castilla y León, Spain. A-A López-Iglesias was supported by a grant from the Spanish Society of Hematology and Hemotherapy.Peer Reviewe

    Stroma-Mediated Resistance to S63845 and Venetoclax through MCL-1 and BCL-2 Expression Changes Induced by miR-193b-3p and miR-21-5p Dysregulation in Multiple Myeloma.

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    BH3-mimetics targeting anti-apoptotic proteins such as MCL-1 (S63845) or BCL-2 (venetoclax) are currently being evaluated as effective therapies for the treatment of multiple myeloma (MM). Interleukin 6, produced by mesenchymal stromal cells (MSCs), has been shown to modify the expression of anti-apoptotic proteins and their interaction with the pro-apoptotic BIM protein in MM cells. In this study, we assess the efficacy of S63845 and venetoclax in MM cells in direct co-culture with MSCs derived from MM patients (pMSCs) to identify additional mechanisms involved in the stroma-induced resistance to these agents. MicroRNAs miR-193b-3p and miR-21-5p emerged among the top deregulated miRNAs in myeloma cells when directly co-cultured with pMSCs, and we show their contribution to changes in MCL-1 and BCL-2 protein expression and in the activity of S63845 and venetoclax. Additionally, direct contact with pMSCs under S63845 and/or venetoclax treatment modifies myeloma cell dependence on different BCL-2 family anti-apoptotic proteins in relation to BIM, making myeloma cells more dependent on the non-targeted anti-apoptotic protein or BCL-XL. Finally, we show a potent effect of the combination of S63845 and venetoclax even in the presence of pMSCs, which supports this combinatorial approach for the treatment of MM
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