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8. OGT controls mammalian cell viability by regulating the proteasome/mTOR/ mitochondrial axis.

Author

Xiang Li, Xiaojing Yue, Sepulveda, Hugo, Burt, Rajan A., Scott, David A., Carr, Steven A., Myers, Samuel A., and Rao, Anjana

Subjects
CELL survival, EMBRYONIC stem cells, MITOCHONDRIA, NUCLEAR proteins, OXIDATIVE phosphorylation
Abstract

O-GlcNAc transferase (OGT) modifies serine and threonine residues on nuclear and cytosolic proteins with O-linked N-acetylglucosamine (GlcNAc). OGT is essential for mammalian cell viability, but the underlying mechanisms are still enigmatic. We performed a genome-wide CRISPR--Cas9 screen in mouse embryonic stem cells (mESCs) to identify candidates whose depletion rescued the block in cell proliferation induced by OGT deficiency. We show that the block in cell proliferation in OGT-deficient cells stems from mitochondrial dysfunction secondary to mTOR (mechanistic target of rapamycin) hyperactivation. In normal cells, OGT maintains low mTOR activity and mitochondrial fitness through suppression of proteasome activity; in the absence of OGT, increased proteasome activity results in increased steady-state amino acid levels, which in turn promote mTOR lysosomal translocation and activation, and increased oxidative phosphorylation. mTOR activation in OGT-deficient mESCs was confirmed by an independent phospho-proteomic screen. Our study highlights a unique series of events whereby OGT regulates the proteasome/ mTOR/ mitochondrial axis in a manner that maintains homeostasis of intracellular amino acid levels, mitochondrial fitness, and cell viability. A similar mechanism operates in CD8+ T cells, indicating its generality across mammalian cell types. Manipulating OGT activity may have therapeutic potential in diseases in which this signaling pathway is impaired. [ABSTRACT FROM AUTHOR]

Published
2023
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9. Program of sanitary handling and use of water rains, in a housing of social interest of the municipality of Tocancipá

Author

Espinosa Sepulveda, Hugo Gildardo and Murillo Moreno, Lida Neidu

Subjects
Manejo Sanitario, AGUAS RESIDUALES, Sanitary Management, Rainwater, AGUAS RESIDUALES - TRATAMIENTO POR PROCESO DE LODO ACTIVADO, Management Programs, Aguas lluvias, Programas de manejo
Abstract

El programa de manejo sanitario y aprovechamiento de aguas lluvias pretende analizar los beneficios que se pueden presentar con la implementación de cada una de las técnicas en las viviendas de interés social del Municipio de Tocancipá, este plantea un diseño de saneamiento básico, así como la ejecución de un programa de manejo sanitario, que será identificado bajo parámetros presupuestales y cronograma de ejecución con la ejecución de cada uno de los programas. Listado De Tablas 4 Listado de Figuras 4 Listado de Anexos 4 1. Descripción del problema 5 2. Planteamiento del problema 9 2.1. Pregunta general 9 2.2. Sistematización del problema 9 3. Objetivos 10 3.1. Objetivo general 10 3.2. Objetivos específicos 10 4. Justificación 11 5. Marco referencial 14 5.1. Marco histórico 14 5.1.1. Captación de agua de lluvia, pasado y actualidad 15 5.2. Marco teórico 16 5.3. Marco conceptual 21 5.4. Marco Normativo 23 6. Marco Metodológico. 27 6.1. Cualitativo – descriptivo 27 6.2. Fuentes De Información 27 6.2.1. Fuente Primaria 27 6.2.2. Fuentes Secundarias 28 6.3. Análisis de Variables 28 6.4. Interpretación de datos 28 6.5. Caso de estudio 28 6.5.1. ubicación geográfica en el territorio: 28 6.5.2. Localización general del proyecto 30 6.5.3. Acceso a la localidad. 30 6.5.4. Hidrografía e hidrología. 31 6.5.5. Hidrogeología. 32 6.5.6. Climatología y meteorología. 33 6.5.7. Precipitación. 34 6.5.8. Temperatura. 35 6.5.9. Humedad relativa. 36 6.5.10. Meteorología. 37 6.5.11. Vivienda en el Municipio de Tocancipá. - caso de estudio. 38 6.5.12. Estructura topológica del sistema de acueducto. 40 6.5.13. Análisis población y demanda: 41 6.5.14. Proyección de demanda de agua en el municipio. 42 7. Marco Técnico 45 7.1. Plan de Manejo Sanitario 45 7.1.1. Memoria de cálculo unidad sanitaria rural. 45 7.1.2. Tanque de almacenamiento. 45 7.1.3. Sistema de Tratamiento. 46 7.1.4. Tanque Séptico. 47 7.1.5. Trampa de Grasas. 48 7.1.6. Campo de Infiltración. 49 7.2. Manejo de Aguas Lluvias 50 7.2.1. Aprovechamiento de aguas de lluvia, análisis conceptual y referenciación de buenas prácticas. 50 8. Manejo de residuos sólidos 67 9. Conclusiones 1 10. Recomendaciones 2 11. Bibliografía 3 12. Anexos 6 The program of sanitary management and use of rainwater aims to analyze the benefits that can be presented with the implementation of each of the techniques in the social interest housing of the Municipality of Tocancipá, this raises a design of basic sanitation, as well as the execution of a health management program, which will be identified under budgetary parameters and execution schedule with the execution of each of the programs.

Published
2019

10. Epigenetic signatures at the runx2-p1 and sp7 gene promoters control osteogenic lineage commitment of umbilical cord-derived mesenchymal stem cells

Author

Sepulveda, Hugo, Aguilar, Rodrigo, Prieto, Catalina P, Bustos, Francisco, Aedo, Socrates, Lattus, José, Van Zundert, Brigitte, Palma-Alvarado, Verónica Alejandra, and Montecino, Martín

Abstract

Wharton's Jelly mesenchymal stem cells (WJ-MSCs) are an attractive potential source of multipotent stem cells for bone tissue replacement therapies. However, the molecular mechanisms involved in their osteogenic conversion are poorly understood. Particul

Published
2017

11. Anti-neoplastic drugs increase caveolin-1-dependent migration, invasion and metastasis of cancer cells

Author

Díaz-Valdivia, Natalia I., primary, Calderón, Claudia C., additional, Díaz, Jorge E., additional, Lobos-González, Lorena, additional, Sepulveda, Hugo, additional, Ortíz, Rina J., additional, Martinez, Samuel, additional, Silva, Veronica, additional, Maldonado, Horacio J., additional, Silva, Patricio, additional, Wehinger, Sergio, additional, Burzio, Verónica A., additional, Torres, Vicente A., additional, Montecino, Martín, additional, Leyton, Lisette, additional, and Quest, Andrew F.G., additional

Published
2017
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12. EFECTO DE BUPROFEZIN, PYRIPROXIFEN Y ACEITE MINERAL EN POSTCOSECHA SOBRE ESCAMA DE SAN JOSÉ (Diaspidiotus perniciosus Comstock) EN MANZANO

Author

Sazo, Luis, Asiain, Eugenio, Sepulveda, Hugo, and Prieto, Mayerly

Subjects
escama de San José, reguladores de crecimiento, growth regulators, fall, San Jose scale, otoño
Abstract

Diaspidiotus perniciosus es una plaga importante de frutales de carozo y pomáceas que puede ser controlada mediante aplicaciones de postcosecha. El objetivo de este estudio fue determinar el efecto de pyriproxyfen y buprofezin sobre los estados juveniles (gorrita negra y gorrita gris) de D. perniciosus, en manzanas var. Royal Gala. El estudio se realizó en otoño del 2012 con aplicaciones de insecticidas solos y en mezcla con aceite mineral al 2% y un testigo aplicado con agua. Las aplicaciones se realizaron con pitón, 250 PSI y 3500 L ha-1, sobre árboles de manzano infestados. La evaluación se realizó bajo lupa estereoscópica en laboratorio, 48 días después de la aplicación (DDA) sobre juveniles fijados en ramillas de la temporada. Los resultados se expresaron en porcentaje de mortalidad. Se empleó un diseño completamente al azar con 6 tratamientos y 4 repeticiones; la unidad experimental fueron 2 árboles contiguos de los cuales se colectó una muestra compuesta de 30 ramillas, para determinar la mortalidad sobre 1000 individuos por repetición. Se concluyó que pyriproxyfen al 0,06% y buprofezin al 0,1% aplicados solos, controlan parcialmente los estados juveniles de este insecto en esta época. Además, buprofezin 0,1% mezclado con aceite mineral 1,5% controla efectivamente los juveniles de D. perniciosus en manzanos y su efecto es similar a la aplicación de aceite mineral 2,0%. Así mismo, la mezcla de pyriproxyfen más aceite mineral 1,5%, ejerce un control mayor que un tratamiento de aceite mineral 2,0%. Diaspidiotus perniciosus is a major pest of pome and stone fruits that can be controlled using post-harvest applications. The objective of this study was to determine the effect of pyriproxyfen and buprofezin on crawlers (insects in their juvenile stage growth) of D. perniciosus(black-cap and grey-cap) on apples var. Royal Gala. The experiment was conducted in the fall of 2012. Insecticides were applied alone and in mixture with mineral oil at 2% and a control treatment applied only with water. Applications were made with a handgun at 250 PSI and 3500 L ha-1 over infested apple trees. Crawlers on twigs were evaluated in the laboratory using a stereoscopic magnifier 48 days after application (DAA). The results were expressed in mortality percentage. A completely randomized experimental design was used with 6 treatments and 4 replications. The experimental unit consisted of 2 adjacent trees; a sample of 30 twigs was collected from the trees to determine the mortality over 1000 specimens per replication. It was concluded that, when applied alone, pyriproxyfen at 0.06% and buprofezin at 0.1% can partially control crawlers of D. perniciosus in fall. It was also found that buprofezin at 0.1% in mixture with mineral oil 1.5% can effectively control San Jose scale crawlers on apple trees, with similar effects to those observed with mineral oil at 2.0%. In addition, the mixture of pyriproxyfen and mineral oil at 1.5% controls crawlers better than the treatment with mineral oil at 2.0%.

Published
2016

20. Whole-Genome Transcript Expression Profiling Reveals Novel Insights into Transposon Genes and Non-Coding RNAs during Atlantic Salmon Seawater Adaptation.

Author

Valenzuela-Muñoz, Valentina, Gallardo-Escárate, Cristian, Benavente, Bárbara P., Valenzuela-Miranda, Diego, Núñez-Acuña, Gustavo, Escobar-Sepulveda, Hugo, and Váldes, Juan Antonio

Subjects
NON-coding RNA, ATLANTIC salmon, SEAWATER, TRANSPOSONS, RNA analysis, TRANSCRIPTOMES
Abstract

Simple Summary: This study proposes a novel approach to analyze transcriptome data sets using the Atlantic salmon seawater adaptation process as a model. Salmon salar smolts were transferred to seawater under two strategies: (i) fish group exposed to gradual salinity changes (GSC) and (ii) fish group exposed to a salinity shock (SS). mRNA and miRNAs sequencing were performed for gills, intestine, and head kidney tissues. The whole-genome transcript expression profiling revealed specific gene expression patterns among the tissues and treatments. A great abundance of transposable elements was observed in chromosome regions differentially expressed under experimental conditions. Moreover, small RNA expression analysis suggested fewer of miRNAs associated with the smoltification process. However, target analysis of these miRNAs suggests a regulatory role of process such as growth, stress response, and immunity. The findings uncover whole-transcriptome modulation during seawater adaptation of Atlantic salmon, evidencing the interplaying among mRNAs and miRNAs. The growing amount of genome information and transcriptomes data available allows for a better understanding of biological processes. However, analysis of complex transcriptomic experimental designs involving different conditions, tissues, or times is relevant. This study proposes a novel approach to analyze complex data sets combining transcriptomes and miRNAs at the chromosome-level genome. Atlantic salmon smolts were transferred to seawater under two strategies: (i) fish group exposed to gradual salinity changes (GSC) and (ii) fish group exposed to a salinity shock (SS). Gills, intestine, and head kidney samples were used for total RNA extraction, followed by mRNA and small RNA illumina sequencing. Different expression patterns among the tissues and treatments were observed through a whole-genome transcriptomic approach. Chromosome regions highly expressed between experimental conditions included a great abundance of transposable elements. In addition, differential expression analysis showed a greater number of transcripts modulated in response to SS in gills and head kidney. miRNA expression analysis suggested a small number of miRNAs involved in the smoltification process. However, target analysis of these miRNAs showed a regulatory role in growth, stress response, and immunity. This study is the first to evidence the interplaying among mRNAs and miRNAs and the structural relationship at the genome level during Atlantic salmon smoltification. [ABSTRACT FROM AUTHOR]

Published
2022
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21. Correlaciónes angulares inducidas por campos mediós exactos en materia nuclear

Author

ROMERO BARRIENTOS, JAIME ALFONSO, ARELLANO SEPULVEDA, HUGO FRANCISCO, and UNIVERSIDAD DE CHILE/FACULTAD DE CIENCIAS /ESCUELA DE POSTGRADO

Abstract

MAGISTER EN CIENCIAS FISICA http://sial.fondecyt.cl/index.php/investigador/f4_tesis_memorias/descarga/7727830/1120396/0/56749/1/ FONDECYT FONDECYT

Published
2014

22. OGT prevents DNA demethylation and suppresses the expression of transposable elements in heterochromatin by restraining TET activity genome-wide.

Author

Sepulveda H, Li X, Yue X, Carlos Angel J, Arteaga-Vazquez LJ, Brown C, Brunelli M, Jansz N, Puddu F, Scotcher J, Creed P, Kennedy P, Manriquez C, Myers SA, Crawford R, Faulkner GJ, and Rao A

Abstract

The O- GlcNAc transferase OGT interacts robustly with all three mammalian TET methylcytosine dioxygenases. We show here that deletion of the Ogt gene in mouse embryonic stem cells (mESC) results in a widespread increase in the TET product 5-hydroxymethylcytosine (5hmC) in both euchromatic and heterochromatic compartments, with concomitant reduction of the TET substrate 5-methylcytosine (5mC) at the same genomic regions. mESC engineered to abolish the TET1-OGT interaction likewise displayed a genome-wide decrease of 5mC. DNA hypomethylation in OGT-deficient cells was accompanied by de-repression of transposable elements (TEs) predominantly located in heterochromatin, and this increase in TE expression was sometimes accompanied by increased cis -expression of genes and exons located 3' of the expressed TE. Thus, the TET-OGT interaction prevents DNA demethylation and TE expression in heterochromatin by restraining TET activity genome-wide. We suggest that OGT protects the genome against DNA hypomethylation and impaired heterochromatin integrity, preventing the aberrant increase in TE expression observed in cancer, autoimmune-inflammatory diseases, cellular senescence and ageing.

Published
2024
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