Ciencias Exactas y Ciencias de la Salud
Permanent URI for this collectionhttps://hdl.handle.net/11285/551039
Pertenecen a esta colección Tesis y Trabajos de grado de las Maestrías correspondientes a las Escuelas de Ingeniería y Ciencias así como a Medicina y Ciencias de la Salud.
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- Phylotranscriptomic Analysis of Pigment Biosynthesis in the Caryophyllales(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2024-12-02) Gutierrez Vences, Alma Yesenia; Rodríguez López, Carlos Eduardo; Chavez Santoscoy, Rocío; Dang, Thu-Thuy; Díaz de la Garza, Rocío; Treviñp, Manuel; School of Engineering and Sciences; Campus MonterreyIn plants, color is given by secondary metabolites, pigments, that absorb and emit color due to their chemical structure. Betalains are a class of tyrosine-derived pigments found exclusively in the Caryophyllales order, where they are concurrent with the anthocyanin pigments. These two types of pigments show a mutually exclusive pattern of expression rooted in a complex homoplastic distribution. Although the genetic events that led to the emergence of betalains in the Caryophyllales is known, the exact genetic evolutionary path that led to mutual exclusion remains elusive with multiple theories with a single or multiple emergences being proposed. This thesis combines orthology-based phylogenetic correlation analyses with comparative transcriptomics to investigate the molecular and evolutionary drivers of pigment biosynthesis, focusing on transcriptional regulation, pigment structural modification, and transport mechanisms. Co-expression analysis revealed potential regulatory co-option, suggesting that betalain-producing species may have repurposed ancestral anthocyanin regulatory mechanisms to drive their pigment emergence. Additionally, candidate enzymes such as UGT, SCPL, and MT were identified as key players in pigment structural modification and stabilization in betalain-producing species. The research also presents novel insights into the role of cellular transport mechanisms in pigment exclusion. Genes in orthogroups with statistically different occupancy annotated in processes related to vesicle trafficking were found to coexpress with biosynthetic modules, suggesting that transport may contribute significantly to the mutual exclusion of anthocyanins and betalains. These findings hint at a possible loss and co-option of anthocyanin transport mechanisms for betalain sequestration in vacuoles, raising questions about how shifts in transport specificity may drive pigment divergence.
- Analysis of cellular senescence in Spinocerebellar ataxia type 7 using bioinformatics and an inducible cell model(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2022-06-15) Ruiz Esparza Palacios, Vanessa; GONZALEZ MELJEM, JOSE MARIO; 316764; González Meljem, José Mario; puemcuervo; Pérez Méndez, Óscar Armando; García Aguirre, Ian Alaín; School of Engineering and Sciences; Campus Monterrey; Magaña Aguirre, Jonathan JavierSpinocerebellar ataxia type 7 (SCA7) is an autosomal dominant inherited disorder manifested by the inability to coordinate balance, gait, and speech. Some experimental evidence suggests that nuclear inclusion of mutant ataxin-7 (ATX7) is part of the molecular basis of this disease and the origin of oxidative stress. In this thesis, we made a bioinformatic analysis that supports the hypothesis that SCA7 could share some mechanisms that are core features of senescent cells. Senescence is a permanent state of cell-cycle arrest, and core features of this phenotype include the expression of anti-proliferative molecules, the activation of a chronic DNA damage response, altered metabolic rates, and many others. We sought to establish a senescence induction protocol in a human fibroblast cell line as a positive control of senescence and found that induction with H2O2 at 1200 μM resulted in 79% of positive SA-β-gal cells. Afterwards, we were able to validate an inducible cell model of MIO-M1 cells, which were stably transduced to express a mutant ATXN7 gene carrying 64 CAG repeats and 10 CAG repeats. Administration of doxycycline (dox) induced the expression of the mutated protein causing the formation of nuclear aggregates. Furthermore, in a preliminary SA-β-gal assay, we found activity of this enzyme in 64 CAG cells, suggesting the presence of senescence features after the induction of the mutated protein. Based on our findings, we propose that the oxidative stress generated by the accumulation of the mutated protein could be leading to a senescence phenotype. Future evaluation of the Senescence-associated secretory phenotype (SASP) and markers of DNA damage will bring better understanding of the possible role of senescence in SCA7.
- Bioinformatic analysis of the expression pattern of an intron-retaining isoform of the Agrp transcript in arcuate nucleus neurons of mice(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2021-12-07) Gómez Montalvo, Jesús; GONZALEZ MELJEM, JOSE MARIO; 316764; González Meljem, José Mario; puemcuervo, emipsanchez; Treviño Alvarado, Víctor Manuel; de Obeso Fernández del Valle, Álvaro; School of Engineering and Sciences; Campus Monterrey; Avendaño Vázquez, Selma EréndiraKnown to be the regulatory center of hunger and satiety, the arcuate nucleus (ARC) harbors two neuronal populations that exert opposite effects on the regulation of food intake. Namely, AgRP and POMC neurons respectively trigger hunger and satiety. Although both neuronal groups are born within the same time interval in the developing hypothalamus of mouse, their peptidergic identities are established at distinct developmental timepoints. While the POMC identity is established as early as the embryonic period, the complete maturation of the AgRP peptidergic identity extends to the postnatal period. Previously, through RT-PCR, our group detected the presence of an Agrp transcript isoform that retained introns 3 and 4 (Agrp-i3,4) in the early postnatal, but not in the adult mouse hypothalamus. In this thesis project, the expression pattern of Agrp-i3,4 is analyzed in public RNA-seq datasets from ARC neurons of mice at different postnatal developmental stages. To identify intron retention events, iREAD was used, and to quantify the proportion of Agrp transcripts that retained introns 3 and 4, ASpli was employed. Using this bioinformatics approach, the largest proportion of Agrp-i3,4 was detected in ARC samples of P12 mice and there was a trend towards decreased retention of Agrp introns 3 and 4 at later developmental stages. Agrp-i3,4 was detected in poly-A RNA extracted from whole AgRP neurons, but not in the ribosomal fraction. On the other hand, food deprivation appeared to exert distinct effects on the proportion of the Agrp-i3,4 transcript depending on the duration of the fast. While in weaned mice fasted for 16 hours Agrp-i3,4 showed a slight increase, in adult mice fasted for 38 hours Agrp-i3,4 appeared to decrease. Unlike fasting, leptin treatment did not exert any effect on the retention of Agrp introns 3 and 4. Of note, IR was found in Agrp but not in other genes that characterize the ARC, such as Npy or Pomc. Taken together, the results presented in this thesis suggest that increased IR of the Agrp transcript may correlate with a lower maturation degree of the ARC during a time interval in which the AgRP peptidergic identity has not yet been fully established.
- In silico identification of cis-regulatory elements in folate biosynthesis and 1C metabolism genes in plants(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2021-11-26) Salinas Espinosa, Jessica Pamela; TREVIÑO ALVARADO, VICTOR MANUEL; 205076; Treviño Alvarado, Víctor Manuel; puemcuervo; Cuevas Díaz Durán, Raquel; Rodríguez López, Carlos; Martínez Ledesma, Juan Emmanuel; School of Engineering and Sciences; Campus Monterrey; Díaz de la Garza, Rocío IsabelFolates (vitamin B9) are enzyme cofactors required for all organisms for one-carbon (1C) transfer reactions. A deficiency of these nutrients can lead to several health problems. Since humans are not natural producers of folates, the intake of these nutrients from plants is vital for human nutrition. Several techniques that involve the genetic modification of organisms have proved to be effective for the fortify plants with essential macronutrients. However, to achieve this, it is necessary to elucidate the metabolic control in plant systems. Although the genes involved in folate biosynthesis and 1C metabolism in plants are known, the mechanisms of transcriptional regulation have not yet been explored. This project focuses on discovering cis-regulatory DNA elements (motifs) using computational data analysis to provide insights regarding the regulation of folate biosynthesis in plants. For this, we first collected a compendium of known genes related to folate biosynthesis. Then, a database comprising the DNA promoter regions of folate biosynthesis and 1C metabolism genes in 19 different plant species was built and analyzed using different motif discovery algorithms. Afterward, the discovered motifs were tested for statistical significance and further associated with their putative biological role using other bioinformatics tools. A total of 149 statistically significant motifs (p < .05) were discovered in 18 of 19 species using the GimmeMotifs ensemble algorithm. These motifs were represented in 104 different regulatory networks built automatically from co-expression clusters obtained from each plant species. The results from this work could provide an insight into the transcriptional regulation of the folate biosynthesis pathway in plants. Furthermore, the elements found could be used for research in gene editing techniques to produce biofortified crops.
- The role of HDL and phospholipids in endothelial cellular senescence(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2021-05-26) De la Cruz Gutiérrez, Luis Fernando; DE LA CRUZ GUTIERREZ, LUIS FERNANDO; 672038; González Meljem, José Mario; puemcuervo; Magaña Aguirre, Jonathan Javier; Chávez Santos, Rocío Alejandra; School of Engineering and Sciences; Campus Monterrey; Pérez Méndez, Oscar ArmandoHigh-density lipoproteins (HDLs) are commonly recognized as antiatherogenic molecules; these possess anti-inflammatory properties and participate in the production of Nitric Oxide (NO) by endothelial cells. In addition, critical patients characterized by a dropdown of HDL-cholesterol plasma levels during the acute phase, have an increased risk of intrahospital death. The molecular mechanisms underlying the beneficial effects of HDL are not well understood. However, current clinical evidence suggests a relationship between HDL and cellular senescence, a stress response characterized by a mostly irreversible loss in the replicative potential of the cell. This permanent cell cycle arrest can be induced through a variety of stimuli including telomere shortening, oxidative stress, DNA damage and oncogenic signals. At the organismal level, senescence contributes to aging and has been associated with numerous age-related pathologies. Now, few studies have documented that cellular senescence exhibits an alteration in lipid composition, leading to morphological changes in membrane remodeling. Additionally, a relationship between the altered expression of regulatory genes of lipid metabolism and senescent cells has been recently uncovered. Therefore, here we aimed to analyze the role of HDLs in endothelial cell senescence induced by doxorubicin and hydrogen peroxide. The results reveal that there is a possible impact of HDL on the onset of cellular senescence, although this may be more associated with membrane homeostasis, as reflected in a decrease in the number of cells positive for the senescence marker SA-β-galactosidase, as well as a decrease in apoptosis associated with the stress generated by the senescence inducer. However, further study of these lipoproteins in senescent cells is needed. Likewise, this study opens the door to consider hydrogen peroxide as a strong candidate to induce senescence in HMEC-1 endothelial cells derived from the oxidative stress that these cells can encounter physiologically.
