Browsing by Author "Andres, Maria E."

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    Diabetic Ketoacidosis in Type 1 Diabetes Onset in Latin American Children
    (2024) Hirschler, Valeria; Gonzalez, Claudio D.; Krochik, Gabriela; Rousos, Adriana M.; Andres, Maria E.; Riera, Francisca; Ibarcena, Paola Pinto; Molinari, Claudia; Porta, Luis F. Palacios; Prieto, Mariana; Mateu, Carolina Martinez; Barcala, Consuelo; Arrigo, Maria A.; Tachetti, Jacqueline.; Raggio, Marcela; Vacarezza, Veronica; Major, Maria L.; Sobrero, Angela Figueroa; Bogado, Ernesto; Lopez, Stella; Povedano, Paula Paz; Scaiola, Edit; Leiva, Fabiana; Pacheco, Gabriela; Pasayo, Patricia; Dupuy, Mariana; Torossi, Maria B.; Benitez, Amanda J.; Marassi, Andrea Escalante; Caballero, Zulema; Garcia, Ana L.; Mazzetti, Sandra; Pugliese, Maria I. Ruiz; Gonzalez, Diana S.; Grabois, Florencia; Villar, Carlos M. Del Aguila; Flores, Adriana B.
    Objective: To describe the patterns of diabetic ketoacidosis (DKA) occurrence in children newly diagnosed with type 1 diabetes (T1DM) across several Latin American pediatric diabetes centers from 2018 to 2022. Methods: A retrospective chart review included children under 18 with new -onset T1DM from 30 Latin American pediatric diabetes centers (Argentina, Chile, and Peru) between 30 December 2018 and 30 December 2022. Multiple logistic regression models examined the relationships between age, gender, medical insurance, BMI, and DKA at new -onset T1DM. As far as we know, there are no large studies in Latin American countries exploring the patterns of DKA in new -onset T1DM. Results: A total of 2,026 (983 females) children, median age 9.12 (5.8 -11.7) years with new-onset-T1DM were included. Approximately 50% had no medical insurance . Mean glucose values were 467 mg/dL, pH 7.21, bicarbonate 13 mEq/L, HbA1c 11.3%, and BMI 18. The frequency of DKA was 1,229 (60.7%), out of which only 447 (36%) were severe. There was a signi fi cant decrease in the frequency of DKA as age increased : 373 (70.2%) in children under 6, 639 (61.6%) in those between 6 and 12, 217 and (47.5%) in those over 12. Children with medical insurance (58.8%) had a signi fi - cantly lower frequency of DKA than those without (62.7%). The multiple logistic regression models showed that DKA was signi fi - cantly and inversely associated with age [OR, 0.72 (95% CI 0.60 - 0.86)], BMI [OR, 0.95 (95% CI 0.92 - 0.99)], and medical insurance [OR, 0.75 (95% CI 0.60 - 0.94)] adjusted for sex. Conclusion: Latin American children with new -onset T1DM exhibited a substantial occurrence of DKA. Younger ages and the lack of medical insurance were signi fi cantly associated with DKA in new -onset T1DM. J Pediatr Health Care. (2024) 38 , 544 - 551
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    Evolution of lysine-specific demethylase 1 and REST corepressor gene families and their molecular interaction
    (2023) Olivares-Costa, Montserrat; Oyarzun, Gianluca Merello; Verbel-Vergara, Daniel; Gonzalez, Marcela P.; Arancibia, Duxan; Andres, Maria E.; Opazo, Juan C.
    Lysine-specific demethylase 1A (LSD1) binds to the REST corepressor (RCOR) protein family of corepressors to erase transcriptionally active marks on histones. Functional diversity in these complexes depends on the type of RCOR included, which modulates the catalytic activity of the complex. Here, we studied the duplicative history of the RCOR and LSD gene families and analyzed the evolution of their interaction. We found that RCOR genes are the product of the two rounds of whole-genome duplications that occurred early in vertebrate evolution. In contrast, the origin of the LSD genes traces back before to the divergence of animals and plants. Using bioinformatics tools, we show that the RCOR and LSD1 interaction precedes the RCOR repertoire expansion that occurred in the last common ancestor of jawed vertebrates. Overall, we trace LSD1-RCOR complex evolution and propose that animal non-model species offer advantages in addressing questions about the molecular biology of this epigenetic complex.
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    Exposure to repeated immobilization stress inhibits cocaine-induced increase in dopamine extracellular levels in the rat ventral tegmental area
    (2015) Sotomayor-Zarate, Ramon; Abarca, Jorge; Araya, Katherine A.; Renard, Georgina M.; Andres, Maria E.; Gysling, Katia
    A higher vulnerability to drug abuse has been observed in human studies of individuals exposed to chronic or persistent stress, as well as in animal models of drug abuse. Here, we explored the effect of repeated immobilization stress on cocaine-induced increase in dopamine extracellular levels in VTA and its regulation by corticotropin-releasing factor (CRF) and GABA systems.
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    Knockout or Knock-in? A Truncated D2 Receptor Protein Is Expressed in the Brain of Functional D2 Receptor Knockout Mice
    (2021) Sanchez, Natalia; Olivares-Costa, Montserrat; Gonzalez, Marcela P.; Munita, Roberto; Escobar, Angelica P.; Meza, Rodrigo; Herrera-Rojas, Mauricio; Albornoz, Jessica; Merello, Gianluca; Andres, Maria E.
    Null mice for the dopamine D2 receptor (D2R) have been instrumental in understanding the function of this protein. For our research, we obtained the functional D2R knockout mouse strain described initially in 1997. Surprisingly, our biochemical characterization showed that this mouse strain is not a true knockout. We determined by sequence analysis of the rapid 3 ' amplification of cDNA ends that functional D2R knockout mice express transcripts that lack only the eighth exon. Furthermore, immunofluorescence assays showed a D2R-like protein in the brain of functional D2R knockout mice. We verified by immunofluorescence that the recombinant truncated D2R is expressed in HEK293T cells, showing intracellular localization, colocalizing in the Golgi apparatus and the endoplasmic reticulum, but with less presence in the Golgi apparatus compared to the native D2R. As previously reported, functional D2R knockout mice are hypoactive and insensitive to the D2R agonist quinpirole. Concordantly, microdialysis studies confirmed that functional D2R knockout mice have lower extracellular dopamine levels in the striatum than the native mice. In conclusion, functional D2R knockout mice express transcripts that lead to a truncated D2R protein lacking from the sixth transmembrane domain to the C-terminus. We share these findings to avoid future confusion and the community considers this mouse strain in D2R traffic and protein-protein interaction studies.
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    OPA1 Modulates Mitochondrial Ca2+ Uptake Through ER-Mitochondria Coupling
    (FRONTIERS MEDIA SA, 2022) Cartes Saavedra, Benjamin; Macuada, Josefa; Lagos, Daniel; Arancibia, Duxan; Andres, Maria E.; Yu Wai Man, Patrick; Hajnoczky, Gyoergy; Eisner, Veronica
    Autosomal Dominant Optic Atrophy (ADOA), a disease that causes blindness and other neurological disorders, is linked to OPA1 mutations. OPA1, dependent on its GTPase and GED domains, governs inner mitochondrial membrane (IMM) fusion and cristae organization, which are central to oxidative metabolism. Mitochondrial dynamics and IMM organization have also been implicated in Ca2+ homeostasis and signaling but the specific involvements of OPA1 in Ca2+ dynamics remain to be established. Here we studied the possible outcomes of OPA1 and its ADOA-linked mutations in Ca2+ homeostasis using rescue and overexpression strategies in Opa1-deficient and wild-type murine embryonic fibroblasts (MEFs), respectively and in human ADOA-derived fibroblasts. MEFs lacking Opa1 required less Ca2+ mobilization from the endoplasmic reticulum (ER) to induce a mitochondrial matrix [Ca2+] rise ([Ca2+](mito)). This was associated with closer ER-mitochondria contacts and no significant changes in the mitochondrial calcium uniporter complex. Patient cells carrying OPA1 GTPase or GED domain mutations also exhibited altered Ca2+ homeostasis, and the mutations associated with lower OPA1 levels displayed closer ER-mitochondria gaps. Furthermore, in Opa1(-/-) MEF background, we found that acute expression of OPA1 GTPase mutants but no GED mutants, partially restored cytosolic [Ca2+] ([Ca2+](cyto)) needed for a prompt [Ca2+](mito) rise. Finally, OPA1 mutants' overexpression in WT MEFs disrupted Ca2+ homeostasis, partially recapitulating the observations in ADOA patient cells. Thus, OPA1 modulates functional ER-mitochondria coupling likely through the OPA1 GED domain in Opa1(-/-) MEFs. However, the co-existence of WT and mutant forms of OPA1 in patients promotes an imbalance of Ca2+ homeostasis without a domain-specific effect, likely contributing to the overall ADOA progress.