43 research outputs found

    Competing roles of DNA end resection and non-homologous end joining functions in the repair of replication-born double-strand breaks by sister-chromatid recombination

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    While regulating the choice between homologous recombination and non-homologous end joining (NHEJ) as mechanisms of double-strand break (DSB) repair is exerted at several steps, the key step is DNA end resection, which in Saccharomyces cerevisiae is controlled by the MRX complex and the Sgs1 DNA helicase or the Sae2 and Exo1 nucleases. To assay the role of DNA resection in sister-chromatid recombination (SCR) as the major repair mechanism of spontaneous DSBs, we used a circular minichromosome system for the repair of replication-born DSBs by SCR in yeast. We provide evidence that MRX, particularly its Mre11 nuclease activity, and Sae2 are required for SCR-mediated repair of DSBs. The phenotype of nuclease-deficient MRX mutants is suppressed by ablation of Yku70 or overexpression of Exo1, suggesting a competition between NHEJ and resection factors for DNA ends arising during replication. In addition, we observe partially redundant roles for Sgs1 and Exo1 in SCR, with a more prominent role for Sgs1. Using human U2OS cells, we also show that the competitive nature of these reactions is likely evolutionarily conserved. These results further our understanding of the role of DNA resection in repair of replication-born DSBs revealing unanticipated differences between these events and repair of enzymatically induced DSBs.Ministerio de Ciencia e Innovación BFU2006-05260, BFU2010-16372, CSD2007-015, SAF2010-21017, SAF2010-14877Junta de Andalucía BIO102, CVI4567European Community’s Seventh Framework Programme HEALTH-F2-2010-259893Cancer Research UK C6/A11224, C6946/A14492Wellcome Trust 09209

    Tasa de publicaciones científicas de resúmenes presentados en Congreso Nacional de Estudiantes de Odontología, Chile 2013-2017

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    Objective: To determine the rate of publication of abstracts presented at the National Congress of Dental Students (CONADEO) 2013-2017 and to analyze publications according to Institution of origin, study design, and journal indexing. Material and Methods: Descriptive cross-sectional study. The abstracts presented were sought in MEDLINE (PubMed), SciELO, and Google Scholar to locate their respective publications. Information was collected regarding the study design, institution of origin of the abstract, name of the journal, indexing, and impact factor. These data were registered in Google Forms and exported to Google Spreadsheets, to be analyzed using descriptive statistics. Results: 627 abstracts were included. The publication rate resulted in 1.75%.  The institution with the most publications was the Universidad de Talca (45.45%). The type of study design with most publications was Bibliographic reviews (45.45%). 54.54% of the publications located were indexed in other databases. Conclusions: The rate of publication of abstracts presented in CONADEO was found to be low compared to the number of abstracts presented. It is suggested further analysis to investigate the possible barriers that prevented achieving a final publication.Objetivo: Determinar la tasa de publicación de resúmenes presentados en el Congreso Nacional de Estudiantes de Odontología (CONADEO) 2013-2017 y analizar publicaciones según Institución, diseño de estudio e indexación de la revista.Material y Métodos: Estudio descriptivo transversal. Los resúmenes presentados fueron revisados en MEDLINE(PubMed), SciELO y Google Scholar, para localizar sus respectivas publicaciones. Se recopiló información acerca del diseño de estudio, institución del resúmen, nombre de la revista, indexación y factor de impacto. Estos datos fueron registrados en Google Forms y exportados a Google Sheets, para ser analizados mediante estadística descriptiva. Resultados: Se incluyeron 627 de los 632 resúmenes presentados. La tasa de publicación resultó ser de un 1,75%. La institución con más publicaciones fue la “Universidad de Talca” (45,45%). El diseño de estudio con más publicaciones fueron “Revisiones bibliográficas” (45,45%). Un 54,54% de las publicaciones fueron indexadas en “otras” bases de datos. Conclusión: La tasa de publicación de resúmenes presentados en CONADEO mostró ser baja en comparación con la cantidad de resúmenes que se presentan. Se sugiere que investigaciones futuras indaguen en las posibles barreras que impidieron llegar a una publicación final

    Factores asociados al éxito académico en estudiantes de odontología durante el ciclo clínico de formación profesional

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    El objetivo de este estudio, fue determinar factores asociados al éxito académico considerado como la aprobación de asignaturas clínicas de la carrera de Odontología de la Universidad Austral de Chile. Se realizó un estudio del tipo analítico con análisis de regresión logística con un nivel de significancia de p<0,05. Fueron estudiadas las variables de: sexo, residencia, tipo de establecimiento de egreso de educación secundaria, historial de reprobación, trabajo, puntajes de prueba de selección universitaria, y notas de enseñanza media. Un total de 119 estudiantes fueron participes de este estudio, de los cuales 70 fueron alumnos pertenecientes al ciclo clínico de cuarto año y 49 de quinto año. El análisis de regresión logística, mostró una asociación estadísticamente significativa para el ciclo clínico de cuarto año entre los factores de: sexo mujer (odds ratio [OR], 5,05;  intervalo de confianza [IC], 3,848-6,261) y PSU lenguaje sobre 660 puntos (odds ratio [OR], 0,28; intervalo de confianza [IC], -0,933-1,504), y para el ciclo clínico de quinto año fue el factor de: sin historial de reprobación (odds ratio [OR], 0,137; intervalo de confianza [IC], -1,550-1,824). Los factores predictores de rendimiento académico son variables durante el ciclo clínico de la carrera de Odontología, existiendo diferencias entre los estudiantes de cuarto y quinto año. Se sugiere tener en consideración estos resultados para brindar apoyo estudiantil de forma oportuna

    Satisfacción del uso de ortodoncia fija, en pacientes de Valdivia y Paillaco, 2017. Estudio observacional

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    Determinar satisfacción usuaria en el uso de aparatos de ortodoncia fija post instalación. Material y métodos: Estudio observacional de corte transversal, en pacientes con tratamiento de ortodoncia fija en centros de salud de la ciudad de Valdivia y Paillaco. El nivel de satisfacción fue medido mediante una encuesta validada al español de Gacitúa et al., (2016). Para establecer diferencias, se realizó la prueba de Friedman con un nivel de significancia p<0,05. Resultados: Participaron 34 pacientes. La edad promedio fue de 14,1 DE ± 3,5 años. El puntaje total de satisfacción para el primer control fue 37,94 (DE ± 7,13) puntos, 40,56 (DE ± 6,35) puntos para el segundo y 41,09 (DE ± 6,92) puntos para el tercero. Conclusión: El nivel de satisfacción en el uso de aparatos de ortodoncia fija, aumenta a medida que transcurre el tratamiento de ortodonci

    Impaired Phagocytosis in Dendritic Cells From Pediatric Patients With Type 1 Diabetes Does Not Hamper Their Tolerogenic Potential

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    Type 1 diabetes (T1D) is prompted by defective immunological tolerance, an event in which dendritic cells (DCs) are crucial as immune response orchestrators. In fact, they contribute to maintaining tolerance to self-antigens, but they can also prompt an immunogenic response against them, leading to autoimmunity. Countless factors can potentially impact on the proper functionality of the DCs, which range from altered subset distribution, impaired phagocytic function to abnormal gene expression. Moreover, in T1D, metabolic dysregulation could impair DC functions as well. Indeed, since T1D clinical course is likely to be more aggressive in children and adolescents and entails severe dysglycemia, the aim of this study was to analyze circulating DCs subpopulations in pediatric T1D at different stages, as well as to characterize their phagocytosis ability and tolerance induction potential. Thus, pediatric patients newly diagnosed with T1D, with established disease and control subjects were recruited. Firstly, DCs subsets from peripheral blood were found quantitatively altered during the first year of disease, but recovered in the second year of progression. Secondly, to study the tolerogenic functionality of DCs, liposomes with phosphatidylserine (PS) were designed to mimic apoptotic beta cells, which are able to induce tolerance, as previously demonstrated by our group in DCs from adult patients with T1D. In this study, monocyte-derived DCs from pediatric patients with T1D and control subjects were assessed in terms of PS-liposomes capture kinetics, and transcriptional and phenotypic changes. DCs from pediatric patients with T1D were found to phagocyte PS-liposomes more slowly and less efficiently than DCs from control subjects, inversely correlating with disease evolution. Nonetheless, the transcription of PS receptors and immunoregulatory genes, cytokine profile, and membrane expression of immunological markers in DCs was consistent with tolerogenic potential after PS-liposomes phagocytosis. In conclusion, T1D progression in childhood entails altered peripheral blood DCs subsets, as well as impaired DCs phagocytosis, although tolerance induction could still function optimally. Therefore, this study provides useful data for patient follow-up and stratification in immunotherapy clinical trials

    Repurposed analog of GLP-1 ameliorates hyperglycemia in type 1 diabetic mice through pancreatic cell reprogramming

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    This work has been funded by Fundació La Marató de TV3 (project 201632_10). CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM) is an initiative from Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation. SR-F was supported by the Generalitat de Catalunya (AGAUR grant).Type 1 diabetes is an autoimmune disease caused by the destruction of the insulin-producing β-cells. An ideal immunotherapy should combine the blockade of the autoimmune response with the recovery of functional target cell mass. With the aim to develop new therapies for type 1 diabetes that could contribute to β-cell mass restoration, a drug repositioning analysis based on systems biology was performed to identify the β-cell regenerative potential of commercially available compounds. Drug repositioning is a strategy used for identifying new uses for approved drugs that are outside the scope of the medical indication. A list of 28 non-synonymous repurposed drug candidates was obtained, and 16 were selected as diabetes mellitus type 1 treatment candidates regarding pancreatic β-cell regeneration. Drugs with poor safety profile were further filtered out. Lastly, we selected liraglutide for its predictive efficacy values for neogenesis, transdifferentiation of α-cells, and/or replication of pre-existing β-cells. Liraglutide is an analog of glucagon-like peptide-1, a drug used in patients with type 2 diabetes. Liraglutide was tested in immunodeficient NOD- Scid IL2rg −/− (NSG) mice with type 1 diabetes. Liraglutide significantly improved the blood glucose levels in diabetic NSG mice. During the treatment, a significant increase in β-cell mass was observed due to a boost in β-cell number. Both parameters were reduced after withdrawal. Interestingly, islet bihormonal glucagon + insulin + cells and insulin + ductal cells arose during treatment. In vitro experiments showed an increase of insulin and glucagon gene expression in islets cultured with liraglutide in normoglycemia conditions. These results point to β-cell replacement, including transdifferentiation and neogenesis, as aiding factors and support the role of liraglutide in β-cell mass restoration in type 1 diabetes. Understanding the mechanism of action of this drug could have potential clinical relevance in this autoimmune disease

    GEHEP 010 study: Prevalence and distribution of hepatitis B virus genotypes in Spain (2000–2016)

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    [Objective] To study the prevalence and distribution of HBV genotypes in Spain for the period 2000–2016.[Methods] Retrospective study recruiting 2559 patients from 17 hospitals. Distribution of HBV genotypes, as well as sex, age, geographical origin, mode of transmission, HDV-, HIV- and/or HCV-coinfection, and treatment were recorded.[Results] 1924 chronically HBV native Spanish patients have been recruited. Median age was 54 years (IQR: 41–62), 69.6% male, 6.3% HIV-coinfected, 3.1% were HCV-coinfected, 1.7% HDV-co/superinfected. Genotype distribution was: 55.9% D, 33.5% A, 5.6% F, 0.8% G, and 1.9% other genotypes (E, B, H and C). HBV genotype A was closely associated with male sex, sexual transmission, and HIV-coinfection. In contrast, HBV genotype D was associated with female sex and vertical transmission. Different patterns of genotype distribution and diversity were found between different geographical regions. In addition, HBV epidemiological patterns are evolving in Spain, mainly because of immigration. Finally, similar overall rates of treatment success across all HBV genotypes were found.[Conclusions] We present here the most recent data on molecular epidemiology of HBV in Spain (GEHEP010 Study). This study confirms that the HBV genotype distribution in Spain varies based on age, sex, origin, HIV-coinfection, geographical regions and epidemiological groups.This study has been funded in part by the funds of the research project GEHEP-2018-010, granted by the Hepatitis Group of the Spanish Society of Infectious Diseases and Clinical Microbiology (Grupo de Hepatitis de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, GEHEP/SEIMC)

    Trends of maxillofacial trauma : an update from the prospective register of a multicenter study in emergency services of Chile

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    Determine the behavior of the maxillofacial trauma of adults treated in 3 tertiary care centers in the central zone of Chile. Descriptive, cross-sectional, multicenter study, based on the prospective records of maxillofacial trauma cases attended between May 2016 and April 2017 by dental and maxillofacial clinical teams of Adult Emergency Units of hospitals Dr. Sótero del Río (metropolitan region), Carlos Van Buren and Dr. Gustavo Fricke (region V). Age, sex, date of occurrence, type of trauma according to ICD-10, etiology, legal medical prognosis and associated injuries were recorded, stratifying by sex and age. Chi square and unpaired Wilcoxon tests were used to compare by groups. 2.485 cases and 3.285 injuries were investigated. The male: female ratio was 1.7: 1 with age under 30 predominant, followed by older adults. Variability was observed in the yearly, weekly and daily presentation. The highest frequencies were in January and September, weekends and at night. The main etiologies were violence (42.3%), falls (13.1%) and road traffic crashes (12.9%) with differences by age and sex (p<0.05). 31,9% of the injuries occurred in hard tissue, being fractures in nasal bones predominant (S02.2). The profile of the maxillofacial trauma in Chile seems to be mixed by age, affecting young people and the elderly. The male sex predominates; the main cause, which varies by age group, is violence. Their surveillance is possible from hospital emergency records
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