115 research outputs found

    Predicting the arrival of the unpredictable: An approach for foreseeing the transition to chaos of wildfire propagation

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    A discrete map for modelling wildfire propagation is derived from a prototypical reaction-diffusion equation for the temperature field. We show that, for a constant fuel concentration at the fire-front, the heat transfer coefficient from fuel to surroundings and as well as an effective heat of reaction are two independent mechanisms that can cause the transition to chaos, when they may depend on temperature as a consequence of the fire-atmosphere coupling and of the fuel inhomogeneity, respectively. In particular, chaos can enter when the coefficient for the heat transfer from the fuel to the surrounding depends linearly on the temperature and when the effective heat of reaction depends quadratically. Moreover, when the fuel concentration field at the fire-front fluctuates, this embodies a third mechanism that may cause the transition to chaos even without any fire-atmosphere coupling or fuel inhomogeneity. Surprisingly, when the effective heat of reaction depends linearly on the temperature, the chaos generated by the non-constant fuel concentration is ceased. This suppression is not observed when the chaos is due to the fire-atmosphere coupling with constant fuel concentration. In all cases, the onset of chaos is related to the logistic map. The application of this approach for setting an alternative method for real-time risk assessment is discussed in the conclusions.This research is supported by the Basque Government through the BERC 2022–2025 program, by the Ministry of Science and Innovation: BCAM Severo Ochoa accreditation CEX2021-001142-S / MICIN / AEI / 10.13039/501100011033 and the project PID2019-107685RB-I00, and by the Spanish State Research Agency (AEI) through the project PDC2022-133115-I00 entitled ”B 2 F 2: Be a Better digital Fire-Fighter” and funded by the European Union Next Generation EU; by the European Regional Development Fund (ERDF) and the Department of Education of the regional government, the Junta of Castilla y Le ́on (Grant contract SA089P20)

    A specific MLH1 gene mutation in families from Mendoza associated with lynch syndrome

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    Lynch syndrome (LS) is the most common cause of hereditary colon cancer which predisposen to colorectal, endometrial, and other cancers. LS is caused by germline mutations in the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2). The MMR system detects and corrects replication errors, maintaining the stability of the genome. Consequently defects in the MMR increase the mutation rate causes microsatellite instability (MSI) and increased cancer risk. The main objective of our study was to analyze clinical characteristics and diagnostic algorithms of two unrelated families from Mendoza, Argentina, carrying a specific mutation in MLH1 gene. The clinical importance of these mutations and their significance in the general population were also examined. After carrying out the genealogical study, MMR proteins MLH1, MSH2, MSH6 and PMS2 were evaluated in paraffin-embedded tissue sections from colorectal tumors using Ventana Benchmark automated immunostaining. MSI analysis was performed using STRs markers (NR-21, NR-24, BAT-25, BAT-26 and Mono-27) and Illumina next-generation sequencing (NGS). Family characteristics and evidences are presented below. Family A: a male patient, 36 years old, with right-sided colon cancer and MLH1/PMS2 proteins absent by immunohistochemistry (IHC). Two sisters with colorectal cancer before 40 years of age. The father and the paternal grandmother died from colon cancer. A pathogenic mutation was localized in MLH1 c.1890dupT (p.Asp631Ter1) by NGS. Family B: a 33-year-old male patient with right-sided colon cancer. IHC staining showed the absence of MLH1 expression. The patient also presented MSI. The mother had endometrial and colon cancer, a maternal uncle had colon cancer and papillary urothelial carcinoma, and the maternal grandfather had colon cancer. Using NGS, a mutation in MLH1 c.1890dupT (p.Asp631Ter1) was found. Our results demonstrate the important implications of clinical and molecular algorithms to improve the efficiency of LS diagnosis, as well as the detection of asymptomatic carriers. These data allow to established guidelines for the follow-up, risk-reduction management and treatment strategies for patients found to has pathogenic mutations. In addition, our data contribute to determine frequencies of specific mutations in the general population. The mutation of the MLH1 gene described above is prevalent among families with LS in South America.Fil: Mampel, Alejandra. Universidad Nacional de Cuyo. Hospital Universitario; ArgentinaFil: Cambados, N.. Hospital Perrupato. Servicio de Anatomía Patológicas y Citología; ArgentinaFil: Valdemoros, Paula. Héritas; ArgentinaFil: Vargas, Ana Lía. Universidad Nacional de Cuyo. Hospital Universitario; ArgentinaFil: Hidalgo, J.. Universidad Nacional de Cuyo. Hospital Universitario; ArgentinaFil: Nadin, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaXXXVI Reunión Científica Anual de la Sociedad de Biología de CuyoMendozaArgentinaSociedad de Biología de Cuy

    Development of a molecular technique for microsatellite instability for use in colon cancer

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    El Cáncer Colorrectal (CCR) es la segun-da causa de muerte por cáncer en Argentina, con más de 11.000 nuevos casos por año. Entre el 3 y el 8% de los casos son producidos por mutaciones heredables. El síndrome más común es el Síndrome de Lynch o Cán-cer Colorrectal Hereditario no Polipósico (CCHNP). Los pacientes afectados tienen un riesgo superior al 80% de desarrollar cáncer de colon y en mujeres, el riesgo de cáncer de endometrio es de 60%. También se encuentra incrementado el riesgo de padecer cáncer de estómago, ovario, intestino delgado, vías biliares y riñón. La patogé-nesis del CCHNP se relaciona con fallas en el sistema de reparación del ADN que lleva a la acumulación de muta-ciones de nucleótido único y cambios en la longitud de secuencias repetitivas, fenómeno conocido como Inesta-bilidad de Microsatélites (MSI). Alta Inestabilidad de mi-crosatélites (MSI-High) se presenta en más del 85% de casos de CCHNP. Además, puede detectarse en el 10-15% de los casos de CCR no asociados a CCHNP debido a metilación de los genes de las enzimas de reparación del ADN. Los tumores colorrectales con MSI tienen carac-terísticas histológicas definidas, mejor pronóstico que los tumores sin MSI y diferente respuesta a la quimioterapia. El descubrimiento de MSI en CCR ha incrementado el co-nocimiento de la diversidad de los CCR y colabora en el diagnóstico, tratamiento y asesoramiento genético. Objetivo: diseñar una técnica molecular para el análisis de MSI de bajo costo y adecuar los algoritmos para me-jorar el diagnóstico de Síndrome de Lynch en la región

    Decreased myocardial Titin expression in chronic alcoholic cardiomyopathy

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    Aims: Cardiomyopathy (CMP) with a reduced ejection fraction develops in a dose-28 dependent manner in one- third of subjects with a long-term history of heavy daily alcohol consumption. Ethanol alters heart transduction signals including excitation- contraction sarcomeric coupling, causing diastolic and systolic left-ventricular (LV) dysfunction. Titin is a giant structural sarcomeric filament macro protein involved in contractile heart function and contributes to cardiac myocyte elastic recoil, a key factor for diastolic LV filling. We evaluated whether titin expression is affected by chronic high-dose ethanol 35 consumption in alcoholic CMP. Methods and Results: We analyzed a total of 30 heart samples from human organ 37 donors: 20 from high alcohol consumers (10 without CMP and 10 with CMP) and 10 healthy controls. Patient evaluation comprised daily and lifetime ethanol consumption, chest X ray, 2-D echocardiography and LV histology. CMP was assessed by functional 40 and histological criteria. Titin activity was evaluated by specific immunohistochemical 41 (IHC) and transcript expression (rtPCR) assays. Titin IHC expression was clearly present in sarcomere areas of myocytes. Compared to healthy donors (82.58±3.36), alcohol consumers showed a significantly lower cardiac titin expression (71.29±3.16; 13.67±3.83% decrease; p=0.04), being significantly lower in alcohol consumers with CMP (62.31±4.18; 24.54±5.06% decrease, p<0.0009), compared to both their counter-parts without CMP (80.27±2.62; 2.80±3.17% decrease 47 vs. controls; p<0.0030 vs. alcoholic CMP). Titin transcript levels confirmed similar patterns of expression

    On and Beyond the Mississippi: Essays honoring Thomas Tredway

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    Excerpt from Introduction: This collection of essays honors Thomas Tredway on his retirement as President of Augustana College in the summer of 2003. The contributors include Augustana graduates from different generations, colleagues at the college, and friends from both on and off campus. The essays focus on themes and subjects that have been important both in the history of Augustana College and in Tom’s own life. Table of Contents: Illustrations -- Introduction -- Contributors -- Roald Tweet / Five Reflections on Living with a Hyphen -- Maria Erling / Nordic and Protestant: Swedish-American Identity in America -- Nils Hasselmo / In the Attic of Denkmann: Reflections on English as a world language, and on the Scandinavian languages which, well, had their fling, too! -- Larry Scott / The Lighter Side of Loneliness: Woody Allen and Ingmar Bergman -- Dag Blanck / American Influences in Sweden? Reflections on a Trans-Atlantic Relationship -- Kenneth R. Johnston / LINES, written a Few Years beyond Augustana College, on Revisiting the Banks of the Mississippi, during a Homecoming/Reunion, anytime. -- Dorothy J. Parkander / Songs of Apollo and Songs of Sion: Milton’s Puritan Poetic -- Richard Swanson / little crick (2001) -- Arthur Mampel / Campus President -- William Bondeson / The Ideals of a Liberal Education or What’s “Blooming” in Higher Education? -- Ronald Goetz / The Sinlessness of Christ?https://digitalcommons.augustana.edu/ahsbooks/1015/thumbnail.jp

    Mitochondrial DNA disturbances and deregulated expression of oxidative phosphorylation and mitochondrial fusion proteins in sporadic inclusion body myositis

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    Sporadic inclusion body myositis (sIBM) is one of the most common myopathies in elderly people. Mitochondrial abnormalities at the histological level are present in these patients. We hypothesize that mitochondrial dysfunction may play a role in disease aetiology. We took the following measurements of muscle and peripheral blood mononuclear cells (PBMCs) from 30 sIBM patients and 38 age-and gender-paired controls: mitochondrial DNA (mtDNA) deletions, amount of mtDNA and mtRNA, mitochondrial protein synthesis, mitochondrial respiratory chain (MRC) complex I and IV enzymatic activity, mitochondrial mass, oxidative stress and mitochondrial dynamics (mitofusin 2 and optic atrophy 1 levels). Depletion of mtDNA was present in muscle from sIBM patients and PBMCs showed deregulated expression of mitochondrial proteins in oxidative phosphorylation. MRC complex IV/citrate synthase activity was significantly decreased in both tissues and mitochondrial dynamics were affected in muscle. Depletion of mtDNA was significantly more severe in patients with mtDNA deletions, which also presented deregulation of mitochondrial fusion proteins. Imbalance in mitochondrial dynamics in muscle was associated with increased mitochondrial genetic disturbances (both depletion and deletions), demonstrating that proper mitochondrial turnover is essential for mitochondrial homoeostasis and muscle function in these patients

    Meteorin-like/ Meteorin-b protects heart against cardiac dysfunction

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    Meteorin-like/Meteorin-β (Metrnl/Metrnβ) is a secreted protein produced by skeletal muscle and adipose tissue that exerts metabolic actions that improve glucose metabolism. The role of Metrnβ in cardiac disease is completely unknown. Here, we show that Metrnβ-null mice exhibit asymmetrical cardiac hypertrophy, fibrosis, and enhanced signs of cardiac dysfunction in response to isoproterenol-induced cardiac hypertrophy and aging. Conversely, adeno-associated virus-mediated specific overexpression of Metrnβ in the heart prevents the development of cardiac remodeling. Furthermore, Metrnβ inhibits cardiac hypertrophy development in cardiomyocytes in vitro, indicating a direct effect on cardiac cells. Antibody-mediated blockage of Metrnβ in cardiomyocyte cell cultures indicated an autocrine action of Metrnβ on the heart, in addition to an endocrine action. Moreover, Metrnβ is highly produced in the heart, and analysis of circulating Metrnβ concentrations in a large cohort of patients reveals that it is a new biomarker of heart failure with an independent prognostic value

    MLPA en el estudio de desórdenes genómicos

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    El término de desórdenes genómicos se utiliza para definir aquellas condiciones que surgen por inestabilidad en la molécula de ADN y, que ocasionan, rearreglos cromosómicos que involucran regiones de uno o varios pares de megabases. Estos rearreglos determinan la pérdida, ganancia o disrupción de genes cuya expresión fenotípica varía de acuerdo a la cantidad de secuencia codificante presente (dosage- sensitive- genes). Estas anormalidades genómicas surgen predominantemente durante eventos de recombinación no alélica entre cromosomas homólogos (NAHR), aunque otros mecanismos también han sido descriptos. Los rearreglos cromosómicos ocurren en puntos de quiebra que concentran regiones inestables de la molécula de ADN como lo son las secuencias repetidas llamadas LCRs (low copy repeats) que sirven como sustrato de recombinación o los sitios palindrómicos ricos en adenina- timina. Entre los desórdenes originados por alteración en la estructura genómica se cita al síndrome de deleción/duplicación 22q11.2, que incluye varios cuadros clínicos con superposición de rasgos fenotípicos. Se estima que la variabilidad clínica en estos pacientes es consecuente con la cantidad de secuencia codificante presente en relación al tamaño de la deleción/ duplicación. El advenimiento de nuevas técnicas moleculares permite actualmente determinar con precisión el segmento delecionado/ duplicado. Una nueva metodología conocida como MLPA (multiplex ligation probe amplification) podría discriminar, para este desorden en particular, cambios en el número de copias genómicas responsables de los diferentes fenotipos. Se considera que la técnica de MLPA es una herramienta de diagnóstico complementaria, con una alta sensibilidad y especificidad en el diagnóstico de desórdenes genómicos, que permite cuantificar microdeleciones/ microduplicaciones no objetivables por otros métodos. Se espera en un futuro que el conocimiento en cuanto a los complejos mecanismos de producción de los diferentes desórdenes genómicos permita definir con claridad la existencia de una relación genotipo- fenotipo que pueda delinear a aquellas entidades con fenotipos intermedios.Fil: Ramírez, Jésica. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Genética.Fil: Echeverría, María. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Genética.Fil: Mampel, Alejandra. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Genética.Fil: Marino, Miguel. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Laboratorio de ADNFil: Gallardo, A.. Hospital Humberto Notti (Mendoza, Argentina). Servicio de CardiologíaFil: Triguy, J.. Hospital Humberto Notti (Mendoza, Argentina). Servicio de CardiologíaFil: Schroh, A.. Hospital Humberto Notti (Mendoza, Argentina). Servicio de InmunologíaFil: Arce, Cecilia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Genética.Fil: Marzese, Diego. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Genética.Fil: Calderón, Enrique. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Genética.Fil: Vargas, Ana. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Genética
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