59 research outputs found

    Genetic ablation of ryanodine receptor 2 phosphorylation at Ser‐2808 aggravates Ca 2+ ‐dependent cardiomyopathy by exacerbating diastolic Ca 2+ release

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    Phosphorylation of the cardiac ryanodine receptor (RyR2) by protein kinase A (PKA) at Ser‐2808 is suggested to mediate the physiological ‘fight or flight’ response and contribute to heart failure by rendering the sarcoplasmic reticulum (SR) leaky for Ca 2+ . In the present study, we examined the potential role of RyR2 phosphorylation at Ser‐2808 in the progression of Ca 2+ ‐dependent cardiomyopathy (CCM) by using mice genetically modified to feature elevated SR Ca 2+ leak while expressing RyR2s that cannot be phosphorylated at this site (S2808A). Surprisingly, rather than alleviating the disease phenotype, constitutive dephosphorylation of Ser‐2808 aggravated CCM as manifested by shortened survival, deteriorated in vivo cardiac function, exacerbated SR Ca 2+ leak and mitochondrial injury. Notably, the deteriorations of cardiac function, myocyte Ca 2+ handling, and mitochondria integrity were consistently worse in mice with heterozygous ablation of Ser‐2808 than in mice with complete ablation. Wild‐type (WT) and CCM myocytes expressing unmutated RyR2s exhibited a high level of baseline phosphorylation at Ser‐2808. Exposure of these CCM cells to protein phosphatase 1 caused a transitory increase in Ca 2+ leak attributable to partial dephosphorylation of RyR2 tetramers at Ser‐2808 from more fully phosphorylated state. Thus, exacerbated Ca 2+ leak through partially dephosphorylated RyR2s accounts for the prevalence of the disease phenotype in the heterozygous S2808A CCM mice. These results do not support the importance of RyR2 hyperphosphorylation in Ca 2+ ‐dependent heart disease, and rather suggest roles for the opposite process, the RyR2 dephosphorylation at this residue in physiological and pathophysiological Ca 2+ signalling.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106986/1/tjp6067.pd

    Preferences, use of and satisfaction with mental health services among a sample of Puerto Rican cancer patients

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    OBJECTIVE: The purpose of this study was to describe the preferences, the use, satisfaction of mental health services (MHS) among a sample of Puerto Rican patients with cancer undergoing oncology treatment. METHODS: A convenience sample of 120 patients diagnosed with cancer was recruited. Self-report questionnaires assessed socio-demographic and background questions, and the Mental Health Service Preference, Utilization and Satisfaction Questionnaire (MHSPUS). The Socio-demographic and Background Questionnaire inquired about participants\u27 demographic and socioeconomic characteristics, and included questions such as history of psychiatric diagnosis and spiritual practices. Univariate and Chi square analyses were used for descriptive purposes. Logistic regressions were used to explore associations between sociodemographic factors and MHS preferences and use. RESULTS: The majority of the sample were females (53.8%), 61 and older (53.8%), and married or living with partner (57.1%), and reported an income equal to or less than $12,000 per year (44.4%), which places them under the US federal poverty line. Most of the participants (66.7%) reported being receptive to seeking services. Findings showed a significant association between living situation and past (p \u3c .05) and lifetime use (p \u3c .05) of MHS and past use of MHS. Participants living alone were more like to have used MHS in the past and during their lifetime. Adjusted logistic regression analyses revealed that living with someone was a protective factor for not using MHS in their lifetime (OR = 0.28; C1 = 0.08-0.95). Participants preferred to receive MHS at the oncology clinic, preferably on the date of their oncology appointments and during morning hours. CONCLUSION: Findings support the integration of mental health services within the oncology practice setting

    Functional Characterization of Nupr1L, A Novel p53-Regulated Isoform of the High-Mobility Group (HMG)-Related Protumoral Protein Nupr1

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    We have previously demonstrated a crucial role of nuclear protein 1 (NUPR1) in tumor development and progression. In this work, we report the functional characterization of a novel Nupr1-like isoform (NUPR1L) and its functional interaction with the protumoral factor NUPR1. Through the use of primary sequence analysis, threading, and homology-based molecular modeling, as well as expression and immunolocalization, studies reveal that NUPR1L displays properties, which are similar to member of the HMG-like family of chromatin regulators, including its ability to translocate to the cell nucleus and bind to DNA. Analysis of the NUPR1L promoter showed the presence of two p53-response elements at positions -37 and -7, respectively. Experiments using reporter assays combined with site-directed mutagenesis and using cells with controllable p53 expression demonstrate that both of these sequences are responsible for the regulation of NUPR1L expression by p53. Congruently, NUPR1L gene expression is activated in response to DNA damage induced by oxaliplatin treatment or cell cycle arrest induced by serum starvation, two well-validated methods to achieve p53 activation. Interestingly, expression of NUPR1L downregulates the expression of NUPR1, its closely related protumoral isoform, by a mechanism that involves the inhibition of its promoter activity. At the cellular level, overexpression of NUPR1L induces G1 cell cycle arrest and a decrease in their cell viability, an effect that is mediated, at least in part, by downregulating NUPR1 expression. Combined, these experiments constitute the first functional characterization of NUPR1L as a new p53-induced gene, which negatively regulates the protumoral factor NUPR1.Fil: Lopez, Maria Belen. Centre de Recherche En Cancerologie de Marseille; FranciaFil: Garcia, Maria Noé. Centre de Recherche En Cancerologie de Marseille; FranciaFil: Grasso, Daniel Hector. Centre de Recherche En Cancerologie de Marseille; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bintz, Jennifer. Centre de Recherche En Cancerologie de Marseille; FranciaFil: Molejon, Maria Ines. Centre de Recherche En Cancerologie de Marseille; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Velez, Gabriel. Mayo Clinic; Estados UnidosFil: Lomberk, Gwen. Mayo Clinic; Estados UnidosFil: Neira, Jose Luis. Universidad de Miguel Hernández; EspañaFil: Urrutia, Raul. Mayo Clinic; Estados UnidosFil: Iovanna, Juan. Centre de Recherche En Cancerologie de Marseille; Franci

    Brief Report: Hispanic Patients\u27 Trajectory of Cancer Symptom Burden, Depression, Anxiety, and Quality of Life

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    Background: Anxiety and depression symptoms are known to increase cancer symptom burden, yet little is known about the longitudinal integrations of these among Hispanic/Latinx patients. The goal of this study was to explore the trajectory and longitudinal interactions among anxiety and depression, cancer symptom burden, and health-related quality of life in Hispanic/Latinx cancer patients undergoing chemotherapy. METHODS: Baseline behavioral assessments were performed before starting chemotherapy. Follow-up behavioral assessments were performed at 3, 6, and 9 months after starting chemotherapy. Descriptive statistics, chi-square tests, Fisher\u27s exact tests, and Mann-Whitney tests explored associations among outcome variables. Adjusted multilevel mixed-effects linear regression models were also used to evaluate the association between HADS scores, follow-up visits, FACT-G scale, MDASI scale, and sociodemographic variables. RESULTS: Increased cancer symptom burden was significantly related to changes in anxiety symptoms\u27 scores (adjusted beta^ = 0.11 [95% CI: 0.02, 0.19]. Increased quality of life was significantly associated with decreased depression and anxiety symptoms (adjusted beta^ = -0.33; 95% CI: -0.47, -0.18, and 0.38 adjusted beta^= -0.38; 95% CI: -0.55, -0.20, respectively). CONCLUSIONS: Findings highlight the need to conduct periodic mental health screenings among cancer patients initiating cancer treatment

    Ciencias de la Biología y Agronomía

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    Este volumen I contiene 17 capítulos arbitrados que se ocupan de estos asuntos en Tópicos Selectos de Ciencias de la Biología y Agronomía, elegidos de entre las contribuciones, reunimos algunos investigadores y estudiantes. Se presenta un Estudio Comparativo de los Recursos Hidrológico-Forestales de la Microcuenca de la Laguna de Epatlan, Pue. (1993 a 2014); la Situación Actual de la Mancha de Asfalto en Maíz (Zea mays L.) en los Municipios de Jiquipilas y Ocozocoautla, Chiapas, México; las poblaciones sobresalientes de maíz de la raza Zapalote Chico, en la Región Istmeña de Oaxaca; Se indica el índice de área foliar de cultivo de Chile Poblano mediante dos métodos en condiciones protegidas; Esquivel, Urzúa y Ramírez exploran el efecto de la biofertilización con Azospirillum en el crecimiento y producción de Jitomate; esbozan su artículo sobre la determinación del nivel de Heterosis en híbridos de Maíz para la Comarca Lagunera; una investigación sobre la estabilización de semilla de Solanum lycopersicum durante el almacenamiento y estimulación de la germinación; acotan sobre el CTAB como una nueva opción para la detección de Huanglongbing en cítricos, plantean su evaluación sobre el aluminio y cómo afecta la vida de florero de Heliconia psittacorum; indican sobre el impacto del H-564C, como un híbrido de maíz con alta calidad de proteina para el trópico húmedo de México; presetan su investigación sobre la producción de Piña Cayena Lisa y MD2 (Ananas comosus L.) en condiciones de Loma Bonita, en Oaxaca; acotan sobre el efecto de coberteras como control biológico por conservación contra áfidos en Nogal Pecanero; esbozan sobre la caracterización de cuatro genotipos de Frijol Negro en Martínez de la Torre, Veracruz, México; presentan una caracterización hidroecológica de la microcuenca de Arroyo Prieto, Yuriría, Gto., y alternativas para su restauración ambiental; presentan su investigación sobre el efecto del hongo Beauveria bassiana sobre solubilización de fosfatos y la disponibilidad de fósforo en el suelo; plantean su investigación sobre la Germinación y regeneración in vitro de Epidendrum falcatum LINDL; esbozan su artículo sobre genotipos de frijol negro y su tolerancia a sequía terminal en Veracruz, México

    Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

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    Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

    Study of Failure Causes of Drives Under Industrial Environments

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    En el presente trabajo se determinan las causas más comunes por las cuales los variadores de frecuencia fallan desde el punto de vista de la calidad de la energía eléctrica, todo esto con los objetivos de plantear posibles causas de mal funcionamiento en los variadores de frecuencia, identificar los fallos recurrentes mediante el análisis de casos de estudio, Formular soluciones preventivas a las fallas presentes en dichos dispositivos, encontrar estrategias para la solución de problemas, abordar los inconvenientes típicos causados por mala instalación y configuración de variadores de frecuencia.In this paper the most common reasons why the inverters fail from the point of view of the quality of electric power are determined, all with the goals of raising possible causes of malfunction frequency inverters, identify recurrent faults by analyzing case studies, formulate preventive faults present in these devices solutions, finding strategies for problem solving, addressing the typical inconveniences caused by improper installation and configuration of inverters.ROCKWELL AUTOMATIO
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