RESUMEN
The helicase MCM and the ribonucleotide reductase RNR are the complexes that provide the substrates (ssDNA templates and dNTPs, respectively) for DNA replication. Here, we demonstrate that MCM interacts physically with RNR and some of its regulators, including the kinase Dun1. These physical interactions encompass small subpopulations of MCM and RNR, are independent of the major subcellular locations of these two complexes, augment in response to DNA damage and, in the case of the Rnr2 and Rnr4 subunits of RNR, depend on Dun1. Partial disruption of the MCM/RNR interactions impairs the release of Rad52 -but not RPA-from the DNA repair centers despite the lesions are repaired, a phenotype that is associated with hypermutagenesis but not with alterations in the levels of dNTPs. These results suggest that a specifically regulated pool of MCM and RNR complexes plays non-canonical roles in genetic stability preventing persistent Rad52 centers and hypermutagenesis.
Asunto(s)
Proteínas de Ciclo Celular , Daño del ADN , Reparación del ADN , Replicación del ADN , Inestabilidad Genómica , Proteína Recombinante y Reparadora de ADN Rad52 , Ribonucleótido Reductasas , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Replicación del ADN/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Daño del ADN/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Proteína Recombinante y Reparadora de ADN Rad52/metabolismo , Proteína Recombinante y Reparadora de ADN Rad52/genética , Ribonucleótido Reductasas/genética , Ribonucleótido Reductasas/metabolismo , Reparación del ADN/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , ADN Helicasas/genética , ADN Helicasas/metabolismo , Proteínas de Mantenimiento de Minicromosoma/metabolismo , Proteínas de Mantenimiento de Minicromosoma/genética , Proteína de Replicación A/metabolismo , Proteína de Replicación A/genética , Ribonucleósido Difosfato Reductasa/genética , Ribonucleósido Difosfato Reductasa/metabolismoRESUMEN
Circuit design for quantum machine learning remains a formidable challenge. Inspired by the applications of tensor networks across different fields and their novel presence in the classical machine learning context, one proposed method to design variational circuits is to base the circuit architecture on tensor networks. Here, we comprehensively describe tensor-network quantum circuits and how to implement them in simulations. This includes leveraging circuit cutting, a technique used to evaluate circuits with more qubits than those available on current quantum devices. We then illustrate the computational requirements and possible applications by simulating various tensor-network quantum circuits with PennyLane, an open-source python library for differential programming of quantum computers. Finally, we demonstrate how to apply these circuits to increasingly complex image processing tasks, completing this overview of a flexible method to design circuits that can be applied to industrially-relevant machine learning tasks.
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Unscheduled R loops can be a source of genome instability, a hallmark of cancer cells. Although targeted proteomic approaches and cellular analysis of specific mutants have uncovered factors potentially involved in R-loop homeostasis, we report a more open screening of factors whose depletion causes R loops based on the ability of activation-induced cytidine deaminase (AID) to target R loops. Immunofluorescence analysis of γH2AX caused by small interfering RNAs (siRNAs) covering 3,205 protein-coding genes identifies 59 potential candidates, from which 13 are analyzed further and show a significant increase of R loops. Such candidates are enriched in factors involved in chromatin, transcription, and RNA biogenesis and other processes. A more focused study shows that the DDX47 helicase is an R-loop resolvase, whereas the MeCP2 methyl-CpG-binding protein uncovers a link between DNA methylation and R loops. Thus, our results suggest that a plethora of gene dysfunctions can alter cell physiology via affecting R-loop homeostasis by different mechanisms.
Asunto(s)
Proteómica , Estructuras R-Loop , Humanos , Cromatina , Cromosomas/metabolismo , ADN Helicasas/metabolismo , Inestabilidad GenómicaRESUMEN
The aim of this study was to study different 'healthy profiles' through the impact of multiple lifestyle behaviours (sleep patterns, screen time and quality diet) on active commuting to school (ACS) in adolescents. Sixteen secondary schools from four Spanish cities were randomly selected. All participants filled in an "Ad-Hoc" questionnaire to measure their mode of commuting and distance from home to school and their lifestyle behaviours. A multivariate logistic regression model was performed to analyse the main predictor variables of ACS. The final sample was 301 adolescents (50.2% girls; mean age ± SD: 14.9 ± 0.48 years). The percentage of ACS was 64.5%. Multiple logistic regressions showed: boys were more active commuters than girls [OR = 2.28 (CI 95%: 1.12−4.64); p = 0.02]; adolescents who lived farther had lower probability to ACS [OR = 0.74 (CI 95%: 0.69−0.80); p < 0.001]; adolescents who met sleep duration recommendations were more likely to ACS [OR = 3.05 (CI 95%: 1.07−8.69); p = 0.04], while with each hour of sleep, the odds of ACS was reduced [OR = 0.51 (CI 95%: 0.30−0.89); p = 0.02]; higher odds were shown to ACS in adolescents who have more adherence to MD [OR = 1.16(CI 95%: 1.00−1.33); p = 0.05]; and habitual breakfast consumption was inversely associated with ACS [OR = 0.41 (CI: 95%: 0.18−0.96); p = 0.04]. ACS was associated with being a boy, living at a shorter distance to school, a daily sleep time ≥ 8 h and presented a higher adherence to MD.
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Purpose: To describe the experience of obese adults following participation in an indoor aerobic interval training (AIT) intervention. Methodology: Qualitative, in-depth semi-structured individual interviews, using phenomenology, with 24 obese adults (body mass index (BMI) ≥30 kg/m2) from the Endocrinology Department, at the Severo Ochoa Hospital in Leganés (Madrid). Questions were related to: (a) The physical activity (PA) programme, (b) their perspectives of the activity and exercise environment and (c) the perceived benefits from participation. Data were analysed with a constant comparison approach. Results: The main patients' reasons for beginning the programme were motivations to take part including weight loss, health improvement and doctors' recommendation. Also, patients showed doubts and feelings of apprehension at the beginning of the intervention. Patients highlighted the role of the instructor, feelings of exercising in a safe environment, a good intervention and accessibility of the facility. They reported an improvement in their quality of life and recommended continuing the program. Conclusions: (1) Common themes in the qualitative analysis included enjoyment of the activity and a desire to maintain physical fitness, (2) AIT was perceived as a suitable exercise programme for this population and (3) recommendations for further investigation to understand the role of PA programmes for people with obesity.
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Ejercicio Físico/fisiología , Hospitales , Obesidad/terapia , Adulto , Índice de Masa Corporal , Femenino , Humanos , Masculino , Motivación , Pacientes Ambulatorios , Aptitud Física , Calidad de Vida , Pérdida de PesoRESUMEN
No disponible
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Humanos , Femenino , Persona de Mediana Edad , Vasos Linfáticos/cirugía , Linfedema/cirugía , Microcirugia/métodos , Anastomosis Quirúrgica/métodos , Venas/cirugíaRESUMEN
Wegener granulomatosis (WG) is a necrotizing vasculitis that involves the upper respiratory tract, the lungs, and the kidneys. It also causes deformities of the nose in practically all patients, altering the cartilaginous and bony structure as well as the inner lining of the nose.The surgical repair of these nasal distortions is a challenge mainly due to the impairment of wound healing and graft take that is caused both by the disease itself and by the prolonged immunosuppressant treatment.Many different reconstruction plans have been developed, using costal or calvarial bone grafts, cartilage grafts and local skin and mucosa flaps. Results have been diverse.The authors present the case of a 56-year-old patient who suffered from WG and consulted for nasal sequelae. She initially underwent several failed attempts at reconstruction; finally, the authors performed a nasal repair using a double strip of fascia lata as a dorsal graft, with no complications and a good aesthetic result.Fascia lata graft is a new and good option for nasal reconstruction in patients with WG because it is easily obtainable, it can be set in place through closed rhinoplasty and it can achieve good vascularization with low risk of resorption or disease reactivation.
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Fascia Lata/trasplante , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/cirugía , Deformidades Adquiridas Nasales/etiología , Deformidades Adquiridas Nasales/cirugía , Rinoplastia/métodos , Femenino , Humanos , Persona de Mediana Edad , Colgajos QuirúrgicosRESUMEN
INTRODUCTION: Sarcopenic obesity (SO) is a term that refers to an increase of fat mass together with a decrease of muscle mass, which is suffered by a high percentage of elderly population. Physical activity seems to be a good strategy to prevent it getting worse. However, genetic factors related to the aging process and to elderly's physical fitness could have an influence on it. AIM: To determine if elderly women > 60 who practice physical activity regularly had differences in sarcopenic obesity according to the I/D polymorphism from the ACE (angiotensin converter enzyme) gen. METHODS: Cross-sectional study of 300 elderly women who have practiced physical exercise at least twice a week for the past two years. Anthropometric data, physical activity and sedentary behaviour questionnaire, sarcopenic obesity (determining the percentage of fat mass and total muscle mass by electrical impedance and grouping the quintiles of these values into four groups) and physical fitness assessment, as well as ACE gen genotype measured by oral mucosa sample, were evaluated. RESULTS: There were significant differences (p < 0.05) in sarcopenic obesity according to ACE I/D genotype (SO values: 2.18 ACE DD vs 2.48 ACE II + ACE ID). CONCLUSIONS: Women who were ACE DD presented lower risk of sarcopenic obesity than those in the ACE II and ACE ID groups.
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Obesidad/genética , Peptidil-Dipeptidasa A/genética , Sarcopenia/genética , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Aptitud Física , Polimorfismo Genético/genéticaRESUMEN
Introducción: la obesidad sarcopénica (OS) es un término que relaciona el aumento de la masa grasa con la disminución de la masa muscular y que afecta a un importante porcentaje de población mayor. La falta de ejercicio regular y factores genéticos relacionados con el envejecimiento y la condición física podrían influir en su aparición. Objetivo: determinar si las mujeres mayores de 60 años que practican de forma continuada ejercicio físico presentan diferencias en la obesidad sarcopénica en función del polimorfismo I/D del gen de la enzima convertidora de angiotensina (ACE). Métodos: estudio transversal de 300 mujeres mayores que realizaban ejercicio físico al menos dos veces a la semana en los últimos dos años. Se tomaron datos de medidas antropométricas, cuestionario de comportamiento actividad-sedentarismo, evaluación de la obesidad sarcopénica (a través de la determinación del porcentaje de masa grasa y masa muscular total mediante impedancia eléctrica y la agrupación de los quintiles de estos valores en cuatro grupos), evaluación de la condición física y genotipado del gen ACE mediante extracción de ADN de mucosa oral. Resultados: se encontraron diferencias significativas en la obesidad sarcopénica en función del genotipo I/D de ACE. Las mujeres del grupo ACE DD presentaron menor riesgo de padecer obesidad sarcopénica que aquellas con genotipo ACE II y ACE ID (valores OS: 2.18 genotipo ACE DD frente a 2.48 genotipo ACE II + ACE ID; p < 0,05). Conclusiones: las mujeres mayores de 60 años con genotipo ACE DD que practican ejercicio regularmente presentan menor riesgo de padecer obesidad sarcopénica (AU)
Introduction: Sarcopenic obesity (SO) is a term that refers to an increase of fat mass together with a decrease of muscle mass, which is suffered by a high percentage of elderly population. Physical activity seems to be a good strategy to prevent it getting worse. However, genetic factors related to the aging process and to elderly's physical fitness could have an influence on it. Aim: To determine if elderly women > 60 who practice physical activity regularly had differences in sarcopenic obesity according to the I/D polymorphism from the ACE (angiotensin converter enzyme) gen. Methods: Cross-sectional study of 300 elderly women who have practiced physical exercise at least twice a week for the past two years. Anthropometric data, physical activity and sedentary behaviour questionnaire, sarcopenic obesity (determining the percentage of fat mass and total muscle mass by electrical impedance and grouping the quintiles of these values into four groups) and physical fitness assessment, as well as ACE gen genotype measured by oral mucosa sample, were evaluated. Results: There were significant differences (p < 0.05) in sarcopenic obesity according to ACE I/D genotype (SO values: 2.18 ACE DD vs 2.48 ACE II + ACE ID). Conclusions: Women who were ACE DD presented lower risk of sarcopenic obesity than those in the ACE II and ACE ID groups (AU)
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Humanos , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Obesidad/complicaciones , Obesidad/dietoterapia , Sarcopenia/complicaciones , /administración & dosificación , Ejercicio Físico , Polimorfismo Genético/fisiología , Antropometría/métodos , Estilo de Vida , 28599RESUMEN
Introducción: Parece necesario educar a los pacientes en la importancia de realizar AF para mejorar su salud, y específicamente, sobre las implicaciones que la intensidad de la AF tiene para la salud. Objetivo: El propósito de este estudio fue evaluar si se cumplían las recomendaciones de actividad física (AF) para la salud en un grupo de pacientes hipertensos controlados de dos centros de atención primaria: La Estación y La Algodonera, situados en Talavera de la Reina (Toledo). Métodos: Diseño: Estudio descriptivo transversal. Emplazamiento: Centros de atención primaria «La Estación» y «La Algodonera», situados en Talavera de la Reina. Participantes: Un total de 80 pacientes hipertensos controlados de 40 a 60 años que cumplían los criterios de inclusión, fueron invitados a formar parte en el estudio, de los cuales fueron analizados los resultados válidos de 52 pacientes. Mediciones principales: Se cuantificó la actividad física diaria con acelerometría, obteniéndose los minutos de AF a intensidad de moderada a vigorosa (AFMV) y de actividad ligera, y el número de pasos. Los datos se presentaron diferenciando los días laborables y los días festivos. Resultados: Sólo un 59,6 % de los sujetos de la muestra cumplía la recomendación de realizar un mínimo de 30 minutos de AF de intensidad de moderada a vigorosa al día para la mejora de la salud. Los hombres realizaron significativamente más minutos de AFMV en los días festivos que las mujeres, y solamente las mujeres, mostraron diferencias significativas en los minutos de AFMV entre en los días laborables respecto a los festivos. Conclusiones: El 59,6% de los pacientes hipertensos controlados de esta muestra cumplían con las recomendaciones mínimas de AF para la salud; el resto debería incrementar su AF para cumplir las recomendaciones y con ello mejorar sus niveles de tensión arterial (AU)
Introduction: It seems necessary to educate patients in the need of realize the importance of physical activity to improve their health, and specifically, about the important implications that the intensity of physical activity has for health and fitness benefits. Objective: The aim of this was to evaluate achievement of physical activity recommendations for health in a group of hypertensive controlled patients from two primary care centers: La Estación y La Algodonera located in Talavera de la Reina (Toledo). Methods: Design: Cross-sectional study. Location: Primary care centers: La Estación y La Algodonera located in Talavera de la Reina. Participants: A total of 80 controlled hypertensive patients aged 40 to 60 years old who met the inclusion criteria were invited to the study. A sample of 52 patients obtained valid results to enter the study. Main measures: Minutes of Moderate to vigorous physical activity (MVPA), minutes of light activity and number steps were measured. Data was displayed by gender and weekdays vs weekend days. Results: Only 59.6% of patients achieved the minimum recommendation of 30 minutes of MVPA at least every day to improve health. Male achieved significantly more MVPA during the weekend than female did. Only women presented significant differences between MVPA during week days vs weekend days. Conclusions: 59.6% of hypertensive controlled patients of our sample achieve the minimal physical activity recommendations for health; the rest of the sample should increase their physical activity to achieve the recommendation and to improve their blood pressure levels (AU)
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Humanos , Masculino , Femenino , Adulto , Anciano , Persona de Mediana Edad , Hipertensión/terapia , Ejercicio Físico , Guías como Asunto , Presión Sanguínea , Estudios Transversales , Educación del Paciente como AsuntoRESUMEN
INTRODUCTION: It seems necessary to educate patients in the need of realize the importance of physical activity to improve their health, and specifically, about the important implications that the intensity of physical activity has for health and fitness benefits. OBJECTIVE: The aim of this was to evaluate achievement of physical activity recommendations for health in a group of hypertensive controlled patients from two primary care centers: La Estación y La Algodonera located in Talavera de la Reina (Toledo). DESIGN: Cross-sectional study. LOCATION: Primary care centers: La Estación y La Algodonera located in Talavera de la Reina. PARTICIPANTS: A total of 80 controlled hypertensive patients aged 40 to 60 years old who met the inclusion criteria were invited to the study. A sample of 52 patients obtained valid results to enter the study. MAIN MEASURES: Minutes of Moderate to vigorous physical activity (MVPA), minutes of light activity and number steps were measured. Data was displayed by gender and weekdays vs weekend days. RESULTS: Only 59.6% of patients achieved the minimum recommendation of 30 minutes of MVPA at least every day to improve health. Male achieved significantly more MVPA during the weekend than female did. Only women presented significant differences between MVPA during week days vs weekend days. CONCLUSIONS: 59.6% of hypertensive controlled patients of our sample achieve the minimal physical activity recommendations for health; the rest of the sample should increase their physical activity to achieve the recommendation and to improve their blood pressure levels.
Introducción: Parece necesario educar a los pacientes en la importancia de realizar AF para mejorar su salud, y específicamente, sobre las implicaciones que la intensidad de la AF tiene para la salud. Objetivo: El propósito de este estudio fue evaluar si se cumplían las recomendaciones de actividad física (AF) para la salud en un grupo de pacientes hipertensos controlados de dos centros de atención primaria: La Estación y La Algodonera, situados en Talavera de la Reina (Toledo). Métodos: Diseño: Estudio descriptivo transversal. Emplazamiento: Centros de atención primaria "La Estación" y "La Algodonera", situados en Talavera de la Reina. Participantes: Un total de 80 pacientes hipertensos controlados de 40 a 60 años que cumplían los criterios de inclusión, fueron invitados a formar parte en el estudio, de los cuales fueron analizados los resultados válidos de 52 pacientes. Mediciones principales: Se cuantificó la actividad física diaria con acelerometría, obteniéndose los minutos de AF a intensidad de moderada a vigorosa (AFMV) y de actividad ligera, y el número de pasos. Los datos se presentaron diferenciando los días laborables y los días festivos. Resultados: Sólo un 59,6 % de los sujetos de la muestra cumplía la recomendación de realizar un mínimo de 30 minutos de AF de intensidad de moderada a vigorosa al día para la mejora de la salud. Los hombres realizaron significativamente más minutos de AFMV en los días festivos que las mujeres, y solamente las mujeres, mostraron diferencias significativas en los minutos de AFMV entre en los días laborables respecto a los festivos. Conclusiones: El 59,6% de los pacientes hipertensos controlados de esta muestra cumplían con las recomendaciones mínimas de AF para la salud; el resto debería incrementar su AF para cumplir las recomendaciones y con ello mejorar sus niveles de tensión arterial.