Finding Efficient Collective Variables: The Case of Crystallization

Several enhanced sampling methods such as umbrella sampling or metadynamics rely on the identification of an appropriate set of collective variables. Recently two methods have been proposed to alleviate the task of determining efficient collective variables. One is based on linear discriminant analysis, the other on a variational approach to conformational dynamics, and uses time-lagged independent component analysis. In this paper, we compare the performance of these two approaches in the study of the homogeneous crystallization of two simple metals. We focus on Na and Al and search for the most efficient collective variables that can be expressed as a linear combination of X-ray diffraction peak intensities. We find that the performances of the two methods are very similar. However, the method based on linear discriminant analysis, in its harmonic version, is to be preferred because it is simpler and much less computationally demanding

Systematic Analysis of Gene Expression Differences between Left and Right Atria in Different Mouse Strains and in Human Atrial Tissue

Background: Normal development of the atria requires left-right differentiation during embryonic development. Reduced expression of Pitx2c (paired-like homeodomain transcription factor 2, isoform c), a key regulator of left-right asymmetry, has recently been linked to atrial fibrillation. We therefore systematically studied the molecular composition of left and right atrial tissue in adult murine and human atria. Methods: We compared left and right atrial gene expression in healthy, adult mice of different strains and ages by employing whole genome array analyses on freshly frozen atrial tissue. Selected genes with enriched expression in either atrium were validated by RT-qPCR and Western blot in further animals and in shock-frozen left and right atrial appendages of patients undergoing open heart surgery. Results: We identified 77 genes with preferential expression in one atrium that were common in all strains and age groups analysed. Independent of strain and age, Pitx2c was the gene with the highest enrichment in left atrium, while Bmp10, a member of the TGFb family, showed highest enrichment in right atrium. These differences were validated by RT-qPCR in murine and human tissue. Western blot showed a 2-fold left-right concentration gradient in PITX2 protein in adult human atria. Several of the genes and gene groups enriched in left atria have a known biological role for maintenance of healthy physiology, specifically the prevention of atrial pathologies involved in atrial fibrillation, including membrane electrophysiology, metabolic cellular function, and regulation of inflammatory processes. Comparison of the array datasets with published array analyses in heterozygous Pitx2c+/2 atria suggested that approximately half of the genes with left-sided enrichment are regulated by Pitx2c. Conclusions: Our study reveals systematic differences between left and right atrial gene expression and supports the hypothesis that Pitx2c has a functional role in maintaining ‘‘leftness’’ in the atrium in adult murine and human hearts

Self-navigation with compressed sensing for 2D translational motion correction in free-breathing coronary MRI:a feasibility study

PURPOSE: Respiratory motion correction remains a challenge in coronary magnetic resonance imaging (MRI) and current techniques, such as navigator gating, suffer from sub-optimal scan efficiency and ease-of-use. To overcome these limitations, an image-based self-navigation technique is proposed that uses "sub-images" and compressed sensing (CS) to obtain translational motion correction in 2D. The method was preliminarily implemented as a 2D technique and tested for feasibility for targeted coronary imaging. METHODS: During a 2D segmented radial k-space data acquisition, heavily undersampled sub-images were reconstructed from the readouts collected during each cardiac cycle. These sub-images may then be used for respiratory self-navigation. Alternatively, a CS reconstruction may be used to create these sub-images, so as to partially compensate for the heavy undersampling. Both approaches were quantitatively assessed using simulations and in vivo studies, and the resulting self-navigation strategies were then compared to conventional navigator gating. RESULTS: Sub-images reconstructed using CS showed a lower artifact level than sub-images reconstructed without CS. As a result, the final image quality was significantly better when using CS-assisted self-navigation as opposed to the non-CS approach. Moreover, while both self-navigation techniques led to a 69% scan time reduction (as compared to navigator gating), there was no significant difference in image quality between the CS-assisted self-navigation technique and conventional navigator gating, despite the significant decrease in scan time. CONCLUSIONS: CS-assisted self-navigation using 2D translational motion correction demonstrated feasibility of producing coronary MRA data with image quality comparable to that obtained with conventional navigator gating, and does so without the use of additional acquisitions or motion modeling, while still allowing for 100% scan efficiency and an improved ease-of-use. In conclusion, compressed sensing may become a critical adjunct for 2D translational motion correction in free-breathing cardiac imaging with high spatial resolution. An expansion to modern 3D approaches is now warranted

AL SER APLICADAS… ¿CIENCIAS BÁSICAS CAMBIÓ?

La materia Ciencias Básicas recorre una larga historia de cambios y estrategias docentes puesta al servicio del estudiante, teniendo como meta la calidad educativa en todos los contenidos que de ella dependen. Según los diferentes planes de estudio, la materia ha adaptado los contenidos y sus formas de transmitirlos de acuerdo con los requerimientos solicitados. Estas propuestas nunca tuvieron tal significatividad como los producidos este año, a raíz del cambio en el plan de estudio y la conciliación lograda por todas las cátedras del primer año de la carrera, que han decidido trabajar mancomunadamente mediante una transversalización horizontal de contenidos

Estrategias para la enseñanza remota de emergencia en la universidad. Adaptación a la virtualidad de la cátedra Ciencias Básicas Aplicadas al Diseño debido a la emergencia de la COVID-19

El período de crisis actual provocado por la emergencia de la COVID-19 ha impactado enormemente en las prácticas educativas. Tal ha sido el estado crítico de la cuestión que se ha creado, en medio de la tormenta, un nuevo concepto en educación: “Docencia No Presencial De Emergencia” o Docencia Remota de Emergencia Emergency Remote Teaching (en inglés). Se trata de un cambio temporal y abrupto de la pedagogía para adaptar la actividad educativa a un entorno virtual, debido a circunstancias de crisis y con el objetivo de garantizar —en la medida de lo posible— el aprendizaje del estudiantado (Pardo Kuklinski & Cobo, 2020). El presente trabajo aborda la temática del rediseño y adaptación de la materia Ciencias Básicas Aplicadas a un entorno virtual, desde los aportes de diversos autores que proponen lineamientos pedagógicos y técnicos para el logro de una enseñanza efectiva en contextos de emergencia

Promoção, prevenção e cuidado da hipertensão arterial no Brasil

OBJETIVO: Estimar a prevalência de ações de promoção, prevenção e cuidado da hipertensão arterial em adultos e identificar sua associação com estado descompensado de hipertensão. MÉTODOS: Estudo epidemiológico transversal de base populacional realizado por meio de entrevista com 12.324 adultos, de 20 a 59 anos, em 100 municípios brasileiros. As variáveis independentes, consideradas como promoção, prevenção e cuidado, foram: ter recebido orientações sobre a manutenção do peso ideal e sobre atividade física; ter consultado um médico e ter realizado eletrocardiograma no último ano. Pressão arterial acima de 140/90 mmHg foi considerada estado descompensado, sendo a variável dependente para a avaliação da qualidade do cuidado. RESULTADOS: Do total, 16,3% (n = 2.004) referiram diagnóstico médico de hipertensão. As maiores prevalências de hipertensão foram observadas na categoria de idade de 50 a 59 anos, concentradas nas regiões Sudeste e Centro-Oeste. Mais da metade (66,1%) esteve em consulta médica por hipertensão no último ano, da qual metade (52,4%) realizou eletrocardiograma. Dos hipertensos que tiveram sua pressão arterial aferida na entrevista (74,6%), menos da metade (42,4%) apresentava cifras tensionais descompensadas. CONCLUSÕES: Não houve associação entre haver consultado médico no último ano e cifras tensionais descompensadas. A proporção de hipertensos descompensados foi significativamente menor entre os que foram orientados para manter o peso ideal, realizar atividade física e os que fizeram eletrocardiograma. Ser do sexo masculino, ter idade acima de 40 anos e habitar na região Sul mostraram-se associados a estado descompensado da hipertensão.OBJECTIVE: To estimate the prevalence of promotion, prevention and arterial hypertension care actions in adults and to identify their association with decompensated hypertension. METHODS: A population-based cross-sectional epidemiological study was conducted by interviewing 12,324 adults aged from 20 to 59 years, in 100 Brazilian cities. The independent variables considered as promotion, prevention and hypertension care were as follows: to have received guidance on ideal weight maintenance and physical activity practice; to have consulted a doctor; and to have had an electrocardiogram performed in the previous year. A blood pressure higher than 140/90 mm/Hg was considered to be decompensated, being the dependent variable adopted to assess quality of care. RESULTS: Of all participants, 16.3% (n = 2,004) reported a medical diagnosis of hypertension. The highest prevalences of hypertension were observed in the 50 to 59 year age group, primarily in the Southeast and Center-West regions. More than half (66.1%) of participants had a medical consultation about hypertension in the previous year, of which half (52.4%) had an electrocardiogram. Of all those with hypertension who had their blood pressure measured during interview (74.6%), less than half (42.4%) had decompensated values. CONCLUSIONS: There was no association between having consulted a doctor in the previous year and decompensated blood pressure values. The proportion of decompensated hypertensive participants was significantly lower among those who had received guidance on ideal weight maintenance and physical activity practice and those who had had an electrocardiogram performed. The following factors were associated with decompensated hypertension: to be male, to be aged more than 40 years and to live in the South region.OBJETIVO: Estimar la prevalencia de acciones de promoción, prevención y cuidado de la hipertensión arterial en adultos e identificar la asociación con el estado descompensado de hipertensión. MÉTODOS: Estudio epidemiológico transversal de base poblacional realizado a través de entrevista en 12.324 adultos, de 20 a 59 años, en 100 municipios brasileños. Las variables independientes, consideradas como promoción, prevención y cuidado fueron: haber recibido orientaciones sobre la manutención del peso ideal y actividad física; haber consultado un médico y haber realizado el electrocardiograma en el último año. Presión arterial por encima de 140/90 mm/Hg se consideró estado descompensado, siendo la variable dependiente para la evaluación de la calidad del cuidado. RESULTADOS: del total, 16,3% (n= 2.004) refirieron diagnóstico médico de hipertensión. Las mayores prevalencias de hipertensión se observaron en la categoría de edad de 50 a 59 años, concentradas en las regiones Sureste y Centro-Oeste. Más de la mitad (66,1%) estuvo en consulta médica por hipertensión en el último año, y la mitad de estos (52,4%) realizó electrocardiograma. De los hipertensos que chequearon la presión arterial en la entrevista, 74,6%, menos de la mitad (42,4%) presentó cifras tensionales descompensadas. CONCLUSIONES: No hubo asociación entre haber consultado el médico en el último año y cifras tensionales descompensadas. La proporción de hipertensos descompensados fue significativamente menor entre los que fueron orientados para mantener el peso ideal, realizar actividad física y los que hicieron electrocardiograma. Ser del sexo masculino, tener edad por encima de 40 años y habitar en la región Sur, se evidenciaron asociados al estado descompensado de la hipertensión

The role of antioxidants in the interplay between oxidative stress and senescence

Cellular senescence is an irreversible state of cell cycle arrest occurring in response to stressful stimuli, such as telomere attrition, DNA damage, reactive oxygen species, and oncogenic proteins. Although beneficial and protective in several physiological processes, an excessive senescent cell burden has been involved in various pathological conditions including aging, tissue dysfunction and chronic diseases. Oxidative stress (OS) can drive senescence due to a loss of balance between pro-oxidant stimuli and antioxidant defences. Therefore, the identification and characterization of antioxidant compounds capable of preventing or counteracting the senescent phenotype is of major interest. However, despite the considerable number of studies, a comprehensive overview of the main antioxidant molecules capable of counteracting OS-induced senescence is still lacking. Here, besides a brief description of the molecular mechanisms implicated in OS-mediated aging, we review and discuss the role of enzymes, mitochondria-targeting compounds, vitamins, carotenoids, organosulfur compounds, nitrogen non-protein molecules, minerals, flavonoids, and non-flavonoids as antioxidant compounds with an anti-aging potential, therefore offering insights into innovative lifespan-extending approaches

The Potential Role of Gut Microbiota in Alzheimer’s Disease: from Diagnosis to Treatment

Gut microbiota is emerging as a key regulator of many disease conditions and its dysregulation is implicated in the pathogenesis of several gastrointestinal and extraintestinal disorders. More recently, gut microbiome alterations have been linked to neurodegeneration through the increasingly defined gut microbiota brain axis, opening the possibility for new microbiota-based therapeutic options. Although several studies have been conducted to unravel the possible relationship between Alzheimer’s Disease (AD) pathogenesis and progression, the diagnostic and therapeutic potential of approaches aiming at restoring gut microbiota eubiosis remain to be fully addressed. In this narrative review, we briefly summarize the role of gut microbiota homeostasis in brain health and disease, and we present evidence for its dysregulation in AD patients. Based on these observations, we then discuss how dysbiosis might be exploited as a new diagnostic tool in early and advanced disease stages, and we examine the potential of prebiotics, probiotics, fecal microbiota transplantation, and diets as complementary therapeutic interventions on disease pathogenesis and progression, thus offering new insights into the diagnosis and treatment of this devastating and progressive disease