Tunable phenotypic variability through an autoregulatory alternative sigma factor circuit.

Genetically identical individuals in bacterial populations can display significant phenotypic variability. This variability can be functional, for example by allowing a fraction of stress prepared cells to survive an otherwise lethal stress. The optimal fraction of stress prepared cells depends on environmental conditions. However, how bacterial populations modulate their level of phenotypic variability remains unclear. Here we show that the alternative sigma factor σV circuit in Bacillus subtilis generates functional phenotypic variability that can be tuned by stress level, environmental history and genetic perturbations. Using single-cell time-lapse microscopy and microfluidics, we find the fraction of cells that immediately activate σV under lysozyme stress depends on stress level and on a transcriptional memory of previous stress. Iteration between model and experiment reveals that this tunability can be explained by the autoregulatory feedback structure of the sigV operon. As predicted by the model, genetic perturbations to the operon also modulate the response variability. The conserved sigma-anti-sigma autoregulation motif is thus a simple mechanism for bacterial populations to modulate their heterogeneity based on their environment.

Synergy with TGFß ligands switches WNT pathway dynamics from transient to sustained during human pluripotent cell differentiation.

WNT/ß-catenin signaling is crucial to all stages of life. It controls early morphogenetic events in embryos, maintains stem cell niches in adults, and is dysregulated in many types of cancer. Despite its ubiquity, little is known about the dynamics of signal transduction or whether it varies across contexts. Here we probe the dynamics of signaling by monitoring nuclear accumulation of ß-catenin, the primary transducer of canonical WNT signals, using quantitative live cell imaging. We show that ß-catenin signaling responds adaptively to constant WNT signaling in pluripotent stem cells, and that these dynamics become sustained on differentiation. Varying dynamics were also observed in the response to WNT in commonly used mammalian cell lines. Signal attenuation in pluripotent cells is observed even at saturating doses, where ligand stability does not affect the dynamics. TGFß superfamily ligands Activin and BMP, which coordinate with WNT signaling to pattern the gastrula, increase the ß-catenin response in a manner independent of their ability to induce new WNT ligand production. Our results reveal how variables external to the pathway, including differentiation status and cross-talk with other pathways, dramatically alter WNT/ß-catenin dynamics.

Patrones de descanso, actividades físico-deportivas extraescolares y rendimiento académico en niños y niñas de primaria / Night-rest patterns, extracurricular sports activities and academic achievement in primary education students / Padrões de descanso, actividades físico-desportivas extra-escolares e rendimento académico em rapazes e rapa-rigas no 1º ciclo

The aim of this paper was to study the connection between students’ rest patterns (appropriate and inappropriate), accumulated hours of extracurricular physical and sports activities, and the academic results of primary school students. The sample includes 573 primary school students from Barcelona and the Balearic Islands (54.62% boys and 45.38% girls). An ad hoc questionnaire gathering both quantitative and qualitative data regarding sociodemographic and psychoeducational questions concerning rest patterns and extracurricular activities was completed by the parents. The study shows that the best academic marks were found as a result of both proper rest patterns and moderate after school exercise (2 to 5 hours a week). The study further reveals that the worst school grades were obtained in cases of inadequate rest patterns combined with a high number of hours of extracurricular sports activities (more than 5 hours a week)

El objetivo del trabajo consiste en estudiar si existe una relación entre patrones de descanso (adecuados e inadecuados), realización de determinado número de horas de actividades físico-deportivas extraescolares, y rendimiento académico en una muestra de 573 alumnos de primaria (54.62% niños y 45.38% niñas) de las provincias de Barcelona e Illes Balears. Un cuestionario con preguntas concernientes a aspectos sociodemográficos y preguntas específicas sobre evaluación cuantitativa y cualitativa del sueño y registro cuantitativo de las actividades extraescolares fue administrado a los padres de los alumnos. Los mejores resultados se observan como consecuencia de unos patrones de descanso adecuados y una práctica moderada del ejercicio físico (entre 2 y 5 horas a la semana). Asimismo, las peores notas escolares se obtienen cuando a unos patrones de descanso inadecuados, se une un elevado número de horas de actividades físico-deportivas extraescolares (más de 5 horas a la semana)

objectivo do trabalho consiste em estudar se existe uma relação entre padrões de descanso (adequados e inadequados), realização de umdeterminado número de horas de actividades físico-deportivas extra-escolares e o rendimento académico numa amostra de 573 alunos do primeiro ciclo (54.62 rapazes e 45.38% raparigas)das províncias de Barcelona e das Ilhas Baleares. Um questionário com perguntas relativas a aspectos sociodemográficos e perguntas específicas sobrea avaliação qualitativa e quantitativa do sono e registo quantitativo das actividades extra-escolares foi administrado aos pais dos alunos. Os melhores re-sultados são observados como consequência dos padrões de descanso adequados e uma prática moderada do exercício (entre 2 e 5 horas por semana).Adicionalmente, as piores notas escolares foram obtidas quando aos padrões de descanso inadequados se junta um elevado número de actividades fí-sico-deportivas extra-escolares (mais de 5 horas por semana)

Association of clinic and ambulatory blood pressure with vascular damage in the elderly: the EPICARDIAN study.

OBJECTIVES: In middle-aged adults, vascular damage correlates better with ambulatory than with clinic blood pressure. This study aimed to determine whether vascular damage evaluated by carotid ultrasonography in the elderly is also more closely related to ambulatory than to clinic blood pressure, and which blood pressure variables are better associated with vascular damage. METHODS: Cross-sectional study of 292 randomly selected >65 years old participants who underwent 24-h noninvasive ambulatory blood pressure monitoring. Blood pressure variables analyzed were (a) clinic blood pressure: systolic and diastolic blood pressure, pulse pressure; (b) ambulatory blood pressure monitoring: mean values of systolic and diastolic blood pressure, systolic and diastolic blood pressure load, pulse pressure, as well as variability, evaluated within 24 h, diurnal and nocturnal periods; and day-night blood pressure difference. A clinical history, physical examination, carotid ultrasonography and laboratory tests were performed. To estimate the relationship between blood pressure and vascular damage, univariate and multivariate analyses were performed. RESULTS: Mean age: 73+/-6 years, 45% men, 76.7% hypertensive patients. In the simple regression analysis, the best significant correlations (P<0.05) were common carotid intima-media thickness with 24-h and nocturnal pulse pressure (r=0.32), and common carotid diameter with 24-h systolic blood pressure load (r=0.47). In the multivariate analysis, the significant associations (P<0.05) were (a) linear regression: nocturnal pulse pressure with common carotid intima-media thickness, and diurnal pulse pressure as well as 24-h systolic blood pressure load with common carotid diameter; (b) logistic regression, adjusted odds ratio: nocturnal pulse pressure and nocturnal diastolic blood pressure load with the presence of carotid atherosclerotic plaques 1.03 and 0.98, respectively. CONCLUSIONS: In the elderly, ambulatory blood pressure monitoring is better associated with carotid damage than clinic blood pressure. Systolic blood pressure variables are the best associated, blood pressure load and pulse pressure being better associated with carotid damage than the mean levels of ambulatory blood pressure.

Elicitation of plants and microbial cell systems.

Plants show physiological and morphological responses to a range of physical and chemical factors known as 'elicitors'. These responses have been considered as defence reactions 'elicited' by the plants' biochemical factory to ensure their survival, persistence and competitiveness. Recently examples have been cited of elicitation in some fungal and bacterial cultures. Through a chronological survey, this Review considers examples of elicitors and elicitation and describes suggested mechanisms of elicitation in plants and microbial cell cultures. The majority of research in this field has been carried out on the plant systems using complex (undefined) biotic elicitors. Carbohydrates are the main class of compounds used as defined elicitors. This Review focuses on carbohydrates as compounds initiating a defence response in cell cultures. Physiological changes brought about on the plant and microbial cultures include expression of novel metabolites and overproduction of already known products. Recent reports confirming elicitation in microbial cultures are of potential importance, as the relative ease of fermentation and scale-up could open an opportunity for the introduction of useful novel metabolites as well as enhancement of commercially useful bioproducts. In this context, a sound knowledge of the elicitor molecules' structure-function relationships and mechanisms of elicitation is essential.