The stem cell zoo for comparative studies of developmental tempo.

The rate of development is highly variable across animal species. However, the mechanisms regulating developmental tempo have remained elusive due to difficulties in performing direct interspecies comparisons. Here, we discuss how pluripotent stem cell-based models of development can be used to investigate cell- and tissue-autonomous temporal processes. These systems enable quantitative comparisons of different animal species under similar experimental conditions. Moreover, the constantly growing stem cell zoo collection allows the extension of developmental studies to a great number of unconventional species. We argue that the stem cell zoo constitutes a powerful platform to perform comparative studies of developmental tempo, as well as to study other forms of biological time control such as species-specific lifespan, heart rate, and circadian clocks.

A stem cell zoo uncovers intracellular scaling of developmental tempo across mammals.

Differential speeds in biochemical reactions have been proposed to be responsible for the differences in developmental tempo between mice and humans. However, the underlying mechanism controlling the species-specific kinetics remains to be determined. Using in vitro differentiation of pluripotent stem cells, we recapitulated the segmentation clocks of diverse mammalian species varying in body weight and taxa: marmoset, rabbit, cattle, and rhinoceros. Together with mouse and human, the segmentation clock periods of the six species did not scale with the animal body weight, but with the embryogenesis length. The biochemical kinetics of the core clock gene HES7 displayed clear scaling with the species-specific segmentation clock period. However, the cellular metabolic rates did not show an evident correlation. Instead, genes involving biochemical reactions showed an expression pattern that scales with the segmentation clock period. Altogether, our stem cell zoo uncovered general scaling laws governing species-specific developmental tempo.

Combination of Genome-Scale Models and Bioreactor Dynamics to Optimize the Production of Commodity Chemicals.

The current production of a number of commodity chemicals relies on the exploitation of fossil fuels and hence has an irreversible impact on the environment. Biotechnological processes offer an attractive alternative by enabling the manufacturing of chemicals by genetically modified microorganisms. However, this alternative approach poses some important technical challenges that must be tackled to make it competitive. On the one hand, the design of biotechnological processes is based on trial-and-error approaches, which are not only costly in terms of time and money, but also result in suboptimal designs. On the other hand, the manufacturing of chemicals by biological processes is almost exclusively carried out by batch or fed-batch cultures. Given that batch cultures are expensive and not easy to scale, technical means must be developed to make continuous cultures feasible and efficient. In order to address these challenges, we have developed a mathematical model able to integrate in a single model both the genome-scale metabolic model for the organism synthesizing the chemical of interest and the dynamics of the bioreactor in which the organism is cultured. Such a model is based on the use of Flexible Nets, a modeling formalism for dynamical systems. The integration of a microscopic (organism) and a macroscopic (bioreactor) model in a single net provides an overall view of the whole system and opens the door to global optimizations. As a case study, the production of citramalate with respect to the substrate consumed by E. coli is modeled, simulated and optimized in order to find the maximum productivity in a steady-state continuous culture. The predicted computational results were consistent with the wet lab experiments.

A shared transcriptional code orchestrates temporal patterning of the central nervous system.

The molecular mechanisms that produce the full array of neuronal subtypes in the vertebrate nervous system are incompletely understood. Here, we provide evidence of a global temporal patterning program comprising sets of transcription factors that stratifies neurons based on the developmental time at which they are generated. This transcriptional code acts throughout the central nervous system, in parallel to spatial patterning, thereby increasing the diversity of neurons generated along the neuraxis. We further demonstrate that this temporal program operates in stem cell-derived neurons and is under the control of the TGFß signaling pathway. Targeted perturbation of components of the temporal program, Nfia and Nfib, reveals their functional requirement for the generation of late-born neuronal subtypes. Together, our results provide evidence for the existence of a previously unappreciated global temporal transcriptional program of neuronal subtype identity and suggest that the integration of spatial and temporal patterning mechanisms diversifies and organizes neuronal subtypes in the vertebrate nervous system.

Species-specific pace of development is associated with differences in protein stability.

Although many molecular mechanisms controlling developmental processes are evolutionarily conserved, the speed at which the embryo develops can vary substantially between species. For example, the same genetic program, comprising sequential changes in transcriptional states, governs the differentiation of motor neurons in mouse and human, but the tempo at which it operates differs between species. Using in vitro directed differentiation of embryonic stem cells to motor neurons, we show that the program runs more than twice as fast in mouse as in human. This is not due to differences in signaling, nor the genomic sequence of genes or their regulatory elements. Instead, there is an approximately two-fold increase in protein stability and cell cycle duration in human cells compared with mouse cells. This can account for the slower pace of human development and suggests that differences in protein turnover play a role in interspecies differences in developmental tempo.

Publisher Correction: Temporal control of gene expression by the pioneer factor Zelda through transient interactions in hubs.

The original version of this Article contained an error in Fig. 4a, in which the "=" sign of the equation was inadvertently replaced with a "-" sign. This has been corrected in the PDF and HTML versions of the Article.

Temporal control of gene expression by the pioneer factor Zelda through transient interactions in hubs.

Pioneer transcription factors can engage nucleosomal DNA, which leads to local chromatin remodeling and to the establishment of transcriptional competence. However, the impact of enhancer priming by pioneer factors on the temporal control of gene expression and on mitotic memory remains unclear. Here we employ quantitative live imaging methods and mathematical modeling to test the effect of the pioneer factor Zelda on transcriptional dynamics and memory in Drosophila embryos. We demonstrate that increasing the number of Zelda binding sites accelerates the kinetics of nuclei transcriptional activation regardless of their transcriptional past. Despite its known pioneering activities, we show that Zelda does not remain detectably associated with mitotic chromosomes and is neither necessary nor sufficient to foster memory. We further reveal that Zelda forms sub-nuclear dynamic hubs where Zelda binding events are transient. We propose that Zelda facilitates transcriptional activation by accumulating in microenvironments where it could accelerate the duration of multiple pre-initiation steps.

Algunas consideraciones sobre la hipertensión arterial / Some considerations on hypertension

La hipertensión arterial es una enfermedad crónica caracterizada por el incremento continuo de las cifras de la presión sanguínea en las arterias. Esta constituye el principal factor de riesgo de las enfermedades cardiovasculares y presenta alta prevalencia en el mundo actual, por lo cual su prevención constituye una necesidad imperiosa. A tales efectos se detallan algunos aspectos de interés, tales como: factores de riesgo, manifestaciones clínicas, complicaciones y tratamiento, entre otros(AU)

Hypertension is a chronic disease characterized by the continuous increment of the blood pressure figures in the arteries. It constitutes the main risk factor of cardiovascular diseases and presents high prevalence in the current world, reason why its prevention constitutes an imperious necessity. To such effects some aspects of interest are detailed, such as: risk factors, clinical features, complications and treatment, among others(AU)

Factores de riesgo de los accidentes cerebrovasculares durante un bienio / Risk factors of strokes during a biennium

Se realizó un estudio analítico, observacional de casos y controles en pacientes del Policlínico Docente Carlos Montalbán del municipio de Palma Soriano, provincia de Santiago de Cuba, a fin de determinar los principales factores de riesgo de los accidentes cerebrovasculares, desde enero de 2014 hasta diciembre de 2015. Fueron seleccionados 2 grupos: uno de 90 integrantes (casos) y otro de 180 (controles). Se calcularon la oportunidad relativa y el intervalo de confianza; se aplicó la prueba de Ji al cuadrado con 95 por ciento de confiabilidad y se utilizó el porcentaje como medida resumen para variables cualitativas. Las condiciones predisponentes que predominaron en la serie fueron: edad, hipertensión arterial, obesidad, sedentarismo, tabaquismo y dislipidemia, las cuales ponen en riesgo la vida del afectado(AU)

An analytic observational case-control study in patients of Carlos Montalbán Teaching Polyclinic in Palma Soriano, Santiago de Cuba, was carried out in order to determine the main risk factors of strokes, from January, 2014 to December, 2015. Two groups were selected: one with 90 members (case) and another one with 180 (control). The relative opportunity and the confidence interval were calculated; the Chi-square test was applied with 95 percent of confidence and the percentage was used as summary measure for qualitative variables. The predisposing conditions that prevailed in the series were: age, hypertension, obesity, sedentary lifestyle, nicotine addiction and dyslipemia, which put at risk the life of the ones affected(AU)

Factores de riesgo de los accidentes cerebrovasculares durante un bienio / Risk factors of strokes during a biennium

Se realizó un estudio analítico, observacional de casos y controles en pacientes del Policlínico Docente "Carlos Montalbán" del municipio de Palma Soriano, provincia de Santiago de Cuba, a fin de determinar los principales factores de riesgo de los accidentes cerebrovasculares, desde enero de 2014 hasta diciembre de 2015. Fueron seleccionados 2 grupos: uno de 90 integrantes (casos) y otro de 180 (controles). Se calcularon la oportunidad relativa y el intervalo de confianza; se aplicó la prueba de Ji al cuadrado con 95 % de confiabilidad y se utilizó el porcentaje como medida resumen para variables cualitativas. Las condiciones predisponentes que predominaron en la serie fueron: edad, hipertensión arterial, obesidad, sedentarismo, tabaquismo y dislipidemia, las cuales ponen en riesgo la vida del afectado.

An analytic observational case-control study in patients of "Carlos Montalbán" Teaching Polyclinic in Palma Soriano, Santiago de Cuba, was carried out in order to determine the main risk factors of strokes, from January, 2014 to December, 2015. Two groups were selected: one with 90 members (case) and another one with 180 (control). The relative opportunity and the confidence interval were calculated; the Chi-square test was applied with 95% of confidence and the percentage was used as summary measure for qualitative variables. The predisposing conditions that prevailed in the series were: age, hypertension, obesity, sedentary lifestyle, nicotine addiction and dyslipemia, which put at risk the life of the ones affected.

Uso de Terapias Complementarias en el Tratamiento de Pacientes con Lumbalgia Crónica del Seguro Social de Salud. La Libertad, 2009 / Use of complementary therapies in the treatment of chronic low back pain in patients from Peruvian Health Insurance (EsSalud). La Libertad, 2009

Objetivo: Describir las variaciones en el consumo de analgésicos en pacientes con lumbalgia crónica que recibieron terapias con medicina complementaria. Materiales y métodos: Estudio descriptivo. Se realizó en el Centro de Atención de Medicina Complementaria (CAMEC) ­ La Libertad en el periodo marzo-mayo de 2009, de seis semanas de seguimiento en 45 pacientes que recibieron terapias con medicina complementaria. Se incluyeron pacientes con diagnóstico de lumbalgia mayor de 12 semanas y tratamiento farmacológico activo. Se evaluaron características clínico-epidemiológicas, factores de riesgo asociados (obesidad, estrés, sedentarismo, polifarmacia), tiempo de enfermedad, terapia utilizada, disminución del consumo de analgésicos y el grado de satisfacción. Resultados: Un 77,8% presentó el diagnóstico de lumbalgia crónica inespecífica. Las terapias complementarias más indicadas fueron acupuntura, masoterapia y fitoterapia; en su mayoría de modo combinado. En seis semanas de seguimiento el 93,3% de la población redujo, en alguna medida, la dosis habitual de analgésicos; mientras que el 40% suspendió totalmente su consumo. El 86,7% de los pacientes manifestaron haber obtenido resultados excelentes o buenos después de la aplicación de terapias alternativas. Conclusiones: El uso de terapias complementarias en el tratamiento de la lumbalgia crónica disminuye el uso de analgésicos y brinda una percepción de satisfacción en los pacientes.

Tendencias de egresos hospitalarios en sala de cuidados intensivos del Hospital Clinicoquirúrgico Docente Doctor Ambrosio Grillo Portuondo / Tendencies of hospital discharges in the Intensive care unit of Doctor Ambrosio Grillo Portuondo Teaching Clinical Surgical Hospital

Se efectuó una investigación de servicios de salud, longitudinal y retrospectiva, de 2 467 pacientes ingresados en la Sala de Cuidados Intensivos del Hospital Clinicoquirúrgico Docente Dr Ambrosio Grillo Portuondo de Santiago de Cuba, en el quinquenio 2003-2007, para determinar las tendencias de los egresos de dicha Unidad y su relación con algunas variables de uso hospitalario. Las tasas de ese indicador disminuyeron en el lustro, predominantemente en los casos de hombres y ancianos. El índice de masculinidad tendió al incremento y la estadía promedio no excedió de 5 días. El traslado de otra sala para este Servicio constituyó la causa más frecuente de ingresos, lo cual coincidió con los motivos de egreso. Las tasas de mortalidad hospitalaria decrecieron, contrariamente a lo ocurrido en relación con el pronóstico de muerte de las féminas.

A longitudinal and retrospective investigation of health services was carried out in 2 467 patients who were admitted to the Intensive Care Unit of Dr Ambrosio Grillo Portuondo¼ Teaching Clinical Surgical Hospital from Santiago de Cuba, in the five year period 2003-2007, to determine the tendencies of discharges in this institution and their relationship with some variables used in the hospital. The rates of that indicator decreased in the 5 years period, predominantly in the cases of men and aged patients. The masculinity index increased and the average stay didn't exceed 5 days. The transfer from another Service to this unit constituted the most frequent cause for admissions, which coincided with the reasons for discharge. The rates of hospital mortality decreased, contrarily to what happened in relation to the death prognosis in the female sex.

Calidad de la ejecución del programa nacional de prevención, diagnóstico, evaluación y control de la hipertensión arterial en el Policlínico Universitario Julián Grimau García / Quality of the implementation of the national program of prevention, diagnosis, evaluation and control of hypertension at

Se realizó una investigación sobre servicios y sistemas de salud para evaluar la calidad de la ejecución del Programa Nacional de Prevención, Diagnóstico, Evaluación y Control de la Hipertensión Arterial en el Policlínico Julián Grimau García de Santiago de Cuba, desde septiembre de 2009 hasta igual mes de 2010, para lo cual se elaboraron los criterios, indicadores y estándares pertinentes, en tanto las dimensiones evaluadas fueron la estructura y el proceso (competencia profesional). Se contó con la participación de todos los especialistas de medicina general integral que se encontraban laborando en la unidad durante ese período y accedieron a colaborar. Se halló que dicho Programa no se ejecutaba con la calidad requerida y que existían dificultades en la estructura por el inadecuado estado de los recursos materiales; sin embargo, los resultados del examen de competencia se consideraron satisfactorios, puesto que los profesionales en cuestión dominaban los contenidos.

A research on health services and systems was carried out to evaluate the quality of the implementation of the National Program of Prevention, Diagnosis, Evaluation and Control of Hypertension at Julián Grimau García Polyclinic of Santiago de Cuba from September 2009 to September 2010. With this purpose relevant approaches, indicators and standards were developed, whereas the dimensions evaluated were the structure and process (professional competence). It is included the participation of all the specialists of comprehensive general medicine who were working in the unit during that period and agreed to cooperate. It was found that this Program was not implemented with the required quality and there were difficulties in the structure because of the inadequacy of material resources; however, the results of the proficiency test were considered satisfactory, since the professionals dominated the contents.

Calidad de la ejecución del Programa Nacional de Prevención, Diagnóstico, Evaluación y Control de la Hipertensión Arterial en el Policlínico Universitario Julián Grimau García / Quality of the implementation of the National Program of Prevention, Diagnosis, Evaluation and Control of Hypertension at

Se realizó una investigación sobre servicios y sistemas de salud para evaluar la calidad de la ejecución del Programa Nacional de Prevención, Diagnóstico, Evaluación y Control de la Hipertensión Arterial en el Policlínico Julián Grimau García de Santiago de Cuba, desde septiembre de 2009 hasta igual mes de 2010, para lo cual se elaboraron los criterios, indicadores y estándares pertinentes, en tanto las dimensiones evaluadas fueron la estructura y el proceso (competencia profesional). Se contó con la participación de todos los especialistas de medicina general integral que se encontraban laborando en la unidad durante ese período y accedieron a colaborar. Se halló que dicho Programa no se ejecutaba con la calidad requerida y que existían dificultades en la estructura por el inadecuado estado de los recursos materiales; sin embargo, los resultados del examen de competencia se consideraron satisfactorios, puesto que los profesionales en cuestión dominaban los contenidos(AU)

A research on health services and systems was carried out to evaluate the quality of the implementation of the National Program of Prevention, Diagnosis, Evaluation and Control of Hypertension at Julián Grimau García Polyclinic of Santiago de Cuba from September 2009 to September 2010. With this purpose relevant approaches, indicators and standards were developed, whereas the dimensions evaluated were the structure and process (professional competence). It is included the participation of all the specialists of comprehensive general medicine who were working in the unit during that period and agreed to cooperate. It was found that this Program was not implemented with the required quality and there were difficulties in the structure because of the inadequacy of material resources; however, the results of the proficiency test were considered satisfactory, since the professionals dominated the contents

Tendencias de egresos hospitalarios en Sala de Cuidados Intensivos del Hospital Clinicoquirúrgico Docente Dr Ambrosio Grillo Portuondo / Tendencies of hospital discharges in the Intensive Care Unit of Dr Ambrosio Grillo Portuondo Teaching Clinical Surgical Hospital

Se efectuó una investigación de servicios de salud, longitudinal y retrospectiva, de 2 467 pacientes ingresados en la Sala de Cuidados Intensivos del Hospital Clinicoquirúrgico Docente Dr Ambrosio Grillo Portuondo de Santiago de Cuba, en el quinquenio 2003-2007, para determinar las tendencias de los egresos de dicha Unidad y su relación con algunas variables de uso hospitalario. Las tasas de ese indicador disminuyeron en el lustro, predominantemente en los casos de hombres y ancianos. El índice de masculinidad tendió al incremento y la estadía promedio no excedió de 5 días. El traslado de otra sala para este Servicio constituyó la causa más frecuente de ingresos, lo cual coincidió con los motivos de egreso. Las tasas de mortalidad hospitalaria decrecieron, contrariamente a lo ocurrido en relación con el pronóstico de muerte de las féminas(AU)

A longitudinal and retrospective investigation of health services was carried out in 2 467 patients who were admitted to the Intensive Care Unit of Dr Ambrosio Grillo Portuondo¼ Teaching Clinical Surgical Hospital from Santiago de Cuba, in the five year period 2003-2007, to determine the tendencies of discharges in this institution and their relationship with some variables used in the hospital. The rates of that indicator decreased in the 5 years period, predominantly in the cases of men and aged patients. The masculinity index increased and the average stay didn't exceed 5 days. The transfer from another Service to this unit constituted the most frequent cause for admissions, which coincided with the reasons for discharge. The rates of hospital mortality decreased, contrarily to what happened in relation to the death prognosis in the female sex(AU)