RESUMEN
The gene regulatory circuitry through which pluripotent embryonic stem (ES) cells choose between self-renewal and differentiation appears vast and has yet to be distilled into an executive molecular program. We developed a data-constrained, computational approach to reduce complexity and to derive a set of functionally validated components and interaction combinations sufficient to explain observed ES cell behavior. This minimal set, the simplest version of which comprises only 16 interactions, 12 components, and three inputs, satisfies all prior specifications for self-renewal and furthermore predicts unknown and nonintuitive responses to compound genetic perturbations with an overall accuracy of 70%. We propose that propagation of ES cell identity is not determined by a vast interactome but rather can be explained by a relatively simple process of molecular computation.
Asunto(s)
Células Madre Embrionarias/metabolismo , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Células Madre Pluripotentes/metabolismo , Factores de Transcripción/metabolismo , Animales , Técnicas de Cultivo de Célula , Biología Computacional , Ratones , Factores de Transcripción/genéticaRESUMEN
A 65-year-old patient with a chief complaint of syncope had an ECG with ventricular preexcitation and intermittent second-degree atrioventricular (AV) block. AV conduction was maintained by the accessory pathway only, with no evidence of AV nodal conduction. Electrophysiological study demonstrated that the QRS duration and morphology did not increase with atrial pacing; however, A-H prolongation occurred with increased pacing rates.
Asunto(s)
Bloqueo Cardíaco/complicaciones , Síndrome de Wolff-Parkinson-White/complicaciones , Anciano , Fascículo Atrioventricular/fisiopatología , Bloqueo de Rama/complicaciones , Bloqueo de Rama/fisiopatología , Estimulación Cardíaca Artificial , Electrocardiografía , Bloqueo Cardíaco/fisiopatología , Sistema de Conducción Cardíaco/fisiopatología , Humanos , Masculino , Síncope/etiología , Síndrome de Wolff-Parkinson-White/fisiopatologíaRESUMEN
The annual sequence of sickness leaves was studied in 162 industrial workers with a high absenteeism level. An investigation of the swings in haemodynamic balance, and imbalances linked to alternations in vessel constriction and dilation throughout the biorhythmic cycle influenced by the alternation of night and day, hot and cold seasons, showed that each period of sick leave coincided with each period of haemodynamic balance caused by particular shifts. It was thus possible to identify groups of workers with syndromic sub groups whose performance was affected by night work and particular seasons. For optimal shift-worker deployment it is therefore suggested that workers should be assigned to shifts to which they are biologically suited.
Asunto(s)
Hemodinámica , Enfermedades Profesionales/patología , Tolerancia al Trabajo Programado , Trabajo , Relojes Biológicos , Humanos , Factores de TiempoAsunto(s)
Bloqueo Cardíaco/diagnóstico , Sistema de Conducción Cardíaco/fisiopatología , Anciano , Ajmalina , Estimulación Cardíaca Artificial , Ecocardiografía , Electrocardiografía , Femenino , Estudios de Seguimiento , Bloqueo Cardíaco/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , RiesgoRESUMEN
We report the case of a 46-year-old man, in whom A-V node electrophysiologic properties was worsened after therapeutic conjunctival instillation of timolol. We suggest that periodic, careful controls of the AV conduction are warranted in patients taking ocular hypertensive chronic timolol therapy.