RESUMEN
BACKGROUND: Ventricular dilation is known as a pivotal predictor in recent-onset cardiomyopathy (ROCM), but its pathophysiology is not fully understood. In the present study we investigated whether single-cell stiffness of right and left ventricular-derived fibroblasts has an effect on cardiac phenotype in patients with ROCM. METHODS AND RESULTS: Patients with endomyocardial biopsy-proven ROCM were included (n=10). Primary cardiac fibroblasts (CFBs) were cultured from left and right ventricular endomyocardial biopsies and their single-cell stiffness was analyzed by quantification of Young's modulus using colloidal probe atomic force microscopy. Cardiac fibrosis was analyzed by Masson's trichrome staining. CFBs from the left ventricle showed significantly decreased stiffness when compared with CFBs from the right ventricle, indexed by decreased stiffness (Young's modulus 3,374±389 vs. 4,837±690 Pa; P<0.05). Young's modulus of CFBs derived from the left ventricle correlated negatively with the left ventricular end-diastolic dimension derived from 2-dimensional echocardiography (R(2)=0.77; P<0.01). Neither left nor right ventricular fibrosis correlated with the respective ventricular dimensions. CONCLUSIONS: Our data suggest that a decrease in single-cell stiffness of left ventricular fibroblasts could trigger left ventricular dilation in patients with ROCM. This implies a new potential mechanism for the ventricular dilation with this disease.
Asunto(s)
Cardiomiopatía Dilatada , Módulo de Elasticidad , Fibroblastos , Ventrículos Cardíacos , Adulto , Anciano , Cardiomiopatía Dilatada/metabolismo , Cardiomiopatía Dilatada/patología , Cardiomiopatía Dilatada/fisiopatología , Femenino , Fibroblastos/metabolismo , Fibroblastos/ultraestructura , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Microscopía de Fuerza Atómica , Persona de Mediana EdadRESUMEN
Molecular processes of cell differentiation often involve reactions with delays. We develop a mathematical model that provides a basis for a rigorous theoretical analysis of these processes as well as for direct simulation. A discrete, stochastic approach is adopted because several molecules appear in small numbers only. Our model is a non-Markovian stochastic process. The main theoretical results include a constructive proof of the existence of the process and a derivation of the rates for initiation and completion of reactions with delays. These results guarantee that the stochastic process is a consistent and realistic description of the molecular system. They also serve as a theoretical justification of recent work on delay stochastic simulation. We apply our model to an important process in developmental biology, the formation of somites in the vertebrate embryo. Simulation of the molecular oscillator controlling this process reveals major differences between stochastic and deterministic models.
Asunto(s)
Biología Computacional/métodos , Regulación del Desarrollo de la Expresión Génica , Modelos Genéticos , Somitos/metabolismo , Procesos Estocásticos , Algoritmos , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/fisiología , Simulación por Computador , Péptidos y Proteínas de Señalización Intracelular , Proteínas de la Membrana/genética , Proteínas de la Membrana/fisiología , Mesodermo/embriología , Mesodermo/metabolismo , Receptores Notch/genética , Receptores Notch/fisiología , Somitos/embriología , Factores de Transcripción/genética , Factores de Transcripción/fisiología , Pez Cebra , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/fisiologíaRESUMEN
Progressing waves of regeneration are observed in forest ecosystems such as Shimagare fir forests. The patterns generated by lattice models for forest dynamics often show similar waves of disturbance and recovery. This paper introduces a method to detect and quantify the directional movement of these waves. The method is based only on the disturbance times of the sites and allows to distinguish three types of wave patterns: patterns with global direction, patterns with local direction, and patterns without direction. We apply this to several grid-based models for forest dynamics which are evaluated analytically or by simulation. The results reveal a clear distinction of the models which earlier studies were not able to detect.
Asunto(s)
Modelos Biológicos , Árboles/crecimiento & desarrollo , Ecosistema , Dinámica PoblacionalRESUMEN
The vegetation height in forest ecosystems is spatially heterogeneous. Canopy gaps (sites with low vegetation) are formed by treefalls, and they recover to canopy sites (with high vegetation) either by growth of small trees or by branch extension of surrounding trees. The dynamics of canopy gaps have been studied using a spatial Markov chain with nearest neighbor interaction. (1) If the canopy recovery rate is constant and if the gap formation rate for a site increases exponentially with the number of neighboring gap sites, the equilibrium distribution is the same as the one generated by the Ising model in statistical mechanics. Here, we extend the equivalence to the situation in which both the gap formation and canopy recovery depend on the neighborhood, as shown in recent forest data. (2) We develop a statistical test of whether a given spatial pattern is a random sample from the Ising model. The test is based on the conditional probability of configurations on a partial lattice. We apply the method to vegetation height data from the Ogawa forest reserve, Japan, measured on a 5x5 m grid in 1976, 1981, 1986, and 1991. The spatial pattern of the original forest data deviates significantly from the Ising model. We examine whether a larger sampling distance or the removal of the effects of the topography can reduce this deviation.