Intrinsic noise profoundly alters the dynamics and steady state of morphogen-controlled bistable genetic switches

During tissue development, patterns of gene expression determine the spatial arrangement of cell types. In many cases, gradients of secreted signaling molecules - morphogens - guide this process. The continuous positional information provided by the gradient is converted into discrete cell types by the downstream transcriptional network that responds to the morphogen. A mechanism commonly used to implement a sharp transition between two adjacent cell fates is the genetic toggle switch, composed of cross-repressing transcriptional determinants. Previous analyses emphasize the steady state output of these mechanisms. Here, we explore the dynamics of the toggle switch and use exact numerical simulations of the kinetic reactions, the Chemical Langevin Equation, and Minimum Action Path theory to establish a framework for studying the effect of gene expression noise on patterning time and boundary position. This provides insight into the time scale, gene expression trajectories and directionality of stochastic switching events between cell states. Taking gene expression noise into account predicts that the final boundary position of a morphogen-induced toggle switch, although robust to changes in the details of the noise, is distinct from that of the deterministic system. Moreover, stochastic switching introduces differences in patterning time along the morphogen gradient that result in a patterning wave propagating away from the morphogen source. The velocity of this wave is influenced by noise; the wave sharpens and slows as it advances and may never reach steady state in a biologically relevant time. This could explain experimentally observed dynamics of pattern formation. Together the analysis reveals the importance of dynamical transients for understanding morphogen-driven transcriptional networks and indicates that gene expression noise can qualitatively alter developmental patterning

Posicionamiento de la Universidad de Talca en los alumnos de tercero y cuarto medio de colegios particulares de la ciudad de Rancagua.

88 p.Ingresar a la Universidad es la gran meta de la mayoría de los estudiantes de enseñanza media de nuestro país, existiendo muchas alternativas académicas para ello, pero las de mayor preferencia siguen siendo hasta hoy las Universidades estatales. Por ello, los esfuerzos que realiza la Universidad de Talca con el propósito de captar potenciales clientes esta dando resultados en los egresados de colegios municipales y en menor medida en los estudiantes provenientes de colegios particulares de la Región Metropolitana, Sexta y Séptima, lo cual significa que en ambos grupos las estrategias de posicionamiento que en la actualidad ocupa la universidad no están dando los mismos resultados. Para detectar este posible problema se realizo el presente estudio con el propósito de determinar como se encuentra posicionada la Universidad de Talca en los estudiantes de colegios particulares y en especial de la ciudad de Rancagua, con el objetivo de que se desarrollen en un futuro cercano nuevas estrategias para poder corregir eventuales distorsiones que llevan a una diferencia entre lo que la UTAL desea proyectar y lo que los estudiantes realmente perciben

Minimum Action Path theory reveals the details of stochastic biochemical transitions out of oscillatory cellular states

Cell state determination is the outcome of intrinsically stochastic biochemical reactions. Tran- sitions between such states are studied as noise-driven escape problems in the chemical species space. Escape can occur via multiple possible multidimensional paths, with probabilities depending non-locally on the noise. Here we characterize the escape from an oscillatory biochemical state by minimizing the Freidlin-Wentzell action, deriving from it the stochastic spiral exit path from the limit cycle. We also use the minimized action to infer the escape time probability density function

Exact solution of stochastic gene expression models with bursting, cell cycle and replication dynamics

The bulk of stochastic gene expression models in the literature do not have an explicit description of the age of a cell within a generation and hence they cannot capture events such as cell division and DNA replication. Instead, many models incorporate cell cycle implicitly by assuming that dilution due to cell division can be described by an effective decay reaction with first-order kinetics. If it is further assumed that protein production occurs in bursts then the stationary protein distribution is a negative binomial. Here we seek to understand how accurate these implicit models are when compared with more detailed models of stochastic gene expression. We derive the exact stationary solution of the chemical master equation describing bursty protein dynamics, binomial partitioning at mitosis, age-dependent transcription dynamics including replication, and random interdivision times sampled from Erlang or more general distributions; the solution is different for single lineage and population snapshot settings. We show that protein distributions are well approximated by the solution of implicit models (a negative binomial) when the mean number of mRNAs produced per cycle is low and the cell cycle length variability is large. When these conditions are not met, the distributions are either almost bimodal or else display very flat regions near the mode and cannot be described by implicit models. We also show that for genes with low transcription rates, the size of protein noise has a strong dependence on the replication time, it is almost independent of cell cycle variability for lineage measurements and increases with cell cycle variability for population snapshot measurements. In contrast for large transcription rates, the size of protein noise is independent of replication time and increases with cell cycle variability for both lineage and population measurements.Comment: 7 figure

Implementación de malla electrosoldada en muros de albañilería tradicional para viviendas unifamiliares Los Olivos 2019

El objetivo de esta investigación fue determinar cuál sería el comportamiento mecánico de los muros de albañilería elaborado con unidades tubulares, con la finalidad de implementar la malla electrosoldada como refuerzo para aumentar la ductilidad y evitar la forma de falla frágil y explosiva. A través de la metodología experimental, un nivel de investigación explicativa y un enfoque de investigación cuantitativa se realizaron ensayos en prismas de albañilería reforzados y sin refuerzo, los cuales serían la representación más aproximada al muro de albañilería, a los que se realizaron ensayos de compresión axial en pilas reforzadas y sin refuerzo, de igual manera ensayos de compresión diagonal en muretes reforzados y sin refuerzo. Entre los primeros resultados, se identificó la forma de falla frágil y explosiva del muro de albañilería tubular, asimismo utilizando el reforzamiento de la malla electrosoldada se identificó una forma de falla controlada, es decir las unidades no se trituraron, por lo tanto, se llegó a la conclusión que el uso de la malla electrosoldada galvanizada como refuerzo en muros de albañilería tubular incrementó un 4.34% la resistencia característica a la compresión axial (f´m), de igual manera incrementó un 14.70% la resistencia característica a la compresión diagonal (v´m) así mismo incrementó un 4.34% el módulo de corte de la albañilería (Gm)