Use of physiological constraints to identify quantitative design principles for gene expression in yeast adaptation to heat shock

Background: Understanding the relationship between gene expression changes, enzyme activity shifts, and the corresponding physiological adaptive response of organisms to environmental cues is crucial in explaining how cells cope with stress. For example, adaptation of yeast to heat shock involves a characteristic profile of changes to the expression levels of genes coding for enzymes of the glycolytic pathway and some of its branches. The experimental determination of changes in gene expression profiles provides a descriptive picture of the adaptive response to stress. However, it does not explain why a particular profile is selected for any given response. Results: We used mathematical models and analysis of in silico gene expression profiles (GEPs) to understand how changes in gene expression correlate to an efficient response of yeast cells to heat shock. An exhaustive set of GEPs, matched with the corresponding set of enzyme activities, was simulated and analyzed. The effectiveness of each profile in the response to heat shock was evaluated according to relevant physiological and functional criteria. The small subset of GEPs that lead to effective physiological responses after heat shock was identified as the result of the tuning of several evolutionary criteria. The experimentally observed transcriptional changes in response to heat shock belong to this set and can be explained by quantitative design principles at the physiological level that ultimately constrain changes in gene expression. Conclusion: Our theoretical approach suggests a method for understanding the combined effect of changes in the expression of multiple genes on the activity of metabolic pathways, and consequently on the adaptation of cellular metabolism to heat shock. This method identifies quantitative design principles that facilitate understating the response of the cell to stress.

Two component systems: physiological effect of a third component

Signal transduction systems mediate the response and adaptation of organisms to environmental changes. In prokaryotes, this signal transduction is often done through Two Component Systems (TCS). These TCS are phosphotransfer protein cascades, and in their prototypical form they are composed by a kinase that senses the environmental signals (SK) and by a response regulator (RR) that regulates the cellular response. This basic motif can be modified by the addition of a third protein that interacts either with the SK or the RR in a way that could change the dynamic response of the TCS module. In this work we aim at understanding the effect of such an additional protein (which we call ‘‘third component’’) on the functional properties of a prototypical TCS. To do so we build mathematical models of TCS with alternative designs for their interaction with that third component. These mathematical models are analyzed in order to identify the differences in dynamic behavior inherent to each design, with respect to functionally relevant properties such as sensitivity to changes in either the parameter values or the molecular concentrations, temporal responsiveness, possibility of multiple steady states, or stochastic fluctuations in the system. The differences are then correlated to the physiological requirements that impinge on the functioning of the TCS. This analysis sheds light on both, the dynamic behavior of synthetically designed TCS, and the conditions under which natural selection might favor each of the designs. We find that a third component that modulates SK activity increases the parameter space where a bistable response of the TCS module to signals is possible, if SK is monofunctional, but decreases it when the SK is bifunctional. The presence of a third component that modulates RR activity decreases the parameter space where a bistable response of the TCS module to signals is possible.

Is the matching function Cobb-Douglas?

[cat] Estudiem les propietats teòriques que una funció d.emparellament ha de satisfer per tal de representar un mercat laboral amb friccions dins d'un model d'equilibri general amb emparellament aleatori. Analitzem el cas Cobb-Douglas, CES i altres formes funcionals per a la funció d.emparellament. Els nostres resultats estableixen restriccions sobre els paràmetres d'aquests formes funcionals per assegurar que l.equilibri és interior. Aquestes restriccions aporten raons teòriques per escollir entre diverses formes funcionals i permeten dissenyar tests d'error d'especificació de model en els treballs empírics.

Is the matching function Cobb-Douglas?

[cat] Estudiem les propietats teòriques que una funció d.emparellament ha de satisfer per tal de representar un mercat laboral amb friccions dins d'un model d'equilibri general amb emparellament aleatori. Analitzem el cas Cobb-Douglas, CES i altres formes funcionals per a la funció d.emparellament. Els nostres resultats estableixen restriccions sobre els paràmetres d'aquests formes funcionals per assegurar que l.equilibri és interior. Aquestes restriccions aporten raons teòriques per escollir entre diverses formes funcionals i permeten dissenyar tests d'error d'especificació de model en els treballs empírics.

Modelling the Evolution and Spread of HIV Immune Escape Mutants.

During infection with human immunodeficiency virus (HIV), immune pressure from cytotoxic T-lymphocytes (CTLs) selects for viral mutants that confer escape from CTL recognition. These escape variants can be transmitted between individuals where, depending upon their cost to viral fitness and the CTL responses made by the recipient, they may revert. The rates of within-host evolution and their concordant impact upon the rate of spread of escape mutants at the population level are uncertain. Here we present a mathematical model of within-host evolution of escape mutants, transmission of these variants between hosts and subsequent reversion in new hosts. The model is an extension of the well-known SI model of disease transmission and includes three further parameters that describe host immunogenetic heterogeneity and rates of within host viral evolution. We use the model to explain why some escape mutants appear to have stable prevalence whilst others are spreading through the population. Further, we use it to compare diverse datasets on CTL escape, highlighting where different sources agree or disagree on within-host evolutionary rates. The several dozen CTL epitopes we survey from HIV-1 gag, RT and nef reveal a relatively sedate rate of evolution with average rates of escape measured in years and reversion in decades. For many epitopes in HIV, occasional rapid within-host evolution is not reflected in fast evolution at the population level.

How to introduce connectance in a frame of an expression for diversity

Systems made of parts that are totally connected do not work, neither ecosys- tems nor artifacts. Relative connectance is inversely related to diversity, and both magnitudes can find a common frame of expression, in which some constant expressing the constraints of any organization might be embodied. If S is Simp- son's index, the expression (1 - S)IS as a measure of diversity offers some advantages or, at least, helps further reasoning. Such expression is the ratio between total interspecific possible interactions and possible intraspecific inter- actions.

Variación regional del coeficiente de atenuación de las ondas Rayleigh en el escudo europeo

A partir del análisis del modo fundamental de las ondas Rayleigh generadas por tres terremotos situados en las Azores, Sicilia y el Mar Negro se obtiene la variación regional del coeficiente de atenuación en el escudo europeo para un intervalo de periodos de 15-80 s. El método de análisis ha consistido en comparar los espectros de amplitudes observados con los calculados teóricamente. Para el calculo de estos últimos se ha utilizado un nuevo método consistente en calcular la función global de la fuente a partir de un proceso de mínimos cuadrados. Los resultados son los siguientes.

Anàlisis del modelo de la telaraña en contexto de incertidumbre

In the present work the behavior of a model acquaintance of market is analyzed with an only one, in that is considered that the parameters that tie the variables that it incorporates the pattern come expressed through uncertain magnitudes. The objective of the study consists on the analysis of the balance from the hypotheses of established uncertainties

Movilidad intergeneracional y emparejamiento selectivo en España

This paper examines the role of assortative mating in the intergenerational economic mobility in Spain. Sons and daughters usually marry individuals with similar characteristics, which may lower mobility. Our empirical strategy employs the Two-sample two-stage least squares estimator to estimate the intergenerational income elasticity in absence of data for two generations not residing in the same household. Our findings suggest that assortative mating plays an important role in the intergenerational transmission process. On average about 50 per 100 of the covariance between parents’ income and child family’s incomecan be accounted for by the person the child is married to

Progress in front propagation research

We review the progress in the field of front propagation in recent years. We survey many physical, biophysical and cross-disciplinary applications, including reduced-variable models of combustion flames, Reid's paradox of rapid forest range expansions, the European colonization of North America during the 19th century, the Neolithic transition in Europe from 13 000 to 5000 years ago, the description of subsistence boundaries, the formation of cultural boundaries, the spread of genetic mutations, theory and experiments on virus infections, models of cancer tumors, etc. Recent theoretical advances are unified in a single framework, encompassing very diverse systems such as those with biased random walks, distributed delays, sequential reaction and dispersion, cohabitation models, age structure and systems with several interacting species. Directions for future progress are outlined

Language extinction and linguistic fronts

Language diversity has become greatly endangered in the past centuries owing to processes of language shift from indigenous languages to other languages that are seen as socially and economically more advantageous, resulting in the death or doom of minority languages. In this paper, we define a new language competition model that can describe the historical decline of minority languages in competition with more advantageous languages. We then implement this non-spatial model as an interaction term in a reactiondiffusion system to model the evolution of the two competing languages. We use the results to estimate the speed at which the more advantageous language spreads geographically, resulting in the shrinkage of the area of dominance of the minority language. We compare the results from our model with the observed retreat in the area of influence of the Welsh language in the UK, obtaining a good agreement between the model and the observed data

HouSI: Heuristic for delimitation of housing submarkets and price homogeneous areas

This paper seeks to address the problem of the empirical identification of housing market segmentation,once we assume that submarkets exist. The typical difficulty in identifying housing submarkets when dealing with many locations is the vast number of potential solutions and, in such cases, the use of the Chow test for hedonic functions is not a practical solution. Here, we solve this problem by undertaking an identification process with a heuristic for spatially constrained clustering, the"Housing Submarket Identifier" (HouSI). The solution is applied to the housing market in the city of Barcelona (Spain), where we estimate a hedonic model for fifty thousand dwellings aggregated into ten groups. In order to determine the utility of the procedure we seek to verify whether the final solution provided by the heuristic is comparable with the division of the city into ten administrative districts.

Front Speed of Language Replacement

We use two coupled equations to analyze the space-time dynamics of two interacting languages. Firstly, we introduce a cohabitation model, which is more appropriate for human populations than classical (non-cohabitation) models. Secondly, using numerical simulations we nd the front speed of a new language spreading into a region where another language was previously used. Thirdly, for a special case we derive an analytical formula that makes it possible to check the validity of our numerical simulations. Finally, as an example, we nd that the observed front speed for the spread of the English language into Wales in the period 1961-1981 is consistent with the model predictions. We also nd that the e¤ects of linguistic parameters are much more important than those of parameters related to population dispersal and reproduction. If the initial population densities of both languages are similar, they have no e¤ect on the front speed. We outline the potential of the new model to analyze relationships between language replacement and genetic replacement

Cultural Diffusion Was the Main Driving Mechanism of the Neolithic Transition in Southern Africa

It is well known that the Neolithic transition spread across Europe at a speed of about 1 km/yr. This result has been previously interpreted as a range expansion of the Neolithic driven mainly by demic diffusion (whereas cultural diffusion played a secondary role). However, a long-standing problem is whether this value (1 km/yr) and its interpretation (mainly demic diffusion) are characteristic only of Europe or universal (i.e. intrinsic features of Neolithic transitions all over the world). So far Neolithic spread rates outside Europe have been barely measured, and Neolithic spread rates substantially faster than 1 km/yr have not been previously reported. Here we show that the transition from hunting and gathering into herding in southern Africa spread at a rate of about 2.4 km/yr, i.e. about twice faster than the European Neolithic transition. Thus the value 1 km/yr is not a universal feature of Neolithic transitions in the world. Resorting to a recent demic-cultural wave-of-advance model, we also find that the main mechanism at work in the southern African Neolithic spread was cultural diffusion (whereas demic diffusion played a secondary role). This is in sharp contrast to the European Neolithic. Our results further suggest that Neolithic spread rates could be mainly driven by cultural diffusion in cases where the final state of this transition is herding/pastoralism (such as in southern Africa) rather than farming and stockbreeding (as in Europe)

Análisis económico de una función cuadrática de gastos de producción con coeficientes borrosos

En el ámbito de la Economía de la Empresa tiene mucha importancia el estudio de los gastos de producción E(Q) que se originarán en el proceso y que generalmente vendrán expresados matemáticamente por una dependencia lineal o cuadrática de las unidades Q que se proponen fabricar. Supondremos, además, que esta función está afectada por dos restricciones: una es de productividad, Q1 ≤ Q2 ≤ Q3 , y otra de limitación de gastos máximos permitidos, E(Q) ≤ EM . En el presente artículo partiremos de una función cuadrática nítida, en la cual justificaremos el signo de los coeficientes que hemos empleado. Después, para adentrarnos en el campo fuzzy, la generalizaremos con otra de coeficientes borrosos. Naturalmente, la nueva función borrosa ya no se expresará a través de una única curva, sino que estará constituida por un haz infinito de curvas nítidas, cada una de ellas con un determinado grado de posibilidad. Centramos nuestra atención en las curvas que llamamos central, inferior y superior. El núcleo de nuestro análisis consistirá básicamente en reducir paulatinamente los soportes de los coeficientes hasta hallar un cierto valor k del α-corte, de manera que a partir de él todas las curvas del haz borroso tengan sentido económico y cumplan las dos restricciones impuestas. En último lugar, y a través de un caso numérico, comprobaremos las deducciones teóricas que hemos obtenido en el análisis anterior