Bifurcation in epigenetics: implications in development, proliferation and diseases

Cells often exhibit different and stable phenotypes from the same DNA sequence. Robustness and plasticity of such cellular states are controlled by diverse transcriptional and epigenetic mechanisms, among them the modification of biochemical marks on chromatin. Here, we develop a stochastic model that describes the dynamics of epigenetic marks along a given DNA region. Through mathematical analysis, we show the emergence of bistable and persistent epigenetic states from the cooperative recruitment of modifying enzymes. We also find that the dynamical system exhibits a critical point and displays, in presence of asymmetries in recruitment, a bifurcation diagram with hysteresis. These results have deep implications for our understanding of epigenetic regulation. In particular, our study allows to reconcile within the same formalism the robust maintenance of epigenetic identity observed in differentiated cells, the epigenetic plasticity of pluripotent cells during differentiation and the effects of epigenetic misregulation in diseases. Moreover, it suggests a possible mechanism for developmental transitions where the system is shifted close to the critical point to benefit from high susceptibility to developmental cues.Comment: accepted in Physical Review E as a Rapid Communicatio

Limited Range Fractality of Randomly Adsorbed Rods

Multiple resolution analysis of two dimensional structures composed of randomly adsorbed penetrable rods, for densities below the percolation threshold, has been carried out using box-counting functions. It is found that at relevant resolutions, for box-sizes, $r$, between cutoffs given by the average rod length and the average inter-rod distance $r_1$, these systems exhibit apparent fractal behavior. It is shown that unlike the case of randomly distributed isotropic objects, the upper cutoff $r_1$ is not only a function of the coverage but also depends on the excluded volume, averaged over the orientational distribution. Moreover, the apparent fractal dimension also depends on the orientational distributions of the rods and decreases as it becomes more anisotropic. For box sizes smaller than the box counting function is determined by the internal structure of the rods, whether simple or itself fractal. Two examples are considered - one of regular rods of one dimensional structure and rods which are trimmed into a Cantor set structure which are fractals themselves. The models examined are relevant to adsorption of linear molecules and fibers, liquid crystals, stress induced fractures and edge imperfections in metal catalysts. We thus obtain a distinction between two ranges of length scales: $r$ where the internal structure of the adsorbed objects is probed, and $< r < r_1$ where their distribution is probed, both of which may exhibit fractal behavior. This distinction is relevant to the large class of systems which exhibit aggregation of a finite density of fractal-like clusters, which includes surface growth in molecular beam epitaxy and diffusion-limited-cluster-cluster-aggregation models.Comment: 10 pages, 7 figures. More info available at http://www.fh.huji.ac.il/~dani/ or http://www.fiz.huji.ac.il/staff/acc/faculty/biham or http://chem.ch.huji.ac.il/employee/avnir/iavnir.htm . Accepted for publication in J. Chem. Phy

Numerical simulation of growth of Escherichia coli in unsaturated porous media

A model for the aerobic and anaerobic growth of Escherichia coli (HB101 K12 pGLO) depending on the concentration of oxygen and DOC as substrate has been developed based on laboratory batch experiments. Using inverse modelling to obtain optimal sets of parameters, it could be shown that a model based on a modified double Contois kinetic can predict cell densities, organic carbon utilisation, oxygen transfer and utilisation rates for a large number of experiments under aerobic and anaerobic conditions with a single unique set of parameters. The model was extended to describe growth of E. coli in unsaturated porous media, combining diffusion, phase exchange and microbiological growth. Experiments in a Hele-Shaw cell, filled with quartz sand, were conducted to study bacterial growth in the capillary fringe above a saturated porous medium. Cell density profiles in the Hele-Shaw cell were predicted with the growth model and the parameters from the batch experiments without any further calibration. They showed a very good qualitative and quantitative agreement with cell densities determined from samples taken from the Hele-Shaw cell by re-suspension and subsequent counting. Thus it could be shown, that it is possible to successfully transfer growth parameters from batch experiments to porous media for both aerobic and anaerobic conditions.Comment: Minor changes in conclusions, results unchange

Regulating the Many to Benefit the Few: Role of Weak Small RNA Targets

AbstractSmall regulatory RNAs are central players in the regulation of many cellular processes across all kingdoms of life. Experiments in mouse and human have shown that a typical small RNA may regulate the expression of many different genes, suggesting that small RNAs act as global regulators. It is noted though that most targets respond only weakly to the presence of the small RNA. At the same time, evidence in bacteria and animals suggest that the phenotypes associated with small RNA mutants are only due to a few of their targets. Here we assume that targets regulated by a small RNA to control function is in fact small, and propose that the role of the many other weak targets is to confer robustness to the regulation of these few principal targets. Through mathematical modeling we show that auxiliary targets may significantly buffer both number and kinetic fluctuations of the principal targets, with only minor slowdown in the kinetics of response. Analysis of genomic data suggests that auxiliary targets experience a nonspecific evolutionary pressure, playing a role at the system level. Our work is of importance for studies on small RNA functions, and impacts on the understanding of small RNA evolution

Orientational wetting and topological transitions in confined solutions of semi-flexible polymers

Despite their considerable practical and biological applications, the link between molecular properties, assembly conditions and self-organized structure in confined polymer solutions remains elusive. Here, we explore the lyotropic nematic ordering of semi-flexible chains in spherical confinement for multiple contour lengths across a wide regime of concentrations. We uncover an original crossover from two distinct quadrupolar states, both characterized by regular tetrahedral patterns of surface topological defects, to either longitudinal, latitudinal or spontaneously-twisted bipolar structures with increasing densities. These transitions, along with the intermediary arrangements that they involve, are attributed to the combination of orientational wetting with subtle variations in their liquid-crystal (LC) elastic anisotropies. Our molecular simulations are corroborated by density functional calculations, and are quantified through the introduction of several order parameters as well as an unsupervised learning scheme for the localization of topological defects. Our results agree quantitatively with the predictions of continuum nematic elasticity theories, and evidence the extent to which the folding of macromolecules and the self-assembly of low-molecular-weight LCs may be guided by the same, universal principles.Comment: arXiv admin note: substantial text overlap with arXiv:2107.0259

Ideology and the limits of self-interest: System justification motivation and conservative advantages in mass politics

It is commonly assumed that political attitudes are driven by self-interest and that poor people heavily favor policies aimed at redistributing wealth. This assumption fails to explain the popularity of economic conservatism and the degree of support for the capitalist system. Such outcomes are typically explained by the suggestion that most poor people believe they will become rich one day. In a representative sample of low-income Americans, we observed that less than one-fourth were optimistic about their economic prospects. Those respondents who believed that they would become rich one day were no more likely to endorse the legitimacy of the system and no more supportive of conservative ideology or the Republican Party, compared to those who did not believe they would become rich. From a system justification perspective, we propose that people are motivated to defend the social systems on which they depend, and this confers a psychological advantage to conservative ideology. Providing ideological support for the status quo serves epistemic motives to reduce uncertainty, existential motives to reduce threat, and relational motives to share reality with members of mainstream society. We summarize evidence from the United States, Argentina, Lebanon, and other countries bearing on these propositions—including a survey administered shortly before the 2016 U.S. Presidential election—and discuss political implications of system justification motivation.Fil: Jost, John T.. University of New York; Estados UnidosFil: Langer, Melanie. University of New York; Estados UnidosFil: Badaan, Vivienne. University of New York; Estados UnidosFil: Azevedo, Flávio. Universitat Zu Köln; AlemaniaFil: Etchezahar, Edgardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Centro Interdisciplinario de Investigaciones en Psicología Matemática y Experimental Dr. Horacio J. A. Rimoldi; ArgentinaFil: Ungaretti, Joaquín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Centro Interdisciplinario de Investigaciones en Psicología Matemática y Experimental Dr. Horacio J. A. Rimoldi; ArgentinaFil: Hennes, Erin P.. Purdue University; Estados Unido

Einfluss von suspendierten und immobilisierten Mikroorganismen auf die Eigenschaften des Kapillarsaumes : Untersuchungen im Rahmen der DFG-Forschergruppe \u27Dynamic Capillary Fringes, A Multidisciplinary Approach\u27

Experiments with capillary fringes (CF) in quartz sand were conducted. The respiratory activity, cell growth or the biofilm formation by different soil bacteria in the CF were examined. Highest bacterial activity and cell adsorption on the sand particles were detected between the almost water saturated and unsaturated CF-region. Primarily in this transition zone the bacteria strongly influenced the vertical oxygen diffusion and reduced the hydraulic conductivity due to biological clogging