A Model of Speciation Preconditions in Terms of Percolation and Self-Organized Criticality Theories

Biophysics - Several models have been considered: those that describe mutation fixation in asexually or sexually reproducing species during speciation and are based on stochastic processes and a...     

Emergent Self-Organized Criticality in Gene Expression Dynamics: Temporal Development of Global Phase Transition Revealed in a Cancer Cell Line

Background

The underlying mechanism of dynamic control of the genome-wide expression is a fundamental issue in bioscience. We addressed it in terms of phase transition by a systemic approach based on both density analysis and characteristics of temporal fluctuation for the time-course mRNA expression in differentiating MCF-7 breast cancer cells.

Methodology

In a recent work, we suggested criticality as an essential aspect of dynamic control of genome-wide gene expression. Criticality was evident by a unimodal-bimodal transition through flattened unimodal expression profile. The flatness on the transition suggests the existence of a critical transition at which up- and down-regulated expression is balanced. Mean field (averaging) behavior of mRNAs based on the temporal expression changes reveals a sandpile type of transition in the flattened profile. Furthermore, around the transition, a self-similar unimodal-bimodal transition of the whole expression occurs in the density profile of an ensemble of mRNA expression. These singular and scaling behaviors identify the transition as the expression phase transition driven by self-organized criticality (SOC).

Principal Findings

Emergent properties of SOC through a mean field approach are revealed: i) SOC, as a form of genomic phase transition, consolidates distinct critical states of expression, ii) Coupling of coherent stochastic oscillations between critical states on different time-scales gives rise to SOC, and iii) Specific gene clusters (barcode genes) ranging in size from kbp to Mbp reveal similar SOC to genome-wide mRNA expression and ON-OFF synchronization to critical states. This suggests that the cooperative gene regulation of topological genome sub-units is mediated by the coherent phase transitions of megadomain-scaled conformations between compact and swollen chromatin states.

Conclusion and Significance

In summary, our study provides not only a systemic method to demonstrate SOC in whole-genome expression, but also introduces novel, physically grounded concepts for a breakthrough in the study of biological regulation.     

Criticality in cell differentiation

Cell differentiation is an important process in living organisms. Differentiation is mostly based on binary decisions with the progenitor cells choosing between two specific lineages. The differentiation dynamics have both deterministic and stochastic components. Several theoretical studies suggest that cell differentiation is a bifurcation phenomenon, well-known in dynamical systems theory. The bifurcation point has the character of a critical point with the system dynamics exhibiting specific features in its vicinity. These include the critical slowing down, rising variance and lag-1 autocorrelation function, strong correlations between the fluctuations of key variables and non-Gaussianity in the distribution of fluctuations. Recent experimental studies provide considerable support to the idea of criticality in cell differentiation and in other biological processes like the development of the fruit fly embryo. In this review, an elementary introduction is given to the concept of criticality in cell differentiation. The correspondence between the signatures of criticality and experimental observations on blood cell differentiation in mice is further highlighted.     

Autoimmunity and hypothyroidism

Primary myxedema and hypothyroid Hashimoto's disease provide a well-documented example of organ-specific autoimmunity in man. Very slight modifications or increased release of thyroglobulin or thyroid antigens in the circulation may cause the rupture of autotolerance for the normal thyroid components, at least when individuals have a genetic predisposition to autoimmune thyroiditis (possibly associated with a predisposition to other autoimmune diseases). The demonstration of an association between HLA and thyroiditis, however, requires additional studies. The basic immunological abnormality responsible for autoimmunization against thyroid components is a defect in suppressor T cells, shown in experimental animals but not firmly established in man. The result of autoimmunization will be the appearance of cytotoxic mechanisms that lead to destruction of the thyroid follicle with progressive fibrosis, antibody-dependent cell-mediated cytotoxicity apparently being of major importance. A recent report shows, in addition, that thyroid atrophy in primary hypothyroidism is associated with the production of antibodies that block the thyroid-growth-promoting activity of TSH. The recent progress made in our understanding of autoimmune thyroiditis will certainly contribute to improving our knowledge of how and when autoimmunization might develop in man.     

Criticality of Seven Specialty Metals

Evaluating metal criticality is a topic that addresses future metals supply and that has inspired research in corporations, academic institutions, and governments. In this article, we apply a comprehensive criticality methodology to seven specialty metals—scandium (Sc), strontium (Sr), antimony (Sb), barium (Ba), mercury (Hg), thallium (Tl), and bismuth (Bi)—at the national and global levels for 2008. The results are presented along with uncertainty estimates in a three‐dimensional “criticality space” comprised of supply risk (SR), vulnerability to supply restriction (VSR), and environmental implications (EI) axes. The SR score is the highest for antimony over the medium term (i.e., 5 to 10 years), followed very closely by bismuth and thallium; for the long term (i.e., a few decades), the highest SR is for thallium, followed very closely by antimony. Strontium and barium, followed very closely by mercury, have the lowest SR over the medium term, and mercury has the lowest SR over the long term. Mercury has the highest EI score. For VSR, thallium is the most vulnerable at both the national level (for the United States) and global level, followed by strontium at both levels. In general, specialty metals are found to possess a unique mix of sparse data, toxicity concerns (in some cases), and inadequate or nonexistent substitutes for a number of specialized uses, a situation that would seem to demand increased effort in acquiring the information needed to characterize specialty metal criticality with more rigor and transparency than is currently possible.     

Tolerance and Autoimmunity

Long-lasting tolerance can be produced by prenatal or perinatal exposure to foreign antigens. Self-tolerance results from embryonic exposure to antigens of the host itself. Several mechanisms that contribute to self-tolerance have been described. They include clonal deletion, anergy, and active suppression. A failure in these mechanisms may lead to autoimmune disease. Some important human diseases are associated with autoimmunity, and immunomethods are regularly employed for their diagnosis. In the future immunomethods will prove to be valuable for the identification of subjects at risk of developing autoimmune disease, thereby permitting preventive interventions.     

Self-Organized Shape and Frontal Density of Fish Schools

Models of swarming (based on avoidance, alignment and attraction) produce patterns of behaviour also seen in schools of fish. However, the significance of such similarities has been questioned, because some model assumptions are unrealistic [e.g. speed in most models is constant with random error, the perception is global and the size of the schools that have been studied is small (up to 128 individuals)]. This criticism also applies to our former model, in which we demonstrated the emergence of two patterns of spatial organization, i.e. oblong school form and high frontal density, which are supposed to function as protection against predators. In our new model we respond to this criticism by making the following improvements: individuals have a preferred ‘cruise speed’ from which they can deviate in order to avoid others or to catch up with them. Their range of perception is inversely related to density, with which we take into account that high density limits the perception of others that are further away. Swarm sizes range from 10 to 2000 individuals. The model is three‐dimensional. Further, we show that the two spatial patterns (oblong shape and high frontal density) emerge by self‐organization as a side‐effect of coordination at two speeds (of two or four body lengths per second) for schools of sizes above 20. Our analysis of the model leads to the development of a new set of hypotheses. If empirical data confirm these hypotheses, then in a school of real fish these patterns may arise as a side‐effect of their coordination in the same way as in the model.     

Evolution of Self-Organized Task Specialization in Robot Swarms

Division of labor is ubiquitous in biological systems, as evidenced by various forms of complex task specialization observed in both animal societies and multicellular organisms. Although clearly adaptive, the way in which division of labor first evolved remains enigmatic, as it requires the simultaneous co-occurrence of several complex traits to achieve the required degree of coordination. Recently, evolutionary swarm robotics has emerged as an excellent test bed to study the evolution of coordinated group-level behavior. Here we use this framework for the first time to study the evolutionary origin of behavioral task specialization among groups of identical robots. The scenario we study involves an advanced form of division of labor, common in insect societies and known as “task partitioning”, whereby two sets of tasks have to be carried out in sequence by different individuals. Our results show that task partitioning is favored whenever the environment has features that, when exploited, reduce switching costs and increase the net efficiency of the group, and that an optimal mix of task specialists is achieved most readily when the behavioral repertoires aimed at carrying out the different subtasks are available as pre-adapted building blocks. Nevertheless, we also show for the first time that self-organized task specialization could be evolved entirely from scratch, starting only from basic, low-level behavioral primitives, using a nature-inspired evolutionary method known as Grammatical Evolution. Remarkably, division of labor was achieved merely by selecting on overall group performance, and without providing any prior information on how the global object retrieval task was best divided into smaller subtasks. We discuss the potential of our method for engineering adaptively behaving robot swarms and interpret our results in relation to the likely path that nature took to evolve complex sociality and task specialization.     

Microbial Adjuvant and Autoimmunity

Definite lesions in the exocrine pancreas were produced when SMA mice were immunized eight times at intervals of 30 days with a mixture of extract of pooled pancreas from syngeneic mice and the capsular polysaccharide of Klebsiella pneumoniae type 1 Kasuya strain (CPS-K), whereas no pancreatic lesions were produced in mice given CPS-K alone or pancreatic extract alone. The typical histological changes were characterized by infiltration with lymphocytes, plasma cells, and other mononuclear cells, degeneration and lysis of the acinar cells, destruction of the lobular architecture, and replacement by fatty tissue and fibrous connective tissue. The endocrine islets were well preserved. No specific histological changes were produced in the organs other than the pancreas in these mice. Most of mice immunized with pancreatic extract mixed with CPS-K produced serum precipitins to syngeneic pancreatic antigens. However, severe pancreatic lesions were also produced in mice showing no definite precipitin production.