Kolmogorov complexity of epithelial pattern formation: The role of regulatory network configuration

The tissues of multicellular organisms are made of differentiated cells arranged in organized patterns. This organization emerges during development from the coupling of dynamic intra- and intercellular regulatory networks. This work applies the methods of information theory to understand how regulatory network structure both within and between cells relates to the complexity of spatial patterns that emerge as a consequence of network operation. A computational study was performed in which undifferentiated cells were arranged in a two dimensional lattice, with gene expression in each cell regulated by identical intracellular randomly generated Boolean networks. Cell–cell contact signalling between embryonic cells is modeled as coupling among intracellular networks so that gene expression in one cell can influence the expression of genes in adjacent cells. In this system, the initially identical cells differentiate and form patterns of different cell types. The complexity of network structure, temporal dynamics and spatial organization is quantified through the Kolmogorov-based measures of normalized compression distance and set complexity. Results over sets of random networks that operate in the ordered, critical and chaotic domains demonstrate that: (1) ordered and critical networks tend to create the most information-rich patterns; (2) signalling configurations in which cell-to-cell communication is non-directional mostly produce simple patterns irrespective of the internal network domain; and (3) directional signalling configurations, similar to those that function in planar cell polarity, produce the most complex patterns, but only when the intracellular networks function in non-chaotic domains.     

Highly covarying residues have a functional role in antibody constant domains

The ability to generate and design antibodies recognizing specific targets has revolutionized the pharmaceutical industry and medical imaging. Engineering antibody therapeutics in some cases requires modifying their constant domains to enable new and altered interactions. Engineering novel specificities into antibody constant domains has proved challenging due to the complexity of inter‐domain interactions. Covarying networks of residues that tend to cluster on the protein surface and near binding sites have been identified in some proteins. However, the underlying role these networks play in the protein resulting in their conservation remains unclear in most cases. Resolving their role is crucial, because residues in these networks are not viable design targets if their role is to maintain the fold of the protein. Conversely, these networks of residues are ideal candidates for manipulating specificity if they are primarily involved in binding, such as the myriad interdomain interactions maintained within antibodies. Here, we identify networks of evolutionarily‐related residues in C‐class antibody domains by evaluating covariation, a measure of propensity with which residue pairs vary dependently during evolution. We computationally test whether mutation of residues in these networks affects stability of the folded antibody domain, determining their viability as design candidates. We find that members of covarying networks cluster at domain‐domain interfaces, and that mutations to these residues are diverse and frequent during evolution, precluding their importance to domain stability. These results indicate that networks of covarying residues exist in antibody domains for functional reasons unrelated to thermodynamic stability, making them ideal targets for antibody design. Proteins 2013. © 2012 Wiley Periodicals, Inc.     

Editorial

Abstract

Grand canonical molecular dynamics (GCMD) simulations are used to study the adsorption and desorption of Lennard-Jones nitrogen in three slit pore junction models of microporous graphite. These networks consist of two narrow pores separated by a wider (cavity) pore. We report results for cases where the narrow pore has a width of only two or three molecular diameters. Using the GCMD technique, a novel freezing transition is observed which results in pore blocking in the narrow pores of the network, which are less than 1 nm wide. This freezing results from the adsorption energy barrier at the junction between the narrow and wider pores. This type of pore blocking could account for the apparent increase in pore volume with increasing temperature that has been experimentally observed in microporous graphite systems. For networks in which the narrower pores are somewhat larger, with a width of 1.28 nm, this pore blocking effect is much reduced, and adsorbate molecules enter and fill the central cavity. In such cases, however, desorption is incomplete, some residual adsorbate remaining in the central cavity even at the lowest pressures.     

‘We all eat the same bread’: the roots and limits of cosmopolitan bridging ties developed by Romanians in London

This paper investigates the social ties forged by Romanians in London with migrants of different origins in work and non-work contexts to offer a more nuanced view of ‘bridging’ social ties and related discussions of ‘everyday’ cosmopolitanism. Contrary to the overemphasis on ethnic ties seen as a form of bonding in migration research, the paper shows how Romanians bridge informally with many other migrants based on shared ‘non-native’ status. Alongside non-ethnically marked commonalities, ethnicity emerges as an important ingredient of cosmopolitan socialization, yet without necessarily signalling coexisting ethnic identities, as commonly assumed. Romanians' experiences further show that despite providing significant social and cultural capital, bridging ties with migrants, rather than natives, rarely accrue effective resources for social mobility. The findings suggest the need to disaggregate and qualify current understandings of ‘bridging’ social ties usually depicted in positive terms and uniformly as cross-ethnic relationships, or only linked with the ‘mainstream’ population.     

How calcium signals in myocytes and pericytes are integrated across in situ microvascular networks and control microvascular tone

The microcirculation is the site of gas and nutrient exchange. Control of central or local signals acting on the myocytes, pericytes and endothelial cells within it, is essential for health. Due to technical problems of accessibility, the mechanisms controlling Ca²⁺ signalling and contractility of myocytes and pericytes in different sections of microvascular networks in situ have not been investigated. We aimed to investigate Ca²⁺ signalling and functional responses, in a microcirculatory network in situ. Using live confocal imaging of ureteric microvascular networks, we have studied the architecture, morphology, Ca²⁺ signalling and contractility of myocytes and pericytes. Ca²⁺ signals vary between distributing arcade and downstream transverse and precapillary arterioles, are modified by agonists, with sympathetic agonists being ineffective beyond transverse arterioles. In myocytes and pericytes, Ca²⁺ signals arise from Ca²⁺ release from the sarcoplasmic reticulum through inositol 1,4,5-trisphosphate-induced Ca²⁺ release and not via ryanodine receptors or Ca²⁺ entry into the cell. The responses in pericytes are less oscillatory, slower and longer-lasting than those in myocytes. Myocytes and pericytes are electrically coupled, transmitting Ca²⁺ signals between arteriolar and venular networks dependent on gap junctions and Ca²⁺ entry via L-type Ca²⁺ channels. Endothelial Ca²⁺ signalling inhibits intracellular Ca²⁺ oscillations in myocytes and pericytes via L-arginine/nitric oxide pathway and intercellular propagating Ca²⁺ signals via EDHF. Increases of Ca²⁺ in pericytes and myocytes constrict all vessels except capillaries. These data reveal the structural and signalling specializations allowing blood flow to be regulated by myocytes and pericytes.     

Immigration,remittances, and transnational social capital formation: a Cuban case study

Social capital takes on distinctive meaning in the context of large-scale immigration from poor to rich countries. In this article, characteristics of social capital embedded in transnational networks and norms, conditions conducive to the formation of such networks, and effects such networks have are extrapolated from an analysis of how and why cross-border relations among Cuban-Americans and Cubans in their homeland have changed since the 1959 Castro-led revolution. The transnational social capital generating benefit on which the study focuses is remittances. Remittances are of growing global importance to less developed countries, and in some countries they generate more revenue than foreign aid and foreign investment. The analysis addresses a range of unintended as well as intended consequences remittances may have.     

Stagnant immigrant social networks and cycles of exploitation

Based on over four years of ethnographic research among street vendors in Los Angeles and on interviews with family members of vendors and former vendors living in Mexico, this article examines the influence of a sending community and its social networks on migrant outcomes in the USA. These social networks affect migration patterns, ease entry into the fruit-vending business but also facilitate exploitation. Furthermore, these social networks do not always function as effective conduits of information because its members, due to feelings of shame or embarrassment, often fail to add to the existing body of knowledge. As a result, international migration patterns, job placement and exploitative practices do not change or improve for subsequent migrants. This creates a cycle in which social networks become stagnant and successively fail to function as effective conduits of information and resources in ways that might help network members equally and in the aggregate.     

THE EVOLUTION OF LOCOMOTOR RHYTHMICITY IN TETRAPODS

Differences in rhythmicity (relative variance in cycle period) among mammal, fish, and lizard feeding systems have been hypothesized to be associated with differences in their sensorimotor control systems. We tested this hypothesis by examining whether the locomotion of tachymetabolic tetrapods (birds and mammals) is more rhythmic than that of bradymetabolic tetrapods (lizards, alligators, turtles, salamanders). Species averages of intraindividual coefficients of variation in cycle period were compared while controlling for gait and substrate. Variance in locomotor cycle periods is significantly lower in tachymetabolic than in bradymetabolic animals for datasets that include treadmill locomotion, non‐treadmill locomotion, or both. When phylogenetic relationships are taken into account the pooled analyses remain significant, whereas the non‐treadmill and the treadmill analyses become nonsignificant. The co‐occurrence of relatively high rhythmicity in both feeding and locomotor systems of tachymetabolic tetrapods suggests that the anatomical substrate of rhythmicity is in the motor control system, not in the musculoskeletal components.