Epistasis between the MHC and the RCAα block in primary Sjögren syndrome

ObjectiveThe RCA alpha block (Regulators of Complement Activation, 1q32) contains critical complement regulatory genes such as CR1 and MCP. This study examined RCA alpha block haplotype associations with both disease susceptibility and diversification of the anti-Ro/La autoantibody response in primary Sjögren syndrome (pSS).Methods115 patients with pSS and 98 controls were included in the study. 93 of 109 (85%) of the patients with pSS were seropositive for Ro/La autoantibodies. The Genomic Matching Technique (GMT) was used to define RCA alpha block ancestral haplotypes (AH).ResultsRCA alpha block haplotypes, AH1 and AH3, were both associated with autoantibody-positive pSS (p = 0.0003). Autoantibody associations with both HLA DR3 and DR15 have been previously defined. There was an epistatic interaction (p = 0.023) between RCA alpha AH1 and HLA DR3, and this genotypic combination was present in 48% of autoantibody-positive patients with pSS compared with 8% of controls. This epistasis is most simply attributable to an interaction between C4 and its receptor, CR1, encoded within the RCA alpha block. Both DR3 and a relative C4 deficiency are carried on the major histocompatibility complex 8.1 ancestral haplotype. Only four of 92 (4%) autoantibody-positive patients with pSS did not carry any risk RCA alpha or HLA haplotype, compared with 36 of 96 (38%) controls, and there were differences in haplotype frequencies within autoantibody subsets of pSS.ConclusionsNormal population variation in the RCA alpha block, in addition to the major histocompatibility complex, contributes genetic susceptibility to systemic autoimmune disease and the autoantibody response. This finding provides evidence for the role of regulation of complement activation in disease pathogenesis.S. Lester, C. McLure, J. Williamson, P. Bardy, M. Rischmueller, R. L. Dawkin

The Anisotropic Bak-Sneppen model

The Bak-Sneppen model is shown to fall into a different universality class with the introduction of a preferred direction, mirroring the situation in spin systems. This is first demonstrated by numerical simulations and subsequently confirmed by analysis of the multitrait version of the model, which admits exact solutions in the extremes of zero and maximal anisotropy. For intermediate anisotropies, we show that the spatiotemporal evolution of the avalanche has a power law `tail' which passes through the system for any non-zero anisotropy but remains fixed for the isotropic case, thus explaining the crossover in behaviour. Finally, we identify the maximally anisotropic model which is more tractable and yet more generally applicable than the isotropic system

Awe and Wonder in Scientific Practice: Implications for the Relationship Between Science and Religion

This paper examines the role of awe and wonder in scientific practice. Drawing on evidence from psychological research and the writings of scientists and science communicators, I argue that awe and wonder play a crucial role in scientific discovery. They focus our attention on the natural world, encourage open-mindedness, diminish the self (particularly feelings of self-importance), help to accord value to the objects that are being studied, and provide a mode of understanding in the absence of full knowledge. I will flesh out implications of the role of awe and wonder in scientific discovery for debates on the relationship between science and religion. Abraham Heschel argued that awe and wonder are religious emotions because they reduce our feelings of self-importance, and thereby help to cultivate the proper reverent attitude towards God. Yet metaphysical naturalists such as Richard Dawkins insist that awe and wonder need not lead to any theistic commitments for scientists. The awe some scientists experience can be regarded as a form of non-theistic spirituality, which is neither a reductive naturalism nor theism. I will attempt to resolve the tension between these views by identifying some common ground

Multi-level selectional stalemate in a simple artificial chemistry

We describe a simple artificial chemistry which abstracts a small number of key features from the origin of life "replicator world" hypotheses. We report how this can already give rise to moderately complex and counter-intuitive evolutionary phenomena, including macro- evolutionary deterioration in replication fidelity (which corresponds to intrinsic replicator fitness in this model). We briefly describe the extension of this model to incorporate a higher, protocell, level of selection. We show that the interaction between the two levels of selection then serves to control parasitic exploitation at the molecular level, while still significantly constraining accessible evolutionary trajectories at the protocell level. We conclude with a brief discussion of the implications for further work

An Optical Lattice Clock with Spin-polarized 87Sr Atoms

We present a new evaluation of an 87Sr optical lattice clock using spin polarized atoms. The frequency of the 1S0-3P0 clock transition is found to be 429 228 004 229 873.6 Hz with a fractional accuracy of 2.6 10^{-15}, a value that is comparable to the frequency difference between the various primary standards throughout the world. This measurement is in excellent agreement with a previous one of similar accuracy

On Meme Self-Adaptation in Spatially-Structured Multimemetic Algorithms

NMA 2014Multimemetic algorithms (MMAs) are memetic algorithms that explicitly exploit the evolution of memes, i.e., non-genetic expressions of problem-solving strategies. We consider a class of MMAs in which these memes are rewriting rules whose length can be fixed during the run of the algorithm or self-adapt during the search process. We analyze this self-adaptation in the context of spatially-structured MMAs, namely MMAs in which the population is endowed with a certain topology to which interactions (from the point of view of selection and variation operators) are constrained. For the problems considered, it is shown that panmictic (i.e., non-structured) MMAs are more sensitive to this self-adaptation, and that using variable-length memes seems to be a robust strategy throughout different population structures.This work is partially supported by MICINN project ANYSELF (TIN2011-28627-C04-01), by Junta de Andaluía project DNEMESIS (P10-TIC-6083) and by Universidad de Málaga, Campus de Excelencia Internacional Andalucía Tech

A simple mathematical model of gradual Darwinian evolution: Emergence of a Gaussian trait distribution in adaptation along a fitness gradient

We consider a simple mathematical model of gradual Darwinian evolution in continuous time and continuous trait space, due to intraspecific competition for common resource in an asexually reproducing population in constant environment, while far from evolutionary stable equilibrium. The model admits exact analytical solution. In particular, Gaussian distribution of the trait emerges from generic initial conditions.Comment: 21 pages, 2 figures, as accepted to J Math Biol 2013/03/1

Towards an analytical framework of science communication models

This chapter reviews the discussion in science communication circles of models for public communication of science and technology (PCST). It questions the claim that there has been a large-scale shift from a ‘deficit model’ of communication to a ‘dialogue model’, and it demonstrates the survival of the deficit model along with the ambiguities of that model. Similar discussions in related fields of communication, including the critique of dialogue, are briefly sketched. Outlining the complex circumstances governing approaches to PCST, the author argues that communications models often perceived to be opposed can, in fact, coexist when the choices are made explicit. To aid this process, the author proposes an analytical framework of communication models based on deficit, dialogue and participation, including variations on each