Methodological Individualism, the We-mode, and Team Reasoning

Raimo Tuomela is one of the pioneers of social action theory and has done as much as anyone over the last thirty years to advance the study of social action and collective intentionality. Social Ontology: Collective Intentionality and Group Agents (2013) presents the latest version of his theory and applications to a range of important social phenomena. The book covers so much ground, and so many important topics in detailed discussions, that it would impossible in a short space to do it even partial justice. In this brief note, I will concentrate on a single, though important, theme in the book, namely, the claim that we must give up methodological individualism in the social sciences and embrace instead irreducibly group notions. I wish to defend methodological individualism as up to the theoretical tasks of the social sciences while acknowledging what is distinctive about the social world and collective intentional action. Tuomela frames the question of the adequacy of methodological individualism in terms of a contrast between what he calls the I-mode and the we-mode. He argues that we-mode phenomena are not reducible to I-mode phenomena, and concludes that we must reject methodological individualism. I will argue that the irreducibility of the we-mode to the I-mode, given how the contrast is set up, does not entail the rejection of methodological individualism. In addition, I will argue that the three conditions that Tuomela places on genuine we-mode activities, the group reason, collectivity, and collective commitment conditions, if they are understood in a way that does not beg the question, can plausibly be satisfied by a reductive account. Finally, I will argue that the specific considerations advanced in the book do not give us reason to think that a reductive account cannot be adequate to the descriptive and explanatory requirements of a theory of the social worl

Chiral Polymerization in Open Systems From Chiral-Selective Reaction Rates

We investigate the possibility that prebiotic homochirality can be achieved exclusively through chiral-selective reaction rate parameters without any other explicit mechanism for chiral bias. Specifically, we examine an open network of polymerization reactions, where the reaction rates can have chiral-selective values. The reactions are neither autocatalytic nor do they contain explicit enantiomeric cross-inhibition terms. We are thus investigating how rare a set of chiral-selective reaction rates needs to be in order to generate a reasonable amount of chiral bias. We quantify our results adopting a statistical approach: varying both the mean value and the rms dispersion of the relevant reaction rates, we show that moderate to high levels of chiral excess can be achieved with fairly small chiral bias, below 10%. Considering the various unknowns related to prebiotic chemical networks in early Earth and the dependence of reaction rates to environmental properties such as temperature and pressure variations, we argue that homochirality could have been achieved from moderate amounts of chiral selectivity in the reaction rates.Comment: 15 pages, 6 figures, accepted for publication in Origins of Life and Evolution of Biosphere

The genetic contribution of single male immigrants to small, inbred populations: A laboratory study using drosophila melanogaster

This study examined the genetic contribution of single male immigrants to small, inbred laboratory populations of Drosophila melanogaster. Genetic contribution was assessed by measuring the relative frequency of immigrant marker alleles in the first and second generations after immigration, while controlling for any selection effects at the marker locus, and for the experience of male immigrants. When immigrants were outbred, the mean frequency of the immigrant allele was significantly higher than its initial frequency, in both the first and second generations after immigration. There was no significant change in allele frequency for populations receiving inbred immigrants. The increase in allele frequency for outbred immigrants was attributed to an initial outbred vigour fitness advantage of immigrant males over resident males experiencing inbreeding depression. Hybrid vigour of immigrant progeny and the rare-male effect did not have a statistically significant role in the fitness advantage of the immigrant allele. The results suggest that inbreeding may have a considerable impact on the contribution of immigrants to the genetic diversity of populations

Integrating transposable elements in the 3D genome

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

Large introns in relation to alternative splicing and gene evolution: a case study of Drosophila bruno-3

Background: Alternative splicing (AS) of maturing mRNA can generate structurally and functionally distinct transcripts from the same gene. Recent bioinformatic analyses of available genome databases inferred a positive correlation between intron length and AS. To study the interplay between intron length and AS empirically and in more detail, we analyzed the diversity of alternatively spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene. This gene was known to encode thirteen exons separated by introns of diverse sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's structure is expected to be conducive to AS, only two ASTs of this gene were previously described. Results: Cloning of RT-PCR products of the entire ORF from four species representing three diverged Drosophila lineages provided an evolutionary perspective, high sensitivity, and long-range contiguity of splice choices currently unattainable by high-throughput methods. Consequently, we identified three new exons, a new exon fragment and thirty-three previously unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the exons surrounded by introns of at least 800 nucleotides, whereas exons split by introns of less than 250 nucleotides were always spliced contiguously in mRNA. Cases of exon loss and creation during Bru-3 evolution in Drosophila were also localized within large introns. Notably, we identified a true de novo exon gain: exon 8 was created along the lineage of the obscura group from intronic sequence between cryptic splice sites conserved among all Drosophila species surveyed. Exon 8 was included in mature mRNA by the species representing all the major branches of the obscura group. To our knowledge, the origin of exon 8 is the first documented case of exonization of intronic sequence outside vertebrates. Conclusion: We found that large introns can promote AS via exon-skipping and exon turnover during evolution likely due to frequent errors in their removal from maturing mRNA. Large introns could be a reservoir of genetic diversity, because they have a greater number of mutable sites than short introns. Taken together, gene structure can constrain and/or promote gene evolution

The spatial range of peripheral collinear facilitation

Contrast detection thresholds for a central Gabor patch (target) can be modulated by the presence of co-oriented and collinear high contrast Gabors flankers. In foveal vision collinear facilitation can be observed for target-to-flankers relative distances beyond two times the wavelength (λ) of the Gabor's carrier, while for shorter relative distances (<2λ) there is suppression. These modulatory influences seem to disappear after 12λ. In this study, we measured contrast detection thresholds for different spatial frequencies (1, 4 and 6 cpd) and target-to-flankers relative distances ranging from 6 to 16λ, but with collinear configurations presented in near periphery at 4° of eccentricity. Results showed that in near periphery collinear facilitation extends beyond 12λ for the higher spatial frequencies tested (4 and 6 cpd), while it decays already at 10λ for the lowest spatial frequency used (i.e., 1 cpd). In addition, we found that increasing the spatial frequency the peak of collinear facilitation shifts towards larger target-to-flankers relative distances (expressed as multiples of the stimulus wavelength), an effect never reported neither for near peripheral nor for central vision. The results suggest that the peak and the spatial extent of collinear facilitation in near periphery depend on the spatial frequency of the stimuli used

Loss of Function in Escherichia coli exposed to Environmentally Relevant Concentrations of Benzalkonium Chloride

Assessing the risk of resistance associated with biocide exposure commonly involves exposing microorganisms to biocides at concentrations close to the MIC. With the aim of representing exposure to environmental biocide residues, MG1655 was grown for 20 passages in the presence or absence of benzalkonium chloride (BAC) at 100 ng/L and 1000 ng/L (0.0002% and 0.002% of the MIC respectively). BAC susceptibility, planktonic growth rates, motility and biofilm-formation were assessed, and differentially expressed genes determined via RNA-sequencing. Planktonic growth rate and biofilm-formation were significantly reduced (p<0.001) following BAC adaptation, whilst BAC minimum bactericidal concentration increased two-fold. Transcriptomic analysis identified 289 upregulated and 391 downregulated genes after long-term BAC adaptation when compared to the respective control organism passaged in BAC-free-media. When the BAC-adapted bacterium was grown in biocide-free medium, 1052 genes were upregulated and 753 were down regulated. Repeated passage solely in biocide-free medium resulted in 460 upregulated and 476 downregulated genes compared to unexposed bacteria. Long-term exposure to environmentally relevant BAC concentrations increased the expression of genes associated with efflux and reduced gene expression associated with outer-membrane porins, motility and chemotaxis. This was manifested phenotypically through loss-of-function (motility). Repeated passage in a BAC-free-environment resulted in the up-regulation of multiple respiration-associated genes, which was reflected by increased growth rate. In summary, repeated exposure of to BAC residues resulted in significant alterations in global gene expression that were associated with minor decreases in biocide susceptibility, reductions in growth-rate and biofilm-formation, and loss of motility. Exposure to very low concentrations of biocide in the environment is a poorly understood risk factor for antimicrobial resistance. Repeated exposure to trace levels of the biocide BAC resulted in loss of function (motility) and a general reduction in bacterial fitness, but relatively minor decreases in susceptibility. These changes were accompanied by widespread changes in the transcriptome. This demonstrates the importance of including phenotypic characterisation in studies designed to assess the risks of biocide exposure. [Abstract copyright: Copyright © 2018 American Society for Microbiology.

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Reduced expression of monocyte CD200R is associated with enhanced proinflammatory cytokine production in sarcoidosis

In sarcoidosis, the proinflammatory cytokines interferon gamma, tumour necrosis factor and interleukin-6 are released by monocyte-derived macrophages and lymphocytes in the lungs and other affected tissues. Regulatory receptors expressed on monocytes and macrophages act to suppress cytokine production, and reduced expression of regulatory receptors may thus promote tissue inflammation. The aim of this study was to characterise the role of regulatory receptors on blood monocytes in patients with sarcoidosis. Cytokine release in response to stimulation of whole blood was measured in healthy controls and Caucasian non-smoking patients with sarcoidosis who were not taking disease modifying therapy. Expression of the regulatory molecules IL-10R, SIRP-α/β, CD47, CD200R, and CD200L was measured by flow cytometry, and functional activity was assessed using blocking antibodies. Stimulated whole blood and monocytes from patients with sarcoidosis produced more TNF and IL-6 compared with healthy controls. 52.9% of sarcoidosis patients had monocytes characterised by low expression of CD200R, compared with 11.7% of controls (p < 0.0001). Patients with low monocyte CD200R expression produced higher levels of proinflammatory cytokines. In functional studies, blocking the CD200 axis increased production of TNF and IL-6. Reduced expression of CD200R on monocytes may be a mechanism contributing to monocyte and macrophage hyper-activation in sarcoidosis

Reptilian Heart Development And The Molecular Basis Of Cardiac Chamber Evolution

The emergence of terrestrial life witnessed the need for more sophisticated circulatory systems. This has evolved in birds, mammals and crocodilians into complete septation of the heart into left and right sides, allowing separate pulmonary and systemic circulatory systems, a key requirement for the evolution of endothermy(1-3). However, the evolution of the amniote heart is poorly understood. Reptilian hearts have been the subject of debate in the context of the evolution of cardiac septation: do they possess a single ventricular chamber or two incompletely septated ventricles(4-7)? Here we examine heart development in the red-eared slider turtle, Trachemys scripta elegans (a chelonian), and the green anole, Anolis carolinensis (a squamate), focusing on gene expression in the developing ventricles. Both reptiles initially form a ventricular chamber that homogenously expresses the T-box transcription factor gene Tbx5. In contrast, in birds and mammals, Tbx5 is restricted to left ventricle precursors(8,9). In later stages, Tbx5 expression in the turtle (but not anole) heart is gradually restricted to a distinct left ventricle, forming a left-right gradient. This suggests that Tbx5 expression was refined during evolution to pattern the ventricles. In support of this hypothesis, we show that loss of Tbx5 in the mouse ventricle results in a single chamber lacking distinct identity, indicating a requirement for Tbx5 in septation. Importantly, misexpression of Tbx5 throughout the developing myocardium to mimic the reptilian expression pattern also results in a single mispatterned ventricular chamber lacking septation. Thus ventricular septation is established by a steep and correctly positioned Tbx5 gradient. Our findings provide a molecular mechanism for the evolution of the amniote ventricle, and support the concept that altered expression of developmental regulators is a key mechanism of vertebrate evolution