A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis

Toll-like receptors (TLRs) and members of their signaling pathway are important in the initiation of the innate immune response to a wide variety of pathogens. The adaptor protein Mal (also known as TIRAP), encoded by TIRAP (MIM 606252), mediates downstream signaling of TLR2 and TLR4 (refs. 4-6). We report a case-control study of 6,106 individuals from the UK, Vietnam and several African countries with invasive pneumococcal disease, bacteremia, malaria and tuberculosis. We genotyped 33 SNPs, including rs8177374, which encodes a leucine substitution at Ser180 of Mal. We found that heterozygous carriage of this variant associated independently with all four infectious diseases in the different study populations. Combining the study groups, we found substantial support for a protective effect of S180L heterozygosity against these infectious diseases (N = 6,106; overall P = 9.6 x 10(-8)). We found that the Mal S180L variant attenuated TLR2 signal transduction.     

A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk

To identify risk variants for colorectal cancer (CRC), we conducted a genome-wide association study, genotyping 550,163 tag SNPs in 940 individuals with familial colorectal tumor (627 CRC, 313 advanced adenomas) and 965 controls. We evaluated selected SNPs in three replication sample sets (7,473 cases, 5,984 controls) and identified three SNPs in SMAD7 (involved in TGF-beta and Wnt signaling) associated with CRC. Across the four sample sets, the association between rs4939827 and CRC was highly statistically significant (P(trend) = 1.0 x 10(-12)).     

Identification of loci associated with schizophrenia by genome-wide association and follow-up

We carried out a genome-wide association study of schizophrenia (479 cases, 2,937 controls) and tested loci with P < 10(-5) in up to 16,726 additional subjects. Of 12 loci followed up, 3 had strong independent support (P < 5 x 10(-4)), and the overall pattern of replication was unlikely to occur by chance (P = 9 x 10(-8)). Meta-analysis provided strongest evidence for association around ZNF804A (P = 1.61 x 10(-7)) and this strengthened when the affected phenotype included bipolar disorder (P = 9.96 x 10(-9)).     

The Left Vienna Circle, Part 2. The Left Vienna Circle, disciplinary history, and feminist philosophy of science

This paper analyzes the claim that the Left Vienna Circle (LVC) offers a theoretical and historical precedent for a politically engaged philosophy of science today. I describe the model for a political philosophy of science advanced by LVC historians. They offer this model as a moderate, properly philosophical approach to political philosophy of science that is rooted in the analytic tradition. This disciplinary-historical framing leads to weaknesses in LVC scholars’ conception of the history of the LVC and its contemporary relevance. In this light, I examine the claim that there are productive enrichments to be gained from the engagement of feminist philosophy of science with the LVC, finding this claim ill-formulated. The case of LVC historiography and feminist philosophy of science presents a revealing study in the uses and ethics of disciplinary history, showing how feminist and other perspectives are misconceived and marginalized by forms of disciplinary self-narrativizing.     

Understanding the role of wrongdoing in technological disasters: Utilizing ecofeminist philosophy to examine commemoration

Stemming from human accident, error, or neglect, technological disasters, such as chemical spills, toxic waste contamination, nuclear radiation, transportation accidents, and factory explosions, are products of the modern industrial complex. Toxic contamination of the land can permanently displace people from their homes and erase places from the landscape. Commemoration provides an opportunity to remember the past and celebrate culturally significant place attachments while contributing to the recovery process by aiding in community healing after devastating events. We focus on two key components regarding commemoration after technological disaster, namely the acknowledgement of wrongdoing and the celebration of a resilient population and landscape. We argue that a combination of ecofeminist philosophy and environmental justice frameworks allows for a better understanding of the cycle of disaster and mitigation as it pertains to targeted groups, and that commemorative acts and artifacts following human-made disasters often fail to successfully reform this cycle. Moreover, the combination of ecofeminist philosophy and environmental justice allows us to examine the complex relationship between responsibility and targeted groups through disaster commemoration, which serves as an important way to communicate wrongdoing to both the local and greater population. Through engagement with ecofeminist philosophy and environmental justice frameworks, we explicate how commemoration after technological disaster can disrupt or reinforce systematic inequalities.     

Stylet jaws of Chrysopetalidae (Annelida)

Micro-CT imaging elucidates jaw and pharynx structure in 14 nominal taxa belonging to Chrysopetalinae, Dysponetinae and Calamyzinae (Chrysopetalidae: Annelida). Systematic evaluation of chrysopetalid jaw form in each taxon is used to compare inter-generic relationships within and between each subfamily and with other polychaete families possessing lateral pairs of jaws. Jaw morphology proves diagnostic at all levels including agreement with current molecular phylogenetic analyses of the Chrysopetalidae. The greatest diversity of pharynx and jaw form, associated with sensory body characters, is found amongst taxa of the epibenthic Chrysopetalinae. It is hypothesized that the paired stylet jaws interlock to pierce prey tissue, and, in concert with a highly muscular pharynx, suck out prey fluids that pass down the internal groove of the stylets. Three generic groups are identified based on congruence of jaw form, and novel buccal structures are revealed in some taxa: a pharyngeal calcareous ‘ring’ and extensive pharyngeal glands. A continuum across free-living and facultative symbiont lifestyles is represented across all Chrysopetalinae. Dysponetinae comprises free-living, very small individuals that exhibit a meiofaunal lifestyle. All species possess one type of simple, tanned rod-like stylet jaws and certain simplified body structures. Calamyzinae species possess polyphyletic jaw forms and grades of radically simplified sensory morphologies. Free-living, bacteriovore calamyzins inhabit extreme chemosynthetic habitats and lack jaws, or possess modified jaws composed of an anterior platelet and posterior grooved jaw, present in the larvae and lost in the adult. New observations of an ectoparasitic Calamyzinae include details of a specialized mouth opening and stylet jaw present in a species that exhibits cryptic coloration, while grooved jaws are revealed for the first time in an obligate symbiont calamyzin. The grooved jaw form is considered a non-homoplasious synapomorphy that supports the monophyly of the family Chrysopetalidae.     

Genetic contributions to stability and change in intelligence from childhood to old age

Understanding the determinants of healthy mental ageing is a priority for society today. So far, we know that intelligence differences show high stability from childhood to old age and there are estimates of the genetic contribution to intelligence at different ages. However, attempts to discover whether genetic causes contribute to differences in cognitive ageing have been relatively uninformative. Here we provide an estimate of the genetic and environmental contributions to stability and change in intelligence across most of the human lifetime. We used genome-wide single nucleotide polymorphism (SNP) data from 1,940 unrelated individuals whose intelligence was measured in childhood (age 11 years) and again in old age (age 65, 70 or 79 years). We use a statistical method that allows genetic (co)variance to be estimated from SNP data on unrelated individuals. We estimate that causal genetic variants in linkage disequilibrium with common SNPs account for 0.24 of the variation in cognitive ability change from childhood to old age. Using bivariate analysis, we estimate a genetic correlation between intelligence at age 11 years and in old age of 0.62. These estimates, derived from rarely available data on lifetime cognitive measures, warrant the search for genetic causes of cognitive stability and change.