Norton's material theory of analogy

In his book, The Material Theory of Induction, Norton argues that the quest for a universal formal theory or ‘schema’ for analogical inference should be abandoned. In its place, he offers the “material theory of analogy”: each analogical inference is “powered” by a local fact of analogy rather than by any formal schema. His minimalist model promises a straightforward, fact-based approach to the evaluation and justification of analogical inferences. This paper argues that although the rejection of universal schemas is justified, Norton's positive theory is limited in scope: it works well only for a restricted class of analogical inferences. Both facts and quasi-formal criteria have roles to play in a theory of analogical reasoning.     

Nest architecture in polydomous grass-cutting ants (Acromyrmex balzani)

Acromyrmex balzani is a grass-cutting ant species frequently found in Cerrado areas. However, little is known about the architecture of the polydomous nests of this ant. Fifteen A. balzani nests located in a cerrado region in Botucatu, São Paulo, Brazil, were studied. The polydomous nests were studied in three ways. First, we investigated the architecture in nests moulded with cement and without moulding. Second, we performed an aggressiveness test among workers in different subnests and nests. Third, we excavated the nest and collected the colony to measure the population, verifying the existence or not of a queen in all nests. A cement mould was made of seven nests to permit better visualization of internal structures such as chambers and tunnels. Eight nests were excavated without moulding and white neutral talc was used to highlight the parts of the nests. After excavation, the depth and dimensions (length, width and height) of the chambers were measured. The results showed that the nests had a single entrance hole whose structure consisted of straw and other plant residues in winter. Mounds of loose soil, if present, were found 6–48 cm from the hole. The number of chambers containing fungus ranged from one to five, with the first being found a few centimetres beneath the ground surface (4 cm) and the last up to a maximum depth of 160 cm. The length of the tunnels ranged from 12 to 28 cm. These tunnels were built in a vertical or inclined position, leading to the chambers. No waste chambers were found, with the waste being deposited externally. Additionally, the polydomous nests contained one to eight subnests. In the aggressiveness test, when concolonial workers were confronted, no aggressiveness was observed. In contrast, when allocolonial workers were confronted, there was a high incidence of aggression among them. Excavation of polydomous nests showed only one queen for each polydomous nest, i.e. subnests with a single queen. Our study contributes to a better understanding of the so far unknown nest architecture of the polydomous grass-cutting ant A. balzani.     

Cryptic subarctic diversity: a new bumblebee species from the Yukon and Alaska (Hymenoptera: Apidae)

It is nearly 90 years since a bumblebee species has been described for the first time from Canada or the USA that was previously unrecognised by science. We describe and illustrate Bombus(Alpinobombus) kluanensis sp. nov. and begin to map its distribution. This species was discovered through analysis of Cytochrome c Oxidase subunit I barcodes and had been unsuspected on the basis of morphological and colour characteristics. So far, 247 female specimens considered to belong to this species are known from the subarctic mountains associated with the Denali Fault running from the Alaska Range (Alaska, USA) to Kluane in the Saint Elias Mountains (Yukon, Canada). A checklist of all species of the subgenus Alpinobombus worldwide is provided.

http://zoobank.org/urn:lsid:zoobank.org:pub:78D524DD-FFBA-4BC4-8D39-3EF4F6BDD39E     

Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis

Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by approximately 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease.     

Analysis of the human protein interactome and comparison with yeast, worm and fly interaction datasets

We present the first analysis of the human proteome with regard to interactions between proteins. We also compare the human interactome with the available interaction datasets from yeast (Saccharomyces cerevisiae), worm (Caenorhabditis elegans) and fly (Drosophila melanogaster). Of >70,000 binary interactions, only 42 were common to human, worm and fly, and only 16 were common to all four datasets. An additional 36 interactions were common to fly and worm but were not observed in humans, although a coimmunoprecipitation assay showed that 9 of the interactions do occur in humans. A re-examination of the connectivity of essential genes in yeast and humans indicated that the available data do not support the presumption that the number of interaction partners can accurately predict whether a gene is essential. Finally, we found that proteins encoded by genes mutated in inherited genetic disorders are likely to interact with proteins known to cause similar disorders, suggesting the existence of disease subnetworks. The human interaction map constructed from our analysis should facilitate an integrative systems biology approach to elucidating the cellular networks that contribute to health and disease states.     

Automating sequence-based detection and genotyping of SNPs from diploid samples

The detection of sequence variation, for which DNA sequencing has emerged as the most sensitive and automated approach, forms the basis of all genetic analysis. Here we describe and illustrate an algorithm that accurately detects and genotypes SNPs from fluorescence-based sequence data. Because the algorithm focuses particularly on detecting SNPs through the identification of heterozygous individuals, it is especially well suited to the detection of SNPs in diploid samples obtained after DNA amplification. It is substantially more accurate than existing approaches and, notably, provides a useful quantitative measure of its confidence in each potential SNP detected and in each genotype called. Calls assigned the highest confidence are sufficiently reliable to remove the need for manual review in several contexts. For example, for sequence data from 47-90 individuals sequenced on both the forward and reverse strands, the highest-confidence calls from our algorithm detected 93% of all SNPs and 100% of high-frequency SNPs, with no false positive SNPs identified and 99.9% genotyping accuracy. This algorithm is implemented in a software package, PolyPhred version 5.0, which is freely available for academic use.     

Genome-wide genetic association of complex traits in heterogeneous stock mice

Difficulties in fine-mapping quantitative trait loci (QTLs) are a major impediment to progress in the molecular dissection of complex traits in mice. Here we show that genome-wide high-resolution mapping of multiple phenotypes can be achieved using a stock of genetically heterogeneous mice. We developed a conservative and robust bootstrap analysis to map 843 QTLs with an average 95% confidence interval of 2.8 Mb. The QTLs contribute to variation in 97 traits, including models of human disease (asthma, type 2 diabetes mellitus, obesity and anxiety) as well as immunological, biochemical and hematological phenotypes. The genetic architecture of almost all phenotypes was complex, with many loci each contributing a small proportion to the total variance. Our data set, freely available at http://gscan.well.ox.ac.uk, provides an entry point to the functional characterization of genes involved in many complex traits.     

The PHYTOCHROME C photoreceptor gene mediates natural variation in flowering and growth responses of Arabidopsis thaliana

Light has an important role in modulating seedling growth and flowering time. We show that allelic variation at the PHYTOCHROME C (PHYC) photoreceptor locus affects both traits in natural populations of A. thaliana. Two functionally distinct PHYC haplotype groups are distributed in a latitudinal cline dependent on FRIGIDA, a locus that together with FLOWERING LOCUS C explains a large portion of the variation in A. thaliana flowering time. In a genome-wide scan for association of 65 loci with latitude, there was an excess of significant P values, indicative of population structure. Nevertheless, PHYC was the most strongly associated locus across 163 strains, suggesting that PHYC alleles are under diversifying selection in A. thaliana. Our work, together with previous findings, suggests that photoreceptor genes are major agents of natural variation in plant flowering and growth response.     

Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch

The epidermis is a highly organized structure, the integrity of which is central to the protection of an organism. Development and subsequent maintenance of this tissue depends critically on the intricate balance between proliferation and differentiation of a resident stem cell population; however, the signals controlling the proliferation-differentiation switch in vivo remain elusive. Here, we show that mice carrying a homozygous missense mutation in interferon regulatory factor 6 (Irf6), the homolog of the gene mutated in the human congenital disorders Van der Woude syndrome and popliteal pterygium syndrome, have a hyperproliferative epidermis that fails to undergo terminal differentiation, resulting in soft tissue fusions. We further demonstrate that mice that are compound heterozygotes for mutations in Irf6 and the gene encoding the cell cycle regulator protein stratifin (Sfn; also known as 14-3-3sigma) show similar defects of keratinizing epithelia. Our results indicate that Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch and that Irf6 and Sfn interact genetically in this process.