Playing with molecules

Recent philosophy of science has seen a number of attempts to understand scientific models by looking to theories of fiction. In previous work, I have offered an account of models that draws on Kendall Walton’s ‘make-believe’ theory of art. According to this account, models function as ‘props’ in games of make-believe, like children’s dolls or toy trucks. In this paper, I assess the make-believe view through an empirical study of molecular models. I suggest that the view gains support when we look at the way that these models are used and the attitude that users take towards them. Users’ interaction with molecular models suggests that they do imagine the models to be molecules, in much the same way that children imagine a doll to be a baby. Furthermore, I argue, users of molecular models imagine themselves viewing and manipulating molecules, just as children playing with a doll might imagine themselves looking at a baby or feeding it. Recognising this ‘participation’ in modelling, I suggest, points towards a new account of how models are used to learn about the world, and helps us to understand the value that scientists sometimes place on three-dimensional, physical models over other forms of representation.     

Cellular mechanisms and signals that coordinate plasma membrane repair

Plasma membrane forms the barrier between the cytoplasm and the environment. Cells constantly and selectively transport molecules across their plasma membrane without disrupting it. Any disruption in the plasma membrane compromises its selective permeability and is lethal, if not rapidly repaired. There is a growing understanding of the organelles, proteins, lipids, and small molecules that help cells signal and efficiently coordinate plasma membrane repair. This review aims to summarize how these subcellular responses are coordinated and how cellular signals generated due to plasma membrane injury interact with each other to spatially and temporally coordinate repair. With the involvement of calcium and redox signaling in single cell and tissue repair, we will discuss how these and other related signals extend from single cell repair to tissue level repair. These signals link repair processes that are activated immediately after plasma membrane injury with longer term processes regulating repair and regeneration of the damaged tissue. We propose that investigating cell and tissue repair as part of a continuum of wound repair mechanisms would be of value in treating degenerative diseases.     

Dimerization leads to changes in APP (amyloid precursor protein) trafficking mediated by LRP1 and SorLA

Proteolytic cleavage of the amyloid precursor protein (APP) by α-, β- and γ-secretases is a determining factor in Alzheimer’s disease (AD). Imbalances in the activity of all three enzymes can result in alterations towards pathogenic Aβ production. Proteolysis of APP is strongly linked to its subcellular localization as the secretases involved are distributed in different cellular compartments. APP has been shown to dimerize in cis-orientation, affecting Aβ production. This might be explained by different substrate properties defined by the APP oligomerization state or alternatively by altered APP monomer/dimer localization. We investigated the latter hypothesis using two different APP dimerization systems in HeLa cells. Dimerization caused a decreased localization of APP to the Golgi and at the plasma membrane, whereas the levels in the ER and in endosomes were increased. Furthermore, we observed via live cell imaging and biochemical analyses that APP dimerization affects its interaction with LRP1 and SorLA, suggesting that APP dimerization modulates its interplay with sorting molecules and in turn its localization and processing. Thus, pharmacological approaches targeting APP oligomerization properties might open novel strategies for treatment of AD.     

Two new species of feather mites (Acarina: Psoroptidia) from the blue-throated blue flycatcher,Cyornis rubeculoides (Passeriformes: Muscicapidae)

The paper describes two new species of feather mites collected from the blue-throated blue flycatcher Cyornis rubeculoides (Vigors) (Passeriformes: Muscicapidae) in India (Meghalaya): Trouessartia kharkhanensis Constantinescu et al. sp. nov. (Trouessartiidae) and Proterothrix cyornissimilis Constantinescu et al. sp. nov. (Proctophyllodidae: Pterodectinae). Both sexes of T. kharkhanensis differ from the closest species, T. rubecula Jablonska, 1968 by having setae si and c2 lanceolate and setae c3 and sRIII with acute apex. In males of the new species, the adanal apodemes have a hook-like retroverse apophysis and the internal margins of terminal lamellae have a shallow invagination at the level of setae h3. Both sexes of P. cyornissimilis differ from the closest species, P. cyornis Mironov and Tolstenkov, 2013, mainly by the ornamentation of the dorsal shields: it is absent on the prodorsal shield and poorly expressed on the hysteronothal shield. In males of the new species, the supranal concavity is triangular and the genital arch has a pair of small ovoid sclerites at its tips.

http:/zoobank.org/urn:lsid:zoobank.org:pub:1671D6D4-8895-467B-A124-05EDBB0DF406     

Following evolution of bacterial antibiotic resistance in real time

A new study reports the development of the 'morbidostat', a device that allows for continuous culture of bacteria under a constant drug selection pressure using computer feedback control of antibiotic concentration. This device, together with bacterial whole-genome sequencing, allowed the authors to follow the evolution of resistance-conferring mutations in Escherichia coli populations in real time, providing support for deterministic evolution of resistance in some situations.     

Recombination rates in admixed individuals identified by ancestry-based inference

Studies of recombination and how it varies depend crucially on accurate recombination maps. We propose a new approach for constructing high-resolution maps of relative recombination rates based on the observation of ancestry switch points among admixed individuals. We show the utility of this approach using simulations and by applying it to SNP genotype data from a sample of 2,565 African Americans and 299 African Caribbeans and detecting several hundred thousand recombination events. Comparison of the inferred map with high-resolution maps from non-admixed populations provides evidence of fine-scale differentiation in recombination rates between populations. Overall, the admixed map is well predicted by the average proportion of admixture and the recombination rate estimates from the source populations. The exceptions to this are in areas surrounding known large chromosomal structural variants, specifically inversions. These results suggest that outside of structurally variable regions, admixture does not substantially disrupt the factors controlling recombination rates in humans.     

Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21

In search of common risk alleles for prostate cancer that could contribute to high rates of the disease in men of African ancestry, we conducted a genome-wide association study, with 1,047,986 SNP markers examined in 3,425 African-Americans with prostate cancer (cases) and 3,290 African-American male controls. We followed up the most significant 17 new associations from stage 1 in 1,844 cases and 3,269 controls of African ancestry. We identified a new risk variant on chromosome 17q21 (rs7210100, odds ratio per allele = 1.51, P = 3.4 × 10(-13)). The frequency of the risk allele is ～5% in men of African descent, whereas it is rare in other populations (<1%). Further studies are needed to investigate the biological contribution of this allele to prostate cancer risk. These findings emphasize the importance of conducting genome-wide association studies in diverse populations.     

Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci

We carried out a meta-analysis of data from three genome-wide association (GWA) studies of type 1 diabetes (T1D), testing 305,090 SNPs in 3,561 T1D cases and 4,646 controls of European ancestry. We obtained further support for 4q27 (IL2-IL21, P = 1.9 x 10(-8)) and, after genotyping an additional 6,225 cases, 6,946 controls and 2,828 families, convincing evidence for four previously unknown and distinct risk loci in chromosome regions 6q15 (BACH2, P = 4.7 x 10(-12)), 10p15 (PRKCQ, P = 3.7 x 10(-9)), 15q24 (CTSH, P = 3.2 x 10(-15)) and 22q13 (C1QTNF6, P = 2.0 x 10(-8)).