Computational study of growth and remodelling in the aortic arch

Opening angles (OAs) are associated with growth and remodelling in arteries. One curiosity has been the relatively large OAs found in the aortic arch of some animals. Here, we use computational models to explore the reasons behind this phenomenon. The artery is assumed to contain a smooth muscle/collagen phase and an elastin phase. In the models, growth and remodelling of smooth muscle/collagen depends on wall stress and fluid shear stress. Remodelling of elastin, which normally turns over very slowly, is neglected. The results indicate that OAs generally increase with longitudinal curvature (torus model), earlier elastin production during development, and decreased wall stiffness. Correlating these results with available experimental data suggests that all of these effects may contribute to the large OAs in the aortic arch. The models also suggest that the slow turnover rate of elastin limits longitudinal growth. These results should promote increased understanding of the causes of residual stress in arteries.     

Bacterial swimming strategies and turbulence

Most bacteria in the ocean can be motile. Chemotaxis allows bacteria to detect nutrient gradients, and hence motility is believed to serve as a method of approaching sources of food. This picture is well established in a stagnant environment. In the ocean a shear microenvironment is associated with turbulence. This shear flow prevents clustering of bacteria around local nutrient sources if they swim in the commonly assumed "run-and-tumble" strategy. Recent observations, however, indicate a "back-and-forth" swimming behavior for marine bacteria. In a theoretical study we compare the two bacterial swimming strategies in a realistic ocean environment. The "back-and-forth" strategy is found to enable the bacteria to stay close to a nutrient source even under high shear. Furthermore, rotational diffusion driven by thermal noise can significantly enhance the efficiency of this strategy. The superiority of the "back-and-forth" strategy suggests that bacterial motility has a control function rather than an approach function under turbulent conditions.     

The power of respect in (and for) the study of stigma and discrimination

This review essay of Getting Respect: Responding to Stigma and Discrimination in the United States, Brazil, and Israel explores how the politics of respectability is employed in vastly different ways as a response to encounters with stigma and discrimination. For such victimized people, the manner and timing of its employment rests in the particular nature of the social and political contexts circumscribing their lives. Differences remain in whether people interpret certain interactions as validating responses as well as in the kinds of responses they ultimately produce. Taking these and other factors into account, the employment of the politics of respectability should not be regarded solely as the self-affirmation of the moral legitimacy of the victimized. Rather, that form of response is predicated on the recognition of the kinds of agency that may (or may not) be available given the large-scale social power dynamics that circumscribe micro-level acts of discrimination and stigmatization.     

Linking fish trait responses to in‐stream habitat in reconstructed valley‐plugged stream reaches of the Coastal Plain,U.S.A.

Valley‐plug formation is a challenging consequence of stream channelization especially in physiographic regions with highly erodible soils. Upstream channel degradation and incision results in accelerated sediment delivery processes wherein downstream aggradation decreases stream power and creates sand‐clogged channels. Channel reconstruction is now meeting hydrogeomorphic goals related to valley‐plug remediation, yet there exists a need to understand how this practice also facilitates ecological restoration. We evaluated fish trait response to in‐stream habitat conditions in channelized, recently restored, and “least‐disturbed” reference reaches of Coastal Plain streams in West Tennessee. Restored reaches were ecologically similar to channelized reaches, having higher proportions of nest‐guarding omnivores that were correlated with higher percentages of pool habitats and lower wetted width:depth ratios compared to reference reaches. Reference reaches had higher proportions of fast‐water dwelling and specialized insectivores that were correlated with high abundance of large woody debris, high‐wetted width:depth ratios, and low percentages of pool habitats. We conclude that in‐stream habitats in reconstructed channels have yet to promote reach‐scale ecological restoration relative to fish assemblage organization because trait‐habitat associations were not similar to reference conditions. However, our results lend to the development of ecological restoration targets that can be incorporated in future channel reconstruction projects in valley‐plugged, channelized streams of the Coastal Plain.     

The return of the frogs: The importance of habitat refugia in maintaining diversity during a disease outbreak

Recent decades have seen the emergence and spread of numerous infectious diseases, often with severe negative consequences for wildlife populations. Nevertheless, many populations survive the initial outbreaks, and even undergo recoveries. Unfortunately, the long‐term effects of these outbreaks on host population genetics are poorly understood; to increase this understanding, we examined the population genetics of two species of rainforest frogs (Litoria nannotis and Litoria serrata) that have largely recovered from a chytridiomycosis outbreak at two national parks in the Wet Tropics of northern Australia. At the wetter, northern park there was little evidence of decreased genetic diversity in either species, and all of the sampled sites had high minor allele frequencies (mean MAF = 0.230–0.235), high heterozygosity (0.318–0.325), and few monomorphic markers (1.4%–4.0%); however, some recovered L. nannotis populations had low N_e values (59.3–683.8) compared to populations that did not decline during the outbreak (1,537.4–1,756.5). At the drier, southern park, both species exhibited lower diversity (mean MAF = 0.084–0.180; heterozygosity = 0.126–0.257; monomorphic markers = 3.7%–43.5%; N_e = 18.4–676.1). The diversity patterns in this park matched habitat patterns, with both species having higher diversity levels and fewer closely related individuals at sites with higher quality habitat. These patterns were more pronounced for L. nannotis, which has lower dispersal rates than L. serrata. These results suggest that refugia with high quality habitat are important for retaining genetic diversity during disease outbreaks, and that gene flow following disease outbreaks is important for re‐establishing diversity in populations where it was reduced.     

Robust classification of protein variation using structural modelling and large-scale data integration

Existing methods for interpreting protein variation focus on annotating mutation pathogenicity rather than detailed interpretation of variant deleteriousness and frequently use only sequence-based or structure-based information. We present VIPUR, a computational framework that seamlessly integrates sequence analysis and structural modelling (using the Rosetta protein modelling suite) to identify and interpret deleterious protein variants. To train VIPUR, we collected 9477 protein variants with known effects on protein function from multiple organisms and curated structural models for each variant from crystal structures and homology models. VIPUR can be applied to mutations in any organism''s proteome with improved generalized accuracy (AUROC .83) and interpretability (AUPR .87) compared to other methods. We demonstrate that VIPUR''s predictions of deleteriousness match the biological phenotypes in ClinVar and provide a clear ranking of prediction confidence. We use VIPUR to interpret known mutations associated with inflammation and diabetes, demonstrating the structural diversity of disrupted functional sites and improved interpretation of mutations associated with human diseases. Lastly, we demonstrate VIPUR''s ability to highlight candidate variants associated with human diseases by applying VIPUR to de novo variants associated with autism spectrum disorders.     

DNA divergence in and around the alcohol dehydrogenase locus in five closely related species of Hawaiian Drosophila

The alcohol dehydrogenase (Adh) region from five planitibia subgroup species of Hawaiian picture-wing Drosophila has been cloned. A total of 15 kb of DNA in and around the Adh gene has been compared among the five species. Genetic distances were calculated to determine evolutionary relationships. These distances agree with previous distances determined by protein polymorphism and DNA hybridization techniques and can be interpreted in terms of specific island colonization and speciation (founder) events over the past 5 Myr. Examination of the restriction maps of the cloned Adh region from the five species shows many instances of small deletions, insertion of a transposable element in D. heteroneura, and the existence of a highly variable region on the 3' side of the Adh gene. Clustering relationships and rates of DNA change are calculated and compared with the relationship found for other species of Drosophila.      

Kinesin-13 regulates the quantity and quality of tubulin inside cilia

Kinesin-13, an end depolymerizer of cytoplasmic and spindle microtubules, also affects the length of cilia. However, in different models, depletion of kinesin-13 either lengthens or shortens cilia, and therefore the exact function of kinesin-13 in cilia remains unclear. We generated null mutations of all kinesin-13 paralogues in the ciliate Tetrahymena. One of the paralogues, Kin13Ap, localizes to the nuclei and is essential for nuclear divisions. The remaining two paralogues, Kin13Bp and Kin13Cp, localize to the cell body and inside assembling cilia. Loss of both Kin13Bp and Kin13Cp resulted in slow cell multiplication and motility, overgrowth of cell body microtubules, shortening of cilia, and synthetic lethality with either paclitaxel or a deletion of MEC-17/ATAT1, the α-tubulin acetyltransferase. The mutant cilia assembled slowly and contained abnormal tubulin, characterized by altered posttranslational modifications and hypersensitivity to paclitaxel. The mutant cilia beat slowly and axonemes showed reduced velocity of microtubule sliding. Thus kinesin-13 positively regulates the axoneme length, influences the properties of ciliary tubulin, and likely indirectly, through its effects on the axonemal microtubules, affects the ciliary dynein-dependent motility.     

A study on mode of antifeedant effects of epilimonol against Leptinotarsa decemlineata

Colorado potato beetle, Leptinotarsa decemlineata (Say), neonate larvae and adults were bioassayed with the antifeedant epilimonol. Three-day exposure of neonate larvae resulted in increasing delays in development (appearance of 4th instars) corresponding to increasing dosages. At a dosage of 20 g/cm², development was delayed by about 40% without other detrimental effects. Mouthpart coating of adult beetles with epilimonol emulsion resulted in significant feeding reductions, while injection of epilimonol into the haemolymph of female adults did not elicit significant feeding reduction or oviposition suppression. The results indicated that epilimonol did not elicit significant internal toxicity, and feeding reductions were most likely exerted by action on chemoreceptors on mouthparts or in the preoral cavity.