Evaluation of demographic history and neutral parameterization on the performance of FST outlier tests

F_ST outlier tests are a potentially powerful way to detect genetic loci under spatially divergent selection. Unfortunately, the extent to which these tests are robust to nonequilibrium demographic histories has been understudied. We developed a landscape genetics simulator to test the effects of isolation by distance (IBD) and range expansion on F_ST outlier methods. We evaluated the two most commonly used methods for the identification of F_ST outliers (FDIST2 and BayeScan, which assume samples are evolutionarily independent) and two recent methods (FLK and Bayenv2, which estimate and account for evolutionary nonindependence). Parameterization with a set of neutral loci (‘neutral parameterization’) always improved the performance of FLK and Bayenv2, while neutral parameterization caused FDIST2 to actually perform worse in the cases of IBD or range expansion. BayeScan was improved when the prior odds on neutrality was increased, regardless of the true odds in the data. On their best performance, however, the widely used methods had high false‐positive rates for IBD and range expansion and were outperformed by methods that accounted for evolutionary nonindependence. In addition, default settings in FDIST2 and BayeScan resulted in many false positives suggesting balancing selection. However, all methods did very well if a large set of neutral loci is available to create empirical P‐values. We conclude that in species that exhibit IBD or have undergone range expansion, many of the published F_ST outliers based on FDIST2 and BayeScan are probably false positives, but FLK and Bayenv2 show great promise for accurately identifying loci under spatially divergent selection.     

Hibernation alters the diversity and composition of mucosa‐associated bacteria while enhancing antimicrobial defence in the gut of 13‐lined ground squirrels

The gut microbiota plays important roles in animal nutrition and health. This relationship is particularly dynamic in hibernating mammals where fasting drives the gut community to rely on host‐derived nutrients instead of exogenous substrates. We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa‐associated bacterial microbiota and host responses in 13‐lined ground squirrels. The mucosal microbiota was less diverse in winter hibernators than in actively feeding spring and summer squirrels. UniFrac analysis revealed distinct summer and late winter microbiota clusters, while spring and early winter clusters overlapped slightly, consistent with their transitional structures. Communities in all seasons were dominated by Firmicutes and Bacteroidetes, with lesser contributions from Proteobacteria, Verrucomicrobia, Tenericutes and Actinobacteria. Hibernators had lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host‐derived mucins. A core mucosal assemblage of nine operational taxonomic units shared among all individuals was identified with an average total sequence abundance of 60.2%. This core community, together with moderate shifts in specific taxa, indicates that the mucosal microbiota remains relatively stable over the annual cycle yet responds to substrate changes while potentially serving as a pool for ‘seeding’ the microbiota once exogenous substrates return in spring. Relative to summer, hibernation reduced caecal crypt length and increased MUC2 expression in early winter and spring. Hibernation also decreased caecal TLR4 and increased TLR5 expression, suggesting a protective response that minimizes inflammation.     

Molecular analysis of common polymorphisms within the human Tyrosinase locus and genetic association with pigmentation traits

We have compared the melanogenic activities of cultured melanocytes carrying two common TYR alleles as homozygous 192S‐402R wild‐type, heterozygous and homozygous variant. This includes assays of TYR protein, DOPAoxidase activity, glycosylation and temperature sensitivity of protein and DOPAoxidase levels. Homozygous wild‐type strains on average had higher levels of TYR protein and enzyme activity than other genotypes. Homozygous 402Q/Q melanocytes produced significantly less TYR protein, displayed altered trafficking and glycosylation, with reduced DOPAoxidase. However, near wild‐type TYR activity levels could be recovered at lower growth temperature. In a sample population from Southeast Queensland, these two polymorphisms were present on four TYR haplotypes, designated as WT 192S‐402R, 192Y‐402R and 192S‐402Q with a double‐variant 192Y‐402Q of low frequency at 1.9%. Based on cell culture findings and haplotype associations, we have used an additive model to assess the penetrance of the ten possible TYR genotypes derived from the combination of these haplotypes.     

MicroRNA‐206 induces G1 arrest in melanoma by inhibition of CDK4 and Cyclin D

Expression profiling of microRNAs in melanoma lesional skin biopsies compared with normal donor skin biopsies, as well as melanoma cell lines compared with normal melanocytes, revealed that hsa‐miR‐206 was down‐regulated in melanoma (?75.4‐fold, P = 1.7 × 10^?4). MiR‐206 has been implicated in a large number of cancers, including breast, lung, colorectal, ovarian, and prostate cancers; however, its role in tumor development remains largely unknown, its biologic function is poorly characterized, and its targets affecting cancer cells are largely unknown. MiR‐206 reduced growth and migration/invasion of multiple melanoma cell lines. Bioinformatics identified cell cycle genes CDK2, CDK4, Cyclin C, and Cyclin D1 as strong candidate targets. Western blots and 3′UTR reporter gene assays revealed that miR‐206 inhibited translation of CDK4, Cyclin D1, and Cyclin C. Additionally, hsa‐miR‐206 transfection induced G1 arrest in multiple melanoma cell lines. These observations support hsa‐miR‐206 as a tumor suppressor in melanoma and identify Cyclin C, Cyclin D1, and CDK4 as miR‐206 targets.     

What Role Do Local Grocery Stores Play in Urban Food Environments? A Case Study of Hartford-Connecticut

Introduction

Research on urban food environments emphasizes limited access to healthy food, with fewer large supermarkets and higher food prices. Many residents of Hartford, Connecticut, which is often considered a food desert, buy most of their food from small and medium-sized grocery stores. We examined the food environment in greater Hartford, comparing stores in Hartford to those in the surrounding suburbs, and by store size (small, medium, and large).

Methods

We surveyed all small (over 1,000 ft²), medium, and large-sized supermarkets within a 2-mile radius of Hartford (36 total stores). We measured the distance to stores, availability, price and quality of a market basket of 25 items, and rated each store on internal and external appearance. Geographic Information System (GIS) was used for mapping distance to the stores and variation of food availability, quality, and appearance.

Results

Contrary to common literature, no significant differences were found in food availability and price between Hartford and suburban stores. However, produce quality, internal, and external store appearance were significantly lower in Hartford compared to suburban stores (all p<0.05). Medium-sized stores had significantly lower prices than small or large supermarkets (p<0.05). Large stores had better scores for internal (p<0.05), external, and produce quality (p<0.01). Most Hartford residents live within 0.5 to 1 mile distance to a grocery store.

Discussion

Classifying urban areas with few large supermarkets as ‘food deserts’ may overlook the availability of healthy foods and low prices that exist within small and medium-sized groceries common in inner cities. Improving produce quality and store appearance can potentially impact the food purchasing decisions of low-income residents in Hartford.     

Eliminating Rabies in Tanzania? Local Understandings and Responses to Mass Dog Vaccination in Kilombero and Ulanga Districts

Background

With increased global attention to neglected diseases, there has been a resurgence of interest in eliminating rabies from developing countries through mass dog vaccination. Tanzania recently embarked on an ambitious programme to repeatedly vaccinate dogs in 28 districts. To understand community perceptions and responses to this programme, we conducted an anthropological study exploring the relationships between dogs, society, geography and project implementation in the districts of Kilombero and Ulanga, Southern Tanzania.

Methodology/Principal Findings

Over three months in 2012, we combined the use of focus groups, semi-structured interviews, a household questionnaire and a population-based survey. Willingness to participate in vaccination was mediated by fear of rabies, high medical treatment costs and the threat of dog culling, as well as broader notions of social responsibility. However, differences between town, rural and (agro-) pastoralist populations in livelihood patterns and dog ownership impacted coverage in ways that were not well incorporated into project planning. Coverage in six selected villages was estimated at 25%, well below official estimates. A variety of problems with campaign mobilisation, timing, the location of central points, equipment and staff, and project organisation created barriers to community compliance. Resource-limitations and institutional norms limited the ability for district staff to adapt implementation strategies.

Conclusions and Significance

In the shadows of resource and institutional limitations in the veterinary sector in Africa, top-down interventions for neglected zoonotic diseases likes rabies need to more explicitly engage with project organisation, capacity and community participation. Greater attention to navigating local realities in planning and implementation is essential to ensuring that rabies, and other neglected diseases, are controlled sustainably.