Why are some animal populations unaffected or positively affected by roads?

In reviews on effects of roads on animal population abundance we found that most effects are negative; however, there are also many neutral and positive responses [Fahrig and Rytwinski (Ecol Soc 14:21, 2009; Rytwinski and Fahrig (Biol Conserv 147:87–98, 2012)]. Here we use an individual-based simulation model to: (1) confirm predictions from the existing literature of the combinations of species traits and behavioural responses to roads that lead to negative effects of roads on animal population abundance, and (2) improve prediction of the combinations of species traits and behavioural responses to roads that lead to neutral and positive effects of roads on animal population abundance. Simulations represented a typical situation in which road mitigation is contemplated, i.e. rural landscapes containing a relatively low density (up to 1.86 km/km²) of high-traffic roads, with continuous habitat between the roads. In these landscapes, the simulations predict that populations of species with small territories and movement ranges, and high reproductive rates, i.e. many small mammals and birds, should not be reduced by roads. Contrary to previous suggestions, the results also predict that populations of species that obtain a resource from roads (e.g. vultures) do not increase with increasing road density. In addition, our simulations support the predation release hypothesis for positive road effects on prey (both small- and large-bodied prey), whereby abundance of a prey species increased with increasing road density due to reduced predation by generalist road-affected predators. The simulations also predict an optimal road density for the large-bodied prey species if it avoids roads or traffic emissions. Overall, the simulation results suggest that in rural landscapes containing high-traffic roads, there are many species for which road mitigation may not be necessary; mitigation efforts should be tailored to the species that show negative population responses to roads.     

Functional landscape heterogeneity and animal biodiversity in agricultural landscapes

Biodiversity in agricultural landscapes can be increased with conversion of some production lands into 'more-natural'- unmanaged or extensively managed - lands. However, it remains unknown to what extent biodiversity can be enhanced by altering landscape pattern without reducing agricultural production. We propose a framework for this problem, considering separately compositional heterogeneity (the number and proportions of different cover types) and configurational heterogeneity (the spatial arrangement of cover types). Cover type classification and mapping is based on species requirements, such as feeding and nesting, resulting in measures of 'functional landscape heterogeneity'. We then identify three important questions: does biodiversity increase with (1) increasing heterogeneity of the more-natural areas, (2) increasing compositional heterogeneity of production cover types and (3) increasing configurational heterogeneity of production cover types? We discuss approaches for addressing these questions. Such studies should have high priority because biodiversity protection globally depends increasingly on maintaining biodiversity in human-dominated landscapes.     

Associations of visceral and liver fat with the metabolic syndrome across the spectrum of obesity: the AGES-Reykjavik study

Visceral adipose tissue (VAT) is a key pathogenic fat depot in the metabolic syndrome (MetS), but liver fat (LF) may also play an important role. We evaluated associations of VAT and LF with MetS in normal weight, overweight, and obese men and women (BMI <25, 25-29.9, and ≥30 kg/m2, respectively). This analysis included 2,495 participants from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik study with computed tomography measurements for VAT and LF. MetS was defined by ≥3 of the following: larger abdominal circumference, hypertension, elevated triglyceride (TG), low high-density lipoprotein (HDL), impaired fasting glucose (IFG), and microalbuminuria. We estimated the odds of MetS per 1-s.d. increase in VAT and LF, adjusting for key covariates. VAT was associated with an increased odds of MetS in normal weight, overweight, and obese women (odds ratios (OR) = 2.78, 1.63, and 1.43, respectively; all P < 0.01) that diminished in magnitude with increasing BMI (VAT × BMI class interaction P < 0.001). In men, VAT was related to MetS only among the overweight (OR = 1.69, P < 0.01). LF was associated with MetS in the overweight and obese groups in women (OR = 1.38 and 1.45; both P < 0.001) and in men (OR = 1.38, P = 0.01; and OR = 1.27, P = 0.10), but not in the normal weight groups. These BMI-specific relationships persisted when both fat depots were included in the model. VAT and LF were associated with MetS independently of each other, and these relationships were modified by BMI class such that, VAT was the more important depot at lower levels of obesity and LF at higher levels. Importantly, fatty liver may be a novel metabolic risk factor in overweight and obese individuals.     

Synthesis and SAR studies of novel heteroaryl fused tetracyclic indole-diamide compounds: potent allosteric inhibitors of the hepatitis C virus NS5B polymerase

Presented here are initial structure-activity relationship (SAR) studies on a series of novel heteroaryl fused tetracyclic indole-based inhibitors of the hepatitis C viral polymerase, NS5B. The introduction of alternative heterocyclic moieties into the indolo-fused inhibitor class significantly expands the reported SAR and resulted in the identification of pyridino analogs, typified by compounds 44 and 45 that displayed excellent potency against the NS5B polymerase of both HCV 1a and HCV 1b genotypes.     

Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women

Body fat distribution, particularly centralized obesity, is associated with metabolic risk above and beyond total adiposity. We performed genome-wide association of abdominal adipose depots quantified using computed tomography (CT) to uncover novel loci for body fat distribution among participants of European ancestry. Subcutaneous and visceral fat were quantified in 5,560 women and 4,997 men from 4 population-based studies. Genome-wide genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), VAT adjusted for body mass index, and VAT/SAT ratio (a metric of the propensity to store fat viscerally as compared to subcutaneously) in the overall sample and in women and men separately. A weighted z-score meta-analysis was conducted. For the VAT/SAT ratio, our most significant p-value was rs11118316 at LYPLAL1 gene (p = 3.1 × 10E-09), previously identified in association with waist-hip ratio. For SAT, the most significant SNP was in the FTO gene (p = 5.9 × 10E-08). Given the known gender differences in body fat distribution, we performed sex-specific analyses. Our most significant finding was for VAT in women, rs1659258 near THNSL2 (p = 1.6 × 10-08), but not men (p = 0.75). Validation of this SNP in the GIANT consortium data demonstrated a similar sex-specific pattern, with observed significance in women (p = 0.006) but not men (p = 0.24) for BMI and waist circumference (p = 0.04 [women], p = 0.49 [men]). Finally, we interrogated our data for the 14 recently published loci for body fat distribution (measured by waist-hip ratio adjusted for BMI); associations were observed at 7 of these loci. In contrast, we observed associations at only 7/32 loci previously identified in association with BMI; the majority of overlap was observed with SAT. Genome-wide association for visceral and subcutaneous fat revealed a SNP for VAT in women. More refined phenotypes for body composition and fat distribution can detect new loci not previously uncovered in large-scale GWAS of anthropometric traits.     

Avian tumor virus interactions with chicken fibroblast plasma membranes

A method is described which will rapidly measure the binding of avian tumor viruses (ATV) to plasma membrane receptors. With this procedure it may be shown that Rous sarcoma virus pseudotypes bind to protease-labile, heat-stable structures on the surface of chicken embryo fibroblast (CEF) plasma membranes. The binding sites for ATV subgroups A and B appear distinct, and membranes from genetically resistant CEF bind as well those of sensitive CEF.     

Fault Tolerance in Protein Interaction Networks: Stable Bipartite Subgraphs and Redundant Pathways

As increasing amounts of high-throughput data for the yeast interactome become available, more system-wide properties are uncovered. One interesting question concerns the fault tolerance of protein interaction networks: whether there exist alternative pathways that can perform some required function if a gene essential to the main mechanism is defective, absent or suppressed. A signature pattern for redundant pathways is the BPM (between-pathway model) motif, introduced by Kelley and Ideker. Past methods proposed to search the yeast interactome for BPM motifs have had several important limitations. First, they have been driven heuristically by local greedy searches, which can lead to the inclusion of extra genes that may not belong in the motif; second, they have been validated solely by functional coherence of the putative pathways using GO enrichment, making it difficult to evaluate putative BPMs in the absence of already known biological annotation. We introduce stable bipartite subgraphs, and show they form a clean and efficient way of generating meaningful BPMs which naturally discard extra genes included by local greedy methods. We show by GO enrichment measures that our BPM set outperforms previous work, covering more known complexes and functional pathways. Perhaps most importantly, since our BPMs are initially generated by examining the genetic-interaction network only, the location of edges in the protein-protein physical interaction network can then be used to statistically validate each candidate BPM, even with sparse GO annotation (or none at all). We uncover some interesting biological examples of previously unknown putative redundant pathways in such areas as vesicle-mediated transport and DNA repair.     

Does forest fragmentation cause an increase in forest temperature?

Forest fragmentation is considered by many to be a primary cause of the current biodiversity crisis. The underlying mechanisms are poorly known, but a potentially important one is associated with altered thermal conditions within the remaining forest patches, especially at forest edges. Yet, large uncertainty remains about the effect of fragmentation on forest temperature, as it is unclear whether temperature decreases from forest edge to forest interior, and whether this local gradient scales up to an effect of fragmentation (landscape attribute) on temperature. We calculated the effect size (correlation coefficient) of distance from forest edge on air temperature, and tested for differences among forest types surrounded by different matrices using meta-analysis techniques. We found a negative edge-interior temperature gradient, but correlation coefficients were highly variable, and significant only for temperate and tropical forests surrounded by a highly contrasting open matrix. Nevertheless, it is unclear if these local-scale changes in temperature can be scaled up to an effect of fragmentation on temperature. Although it may be valid when considering “fragmentation” as forest loss only, the landscape-scale inference is not so clear when we consider the second aspect of fragmentation, where a given amount of forest is divided into a large number of small patches (fragmentation per se). Therefore, care is needed when assuming that fragmentation changes forest temperature, as thermal changes at forest edges depend on forest type and matrix composition, and it is still uncertain if this local gradient can be scaled up to the landscape.