Structural and functional analysis of E6 oncoprotein: insights in the molecular pathways of human papillomavirus-mediated pathogenesis

Oncoprotein E6 is essential for oncogenesis induced by human papillomaviruses (HPVs). The solution structure of HPV16-E6 C-terminal domain reveals a zinc binding fold. A model of full-length E6 is proposed and analyzed in the context of HPV evolution. E6 appears as a chameleon protein combining a conserved structural scaffold with highly variable surfaces participating in generic or specialized HPV functions. We investigated surface residues involved in two specialized activities of high-risk genital HPV E6: p53 tumor suppressor degradation and nucleic acid binding. Screening of E6 surface mutants identified an in vivo p53 degradation-defective mutant that fails to recruit p53 to ubiquitin ligase E6AP and restores high p53 levels in cervical carcinoma cells by competing with endogeneous E6. We also mapped the nucleic acid binding surface of E6, the positive potential of which correlates with genital oncogenicity. E6 structure-function analysis provides new clues for understanding and counteracting the complex pathways of HPV-mediated pathogenesis.     

Tertiary motifs as building blocks for the design of protein‐binding peptides

Despite advances in protein engineering, the de novo design of small proteins or peptides that bind to a desired target remains a difficult task. Most computational methods search for binder structures in a library of candidate scaffolds, which can lead to designs with poor target complementarity and low success rates. Instead of choosing from pre‐defined scaffolds, we propose that custom peptide structures can be constructed to complement a target surface. Our method mines tertiary motifs (TERMs) from known structures to identify surface‐complementing fragments or “seeds.” We combine seeds that satisfy geometric overlap criteria to generate peptide backbones and score the backbones to identify the most likely binding structures. We found that TERM‐based seeds can describe known binding structures with high resolution: the vast majority of peptide binders from 486 peptide‐protein complexes can be covered by seeds generated from single‐chain structures. Furthermore, we demonstrate that known peptide structures can be reconstructed with high accuracy from peptide‐covering seeds. As a proof of concept, we used our method to design 100 peptide binders of TRAF6, seven of which were predicted by Rosetta to form higher‐quality interfaces than a native binder. The designed peptides interact with distinct sites on TRAF6, including the native peptide‐binding site. These results demonstrate that known peptide‐binding structures can be constructed from TERMs in single‐chain structures and suggest that TERM information can be applied to efficiently design novel target‐complementing binders.     

Ant community composition and functional traits in new grassland strips within agricultural landscapes

1. Ongoing intensification and fragmentation of European agricultural landscapes dramatically reduce biodiversity and associated functions. Enhancing perennial noncrop areas holds great potential to support ecosystem services such as ant‐mediated pest control.
2. To study the potential of newly established grassland strips to enhance ant diversity and associated functions, we used hand collection data and predation experiments to investigate differences in (a) ant community composition and (b) biocontrol‐related functional traits, and (c) natural pest control across habitats in cereal fields, old grasslands, and new grassland transects of three years of age.
3. Ant species diversity was similar between new and old grasslands, but significantly higher in new grasslands than in surrounding cereal fields. Contrary, ant community composition of new grasslands was more similar to cereal fields and distinct from the species pool of old grasslands. The functional trait space covered by the ant communities showed the same distribution between old and new grasslands. Pest control did not differ significantly between habitat types and therefore could not be linked to the prevalence of functional ant traits related to biocontrol services in new grasslands.
4. Our findings not only show trends of convergence between old and new grasslands, but also indicate that enhancing ant diversity through new grasslands takes longer than three years to provide comparable biodiversity and functionality.
5. Synthesis and applications: Newly established grasslands can increase ant species richness and abundance and provide a consistent amount of biocontrol services in agroecosystems. However, three years after their establishment, new grasslands were still dominated by common agrobiont ant species and lacked habitat specialists present in old grasslands, which require a constant supply of food resources and long colony establishment times. New grasslands represent a promising measure for enhancing agricultural landscapes but must be preserved in the longer term to promote biodiversity and resilience of associated ecosystem services.

     

Relieving efforts in palm‐tree tissue sampling for population genetics analyses

1. The young leaves are the main source of nucleic acids for population genetic studies in palm‐trees; however, the access to this tissue may be limited by specific features of each species. Using root tissues as an alternative source of nucleic acids could facilitate the sampling in large populations.
2. This study tests root tissue viability as an alternative nucleic acid source (root versus. leaf) and explores different protocols (tissue storage and DNA extraction methods) to obtain high‐quality DNA samples.
3. The results showed no significant differences in DNA concentration (603.7 vs. 599.1 ng/μl) and quality ratios (A260/280:2.1 vs. 1.9, and A260/230:2.1 vs. 2.0) for the comparisons of tissue source (leaf vs. root) and DNA extraction method (manual vs. kit). For tissue storage method, DNA concentration was significantly higher for root tissues stored in 70% and 90% alcohol solutions (692.8 and 822.6 ng/μl, respectively) versus those obtained from leaf tissue (603.7 ng/μl); however, for the quality parameters, no differences were found.
4. Results showed the effective potential of using root tissue as an alternative source for nucleic acids, which could facilitate population sampling of palm‐tree species for future studies, and this methodological alternative could be applied to other plant systems with similar sampling challenges.

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Evolutionary trade-offs at the Arabidopsis WRR4A resistance locus underpin alternate Albugo candida race recognition specificities

The oomycete Albugo candida causes white rust of Brassicaceae, including vegetable and oilseed crops, and wild relatives such as Arabidopsis thaliana. Novel White Rust Resistance (WRR) genes from Arabidopsis enable new insights into plant/parasite co-evolution. WRR4A from Arabidopsis accession Columbia (Col-0) provides resistance to many but not all white rust races, and encodes a nucleotide-binding, leucine-rich repeat immune receptor. Col-0 WRR4A resistance is broken by AcEx1, an isolate of A. candida. We identified an allele of WRR4A in Arabidopsis accession Øystese-0 (Oy-0) and other accessions that confers full resistance to AcEx1. WRR4A^Oy-0 carries a C-terminal extension required for recognition of AcEx1, but reduces recognition of several effectors recognized by the WRR4A^Col-0 allele. WRR4A^Oy-0 confers full resistance to AcEx1 when expressed in the oilseed crop Camelina sativa.     

Social Network Analysis Predicts Health Behaviours and Self-Reported Health in African Villages

The provision of healthcare in rural African communities is a highly complex and largely unsolved problem. Two main difficulties are the identification of individuals that are most likely affected by disease and the prediction of responses to health interventions. Social networks have been shown to capture health outcomes in a variety of contexts. Yet, it is an open question as to what extent social network analysis can identify and distinguish among households that are most likely to report poor health and those most likely to respond to positive behavioural influences. We use data from seven highly remote, post-conflict villages in Liberia and compare two prominent network measures: in-degree and betweenness. We define in-degree as the frequency in which members from one household are named by another household as a friends. Betweenness is defined as the proportion of shortest friendship paths between any two households in a network that traverses a particular household. We find that in-degree explains the number of ill family members, whereas betweenness explains engagement in preventative health. In-degree and betweenness independently explained self-reported health and behaviour, respectively. Further, we find that betweenness predicts susceptibility to, instead of influence over, good health behaviours. The results suggest that targeting households based on network measures rather than health status may be effective for promoting the uptake of health interventions in rural poor villages.     

Thermal ecology and baseline energetic requirements of a large‐bodied ectotherm suggest resilience to climate change

1. Most studies on how rising temperatures will impact terrestrial ectotherms have focused on single populations or multiple sympatric species. Addressing the thermal and energetic implications of climatic variation on multiple allopatric populations of a species will help us better understand how a species may be impacted by altered climates.
2. We used eight years of thermal and behavioral data collected from four populations of Pacific rattlesnakes (Crotalus oreganus) living in climatically distinct habitat types (inland and coastal) to determine the field‐active and laboratory‐preferred body temperatures, thermoregulatory metrics, and maintenance energetic requirements of snakes from each population.
3. Physical models showed that thermal quality was best at coastal sites, but inland snakes thermoregulated more accurately despite being in more thermally constrained environments. Projected increases of 1 and 2°C in ambient temperature result in an increase in overall thermal quality at both coastal and inland sites.
4. Population differences in modeled standard metabolic rate estimates were driven by body size and not field‐active body temperature, with inland snakes requiring 1.6× more food annually than coastal snakes.
5. All snakes thermoregulated with high accuracy, suggesting that small increases in ambient temperature are unlikely to impact the maintenance energetic requirements of individual snakes and that some species of large‐bodied reptiles may be robust to modest thermal perturbations under conservative climate change predictions.

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Enhanced regional terrestrial carbon uptake over Korea revealed by atmospheric CO2 measurements from 1999 to 2017

Understanding changes in terrestrial carbon balance is important to improve our knowledge of the regional carbon cycle and climate change. However, evaluating regional changes in the terrestrial carbon balance is challenging due to the lack of surface flux measurements. This study reveals that the terrestrial carbon uptake over the Republic of Korea has been enhanced from 1999 to 2017 by analyzing long‐term atmospheric CO₂ concentration measurements at the Anmyeondo Station (36.53°N, 126.32°E) located in the western coast. The influence of terrestrial carbon flux on atmospheric CO₂ concentrations (ΔCO₂) is estimated from the difference of CO₂ concentrations that were influenced by the land sector (through easterly winds) and the Yellow Sea sector (through westerly winds). We find a significant trend in ΔCO₂ of ?4.75 ppm per decade (p < .05) during the vegetation growing season (May through October), suggesting that the regional terrestrial carbon uptake has increased relative to the surrounding ocean areas. Combined analysis with satellite measured normalized difference vegetation index and gross primary production shows that the enhanced carbon uptake is associated with significant nationwide increases in vegetation and its production. Process‐based terrestrial model and inverse model simulations estimate that regional terrestrial carbon uptake increases by up to 18.9 and 8.0 Tg C for the study period, accounting for 13.4% and 5.7% of the average annual domestic carbon emissions, respectively. Atmospheric chemical transport model simulations indicate that the enhanced terrestrial carbon sink is the primary reason for the observed ΔCO₂ trend rather than anthropogenic emissions and atmospheric circulation changes. Our results highlight the fact that atmospheric CO₂ measurements could open up the possibility of detecting regional changes in the terrestrial carbon cycle even where anthropogenic emissions are not negligible.