Longitudinal data methods for evaluating genome-by-epigenome interactions in families

Background

Longitudinal measurement is commonly employed in health research and provides numerous benefits for understanding disease and trait progression over time. More broadly, it allows for proper treatment of correlated responses within clusters. We evaluated 3 methods for analyzing genome-by-epigenome interactions with longitudinal outcomes from family data.

Results

Linear mixed-effect models, generalized estimating equations, and quadratic inference functions were used to test a pharmacoepigenetic effect in 200 simulated posttreatment replicates. Adjustment for baseline outcome provided greater power and more accurate control of Type I error rates than computation of a pre-to-post change score.

Conclusions

Comparison of all modeling approaches indicated a need for bias correction in marginal models and similar power for each method, with quadratic inference functions providing a minor decrement in power compared to generalized estimating equations and linear mixed-effects models.

     

Genetic diversity of a hitchhiker and prized food source in the Anthropocene: the Asian green mussel <Emphasis Type="Italic">Perna viridis</Emphasis> (Mollusca,Mytilidae)

Insight into a species’ native and introduced range is essential in understanding the invasion process. Genetic diversity, propagule pressure and environmental conditions all have been recognised as playing a determinant role in invasion success. Here, we aimed to investigate the genetic diversity and population genetic structure (using the COI mtDNA gene region and 22 nDNA microsatellite markers) of the Asian green mussel Perna viridis within its potential native range in Asia and at introduced locations in the USA and the Caribbean. We also analyse genetic data from vessel intercepts and an incursion. By doing so, we aimed to identify genetic signatures that could allow to track vessel samples to their source and provide further insight into potential high-risk invasive populations or areas. Three top hierarchical clusters were identified using the individual-based Bayesian clustering method in STRUCTURE, corresponding to populations in three world regions: (1) USA and Caribbean, (2) India and (3) Southeast Asia. Within Southeast Asia, additional analysis indicate a shallow genetic differentiation of three subgroups consisting of (3a) Thailand, (3b) Taiwan and Hong-Kong, and (3c) a cluster of Singapore–Indonesia samples. Overall, the population structure found in this study suggests that the markers used could be useful in identifying source populations, particularly between the three mains world regions. Most surprisingly however, this study shows that the genetic diversity of samples collected from vessel intercepts and incursions did not differ significantly from established populations in Southeast Asia. In this region, in addition to the high vessel connectivity and number of P. viridis transported, all sampled populations are likely to pose a comparable risk in terms of genetic diversity. The present work represents the most comprehensive population genetic study of P. viridis, and the first to address the potential genetic introduction risk posed by populations of this species. The information and genetic markers in this study constitute a valuable addition to the tools already used to infer on potential high-risk source populations of P. viridis. They should therefore prove useful for biosecurity surveillance and management actions directed at this species.     

Does Nutrient Availability Regulate Seagrass Response to Elevated CO<Subscript>2</Subscript>?

Future increases in oceanic carbon dioxide concentrations (CO_2(aq)) may provide a benefit to submerged plants by alleviating photosynthetic carbon limitation. However, other environmental factors (for example, nutrient availability) may alter how seagrasses respond to CO_2(aq) by regulating the supply of additional resources required to support growth. Thus, questions remain in regard to how other factors influence CO_2(aq) effects on submerged vegetation. This study factorially manipulated CO_2(aq) and nutrient availability, in situ, within a subtropical seagrass bed for 350 days, and examined treatment effects on leaf productivity, shoot density, above- and belowground biomass, nutrient content, carbohydrate storage, and sediment organic carbon (C_org). Clear, open-top chambers were used to replicate CO_2(aq) forecasts for the year 2100, whereas nutrient availability was manipulated via sediment amendments of nitrogen (N) and phosphorus (P) fertilizer. We provide modest evidence of a CO₂ effect, which increased seagrass aboveground biomass. CO_2(aq) enrichment had no effect on nutrient content, carbohydrate storage, or sediment C_org content. Nutrient addition increased leaf productivity and leaf N content, however did not alter above- or belowground biomass, shoot density, carbohydrate storage, or C_org content. Treatment interactions were not significant, and thus NP availability did not influence seagrass responses to elevated CO_2(aq). This study demonstrates that long-term carbon enrichment may alter the structure of shallow seagrass meadows, even in relatively nutrient-poor, oligotrophic systems.     

Poplar and shrub willow energy crops in the United States: field trial results from the multiyear regional feedstock partnership and yield potential maps based on the PRISM‐ELM model

To increase the understanding of poplar and willow perennial woody crops and facilitate their deployment for the production of biofuels, bioproducts, and bioenergy, there is a need for broadscale yield maps. For national analysis of woody and herbaceous crops production potential, biomass feedstock yield maps should be developed using a common framework. This study developed willow and poplar potential yield maps by combining data from a network of willow and poplar field trials and the modeling power of PRISM‐ELM. Yields of the top three willow cultivars across 17 sites ranged from 3.60 to 14.6 Mg ha^?1 yr^?1 dry weight, while the yields from 17 poplar trials ranged from 7.5 to 15.2 Mg ha^?1 yr^?1. Relationships between the environmental suitability estimates from the PRISM‐ELM model and results from field trials had an R² of 0.60 for poplar and 0.81 for willow. The resulting potential yield maps reflected the range of poplar and willow yields that have been reported in the literature. Poplar covered a larger geographic range than willow, which likely reflects the poplar breeding efforts that have occurred for many more decades using genotypes from a broader range of environments than willow. While the field trial data sets used to develop these models represent the most complete information at the time, there is a need to expand and improve the model by monitoring trials over multiple cutting cycles and across a broader range of environmental gradients. Despite some limitations, the results of these models represent a dramatic improvement in projections of potential yield of poplar and willow crops across the United States.     

Chaperone-mediated reduction of RepA dimerization is associated with RepA conformational change

RepA, the initiator protein of plasmid P1, binds to multiple sites (iterons) in the origin. The binding normally requires participation of chaperones, DnaJ, DnaK and GrpE. When purified, RepA appears dimeric and is inactive in iteron binding. On reaction with chaperones, a species active in iteron binding is formed and found to be monomeric. To test whether the chaperones can reduce dimerization, RepA was used to replace the dimerization domain of the λ repressor. The hybrid protein repressed the λ operator efficiently, indicating that RepA can dimerize in vivo . A further increase in repressor activity was seen in dnaJ mutant cells. These results are consistent with a chaperone-mediated reduction of RepA dimerization. We also found that RepA mutants defective in dimerization still depend on DnaJ for iteron binding. Conversely, RepA mutants that no longer require chaperones for iteron binding remain dimerization proficient. These results indicate that the chaperone dependence of RepA activity is not solely owing to RepA dimerization. Our results are most simply explained by a chaperone-mediated conformational change in RepA protomer that activates iteron binding. This conformational change also results in reduced RepA dimerization.     

A trait‐based approach for predicting species responses to environmental change from sparse data: how well might terrestrial mammals track climate change?

Estimating population spread rates across multiple species is vital for projecting biodiversity responses to climate change. A major challenge is to parameterise spread models for many species. We introduce an approach that addresses this challenge, coupling a trait‐based analysis with spatial population modelling to project spread rates for 15 000 virtual mammals with life histories that reflect those seen in the real world. Covariances among life‐history traits are estimated from an extensive terrestrial mammal data set using Bayesian inference. We elucidate the relative roles of different life‐history traits in driving modelled spread rates, demonstrating that any one alone will be a poor predictor. We also estimate that around 30% of mammal species have potential spread rates slower than the global mean velocity of climate change. This novel trait‐space‐demographic modelling approach has broad applicability for tackling many key ecological questions for which we have the models but are hindered by data availability.     

Drought and leaf herbivory influence floral volatiles and pollinator attraction

The effects of climate change on species interactions are poorly understood. Investigating the mechanisms by which species interactions may shift under altered environmental conditions will help form a more predictive understanding of such shifts. In particular, components of climate change have the potential to strongly influence floral volatile organic compounds (VOCs) and, in turn, plant–pollinator interactions. In this study, we experimentally manipulated drought and herbivory for four forb species to determine effects of these treatments and their interactions on (1) visual plant traits traditionally associated with pollinator attraction, (2) floral VOCs, and (3) the visitation rates and community composition of pollinators. For all forbs tested, experimental drought universally reduced flower size and floral display, but there were species‐specific effects of drought on volatile emissions per flower, the composition of compounds produced, and subsequent pollinator visitation rates. Moreover, the community of pollinating visitors was influenced by drought across forb species (i.e. some pollinator species were deterred by drought while others were attracted). Together, these results indicate that VOCs may provide more nuanced information to potential floral visitors and may be relatively more important than visual traits for pollinator attraction, particularly under shifting environmental conditions.     

Selective Inhibition of the Mitochondrial Permeability Transition Pore Protects against Neurodegeneration in Experimental Multiple Sclerosis

The mitochondrial permeability transition pore is a recognized drug target for neurodegenerative conditions such as multiple sclerosis and for ischemia-reperfusion injury in the brain and heart. The peptidylprolyl isomerase, cyclophilin D (CypD, PPIF), is a positive regulator of the pore, and genetic down-regulation or knock-out improves outcomes in disease models. Current inhibitors of peptidylprolyl isomerases show no selectivity between the tightly conserved cyclophilin paralogs and exhibit significant off-target effects, immunosuppression, and toxicity. We therefore designed and synthesized a new mitochondrially targeted CypD inhibitor, JW47, using a quinolinium cation tethered to cyclosporine. X-ray analysis was used to validate the design concept, and biological evaluation revealed selective cellular inhibition of CypD and the permeability transition pore with reduced cellular toxicity compared with cyclosporine. In an experimental autoimmune encephalomyelitis disease model of neurodegeneration in multiple sclerosis, JW47 demonstrated significant protection of axons and improved motor assessments with minimal immunosuppression. These findings suggest that selective CypD inhibition may represent a viable therapeutic strategy for MS and identify quinolinium as a mitochondrial targeting group for in vivo use.