Linking rhizosphere processes across scales: opinion

Purpose: Simultaneously interacting rhizosphere processes determine emergent plant behaviour, including growth, transpiration, nutrient uptake, soil carbon storage and transformation by microorganisms. However, these processes occur on multiple scales, challenging modelling of rhizosphere and plant behaviour. Current advances in modelling and experimental methods open the path to unravel the importance and interconnectedness of those processes across scales. Methods: We present a series of case studies of state-of-the art simulations addressing this multi-scale, multi-process problem from a modelling point of view, as well as from the point of view of integrating newly available rhizosphere data and images. Results: Each case study includes a model that links scales and experimental data to explain and predict spatial and temporal distribution of rhizosphere components. We exemplify the state-of-the-art modelling tools in this field: image-based modelling, pore-scale modelling, continuum scale modelling, and functional-structural plant modelling. We show how to link the pore scale to the continuum scale by homogenisation or by deriving effective physical parameters like viscosity from nano-scale chemical properties. Furthermore, we demonstrate ways of modelling the links between rhizodeposition and plant nutrient uptake or soil microbial activity. Conclusion: Modelling allows to integrate new experimental data across different rhizosphere processes and scales and to explore more variables than is possible with experiments. Described models are tools to test hypotheses and consequently improve our mechanistic understanding of how rhizosphere processes impact plant-scale behaviour. Linking multiple scales and processes including the dynamics of root growth is the logical next step for future research.Natural Environment Research Council (NERC): NE/S004920/

A common SCN1A splice-site polymorphism modifies the effect of carbamazepine on cortical excitability-A pharmacogenetic transcranial magnetic stimulation study

Objective SCN1A encodes the alpha subunit of the voltage-gated sodium channel and plays a crucial role in several epilepsy syndromes. The common SCN1A splice-site polymorphism rs3812718 (IVS5N+5 G>A) might contribute to the pathophysiology underlying genetic generalized epilepsies and is associated with electrophysiologic properties of the channel and the effect of sodium-channel blocking antiepileptic drugs. We assessed the effects of the rs3812718 genotype on cortical excitability at baseline and after administration of carbamazepine in order to investigate the mechanism of this association. Methods Paired-pulse transcranial magnetic stimulation (TMS) was applied in 92 healthy volunteers with the homozygous genotypes AA or GG of rs3812718 at baseline and after application of 400mg of carbamazepine or placebo in a double-blind, randomized, crossover design. Resting motor threshold (RMT), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP) were determined. Results At baseline there was no significant difference in any TMS parameter. Genotype GG was associated with a higher carbamazepine-induced increase in CSP duration as compared to AA (multivariate analysis of covariance [MANCOVA], p=0.013). An expected significant increase in RMT was genotype independent. Significance We found that the rs3812718 genotype modifies the effect of carbamazepine on CSP duration (mainly reflecting modulation of gamma-aminobutyric acid (GABA)ergic inhibition), but not on RMT (mainly reflecting modulation of voltage-gated sodium channels). This provides evidence that rs3812718 affects the pharmacoresponse to carbamazepine via an effect on GABAergic cortical interneurons. Our results also confirm that TMS is useful to investigate the effect of genetic variants on cortical excitability and pharmacoresponse

A common SCN1A splice-site polymorphism modifies the effect of carbamazepine on cortical excitability - A pharmacogenetic transcranial magnetic stimulation study

Objective SCN1A encodes the alpha subunit of the voltage-gated sodium channel and plays a crucial role in several epilepsy syndromes. The common SCN1A splice-site polymorphism rs3812718 (IVS5N+5 G>A) might contribute to the pathophysiology underlying genetic generalized epilepsies and is associated with electrophysiologic properties of the channel and the effect of sodium-channel blocking antiepileptic drugs. We assessed the effects of the rs3812718 genotype on cortical excitability at baseline and after administration of carbamazepine in order to investigate the mechanism of this association. Methods Paired-pulse transcranial magnetic stimulation (TMS) was applied in 92 healthy volunteers with the homozygous genotypes AA or GG of rs3812718 at baseline and after application of 400 mg of carbamazepine or placebo in a double-blind, randomized, crossover design. Resting motor threshold (RMT), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP) were determined. Results At baseline there was no significant difference in any TMS parameter. Genotype GG was associated with a higher carbamazepine-induced increase in CSP duration as compared to AA (multivariate analysis of covariance [MANCOVA], p = 0.013). An expected significant increase in RMT was genotype independent. Significance We found that the rs3812718 genotype modifies the effect of carbamazepine on CSP duration (mainly reflecting modulation of \u3b3-aminobutyric acid (GABA)ergic inhibition), but not on RMT (mainly reflecting modulation of voltage-gated sodium channels). This provides evidence that rs3812718 affects the pharmacoresponse to carbamazepine via an effect on GABAergic cortical interneurons. Our results also confirm that TMS is useful to investigate the effect of genetic variants on cortical excitability and pharmacoresponse. \ua9 Wiley Periodicals, Inc. \ua9 2014 International League Against Epilepsy