Dehydration and ionic conductance quantization in nanopores

There has been tremendous experimental progress in the last decade in identifying the structure and function of biological pores (ion channels) and fabricating synthetic pores. Despite this progress, many questions still remain about the mechanisms and universal features of ionic transport in these systems. In this paper, we examine the use of nanopores to probe ion transport and to construct functional nanoscale devices. Specifically, we focus on the newly predicted phenomenon of quantized ionic conductance in nanopores as a function of the effective pore radius - a prediction that yields a particularly transparent way to probe the contribution of dehydration to ionic transport. We study the role of ionic species in the formation of hydration layers inside and outside of pores. We find that the ion type plays only a minor role in the radial positions of the predicted steps in the ion conductance. However, ions with higher valency form stronger hydration shells, and thus, provide even more pronounced, and therefore, more easily detected, drops in the ionic current. Measuring this phenomenon directly, or from the resulting noise, with synthetic nanopores would provide evidence of the deviation from macroscopic (continuum) dielectric behavior due to microscopic features at the nanoscale and may shed light on the behavior of ions in more complex biological channels.Comment: 13 pages, 10 figure

A simple soil organic-matter model for biomass data assimilation in community-level carbon contracts

Soil carbon (C) sequestration has been proposed as a transitional win-win strategy to help replenish organic-matter content in depleted agricultural soils and counter increases in atmospheric greenhouse gases. Data assimilation and remote sensing can reduce uncertainty in sequestered C mass estimates, but simple soil organic carbon (SOC) models are required to make operational predictions of tradeable amounts over large, heterogenous areas. Our study compared the performance of RothC26.3 and a reduced compartmental model on an 11-year fertilizer trial in subhumid West Africa. Root mean square error (RMSE) differences of 0.05 Mg C/ha between models on total SOC predictions suggest that for contractual purposes, SOC dynamics can be simulated by a two-pool structure with labile and stable components. Faster (seasonal) and slower (semicentennial and beyond) rates can be approximated by constants as instantaneous and infinite decay. In these systems, simulations indicate that cereal residue incorporation holds most potential for mitigation of transient C loss associated with recent land conversion to agriculture

Modern Electronic Techniques Applied to Physics and Engineering

Contains reports on seven research projects.Office of Scientific Research and Development (OSRD) OEMsr-26

Soil organic carbon dynamics and crop yield for different crop rotations in a degraded ferruginous tropical soil in a semi-arid region: a simulation approach

In recent years, simulation models have been used as a complementary tool for research and for quantifying soil carbon sequestration under widely varying conditions. This has improved the understanding and prediction of soil organic carbon (SOC) dynamics and crop yield responses to soil and climate conditions and crop management scenarios. The goal of the present study was to estimate the changes in SOC for different cropping systems in West Africa using a simulation model. A crop rotation experiment conducted in Farakô-Ba, Burkina Faso was used to evaluate the performance of the cropping system model (CSM) of the Decision Support System for Agrotechnology Transfer (DSSAT) for simulating yield of different crops. Eight crop rotations that included cotton, sorghum, peanut, maize and fallow, and three different management scenarios, one without N (control), one with chemical fertilizer (N) and one with manure applications, were studied. The CSM was able to simulate the yield trends of various crops, with inconsistencies for a few years. The simulated SOC increased slightly across the years for the sorghum–fallow rotation with manure application. However, SOC decreased for all other rotations except for the continuous fallow (native grassland), in which the SOC remained stable. The model simulated SOC for the continuous fallow system with a high degree of accuracy normalized root mean square error (RMSE)=0·001, while for the other crop rotations the simulated SOC values were generally within the standard deviation (s.d.) range of the observed data. The crop rotations that included a supplemental N-fertilizer or manure application showed an increase in the average simulated aboveground biomass for all crops. The incorporation of this biomass into the soil after harvest reduced the loss of SOC. In the present study, the observed SOC data were used for characterization of production systems with different SOC dynamics. Following careful evaluation of the CSM with observed soil organic matter (SOM) data similar to the study presented here, there are many opportunities for the application of the CSM for carbon sequestration and resource management in Sub-Saharan Africa

Voltage-Gated Ion Channel Dysfunction Precedes Cardiomyopathy Development in the Dystrophic Heart

Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is associated with severe cardiac complications including cardiomyopathy and cardiac arrhythmias. Recent research suggests that impaired voltage-gated ion channels in dystrophic cardiomyocytes accompany cardiac pathology. It is, however, unknown if the ion channel defects are primary effects of dystrophic gene mutations, or secondary effects of the developing cardiac pathology.To address this question, we first investigated sodium channel impairments in cardiomyocytes derived from dystrophic neonatal mice prior to cardiomyopahty development, by using the whole cell patch clamp technique. Besides the most common model for DMD, the dystrophin-deficient mdx mouse, we also used mice additionally carrying an utrophin mutation. In neonatal cardiomyocytes, dystrophin-deficiency generated a 25% reduction in sodium current density. In addition, extra utrophin-deficiency significantly altered sodium channel gating parameters. Moreover, also calcium channel inactivation was considerably reduced in dystrophic neonatal cardiomyocytes, suggesting that ion channel abnormalities are universal primary effects of dystrophic gene mutations. To assess developmental changes, we also studied sodium channel impairments in cardiomyocytes derived from dystrophic adult mice, and compared them with the respective abnormalities in dystrophic neonatal cells. Here, we found a much stronger sodium current reduction in adult cardiomyocytes. The described sodium channel impairments slowed the upstroke of the action potential in adult cardiomyocytes, and only in dystrophic adult mice, the QRS interval of the electrocardiogram was prolonged.Ion channel impairments precede pathology development in the dystrophic heart, and may thus be considered potential cardiomyopathy triggers

Reduced GABAergic Neuron Excitability, Altered Synaptic Connectivity, and Seizures in a KCNT1 Gain-of-Function Mouse Model of Childhood Epilepsy.

Gain-of-function (GOF) variants in K+ channels cause severe childhood epilepsies, but there are no mechanisms to explain how increased K+ currents lead to network hyperexcitability. Here, we introduce a human Na+-activated K+ (KNa) channel variant (KCNT1-Y796H) into mice and, using a multiplatform approach, find motor cortex hyperexcitability and early-onset seizures, phenotypes strikingly similar to those of human patients. Although the variant increases KNa currents in cortical excitatory and inhibitory neurons, there is an increase in the KNa current across subthreshold voltages only in inhibitory neurons, particularly in those with non-fast-spiking properties, resulting in inhibitory-neuron-specific impairments in excitability and action potential (AP) generation. We further observe evidence of synaptic rewiring, including increases in homotypic synaptic connectivity, accompanied by network hyperexcitability and hypersynchronicity. These findings support inhibitory-neuron-specific mechanisms in mediating the epileptogenic effects of KCNT1 channel GOF, offering cell-type-specific currents and effects as promising targets for therapeutic intervention

Modern Electronic Techniques Applied to Physics and Engineering

Contains reports on five research projects

The development of a stakeholder-endorsed national strategic plan for advancing pain education across Canadian physiotherapy programs

Abstract Background The Canadian Pain Task Force recently advanced an action plan calling for improved entry-level health professional pain education. However, there is little research to inform the collaboration and coordination across stakeholders that is needed for its implementation. Aims This manuscript reports on the development of a stakeholder-generated strategic plan to improve pain education across all Canadian physiotherapy (PT) programs. Methods Participants included representatives from the following stakeholder groups: people living with pain (n = 1); PT students and recent graduates (n = 2); educators and directors from every Canadian PT program (n = 24); and leaders of Canada?s national PT professional association (n = 2). Strategic priorities were developed through three steps (1) stakeholder-generated data was collected and analyzed; (2) a draft strategic plan was developed and refined; and (2) stakeholder endorsement of the final plan was assessed. The project was primarily implemented online, between 2016 and 2018. Results The plan was developed through five iterative versions. Stakeholders unanimously endorsed a plan that included five priorities focusing on uptake of best evidence across (1) national PT governance groups and (2) within individual PT programs; (3) partnering with people living with pain in pain education; (4) advocacy for the PT role in pain management; and (5) advancing pain education research. Conclusion This plan is expected to help Canadian stakeholders work toward national improvements in PT pain education and to serve as a useful template for informing collaboration on entry-level pain education within other professions and across different geographic regions

AXR1-ECR1 and AXL1-ECR1 heterodimeric RUB-activating enzymes diverge in function in Arabidopsis thaliana

RELATED TO UBIQUITIN (RUB) modification of CULLIN (CUL) subunits of the CUL-RING ubiquitin E3 ligase (CRL) superfamily regulates CRL ubiquitylation activity. RUB modification requires E1 and E2 enzymes that are analogous to, but distinct from, those activities required for UBIQUITIN (UBQ) attachment. Gene duplications are widespread in angiosperms, and in line with this observation, components of the RUB conjugation pathway are found in multiples in Arabidopsis. To further examine the extent of redundancy within the RUB pathway, we undertook biochemical and genetic characterizations of one such duplication event- the duplication of the genes encoding a subunit of the RUB E1 into AUXIN RESISTANT1 (AXR1) and AXR1-LIKE1 (AXL1). In vitro, the two proteins have similar abilities to function with E1 C-TERMINAL-RELATED1 (ECR1) in catalyzing RUB1 activation and RUB1-ECR1 thioester formation. Using mass spectrometry, endogenous AXR1 and AXL1 proteins were found in complex with 3HA-RUB1, suggesting that AXR1 and AXL1 exist in parallel RUB E1 complexes in Arabidopsis. In contrast, AXR1 and AXL1 differ in ability to correct phenotypic defects in axr1-30, a severe loss-of-function AXR1 mutant, when the respective coding sequences are expressed from the same promoter, suggesting differential in vivo functions. These results suggest that while both proteins function in the RUB pathway and are biochemically similar in RUB-ECR1 thioester formation, they are not functionally equivalent