Regional and Developmental Differences in Na+ Currents in Vestibular Primary Afferent Neurons

The vestibular system relays information about head position via afferent nerve fibers to the brain in the form of action potentials. Voltage-gated Na+ channels in vestibular afferents drive the initiation and propagation of action potentials, but their expression during postnatal development and their contributions to firing in diverse mature afferent populations are unknown. Electrophysiological techniques were used to determine Na+ channel subunit types in vestibular calyx-bearing afferents at different stages of postnatal development. We used whole cell patch clamp recordings in thin slices of gerbil crista neuroepithelium to investigate Na+ channels and firing patterns in central zone (CZ) and peripheral zone (PZ) afferents. PZ afferents are exclusively dimorphic, innervating type I and type II hair cells, whereas CZ afferents can form dimorphs or calyx-only terminals which innervate type I hair cells alone. All afferents expressed tetrodotoxin (TTX)-sensitive Na+ currents, but TTX-sensitivity varied with age. During the fourth postnatal week, 200–300 nM TTX completely blocked sodium currents in PZ and CZ calyces. By contrast, in immature calyces [postnatal day (P) 5–11], a small component of peak sodium current remained in 200 nM TTX. Application of 1 μM TTX, or Jingzhaotoxin-III plus 200 nM TTX, abolished sodium current in immature calyces, suggesting the transient expression of voltage-gated sodium channel 1.5 (Nav1.5) during development. A similar TTX-insensitive current was found in early postnatal crista hair cells (P5–9) and constituted approximately one third of the total sodium current. The Nav1.6 channel blocker, 4,9-anhydrotetrodotoxin, reduced a component of sodium current in immature and mature calyces. At 100 nM 4,9-anhydrotetrodotoxin, peak sodium current was reduced on average by 20% in P5–14 calyces, by 37% in mature dimorphic PZ calyces, but by less than 15% in mature CZ calyx-only terminals. In mature PZ calyces, action potentials became shorter and broader in the presence of 4,9-anhydrotetrodotoxin implicating a role for Nav1.6 channels in firing in dimorphic afferents

Visualising future behaviour: Effects for snacking on biscuit bars, but no effects for snacking on fruit.

In this study, participants (N = 223) were randomised to visualise snacking on fruit, visualise snacking on biscuit bars or no visualisation, and intentions and attitudes towards fruit and biscuit bars, immediate selection of fruit or biscuit bars and subsequent consumption were measured. No effects of visualising snacking on fruit were found once background variables were taken into account. Visualising snacking on biscuit bars, however, resulted in greater intentions to consume biscuit bars (smallest β = 0.19, p < 0.01). These findings suggest that specifics of the visualised target behaviour may be important in visualisation. Further investigation is needed before recommending visualisation for increasing fruit consumption

Transmitochondrial embryonic stem cells containing pathogenic mtDNA mutations are compromised in neuronal differentiation

Objectives:  Defects of the mitochondrial genome (mtDNA) cause a series of rare, mainly neurological disorders. In addition, they have been implicated in more common forms of movement disorders, dementia and the ageing process. In order to try to model neuronal dysfunction associated with mitochondrial disease, we have attempted to establish a series of transmitochondrial mouse embryonic stem cells harbouring pathogenic mtDNA mutations. Materials and methods: Transmitochondrial embryonic stem cell cybrids were generated by fusion of cytoplasts carrying a variety of mtDNA mutations, into embryonic stem cells that had been pretreated with rhodamine 6G, to prevent transmission of endogenous mtDNA. Cybrids were differentiated into neurons and assessed for efficiency of differentiation and electrophysiological function. Results:  Neuronal differentiation could occur, as indicated by expression of neuronal markers. Differentiation was impaired in embryonic stem cells carrying mtDNA mutations that caused severe biochemical deficiency. Electrophysiological tests showed evidence of synaptic activity in differentiated neurons carrying non-pathogenic mtDNA mutations or in those that caused a mild defect of respiratory activity. Again, however, neurons carrying mtDNA mutations that resulted in severe biochemical deficiency had marked reduction in post-synaptic events. Conclusions:  Differentiated neurons carrying severely pathogenic mtDNA defects can provide a useful model for understanding how such mutations can cause neuronal dysfunction

High impact exercise increased femoral neck bone mineral density in older men: a randomised unilateral intervention

Introduction: There is little evidence as towhether exercise can increase BMD in oldermenwith no investigation of high impact exercise. Lifestyle changes and individual variability may confound exercise trials but can be minimised using a within-subject unilateral design (exercise leg [EL] vs. control leg [CL]) that has high statistical power. Purpose: This study investigated the influence of a 12 month high impact unilateral exercise intervention on femoral neck BMD in older men. Methods: Fifty, healthy, community-dwelling older men commenced a 12 month high impact unilateral exercise intervention which increased to 50 multidirectional hops, 7 days a week on one randomly allocated leg. BMD of both femurswasmeasured using dual energy X-ray absorptiometry (DXA) before and after 12 months of exercise, by an observer blind to the leg allocation. Repeated measures ANOVAwith post hoc tests was used to detect significant effects of time, leg and interaction. Results: Thirty-five men (mean±SD, age 69.9±4.0 years) exercised for 12 months and intervention adherence was 90.5±9.1% (304±31 sessions completed out of 336 prescribed sessions). Fourteen men did not complete the 12 month exercise intervention due to: health problems or injuries unrelated to the intervention (n=9), time commitments (n=2), or discomfort during exercise (n=3), whilst BMD data were missing for one man. Femoral neck BMD, BMC and cross-sectional area all increased in the EL (+0.7, +0.9 and +1.2 % respectively) compared to the CL (−0.9,−0.4 and −1.2%); interaction effect Pb0.05. Although the interaction term was not significant (P>0.05), there were significantmain effects of time for sectionmodulus (P=0.044) and minimum neck width (P=0.006). Sectionmodulus increased significantly in the EL (P=0.016) but not in the CL (P=0.465); mean change+2.3% and+0.7% respectively, whereasminimumneck width increased significantly in the CL (P=0.004) but not in the EL (P=0.166); mean changes being +0.7% and +0.3% respectively. Conclusion: A 12 month high impact unilateral exercise intervention was feasible and effective for improving femoral neck BMD, BMC and geometry in older men. Carefully targeted high impact exercises may be suitable for incorporation into exercise interventions aimed at preventing fractures in healthy community-dwelling older men

Successful Establishment of Oversown Chicory and Plantain on Uncultivatable Hill Country

All-year grazing of livestock on steep, non-arable hill country (\u3e 20o slope angle, \u3c 1,000 m elevation) is a significant feature of New Zealand agriculture. Hill country pastures are in various states of improvement depending on factors such as extent of subdivision, fertiliser inputs, plant species introduction, and grazing management. Numerous introduced grass, legume and herb species are available to match the many micro-sites in steep hill country (Kemp et al. 1999). There has been increasing use of the perennial herbs chicory (Chicorium intybus L.) and plantain (Plantago lanceolata L.) in seed mixtures used on a range of topographies, mostly flat to undulating terrain. Advantages of these species include tolerance of drought and high summer temperatures, highly palatable foliage, enhanced mineral content, and high animal growth rates (Stewart 1996; Li and Kemp 2005). Farmers have sown these species on hill country but there is negligible information on their establishment in such landscapes. As part of a large, New Zealand-wide programme to increase pasture productivity on non-arable hill country through new germplasm introduction, chicory and plantain were included in a seed mixture broadcast-sown at a range of sites. This paper reports on the seedling establishment of these two species

The Influence of High-Impact Exercise on Cortical and Trabecular Bone Mineral Content and 3D Distribution Across the Proximal Femur in Older Men: A Randomized Controlled Unilateral Intervention.

Regular exercisers have lower fracture risk, despite modest effects of exercise on bone mineral content (BMC). Exercise may produce localized cortical and trabecular bone changes that affect bone strength independently of BMC. We previously demonstrated that brief, daily unilateral hopping exercises increased femoral neck BMC in the exercise leg versus the control leg of older men. This study evaluated the effects of these exercises on cortical and trabecular bone and its 3D distribution across the proximal femur, using clinical CT. Fifty healthy men had pelvic CT scans before and after the exercise intervention. We used hip QCT analysis to quantify BMC in traditional regions of interest and estimate biomechanical variables. Cortical bone mapping localized cortical mass surface density and endocortical trabecular density changes across each proximal femur, which involved registration to a canonical proximal femur model. Following statistical parametric mapping, we visualized and quantified statistically significant changes of variables over time in both legs, and significant differences between legs. Thirty-four men aged mean (SD) 70 (4) years exercised for 12-months, attending 92% of prescribed sessions. In traditional regions of interest, cortical and trabecular BMC increased over time in both legs. Cortical BMC at the trochanter increased more in the exercise than control leg, whereas femoral neck buckling ratio declined more in the exercise than control leg. Across the entire proximal femur, cortical mass surface density increased significantly with exercise (2.7%; p 6%) at anterior and posterior aspects of the femoral neck and anterior shaft. Endocortical trabecular density also increased (6.4%; p 12% at the anterior femoral neck, trochanter, and inferior femoral head. Odd impact exercise increased cortical mass surface density and endocortical trabecular density, at regions that may be important to structural integrity. These exercise-induced changes were localized rather than being evenly distributed across the proximal femur.This research was financially supported by a National Osteoporosis Innovative Award, Medical Research Council UK Interdisciplinary Bridging Award, and a Loughborough University Scholarship. KESP acknowledges support of the Cambridge NIHR Biomedical Research Centre.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/jbmr.249

Changes to lung surfactant monolayers upon exposure to gas phase ozone observed using X-ray and neutron reflectivity

Exposure to the secondary pollutant ozone in ambient air is associated with adverse health effects when inhaled. In this work we use surface pressure measurements, combined with X-ray and neutron reflection, to observe changes in a layer of lung surfactant at the air water interface when exposed to gas phase ozone. The results demonstrate that the layer reacts with ozone changing its physical characteristics. A slight loss of material, a significant thinning of the layer and increased hydration of the surfactant material is observed. The results support the hypothesis that unsaturated lipids present in lung surfactant are still susceptible to rapid reaction with ozone and the reaction changes the properties of the interfacial layer

Brief high impact exercise increased cortical mass and trabecular density at regions predictive of femoral neck and trochanteric fracture [Abstract]

Brief high impact exercise increased cortical mass and trabecular density at regions predictive of femoral neck and trochanteric fracture [Abstract

The influence of high impact exercise on cortical and trabecular bone mineral content and 3D distribution across the proximal femur in older men: a randomised controlled unilateral intervention

Regular exercisers have lower fracture risk, despite modest effects of exercise on BMC. Exercise may produce localised cortical and trabecular bone changes that affect bone strength independently of BMC. We previously demonstrated that brief, daily unilateral hopping exercises increased femoral neck BMC in the exercise leg versus the control leg of older men. This study evaluated the effects of these exercises on cortical and trabecular bone and its 3D distribution across the proximal femur, using clinical computed tomography (CT). Fifty healthy men had pelvic CT scans before and after the exercise intervention. We used hip QCT analysis to quantify BMC in traditional regions of interest and estimate biomechanical variables. Cortical bone mapping localised cortical mass surface density and endocortical trabecular density changes across each proximal femur, which involved registration to a canonical proximal femur model. Following statistical parametric mapping, we visualised and quantified statistically significant changes of variables over time in both legs, and significant differences between legs. Thirty-four men aged 70 (4) years exercised for 12-months, attending 92% of prescribed sessions. In traditional ROIs, cortical and trabecular BMC increased over time in both legs. Cortical BMC at the trochanter increased more in the exercise than control leg, whilst femoral neck buckling ratio declined more in the exercise than control leg. Across the entire proximal femur, cortical mass surface density increased significantly with exercise (2.7%; P 6%) at anterior and posterior aspects of the femoral neck and anterior shaft. Endocortical trabecular density also increased (6.4%; P 12% at the anterior femoral neck, trochanter and inferior femoral head. Odd impact exercise increased cortical mass surface density and endocortical trabecular density, at regions that may be important to structural integrity. These exercise-induced changes were localised rather than being evenly distributed across the proximal femur. This article is protected by copyright. All rights reserved

The reaction of oleic acid monolayers with gas-phase ozone at the air water interface: the effect of sub-phase viscosity, and inert secondary components

Organic films that form on atmospheric particulate matter change the optical and cloud condensation nucleation properties of the particulate matter and consequently have implications for modern climate and climate models. The organic films are subject to attack from gas-phase oxidants present in ambient air. Here we revisit in greater detail the oxidation of a monolayer of oleic acid by gas-phase ozone at the air–water interface as this provides a model system for the oxidation reactions that occur at the air–water interface of aqueous atmospheric aerosol. Experiments were performed on monolayers of oleic acid at the air–liquid interface at atmospherically relevant ozone concentrations to investigate if the viscosity of the sub-phase influences the rate of the reaction and to determine the effect of the presence of a second component within the monolayer, stearic acid, which is generally considered to be non-reactive towards ozone, on the reaction kinetics as determined by neutron reflectometry measurements. Atmospheric aerosol can be extremely viscous. The kinetics of the reaction were found to be independent of the viscosity of the sub-phase below the monolayer over a range of moderate viscosities, Image ID:d0cp03934a-t1.gif, demonstrating no involvement of aqueous sub-phase oxidants in the rate determining step. The kinetics of oxidation of monolayers of pure oleic acid were found to depend on the surface coverage with different behaviour observed above and below a surface coverage of oleic acid of ∼1 × 1018 molecule m−2. Atmospheric aerosol are typically complex mixtures, and the presence of an additional compound in the monolayer that is inert to direct ozone oxidation, stearic acid, did not significantly change the reaction kinetics. It is demonstrated that oleic acid monolayers at the air–water interface do not leave any detectable material at the air–water interface, contradicting the previous work published in this journal which the authors now believe to be erroneous. The combined results presented here indicate that the kinetics, and thus the atmospheric chemical lifetime for unsaturated surface active materials at the air–water interface to loss by reaction with gas-phase ozone, can be considered to be independent of other materials present at either the air–water interface or in the aqueous sub-phase