A Judo-Based Exercise Program to Reduce Falls and Frailty Risk in Community-Dwelling Older Adults: A Feasibility Study.

OBJECTIVES: This study aimed to explore the feasibility (including recruitment, safety and adherence) and the effects of a twice weekly supervised Judo-based exercise program over eight weeks on mobility, balance, physical performance, quality of life, fear of falling and physical activity (including by frailty status) in community-dwelling older people aged ≥65 years. DESIGN: Pre-post study. PARTICIPANTS: A total of 17 participants (mean age 74.3±6.2; range 66-87 years; 76.5% female). INTERVENTION: A Judo-based exercise program conducted twice weekly for 60 minutes per session over eight weeks. MEASUREMENTS: Pre and post assessments included the Timed Up and Go (TUG); the Berg Balance Scale (BBS); the Short Physical Performance Battery (SPPB); the Short Form Health Survey-36 (SF-36); the Falls Efficiency Scale International (FES-I); and an ActivPal accelerometer to measure participants' physical activity. RESULTS: Most participants had low (≤3) Charlson's Comorbidity Index scores (n=17, 100%), were well nourished (n=16, 94.1%), not sarcopenic (n=16, 94.1%), and not cognitively impaired (n=13, 76.5%), anxious or depressed (n=14, 82.4%). Ten participants (58.8%) were non-frail and seven were pre-frail (41.2%). Significant improvements (p<0.05) were seen for mobility (TUG), balance (BBS) and physical performance (SPPB). Pre-frail participants showed greater improvement in mobility (TUG) than non-frail participants (p=0.020). No changes (p≥0.05) were seen in quality of life, fear of falling, or physical activity. Participants' adherence (i.e., attending sessions) was high (i.e., ≥81.2%). No serious adverse events or withdrawals were reported. CONCLUSION: Findings suggest that the eight week Judo-based exercise program can be delivered safely to older adults aged ≥65 years, including those at-risk of frailty, as long as there is close supervision with individualisation of the program in response to emergent health symptoms and the program is conducted on requisite Judo mats. This Judo-based exercise program is effective in improving physical function with potential to prevent falls and frailty risk.

Expanded statistical analysis of squats on the Great Britain (GB) mainline network.

Squat defects are one of the most common rail surface defects. Significant research effort has gone into understand squat defects over the last 10 years which has brought about important developments in the understanding of their initiation mechanism; however, further work is still required to fully understand squat and the best methods to control them. This study considers records of squat defects over a period 9 years, considering 2600 km of track across 8 different routes on the GB mainline network. The analysis separately reviews squats on: plainline, crossings, joints and welds. Results include an overview of the main factors influencing the development of each type of squats, practical methods to immediately reduce and manage squat defects and recommends focus areas for further research to understand squat defects. Results suggest that squats on plainline, crossings, joints and welds, all correlate with different influencing factors; headcheck defects appear to significantly influence the probability of squats and how other factors influence squat development. There is a strong connection between total head wear rate (combined material removal due to traffic and grinding) and squats; 90 % of all squats appear on rail with a headwear rate of <0.2 mm/year. Overall larger section rail (60 kg/m vs 56 kg/m) and harder material (260 Brinell vs 220 Brinell) is significantly less susceptible to squat damage. Track curvature has an influence of squat development, especially in rail with no headcheck cracking, where the tightest curves are significantly more likely to sustain squat damage. The probability of squat at vertical discontinuities, i.e. joints and crossings are significantly more likely as train speed increases. Whilst squats on joints are 1000 time more likely than squats on welds.

Stimulus contrast modulates burst activity in the lateral geniculate nucleus.

Burst activity is a ubiquitous feature of thalamic neurons and is well documented for visual neurons in the lateral geniculate nucleus (LGN). Although bursts are often associated with states of drowsiness, they are also known to convey visual information to cortex and are particularly effective in evoking cortical responses. The occurrence of thalamic bursts depends on (1) the inactivation gate of T-type Ca2+ channels (T-channels), which become de-inactivated following periods of increased membrane hyperpolarization, and (2) the opening of the T-channel activation gate, which has voltage-threshold and rate-of-change (δv/δt) requirements. Given the time/voltage relationship for the generation of Ca2+ potentials that underlie burst events, it is reasonable to predict that geniculate bursts are influenced by the luminance contrast of drifting grating stimuli, with the null phase of higher contrast stimuli evoking greater hyperpolarization followed by a larger dv/dt than the null phase of lower contrast stimuli. To determine the relationship between stimulus contrast and burst activity, we recorded the spiking activity of cat LGN neurons while presenting drifting sine-wave gratings that varied in luminance contrast. Results show that burst rate, reliability, and timing precision are significantly greater with higher contrast stimuli compared with lower contrast stimuli. Additional analysis from simultaneous recordings of synaptically connected retinal ganglion cells and LGN neurons further reveals the time/voltage dynamics underlying burst activity. Together, these results support the hypothesis that stimulus contrast and the biophysical properties underlying the state of T-type Ca2+ channels interact to influence burst activity, presumably to facilitate thalamocortical communication and stimulus detection.

Choice of end-state comfort is dependent upon the time spent at the beginning-state and the precision requirement of the end-state.

Choice of posture while grasping an object typically depends upon several factors including the time spent in that posture, what postures were held prior to choosing that posture, and the precision required by the posture. The purpose of this study was to test choice of end-state thumb-up posture based on time spent at the beginning-state and the precision requirement of the end-state. To determine choice of thumb-up based on time or precision, we varied how long a subject had to hold the beginning state before moving an object to an end location. We made end-state precision either small or large and eliminated the precision needed to stand the object up at the end of the movement. A choice between "comfort" at the beginning or precision at the end-state would be demanded by the conditions with long beginning-state hold times and high precision demands. We aimed to determine which aspect of movement was of greater importance to individuals, overall "comfort" or precision. When the requirement was to hold the initial grasp longer, and the end-target was large, we predicted that we would see more thumb-up postures adopted at the beginning state. When the final placement was small and the initial posture was not constrained, we predicted we would see thumb-up postures adopted at the end state. On average, we found that, as beginning-state grasp time increased, more individuals chose beginning-state thumb-up postures. Perhaps, not surprisingly, we found distinct individual differences within our sample. Some individuals seemed to choose beginning-state thumb-up postures nearly 100% of the time, while other individuals chose end-state thumb-up postures nearly 100% of the time. Both the time spent in a posture and its precision requirements influenced planning, but not necessarily in a systematic way.

Dynamics of Temporal Integration in the Lateral Geniculate Nucleus.

Before visual information from the retina reaches primary visual cortex (V1), it is dynamically filtered by the lateral geniculate nucleus (LGN) of the thalamus, the first location within the visual hierarchy at which nonretinal structures can significantly influence visual processing. To explore the form and dynamics of geniculate filtering we used data from monosynpatically connected pairs of retinal ganglion cells (RGCs) and LGN relay cells in the cat that, under anesthetized conditions, were stimulated with binary white noise and/or drifting sine-wave gratings to train models of increasing complexity to predict which RGC spikes were relayed to cortex, what we call "relay status." In addition, we analyze and compare a smaller dataset recorded in the awake state to assess how anesthesia might influence our results. Consistent with previous work, we find that the preceding retinal interspike interval (ISI) is the primary determinate of relay status with only modest contributions from longer patterns of retinal spikes. Including the prior activity of the LGN cell further improved model predictions, primarily by indicating epochs of geniculate burst activity in recordings made under anesthesia, and by allowing the model to capture gain control-like behavior within the awake LGN. Using the same modeling framework, we further demonstrate that the form of geniculate filtering changes according to the level of activity within the early visual circuit under certain stimulus conditions. This finding suggests a candidate mechanism by which a stimulus specific form of gain control may operate within the LGN.

Topological magnon band structure of emergent Landau levels in a skyrmion lattice.

The motion of a spin excitation across topologically nontrivial magnetic order exhibits a deflection that is analogous to the effect of the Lorentz force on an electrically charged particle in an orbital magnetic field. We used polarized inelastic neutron scattering to investigate the propagation of magnons (i.e., bosonic collective spin excitations) in a lattice of skyrmion tubes in manganese silicide. For wave vectors perpendicular to the skyrmion tubes, the magnon spectra are consistent with the formation of finely spaced emergent Landau levels that are characteristic of the fictitious magnetic field used to account for the nontrivial topological winding of the skyrmion lattice. This provides evidence of a topological magnon band structure in reciprocal space, which is borne out of the nontrivial real-space topology of a magnetic order.

The effects of exogenous xylanase supplementation on the in vivo generation of xylooligosaccharides and monosaccharides in broilers fed a wheat-based diet.

1. This study quantified xylanase-induced changes in soluble monosaccharides, xylooligosaccharides (XOS) and volatile fatty acid (VFA) contents of the different sections of the gastrointestinal tract (GIT) and whether these were related to altered bird performance. 2. An in vitro digestion of the wheat-based diet was carried out with the xylanase (Econase XT at 16,000BXU/kg diet) to compare the in vitro and in vivo generation of these XOS and monosaccharides. For the in vivo study, 80 male Ross 508 b roiler chicks were split into two groups fed a wheat-based diet with or without Econase XT (16,000BXU/kg diet) for 21 days. 3. There were no effects of Econase XT inclusion on growth performance characteristics, likely a result of the high-quality wheat diet, the corresponding high performance of the control group (FCR average of 1.45 in controls) and the relatively young age of the birds (from four to 26 days of age). 4. Econase XT supplementation increased the xylotetraose (X4) content in the colon (P = 0.046, enzyme x GIT section interaction) and the xylose contents in the colon and caeca (P < 0.001, enzyme x GIT section interaction). 5. The trend for increased acetate production in the caeca of Econase XT treated birds (P = 0.062) suggested that the XOS generated were subsequently fermented in the caeca, potentially impacting upon the types of microbiota present. 6. The present study suggested that wheat arabinoxylan degradation was enhanced by xylanase supplementation, which may have increased the production of beneficial volatile fatty acids (VFA) in the caeca, and thereby potentially modulated the caecal microbiome, but without affecting bird performance at this early age.

Multiple Magnetic Bilayers and Unconventional Criticality without Frustration in BaCuSi_{2}O_{6}.

The dimerized quantum magnet BaCuSi_{2}O_{6} was proposed as an example of "dimensional reduction" arising near the magnetic-field-induced quantum critical point (QCP) due to perfect geometrical frustration of its interbilayer interactions. We demonstrate by high-resolution neutron spectroscopy experiments that the effective intrabilayer interactions are ferromagnetic, thereby excluding frustration. We explain the apparent dimensional reduction by establishing the presence of three magnetically inequivalent bilayers, with ratios 3∶2∶1, whose differing interaction parameters create an extra field-temperature scaling regime near the QCP with a nontrivial but nonuniversal exponent. We demonstrate by detailed quantum Monte Carlo simulations that the magnetic interaction parameters we deduce can account for all the measured properties of BaCuSi_{2}O_{6}, opening the way to a quantitative understanding of nonuniversal scaling in any modulated layered system.

Exploring the Role of Cereal Dietary Fiber in Digestion.

Increasing the dietary fiber of staple foods such as bread is an attractive way to promote healthy eating in a large part of the population, where dietary fiber consumption is reportedly below the recommended values. However, many consumers prefer white breads, which are typically low in dietary fiber. In this work, white bread was made from two wheat cultivars with differing fiber contents. The resulting breads showed similar quality parameters (volume, specific volume, firmness, inner structure characteristics) with any differences maintained below 7%. Bread digestibility was evaluated using a novel dynamic in vitro digestion model. Reduced digestion rates of 30% were estimated for the high-fiber white bread compared to that in the control. Overall, this work demonstrates the potential to produce healthy, high-fiber white breads that are acceptable to consumers, with a reduced rate of starch digestion, by exploiting a genetic variation in the dietary fiber content of wheat cultivars.

Contrast gain control and retinogeniculate communication.

Visual information processed in the retina is transmitted to primary visual cortex via relay cells in the lateral geniculate nucleus (LGN) of the dorsal thalamus. Although retinal ganglion cells are the primary source of driving input to LGN neurons, not all retinal spikes are transmitted to the cortex. Here, we investigate the relationship between stimulus contrast and retinogeniculate communication and test the hypothesis that both the time course and strength of retinogeniculate interactions are dynamic and dependent on stimulus contrast. By simultaneously recording the spiking activity of synaptically connected retinal ganglion cells and LGN neurons in the cat, we show that the temporal window for retinogeniculate integration and the effectiveness of individual retinal spikes are inversely proportional to stimulus contrast. This finding provides a mechanistic understanding for the phenomenon of augmented contrast gain control in the LGN-a nonlinear receptive field property of LGN neurons whereby response gain during low-contrast stimulation is enhanced relative to response gain during high-contrast stimulation. In addition, these results support the view that network interactions beyond the retina play an essential role in transforming visual signals en route from retina to cortex.

Development and applications of a physiologically-based model of paediatric oral drug absorption.

There is increasing interest in paediatric drug absorption and the development of biopharmaceutics tools to facilitate the development of oral formulations for neonates, infants and children. We describe the development and application of a physiologically-based model of paediatric drug absorption applicable from full term birth onwards. Paediatric age-specific parameters were included for salivary flow, gastric pH, gastric emptying (and associated food effects) and duodenal bile salt concentrations and the associated algorithms were integrated into a dissolution, absorption and metabolism model as part of a PBPK platform. For other parameters, there was either evidence for no age-related changes or a lack of data, so that adult values were applied. An initial assessment of the model was carried out by simulating the oral absorption of theophylline, paracetamol and ketoconazole over a range of paediatric ages. The absorption of the first two drugs, both BCS class 1 compounds, was predicted to be slower in early neonates compared to older age groups (median tmax values of 3 vs 2h, respectively), but with invariant fraction absorbed (fa). This is in agreement with clinical observations. The tmax of ketoconazole, a BCS class 2 compound, was predicted to be about 1h in both neonates and adults, but the fa value was higher in the former (0.87 vs 0.69). There is clearly a need to expand the components of the model as new information on the ontogeny of GI tract parameters becomes available, and to assess it against more in vivo data with evidence of specific age-related changes in oral drug absorption.

Molecular dynamics studies of defect formation during heteroepitaxial growth of InGaN alloys on (0001) GaN surfaces.

We investigate the formation of extended defects during molecular-dynamics (MD) simulations of GaN and InGaN growth on (0001) and ([Formula: see text]) wurtzite-GaN surfaces. The simulated growths are conducted on an atypically large scale by sequentially injecting nearly a million individual vapor-phase atoms towards a fixed GaN surface; we apply time-and-position-dependent boundary constraints that vary the ensemble treatments of the vapor-phase, the near-surface solid-phase, and the bulk-like regions of the growing layer. The simulations employ newly optimized Stillinger-Weber In-Ga-N-system potentials, wherein multiple binary and ternary structures are included in the underlying density-functional-theory training sets, allowing improved treatment of In-Ga-related atomic interactions. To examine the effect of growth conditions, we study a matrix of >30 different MD-growth simulations for a range of In x Ga 1-x N-alloy compositions (0 ≤ x ≤ 0.4) and homologous growth temperatures [0.50 ≤ T/T*m (x) ≤ 0.90], where T*m (x) is the simulated melting point. Growths conducted on polar (0001) GaN substrates exhibit the formation of various extended defects including stacking faults/polymorphism, associated domain boundaries, surface roughness, dislocations, and voids. In contrast, selected growths conducted on semi-polar ([Formula: see text]) GaN, where the wurtzite-phase stacking sequence is revealed at the surface, exhibit the formation of far fewer stacking faults. We discuss variations in the defect formation with the MD growth conditions, and we compare the resulting simulated films to existing experimental observations in InGaN/GaN. While the palette of defects observed by MD closely resembles those observed in the past experiments, further work is needed to achieve truly predictive large-scale simulations of InGaN/GaN crystal growth using MD methodologies.

Electroconvulsive therapy modulates plasma pigment epithelium-derived factor in depression: a proteomics study.

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, yet its mechanism of action is not fully understood. Peripheral blood proteomic analyses may offer insights into the molecular mechanisms of ECT. Patients with a major depressive episode were recruited as part of the EFFECT-Dep trial (enhancing the effectiveness of electroconvulsive therapy in severe depression; ISRCTN23577151) along with healthy controls. As a discovery-phase study, patient plasma pre-/post-ECT (n=30) was analyzed using 2-dimensional difference in gel electrophoresis and mass spectrometry. Identified proteins were selected for confirmation studies using immunodetection methods. Samples from a separate group of patients (pre-/post-ECT; n=57) and matched healthy controls (n=43) were then used to validate confirmed changes. Target protein mRNA levels were also assessed in rat brain and blood following electroconvulsive stimulation (ECS), the animal model of ECT. We found that ECT significantly altered 121 protein spots with 36 proteins identified by mass spectrometry. Confirmation studies identified a post-ECT increase (P<0.01) in the antiangiogenic and neuroprotective mediator pigment epithelium-derived factor (PEDF). Validation work showed an increase (P<0.001) in plasma PEDF in depressed patients compared with the controls that was further increased post-ECT (P=0.03). PEDF levels were not associated with mood scores. Chronic, but not acute, ECS increased PEDF mRNA in rat hippocampus (P=0.02) and dentate gyrus (P=0.03). This study identified alterations in blood levels of PEDF in depressed patients and further alterations following ECT, as well as in an animal model of ECT. These findings implicate PEDF in the biological response to ECT for depression.

Retinal and Nonretinal Contributions to Extraclassical Surround Suppression in the Lateral Geniculate Nucleus.

Extraclassical surround suppression is a prominent receptive field property of neurons in the lateral geniculate nucleus (LGN) of the dorsal thalamus, influencing stimulus size tuning, response gain control, and temporal features of visual responses. Despite evidence for the involvement of both retinal and nonretinal circuits in the generation of extraclassical suppression, we lack an understanding of the relative roles played by these pathways and how they interact during visual stimulation. To determine the contribution of retinal and nonretinal mechanisms to extraclassical suppression in the feline, we made simultaneous single-unit recordings from synaptically connected retinal ganglion cells and LGN neurons and measured the influence of stimulus size on the spiking activity of presynaptic and postsynaptic neurons. Results show that extraclassical suppression is significantly stronger for LGN neurons than for their retinal inputs, indicating a role for extraretinal mechanisms. Further analysis revealed that the enhanced suppression can be accounted for by mechanisms that suppress the effectiveness of retinal inputs in evoking LGN spikes. Finally, an examination of the time course for the onset of extraclassical suppression in the LGN and the size-dependent modulation of retinal spike efficacy suggests the early phase of augmented suppression involves local thalamic circuits. Together, these results demonstrate that the LGN is much more than a simple relay for retinal signals to cortex; it also filters retinal spikes dynamically on the basis of stimulus statistics to adjust the gain of visual signals delivered to cortex. SIGNIFICANCE STATEMENT: The lateral geniculate nucleus (LGN) is the gateway through which retinal information reaches the cerebral cortex. Within the LGN, neuronal responses are often suppressed by stimuli that extend beyond the classical receptive field. This form of suppression, called extraclassical suppression, serves to adjust the size tuning, response gain, and temporal response properties of neurons. Given the important influence of extraclassical suppression on visual signals delivered to cortex, we performed experiments to determine the circuit mechanisms that contribute to extraclassical suppression in the LGN. Results show that suppression is augmented beyond that provided by direct retinal inputs and delayed, consistent with polysynaptic inhibition. Importantly, these mechanisms influence the effectiveness of incoming retinal signals, thereby filtering the signals ultimately conveyed to cortex.

Magnetodielectric detection of magnetic quadrupole order in Ba(TiO)Cu4(PO4)4 with Cu4O12 square cupolas.

In vortex-like spin arrangements, multiple spins can combine into emergent multipole moments. Such multipole moments have broken space-inversion and time-reversal symmetries, and can therefore exhibit linear magnetoelectric (ME) activity. Three types of such multipole moments are known: toroidal; monopole; and quadrupole moments. So far, however, the ME activity of these multipole moments has only been established experimentally for the toroidal moment. Here we propose a magnetic square cupola cluster, in which four corner-sharing square-coordinated metal-ligand fragments form a noncoplanar buckled structure, as a promising structural unit that carries an ME-active multipole moment. We substantiate this idea by observing clear magnetodielectric signals associated with an antiferroic ME-active magnetic quadrupole order in the real material Ba(TiO)Cu4(PO4)4. The present result serves as a useful guide for exploring and designing new ME-active materials based on vortex-like spin arrangements.

Metformin and cimetidine: Physiologically based pharmacokinetic modelling to investigate transporter mediated drug-drug interactions.

Metformin is used as a probe for OCT2 mediated transport when investigating possible DDIs with new chemical entities. The aim of the current study was to investigate the ability of physiologically-based pharmacokinetic (PBPK) models to simulate the effects of OCT and MATE inhibition by cimetidine on metformin kinetics. PBPK models were developed, incorporating mechanistic kidney and liver sub-models for metformin (OCT and MATE substrate) and a mechanistic kidney sub-model for cimetidine. The models were used to simulate inhibition of the MATE1, MATE2-K, OCT1 and OCT2 mediated transport of metformin by cimetidine. Assuming competitive inhibition and using cimetidine Ki values determined in vitro, the predicted metformin AUC ratio was 1.0 compared to an observed value of 1.46. The observed AUC ratio could only be recovered with this model when the cimetidine Ki for OCT2 was decreased 1000-fold or the Ki's for both OCT1 and OCT2 were decreased 500-fold. An alternative description of metformin renal transport by OCT1 and OCT2, incorporating electrochemical modulation of the rate of metformin uptake together with 8-18-fold decreases in cimetidine Ki's for OCTs and MATEs, allowed recovery of the extent of the observed effect of cimetidine on metformin AUC. While the final PBPK model has limitations, it demonstrates the benefit of allowing for the complexities of passive permeability combined with active cellular uptake modulated by an electrochemical gradient and active efflux.

Prevalence and associations of gout and hyperuricaemia: results from an Australian population-based study.

BACKGROUND: Despite gout and hyperuricaemia being major comorbid health issues worldwide, there is a knowledge gap regarding their impact in the Australian community. AIMS: To determine the prevalence and associations of self-reported medically diagnosed gout and hyperuricaemia in an Australian population-based cohort. METHODS: The North West Adelaide Health Study is a longitudinal cohort study consisting of three stages of data collection. Each stage comprised a self-complete questionnaire, clinic assessment and computer-assisted telephone interview. In Stage 3 (2008-2010), participants were asked if a doctor had ever diagnosed them with gout. Additional data included demographics, comorbidities, laboratory data and Short Form 36 (SF-36). Participants were defined as having gout if they had self-reported medically diagnosed gout or were taking any gout-specific medication (allopurinol, colchicine, probenecid). Hyperuricaemia was defined as a serum uric acid (SUA) level >0.42 mmol/L in men and >0.34 mmol/L in women. RESULTS: The overall prevalence of gout was 5.2%. Males were significantly more likely to have gout than females (8.5 vs 2.1%, P < 0.001). The overall prevalence of hyperuricaemia was 16.6%, with being male again identified as a significant risk factor (17.8 vs 15.4%, P < 0.01). Both gout and hyperuricaemia were associated with male sex, body mass index and renal disease after multivariable adjustment. There was no significant difference reported in quality of life (mean SF-36) scores in participants with gout compared to unaffected individuals. CONCLUSION: The prevalence of gout and hyperuricaemia is high in the South Australian population. This study emphasises the need for optimal diagnosis and management of gout in Australia.

Sociodemographic correlates of smoking in pregnancy and antenatal-care attendance in Indigenous and non-Indigenous women in South Australia.

Smoking in pregnancy is a key health issue in Australia, particularly among Indigenous women. However, few studies have examined the sociodemographic factors associated with smoking in pregnancy or the predictors of antenatal-care attendance among Indigenous and non-Indigenous Australian women who smoke. Data from the South Australian perinatal statistics collection of all births from 2000-2010 (n=197538) were analysed separately by Indigenous status to determine the sociodemographic factors associated with smoking in pregnancy and antenatal-care attendance by women who smoke. For Indigenous and non-Indigenous women, smoking in pregnancy was significantly independently associated with socioeconomic disadvantage, residing in regional or remote areas, increased parity, unemployment, being a public patient and attending fewer antenatal care visits. Smoking in pregnancy was associated with younger age and not being partnered only for non-Indigenous women. For Indigenous and non-Indigenous pregnant women who smoked, antenatal-care attendance was lower among women who were of younger age, higher parity, unemployed and not partnered. Differences in attendance within sociodemographic factors were greater for Indigenous women. Therefore, while sociodemographic correlates of smoking in pregnancy and antenatal-care attendance are largely similar for Indigenous and non-Indigenous women, tailored cessation and antenatal-care programs that reflect the differences in sociodemographic groups most at risk may be beneficial.

Expression of RCK2 MAPKAP (MAPK-activated protein kinase) rescues yeast cells sensitivity to osmotic stress.

BACKGROUND: Saccharomyces cerevisiae is the micro-organism of choice for the conversion of fermentable sugars during beverage or bioethanol fermentations. These fermentations are characterised by high osmotic stress on a yeast cell, with selected brewing fermentations beginning at 20-25% fermentable sugars and bioethanol fermentations at 13% fermentable sugars. RESULTS: RCK2 encodes for a MAPKAP (MAPK-activated protein kinase) enzyme and was identified on a locus by QTL analysis in yeast cells under osmotic stress, RCK2 expression was placed under a tetracycline regulatable vector and rescued glucose, sorbitol or glycerol induced osmotic stress in an rck2 null strain. A strain overexpressing RCK2 had significantly faster fermentation rates when compared with the empty vector control strain. CONCLUSIONS: Presence of RCK2 increased rates of glucose utilisation (~40 g glucose in first 8 h) during a 15% glucose fermentation and concurrent production of ethanol when compared with empty vector controls. Tolerance to osmotic stress using the tetracycline regulatable vectors could be turned off with the addition of tetracycline returning a rck2 null strain back to osmotic sensitivity.