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Global climate change is predicted to cause more frequent extreme weather events over the next century. These events will exacerbate various abiotic stresses, including drought and high temperatures, each of which can inhibit growth and threaten survival of natural and managed plant systems. This study postulates that wild Australian relatives of Nicotiana from very arid sites might reveal unique characteristics that confer tolerance of hot environments. This may serve high implications in managing agricultural systems and understanding plant species that are sensitive to increased heat. A multi-disciplinary approach investigated heat tolerance at plant, leaf, cell and gene levels. Physiological analysis including growth analysis and gas exchange, suggested that N. megalosiphon and N. tabacum L. tolerated heat stress best among the five species tested. However, solute leakage from leaves of N. megalosiphon did not reveal superior cell membrane integrity under heat stress. A preliminary molecular analysis of a gene known to be vulnerable to heat-stress, Rubisco activase (RCA), revealed some putative amino acid changes between N. tabacum L. and N. benthamiana. This could imply divergent evolution between these two species, particularly in N. tabacum L. which has been highly selected for hot environments under cultivation.

We do not have a full understanding of the mechanisms underlying plasticity in the human brain. Mouse models have well controlled environments and genetics, and provide tools to help dissect the mechanisms underlying the observed responses to therapies devised for humans recovering from injury of ischemic nature or trauma. We aimed to detect plasticity following learning of a unilateral reaching movement, and relied on MRI performed with a rapid structural protocol suitable for in vivo brain imaging, and a longer diffusion tensor imaging (DTI) protocol executed ex vivo. In vivo MRI detected contralateral volume increases in trained animals (reachers), in circuits involved in motor control, sensory processing, and importantly, learning and memory. The temporal association area, parafascicular and mediodorsal thalamic nuclei were also enlarged. In vivo MRI allowed us to detect longitudinal effects over the ~25 days training period. The interaction between time and group (trained versus not trained) supported a role for the contralateral, but also the ipsilateral hemisphere. While ex vivo imaging was affected by shrinkage due to the fixation, it allowed for superior resolution and improved contrast to noise ratios, especially for subcortical structures. We examined microstructural changes based on DTI, and identified increased fractional anisotropy and decreased apparent diffusion coefficient, predominantly in the cerebellum and its connections. Cortical thickness differences did not survive multiple corrections, but uncorrected statistics supported the contralateral effects seen with voxel based volumetric analysis, showing thickening in the somatosensory, motor and visual cortices. In vivo and ex vivo analyses identified plasticity in circuits relevant to selecting actions in a sensory-motor context, through exploitation of learned association and decision making. By mapping a connectivity atlas into our ex vivo template we revealed that changes due to skilled motor learning occurred in a network of 35 regions, including the primary and secondary motor (M1, M2) and sensory cortices (S1, S2), the caudate putamen (CPu), visual (V1) and temporal association cortex. The significant clusters intersected tractography based networks seeded in M1, M2, S1, V1 and CPu at levels > 80%. We found that 89% of the significant cluster belonged to a network seeded in the contralateral M1, and 85% to one seeded in the contralateral M2. Moreover, 40% of the M1 and S1 cluster by network intersections were in the top 80th percentile of the tract densities for their respective networks. Our investigation may be relevant to studies of rehabilitation and recovery, and points to widespread network changes that accompany motor learning that may have potential applications to designing recovery strategies following brain injury.

Devices that utilize reversible electrochemical mirrors (REM) have a number of applications including thermal and light management for terrestrial and space based systems. These systems use the concept of reversible electrodeposition to plate and strip highly reflective metallic films, i.e. mirrors, in the device to facilitate reflection and transmission or absorption of radiation. Figure 1 provides an illustration of a REM device whereby a transparent support, typically glass or plastic contains a transparent conducting layer that functions as the mirror electrode. An electrolyte containing the metal ions available for reduction and oxidation of the optically tailored metallic film is contained between the mirror electrode and the counter electrode, which may or may not be transmissive depending on the technology application. Electrodeposition of species such as silver, copper, tin, aluminum or gold generates a mirror like surface through the transparent electrode that facilitates reflection of radiation that aids in thermal management for satellite applications or light management for smart window applications. The mirror deposit can then be oxidized from the transparent electrode by applying a less negative or positive voltage with respect to the deposition voltage, permitting transmission of radiation. The cell may also be designed such as to cycle between reflective and absorptive states by changing the nature of the counter electrode. Conventional REM devices utilize electrolytes based on organic solvents such as gamma-butylrolactone and dimethyl sulfoxide. For space based applications, these electrolytes are unsuitable due to their vapor pressures and potential for evaporation if the cell seal is compromised. Room temperature ionic liquid electrolytes (RTIL) are an attractive alternative to these conventional systems due to their negligible vapor pressure in addition to their excellent chemical and thermal stability and their large electrochemical windows. RTIL base electrolytes may be tailored to deliver specific properties based on their cation and anion species, making the electrolytes tunable for specific applications. RTILs with anionic species such as chloride, bromide and iodide have been evaluated as potential alternatives to the conventional organic electrolytes for REM devices. These systems have shown promise in terms of mirror formation and long cycle life; however, they exhibit high sensitivity to water, including atmospheric moisture, which can limit their usefulness in REM devices. The present work focuses on deposition and stripping of silver thin films from RTIL with relative low moisture sensitivity. Simple, two electrode cells were built using transparent electrodes with electrically conductive films (i.e. indium tin oxide, platinum and silver) and air and moisture stable RTIL electrolytes for electrochemical characterization and plating/stripping cycling experiments. Highly reflective and reproducible silver mirror formation using air and moisture stable RTIL based electrolytes has been demonstrated. Limited cycle lifetime in terms of the number of plating and stripping cycles with acceptable mirror formation was initially encountered. The thin conductive films applied to the transparent electrodes are susceptible to redox reactions which can limit their lifetimes, and as such relatively low voltages are applied in attempts to maintain the integrity of the electrodes and thus the REM device. Furthermore, the primary challenge with extended cycling of REM devices is the incomplete removal of the reflective surface leading to degradation of the mirror’s reflectivity with cycling. It is speculated that residual surface oxide effectively blocks complete stripping of the silver deposit and/or deposition of an acceptable reflecting mirror, adversely affecting device cycling lifetime. Therefore, a major challenge in the development of REM devices, whereby a reflective surface such as silver is alternatively plated and dissolved on a transparent conductive substrate, is that a buildup of undissolved reflective material on the electrode surface over successive cycles causes a loss of reflectivity and transmission. To counter this, an electrode maintenance cycle was introduced periodically within mirror plating and stripping cycles to aid in complete oxide removal, preparing the electrode surface for the next plating cycle. This maintenance cycle is introduced as a multiple cyclic voltammetry scan (cyclic potential sweep cleaning) and was found to extend device cycling lifetime. Data is presented on the development of conditions for plating and stripping cycles as well as the electrode maintenance cycle and scale up considerations and activities are also discussed. Acknowledgement: Funding for this work is gratefully acknowledged from Air Force STTR Grant Number FA9453-17-C-0490. Platinum coated ITO electrodes were prepared by Dr. John Bryan Plumley. Figure 1

Contains fulltext : 155360.pdf (Publisher’s version ) (Closed access) Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91,462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P

Genome-wide association studies (GWASs) have identified 19 susceptibility loci for Alzheimer’s disease (AD). However, understanding how these genes are involved in the pathophysiology of AD is one of the main challenges of the “post-GWAS” era. At least 123 genes are located within the 19 susceptibility loci; hence, a conventional approach (studying the genes one by one) would not be time- and cost-effective. We therefore developed a genome-wide, high-content siRNA screening approach and used it to assess the functional impact of gene under-expression on APP metabolism. We found that 832 genes modulated APP metabolism. Eight of these genes were located within AD susceptibility loci. Only FERMT2 (a β3-integrin co-activator) was also significantly associated with a variation in cerebrospinal fluid Aβ peptide levels in 2886 AD cases. Lastly, we showed that the under-expression of FERMT2 increases Aβ peptide production by raising levels of mature APP at the cell surface and facilitating its recycling. Taken as a whole, our data suggest that FERMT2 modulates the AD risk by regulating APP metabolism and Aβ peptide production. Electronic supplementary material The online version of this article (doi:10.1007/s00401-016-1652-z) contains supplementary material, which is available to authorized users.

Aims Reported associations between liver enzymes and mortality may not hold true in type 2 diabetes, owing to a high prevalence of non-alcoholic fatty liver disease, which has been linked to cardiovascular disease and mortality in its own right. Our study aimed to determine whether alanine aminotransferase (ALT) or γ-glutamyl transferase (GGT) levels predict mortality in type 2 diabetes, and to examine possible mechanisms. Methods Data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study were analysed to examine the relationship between liver enzymes and all-cause and cause-specific mortality over 5 years. Results Over 5 years, 679 (6.9%) individuals died. After adjustment, for every standard deviation increase in ALT (13.2U/L), the HR for death on study was 0.85 (95% CI 0.78-0.93), p70 U/L, compared with GGT ≤70 U/L, had HR 1.82 (1.48−2.24), p70 U/L was associated with higher risks of death due to cardiovascular disease, cancer and non-cancer/non-cardiovascular causes. The relationship for ALT persisted after adjustment for indirect measures of frailty but was attenuated by elevated hsCRP. Conclusions As in the general population, ALT has a negative, and GGT a positive, correlation with mortality in type 2 diabetes when ALT is less than two times the upper limit of normal. The relationship 4 for ALT appears specific for death due to cardiovascular disease. Links of low ALT with frailty, as a potential mechanism for relationships seen, were neither supported nor conclusively refuted by our analysis and other factors are also likely to be important in those with type 2 diabetes.

The next grand challenges for society and science are in the brain sciences. A collection of 60+ scientists from around the world, together with 10+ observers from national, private, and foundations, spent two days together discussing the top challenges that we could solve as a global community in the next decade. We eventually settled on three challenges, spanning anatomy, physiology, and medicine. Addressing all three challenges requires novel computational infrastructure. The group proposed the advent of The International Brain Station (TIBS), to address these challenges, and launch brain sciences to the next level of understanding., Comment: 6 pages

The ·dissertation is divided into six chapters. The first chapter contains introductory remarks and sets the scene for the work that is to follow. Chapter 2 is devoted to the conduction of heat or electricity through granular materials, the conductivity of the grains greatly exceeds that of the matrix and the grains are closely-packed. Frornan analysis of the temperature distribution near the point of contact between a pair of particles we derive an expression for the effective conductivity of this type of material. In chapter 3 we study the conduction of heat across a bundle of fibres. It is shown that small deviations in fibre straightness or in fibre alignment have a marked effect on the conductivity of these types of materials, and expressions are obtained for the effective conductivity of two classes of fibre bundles. The work in chapter 4 is concerned with general aspects of the determination of effective transport properties. A new method is described for obtaining the effective transport properties of suspensions of interacting spherical particles in both regular and random arrays. This new method does not encounter divergence difficulties, and provides a rigorous basis for the rather ad hoc procedures devised earlier to deal with divergence difficulties. Some old results are rederived by these new techniques and expressions are obtained for the effective modulus of compr ession of r igid spheres in random and regular arrays in an elastic matrix. Chapter 5 is devoted to a study of the coagulation of particles in shear flow. We are mainly concerned with the coagulation of particles at "high" shear_ rates, in which case the Brew nian motion of the particles is negligible and the Van der Waals forces between the particles only affect the motion of nearly touching particles. Expressions are obtained for the rate at which single spherical particles coagulate for form doublets, per unit volume of suspension. Finally, in chapter 6 we present the results of a numerical study on the effect of Van der Waals attraction and electrical repulsion on the motion of a pair of spherical particles in shear flow. It is shown that at very low shear rates, pairs execute closed orbits about each other. As the shear rate increases the pairs are pulled apart, and finally, at very high shear rates pairs are pushed together with such force by the flow that some are able to overcome the electrical repulsive forces and coagulation occurs.

Parkinson's disease (PD) has a number of known genetic risk factors. Clinical and epidemiological studies have suggested the existence of intermediate factors that may be associated with additional risk of PD. We construct genetic risk profiles for additional epidemiological and clinical factors using known genome-wide association studies (GWAS) loci related to these specific phenotypes to estimate genetic comorbidity in a systematic review. We identify genetic risk profiles based on GWAS variants associated with schizophrenia and Crohn's disease as significantly associated with risk of PD. Conditional analyses adjusting for SNPs near loci associated with PD and schizophrenia or PD and Crohn's disease suggest that spatially overlapping loci associated with schizophrenia and PD account for most of the shared comorbidity, while variation outside of known proximal loci shared by PD and Crohn's disease accounts for their shared genetic comorbidity. We examine brain methylation and expression signatures proximal to schizophrenia and Crohn's disease loci to infer functional changes in the brain associated with the variants contributing to genetic comorbidity. We compare our results with a systematic review of epidemiological literature, while the findings are dissimilar to a degree; marginal genetic associations corroborate the directionality of associations across genetic and epidemiological data. We show a strong genetically defined level of comorbidity between PD and Crohn's disease as well as between PD and schizophrenia, with likely functional consequences of associated variants occurring in brain.

Familial Hypercholesterolemia (FH) is the most common and serious monogenic disorder of lipoprotein metabolism that leads to premature coronary heart disease. There are over 65,000 people estimated to have FH in Australia, but many remain undiagnosed. Patients with FH are often undertreated, but with early detection, cascade family testing and adequate treatment, patient outcomes can improve. Patient registries are key tools for providing new information on FH and enhancing care worldwide. The development and design of the FH Australasia Network Registry is a crucial component in the comprehensive model of care for FH, which aims to provide a standardized, highquality and cost-effective system of care that is likely to have the highest impact on patient outcomes. Informed by stakeholder engagement, the FH Australasia Network Registry was collaboratively developed by government, patient and clinical networks and research groups. The open-source, webbased Rare Disease Registry Framework was the architecture chosen for this registry owing to its open-source standards, modular design, interoperability, scalability and security features; all these are key components required to meet the ever changing clinical demands across regions. This paper provides a high level blueprint for other countries and jurisdictions to help inform and map out the critical features of an FH registry to meet their particular health system needs. Refereed/Peer-reviewed

Familial hypercholesterolaemia (FH) is a co-dominantly inherited disorder that causes marked elevation in plasma cholesterol and premature coronary heart disease. There are at least 45,000 people with FH in Australia and New Zealand, but most remain undiagnosed and undertreated. To bridge this gap in coronary prevention the FH Australasia Network has developed a model of care for FH. We present the executive summary, with a commentary contrasting the recommendations with other international guidelines and highlighting the role of the cardiologist. Refereed/Peer-reviewed