Simultaneous topography and reaction flux mapping at and around electrocatalytic nanoparticles

The characterization of electrocatalytic reactions at individual nanoparticles (NPs) is presently of considerable interest but very challenging. Herein, we demonstrate how simple-to-fabricate nanopipette probes with diameters of approximately 30 nm can be deployed in a scanning ion conductance microscopy (SICM) platform to simultaneously visualize electrochemical reactivity and topography with high spatial resolution at electrochemical interfaces. By employing a self-referencing hopping mode protocol, whereby the probe is brought from bulk solution to the near-surface at each pixel, and with potential-time control applied at the substrate, current measurements at the nanopipette can be made with high precision and resolution (30 nm resolution, 2600 pixels μm–2, <0.3 s pixel−1) to reveal a wealth of information on the substrate physicochemical properties. This methodology has been applied to image the electrocatalytic oxidation of borohydride at ensembles of AuNPs on a carbon fiber support in alkaline media, whereby the depletion of hydroxide ions and release of water during the reaction results in a detectable change in the ionic composition around the NPs. Through the use of finite element method simulations, these observations are validated and analyzed to reveal important information on heterogeneities in ion flux between the top of a NP and the gap at the NP-support contact, diffusional overlap and competition for reactant between neighboring NPs, and differences in NP activity. These studies highlight key issues that influence the behavior of NP assemblies at the single NP level and provide a platform for the use of SICM as an important tool for electrocatalysis studies

Nested-grid simulation of mercury over North America

We have developed a new nested-grid mercury (Hg) simulation over North America with a 1/2° latitude by 2/3° longitude horizontal resolution employing the GEOS-Chem global chemical transport model. Emissions, chemistry, deposition, and meteorology are self-consistent between the global and nested domains. Compared to the global model (4° latitude by 5° longitude), the nested model shows improved skill at capturing the high spatial and temporal variability of Hg wet deposition over North America observed by the Mercury Deposition Network (MDN) in 2008–2009. The nested simulation resolves features such as higher deposition due to orographic precipitation, land/ocean contrast and and predicts more efficient convective rain scavenging of Hg over the southeast United States. However, the nested model overestimates Hg wet deposition over the Ohio River Valley region (ORV) by 27%. We modify anthropogenic emission speciation profiles in the US EPA National Emission Inventory (NEI) to account for the rapid in-plume reduction of reactive to elemental Hg (IPR simulation). This leads to a decrease in the model bias to −2.3% over the ORV region. Over the contiguous US, the correlation coefficient (<i>r</i>) between MDN observations and our IPR simulation increases from 0.60 to 0.78. The IPR nested simulation generally reproduces the seasonal cycle in surface concentrations of speciated Hg from the Atmospheric Mercury Network (AMNet) and Canadian Atmospheric Mercury Network (CAMNet). In the IPR simulation, annual mean gaseous and particulate-bound Hg(II) are within 140% and 11% of observations, respectively. In contrast, the simulation with unmodified anthropogenic Hg speciation profiles overestimates these observations by factors of 4 and 2 for gaseous and particulate-bound Hg(II), respectively. The nested model shows improved skill at capturing the horizontal variability of Hg observed over California during the ARCTAS aircraft campaign. The nested model suggests that North American anthropogenic emissions account for 10–22% of Hg wet deposition flux over the US, depending on the anthropogenic emissions speciation profile assumed. The modeled percent contribution can be as high as 60% near large point sources in ORV. Our results indicate that the North American anthropogenic contribution to dry deposition is 13–20%

Evaluation of a commercially developed semiautomated PCR-surface-enhanced Raman scattering assay for diagnosis of invasive fungal disease

Nonculture-based tests are gaining popularity in the diagnosis of invasive fungal disease (IFD), but PCR is excluded from disease-defining criteria because of limited standardization and a lack of commercial assays. Commercial PCR assays may have a standardized methodology while providing quality assurance. The detection of PCR products by a surface-enhanced Raman scattering (SERS) assay potentially provides superior analytical sensitivity and multiplexing capacity compared to that of real-time PCR. Using this approach, the RenDx Fungiplex assay was developed to detect Candida and Aspergillus. Analytical and clinical evaluations of the assay were undertaken using extraction methods according to European Aspergillus PCR Initiative (EAPCRI) recommendations. A total of 195 previously extracted samples (133 plasma, 49 serum, and 13 whole blood) from 112 patients (29 with proven/probable IFD) were tested. The 95% limit of detection of Candida and Aspergillus was 200 copies per reaction, with an overall reproducibility of 92.1% for detecting 20 input copies per PCR, and 89.8% for the nucleic acid extraction–PCR-SERS process for detecting fungal burdens of <20 genome equivalents per sample. A clinical evaluation showed that assay positivity significantly correlated with IFD (P < 0.0001). The sensitivity of the assay was 82.8% and was similar for both Candida (80.0%) and Aspergillus (85.7%). The specificity was 87.5% and was increased (97.5%) by using a multiple (≥2 samples) PCR-positive threshold. In summary, the RenDx Fungiplex assay is a PCR-SERS assay for diagnosing IFD and demonstrates promising clinical performance on a variety of samples. This was a retrospective clinical evaluation, and performance is likely to be enhanced through a prospective analysis of clinical validity and by determining clinical utility

Crop Updates 2010 - Farming Systems

This session covers twenty papers from different authors: Pests and Disease 1. Preserving phosphine for use in Grain Storage Industry, Christopher R Newman, Department of Agriculture and Food Farming Systems Research 2. Demonstrating the benefits of grazing canola in Western Australia, Jonathan England, Stephen Gherardi and Mohammad Amjad, Department of Agriculture and Food 3. Buloke barley yield when pasture-cropped across subtropical perennial pastures, David Ferris, Department of Agriculture and Food, Phil Ward and Roger Lawes, CSIRO 4. Is pasture cropping viable in WA? Grower perceptions and EverCrop initiatives to evaluate, David Ferris, Tim Wiley, Perry Dolling, Department of Agriculture and Food, Philip Barrett-Lennard, Evergreen farming 5. Best-bet management for dual-purpose canola, John Kirkegaard, Susan Sprague, Hugh Dove and Walter Kelman, CSIRO, Canberra, Peter Hamblin, Agritech Research, Young, NSW 6. Pasture in cropping systems – with and without sheep, Brad Nutt and Angelo Loi, Department of Agriculture and Food 7. Can technology substitute for a lupin break? Wayne Parker, Department of Agriculture and Food 8. Canola row spacing with and without long term stubble retention on a sandy clay loam at Merredin, Glen Riethmuller, Department of Agriculture and Food 9. Impact of stubble retention on water balance and crop yield, Phil Ward1, Ken Flower2,3, Neil Cordingley2 and Shayne Micin1, 1CSIRO, Wembley, Western Australia, 2Western Australian No-Till Farmers Association, 3University of Western Australia Analysis and Modelling 10. Using POAMA rainfall forecasts for crop management in South-West WA, Senthold Asseng1, Peter McIntosh2,3, Mike Pook2,3, James Risbey2,3, Guomin Wang3, Oscar Alves3, Ian Foster4, Imma Farre4 and Nirav Khimashia1, 1CSIRO Plant Industry, Perth, 2CSIRO Marine and Atmospheric Research, Hobart, 3Centre for Australian Weather and Climate Research (CAWCR), A partnership between the Australian Bureau of Meteorology and CSIRO, Melbourne, 4Department of Agriculture and Food 11. Adaption to changing climates and variability – results of the Agribusiness Changing Climates regional workshop, Anderson W3, Beard D3, Blake J3, Grieve R1, Lang M3, Lemon J3, McTaggart R3, Gray D3, Price M2 and Stephens D3, 1Roderick Grieve Farm Management Consultants, 2Coffey International P/L, 3Department of Agriculture and Food 12. Farmers’ management of seasonal variability and climate change in WA, DA Beard, DM Gray, P Carmody, Department of Agriculture and Food 13. Is there a value in having a frost forecast for wheat in South-West WA? Imma Farre1, Senthold Asseng2, Ian Foster1 and Doug Abrecht3, 1Department of Agriculture and Food, CSIRO, Floreat, 2CSIRO Plant Industry, Perth 3Department of Agriculture and Food, Centre for Cropping Systems 14. Does buying rainfall pay? Greg Kirk, Planfarm Agricultural Consultants 15. Which region in the WA wheatbelt makes best use of rainfall? Peter Rowe, Bankwest Agribusiness 16. POAMA – the Predictive Ocean-Atmosphere Model for Australia, Guomin Wang and Oscar Alves, Centre for Australian Weather and Climate Research (CAWCR), A partnership between the Australian Bureau of Meteorology and CSIRO, Melbourne 17. Exploring the link between water use efficiency and farm profitability, Cameron Weeks, Planfarm and Peter Tozer, PRT Consulting Precision Agriculture 18. A plethora of paddock information is available – how does it stack up? Derk Bakker, Department of Agriculture and Food 18. Variable rate prescription mapping for lime inputs based on electromagnetic surveying and deep soil testing, Frank D’Emden, Quenten Knight and Luke Marquis, Precision Agronomics, Australia 19. Trial design and analysis using precision agriculture and farmer’s equipment, Roger Lawes, CSIRO Sustainable Ecosystems, Centre for Environment and Life Sciences, Floreat 20. Farmer perspectives of precision agriculture in Western Australia: Issues and the way forward, Dr Roger Mandel, Curtin Universit

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke

Background and Objectives Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke. Methods We performed a meta-analysis of genome-wide association studies of early-onset stroke (EOS), ages 18-59 years, using individual-level data or summary statistics in 16,730 cases and 599,237 nonstroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late-onset stroke (LOS) and compared polygenic risk scores (PRS) for venous thromboembolism (VTE) between EOS and LOS. Results We observed genome-wide significant associations of EOS with 2 variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared with LOS. The odds ratio (OR) for rs529565, tagging O1, was 0.88 (95% confidence interval [CI]: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using PRSs, we observed that greater genetic risk for VTE, another prothrombotic condition, was more strongly associated with EOS compared with LOS (p = 0.008). Discussion The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.Peer reviewe

Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke.

OBJECTIVE: For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms. METHODS: We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations. RESULTS: There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-analysis of the genome-wide significant and suggestive loci (p < 5 × 10(-6)) from community populations (15 single nucleotide polymorphisms in total) and from stroke patients, 6 independent loci were associated with WMHV in both populations. Four of these are novel associations at the genome-wide level (rs72934505 [NBEAL1], p = 2.2 × 10(-8); rs941898 [EVL], p = 4.0 × 10(-8); rs962888 [C1QL1], p = 1.1 × 10(-8); rs9515201 [COL4A2], p = 6.9 × 10(-9)). CONCLUSIONS: Genetic associations with WMHV are shared in otherwise healthy individuals and patients with stroke, indicating common genetic susceptibility in cerebral small vessel disease.Funding for collection, genotyping, and analysis of stroke samples was provided by Wellcome Trust Case Control Consortium-2, a functional genomics grant from the Wellcome Trust (DNA-Lacunar), the Stroke Association (DNA-lacunar), the Intramural Research Program of National Institute of Ageing (Massachusetts General Hospital [MGH] and Ischemic Stroke Genetics Study [ISGS]), National Institute of Neurological Disorders and Stroke (Siblings With Ischemic Stroke Study, ISGS, and MGH), the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (MGH), Deane Institute for Integrative Study of Atrial Fibrillation and Stroke (MGH), National Health and Medical Research Council (Australian Stroke Genetics Collaborative), and Italian Ministry of Health (Milan). Additional support for sample collection came from the Medical Research Council, National Institute of Health Research Biomedical Research Centre and Acute Vascular Imaging Centre (Oxford), Wellcome Trust and Binks Trust (Edinburgh), and Vascular Dementia Research Foundation (Munich). MT is supported by a project grant from the Stroke Association (TSA 2013/01). HSM is supported by an NIHR Senior Investigator award. HSM and SB are supported by the NIHR Cambridge University Hospitals Comprehensive Biomedical Research Centre. VT and RL are supported by grants from FWO Flanders. PR holds NIHR and Wellcome Trust Senior Investigator Awards. PAS is supported by an MRC Fellowship. CML’s research is supported by the National Institute for Health Research Biomedical Research Centre (BRC) based at Guy's and St Thomas' NHS Foundation Trust and King's College London, and the BRC for Mental Health at South London and Maudsley NHS Foundation Trust and King’s College London. This is the final version of the article. It first appeared from Wolters Kluwer via http://dx.doi.org/10.1212/WNL.000000000000226

Chromosomal organization at the level of gene complexes

Metazoan genomes primarily consist of non-coding DNA in comparison to coding regions. Non-coding fraction of the genome contains cis-regulatory elements, which ensure that the genetic code is read properly at the right time and space during development. Regulatory elements and their target genes define functional landscapes within the genome, and some developmentally important genes evolve by keeping the genes involved in specification of common organs/tissues in clusters and are termed gene complex. The clustering of genes involved in a common function may help in robust spatio-temporal gene expression. Gene complexes are often found to be evolutionarily conserved, and the classic example is the hox complex. The evolutionary constraints seen among gene complexes provide an ideal model system to understand cis and trans-regulation of gene function. This review will discuss the various characteristics of gene regulatory modules found within gene complexes and how they can be characterized

Neuromuscular disease genetics in under-represented populations: increasing data diversity

Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses ‘solved’ or ‘possibly solved’ ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% ‘solved’ and ∼13% ‘possibly solved’ outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally