Regional AT-8 reactive tau species correlate with intracellular Aβ levels in cases of low AD neuropathologic change

The amyloid cascade hypothesis states that Aβ aggregates induce pathological changes in tau, leading to neurofibrillary tangles (NFTs) and cell death. A caveat with this hypothesis is the spatio-temporal divide between plaques and NFTs. This has been addressed by the inclusion of soluble Aβ and tau species in the revised amyloid cascade hypothesis. Nevertheless, despite the potential for non-plaque Aβ to contribute to tau pathology, few studies have examined relative correlative strengths between total Aβ, plaque Aβ and intracellular Aβ with tau pathology within a single tissue cohort. Employing frozen and fixed frontal cortex grey and white matter tissue from non-AD controls (Con; n = 39) and Alzheimer’s disease (AD) cases (n = 21), biochemical and immunohistochemical (IHC) measures of Aβ and AT-8 phosphorylated tau were assessed. Biochemical native-state dot blots from crude tissue lysates demonstrated robust correlations between total Aβ and AT-8 tau, when considered as a combined cohort (Con and AD) and when as Con and AD cases, separately. In contrast, no associations between Aβ plaques and AT-8 were reported when using IHC measurements in either Con or AD cases. However, when intracellular Aβ was measured via the Aβ specific antibody MOAB-2, a correlative relationship with AT-8 tau was reported in non-AD controls but not in AD cases. Collectively the data suggests that accumulating intracellular Aβ may influence AT-8 pathology, early in AD-related neuropathological change. Despite the lower levels of phospho-tau and Aβ in controls, the robust correlative relationships observed suggest a physiological association of Aβ production and tau phosphorylation, which may be modified during disease. This study is supportive of a revised amyloid cascade hypothesis and demonstrates regional associative relationships between tau pathology and intracellular Aβ, but not extracellular Aβ plaques

Regional AT-8 reactive tau species correlate with intracellular Aβ levels in cases of low AD neuropathologic change

The amyloid cascade hypothesis states that Aβ aggregates induce pathological changes in tau, leading to neurofibrillary tangles (NFTs) and cell death. A caveat with this hypothesis is the spatio-temporal divide between plaques and NFTs. This has been addressed by the inclusion of soluble Aβ and tau species in the revised amyloid cascade hypothesis. Nevertheless, despite the potential for non-plaque Aβ to contribute to tau pathology, few studies have examined relative correlative strengths between total Aβ, plaque Aβ and intracellular Aβ with tau pathology within a single tissue cohort. Employing frozen and fixed frontal cortex grey and white matter tissue from non-AD controls (Con; n = 39) and Alzheimer’s disease (AD) cases (n = 21), biochemical and immunohistochemical (IHC) measures of Aβ and AT-8 phosphorylated tau were assessed. Biochemical native-state dot blots from crude tissue lysates demonstrated robust correlations between total Aβ and AT-8 tau, when considered as a combined cohort (Con and AD) and when as Con and AD cases, separately. In contrast, no associations between Aβ plaques and AT-8 were reported when using IHC measurements in either Con or AD cases. However, when intracellular Aβ was measured via the Aβ specific antibody MOAB-2, a correlative relationship with AT-8 tau was reported in non-AD controls but not in AD cases. Collectively the data suggests that accumulating intracellular Aβ may influence AT-8 pathology, early in AD-related neuropathological change. Despite the lower levels of phospho-tau and Aβ in controls, the robust correlative relationships observed suggest a physiological association of Aβ production and tau phosphorylation, which may be modified during disease. This study is supportive of a revised amyloid cascade hypothesis and demonstrates regional associative relationships between tau pathology and intracellular Aβ, but not extracellular Aβ plaques

Post-mortem AT-8 reactive tau species correlate with non-plaque Aβ levels in the frontal cortex of non-AD and AD brains

The amyloid cascade hypothesis states that Aβ and its aggregates induce pathological changes in tau, leading to formation of neurofibrillary tangles (NFTs) and cell death. A caveat with this hypothesis is the temporo-spatial divide between plaques and NFTs. This has been addressed by the inclusion of soluble species of Aβ and tau in the revised amyloid cascade hypothesis, however, the demonstration of a correlative relationship between Aβ and tau burden in post-mortem human tissue has remained elusive. Employing frozen and fixed frontal cortex grey and associated white matter tissue from non-AD controls (Con; n=39) and Alzheimer’s diseases (AD) cases (n=21), biochemical and immunohistochemical measures of Aβ and AT-8 phosphorylated tau were assessed. Native-state dot-blot from crude tissue lysates demonstrated robust correlations between intraregional Aβ and AT-8 tau, such increases in Aβ immunoreactivity conferred increases in AT-8 immunoreactivity, both when considered across the entire cohort as well as separately in Con and AD cases. In contrast, no such association between Aβ plaques and AT-8 were reported when using immunohistochemical measurements. However, when using the non-amyloid precursor protein cross reactive MOAB-2, antibody to measure intracellular Aβ within a subset of cases, a similar correlative relationship with AT-8 tau as that observed in biochemical analysis was observed. Collectively our data suggests that accumulating intracellular Aβ may influence AT-8 pathology. Despite the markedly lower levels of phospho-tau in non-AD controls correlative relationships between AT-8 phospho-tau and Aβ as measured in both biochemical and immunohistochemical assays were more robust in non-AD controls, suggesting a physiological association of Aβ production and tau phosphorylation, at least within the frontal cortex. Such interactions between regional Aβ load and phospho-tau load may become modified with disease potentially, as a consequence of interregional tau seed propagation, and thus may diminish the linear relationship observed between Aβ and phospho-tau in non-AD controls. This study provides evidence supportive of the revised amyloid cascade hypothesis, and demonstrates an associative relationship between AT-8 tau pathology and intracellular Aβ but not extracellular Aβ plaques

Post-mortem AT-8 reactive tau species correlate with non-plaque Aβ levels in the frontal cortex of non-AD and AD brains

The amyloid cascade hypothesis states that Aβ and its aggregates induce pathological changes in tau, leading to formation of neurofibrillary tangles (NFTs) and cell death. A caveat with this hypothesis is the temporo-spatial divide between plaques and NFTs. This has been addressed by the inclusion of soluble species of Aβ and tau in the revised amyloid cascade hypothesis, however, the demonstration of a correlative relationship between Aβ and tau burden in post-mortem human tissue has remained elusive. Employing frozen and fixed frontal cortex grey and associated white matter tissue from non-AD controls (Con; n=39) and Alzheimer’s diseases (AD) cases (n=21), biochemical and immunohistochemical measures of Aβ and AT-8 phosphorylated tau were assessed. Native-state dot-blot from crude tissue lysates demonstrated robust correlations between intraregional Aβ and AT-8 tau, such increases in Aβ immunoreactivity conferred increases in AT-8 immunoreactivity, both when considered across the entire cohort as well as separately in Con and AD cases. In contrast, no such association between Aβ plaques and AT-8 were reported when using immunohistochemical measurements. However, when using the non-amyloid precursor protein cross reactive MOAB-2, antibody to measure intracellular Aβ within a subset of cases, a similar correlative relationship with AT-8 tau as that observed in biochemical analysis was observed. Collectively our data suggests that accumulating intracellular Aβ may influence AT-8 pathology. Despite the markedly lower levels of phospho-tau in non-AD controls correlative relationships between AT-8 phospho-tau and Aβ as measured in both biochemical and immunohistochemical assays were more robust in non-AD controls, suggesting a physiological association of Aβ production and tau phosphorylation, at least within the frontal cortex. Such interactions between regional Aβ load and phospho-tau load may become modified with disease potentially, as a consequence of interregional tau seed propagation, and thus may diminish the linear relationship observed between Aβ and phospho-tau in non-AD controls. This study provides evidence supportive of the revised amyloid cascade hypothesis, and demonstrates an associative relationship between AT-8 tau pathology and intracellular Aβ but not extracellular Aβ plaques

Digital Signal Processing

Contains research objectives and reports on sixteen research projects.U.S. Navy - Office of Naval Research (Contract N00014-75-C-0852)National Science Foundation FellowshipNational Science Foundation (Grant ENG76-24117)U.S. Navy - Office of Naval Research (Contract N00014-77-C-0257)U.S. Air Force (Contract F19628-80-C-0002)U.S. Navy - Office of Naval Research (Contract N00014-75-C-0951)Schlumberger-Doll Research Center FellowshipHertz Foundation FellowshipGovernment of Pakistan ScholarshipU.S. Navy - Office of Naval Research (Contract N00014-77-C-0196

Digital Signal Processing

Contains summary of research and reports on sixteen research projects.U.S. Navy - Office of Naval Research (Contract N00014-75-C-0852)National Science Foundation FellowshipNATO FellowshipU.S. Navy - Office of Naval Research (Contract N00014-75-C-0951)National Science Foundation (Grant ECS79-15226)U.S. Navy - Office of Naval Research (Contract N00014-77-C-0257)Bell LaboratoriesNational Science Foundation (Grant ECS80-07102)Schlumberger-Doll Research Center FellowshipHertz Foundation FellowshipGovernment of Pakistan ScholarshipU.S. Navy - Office of Naval Research (Contract N00014-77-C-0196)U.S. Air Force (Contract F19628-81-C-0002)Hughes Aircraft Company Fellowshi

Digital Signal Processing

Contains an introduction and reports on seventeen research projects.U.S. Navy - Office of Naval Research (Contract N00014-77-C-0266)Amoco Foundation FellowshipU.S. Navy - Office of Naval Research (Contract N00014-81-K-0742)National Science Foundation (Grant ECS80-07102)U.S. Army Research Office (Contract DAAG29-81-K-0073)Hughes Aircraft Company FellowshipAmerican Edwards Labs. GrantWhitaker Health Sciences FundPfeiffer Foundation GrantSchlumberger-Doll Research Center FellowshipGovernment of Pakistan ScholarshipU.S. Navy - Office of Naval Research (Contract N00014-77-C-0196)National Science Foundation (Grant ECS79-15226)Hertz Foundation Fellowshi

Crop Updates 2008 - Lupins, Pulses and Oilseeds

This session covers twenty six papers from different authors: Regional Roundup 1. SOUTH EAST AGRICULTURAL REGION, Mark Seymour Department of Agriculture and Food, and Robert Johnson CBH Group, Esperance 2. CENTRAL AGRICULTURAL REGION, Ian Pritchard, Department of Agriculture and Food 3. GREAT SOUTHERN AND LAKES REGION, Raj Malik, Department of Agriculture and Food 4. NORTHERN AGRICULTURAL REGION, Wayne Parker and Martin Harries, Department of Agriculture and Food LUPINS 5. Cropping lupins in wide rows in Western Australia, Martin Harries and Bob French, Department of Agriculture and Food 6. The effect of sowing time and radish density on lupin yield, Martin Harries and Jo Walker, Department of Agriculture and Food 7. Lupin agronomy affects crop competitiveness with annual ryegrass, Bob French and Laurie Maiolo, Department of Agriculture and Food 8. Identification of lupin mutants with tolerance to isoxaflutole, Leigh Smith, Department of Agriculture and Food PULSES 9. Chickpea 2007 Crop Variety Testing (CVT) and National Variety Testing (NVT), Alan Harris, Rod Hunter, Tanveer Khan and Jenny Garlinge, Department of Agriculture and Food 10. Desi chickpea breeding: Evaluation of advanced lines, Tanveer Khan1, Poran Gaur2, Kadambot Siddique3, Heather Clarke4, Neil Turner4, William MacLeod4, Stuart Morgan1, Alan Harris1, 1Department of Agriculture and Food, 2International Crop Research Institute for the Semi Arid Tropics (ICRISAT); 3The University of Western Australia; 4Centre for Legumes in Mediterranean Agriculture 11. Can wide rows buffer chickpea growth against dry environments? Bob French and Wendy Vance, Department of Agriculture and Food, and School of Environmental Sciences, Murdoch University 12. Field pea 2007 Crop Variety Testing (CVT) and National Variety Testing (NVT), Alan Harris, Rod Hunter, Tanveer Khan and Jenny Garlinge, Department of Agriculture and Food 13. Australian Field Pea improvement Program (AFPIP): Evaluation of advanced breeding lines, Tanveer Khan1, Phillip Chambers1, Chris Veitch1, Stuart Morgan1, Alan Harris1, and Tony Leonforte 2, 1Department of Agriculture and Food, 2Department of Primary Industries, Victoria 14. Ability of semi-leafless field peas to recover after rolling, Mark Seymour and Rodger Beermier, Department of Agriculture and Food 15. Field pea germplasm enhancement for black spot resistance, Tanveer Khan, Stuart Morgan, Alan Harris and Phillip Chambers, Department of Agriculture and Food 16. Application of ‘Blackspot Manager’ model to identifying a low risk sowing date for field pea in South Australia and Western Australia in 2007, Moin Salam1, Jenny Davidson2, Jean Galloway1, Pip Payne2, Tess Humphries2, Bill MacLeod1 and Art Diggle1, 1Department of Agriculture and Food, 2SARDI, South Australia 17. Late post emergent herbicide sprays for field pea, Mark Seymour and Rodger Beermier, Department of Agriculture and Food 18. Adding triasulfuron to croptopping mixes does not affect the yield of field pea, Mark Seymour, Department of Agriculture and Food 18. Herbicide tolerance of field pea varieties, Harmohinder Dhammu and Mark Seymour, Department of Agriculture and Food 19. Breeding highlights of the PBA lentil program, Michael Materne1, Kerry Regan2, Chris Veitch2 and Phil Chambers2, 1Department of Primary Industries, Victoria 2Department of Agriculture and Food CANOLA 20. How late can I sow canola in 2008? Mohammad Amjad, Andy Sutherland and Pat Fels, Department of Agriculture and Food 21. Direct harvesting canola, Glen Riethmuller1, Wallace Cowling2, Milton Sanders2, Eliot Jones2 and Chris Newman1, 1Department of Agriculture and Food, Western Australia, 2Canola Breeders Western Australia Pty Ltd 22. Agronomic performance of new hybrid canola and juncea canola in low, medium and high rainfall environments of Western Australia, Mohammad Amjad, Andy Sutherland and Pat Fels, Department of Agriculture and Food 23. Comparative performance of new canola varieties in commercial-scale field trials of Oilseeds WA – 2007, Mohammad Amjad1, John Duff2 and David Sermon3 1Department of Agriculture and Food, 2Oilseeds Western Australia and John Duff & Associates, Perth; 3ConsultAg, Perth 24. The effect of rotation crops, trash retention and prophylactic sprays on arthropod abundance in a following canola crop, Svetlana Micic, Anthony Dore and Geoff Strickland, Department of Agriculture and Food OATS 25. Fungicide options for controlling disease in oats, Raj Malik and Blakely Paynter, Department of Agriculture and Food 26. Herbicide tolerance of new oat varieties, Harmohinder Dhammu, Vince Lambert and Chris Roberts, Department of Agriculture and Foo

BioSimulators: a central registry of simulation engines and services for recommending specific tools

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations

Exome Sequencing and Rare Variant Analysis Reveals Multiple Filaggrin Mutations in Bangladeshi Families with Atopic Eczema and Additional Risk Genes

M.P was supported by a Fellowship from the German Research Foundation (DFG). This work received infrastructure support through the DFG Cluster of Excellence “Inflammation at Interfaces” (grants EXC306 and EXC306/2), and was supported by grants (WE2678/6-1, WE2678/6-2, WE2678/9) from the DFG and the e:Med sysINFLAME grant no. 01ZX1306A from the German Federal Ministry of Education and Research (BMBF). J.E.A.C. and X.F.C.C.W. are funded by A*STAR SPF funding for translational skin research and genetic orphan disease