Targeted overexpression of a golli–myelin basic protein isoform to oligodendrocytes results in aberrant oligodendrocyte maturation and myelination

Recently, several in vitro studies have shown that the golli–myelin basic proteins regulate Ca2+ homoeostasis in OPCs (oligodendrocyte precursor cells) and immature OLs (oligodendrocytes), and that a number of the functions of these cells are affected by cellular levels of the golli proteins. To determine the influence of golli in vivo on OL development and myelination, a transgenic mouse was generated in which the golli isoform J37 was overexpressed specifically within OLs and OPCs. The mouse, called JOE (J37-overexpressing), is severely hypomyelinated between birth and postnatal day 50. During this time, it exhibits severe intention tremors that gradually abate at later ages. After postnatal day 50, ultrastructural studies and Northern and Western blot analyses indicate that myelin accumulates in the brain, but never reaches normal levels. Several factors appear to underlie the extensive hypomyelination. In vitro and in vivo experiments indicate that golli overexpression causes a significant delay in OL maturation, with accumulation of significantly greater numbers of pre-myelinating OLs that fail to myelinate axons during the normal myelinating period. Immunohistochemical studies with cell death and myelin markers indicate that JOE OLs undergo a heightened and extended period of cell death and are unable to effectively myelinate until 2 months after birth. The results indicate that increased levels of golli in OPC/OLs delays myelination, causing significant cell death of OLs particularly in white matter tracts. The results provide in vivo evidence for a significant role of the golli proteins in the regulation of maturation of OLs and normal myelination

Falls among middle-aged women in the Women’s Interagency HIV Study

To determine the frequency and risk factors for falls among middle-aged HIV+ and HIV− women in the Women's Interagency HIV Study (WIHS)

Rapid soil analytical techniques for international agricultural research and development

Soil analysis is used to assess natural resources and inform management to improve long-term farming profitability. Conventional techniques typically use different methods, equipment, reagents and skills to measure each soil property of interest. The consequence is that a conventional soil laboratory is expensive to set up, maintain and run. These issues result in many countries (and organisations) having to do without a well-functioning conventional soil laboratory. Developments in spectroscopic and potentiometric methods of soil analysis means that these countries need not go without reliable soil analysis

Genome-wide linkage analyses of non-Hispanic white families identify novel loci for familial late-onset Alzheimer's disease

INTRODUCTION: Few high penetrance variants that explain risk in late-onset Alzheimer's disease (LOAD) families have been found. METHODS: We performed genome-wide linkage and identity-by-descent (IBD) analyses on 41 non-Hispanic white families exhibiting likely dominant inheritance of LOAD, and having no mutations at known familial Alzheimer's disease (AD) loci, and a low burden of APOE ε4 alleles. RESULTS: Two-point parametric linkage analysis identified 14 significantly linked regions, including three novel linkage regions for LOAD (5q32, 11q12.2-11q14.1, and 14q13.3), one of which replicates a genome-wide association LOAD locus, the MS4A6A-MS4A4E gene cluster at 11q12.2. Five of the 14 regions (3q25.31, 4q34.1, 8q22.3, 11q12.2-14.1, and 19q13.41) are supported by strong multipoint results (logarithm of odds [LOD*] ≥1.5). Nonparametric multipoint analyses produced an additional significant locus at 14q32.2 (LOD* = 4.18). The 1-LOD confidence interval for this region contains one gene, C14orf177, and the microRNA Mir_320, whereas IBD analyses implicates an additional gene BCL11B, a regulator of brain-derived neurotrophic signaling, a pathway associated with pathogenesis of several neurodegenerative diseases. DISCUSSION: Examination of these regions after whole-genome sequencing may identify highly penetrant variants for familial LOAD

Pulse‐labeling studies of carbon cycling in arctic tundra ecosystems: Contribution of photosynthates to soil organic matter

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95486/1/gbc827.pd

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

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

Crop Updates 2005 - Lupins and Pulses

This session covers sixty five papers from different authors: 1. 2004 LUPIN AND PULSE INDUSTRY HIGHLIGHTS, Peter White Department of Agriculture 2. BACKGROUND, Peter White Department of Agriculture 2004 REGIONAL ROUNDUP 3. Northern Agricultural Region, Martin Harries, Department of Agriculture 4. Central Agricultural Region, Ian Pritchard, Department of Agriculture 5. Great Southern and Lakes, Rodger Beermier, Department of Agriculture 6. Esperance Port Zone, Mark Seymour, Department of Agriculture, and David Syme, The Grain Pool of WA LUPIN AND PULSE PRODUCTION AGRONOMY AND GENETIC IMPROVEMENT 7. Lupin, Martin Harries, Department of Agriculture 8. Narrow-leafed lupin breeding, Bevan Buirchell, Department of Agriculture 9. Yellow lupin breeding in Western Australia, Kedar Adhikari, Mark Sweetingham and Bevan Buirchell, Department of Agriculture 10. WALAB2000 - First Anthracnose resistant albus lupins, Kedar Adhikari, Bevan Buirchell, MarkSweetingham and Geoff Thomas, Department of Agriculture 11. Improving lupin grain quality and yield through genetic manipulation of key physiological traits, Jon Clements1 and Bevan Buirchell2,1CLIMA, The University of Western Australia 2Department of Agriculture 12. Lupin alkaloids in four Australian species, Shao Fang Wang, Chemistry Centre (WA), CLIMA, The University of Western Australia 13. Improving lupin tolerance to herbicides of metribuzin, isoxaflutole and carfentrazone-ethyl, Ping Si1, Mark Sweetingham12, Bevan Buirchell12, David Bowran2 and Huaan Yang12 , 1CLIMA, The University of Western Australia, 2Department of Agriculture 14. Combined cultural and shielded sprayer herbicide application for weed management, Martin Harries and Mike Baker Department of Agriculture 15. Field testing of lupin seed of various sources with and without post maturity, pre harvest rain for field establishment, Martin Harries, Wayne Parker, Mike Baker, Department of Agriculture 16. Lupin seed rate by wide row spacing, Martin Harries, Bob French, Damien Owen D’arcy, Department of Agriculture 17. How environment influences row spacing response in lupins, Bob French, Department of Agriculture 18. The effect of wider row spacing on lupin architecture, growth and nutrient uptake dynamics, Bill Bowden and Craig Scanlan, Department of Agriculture 19. Fertiliser placement and application rate in wide rows, Martin Harries, Damien Owen D’arcy, Department of Agriculture 20. The pros and cons of cowing lupins in ‘wide’ rows, Wayne Parker, Bob French and Martin Harries, Department of Agriculture 21. Investigation into the influence of row orientation in lupin crops, Jeff Russell1 and Angie Roe2, 1Department of Agriculture, 2Farm Focus Consultants 22. Making the most of Mandelup, Greg Shea and Chris Matthews, Department of Agriculture 23. The effect of wild radish density and lupin cultivars on their competition at Merredin, Shahab Pathan, Abul Hashem and Bob French, Department of Agriculture 24. The potential of pearl lupin (Lupinus mutabilis) for southern Australia, Jon Clements1, Mark Sweetingham2, Bevan Buirchell2, Sofia Sipsas2, Geoff Thomas2, John Quealy1, Roger Jones2, Clive Francis1, Colin Smith2 and Gordon Francis1, 1CLIMA, University of Western Australia 2Department of Agriculture 25. Field pea, Mark Seymour, Department of Agriculture 26. Breeding highlights, Tanveer. Khan and Bob French, Department of Agriculture 27. Variety evaluation, Tanveer Khan, Kerry Regan, Jenny Garlinge and Rod Hunter, Department of Agriculture 28. Large scale field pea variety trials, Martin Harries, Department of Agriculture 29. Kaspa demonstrations, Rodger Beermier, Mark Seymour, Ian Pritchard, Graham Mussell, Department of Agriculture 30. Field pea harvesting demonstration at Merredin, Glen Riethmuller, Greg Shea and Bob French, Department of Agriculture 31. Does Kaspa respond differently to disease, fungicides, time of sowing or seed rate, Mark Seymour, Department of Agriculture 32. Field pea response to foliar Manganese in mallee district, Mark Seymour, Department of Agriculture 33. Kaspa harvesting observations 2004, Mark Seymour, Ian Pritchard, Glen Riethmuller, Department of Agriculture 34. ‘Blackspot Manager’ for understanding blackspot of peas and ascochyta blight management, Moin Salam and Jean Galloway, Department of Agriculture 35. 250,000 ha of field pea in WA – Is it sustainable? Larn McMurray1 and Mark Seymour2, 1South Australian Research and Development Institute, 2Department of Agriculture 36. Desi chickpea, Wayne Parker, Department of Agriculture 37. Breeding highlights, Tanveer Khan1,2 and Kadambot Siddique2,1Department of Agriculture, 2CLIMA, The University of Western Australia 38. Variety evaluation, Tanveer Khan, Kerry Regan, Jenny Garlinge and Rod Hunter, Department of Agriculture 39. Large scale variety testing of desi chickpeas, Martin Harries, Greg Shea, Mike Baker, Dirranie Kirby, Department of Agriculture 40. Desi variety chickpea trial, Martin Harries and Murray Blyth, Department of Agriculture 41. Seeding rates and row spacing of chickpea desi, Martin Harries, MurrayBlyth, Damien Owen D’arcy, Department of Agriculture 42. Molecular characterisation of chickpea wild relatives, Fucheng Shan, Heather Clarke and Kadambot Siddique, CLIMA, The University of Western Australia 43. Plant phosphorus status has a limited influence on the concentration of phosphorus-mobilising carboxylates in the rhizosphere of chickpea, Madeleine Wouterlood, Hans Lambers and Erik Veneklaas, The University of Western Australia 44. Kabuli chickpea, Kerry Regan, Department of Agriculture, and CLIMA, The University of Western Australia 45. ‘Kimberly Large’ A high quality and high yielding new variety for the Ord River Irrigation Area, Kerry Regan1,2, Kadambot Siddique2, Peter White1,2, Peter Smith1 and Gae Plunkett1,1Department of Agriculture, 2CLIMA, University of Western Australia 46. Development of ascochyta resistant and high quality varieties for Australia, Kadambot Siddique1, Kerry Regan1,2, Tim Pope1 and Mike Baker2, 1CLIMA, The University of Western Australia 2Department of Agriculture 47. Towards double haploids in chickpeas and field pea, Janine Croser, Julia Wilson and Kadambot Siddique, CLIMA, The University of Western Australia 48. Crossing chickpea with wild Cicer relatives to introduce resistance to disease and tolerance to environmental stress, Heather Clarke and Kadambot Siddique, CLIMA, The University of Western Australia 49. Faba bean, Peter White, Department of Agriculture 50. Germplasm evaluation, Peter White1,2, Kerry Regan1,2, Tim Pope2, Martin Harries1, Mark Seymour1, Rodger Beermier1 and Leanne Young1, 1Department of Agriculture, 2CLIMA, The University of Western Australia 51. Lentil, Kerry Regan, Department of Agriculture, and CLIMA, The University of Western Australia 52. Variety and germplasm evaluation, Kerry Regan1,2, Tim Pope2, Leanne Young1, Martin Harries1, Murray Blyth1 and Michael Materne3, 1Department of Agriculture, 2CLIMA, University of Western Australia, 3Department of Primary Industries, Victoria 53. Lathyrus species, Kadambot Siddique1, Kerry Regan2, and Colin Hanbury2, 1CLIMA, the University of Western Australia, 2Department of Agricultur

The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism.

International audienceAlthough multiple reports show that defective genetic networks underlie the aetiology of autism, few have translated into pharmacotherapeutic opportunities. Since drugs compete with endogenous small molecules for protein binding, many successful drugs target large gene families with multiple drug binding sites. Here we search for defective gene family interaction networks (GFINs) in 6,742 patients with the ASDs relative to 12,544 neurologically normal controls, to find potentially druggable genetic targets. We find significant enrichment of structural defects (P≤2.40E-09, 1.8-fold enrichment) in the metabotropic glutamate receptor (GRM) GFIN, previously observed to impact attention deficit hyperactivity disorder (ADHD) and schizophrenia. Also, the MXD-MYC-MAX network of genes, previously implicated in cancer, is significantly enriched (P≤3.83E-23, 2.5-fold enrichment), as is the calmodulin 1 (CALM1) gene interaction network (P≤4.16E-04, 14.4-fold enrichment), which regulates voltage-independent calcium-activated action potentials at the neuronal synapse. We find that multiple defective gene family interactions underlie autism, presenting new translational opportunities to explore for therapeutic interventions