Genome-wide linkage scan for loci associated with epilepsy in Belgian shepherd dogs.

BackgroundIdiopathic epilepsy in the Belgian shepherd dog is known to have a substantial genetic component. The objective of this study was to identify genomic regions associated with the expression of generalized seizures in the Belgian Tervuren and Sheepdog.ResultsDNA from 366 dogs, of which 74 were classified as epileptic, representing two extended families were subjected to a genome-wide linkage scan using 410 microsatellite markers yielding informative coverage averaging 5.95 +/- 0.21 Mb. Though previous studies based on pedigree analyses proposed a major gene of influence, the present study demonstrated the trait to be highly polygenic. Studies of complex disorders in humans indicate that a liberal composite evaluation of genetic linkage is needed to identify underlying quantitative trait loci (QTLs). Four chromosomes yielded tentative linkage based upon LOD scores in excess of 1.0. Possible QTLs within these regions were supported also by analyses of multipoint linkage, allele frequency, TDT, and transmission of haplotype blocks.ConclusionsTaken together the data tentatively indicate six QTLs, three on CFA 2, and one on each of CFA 6, 12, and 37, that support fine mapping for mutations associated with epilepsy in the Belgian shepherd. The study also underscores the complexity of genomic linkage studies for polygenic disorders

Oligo- and Polymetastatic Progression in Lung Metastasis(es) Patients Is Associated with Specific MicroRNAs

Rationale: Strategies to stage and treat cancer rely on a presumption of either localized or widespread metastatic disease. An intermediate state of metastasis termed oligometastasis(es) characterized by limited progression has been proposed. Oligometastases are amenable to treatment by surgical resection or radiotherapy.Methods: We analyzed microRNA expression patterns from lung metastasis samples of patients with ≤5 initial metastases resected with curative intent.Results: Patients were stratified into subgroups based on their rate of metastatic progression. We prioritized microRNAs between patients with the highest and lowest rates of recurrence. We designated these as high rate of progression (HRP) and low rate of progression (LRP); the latter group included patients with no recurrences. The prioritized microRNAs distinguished HRP from LRP and were associated with rate of metastatic progression and survival in an independent validation dataset.Conclusion: Oligo- and poly- metastasis are distinct entities at the clinical and molecular level.</p

Proliferation and estrogen signaling can distinguish patients at risk for early versus late relapse among estrogen receptor positive breast cancers

Introduction: We examined if a combination of proliferation markers and estrogen receptor (ER) activity could predict early versus late relapses in ER-positive breast cancer and inform the choice and length of adjuvant endocrine therapy. Methods: Baseline affymetrix gene-expression profiles from ER-positive patients who received no systemic therapy (n = 559), adjuvant tamoxifen for 5 years (cohort-1: n = 683, cohort-2: n = 282) and from 58 patients treated with neoadjuvant letrozole for 3 months (gene-expression available at baseline, 14 and 90 days) were analyzed. A proliferation score based on the expression of mitotic kinases (MKS) and an ER-related score (ERS) adopted from Oncotype DX® were calculated. The same analysis was performed using the Genomic Grade Index as proliferation marker and the luminal gene score from the PAM50 classifier as measure of estrogen-related genes. Median values were used to define low and high marker groups and four combinations were created. Relapses were grouped into time cohorts of 0-2.5, 0-5, 5-10 years. Results: In the overall 10 years period, the proportional hazards assumption was violated for several biomarker groups indicating time-dependent effects. In tamoxifen-treated patients Low-MKS/Low-ERS cancers had continuously increasing risk of relapse that was higher after 5 years than Low-MKS/High-ERS cancers [0 to 10 year, HR 3.36; p = 0.013]. High-MKS/High-ERS cancers had low risk of early relapse [0-2.5 years HR 0.13; p = 0.0006], but high risk of late relapse which was higher than in the High-MKS/Low-ERS group [after 5 years HR 3.86; p = 0.007]. The High-MKS/Low-ERS subset had most of the early relapses [0 to 2.5 years, HR 6.53; p < 0.0001] especially in node negative tumors and showed minimal response to neoadjuvant letrozole. These findings were qualitatively confirmed in a smaller independent cohort of tamoxifen-treated patients. Using different biomarkers provided similar results. Conclusions: Early relapses are highest in highly proliferative/low-ERS cancers, in particular in node negative tumors. Relapses occurring after 5 years of adjuvant tamoxifen are highest among the highly-proliferative/high-ERS tumors although their risk of recurrence is modest in the first 5 years on tamoxifen. These tumors could be the best candidates for extended endocrine therapy

Crop Updates - 2003 Pulses

This session covers fifty one papers from different authors 2002 PULSE INDUSTRY HIGHLIGHTS CONTRIBUTORS BACKGROUND 2002 REGIONAL ROUNDUP 1.Northern Agricultural Region, M. Harries, Department of Agriculture 2.Central agricultural Region, R. French and I. Pritchard, Department of Agriculture 3.Great Southern and Lakes, R. Beermier, N. Poulish and S. White, Department of Agriculture 4.Esperance Mallee, M. Seymour, Department of Agriculture PULSE PRODUCTION ECONOMY AND GENETIC IMPROVEMENT 5.Faba Bean, P. White, Department of Agriculture 6.Germplasm evaluation, P. White, T. Pope, M. Harries and M. Seymour, Department of Agriculture 7.Row spacing and sowing rate, M. Seymour, Department of Agriculture 8.Tolerance to post emergent herbicides, M. Seymour, M. Harries, R. Beermier, M. Blyth and L. Young, Department of Agriculture 9.Investigation of environmental staining and storage discolouration, N. Abbas1,2, J. Plummer1, P. White3, D. Harris4 and K. Siddique1,2, 1Plant Biology, The University of Western Australia, 2CLIMA, The University of Western Australia, 3Department of Agriculture, 4Chemistry Centre of Western Australia. Desi chickpea 10.Breeding highlights, T. Khan1,2 and K. Siddique2 1Department of Agriculture, 2CLIMA, The University of Western Australia 11. Variety evaluation, T. Khan and K. Regan, Department of Agriculture 12. Residual effect of chickpea row spacing and sowing rate on wheat yield, G. Riethmuller and B. MacLeod, Department of Agriculture 13. Genotype x environmental interaction studies to help explain adaptation, J. Berger1, N. Turner1,2, K. Siddique1, 1CLIMA, The University of Western Australia, 2CSIRO Plant Industry 14. Genetic characterisation of wild relatives, F. Shan and H. Clarke, CLIMA, The University of Western Australia 15. Tolerance to chilling at flowering, H. Clarke, CLIMA, The University of Western Australia 16. Kabuli chickpea, K. Regan, Department of Agriculture 17. Premium quality varieties for the Ord River Irrigation Area, K. Siddique1, K. Regan2 and P. Smith2 1CLIMA, The University of Western Australia, 2Department of Agriculture 18. Development of aschochyta resistant varieties for Australia, K. Siddique1, K. Regan2 and M. Baker2 1CLIMA, University of Western Australia, 2Department of Agriculture Field pea 19. Breeding highlights, T. Khan and B. French, Department of Agriculture 20. Variety evaluation, T. Khan, Department of Agriculture 21. Specialty types for the high rainfall regions, P. White and T. Khan, Department of Agriculture 22. Are new varieties more sensitive to delayed sowing than Dundale? R. French, M. Seymour and R. Beermier, Department of Agriculture 23. Does the size of sown seed affect seed size and yield at harvest? R. Beermier and N. Poulish, Department of Agriculture 24. Tolerance to post emergent herbicides, H. Dhammu, T. Piper and D. Nicholson, Department of Agriculture 25. Lentil, K. Regan, Department of Agriculture 26. Variety evaluation, K. Regan and M. Harries, Department of Agriculture 27. Interstate evaluation of advanced breeding lines, K. Regan1 and M. Materne2 1Department of Agriculture, 2Victorian Institute for Dryland Agriculture, Agriculture Victoria 28. Timing of harvest for the best seed yield, M. Harries and M. Blyth, Department of Agriculture 29. Tolerance to post emergent herbicides, M. Harries and D. Nicholson, Department of Agriculture, H. Dhammu, T. Piper and L. Young, Department of Agriculture 30. Row spacing and stubble, G. Riethmuller, Department of Agriculture Pulse species 31. High value pulses for the high rainfall areas, N. Poulish1, P. White1,2 and K. Siddique1,2 , 1Department of Agriculture, 2CLIMA, The University of Western Australia 32. Alternative Rhizobium inoculant carrier technologies, J. Howieson and R. Yates, Centre for Rhizobium Studies (CRS), Murdoch University 33. Time of harvest to improve seed yield and quality of pulses, G. Riethmuller and R. French, Department of Agriculture 34. Phosphorus and zinc responses in pulses, S. Loss1, Z. Rengel2, B. Bowden3, M. Bolland3 and K. Siddique4 , 1Wesfarmers CSBP, 2Soil Science and Plant Nutrition, The University of Western Australia, 3Department of Agriculture, 4CLIMA, The University of Western Australia 35. Robust protocols for doubled haploid production in field pea and chickpea, J. Croser and K. Siddique, CLIMA, The University of Western Australia DEMONSTRATION OF PULSES IN THE FARMING SYSTEM 36. Field pea and lentil on clayed sandplain, M. Seymour, Department of Agriculture 37. Field pea variety demonstration, M. Harries and M. Blyth, Department of Agriculture 38. The benefit of field peas compared to lupins, R. Beermier, Department of Agriculture DISEASE AND PEST MANAGEMENT 39. Ascochyta blight of chickpea, B. MacLeod, Department of Agriculture 40. Management of chickpeas with improved ascochyta resistance, B. Macleod, A. Harrod, M. Harries and M. Blyth, Department of Agriculture 41. Chlorothalonil provides the most effective control, B. Macleod, A. Harrod, M. Harries and M. Blyth, Department of Agriculture 42. Importance of early sprays and value of seed dressing (post emergence), B. Macleod and A. Harrod, Department of Agriculture 43. A windborne stage of ascochyta blight in WA, J. Galloway and B. MacLeod, Department of Agriculture Ascochyta disease of pulses 44. Geographic location effects ascochyta spore maturation on pulse stubble, J. Galloway and B. MacLeod, Department of Agriculture Blackspot of field pea 45. Rapid recurrent selection to improve resistance to black spot, C. Beeck1, J. Wroth1, W. Cowling1 and T. Khan2, 1Plant Science, The University of Western Australia, 2Department of Agriculture 46. Survival of blackspot on old field pea stubble, J. Galloway and B. MacLeod, Department of Agriculture 47. Blackspot spores mature earlier in the southern regions, M. Salam, J. Galloway, A. Diggle and B. MacLeod, Department of Agriculture Viruses in pulses 48. Early insecticide application suppresses spread of Beet Western Yellows virus in field pea, R. Jones, B. Coutts and L. Smith, Department of Agriculture, and CLIMA, The University of Western Australia Insect pests and nematodes 49. Incorporation of pea weevil resistance from Pisum fulvum into field pea, O. Byrne1 and D. Hardie2, 1CLIMA, The University of Western Australia 2Department of Agriculture 50. Resistance to Helicoverpa in wild species of chickpea, J. Ridsdill-Smith1, H. Sharma2 and K. Mann1, 1CSIRO Entomology, Western Australia, 2 ICRISAT, Hyderabad, India 51. Relative hosting ability of field pea genotypes to root lesion nematode, S. Kelly, S. Sharma, H. Hunter and V. Vanstone, Department of Agriculture ACKNOWLEDGEMENTS APPENDIX I: Publications by Pulse Productivity Project Staff 2002 APPENDIX II: Summary of previous results APPENDIX III: List of common acronym

Demonstration of Fuel Hot-Spot Pressure in Excess of 50 Gbar for Direct-Drive, Layered Deuterium-Tritium Implosions on OMEGA

A record fuel hot-spot pressure P[subscript hs] = 56±7  Gbar was inferred from x-ray and nuclear diagnostics for direct-drive inertial confinement fusion cryogenic, layered deuterium–tritium implosions on the 60-beam, 30-kJ, 351-nm OMEGA Laser System. When hydrodynamically scaled to the energy of the National Ignition Facility, these implosions achieved a Lawson parameter ∼60% of the value required for ignition [A. Bose et al., Phys. Rev. E 93, LM15119ER (2016)], similar to indirect-drive implosions [R. Betti et al., Phys. Rev. Lett. 114, 255003 (2015)], and nearly half of the direct-drive ignition-threshold pressure. Relative to symmetric, one-dimensional simulations, the inferred hot-spot pressure is approximately 40% lower. Three-dimensional simulations suggest that low-mode distortion of the hot spot seeded by laser-drive nonuniformity and target-positioning error reduces target performance.United States. Department of Energy (DE-NA0001944

Spatially Resolved Ultraviolet, H-alpha, Infrared, and Radio Star Formation in M81

We present Multiband Imaging Photometer for Spitzer (MIPS) observations of M81 at 24, 70, and 160 micron. The grand design nature of M81 is clearly seen, showing two well resolved spiral arms containing numerous bright star forming regions. The MIPS images reveal a significant amount of cold dust associated with the spiral arms. We investigate the variation of the ultraviolet (UV), H-alpha, and infrared (IR) luminosities and star formation rate (SFR) indicators across the face of M81 using the MIPS images and archival UV and H-alpha images. For regions in M81, we find that UV and H-alpha SFRs (uncorrected for dust attenuation) are always lower than the IR SFR. The cause of this behavior is dust attenuation and/or using SFR calibrations appropriate for entire galaxies, not regions in galaxies. The characteristics of the dust attenuation for the regions indicate the dust grains and/or geometry are different from those in starburst galaxies. The behavior of the infrared-radio correlation in M81 is seen to vary from the global average, with variations correlated with the morphology of M81.Comment: 7 pages, 6 embedded figures, paper with full resolution figures available at http://dirty.as.arizona.edu/~kgordon/papers/PS_files/m81_mips.pd

Fifteen years of the Australian imaging, biomarkers and lifestyle (AIBL) study: Progress and observations from 2,359 older adults spanning the spectrum from cognitive normality to Alzheimer\u27s disease

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study commenced in 2006 as a prospective study of 1,112 individuals (768 cognitively normal (CN), 133 with mild cognitive impairment (MCI), and 211 with Alzheimer\u27s disease dementia (AD)) as an \u27Inception cohort\u27 who underwent detailed ssessments every 18 months. Over the past decade, an additional 1247 subjects have been added as an \u27Enrichment cohort\u27 (as of 10 April 2019). Objective: Here we provide an overview of these Inception and Enrichment cohorts of more than 8,500 person-years of investigation. Methods: Participants underwent reassessment every 18 months including comprehensive cognitive testing, neuroimaging (magnetic resonance imaging, MRI; positron emission tomography, PET), biofluid biomarkers and lifestyle evaluations. Results: AIBL has made major contributions to the understanding of the natural history of AD, with cognitive and biological definitions of its three major stages: preclinical, prodromal and clinical. Early deployment of Aβ-amyloid and tau molecular PET imaging and the development of more sensitive and specific blood tests have facilitated the assessment of genetic and environmental factors which affect age at onset and rates of progression. Conclusion: This fifteen-year study provides a large database of highly characterized individuals with longitudinal cognitive, imaging and lifestyle data and biofluid collections, to aid in the development of interventions to delay onset, prevent or treat AD. Harmonization with similar large longitudinal cohort studies is underway to further these aims