In vivo assessment of serotonergic signaling pathways underlying the corticolimbic response to threat in humans

A corticolimbic circuit including the amygdala and medial prefrontal cortex (mPFC) affects sensitivity to threat, related aspects of personality and risk for psychopathology. Serotonin (5‐HT) is a potent neuromodulator of this circuit, however, 5‐HT receptors mediating these effects and genetic sources of variability in 5‐HT receptor availability are not understood. We determined the association between 5‐HT1A and 5‐HT2A binding and the response to threat within this corticolimbic circuit using a multimodal neuroimaging strategy in humans in vivo. Corticolimbic circuit function was assessed with a threat‐related faces matching paradigm using functional magnetic resonance imaging (fMRI). Regional 5‐HT1A and 5‐HT2A binding was assessed with [11C]WAY100635 and [18F]altanserin PET, respectively. We evaluated the association between receptor binding and common polymorphisms (rs6295, rs6311 and 5‐HTTLPR) in 5‐HT related genes.In Study 1 we found that 5‐HT1A binding within the dorsal raphe nucleus was inversely associated with threat‐related amygdala reactivity. This is consistent with 5‐HT1A autoreceptors negatively regulating 5‐HT release, which within the amygdalapotentiates its response to threat. In Study 2 we found that mPFC 5‐HT2A binding was inversely associated with threat‐related amygdala reactivity and positively associated with amygdala habituation and amygdala‐mPFC functional connectivity. In Study 3 we found that mPFC 5‐HT1A binding significantly moderated the inverse association between mPFC 5‐HT2A binding and amygdala reactivity.These findings are consistent with the co‐localization of 5‐HT1A and 5‐HT2A on glutamatergic neurons within mPFC indicating the 5‐HT2A receptor is localized to facilitate regulation of the amygdala and the 5‐HT1A receptor is localized to moderate its effects within mPFC. In Study 4 we found that 5‐HTTLPR genotype predicted 5‐HT1A and 5‐HT2A binding in brain regions within this circuit such that the S and LG alleles were associated with reduced 5‐HT1A and 5‐HT2A binding.These findings provide novel insight into mechanisms that mediate the effects of 5‐HT signaling on the response to threat of a key corticolimbic circuit in humans. Our findings indicate that 5‐HT1A and 5‐HT2A receptors contribute significantly to threat‐related corticolimbic circuit function in humans. Furthermore, the 5‐HTTLPR may contribute to individual variability in neural and behavioral sensitivity to threat by biasing 5‐HT1A and 5‐HT2A availability

A practical drug discovery project at the undergraduate level

A practical drug discovery project for third-year undergraduates is described. No previous knowledge of medicinal chemistry is assumed. Initial lecture-workshops cover the basic principles; then students are asked to improve the profile of a weakly potent, poorly soluble PI3K inhibitor (1). Compound array design, molecular modelling and screening data analysis are followed by laboratory work in which each student, as part of a team, attempts to synthesise at least two target compounds. The project benefits from significant industrial support, including lectures, student mentoring and consumables. The aim is to make the learning experience as close as possible to real-life industrial situations. Forty-eight target compounds have been prepared, the best of which (5b, 5j, 6b and 6ap) improved the potency and aqueous solubility of the lead compound (1) by 100-1000 fold and 10-fold, respectively

Crop Updates 2001 - Cereals

This session covers forty two papers from different authors: PLENARY 1. Planning your cropping program in season 2001, Dr Ross Kingwell, Agriculture Western Australia and University of Western Australia WORKSHOP 2. Can we produce high yields without high inputs? Wal Anderson, Centre for Cropping Systems, Agriculture Western Australia VARIETIES 3. Local and interstate wheat variety performance and $ return to WA growers, Eddy Pol, Peter Burgess and Ashley Bacon, Agritech Crop Research CROP ESTABLISHMENT 4 Soil management of waterlogged soils, D.M. Bakker, G.J. Hamilton, D. Houlbrooke and C. Spann, Agriculture Western Australia 5. Effect of soil amelioration on wheat yield in a very dry season, M.A Hamza and W.K. Anderson, Agriculture Western Australia 6. Fuzzy tramlines for more yield and less weed, Paul Blackwell1 and Maurice Black2 1Agriculture Western Australia, 2Harbour Lights Estate, Geraldton 7. Tramline farming for dollar benefits, Paul Blackwell, Agriculture Western Australia NUTRITION 8. Soil immobile nutrients for no-till crops, M.D.A. Bolland1, R.F. Brennan1,and W.L. Crabtree2, 1Agriculture Western Australia, 2Western Australian No-Tillage Farmers Association 9. Burn stubble windrows: to diagnose soil fertility problems, Bill Bowden, Chris Gazey and Ross Brennan, Agriculture Western Australia 10. Calcium: magnesium ratios; are they important? Bill Bowden1, Rochelle Strahan2, Bob Gilkes2 and Zed Rengel2 1Agriculture Western Australia, 2Department of Soil Science and Plant Nutrition, UWA 11. Responses to late foliar applications of Flexi-N, Stephen Loss, Tim O’Dea, Patrick Gethin, Ryan Guthrie, Lisa Leaver, CSBP futurefarm 12. A comparison of Flexi-N placements, Stephen Loss, Tim O’Dea, Patrick Gethin, Ryan Guthrie, Lisa Leaver, CSBP futurefarm 13. What is the best way to apply potassium? Stephen Loss, Tim O’Dea, Patrick Gethin, Ryan Guthrie, CSBP futurefarm 14. Claying affects potassium nutrition in barley, Stephen Loss, David Phelps, Tim O’Dea, Patrick Gethin, Ryan Guthrie, Lisa Leaver, CSBP futurefarm 15. Nitrogen and potassium improve oaten hay quality, Stephen Loss, Tim O’Dea, Patrick Gethin, Ryan Guthrie, Lisa Leaver, CSBP futurefarm AGRONOMY 16. Agronomic responses of new wheat varieties in the northern wheatbelt, Darshan Sharma and Wal Anderson, Agriculture Western Australia 17. Wheat agronomy research on the south coast, Mohammad Amjad and Wal Anderson, Agriculture Western Australia 18. Influence of sowing date on wheat yield and quality in the south coast environment, Mohammad Amjadand Wal Anderson, Agriculture Western Australia 19. More profit from durum, Md.Shahajahan Miyan and Wal Anderson, Agriculture Western Australia 20. Enhancing recommendations of flowering and yield in wheat, JamesFisher1, Senthold Asseng2, Bill Bowden1 and Michael Robertson3 ,1AgricultureWestern Australia, 2CSIRO Plant Industry, 3CSIRO Sustainable Ecosystems 21. When and where to grow oats, Glenn McDonald, Agriculture Western Australia 22. Managing Gaidner barley for quality, Kevin Young and Blakely Paynter, Agriculture Western Australia PESTS AND DISEASES 23. Strategies for leaf disease management in wheat, Jatinderpal Bhathal1, Cameron Weeks2, Kith Jayasena1 and Robert Loughman1 ,1Agriculture Western Australia. 2Mingenew-Irwin Group Inc 24. Strategies for leaf disease management in malting barley, K. Jayasena1, Q. Knight2 and R. Loughman1, 1Agriculture Western Australia, 2IAMA Agribusiness 25. Cereal disease diagnostics, Dominie Wright and Nichole Burges, Agriculture Western Australia 26. The big rust: Did you get your money back!! Peter Burgess, Agritech Crop Research 27. Jockey – winning the race against disease in wheat, Lisa-Jane Blacklow, Rob Hulme and Rob Giffith, Aventis CropScience 28. Distribution and incidence of aphids and barley yellow dwarf virus in over-summering grasses in WA wheatbelt, Jenny Hawkes and Roger Jones, CLIMA and Agriculture Western Australia 29. Further developments in forecasting aphid and virus risk in cereals, Debbie Thackray, Jenny Hawkes and Roger Jones, Agriculture Western Australia and Centre for Legumes in Mediterranean Agriculture 30. Effect of root lesion nematodes on wheat yields in Western Australia, S. B. Sharma, S. Kelly and R. Loughman, Crop Improvement Institute, Agriculture Western Australia 31. Rotational crops and varieties for management of root lesion nematodes in Western Australia, S.B. Sharma, S. Kelly and R. Loughman, Crop Improvement Institute, Agriculture Western Australia WEEDS 32. Phenoxy herbicide tolerance of wheat, Peter Newman and Dave Nicholson, Agriculture Western Australia 33. Tolerance of wheat to phenoxy herbicides,Harmohinder S. Dhammu, Terry Piper and Mario F. D\u27Antuono, Agriculture Western Australia 34. Herbicide tolerance of durum wheats, Harmohinder S. Dhammu, Terry Piper and David Nicholson, Agriculture Western Australia 35. Herbicide tolerance of new wheats, Harmohinder S. Dhammu, Terry Piper and David F. Nicholson, Agriculture Western Australia BREEDING 36. Towards molecular breeding of barley: construction of a molecular genetic map, Mehmet Cakir1, Nick Galwey1, David Poulsen2, Garry Ablett3, Reg Lance4, Rob Potter5 and Peter Langridge6,1Plant Sciences, Faculty of Agriculture, UWA, 2Queensland Department of Primary Industries, Qld, 3Centre for Plant Conservation Genetics Southern Cross University, Lismore NSW, 5SABC Murdoch University, WA, 6Department of Plant Science University of Adelaide, Glen Osmond SA 37. Toward molecular breeding of barley: Identifying markers linked to genes for quantitative traits, Mehmet Cakir1, Nick Galwey1, David Poulsen2, Reg Lance3, Garry Ablett4, Greg Platz2, Joe Panozzo5, Barbara Read6, David Moody5, Andy Barr7 and Peter Langridge7 , 1Plant Sciences, Faculty of Agriculture, UWA, 2Queensland Department of Primary Industries, Warwick, QLD,3Agriculture Western Australia, 4Centre for Plant Conservation Genetics, Southern Cross University, Lismore NSW, 5VIDA Private Bag 260, Horsham VIC, 6NSW Dept. of Agriculture, Wagga Wagga NSW, 7Department of Plant Science, University of Adelaide, Glen Osmond SA 38. Can we improve grain yield by breeding for greater early vigour in wheat? Tina Botwright1, Tony Condon1, Robin Wilson2 and Iain Barclay2, 1CSIRO Plant Industry, 2Agriculture Western Australia MARKETING AND QUALITY 39. The Crop Improvement Royalty, Howard Carr, Agriculture Western Australia 40. GrainGuardÔ - The development of a protection plan for the wheat industry, Greg Shea, Agriculture Western Australia CLIMATE 41. Rainfall – what happened in 2000 and the prospects for 2001, Ian Foster, Agriculture Western Australia 42. Software for climate management issues, David Tennant,Agriculture Western Australia CONTRIBUTING AUTHOR CONTACT DETAIL

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Search for post-merger gravitational waves from the remnant of the binary neutron star merger GW170817

In Advanced LIGO, detection and astrophysical source parameter estimation of the binary black hole merger GW150914 requires a calibrated estimate of the gravitational-wave strain sensed by the detectors. Producing an estimate from each detector's differential arm length control loop readout signals requires applying time domain filters, which are designed from a frequency domain model of the detector's gravitational-wave response. The gravitational-wave response model is determined by the detector's opto-mechanical response and the properties of its feedback control system. The measurements used to validate the model and characterize its uncertainty are derived primarily from a dedicated photon radiation pressure actuator, with cross-checks provided by optical and radio frequency references. We describe how the gravitational-wave readout signal is calibrated into equivalent gravitational-wave-induced strain and how the statistical uncertainties and systematic errors are assessed. Detector data collected over 38 calendar days, from September 12 to October 20, 2015, contain the event GW150914 and approximately 16 of coincident data used to estimate the event false alarm probability. The calibration uncertainty is less than 10% in magnitude and 10 degrees in phase across the relevant frequency band 20 Hz to 1 kHz

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands