A Transcriptional Profile of Aging in the Human Kidney

In this study, we found 985 genes that change expression in the cortex and the medulla of the kidney with age. Some of the genes whose transcripts increase in abundance with age are known to be specifically expressed in immune cells, suggesting that immune surveillance or inflammation increases with age. The age-regulated genes show a similar aging profile in the cortex and the medulla, suggesting a common underlying mechanism for aging. Expression profiles of these age-regulated genes mark not only age, but also the relative health and physiology of the kidney in older individuals. Finally, the set of aging-regulated kidney genes suggests specific mechanisms and pathways that may play a role in kidney degeneration with age

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Crop Updates 2006 - Weeds

This session covers thirty seven papers from different authors: 1. ACKNOWLEDGEMENTS, Alexandra Douglas, CONVENOR – WEEDS DEPARTMENT OF AGRICULTURE SPRAY TECHNOLOGY 2. Meeting the variable application goals with new application technology, Thomas M. Wolf, Agriculture and Agri-Food Canada, Saskatoon Research Centre 3. Spray nozzles for grass weed control, Harm van Rees, BCG (Birchip Cropping Group) 4. Boom sprayer setups – achieving coarse droplets with different operating parameters, Bill Gordon, Bill Gordon Consulting 5. Complying with product label requirements, Bill Gordon, Bill Gordon Consulting 6. IWM a proven performer over 5 years in 33 focus paddocks, Peter Newman and Glenn Adam, Department of Agriculture 7. Crop topping of wild radish in lupins and barley, how long is a piece of string? Peter Newman and Glenn Adam, Department of Agriculture 8. Determining the right timing to maximise seed set control of wild radish, Aik Cheam and Siew Lee, Department of Agriculture 9. Why weed wiping varies in success rates in broadacre crops? Aik Cheam1, Katherine Hollaway2, Siew Lee1, Brad Rayner1 and John Peirce1,1Department of Agriculture, 2Department of Primary Industries, Victoria 10. Are WA growers successfully managing herbicide resistant annual ryegrass? Rick Llewellynabc, Frank D’Emdena, Mechelle Owenb and Stephen Powlesb aCRC Australian Weed Management, School of Agricultural and Resource Economics, University of Western Australia; bWA Herbicide Resistance Initiative, University of Western Australia. cCurrent address: CSIRO Sustainable Ecosystems 11. Do herbicide resistant wild radish populations look different? Michael Walsh, Western Australian Herbicide Resistance Initiative, University of Western Australia 12. Can glyphosate and paraquat annual ryegrass reduce crop topping efficacy? Emma Glasfurd, Michael Walsh and Kathryn Steadman, Western Australian Herbicide Resistance Initiative, University of Western Australia 13. Tetraploid ryegrass for WA. Productive pasture phase AND defeating herbicide resistant ryegrass, Stephen Powlesa, David Ferrisab and Bevan Addisonc, aWA Herbicide Resistance Initiative, University of Western Australia; bDepartment of Agriculture, and cElders Limited 14. Long-term management impact on seedbank of wild radish with multiple resistance to diflufenican and triazines, Aik Cheam, Siew Lee, Dave Nicholson and Ruben Vargas, Department of Agriculture 15. East-west crop row orientation improves wheat and barley yields, Dr Shahab Pathan, Dr Abul Hashem, Nerys Wilkins and Catherine Borger3, Department of Agriculture, 3WAHRI, The University ofWestern Australia 16. Competitiveness of different lupin cultivars with wild radish, Dr Shahab Pathan, Dr Bob French and Dr Abul Hashem, Department of Agriculture 17. Managing herbicide resistant weeds through farming systems, Kari-Lee Falconer, Martin Harries and Chris Matthews, Department of Agriculture 18. Lupins tolerate in-row herbicides well, Peter Newman and Martin Harries, Department of Agriculture 19. Summer weeds can reduce wheat grain yield and protein, Dr Abul Hashem1, Dr Shahab Pathan1 and Vikki Osten3, 1Department Agriculture, 3Senior Agronomist, CRC for Australian Weed Management, Queensland Department of Primary Industries and Fisheries 20. Diuron post-emergent in lupins, the full story, Peter Newman and Glenn Adam, Department of Agriculture 21. Double incorporation of trifluralin, Peter Newman and Glenn Adam, Department of Agriculture 22. Herbicide tolerance of narrow leafed and yellow lupins, Harmohinder Dhammu, David Nicholson, Department of Agriculture 23. MIG narrow leaf lupin herbicide tolerance trial, Richard Quinlan, Planfarm Pty Ltd, Trials Coordinator MIG; Debbie Allen, Research Agronomist – MIG 24. Herbicide tolerance of new albus lupins, Harmohinder Dhammu, David Nicholson, Department of Agriculture 25. Field pea x herbicide tolerance, Mark Seymour and Harmohinder Dhammu, Research Officers, and Pam Burgess, Department of Agriculture 26. Faba bean variety x herbicide tolerance, Mark Seymour and Harmohinder Dhammu, Research Officers, and Pam Burgess, Department of Agriculture 27. Herbicide tolerance of new Kabili chickpeas, Harmohinder Dhammu, Owen Coppen and Chris Roberts, Department of Agriculture 28. Timing of phenoxys application in EAG Eagle Rock, Harmohinder Dhammu, David Nicholson, Department of Agriculture 29. Herbicide tolerance of new wheat varieties, Harmohinder Dhammu, David Nicholson, Department of Agriculture 30. Lathyrus sativus x herbicide tolerance, Mark Seymour, Department of Agriculture 31. Tolerance of annual pasture species to herbicides and mixtures containing diuron, Christiaan Valentine and David Ferris, Department of Agriculture 32. The impact of herbicides on pasture legume species – a summary of scientific trial results across 8 years, Christiaan Valentine and David Ferris, Department of Agriculture 33. The impact of spraytopping on pasture legume seed set, Christiaan Valentine and David Ferris, Department of Agriculture 34. Ascochyta interaction with Broadstrike in chickpeas, H.S. Dhammu1, A.K. Basandrai2,3, W.J. MacLeod1, 3 and C. Roberts1, 1Department of Agriculture, 2CSKHPAU, Dhaulakuan, Sirmour (HP), India and 3CLIMA 35. Best management practices for atrazine in broadacre crops, John Moore, Department of Agriculture, Neil Rothnie, Chemistry Centre of WA, Russell Speed, Department of Agriculture, John Simons, Department of Agriculture, and Ted Spadek, Chemistry Centre of WA 36. Biology and management of red dodder (Cuscuta planiflolia) – a new threat to the grains industry, Abul Hashem, Daya Patabendige and Chris Roberts, Department Agriculture 37. Help the wizard stop the green invaders! Michael Renton, Sally Peltzer and Art Diggle, Department of Agricultur

HIV-1 Nef Protein Structures Associated with Brain Infection and Dementia Pathogenesis

The difference between regional rates of HIV-associated dementia (HAD) in patients infected with different subtypes of HIV suggests that genetic determinants exist within HIV that influence the ability of the virus to replicate in the central nervous system (in Uganda, Africa, subtype D HAD rate is 89%, while subtype A HAD rate is 24%). HIV-1 nef is a multifunctional protein with known toxic effects in the brain compartment. The goal of the current study was to identify if specific three-dimensional nef structures may be linked to patients who developed HAD. HIV-1 nef structures were computationally derived for consensus brain and non-brain sequences from a panel of patients infected with subtype B who died due to varied disease pathologies and consensus subtype A and subtype D sequences from Uganda. Site directed mutation analysis identified signatures in brain structures that appear to change binding potentials and could affect folding conformations of brain-associated structures. Despite the large sequence variation between HIV subtypes, structural alignments confirmed that viral structures derived from patients with HAD were more similar to subtype D structures than to structures derived from patient sequences without HAD. Furthermore, structures derived from brain sequences of patients with HAD were more similar to subtype D structures than they were to their own non-brain structures. The potential finding of a brain-specific nef structure indicates that HAD may result from genetic alterations that alter the folding or binding potential of the protein

Mechanistic Elucidation of the Arylation of Non-Spectator N-Heterocyclic Carbenes at Copper Using a Combined Experimental and Computational Approach

CuI(NHC)Br complexes (NHC = N-heterocyclic carbene) undergo a direct reaction with iodobenzene to give 2-arylated benzimidazolium products. The nature of the N-substituent on the NHC ligand influences the reactivity of the CuI(NHC)Br complex toward arylation. N-Benzyl or N-phenyl substituents facilitate arylation, whereas N-mesityl substituents hinder arylation. Density functional theory calculations show that an oxidative addition/reductive elimination pathway involving CuIII species is energetically feasible. A less hindered CuI(NHC)Br complex with N-benzyl groups is susceptible to oxidation reactions to give 1,3-dibenzylbenzimidazolium cations containing a CuIBr anion (various polymorphs). The results described herein are of relevance to C–H functionalization of (benz)azoles

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study

Background We hypothesised that host-response biomarkers of viral infections might contribute to early identification of individuals infected with SARS-CoV-2, which is critical to breaking the chains of transmission. We aimed to evaluate the diagnostic accuracy of existing candidate whole-blood transcriptomic signatures for viral infection to predict positivity of nasopharyngeal SARS-CoV-2 PCR testing.Methods We did a nested case-control diagnostic accuracy study among a prospective cohort of health-care workers (aged ≥18 years) at St Bartholomew’s Hospital (London, UK) undergoing weekly blood and nasopharyngeal swab sampling for whole-blood RNA sequencing and SARS-CoV-2 PCR testing, when fit to attend work. We identified candidate blood transcriptomic signatures for viral infection through a systematic literature search. We searched MEDLINE for articles published between database inception and Oct 12, 2020, using comprehensive MeSH and keyword terms for “viral infection”, “transcriptome”, “biomarker”, and “blood”. We reconstructed signature scores in blood RNA sequencing data and evaluated their diagnostic accuracy for contemporaneous SARS-CoV-2 infection, compared with the gold standard of SARS-CoV-2 PCR testing, by quantifying the area under the receiver operating characteristic curve (AUROC), sensitivities, and specificities at a standardised Z score of at least 2 based on the distribution of signature scores in test-negative controls. We used pairwise DeLong tests compared with the most discriminating signature to identify the subset of best performing biomarkers. We evaluated associations between signature expression, viral load (using PCR cycle thresholds), and symptom status visually and using Spearman rank correlation. The primary outcome was the AUROC for discriminating between samples from participants who tested negative throughout the study (test-negative controls) and samples from participants with PCR-confirmed SARS-CoV-2 infection (test-positive participants) during their first week of PCR positivity.Findings We identified 20 candidate blood transcriptomic signatures of viral infection from 18 studies and evaluated their accuracy among 169 blood RNA samples from 96 participants over 24 weeks. Participants were recruited between March 23 and March 31, 2020. 114 samples were from 41 participants with SARS-CoV-2 infection, and 55 samples were from 55 test-negative controls. The median age of participants was 36 years (IQR 27–47) and 69 (72%) of 96 were women. Signatures had little overlap of component genes, but were mostly correlated as components of type I interferon responses. A single blood transcript for IFI27 provided the highest accuracy for discriminating between test-negative controls and test-positive individuals at the time of their first positive SARS-CoV-2 PCR result, with AUROC of 0·95 (95% CI 0·91–0·99), sensitivity 0·84 (0·70–0·93), and specificity 0·95 (0·85–0·98) at a predefined threshold (Z score >2). The transcript performed equally well in individuals with and without symptoms. Three other candidate signatures (including two to 48 transcripts) had statistically equivalent discrimination to IFI27 (AUROCs 0·91–0·95).Interpretation Our findings support further urgent evaluation and development of blood IFI27 transcripts as a biomarker for early phase SARS-CoV-2 infection for screening individuals at high risk of infection, such as contacts of index cases, to facilitate early case isolation and early use of antiviral treatments as they emerge