A complete set of nascent transcription rates for yeast genes

The amount of mRNA in a cell is the result of two opposite reactions: transcription and mRNA degradation. These reactions are governed by kinetics laws, and the most regulated step for many genes is the transcription rate. The transcription rate, which is assumed to be exercised mainly at the RNA polymerase recruitment level, can be calculated using the RNA polymerase densities determined either by run-on or immunoprecipitation using specific antibodies. The yeast Saccharomyces cerevisiae is the ideal model organism to generate a complete set of nascent transcription rates that will prove useful for many gene regulation studies. By combining genomic data from both the GRO (Genomic Run-on) and the RNA pol ChIP-on-chip methods we generated a new, more accurate nascent transcription rate dataset. By comparing this dataset with the indirect ones obtained from the mRNA stabilities and mRNA amount datasets, we are able to obtain biological information about posttranscriptional regulation processes and a genomic snapshot of the location of the active transcriptional machinery. We have obtained nascent transcription rates for 4,670 yeast genes. The median RNA polymerase II density in the genes is 0.078 molecules/kb, which corresponds to an average of 0.096 molecules/gene. Most genes have transcription rates of between 2 and 30 mRNAs/hour and less than 1% of yeast genes have >1 RNA polymerase molecule/gene. Histone and ribosomal protein genes are the highest transcribed groups of genes and other than these exceptions the transcription of genes is an infrequent phenomenon in a yeast cell

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

Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype

African Financial Development Dynamics: Big Time Convergence

In the first critical assessment of convergence in financial development dynamics in Africa, we find overwhelming support for integration. The empirical evidence is premised on 11 homogenous panels based on regions(Sub-Saharan and North Africa), income-levels(low, middle, lower-middle and upper-middle), legal-origins(English common-law and French civil-law) and religious dominations(Christianity and Islam). We examine convergence in financial intermediary dynamics of depth, efficiency, activity and size. Findings suggest that countries with small-sized financial intermediary depth, efficiency, activity and size are catching-up with countries with large-sized financial intermediary depth, efficiency, activity and size respectively. We also provide the speeds of convergence and time necessary to achieve a full(100%) convergence. As a policy implication African governments should not relent in structural and institutional reforms

Publisher Correction: Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Direct-acting antivirals and viral RNA targeting for hepatitis B cure

International audiencePurpose of review: The current aim in the HBV landscape is to develop therapeutic strategies to achieve a functional cure of infection, characterized by a sustained loss of HBsAg off-treatment. Current treatment options, that is, nucleos(t)ide analogues and IFN are effective at viral suppression but very poor at achieving HBsAg loss. This article is designed to summarize the HBV life cycle in order to review the current treatment strategies and compounds targeting different points of the virus life cycle, which are either in preclinical or clinical phases.Recent findings: Recently our developed understanding of the HBV life cycle has enabled the development of multiple novel treatment options, all aiming for functional cure.Summary: It is likely that combinations of novel treatments will be needed to achieve a functional cure, including those that target the virus itself as well as those that target the immune system