Atrial Fibrillation-Linked Germline GJA5/Connexin40 Mutants Showed an Increased Hemichannel Function

Mutations in GJA5 encoding the gap junction protein connexin40 (Cx40) have been linked to lone atrial fibrillation (AF). Some of these mutants result in impaired gap junction function due to either abnormal connexin localization or impaired gap junction channels, which may play a role in promoting AF. However, the effects of the AF-linked Cx40 mutants on hemichannel function has not been studied. Here we investigated two AF-linked germline Cx40 mutants, V85I and L221I. These two mutants formed putative gap junction plaques at cell-cell interfaces, with similar gap junction coupling conductance as that of wild-type Cx40. Connexin deficient HeLa cells expressing either of these two mutants displayed prominent propidium iodide (PI)-uptake distinct from cells expressing wild-type Cx40 or other AF-linked Cx40 mutants, I75F, L229M and Q49X. The PI-uptake was sensitive to [Ca2+]o and carbenoxolone, but was not affected by probenecid, indicating that uptake is mediated via connexin hemichannels. A gain-of-hemichannel function in these two AF-linked Cx40 mutants may provide a novel mechanism underlying the etiology of AF

Time-Series Photometry of M67: W UMa Systems, Blue Stragglers, and Related Systems

We present an analysis of over 2200 V images taken on 14 nights at the Mt. Laguna 1 m telescope of the open cluster M67. Our observations overlap but extend beyond the field analyzed by Gilliland et al. (1991), and complement data recently published by van den Berg et al. (2002) and Stassun et al. (2002). We show variability in the light curves of all 4 of the known W UMa variables on timescales ranging from a day to decades (for AH Cnc). We have modeled the light curve of AH Cnc, and the total eclipses allow us to determine q = 0.16 +0.03/-0.02 and i = 86 +4/-8 degrees. The position of this system near the turnoff of M67 makes it useful for constraining the turnoff mass for the cluster. We have also detected two unusual features in the light curve of AH Cnc that may be caused by prominences. We have also monitored cluster blue stragglers for variability, and we present evidence hinting at low level variations in the stragglers S752, S968, and S1263, and we place limits on the variability of a number of other cluster blue stragglers. Finally, we provide photometry of the sub-subgiant branch star S1063 showing variability on timescales similar to the orbital period, while the ``red straggler'' S1040 shows evidence of an unexplained drop in brightness at phases corresponding to the passage of the white dwarf in front of the giant.Comment: 44 pages, 16 figures, AASTeX, accepted for A

Does wage rank affect employees' well-being?

How do workers make wage comparisons? Both an experimental study and an analysis of 16,000 British employees are reported. Satisfaction and well-being levels are shown to depend on more than simple relative pay. They depend upon the ordinal rank of an individual's wage within a comparison group. “Rank” itself thus seems to matter to human beings. Moreover, consistent with psychological theory, quits in a workplace are correlated with pay distribution skewness

Evolution of chloroplast retrograde signaling facilitates green plant adaptation to land

Chloroplast retrograde signaling networks are vital for chloroplast biogenesis, operation, and signaling, including excess light and drought stress signaling. To date, retrograde signaling has been considered in the context of land plant adaptation, but not regarding the origin and evolution of signaling cascades linking chloroplast function to stomatal regulation. We show that key elements of the chloroplast retrograde signaling process, the nucleotide phosphatase (SAL1) and 3'-phosphoadenosine-5'-phosphate (PAP) metabolism, evolved in streptophyte algae-the algal ancestors of land plants. We discover an early evolution of SAL1-PAP chloroplast retrograde signaling in stomatal regulation based on conserved gene and protein structure, function, and enzyme activity and transit peptides of SAL1s in species including flowering plants, the fern Ceratopteris richardii, and the moss Physcomitrella patens Moreover, we demonstrate that PAP regulates stomatal closure via secondary messengers and ion transport in guard cells of these diverse lineages. The origin of stomata facilitated gas exchange in the earliest land plants. Our findings suggest that the conquest of land by plants was enabled by rapid response to drought stress through the deployment of an ancestral SAL1-PAP signaling pathway, intersecting with the core abscisic acid signaling in stomatal guard cells

Influence of daily beer or ethanol consumption on physical fitness in response to a high-intensity interval training program. The BEER-HIIT study

The authors would like to thank all the participants that took part of the study for their time and effort. We are grateful to Ms. Ana Yara PostigoFuentes for her assistance with the English language. This study is part of Cristina Molina-Hidalgo’s Doctoral Thesis conducted in the Official Doctoral Programme in Psychology of the University of Granada, Spain.Background: High-intensity interval training (HIIT) is an effective approach to improve physical fitness, but consuming beer, which is a regular practice in many physically active individuals, may interfere with these effects. The purposes of this study were to investigate the effects of a 10-week (2 days/week) HIIT program on cardiorespiratory fitness, muscle strength and power parameters, and also to assess the possible influence on them of a moderate consumption of beer (at least from Monday to Friday) or its alcohol equivalent. Methods: Young (24 ± 6 years old) healthy adults (n = 73, 35 females) were allocated to five groups. Four groups participated in the HIIT intervention program while the fifth group was a control Non-Training group (n = 15). Participants in the training groups chose whether they preferred receiving alcohol or alcohol-free beverages. Those choosing alcohol were randomized to either beer or ethanol intake: (i) T-Beer group (alcohol beer, 5.4%; n = 13) or (ii) T-Ethanol (sparkling water with vodka, 5.4%; n = 14). Those choosing alcohol-free intake were randomized to (iii) T-Water group (sparkling water, 0.0%; n = 16), or (iv) T-0.0Beer group (alcohol-free beer, 0.0%; n = 15). Men ingested 330 ml of the beverage at lunch and 330 ml at dinner; women ingested 330 ml at dinner. Before and after the intervention, maximal oxygen uptake in absolute and relative terms (VO2max.), maximal heart rate, total test duration, hand grip strength and four types of vertical jumps were measured. Results: HIIT induced significant improvements in absolute and relative values of VO2max, and total test duration (all p < 0.05) in all the training groups; also, clinical improvements were found in hand grip strength. These positive effects were not influenced by the regular intake of beer or alcohol. No changes in the vertical jumps occurred in any of the groups. Conclusions: A moderate beer or alcohol intake does not mitigate the positive effect of a 10-week HIIT on physical fitness in young healthy adults. Trial registration: ClinicalTrials.gov ID: NCT03660579. Registered 20 September 2018. Retrospectively registered.Centro de Informacion Cerveza y Salud (CICS), Madrid, SpainSpanish Government FPU14/04172 FPU15/0396

PRNP Haplotype Associated with Classical BSE Incidence in European Holstein Cattle

Background: Classical bovine spongiform encephalopathy (BSE) is an acquired prion disease of cattle. The bovine prion gene (PRNP) contains regions of both high and low linkage disequilibrium (LD) that appear to be conserved across Bos taurus populations. The region of high LD, which spans the promoter and part of intron 2, contains polymorphic loci that have been associated with classical BSE status. However, the complex genetic architecture of PRNP has not been systematically tested for an association with classical BSE. Methodology/Principal Findings: In this study, haplotype tagging single nucleotide polymorphisms (htSNPs) within PRNP were used to test for association between PRNP haplotypes and BSE disease. A combination of Illumina goldengate assay, sequencing and PCR amplification was used to genotype 18 htSNPs and 2 indels in 95 BSE case and 134 control animals. A haplotype within the region of high LD was found to be associated with BSE unaffected animals (p-value = 0.000114). Conclusion/Significance: A PRNP haplotype association with classical BSE incidence has been identified. This result suggests that a genetic determinant in or near PRNP may influence classical BSE incidence in cattle

Crop Updates 2005 - Farming Systems

This session covers forty four papers from different authors: PLENARY 1. 2005 Outlook, David Stephens and Nicola Telcik, Department of Agriculture FERTILITY AND NUTRITION 2. The effect of higher nitrogen fertiliser prices on rotation and fertiliser strategies in cropping systems, Ross Kingwell, Department of Agriculture and University of Western Australia 3. Stubble management: The short and long term implications for crop nutrition and soil fertility, Wayne Pluske, Nutrient Management Systems and Bill Bowden, Department of Agriculture 4. Stubble management: The pros and cons of different methods, Bill Bowden, Department of Agriculture, Western Australia and Mike Collins, WANTFA 5. Effect of stubble burning and seasonality on microbial processes and nutrient recycling, Frances Hoyle, The University of Western Australia 6. Soil biology and crop production in Western Australian farming systems, D.V. Murphy, N. Milton, M. Osman, F.C. Hoyle, L.K Abbott, W.R. Cookson and S. Darmawanto, The University of Western Australia 7. Urea is as effective as CAN when no rain for 10 days, Bill Crabtree, Crabtree Agricultural Consulting 8. Fertiliser (N,P,S,K) and lime requirements for wheat production in the Merredin district, Geoff Anderson, Department of Agriculture and Darren Kidson, Summit Fertilizers 9. Trace element applications: Up-front verses foliar? Bill Bowden and Ross Brennan, Department of Agriculture 10. Fertcare®, Environmental Product Stewardship and Advisor Standards for thee Fertiliser Industry, Nick Drew, Fertilizer Industry Federation of Australia (FIFA) SOIL AND LAND MANAGEMENT 11. Species response to row spacing, density and nutrition, Bill Bowden, Craig Scanlan, Lisa Sherriff, Bob French and Reg Lunt, Department of Agriculture 12. Investigation into the influence of row orientation in lupin crops, Jeff Russell, Department of Agriculture and Angie Roe, Farm Focus Consultants 13. Deriving variable rate management zones for crops, Ian Maling, Silverfox Solutions and Matthew Adams, DLI 14. In a world of Precision Agriculture, weigh trailers are not passé, Jeff Russell, Department of Agriculture 15. Cover crop management to combat ryegrass resistance and improve yields, Jeff Russell, Department of Agriculture and Angie Roe, Farm Focus Consultants 16. ARGT home page, the place to find information on annual ryegrass toxicity on the web, Dr George Yan, BART Pty Ltd 17. Shallow leading tine (SLT) ripper significantly reduces draft force, improves soil tilth and allows even distribution of subsoil ameliorants, Mohammad Hamza, Glen Riethmuller and Wal Anderson, Department of Agriculture PASTURE ANS SUMMER CROP SYSTEMS 18. New annual pasture legumes for Mediteranean farming systems, Angelo Loi, Phil Nichols, Clinton Revell and David Ferris, Department of Agriculture 19. How sustainable are phase rotations with Lucerne? Phil Ward, CSIRO Plant Industry 20. Management practicalities of summer cropping, Andrea Hills and Sally-Anne Penny, Department of Agriculture 21. Rainfall zone determines the effect of summer crops on winter yields, Andrea Hills, Sally-Anne Penny and David Hall, Department of Agriculture 22. Summer crops and water use, Andrea Hills, Sally-Anne Penny and David Hall, Department of Agriculture, and Michael Robertson and Don Gaydon, CSIRO Brisbane 23. Risk analysis of sorgum cropping, Andrea Hills and Sally-Anne Penny, Department of Agriculture, and Dr Michael Robertson and Don Gaydon, CSIRO Brisbane FARMER DECISION SUPPORT AND ADOPTION 24. Variety release and End Point Royalties – a new system? Tress Walmsley, Department of Agriculture 25. Farming system analaysis using the STEP Tool, Caroline Peek and Megan Abrahams, Department of Agriculture 26. The Leakage Calculator: A simple tool for groundwater recharge assessment, Paul Raper, Department of Agriculture 27. The cost of Salinity Calculator – your tool to assessing the profitability of salinity management options, Richard O’Donnell and Trevor Lacey, Department of Agriculture 28. Climate decision support tools, Meredith Fairbanks and David Tennant, Department of Agriculture 29. Horses for courses – using the best tools to manage climate risk, Cameron Weeks, Mingenew-Irwin Group/Planfarm and Richard Quinlan, Planfarm Agronomy 30. Use of seasonal outlook for making N decisions in Merredin, Meredith Fairbanks and Alexandra Edward, Department of Agriculture 31. Forecasts and profits, Benefits or bulldust? Chris Carter and Doug Hamilton, Department of Agriculture 32. A tool to estimate fixed and variable header and tractor depreciation costs, Peter Tozer, Department of Agriculture 33. Partners in grain: ‘Putting new faces in new places’, Renaye Horne, Department of Agriculture 34. Results from the Grower group Alliance, Tracey Gianatti, Grower Group Alliance 35. Local Farmer Group Network – farming systems research opportunities through local groups, Paul Carmody, Local Farmer Group Network GREENHOUSE GAS AND CLIMATE CHANGE 36. Changing rainfall patterns in the grainbelt, Ian Foster, Department of Agriculture 37. Vulnerability of broadscale agriculture to the impacts of climate change, Michele John, CSIRO (formerly Department of Agriculture) and Ross George, Department of Agriculture 38. Impacts of climate change on wheat yield at Merredin, Imma Farré and Ian Foster, Department of Agriculture 39. Climate change, land use suitability and water security, Ian Kininmonth, Dennis van Gool and Neil Coles, Department of Agriculture 40. Nitrous oxide emissions from cropping systems, Bill Porter, Department of Agriculture, Louise Barton, University of Western Australia 41. The potential of greenhouse sinks to underwrite improved land management in Western Australia, Richard Harper and Peter Ritson, CRC for Greenhouse Accounting and Forest Products Commission, Tony Beck, Tony Beck Consulting Services, Chris Mitchell and Michael Hill, CRC for Greenhouse Accounting 42. Removing uncertainty from greenhouse emissions, Fiona Barker-Reid, Will Gates, Ken Wilson and Rob Baigent, Department of Primary Industries - Victoria and CRC for Greenhouse Accounting (CRCGA), and Ian Galbally, Mick Meyer and Ian Weeks, CSIRO Atmospheric Research and CRCGA 43. Greenhouse in Agriculture Program (GIA), Traci Griffin, CRC for Greenhouse Accounting 44. Grains Greenhouse Accounting framework, D. Rodriguez, M. Probust, M. Meyers, D. Chen, A. Bennett, W. Strong, R. Nussey, I. Galbally and M. Howden CONTACT DETAILS FOR PRINCIPAL AUTHOR

Modeling Signal Propagation Mechanisms and Ligand-Based Conformational Dynamics of the Hsp90 Molecular Chaperone Full-Length Dimer

Hsp90 is a molecular chaperone essential for protein folding and activation in normal homeostasis and stress response. ATP binding and hydrolysis facilitate Hsp90 conformational changes required for client activation. Hsp90 plays an important role in disease states, particularly in cancer, where chaperoning of the mutated and overexpressed oncoproteins is important for function. Recent studies have illuminated mechanisms related to the chaperone function. However, an atomic resolution view of Hsp90 conformational dynamics, determined by the presence of different binding partners, is critical to define communication pathways between remote residues in different domains intimately affecting the chaperone cycle. Here, we present a computational analysis of signal propagation and long-range communication pathways in Hsp90. We carried out molecular dynamics simulations of the full-length Hsp90 dimer, combined with essential dynamics, correlation analysis, and a signal propagation model. All-atom MD simulations with timescales of 70 ns have been performed for complexes with the natural substrates ATP and ADP and for the unliganded dimer. We elucidate the mechanisms of signal propagation and determine “hot spots” involved in interdomain communication pathways from the nucleotide-binding site to the C-terminal domain interface. A comprehensive computational analysis of the Hsp90 communication pathways and dynamics at atomic resolution has revealed the role of the nucleotide in effecting conformational changes, elucidating the mechanisms of signal propagation. Functionally important residues and secondary structure elements emerge as effective mediators of communication between the nucleotide-binding site and the C-terminal interface. Furthermore, we show that specific interdomain signal propagation pathways may be activated as a function of the ligand. Our results support a “conformational selection model” of the Hsp90 mechanism, whereby the protein may exist in a dynamic equilibrium between different conformational states available on the energy landscape and binding of a specific partner can bias the equilibrium toward functionally relevant complexes

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

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care