The eigenvalue approach to groundwater modelling for resource evaluation at regional scale

A conference paper presented at ModelCARE 2002, 4th International Conference on Calibration and Reliability in Groundwater Modelling, Prague, Czech Republic, 17-29 June 2002.The dynamic response of piezometric head at any location in an aquifer to time variation of regional land surface recharge and abstraction can be expressed as a linear system comprising only a few conceptual water storages. Model structure and parameters are related to aquifer characteristics and spatial pattern of recharge by the eigenvalues and eigenfunctions of a general analytical solution to the linearised Boussinesq equation. The model is implemented as a stochastic ARMA difference equation, independently for each location. This modelling approach is demonstrated for an aquifer of 2000 km² area, yielding additional information about unobservable recharge and aquifer boundaries.Development of methodology was funded by the Foundation for Research, Science and Technology. Demonstration results are from a water resource study for Environment Canterbury, Ministry for the Environment and Ministry of Agriculture and Forestry, New Zealand

Identification of Genetic and Epigenetic Marks Involved in Population Structure

Population structure is well known as a prevalent and important factor in genetic studies, but its relevance in epigenetics is unclear. Very little is known about the affected epigenetic markers and their connections with genetics. In this study we assessed the impact of population diversity on genome wide single nucleotide polymorphisms (SNPs) and DNA methylation levels in 196 participants from five ethnic groups, using principle and independent component analyses. Three population stratification factors (PSFs) were identified in the genomic SNP dataset, accounting for a relatively large portion of total variance (6%). In contrast, only one PSF was identified in genomic methylation dataset accounting for 0.2% of total variance. This methylation PSF, however, was significantly correlated with the largest SNP PSF (r = 0.72, p<1E-23). We then investigated the top contributing markers in these two linked PSFs. The SNP PSF predominantly consists of 8 SNPs from three genes, SLC45A2, HERC2 and CTNNA2, known to encode skin/hair/eye color. The methylation PSF includes 48 methylated sites in 44 genes coding for basic molecular functions, including transcription regulation, DNA binding, cytokine, and transferase activity. Among them, 8 sites are either hypo- or hyper-methylated correlating to minor alleles of SNPs in the SNP PSF. We found that the genes in SNP and methylation PSFs share common biological processes including sexual/multicellular organism reproduction, cell-cell signaling and cytoskeleton organization. We further investigated the transcription regulatory network operating at these genes and identified that most of genes closely interact with ID2, which encodes for a helix-loop-helix inhibitor of DNA binding. Overall, our results show a significant correlation between genetic and epigenetic population stratification, and suggest that the interrelationship between genetic and epigenetic population structure is mediated via complex multiple gene interactions in shared biological processes, through possibly, SNP-dependent modulation and ID2 repressor function

Novel recombinant SARS-CoV-2 lineage detected through genomic surveillance in Wales, UK

Recombination, the process whereby a segment of genetic material from one genome is inserted into another, producing a new chimeric genome, is an important evolutionary mechanism frequently observed in coronaviruses. The risks posed by recombination include the shuffling of advantageous mutations that may increase transmissibility, severity or vaccine escape. We present a genomic and epidemiological description of a new recombinant lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), XR, first identified in Wales. The Pathogen Genomics Unit (Public Health Wales, UK) sequences positive SARS-CoV-2 PCR tests using the ARTIC SARS-CoV-2 sequencing protocol. Recombinants were detected using an in-house pipeline and the epidemiological data analysed in R. Nosocomial cases were defined as those with samples taken after >7 days in hospital. Between February and March 2022, we identified 78 samples with highly similar genomes, comprising a BA.1-like 5' end, a BA.2-like 3' end and a BA.2-like spike protein. This signature is consistent with recombination and was defined as XR by Pangolin (PANGO v1.8). A total of 50 % of cases had a sample collected whilst in hospital and the first three cases were immunocompromised patients. The patient median age was 58 years (range: 4–95 years) and most of the patients were fully vaccinated against SARS-CoV-2 (74 % third dose/booster). Three patients died within 28 days of their sample collection date, one of whom had COVID-19 listed amongst ICD10 (International Classification of Diseases 10) coded causes of death. Our integrated system enabled real-time monitoring of recombinant SARS-CoV-2 for early detection, in order to rapidly risk assess and respond. This work highlights the importance of setting-based surveillance of recombinant SARS-CoV-2, as well as the need to monitor immunocompromised populations through repeat testing and sequencing

Bicarbonate Recycling by HIF‐1–Dependent Carbonic Anhydrase Isoforms 9 and 12 Is Critical in Maintaining Intracellular pH and Viability of Nucleus Pulposus Cells

Intervertebral disc degeneration is a ubiquitous condition closely linked to chronic low‐back pain. The health of the avascular nucleus pulposus (NP) plays a crucial role in the development of this pathology. We tested the hypothesis that a network comprising HIF‐1α, carbonic anhydrase (CA) 9 and 12 isoforms, and sodium‐coupled bicarbonate cotransporters (NBCs) buffer intracellular pH through coordinated bicarbonate recycling. Contrary to the current understanding of NP cell metabolism, analysis of metabolic‐flux data from Seahorse XF analyzer showed that CO2 hydration contributes a significant source of extracellular proton production in NP cells, with a smaller input from glycolysis. Because enzymatic hydration of CO2 is catalyzed by plasma membrane‐associated CAs we measured their expression and function in NP tissue. NP cells robustly expressed isoforms CA9/12, which were hypoxia‐inducible. In addition to increased mRNA stability under hypoxia, we observed binding of HIF‐1α to select hypoxia‐responsive elements on CA9/12 promoters using genomic chromatin immunoprecipitation. Importantly, in vitro loss of function studies and analysis of discs from NP‐specific HIF‐1α null mice confirmed the dependency of CA9/12 expression on HIF‐1α. As expected, inhibition of CA activity decreased extracellular acidification rate independent of changes in HIF activity or lactate/H+ efflux. Surprisingly, CA inhibition resulted in a concomitant decrease in intracellular pH that was mirrored by inhibition of sodium‐bicarbonate importers. These results suggested that extracellular bicarbonate generated by CA9/12 is recycled to buffer cytosolic pH fluctuations. Importantly, long‐term intracellular acidification from CA inhibition lead to compromised cell viability, suggesting that plasma‐membrane proton extrusion pathways alone are not sufficient to maintain homeostatic pH in NP cells. Taken together, our studies show for the first time that bicarbonate buffering through the HIF‐1α–CA axis is critical for NP cell survival in the hypoxic niche of the intervertebral disc. © 2017 American Society for Bone and Mineral Research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142506/1/jbmr3293.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142506/2/jbmr3293-sup-0001-SuppData-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142506/3/jbmr3293_am.pd

A Study of the Influence of Sex on Genome Wide Methylation

Sex differences in methylation status have been observed in specific gene-disease studies and healthy methylation variation studies, but little work has been done to study the impact of sex on methylation at the genome wide locus-to-locus level or to determine methods for accounting for sex in genomic association studies. In this study we investigate the genomic sex effect on saliva DNA methylation of 197 subjects (54 females) using 20,493 CpG sites. Three methods, two-sample T-test, principle component analysis and independent component analysis, all successfully identify sex influences. The results show that sex not only influences the methylation of genes in the X chromosome but also in autosomes. 580 autosomal sites show strong differences between males and females. They are found to be highly involved in eight functional groups, including DNA transcription, RNA splicing, membrane, etc. Equally important is that we identify some methylation sites associated with not only sex, but also other phenotypes (age, smoking and drinking level, and cancer). Verification was done through an independent blood cell DNA methylation data (1298 CpG sites from a cancer panel array). The same genomic site-specific influence pattern and potential confounding effects with cancer were observed. The overlapping rate of identified sex affected genes between saliva and blood cell is 81% for X chromosome, and 8% for autosomes. Therefore, correction for sex is necessary. We propose a simple correction method based on independent component analysis, which is a data driven method and accommodates sample differences. Comparison before and after the correction suggests that the method is able to effectively remove the potentially confounding effects of sex, and leave other phenotypes untouched. As such, our method is able to disentangle the sex influence on a genome wide level, and paves the way to achieve more accurate association analyses in genome wide methylation studies

Crop Updates 2008 - Lupins, Pulses and Oilseeds

This session covers twenty six papers from different authors: Regional Roundup 1. SOUTH EAST AGRICULTURAL REGION, Mark Seymour Department of Agriculture and Food, and Robert Johnson CBH Group, Esperance 2. CENTRAL AGRICULTURAL REGION, Ian Pritchard, Department of Agriculture and Food 3. GREAT SOUTHERN AND LAKES REGION, Raj Malik, Department of Agriculture and Food 4. NORTHERN AGRICULTURAL REGION, Wayne Parker and Martin Harries, Department of Agriculture and Food LUPINS 5. Cropping lupins in wide rows in Western Australia, Martin Harries and Bob French, Department of Agriculture and Food 6. The effect of sowing time and radish density on lupin yield, Martin Harries and Jo Walker, Department of Agriculture and Food 7. Lupin agronomy affects crop competitiveness with annual ryegrass, Bob French and Laurie Maiolo, Department of Agriculture and Food 8. Identification of lupin mutants with tolerance to isoxaflutole, Leigh Smith, Department of Agriculture and Food PULSES 9. Chickpea 2007 Crop Variety Testing (CVT) and National Variety Testing (NVT), Alan Harris, Rod Hunter, Tanveer Khan and Jenny Garlinge, Department of Agriculture and Food 10. Desi chickpea breeding: Evaluation of advanced lines, Tanveer Khan1, Poran Gaur2, Kadambot Siddique3, Heather Clarke4, Neil Turner4, William MacLeod4, Stuart Morgan1, Alan Harris1, 1Department of Agriculture and Food, 2International Crop Research Institute for the Semi Arid Tropics (ICRISAT); 3The University of Western Australia; 4Centre for Legumes in Mediterranean Agriculture 11. Can wide rows buffer chickpea growth against dry environments? Bob French and Wendy Vance, Department of Agriculture and Food, and School of Environmental Sciences, Murdoch University 12. Field pea 2007 Crop Variety Testing (CVT) and National Variety Testing (NVT), Alan Harris, Rod Hunter, Tanveer Khan and Jenny Garlinge, Department of Agriculture and Food 13. Australian Field Pea improvement Program (AFPIP): Evaluation of advanced breeding lines, Tanveer Khan1, Phillip Chambers1, Chris Veitch1, Stuart Morgan1, Alan Harris1, and Tony Leonforte 2, 1Department of Agriculture and Food, 2Department of Primary Industries, Victoria 14. Ability of semi-leafless field peas to recover after rolling, Mark Seymour and Rodger Beermier, Department of Agriculture and Food 15. Field pea germplasm enhancement for black spot resistance, Tanveer Khan, Stuart Morgan, Alan Harris and Phillip Chambers, Department of Agriculture and Food 16. Application of ‘Blackspot Manager’ model to identifying a low risk sowing date for field pea in South Australia and Western Australia in 2007, Moin Salam1, Jenny Davidson2, Jean Galloway1, Pip Payne2, Tess Humphries2, Bill MacLeod1 and Art Diggle1, 1Department of Agriculture and Food, 2SARDI, South Australia 17. Late post emergent herbicide sprays for field pea, Mark Seymour and Rodger Beermier, Department of Agriculture and Food 18. Adding triasulfuron to croptopping mixes does not affect the yield of field pea, Mark Seymour, Department of Agriculture and Food 18. Herbicide tolerance of field pea varieties, Harmohinder Dhammu and Mark Seymour, Department of Agriculture and Food 19. Breeding highlights of the PBA lentil program, Michael Materne1, Kerry Regan2, Chris Veitch2 and Phil Chambers2, 1Department of Primary Industries, Victoria 2Department of Agriculture and Food CANOLA 20. How late can I sow canola in 2008? Mohammad Amjad, Andy Sutherland and Pat Fels, Department of Agriculture and Food 21. Direct harvesting canola, Glen Riethmuller1, Wallace Cowling2, Milton Sanders2, Eliot Jones2 and Chris Newman1, 1Department of Agriculture and Food, Western Australia, 2Canola Breeders Western Australia Pty Ltd 22. Agronomic performance of new hybrid canola and juncea canola in low, medium and high rainfall environments of Western Australia, Mohammad Amjad, Andy Sutherland and Pat Fels, Department of Agriculture and Food 23. Comparative performance of new canola varieties in commercial-scale field trials of Oilseeds WA – 2007, Mohammad Amjad1, John Duff2 and David Sermon3 1Department of Agriculture and Food, 2Oilseeds Western Australia and John Duff & Associates, Perth; 3ConsultAg, Perth 24. The effect of rotation crops, trash retention and prophylactic sprays on arthropod abundance in a following canola crop, Svetlana Micic, Anthony Dore and Geoff Strickland, Department of Agriculture and Food OATS 25. Fungicide options for controlling disease in oats, Raj Malik and Blakely Paynter, Department of Agriculture and Food 26. Herbicide tolerance of new oat varieties, Harmohinder Dhammu, Vince Lambert and Chris Roberts, Department of Agriculture and Foo

A Frameshift Mutation in Golden Retriever Dogs with Progressive Retinal Atrophy Endorses SLC4A3 as a Candidate Gene for Human Retinal Degenerations

Progressive retinal atrophy (PRA) in dogs, the canine equivalent of retinitis pigmentosa (RP) in humans, is characterised by vision loss due to degeneration of the photoreceptor cells in the retina, eventually leading to complete blindness. It affects more than 100 dog breeds, and is caused by numerous mutations. RP affects 1 in 4000 people in the Western world and 70% of causal mutations remain unknown. Canine diseases are natural models for the study of human diseases and are becoming increasingly useful for the development of therapies in humans. One variant, prcd-PRA, only accounts for a small proportion of PRA cases in the Golden Retriever (GR) breed. Using genome-wide association with 27 cases and 19 controls we identified a novel PRA locus on CFA37 (praw = 1.94×10−10, pgenome = 1.0×10−5), where a 644 kb region was homozygous within cases. A frameshift mutation was identified in a solute carrier anion exchanger gene (SLC4A3) located within this region. This variant was present in 56% of PRA cases and 87% of obligate carriers, and displayed a recessive mode of inheritance with full penetrance within those lineages in which it segregated. Allele frequencies are approximately 4% in the UK, 6% in Sweden and 2% in France, but the variant has not been found in GRs from the US. A large proportion of cases (approximately 44%) remain unexplained, indicating that PRA in this breed is genetically heterogeneous and caused by at least three mutations. SLC4A3 is important for retinal function and has not previously been associated with spontaneously occurring retinal degenerations in any other species, including humans

The COVID-OUT study protocol: COVID-19 outbreak investigation to understand workplace SARS-CoV-2 transmission in the United Kingdom

Preventing SARS-CoV-2 transmission and protecting people from COVID-19 is the most significant public health challenge faced in recent years. COVID-19 outbreaks are occurring in workplaces and evidence is needed to support effective strategies to prevent and control these outbreaks. Investigations into these outbreaks are routinely undertaken by public health bodies and regulators in the United Kingdom (UK); however, such investigations are typically disparate in nature with a lack of consistency across all investigations, preventing meaningful analysis of the data collected. The COVID-OUT (COVID-19 Outbreak investigation to Understand Transmission) study aims to collect a consistent set of data in a systematic way from workplaces that are experiencing outbreaks, to understand SARS-CoV-2 transmission risk factors, transmission routes, and the role they play in the COVID-19 outbreaks. Suitable outbreak sites are identified from public health bodies. Following employer consent to participate, the study will recruit workers from workplaces where there are active outbreaks. The study will utilise data already collected as part of routine public health outbreak investigations and collect additional data through a comprehensive questionnaire, viral and serologic testing of workers, surface sampling, viral genome sequencing, and an environmental assessment of building plans, ventilation and current control measures. At each site, a detailed investigation will be carried out to evaluate transmission routes. A case-control approach will be used to compare workers who have and have not had SARS-CoV-2 infections during the outbreak period to assess transmission risk factors. Data from different outbreaks will be combined for pooled analyses to identify common risk factors, as well as factors that differ between outbreaks. The COVID-OUT study can contribute to a better understanding of why COVID-19 outbreaks associated with workplaces occur and how to prevent these outbreaks from happening in the future.</ns3:p