Mycorrhizal colonization and nutrient uptake of dry bean in manure and compost manure treated subsoil and untreated topsoil and subsoil

Eroded or leveled Portneuf silt loam soils (coarse-silty mixed mesic Durixerollic Calciorthid) have been restored to topsoil productivity levels by manure application, but not by other organic sources such as cheese whey. In dry bean (Phaseolus vulgaris L. cv. Viva), only soil organic matter and Zn concentration of leaf tissue correlated with improved yields. Manure application could potentially increase or decrease mycorrhizal colonization depending on which factors dominate. Manured and unmanured soils from a long-term field experiment were sampled and mycorrhizal spores were quantified, but there was no significant manure treatment effect on spore numbers. A greenhouse study was conducted to see if manure or composted manure freshly applied to subsoils would facilitate mycorrhizal colonization in dry bean roots compared to untreated topsoil or conventionally fertilized subsoil. Low level colonization (< 5%) was observed 21 days after planting and that increased to 58% by 56 days after planting. Roots grown on subsoil treated with manure or composted manure showed higher percent colonization than roots from untreated subsoil, but roots on topsoil had highest colonization. This increase in colonization was statistically significant for the last two sampling dates. Topsoil promoted the greatest percent colonization in early bean growth and this was reflected in greater Zn uptake during early growth stages. By day 56, plants grown in manured subsoil absorbed Zn equal to topsoil and at higher levels than the subsoil control. However, this increase in Zn uptake was not seen in plants grown in compost manured subsoil. A decrease in root and shoot weight was observed in the composted manure treatment and this seemed to decrease mycorrhizal efficiency. Uptake of other nutrients was either not related or was negatively related to mycorrhizal infection. The higher percent colonization of roots by mycorrhizal fungi stimulated by manure could explain the field observations of higher bean yield and Zn contents in dry bean in manured than in untreated subsoils

Preparing and staining mycorrhizal structures in dry bean, sweet corn, and wheat using a block digester

The use of safe staining techniques in the evaluation of mycorrhizal colonization is critical to the continued understanding of this important symbiosis. Several procedures being utilized currently involve regulated and/ or toxic chemicals. The integration of unregulated and nontoxic chemicals into these procedures is important to alleviate potential dangers currently used chemicals pose. We eliminated all regulated reagents by combining portions of several previously published staining and root preservation procedures. A block digester for plant tissue digestion was used as a heating unit and proved to be easier to use, quicker and more reliable than either a water bath or a circulating air oven. Optimum clearing time in KOH varied from 8 to 10 min and 30 to 40 min for wheat, sweet corn, and dry bean roots, respectively. We also successfully used both drying and freezing of roots for storage prior to staining. These modified procedures were quick and easy and provided reliable temperature control and excellent staining while protecting individuals and the environment from toxic chemicals

Data Linkage: A powerful research tool with potential problems

Background: Policy makers, clinicians and researchers are demonstrating increasing interest in using data linked from multiple sources to support measurement of clinical performance and patient health outcomes. However, the utility of data linkage may be compromised by sub-optimal or incomplete linkage, leading to systematic bias. In this study, we synthesize the evidence identifying participant or population characteristics that can influence the validity and completeness of data linkage and may be associated with systematic bias in reported outcomes

Trends in invasive bacterial diseases during the first 2 years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries and territories in the IRIS Consortium.

BACKGROUND The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases during the first 2 years of the COVID-19 pandemic compared to the 2 years preceding the pandemic. METHODS For this prospective analysis, laboratories in 30 countries and territories representing five continents submitted surveillance data from Jan 1, 2018, to Jan 2, 2022, to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype or group were examined. Interrupted time-series analyses were done to quantify the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models were used to estimate effect sizes and forecast counterfactual trends by hemisphere. FINDINGS Overall, 116 841 cases were analysed: 76 481 in 2018-19, before the pandemic, and 40 360 in 2020-21, during the pandemic. During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio 0·47; 95% CI 0·40-0·55), H influenzae (0·51; 0·40-0·66) and N meningitidis (0·26; 0·21-0·31), while no significant changes were observed for S agalactiae (1·02; 0·75-1·40), which is not transmitted via the respiratory route. No major changes in the distribution of cases were observed when stratified by patient age or serotype or group. An estimated 36 289 (95% prediction interval 17 145-55 434) cases of invasive bacterial disease were averted during the first 2 years of the pandemic among IRIS-participating countries and territories. INTERPRETATION COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae, and N meningitidis during the first 2 years of the pandemic, but cases began to increase in some countries towards the end of 2021 as pandemic restrictions were lifted. These IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to health-care service planning and provision of policies. FUNDING Wellcome Trust, NIHR Oxford Biomedical Research Centre, Spanish Ministry of Science and Innovation, Korea Disease Control and Prevention Agency, Torsten Söderberg Foundation, Stockholm County Council, Swedish Research Council, German Federal Ministry of Health, Robert Koch Institute, Pfizer, Merck, and the Greek National Public Health Organization

Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis

Background Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes. Methods We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses. Findings A locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55–2·08], p=5·13×10– ¹⁵) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42–1·71], p=7·65×10– ²⁰) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25–1·48], p=1·69×10– ¹²; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI 12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02–8·05]), despite similar baseline disease severity. Interpretation This is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials. Funding UK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR

Germline selection shapes human mitochondrial DNA diversity.

Approximately 2.4% of the human mitochondrial DNA (mtDNA) genome exhibits common homoplasmic genetic variation. We analyzed 12,975 whole-genome sequences to show that 45.1% of individuals from 1526 mother-offspring pairs harbor a mixed population of mtDNA (heteroplasmy), but the propensity for maternal transmission differs across the mitochondrial genome. Over one generation, we observed selection both for and against variants in specific genomic regions; known variants were more likely to be transmitted than previously unknown variants. However, new heteroplasmies were more likely to match the nuclear genetic ancestry as opposed to the ancestry of the mitochondrial genome on which the mutations occurred, validating our findings in 40,325 individuals. Thus, human mtDNA at the population level is shaped by selective forces within the female germ line under nuclear genetic control, which ensures consistency between the two independent genetic lineages.NIHR, Wellcome Trust, MRC, Genomics Englan

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

Mycorrhizal Colonization and Nutrition of Wheat and Sweet Corn Grown in Manure-Treated and Untreated Topsoil and Subsoil

Dry bean yields (Phaseolus vulgaris L.) were raised to similar levels as the topsoil by manure application to eroded or leveled Portneuf silt loam soil (coarse-silty mixed mesic Durixerollic Calciorthid). Only soil organic matter and zinc (Zn) content of leaf tissue were correlated with improved yields. Manure application increased mycorrhizal colonization and Zn uptake in pot experiments with dry bean which would explain the increased yields in the field. A field study was conducted to see if similar effects of manure and mycorrhizal colonization could be observed in field grown spring wheat (Triticum aestivum L.) and sweet corn (Zea mays L.). This study was conducted on existing experiments established in the spring of 1991 at the USDA-ARS farm in Kimberly, Idaho, to study crop rotation/organic matter amendment treatments on exposed subsoils and focused on mycorrhizal colonization as related to topsoils and subsoils treated with conventional fertilizer (untreated) or dairy manure. Mycorrhizal root colonization was higher with untreated than with manure-treated-wheat and sweet corn. Root colonization was also higher in subsoil than in topsoil for wheat, but there were no differences between soils for sweet corn. Shoot Zn and manganese (Mn) concentrations generally increased with increased root colonization for both species (except between soils with corn Mn contents). Wheat shoot potassium (K) concentration was increased by manure application, but the affect declined with time, was the opposite of colonization and was not observed with sweet corn. Phosphorus (P), calcium (Ca), magnesium (Mg), iron (Fe), and copper (Cu) concentrations either were not influenced or were erratically affected by mycorrhizal colonization. Yields of wheat were highest for manure-treated subsoil and topsoil compared to untreated soils. Mycorrhizal colonization was different between conventional and manure-treated soils and between topsoil and subsoil and these differences increased Zn and Mn uptake, but they did not explain the improvement in wheat yields obtained with manure application