Pleiotropic Effect Analysis and Marker Development for Grain Zinc and Iron Concentrations in Spring wheat

Wheat (Triticum aestivum L.) is one of the main food crops in the world and a primary source of zinc (Zn) and iron (Fe) in the human body. The genetic mechanisms underlying related traits have been clarified, thereby providing a molecular theoretical foundation for the development of germplasm resources. In this study, 23,536 high-quality DArT markers were used to map quantitative trait loci (QTL) of grain Zn (GZn) and grain Fe (GFe) concentrations in recombinant inbred lines from Avocet/Chilero. A total of 17 QTLs located on chromosomes 1BL, 2BL, 3BL, 4AL, 4BS, 5AL, 5DL, 6AS, 6BS, 6DS, and 7AS accounted for 0.38–16.62% of the phenotypic variance. QGZn.haust-4AL, QGZn.haust-7AS.1, and QGFe.haust-6BS were detected on chromosomes 4AL, 6BS, and 7AS, accounting for 10.63–16.62% of the phenotypic variance. Four stable QTLs, QGZn.haust-4AL, QGFe.haust-1BL, QGFe.haust-4AL, and QGFe.haust-5DL were located on chromosomes 1BL, 4AL, and 5DL. Three pleiotropic effects locus for GZn and GFe concentrations were located on chromosomes 1BL, 4AL, and 5DL. Two high-throughput Kompetitive Allele Specific PCR markers were developed by closely linking single nucleotide polymorphisms on chromosomes 4AL and 5DL, which were validated by a germplasm panel. Therefore, it is the most important that quantitative trait loci and KASP marker for grain zinc and iron concentrations were developed for utilizing in marker-assisted breeding and biofortification of wheat grain in breeding programs.

Field Trial of an Automated Batch Chlorinator System at Two Shared Shallow Tubewells among Camps for Forcibly Displaced Myanmar Nationals (FDMN) in Cox’s Bazar, Bangladesh

Chlorination of shallow tubewell water is challenging due to various iron concentrations. A mixed-method, small-scale before-and-after field trial assessed the accuracy and consistency of an automated chlorinator, Zimba, in Rohingya camp housing, Cox’s Bazar. From August–September 2018, two shallow tubewells (iron concentration = 6.5 mg/L and 1.5 mg/L) were selected and 20 households were randomly enrolled to participate in household surveys and water testing. The field-team tested pre-and post-treated tubewell and household stored water for iron, free and total chlorine, and E. coli. A sub-set of households (n = 10) also received safe storage containers (5 L jerry cans). Overall mean iron concentrations were 5.8 mg/L in Zimba water, 1.9 mg/L in household storage containers, and 2.8 mg/L in the project-provided safe storage containers. At baseline, 0% samples at source and 60% samples stored in household vessels were contaminated with E. coli (mean log10 = 0.62 MPN/100 mL). After treatment, all water samples collected from source and project-provided safe storage containers were free from E. coli, but 41% of post-treated water stored in the household was contaminated with E. coli. E. coli concentrations were significantly lower in the project-provided safe storage containers (log10 mean difference = 0.92 MPN, 95% CI = 0.59–1.14) compared with baseline and post-treated water stored in household vessels (difference = 0.57 MPN, 95% CI = 0.32–0.83). Zimba is a potential water treatment technology for groundwater extracted through tubewells with different iron concentrations in humanitarian settings.

Association between congenital heart defects and maternal manganese and iron concentrations: a case–control study in China

To investigate the correlation between maternal manganese and iron concentrations and the risk of CHD among their infant. A multi-center hospital-based case control study was conducted in China. There were 322 cases and 333 controls have been selected from pregnant women who received prenatal examinations. Correlations between CHDs and maternal manganese and iron concentrations were estimated by conditional logistic regression. Moreover, the interaction between manganese and iron on CHDs was analyzed. Compared with the controls, mothers whose hair manganese concentration was 3.01 μg/g or more were more likely to have a child with CHD than those with a lower concentration. The adjusted OR was 2.68 (95%CI = 1.44–4.99). The results suggested that mothers whose iron content was 52.95 μg/g or more had a significantly higher risk of having a child with CHD (aOR = 2.87, 95%CI = 1.54–5.37). No interaction between maternal manganese and iron concentrations was observed in the multiplicative or additive model. The concurrently existing high concentration of manganese and iron may bring higher risk of CHD (OR = 7.02). Women with excessive manganese concentrations have a significantly increased risk of having offspring with CHDs. The high maternal iron status also correlates with CHDs. The concurrently existing high concentration of manganese and iron may bring higher risk of CHD.

In vitro plant growth promoter assay of actinobacteria potential for tidal land farming

The use of tidal land for agricultural still faces constraints, mainly due to high iron content. Actinobacteria produce bioactive compound with many functions. The aim of this work was to assess the growth of actinobacteria at various iron concentrations and its capability as plant growth promoter. Four actinobacteria isolates (Cal31t, Dbi28t, Crc32t and Cal24h) were grown at various iron concentrations. The isolates were examined for their capability to produce IAA and fix N2 under in vitro assay. The growth of actinobacteria under stress conditions was examined by cultivating them in ISP2 medium at pH 4, 3% NaCl, 750 mg.L−1 AlCl3 and 8 concentrations of FeCl3, i.e. 0, 500, 1000, 2000, 4000, 8000, 16000, 32000 mg.L−1. Actinobacteria isolates were able to grow under iron stress condition up to 32.000 mg.L−1. Both Cal3t and Dbi28t produced higher cell biomass compared with the other two tested isolates. All isolates produced IAA when grown under iron stress condition up to 4000 mg.L−1 of FeCl3, were able to grow under N-free medium and capable to produce ammonia at various concentrations. Crc32t produced the highest number of ammonia (0,354 mg.L−1). Cal31t and Crc32t isolates have the potency as plant growth promoter in tidal land farming.

Comparative Analysis of Aminopolycarboxylate Chelants Improves Iron Control in Acidizing Operations

Aminopolycarboxylate-based chelants are used to control iron precipitation during acidizing operations by interacting directly with the iron, resulting in water-soluble complexes. This paper highlights that, in order to improve the effectiveness of iron control during acidizing operations, the type and the concentration of the chelants should be based on the formation properties and the well characteristics by comparing the cheltors’ performance as iron-control agents at different temperatures and pH environments with different levels of iron concentrations and chelant to iron molar ratios in acid (HCl). This study also addresses the interactions between the tested iron-control additives and acid, as well as the performance of the chelants in carbonate cores. Laboratory experiments were conducted to investigate the performance of nitrilotriacetic acid (NTA), glutamic acid, N, N-diacetic acid (GLDA), diethylenetriaminepentaacetic acid (DTPA), ethylenediamine-tetraacetic acid (EDTA), and hydroxyethylethylenediaminetriacetic acid (HEDTA) as iron control additives in 5 wt% HCl at pH values 0 to 4.5 to simulate carbonate acidizing at temperatures of 70 to 300°F, and initial iron concentrations of 2000 ppm. The performance of NTA and EDTA was also compared at higher initial iron concentration (4000 ppm). This work also quantified the effects of acid additives such as corrosion inhibitor and non-ionic surfactant on the chelation performance. Coreflood experiments using carbonate cores in acid with chelant helped determine its influence on permeability. Testing chelant-to-acid molar ratios of 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, and 2:1 relative to iron concentration yielded optimal values. Additional tests monitored iron precipitation in solution using an inductively coupled argon plasma (ICAP) emission spectroscopy. Precipitates were filtered and analyzed using X-ray diffraction (XRD), X-ray fluorescence (XRF), and scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS). Without chelant, at 70°F and 2000 ppm initial iron concentration, precipitation began at pH 1.45 and completed by pH 2.42. At 150 and 210°F, iron precipitated at pH 0.68 and 0.3 and completed by pH 1.3 and 1, respectively. At 70°F, NTA showed a minimum of 98% chelation at pH 4.3; however, its performance declined at 150°F to 74% chelation at pH 4.24, and at 210°F to 53% chelation at pH 4.0. Although DTPA dissolves completely in live acid, precipitations occurred at partially spent acid. At pH 0.15, SEM-EDS showed that the precipitate contains as much as 13 wt% iron. Thus, DTPA is not a suitable iron-control agent. HEDTA showed a 90% chelation at 210°F and pH 4.8. GLDA's performance declined to less than 50% at 150°F. At higher iron concentrations of 4000 ppm, Na3NTA kept all iron in solution in a 5 wt% HCl up to pH 4.0 at 70°F and its performance declined to a minimum of 97% at pH 4.7 at same temperature. At 150°F, and 210°F, Na3NTA started to gradually decline at pH values greater than 3.9, and 3.5, respectively. The minimum chelation reached by NTA was 91% at pH 4.4, at 150°F, and 73% at pH 4 at 210°F. Upon comparing the NTA's results at high iron concentrations to the popular EDTA, Na4EDTA at 1-to-1 mole ratio with iron exceeded its maximum solubility in 5 wt% HCl and precipitated in the original solution. For NTA, a molar ratio of 1.4:1 is optimal at 70 and 150°F, showing chelation performance of 95% and 94%, respectively, while a molar ratio of 1.5:1 is optimal at 210°F, showing a chelation performance of 87%. This study's results improve field operations by identifying NTA and HEDTA as having the best iron-control chelation performance of the five additives tested, thus reducing guesswork and streamlining production. The work also provided recommendations for choosing the best type of iron-control agent based on solubility and coreflood analysis. The results can be used to design more efficient acidizing fluids. This work won second place in the Masters division of the 2020 Gulf Coast Regional Student Paper Contest, April 2020.

Erythroferrone Modulates Iron Distribution for Fetal Erythropoiesis

Erythroferrone (ERFE) is an erythroblast-derived regulator of iron metabolism, and its production increases during stress erythropoiesis. ERFE decreases expression of the iron-regulatory hormone hepcidin to enhance iron availability for erythropoiesis 1. Pregnancy requires a substantial increase in iron availability to sustain a dramatic increase in maternal RBC volume and support fetal development. Whether maternal or fetal ERFE plays a role in regulating iron homeostasis during pregnancy is unknown. In humans, maternal ERFE concentrations were elevated in anemic pregnancies at mid gestation and delivery 2. To define the role of ERFE during iron-replete or iron-deficient pregnancy, we utilized Erfe transgenic (ETg) 3 and Erfe knockout (EKO) 1 mice. Maternal iron status of ETg, WT and EKO mice was altered by placing animals on adequate iron (100ppm) or low iron (4ppm) diet 2 weeks prior to and throughout pregnancy. ETg and WT dams were mated with WT sires to generate ETg and WT embryos while EKO dams were mated with EKO sires to generate EKO embryos. Analysis was performed at embryonic day 18.5. To examine the effect of pregnancy on ERFE expression, we compared non-pregnant females to WT dams at E18.5. Serum ERFE was mildly elevated from 0.01 to 0.2 ng/mL in iron-replete dams, but substantially elevated from 0.01 to 3.1 ng/mL in iron-deficient dams, similarly to human pregnancy 2. We next assessed iron and hematological parameters in pregnant dams with different Erfe genotypes. Under iron-replete conditions, all three groups had similar serum hepcidin, serum iron and hemoglobin concentrations, but ETg dams had 3-fold higher liver iron than WT and EKO dams, presumably because they are mildly iron-overloaded before pregnancy. On iron-deficient diet, maternal hepcidin was decreased in all three genotypes but more so in ETg dams; however, all three Erfe genotypes had similarly depleted liver iron stores, hypoferremia and anemia. MCV was the only parameter that was decreased in EKO compared to WT dams under both iron conditions. Overall, maternal ERFE played a minor role in regulation of maternal erythropoiesis and iron homeostasis, with the lack of ERFE resulting in smaller RBCs but not anemia. Among embryos, we observed a significant effect of Erfe genotype on embryo hepcidin. ETg embryos had significantly lower liver hepcidin compared to WT embryos under both iron-replete and iron-deficient conditions. Conversely, Erfe KO embryos had higher hepcidin compared to WTs under iron-deficient conditions, indicating that embryo ERFE regulates embryo hepcidin during pregnancy. Under iron-replete conditions however, all three embryo genotypes had similar hematologic parameters, and embryo liver iron was dependent on maternal iron levels, with both ETg and WT embryos from ETg dams having increased liver iron concentrations, indicating that embryo ERFE does not regulate placental iron transfer. Under iron-deficient conditions, there was no difference between ETg and WT embryos in hematological or iron parameters, and both genotypes developed iron deficiency and anemia. However, Erfe KO embryos, which had elevated hepcidin, had maldistribution of iron and worse anemia. EKO embryo liver iron concentrations were 6-fold higher compared to WT iron-deficient embryos, whereas hemoglobin was significantly decreased compared to WT iron-deficient embryos. These findings indicate that under iron-limiting conditions, embryo ERFE is important for the suppression of embryo hepcidin to ensure iron redistribution for embryo erythropoiesis. In summary, during iron replete pregnancy, ERFE plays a minor role in maternal and fetal iron homeostasis and erythropoiesis. However, in response to iron-deficiency anemia during pregnancy, ERFE is important for the redistribution of iron within the embryo to support embryo erythropoiesis. 1Kautz L et al, Nat Genet, 2014 2Delaney K et al, Curr Dev Nutr, 2020 3Coffey R et al, Blood, 2020 Disclosures Ganz: Ambys: Consultancy; Sierra Oncology: Consultancy, Research Funding; Rockwell: Consultancy; Pharmacosmos: Consultancy; Ionis: Consultancy; Protagonist: Consultancy; Intrinsic LifeSciences: Consultancy; RallyBio: Consultancy; Silence Therapeutics: Consultancy; Silarus Pharma: Consultancy; Alnylam: Consultancy; American Regent: Consultancy; Disc Medicine: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZenecaFibrogen: Consultancy; Global Blood Therapeutics: Consultancy; Gossamer Bio: Consultancy; Akebia: Consultancy, Honoraria. Nemeth: Silarus Pharma: Consultancy; Intrinsic LifeSciences: Consultancy; Protagonist: Consultancy; Vifor: Consultancy; Ionis: Consultancy.

Association between serum iron concentrations and cognitive impairment in older adults aged 60 years and older: A dose-response analysis of National Health and Nutrition Examination Survey

Epidemiological evidence on peripheral iron and cognitive impairment in older adults is sparse and limited. Results on serum iron and cognitive impairment in older adults from the National Health and Nutrition Examination Survey have not been reported. Data on serum iron and cognitive impairment from individuals ≥ 60 years of age were obtained from the 2011–2014 NHANES (N = 3,131). Serum iron concentrations were determined with DcX800 method. Cognitive impairment was assessed with four cognitive tests: the Digit Symbol Substitution Test (DSST), the Animal Fluency (AF), the Consortium to Establish a Registry for Alzheimer’s Disease Delayed Recall (CERAD-DR) and Word Learning (CERAD-WL) tests. Logistic regression and restricted cubic splines were adopted to explore the dose-response relationship between serum iron concentrations and cognitive impairment. Comparing the highest to lowest tertile of serum iron concentrations, the multivariate-adjusted odds ratios of scoring low on the DSST were 0.70 (0.49–1.00), 0.88 (0.65–1.20) for CERAD-WL, 0.65 (0.48–0.88) for CERAD-DR, and 0.78 (0.53–1.15) for AF. Stratified analyses by sex showed that the above-mentioned associations were mainly found in men; however, the interaction with sex was not significant. Dose-response analysis showed that relationships between serum iron and cognitive impairment evaluated by DSST and CERAD-DR were linear, respectively.

Melatonin and Indole-3-Propionic Acid Reduce Oxidative Damage to Membrane Lipids Induced by High Iron Concentrations in Porcine Skin

Iron excess in tissues results in increased oxidative damage. Among different tissues, the skin can particularly be severely damaged by oxidative stress, as it is exposed not only to endogenous but also directly to exogenous pro-oxidants. The skin is especially vulnerable to harmful oxidative stress. Melatonin and indole-3-propionic acid (IPA), two indole substances, are efficient antioxidants. This study aims to evaluate the potential protective effects of melatonin and IPA against oxidative damage to membrane lipids (lipid peroxidation (LPO)), induced in porcine skin homogenates by the Fenton reaction (Fe2+ + H2O2 → Fe3+ + •OH + OH−) when iron is used in extremely high concentrations. Skin homogenates were incubated in the presence of FeSO4 (2400, 1200, 600, 300, 150 and 75 µM) + H2O2 (5 mM) with/without melatonin or IPA. LPO level (MDA + 4-HDA/mg protein) was measured spectrophotometrically. Melatonin, in its highest used concentration (5.0 mM), prevented FeSO4 (1200 mM)-induced LPO, whereas it was effective in concentrations as low as 2.5 mM against all lower iron concentrations. IPA was protective in concentrations as low as 2.5 mM independently of FeSO4 concentration. In conclusion, melatonin and IPA effectively protect against oxidative damage to membrane lipids induced by high concentrations of iron in porcine skin; therefore, both can be considered pharmacological agents in the case of disorders associated with excessive iron accumulation in the skin.