Soil acidity and mobile aluminum status in pseudogley soils in the Čačak-Kraljevo Basin

Soil acidity and aluminum toxicity are considered the most damaging soil conditions affecting the growth of most crops. This paper reviews the results of tests of pH, exchangeable acidity and the mobile aluminum (Al) concentration in profiles of pseudogley soils from the Čačak-Kraljevo Basin. For these purposes, 102 soil pits were dug in 2009 in several sites around the Čačak-Kraljevo Basin. The tests encompassed 54 field, 28 meadow, and 20 forest soil samples. Samples of soil in a disturbed state were taken from the Ah and Eg horizons (102 samples), from the B1tg horizon in 39 field, 24 meadow and 15 forest pits (a total of 78 samples) and from the B2tg horizon in 14 field, 11 meadow, and 4 forest pits (a total of 29 samples). The mean pH values (1 M KCl) of the tested soil profiles were 4.28, 3.90 and 3.80 for the Ah, Eg and B1tg horizons, respectively. The soil pH of the forest samples was lower than those in the meadow and arable land samples (mean values of 4.06, 3.97 and 3.85 for arable land, meadow and forest samples, respectively). The soil acidification was especially intensive in the deep horizons; thus, 27 (Ah), 77 (Eg) and 87 % (B1tg) of the soil samples had a pH value below 4.0. The mean values of the total exchangeable acidity (TEA) were 1.55, 2.33 and 3.40 meq (100 g)-1 for the Ah, Eg and B1tg horizons, respectively. The TEA values in the forest soils were considerably higher (3.39 meq (100 g)-1) than those in the arable and meadow soils (1.96 and 1.93 meq (100 g)-1, respectively). The mean mobile Al contents of the tested soil samples were 11.02, 19.58 and 28.33 mg Al (100 g)-1 for the Ah, Eg and B1tg horizons, respectively. According to the pH and TEA values, mobile Al was considerably higher in the forest soils (a mean value of 26.08 mg Al (100 g)-1) than in the arable and meadow soils (mean values of 16.85 and 16.00 mg Al (100 g) -1, respectively). The Eg and B1tg horizons of the forest soil had especially high mobile Al contents (mean values of 28.50 and 32.95 mg Al (100 g)-1, respectively). High levels of mobile Al were especially frequent in the forest soils, with 35 (Ah), 85.0 (Eg) and 93.3 % (B 1tg) of the tested samples ranging above 10 mg Al (100 g) -1

Dose imbalance of DYRK1A kinase causes systemic progeroid status in Down syndrome by increasing the un-repaired DNA damage and reducing LaminB1 levels.

BACKGROUND: People with Down syndrome (DS) show clinical signs of accelerated ageing. Causative mechanisms remain unknown and hypotheses range from the (essentially untreatable) amplified-chromosomal-instability explanation, to potential actions of individual supernumerary chromosome-21 genes. The latter explanation could open a route to therapeutic amelioration if the specific over-acting genes could be identified and their action toned-down. METHODS: Biological age was estimated through patterns of sugar molecules attached to plasma immunoglobulin-G (IgG-glycans, an established "biological-ageing-clock") in n = 246 individuals with DS from three European populations, clinically characterised for the presence of co-morbidities, and compared to n = 256 age-, sex- and demography-matched healthy controls. Isogenic human induced pluripotent stem cell (hiPSCs) models of full and partial trisomy-21 with CRISPR-Cas9 gene editing and two kinase inhibitors were studied prior and after differentiation to cerebral organoids. FINDINGS: Biological age in adults with DS is (on average) 18.4-19.1 years older than in chronological-age-matched controls independent of co-morbidities, and this shift remains constant throughout lifespan. Changes are detectable from early childhood, and do not require a supernumerary chromosome, but are seen in segmental duplication of only 31 genes, along with increased DNA damage and decreased levels of LaminB1 in nucleated blood cells. We demonstrate that these cell-autonomous phenotypes can be gene-dose-modelled and pharmacologically corrected in hiPSCs and derived cerebral organoids. Using isogenic hiPSC models we show that chromosome-21 gene DYRK1A overdose is sufficient and necessary to cause excess unrepaired DNA damage. INTERPRETATION: Explanation of hitherto observed accelerated ageing in DS as a developmental progeroid syndrome driven by DYRK1A overdose provides a target for early pharmacological preventative intervention strategies. FUNDING: Main funding came from the "Research Cooperability" Program of the Croatian Science Foundation funded by the European Union from the European Social Fund under the Operational Programme Efficient Human Resources 2014-2020, Project PZS-2019-02-4277, and the Wellcome Trust Grants 098330/Z/12/Z and 217199/Z/19/Z (UK). All other funding is described in details in the "Acknowledgements"