Mitochondrial iron chelation ameliorates cigarette-smoke induced bronchitis and emphysema in mice

Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants. We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene, with IRP2 protein increased in the lungs of individuals with COPD. Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD. By integrating RIP-Seq, RNA-Seq, gene expression and functional enrichment clustering analysis, we identified IRP2 as a regulator of mitochondrial function in the lung. IRP2 increased mitochondrial iron loading and cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD. Frataxin-deficient mice with higher mitochondrial iron loading had impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas synthesis of cytochrome c oxidase (Sco2)-deficient mice with reduced COX were protected from CS-induced pulmonary inflammation and impairment of MCC. Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD. Mitochondrial iron chelation also alleviated CS-impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD

Sources and rates of potassium for sweet orange production

Fruit yield and quality of citrus trees (Citrus spp.) is markedly affected by potassium (K) fertilization. Potassium chloride is the major source of K, even though other sources are also available for agricultural use when crops are sensitive to chloride or where potential for accumulation of salts in soils exists. Only few studies addressed the effect of K sources on yield and quality of citrus fruits. Therefore, the present study was conducted to evaluate K2SO4 and KCl fertilizer sources at 0, 100, 200, and 300 kg ha-1 per year K2O on fruit yield and quality of 'Pêra' and 'Valencia' sweet orange trees in the field. The experiments were carried out in a 4 × 2 factorial design under randomized complete blocks, with four replicates from 2001 to 2004. Fruit yield increased with increased K fertilization. Nutrient rate for maximum economic yield of 'Pêra' was 200 kg ha-1 of K2O and for 'Valencia', 270 kg ha-1 of K2O. Differences were attributed to higher production and K exportation by fruits of 'Valencia'. Fruit mass also increased with increased K fertilization what decreased total soluble solids in juice, and which correlated with leaf K concentrations for 'Valencia' (r = 0.76; p < 0.05). Leaf Ca, Mg and B concentrations decreased with K rates. Additionally, leaf Cl increased up to 440 mg kg-1 with KCl rates, even though no negative effects occurred either on fruit yield or quality of trees

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease