An iron sickle found in an ancient burial urn at Parudur near Thrithala in Pattambi taluk of Palakkad district has triggered the curiosity of researchers about the agricultural practices that prevailed in the megalithic period.

K. Rajan, professor of history from Sree Neelakanta Government Sanskrit College, Pattambi, estimated the sickle to be around 2,500 years old. He had found similar iron tools dating back to megalithic period from different sites in Palakkad district.

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Thirty-eight % of obese children and adolescents showed a variable impairment of cell-mediated immune responses in vivo and in vitro and reduction of intracellular bacterial killing by polymorphonuclear leukocytes. The obese group had a higher incidence of iron deficiency and moderately lower serum zinc concentrations. Levels of serum immunoglobulins, complement components C3 and C4, and numbers of T and B lymphocytes were comparable in the two groups. Serum triglycerides, cholesterol and lipoproteins were normal in all subjects. Immunologic changes correlated with the presence of subclinical deficiencies of iron and zinc. Therapy with these micronutrients for 4 weeks resulted in improvement in immunologic responses.

Abstract:Oil and gas effluents contains highly toxic and harmful organic pollutants. Therefore, it is necessary to eliminate and/or reduced the concertation of organic pollutants to a technologically acceptable levels before their discharge into water streams. This study investigates the application of nanoscale zero-valent iron (nZVI), and hydrogen peroxide (H2O2) for removal of organic pollutants from real oily produced water. Batch studies were performed and effect of different operating parameters, including concentration of nZVI and H2O2, pH and reaction time were studied. Moreover, optimization of independent variables was performed using central composite design (CCD) in response surface methodology (RSM). The experimental set up provided maximum removal efficiencies of 89.5% and 75.3% for polycyclic aromatic hydrocarbons (PAHs) and chemical oxygen demand (COD), respectively. The optimum values of independent variables such as concentrations of nZVI, and H2O2, contact time and pH were obtained as 4.35 g/L, 1.60 g/L, 199.9 min and 2.9, respectively. Predicted PAHs and COD removal efficiencies at the optimum values of independent variables were found as 89.3% and 75.7%, respectively which are in line with the experimental values. The study indicates that application of heterogeneous Fenton like oxidation system using nZVI as a catalyst is an efficient treatment method for removal of organic pollutants from real produced water.Keywords: produced water; polycyclic aromatic hydrocarbon; COD; nanoscale zero-valent iron; response surface methodology

Histochemical detection of iron in AD (A) compared with control cases (B) show striking association of iron with neurofibrillary tangles (arrowheads) and senile plaques (arrows) characteristic of the AD brain. (Scale bar = 200 m.)

While the source of iron that is associated with the lesions is unknown, it is of note that the pattern of redox-available iron in neurons is strikingly similar to the localization of heme oxygenase-1 (3), an enzyme responsible for the conversion of heme into antioxidant tetrapyrroles and free iron. Thus, in cases where there is chronic induction of heme oxygenase, such as in AD, enzyme inhibitors such as zinc protoporphyrin, along with iron chelation therapies, may slow iron accumulation.

A. fumigatus is isolated in 60% of the cystic fibrosis patients with P. aeruginosa infection14, demonstrating a close relationship between the established colonization by P. aeruginosa and a superinfection by A. fumigatus. While numerous studies have investigated P. aeruginosa/C. albicans interactions, interactions between P. aeruginosa and A. fumigatus remain poorly understood despite yearly increases in this coinfection but with the bacterial/yeast infections remaining stable15. A. fumigatus and P. aeruginosa share common features, such as the adhesion to basal membrane, chronic colonization of the upper respiratory track, induction of inflammation, causing damage to the respiratory functions of the patients. Previous studies demonstrated that phenazines inhibited growth of A. fumigatus but the underlying mechanisms were not characterized16,17. Moreover, nothing is known about the impact of these four phenazines on A. fumigatus biology apart from the fact that 1-HP induces production of siderophores by this fungus. Based on the functions of P. aeruginosa on host cells, it was hypothesized that these phenazines could be inhibitory to A. fumigatus growth due to ROS stimulation and perturbation in the availability of iron.

A. fumigatus produces two extracellular siderophores for iron acquisition, i.e., fusarinine C (FsC) and triacetylfusarinine C (TAFC) and two intracellular siderophores for storage and transport of iron, i.e, ferricrocin (FC) and hydroxyferricrocin (HFC)22. Extracellular siderophores are essential for fungal growth in the host because they help to acquire iron from transferrin during the course of infection23,24. The siderophore biosynthetic pathway is schematized in Supplementary Figure 2. SidAp catalyzes the first committed step in biosynthesis of extra- and intracellular siderophores and consequently, the sidA mutant is unable to produce any siderophores25. The subsequent, pathways for downstream synthesis of extra- and intracellular siderophores split, with SidFp and SidDp are required for production of the extracellular siderophores while SidCp is required for production of intracellular siderophores22. The expression of these genes is alternately regulated by two transcription factors, SreAp and HapXp. SREA is expressed in presence of iron repressing the synthesis of siderophores and alternative reductive iron assimilation. During iron starvation conditions however, HAPX is expressed, activating the synthesis of siderophores and simultaneously repressing iron-consuming pathways26,27,28.

To study the role of phenazines in iron acquisition by A. fumigatus, we tested the effect of phenazines on the growth of A. fumigatus mutant strains lacking (i) the major iron-regulatory transcription factors, sreA and hapX, (ii) extracellular siderophore biosynthesis due to deficiency in two enzymes, SidDp and SidFp, or (iii) intracellular siderophores due to deficiency the SidCp enzyme. The MICs of PYO, PCN and PCA were similar between the control strains and mutants (Table 2) suggesting an iron-independent inhibitory effect of these three phenazines. However, while the MIC of 1-HP was similar against sreA, sidC and the parental strain, the hapX, sidD and sidF mutants, in contrast, were two to four times more susceptible to 1-HP compared to the parental strain (Table 2). Previous studies showed that HAPX, SIDD and SIDF were transcriptionally induced during iron starvation and were required for adaptation under iron-depleted conditions27,28. In comparison, SIDC was less activated during iron-limiting conditions and consequently, sidC growth was less affected27,28. The increased susceptibility of hapX, sidD and sidF mutants to 1-HP suggests that this phenazine causes iron starvation conditions for A. fumigatus, possibly by chelation of iron, which is thereby compensated by the activity of HapXp and extracellular siderophore biosynthesis. In agreement with this line of reasoning, supplementation with exogenous purified TAFC restored 1-HP susceptibility of hapX, sidD and sidF mutants to parental strain levels (Table 2).

To further characterize the effects of 1-HP on the metabolism of iron in A. fumigatus, we studied the short-term impact of phenazines at the transcriptional level, by analyzing genes involved in iron responses. Northern blot analyses in figure 6 show that 1-HP caused an induction of genes previously shown to be induced by iron starvation including the iron regulator-encoding gene HAPX, the siderophore transporter-encoding gene MIRB, as well as the siderophore biosynthetic genes SIDA, SIDF and SIDG27,28. Inversely, 1-HP caused down-regulation of genes that have previously been shown to be repressed during iron-depleted conditions including aconitase-encoding ACOA and cytochrome c-encoding CYCA27,28 (Figure 6). These data clearly demonstrate that 1-HP causes an iron starvation response in A. fumigatus, which is in accordance with the 1-HP hypersensitivity of mutants impaired in adaptation to iron starvation as well as the previously shown 1-HP-mediated stimulation of siderophore production in A. fumigatus17. Taken together, these results indicated that these mechanisms were required to compensate the iron starvation caused by 1-HP and were in agreement with the increased susceptibility of mutants impaired in adaptation to iron starvation (hapX, sidD and sidF, see above).

Fe(II) could penetrate in the A. fumigatus cells through the low-affinity ferrous iron uptake, which has not yet been identified at the molecular level yet, or Fe(II) is reoxidized and imported by the protein complex consisting of the ferroxidase FetCp and the ferric iron permease FtrAp25. In presence of sub-inhibitory concentrations of PYO, PCN and PCA, the growth defect of sidAftrA in 2YT was not restored (Figure 9). This result shows that PYO, PCN and PCA generate Fe(II) by the reduction of Fe(III), which is then taken up by the FetC/FtrA complex and not by the low-affinity Fe(II) uptake system.

1-HP was found to be the most active phenazine against A. fumigatus. In addition to the ROS production, its high inhibitory activity is due to a characteristic specific to this phenazine. We demonstrate for the first time that 1-HP is able to chelate iron. Previous data showed that 1-HP induces the production of the extracellular siderophores FsC and TAFC by A. fumigatus17. Here we found that (i) mutants impaired in iron adaptation (hapX sidD and sidF) are hypersusceptible to 1-HP, (ii) addition of TAFC reduces the inhibitory activity of 1-HP against hapX, sidD and sidF, (iii) 1-HP transcriptionally induces an iron starvation response, i.e. it induces genes required for adaptation to iron starvation (HAPX, SIDA, SIDF, SIDG, MIRB) and represses genes encoding iron-dependent proteins (ACOA, CYCA) and (iv) 1-HP is able to chelate iron (Figure 8). Taken together, these results strongly suggest that 1-HP causes iron starvation in A. fumigatus by chelating iron, which is partially compensated by the fungal enzymatic and regulatory mechanisms involved in adaptation to iron starvation. As shown before, PYO, PCA and PCN were not found to be chelators41. 589ccfa754

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