Macrophage angiotensin AT2 receptor activation is protective against early phases of LPS-induced acute kidney injury.

Lipopolysaccharide (LPS)-induced acute kidney injury (AKI) is characterized by inflammation and infiltration of immune cells, mainly neutrophils and macrophages, and results in sudden renal dysfunction. Previously, we have reported the anti-inflammatory and renoprotective role of the angiotensin II type 2 receptor (AT2R), expressed on kidney tubular cells and immune cells, in LPS-induced AKI. Moreover, in vitro studies revealed macrophage AT2R activation shifts the cells to the anti-inflammatory M2 subtype. However, the protective role of the macrophage AT2R in a model of AKI is unknown. The present study addressed this question by adoptive transfer of bone marrow-derived macrophages (BMDMs) in systemic macrophage-depleted mice. We acquired significant systemic macrophage depletion by two doses of liposomal clodronate (CLD), and the mice were repopulated with BMDMs (CD11b+F4/80+, double positive) primed with AT2R agonist C21 (CLD + MacC21 + LPS) or vehicle (CLD + Mac + LPS) in vitro for 60 min, followed by LPS (5 mg/kg body wt ip) challenge. We observed a gradual increase in the CD11b+ cells at 2 and 24 h after the LPS challenge. However, kidney CD11b+ cells in the CLD + Mac + LPS group were elevated compared with the CLD + MacC21 + LPS group at 2 h after the LPS challenge. The level of inflammatory cytokine (tumor necrosis factor-α) was elevated at 2 h, which was reduced significantly in CLD + MacC21 + LPS-treated animals. Also, CLD + MacC21 + LPS-treated animals had elevated plasma and renal IL-10, indicating an anti-inflammatory role of C21-treated BMDMs. Renal functional injury in CLD + MacC21 + LPS-treated animals was partially improved. Collectively, the data demonstrate that BMDM AT2R stimulation results in anti-inflammation and partial renoprotection against early stages of LPS-induced AKI.NEW & NOTEWORTHY Endotoxin such as lipopolysaccharide (LPS) induces acute kidney injury (AKI), which is a risk factor for and often leads to chronic kidney diseases. The present study revealed that bone marrow-derived macrophage activation of the angiotensin II type 2 receptor (AT2R) contributes to the anti-inflammation and partial renoprotection against early stages of LPS-induced AKI. Since AT2R is an emerging anti-inflammatory and organ-protective target, this study advances our understanding of AT2R's anti-inflammatory mechanisms associated with renoprotection.

Angiotensin II type 2 receptor activation preserves megalin in the kidney and prevents proteinuria in high salt diet fed rats.

Proteinuria is a risk factor for and consequence of kidney injury. Angiotensin II type 2 receptor (AT2R) is an emerging reno-protective target and is anti-proteinuric under pathological conditions, including high salt-fed obese animals. However, the mechanisms remain unknown, particularly whether the anti-proteinuric activity of AT2R is independent of its anti-hypertensive and anti-inflammatory effects. In the present study, obese Zucker rats were fed high sodium (4%) diet (HSD) for 48 h, a time in which blood pressure does not change. HSD caused proteinuria without affecting glomerular slit diaphragm proteins (nephrin and podocin), glomerular filtration rate, inflammatory and fibrotic markers (TNFα, IL-6, and TGF-ß), ruling out glomerular injury, inflammation and fibrosis but indicating tubular mechanisms of proteinuria. At cellular and molecular levels, we observed a glycogen synthase kinase (GSK)-3ß-mediated megalin phosphorylation, and its subsequent endocytosis and lysosomal degradation in HSD-fed rat kidneys. Megalin is a major proximal tubular endocytic protein transporter. The AT2R agonist C21 (0.3 mg/kg/day, i.p.) administration prevented proteinuria and rescued megalin surface expression potentially by activating Akt-mediated phosphorylation and inactivation of GSK-3ß in HSD-fed rat kidneys. Overall, AT2R has a direct anti-proteinuric activity, potentially via megalin regulation, and is suggested as a novel target to limit kidney injury.

Protecting glomerulus: role of angiotensin-II type 2 receptor.

Podocyte injury due to either drug, toxin, infection, or metabolic abnormality is a great concern as it increases the risk of developing focal segmental glomerulosclerosis (FSGS) and proteinuric kidney diseases. The direct podocyte injury due to doxorubicin is associated with an increase in proinflammatory cytokines and induction of cathepsin L. The increased activity of cathepsin L in turn may degrade the glomerular slit diaphragm resulting in proteinuric kidney injury. The angiotensin-II type 2 receptor (AT2R) has earlier been reported to be associated with the preservation of slit diaphragm proteins and prevention of proteinuria. Recent in vivo findings by Zhang and colleagues further support the anti-proteinuric role of AT2R in preventing podocyte injury via down-regulating cytokines ccl2, and hence, cathepsin L, thereby, limiting the progression of FSGS.

Correction: Transporter genes identified in landraces associated with high zinc in polished rice through panicle transcriptome for biofortification.

[This corrects the article DOI: 10.1371/journal.pone.0192362.].

Transporter genes identified in landraces associated with high zinc in polished rice through panicle transcriptome for biofortification.

Polished rice is poor source of micronutrients, however wide genotypic variability exists for zinc uptake and remobilization and zinc content in brown and polished grains in rice. Two landraces (Chittimutyalu and Kala Jeera Joha) and one popular improved variety (BPT 5204) were grown under zinc sufficient soil and their analyses showed high zinc in straw of improved variety, but high zinc in polished rice in landraces suggesting better translocation ability of zinc into the grain in landraces. Transcriptome analyses of the panicle tissue showed 41182 novel transcripts across three samples. Out of 1011 differentially expressed exclusive transcripts by two landraces, 311 were up regulated and 534 were down regulated. Phosphate transporter-exporter (PHO), proton-coupled peptide transporters (POT) and vacuolar iron transporter (VIT) showed enhanced and significant differential expression in landraces. Out of 24 genes subjected to quantitative real time analyses for confirmation, eight genes showed significant differential expression in landraces. Through mapping, six rice microsatellite markers spanning the genomic regions of six differentially expressed genes were validated for their association with zinc in brown and polished rice using recombinant inbred lines (RIL) of BPT 5204/Chittimutyalu. Thus, this study reports repertoire of genes associated with high zinc in polished rice and a proof concept for deployment of transcriptome information for validation in mapping population and its use in marker assisted selection for biofortification of rice with zinc.

Green solvents and technologies for oil extraction from oilseeds.

Oilseeds are crucial for the nutritional security of the global population. The conventional technology used for oil extraction from oilseeds is by solvent extraction. In solvent extraction, n-hexane is used as a solvent for its attributes such as simple recovery, non-polar nature, low latent heat of vaporization (330 kJ/kg) and high selectivity to solvents. However, usage of hexane as a solvent has lead to several repercussions such as air pollution, toxicity and harmfulness that prompted to look for alternative options. To circumvent the problem, green solvents could be a promising approach to replace solvent extraction. In this review, green solvents and technology like aqueous assisted enzyme extraction are better solution for oil extraction from oilseeds. Enzyme mediated extraction is eco-friendly, can obtain higher yields, cost-effective and aids in obtaining co-products without any damage. Enzyme technology has great potential for oil extraction in oilseed industry. Similarly, green solvents such as terpenes and ionic liquids have tremendous solvent properties that enable to extract the oil in eco-friendly manner. These green solvents and technologies are considered green owing to the attributes of energy reduction, eco-friendliness, non-toxicity and non-harmfulness. Hence, the review is mainly focussed on the prospects and challenges of green solvents and technology as the best option to replace the conventional methods without compromising the quality of the extracted products.

De novo Transcriptome Sequencing to Dissect Candidate Genes Associated with Pearl Millet-Downy Mildew (Sclerospora graminicola Sacc.) Interaction.

Understanding the plant-pathogen interactions is of utmost importance to design strategies for minimizing the economic deficits caused by pathogens in crops. With an aim to identify genes underlying resistance to downy mildew, a major disease responsible for productivity loss in pearl millet, transcriptome analysis was performed in downy mildew resistant and susceptible genotypes upon infection and control on 454 Roche NGS platform. A total of ~685 Mb data was obtained with 1 575 290 raw reads. The raw reads were pre-processed into high-quality (HQ) reads making to ~82% with an average of 427 bases. The assembly was optimized using four assemblers viz. Newbler, MIRA, CLC and Trinity, out of which MIRA with a total of 14.10 Mb and 90118 transcripts proved to be the best for assembling reads. Differential expression analysis depicted 1396 and 936 and 1000 and 1591 transcripts up and down regulated in resistant inoculated/resistant control and susceptible inoculated/susceptible control respectively with a common of 3644 transcripts. The pathways for secondary metabolism, specifically the phenylpropanoid pathway was up-regulated in resistant genotype. Transcripts up-regulated as a part of defense response included classes of R genes, PR proteins, HR induced proteins and plant hormonal signaling transduction proteins. The transcripts for skp1 protein, purothionin, V type proton ATPase were found to have the highest expression in resistant genotype. Ten transcripts, selected on the basis of their involvement in defense mechanism were validated with qRT-PCR and showed positive co-relation with transcriptome data. Transcriptome analysis evoked potentials of hypersensitive response and systemic acquired resistance as possible mechanism operating in defense mechanism in pearl millet against downy mildew infection.

Urorectal septum malformation sequence: a report of seven cases.

Urorectal septum malformation (URSM) sequence is an extremely uncommon anomaly. We report herein seven cases of URSM sequence that were identified after reviewing all autopsies conducted at our hospital over a period of 26 years (1981-2006). The URSM spectrum includes partial and full URSM sequences. Absent perineal and anal openings with ambiguous genitalia are included under 'full URSM sequence', and a single perineal or anal opening draining a common cloaca with an imperforate anus is called 'partial URSM sequence'. Of our seven cases of URSM, three were full URSM sequence and four were partial URSM sequence. Associated renal anomalies were found in all of the cases. Three cases had unilateral renal agenesis and one each had bilateral renal agenesis and bilateral renal dysplasia, respectively. The remaining two cases had unilateral renal agenesis with contralateral kidney showing features of cystic dysplastic kidney and renal hypoplasia, respectively. Congenital anomalies involving other organs were also found in some of the cases. The longest survival period in our series was 10 days, in accordance with the short survival period usually associated with URSM. Five of the patients were females, one was male, and the sex of one neonate could not be ascertained. One of the neonates was from a twin pregnancy; the other twin was normal.

Management challenges in a child with hyperinsulinemic hypoglycemia.

Malignant insulinoma is very rare in children. Herein, we present a case of a child with malignant insulinoma along with islet cell hyperplasia. She initially presented with features of hyperinsulinemic hypoglycemia at 18 mo of age. Magnetic resonance imaging (MRI) of the abdomen showed a mass at the junction of the head and body of the pancreas. The tumor was enucleated. Five months later symptoms of hypoglycemia recurred. A subtotal pancreatectomy was performed. She continued to have hypoglycemia, although less frequently. She was put on increasing doses of diazoxide. Seven months later, MRI of the abdomen and a PET scan revealed metastatic deposits in the liver, which were confirmed by histopathology and immunostaining. To the best of our knowledge, this is the youngest child with metastatic insulinoma reported so far.