Platelet derived growth factor B and epithelial mesenchymal transition of peritoneal mesothelial cells

Platelet derived growth factor (PDGF) is involved in wound healing in various organ systems. Its potential role in the context of peritoneal injury following long-term peritoneal dialysis is unclear. We used an adenovirus expressing the B chain of PDGF (AdPDGF-B) to assess its effect on pro-fibrotic pathways in the peritoneal membrane. To assess the transforming growth factor (TGF) β independent effects of PDGF, we over-expressed PDGF-B in the peritoneum of either wild-type mice (Smad3^+/+) or those with a deletion of the TGFβ signaling protein Smad3 (Smad3^?/?). PDGF-B induced sustained angiogenesis in both Smad3^+/+ and Smad3^?/? mice. Despite increased collagen gene expression, collagen accumulation was transient and fibrogenesis was associated with induction of collagenase activity. We observed epithelial to mesenchymal transition (EMT) involving the peritoneal mesothelial cells, as shown by increased SNAIL and decreased E-Cadherin expression with evidence of mesothelial cells expressing both epithelial and mesenchymal markers. Unlike TGFβ-induced EMT, PDGF-B exposure did not lead to mobilization of the mesothelial cells; they remained as a single monolayer throughout the observation period. This “non-invasive” EMT phenomenon is a novel finding and may have implications concerning the role of EMT in peritoneal fibrosis and injury to other organ systems. The observed effects were similar in Smad3^?/? and Smad3^+/+ animals, suggesting that the PDGF-B effects were independent of TGFβ or Smad signaling.     

Neotrygon indica sp. nov., the Indian Ocean blue-spotted maskray (Myliobatoidei,Dasyatidae)

The blue-spotted maskray, previously N. kuhlii, consists of up to eleven lineages representing separate species. Nine of these species (N. australiae, N. bobwardi, N. caeruleopunctata, N. malaccensis, N. moluccensis, N. orientale, N. vali, N. varidens, N. westpapuensis) have already been formally described and two (Indian Ocean maskray and Ryukyu maskray) remain undescribed. Here, the Indian Ocean maskray is described as a new species, Neotrygon indica sp. nov. Specimens of the new species were generally characterized on their dorsal side by a moderately large number of small ocellated blue spots, a low number of medium-sized ocellated blue spots, the absence of large ocellated blue spots, a high number of dark speckles, a few dark spots, and a conspicuous occipital mark. The new species formed a distinct haplogroup in the tree built from concatenated nucleotide sequences at the CO1 and cytochrome b loci. A diagnosis based on colour patterns and nucleotide sequences at the CO1 and cytochrome b loci is proposed. The distribution of N. indica sp. nov. includes the Indian coast of the Bay of Bengal, the Indian coast of the Laccadives Sea, and Tanzania. Considerable sampling effort remains necessary for an in-depth investigation of the phylogeographic structure of the Indian Ocean maskray.     

The fungus Gliocephalotrichum simplex as a source of abundant, extracellular melanin for biotechnological applications

Melanins are commonly produced by bacteria, fungi, plants and animals, where they play a role in many biological functions. They protect organisms against UV and ionizing radiations. Their potential applications in biotechnological industries such as cosmetics and paints, where UV protection is required, are hampered by the lack of suitable organisms or methods to produce them abundantly. We report here the production of high amounts of extracellular melanin by the fungus Gliocephalotrichum simplex in cultures supplemented with tyrosine. Their typical UV-absorbance, as well as i.r., ¹³C solid-state and ¹H NMR spectra indicated that the melanin is a eumelanin, being a copolymer of dihydroxyindole carboxylic acid and dihydroxyindole, associated with some carbohydrates and proteinaceous matter. Optimal culture conditions established by a Plackett-Burman experiment, followed by a full factorial experiment based on tyrosine and peptone yielded a maximum of up to 6.6 g melanin l⁻¹. The high yields of extracellular melanin from G. simplex enables its use in biotechnology.     

Hybrid Nature Inspired SMO-GBM Classifier for Exudate Classification on Fundus Retinal Images

Background: The diabetic retinopathy can result in loss of vision if not detected in the earlier stages. Exudates are the lesions which play a crucial role in early diagnosis of diabetic retinopathy. The localization of exudates lesions with high values of performance metrics is complicated due to presence of blood vessels and other noisy artifacts. Method: We present computer aided system for classification of retinal fundus images using a novel nature inspired spider monkey optimization for parameter tuning of gradient boosting machines classifier. The image enhancement has been performed with histogram equalization and contourlet transform. The pixels belonging to optic disc region are detected and eliminated using circular Hough transform and Otsu's segmentation method. We have employed Kirsch's matrices for blood vessel detection. The GLCM based feature vector extraction has been employed for textural features. The classification has been performed with hybrid SMO-GBM classifier. Result: We have utilized the STARE database for validation of proposed technique. The proposed system can effectively classify entire image set from test data. The SMO-GBM classifier can further sub-segregate into sub classes with an average accuracy of 97.5%. Conclusion: The proposed approach provides detection and grading of diabetic retinopathy. The abnormality is further categories as soft, moderate and severe. The hybrid SMO-GBM classifier yields a better statistical metrics than the existing exudates classification approaches.     

Coordinate regulation of lipid metabolism by novel nuclear receptor partnerships

Mammalian nuclear receptors broadly influence metabolic fitness and serve as popular targets for developing drugs to treat cardiovascular disease, obesity, and diabetes. However, the molecular mechanisms and regulatory pathways that govern lipid metabolism remain poorly understood. We previously found that the Caenorhabditis elegans nuclear hormone receptor NHR-49 regulates multiple genes in the fatty acid beta-oxidation and desaturation pathways. Here, we identify additional NHR-49 targets that include sphingolipid processing and lipid remodeling genes. We show that NHR-49 regulates distinct subsets of its target genes by partnering with at least two other distinct nuclear receptors. Gene expression profiles suggest that NHR-49 partners with NHR-66 to regulate sphingolipid and lipid remodeling genes and with NHR-80 to regulate genes involved in fatty acid desaturation. In addition, although we did not detect a direct physical interaction between NHR-49 and NHR-13, we demonstrate that NHR-13 also regulates genes involved in the desaturase pathway. Consistent with this, gene knockouts of these receptors display a host of phenotypes that reflect their gene expression profile. Our data suggest that NHR-80 and NHR-13's modulation of NHR-49 regulated fatty acid desaturase genes contribute to the shortened lifespan phenotype of nhr-49 deletion mutant animals. In addition, we observed that nhr-49 animals had significantly altered mitochondrial morphology and function, and that distinct aspects of this phenotype can be ascribed to defects in NHR-66- and NHR-80-mediated activities. Identification of NHR-49's binding partners facilitates a fine-scale dissection of its myriad regulatory roles in C. elegans. Our findings also provide further insights into the functions of the mammalian lipid-sensing nuclear receptors HNF4α and PPARα.     

Design and synthesis of novel furoquinoline based inhibitors of multiple targets in the PI3K/Akt-mTOR pathway

We herein report the design and synthesis of furoquinoline based novel molecules (16-36) and their in vitro multiple targeted inhibitory potency against PI3K/Akt phosphorylation and mTOR using cell based and cell-free kinase assay. In particular, compound 23 in addition to PI3K-mTOR inhibitory potency, it has shown potent inhibition of hypoxia-induced accumulation of HIF-1alpha protein in U251-HRE cell line. The inhibitory activities of compound 23 were confirmed by Western blot analysis, using human non-small cell lung carcinoma H-460 cell line and glioblastoma U251 cell lines.     

High-frequency plant regeneration from leaf-disc cultures of Jatropha curcas L.: an important biodiesel plant

A simple, high-frequency and reproducible protocol for induction of adventitious shoot buds and plant regeneration from leaf-disc cultures of Jatropha curcas L. has been developed. Adventitious shoot buds were induced from very young leaf explants of in vitro germinated seedlings as well as mature field-grown plants cultured on Murashige and Skoog’s (MS) medium supplemented with thidiazuron (TDZ) (2.27 μM), 6-benzylaminopurine (BA) (2.22 μM) and indole-3-butyric acid (IBA) (0.49 μM). The presence of TDZ in the induction medium has greater influence on the induction of adventitious shoot buds, whereas BA in the absence of TDZ promoted callus induction rather than shoot buds. Induced shoot buds were multiplied and elongated into shoots following transfer to the MS medium supplemented with BA (4.44 μM), kinetin (Kn) (2.33 μM), indole-3-acetic acid (IAA) (1.43 μM), and gibberellic acid (GA₃) (0.72 μM). Well-developed shoots were rooted on MS medium supplemented with IBA (0.5 μM) after 30 days. Regenerated plants after 2 months of acclimatization were successfully transferred to the field without visible morphological variation. This protocol might find use in mass production of true-to-type plants and in production of transgenic plants through Agrobacterium/biolistic-mediated transformation.     

Novel hybrids of fluconazole and furanones: design, synthesis and antifungal activity

During our efforts to develop new antifungal agents, a number of hybrid molecules containing furanones and fluconazole pharmacophores were designed and synthesized. The new chemical entities thus synthesized were tested for their potential as antifungal agents against various fungal strains and it was observed that the compounds with general structure 7 were potent inhibitors of Candida albicans ATCC 24433, Candida glabrata ATCC 90030, Candida tropicalis ATCC 750 and Candida neoformans ATCC 34664 while the fluconazole analogues 12 exhibited antifungal activity against Candida albicans ATCC 24433 and Candida glabrata ATCC 90030. The structure-activity relationship for these compounds is discussed. The synthetic strategies used in the present work have potential to prepare a large number of compounds for further refinement of structures to obtain molecules suitable for development as antifungal drugs.     

Novel imidazo[2,1-b][1,3,4]thiadiazole carrying rhodanine-3-acetic acid as potential antitubercular agents

The increase in the prevalence of multi drug-resistant and extensively drug-resistant strains of Mycobacteriumtuberculosis case demonstrates the urgent need of discovering new promising compounds with antimycobacterial activity. As part of our research program and with a aim of identifying new antitubercular drug candidates, a new class of 2-(trifluoromethyl)-6-arylimidazo[2,1-b][1,3,4]thiadiazole derivatives has been synthesized by both conventional as well as microwave assisted method and evaluated for their in vitro antitubercular activity against M. tuberculosis H(37)Rv. Moreover, various drug-likeness properties of new compounds were predicted. Seven compounds from the series exhibited good activity with MIC in range 3.12-1.56μg/ml. The present study suggests that compounds 6b, 6c, 6d, 6e and 6f may serve as promising lead scaffolds for further generation of new anti-TB agents.