Fish venom (Pterios volitans) peptide reduces tumor burden and ameliorates oxidative stress in Ehrlich's ascites carcinoma xenografted mice

The present study was carried out to assess the effect of Pterios volitans venom (mixture of peptides) on Ehrlich’s ascites carcinoma (EAC) and its influence on antioxidant status in the liver. Among six groups of albino mice, three were treated with sublethal doses of venom, along with the standard drug, 5-fluorouracil. In EAC-bearing mice, mean life span and antioxidants were significantly decreased, whereas, body weight, tumor volume, viable tumor cell count, lipid peroxidation and expression of proliferating cell nuclear antigen were significantly increased. These changes were brought back to near normal in treatment groups. The findings are further confirmed by histopathological observations.     

Receptor Specificity and Transmission of H2N2 Subtype Viruses Isolated from the Pandemic of 1957

Influenza viruses of the H2N2 subtype have not circulated among humans in over 40 years. The occasional isolation of avian H2 strains from swine and avian species coupled with waning population immunity to H2 hemagglutinin (HA) warrants investigation of this subtype due to its pandemic potential. In this study we examined the transmissibility of representative human H2N2 viruses, A/Albany/6/58 (Alb/58) and A/El Salvador/2/57 (ElSalv/57), isolated during the 1957/58 pandemic, in the ferret model. The receptor binding properties of these H2N2 viruses was analyzed using dose-dependent direct glycan array-binding assays. Alb/58 virus, which contains the 226L/228S amino acid combination in the HA and displayed dual binding to both alpha 2,6 and alpha 2,3 glycan receptors, transmitted efficiently to naïve ferrets by respiratory droplets. Inefficient transmission was observed with ElSalv/57 virus, which contains the 226Q/228G amino acid combination and preferentially binds alpha 2,3 over alpha 2,6 glycan receptors. However, a unique transmission event with the ElSalv/57 virus occurred which produced a 226L/228G H2N2 natural variant virus that displayed an increase in binding specificity to alpha 2,6 glycan receptors and enhanced respiratory droplet transmissibility. Our studies provide a correlation between binding affinity to glycan receptors with terminal alpha 2,6-linked sialic acid and the efficiency of respiratory droplet transmission for pandemic H2N2 influenza viruses.     

Allosteric interactions of DNA and nucleotides with S. cerevisiae RSC

RSC (remodel the structure of chromatin) is an essential chromatin remodeler of Saccharomyces cerevisiae that has been shown to have DNA translocase properties. We studied the DNA binding properties of a "trimeric minimal RSC" (RSCt) of the RSC chromatin remodeling complex and the effect of nucleotides on this interaction using fluorescence anisotropy. RSCt binds to 20 bp fluorescein-labeled double-stranded DNA with a K(d) of ～100 nM. The affinity of RSCt for DNA is reduced in the presence of AMP-PNP and ADP in a concentration-dependent manner with the addition of AMP-PNP having more pronounced effect. These differences in the magnitude at which the binding of ADP and AMP-PNP affects the affinity of DNA binding by RSCt suggest that the physical movement of the enzyme along DNA begins between the binding of ATP and its subsequent hydrolysis. Furthermore, the fact that the highest affinity for DNA binding by RSCt occurs in the absence of bound nucleotide offers a mechanistic explanation for the apparent low processivity of DNA translocation by the enzyme.     

Expression of antioxidant defense genes in mung bean (<Emphasis Type="Italic">Vigna radiata</Emphasis> L.) roots under water-logging is associated with hypoxia tolerance

This study was conducted to examine the extent of oxidative stress and the role of antioxidant enzymes on hypoxia tolerance in highly tolerant wild species Vigna luteola, and mung bean (Vigna radiata) cvs. T 44 (tolerant) and Pusa Baisakhi (susceptible). Two days of water-logging caused about 40–50% decline in superoxide radical (O₂ ^·−) and hydrogen peroxide (H₂O₂) contents in all the genotypes, however, further water-logging to 8 days caused significant increase in O₂ ^·− and H₂O₂ contents, and the values were 80–90% of the control values. In control and revived plants O₂ ^·− and H₂O₂ contents were higher in Pusa Baisakhi, while under water-logging stress T 44 and V. luteola showed greater increases in the O₂ ^·− and H₂O₂ contents. Hypoxia induced increase in superoxide dismutase, ascorbate peroxidase, and glutathione reductase activities were higher in T 44 and V. luteola compared with Pusa Baisakhi; and the increases in T 44 and V. luteola continued up to 8th day of water-logging, while in case of Pusa Baisakhi, the maximum increase was observed only on the 2nd day of water-logging. Gene expression studies showed enhanced expression of cytosolic-Cu/Zn-superoxide dismutase (SOD) and cytosolic-ascorbate peroxidase (APX) in the roots of waterlogged V. luteola and T 44, while little expression was observed in control or treated plants of Pusa Baisakhi. PCR band products were cloned and sequenced, and partial cDNAs of Cu/Zn-SOD and APX, respectively, were obtained. Results suggest that increase in the activity of antioxidant enzymes is to scavenge reactive oxygen species produced both during and after relief from water-logging stress.     

Experimental RNomics and genomic comparative analysis reveal a large group of species-specific small non-message RNAs in the silkworm Bombyx mori

Accumulating evidences show that small non-protein coding RNAs (ncRNAs) play important roles in development, stress response and other cellular processes. The silkworm is an important model for studies on insect genetics and control of lepidopterous pests. Here, we have performed the first systematic identification and analysis of intermediate size ncRNAs (50-500 nt) in the silkworm. We identified 189 novel ncRNAs, including 141 snoRNAs, six snRNAs, three tRNAs, one SRP and 38 unclassified ncRNAs. Forty ncRNAs showed significantly altered expression during silkworm development or across specific stage transitions. Genomic comparisons revealed that 123 of these ncRNAs are potentially silkworm-specific. Analysis of the genomic organization of the ncRNA loci showed that 32.62% of the novel snoRNA loci are intergenic, and that all the intronic snoRNAs follow the pattern of one-snoRNA-per-intron. Target site analysis predicted a total of 95 2'-O-methylation and pseudouridylation modification sites of rRNAs, snRNAs and tRNAs. Together, these findings provide new clues for future functional study of ncRNA during insect development and evolution.     

MicroRNA-21 orchestrates high glucose-induced signals to TOR complex 1, resulting in renal cell pathology in diabetes

Hyperglycemia induces a wide array of signaling pathways in the kidney that lead to hypertrophy and matrix expansion, eventually culminating in progressive kidney failure. High glucose-induced reduction of the tumor suppressor protein phosphatase and tensin homolog deleted in chromosome 10 (PTEN) contributes to renal cell hypertrophy and matrix expansion. We identified microRNA-21 (miR-21) as the molecular link between high glucose and PTEN suppression. Renal cortices from OVE26 type 1 diabetic mice showed significantly elevated levels of miR-21 associated with reduced PTEN and increased fibronectin content. In renal mesangial cells, high glucose increased the expression of miR-21, which targeted the 3'-UTR of PTEN mRNA to inhibit PTEN protein expression. Overexpression of miR-21 mimicked the action of high glucose, which included a reduction in PTEN expression and a concomitant increase in Akt phosphorylation. In contrast, expression of miR-21 Sponge, to inhibit endogenous miR-21, prevented down-regulation of PTEN and phosphorylation of Akt induced by high glucose. Interestingly, high glucose-stimulated miR-21 inactivated PRAS40, a negative regulator of TORC1. Finally, miR-21 enhanced high glucose-induced TORC1 activity, resulting in renal cell hypertrophy and fibronectin expression. Thus, our results identify a previously unrecognized function of miR-21 that is the reciprocal regulation of PTEN levels and Akt/TORC1 activity that mediate critical pathologic features of diabetic kidney disease.