Epithelial Membrane Protein-2 (EMP2) Activates Src Protein and Is a Novel Therapeutic Target for Glioblastoma

Despite recent advances in molecular classification, surgery, radiotherapy, and targeted therapies, the clinical outcome of patients with malignant brain tumors remains extremely poor. In this study, we have identified the tetraspan protein epithelial membrane protein-2 (EMP2) as a potential target for glioblastoma (GBM) killing. EMP2 had low or undetectable expression in normal brain but was highly expressed in GBM as 95% of patients showed some expression of the protein. In GBM cells, EMP2 enhanced tumor growth in vivo in part by up-regulating αvβ3 integrin surface expression, activating focal adhesion kinase and Src kinases, and promoting cell migration and invasion. Consistent with these findings, EMP2 expression significantly correlated with activated Src kinase in patient samples and promoted tumor cell invasion using intracranial mouse models. As a proof of principle to determine whether EMP2 could serve as a target for therapy, cells were treated using specific anti-EMP2 antibody reagents. These reagents were effective in killing GBM cells in vitro and in reducing tumor load in subcutaneous mouse models. These results support the role of EMP2 in the pathogenesis of GBM and suggest that anti-EMP2 treatment may be a novel therapeutic treatment.     

Optical analysis of RE3+ (RE = Nd or Er):B2O3–P2O5–CaF2–ZnO–(Li2O/Na2O/K2O) glasses

Calcium boro fluoro zinc phosphate glasses modified using alkali oxide and doped with Nd³⁺ and Er³⁺ ions with the chemical composition of 69.5 (B₂O₃) + 10 (P₂O₅) + 10 (CaF₂) + 5 (ZnO) + 5 (Na₂O/Li₂O/K₂O) + 0.5 (Er₂O₃/Nd₂O₃) were prepared using a conventional melt quenching technique. The results of X-ray diffraction patterns indicated the amorphous nature of all the prepared glasses. The visible–near-infrared red (NIR) absorption spectra of these glasses were analyzed systematically. The NIR emission spectra of Er³⁺ and Nd³⁺:calcium boro fluoro zinc phosphate glasses showed prominent emission bands at 1536 nm (⁴I_13/2→⁴I_15/2) and 1069 nm (⁴F_3/2→⁴I_11/2) respectively with λ_exci = 514.5 nm (Ar⁺ laser) as the excitation source.     

Stability of sheath blight resistance in transgenic ASD16 rice lines expressing a rice <Emphasis Type="Italic">chi11</Emphasis> gene encoding chitinase

Development of transgenic plants by introducing defense genes is one of the strategies to engineer disease resistance. Transgenic ASD16 rice plants harbouring rice chitinase chi11 gene, belonging to a PR-3 group of defense gene conferring sheath blight (Rhizoctonia solani Kuhn) resistance, were used in this study. Three T₂ homozygous lines (ASD16-4-1-1, 5-1-1, and 6-1-1) were identified from seven putative (T₀) transgenic lines expressing chi11 using Western blotting analysis. The inheritance of sheath blight resistance in those lines was studied over generations. The stability of chi11 expression up to T₄ generation in all the three homozygous lines was proved by Western blot and the stability of sheath blight resistance in the homozygous lines was proved up to T₄ generation using detached leaf and intact leaf sheath assays. Among the three homozygous lines tested, ASD16-4-1-1 showed consistent results in all the generations and gave a better protection against the sheath blight pathogen than the other two lines.     

Differential expression of LEA proteins in two genotypes of mulberry under salinity

The relative water content (RWC), cell membrane integrity, protein pattern and the expression of late embryogenesis abundant proteins (LEA; group 1, 2, 3 and 4) under different levels of salt stress (0, 1.0, 1.5 and 2.0 % NaCl) were investigated in mulberry (Morus alba L.) cultivars (S1 and ATP) with contrasting salt tolerance. RWC and membrane integrity decreased with increase in NaCl concentration more in cv. ATP than in cv. S1. SDS-PAGE protein profile of mulberry leaves after the NaCl treatments showed a significant increase in 35, 41, 45 and 70 kDa proteins and significant decrease in 14.3, 18, 23, 28, 30, 42, 47 and 65 kDa proteins. Exposure of plants to NaCl resulted in higher accumulation of LEA proteins in S1 than ATP. The maximum content of LEA (group 3 and 4) was detected in S1 at 2.0 % NaCl, which correlates with its salt tolerance.     

Novel function of transcription factor Nrf2 as an inhibitor of RON tyrosine kinase receptor-mediated cancer cell invasion

Recepteur d' origine nantais (RON), a tyrosine kinase receptor, is aberrantly expressed in human tumors and promotes cancer cell invasion. RON receptor activation is also associated with resistance to tamoxifen treatment in breast cancer cells. Nrf2 is a positive regulator of cytoprotective genes. Using chromatin immunoprecipitation (ChIP) and site-directed mutagenesis studies of the RON promoter, we identified Nrf2 as a negative regulator of RON gene expression. High Nrf2 and low RON expression was observed in normal mammary tissue whereas high RON and low or undetectable expression of Nrf2 was observed in breast tumors. The Nrf2 inducer sulforaphane (SFN) as well as ectopic Nrf2 expression or knock-down of the Nrf2 negative regulator keap1, which stabilizes Nrf2, inhibited RON expression and invasion of carcinoma cells. Consequently, our studies identified a novel functional role for Nrf2 as a "repressor" and RON kinase as a molecular target of SFN, which mediates the anti-tumor effects of SFN. These results are not limited to breast cancer cells since the Nrf2 inducer SFN stabilized Nrf2 and inhibited RON expression in carcinoma cells from various tumor types.     

Jasmonic acid induced changes in protein pattern, antioxidative enzyme activities and peroxidase isozymes in peanut seedlings

Protein pattern, ammonia content, glutamine synthetase activity, lipid peroxidation, superoxide dismutase, catalase, peroxidase and peroxidase isoforms were studied in the leaves and roots of 7-d-old peanut (Arachis hypogaea L. cv. JL-24) seedlings treated by 25, 100 and 250 μM jasmonic acid (JA). SDS-PAGE protein profile of leaves and roots after JA application showed a significant increase in 18, 21, 30, 45, 47 and 97.4 kDa proteins and significant decrease in 22 and 36 kDa proteins. Pathogenesis related PR-18 was specific in leaves at 250 μM JA and PR-21 have cross reacted differently with 21 and 30 kDa proteins in leaves and roots treated by all JA concentrations. Further, the immunoblot analysis with glutamine synthetase, GS-45 antibodies revealed a specific cross reaction with 45 and 47 kDa proteins of both control and JA treated leaves, however, higher at 100 and 250 μM JA treated leaves than control ones. Further, the malondialdehyde (MDA) content significantly increased in leaves and roots treated with JA, indicated membrane damage with JA treatments that led to the generation of peroxidation products. The peroxidase isozymic pattern showed two specific isoforms. Besides, the activities of SOD and catalase were significantly elevated in JA treated leaves.     

Relationships between fish size and otolith size of four bathydemersal fish species from the south eastern Arabian Sea,India

The objective of this study was to estimate a prey body size from the hard parts (e.g. otoliths) of a fish species frequently found in the guts of predators. Length–weight relationships between otolith size (length, height, weight and aspect ratio) and fish size (total length and weight) were determined for four fish species captured in the Arabian Sea by bottom trawl (2015 survey on‐board FORV Sagar Sampada, 200–300 m depth), off the west coast of India: Psenopsis cyanea, Pterygotrigla hemisticta, Bembrops caudimacula and Hoplostethus rubellopterus. No significant differences were noted between the size of the left and right otoliths (t test) in any of the four species. The length–weight relationship of the otolith in all four species showed a negative allometric growth pattern (t test, p < .05). The data fitted well to the regression model for otolith length (OL), otolith height (OH) and otolith weight (OW) to total length (TL) and total weight (TW). Results showed that these relationships are a helpful tool in predicting fish size from the otoliths and in calculating the biomass of these less‐studied fish species during feeding studies and palaentology.     

Emission analysis of Tb3+‐and Sm3+‐ion‐doped (Li2O/Na2O/K2O) and (Li2O + Na2O/Li2O + K2O/K2O + Na2O)‐modified borosilicate glasses

Four series of borosilicate glasses modified by alkali oxides and doped with Tb³⁺ and Sm³⁺ ions were prepared using the conventional melt quenching technique, with the chemical composition 74.5B₂O₃ + 10SiO₂ + 5MgO + R + 0.5(Tb₂O₃/Sm₂O₃) [where R = 10(Li₂O /Na₂O/K₂O) for series A and C, and R = 5(Li₂O + Na₂O/Li₂O + K₂O/K₂O + Na₂O) for series B and D]. The X‐ray diffraction (XRD) patterns of all the prepared glasses indicate their amorphous nature. The spectroscopic properties of the prepared glasses were studied by optical absorption analysis, photoluminescence excitation (PLE) and photoluminescence (PL) analysis. A green emission corresponding to the ⁵D₄ → ⁷F₅ (543 nm) transition of the Tb³⁺ ions was registered under excitation at 379 nm for series A and B glasses. The emission spectra of the Sm³⁺ ions with the series C and D glasses showed strong reddish‐orange emission at 600 nm (⁴G_5/2 →⁶H_7/2) with an excitation wavelength λ_exci = 404 nm (⁶H_5/2→⁴F_7/2). Furthermore, the change in the luminescence intensity with the addition of an alkali oxide and combinations of these alkali oxides to borosilicate glasses doped with Tb³⁺ and Sm³⁺ ions was studied to optimize the potential alkali‐oxide‐modified borosilicate glass.