An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes

Cancers are characterized by non-random chromosome copy number alterations that presumably contain oncogenes and tumor-suppressor genes (TSGs). The affected loci are often large, making it difficult to pinpoint which genes are driving the cancer. Here we report a cross-species in vivo screen of 84 candidate oncogenes and 39 candidate TSGs, located within 28 recurrent chromosomal alterations in ependymoma. Through a series of mouse models, we validate eight new ependymoma oncogenes and ten new ependymoma TSGs that converge on a small number of cell functions, including vesicle trafficking, DNA modification and cholesterol biosynthesis, identifying these as potential new therapeutic targets.We are grateful to F.B. Gertler (Massachusetts Institute of Technology) and S. Gupton (University of North Carolina) for the generous gift of the VAMP7-phlorin construct and the staffs of the Hartwell Center for Bioinformatics and Biotechnology, the Small Animal Imaging Center, the Animal Resources Center, the Cell and Tissue Imaging Center, and the Flow Cytometry and Cell Sorting Shared Resource at St. Jude Children's Research Hospital for technical assistance. This work was supported by grants from the US National Institutes of Health (R01CA129541, P01CA96832 and P30CA021765, R.J.G.), by the Collaborative Ependymoma Research Network (CERN) and by the American Lebanese Syrian Associated Charities (ALSAC)

Packing polymorphs of 4H-pyrido[1,2-a]pyrimidin-4-one derivative, a drug intermediate with anti-proliferative property - a qualitative analysis

by Althaf Shaik, R. Srimadhavi, Sivapriya Kirubakaran and Vijay Thiruvenkata

Development of novel drug like small molecules for treating Helicobacter pylori infection by inhibiting IMPDH

BY Srimadhavi R., Kapil Juvale, Gayathri Purushothaman, Vijay Thiruvenkatam and Sivapriya Kirubakara

Tracing the GSAP-APP C-99 Interaction Site in the β-Amyloid Pathway Leading to Alzheimer's Disease

Gamma secretase activating protein (GSAP) present in β-amyloid pathway orchestrates the formation of β-amyloid plaques by γ-secretase activation and is an emerging therapeutic target for the treatment of Alzheimer’s disease. It forms a ternary complex with γ secretase and APP C-99. However, there are limited reports for the interaction of APP C-99 with GSAP. Here, we report the characterization of purified maltose binding protein tagged human GSAP and its interaction with synthetic APP C-99 peptide fragments (712IATVIVITLVMLKKQ727 (712IQ727), 719TLVMLKKKQYTSIHHGVVEVDAAVT743 (719TT743) 734GVVEVDAAVTPEERHLSKMQQNGY757 (734GY757), and 746ERHLSKMQQNGYENPTYKFFEQMQN770 (746EN770)). The results emphasize the selective interaction of peptide (719TT743) with MBP-GSAP with a dissociation constant of 0.136 µM. Further, computational modeling of the GSAP - 719TT743 complex finds an optimal bound pose of 719TT743 within an extended groove on the surface of GSAP. The preliminary results highlight the interaction between the two major proteins in the plausible ternary complex; APP C-99-GSAP- γ secretase. It paves a futuristic path to investigate the GSAP- APP C-99 binding in detail and accentuate the role of GSAP in the β-amyloid pathway.by Deekshi Angira, Rupesh Chikhale, Kapilkumar Mehta, Richard A. Bryce and Vijay Thiruvenkata

Design and synthesis of small molecules as effective inhibitors of ataxia telangiectasia mutated - a key mediator of the DNA damage and response pathway

by SrimadhaviR., Althaf Shaik, Parul Duhan, Vijay Thiruvenkatam, and Sivapriya Kirubakara

Kinetics and inhibitory studies on IMPDH protein against Helicobacter pylori

by Gayathri Purushothaman, Gaurav Sharma, Srimadhavi R, Sachin Jangra, Vijay Thiruvenkatam and Sivapriya Kirubakara

Kinetics and structural features of IMPDH: possible target for treating H pylori infection

by Gayathri Purushothaman, Gaurav Sharma, Srimadhavi R., Sachin Jangra, Vijay Thiruvenkatam, and Sivapriya Kirubakara

Molecular interactions in bis(2-aminopyridinium) malonate: A crystal isostructural to bis(2-aminopyridinium) maleate crystal

Crystals of a new salt in 2:1 ratio of 2-aminopyridine and malonic acid are grown by slow evaporation. These crystals of bis(2-aminopyridinium) malonate are orthorhombic and belong to the non-centrosymmetric space group, Fdd2 with parameters a = 22.0786(6), b = 23.0218(6), c = 5.5595(1)angstrom and Z=8 at 300 K. The crystals are isostructural to those of bis(2-aminopyridinium) maleate, which is a NLO material. The isostructurality index between bis(2-aminopyridinium) maleate and bis(2-aminopyridinium) malonate was also calculated. The hyperpolarizability calculated using semi empirical method MOPAC2009 showed that bis(2-aminopyridinium) malonate has slightly higher beta value compared to that of bis(2-aminopyridinium) maleate. (C) 2011 Elsevier B.V. All rights reserved

Bis(glycinium) oxalate: evidence of strong hydrogen bonding

In the title 2:1 salt, 2C(2)H(6)NO(2)(+)center dot C2O42-, the glycine mol-ecule is in the cationic form with a positively charged amino group and an uncharged carboxylic acid group. The doubly charged oxalate anion lies across a crystallographic inversion centre. One of the reasons why the 1:1 glycinium oxalate salt has a higher melting point than the title compound may be the difference in their hydrogen-bonding patterns. A database search for salts formed between amino acids or substituted amino acids and oxalic acid revealed that, in most of the structures, the conformation about the O=C-OH bond is synplanar. D-Tryptophan oxalate is the only example where the OH group of a semi-oxalate adopts an anti-planar conformation. The 2:1 stoichiometry seen in the present salt is observed only in the salts of DL-serine, DL-aspartic acid and betaine with oxalic acid