Purine metabolism regulates DNA repair and therapy resistance in glioblastoma

Intratumoral genomic heterogeneity in glioblastoma (GBM) is a barrier to overcoming therapy resistance. Treatments that are effective independent of genotype are urgently needed. By correlating intracellular metabolite levels with radiation resistance across dozens of genomically-distinct models of GBM, we find that purine metabolites, especially guanylates, strongly correlate with radiation resistance. Inhibiting GTP synthesis radiosensitizes GBM cells and patient-derived neurospheres by impairing DNA repair. Likewise, administration of exogenous purine nucleosides protects sensitive GBM models from radiation by promoting DNA repair. Neither modulating pyrimidine metabolism nor purine salvage has similar effects. An FDA-approved inhibitor of GTP synthesis potentiates the effects of radiation in flank and orthotopic patient-derived xenograft models of GBM. High expression of the rate-limiting enzyme of de novo GTP synthesis is associated with shorter survival in GBM patients. These findings indicate that inhibiting purine synthesis may be a promising strategy to overcome therapy resistance in this genomically heterogeneous disease

Enhancing mechanical strength and microstructural properties of alkali-activated systems through nano graphene oxide dispersion and polycarboxylate ether admixture

The dispersion of graphene oxide (GO) nanoparticles in alkali-activated concrete with / without superplasticizers can help in understanding the effect it has on its mechanical strength and microstructural properties. The dispersion of GO in alkali activator fluid of 10(M) and 12(M) with / without polycarboxylate ether (PCE) admixture has been explored in this study. The alkali activator solution of 10(M) NaOH solution with PCE shows better dispersion than 12(M) NaOH solution, as higher alkalinity leads to agglomeration of GO. The study investigated the effect of incorporating PCE in GO-based alkali-activated slag (AAS) mortar with 8(M), 10(M) and 12(M) of alkaline activator solution. The mechanical strength and microstructural characteristics of conventional AAS (without both GO and PCE), GO-based AAS (without PCE) and GO-based AAS with PCE of the respective molar concentration of activator fluid are analysed. The mechanical strength of the AAS mortars has been evaluated using compressive, flexural, and splitting tensile strength testing. The micro-structural and mineralogical characteristics of the binders are evaluated using Field Emission Scanning Electron Microscopy (FESEM with EDS), X-ray Diffraction (XRD), and Fourier Transform Infrared Spectroscopy (FTIR) analysis. The addition of only GO (0.06 % of binder w/w) and the addition of both GO and PCE in AAS have shown up to 30 % and 40 % mechanical strength improvement with respect to conventional AAS, respectively. The effectiveness of PCE and percentages of strength improvement are higher with a lower molarity of activator fluid, and vice versa. Adding GO and PCE to the AAS system improves its hydration rate and denser microstructure, enhancing its strength

MUSHROOM POISONING: IDENTIFICATION AND QUANTIFICATION OF TOXINS WILL TOXINS IDENTIFICATION HELP IN PREVENTION OF ACCIDENTAL POISONING?

Amatoxins commonly found in Amanita phalloides is the main constituents of toxins present in most toxic mushroom specimens containing α-amanitin,β-amanitin,γ-amanitin,ε-amanitin,amanin,amaninamide,amanullin,amanullinic acid, and proamanullin.RP-HPLC analysis of toxins Chromatography:The method of Ismail Yilmaz et.al,is followed using C18 (Agilent Technologies) at UV detection 303nm for amatoxins and 291nm for phallotoxins.The mobile phase in isocratic pump with a flow rate of 1ml/min consisting of 0.05M ammonium acetate (pH 5.5 with acetic acid) and acetonitrile (90:10v/v).The geographical variations determine the content of the toxins and it brings a landmark to create awareness to the community for such mushroom specimens.We hope that analyzing the toxin content in the coming years will be of great service to the Physician and the community as well.</jats:p

A new Record of Monotropa Hypopitys L., a Myco heterotrophic Plant from India

Volume: 106Start Page: 127End Page: 12