TOPORS E3 ligase mediates resistance to hypomethylating agent cytotoxicity in acute myeloid leukemia cells

Hypomethylating agents (HMAs) are frontline therapies for Myelodysplastic Neoplasms (MDS) and Acute Myeloid Leukemia (AML). However, acquired resistance and treatment failure are commonplace. To address this, we perform a genome-wide CRISPR-Cas9 screen in a human MDS-derived cell line, MDS-L, and identify TOPORS as a loss-of-function target that synergizes with HMAs, reducing leukemic burden and improving survival in xenograft models. We demonstrate that depletion of TOPORS mediates sensitivity to HMAs by predisposing leukemic blasts to an impaired DNA damage response (DDR) accompanied by an accumulation of SUMOylated DNMT1 in HMA-treated TOPORS-depleted cells. The combination of HMAs with targeting of TOPORS does not impair healthy hematopoiesis. While inhibitors of TOPORS are unavailable, we show that inhibition of protein SUMOylation with TAK-981 partially phenocopies HMA-sensitivity and DDR impairment. Overall, our data suggest that the combination of HMAs with inhibition of SUMOylation or TOPORS is a rational treatment option for High-Risk MDS (HR-MDS) or AML

Branching fraction measurements of B+->rho(+)gamma, B-0 ->rho(0)gamma, and B-0 ->omega gamma

We present a study of the decays B+->rho(+)gamma, B-0 ->rho(0)gamma, and B-0 ->omega gamma. The analysis is based on data containing 347x10(6) B (B) over bar events recorded with the BABAR detector at the PEP-II asymmetric B factory. We measure the branching fractions B(B+->rho(+)gamma)=(1.10(-0.33)(+0.37)+/- 0.09)x10(-6) and B(B-0 ->rho(0)gamma)=(0.79(-0.20)(+0.22)+/- 0.06)x10(-6), and set a 90% C.L. upper limit B(B-0 ->omega gamma)(rho/omega)gamma)=(1.25(-0.24)(+0.25)+/- 0.09)x10(-6), from which we determine vertical bar V-td/V-ts vertical bar=0.200(-0.020)(+0.021)+/- 0.015, where the first uncertainty is experimental and the second is theoretical

Novel fabrication of functionalized graphene oxide via magnetite and 1-butyl-3-methylimidazolium tetrafluoroborate

© 2018 Elsevier B.V. The fabrication of functionalized graphene oxide via magnetite (Fe3O4) and ionic liquid into ferrofluid is investigated in this study. Several characterizations of the samples were made via Fourier-transform infrared spectroscopy (FTIR), field emission scanning electron microscope (FESEM), energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), and flame atomic absorption spectroscopy (FAAS)