The role of EGFR double minutes in modulating the response of malignant gliomas to radiotherapy.

EGFR amplification in cells having double minute chromosomes (DM) is commonly found in glioblastoma multiforme (GBM); however, how much it contributes to the current failure to treat GBM successfully is unknown. We studied two syngeneic primary cultures derived from a GBM with and without cells carrying DM, for their differential molecular and metabolic profiles, in vivo growth patterns, and responses to irradiation (IR). Each cell line has a distinct molecular profile consistent with an invasive "go" (with DM) or angiogenic "grow" phenotype (without DM) demonstrated in vitro and in intracranial xenograft models. Cells with DM were relatively radio-resistant and used higher glycolytic respiration and lower oxidative phosphorylation in comparison to cells without them. The DM-containing cell was able to restore tumor heterogeneity by mis-segregation of the DM-chromosomes, giving rise to cell subpopulations without them. As a response to IR, DM-containing cells switched their respiration from glycolic metabolism to oxidative phosphorylation and shifted molecular profiles towards that of cells without DM. Irradiated cells with DM showed the capacity to alter their extracellular microenvironment to not only promote invasiveness of the surrounding cells, regardless of DM status, but also to create a pro-angiogenic tumor microenvironment. IR of cells without DM was found primarily to increase extracellular MMP2 activity. Overall, our data suggest that the DM-containing cells of GBM are responsible for tumor recurrence due to their high invasiveness and radio-resistance and the mis-segregation of their DM chromosomes, to give rise to fast-growing cells lacking DM chromosomes

Chlorophyll, crop growth rate and forage yield of Brachiaria (Brachiaria brizantha Stapf) as the result of goat manure in various nitrogen dosage

growth rate (CGR), forage yield, dry matter ((DM) yield and DM content of BrachiariabrizanthaStapf. The experiment used manure (0 and 5 ton/ha) and nitrogen dosage (50, 100, 150 kg N ha-1) set in factorial design 2 x 3, repeated three times. The result showed that manure increased chlorophyll content, plant height, CGR, forage yield, DM yield and DM content. N dosage increased chlorophyll content, plant height, CGR, forage yield, DM yield and DM content. The interaction between manure and N dosage increased chlorophyll content, plant height, CGR, forage yield, DM yield and DM content. The result showed that manure usage and nitrogen dosage 150 kg N ha-1 increased chlorophyll content, plant height, CGR, forage yield, DM yield and DM content in the amount of 27.5; 20.5; 98.4; 68.5; 103.4 and 20.5% compared to without manure and nitrogen dosage in the amount of 150 kg N ha-1

Self-heating dark matter via semi-annihilation

The freeze-out of dark matter (DM) depends on the evolution of the DM temperature. The DM temperature does not have to follow the standard model one, when the elastic scattering is not sufficient to maintain the kinetic equilibrium. We study the temperature evolution of the semi-annihilating DM, where a pair of the DM particles annihilate into one DM particle and another particle coupled to the standard model sector. We find that the kinetic equilibrium is maintained solely via semi-annihilation until the last stage of the freeze-out. After the freeze-out, semi-annihilation converts the mass deficit to the kinetic energy of DM, which leads to non-trivial evolution of the DM temperature. We argue that the DM temperature redshifts like radiation as long as the DM self-interaction is efficient. We dub this novel temperature evolution as self-heating. Notably, the structure formation is suppressed at subgalactic scales like keV-scale warm DM but with GeV-scale self-heating DM if the self-heating lasts roughly until the matter-radiation equality. The long duration of the self-heating requires the large self-scattering cross section, which in turn flattens the DM density profile in inner halos. Consequently, self-heating DM can be a unified solution to apparent failures of cold DM to reproduce the observed subgalactic scale structure of the Universe.Comment: 6 pages, 4 figures. v2: discussed improved, matches published versio