The effects of acute and chronic morphine on regional distribution of cardiac output in brain

Summary Both acute and chronic administration of morphine resulted in an increase in the percent cardiac output received by brain. However, various brain regions were affected differently by the drug treatments. The greatest increases in percent cardiac output received after chronic administration of morphine occurred in pons and cerebellum, while the greatest increases after acute administration occurred in cortex and midbrain. The changes found are in contrast with earlier studies which suggest that morphine has no effect on cerebral blood flow.     

Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells

Recent advances have highlighted extensive phenotypic and functional similarities between normal stem cells and cancer stem cells. This raises the question of whether disease therapies can be developed that eliminate cancer stem cells without eliminating normal stem cells. Here we address this issue by conditionally deleting the Pten tumour suppressor gene in adult haematopoietic cells. This led to myeloproliferative disease within days and transplantable leukaemias within weeks. Pten deletion also promoted haematopoietic stem cell (HSC) proliferation. However, this led to HSC depletion via a cell-autonomous mechanism, preventing these cells from stably reconstituting irradiated mice. In contrast to leukaemia-initiating cells, HSCs were therefore unable to maintain themselves without Pten. These effects were mostly mediated by mTOR as they were inhibited by rapamycin. Rapamycin not only depleted leukaemia-initiating cells but also restored normal HSC function. Mechanistic differences between normal stem cells and cancer stem cells can thus be targeted to deplete cancer stem cells without damaging normal stem cells.     

Long gamma-ray bursts and core-collapse supernovae have different environments

When massive stars exhaust their fuel, they collapse and often produce the extraordinarily bright explosions known as core-collapse supernovae. On occasion, this stellar collapse also powers an even more brilliant relativistic explosion known as a long-duration gamma-ray burst. One would then expect that these long gamma-ray bursts and core-collapse supernovae should be found in similar galactic environments. Here we show that this expectation is wrong. We find that the gamma-ray bursts are far more concentrated in the very brightest regions of their host galaxies than are the core-collapse supernovae. Furthermore, the host galaxies of the long gamma-ray bursts are significantly fainter and more irregular than the hosts of the core-collapse supernovae. Together these results suggest that long-duration gamma-ray bursts are associated with the most extremely massive stars and may be restricted to galaxies of limited chemical evolution. Our results directly imply that long gamma-ray bursts are relatively rare in galaxies such as our own Milky Way.