Glioblastoma (GBM) is a devastating and incurable brain tumour, with a median overall survival of fifteen months. Identifying the cell of origin that harbours mutations that drive GBM could provide a fundamental basis for understanding disease progression and developing new treatments. Given that the accumulation of somatic mutations has been implicated in gliomagenesis, studies have suggested that neural stem cells (NSCs), with their self-renewal and proliferative capacities, in the subventricular zone (SVZ) of the adult human brain may be the cells from which GBM originates. However, there is a lack of direct genetic evidence from human patients with GBM. Here we describe direct molecular genetic evidence from patient brain tissue and genome-edited mouse models that show astrocyte-like NSCs in the SVZ to be the cell of origin that contains the driver mutations of human GBM. First, we performed deep sequencing of triple-matched tissues, consisting of (i) normal SVZ tissue away from the tumour mass, (ii) tumour tissue, and (iii) normal cortical tissue (or blood), from 28 patients with isocitrate dehydrogenase (IDH) wild-type GBM or other types of brain tumour. We found that normal SVZ tissue away from the tumour in 56.3% of patients with wild-type IDH GBM contained low-level GBM driver mutations (down to approximately 1% of the mutational burden) that were observed at high levels in their matching tumours. Moreover, by single-cell sequencing and laser microdissection analysis of patient brain tissue and genome editing of a mouse model, we found that astrocyte-like NSCs that carry driver mutations migrate from the SVZ and lead to the development of high-grade malignant gliomas in distant brain regions. Together, our results show that NSCs in human SVZ tissue are the cells of origin that contain the driver mutations of GBM.

Understanding the chemical evolution in star-forming cores is a necessary pre-condition to correctly assess physical conditions when using molecular emission. We follow the evolution of chemistry and molecular line profiles through the entire star formation process, including a self-consistent treatment of dynamics, dust continuum radiative transfer, gas energetics, chemistry, molecular excitation, and line radiative transfer. In particular, the chemical code follows a gas parcel as it falls toward the center, passing through regimes of density, dust temperature, and gas temperature that are changing both because of the motion of the parcel and the evolving luminosity of the central source. We combine a sequence of Bonnor-Ebert spheres and the inside-out collapse model to describe dynamics from the pre-protostellar stage to later stages. The overall structures of abundance profiles show complex behavior that can be understood as interactions between freeze-out and evaporation of molecules. We find that the presence or absence of gas-phase CO has a tremendous effect on the less abundant species. In addition, the ambient radiation field and the grain properties have important effects on the chemical evolution, and the variations in abundance have strong effects on the predicted emission line profiles. Multi-transition and multi-position observations are necessary to constrain the parameters and interpret observations correctly in terms of physical conditions. Good spatial and spectral resolution is also important in distinguishing evolutionary stages. Subject headings:

We present a survey of 28 molecular outflows driven by low-mass protostars, all of which are sufficiently isolated spatially and/or kinematically to fully separate into individual outflows. Using a combination of new and archival data from several single-dish telescopes, 17 outflows are mapped in 12 CO (2-1) and 17 are mapped in 12 CO (3-2), with 6 mapped in both transitions. For each outflow, we calculate and tabulate the mass (M flow ), momentum (P flow ), kinetic energy (E flow ), mechanical luminosity (L flow ), and force (F flow ) assuming optically thin emission in LTE at an excitation temperature, T ex , of 50 K. We show that all of the calculated properties are underestimated when calculated under these assumptions. Taken together, the effects of opacity, outflow emission at low velocities confused with ambient cloud emission, and emission below the sensitivities of the observations increase outflow masses and dynamical properties by an order of magnitude, on average, and factors of 50-90 in the most extreme cases. Different (and non-uniform) excitation temperatures, inclination effects, and dissociation of molecular gas will all work to further increase outflow properties. Molecular outflows are thus almost certainly more massive and energetic than commonly reported. Additionally, outflow properties are lower, on average, by almost an order of magnitude when calculated from the 12 CO (3-2) maps compared to the 12 CO (2-1) maps, even after accounting for different opacities, map sensitivities, and possible excitation temperature variations. It has recently been argued in the literature that the 12 CO (3-2) line is subthermally excited in outflows, and our results support this finding. Data ReductionLow-order polynomial baselines were subtracted from all of the raw data using the default software package for each telescope: Continuum and Line Analysis Singledish Software (CLASS 11 ) for APEX, CSO, SRAO, and SMT, NEWSTAR 12 for ASTE, and Starlink 13 for the JCMT. These packages were then used to combine together all observations of a particular source and write out FITS datacubes on grids of Nyquist sampled spatial pixels. Further analysis was performed using custom IDL procedures. RESULTS

Spitzer Space Telescope IRAC 3 − 8 µm and AKARI IRC 2 − 4 µm photometry are reported for ten white dwarfs with photospheric heavy elements; nine relatively cool stars with photospheric calcium, and one hotter star with a peculiar high carbon abundance. A substantial infrared excess is detected at HE 2221−1630, while modest excess emissions are identified at HE 0106−3253 and HE 0307+0746, implying these latter two stars have relatively narrow (∆r < 0.1 R ⊙ ) rings of circumstellar dust. A likely 7.9 µm excess is found at PG 1225−079 and may represent, together with G166-58, a sub-class of dust ring with a large inner hole. The existence of attenuated disks at white dwarfs substantiates the connection between their photospheric heavy elements and the accretion of disrupted minor planets, indicating many polluted white dwarfs may harbor orbiting dust, even those lacking an obvious infrared excess.