Stem cells and the origin of gliomas: A historical reappraisal with molecular advancements.

The biology of both normal and tumor development clearly possesses overlapping and parallel features. Oncogenes and tumor suppressors are relevant not only in tumor biology, but also in physiological developmental regulators of growth and differentiation. Conversely, genes identified as regulators of developmental biology are relevant to tumor biology. This is particularly relevant in the context of brain tumors, where recent evidence is mounting that the origin of brain tumors, specifically gliomas, may represent dysfunctional developmental neurobiology. Neural stem cells are increasingly being investigated as the cell type that originally undergoes malignant transformation - the cell of origin - and the evidence for this is discussed

Posterior Cerebral Artery Angle and the Rupture of Basilar Tip Aneurysms

Since the initial publication of the International Study of Unruptured Intracranial Aneurysms (ISUIA), management of unruptured intracranial aneurysms has been mainly based on the size of the aneurysm. The contribution of morphological characteristics to treatment decisions of unruptured aneurysms has not been well studied in a systematic and location specific manner. We present a large sample of basilar artery tip aneurysms (BTA) that were assessed using a diverse array of morphological variables to determine the parameters associated with ruptured aneurysms. Demographic and clinical risk factors of aneurysm rupture were obtained from chart review. CT angiograms (CTA) were evaluated with Slicer, an open source visualization and image analysis software, to generate 3-D models of the aneurysms and surrounding vascular architecture. Morphological parameters examined in each model included aneurysm volume, aspect ratio, size ratio, aneurysm angle, basilar vessel angle, basilar flow angle, and vessel to vessel angles. Univariate and multivariate analyses were performed to determine statistical significance. From 2008–2013, 54 patients with BTA aneurysms were evaluated in a single institution, and CTAs from 33 patients (15 ruptured, 18 unruptured) were available and analyzed. Aneurysms that underwent reoperation, that were associated with arteriovenous malformations, or that lacked preoperative CTA were excluded. Multivariate logistic regression revealed that a larger angle between the posterior cerebral arteries (P1-P1 angle, p = 0.037) was most strongly associated with aneurysm rupture after adjusting for other morphological variables. In this location specific study of BTA aneurysms, the larger the angle formed between posterior cerebral arteries was found to be a new morphological parameter significantly associated with ruptured BTA aneurysms. This is a physically intuitive parameter that can be measured easily and readily applied in the clinical setting

A New H I Survey of Active Galaxies

We have conducted a new Arecibo survey for H I emission for 113 galaxies with broad-line (type 1) active galactic nuclei (AGNs) out to recession velocities as high as 35,000 km/s. The primary aim of the study is to obtain sensitive H I spectra for a well-defined, uniformly selected sample of active galaxies that have estimates of their black hole masses in order to investigate correlations between H I properties and the characteristics of the AGNs. H I emission was detected in 66 out of the 101 (65%) objects with spectra uncorrupted by radio frequency interference, among which 45 (68%) have line profiles with adequate signal-to-noise ratio and sufficiently reliable inclination corrections to yield robust deprojected rotational velocities. This paper presents the basic survey products, including an atlas of H I spectra, measurements of H I flux, line width, profile asymmetry, optical images, optical spectroscopic parameters, as well as a summary of a number of derived properties pertaining to the host galaxies. To enlarge our primary sample, we also assemble all previously published H I measurements of type 1 AGNs for which can can estimate black hole masses, which total an additional 53 objects. The final comprehensive compilation of 154 broad-line active galaxies, by far the largest sample ever studied, forms the basis of our companion paper, which uses the H I database to explore a number of properties of the AGN host galaxies.Comment: To appear in ApJS; 31 pages. Preprint will full-resolution figures can be downloaded from http://www.ociw.edu/~lho/preprints/ms1.pd

Analysis of Morphological Parameters to Differentiate Rupture Status in Anterior Communicating Artery Aneurysms

In contrast to size, the association of morphological characteristics of intracranial aneurysms with rupture has not been established in a systematic manner. We present an analysis of the morphological variables that are associated with rupture in anterior communicating artery aneurysms to determine site-specific risk variables. One hundred and twenty-four anterior communicating artery aneurysms were treated in a single institution from 2005 to 2010, and CT angiograms (CTAs) or rotational angiography from 79 patients (42 ruptured, 37 unruptured) were analyzed. Vascular imaging was evaluated with 3D Slicer© to generate models of the aneurysms and surrounding vasculature. Morphological parameters were examined using univariate and multivariate analysis and included aneurysm volume, aspect ratio, size ratio, distance to bifurcation, aneurysm angle, vessel angle, flow angle, and parent-daughter angle. Multivariate logistic regression revealed that size ratio, flow angle, and parent-daughter angle were associated with aneurysm rupture after adjustment for age, sex, smoking history, and other clinical risk factors. Simple morphological parameters such as size ratio, flow angle, and parent-daughter angle may thus aid in the evaluation of rupture risk of anterior communicating artery aneurysms

Morphological Parameters Associated with Ruptured Posterior Communicating Aneurysms

The rupture risk of unruptured intracranial aneurysms is known to be dependent on the size of the aneurysm. However, the association of morphological characteristics with ruptured aneurysms has not been established in a systematic and location specific manner for the most common aneurysm locations. We evaluated posterior communicating artery (PCoA) aneurysms for morphological parameters associated with aneurysm rupture in that location. CT angiograms were evaluated to generate 3-D models of the aneurysms and surrounding vasculature. Univariate and multivariate analyses were performed to evaluate morphological parameters including aneurysm volume, aspect ratio, size ratio, distance to ICA bifurcation, aneurysm angle, vessel angles, flow angles, and vessel-to-vessel angles. From 2005–2012, 148 PCoA aneurysms were treated in a single institution. Preoperative CTAs from 63 patients (40 ruptured, 23 unruptured) were available and analyzed. Multivariate logistic regression revealed that smaller volume (p = 0.011), larger aneurysm neck diameter (0.048), and shorter ICA bifurcation to aneurysm distance (p = 0.005) were the most strongly associated with aneurysm rupture after adjusting for all other clinical and morphological variables. Multivariate subgroup analysis for patients with visualized PCoA demonstrated that larger neck diameter (p = 0.018) and shorter ICA bifurcation to aneurysm distance (p = 0.011) were significantly associated with rupture. Intracerebral hemorrhage was associated with smaller volume, larger maximum height, and smaller aneurysm angle, in addition to lateral projection, male sex, and lack of hypertension. We found that shorter ICA bifurcation to aneurysm distance is significantly associated with PCoA aneurysm rupture. This is a new physically intuitive parameter that can be measured easily and therefore be readily applied in clinical practice to aid in the evaluation of patients with PCoA aneurysms

The Narrow-Line Regions of LINERs as Resolved with the Hubble Space Telescope

LINERs exist in the nuclei of a large fraction of luminous galaxies, but their connection with the AGN phenomenon has remained elusive. We present Hubble Space Telescope narrowband [O III]5007 and H-alpha+[N II] emission-line images of the central regions of 14 galaxies with LINER nuclei. The compact, ~1 arcsec-scale, unresolved emission that dominates the line flux in ground-based observations is mostly resolved by HST. The bulk of this emission comes from regions with sizes of tens to hundreds of parsecs that are resolved into knots, filaments, and diffuse gas whose morphology differs from galaxy to galaxy. Most of the galaxies do not show clear linear structures or ionization cones analogous to those often seen in Seyfert galaxies. An exception is NGC 1052, the prototypical LINER, in which we find a 3 arcsec-long (~ 250 pc) biconical structure that is oriented on the sky along the galaxy's radio jet axis. Seven of the galaxies have been shown in previously published HST images to have a bright compact ultraviolet nuclear source, while the other seven do not have a central UV source. Our images find evidence of dust in the nuclear regions of all 14 galaxies, with clear indications of nuclear obscuration in most of the "UV-dark" cases. The data suggest that the line-emitting gas in most LINERs is photoionized by a central source (which may be stellar, nonstellar, or a combination thereof) but that this source is often hidden from direct view. We find no obvious morphological differences between LINERs with detected weak broad H-alpha wings in their spectra and those with only narrow lines. Likewise, there is no clear morphological distinction between objects whose UV spectra are dominated by hot stars (e.g., NGC 4569) and those that are AGN-like (e.g., NGC 4579).Comment: Accepted for publication in the ApJ. 25 pages, 3 tables, 9 JPEG Figure

Predicting base editing outcomes using position-specific sequence determinants.

CRISPR/Cas base editors promise nucleotide-level control over DNA sequences, but the determinants of their activity remain incompletely understood. We measured base editing frequencies in two human cell lines for two cytosine and two adenine base editors at ∼14 000 target sequences and find that base editing activity is sequence-biased, with largest effects from nucleotides flanking the target base. Whether a base is edited depends strongly on the combination of its position in the target and the preceding base, acting to widen or narrow the effective editing window. The impact of features on editing rate depends on the position, with sequence bias efficacy mainly influencing bases away from the center of the window. We use these observations to train a machine learning model to predict editing activity per position, with accuracy ranging from 0.49 to 0.72 between editors, and with better generalization across datasets than existing tools. We demonstrate the usefulness of our model by predicting the efficacy of disease mutation correcting guides, and find that most of them suffer from more unwanted editing than pure outcomes. This work unravels the position-specificity of base editing biases and allows more efficient planning of editing campaigns in experimental and therapeutic contexts

NGC 839: Shocks in an M82-like Superwind

We present observations of NGC 839 made with the Wide Field Spectrograph (WiFeS) on the ANU 2.3m telescope. Our data cover a region 25" x 60" at a spatial resolution of ~1.5". The long axis of the field is aligned with the superwind we have discovered in this starburst galaxy. The data cover the range of 3700-7000 {\AA}, with a spectral resolution R~7000 in the red, and R~3000 in the blue. We find that the stellar component of the galaxy is strongly dominated by a fast rotating intermediate-age (~400 Myr) A-Type stellar population, while the gas is concentrated in a bi-conical polar funnel. We have generated flux distributions, emission line ratio diagnostics and velocity maps in both emission and absorption components. We interpret these in the context of a new grid of low-velocity shock models appropriate for galactic-scale outflows. These models are remarkably well fit to the data, providing for the first time model diagnostics for shocks in superwinds and strongly suggesting that shock excitation is largely responsible for the extended LINER emission in the outflowing gas in NGC 839. Our work may have important implications both for extended LINER emission seen in other galaxies, as well as in the interpretation of objects with "composite" spectra. Finally, we present a scenario for the formation of E+A galaxies based upon our observations of NGC 839, and its relation to M82.Comment: 12 pages and 13 figures. Accepted for publication in Ap