Single-cell epigenomic variability reveals functional cancer heterogeneity.

BackgroundCell-to-cell heterogeneity is a major driver of cancer evolution, progression, and emergence of drug resistance. Epigenomic variation at the single-cell level can rapidly create cancer heterogeneity but is difficult to detect and assess functionally.ResultsWe develop a strategy to bridge the gap between measurement and function in single-cell epigenomics. Using single-cell chromatin accessibility and RNA-seq data in K562 leukemic cells, we identify the cell surface marker CD24 as co-varying with chromatin accessibility changes linked to GATA transcription factors in single cells. Fluorescence-activated cell sorting of CD24 high versus low cells prospectively isolated GATA1 and GATA2 high versus low cells. GATA high versus low cells express differential gene regulatory networks, differential sensitivity to the drug imatinib mesylate, and differential self-renewal capacity. Lineage tracing experiments show that GATA/CD24hi cells have the capability to rapidly reconstitute the heterogeneity within the entire starting population, suggesting that GATA expression levels drive a phenotypically relevant source of epigenomic plasticity.ConclusionSingle-cell chromatin accessibility can guide prospective characterization of cancer heterogeneity. Epigenomic subpopulations in cancer impact drug sensitivity and the clonal dynamics of cancer evolution

An epidemiological study of season of birth, mental health, and neuroimaging in the UK Biobank

Environmental exposures during the perinatal period are known to have a long-term effect on adult physical and mental health. One such influential environmental exposure is the time of year of birth which affects the amount of daylight, nutrients, and viral load that an individual is exposed to within this key developmental period. Here, we investigate associations between season of birth (seasonality), four mental health traits (n = 137,588) and multi-modal neuroimaging measures (n = 33,212) within the UK Biobank. Summer births were associated with probable recurrent Major Depressive Disorder (β = 0.026, pcorr = 0.028) and greater mean cortical thickness in temporal and occipital lobes (β = 0.013 to 0.014, pcorr<0.05). Winter births were associated with greater white matter integrity globally, in the association fibers, thalamic radiations, and six individual tracts (β = -0.013 to -0.022, pcorr<0.05). Results of sensitivity analyses adjusting for birth weight were similar, with an additional association between winter birth and white matter microstructure in the forceps minor and between summer births, greater cingulate thickness and amygdala volume. Further analyses revealed associations between probable depressive phenotypes and a range of neuroimaging measures but a paucity of interactions with seasonality. Our results suggest that seasonality of birth may affect later-life brain structure and play a role in lifetime recurrent Major Depressive Disorder. Due to the small effect sizes observed, and the lack of associations with other mental health traits, further research is required to validate birth season effects in the context of different latitudes, and by co-examining genetic and epigenetic measures to reveal informative biological pathways

Interplanetary and Geomagnetic Consequences of Interacting CMEs of 13-14 June 2012

We report on the kinematics of two interacting CMEs observed on 13 and 14 June 2012. Both CMEs originated from the same active region NOAA 11504. After their launches which were separated by several hours, they were observed to interact at a distance of 100 Rs from the Sun. The interaction led to a moderate geomagnetic storm at the Earth with Dst index of approximately, -86 nT. The kinematics of the two CMEs is estimated using data from the Sun Earth Connection Coronal and Heliospheric Investigation (SECCHI) onboard the Solar Terrestrial Relations Observatory (STEREO). Assuming a head-on collision scenario, we find that the collision is inelastic in nature. Further, the signatures of their interaction are examined using the in situ observations obtained by Wind and the Advance Composition Explorer (ACE) spacecraft. It is also found that this interaction event led to the strongest sudden storm commencement (SSC) (approximately 150 nT) of the present Solar Cycle 24. The SSC was of long duration, approximately 20 hours. The role of interacting CMEs in enhancing the geoeffectiveness is examined.Comment: 17 pages, 5 figures, Accepted in Solar Physics Journa

Student Satisfaction and Performance in an Online Teacher Certification Program

The article presents a study which demonstrates the effectiveness of an online post baccalaureate teacher certification program developed by a Wisconsin university. The case method approach employing multiple methods and multiple data sources were used to investigate the degree to which pre-service teachers were prepared to teach. It was concluded that the study supports online delivery as an effective means of teacher preparation, but it was limited in the number of students followed into their first year of teaching

3D kinematics through the X-shaped Milky Way bulge

Context. It has recently been discovered that the Galactic bulge is X-shaped, with the two southern arms of the X both crossing the lines of sight at l = 0 and | b| > 4, hence producing a double red clump in the bulge color magnitude diagram. Dynamical models predict the formation of X-shaped bulges as extreme cases of boxy-peanut bulges. However, since X-shaped bulges were known to be present only in external galaxies, models have never been compared to 3D kinematical data for individual stars. Aims. We study the orbital motion of Galactic bulge stars in the two arms (overdensities) of the X in the southern hemisphere. The goal is to provide observational constraints to bulge formation models that predict the formation of X-shapes through bar dynamical instabilities. Methods. Radial velocities have been obtained for a sample of 454 bulge giants, roughly equally distributed between the bright and the faint red clump, in a field at (l,b) = (0, −6). Proper motions were derived for all red clump stars in the same field by combining images from two epochs, which were obtained 11 years apart, with WFI at the 2.2 m at La Silla. The observed field contains the globular cluster NGC 6558, whose member stars were used to assess the accuracy of the proper motion measurement. At the same time, as a by-product, we provide the first proper motion measurement of NGC 6558. The proper motions for the spectroscopic subsample are analyzed for a subsample of 352 stars, taking into account the radial velocities and metallicities measured from near-infrared calcium triplet lines. Results. The radial velocity distribution of stars in the bright red clump, which traces the closer overdensity of bulge stars, shows an excess of stars moving towards the Sun. Similarly, an excess of stars receding from the Sun is seen in the far overdensity, which is traced by faint red clump stars. This is explained by the presence of stars on elongated orbits, which are most likely streaming along the arms of the X-shaped bulge. Proper motions for these stars are consistent with qualitative predictions of dynamical models of peanut-shaped bulges. Surprisingly, stars on elongated orbits have preferentially metal-poor (subsolar) metallicities, while the metal rich ones, in both overdensities, are preferentially found in more axisymmetric orbits. The observed proper motion of NGC 6558 has been measured as (μlcos   (b),μb) = (0.30   ±   0.14, −0.43 ± 0.13), with a velocity dispersion of (σlcos(b),σb) = (1.8,1.7) mas/yr. This is the first proper motion measurement for this cluster

Alpha element abundances and gradients in the Milky Way bulge from FLAMES-GIRAFFE spectra of 650 K giants

We obtained FLAMES-GIRAFFE spectra (R=22,500) at the ESO Very Large Telescope for 650 bulge red giant branch (RGB) stars and performed spectral synthesis to measure Mg, Ca, Ti, and Si abundances. This sample is composed of 474 giant stars observed in 3 fields along the minor axis of the Galactic bulge and at latitudes b=-4, b=-6, b=-12. Another 176 stars belong to a field containing the globular cluster NGC 6553, located at b=-3 and 5 degrees away from the other three fields along the major axis. Our results confirm, with large number statistics, the chemical similarity between the Galactic bulge and thick disk, which are both enhanced in alpha elements when compared to the thin disk. In the same context, we analyze [alpha/Fe] vs. [Fe/H] trends across different bulge regions. The most metal rich stars, showing low [alpha/Fe] ratios at b=-4 disappear at higher Galactic latitudes in agreement with the observed metallicity gradient in the bulge. Metal-poor stars ([Fe/H]<-0.2) show a remarkable homogeneity at different bulge locations. We have obtained further constrains for the formation scenario of the Galactic bulge. A metal-poor component chemically indistinguishable from the thick disk hints for a fast and early formation for both the bulge and the thick disk. Such a component shows no variation, neither in abundances nor kinematics, among different bulge regions. A metal-rich component showing low [alpha/Fe] similar to those of the thin disk disappears at larger latitudes. This allows us to trace a component formed through fast early mergers (classical bulge) and a disk/bar component formed on a more extended timescale.Comment: 13 pages, 17 figures. Accepted for publication in Astronomy and Astrophysic

N-body simulation insights into the X-shaped bulge of the Milky Way: kinematics and distance to the Galactic Centre

Using simulations of box/peanut- (B/P-) shaped bulges, we explore the nature of the X-shape of the Milky Way's bulge. An X-shape can be associated with a B/P-shaped bulge driven by a bar. By comparing in detail the simulations and the observations we show that the principal kinematic imprint of the X-shape is a minimum in the difference between the near and far side mean line-of-sight velocity along the minor axis. This minimum occurs at around |b| = 4°, which is close to the lower limit at which the X-shape can be detected. No coherent signature of an X-shape can be found in Galactocentric azimuthal velocities, vertical velocities or any of the dispersions. After scaling our simulations, we find that a best fit to the Bulge Radial Velocity Assay data leads to a bar angle of 15°. We also explore a purely geometric method for determining the distance to the Galactic Centre by tracing the arms of the X-shape. We find that we are able to determine this ill-known distance to an accuracy of about 5 per cent with sufficiently accurate distance measurements for the red clump stars in the arm