Pulsar Magnetospheric Emission Mapping: Images and Implications of Polar-Cap Weather

The beautiful sequences of ``drifting'' subpulses observed in some radio pulsars have been regarded as among the most salient and potentially instructive characteristics of their emission, not least because they have appeared to represent a system of subbeams in motion within the emission zone of the star. Numerous studies of these ``drift'' sequences have been published, and a model of their generation and motion articulated long ago by Ruderman & Sutherland (1975); but efforts thus far have failed to establish an illuminating connection between the drift phemomenon and the actual sites of radio emission. Through a detailed analysis of a nearly coherent sequence of ``drifting'' pulses from pulsar B0943+10, we have in fact identified a system of subbeams circulating around the magnetic axis of the star. A mapping technique, involving a ``cartographic'' transform and its inverse, permits us to study the character of the polar-cap emission ``map'' and then to confirm that it, in turn, represents the observed pulse sequence. On this basis, we have been able to trace the physical origin of the ``drifting-subpulse'' emission to a stably rotating and remarkably organized configuration of emission columns, in turn traceable possibly to the magnetic polar-cap ``gap'' region envisioned by some theories.Comment: latex with five eps figure

C2D Spitzer-IRS spectra of disks around T Tauri stars: I. Silicate emission and grain growth

Infrared ~5--35 um spectra for 40 solar-mass T Tauri stars and 7 intermediate-mass Herbig Ae stars with circumstellar disks were obtained using the Spitzer Space Telescope as part of the c2d IRS survey. This work complements prior spectroscopic studies of silicate infrared emission from disks, which were focused on intermediate-mass stars, with observations of solar-mass stars limited primarily to the 10 um region. The observed 10 and 20 um silicate feature strengths/shapes are consistent with source-to-source variations in grain size. A large fraction of the features are weak and flat, consistent with um-sized grains indicating fast grain growth (from 0.1--1.0 um in radius). In addition, approximately half of the T Tauri star spectra show crystalline silicate features near 28 and 33 um indicating significant processing when compared to interstellar grains. A few sources show large 10-to-20 um ratios and require even larger grains emitting at 20 um than at 10 um. This size difference may arise from the difference in the depth into the disk probed by the two silicate emission bands in disks where dust settling has occurred. The 10 um feature strength vs. shape trend is not correlated with age or Halpha equivalent width, suggesting that some amount of turbulent mixing and regeneration of small grains is occurring. The strength vs. shape trend is related to spectral type, however, with M stars showing significantly flatter 10 um features (larger grain sizes) than A/B stars. The connection between spectral type and grain size is interpreted in terms of the variation in the silicate emission radius as a function of stellar luminosity, but could also be indicative of other spectral-type dependent factors (e.g, X-rays, UV radiation, stellar/disk winds, etc.).Comment: 17 pages, 13 figures, accepted for publication by ApJ, formatted with emulateapj using revtex4 v4.

Characterization of multifocal T2*-weighted MRI hypointensities in the basal ganglia of elderly, community-dwelling subjects

AbstractMultifocal T2*-weighted (T2*w) hypointensities in the basal ganglia, which are believed to arise predominantly from mineralized small vessels and perivascular spaces, have been proposed as a biomarker for cerebral small vessel disease. This study provides baseline data on their appearance on conventional structural MRI for improving and automating current manual segmentation methods. Using a published thresholding method, multifocal T2*w hypointensities were manually segmented from whole brain T2*w volumes acquired from 98 community-dwelling subjects in their early 70s. Connected component analysis was used to derive the average T2*w hypointensity count and load per basal ganglia nucleus, as well as the morphology of their connected components, while nonlinear spatial probability mapping yielded their spatial distribution. T1-weighted (T1w), T2-weighted (T2w) and T2*w intensity distributions of basal ganglia T2*w hypointensities and their appearance on T1w and T2w MRI were investigated to gain further insights into the underlying tissue composition. In 75/98 subjects, on average, 3 T2*w hypointensities with a median total volume per intracranial volume of 50.3ppm were located in and around the globus pallidus. Individual hypointensities appeared smooth and spherical with a median volume of 12mm3 and median in-plane area of 4mm2. Spatial probability maps suggested an association between T2*w hypointensities and the point of entry of lenticulostriate arterioles into the brain parenchyma. T1w and T2w and especially the T2*w intensity distributions of these hypointensities, which were negatively skewed, were generally not normally distributed indicating an underlying inhomogeneous tissue structure. Globus pallidus T2*w hypointensities tended to appear hypo- and isointense on T1w and T2w MRI, whereas those from other structures appeared iso- and hypointense. This pattern could be explained by an increased mineralization of the globus pallidus. In conclusion, the characteristic spatial distribution and appearance of multifocal basal ganglia T2*w hypointensities in our elderly cohort on structural MRI appear to support the suggested association with mineralized proximal lenticulostriate arterioles and perivascular spaces

A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression

Introduction: We hypothesized that common Alzheimer's disease (AD)-associated variants within the triggering receptor expressed on myeloid (TREM) gene cluster influence disease through gene expression. Methods: Expression microarrays on temporal cortex and cerebellum from ∼400 neuropathologically diagnosed subjects and two independent RNAseq replication cohorts were used for expression quantitative trait locus analysis. Results: A variant within a DNase hypersensitive site 5′ of TREM2, rs9357347-C, associates with reduced AD risk and increased TREML1 and TREM2 levels (uncorrected P = 6.3 × 10−3 and 4.6 × 10−2, respectively). Meta-analysis on expression quantitative trait locus results from three independent data sets (n = 1006) confirmed these associations (uncorrected P = 3.4 × 10−2 and 3.5 × 10−3, Bonferroni-corrected P = 6.7 × 10−2 and 7.1 × 10−3, respectively). Discussion: Our findings point to rs9357347 as a functional regulatory variant that contributes to a protective effect observed at the TREM locus in the International Genomics of Alzheimer's Project genome-wide association study meta-analysis and suggest concomitant increase in TREML1 and TREM2 brain levels as a potential mechanism for protection from AD

Sequence-Based Analysis Uncovers an Abundance of Non-Coding RNA in the Total Transcriptome of Mycobacterium tuberculosis

RNA sequencing provides a new perspective on the genome of Mycobacterium tuberculosis by revealing an extensive presence of non-coding RNA, including long 5’ and 3’ untranslated regions, antisense transcripts, and intergenic small RNA (sRNA) molecules. More than a quarter of all sequence reads mapping outside of ribosomal RNA genes represent non-coding RNA, and the density of reads mapping to intergenic regions was more than two-fold higher than that mapping to annotated coding sequences. Selected sRNAs were found at increased abundance in stationary phase cultures and accumulated to remarkably high levels in the lungs of chronically infected mice, indicating a potential contribution to pathogenesis. The ability of tubercle bacilli to adapt to changing environments within the host is critical to their ability to cause disease and to persist during drug treatment; it is likely that novel post-transcriptional regulatory networks will play an important role in these adaptive responses

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Cerebral small vessel disease genomics and its implications across the lifespan

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.Peer reviewe