Three-Dimensional Structure of the Magnetic Field in the Disk of the Milky Way

We present Rotation Measures (RM) of the diffuse Galactic synchrotron emission from the Canadian Galactic Plane Survey (CGPS) and compare them to RMs of extragalactic sources in order to study the large-scale reversal in the Galactic magnetic field (GMF). Using Stokes Q, U and I measurements of the Galactic disk collected with the Synthesis Telescope at the Dominion Radio Astrophysical Observatory, we calculate RMs over an extended region of the sky, focusing on the low longitude range of the CGPS (l=52deg to l=72deg). We note the similarity in the structures traced by the compact sources and the extended emission and highlight the presence of a gradient in the RM map across an approximately diagonal line, which we identify with the well-known field reversal of the Sagittarius-Carina arm. We suggest that the orientation of this reversal is a geometric effect resulting from our location within a GMF structure arising from current sheets that are not perpendicular to the Galactic plane, as is required for a strictly radial field reversal, but that have at least some component parallel to the disk. Examples of models that fit this description are the three-dimensional dynamo-based model of Gressel et al. (2013) and a Galactic scale Parker spiral (Akasofu & Hakamada 1982), although the latter may be problematic in terms of Galactic dynamics. We emphasize the importance of constructing three-dimensional models of the GMF to account for structures like the diagonal RM gradient observed in this dataset.Comment: Published in Astronomy and Astrophysics, Accepted 23 April, 201

Membrane-To-Nucleus Signaling Links Insulin-Like Growth Factor-1- and Stem Cell Factor-Activated Pathways

Stem cell factor (mouse: Kitl, human: KITLG) and insulin-like growth factor-1 (IGF1), acting via KIT and IGF1 receptor (IGF1R), respectively, are critical for the development and integrity of several tissues. Autocrine/paracrine KITLG-KIT and IGF1-IGF1R signaling are also activated in several cancers including gastrointestinal stromal tumors (GIST), the most common sarcoma. In murine gastric muscles, IGF1 promotes Kitl-dependent development of interstitial cells of Cajal (ICC), the non-neoplastic counterpart of GIST, suggesting cooperation between these pathways. Here, we report a novel mechanism linking IGF1-IGF1R and KITLG-KIT signaling in both normal and neoplastic cells. In murine gastric muscles, the microenvironment for ICC and GIST, human hepatic stellate cells (LX-2), a model for cancer niches, and GIST cells, IGF1 stimulated Kitl/KITLG protein and mRNA expression and promoter activity by activating several signaling pathways including AKT-mediated glycogen synthase kinase-3β inhibition (GSK3i). GSK3i alone also stimulated Kitl/KITLG expression without activating mitogenic pathways. Both IGF1 and GSK3i induced chromatin-level changes favoring transcriptional activation at the Kitl promoter including increased histone H3/H4 acetylation and H3 lysine (K) 4 methylation, reduced H3K9 and H3K27 methylation and reduced occupancy by the H3K27 methyltransferase EZH2. By pharmacological or RNA interference-mediated inhibition of chromatin modifiers we demonstrated that these changes have the predicted impact on KITLG expression. KITLG knock-down and immunoneutralization inhibited the proliferation of GIST cells expressing wild-type KIT, signifying oncogenic autocrine/paracrine KITLG-KIT signaling. We conclude that membrane-to-nucleus signaling involving GSK3i establishes a previously unrecognized link between the IGF1-IGF1R and KITLG-KIT pathways, which is active in both physiologic and oncogenic contexts and can be exploited for therapeutic purposes

The effects of repetitive use and pathological remodeling on channelrhodopsin function in cardiomyocytes

Aim: Channelrhodopsins (ChRs) are a large family of light-gated ion channels with distinct properties, which is of great importance in the selection of a ChR variant for a given application. However, data to guide such selection for cardiac optogenetic applications are lacking. Therefore, we investigated the functioning of different ChR variants in normal and pathological hypertrophic cardiomyocytes subjected to various illumination protocols.Methods and Results: Isolated neonatal rat ventricular cardiomyocytes (NRVMs) were transduced with lentiviral vectors to express one of the following ChR variants: H134R, CatCh, ReaChR, or GtACR1. NRVMs were treated with phenylephrine (PE) to induce pathological hypertrophy (PE group) or left untreated [control (CTL) group]. In these groups, ChR currents displayed unique and significantly different properties for each ChR variant on activation by a single 1-s light pulse (1 mW/mm(2): 470, 565, or 617 nm). The concomitant membrane potential (V-m) responses also showed a ChR variant-specific profile, with GtACR1 causing a slight increase in average V-m during illumination (V-plateau: -38 mV) as compared with a V-plateau > -20 mV for the other ChR variants. On repetitive activation at increasing frequencies (10-ms pulses at 1-10 Hz for 30 s), peak currents, which are important for cardiac pacing, decreased with increasing activation frequencies by 17-78% (p 0.05).Conclusion: Our data show that ChR variants function equally well in cell culture models of healthy and pathologically hypertrophic myocardium but show strong, variant-specific use-dependence. This use-dependent nature of ChR function should be taken into account during the design of cardiac optogenetic studies and the interpretation of the experimental findings thereof.Cardiolog

Faraday moments of the Southern Twenty-centimeter All-sky Polarization Survey (STAPS)

Faraday tomography of broadband radio polarization surveys enables us to study magnetic fields and their interaction with the interstellar medium (ISM). Such surveys include the Global Magneto-Ionic Medium Survey (GMIMS), which covers the northern and southern hemispheres at $\sim$ 300-1800 MHz. In this work, we used the GMIMS High Band South (1328-1768 MHz), also named the Southern Twenty-centimeter All-sky Polarization Survey (STAPS), which observes the southern sky at a resolution of 18\arcmin. To extract the key parameters of the magnetized ISM from STAPS, we computed the Faraday moments of the tomographic data cubes. These moments include the total polarized intensity, the mean Faraday depth weighted by the polarized intensity, the weighted dispersion of the Faraday spectrum, and its skewness. We compared the Faraday moments to those calculated over the same frequency range in the northern sky (using the Dominion Radio Astrophysical Observatory, DRAO), in a strip of 360\degr \times 30\degr that overlaps with STAPS coverage. We find that the total polarized intensity is generally dominated by diffuse emission that decreases at longitudes of l \leq 300\degr. The Faraday moments reveal a variety of polarization structures. Low-intensity regions at high latitudes usually have a single Faraday depth component. Due to its insufficiently large frequency coverage, STAPS cannot detect Faraday thick structures. Comparing the Faraday depths from STAPS to total rotation measures from extragalactic sources suggests that STAPS frequencies are high enough that the intervening ISM causes depolarization to background emission at intermediate and high Galactic latitudes. Where they overlap, the STAPS and DRAO surveys exhibit broad correspondence but differ in polarized intensity by a factor of $\sim$1.8.Comment: Revision in progress in Astronomy and Astrophysic

Structure in the Magnetic Field of the Milky Way Disk and Halo traced by Faraday Rotation

Magnetic fields in the ionized medium of the disk and halo of the Milky Way impose Faraday rotation on linearly polarized radio emission. We compare two surveys mapping the Galactic Faraday rotation, one showing the rotation measures of extragalactic sources seen through the Galaxy (from Hutschenreuter et al 2022), and one showing the Faraday depth of the diffuse Galactic synchrotron emission from the Global Magneto-Ionic Medium Survey. Comparing the two data sets in 5deg x 10deg bins shows good agreement at intermediate latitudes, 10 < |b| < 50 deg, and little correlation between them at lower and higher latitudes. Where they agree, both tracers show clear patterns as a function of Galactic longitude: in the Northern Hemisphere a strong sin(2 x longitude) pattern, and in the Southern hemisphere a sin(longitude + pi) pattern. Pulsars with height above or below the plane |z| > 300 pc show similar longitude dependence in their rotation measures. Nearby non-thermal structures show rotation measure shadows as does the Orion-Eridanus superbubble. We describe families of dynamo models that could explain the observed patterns in the two hemispheres. We suggest that a field reversal, known to cross the plane a few hundred pc inside the solar circle, could shift to positive z with increasing Galactic radius to explain the sin(2xlongitude) pattern in the Northern Hemisphere. Correlation shows that rotation measures from extragalactic sources are one to two times the corresponding rotation measure of the diffuse emission, implying Faraday complexity along some lines of sight, especially in the Southern hemisphere.Comment: 37 pages, 26 figures, Ap. J. accepte

p21 produces a bioactive secretome that places stressed cells under immunosurveillance

Immune cells identify and destroy damaged cells to prevent them from causing cancer or other pathologies by mechanisms that remain poorly understood. Here, we report that the cell-cycle inhibitor p21 places cells under immunosurveillance to establish a biological timer mechanism that controls cell fate. p21 activates retinoblastoma protein (Rb)-dependent transcription at select gene promoters to generate a complex bioactive secretome, termed p21-activated secretory phenotype (PASP). The PASP includes the chemokine CXCL14, which promptly attracts macrophages. These macrophages disengage if cells normalize p21 within 4 days, but if p21 induction persists, they polarize toward an M1 phenotype and lymphocytes mount a cytotoxic T cell response to eliminate target cells, including preneoplastic cells. Thus, p21 concurrently induces proliferative arrest and immunosurveillance of cells under duress

The Global Magneto-Ionic Medium Survey (GMIMS): The brightest polarized region in the Southern sky at 75cm and its implications for Radio Loop II

Using the Global Magneto-Ionic Medium Survey (GMIMS) Low-Band South (LBS) southern sky polarization survey, covering 300 to 480 MHz at 81 arcmin resolution, we reveal the brightest region in the Southern polarized sky at these frequencies. The region, G150-50, covers nearly 20deg$^2$, near (l,b)~(150 deg,-50 deg). Using GMIMS-LBS and complementary data at higher frequencies (~0.6--30 GHz), we apply Faraday tomography and Stokes QU-fitting techniques. We find that the magnetic field associated with G150-50 is both coherent and primarily in the plane of the sky, and indications that the region is associated with Radio Loop II. The Faraday depth spectra across G150-50 are broad and contain a large-scale spatial gradient. We model the magnetic field in the region as an expanding shell, and we can reproduce both the observed Faraday rotation and the synchrotron emission in the GMIMS-LBS band. Using QU-fitting, we find that the Faraday spectra are produced by several Faraday dispersive sources along the line-of-sight. Alternatively, polarization horizon effects that we cannot model are adding complexity to the high-frequency polarized spectra. The magnetic field structure of Loop II dominates a large fraction of the sky, and studies of the large-scale polarized sky will need to account for this object. Studies of G150-50 with high angular resolution could mitigate polarization horizon effects, and clarify the nature of G150-50.Comment: 25 pages, 14 figures. Accepted for publication in MNRA

Differential gene expression profile in the small intestines of mice lacking pacemaker interstitial cells of Cajal

BACKGROUND: We previously identified eight known and novel genes differentially expressed in the small intestines of wild type and W/W(V )mice, which have greatly reduced populations of the interstitial cells of Cajal, that are responsible for the generation of electrical slow waves, by using a differential gene display method. METHODS: By using the same method we isolated additional candidate genes that were specifically down- or up-regulated in W/W(V )mice. Novel transcripts were designated as DDWMEST. RESULTS: We isolated seven candidates that were specifically down- or up-regulated in W/W(V )mice. Two novel transcripts, DDWMEST 1 and -91 were increased in both fed and fasted W/W(V )mice. Expression of another five genes was suppressed in W/W(V )mice: ARG2 (Arginase II), ONZIN (encoding leukemia inhibitory factor regulated protein), and three novel transcripts: DDWMEST62, -84, and -100. Together with the previous report, we identified fifteen differentially expressed genes in total in the small intestines of W/W(V )mice. Eight of these genes were reduced in the jejunums of W/W(V )mice compared to age matched wild type mice, whereas the other seven genes showed an increase in expression. Differential expression was the same in fasted and fed animals, suggesting that the differences were independent of the dietetic state of the animal. CONCLUSIONS: Several known and novel genes are differentially expressed in the small intestines of W/W(V )mice. Differential gene comparison might contribute to our understanding of motility disorders associated with the loss of the interstitial cells of Cajal

Characterization of the John A. Galt telescope for radio holography with CHIME

The Canadian Hydrogen Intensity Mapping Experiment (CHIME) will measure the 21 cm emission of astrophysical neutral hydrogen to probe large scale structure at redshifts z=0.8-2.5. However, detecting the 21 cm signal beneath substantially brighter foregrounds remains a key challenge. Due to the high dynamic range between 21 cm and foreground emission, an exquisite calibration of instrument systematics, notably the telescope beam, is required to successfully filter out the foregrounds. One technique being used to achieve a high fidelity measurement of the CHIME beam is radio holography, wherein signals from each of CHIME's analog inputs are correlated with the signal from a co-located reference antenna, the 26 m John A. Galt telescope, as the 26 m Galt telescope tracks a bright point source transiting over CHIME. In this work we present an analysis of several of the Galt telescope's properties. We employ driftscan measurements of several bright sources, along with background estimates derived from the 408 MHz Haslam map, to estimate the Galt system temperature. To determine the Galt telescope's beam shape, we perform and analyze a raster scan of the bright radio source Cassiopeia A. Finally, we use early holographic measurements to measure the Galt telescope's geometry with respect to CHIME for the holographic analysis of the CHIME and Galt interferometric data set

The Global Magneto-Ionic Medium Survey: A Faraday Depth Survey of the Northern Sky Covering 1280-1750 MHz

The Galactic interstellar medium hosts a significant magnetic field, which can be probed through the synchrotron emission produced from its interaction with relativistic electrons. Linearly polarized synchrotron emission is generated throughout the Galaxy, and at longer wavelengths, modified along nearly every path by Faraday rotation in the intervening magneto-ionic medium. Full characterization of the polarized emission requires wideband observations with many frequency channels. We have surveyed polarized radio emission from the Northern sky over the the range 1280-1750 MHz, with channel width 236.8 kHz, using the John A. Galt Telescope (diameter 25.6 m) at the Dominion Radio Astrophysical Observatory, as part of the Global Magneto-Ionic Medium Survey. The survey covered 72% of the sky, declinations -30 to +87 degrees at all right ascensions. The intensity scale was absolutely calibrated, based on the flux density and spectral index of Cygnus A. Polarization angle was calibrated using the extended polarized emission of the Fan Region. Data are presented as brightness temperatures with angular resolution 40'. Sensitivity in Stokes Q and U is 45 mK rms in a 1.18 MHz band. We have applied rotation measure synthesis to the data to obtain a Faraday depth cube of resolution 150 radians per square metre and sensitivity 3 mK rms of polarized intensity. Features in Faraday depth up to a width of 110 radians per square metre are represented. The maximum detectable Faraday depth is +/- 20,000 radians per square metre. The survey data are available at the Canadian Astronomy Data Centre.Comment: Accepted for publication in the Astronomical Journa