The neuroprotective effects of human bone marrow mesenchymal stem cells are dose-dependent in TNBS colitis

The incidence of inflammatory bowel diseases (IBD) is increasing worldwide with patients experiencing severe impacts on their quality of life. It is well accepted that intestinal inflammation associates with extensive damage to the enteric nervous system (ENS), which intrinsically innervates the gastrointestinal tract and regulates all gut functions. Hence, treatments targeting the enteric neurons are plausible for alleviating IBD and associated complications. Mesenchymal stem cells (MSCs) are gaining wide recognition as a potential therapy for many diseases due to their immunomodulatory and neuroprotective qualities. However, there is a large discrepancy regarding appropriate cell doses used in both clinical trials and experimental models of disease. We have previously demonstrated that human bone marrow MSCs exhibit neuroprotective and anti-inflammatory effects in a Guinea-pig model of 2,4,6-trinitrobenzene-sulfonate (TNBS)-induced colitis; but an investigation into whether this response is dose-dependent has not been conducted. Methods: Hartley Guinea-pigs were administered TNBS or sham treatment intra-rectally. Animals in the MSC treatment groups received either 1 × 10 5 , 1 × 10 6 or 3 × 10 6 MSCs by enema 3 hours after induction of colitis. Colon tissues were collected 72 hours after TNBS administration to assess the effects of MSC treatments on the level of inflammation and damage to the ENS by immunohistochemical and histological analyses. Results: MSCs administered at a low dose, 1 × 10 5 cells, had little or no effect on the level of immune cell infiltrate and damage to the colonic innervation was similar to the TNBS group. Treatment with 1 × 10 6 MSCs decreased the quantity of immune infiltrate and damage to nerve processes in the colonic wall, prevented myenteric neuronal loss and changes in neuronal subpopulations. Treatment with 3 × 10 6 MSCs had similar effects to 1 × 10 6 MSC treatments. Conclusions: The neuroprotective effect of MSCs in TNBS colitis is dose-dependent. Increasing doses higher than 1 × 10 6 MSCs demonstrates no further therapeutic benefit than 1 × 10 6 MSCs in preventing enteric neuropathy associated with intestinal inflammation. Furthermore, we have established an optimal dose of MSCs for future studies investigating intestinal inflammation, the enteric neurons and stem cell therapy in this model

Discovery of a new Transient X-ray Pulsar in the Small Magellanic Cloud

Rossi X-Ray Timing Explorer observations of the Small Magellanic Cloud have revealed a previously unknown transient X-ray pulsar with a pulse period of 95s. Provisionally designated XTE SMC95, the pulsar was detected in three Proportional Counter Array observations during an outburst spanning 4 weeks in March/April 1999. The pulse profile is double peaked reaching a pulse fraction \~0.8. The source is proposed as a Be/neutron star system on the basis of its pulsations, transient nature and characteristically hard X-ray spectrum. The 2-10 keV X-ray luminosity implied by our observations is > 2x10^37 erg/s which is consistent with that of normal outbursts seen in Galactic systems. This discovery adds to the emerging picture of the SMC as containing an extremely dense population of transient high mass X-ray binaries.Comment: Accepted by A&A. 7 pages, 6 figure

WALLABY pre-pilot survey: ultra-diffuse galaxies in the Eridanus supergroup

We present a pilot study of the atomic neutral hydrogen gas (H I) content of ultra-diffuse galaxy (UDG) candidates. In this paper, we use the pre-pilot Eridanus field data from the Widefield ASKAP L-band Legacy All-sky Blind Survey to search for H I in UDG candidates found in the Systematically Measuring Ultra-diffuse Galaxies survey (SMUDGes). We narrow down to 78 SMUDGes UDG candidates within the maximum radial extents of the Eridanus subgroups for this study. Most SMUDGes UDGs candidates in this study have effective radii smaller than 1.5 kpc and thus fail to meet the defining size threshold. We only find one H I detection, which we classify as a low-surface-brightness dwarf. Six putative UDGs are H I-free. We show the overall distribution of SMUDGes UDG candidates on the size–luminosity relation and compare them with low-mass dwarfs on the atomic gas fraction versus stellar mass scaling relation. There is no correlation between gas-richness and colour indicating that colour is not the sole parameter determining their H I content. The evolutionary paths that drive galaxy morphological changes and UDG formation channels are likely the additional factors to affect the H I content of putative UDGs. The actual numbers of UDGs for the Eridanus and NGC 1332 subgroups are consistent with the predicted abundance of UDGs and the halo virial mass relation, except for the NGC 1407 subgroup, which has a smaller number of UDGs than the predicted number. Different group environments suggest that these putative UDGs are likely formed via the satellite accretion scenario

WALLABY – An SKA Pathfinder HiSurvey

The Widefield ASKAP L-band Legacy All-sky Blind surveY (WALLABY) is a next-generation survey of neutral hydrogen (HI) in the Local Universe. It uses the widefield, high-resolution capability of the Australian Square Kilometer Array Pathfinder (ASKAP), a radio interferometer consisting of 36 x 12-m dishes equipped with Phased-Array Feeds (PAFs), located in an extremely radio-quiet zone in Western Australia. WALLABY aims to survey three-quarters of the sky (-90 degr \u3c Dec \u3c +30 degr) to a redshift of z \u3c 0.26, and generate spectral line image cubes at ~30 arcsec resolution and ~1.6 mJy/beam per 4 km/s channel sensitivity. ASKAP\u27s instantaneous field of view at 1.4 GHz, delivered by the PAF\u27s 36 beams, is about 30 sq deg. At an integrated signal-to-noise ratio of five, WALLABY is expected to detect over half a million galaxies with a mean redshift of z ~ 0.05 (~200 Mpc). The scientific goals of WALLABY include: (a) a census of gas-rich galaxies in the vicinity of the Local Group; (b) a study of the HI properties of galaxies, groups and clusters, in particular the influence of the environment on galaxy evolution; and (c) the refinement of cosmological parameters using the spatial and redshift distribution of low-bias gas-rich galaxies. For context we provide an overview of previous large-scale HI surveys. Combined with existing and new multi-wavelength sky surveys, WALLABY will enable an exciting new generation of panchromatic studies of the Local Universe. - First results from the WALLABY pilot survey are revealed, with initial data products publicly available in the CSIRO ASKAP Science Data Archive (CASDA)

HI Observations of Flat Galaxies

We present the HI observations of 94 flat spiral galaxies from RFGC (the Revised Flat Galaxy Catalog) and 14 galaxies from 2MFGC (the 2MASS selected Flat Galaxy Catalog) performed with the 100-m radio telescope in Effelsberg (Germany). HI fluxes, heliocentric radial velocities, and HI line widths are given for 65 detected galaxies. We present a mosaic of HI profiles. We calculated some of the global parameters of the galaxies and analyzed the linear correlations between them. The ratios of the total (indicative) masses of the galaxies to their luminosities lie within the range 0.4 with a mean of 3.8 (M_{\sun}/L_{\sun}), and the mean mass fraction of neutral hydrogen is 13%. Upper limits are given for the radio fluxes from 43 undetected galaxies.Comment: 24 pages, 7 figure

The Dust-to-Gas Ratio in the Small Magellanic Cloud Tail

The Tail region of the Small Magellanic Cloud (SMC) was imaged using the MIPS instrument on the Spitzer Space Telescope as part of the SAGE-SMC Spitzer Legacy. Diffuse infrared emission from dust was detected in all the MIPS bands. The Tail gas-to-dust ratio was measured to be 1200 +/- 350 using the MIPS observations combined with existing IRAS and HI observations. This gas-to-dust ratio is higher than the expected 500-800 from the known Tail metallicity indicating possible destruction of dust grains. Two cluster regions in the Tail were resolved into multiple sources in the MIPS observations and local gas-to-dust ratios were measured to be ~440 and ~250 suggests dust formation and/or significant amounts of ionized gas in these regions. These results support the interpretation that the SMC Tail is a tidal tail recently stripped from the SMC that includes gas, dust, and young stars.Comment: 6 pages, 3 figures, ApJ Letters, in press, (version with full resolution figures at http://www.stsci.edu/~kgordon/papers/PS_files/sage-smc_taildust_v1.62.pdf

Gas Rich Galaxies and the HI Mass Function

We have developed an automated cross-correlation technique to detect 21cm emission in sample spectra obtained from the HI Parkes All Sky Survey. The initial sample selection was the nearest spectra to 2435 low surface brightness galaxies in the catalogue of Morshidi-Esslinger et al. (1999). The galaxies were originally selected to have properties similar to Fornax cluster dE galaxies. As dE galaxies are generally gas poor it is not surprising that there were only 26 secure detections. All of the detected galaxies have very high values of $(M_{H}/L_{B})_{\odot}$. Thus the HI selection of faint optical sources leads to the detection of predominately gas rich galaxies. The gas rich galaxies tend to reside on the outskirts of the large scale structure delineated by optically selected galaxies, but they do appear to be associated with it. These objects appear to have similar relative dark matter content to optically selected galaxies. The HI column densities are lower than the 'critical density' necessary for sustainable star formation and they appear, relatively, rather isolated from companion galaxies. These two factors may explain their high relative gas content. We have considered the HI mass function by looking at the distribution of velocities of HI detections in random spectra on the sky. The inferred HI mass function is steep though confirmation of this results awaits a detailed study of the noise characteristics of the HI survey.Comment: MNRAS in pres

A Pressure Anomaly for HII Regions in Irregular Galaxies

The pressures of giant HII regions in 6 dwarf Irregular galaxies are a factor of ~10 larger than the average pressures of the corresponding galaxy disks, obtained from the stellar and gaseous column densities. Either the visible HII regions in these dwarfs are all so young that they are still expanding, or there is an unexpected source of disk self-gravity that increases the background pressure. We consider the possibility that the additional self-gravity comes from disk dark matter, but suggest this is unlikely because the vertical scale heights inferred for Irregular galaxies are consistent with the luminous matter alone. Some of the HII region overpressure is probably the result of local peaks in the gravitational field that come from large gas concentrations, many of which are observed directly. These peaks also explain the anomalously low average column density thresholds for star formation that were found earlier for Irregular galaxies, and they permit the existence of a cool HI phase as the first step toward dense molecular cores. Many of the HII regions could also be so strongly over-pressured that they will expand for a long time. In this case, the observed population would be only 7% of the total, and the aging HII regions, now too faint to see, should occupy nearly the entire dwarf galaxy volume. Such prolonged HII region expansion would explain the origin of the giant HI shells that are seen in these galaxies, and account for the lack of bright central clusters inside these shells.Comment: 27 pages, 4 figures, Astrophysical Journal, 540, Sep 10, 2000, in pres

The Onset and Progression of Chronic Colitis Parallels Increased Mucosal Serotonin Release via Enterochromaffin Cell Hyperplasia and Downregulation of the Serotonin Reuptake Transporter

Background Serotonin (5-hydroxytryptamine, 5-HT) has been linked with several inflammation-associated intestinal diseases, including ulcerative colitis (UC). The largest pool of 5-HT in the body is in enterochromaffin (EC) cells located throughout the intestinal tract. EC cells are mechanosensitive and detect noxious stimuli, inducing secretion of 5-HT, which plays an important role in enteric reflexes and immunomodulation. In this study, we evaluated intestinal 5-HT levels in the Winnie mouse model of spontaneous chronic colitis, which closely replicates UC. Methods Real-time electrochemical recordings of 5-HT oxidation currents were obtained from ex vivo preparations of jejunum, ileum, proximal, and distal colon from Winnie (5-25 weeks old) and age matched C57BL/6 mice. EC cells were examined by immunohistochemistry, and the gene expression of tryptophan hydroxylase 1 (5-HT synthesis) and the serotonin reuptake transporter (SERT) were determined by quantitative Real-Time Polymerase Chain Reaction (RT-qPCR). Results Compression-evoked and basal 5-HT concentrations were elevated in the distal and proximal colon of Winnie mice. EC cell hyperplasia and downregulation of SERT on the transcriptional level were identified as mechanisms underlying increased levels of 5-HT. Increase in mucosal 5-HT release was observed at the onset of disease at 7-14 weeks, confirmed by disease activity scores. Furthermore, increases in 5-HT levels and progression of disease activity correlated linearly with age, but not sex. Conclusions Our findings in the Winnie mouse model of spontaneous chronic colitis demonstrate for the first time that the onset and progression of chronic UC-like intestinal inflammation is associated with increased 5-HT levels in the colonic mucosa

Oxaliplatin-induced changes in microbiota, TLR4+ cells and enhanced HMGB1 expression in the murine colon

<div><p>Oxaliplatin is a platinum-based chemotherapeutic used for cancer treatment. Its use associates with peripheral neuropathies and chronic gastrointestinal side-effects. Oxaliplatin induces immunogenic cell death by provoking the presentation of damage associated molecular patterns. The damage associated molecular patterns high-mobility group box 1 (HMGB1) protein exerts pro-inflammatory cytokine-like activity and binds to toll-like receptors (namely TLR4). Gastrointestinal microbiota may influence chemotherapeutic efficacy and contribute to local and systemic inflammation. We studied effects of oxaliplatin treatment on 1) TLR4 and high-mobility group box 1 expression within the colon; 2) gastrointestinal microbiota composition; 3) inflammation within the colon; 4) changes in Peyer’s patches and mesenteric lymph nodes immune populations in mice. TLR4⁺ cells displayed pseudopodia-like extensions characteristic of antigen sampling co-localised with high-mobility group box 1 -overexpressing cells in the colonic lamina propria from oxaliplatin-treated animals. Oxaliplatin treatment caused significant reduction in <i>Parabacteroides</i> and <i>Prevotella</i>_<i>1</i>, but increase in <i>Prevotella</i>_<i>2</i> and <i>Odoribacter</i> bacteria at the genus level. Downregulation of pro-inflammatory cytokines and chemokines in colon samples, a reduction in macrophages and dendritic cells in mesenteric lymph nodes were found after oxaliplatin treatment. In conclusion, oxaliplatin treatment caused morphological changes in TLR4+ cells, increase in gram-negative microbiota and enhanced HMGB1 expression associated with immunosuppression in the colon.</p></div