Investigating the role of pannexin 3 in intervertebral disc health and disease

Pannexin 3 (Panx3) is a mechanosensitive, channel-forming glycoprotein implicated in the progression of post-traumatic osteoarthritis. Despite evidence for Panx3 expression in intervertebral discs (IVDs), its function here remained unknown. Using Panx3-/- mice, this study investigated the role of Panx3 in age-associated and injury-induced models of IVD degeneration. While loss of Panx3 did not significantly impact the progression of age-associated IVD degeneration, it was associated with a protective phenotype in an injury model of IVD degeneration, specifically in the annulus fibrosus (AF). Following IVD injury, WT mice showed an accumulation of enlarged cells that appeared to contribute to disrupted AF structure. In Panx3-/- IVDs, enlarged cells were rarely detected and AF structure was retained post-injury. Interestingly, uninjured IVDs adjacent to the site of injury were disrupted in Panx3-/- mice but remained healthy in WT mice. These studies suggest a role for Panx3 in mediating adaptive AF cellular responses to acute mechanical stress

The mechano-response of murine annulus fibrosus cells to cyclic tensile strain is frequency dependent

The intervertebral disk (IVD) is a composite structure essential for spine stabilization, load bearing, and movement. Biomechanical factors are important contributors to the IVD microenvironment regulating joint homeostasis; however, the cell type-specific effectors of mechanotransduction in the IVD are not fully understood. The current study aimed to determine the effects of cyclic tensile strain (CTS) on annulus fibrosus (AF) cells and identify mechano-sensitive pathways. Using a cell-type specific reporter mouse to differentiation NP and AF cells from the murine IVD, we characterized AF cells in dynamic culture exposed to CTS (6% strain) at specific frequencies (0.1 Hz, 1.0 Hz, or 2.0 Hz). We demonstrate that our culture model maintains the phenotype of primary AF cells and that the bioreactor system delivers uniform biaxial strain across the cell culture surface. We show that exposure of AF cells to CTS induces cytoskeleton reorganization resulting in stress fiber formation, with acute exposure to CTS at 2.0 Hz inducing a significant yet transient increase ERK1/2 pathway activation. Using SYBPR-based qPCR to assess the expression of extracellular matrix (ECM) genes, ECM-remodeling genes, candidate mechano-sensitive genes, inflammatory cytokines and cell surface receptors, we demonstrated that exposure of AF cells to CTS at 0.1 Hz increased Acan, Prg4, Col1a1 and Mmp3 expression. AF cells exposed to CTS at 1.0 Hz showed a significant increase in the expression of Acan, Myc, and Tnfα. Exposure of AF cells to CTS at 2.0 Hz induced a significant increase in Acan, Prg4, Cox2, Myc, Fos, and Tnfα expression. Among the cell surface receptors assessed, AF cells exposed to CTS at 2.0 Hz showed a significant increase in Itgβ1, Itgα5, and Trpv4 expression. Our findings demonstrate that the response of AF cells to CTS is frequency dependent and suggest that mechanical loading may directly contribute to matrix remodeling and the onset of local tissue inflammation in the murine IVD

Mid-infrared sources in the ELAIS Deep X-ray Survey

We present a cross‐correlation of the European Large Area Infrared Space Observatory (ISO) survey (ELAIS) with the ELAIS Deep X‐ray Survey of the N1 and N2 fields. There are seven Chandra point sources with matches in the ELAIS Final Analysis 15‐μm catalogue, out of a total of 28 extragalactic ISO sources present in the Chandra fields. Five of these are consistent with active galactic nuclei (AGN) giving an AGN fraction of ∼19 per cent in the 15‐μm flux range 0.8–6 mJy. We have co‐added the hard X‐ray fluxes of the individually undetected ISO sources and find a low significance detection consistent with star formation in the remaining population. We combine our point source cross‐correlation fraction with the XMM–Newton observations of the Lockman Hole and Chandra observations of the Hubble Deep Field North to constrain source count models of the mid‐infrared galaxy population. The low dust‐enshrouded AGN fraction in ELAIS implied by the number of cross‐identifications between the ELAIS mid‐infrared sample and the Chandra point sources is encouraging for the use of mid‐infrared surveys to constrain the cosmic star formation history, provided there are not further large undetected populations of Compton‐thick AGN

The SCUBA 8-mJy survey - I: Sub-millimetre maps, sources and number counts

We present maps, source lists, and number counts from the largest, unbiassed, extragalactic sub-mm survey so far undertaken with the SCUBA camera on the JCMT. Our maps cover 260 sq. arcmin, to a noise level S(850)=2.5 mJy/beam. We have reduced the data using both SURF, and our own pipeline which produces zero-footprint maps and noise images. The uncorrelated noise maps produced by the latter approach have allowed application of a maximum-likelihood method to measure the statistical significance of each peak, leading to properly quantified flux-density errors for all potential sources. We detect 19 sources with S/N > 4, 38 with S/N > 3.5, and 72 with S/N > 3. To assess completeness and the impact of source confusion we have applied our source extraction algorithm to a series of simulated images. The result is a new estimate of the sub-mm source counts in the flux-density range S(850)=5-15mJy, which we compare with other estimates, and with model predictions. Our estimate of the cumulative source count at S(850) > 8 mJy is 320 (+80,-100) per square degree. Assuming that the majority of sources have z > 1.5, the co-moving number density of high-z galaxies forming stars at a rate >1000 solar masses per year is 10^-5 per Mpc^3, with only a weak dependence on the precise redshift distribution. This number density corresponds to that of massive ellipticals with L > 3-4 L* at low redshift and is also the same as the co-moving number density of comparably massive, passively-evolving objects in the redshift band 1<z<2 inferred from recent surveys of extremely red objects. Thus the bright sub-mm sources can plausibly account for the formation of all present-day massive ellipticals. Improved z constraints, and a proper measurement of sub-mm clustering can refine or refute this picture.Comment: Minor revisions. 27 pages, 13 figures. Higher resolution versions of Figs 5,6,7 and 8 are available from the autho

The ELAIS Deep X-ray Survey

We present initial follow-up results of the ELAIS Deep X-ray Survey which is being undertaken with the Chandra and XMM-Newton Observatories. 235 X-ray sources are detected in our two 75 ks ACIS-I observations in the well-studied ELAIS N1 and N2 areas. 90% of the X-ray sources are identified optically to R=26 with a median magnitude of R=24. We show that objects which are unresolved optically (i.e. quasars) follow a correlation between their optical and X-ray fluxes, whereas galaxies do not. We also find that the quasars with fainter optical counterparts have harder X-ray spectra, consistent with absorption at both wavebands. Initial spectroscopic follow-up has revealed a large fraction of high-luminosity Type 2 quasars. The prospects for studying the evolution of the host galaxies of X-ray selected Type 2 AGN are considered.Comment: 9 pages, 5 figures, To appear in Proceedings of XXI Moriond Conference: "Galaxy Clusters and the High Redshift Universe Observed in X-rays", edited by D. Neumann, F.Durret, & J. Tran Thanh Va

The ELAIS deep X-ray survey - I. Chandra source catalogue and first results

We present an analysis of two deep (75 ks) Chandra observations of the European Large Area Infrared Space Observatory (ISO) Survey (ELAIS) fields N1 and N2 as the first results from the ELAIS deep X-ray survey. This survey is being conducted in well-studied regions with extensive multiwavelength coverage. Here we present the Chandra source catalogues along with an analysis of source counts, hardness ratios and optical classifications. A total of 233 X-ray point sources are detected in addition to two soft extended sources, which are found to be associated with galaxy clusters. An overdensity of sources is found in N1 with 30 per cent more sources than N2, which we attribute to large-scale structure. A similar variance is seen between other deep Chandra surveys. The source count statistics reveal an increasing fraction of hard sources at fainter fluxes. The number of galaxy-like counterparts also increases dramatically towards fainter fluxes, consistent with the emergence of a large population of obscured sources

Observations of the Hubble Deep Field with the Infrared Space Observatory. I. Data reduction, maps and sky coverage

We present deep imaging at 6.7 micron and 15 micron from the CAM instrument on the Infrared Space Observatory (ISO), centred on the Hubble Deep Field (HDF). These are the deepest integrations published to date at these wavelengths in any region of sky. We discuss the observation strategy and the data reduction. The observed source density appears to approach the CAM confusion limit at 15 micron, and fluctuations in the 6.7 micron sky background may be identifiable with similar spatial fluctuations in the HDF galaxy counts. ISO appears to be detecting comparable field galaxy populations to the HDF, and our data yields strong evidence that future IR missions (such as SIRTF, FIRST and WIRE) as well as SCUBA and millimetre arrays will easily detect field galaxies out to comparably high redshifts.Comment: 7 pages, LaTeX (using mn.sty), 9 figures included as GIFs. Gzipped Postscipt version available from http://artemis.ph.ic.ac.uk/hdf/papers/ps/. Further information on ISO-HDF project can be found at http://artemis.ph.ic.ac.uk/hdf

Observations of the Hubble Deep Field South with the Infrared Space Observatory - II. Associations and star formation rates

We present results from a deep mid-IR survey of the Hubble Deep Field South (HDF-S) region performed at 7 and 15um with the CAM instrument on board ISO. We found reliable optical/near-IR associations for 32 of the 35 sources detected in this field by Oliver et al. (2002, Paper I): eight of them were identified as stars, one is definitely an AGN, a second seems likely to be an AGN, too, while the remaining 22 appear to be normal spiral or starburst galaxies. Using model spectral energy distributions (SEDs) of similar galaxies, we compare methods for estimating the star formation rates (SFRs) in these objects, finding that an estimator based on integrated (3-1000um) IR luminosity reproduces the model SFRs best. Applying this estimator to model fits to the SEDs of our 22 spiral and starburst galaxies, we find that they are forming stars at rates of ~1-100 M_sol/yr, with a median value of ~40M_sol/yr, assuming an Einstein - de Sitter universe with a Hubble constant of 50 km/s/Mpc, and star formation taking place according to a Salpeter (1955) IMF across the mass range 0.1-100M_sol. We split the redshift range 0.0<z<0.6 into two equal-volume bins to compute raw estimates of the star formation rate density contributed by these sources, assuming the same cosmology and IMF as above and computing errors based on estimated uncertainties in the SFRs of individual galaxies. We compare these results with other estimates of the SFR density made with the same assumptions, showing them to be consistent with the results of Flores et al. (1999) from their ISO survey of the CFRS 1415+52 field. However, the relatively small volume of our survey means that our SFR density estimates suffer from a large sampling variance, implying that our results, by themselves, do not place tight constraints on the global mean SFR density.Comment: Accepted for MNRAS. 23 pages, 10 figures (Figs. 4&6 included here as low resolution JPEGS), latex, uses mn,epsfig. Further information and full resolution versions of Figs 4&6 available at http://astro.ic.ac.uk/hdfs (v2: full author list added

The coincidence and angular clustering of Chandra and SCUBA sources

NRC publication: N

Near and mid-infrared colours of star-forming galaxies in ELAIS fields

We present J and K-band near-infrared photometry of a sample of mid-infrared sources detected by the Infrared Space Observatory (ISO) as part of the European Large Area ISO-Survey (ELAIS) and study their classification and star-forming properties. We have used the Preliminary ELAIS Catalogue for the 6.7 micron (LW2) and 15 micron (LW3) fluxes. All of the high-reliability LW2 sources and 80 per cent of the LW3 sources are identified in the near-IR survey reaching K = 17.5 mag. The near- to mid-IR flux ratios can effectively be used to separate stars from galaxies in mid-IR surveys. The stars detected in our survey region are used to derive a new accurate calibration for the ELAIS ISOCAM data in both the LW2 and LW3 filters. We show that near to mid-IR colour-colour diagrams can be used to further classify galaxies, as well as study star-formation. The ISOCAM ELAIS survey is found to mostly detect strongly star-forming late-type galaxies, possibly starburst powered galaxies, and it also picks out obscured AGN. The ELAIS galaxies yield an average mid-IR flux ratio LW2/LW3 = 0.67 +/- 0.27. We discuss this [6.7/15] ratio as a star formation tracer using ISO and IRAS data of a local comparison sample. We find that the [K/15] ratio is also agood indicator of activity level in galaxies and conclude that the drop in the [6.7/15] ratio seen in strongly star-forming galaxies is a result of both an increase of 15 mic emission and an apparent depletion of 6.7 mic emission. Near-IR data together with the mid-IR give the possibility to estimate the relative amount of interstellar matter in the galaxies.Comment: 18 pages, 15 figures; accepted for publication in MNRA