A role for the extracellular calcium-sensing receptor in cell-cell communication in pancreatic islets of Langerhans

Background: The extracellular calcium-sensing receptor (CaR) is expressed in many tissues that are not associated with Ca2+ homeostasis, including the endocrine cells in pancreatic islets of Langerhans. We have demonstrated previously that pharmacological activation of the CaR stimulates insulin secretion from islet -cells and insulin-secreting MIN6 cells. Methods: In the present study we have investigated the effects of CaR activation on MIN6 cell proliferation and have used shRNA-mediated CaR knockdown to determine whether the CaR is involved in the regulation of insulin secretion via cell-cell communication. Results: CaR activation caused the phosphorylation and activation of the p42/44 MAPK signalling cascade, and this activation was prevented by the shRNA-induced down-regulation of CaR mRNA expression. CaR activation also resulted in increased proliferation of MIN6 cells, consistent with the known role of the p42/44 MAPK system in the regulation of -cell proliferation. Down-regulation of CaR expression had no detectable effects on glucose-induced insulin secretion from MIN6 cells maintained as monolayers, but blocked the increases in insulin secretion that were observed when the cells were configured as three-dimensional islet-like structures (pseudoislets), consistent with a role for the CaR in cell-cell communication in pseudoislets. Conclusion: It is well established that islet function is dependent on communication between islet cells and the results of this study suggest that the CaR is required for -cell to -cell interactions within islet-like structures

The Properties of Radio Galaxies and the Effect of Environment in Large Scale Structures at z∼1z\sim1

In this study we investigate 89 radio galaxies that are spectroscopically-confirmed to be members of five large scale structures in the redshift range of $0.65 \le z \le 0.96$. Based on a two-stage classification scheme, the radio galaxies are classified into three sub-classes: active galactic nucleus (AGN), hybrid, and star-forming galaxy (SFG). We study the properties of the three radio sub-classes and their global and local environmental preferences. We find AGN hosts are the most massive population and exhibit quiescence in their star-formation activity. The SFG population has a comparable stellar mass to those hosting a radio AGN but are unequivocally powered by star formation. Hybrids, though selected as an intermediate population in our classification scheme, were found in almost all analyses to be a unique type of radio galaxies rather than a mixture of AGN and SFGs. They are dominated by a high-excitation radio galaxy (HERG) population. We discuss environmental effects and scenarios for each sub-class. AGN tend to be preferentially located in locally dense environments and in the cores of clusters/groups, with these preferences persisting when comparing to galaxies of similar colour and stellar mass, suggesting that their activity may be ignited in the cluster/group virialized core regions. Conversely, SFGs exhibit a strong preference for intermediate-density global environments, suggesting that dusty starbursting activity in LSSs is largely driven by galaxy-galaxy interactions and merging.Comment: 28 pages, 10 figures, accepted to MNRA

Influenza research database: an integrated bioinformatics resource for influenza research and surveillance.

BackgroundThe recent emergence of the 2009 pandemic influenza A/H1N1 virus has highlighted the value of free and open access to influenza virus genome sequence data integrated with information about other important virus characteristics.DesignThe Influenza Research Database (IRD, http://www.fludb.org) is a free, open, publicly-accessible resource funded by the U.S. National Institute of Allergy and Infectious Diseases through the Bioinformatics Resource Centers program. IRD provides a comprehensive, integrated database and analysis resource for influenza sequence, surveillance, and research data, including user-friendly interfaces for data retrieval, visualization and comparative genomics analysis, together with personal log in-protected 'workbench' spaces for saving data sets and analysis results. IRD integrates genomic, proteomic, immune epitope, and surveillance data from a variety of sources, including public databases, computational algorithms, external research groups, and the scientific literature.ResultsTo demonstrate the utility of the data and analysis tools available in IRD, two scientific use cases are presented. A comparison of hemagglutinin sequence conservation and epitope coverage information revealed highly conserved protein regions that can be recognized by the human adaptive immune system as possible targets for inducing cross-protective immunity. Phylogenetic and geospatial analysis of sequences from wild bird surveillance samples revealed a possible evolutionary connection between influenza virus from Delaware Bay shorebirds and Alberta ducks.ConclusionsThe IRD provides a wealth of integrated data and information about influenza virus to support research of the genetic determinants dictating virus pathogenicity, host range restriction and transmission, and to facilitate development of vaccines, diagnostics, and therapeutics

No Evidence of Quasar-Mode Feedback in a Four-Way Group Merger at z~0.84

We report on the results of a Chandra search for evidence of triggered nuclear activity within the Cl0023+0423 four-way group merger at z ~ 0.84. The system consists of four interacting galaxy groups in the early stages of hierarchical cluster formation and, as such, provides a unique look at the level of processing and evolution already under way in the group environment prior to cluster assembly. We present the number counts of X-ray point sources detected in a field covering the entire Cl0023 structure, as well as a cross-correlation of these sources with our extensive spectroscopic database. Both the redshift distribution and cumulative number counts of X-ray sources reveal little evidence to suggest that the system contains X-ray luminous active galactic nuclei (AGNs) in excess to what is observed in the field population. If preprocessing is under way in the Cl0023 system, our observations suggest that powerful nuclear activity is not the predominant mechanism quenching star formation and driving the evolution of Cl0023 galaxies. We speculate that this is due to a lack of sufficiently massive nuclear black holes required to power such activity, as previous observations have found a high late-type fraction among the Cl0023 population. It may be that disruptive AGN-driven outflows become an important factor in the preprocessing of galaxy populations only during a later stage in the evolution of such groups and structures when sufficiently massive galaxies (and central black holes) have built up, but prior to hydrodynamical processes stripping them of their gas reservoirs.Comment: Published in ApJ

The Evolution and Environments of X-ray Emitting Active Galactic Nuclei in High-Redshift Large-Scale Structures

We use deep Chandra imaging and an extensive optical spectroscopy campaign on the Keck 10-m telescopes to study the properties of X-ray point sources in five large-scale structures at redshifts of z ~ 0.7-0.9. We first study X-ray point sources using the statistical measure of cumulative source counts, finding that the measured overdensities are consistent with previous results, but we recommend caution in overestimating the precision of the technique. Optical spectroscopy of objects matched to X-ray point sources confirms a total of 27 AGN within the five structures, and we find that their host galaxies tend to be located away from dense cluster cores. More than 36% of host galaxies are located in the `green valley', which suggests they are a transitional population. Based on analysis of OII and Hd line strengths, the average spectral properties of the AGN host galaxies in all structures indicate either on-going star formation or a starburst within ~ 1 Gyr, and the host galaxies are younger than the average galaxy in the parent population. These results indicate a clear connection between starburst and nuclear activity. We use composite spectra of the spectroscopically confirmed members in each structure to separate them based on a measure of the overall evolutionary state of their constituent galaxies. We define structures as having more evolved populations if their average galaxy has lower EW(OII) and EW(Hd). The AGN in the more evolved structures have lower rest-frame 0.5-8 keV X-ray luminosities (all below 10^43.3 erg s^-1) and longer times since a starburst than those in the less evolved structures, suggesting that the peak of both star formation and AGN activity has occurred at earlier times. With the wide range of evolutionary states and timeframes in the structures, we use our results to analyze the evolution of X-ray AGN and evaluate potential triggering mechanisms.Comment: 29 pages, 13 figure

Use of the Three-Spined Stickleback (Gasterosteus aculeatus) As a Sensitive in Vivo Test for Detection of Environmental Antiandrogens

We have previously shown that exposure to exogenous androgens causes female sticklebacks (Gasterosteus aculeatus) to produce the glue protein, spiggin, in their kidneys. This protein can be quantified by an enzyme-linked immunosorbent assay developed and validated at the Centre for Environment, Fisheries and Aquaculture Science. Here we report the development of an in vivo test for the detection of environmental antiandrogens. The system involves the simultaneous exposure of female sticklebacks to 17α-methyltestosterone (a model androgen) at 500 ng/L and suspected environmental antiandrogens over a period of 21 days. The spiggin content of the kidneys is then measured, and any antiandrogenic activity is evaluated by comparing the spiggin levels of female fish exposed to antiandrogens to those of female fish exposed solely to the model androgen. The assay detects the antiandrogenic activity of flutamide, vinclozolin (both used at 250 μg/L), linuron (at 150 μg/L), and fenitrothion (at 15 and 150 μg/L). These results provide the first evidence of in vivo antiandrogenic activity of both linuron and fenitrothion in teleosts. Although there are other suggested fish species that could be used for this purpose, the stickleback is the only widely available species in which it is now possible to study both estrogenic and antiandrogenic end points in the same individual. Furthermore, the species is endemic and ubiquitous in Europe, and it possesses many ecological traits that make it better suited than other potential species for field research into endocrine disruption

Possible evidence of the radio AGN quenching of neighbouring galaxies at z ∼ 1

Using 57 radio active galactic nuclei (RAGNs) at 0.55 ≤ z ≤ 1.3 drawn from five fields of the Observations of Redshift Evolution in Large-Scale Environments (ORELSE) survey, we study the effect of injection of energy from outbursts of RAGN on their spectroscopically confirmed neighbouring galaxies (SNGs). We observe an elevated fraction of quenched neighbours (f_q) within 500 kpc projected radius of RAGN in the most dense local environments compared to those of non-RAGN control samples matched to the RAGN population in colour, stellar mass, and local environment at 2σ significance. Further analyses show that there are offsets at similar significance between f_qs of RAGN-SNGs and the appropriate control samples for galaxies specifically in cluster environments and those hosted by most massive cluster galaxies, which tentatively suggests that some negative feedback from the RAGN is occurring in these dense environments. In addition, we find that the median radio power of RAGN increases with increasing local overdensity, an effect which may lend itself to the quenching of neighbouring galaxies. Furthermore, we find that, in the highest local overdensities, the f_q of the sub-sample of lower stellar mass RAGN-SNGs is larger than that of the higher stellar mass RAGN-SNGs sub-sample, which indicates a more pronounced effect from RAGN on lower stellar mass galaxies. We propose a scenario in which RAGN residing within clusters might heat the intracluster medium (ICM) affecting both in situ star formation and any inflowing gas that remains in their neighbouring galaxies

The properties of radio and mid-infrared detected galaxies and the effect of environment on the co-evolution of AGN and star formation at z ∼ 1

In this study, we investigate 179 radio-infrared (IR) galaxies drawn from a sample of spectroscopically confirmed galaxies, which are detected in radio and mid-IR (MIR) in the redshift range of 0.55 ≤ z ≤ 1.30 in the Observations of Redshift Evolution in Large Scale Environments (ORELSE) survey. We constrain the active galactic nuclei (AGN) contribution to the total IR luminosity (f_(AGN)), and estimate the AGN luminosity (L_(AGN)) and the star formation rate (SFR). Based on the f_(AGN) and radio luminosity, radio–IR galaxies are split into galaxies that host either high- or low-f_(AGN) AGN (high-/low-f_(AGN)), and star-forming galaxies (SFGs) with little to no AGN activity. We study the properties of the three radio–IR sub-samples comparing to an underlying parent sample. In the comparison of radio luminosity of three sub-samples, no significant difference was found, which could be due to the combined contribution of radio emission from AGN and star formation. We find a positive relationship between L_(AGN) and specific SFR (sSFR) for both AGN sub-samples, strongly suggesting a co-evolution scenario of AGN and SF in these galaxies. A toy model is designed to demonstrate this co-evolution scenario, where we find that, in almost all cases, a rapid quenching time-scale is required, which we argue is a signature of AGN quenching. The environmental preference for intermediate/infall regions of clusters/groups remains across the co-evolution scenario, which suggests that galaxies might be in an orbital motion around the cluster/group during the scenario