ACCESS II: A Complete Census of Star Formation in the Shapley Supercluster - UV and IR Luminosity Functions

We present panoramic Spitzer/MIPS mid- and far-infrared and GALEX ultraviolet imaging of the the most massive and dynamically active system in the local Universe, the Shapley supercluster at z=0.048, covering the 5 clusters which make up the supercluster core. We combine these data with existing spectroscopic data from 814 confirmed supercluster members to produce the first study of a local rich cluster including both ultraviolet and infrared luminosity functions (LFs). This joint analysis allows us to produce a complete census of star-formation (both obscured and unobscured), extending down to SFRs~0.02-0.05Msun/yr, and quantify the level of obscuration of star formation among cluster galaxies, providing a local benchmark for comparison to ongoing and future studies of cluster galaxies at higher redshifts with Spitzer and Herschel. The GALEX NUV and FUV LFs obtained have steeper faint-end slopes than the local field population, due largely to the contribution of massive, quiescent galaxies at M_FUV>-16. The 24um and 70um galaxy LFs for the Shapley supercluster instead have shapes fully consistent with those obtained for the Coma cluster and for the local field galaxy population. This apparent lack of environmental dependence for the shape of the FIR luminosity function suggests that the bulk of the star-forming galaxies that make up the observed cluster infrared LF have been recently accreted from the field and have yet to have their star formation activity significantly affected by the cluster environment. We estimate a global SFR of 327 Msun/yr over the whole supercluster core, of which just ~20% is visible directly in the UV continuum and ~80% is reprocessed by dust and emitted in the infrared. The level of obscuration (L_IR/L_FUV) in star-forming galaxies is seen to increase linearly with L_K over two orders of magnitude in stellar mass.Comment: 19 pages, 17 figures. Accepted for publication in MNRA

ACCESS III: The Nature of Star Formation in the Shapley Supercluster

We present a joint analysis of panoramic Spitzer/MIPS mid-infrared and GALEX ultraviolet imaging of the Shapley supercluster at z=0.048. Combining this with spectra of 814 supercluster members and 1.4GHz radio continuum maps, this represents the largest complete census of star-formation (both obscured and unobscured) in local cluster galaxies to date, reaching SFRs~0.02Msun/yr. We take advantage of this comprehensive panchromatic dataset to perform a detailed analysis of the nature of star formation in cluster galaxies, using several quite independent diagnostics of the quantity and intensity of star formation to develop a coherent view of the types of star formation within cluster galaxies. We observe a robust bimodality in the infrared (f_24/f_K) galaxy colours, which we are able to identify as another manifestation of the broad split into star-forming spiral and passive elliptical galaxy populations seen in UV-optical surveys. This diagnostic also allows the identification of galaxies in the process of having their star formation quenched as the infrared analogue to the UV "green valley" population. The bulk of supercluster galaxies on the star-forming sequence have specific-SFRs consistent with local field specific-SFR-M* relations, and form a tight FIR-radio correlation confirming that their FIR emission is due to star formation. We show that 85% of the global SFR is quiescent star formation within spiral disks, as manifest by the observed sequence in the IRX-beta relation being significantly offset from the starburst relation of Kong et al. (2004), while their FIR-radio colours indicate dust heated by low-intensity star formation. Just 15% of the global SFR is due to nuclear starbursts. The vast majority of star formation seen in cluster galaxies comes from normal infalling spirals who have yet to be affected by the cluster environment.Comment: 17 pages, 9 figures. Accepted for publication in MNRA

Activation of p107 by Fibroblast Growth Factor, Which Is Essential for Chondrocyte Cell Cycle Exit, Is Mediated by the Protein Phosphatase 2A/B55α Holoenzyme

The phosphorylation state of pocket proteins during the cell cycle is determined at least in part by an equilibrium between inducible cyclin-dependent kinases (CDKs) and serine/threonine protein phosphatase 2A (PP2A). Two trimeric holoenzymes consisting of the core PP2A catalytic/scaffold dimer and either the B55α or PR70 regulatory subunit have been implicated in the activation of p107/p130 and pRB, respectively. While the phosphorylation state of p107 is very sensitive to forced changes of B55α levels in human cell lines, regulation of p107 in response to physiological modulation of PP2A/B55α has not been elucidated. Here we show that fibroblast growth factor 1 (FGF1), which induces maturation and cell cycle exit in chondrocytes, triggers rapid accumulation of p107-PP2A/B55α complexes coinciding with p107 dephosphorylation. Reciprocal solution-based mass spectrometric analysis identified the PP2A/B55α complex as a major component in p107 complexes, which also contain E2F/DPs, DREAM subunits, and/or cyclin/CDK complexes. Of note, p107 is one of the preferred partners of B55α, which also associates with pRB in RCS cells. FGF1-induced dephosphorylation of p107 results in its rapid accumulation in the nucleus and formation of larger complexes containing p107 and enhances its interaction with E2F4 and other p107 partners. Consistent with a key role of B55α in the rapid activation of p107 in chondrocytes, limited ectopic expression of B55α results in marked dephosphorylation of p107 while B55α knockdown results in hyperphosphorylation. More importantly, knockdown of B55α dramatically delays FGF1-induced dephosphorylation of p107 and slows down cell cycle exit. Moreover, dephosphorylation of p107 in response to FGF1 treatment results in early recruitment of p107 to the MYC promoter, an FGF1/E2F-regulated gene. Our results suggest a model in which FGF1 mediates rapid dephosphorylation and activation of p107 independently of the CDK activities that maintain p130 and pRB hyperphosphorylation for several hours after p107 dephosphorylation in maturing chondrocytes

FXR1 Is an IL-19-Responsive RNA-Binding Protein that Destabilizes Pro-inflammatory Transcripts in Vascular Smooth Muscle Cells

This work identifies the fragile-X-related protein (FXR1) as a reciprocal regulator of HuR target transcripts in vascular smooth muscle cells (VSMCs). FXR1 was identified as an HuR-interacting protein by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The HuR-FXR1 interaction is abrogated in RNase-treated extracts, indicating that their association is tethered by mRNAs. FXR1 expression is induced in diseased but not normal arteries. siRNA knockdown of FXR1 increases the abundance and stability of inflammatory mRNAs, while overexpression of FXR1 reduces their abundance and stability. Conditioned media from FXR1 siRNA-treated VSMCs enhance activation of naive VSMCs. RNA EMSA and RIP demonstrate that FXR1 interacts with an ARE and an element in the 3′ UTR of TNFα. FXR1 expression is increased in VSMCs challenged with the anti-inflammatory cytokine IL-19, and FXR1 is required for IL-19 reduction of HuR. This suggests that FXR1 is an anti-inflammation responsive, HuR counter-regulatory protein that reduces abundance of pro-inflammatory transcripts

Protein Interaction Profiling of the p97 Adaptor UBXD1 Points to a Role for the Complex in Modulating ERGIC-53 Trafficking

UBXD1 is a member of the poorly understood subfamily of p97 adaptors that do not harbor a ubiquitin association domain or bind ubiquitin-modified proteins. Of clinical importance, p97 mutants found in familial neurodegenerative conditions Inclusion Body Myopathy Paget's disease of the bone and/or Frontotemporal Dementia and Amyotrophic Lateral Sclerosis are defective at interacting with UBXD1, indicating that functions regulated by a p97-UBXD1 complex are altered in these diseases. We have performed liquid chromatography-mass spectrometric analysis of UBXD1-interacting proteins to identify pathways in which UBXD1 functions. UBXD1 displays prominent association with ERGIC-53, a hexameric type I integral membrane protein that functions in protein trafficking. The UBXD1-ERGIC-53 interaction requires the N-terminal 10 residues of UBXD1 and the C-terminal cytoplasmic 12 amino acid tail of ERGIC-53. Use of p97 and E1 enzyme inhibitors indicate that complex formation between UBXD1 and ERGIC-53 requires the ATPase activity of p97, but not ubiquitin modification. We also performed SILAC-based quantitative proteomic profiling to identify ERGIC-53 interacting proteins. This analysis identified known (e.g. COPI subunits) and novel (Rab3GAP1/2 complex involved in the fusion of vesicles at the cell membrane) interactions that are also mediated through the C terminus of the protein. Immunoprecipitation and Western blotting analysis confirmed the proteomic interaction data and it also revealed that an UBXD1-Rab3GAP association requires the ERGIC-53 binding domain of UBXD1. Localization studies indicate that UBXD1 modules the sub-cellular trafficking of ERGIC-53, including promoting movement to the cell membrane. We propose that p97-UBXD1 modulates the trafficking of ERGIC-53-containing vesicles by controlling the interaction of transport factors with the cytoplasmic tail of ERGIC-53

ACCESS IV: The quenching of star formation in a cluster population of dusty S0s

We present an analysis of the mid-infrared (MIR) colours of 165 70um-detected galaxies in the Shapley supercluster core (SSC) at z=0.048 using panoramic Spitzer/MIPS 24 and 70um imaging. While the bulk of galaxies show f70/f24 colours typical of local star-forming galaxies, we identify a significant sub-population of 23 70micron-excess galaxies, whose MIR colours (f70/f24>25) are much redder and cannot be reproduced by any of the standard model infrared SEDs. These galaxies are found to be strongly concentrated towards the cores of the five clusters that make up the SSC, and also appear rare among local field galaxies, confirming them as a cluster-specific phenomenon. Their optical spectra and lack of significant UV emission imply little or no ongoing star formation, while fits to their panchromatic SEDs require the far-IR emission to come mostly from a diffuse dust component heated by the general interstellar radiation field rather than ongoing star formation. Most of these 70micron-excess galaxies are identified as ~L* S0s with smooth profiles. We find that almost every cluster galaxy in the process of star-formation quenching is already either an S0 or Sa, while we find no passive galaxies of class Sb or later. Hence the formation of passive early-type galaxies in cluster cores must involve the prior morphological transformation of late-type spirals into Sa/S0s, perhaps via pre-processing or the impact of cluster tidal fields, before a subsequent quenching of star formation once the lenticular encounters the dense environment of the cluster core. In the cases of many cluster S0s, this phase of star-formation quenching is characterised by an excess of 70um emission, indicating that the cold dust content is declining at a slower rate than star formation.Comment: 17 pages, 12 figures. Accepted for publication in MNRA

JNK associated leucine zipper protein functions as a docking platform for Polo like kinase 1 and regulation of the associating transcription factor Forkhead box protein K1

JLP (JNK associated Leucine zipper protein) is a scaffolding protein that interacts with various signaling proteins associated with coordinated regulation of cellular process such as endocytosis, motility, neurite outgrowth, cell proliferation and apoptosis. Here we identified Polo like kinase 1 (PLK1) as a novel interaction partner of JLP through mass spectrometric approaches. Our results indicate that JLP is phospho-primed by PLK1 on Thr 351, which is recognized by the PBD of PLK1 leading to phosphorylation of JLP at additional sites. SILAC and quantitative LC-MS/MS analysis was performed to identify PLK1 dependent JLP interacting proteins. Treatment of cells with the PLK1 kinase inhibitor BI2536 suppressed binding of the Forkhead box protein K1 (FOXK1) transcriptional repressor to JLP. JLP was found to interact with PLK1 and FOXK1 during mitosis. Moreover, knockdown of PLK1 affected the interaction between JLP and FOXK1. FOXK1 is a known transcriptional repressor of the CDK inhibitor p21/WAF1 and knockdown of JLP resulted in increased FOXK1 protein levels and a reduction of p21 transcript levels. Our results suggest a novel mechanism by which FOXK1 protein levels and activity are regulated by associating with JLP and PLK1

Attenuation of the Sensing Capabilities of PhoQ in Transition to Obligate Insect–Bacterial Association

Sodalis glossinidius, a maternally inherited endosymbiont of the tsetse fly, maintains genes encoding homologues of the PhoP-PhoQ two-component regulatory system. This two-component system has been extensively studied in facultative bacterial pathogens and is known to serve as an environmental magnesium sensor and a regulator of key virulence determinants. In the current study, we show that the inactivation of the response regulator, phoP, renders S. glossinidius sensitive to insect derived cationic antimicrobial peptides (AMPs). The resulting mutant strain displays reduced expression of genes involved in the structural modification of lipid A that facilitates resistance to AMPs. In addition, the inactivation of phoP alters the expression of type-III secretion system (TTSS) genes encoded within three distinct chromosomal regions, indicating that PhoP-PhoQ also serves as a master regulator of TTSS gene expression. In the absence of phoP, S. glossinidius is unable to superinfect either its natural tsetse fly host or a closely related hippoboscid louse fly. Furthermore, we show that the S. glossinidius PhoQ sensor kinase has undergone functional adaptations that result in a substantially diminished ability to sense ancestral signals. The loss of PhoQ's sensory capability is predicted to represent a novel adaptation to the static symbiotic lifestyle, allowing S. glossinidius to constitutively express genes that facilitate resistance to host derived AMPs

We are all one together : peer educators\u27 views about falls prevention education for community-dwelling older adults - a qualitative study

Background: Falls are common in older people. Despite strong evidence for effective falls prevention strategies, there appears to be limited translation of these strategies from research to clinical practice. Use of peers in delivering falls prevention education messages has been proposed to improve uptake of falls prevention strategies and facilitate translation to practice. Volunteer peer educators often deliver educational presentations on falls prevention to community-dwelling older adults. However, research evaluating the effectiveness of peer-led education approaches in falls prevention has been limited and no known study has evaluated such a program from the perspective of peer educators involved in delivering the message. The purpose of this study was to explore peer educators’ perspective about their role in delivering peer-led falls prevention education for community-dwelling older adults. Methods: A two-stage qualitative inductive constant comparative design was used.In stage one (core component) focus group interviews involving a total of eleven participants were conducted. During stage two (supplementary component) semi-structured interviews with two participants were conducted. Data were analysed thematically by two researchers independently. Key themes were identified and findings were displayed in a conceptual framework. Results: Peer educators were motivated to deliver educational presentations and importantly, to reach an optimal peer connection with their audience. Key themes identified included both personal and organisational factors that impact on educators’ capacity to facilitate their peers’ engagement with the message. Personal factors that facilitated message delivery and engagement included peer-to-peer connection and perceived credibility, while barriers included a reluctance to accept the message that they were at risk of falling by some members in the audience. Organisational factors, including ongoing training for peer educators and formative feedback following presentations, were perceived as essential because they affect successful message delivery. Conclusions: Peer educators have the potential to effectively deliver falls prevention education to older adults and influence acceptance of the message as they possess the peer-to-peer connection that facilitates optimal engagement. There is a need to consider incorporating learnings from this research into a formal large scale evaluation of the effectiveness of the peer education approach in reducing falls in older adults

LoCuSS: The mid-infrared Butcher-Oemler effect

We study the mid-infrared (MIR) properties of galaxies in 30 massive galaxy clusters at 0.02<z<0.40, using panoramic Spitzer/MIPS 24micron and NIR data. This is the largest sample of clusters to date with MIR data covering not only the cluster cores, but extending into the infall regions. We revisit the Butcher-Oemler effect, measuring the fraction of massive infrared-luminous galaxies (K5x10^10L_sun) within r_200, finding a steady increase in the fraction with redshift from ~3% at z=0.02 to ~10% by z=0.30, and an rms cluster-to-cluster scatter about this trend of 0.03. The best-fit redshift evolution model is of the form f_SF ~ (1+z)^5.7, which is stronger redshift evolution than that of L*_IR in both clusters and the field. We find that, statistically, this excess is associated with galaxies found at large cluster-centric radii, implying that the MIR Butcher-Oemler effect can be explained by a combination of both the global decline in star-formation in the universe since z~1 and enhanced star formation in the infall regions of clusters at intermediate redshifts. This picture is supported by a simple infall model based on the Millennium Simulation semi-analytic galaxy catalogs, whereby star-formation in infalling galaxies is instantaneously quenched upon their first passage through the cluster, in that the observed radial trends of f_SF trace those inferred from the simulations. We also find that f_SF does not depend on simple indicators of the dynamical state of clusters, including the offset between the brightest cluster galaxy and the peak of the X-ray emission. This is consistent with the picture described above in that most new star-formation in clusters occurs in the infall regions, and is thus not sensitive to the details of cluster-cluster mergers in the core regions.Comment: 11 pages, 7 figures, accepted for publication in Ap