Driving chronicity in rheumatoid arthritis: perpetuating role of myeloid cells

Acute inflammation is a complex and tightly regulated homeostatic process that includes leukocyte migration from the vasculature into tissues to eliminate the pathogen/injury, followed by a pro-resolving response promoting tissue repair. However, if inflammation is uncontrolled as in chronic diseases such as Rheumatoid Arthritis (RA) it leads to tissue damage and disability. Synovial tissue inflammation in RA patients is maintained by sustained activation of multiple inflammatory positive-feedback regulatory pathways in a variety of cells including myeloid cells. In this review, we will highlight recent evidence uncovering biological mechanisms contributing to the aberrant activation of myeloid cells that contributes to perpetuation of inflammation in RA, and discuss emerging data on anti-inflammatory mediators contributing to sustained remission that may inform a novel category of therapeutic targets

HiggsBounds: Confronting Arbitrary Higgs Sectors with Exclusion Bounds from LEP and the Tevatron

HiggsBounds is a computer code that tests theoretical predictions of models with arbitrary Higgs sectors against the exclusion bounds obtained from the Higgs searches at LEP and the Tevatron. The included experimental information comprises exclusion bounds at 95% C.L. on topological cross sections. In order to determine which search topology has the highest exclusion power, the program also includes, for each topology, information from the experiments on the expected exclusion bound, which would have been observed in case of a pure background distribution. Using the predictions of the desired model provided by the user as input, HiggsBounds determines the most sensitive channel and tests whether the considered parameter point is excluded at the 95% C.L. HiggsBounds is available as a Fortran 77 and Fortran 90 code. The code can be invoked as a command line version, a subroutine version and an online version. Examples of exclusion bounds obtained with HiggsBounds are discussed for the Standard Model, for a model with a fourth generation of quarks and leptons and for the Minimal Supersymmetric Standard Model with and without CP-violation. The experimental information on the exclusion bounds currently implemented in HiggsBounds will be updated as new results from the Higgs searches become available.Comment: 64 pages, 15 tables, 8 figures; three typos which made it to the published version corrected; the code (currently version 3.0.0beta including LHC Higgs search results) is available via: http://projects.hepforge.org/higgsbounds

Between stigma and pink positivity: women’s perceptions of social interactions during and after breast cancer treatment

This study explores women’s perceptions of social interaction during and after their treatment for early stage breast cancer. Analysis of interviews with 24 women between 6 months-29 years post-diagnosis, reveals that interactions can be influenced by conflicting public discourses surrounding breast cancer. For example, there is the continuing association of cancer with death and the resulting potential for a stigmatised identity (Goffman, 1963). In contrast is the ultra-positive discourse around cancer survivorship, with breast cancer in particular being associated with pink campaigning and a push towards positive thinking. Participants described ‘managing’ conversations during treatment; sometimes playing down their ‘private’ suffering and presenting a positive (‘public’) image rather than risk alienating support. After treatment they were encouraged to move on and get back to ‘normal’. Whilst other breast cancer patients/survivors were often good sources of support, there was also a danger of assuming that all experiences will be the same. We present data to illustrate that women often present ‘public’ accounts which are driven by an expectation of positivity and fear of stigmatization at all stages of breast cancer treatment and beyond

Sequential Delivery of Host-Induced Virulence Effectors by Appressoria and Intracellular Hyphae of the Phytopathogen Colletotrichum higginsianum

Phytopathogens secrete effector proteins to manipulate their hosts for effective colonization. Hemibiotrophic fungi must maintain host viability during initial biotrophic growth and elicit host death for subsequent necrotrophic growth. To identify effectors mediating these opposing processes, we deeply sequenced the transcriptome of Colletotrichum higginsianum infecting Arabidopsis. Most effector genes are host-induced and expressed in consecutive waves associated with pathogenic transitions, indicating distinct effector suites are deployed at each stage. Using fluorescent protein tagging and transmission electron microscopy-immunogold labelling, we found effectors localised to stage-specific compartments at the host-pathogen interface. In particular, we show effectors are focally secreted from appressorial penetration pores before host invasion, revealing new levels of functional complexity for this fungal organ. Furthermore, we demonstrate that antagonistic effectors either induce or suppress plant cell death. Based on these results we conclude that hemibiotrophy in Colletotrichum is orchestrated through the coordinated expression of antagonistic effectors supporting either cell viability or cell death

Film remakes, the black sheep of translation

Film remakes have often been neglected by translation studies in favour of other forms of audiovisual translation such as subtitling and dubbing. Yet, as this article will argue, remakes are also a form of cinematic translation. Beginning with a survey of previous, ambivalent approaches to the status of remakes, it proposes that remakes are multimodal, adaptive translations: they translate the many modes of the film being remade and offer a reworking of that source text. The multimodal nature of remakes is explored through a reading of Breathless, Jim McBride's 1983 remake of Jean-Luc Godard's À bout de souffle (1959), which shows how remade films may repeat the narrative of, but differ on multiple levels from, their source films. Due to the collaborative nature of film production, remakes involve multiple agents of translation. As such, remakes offer an expanded understanding of audiovisual translation

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

A first generation BAC-based physical map of the rainbow trout genome

Background: Rainbow trout (Oncorhynchus mykiss) are the most-widely cultivated cold freshwater fish in the world and an important model species for many research areas. Coupling great interest in this species as a research model with the need for genetic improvement of aquaculture production efficiency traits justifies the continued development of genomics research resources. Many quantitative trait loci (QTL) have been identified for production and life-history traits in rainbow trout. A bacterial artificial chromosome (BAC) physical map is needed to facilitate fine mapping of QTL and the selection of positional candidate genes for incorporation in marker-assisted selection (MAS) for improving rainbow trout aquaculture production. This resource will also facilitate efforts to obtain and assemble a whole-genome reference sequence for this species.[br/] Results: The physical map was constructed from DNA fingerprinting of 192,096 BAC clones using the 4-color high-information content fingerprinting (HICF) method. The clones were assembled into physical map contigs using the finger-printing contig (FPC) program. The map is composed of 4,173 contigs and 9,379 singletons. The total number of unique fingerprinting fragments (consensus bands) in contigs is 1,185,157, which corresponds to an estimated physical length of 2.0 Gb. The map assembly was validated by 1) comparison with probe hybridization results and agarose gel fingerprinting contigs; and 2) anchoring large contigs to the microsatellite-based genetic linkage map.[br/] Conclusion: The production and validation of the first BAC physical map of the rainbow trout genome is described in this paper. We are currently integrating this map with the NCCCWA genetic map using more than 200 microsatellites isolated from BAC end sequences and by identifying BACs that harbor more than 300 previously mapped markers. The availability of an integrated physical and genetic map will enable detailed comparative genome analyses, fine mapping of QTL, positional cloning, selection of positional candidate genes for economically important traits and the incorporation of MAS into rainbow trout breeding programs

Luminous Thermal Flares from Quiescent Supermassive Black Holes

A dormant supermassive black hole lurking in the center of a galaxy will be revealed when a star passes close enough to be torn apart by tidal forces, and a flare of electromagnetic radiation is emitted when the bound fraction of the stellar debris falls back onto the black hole and is accreted. Here we present the third candidate tidal disruption event discovered in the GALEX Deep Imaging Survey: a 1.6x10^{43} erg s^{-1} UV/optical flare from a star-forming galaxy at z=0.1855. The UV/optical SED during the peak of the flare measured by GALEX and Palomar LFC imaging can be modeled as a single temperature blackbody with T_{bb}=1.7x10^{5} K and a bolometric luminosity of 3x10^{45} erg s^{-1}, assuming an internal extinction with E(B-V)_{gas}=0.3. The Chandra upper limit on the X-ray luminosity during the peak of the flare, L_{X}(2-10 keV)< 10^{41} erg s^{-1}, is 2 orders of magnitude fainter than expected from the ratios of UV to X-ray flux density observed in active galaxies. We compare the light curves and broadband properties of all three tidal disruption candidates discovered by GALEX, and find that (1) the light curves are well fitted by the power-law decline expected for the fallback of debris from a tidally disrupted solar-type star, and (2) the UV/optical SEDs can be attributed to thermal emission from an envelope of debris located at roughly 10 times the tidal disruption radius of a ~10^{7} M_sun central black hole. We use the observed peak absolute optical magnitudes of the flares (-17.5 > M_{g} > -18.9) to predict the detection capabilities of upcoming optical synoptic surveys. (Abridged)Comment: Accepted for Publication in ApJ, 19 pages, 10 figures, 2 tables, emulateapj, corrections from proofs adde

Combined Analysis of Murine and Human Microarrays and ChIP Analysis Reveals Genes Associated with the Ability of MYC To Maintain Tumorigenesis

The MYC oncogene has been implicated in the regulation of up to thousands of genes involved in many cellular programs including proliferation, growth, differentiation, self-renewal, and apoptosis. MYC is thought to induce cancer through an exaggerated effect on these physiologic programs. Which of these genes are responsible for the ability of MYC to initiate and/or maintain tumorigenesis is not clear. Previously, we have shown that upon brief MYC inactivation, some tumors undergo sustained regression. Here we demonstrate that upon MYC inactivation there are global permanent changes in gene expression detected by microarray analysis. By applying StepMiner analysis, we identified genes whose expression most strongly correlated with the ability of MYC to induce a neoplastic state. Notably, genes were identified that exhibited permanent changes in mRNA expression upon MYC inactivation. Importantly, permanent changes in gene expression could be shown by chromatin immunoprecipitation (ChIP) to be associated with permanent changes in the ability of MYC to bind to the promoter regions. Our list of candidate genes associated with tumor maintenance was further refined by comparing our analysis with other published results to generate a gene signature associated with MYC-induced tumorigenesis in mice. To validate the role of gene signatures associated with MYC in human tumorigenesis, we examined the expression of human homologs in 273 published human lymphoma microarray datasets in Affymetrix U133A format. One large functional group of these genes included the ribosomal structural proteins. In addition, we identified a group of genes involved in a diverse array of cellular functions including: BZW2, H2AFY, SFRS3, NAP1L1, NOLA2, UBE2D2, CCNG1, LIFR, FABP3, and EDG1. Hence, through our analysis of gene expression in murine tumor models and human lymphomas, we have identified a novel gene signature correlated with the ability of MYC to maintain tumorigenesis