2,290 research outputs found

    p63 is a key regulator of iRHOM2 signalling in the keratinocyte stress response.

    Get PDF
    Hyperproliferative keratinocytes induced by trauma, hyperkeratosis and/or inflammation display molecular signatures similar to those of palmoplantar epidermis. Inherited gain-of-function mutations in RHBDF2 (encoding iRHOM2) are associated with a hyperproliferative palmoplantar keratoderma and squamous oesophageal cancer syndrome (termed TOC). In contrast, genetic ablation of rhbdf2 in mice leads to a thinning of the mammalian footpad, and reduces keratinocyte hyperproliferation and migration. Here, we report that iRHOM2 is a novel target gene of p63 and that both p63 and iRHOM2 differentially regulate cellular stress-associated signalling pathways in normal and hyperproliferative keratinocytes. We demonstrate that p63-iRHOM2 regulates cell survival and response to oxidative stress via modulation of SURVIVIN and Cytoglobin, respectively. Furthermore, the antioxidant compound Sulforaphane downregulates p63-iRHOM2 expression, leading to reduced proliferation, inflammation, survival and ROS production. These findings elucidate a novel p63-associated pathway that identifies iRHOM2 modulation as a potential therapeutic target to treat hyperproliferative skin disease and neoplasia

    The Relationship Between HR Practices and Firm Performance: Examining Causal Order

    Get PDF
    Significant research attention has been devoted to examining the relationship between HR practices and firm performance, and the research support has assumed HR as the causal variable. Using data from 45 business units (with 62 data points), this study examines how measures of HR practices correlate with past, concurrent, and future operational performance measures. The results indicate that correlations with performance measures at all three times are both high and invariant, and that controlling for past or concurrent performance virtually eliminates the correlation of HR with future performance. Implications are discussed

    Autonomy of Nations and Indigenous Peoples and the Environmental Release of Genetically Engineered Animals with Gene Drives

    Get PDF
    This article contends that the environmental release of genetically engineered (GE) animals with heritable traits that are patented will present a challenge to the efforts of nations and indigenous peoples to engage in self‐determination. The environmental release of such animals has been proposed on the grounds that they could function as public health tools or as solutions to the problem of agricultural insect pests. This article brings into focus two political‐economic‐legal problems that would arise with the environmental release of such organisms. To address those challenges, it is proposed that nations considering the environmental release of GE animals must take into account the underlying circumstances and policy failures that motivate arguments for the use of the modified animals. Moreover, countries must recognize that the UN International Covenant on Civil and Political Rights and the UN International Covenant on Economic, Social and Cultural Rights place on them an obligation to ensure that GE animals with patented heritable traits are not released without the substantive consent of the nations or indigenous peoples that could be affected

    Supernova Remnants as Clues to Their Progenitors

    Full text link
    Supernovae shape the interstellar medium, chemically enrich their host galaxies, and generate powerful interstellar shocks that drive future generations of star formation. The shock produced by a supernova event acts as a type of time machine, probing the mass loss history of the progenitor system back to ages of \sim 10 000 years before the explosion, whereas supernova remnants probe a much earlier stage of stellar evolution, interacting with material expelled during the progenitor's much earlier evolution. In this chapter we will review how observations of supernova remnants allow us to infer fundamental properties of the progenitor system. We will provide detailed examples of how bulk characteristics of a remnant, such as its chemical composition and dynamics, allow us to infer properties of the progenitor evolution. In the latter half of this chapter, we will show how this exercise may be extended from individual objects to SNR as classes of objects, and how there are clear bifurcations in the dynamics and spectral characteristics of core collapse and thermonuclear supernova remnants. We will finish the chapter by touching on recent advances in the modeling of massive stars, and the implications for observable properties of supernovae and their remnants.Comment: A chapter in "Handbook of Supernovae" edited by Athem W. Alsabti and Paul Murdin (18 pages, 6 figures

    Theory- and evidence-based best practices for physical activity counseling for adults with spinal cord injury

    Get PDF
    This project used a systematic and integrated knowledge translation (IKT) approach to co-create theory- and evidence-based best practices for physical activity counseling for adults with spinal cord injury (SCI). Guided by the IKT Guiding Principles, we meaningfully engaged research users throughout this project. A systematic approach was used. An international, multidisciplinary expert panel (n = 15), including SCI researchers, counselors, and people with SCI, was established. Panel members participated in two online meetings to discuss the best practices by drawing upon new knowledge regarding counselor-client interactions, current evidence, and members’ own experiences. We used concepts from key literature on SCI-specific physical activity counseling and health behavior change theories. An external group of experts completed an online survey to test the clarity, usability and appropriateness of the best practices. The best practices document includes an introduction, the best practices, things to keep in mind, and a glossary. Best practices focused on how to deliver a conversation and what to discuss during a conversation. Examples include: build rapport, use a client-centred approach following the spirit of motivational interviewing, understand your client’s physical activity barriers, and share the SCI physical activity guidelines. External experts (n = 25) rated the best practices on average as clear, useful, and appropriate. We present the first systematically co-developed theory- and evidence-based best practices for SCI physical activity counseling. The implementation of the best practices will be supported by developing training modules. These new best practices can contribute to optimizing SCI physical activity counseling services across settings.</p

    Density functional theory calculations of the carbon ELNES of small diameter armchair and zigzag nanotubes: core-hole, curvature and momentum transfer orientation effects

    Full text link
    We perform density functional theory calculations on a series of armchair and zigzag nanotubes of diameters less than 1nm using the all-electron Full-Potential(-Linearised)-Augmented-Plane-Wave (FPLAPW) method. Emphasis is laid on the effects of curvature, the electron beam orientation and the inclusion of the core-hole on the carbon electron energy loss K-edge. The electron energy loss near-edge spectra of all the studied tubes show strong curvature effects compared to that of flat graphene. The curvature induced πσ\pi-\sigma hybridisation is shown to have a more drastic effect on the electronic properties of zigzag tubes than on those of armchair tubes. We show that the core-hole effect must be accounted for in order to correctly reproduce electron energy loss measurements. We also find that, the energy loss near edge spectra of these carbon systems are dominantly dipole selected and that they can be expressed simply as a proportionality with the local momentum projected density of states, thus portraying the weak energy dependence of the transition matrix elements. Compared to graphite, the ELNES of carbon nanotubes show a reduced anisotropy.Comment: 25 pages, 15 figures, revtex4 submitted for publication to Phys. Rev.

    Galactic and Extragalactic Samples of Supernova Remnants: How They Are Identified and What They Tell Us

    Full text link
    Supernova remnants (SNRs) arise from the interaction between the ejecta of a supernova (SN) explosion and the surrounding circumstellar and interstellar medium. Some SNRs, mostly nearby SNRs, can be studied in great detail. However, to understand SNRs as a whole, large samples of SNRs must be assembled and studied. Here, we describe the radio, optical, and X-ray techniques which have been used to identify and characterize almost 300 Galactic SNRs and more than 1200 extragalactic SNRs. We then discuss which types of SNRs are being found and which are not. We examine the degree to which the luminosity functions, surface-brightness distributions and multi-wavelength comparisons of the samples can be interpreted to determine the class properties of SNRs and describe efforts to establish the type of SN explosion associated with a SNR. We conclude that in order to better understand the class properties of SNRs, it is more important to study (and obtain additional data on) the SNRs in galaxies with extant samples at multiple wavelength bands than it is to obtain samples of SNRs in other galaxiesComment: Final 2016 draft of a chapter in "Handbook of Supernovae" edited by Athem W. Alsabti and Paul Murdin. Final version available at https://doi.org/10.1007/978-3-319-20794-0_90-

    Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

    Get PDF
    Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression

    Revisión bibliográfica de implantología bucofacial del año 2011. Segunda parte

    Get PDF
    La gran diversidad de fuentes de información que nos proporciona la literatura científica junto al escaso tiempo de que disponen los profesionales de la Odontología para consultarlas, ha motivado a los autores a efectuar una revisión de la literatura científica publicada a lo largo del año 2011 en el campo de la Implantología Bucofacial. Con este fin se han agrupado los diferentes artículos indexados consultados en distintos apartados (elevación del seno maxilar, cirugía guiada y cirugía mínimamente invasiva, regeneración ósea guiada, implantes ci-gomáticos y factores de crecimiento), con el fin de facilitar una buena puesta al día
    corecore