2,112 research outputs found

    Alternate cyclin D1 mRNA splicing modulates P27\u3csup\u3eKlP1\u3c/sup\u3e binding and cell migration

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    Cyclin D1 is an important cell cycle regulator but in cancer its overexpression also increases cellular migration mediated by p27KlP1 stabilization and RhoA inhibition. Recently, a common polymorphism at the exon 4-intron 4 boundary of the human cyclin D1 gene within a splice donor region was associated with an altered risk of developing cancer. Altered RNA splicing caused by this polymorphism gives rise to a variant cyclin D1 isoform termed cyclin D1b, which has the same N-terminus as the canonical cyclin D1a isoform but a distinct C-terminus. In this study we show that these different isoforms have unique properties with regard to the cellular migration function of cyclin D1. Whereas they displayed little difference in transcriptional co-repression assays on idealized reporter genes, microarray cDNA expression analysis revealed differential regulation of genes including those that influence cellular migration. Additionally, while cyclin D1a stabilized p27KIP1 and inhibited RhoA-induced ROCK kinase activity, promoting cellular migration, cyclin D1b failed to stabilize p27KIP1 or inhibit ROCK kinase activity and had no effect on migration. Our findings argue that alternate splicing is an important determinant of the function of cyclin D1 in cellular migration

    NMR h3 JNC’ Couplings Provide Comprehensive Geometrical Constraints for Protein H-bonds in Solution

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    Protein backbone H-bonds (>N–H···O–C<) show relationships between NMR h3JNC\u27 couplings measured in solution and H-bond geometry parameters seen in X-ray crystal structures. Assuming that the solution and crystal structure of protein backbone is the same, the h3JNC\u27 couplings can be calibrated to provide good estimates of both angular and radial H-bond parameters in a solution. The crucial premise of equality between the solution and the crystal structure of protein backbone we validated on the level of the NH-bonds orientation, by comparing the orientations inferred from X-ray crystal structures with the solution ones determined from NMR residual dipolar couplings

    Nurses\u27 Alumnae Association Bulletin, April 1962

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    Staff Nurses Association Alumnae Meetings 1961 Social Committee Clara Melville Scholarship Fund Ways and Means Report Cook Book Report Bulletin Committee Private Duty Nurse\u27s Section Hospital Report and Nursing Service Federal Nursing Service Practice of Nursing Report of Student Council Activities Medical Work in Ghan

    Tracking of Salmonella Positive Pigs from Farm to Fork in the Republic of Ireland

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    In this study, individual pigs from selected herds of known Salmonella serological status were tracked through the slaughter and dressing process. From all tracked animals, caecal contents, rectal faeces, carcasses (before washing and chilling and after chilling) and pork primal cuts were examined for the presence of Salmonella. All samples were screened for Salmonella using real time PCR and all suspect positive samples were confirmed using the ISO 6579 method for Salmonella. To determine the relationship between Salmonella isolates from different parts of the chain , all isolates are being characterised by Pulse Field Gel Electrophoresis (PFGE). The results suggest that the slaughter and dressing operations have a significant effect on the incidence of Salmonella and that even if pigs are presented for slaughter with caecal or rectal carriage of Salmonella then good slaughter practices can prevent carcass contamination. All data generated in the study is being fed into a quantitative risk assessment model for Salmonella in pork

    Monitoring and Pay: An Experiment on Employee Performance under Endogenous Supervision

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    We present an experimental test of a shirking model where monitoring intensity is endogenous and effort a continuous variable. Wage level, monitoring intensity and consequently the desired enforceable effort level are jointly determined by the maximization problem of the firm. As a result, monitoring and pay should be complements. In our experiment, between and within treatment variation is qualitatively in line with the normative predictions of the model under standard assumptions. Yet, we also find evidence for reciprocal behavior. Our data analysis shows, however, that it does not pay for the employer to solely rely on the reciprocity of employees

    Self-consistent nonspherical isothermal halos embedding zero-thickness disks

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    Disk-halo decompositions of galaxy rotation curves are generally performed in a parametric way. We construct self-consistent models of nonspherical isothermal halos embedding a zero-thickness disk, by assuming that the halo distribution function is a Maxwellian. The method developed here can be used to study other physically-based choices for the halo distribution function and the case of a disk accompanied by a bulge. In a preliminary investigation we note the existence of a fine tuning between the scalelengths R_{\Omega} and h, respectively characterizing the rise of the rotation curve and the luminosity profile of the disk, which surprisingly applies to both high surface brightness and low surface brightness galaxies. This empirical correlation identifies a much stronger conspiracy than the one required by the smoothness and flatness of the rotation curve (disk-halo conspiracy). The self-consistent models are characterized by smooth and flat rotation curves for very different disk-to-halo mass ratios, hence suggesting that conspiracy is not as dramatic as often imagined. For a typical rotation curve, with asymptotically flat rotation curve at V_{\infty} (the precise value of which can also be treated as a free parameter), and a typical density profile of the disk, self-consistent models are characterized by two dimensionless parameters, which correspond to the dimensional scales (the disk mass-to-light ratio M/L and the halo central density) of standard disk-halo decompositions. We show that if the rotation curve is decomposed by means of our self-consistent models, the disk-halo degeneracy is removed and typical rotation curves are fitted by models that are below the maximum-disk prescription. Similar results are obtained from a study of NGC 3198. Finally, we quantify the flattening of the spheroidal halo, which is significant, especially on the scale of the visible disk.Comment: accepted for publication in A&

    Gene expression by marrow stromal cells in a porous collagen-glycosaminoglycan scaffold is affected by pore size and mechanical stimulation.

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    Marrow stromal cell (MSC) populations, which are a potential source of undifferentiated mesenchymal cells, and culture scaffolds that mimic natural extracellular matrix are attractive options for orthopaedic tissue engineering. A type I collagen-glycosaminoglycan (CG) scaffold that has previously been used clinically for skin regeneration was recently shown to support expression of bone-associated proteins and mineralisation by MSCs cultured in the presence of osteogenic supplements. Here we follow RNA markers of osteogenic differentiation in this scaffold. We demonstrate that transcripts of the late stage markers bone sialoprotein and osteocalcin are present at higher levels in scaffold constructs than in two-dimensional culture, and that considerable gene induction can occur in this scaffold even in the absence of soluble osteogenic supplements. We also find that bone-related gene expression is affected by pore size, mechanical constraint, and uniaxial cyclic strain of the CG scaffold. The data presented here further establish the CG scaffold as a potentially valuable substrate for orthopaedic tissue engineering and for research on the mechanical interactions between cells and their environment, and suggest that a more freely-contracting scaffold with larger pore size may provide an environment more conducive to osteogenesis than constrained scaffolds with smaller pore sizes

    Challenging Perceptions of Disability through Performance Poetry Methods: The "Seen but Seldom Heard" Project.

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    This paper considers performance poetry as a method to explore lived experiences of disability. We discuss how poetic inquiry used within a participatory arts-based research framework can enable young people to collectively question society’s attitudes and actions towards disability. Poetry will be considered as a means to develop a more accessible and effective arena in which young people with direct experience of disability can be empowered to develop new skills that enable them to tell their own stories. Discussion of how this can challenge audiences to critically reflect upon their own perceptions of disability will also be developed

    ‘Don’t just travel’: thinking poetically on the way to professional knowledge

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    This paper describes how the medium of ‘found poetry’ is incorporated into a doctoral programme for nurses, educators and allied health and social care professionals at the start of their various doctoral journeys. It advocates a narrative practice approach to issues of researcher identity and reflexivity. ‘Finding’ the poems begins with the creation of collages as representational anchors for students to talk about themselves, their professional practice, their hopes and expectations of the doctoral experience, and their research ideas. (Re)presenting their transcribed talk as poetry involves culling and playing with words, phrases and segments, making changes in spacing, lines and rhythm to arrive at an evocative distillation (Butler-Kisber, 2002). This process enables each person to bring stories and/or fragments of experience into critical engagement with others. Poetic thinking functions pedagogically, helping students find a critical voice to enliven and hone their reflexive writing in relation to their doctoral experience and their research positioning. Arts-based methods of inquiry are an ongoing topic of interest in research communities. Found poetry is a useful starting point to explore creative means by which research participants can recount their stories, and equally, by which researchers can witness and disseminate what they have to tell.self funde
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