349 research outputs found

    Sp1 acetylation is associated with loss of DNA binding at promoters associated with cell cycle arrest and cell death in a colon cell line

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    Butyrate, a known histone deacetylase inhibitor (HDACi) and product of fibre fermentation, is postulated to mediate the protective effect of dietary fibre against colon cancer. The transcription factor Sp1 is a target of acetylation and is known to be associated with class I HDACs, including HDAC1. Sp1 is a ubiquitous transcription factor and Sp1-regulated genes include those involved in cell cycle regulation, apoptosis and lipogenesis: all major pathways in cancer development. The only known acetylated residue of Sp1 is lysine703 which resides in the DNA binding domain. Here we show that acetylated Sp1 loses p21- and bak-promoter -binding function in vitro. Furthermore treatment with a panel of HDAC inhibitors showed clustering of activities for a subset of inhibitors, causing G2 cell cycle arrest, Sp1 acetylation, p21 and Bak over-expression, all with very similar EC50 concentrations. These HDACi activities were not distributed according to the molecular class of compound. In order to mimic loss of binding, an siRNA strategy was used to reduce Sp1 expression. This resulted in altered expression of multiple elements of the p53/p21 pathway. Taken together our data suggest a mechanistic model for the chemopreventive actions of butyrate in colon epithelial cells, and provide new insight into the differential activities some classes of HDAC inhibitors

    Modelling fine scale route choice of upstream migrating fish as they approach an instream structure

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    This study used pattern-oriented modelling (POM) to investigate the space use and behavioural response of upstream migrating European river lamprey (Lampetra fluviatilis) to the two-dimensional hydrodynamic conditions created by an instream structure (triangular profile gauging weir). Passive Integrated Transponder (PIT) and acoustic telemetry were used to map the spatial-temporal distribution patterns of lamprey as they migrated upstream. Acoustic Doppler velocimetry and computer modelling were used to quantify the hydrodynamic environment. In adherence with the POM methodology, multiple movement models, incorporating increasingly complex environmental feedback mechanisms and behavioural rules were created and systematically assessed to identify which factors might reproduce the observed patterns. The best model was a spatially explicit Eulerian-Lagrangian Individual Based Model (IBM) that included two simple behaviours: 1) tortuous non-directed swimming when in low flow velocity (< 0.1 m s−1) and 2) persistent directed (against the flow) swimming in moderate to high flow velocity (≄ 0.1 m s−1). The POM indicated that flow heterogeneity was an important influence of lamprey space use and that simple behavioural rules (i.e. two separate movement behaviours in response to flow velocity) were sufficient to reproduce the main movement pattern observed: avoidance of flow recirculating regions near the banks. The combination of field telemetry, hydrodynamic modelling and POM provided a useful framework for systematically identifying the key factors (hydrodynamic and behavioural) that governed the space use of the target species and would likely work well for investigating similar relationships in other aquatic species

    Bose-Einstein condensation for interacting scalar fields in curved spacetime

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    We consider the model of self-interacting complex scalar fields with a rigid gauge invariance under an arbitrary gauge group GG. In order to analyze the phenomenon of Bose-Einstein condensation finite temperature and the possibility of a finite background charge is included. Different approaches to derive the relevant high-temperature behaviour of the theory are presented.Comment: 28 pages, LaTe

    Bose-Einstein Condensation and Free DKP field

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    The thermodynamical partition function of the Duffin-Kemmer-Petiau theory is evaluated using the imaginary-time formalism of quantum field theory at finite temperature and path integral methods. The DKP partition function displays two features: (i) full equivalence with the partition function for charged scalar particles and charged massive spin 1 particles; and (ii) the zero mode sector which is essential to reproduce the well-known relativistic Bose-Einstein condensation for both theories.Comment: 12 pages, 2 eps figures. To be published in Physics Letter

    Understanding the process of psychological development in youth athletes attending an intensive wrestling camp

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    This study used a grounded theory methodology to understand if and how psychological development in youth athletes was facilitated by an ‘intensive’ summer wrestling camp experience. The theoretical sampling approach involved 10 athlete participants of the camp, nine parents of athletes, the director of the camp, and four camp staff members, who took part in a series of interviews before, during, and after the camp. Two researchers were also embedded in the camp and attended all sessions, took detailed notes, collected camp materials, and conducted observations. Following a grounded theory analysis approach, a model is presented that outlines how youth participants’ developed psychological qualities from the coach created hallenges and adversity that were systematically designed to facilitate sport performance enhancement and life skills. Variations emerged in psychological antecedents and characteristics, how the challenging wrestling camp environment was interpreted and experienced, and how learning was transferred to sport and life domains outside of the wrestling camp. This study provided insight into a unique youth sport context that was able to simultaneously develop psychological qualities to be used as sport performance enhancement and life skills

    Implementation of a pharmacogenomics consult service to support the INGENIOUS trial

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    Hospital systems increasingly utilize pharmacogenomic testing to inform clinical prescribing. Successful implementation efforts have been modeled at many academic centers. In contrast, this report provides insights into the formation of a pharmacogenomics consultation service at a safety-net hospital, which predominantly serves low-income, uninsured, and vulnerable populations. The report describes the INdiana GENomics Implementation: an Opportunity for the UnderServed (INGENIOUS) trial and addresses concerns of adjudication, credentialing, and funding

    Understanding Galaxy Formation and Evolution

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    The old dream of integrating into one the study of micro and macrocosmos is now a reality. Cosmology, astrophysics, and particle physics intersect in a scenario (but still not a theory) of cosmic structure formation and evolution called Lambda Cold Dark Matter (LCDM) model. This scenario emerged mainly to explain the origin of galaxies. In these lecture notes, I first present a review of the main galaxy properties, highlighting the questions that any theory of galaxy formation should explain. Then, the cosmological framework and the main aspects of primordial perturbation generation and evolution are pedagogically detached. Next, I focus on the ``dark side'' of galaxy formation, presenting a review on LCDM halo assembling and properties, and on the main candidates for non-baryonic dark matter. It is shown how the nature of elemental particles can influence on the features of galaxies and their systems. Finally, the complex processes of baryon dissipation inside the non-linearly evolving CDM halos, formation of disks and spheroids, and transformation of gas into stars are briefly described, remarking on the possibility of a few driving factors and parameters able to explain the main body of galaxy properties. A summary and a discussion of some of the issues and open problems of the LCDM paradigm are given in the final part of these notes.Comment: 50 pages, 10 low-resolution figures (for normal-resolution, DOWNLOAD THE PAPER (PDF, 1.9 Mb) FROM http://www.astroscu.unam.mx/~avila/avila.pdf). Lectures given at the IV Mexican School of Astrophysics, July 18-25, 2005 (submitted to the Editors on March 15, 2006
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