9,010 research outputs found

    Regulation of cAMP responses by the G12/13 pathway converges on adenylyl cyclase VII

    Get PDF
    Regulation of intracellular cyclic adenosine 3’, 5’-monophosphate (cAMP) by multiple pathways enables differential function of this ubiquitous second messenger in a context dependent manner. Modulation of Gs-stimulated intracellular cAMP has long been known to be modulated by the Gi and Gq/Ca2+ pathways. Recently, the G13 pathway was also shown to facilitate cAMP responses in murine macrophage cells. We report here that this synergistic regulation of cAMP synthesis by the Gs and G13 pathways is mediated by a specific isoform of adenylyl cyclase, AC7. Furthermore, this signaling paradigm exists in several hematopoietic lineages and can be recapitulated by exogenous expression of AC7 in HEK 293 cells. Mechanistic characterization of this synergistic interaction indicates that it occurs downstream of receptor activation and it can be mediated by the alpha subunit of either G12 or G13. Our results demonstrate that AC7 is a specific downstream effector of the G12/13 pathway

    Increased Training Volume Improves Bone Density and Cortical Area in Adolescent Football Players

    Get PDF
    Habitual football participation has been shown to be osteogenic, although the specific volume of football participation required to cause bone adaptations are not well established. The aim of the present study is to investigate tibial bone adaptations in response to 12 weeks of increased training volume in elite adolescents who are already accustomed to irregular impact training. 99 male adolescent elite footballers participated (age 16±0 y; height 1.76±0.66 m; body mass 70.2±8.3 kg). Tibial scans were performed using peripheral quantitative computed tomography immediately before and 12 weeks after an increase in football training volume. Scans were obtained at 4, 14, 38 and 66% of tibial length. Trabecular density (mg/cm3), cortical density (mg/cm3), cross-sectional area, cortical area (mm2), cortical thickness (mm) and strength strain index (mm3) were assessed. Trabecular (4%) and cortical density (14, 38%), cortical cross-sectional area (14, 38%), total cross-sectional area (66%), cortical thickness (14, 38%) and strength strain index (14, 38%) increased following 12 weeks of augmented volume training (P<0.05). Increased density of trabecular and cortical compartments and cortical thickening were shown following an increased volume of training. These adaptive responses may have been enhanced by the adolescent status of the cohort, supporting the role of early exercise intervention in improving bone strength

    Controls on geothermal heat recovery from a hot sedimentary aquifer in Guardbridge, Scotland:Field measurements, modelling and long term sustainability

    Get PDF
    Geothermal heat from Hot Sedimentary Aquifers represents a promising intermediate (30°C) resource for district heating systems. A key control on the geothermal productivity of these aquifers is the architecture of faults, which can significantly enhance or reduce the natural permeability of these systems. We present the first three-dimensional coupled groundwater flow and heat transport numerical model, combining multiple data from field mapping and fracture surveys, of two intersecting major fault systems in Central-East Scotland. This includes fault-zone fracture permeability modelling, depth-dependent permeability modelling, geo-mechanical facies assessment and heat productivity estimates for single well and multiple well extraction scenarios. Simulations indicate that with careful location of extraction wells within permeable fault systems, production is sustainable for over 50 years for multiple-well extraction scenarios in this region

    Renormalization Group Flow Equations and the Phase Transition in O(N)-models

    Get PDF
    We derive and solve flow equations for a general O(N)-symmetric effective potential including wavefunction renormalization corrections combined with a heat-kernel regularization. We investigate the model at finite temperature and study the nature of the phase transition in detail. Beta functions, fixed points and critical exponents \beta, \nu, \delta and \eta for various N are independently calculated which allow for a verification of universal scaling relations.Comment: 34 pages, 3 tables, 11 postscript figures, LaTe

    The Automatic Real-Time GRB Pipeline of the 2-m Liverpool Telescope

    Get PDF
    The 2-m Liverpool Telescope (LT), owned by Liverpool John Moores University, is located in La Palma (Canary Islands) and operates in fully robotic mode. In 2005, the LT began conducting an automatic GRB follow-up program. On receiving an automatic GRB alert from a Gamma-Ray Observatory (Swift, INTEGRAL, HETE-II, IPN) the LT initiates a special override mode that conducts follow-up observations within 2-3 min of the GRB onset. This follow-up procedure begins with an initial sequence of short (10-s) exposures acquired through an r' band filter. These images are reduced, analyzed and interpreted automatically using pipeline software developed by our team called "LT-TRAP" (Liverpool Telescope Transient Rapid Analysis Pipeline); the automatic detection and successful identification of an unknown and potentially fading optical transient triggers a subsequent multi-color imaging sequence. In the case of a candidate brighter than r'=15, either a polarimetric (from 2006) or a spectroscopic observation (from 2007) will be triggered on the LT. If no candidate is identified, the telescope continues to obtain z', r' and i' band imaging with increasingly longer exposure times. Here we present a detailed description of the LT-TRAP and briefly discuss the illustrative case of the afterglow of GRB 050502a, whose automatic identification by the LT just 3 min after the GRB, led to the acquisition of the first early-time (< 1 hr) multi-color light curve of a GRB afterglow.Comment: PASP, accepted (8 pages, 3 figures

    UV-B perceived by the UVR8 photoreceptor inhibits plant thermomorphogenesis

    Get PDF
    Small increases in ambient temperature can elicit striking effects on plant architecture, collectively termed thermomorphogenesis [1]. In Arabidopsis thaliana, these include marked stem elongation and leaf elevation, responses that have been predicted to enhance leaf cooling [ 2, 3, 4 and 5]. Thermomorphogenesis requires increased auxin biosynthesis, mediated by the bHLH transcription factor PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) [ 6, 7 and 8], and enhanced stability of the auxin co-receptor TIR1, involving HEAT SHOCK PROTEIN 90 (HSP90) [9]. High-temperature-mediated hypocotyl elongation additionally involves localized changes in auxin metabolism, mediated by the indole-3-acetic acid (IAA)-amido synthetase Gretchen Hagen 3 (GH3).17 [10]. Here we show that ultraviolet-B light (UV-B) perceived by the photoreceptor UV RESISTANCE LOCUS 8 (UVR8) [11] strongly attenuates thermomorphogenesis via multiple mechanisms inhibiting PIF4 activity. Suppression of thermomorphogenesis involves UVR8 and CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1)-mediated repression of PIF4 transcript accumulation, reducing PIF4 abundance. UV-B also stabilizes the bHLH protein LONG HYPOCOTYL IN FAR RED (HFR1), which can bind to and inhibit PIF4 function. Collectively, our results demonstrate complex crosstalk between UV-B and high-temperature signaling. As plants grown in sunlight would most likely experience concomitant elevations in UV-B and ambient temperature, elucidating how these pathways are integrated is of key importance to the understanding of plant development in natural environments

    The VLT-FLAMES Tarantula Survey V. The peculiar B[e]-like supergiant, VFTS698, in 30 Doradus

    Get PDF
    We present an analysis of a peculiar supergiant B-type star (VFTS698/Melnick 2/Parker 1797) in the 30 Doradus region of the Large Magellanic Cloud which exhibits characteristics similar to the broad class of B[e] stars. We analyse optical spectra from the VLT-FLAMES survey, together with archival optical and infrared photometry and X-ray imaging to characterise the system. We find radial velocity variations of around 400 km/s in the high excitation Si IV, N III and He II spectra, and photometric variability of ~0.6 mag with a period of 12.7 days. In addition, we detect long-term photometric variations of ~0.25 mag, which may be due to a longer-term variability with a period of ~400 days. We conclude that VFTS698 is likely an interacting binary comprising an early B-type star secondary orbiting a veiled, more massive companion. Spectral evidence suggests a mid-to-late B-type primary, but this may originate from an optically-thick accretion disc directly surrounding the primary.Comment: 18 pages, 14 figures and 8 tables. Table 8 to be published onlin
    corecore