13,182 research outputs found

    Reaper is regulated by IAP-mediated ubiquitination

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    In most cases, apoptotic cell death culminates in the activation of the caspase family of cysteine proteases, leading to the orderly dismantling and elimination of the cell. The IAPs (inhibitors of apoptosis) comprise a family of proteins that oppose caspases and thus act to raise the apoptotic threshold. Disruption of IAP-mediated caspase inhibition has been shown to be an important activity for pro-apoptotic proteins in Drosophila (Reaper, HID, and Grim) and in mammalian cells (Smac/DIABLO and Omi/HtrA2). In addition, in the case of the fly, these proteins are able to stimulate the ubiquitination and degradation of IAPs by a mechanism involving the ubiquitin ligase activity of the IAP itself. In this report, we show that the Drosophila RHG proteins (Reaper, HID, and Grim) are themselves substrates for IAP-mediated ubiquitination. This ubiquitination of Reaper requires IAP ubiquitin-ligase activity and a stable interaction between Reaper and the IAP. Additionally, degradation of Reaper can be blocked by mutating its potential ubiquitination sites. Most importantly, we also show that regulation of Reaper by ubiquitination is a significant factor in determining its biological activity. These data demonstrate a novel function for IAPs and suggest that IAPs and Reaper-like proteins mutually control each other's abundance

    The S-Cycle performance matrix : supporting comprehensive sustainability performance evaluation of technical systems

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    The work reported in this paper consolidates and rationalises disparate evaluation methods in a novel, generic framework to support the selection of comprehensive material/energetic sustainability performance indicators (SPIs) for technical systems. The S-Cycle Performance Matrix (S-CPMatrix) is comprised of 6 generic sustainability goals, 11 SPI archetypes, and 23 corresponding metrics identified from a model of technical system sustainability (the S-Cycle). The matrix was evaluated by interpreting and classifying 324 indicators currently applied to evaluate technical system sustainability performance in the literature, with 94.1% found to be fully classifiable with respect to the matrix following several refinements. The remaining 5.9% suggested additional SPI archetypes and a goal that were not initially identified. The matrix is intended to support decision makers in meeting three criteria for comprehensiveness identified from the literature: (C1) inclusion of indicators measuring performance at all relevant scales; (C2) inclusion of efficiency and effectiveness indicators; and (C3) coverage of all system sustainability goals. It may be applied to different systems in conjunction with different evaluation methods, thereby contributing to more consistent guidance on the selection of comprehensive SPIs for technical systems. In addition to industrial evaluation and comparison with existing evaluation methods, four avenues for future research were identified: (i) use of the S-CPMatrix to support systems comparison/benchmarking; (ii) further investigation of unsupported metrics; (iii) the nature and measurement of contaminants; and (iv) the comprehensiveness of SPI sets currently used in sustainability performance evaluation of technical systems

    Measured Sensitivity of the First Mark II Phased Array Feed on an ASKAP Antenna

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    This paper presents the measured sensitivity of CSIRO's first Mk. II phased array feed (PAF) on an ASKAP antenna. The Mk. II achieves a minimum system-temperature-over-efficiency Tsys/ηT_\mathrm{sys}/\eta of 78 K at 1.23 GHz and is 95 K or better from 835 MHz to 1.8 GHz. This PAF was designed for the Australian SKA Pathfinder telescope to demonstrate fast astronomical surveys with a wide field of view for the Square Kilometre Array (SKA).Comment: 5 pages, 2 figures, accepted for publication in Electromagnetics in Advanced applications (ICEAA), 2015 International Conference o

    Testing the recovery of stellar rotation signals from Kepler light curves using a blind hare-and-hounds exercise

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    We present the results of a blind exercise to test the recoverability of stellar rotation and differential rotation in Kepler light curves. The simulated light curves lasted 1000 days and included activity cycles, Sun-like butterfly patterns, differential rotation and spot evolution. The range of rotation periods, activity levels and spot lifetime were chosen to be representative of the Kepler data of solar like stars. Of the 1000 simulated light curves, 770 were injected into actual quiescent Kepler light curves to simulate Kepler noise. The test also included five 1000-day segments of the Sun's total irradiance variations at different points in the Sun's activity cycle. Five teams took part in the blind exercise, plus two teams who participated after the content of the light curves had been released. The methods used included Lomb-Scargle periodograms and variants thereof, auto-correlation function, and wavelet-based analyses, plus spot modelling to search for differential rotation. The results show that the `overall' period is well recovered for stars exhibiting low and moderate activity levels. Most teams reported values within 10% of the true value in 70% of the cases. There was, however, little correlation between the reported and simulated values of the differential rotation shear, suggesting that differential rotation studies based on full-disk light curves alone need to be treated with caution, at least for solar-type stars. The simulated light curves and associated parameters are available online for the community to test their own methods.Comment: Accepted for publication in MNRAS. Accepted, 13 April 2015. Received, 26 March 2015; in original form, 9 November 201

    The Drosophila caspase Ice is important for many apoptotic cell deaths and for spermatid individualization, a nonapoptotic process

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    Caspase family proteases play important roles in the regulation of apoptotic cell death. Initiator caspases are activated in response to death stimuli, and they transduce and amplify these signals by cleaving and thereby activating effector caspases. In Drosophila, the initiator caspase Nc (previously Dronc) cleaves and activates two short-prodomain caspases, Dcp-1 and Ice (previously Drice), suggesting these as candidate effectors of Nc killing activity. dcp-1-null mutants are healthy and possess few defects in normally occurring cell death. To explore roles for Ice in cell death, we generated and characterized an Ice null mutant. Animals lacking Ice show a number of defects in cell death, including those that occur during embryonic development, as well as during formation of adult eyes, arista and wings. Ice mutants exhibit subtle defects in the destruction of larval tissues, and do not prevent destruction of salivary glands during metamorphosis. Cells from Ice animals are also markedly resistant to several stresses, including X-irradiation and inhibition of protein synthesis. Mutations in Ice also suppress cell death that is induced by expression of Rpr, Wrinkled (previously Hid) and Grim. These observations demonstrate that Ice plays an important non-redundant role as a cell death effector. Finally, we demonstrate that Ice participates in, but is not absolutely required for, the non-apoptotic process of spermatid differentiation

    Calcitonin receptors in GtoPdb v.2023.1

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    This receptor family comprises a group of receptors for the calcitonin/CGRP family of peptides. The calcitonin (CT), amylin (AMY), calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on CGRP, AM, AMY, and CT receptors [131, 74, 71]) are generated by the genes CALCR (which codes for the CT receptor, CTR) and CALCRL (which codes for the calcitonin receptor-like receptor, CLR, previously known as CRLR). Their function and pharmacology are altered in the presence of RAMPs (receptor activity-modifying proteins), which are single TM domain proteins of ca. 150 amino acids, identified as a family of three members; RAMP1, RAMP2 and RAMP3. There are splice variants of the CTR; these in turn produce variants of AMY receptors [131], some of which can be potently activated by CGRP. The endogenous agonists are the peptides calcitonin, α-CGRP (formerly known as CGRP-I), β-CGRP (formerly known as CGRP-II), amylin (occasionally called islet-amyloid polypeptide, diabetes-associated polypeptide), adrenomedullin and adrenomedullin 2/intermedin. There are species differences in peptide sequences, particularly for the CTs. CTR-stimulating peptide (CRSP) is another member of the family with selectivity for the CTR but it is not expressed in humans [93]. CLR (calcitonin receptor-like receptor) by itself binds no known endogenous ligand, but in the presence of RAMPs it gives receptors for CGRP, adrenomedullin and adrenomedullin 2/intermedin. There are several approved drugs that target this receptor family, such as pramlintide, erenumab, and the "gepant" class of CGRP receptor antagonists. There are also species differences in agonist pharmacology; for example, CGRP displays potent activity at multiple rat and mouse receptors [58, 15]. The summary table only reflects human receptor pharmacology

    Apps-olutely fabulous? - The quality of PFMT smartphone app content and design rated using the Mobile App Rating Scale, Behaviour Change Taxonomy, and guidance for exercise prescription

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    This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordICS 2019: International Continence Society 49th Annual Meeting, 3-6 September 2019, Gothenburg, SwedenDunedin School of MedicineNational Institute for Health Research (NIHR

    Internet of Things of Trees - Conversational objects via SMS protocols

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    The paper describes a ‘work in progress’ to develop a system to enable users to engage with the historical and environmental story behind veteran trees in Hampstead Heath in the spirit of the Internet of Things. Unlike other ‘Internet of Trees’ projects, this study focuses on story telling rather than sensor networks. Building on previous work, conversational agents (‘chatbots’) are used as proxies for the trees to enable a two-way narrative exchange between the user and the ‘tree’. Two interaction pathways are proposed (direct SMS and web-based geofencing) and the technical development of both approaches is described, as well as ethnographic studies undertaken on Hampstead Heath to elicit engaging content for the chatbot. An initial deployment of the SMS-based interaction at Tate Exchange, a project space within Tate Modern, London is discussed and a preliminary evaluation presented
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