311 research outputs found

    Correspondence regarding John Fowles' judging fee: Part 2

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    Correspondence regarding the whereabouts of one of the judges's fee cheque, 7 Jun-29 Aug 197

    University-Community Engagement and the Role of ICT for Development Initiatives

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    There has been increasing interest in university-community engagement, and the various aspects to be considered in implementing initiatives to support the engagement. This paper explores a university’s formal engagement at the institutional level with two neighbouring communities, and the role of information and communication technologies in these initiatives. Through content analysis of focus group discussions, themes are identified which may be useful to universities and communities in planning and implementing ICT for development initiatives to support university-community partnerships

    The effect of a decaffeinated green tea extract formula on fat oxidation, body composition and exercise performance

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    Background: The cardio-metabolic and antioxidant health benefits of caffeinated green tea (GT) relate to its catechin polyphenol content. Less is known about decaffeinated extracts, particularly in combination with exercise. The aim of this study was therefore to determine whether a decaffeinated green tea extract (dGTE) positively influenced fat oxidation, body composition and exercise performance in recreationally active participants. Methods: Fourteen, recreationally active males participated in a double-blind, placebo-controlled, parallel design intervention (mean±SE; age = 21.4±0.3 yrs; weight = 76.37±1.73 kg; body fat = 16.84±0.97 %, peak oxygen consumption [V̇O2peak] = 3.00±0.10 L·min-1). Participants were randomly assigned capsulated dGTE (571 mg·d-1; n=7) or placebo (PL; n=7) for 4 weeks. Following body composition and resting cardiovascular measures, participants cycled for 1 hour at 50% V̇O2peak, followed by a 40 minute performance trial at week 0, 2 and 4. Fat and carbohydrate oxidation was assessed via indirect calorimetry. Pre-post exercise blood samples were collected for determination of total fatty acids (TFA). Distance covered (km) and average power output (W) were assessed as exercise performance criteria. Results: Total fat oxidation rates increased by 24.9 % from 0.241±0.025 to 0.301±0.009 g·min-1 with dGTE (P=0.05; ηp2 = 0.45) by week 4, whereas substrate utilisation was unaltered with PL. Body fat significantly decreased with dGTE by 1.63±0.16 % in contrast to PL over the intervention period (P<0.001; ηp2 = 0.84). No significant changes for FFA or blood pressure between groups were observed. dGTE resulted in a 10.9 % improvement in performance distance covered from 20.23±0.54 km to 22.43 ± 0.40 km by week 4 (P<0.001; ηp2 = 0.85). Conclusions: A 4 week dGTE intervention favourably enhanced substrate utilisation and subsequent performance indices, but did not alter TFA concentrations in comparison to PL. The results support the use of catechin polyphenols from dGTE in combination with exercise training in recreationally active volunteers

    Gamma-ray Absorption and the distance to Cyg X-3

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    If the effect of gamma ray absorption by photon-photon pair production is taken into account, the gamma ray luminosity of Cygnus X-3 above 1015 eV is significantly increased. This would have the effect of favoring the minimum distance (11.4 kpc) to the source

    Human cytomegalovirus: taking the strain

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    In celebrating the 60th anniversary of the first isolation of human cytomegalovirus (HCMV), we reflect on the merits and limitations of the viral strains currently being used to develop urgently needed treatments. HCMV research has been dependent for decades on the high-passage strains AD169 and Towne, heavily exploiting their capacity to replicate efficiently in fibroblasts. However, the genetic integrity of these strains is so severely compromised that great caution needs to be exercised when considering their past and future use. It is now evident that wild-type HCMV strains are not readily propagated in vitro. HCMV mutants are rapidly selected during isolation in fibroblasts, reproducibly affecting gene RL13, the UL128 locus (which includes genes UL128, UL130 and UL131A) and often the UL/b′ region. As a result, the virus becomes less cell associated, altered in tropism and less pathogenic. This problem is not restricted to high-passage strains, as even low-passage strains can harbour biologically significant mutations. Cloning and manipulation of the HCMV genome as a bacterial artificial chromosome (BAC) offers a means of working with stable, genetically defined strains. To this end, the low-passage strain Merlin genome was cloned as a BAC and sequentially repaired to match the viral sequence in the original clinical sample from which Merlin was derived. Restoration of UL128L to wild type was detrimental to growth in fibroblasts, whereas restoration of RL13 impaired growth in all cell types tested. Stable propagation of phenotypically wild-type virus could be achieved only by placing both regions under conditional expression. In addition to the development of these tools, the Merlin transcriptome and proteome have been characterized in unparalleled detail. Although Merlin may be representative of the clinical agent, high-throughput whole-genome deep sequencing studies have highlighted the remarkable high level of interstrain variation present in circulating virus. There is a need to develop systems capable of addressing the significance of this diversity, free from the confounding effects of genetic changes associated with in vitro adaptation. The generation of a set of BAC clones, each containing the genome of a different HCMV strain repaired to match the sequence in the clinical sample, would provide a pathway to address the biological and clinical effects of natural variation in wild-type HCMV

    The Proteasome Distinguishes between Heterotypic and Homotypic Lysine-11-Linked Polyubiquitin Chains.

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    Proteasome-mediated degradation occurs with proteins principally modified with lysine-48 polyubiquitin chains. Whether the proteasome also can bind atypical ubiquitin chains, including those linked by lysine-11, has not been well established. This is critically important, as lysine-11 polyubiquitination has been implicated in both proteasome-mediated degradation and non-degradative outcomes. Here we demonstrate that pure homotypic lysine-11-linked chains do not bind strongly to the mammalian proteasome. By contrast, heterotypic polyubiquitin chains, containing lysine-11 and lysine-48 linkages, not only bind to the proteasome but also stimulate the proteasomal degradation of the cell-cycle regulator cyclin B1. Thus, while heterotypic lysine-11-linked chains facilitate proteasomal degradation, homotypic lysine-11 linkages adopt conformations that prevent association with the proteasome. Our data demonstrate the capacity of the proteasome to bind ubiquitin chains of distinct topology, with implications for the recognition and diverse biological functions of mixed ubiquitin chains.This work is supported by a Wellcome Trust Senior Clinical Research Fellowship to JAN (102770/Z/13/Z), a Wellcome Trust Fellowship to MPW (093966/Z/10/Z) and a National Institute of Health grant (GM067945) to SPG. The Cambridge Institutefor Medical Research is in receipt of a Wellcome Trust Strategic Award [100140].This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.celrep.2015.06.06

    Human cytomegalovirus protein pUL36: A dual cell death pathway inhibitor.

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    Human cytomegalovirus (HCMV) is an important human pathogen and a paradigm of intrinsic, innate, and adaptive viral immune evasion. Here, we employed multiplexed tandem mass tag-based proteomics to characterize host proteins targeted for degradation late during HCMV infection. This approach revealed that mixed lineage kinase domain-like protein (MLKL), a key terminal mediator of cellular necroptosis, was rapidly and persistently degraded by the minimally passaged HCMV strain Merlin but not the extensively passaged strain AD169. The strain Merlin viral inhibitor of apoptosis pUL36 was necessary and sufficient both to degrade MLKL and to inhibit necroptosis. Furthermore, mutation of pUL36 Cys131 abrogated MLKL degradation and restored necroptosis. As the same residue is also required for pUL36-mediated inhibition of apoptosis by preventing proteolytic activation of procaspase-8, we define pUL36 as a multifunctional inhibitor of both apoptotic and necroptotic cell death
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