380 research outputs found

    Quantifying microcracks on fractured bone surfaces – Potential use in forensic anthropology

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    Bone fracture surface morphology (FSM) can provide valuable information on the cause of failure in forensic and archaeological applications and it depends primarily on three factors, the loading conditions (like strain rate), the ambient conditions (wet or dry bone material) and the quality of bone material itself. The quality of bone material evidently changes in taphonomy as a result of the decomposition process and that in turn is expected to affect FSM. Porcine bones were fractured by a standardised impact during the course of soft tissue decomposition, at 28-day intervals, over 140 days (equivalent to 638 cooling degree days). Measurements of the associated microcracks on the fractured cortical bone surfaces indicated a progressive increase in mean length during decomposition from around 180 μm–375 μm. The morphology of these microcracks also altered, from multiple intersecting microcracks emanating from a central point at 0–28 cumulative cooling degree days, to longer linear cracks appearing to track lamellae as soft tissue decomposition progressed. The implications of these findings are that taphonomic changes of bone may offer the real possibility of distinguishing perimortem and taphonomic damage and also provide a new surrogate parameter for estimation of post-mortem interval (PMI) in forensics

    Puf3p induces translational repression of genes linked to oxidative stress

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    In response to stress, the translation of many mRNAs in yeast can change in a fashion discordant with the general repression of translation. Here, we use machine learning to mine the properties of these mRNAs to determine specific translation control signals. We find a strong association between transcripts acutely translationally repressed under oxidative stress and those associated with the RNA-binding protein Puf3p, a known regulator of cellular mRNAs encoding proteins targeted to mitochondria. Under oxidative stress, a PUF3 deleted strain exhibits more robust growth than wild-type cells and the shift in translation from polysomes to monosomes is attenuated, suggesting puf3Δ cells perceive less stress. In agreement, the ratio of reduced:oxidized glutathione, a major antioxidant and indicator of cellular redox state, is increased in unstressed puf3Δ cells but remains lower under stress. In untreated conditions, Puf3p migrates with polysomes rather than ribosome-free fractions, but this is lost under stress. Finally, reverse transcriptase-polymerase chain reaction (RT-PCR) of Puf3p targets following affinity purification shows Puf3p-mRNA associations are maintained or increased under oxidative stress. Collectively, these results point to Puf3p acting as a translational repressor in a manner exceeding the global translational response, possibly by temporarily limiting synthesis of new mitochondrial proteins as cells adapt to the stress

    Density-matrix formalism with three-body ground-state correlations

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    A density-matrix formalism which includes the effects of three-body ground- state correlations is applied to the standard Lipkin model. The reason to consider the complicated three-body correlations is that the truncation scheme of reduced density matrices up to the two-body level does not give satisfactory results to the standard Lipkin model. It is shown that inclusion of the three-body correlations drastically improves the properties of the ground states and excited states. It is pointed out that lack of mean-field effects in the standard Lipkin model enhances the relative importance of the three-body ground-state correlations. Formal aspects of the density-matrix formalism such as a relation to the variational principle and the stability condition of the ground state are also discussed. It is pointed out that the three-body ground-state correlations are necessary to satisfy the stability condition

    The School Sport Co-ordinator Programme: Changing the Role of the Physical Education Teacher?

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    Over the last decade or so, young people have increasingly become a focus of UK sport policy. Fuelled in part by concerns such as the increasing levels of childhood inactivity and obesity, and the lack of international success in sport, a plethora of policy initiatives aimed at young people have been developed. In April 2000, the government published its sport strategy document, A Sporting Future for All, pulling together all the threads of recent policies, and in it, restating its commitment to youth sport, sport in education, excellence and sport in the community. One such policy initiative, the School Sport Co-ordinator programme, is the focus of this paper. The School Sport Co-ordinator programme, currently being introduced into schools in England, is an initiative that involves two government departments (sport and education) and a number of other agencies, reflecting the government's current agenda to ensure 'joined up policy' thinking. It aims to develop opportunities for youth sport through co-ordinated links between PE and sport in schools, both within and outside of the formal curriculum, with those in local community sports settings. The essence of the School Sport Co-ordinator programme is to free up nominated teachers in schools from teaching to allow them time for development activities, specifically to encourage schools and community sports providers to work in partnership. This paper draws on data from an ongoing research project examining the implementation of one School Sport Co-ordinator partnership, 'northbridge'. Drawing on in-depth interviews, it explores the perceptions of the newly established School Sport Co-ordinators of their changing role. The paper highlights some of the initial tensions and challenges for them in their task of working across different educational and sporting contexts

    AROMA - Agri-Environment Reduction Options for Mitigating Ammonia: assessment of the effects of RDPE environmental land management schemes on air quality

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    Measures available under agri-environment and grant schemes were assessed for their ammonia mitigation potential

    Identification of potential “Remedies” for Air Pollution (nitrogen) Impacts on Designated Sites (RAPIDS)

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    Atmospheric nitrogen (N) deposition is a significant threat to semi-natural habitats and species in the UK, resulting in on-going erosion of habitat quality and declines in many species of high conservation value. The project focused on impacts and remedies for designated conservation sites, especially Natura 2000 sites protected under the EU Habitats Directive. However, the approach and certainly the measures could be equally applied to other areas of high conservation value. Evidence was drawn together to develop a framework for identifying key N threats at individual sites as a basis to target mitigation options in the context of potential legislative, voluntary and financial instruments

    New York: the animated city

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    The urban landscape of New York City is one that is familiar to many, but, through the medium of animation, this familiarity has been consistently challenged. Often metamorphic, and always meticulously constructed, animated imagery encourages reflective thinking. Focusing on the themes of construction, destruction, and interactivity, this article seeks to cast critical light upon the animated double life that New York City has lived through the following moving image texts: Disney’s Fantasia 2000 (1999), Patrick Jean’s computer-generated short Pixels (2009), and Rockstar Games’ open-world blockbuster Grand Theft Auto IV (2008)

    Interregional compensatory mechanisms of motor functioning in progressing preclinical neurodegeneration.

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    Understanding brain reserve in preclinical stages of neurodegenerative disorders allows determination of which brain regions contribute to normal functioning despite accelerated neuronal loss. Besides the recruitment of additional regions, a reorganisation and shift of relevance between normally engaged regions are a suggested key mechanism. Thus, network analysis methods seem critical for investigation of changes in directed causal interactions between such candidate brain regions. To identify core compensatory regions, fifteen preclinical patients carrying the genetic mutation leading to Huntington's disease and twelve controls underwent fMRI scanning. They accomplished an auditory paced finger sequence tapping task, which challenged cognitive as well as executive aspects of motor functioning by varying speed and complexity of movements. To investigate causal interactions among brain regions a single Dynamic Causal Model (DCM) was constructed and fitted to the data from each subject. The DCM parameters were analysed using statistical methods to assess group differences in connectivity, and the relationship between connectivity patterns and predicted years to clinical onset was assessed in gene carriers. In preclinical patients, we found indications for neural reserve mechanisms predominantly driven by bilateral dorsal premotor cortex, which increasingly activated superior parietal cortices the closer individuals were to estimated clinical onset. This compensatory mechanism was restricted to complex movements characterised by high cognitive demand. Additionally, we identified task-induced connectivity changes in both groups of subjects towards pre- and caudal supplementary motor areas, which were linked to either faster or more complex task conditions. Interestingly, coupling of dorsal premotor cortex and supplementary motor area was more negative in controls compared to gene mutation carriers. Furthermore, changes in the connectivity pattern of gene carriers allowed prediction of the years to estimated disease onset in individuals. Our study characterises the connectivity pattern of core cortical regions maintaining motor function in relation to varying task demand. We identified connections of bilateral dorsal premotor cortex as critical for compensation as well as task-dependent recruitment of pre- and caudal supplementary motor area. The latter finding nicely mirrors a previously published general linear model-based analysis of the same data. Such knowledge about disease specific inter-regional effective connectivity may help identify foci for interventions based on transcranial magnetic stimulation designed to stimulate functioning and also to predict their impact on other regions in motor-associated networks

    Archetypal transcriptional blocks underpin yeast gene regulation in response to changes in growth conditions

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    The transcriptional responses of yeast cells to diverse stresses typically include gene activation and repression. Specific stress defense, citric acid cycle and oxidative phosphorylation genes are activated, whereas protein synthesis genes are coordinately repressed. This view was achieved from comparative transcriptomic experiments delineating sets of genes whose expression greatly changed with specific stresses. Less attention has been paid to the biological significance of 1) consistent, albeit modest, changes in RNA levels across multiple conditions, and 2) the global gene expression correlations observed when comparing numerous genome-wide studies. To address this, we performed a meta-analysis of 1379 microarray-based experiments in yeast, and identified 1388 blocks of RNAs whose expression changes correlate across multiple and diverse conditions. Many of these blocks represent sets of functionally-related RNAs that act in a coordinated fashion under normal and stress conditions, and map to global cell defense and growth responses. Subsequently, we used the blocks to analyze novel RNA-seq experiments, demonstrating their utility and confirming the conclusions drawn from the meta-analysis. Our results provide a new framework for understanding the biological significance of changes in gene expression: ‘archetypal’ transcriptional blocks that are regulated in a concerted fashion in response to external stimuli

    The 4E-BP Caf20p Mediates Both eIF4E-Dependent and Independent Repression of Translation

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    Translation initiation factor eIF4E mediates mRNA selection for protein synthesis via the mRNA 5’cap. A family of binding proteins, termed the 4E-BPs, interact with eIF4E to hinder ribosome recruitment. Mechanisms underlying mRNA specificity for 4E-BP control remain poorly understood. Saccharomyces cerevisiae 4E-BPs, Caf20p and Eap1p, each regulate an overlapping set of mRNAs. We undertook global approaches to identify protein and RNA partners of both 4E-BPs by immunoprecipitation of tagged proteins combined with mass spectrometry or next-generation sequencing. Unexpectedly, mass spectrometry indicated that the 4E-BPs associate with many ribosomal proteins. 80S ribosome and polysome association was independently confirmed and was not dependent upon interaction with eIF4E, as mutated forms of both Caf20p and Eap1p with disrupted eIF4E-binding motifs retain ribosome interaction. Whole-cell proteomics revealed Caf20p mutations cause both up and down-regulation of proteins and that many changes were independent of the 4E-binding motif. Investigations into Caf20p mRNA targets by immunoprecipitation followed by RNA sequencing revealed a strong association between Caf20p and mRNAs involved in transcription and cell cycle processes, consistent with observed cell cycle phenotypes of mutant strains. A core set of over 500 Caf20p-interacting mRNAs comprised of both eIF4E-dependent (75%) and eIF4E-independent targets (25%), which differ in sequence attributes. eIF4E-independent mRNAs share a 3’ UTR motif. Caf20p binds all tested motif-containing 3’ UTRs. Caf20p and the 3’UTR combine to influence ERS1 mRNA polysome association consistent with Caf20p contributing to translational control. Finally ERS1 3’UTR confers Caf20-dependent repression of expression to a heterologous reporter gene. Taken together, these data reveal conserved features of eIF4E-dependent Caf20p mRNA targets and uncover a novel eIF4E-independent mode of Caf20p binding to mRNAs that extends the regulatory role of Caf20p in the mRNA-specific repression of protein synthesis beyond its interaction with eIF4E
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