3,505 research outputs found

    Contrasting The Morbidity Pattern In An African Practice With That In A European General Practice In Salisbury

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    A CAJM article comparing and contrasting Morbidity Patterns between African and European General Practices in Harare (Salisbury).In Rhodesia, general practice among Europeans is fairly typical of practice in developed countries, and an analysis of morbidity statistics is fairly easy. In contrast, general practice among the African people in Rhodesia is more typical of developing countries, and with heavier work loads and fewer diagnostic facilities the morbidity picture is blurred. Yet the contrasting patterns in a multiracial society are of great importance epi- demiologically and administratively. This is especially so in a developing country such as Rhodesia, which is producing its first medical graduates. For these reasons no apology is made for presenting, as a pilot survey, the contrasting morbidity patterns in two general practices in Salisbury, Rhodesia, even though morbidity statistics, at best unreliable, are particularly unreliable in the case of the African practice

    Characterising a Novel Interaction between Rap1b and Rhea sheds light on new Mechanisms for Focal Adhesion Assembly

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    For the first time, we reveal a direct interaction between Rap1b and the fly homolog of talin, Rhea. Using a combination of biochemical and biophysical techniques, the Rap1 binding site on Rhea has been successfully mapped. Additionally, we reveal that an acidic-to-basic K17E substitution, on Rhea, completely abolishes Rap1 binding. Our collaborators have shown that this mutation results in non-viable embryos and our data links the Rap1:Rhea interaction to this lethal phenotype. The implications of our findings support currently proposed mechanisms of RIAM-independent integrin activation, that would challenge our understanding of focal adhesion formation. Furthermore, we propose a double-dependent Rap1 integrin-activation pathway, involving Rap1 directly interacting with the FERM domain, alongside the known Rap1-dependent recruitment of talin. Optimisations have allowed us to express both the wild-type and mutant Rhea F0 domain in E.coli BL21(DE3) cells. Efficient purification via Ni-NTA-based affinity chromatography results in yields of ~50-60 mg/litre being obtained. Using circular dichroism, it is shown that substitution of the K17 residue does not interfere with the structural integrity of Rhea; both proteins have identical full spectrum measurements and Tm values. Optimal expression of the conserved G-domain of mouse Rap1b was achieved in the CK600K cell line. This region is highly conserved to that in fly (90% identical). NMR was used to show direct interaction between drosophila Rhea F0 and Rap1b; whilst additionally confirming that Rap1b was unable to induce chemical shifts in the F0-K17E mutant. Triple resonance NMR experiments revealed the location of the Rap1 binding site on the wild-type Rhea F0, with V15, K17, T18, K37 and E40 being highlighted at the centre of this interaction. Structural models of Rap1:Rhea F0 binding agree with our findings, with the 5 highlighted residues seen to make close contact with the Rap1 switch I domain. Together this work confirms a direct interaction between Rhea and Rap1 whilst providing biochemical validation for the lethal phenotypes observed in mutant flies. It also provides further insight into new mechanisms of focal adhesion formation and integrin activation

    Evolutionarily conserved and diverged alternative splicing events show different expression and functional profiles

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    To better decipher the functional impact of alternative splicing, we classified alternative splicing events in 10 818 pairs of human and mouse genes based on conservation at genome and transcript levels. Expression levels of conserved alternative splices in human and mouse expressed sequence tag databases show strong correlation, indicating that alternative splicing is similarly regulated in both species. A total of 43% (8921) of mouse alternative splices could be found in the human genome but not in human transcripts. Five of eleven tested mouse predictions were observed in human tissues, demonstrating that mouse transcripts provide a valuable resource for identifying alternative splicing events in human genes. Combining gene-specific measures of conserved and diverged alternative splicing with both gene classification based on Gene Ontology (GO) and microarray-determined gene expression in 52 diverse human tissues and cell lines, we found conserved alternative splicing most enriched in brain-expressed signaling pathways. Diverged alternative splicing is more prevalent in testis and cancerous cell line up-regulated processes, including protein biosynthesis, responses to stress and responses to endogenous stimuli. Using conservation as a surrogate for functional significance, these results suggest that alternative splicing plays an important role in enhancing the functional capacity of central nervous systems, while non-functional splicing more frequently occurs in testis and cell lines, possibly as a result of cellular stress and rapid proliferation

    What lies beneath? The role of informal and hidden networks in the management of crises

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    Crisis management research traditionally focuses on the role of formal communication networks in the escalation and management of organisational crises. Here, we consider instead informal and unobservable networks. The paper explores how hidden informal exchanges can impact upon organisational decision-making and performance, particularly around inter-agency working, as knowledge distributed across organisations and shared between organisations is often shared through informal means and not captured effectively through the formal decision-making processes. Early warnings and weak signals about potential risks and crises are therefore often missed. We consider the implications of these dynamics in terms of crisis avoidance and crisis management

    Mineralogy of Vera Rubin Ridge in Gale Crater from the Mars Science Laboratory CheMin instrument

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    Gale crater was selected as the landing site for the Mars Science Laboratory Curiosity rover because of orbital evidence for a variety of secondary minerals in the lower slopes of Aeolis Mons (aka Mount Sharp) that indicate changes in aqueous conditions over time. Distinct units demonstrate orbital spectral signatures of hematite, phyllosilicate (smectite), and sulfate minerals, which suggest that ancient aqueous environments in Gale crater varied in oxidation potential, pH, and water activity. Vera Rubin ridge (VRR) is the first of these units identified from orbit to have been studied by Curiosity. Orbital near-infrared data from VRR show a strong band at 860 nm indicative of hematite. Before Curiosity arrived at VRR, the hypotheses to explain the formation of hematite included (1) precipitation at a redox interface where aqueous Fe2+ was oxidized to Fe3+, and (2) acidic alteration of olivine in oxic fluids. Studying the composition and sedimentology of the rocks on VRR allow us to test and refine these hypotheses and flesh out the depositional and diagenetic history of the ridge. Here, we focus on the mineralogical results of four rock powders drilled from and immediately below VRR as determined by CheMin

    The elastic constants of MgSiO3 perovskite at pressures and temperatures of the Earth's mantle

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    The temperature anomalies in the Earth's mantle associated with thermal convection1 can be inferred from seismic tomography, provided that the elastic properties of mantle minerals are known as a function of temperature at mantle pressures. At present, however, such information is difficult to obtain directly through laboratory experiments. We have therefore taken advantage of recent advances in computer technology, and have performed finite-temperature ab initio molecular dynamics simulations of the elastic properties of MgSiO3 perovskite, the major mineral of the lower mantle, at relevant thermodynamic conditions. When combined with the results from tomographic images of the mantle, our results indicate that the lower mantle is either significantly anelastic or compositionally heterogeneous on large scales. We found the temperature contrast between the coldest and hottest regions of the mantle, at a given depth, to be about 800K at 1000 km, 1500K at 2000 km, and possibly over 2000K at the core-mantle boundary.Comment: Published in: Nature 411, 934-937 (2001

    Are lay people good at recognising the symptoms of schizophrenia?

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    ©2013 Erritty, Wydell. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Aim: The aim of this study was to explore the general public’s perception of schizophrenia symptoms and the need to seekhelp for symptoms. The recognition (or ‘labelling’) of schizophrenia symptoms, help-seeking behaviours and public awareness of schizophrenia have been suggested as potentially important factors relating to untreated psychosis. Method: Participants were asked to rate to what extent they believe vignettes describing classic symptoms (positive and negative) of schizophrenia indicate mental illness. They were also asked if the individuals depicted in the vignettes required help or treatment and asked to suggest what kind of help or treatment. Results: Only three positive symptoms (i.e., Hallucinatory behaviour, Unusual thought content and Suspiciousness) of schizophrenia were reasonably well perceived (above 70%) as indicating mental illness more than the other positive or negative symptoms. Even when the participants recognised that the symptoms indicated mental illness, not everyone recommended professional help. Conclusion: There may be a need to improve public awareness of schizophrenia and psychosis symptoms, particularly regarding an awareness of the importance of early intervention for psychosis

    Glen Torridon Mineralogy and the Sedimentary History of the Clay Mineral Bearing Unit

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    Clay minerals are common in ancient terrains on Mars and their presence at the surface alludes to aqueous processes in the Noachian to Early Hesperian (>3.5 Ga). Gale crater was selected as Curiositys landing site largely because of the identification of clay mineral rich strata from orbit. On Earth, the types of clay minerals (i.e., smectites) identified in Gale crater are typically juvenile weathering products that ultimately record the interaction between primary igneous minerals with the hydrosphere, atmosphere, and biosphere. Trioctahedral and dioctahedral smectite were identified by Curiosity in units stratigraphically below the Clay Mineral-Bearing Unit (CBU) identified from orbit. Compositional and sedimentological data suggest the smectite formed via authigenesis in a lake environment and may have been altered during early diagenesis. The CBU is stratigraphically equivalent to a hematite-rich unit to the north and stratigraphically underlies sulfate-rich units to the south, suggesting a dynamic environment and evolving history of water in the ancient Gale crater lake. Targeting these clay mineral rich areas on Mars with rover missions provides an opportunity to explore the aqueous and sedimentary history of the planet
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