771 research outputs found

    Five fathers' experience of an adult son sustaining a cervical spinal cord injury: an Interpretative Phenomenological Analysis

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    The paper presents an in-depth idiographic study exploring the experience of fathers who have an adult son with a cervical spinal cord injury (SCI). Five participants were recruited and individual semi-structured interviews were conducted. The interviews were transcribed verbatim and analysed using Interpretative Phenomenological Analysis (IPA). Two super-ordinate themes are presented highlighting. Firstly, the ongoing negative impact of their sons’ injury on the participants’ role as fathers’. This comprises the negative impact on emotions with guilt common for failing in their perceived role as a father. The dissonance experienced between wanting to help encourage their sons’ independence. Concern experienced due to their sons altered life trajectory and anxiety because they won’t be alive to protect their son in the future. Secondly, how participants cope and adjust to their son’s SCI are presented. Comprising of how positive thinking, such as focusing on their son surviving the trauma; and the influence of seeing their son cope well affects how participants cope. Also, reflecting on how the injury has changed their life helps participants, to an extent, make sense of the trauma. The results are discussed in relation to the relevant extant literature to give a unique perspective about how SCI impacts their perceived role as fathers and the struggle to cope and adjust to the trauma. Future research investigating the impact of SCI on the family is warranted to better understand the wider implications

    A mammalian functional-genetic approach to characterizing cancer therapeutics

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    Supplementary information is available online at http://www.nature.com/naturechemicalbiology/. Reprints and permissions information is available online at http://npg.nature.com/reprintsandpermissions/.Identifying mechanisms of drug action remains a fundamental impediment to the development and effective use of chemotherapeutics. Here we describe an RNA interference (RNAi)–based strategy to characterize small-molecule function in mammalian cells. By examining the response of cells expressing short hairpin RNAs (shRNAs) to a diverse selection of chemotherapeutics, we could generate a functional shRNA signature that was able to accurately group drugs into established biochemical modes of action. This, in turn, provided a diversely sampled reference set for high-resolution prediction of mechanisms of action for poorly characterized small molecules. We could further reduce the predictive shRNA target set to as few as eight genes and, by using a newly derived probability-based nearest-neighbors approach, could extend the predictive power of this shRNA set to characterize additional drug categories. Thus, a focused shRNA phenotypic signature can provide a highly sensitive and tractable approach for characterizing new anticancer drugs.National Institute of Mental Health (U.S.) (grant RO1 CA128803-03)American Association for Cancer ResearchMassachusetts Institute of Technology. Dept. of BiologyNational Cancer Institute (U.S.). Integrative Cancer Biology Program (grant 1-U54-CA112967

    A cotton miRNA is involved in regulation of plant response to salt stress

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    The present study functionally identified a new microRNA (microRNA ovual line 5, miRNVL5) with its target gene GhCHR from cotton (Gossypium hirsutum). The sequence of miRNVL5 precursor is 104 nt long, with a well developed secondary structure. GhCHR contains two DC1 and three PHD Cys/His-rich domains, suggesting that GhCHR encodes a zinc-finger domain-containing transcription factor. miRNVL5 and GhCHR express at various developmental stages of cotton. Under salt stress (50–400 mM NaCl), miRNVL5 expression was repressed, with concomitant high expression of GhCHR in cotton seedlings. Ectopic expression of GhCHR in Arabidopsis conferred salt stress tolerance by reducing Na+ accumulation in plants and improving primary root growth and biomass. Interestingly, Arabidopsis constitutively expressing miRNVL5 showed hypersensitivity to salt stress. A GhCHR orthorlous gene At2g44380 from Arabidopsis that can be cleaved by miRNVL5 was identified by degradome sequencing, but no confidential miRNVL5 homologs in Arabidopsis have been identified. Microarray analysis of miRNVL5 transgenic Arabidopsis showed six downstream genes (CBF1, CBF2, CBF3, ERF4, AT3G22920, and AT3G49200), which were induced by salt stress in wild-type but repressed in miRNVL5-expressing Arabidopsis. These results indicate that miRNVL5 is involved in regulation of plant response to salt stress

    Friction and Wear Performance Evaluation of Bio-Lubricants and DLC Coatings on Cam/Tappet Interface of Internal Combustion Engines.

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    The environmental concerns associated with artificially formulated engine oils have forced a shift towards bio-based lubricants. The deposition of hard coatings on engine components and migrating to environmentally friendly green lubricants can help in this regard. Chemically modified forms of vegetable oils, with better low-temperature characteristics and enhanced thermo-oxidative stability, are suitable substitutes to conventional lubricant base oils. The research presented in this manuscript was undertaken to experimentally investigate the wear and friction performance of a possible future generation of an environmentally friendly bio-based lubricant as a potential replacement for conventional engine lubricants. In order to quantify the tribological benefits which can be gained by the deposition of DLC coatings, (an (a-C:H) hydrogenated DLC coating and an (a-C:H:W) tungsten-doped DLC coating) were applied on the cam/tappet interface of a direct acting valve train assembly of an internal combustion engine. The tribological correlation between DLC-coated engine components, lubricant base oils and lubricant additives have been thoroughly investigated in this study using actual engine operating conditions. Two additive-free base oils (polyalphaolefines (PAO) and chemically-modified palm oil (TMP)) and two multi-additive-containing lubricants were used in this investigation. Real-time drive torque was measured to determine the friction force, detailed post-test analysis was performed, which involved the use of a specialized jig to measure camlobe wear. An optical profilometer was used to measure the wear on the tappet, high-resolution scanning electron microscopy was employed to study the wear mechanism and energy-dispersive X-ray spectroscopy was performed on the tested samples to qualitatively access the degradation of the coating. When using additive-free TMP, a low friction coefficient was observed for the cam/tappet interface. The presence of additives further improved the friction characteristics of TMP, resulting in reduced average friction torque values. A tremendous enhancement in wear performance was recorded with a-C:H-coated parts and the coating was able to withstand the test conditions with little or no delamination

    Exploring perceptions of advertising ethics: an informant-derived approach

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    Whilst considerable research exists on determining consumer responses to pre-determined statements within numerous ad ethics contexts, our understanding of consumer thoughts regarding ad ethics in general remains lacking. The purpose of our study therefore is to provide a first illustration of an emic and informant-based derivation of perceived ad ethics. The authors use multi-dimensional scaling as an approach enabling the emic, or locally derived deconstruction of perceived ad ethics. Given recent calls to develop our understanding of ad ethics in different cultural contexts, and in particular within the Middle East and North Africa (MENA) region, we use Lebanon—the most ethically charged advertising environment within MENA—as an illustrative context for our study. Results confirm the multi-faceted and pluralistic nature of ad ethics as comprising a number of dimensional themes already salient in the existing literature but in addition, we also find evidence for a bipolar relationship between individual themes. The specific pattern of inductively derived relationships is culturally bound. Implications of the findings are discussed, followed by limitations of the study and recommendations for further research

    A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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    Increased peri-ductal collagen micro-organization may contribute to raised mammographic density

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    BACKGROUND: High mammographic density is a therapeutically modifiable risk factor for breast cancer. Although mammographic density is correlated with the relative abundance of collagen-rich fibroglandular tissue, the causative mechanisms, associated structural remodelling and mechanical consequences remain poorly defined. In this study we have developed a new collaborative bedside-to-bench workflow to determine the relationship between mammographic density, collagen abundance and alignment, tissue stiffness and the expression of extracellular matrix organising proteins. METHODS: Mammographic density was assessed in 22 post-menopausal women (aged 54–66 y). A radiologist and a pathologist identified and excised regions of elevated non-cancerous X-ray density prior to laboratory characterization. Collagen abundance was determined by both Masson’s trichrome and Picrosirius red staining (which enhances collagen birefringence when viewed under polarised light). The structural specificity of these collagen visualisation methods was determined by comparing the relative birefringence and ultrastructure (visualised by atomic force microscopy) of unaligned collagen I fibrils in reconstituted gels with the highly aligned collagen fibrils in rat tail tendon. Localised collagen fibril organisation and stiffness was also evaluated in tissue sections by atomic force microscopy/spectroscopy and the abundance of key extracellular proteins was assessed using mass spectrometry. RESULTS: Mammographic density was positively correlated with the abundance of aligned periductal fibrils rather than with the abundance of amorphous collagen. Compared with matched tissue resected from the breasts of low mammographic density patients, the highly birefringent tissue in mammographically dense breasts was both significantly stiffer and characterised by large (>80 μm long) fibrillar collagen bundles. Subsequent proteomic analyses not only confirmed the absence of collagen fibrosis in high mammographic density tissue, but additionally identified the up-regulation of periostin and collagen XVI (regulators of collagen fibril structure and architecture) as potential mediators of localised mechanical stiffness. CONCLUSIONS: These preliminary data suggest that remodelling, and hence stiffening, of the existing stromal collagen microarchitecture promotes high mammographic density within the breast. In turn, this aberrant mechanical environment may trigger neoplasia-associated mechanotransduction pathways within the epithelial cell population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-015-0664-2) contains supplementary material, which is available to authorized users

    Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

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    Human matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn(2+) atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes

    Test System Stability and Natural Variability of a Lemna Gibba L. Bioassay

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    BACKGROUND: In ecotoxicological and environmental studies Lemna spp. are used as test organisms due to their small size, rapid predominantly vegetative reproduction, easy handling and high sensitivity to various chemicals. However, there is not much information available concerning spatial and temporal stability of experimental set-ups used for Lemna bioassays, though this is essential for interpretation and reliability of results. We therefore investigated stability and natural variability of a Lemna gibba bioassay assessing area-related and frond number-related growth rates under controlled laboratory conditions over about one year. METHODOLOGY/PRINCIPAL FINDINGS: Lemna gibba L. was grown in beakers with Steinberg medium for one week. Area-related and frond number-related growth rates (r(area) and r(num)) were determined with a non-destructive image processing system. To assess inter-experimental stability, 35 independent experiments were performed with 10 beakers each in the course of one year. We observed changes in growth rates by a factor of two over time. These did not correlate well with temperature or relative humidity in the growth chamber. In order to assess intra-experimental stability, we analysed six systematic negative control experiments (nontoxicant tests) with 96 replicate beakers each. Evaluation showed that the chosen experimental set-up was stable and did not produce false positive results. The coefficient of variation was lower for r(area) (2.99%) than for r(num) (4.27%). CONCLUSIONS/SIGNIFICANCE: It is hypothesised that the variations in growth rates over time under controlled conditions are partly due to endogenic periodicities in Lemna gibba. The relevance of these variations for toxicity investigations should be investigated more closely. Area-related growth rate seems to be more precise as non-destructive calculation parameter than number-related growth rate. Furthermore, we propose two new validity criteria for Lemna gibba bioassays: variability of average specific and section-by-section segmented growth rate, complementary to average specific growth rate as the only validity criterion existing in guidelines for duckweed bioassays
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