434 research outputs found

    The Failure of Anthropometry as a Nutritional Assessment Tool

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    Anthropometric measurements are commonly used to assess body composition changes and adequacy of nutritional support in the hospitalized patient. To test their utility as nutritional assessment tools in the intensive care unit (ICU) patient, body weight, triceps skinfold (TSF), mid-arm muscle circumference (MAMC). and fluid balance and intake were collected on 21 critically ill patients during their ICU stay. Correlations were sought between adequacy of nutritional support and changes over time in weight. MAMC, fluid balance, and TSF. A significant change over time in mean body weight (p \u3c 0.0001) was seen, reflecting a mean weight loss despite a positive cumulative fluid balance of almost 20 L by day 14 for all patients (p \u3c 0.0001). There was a significant change over time in the mean fractional intake of required calories ranging from 41.7% on observation day 1 to a peak of 84.0% on day 22 (p \u3c 0.001). TSF and MAMC could not be obtained on a large percentage of ICU patients due to severe edema including the mid-upper arm. Obtained measurements showed no change over the study period in TSF (p = 0.24) and MAMC (p = 0.71) despite significant changes in weight (p \u3c 0.0001). caloric intake (p = 0.0001). and cumulative fluid balance (p = 0.0001). From these data it appears that anthropometric indices of TSF and MAMC are unrelated to nutritional intake and weight in ICU patients and are therefore not of use in the nutritional assessment of this population

    Modifying the product distribution of a reaction within the controlled microenvironment of a colloidosome

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    A water-soluble colloidosome composed of PGMA–PS latex was used as a microcapsule to host a catalyzed oxidation reaction within its dodecane core. When compared to a control reaction a significant colloidosome effect was observed. Specifically, a 233% increase in the relative yield of all products was observed for the colloidosome reaction. Furthermore, when the product distributions were calculated it was evident that a switch in selectivity had taken place. These studies showed there is a significant reduction in the relative yield of the epoxide product compared to the remaining oxidation products. Additional control experiments confirmed that rate enhancements were not simply a result of concentration and that reactions were not occurring in the outer latex phase. As a consequence of these control experiments, we suggest that the colloidosome enhancement and shift in product distribution, comes about from differences in electronic environment at or close to the interface between the internal oil phase and the outer colloidal particles. This environment is able to stabilize any specific intermediates and or transition states leading to enhanced reactions for these products and higher relative yields

    Pentobarbital and picrotoxin have reciprocal actions on single GABAA receptor channels

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    Pentobarbital (PB) and picrotoxin (PIC) bind to allosterically coupled sites on the GABAA receptor complex but have opposite effects on GABA receptor currents. PB, an anesthetic/anticonvulsant, enhances, and PIC, a convulsant, inhibits GABA receptor currents. PB and PIC also had opposite effects on single main conductance channel GABA receptor currents recorded from excised outside-out patches from mouse spinal neurons in culture. PB prolonged bursts of channel openings by increasing mean duration and number of intraburst openings. PIC shortened bursts by reducing mean duration and number of intraburst openings. The results demonstrate the reciprocal regulation of GABA receptor channels by PB and PIC and suggest that their allosterically coupled binding sites are coupled to the chloride channel in an opposite manner.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28094/1/0000541.pd

    A mechanism for morphogen-controlled domain growth

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    Many developmental systems are organised via the action of graded distributions of morphogens. In the Drosophila wing disc, for example, recent experimental evidence has shown that graded expression of the morphogen Dpp controls cell proliferation and hence disc growth. Our goal is to explore a simple model for regulation of wing growth via the Dpp gradient: we use a system of reaction-diffusion equations to model the dynamics of Dpp and its receptor Tkv, with advection arising as a result of the flow generated by cell proliferation. We analyse the model both numerically and analytically, showing that uniform domain growth across the disc produces an exponentially growing wing disc

    Preparation, structural characterisation and antibacterial properties of Ga-doped sol-gel phosphate-based glass

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    A sol-gel preparation of Ga-doped phosphate-based glass with potential application in antimicrobial devices has been developed. Samples of composition (CaO)(0.30)(Na2O)(0.20-x) (Ga2O3) (x) (P2O5)(0.50) where x = 0 and 0.03 were prepared, and the structure and properties of the gallium-doped sample compared with those of the sample containing no gallium. Analysis of the P-31 MAS NMR data demonstrated that addition of gallium to the sol-gel reaction increases the connectivity of the phosphate network at the expense of hydroxyl groups. This premise is supported by the results of the elemental analysis, which showed that the gallium-free sample contains significantly more hydrogen and by FTIR spectroscopy, which revealed a higher concentration of -OH groups in that sample. Ga K-edge extended X-ray absorption fine structure and X-ray absorption near-edge structure data revealed that the gallium ions are coordinated by six oxygen atoms. In agreement with the X-ray absorption data, the high-energy XRD results also suggest that the Ga3+ ions are octahedrally coordinated with respect to oxygen. Antimicrobial studies demonstrated that the sample containing Ga3+ ions had significant activity against Staphylococcus aureus compared to the control

    Hyperpolarised 13C MRI: a new horizon for non-invasive diagnosis of aggressive breast cancer

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    Hyperpolarised 13C MRI (HP-MRI) is a novel imaging technique that allows real-time analysis of metabolic pathways in vivo. 1 The technology to conduct HP-MRI in humans has recently become available and is starting to be clinically applied. As knowledge of molecular biology advances, it is increasingly apparent that cancer cell metabolism is related to disease outcomes, with lactate attracting specific attention. 2 Recent reviews of breast cancer screening programs have raised concerns and increased public awareness of over treatment. The scientific community needs to shift focus from improving cancer detection alone to pursuing novel methods of distinguishing aggressive breast cancers from those which will remain indolent. HP-MRI offers the opportunity to identify aggressive tumour phenotypes and help monitor/predict therapeutic response. Here we report one of the first cases of breast cancer imaged using HP-MRI alongside correlative conventional imaging, including breast MRI

    Spontaneous Reorientation Is Guided by Perceived Surface Distance, Not by Image Matching Or Comparison

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    Humans and animals recover their sense of position and orientation using properties of the surface layout, but the processes underlying this ability are disputed. Although behavioral and neurophysiological experiments on animals long have suggested that reorientation depends on representations of surface distance, recent experiments on young children join experimental studies and computational models of animal navigation to suggest that reorientation depends either on processing of any continuous perceptual variables or on matching of 2D, depthless images of the landscape. We tested the surface distance hypothesis against these alternatives through studies of children, using environments whose 3D shape and 2D image properties were arranged to enhance or cancel impressions of depth. In the absence of training, children reoriented by subtle differences in perceived surface distance under conditions that challenge current models of 2D-image matching or comparison processes. We provide evidence that children’s spontaneous navigation depends on representations of 3D layout geometry.National Institutes of Health (U.S.) (Grant HD 23103

    Nicotiana benthamiana as a Production Platform for Artemisinin Precursors

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    Background Production of pharmaceuticals in plants provides an alternative for chemical synthesis, fermentation or natural sources. Nicotiana benthamiana is deployed at commercial scale for production of therapeutic proteins. Here the potential of this plant is explored for rapid production of precursors of artemisinin, a sesquiterpenoid compound that is used for malaria treatment. Methodology/Principal Findings Biosynthetic genes leading to artemisinic acid, a precursor of artemisinin, were combined and expressed in N. benthamiana by agro-infiltration. The first committed precursor of artemisinin, amorpha-4,11-diene, was produced upon infiltration of a construct containing amorpha-4,11-diene synthase, accompanied by 3-hydroxy-3-methylglutaryl-CoA reductase and farnesyl diphosphate synthase. Amorpha-4,11-diene was detected both in extracts and in the headspace of the N. benthamiana leaves. When the amorphadiene oxidase CYP71AV1 was co-infiltrated with the amorphadiene-synthesizing construct, the amorpha-4,11-diene levels strongly decreased, suggesting it was oxidized. Surprisingly, no anticipated oxidation products, such as artemisinic acid, were detected upon GC-MS analysis. However, analysis of leaf extracts with a non-targeted metabolomics approach, using LC-QTOF-MS, revealed the presence of another compound, which was identified as artemisinic acid-12-ß-diglucoside. This compound accumulated to 39.5 mg.kg-1 fwt. Apparently the product of the heterologous pathway that was introduced, artemisinic acid, is further metabolized efficiently by glycosyl transferases that are endogenous to N. benthamiana. Conclusion/Significance This work shows that agroinfiltration of N. bentamiana can be used as a model to study the production of sesquiterpenoid pharmaceutical compounds. The interaction between the ectopically introduced pathway and the endogenous metabolism of the plant is discussed

    Ubiquitin fusion expression and tissue-dependent targeting of hG-CSF in transgenic tobacco

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    <p>Abstract</p> <p>Background</p> <p>Human granulocyte colony-stimulating factor (hG-CSF) is an important human cytokine which has been widely used in oncology and infection protection. To satisfy clinical needs, expression of recombinant hG-CSF has been studied in several organisms, including rice cell suspension culture and transient expression in tobacco leaves, but there was no published report on its expression in stably transformed plants which can serve as a more economical expression platform with potential industrial application.</p> <p>Results</p> <p>In this study, hG-CSF expression was investigated in transgenic tobacco leaves and seeds in which the accumulation of hG-CSF could be enhanced through fusion with ubiquitin by up to 7 fold in leaves and 2 fold in seeds, leading to an accumulation level of 2.5 mg/g total soluble protein (TSP) in leaves and 1.3 mg/g TSP in seeds, relative to hG-CSF expressed without a fusion partner. Immunoblot analysis showed that ubiquitin was processed from the final protein product, and ubiquitination was up-regulated in all transgenic plants analyzed. Driven by <it>CaMV </it>35S promoter and phaseolin signal peptide, hG-CSF was observed to be secreted into apoplast in leaves but deposited in protein storage vacuole (PSV) in seeds, indicating that targeting of the hG-CSF was tissue-dependent in transgenic tobacco. Bioactivity assay showed that hG-CSF expressed in both seeds and leaves was bioactive to support the proliferation of NFS-60 cells.</p> <p>Conclusions</p> <p>In this study, the expression of bioactive hG-CSF in transgenic plants was improved through ubiquitin fusion strategy, demonstrating that protein expression can be enhanced in both plant leaves and seeds through fusion with ubiquitin and providing a typical case of tissue-dependent expression of recombinant protein in transgenic plants.</p

    Transcriptional Upregulation of NLRC5 by Radiation Drives STING- and Interferon-Independent MHC-I Expression on Cancer Cells and T Cell Cytotoxicity.

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    Radiation therapy has been shown to enhance the efficacy of various T cell-targeted immunotherapies that improve antigen-specific T cell expansion, T regulatory cell depletion, or effector T cell function. Additionally, radiation therapy has been proposed as a means to recruit T cells to the treatment site and modulate cancer cells as effector T cell targets. The significance of these features remains unclear. We set out to determine, in checkpoint inhibitor resistant models, which components of radiation are primarily responsible for overcoming this resistance. In order to model the vaccination effect of radiation, we used a Listeria monocytogenes based vaccine to generate a large population of tumor antigen specific T cells but found that the presence of cells with cytotoxic capacity was unable to replicate the efficacy of radiation with combination checkpoint blockade. Instead, we demonstrated that a major role of radiation was to increase the susceptibility of surviving cancer cells to CD8+ T cell-mediated control through enhanced MHC-I expression. We observed a novel mechanism of genetic induction of MHC-I in cancer cells through upregulation of the MHC-I transactivator NLRC5. These data support the critical role of local modulation of tumors by radiation to improve tumor control with combination immunotherapy
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