182 research outputs found

    Structure and expression of the maize (Zea mays L.) SUN-domain protein gene family: evidence for the existence of two divergent classes of SUN proteins in plants

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    <p>Abstract</p> <p>Background</p> <p>The nuclear envelope that separates the contents of the nucleus from the cytoplasm provides a surface for chromatin attachment and organization of the cortical nucleoplasm. Proteins associated with it have been well characterized in many eukaryotes but not in plants. SUN (Sad1p/Unc-84) domain proteins reside in the inner nuclear membrane and function with other proteins to form a physical link between the nucleoskeleton and the cytoskeleton. These bridges transfer forces across the nuclear envelope and are increasingly recognized to play roles in nuclear positioning, nuclear migration, cell cycle-dependent breakdown and reformation of the nuclear envelope, telomere-led nuclear reorganization during meiosis, and karyogamy.</p> <p>Results</p> <p>We found and characterized a family of maize SUN-domain proteins, starting with a screen of maize genomic sequence data. We characterized five different maize <it>ZmSUN </it>genes <it>(ZmSUN1-5)</it>, which fell into two classes (probably of ancient origin, as they are also found in other monocots, eudicots, and even mosses). The first (<it>ZmSUN1</it>, <it>2</it>), here designated canonical C-terminal SUN-domain (CCSD), includes structural homologs of the animal and fungal SUN-domain protein genes. The second (<it>ZmSUN3, 4, 5</it>), here designated plant-prevalent mid-SUN 3 transmembrane (PM3), includes a novel but conserved structural variant SUN-domain protein gene class. Mircroarray-based expression analyses revealed an intriguing pollen-preferred expression for <it>ZmSUN5 </it>mRNA but low-level expression (50-200 parts per ten million) in multiple tissues for all the others. Cloning and characterization of a full-length cDNA for a PM3-type maize gene, <it>ZmSUN4</it>, is described. Peptide antibodies to ZmSUN3, 4 were used in western-blot and cell-staining assays to show that they are expressed and show concentrated staining at the nuclear periphery.</p> <p>Conclusions</p> <p>The maize genome encodes and expresses at least five different SUN-domain proteins, of which the PM3 subfamily may represent a novel class of proteins with possible new and intriguing roles within the plant nuclear envelope. Expression levels for <it>ZmSUN</it>1-4 are consistent with basic cellular functions, whereas <it>ZmSUN</it>5 expression levels indicate a role in pollen. Models for possible topological arrangements of the CCSD-type and PM3-type SUN-domain proteins are presented.</p

    Aerospike Rockets for Increased Space Launch Capability

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    The US Department of Defense DOD increasingly depends on space assets for everyday operations. Precision navigation communications and intelligence, surveillance, and reconnaissance satellites are highly leveraged space assets. The launch vehicles that place these satellites in orbit are a major limitation of current space systems. If higher-performing launch vehicles were available, many satellites could accommodate additional capabilities, whether in terms of more sensor channels, types of payloads, electrical power, or propellant for orbital maneuvering and station keeping. Space assets are typically designed to conform to a particular launch vehicle s limitations e.g., engineers might design a satellite to be carried by a Delta IV-2 medium launch vehicle. Essentially, this choice of vehicle fixes the maximum mass of the satellite and, thus, its capabilities. If a launcher capable of placing more mass in the desired orbit were available at similar cost, the satellite s design could allow for additional capability. Furthermore, some payloads are too heavy for present-day launch vehicles to place into a particular orbit. A better-performing launcher would enable us to put those payloads into the desired orbits, permitting new missions and capabilities

    A review of metrology in lithium-ion electrode coating processes

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    Lithium-ion battery electrode design and manufacture is a multi-faceted process where the link between underlying physical processes and manufacturing outputs is not yet fully understood. This is in part due to the many parameters and variables involved and the lack of complete data sets under different processing conditions. The slurry coating step has significant implications for electrode design and advanced metrology offers opportunities to improve understanding and control at this stage. Here, metrology options for slurry coating are reviewed as well as opportunities for in-line integration, discussing the benefits of combining advanced metrology to provide comprehensive characterisation, improve understanding and feed into predictive design models. There is a comprehensive range of metrology which needs little improvement to provide the relevant quantifiable measures during coating, with one exception of particle sizing, where more precise, in-line measurement would be beneficial. However, there is a lack of studies that bring together the latest advancements in electrode coating metrology which is crucial to understanding the interdependency of myriad processing and product parameters. This review highlights the need for a comprehensive metrological picture whose value would be much greater than the sum of its parts for the next generation of multiphysics and data-driven models

    Outcomes of a research project to identify the enablers and barriers to effective preceptorship for newly qualified nurses

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    Poster presentationFunded by Chesterfield Royal Hospital NHS Trus

    Three new species

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    14 p. : ill. ; 24 cm.Includes bibliographical references (p. 14)

    Prospective exploratory muscle biopsy, imaging, and functional assessment in patients with late-onset Pompe disease treated with alglucosidase alfa: The EMBASSY Study

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    Background Late-onset Pompe disease is characterized by progressive skeletal myopathy followed by respiratory muscle weakness, typically leading to loss of ambulation and respiratory failure. In this population, enzyme replacement therapy (ERT) with alglucosidase alfa has been shown to stabilize respiratory function and improve mobility and muscle strength. Muscle pathology and glycogen clearance from skeletal muscle in treatment-naïve adults after ERT have not been extensively examined. Methods This exploratory, open-label, multicenter study evaluated glycogen clearance in muscle tissue samples collected pre- and post- alglucosidase alfa treatment in treatment-naïve adults with late-onset Pompe disease. The primary endpoint was the quantitative reduction in percent tissue area occupied by glycogen in muscle biopsies from baseline to 6 months. Secondary endpoints included qualitative histologic assessment of tissue glycogen distribution, secondary pathology changes, assessment of magnetic resonance images (MRIs) for intact muscle and fatty replacement, and functional assessments. Results Sixteen patients completed the study. After 6 months of ERT, the percent tissue area occupied by glycogen in quadriceps and deltoid muscles decreased in 10 and 8 patients, respectively. No changes were detected on MRI from baseline to 6 months. A majority of patients showed improvements on functional assessments after 6 months of treatment. All treatment-related adverse events were mild or moderate. Conclusions This exploratory study provides novel insights into the histopathologic effects of ERT in late-onset Pompe disease patients. Ultrastructural examination of muscle biopsies demonstrated reduced lysosomal glycogen after ERT. Findings are consistent with stabilization of disease by ERT in treatment-naïve patients with late-onset Pompe disease

    The state of the Martian climate

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    60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

    Roadmap on Li-ion battery manufacturing research

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    Growth in the Li-ion battery market continues to accelerate, driven primarily by the increasing need for economic energy storage for electric vehicles. Electrode manufacture by slurry casting is the first main step in cell production but much of the manufacturing optimisation is based on trial and error, know-how and individual expertise. Advancing manufacturing science that underpins Li-ion battery electrode production is critical to adding to the electrode manufacturing value chain. Overcoming the current barriers in electrode manufacturing requires advances in materials, manufacturing technology, in-line process metrology and data analytics, and can enable improvements in cell performance, quality, safety and process sustainability. In this roadmap we explore the research opportunities to improve each stage of the electrode manufacturing process, from materials synthesis through to electrode calendering. We highlight the role of new process technology, such as dry processing, and advanced electrode design supported through electrode level, physics-based modelling. Progress in data driven models of electrode manufacturing processes is also considered. We conclude there is a growing need for innovations in process metrology to aid fundamental understanding and to enable feedback control, an opportunity for electrode design to reduce trial and error, and an urgent imperative to improve the sustainability of manufacture

    "I did not intend to stop. I just could not stand cigarettes any more." A qualitative interview study of smoking cessation among the elderly

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    <p>Abstract</p> <p>Background</p> <p>Every year, more than 650,000 Europeans die because they smoke. Smoking is considered to be the single most preventable factor influencing health. General practitioners (GP) are encouraged to advise on smoking cessation at all suitable consultations. Unsolicited advice from GPs results in one of 40-60 smokers stopping smoking. Smoking cessation advice has traditionally been given on an individual basis. Our aim was to gain insights that may help general practitioners understand why people smoke, and why smokers stop and then remain quitting and, from this, to find fruitful approaches to the dialogue about stopping smoking.</p> <p>Methods</p> <p>Interviews with 18 elderly smokers and ex-smokers about their smoking and decisions to smoke or quit were analysed with qualitative content analysis across narratives. A narrative perspective was applied.</p> <p>Results</p> <p>Six stages in the smoking story emerged, from the start of smoking, where friends had a huge influence, until maintenance of the possible cessation. The informants were influenced by "all the others" at all stages. Spouses had vital influence in stopping, relapses and continued smoking. The majority of quitters had stopped by themselves without medication, and had kept the tobacco handy for 3-6 months. Often smoking cessation seemed to happen unplanned, though sometimes it was planned. With an increasingly negative social attitude towards smoking, the informants became more aware of the risks of smoking.</p> <p>Conclusion</p> <p>"All the others" is a clue in the smoking story. For smoking cessation, it is essential to be aware of the influence of friends and family members, especially a spouse. People may stop smoking unplanned, even when motivation is not obvious. Information from the community and from doctors on the negative aspects of smoking should continue. Eliciting life-long smoking narratives may open up for a fruitful dialogue, as well as prompting reflection about smoking and adding to the motivation to stop.</p

    NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease.

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    Genetic defects that affect intestinal epithelial barrier function can present with very early-onset inflammatory bowel disease (VEOIBD). Using whole-genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 pediatric patients identified further seven male inflammatory bowel disease (IBD) patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p.Y470H, p.R287Q, p.I67M, p.Q293R as well as the previously described p.P330S, and the common NOX1 SNP p.D360N (rs34688635) variant. The missense mutation p.N122H abrogated reactive oxygen species (ROS) production in cell lines, ex vivo colonic explants, and patient-derived colonic organoid cultures. Within colonic crypts, NOX1 constitutively generates a high level of ROS in the crypt lumen. Analysis of 9,513 controls and 11,140 IBD patients of non-Jewish European ancestry did not reveal an association between p.D360N and IBD. Our data suggest that loss-of-function variants in NOX1 do not cause a Mendelian disorder of high penetrance but are a context-specific modifier. Our results implicate that variants in NOX1 change brush border ROS within colonic crypts at the interface between the epithelium and luminal microbes
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