4,895 research outputs found

    The Drosophila Anion Exchanger (DAE) lacks a detectable interaction with the spectrin cytoskeleton

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    <p>Abstract</p> <p>Background</p> <p>Current models suggest that the spectrin cytoskeleton stabilizes interacting ion transport proteins at the plasma membrane. The human erythrocyte anion exchanger (AE1) was the first membrane transport protein found to be associated with the spectrin cytoskeleton. Here we evaluated a conserved anion exchanger from Drosophila (DAE) as a marker for studies of the downstream effects of spectrin cytoskeleton mutations.</p> <p>Results</p> <p>Sequence comparisons established that DAE belongs to the SLC4A1-3 subfamily of anion exchangers that includes human AE1. Striking sequence conservation was observed in the C-terminal membrane transport domain and parts of the N-terminal cytoplasmic domain, but not in the proposed ankyrin-binding site. Using an antibody raised against DAE and a recombinant transgene expressed in <it>Drosophila </it>S2 cells DAE was shown to be a 136 kd plasma membrane protein. A major site of expression was found in the stomach acid-secreting region of the larval midgut. DAE codistributed with an infolded subcompartment of the basal plasma membrane of interstitial cells. However, spectrin did not codistribute with DAE at this site or in anterior midgut cells that abundantly expressed both spectrin and DAE. Ubiquitous knockdown of DAE with dsRNA eliminated antibody staining and was lethal, indicating that DAE is an essential gene product in <it>Drosophila</it>.</p> <p>Conclusions</p> <p>Based on the lack of colocalization and the lack of sequence conservation at the ankyrin-binding site, it appears that the well-characterized interaction between AE1 and the spectrin cytoskeleton in erythrocytes is not conserved in <it>Drosophila</it>. The results establish a pattern in which most of the known interactions between the spectrin cytoskeleton and the plasma membrane in mammals do not appear to be conserved in <it>Drosophila</it>.</p

    Cooperative coupling of ultracold atoms and surface plasmons

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    Cooperative coupling between optical emitters and light fields is one of the outstanding goals in quantum technology. It is both fundamentally interesting for the extraordinary radiation properties of the participating emitters and has many potential applications in photonics. While this goal has been achieved using high-finesse optical cavities, cavity-free approaches that are broadband and easy to build have attracted much attention recently. Here we demonstrate cooperative coupling of ultracold atoms with surface plasmons propagating on a plane gold surface. While the atoms are moving towards the surface they are excited by an external laser pulse. Excited surface plasmons are detected via leakage radiation into the substrate of the gold layer. A maximum Purcell factor of ηP=4.9\eta_\mathrm{P}=4.9 is reached at an optimum distance of z=250 nmz=250~\mathrm{nm} from the surface. The coupling leads to the observation of a Fano-like resonance in the spectrum.Comment: 9 pages, 4 figure

    Non-Redundant Spectral Dimensionality Reduction

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    Spectral dimensionality reduction algorithms are widely used in numerous domains, including for recognition, segmentation, tracking and visualization. However, despite their popularity, these algorithms suffer from a major limitation known as the "repeated Eigen-directions" phenomenon. That is, many of the embedding coordinates they produce typically capture the same direction along the data manifold. This leads to redundant and inefficient representations that do not reveal the true intrinsic dimensionality of the data. In this paper, we propose a general method for avoiding redundancy in spectral algorithms. Our approach relies on replacing the orthogonality constraints underlying those methods by unpredictability constraints. Specifically, we require that each embedding coordinate be unpredictable (in the statistical sense) from all previous ones. We prove that these constraints necessarily prevent redundancy, and provide a simple technique to incorporate them into existing methods. As we illustrate on challenging high-dimensional scenarios, our approach produces significantly more informative and compact representations, which improve visualization and classification tasks

    "Detachment of the carinal hook following endobronchial intubation with a double lumen tube"

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    <p>Abstract</p> <p>Background</p> <p>Carinal hooks increases difficulty at endotracheal intubation. Amputation of the carinal hook during passage and malpositioning of the tube to the hook are some of the potential problems related with left-sided Carlens double lumen tube (DLT). This article reports an amputation of the hook during a difficult selective intubation and aimed at calling the attention to complications associated with DLTs and the importance of fiberoptic bronchoscopy.</p> <p>Case presentation</p> <p>A 68 year-old woman was scheduled for right-sided thoracotomy in whom blind DLT insertion was performed. Narrowed trachea causes difficulty in rotating the DLT 90° counter-clockwise. After carinal hook was noticed upon visual inspection of the DLT, fiberoptic bronchoscopy was used to remove the missing part (with the use of forceps) from the right mainstem bronchus.</p> <p>Conclusion</p> <p>Insertion of DLTs with carinal hook is associated with technical problems and potentially life-threatening hazards have discouraged their use. Fiberoptic evaluation and repositioning solves most of the problems. Although amputation of the carinal hook has not been previously reported, clinicians should be alert. This case report emphasizes the utility of the fiberoptic bronchoscopy in the operating theatre for placement, positioning and inspection of the carinal hook DLT.</p

    Router-level community structure of the Internet Autonomous Systems

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    The Internet is composed of routing devices connected between them and organized into independent administrative entities: the Autonomous Systems. The existence of different types of Autonomous Systems (like large connectivity providers, Internet Service Providers or universities) together with geographical and economical constraints, turns the Internet into a complex modular and hierarchical network. This organization is reflected in many properties of the Internet topology, like its high degree of clustering and its robustness. In this work, we study the modular structure of the Internet router-level graph in order to assess to what extent the Autonomous Systems satisfy some of the known notions of community structure. We show that the modular structure of the Internet is much richer than what can be captured by the current community detection methods, which are severely affected by resolution limits and by the heterogeneity of the Autonomous Systems. Here we overcome this issue by using a multiresolution detection algorithm combined with a small sample of nodes. We also discuss recent work on community structure in the light of our results

    30 inch Roll-Based Production of High-Quality Graphene Films for Flexible Transparent Electrodes

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    We report that 30-inch scale multiple roll-to-roll transfer and wet chemical doping considerably enhance the electrical properties of the graphene films grown on roll-type Cu substrates by chemical vapor deposition. The resulting graphene films shows a sheet resistance as low as ~30 Ohm/sq at ~90 % transparency which is superior to commercial transparent electrodes such as indium tin oxides (ITO). The monolayer of graphene shows sheet resistances as low as ~125 Ohm/sq with 97.4% optical transmittance and half-integer quantum Hall effect, indicating the high-quality of these graphene films. As a practical application, we also fabricated a touch screen panel device based on the graphene transparent electrodes, showing extraordinary mechanical and electrical performances

    Cysteine oxidation targets peroxiredoxins 1 and 2 for exosomal release through a novel mechanism of redox-dependent secretion

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    Non-classical protein secretion is of major importance as a number of cytokines and inflammatory mediators are secreted via this route. Current evidence indicates that there are several mechanistically distinct methods of non-classical secretion. We have recently shown that peroxiredoxin (Prdx) 1 and Prdx2 are released by various cells upon exposure to inflammatory stimuli such as LPS or TNF-α. The released Prdx then acts to induce production of inflammatory cytokines. However, Prdx1 and 2 do not have signal peptides and therefore must be secreted by alternative mechanisms as has been postulated for the inflammatory mediators IL-1β and HMGB1. We show here that circulating Prdx1 and 2 are present exclusively as disulphide-linked homodimers. Inflammatory stimuli also induce in vitro release of Prdx1 and 2 as disulfide-linked homodimers. Mutation of cysteines Cys51 or Cys172 (but not Cys70) in Prdx2, and Cys52 or Cys173 (but not Cys71 or Cys83) in Prdx1 prevented dimer formation and this was associated with inhibition of their TNF-α-induced release. Thus, the presence and oxidation of key cysteine residues in these proteins are a prerequisite for their secretion in response to TNF-α and this release can be induced with an oxidant. In contrast, the secretion of the nuclear-associated danger signal HMGB1 is independent of cysteine oxidation, as shown by experiments with a cysteine-free HMGB1 mutant. Release of Prdx1 and 2 is not prevented by inhibitors of the classical secretory pathway; instead, both Prdx1 and 2 are released in exosomes from both HEK cells and monocytic cells. Serum Prdx1 and 2 are also associated with the exosomes. These results describe a novel pathway of protein secretion mediated by cysteine oxidation that underlines the importance of redox-dependent signalling mechanisms in inflammation

    Haemoglobin mass and running time trial performance after recombinant human erythropoietin administration in trained men

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    &lt;p&gt;Recombinant human erythropoietin (rHuEpo) increases haemoglobin mass (Hbmass) and maximal oxygen uptake (v˙ O2 max).&lt;/p&gt; &lt;p&gt;Purpose: This study defined the time course of changes in Hbmass, v˙ O2 max as well as running time trial performance following 4 weeks of rHuEpo administration to determine whether the laboratory observations would translate into actual improvements in running performance in the field.&lt;/p&gt; &lt;p&gt;Methods: 19 trained men received rHuEpo injections of 50 IUNkg21 body mass every two days for 4 weeks. Hbmass was determined weekly using the optimized carbon monoxide rebreathing method until 4 weeks after administration. v˙ O2 max and 3,000 m time trial performance were measured pre, post administration and at the end of the study.&lt;/p&gt; &lt;p&gt;Results: Relative to baseline, running performance significantly improved by ,6% after administration (10:3061:07 min:sec vs. 11:0861:15 min:sec, p,0.001) and remained significantly enhanced by ,3% 4 weeks after administration (10:4661:13 min:sec, p,0.001), while v˙ O2 max was also significantly increased post administration (60.765.8 mLNmin21Nkg21 vs. 56.066.2 mLNmin21Nkg21, p,0.001) and remained significantly increased 4 weeks after rHuEpo (58.065.6 mLNmin21Nkg21, p = 0.021). Hbmass was significantly increased at the end of administration compared to baseline (15.261.5 gNkg21 vs. 12.761.2 gNkg21, p,0.001). The rate of decrease in Hbmass toward baseline values post rHuEpo was similar to that of the increase during administration (20.53 gNkg21Nwk21, 95% confidence interval (CI) (20.68, 20.38) vs. 0.54 gNkg21Nwk21, CI (0.46, 0.63)) but Hbmass was still significantly elevated 4 weeks after administration compared to baseline (13.761.1 gNkg21, p&#60;0.001).&lt;/p&gt; &lt;p&gt;Conclusion: Running performance was improved following 4 weeks of rHuEpo and remained elevated 4 weeks after administration compared to baseline. These field performance effects coincided with rHuEpo-induced elevated v˙ O2 max and Hbmass.&lt;/p&gt

    Risk factors for recurrent injurious falls that require hospitalization for older adults with dementia: a population based study

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    Background: Older adults with dementia are at an increased risk of falls, however, little is known about risk factors for recurrent injurious falls (a subsequent fall after the first fall has occurred) among this group. This study aimed to identify risk factors for recurrent injurious falls requiring hospitalization among adults aged 60+ years with dementia. Methods: This retrospective, whole-population cohort study was conducted using the Western Australian Hospital Morbidity Data System and Western Australian Death Registrations from 2001 to 2013. Survival analysis using a stratified conditional Cox model (type 1) was undertaken to identify risk factors for recurrent injurious falls requiring hospitalization. Results: There were 32,519 participants with an index hospital admission with dementia during the study period. Over 27 % (n = 8970) of the cohort experienced a total of 11,073 injurious falls requiring hospitalization during follow up with 7297 individuals experiencing a single fall, 1330 experiencing two falls and 343 experiencing three or more falls. The median follow-up time for each individual was 2.49 years. Females were at a significantly increased risk of 7 % for recurrent injurious falls resulting in hospitalization (adjusted hazard ratio 1.07, 95 % CI 1.01–1.12), compared to males. Increasing age, living in rural areas, and having an injurious fall in the year prior to the index hospital admission with dementia also increased the risk of recurrent injurious falls resulting in hospitalization. Conclusions: Screening those with dementia for injurious falls history could help to identify those most at risk of recurrent injurious falls. Improvement of heath care an

    Regulation of cytokinesis by spindle-pole bodies

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    Author Posting. © The Author(s), 2006. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Cell Biology 8 (2006): 891-893, doi:10.1038/ncb1449.In the fission yeast Schizosaccharomyces pombe, cytokinesis is thought to be controlled by the daughter spindle pole body (SPB) through a regulatory pathway, the Septation Initiation Network (SIN). Here we demonstrate that laser ablation of both but not a single SPB results in cytokinesis failure. Ablation of just the daughter SPB often leads to activation of the SIN on the mother and successful cytokinesis. Thus, either SPB can drive cytokinesis.This work was supported by National Institutes of Health grants GMS 59363 (to A.K.), GMS 69670 (to F.C), and by the Human Frontiers Science Program grant RGP0064 (to AK)
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