4,758 research outputs found

    An endogenous F-box protein regulates ARGONAUTE1 in Arabidopsis thaliana

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    ARGONAUTE1 (AGO1) mediates microRNA- and small interfering RNA-directed posttranscriptional gene silencing in Arabidopsis thaliana. Mutant alleles of SQUINT (SQN) slightly reduce AGO1 activity and have weak effects on shoot morphology. A screen for mutations that suppress the sqn phenotype produced loss-of-function mutations in the F-box gene FBW2. Mutations in FBW2 not only suppress sqn but also suppress many of the developmental phenotypes of weak, but not null, alleles of AGO1 by increasing AGO1 protein levels. Conversely, over-expression of FBW2 decreases the abundance of the AGO1 protein but not AGO1 messenger RNA, further indicating that FBW2 regulates AGO1 protein levels. fbw2 mutants have no obvious morphological phenotype, but display a reduced sensitivity to abscisic acid (ABA) that can be attributed to increased AGO1 activity. Our results indicate that FBW2 is a novel negative regulator of AGO1 and suggest that it plays a role in ABA signalling and/or response

    The role of galaxies and AGN in reionising the IGM -- III : IGM-galaxy cross-correlations at z~6 from 8 quasar fields with DEIMOS and MUSE

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    We present improved results of the measurement of the correlation between galaxies and the intergalactic medium transmission at the end of reionization. We have gathered a sample of 13 spectroscopically confirmed Lyman-break galaxies (LBGs) and 21 Lyman-α emitters (LAEs) at angular separations 20 arcsec ≲ θ ≲ 10 arcmin (∼0.1–4 pMpc at z ∼ 6) from the sightlines to eight background z ≳ 6 quasars. We report for the first time the detection of an excess of Lyman-α transmission spikes at ∼10–60 cMpc from LAEs (3.2σ) and LBGs (1.9σ). We interpret the data with an improved model of the galaxy–Lyman-α transmission and two-point cross-correlations, which includes the enhanced photoionization due to clustered faint sources, enhanced gas densities around the central bright objects and spatial variations of the mean free path. The observed LAE(LBG)–Lyman-α transmission spike two-point cross-correlation function (2PCCF) constrains the luminosity-averaged escape fraction of all galaxies contributing to reionization to ⟨fesc⟩MUV−20(2σ)⁠) is necessary to reproduce the observed 2PCCF and that reionization might be driven by different sub-populations around LBGs and LAEs at z ∼ 6

    Chronic bilateral heel pain in a child with Sever disease: case report and review of literature

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    We are presenting a case report of a 10-year-old male with a 1 year history of bilateral heel pain. Sever disease is self limiting condition of calcaneal apophysis. It is the most common cause of heel pain in the growing child. There is no documented case of this condition in this region. This case highlights the clinical features of this self limiting disorder as seen in this patient and reviews the current literature

    Clathrin light chain A drives selective myosin VI recruitment to clathrin-coated pits under membrane tension

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    Clathrin light chains (CLCa and CLCb) are major constituents of clathrin-coated vesicles. Unique functions for these evolutionary conserved paralogs remain elusive, and their role in clathrin-mediated endocytosis in mammalian cells is debated. Here, we find and structurally characterize a direct and selective interaction between CLCa and the long isoform of the actin motor protein myosin VI, which is expressed exclusively in highly polarized tissues. Using genetically-reconstituted Caco-2 cysts as proxy for polarized epithelia, we provide evidence for coordinated action of myosin VI and CLCa at the apical surface where these proteins are essential for fission of clathrin-coated pits. We further find that myosin VI and Huntingtin-interacting protein 1-related protein (Hip1R) are mutually exclusive interactors with CLCa, and suggest a model for the sequential function of myosin VI and Hip1R in actin-mediated clathrin-coated vesicle budding

    Social Network Analytics for Advanced Bibliometrics: Referring to Actor Roles of Management Journals instead of Journal Rankings

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    Impact factors are commonly used to assess journals relevance. This implies a simplified view on science as a single-stage linear process. Therefore, few top-tier journals are one-sidedly favored as outlets, such that submissions to top-tier journals explode whereas others are short of submissions. Consequently, the often claimed gap between research and practical application in application-oriented disciplines as business administration is not narrowing but becoming entrenched. A more complete view of the scientific system is needed to fully capture journals ´ contributions in the development of a discipline. Simple citation measures, as e.g. citation counts, are commonly used to evaluate scientific work. There are many known dangers of miss- or over-interpretation of such simple data and this paper adds to this discussion by developing an alternative way of interpreting a discipline based on the positions and roles of journals in their wider network. Specifically, we employ ideas from the network analytic approach. Relative positions allow the direct comparison between different fields. Similarly, the approach provides a better understanding of the diffusion process of knowledge as it differentiates positions in the knowledge creation process. We demonstrate how different modes of social capital create different patterns of action that require a multidimensional evaluation of scientific research. We explore different types of social capital and intertwined relational structures of actors to compare journals with different bibliometric profiles. Ultimately, we develop a multi-dimensional evaluation of actor roles based upon multiple indicators and we test this approach by classifying management journals based on their bibliometric environment

    Monocytes regulate the mechanism of T-cell death by inducing Fas-mediated apoptosis during bacterial infection.

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    Monocytes and T-cells are critical to the host response to acute bacterial infection but monocytes are primarily viewed as amplifying the inflammatory signal. The mechanisms of cell death regulating T-cell numbers at sites of infection are incompletely characterized. T-cell death in cultures of peripheral blood mononuclear cells (PBMC) showed 'classic' features of apoptosis following exposure to pneumococci. Conversely, purified CD3(+) T-cells cultured with pneumococci demonstrated necrosis with membrane permeabilization. The death of purified CD3(+) T-cells was not inhibited by necrostatin, but required the bacterial toxin pneumolysin. Apoptosis of CD3(+) T-cells in PBMC cultures required 'classical' CD14(+) monocytes, which enhanced T-cell activation. CD3(+) T-cell death was enhanced in HIV-seropositive individuals. Monocyte-mediated CD3(+) T-cell apoptotic death was Fas-dependent both in vitro and in vivo. In the early stages of the T-cell dependent host response to pneumococci reduced Fas ligand mediated T-cell apoptosis was associated with decreased bacterial clearance in the lung and increased bacteremia. In summary monocytes converted pathogen-associated necrosis into Fas-dependent apoptosis and regulated levels of activated T-cells at sites of acute bacterial infection. These changes were associated with enhanced bacterial clearance in the lung and reduced levels of invasive pneumococcal disease

    The lumbosacral angle does not reflect progressive tethered cord syndrome in children with spinal dysraphism

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    Purpose: Our goal was to validate the hypothesis that the lumbosacral angle (LSA) increases in children with spinal dysraphism who present with progressive symptoms and signs of tethered cord syndrome (TCS), and if so, to determine for which different types and/or levels the LSA would be a valid indicator of progressive TCS. Moreover, we studied the influence of surgical untethering and eventual retethering on the LSA. Methods: We retrospectively analyzed the data of 33 children with spinal dysraphism and 33 controls with medulloblastoma. We measured the LSA at different moments during follow-up and correlated this with progression in symptomatology. Results: LSA measurements had an acceptable intra- and interobserver variability, however, some children with severe deformity of the caudal part of the spinal column, and for obvious reasons those with caudal regression syndrome were excluded. LSA measurements in children with spinal dysraphism were significantly different from the control group (mean LSA change, 21.0° and 3.1° respectively). However, both groups were not age-matched, and when dividing both groups into comparable age categories, we no longer observed a significant difference. Moreover, we did not observe a significant difference between 26 children with progressive TCS as opposed to seven children with stable TCS (mean LSA change, 20.6° and 22.4° respectively). Conclusions: We did not observe significant differences in LSA measurements for children with clinically progressive TCS as opposed to clinically stable TCS. Therefore, the LSA does not help the clinician to dete

    Pasteurella multocida Heddleston serovar 3 and 4 strains share a common lipopolysaccharide biosynthesis locus but display both inter- and intrastrain lipopolysaccharide heterogeneity

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    Pasteurella multocida is a Gram-negative multispecies pathogen and the causative agent of fowl cholera, a serious disease of poultry which can present in both acute and chronic forms. The major outer membrane component lipopolysaccharide (LPS) is both an important virulence factor and a major immunogen. Our previous studies determined the LPS structures expressed by different P. multocida strains and revealed that a number of strains belonging to different serovars contain the same LPS biosynthesis locus but express different LPS structures due to mutations within glycosyltransferase genes. In this study, we report the full LPS structure of the serovar 4 type strain, P1662, and reveal that it shares the same LPS outer core biosynthesis locus, L3, with the serovar 3 strains P1059 and Pm70. Using directed mutagenesis, the role of each glycosyltransferase gene in LPS outer core assembly was determined. LPS structural analysis of 23 Australian field isolates that contain the L3 locus revealed that at least six different LPS outer core structures can be produced as a result of mutations within the LPS glycosyltransferase genes. Moreover, some field isolates produce multiple but related LPS glycoforms simultaneously, and three LPS outer core structures are remarkably similar to the globo series of vertebrate glycosphingolipids. Our in-depth analysis showing the genetics and full range of P. multocida lipopolysaccharide structures will facilitate the improvement of typing systems and the prediction of the protective efficacy of vaccines
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