70 research outputs found

    Combined exome and whole-genome sequencing identifies mutations in ARMC4 as a cause of primary ciliary dyskinesia with defects in the outer dynein arm

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    Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous ciliopathy disorder affecting cilia and sperm motility. A range of ultrastructural defects of the axoneme underlie the disease, which is characterised by chronic respiratory symptoms and obstructive lung disease, infertility and body axis laterality defects. We applied a next-generation sequencing approach to identify the gene responsible for this phenotype in two consanguineous families

    Design and optimization of an advanced time-of-flight neutron spectrometer for deuterium plasmas of the large helical device

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    A time-of-flight neutron spectrometer based on the Time-Of-Flight Enhanced Diagnostic (TOFED) concept has been designed and is under development for the Large Helical Device (LHD). It will be the first advanced neutron spectrometer to measure the 2.45 MeV D–D neutrons (DDNs) from helical/stellarator plasmas. The main mission of the new TOFED is to study the supra-thermal deuterons generated from the auxiliary heating systems in helical plasmas by measuring the time-of-flight spectra of DDN. It will also measure the triton burnup neutrons (TBNs) from the d+t reactions, unlike the original TOFED in the EAST tokamak. Its capability of diagnosing the TBN ratios is evaluated in this work. This new TOFED is expected to be installed in the basement under the LHD hall and shares the collimator with one channel of the vertical neutron camera to define its line of sight. The distance from its primary scintillators to the equatorial plane of LHD plasmas is about 15.5 m. Based on Monte Carlo simulation by a GEANT4 model, the resolution of the DDN energy spectra is 6.6%. When projected onto the neutron rates that are typically obtained in LHD deuterium plasmas (an order of 1015 n/s with neutral beam injection), we expect to obtain the DDN and TBN counting rates of about 2.5 · 105 counts/s and 250 counts/s, respectively. This will allow us to analyze the DDN time-of-flight spectra on time scales of 0.1 s and diagnose the TBN emission rates in several seconds with one instrument, for the first time in helical/stellarator plasmas

    Induction of antigen-specific tolerance through hematopoietic stem cell-mediated gene therapy: the future for therapy of autoimmune disease?

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    Based on the principle that immune ablation followed by HSC-mediated recovery purges disease-causing leukocytes to interrupt autoimmune disease progression, hematopoietic stem cell transplantation (HSCT) has been increasingly used as a treatment for severe autoimmune diseases. Despite clinically-relevant outcomes, HSCT is associated with serious iatrogenic risks and is suitable only for the most serious and intractable diseases. A further limitation of autologous HSCT is that relapse rates can be high, suggesting disease-causing leukocytes are incompletely purged or the environmental and genetic determinants that drive disease remain active. Incorporation of antigen-specific tolerance approaches that synergise with autologous HSCT could reduce or prevent relapse. Further, by reducing the requirement for highly toxic immune-ablation and instead relying on antigen-specific tolerance, the clinical utility of HSCT could be significantly diversified. Substantial progress has been made exploring HSCT-mediated induction of antigen-specific tolerance in animal models but studies have focussed on primarily on prevention of autoimmune diseases. However, as diagnosis of autoimmune disease is often not made until autoimmune disease is well developed and populations of autoantigen-specific pathogenic effector and memory T cells have become well established, immunotherapies must be developed to address effector and memory T-cell responses which have traditionally been considered the key impediment to immunotherapy. Here, focusing on T-cell mediated autoimmune diseases we review progress made in antigen-specific immunotherapy using HSCT-mediated approaches, induction of tolerance in effector and memory T cells and the challenges for progression and clinical application of antigen-specific ‘tolerogenic’ HSCT therapy

    26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

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    This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

    Two new records of the fern genus Coniogramme (Pteridaceae) from Vietnam

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    Two new records of the fern genus Coniogramme Fée from Vietnam, C. japonica and C. procera, are presented. In addition, a key to recognising the species of Coniogramme in Vietnam is given in this paper

    Insights into the evolutionary history and taxonomic status of Sinopteris (Pteridaceae)

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    As an endemic Chinese genus, Sinopteris C. Chr. & Ching was once considered an early diverged taxon of chei-lanthoid ferns, and its taxonomic status has long been controversial. In this study, eight datasets spanning the complete chloroplast genomes and three nuclear genes were used to reconstruct the phylogeny of Sinopteris and its relatives. In addition, combining morphological analyses, divergence time estimation, and ancestral trait reconstruction, the origin and evolutionary history of Sinopteris were comprehensively discussed. Based on the complete chloroplast genome dataset, our analyses yielded a phylogram with all clades strongly supported (ML -BS = 100, BI-PP = 1.0), and the topology was almost identical to that based on the concatenated sequences of nrDNA, CRY2, and IBR3. Two species of Sinopteris were united and sister to Aleuritopteris niphobola (C. Chr.) Ching. They constituted a stable monophyletic group embedded in Aleuritopteris Fe ' e. This was also consistent with the results of morphological analyses. Divergence time estimation indicated that the clade of Aleuritopteris and Sinopteris originated in the early Miocene (ca. 16.80 Ma) and experienced two rapid diversifications, which could coincide with environmental heterogeneity caused by the progressive uplift of the Himalayas and the intense uplift of the Hengduan Mountains. Sinopteris originated in the late Miocene (ca. 6.96 Ma), accompanied by the sharp intensifications of Asian Monsoon, and began to diversify at 2.34 Ma, following the intense uplift of the Hengduan Mountains. Ancestral character reconstruction showed that monangial sori and subsessile sporangia were clearly late derived states rather than early diverged states. Both the molecular phylogenetic and morphological analyses support the inclusion of Sinopteris in Aleuritopteris

    Two new records of the fern genus Coniogramme (Pteridaceae) from Vietnam

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    Two new records of the fern genus Coniogramme Fée from Vietnam, C. japonica and C. procera, are presented. In addition, a key to recognising the species of Coniogramme in Vietnam is given in this paper

    Selection of a novel DNA aptamer for assay of intracellular interferon-gamma.

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    Interferon-gamma (IFN-γ) is a glycoprotein generated by lymphocytes that possesses anti-tumor, antiviral and immunomodulatory functions. IFN-γ assays are broadly employed in immunological research and clinical diagnostic tests. Intracellular IFN-γ staining, in particular, is an important immune assay that allows simultaneous determination of cellular phenotype and antigen-specific T cell response. Aptamers have great potential for molecule detection and can bind to target molecules with high affinity and specificity. In this study, a novel 59-mer DNA aptamer (B1-4) was developed for assay of intracellular IFN-γ. The selected aptamer bound to IFN-γ with a Kd of 74.5 nM, with minimal cross-reactivity to albumin. The aptamer was also found capable of binding with paraformaldehyde-fixed IFN-γ. Moreover, B1-4 could enter permeated and paraformaldehyde-fixed lymphocytes, and bound to intracellular IFN-γ produced by these cells. When FITC-labeled B1-4 was used to stain a group of lymphocytes, the average fluorescence of the cells was positively correlated with the number of PMA-stimulated lymphocytes within the group. A standard curve could thus be established for assessing the fraction of IFN-γ-producing cells in a cluster of lymphocytes. The selected aptamer hence provides a novel approach for assaying intracellular IFN-γ generated by a group of lymphocytes, and may have application potential in both scientific research and clinical laboratory test

    The complete chloroplast genome of a distinctive fern, Coniogramme intermedia Hieron. (Pteridaceae)

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    Coniogramme intermedia Hieron. is a morphologically distinctive species in the genus. It is identified by lanceolate pinnules with serrated margins, free veins, hydathodes extending into teeth, and laminae abaxially hairy. It is mainly distributed in the tropical and subtropical regions of Asia. Herein, we report the first complete chloroplast genome sequence of C. intermedia. Also, it is the opening one of the genus Coniogramme Fée. The chloroplast genome sequence is 153,561 bp in length. The genome has a typical quadripartite structure, including a large single-copy (LSC) region of 82,817 bp, a small single-copy (SSC) region of 21,236 bp, and two inverted repeat (IR) regions of 24,754bp each. The total GC content is 45.0%. The complete plastome sequence contains 114 genes, including, 81 protein-coding, 29 tRNA, and four rRNA genes. The phylogenetic analysis of Pteridaceae based on the complete chloroplast genomes was also presented in this study
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