40 research outputs found

    Extracellular matrix protein anosmin-1 modulates olfactory ensheathing cell maturation in chick olfactory bulb development

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    Olfactory ensheathing cells (OECs) are a specialized class of glia, wrapping around olfactory sensory axons that target the olfactory bulb (OB) and cross the peripheral nervous system/central nervous system boundary during development and continue to do so post-natally. OEC subpopulations perform distinct subtype-specific functions dependent on their maturity status. Disrupted OEC development is thought to be associated with abnormal OB morphogenesis, leading to anosmia, a defining characteristic of Kallmann syndrome. Hence, anosmin-1 encoded by Kallmann syndrome gene (KAL-1) might modulate OEC differentiation/maturation in the OB. We performed in ovo electroporation of shRNA in the olfactory placode to knock-down kal in chick embryos, resulting in abnormal OB morphogenesis and loss of olfactory sensory axonal innervation into OB. BLBP-expressing OECs appeared to form a thinner and poorly organized outmost OB layer where SOX10 expressing OECs were completely absent with emergence of GFAP-expressing OECs. Furthermore, in embryonic day 10 chick OB explant cultures, GFAP expression in OECs accumulating along the OB nerve layers was dramatically reduced by recombinant anosmin-1. We then purified immature OECs from embryonic day 10 chick OB. These cells express GFAP after 7 days in vitro, exhibiting a multipolar morphology. Overexpression of chick anosmin, exogenous anosmin-1 or FGF2 could inhibit GFAP expression with cells presenting elongated morphology, which was blocked by the FGF receptor inhibitor Su5402. These data demonstrate that anosmin-1 functions via FGF signalling in regulating OEC maturation, thereby providing a permissive glial environment for axonal innervation into the OB during development

    Insight-HXMT observations of Swift J0243.6+6124 during its 2017-2018 outburst

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    The recently discovered neutron star transient Swift J0243.6+6124 has been monitored by {\it the Hard X-ray Modulation Telescope} ({\it Insight-\rm HXMT). Based on the obtained data, we investigate the broadband spectrum of the source throughout the outburst. We estimate the broadband flux of the source and search for possible cyclotron line in the broadband spectrum. No evidence of line-like features is, however, found up to 150 keV\rm 150~keV. In the absence of any cyclotron line in its energy spectrum, we estimate the magnetic field of the source based on the observed spin evolution of the neutron star by applying two accretion torque models. In both cases, we get consistent results with B∼1013 GB\rm \sim 10^{13}~G, D∼6 kpcD\rm \sim 6~kpc and peak luminosity of >1039 erg s−1\rm >10^{39}~erg~s^{-1} which makes the source the first Galactic ultraluminous X-ray source hosting a neutron star.Comment: publishe

    <html>Prognostic impact of concurrent <i>MYC</i> and <i>BCL6</i> rearrangements and expression in <i>de novo</i> diffuse large B-cell lymphoma</html>

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    Double-hit B-cell lymphoma is a common designation for a group of tumors characterized by concurrent translocations of MYC and BCL2, BCL6, or other genes. The prognosis of concurrent MYC and BCL6 translocations is not well known. In this study, we assessed rearrangements and expression of MYC, BCL2 and BCL6 in 898 patients with de novo diffuse large B-cell lymphoma treated with standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab). Neither BCL6 translocation alone (more frequent in activated B-cell like diffuse large B-cell lymphoma) nor in combination with MYC translocation (observed in 2.0% of diffuse large B-cell lymphoma) predicted poorer survival in diffuse large B-cell lymphoma patients. Diffuse large B-cell lymphoma patients with MYC/BCL6 co-expression did have significantly poorer survival, however, MYC/BCL6 co-expression had no effect on prognosis in the absence of MYC/BCL2 co-expression, and had no additive impact in MYC+/BCL2+ cases. The isolated MYC+/BCL6+/BCL2− subset, more frequent in germinal center B-cell like diffuse large B-cell lymphoma, had significantly better survival compared with the isolated MYC+/BCL2+/BCL6− subset (more frequent in activated B-cell like diffuse large B-cell lymphoma). In summary, diffuse large B-cell lymphoma patients with either MYC/BCL6 rearrangements or MYC/BCL6 co-expression did not always have poorer prognosis; MYC expression levels should be evaluated simultaneously; and double-hit B-cell lymphoma needs to be refined based on the specific genetic abnormalities present in these tumors

    Overview to the Hard X-ray Modulation Telescope (Insight-HXMT) Satellite

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    As China's first X-ray astronomical satellite, the Hard X-ray Modulation Telescope (HXMT), which was dubbed as Insight-HXMT after the launch on June 15, 2017, is a wide-band (1-250 keV) slat-collimator-based X-ray astronomy satellite with the capability of all-sky monitoring in 0.2-3 MeV. It was designed to perform pointing, scanning and gamma-ray burst (GRB) observations and, based on the Direct Demodulation Method (DDM), the image of the scanned sky region can be reconstructed. Here we give an overview of the mission and its progresses, including payload, core sciences, ground calibration/facility, ground segment, data archive, software, in-orbit performance, calibration, background model, observations and some preliminary results.Comment: 29 pages, 40 figures, 6 tables, to appear in Sci. China-Phys. Mech. Astron. arXiv admin note: text overlap with arXiv:1910.0443

    Functional and structural study of anosmin-1, the protein implicated in X-linked Kallmann's syndrome

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    EThOS - Electronic Theses Online ServiceGBUnited Kingdo

    GnRH neuronal migration and olfactory bulb neurite outgrowth are dependent on FGF receptor 1 signalling, specifically via the PI3K p110α isoform in chick embryo

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    Fibroblast growth factor (FGF) signaling is essential for both olfactory bulb (OB) morphogenesis and the specification, migration, and maturation of the GnRH-secreting neurons. Disruption of FGF signaling contributes to Kallmann syndrome characterized by both anosmia and sexual immaturity. However, several unanswered questions remain as to which specific FGF receptor (FGFR)-1 signaling pathways are necessary for OB and GnRH neuronal development. Here, using pharmacological phosphatidylinositol 3-kinase (PI3K) isoform-specific inhibitors, we demonstrate a central role for the PI3K p110α isoform as a downstream effector of FGFR1 signaling for both GnRH neuronal migration and OB development. We show that signaling via the PI3K p110α isoform is required for GnRH neuronal migration in explant cultures of embryonic day (E) 4 chick olfactory placodes. We also show that in ovo administration of LY294002, a global PI3K inhibitor as well as an inhibitor to the PI3K p110α isoform into the olfactory placode of E3 chick embryo impairs GnRH neuronal migration toward the forebrain. In contrast, in ovo PI3K inhibitor treatment produced no obvious defects on primary olfactory sensory neuron axonal targeting and bundle formation. We also demonstrate that anosmin-1 and FGF2 induced neuronal migration of immortalized human embryonic GnRH neuroblast cells (FNC-B4-hTERT) is mediated by modulating FGFR1 signaling via the PI3K p110α isoform, specifically through phosphorylation of the PI3K downstream effectors, Akt and glycogen synthase kinase-3β. Finally, we show that neurite outgrowth and elongation of OB neurons in E10 chick OB explants are also dependent on the PI3K p110α isoform downstream of FGFR1. This study provides mechanistic insight into the etiology of Kallmann syndrome.</jats:p

    Virtual Reality–Based Training in Chronic Low Back Pain: Systematic Review and Meta-Analysis of Randomized Controlled Trials

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    BackgroundLow back pain is one of the most prevalent pain conditions worldwide. Virtual reality–based training has been used for low back pain as a new treatment strategy. Present evidence indicated that the effectiveness of virtual reality–based training for people with chronic low back pain is inconclusive. ObjectiveThis study conducted a meta-analysis to evaluate the immediate- and short-term effects of virtual reality–based training on pain, pain-related fear, and disability in people with chronic low back pain. MethodsWe searched the PubMed, Embase, Web of Science, PEDro, CENTRAL, and CINAHL databases from inception until January 2024. Only randomized controlled trials assessing the effects of virtual reality–based training on individuals with chronic low back pain were selected. The outcomes were focused on pain, pain-related fear measured by the Tampa Scale of Kinesiophobia, and disability measured by the Oswestry Disability Index. The immediate term was defined as the immediate period after intervention, and the short term was defined as 3 to 6 months after intervention. The Cochrane Risk of Bias tool and the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach were used to evaluate the quality of the methodology and evidence, respectively. ResultsIn total, 20 randomized controlled trials involving 1059 patients were eligible for analysis. Virtual reality–based training showed significant improvements in pain (mean difference [MD] –1.43; 95% CI –1.86 to –1.00; I2=95%; P<.001), pain-related fear using the Tampa Scale of Kinesiophobia (MD –5.46; 95% CI –9.40 to 1.52; I2=90%; P=.007), and disability using the Oswestry Disability Index (MD –11.50; 95% CI –20.00 to –3.01; I2=95%; P=.008) in individuals with chronic low back pain immediately after interventions. However, there were no significant differences observed in pain (P=.16), pain-related fear (P=.10), and disability (P=.43) in the short term. ConclusionsThese findings indicated that virtual reality–based training can be used effectively for individuals with chronic low back pain in the immediate term, especially to reduce pain, alleviate pain-related fear, and improve disability. However, the short-term benefits need more high-quality trials to be demonstrated. Trial RegistrationPROSPERO CRD42021292633; http://tinyurl.com/25mydxp

    Nondestructive Testing Model of Mango Dry Matter Based on Fluorescence Hyperspectral Imaging Technology

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    The dry matter test of mango has important practical significance for the quality classification of mango. Most of the common fruit and vegetable quality nondestructive testing methods based on fluorescence hyperspectral imaging technology use a single algorithm in algorithms such as Uninformative Variable Elimination (UVE), Random Frog (RF), Competitive Adaptive Reweighted Sampling (CARS) and Continuous Projection Algorithm (SPA) to extract feature spectral variables, and the use of these algorithms alone can easily lead to the insufficient stability of prediction results. In this regard, a nondestructive detection method for the dry matter of mango based on hyperspectral fluorescence imaging technology was carried out. Taking the &lsquo;Keitt&rsquo; mango as the research object, the mango samples were numbered in sequence, and their fluorescence hyperspectral images in the wavelength range of 350&ndash;1100 nm were collected, and the average spectrum of the region of interest was used as the effective spectral information of the sample. Select SPXY algorithm to divide samples into a calibration set and prediction set, and select Orthogonal Signal Correction (OSC) as preprocessing method. For the preprocessed spectra, the primary dimensionality reduction (UVE, SPA, RF, CARS), the primary combined dimensionality reduction (UVE + RF, CARS + RF, CARS + SPA), and the secondary combined dimensionality reduction algorithm ((CARS + SPA)-SPA, (UVE + RF)-SPA) and other 12 algorithms were used to extract feature variables. Separately constructed predictive models for predicting the dry matter of mangoes, namely, Support Vector Regression (SVR), Extreme Learning Machine (ELM), and Back Propagation Neural Network (BPNN) model, were used; The results show that (CARS + RF)-SPA-BPNN has the best prediction performance for mango dry matter, its correlation coefficients were RC2 = 0.9710, RP2 = 0.9658, RMSEC = 0.1418, RMSEP = 0.1526, this method provides a reliable theoretical basis and technical support for the non-destructive detection, and precise and intelligent development of mango dry matter detection
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