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  • 1
    Publication Date: 2018-05-15
    Description: H7N9 virus has caused five infection waves since it emerged in 2013. The highest number of human cases was seen in wave 5; however, the underlying reasons have not been thoroughly elucidated. In this study, the geographical distribution, phylogeny, and genetic evolution of 240 H7N9 viruses in wave 5, including 35 new isolates from patients and poultry in nine provinces, were comprehensively analyzed together with strains from first four waves. Geographical distribution analysis indicated that the newly emerging highly pathogenic (HP) and low-pathogenicity (LP) H7N9 viruses were cocirculating, causing human and poultry infections across China. Genetic analysis indicated that dynamic reassortment of the internal genes among LP-H7N9/H9N2/H6Ny and HP-H7N9, as well as of the surface genes, between the Yangtze and Pearl River Delta lineages resulted in at least 36 genotypes, with three major genotypes (G1 [A/chicken/Jiangsu/SC537/2013-like], G3 [A/Chicken/Zhongshan/ZS/2017-like], and G11 [A/Anhui/40094/2015-like]). The HP-H7N9 genotype likely evolved from G1 LP-H7N9 by the insertion of a KRTA motif at the cleavage site (CS) and then evolved into 15 genotypes with four different CS motifs, including PKG KRTA R/G, PKG KRIA R/G, PKR KRAA R/G, and PKR KRTA R/G. Approximately 46% (28/61) of HP strains belonged to G3. Importantly, neuraminidase (NA) inhibitor (NAI) resistance (R292K in NA) and mammalian adaptation (e.g., E627K and A588V in PB2) mutations were found in a few non-human-derived HP-H7N9 strains. In summary, the enhanced prevalence and diverse genetic characteristics that occurred with mammalian-adapted and NAI-resistant mutations may have contributed to increased numbers of human infections in wave 5. IMPORTANCE The highest numbers of human H7N9 infections were observed during wave 5 from October 2016 to September 2017. Our results showed that HP-H7N9 and LP-H7N9 had spread virtually throughout China and underwent dynamic reassortment with different subtypes (H7N9/H9N2 and H6Ny) and lineages (Yangtze and Pearl River Delta lineages), resulting in totals of 36 and 3 major genotypes, respectively. Notably, the NAI drug-resistant (R292K in NA) and mammalian-adapted (e.g., E627K in PB2) mutations were found in HP-H7N9 not only from human isolates but also from poultry and environmental isolates, indicating increased risks for human infections. The broad dissemination of LP- and HP-H7N9 with high levels of genetic diversity and host adaptation and drug-resistant mutations likely accounted for the sharp increases in the number of human infections during wave 5. Therefore, more strategies are needed against the further spread and damage of H7N9 in the world.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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  • 2
    Publication Date: 2018-08-23
    Description: In experimental investigations on axial symmetry, over-ventilated CH 4 /air diffusion combustion in a packed bed is executed to study the height, shape and stability of the flame. The combustor is a quartz tube packed with alumina pellets in which a cylindrical fuel stream is surrounded by a coflow air nozzle. The results show that the bed length and pellet diameter have a significant influence on the flame properties. In general, the flame above the pellet surface has axial symmetry, and its shape and colour are similar to those of a conventional diffusion flame when the bed length is smaller. The colour of the flame front varies with the bed length. The changed colour indicates an increased flame front temperature and that the combustion regime above the bed surface may change from non-premixed combustion to partially premixed combustion or even premixed combustion owing to the mix and dispersion effect in the packed bed. In addition, multiple flame behaviours, such as an inclined flame front, isolated reaction zone and oscillatory motion followed by a pulsating sound with a few hertz in a packed bed, are observed experimentally. The possible reasons for these phenomena are discussed.
    Keywords: energy
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 3
    Keywords: CANCER ; EXPRESSION ; COMBINATION ; LUNG ; MODEL ; MODELS ; TOXICITY ; CLASSIFICATION ; liver ; GENE ; GENE-EXPRESSION ; microarray ; validation ; QUALITY ; BREAST ; breast cancer ; BREAST-CANCER ; PERFORMANCE ; gene expression ; MICROARRAY DATA ; HUMANS ; microarrays ; PREDICTION ; PROJECT ; FOLLICULAR LYMPHOMA ; MULTIPLE-MYELOMA ; rodent ; neuroblastoma ; development ; methods ; GENE-EXPRESSION DATA ; DNA MICROARRAYS ; rodents ; RECOMMENDATIONS ; EXPRESSION DATA ; CONTROL MAQC PROJECT ; PUBLISHED MICROARRAY ; RISK-STRATIFICATION
    Abstract: Gene expression data from microarrays are being applied to predict preclinical and clinical endpoints, but the reliability of these predictions has not been established. In the MAQC-II project, 36 independent teams analyzed six microarray data sets to generate predictive models for classifying a sample with respect to one of 13 endpoints indicative of lung or liver toxicity in rodents, or of breast cancer, multiple myeloma or neuroblastoma in humans. In total, 〉30,000 models were built using many combinations of analytical methods. The teams generated predictive models without knowing the biological meaning of some of the endpoints and, to mimic clinical reality, tested the models on data that had not been used for training. We found that model performance depended largely on the endpoint and team proficiency and that different approaches generated models of similar performance. The conclusions and recommendations from MAQC-II should be useful for regulatory agencies, study committees and independent investigators that evaluate methods for global gene expression analysis
    Type of Publication: Journal article published
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  • 4
    Publication Date: 2018-07-19
    Description: We present the first known fossilized snake embryo/neonate preserved in early Late Cretaceous (Early Cenomanian) amber from Myanmar, which at the time, was an island arc including terranes from Austral Gondwana. This unique and very tiny snake fossil is an articulated postcranial skeleton, which includes posterior precloacal, cloacal, and caudal vertebrae, and details of squamation and body shape; a second specimen preserves a fragment of shed skin interpreted as a snake. Important details of skeletal ontogeny, including the stage at which snake zygosphene-zygantral joints began to form along with the neural arch lamina, are preserved. The vertebrae show similarities to those of fossil Gondwanan snakes, suggesting a dispersal route of Gondwanan faunas to Laurasia. Finally, the new species is the first Mesozoic snake to be found in a forested environment, indicating greater ecological diversity among early snakes than previously thought.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 5
    Publication Date: 2018-05-30
    Description: As a prevalent agent in cats, feline herpesvirus 1 (FHV-1) infection contributes to feline respiratory disease and acute and chronic conjunctivitis. FHV-1 can successfully evade the host innate immune response and persist for the lifetime of the cat. Several mechanisms of immune evasion by human herpesviruses have been elucidated, but the mechanism of immune evasion by FHV-1 remains unknown. In this study, we screened for FHV-1 open reading frames (ORFs) responsible for inhibiting the type I interferon (IFN) pathway with an IFN-β promoter reporter and analysis of IFN-β mRNA levels in HEK 293T cells and the Crandell-Reese feline kidney (CRFK) cell line, and we identified the Ser/Thr kinase US3 as the most powerful inhibitor. Furthermore, we found that the anti-IFN activity of US3 depended on its N terminus (amino acids 1 to 75) and was independent of its kinase activity. Mechanistically, the ectopic expression of US3 selectively inhibited IFN regulatory factor 3 (IRF3) promoter activation. Furthermore, US3 bound to the IRF association domain (IAD) of IRF3 and prevented IRF3 dimerization. Finally, US3-deleted recombinant FHV-1 and US3-repaired recombinant FHV-1 (rFHV-dUS3 and rFHV-rUS3, respectively) were constructed. Compared with wild-type FHV-1 and rFHV-rUS3, infection with rFHV-dUS3 induced large amounts of IFN-β in vitro and in vivo . More importantly, US3 deletion significantly attenuated virulence, reduced virus shedding, and blocked the invasion of trigeminal ganglia. These results indicate that FHV-1 US3 efficiently inhibits IFN induction by using a novel immune evasion mechanism and that FHV-1 US3 is a potential regulator of neurovirulence. IMPORTANCE Despite widespread vaccination, the prevalence of FHV-1 remains high, suggesting that it can successfully evade the host innate immune response and infect cats. In this study, we screened viral proteins for inhibiting the IFN pathway and identified the Ser/Thr kinase US3 as the most powerful inhibitor. In contrast to other members of the alphaherpesviruses, FHV-1 US3 blocked the host type I IFN pathway in a kinase-independent manner and via binding to the IRF3 IAD and preventing IRF3 dimerization. More importantly, the depletion of US3 attenuated the anti-IFN activity of FHV-1 and prevented efficient viral replication in vitro and in vivo . Also, US3 deletion significantly attenuated virulence and blocked the invasion of trigeminal ganglia. We believe that these findings not only will help us to better understand the mechanism of how FHV-1 manipulates the host IFN response but also highlight the potential role of US3 in the establishment of latent infection in vivo .
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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  • 6
    Publication Date: 2018-06-21
    Description: The surface characteristics of fractured specimens are important in hydraulic fracturing laboratory experiments. In this paper, we present a three-dimensional (3D) scanning device assembled to study these surface characteristics. Cube-shaped rock specimens were produced in the laboratory and subjected to triaxial loading until the specimen split in two in a hydraulic fracturing experiment. Each fractured specimen was placed on a rotating platform and scanned to produce 3D superficial coordinates of the surface of the fractured specimen. The scanned data were processed to produce high-precision digital images of the fractured model, a surface contour map and accurate values of the superficial area and specimen volume. The images produced by processing the 3D scanner data provided detailed information on the morphology of the fractured surface and mechanism of fracture propagation. High-precision 3D mapping of the fractured surfaces is essential for quantitative analysis of fractured specimens. The 3D scanning technology presented here is an important tool for the study of fracture characteristics in hydraulic fracturing experiments.
    Keywords: energy, civil engineering
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 7
    Publication Date: 2018-12-02
    Description: Production of 25-hydroxycholesterol (25HC), a potent inhibitor of viral infection, is catalyzed by cholesterol 25-hydroxylase (CH25H). We previously reported that 25HC induced CH25H expression in a liver X receptor (LXR)-dependent manner, implying that LXR can play an important role in antiviral infection. In this study, we determined that activation of LXR by 25HC or synthetic ligands [T0901317 (T317) or GW3965] inhibited infection of herpes simplex virus type 1 (HSV-1) or MLV-(VSV)-GFP in HepG2 cells or RAW 264.7 macrophages. Genetic deletion of LXRα, LXRβ, or CH25H expression in HepG2 cells by CRISPR/Cas9 method increased cell susceptibility to HSV-1 infection and attenuated the inhibition of LXR on viral infection. Lack of interferon (IFN)- expression also increased cell susceptibility to viral infection. However, it attenuated, but did not block, the inhibition of LXR on HSV-1 infection. In addition, expression of CH25H, but not IFN-, was inversely correlated to cell susceptibility to viral infection and the antiviral actions of LXR. Metabolism of 25HC into 25HC-3-sulfate (25HC3S) by cholesterol sulfotransferase-2B1b moderately reduced the antiviral actions of 25HC because 25HC3S is a weaker inhibitor of HSV-1 infection than 25HC. Furthermore, administration of T317 to BALB/c mice reduced HSV-1 growth in mouse tissues. Taken together, we demonstrate an antiviral system of 25HC with involvement of LXR activation, interaction between CH25H and IFN-, and 25HC metabolism.
    Print ISSN: 0022-2275
    Electronic ISSN: 1539-7262
    Topics: Biology , Chemistry and Pharmacology , Medicine
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  • 8
    Publication Date: 2018-09-13
    Description: The present study introduces thermogravimetry with gas chromatography–mass spectrometry (TG-GC-MS) at four different heating rates to investigate the activation energy and thermal degradation behaviour of walnut shell pyrolysis. The distributed activation energy model (DAEM) was applied to investigate the activation energy. According to values of the activation energy and the correlation coefficient by the DAEM, the activation energy (98.69–267.75 kJ mol –1 ) and correlation coefficient (0.914–0.999) were determined for pyrolysis of walnut shells. GC-MS was performed to investigate the pyrolysis products from walnut shells at different critical temperature points. More than 20 different substances were identified at different temperatures from GC-MS results. With the increasing pyrolysis temperature, furan, furfural, benzene and long chain alkanes were successively identified in different GC-MS experimental results.
    Keywords: energy
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 9
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-19
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2018-05-24
    Description: The co-silencing of multiple tumor suppressor genes can lead to escalated malignancy in cancer cells. Given the limited efficacy of anticancer therapies targeting single tumor suppressor genes, we developed small circular single-stranded DNA (CSSD) that can up-regulate the expression of co-silenced tumor suppressor genes by sequestering microRNAs (miRNAs) that negatively regulate these genes. We found that cancer patients with low tumor expression of the tumor suppressor genes KLF17 , CDH1 , and LASS2 had shortened survival times. The up-regulation of these genes upon transfection of artificial CSSD-9 inhibited tumor proliferation and metastasis and promoted apoptosis in vitro as well as in ex vivo and patient-derived xenograft models. In addition, CSSD is more stable and effective than current miRNA inhibitors, and transfecting CSSDs via nanoparticles substantially improved delivery efficiency. The use of a single CSSD can promote the inhibition of multiple tumor suppressor genes. This study provides evidence for the possibility of using CSSDs as therapeutic miRNA inhibitors to target the co-silencing of multiple tumor suppressor genes.
    Print ISSN: 1946-6234
    Electronic ISSN: 1946-6242
    Topics: Medicine
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