111 research outputs found

    A two years longitudinal study of a transgenic Huntington disease monkey

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    BACKGROUND: A two-year longitudinal study composed of morphometric MRI measures and cognitive behavioral evaluation was performed on a transgenic Huntington’s disease (HD) monkey. rHD1, a transgenic HD monkey expressing exon 1 of the human gene encoding huntingtin (HTT) with 29 CAG repeats regulated by a human polyubiquitin C promoter was used together with four age-matched wild-type control monkeys. This is the first study on a primate model of human HD based on longitudinal clinical measurements. RESULTS: Changes in striatal and hippocampal volumes in rHD1 were observed with progressive impairment in motor functions and cognitive decline, including deficits in learning stimulus-reward associations, recognition memory and spatial memory. The results demonstrate a progressive cognitive decline and morphometric changes in the striatum and hippocampus in a transgenic HD monkey. CONCLUSIONS: This is the first study on a primate model of human HD based on longitudinal clinical measurements. While this study is based a single HD monkey, an ongoing longitudinal study with additional HD monkeys will be important for the confirmation of our findings. A nonhuman primate model of HD could complement other animal models of HD to better understand the pathogenesis of HD and future development of diagnostics and therapeutics through longitudinal assessment

    MicroRNAs Up-Regulated by CagA of Helicobacter pylori Induce Intestinal Metaplasia of Gastric Epithelial Cells

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    CagA of Helicobacter pylori is a bacterium-derived oncogenic protein closely associated with the development of gastric cancers. MicroRNAs (miRNAs) are a class of widespread non-coding RNAs, many of which are involved in cell growth, cell differentiation and tumorigenesis. The relationship between CagA protein and miRNAs is unclear. Using mammalian miRNA profile microarrays, we found that miRNA-584 and miRNA-1290 expression was up-regulated in CagA-transformed cells, miRNA-1290 was up-regulated in an Erk1/2-dependent manner, and miRNA-584 was activated by NF-ÎșB. miRNA-584 sustained Erk1/2 activities through inhibition of PPP2a activities, and miRNA-1290 activated NF-ÎșB by knockdown of NKRF. Foxa1 was revealed to be an important target of miRNA-584 and miRNA-1290. Knockdown of Foxa1 promoted the epithelial-mesenchymal transition significantly. Overexpression of miRNA-584 and miRNA-1290 induced intestinal metaplasia of gastric epithelial cells in knock-in mice. These results indicate that miRNA-584 and miRNA-1290 interfere with cell differentiation and remodel the tissues. Thus, the miRNA pathway is a new pathogenic mechanism of CagA

    Riser lift system for deep sea mining

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    The growing global demand for rare metals and the declining land mineral resources impel the research on exploring deep sea minerals resources. This thesis focuses on one case, which is within the Norwegian interest zone along the North-East part of the Mid-Atlantic Ridge outside Svalbard, the water depth is in excess of 3000 m. The objective of this master thesis is to explore the limitations of operating such a riser system at large water depths with focus on the dynamic behaviour of the system. In addition, based on the dynamic response and the limiting criteria, perform the fatigue analysis to find the fatigue life of the riser lift system. Then, comparing the difference of the dynamic behavior and fatigue life of the riser lift system under the two topside connection conditions. A case study was performed for representative sea states with regard to two working conditions by the Riflex module of SIMA. The results of this study indicated that the topside connection of the riser has a big impact on the riser. The bending moment and stress of the riser with fixed topside connection is much larger than it with pinned topside connection.In this case, the fatigue life of the riser is too short whatever the topside connection is. In general, it is difficult to apply a steel riser under these conditions, even if the vortex induced vibration is not considered in this study

    Efficacy of glycyrrhizin in patients with chronic severe hepatitis B: a meta-analysis

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    ObjectiveTo systematically evaluate the efficacy and safety of glycyrrhizin in patients with chronic severe hepatitis B. MethodsLiterature published from January 1990 to July 2014 were searched in databases including PubMed, Cochrane Library, CBMdisc, CNKI, VIP, and Wanfang Data. The randomized controlled trials comparing the efficacy of glycyrrhizin combined with internal comprehensive therapy versus internal comprehensive therapy alone in patients with chronic severe hepatitis B were included in the analysis. The methodological quality of included trials was independently assessed and the data were extracted. Meta-analysis was carried out with Review Manager Software 5.1, and the heterogeneity, sensitivity, and bias of the analysis were evaluated. ResultsSeven randomized controlled trials involving 298 patients in the test group and 294 in the control group were included in the analysis. The results of meta-analysis showed that glycyrrhizin combined with internal comprehensive therapy was remarkably more effective than internal comprehensive therapy alone, indicated by significantly reduced mortality rate relative risk(RR)=0.56, 95% confidenceinterval(CI):0.42~0.76, P0.01, significantly decreased level of total bilirubin (TBil) mean difference(MD)=-92.56, 95%CI:-122.92~-62.20, P0.01, and significantly higher prothrombin activity (PTA) mean difference(MD)=11.14, 95% CI:5.40~16.87, P0.01. No severe adverse reactions were found in all patients. ConclusionGlycyrrhizin can significantly reduce the mortality and improve TBil and PTA in patients with chronic severe hepatitis B

    Three-Dimensional Analysis of the Flow Characteristics Induced by a Cubic Artificial Reef with Diversions

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    In this paper, the flow characteristics induced by a cubic artificial reef with diversions (DCAR) were investigated using computational fluid dynamics (CFD). The results showed that the design of a DCAR can greatly improve the flow field range compared to typical cubic artificial reefs. The upwelling volume of the DCAR was more than 16 times that of a typical cubic artificial reef. The flow field effect produced the best results when the cut-opening ratio (COR) was 0.1–0.2 with constant flow. The parameters of the upwelling and back vortex increased with an increase in the flow velocity, and it decreased with an increase in the COR. The drag coefficient was less affected by the flow velocity, which remained between 1.32 and 1.44. The new type of artificial reef can improve the flow characteristics around the reefs

    Land Cover Classification with GF-3 Polarimetric Synthetic Aperture Radar Data by Random Forest Classifier and Fast Super-Pixel Segmentation

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    Chinese Gaofen-3 (GF-3), a vital satellite for high-resolution earth observation, was the first C-band polarimetric synthetic aperture radar (SAR) launched in China with a resolution of up to one meter. Polarimetric SAR can obtain the complete physical scattering mechanisms of targets, thereby having the potential to differentiate objects. In this paper, several classification methods are briefly summarized and the types of features that should be chosen during classification are discussed. A pre-classification step is introduced to reduce the workload of precise labeling. The Random Forest classifier, which performs well for many other classification tasks, is used for the initial land cover classification. Then, based on a polarimetric constant false-alarm rate (CFAR) edge detector, a fast super-pixel generation method for polarimetric SAR image is proposed, which does not require the adjustment of parameters in advance. Following that, majority vote is conducted on the initial classification result based on the super-pixels, so that the classification result can be optimized to better meet the mapping requirements. The experimental results based on GF-3 polarimetric SAR data verify the effectiveness of proposed procedure and demonstrate that GF-3 data has excellent performance in land cover classification

    Transcriptomic Analysis of the Chicken MDA5 Response Genes

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    RIG-I and MDA5 are two key pattern recognition receptors that sense RNA virus invasion, but RIG-I is absent in chickens. Although chickens have intact MDA5, the genes downstream of chicken MDA5 (chMDA5) that may mediate antiviral response are not well studied. We compared the transcriptional profile of chicken embryonic fibroblasts (DF1) transfected with chMDA5, and poly(I:C), using RNA-seq. Transfected chMDA5 and poly(I:C) in DF1 cells were associated with the marked induction of many antiviral innate immune genes compared with control. Interestingly, nine interferon-stimulated genes (ISGs) were listed in the top 15 upregulated genes by chMDA5 and poly(I:C) transfection. We used real-time PCR to confirm the upregulation of the nine ISGs, namely, MX1, IFI6, IFIT5, RSAD2, OASL, CMPK2, HELZ2, EPSTI1, and OLFML1, by chMDA5 and poly(I:C) transfection in DF1 cells. However, avian influenza virus H5N6 infection only increased MX1, IFI6, IFIT5, RSAD2, and OASL expression levels. Further study showed that the overexpression of these five genes could significantly inhibit H5N6 virus replication. These results provide some insights into the gene expression pattern induced by chMDA5, which would be beneficial for understanding and identifying innate immune genes of chicken that may lead to new antiviral therapies

    Coping strategies in patients undergoing surgery treatment for pituitary tumour in China: A cross‐sectional survey

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    Abstract Aim To explore the coping strategies and corresponding influence factors in patients undergone surgeries for pituitary tumours. Design A cross‐sectional study. Methods Patients diagnosed with pituitary tumours were included. The Medical Coping Questionnaire (MCMQ) and a demographic questionnaire were used for data collection. Results A total of 150 patients with pituitary tumour undergoing surgery treatment were included. Compared with the a‐select sample, patients with pituitary tumours reported more avoidant coping (p < .0001) and more resigned coping (p = .031) but less confrontation coping (p = .026). Multiple regression analysis showed the regardless of recurrence or not, the type and size of pituitary tumour, education level, family income are the factors influencing the coping style (all p < .05). Conclusions Clinical workers should pay more attention to the patients with multiplied pituitary tumour, huge adenoma, recurred tumour, low levels of education and low monthly income
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