tgm

Tgm
  • 文章类型: Journal Article
    使用光学泵浦磁力计的可穿戴脑磁图的应用在神经科学领域引起了广泛关注。脑电图系统可以覆盖整个头部,并反映大量神经元的整体活动。可以通过脑电图结果来验证光泵浦磁力计在检测事件相关分量中的功效。多变量模式分析能够跟踪神经认知过程随时间的演变。在本文中,我们采用了经典的中文语义一致性范式,并分别收集了脑电图和光泵浦磁力计信号。然后,我们验证了光泵浦磁力计和脑电图在使用互信息指数检测N400中的一致性。多元模式分析揭示了这两种模式的解码性能差异,这可以通过对时间泛化矩阵的动态/稳定编码分析进一步验证。探照灯分析的结果为脑磁图源水平和脑电图传感器水平的这种差异提供了神经基础。这项研究为使用可穿戴脑磁图研究大脑的编码模式开辟了一条新途径,并揭示了两种模式在反映神经元表示模式方面的敏感性差异。
    The application of wearable magnetoencephalography using optically-pumped magnetometers has drawn extensive attention in the field of neuroscience. Electroencephalogram system can cover the whole head and reflect the overall activity of a large number of neurons. The efficacy of optically-pumped magnetometer in detecting event-related components can be validated through electroencephalogram results. Multivariate pattern analysis is capable of tracking the evolution of neurocognitive processes over time. In this paper, we adopted a classical Chinese semantic congruity paradigm and separately collected electroencephalogram and optically-pumped magnetometer signals. Then, we verified the consistency of optically-pumped magnetometer and electroencephalogram in detecting N400 using mutual information index. Multivariate pattern analysis revealed the difference in decoding performance of these two modalities, which can be further validated by dynamic/stable coding analysis on the temporal generalization matrix. The results from searchlight analysis provided a neural basis for this dissimilarity at the magnetoencephalography source level and the electroencephalogram sensor level. This study opens a new avenue for investigating the brain\'s coding patterns using wearable magnetoencephalography and reveals the differences in sensitivity between the two modalities in reflecting neuron representation patterns.
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  • 文章类型: Journal Article
    北极地区形成了一个独特的环境,具有特定的物理,化学,和影响汞(Hg)循环和有限的人为汞来源的生物过程。然而,历史性的全球排放和远距离大气传输导致北极野生动物和水道中汞含量升高。连续大气汞测量,跨越20年,增加的监测点可以更全面地了解北极大气汞随时间的变化。从10个环极空气监测站进行了空气中TGM(总气态汞)的时间序列趋势分析,包括高北极地区,和亚北极地区。GOM(气态氧化汞)和PHg(颗粒结合汞)测量也可在2个北极高地点获得。秋季,亚北极地区的季节平均TGM最低,范围从1.1ngm-3Hyytiälä到1.3ngm-3,小狐狸湖。高北极地区的平均TGM浓度表现出最大的变异性,春季最高的每日平均值在Amderma的4.2ngm-3和齐柏林飞艇的2.4ngm-3之间,主要由当地化学驱动。10个站点中的8个站点的年度TGM趋势分析为阴性。高北极季节性TGM趋势在夏季下降幅度最小。下降趋势从-0.8%到-2.6%yr-1。在亚北极地区,春季出现了最大的显着下降,yr-1在-7.7%至-0.36%之间,而下降一般没有显著趋势。Alert和Zeppelin的GOM和PHg的高北极形态表明,大气汞沉积事件的时间和组成正在发生变化。警惕GOM趋势全年都在增加,而PHg趋势下降或不显著。齐柏林看到了相反的情况,朝着增加PHG和减少GOM的方向发展。过去20年的大气汞趋势表明,整个北极的汞浓度正在下降,虽然不是统一的。这可能是由环境变化驱动的,如植物生产力和海冰动态。
    The Arctic region forms a unique environment with specific physical, chemical, and biological processes affecting mercury (Hg) cycles and limited anthropogenic Hg sources. However, historic global emissions and long range atmospheric transport has led to elevated Hg in Arctic wildlife and waterways. Continuous atmospheric Hg measurements, spanning 20 years, and increased monitoring sites has allowed a more comprehensive understanding of how Arctic atmospheric mercury is changing over time. Time-series trend analysis of TGM (Total Gaseous Mercury) in air was performed from 10 circumpolar air monitoring stations, comprising of high-Arctic, and sub-Arctic sites. GOM (gaseous oxidised mercury) and PHg (particulate bound mercury) measurements were also available at 2 high-Arctic sites. Seasonal mean TGM for sub-Arctic sites were lowest during fall ranging from 1.1 ng m-3 Hyytiälä to 1.3 ng m-3, Little Fox Lake. Mean TGM concentrations at high-Arctic sites showed the greatest variability, with highest daily means in spring ranging between 4.2 ng m-3 at Amderma and 2.4 ng m-3 at Zeppelin, largely driven by local chemistry. Annual TGM trend analysis was negative for 8 of the 10 sites. High-Arctic seasonal TGM trends saw smallest decline during summer. Fall trends ranged from -0.8% to -2.6% yr-1. Across the sub-Arctic sites spring showed the largest significant decreases, ranging between -7.7% to -0.36% yr-1, while fall generally had no significant trends. High-Arctic speciation of GOM and PHg at Alert and Zeppelin showed that the timing and composition of atmospheric mercury deposition events are shifting. Alert GOM trends are increasing throughout the year, while PHg trends decreased or not significant. Zeppelin saw the opposite, moving towards increasing PHg and decreasing GOM. Atmospheric mercury trends over the last 20 years indicate that Hg concentrations are decreasing across the Arctic, though not uniformly. This is potentially driven by environmental change, such as plant productivity and sea ice dynamics.
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  • 文章类型: Journal Article
    小鼠肠道蠕虫通过分泌转化生长因子(TGF)-β模拟物(TGM)来调节宿主的免疫反应,扩大Foxp3+Tregs的种群。TGM包含五个补体控制蛋白(CCP)样结构域,指定D1-D5。虽然缺乏与TGF-β的同源性,TGM直接结合TGF-β受体TβRI和TβRII并刺激初始T细胞分化为Treg。然而,结合的分子决定因素尚不清楚。这里,我们使用表面等离子体共振,等温量热法,核磁共振波谱,和诱变研究TGM如何结合TGF-β受体。我们证明绑定是模块化的,D1-D2与TβRI结合,D3与TβRII结合。D1-D2和D3进一步显示与TGF-β(TβRII)2和TGF-β竞争结合TβRI和TβRII,分别。TGM-D3的溶液结构表明,TGM采用CCP样折叠,但也经过修饰以允许C末端链发散,导致域的扩展和开放潜在的相互作用表面。TGM-D3还包含一个长的结构有序超变环,增加更多潜在的相互作用位点。通过TGM-D3和TβRII变体的NMR位移扰动和结合研究,使用新的相互作用表面和高变环,显示TGM-D3占据与TGF-β结合的TβRII的相同位点。这些结果,结合其他分泌的具有免疫调节活性的CCP样蛋白的鉴定,表明TGM是一个更大的进化可塑性寄生虫效应分子家族的一部分,该分子介导与宿主的新型相互作用。
    The mouse intestinal helminth Heligmosomoides polygyrus modulates host immune responses by secreting a transforming growth factor (TGF)-β mimic (TGM), to expand the population of Foxp3+ Tregs. TGM comprises five complement control protein (CCP)-like domains, designated D1-D5. Though lacking homology to TGF-β, TGM binds directly to the TGF-β receptors TβRI and TβRII and stimulates the differentiation of naïve T-cells into Tregs. However, the molecular determinants of binding are unclear. Here, we used surface plasmon resonance, isothermal calorimetry, NMR spectroscopy, and mutagenesis to investigate how TGM binds the TGF-β receptors. We demonstrate that binding is modular, with D1-D2 binding to TβRI and D3 binding to TβRII. D1-D2 and D3 were further shown to compete with TGF-β(TβRII)2 and TGF-β for binding to TβRI and TβRII, respectively. The solution structure of TGM-D3 revealed that TGM adopts a CCP-like fold but is also modified to allow the C-terminal strand to diverge, leading to an expansion of the domain and opening potential interaction surfaces. TGM-D3 also incorporates a long structurally ordered hypervariable loop, adding further potential interaction sites. Through NMR shift perturbations and binding studies of TGM-D3 and TβRII variants, TGM-D3 was shown to occupy the same site of TβRII as bound by TGF-β using both a novel interaction surface and the hypervariable loop. These results, together with the identification of other secreted CCP-like proteins with immunomodulatory activity in H. polygyrus, suggest that TGM is part of a larger family of evolutionarily plastic parasite effector molecules that mediate novel interactions with their host.
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  • 文章类型: Journal Article
    炎症性肠病(IBD)是一组免疫疾病,可以产生与炎症症状相关的慢性疼痛和疲劳。IBD的治疗仍然是一个重要的障碍,目前的治疗方法仅部分有效或具有显著的副作用。提示需要引发不同作用方式和给药策略的新疗法.TGM1是一种TGF-β模拟物,是从肠道蠕虫寄生虫螺旋多回中发现的,被认为是由寄生虫产生的,以抑制肠道炎症反应,帮助逃避宿主免疫,使其成为一种新型抗炎生物治疗剂的理想候选者。在这里,我们利用了可食用绿藻衣藻莱茵衣藻的表达系统,以可以摄取的形式重组产生活性TGM1。Reinhardtii强表达TGM1,并且如通过调节性T细胞诱导所测量的,所得重组蛋白具有生物活性。当口服给小鼠时,藻类表达的TGM1能够改善体重减轻,淋巴结病,和DSS诱导结肠炎小鼠模型的疾病症状,证明了这种生物制剂作为IBD新型治疗方法的潜力。
    Inflammatory bowel disease (IBD) is a set of immunological disorders which can generate chronic pain and fatigue associated with the inflammatory symptoms. The treatment of IBD remains a significant hurdle with current therapies being only partially effective or having significant side effects, suggesting that new therapies that elicit different modes of action and delivery strategies are required. TGM1 is a TGF-β mimic that was discovered from the intestinal helminth parasite Heligmosomoides polygyrus and is thought to be produced by the parasite to suppress the intestinal inflammation response to help evade host immunity, making it an ideal candidate to be developed as a novel anti-inflammatory bio-therapeutic. Here we utilized the expression system of the edible green algae Chlamydomonas reinhardtii in order to recombinantly produce active TGM1 in a form that could be ingested. C. reinhardtii robustly expressed TGM1, and the resultant recombinant protein is biologically active as measured by regulatory T cell induction. When delivered orally to mice, the algal expressed TGM1 is able to ameliorate weight loss, lymphadenopathy, and disease symptoms in a mouse model of DSS-induced colitis, demonstrating the potential of this biologic as a novel treatment of IBD.
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  • 文章类型: Journal Article
    水稻植物从土壤和环境空气中积累汞,然而,评估这两种来源的汞的贡献仍然具有挑战性。这里,提出了一种实用的方法来预测万山汞矿区(WMM)白米中气态总汞(TGM)对汞的贡献。在这项研究中,水稻种植在不同TGM水平的WMM不同地点的相同低汞土壤中。与IG(地球化学研究所的对照地点相比,贵阳),TGM是WMM的TB(田坝)和ZJW(张家湾)站点水稻叶片和白米中汞的主要来源。随后,水稻叶片中的Hg浓度与TGM对白米中Hg的浓度贡献之间具有良好的相关性。这种相关性使从万山汞矿收集的白米中TGM对汞的贡献成为可能。还估计了整个WMM地区TGM对白米中Hg的贡献,证明白米从空气中吸收14-83%的汞。考虑到TGM对白米中汞的高贡献,我们比较了汞通过吸入和大米消费的相对健康风险,而不是大米消费,是高TGM点成人生物可接触汞的主要途径。本研究提供了汞矿区汞生物地球化学的新知识。
    Rice plants accumulate Hg from the soil and ambient air, however, evaluating the contribution of Hg from these two sources remains challenging. Here, we proposed a practical method to predict the contribution of total gaseous mercury (TGM) to Hg in white rice in Wanshan Hg mine area (WMM). In this study, rice was planted in the same low-Hg soil at different sites of WMM with varying TGM levels. Comparing to the control sites at IG (Institute of Geochemistry, Guiyang), TGM is the dominant source of Hg in rice leaves and white rice at TB (Tianba) and ZJW (Zhangjiawan) sites of WMM. Subsequently, a good correlation between the Hg concentrations in rice leaves and the concentration contributions of TGM to Hg in white rice was obtained. Such a correlation enabled feasible quantification of the contribution of TGM to Hg in white rice collected from the Wanshan Hg mine. The contribution of TGM to Hg in white rice across the WMM area was also estimated, demonstrating that white rice receives 14-83% of Hg from the air. Considering the high contribution of TGM to Hg in white rice, we compared the relative health risks of Hg via inhalation and rice consumption and found that inhalation, rather than rice consumption, was the major pathway for bioaccessible Hg exposure in adults at high-TGM sites. This study provides new knowledge of Hg biogeochemistry in Hg-mining areas.
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  • 文章类型: Journal Article
    这项研究涉及两个波兰地点的环境空气中存在的气态和颗粒结合汞的浓度,在排放结构方面不同,以及与这些汞物种相关的吸入风险估计。总气态汞(TGM)和PM2.5结合汞(PBM)的测量是在Zabrze的城市站和ZswotyPotok的农村站进行的,2014-2015年。这两个地点都位于西里西亚,被认为是欧洲空气污染热点之一。TGM在线测量(Tekran2537)。PM2.5样品是使用低容量采样器采集的。热分解后,通过CVAAS法测定PM中的Hg含量。Zabrze中TGM和PBM的中值浓度分别为2.48ngm-3和37.87pgm-3;同时在兹罗提波托克,分别为1.69ngm-3和27.82pgm-3。显然,观察到TGM和PBM浓度的季节性变化,反映了煤炭燃烧对电力和供暖用途的汞和PM排放的重要性。在最保守的暴露情况下,使用确定性方法进行健康风险评估。获得的HQ比率和累积HI指数低于极限值(<1)。这意味着吸入汞不太可能对健康造成危害。
    This study concerns the concentrations of gaseous and particle-bound mercury present in ambient air of two Polish sites, differing in terms of emission structure, and the estimation of inhalation risks related to those Hg species. The measurements of total gaseous mercury (TGM) and PM2.5-bound mercury (PBM) were performed at an urban station in Zabrze and a rural station in Złoty Potok, in 2014-2015. Both sites are located in Silesia, considered one of the European air pollution hot-spots. TGM was measured on-line (Tekran 2537). PM2.5 samples were taken with the use of low volume samplers. Hg contents in PM were determined by the CVAAS method following thermal decomposition. The median concentrations of TGM and PBM in Zabrze were 2.48 ng m-3 and 37.87 pg m-3, respectively; meanwhile in Zloty Potok, these were 1.69 ng m-3 and 27.82 pg m-3, respectively. Clearly, seasonal variability of TGM and PBM concentrations were observed, reflecting the importance of Hg and PM emissions from coal combustion for power and heating purposes. Health risk assessment was performed using a deterministic approach by the most conservative exposure scenario. The obtained HQ ratios and the cumulative HI indexes were below the limit value (<1). This means an unlikely health hazard due mercury inhalation.
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  • 文章类型: Journal Article
    转移RNA(tRNA)基因和其他RNA聚合酶III转录单位分散在整个核基因组中的高拷贝,并且可以拮抗RNA聚合酶II在其直接染色体位点的转录。先前在酿酒酵母中的工作发现,这种局部沉默需要靠近核仁的tRNA基因的亚核聚类。在这里,我们表明沉默也需要核小体的参与,尽管核小体相互作用的性质似乎与其他形式的转录沉默不同。对组蛋白氨基酸取代的广泛文库的分析发现了影响沉默的大量残基,在组蛋白N末端尾巴和核小体盘表面。所涉及的磁盘表面上的残留物与影响其他调节现象的残留物大不相同。与影响tgm沉默的大量组蛋白残基一致,对染色质修饰突变的调查表明,还需要几种已知影响核小体修饰和定位的酶。这些酶包括Rpd3脱乙酰酶复合物,Hos1脱乙酰酶,Glc7磷酸酶,和RSC核小体重塑活性,但不是其他沉默形式或tRNA基因位点的边界元件功能所需的多种其他活性。讨论了tRNA基因转录复合物与局部染色质之间的通讯模型。
    Transfer RNA (tRNA) genes and other RNA polymerase III transcription units are dispersed in high copy throughout nuclear genomes, and can antagonize RNA polymerase II transcription in their immediate chromosomal locus. Previous work in Saccharomyces cerevisiae found that this local silencing required subnuclear clustering of the tRNA genes near the nucleolus. Here we show that the silencing also requires nucleosome participation, though the nature of the nucleosome interaction appears distinct from other forms of transcriptional silencing. Analysis of an extensive library of histone amino acid substitutions finds a large number of residues that affect the silencing, both in the histone N-terminal tails and on the nucleosome disk surface. The residues on the disk surfaces involved are largely distinct from those affecting other regulatory phenomena. Consistent with the large number of histone residues affecting tgm silencing, survey of chromatin modification mutations shows that several enzymes known to affect nucleosome modification and positioning are also required. The enzymes include an Rpd3 deacetylase complex, Hos1 deacetylase, Glc7 phosphatase, and the RSC nucleosome remodeling activity, but not multiple other activities required for other silencing forms or boundary element function at tRNA gene loci. Models for communication between the tRNA gene transcription complexes and local chromatin are discussed.
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  • 文章类型: Congress
    第八届国际双年度RNA聚合酶I和III会议(“OddPos”)于2012年6月7日至11日在弗吉尼亚州沃伦顿的Airlie中心举行,美国。它由拉瓦尔大学和尤尼斯·肯尼迪·施莱弗国家儿童健康与人类发展研究所赞助,NIH,由RichMaraia和TomMoss组织.会议纪念了PierreThuriaux(1950年1月1日至2012年3月18日),DavidSchneider回忆了他的导师MasayasuNomura(1927-2011)的重要成就。会议的目的是汇集世界上RNA聚合酶I和RNA聚合酶III的专家,以强调和分享他们的最新结果和各种实验方法。会议吸引了来自十二个国家的与会者,大多数人通过口头和海报介绍做出了贡献。会谈分为几场会议,分为10个不同的主题。主旨发言人,伊恩·威利斯,会议以题为“向奇怪的波尔斯发出信号的新监管机构”的演讲开幕,最后由PatrickCramer以他的演讲“保护RNA聚合酶I,II和III转录起始机器。“在这里,我们使用与会者提供的摘要介绍会议的一些亮点。
    The Eighth International Biennial Conference on RNA polymerases I and III (the \'Odd Pols\') was held June 7-11, 2012 at The Airlie Center in Warrenton Virginia, USA. It was sponsored by the Universite Laval and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, and organized by Rich Maraia and Tom Moss. The meeting honored the memory of Pierre Thuriaux (Jan 1, 1950-March 18, 2012) and David Schneider reminisced on the important accomplishments his mentor Masayasu Nomura (1927-2011). The goal of the conference was to bring together the world\'s experts on RNA polymerase I and RNA polymerase III to highlight and share their latest results and varied experimental approaches. The meeting drew attendees from twelve countries and most contributed through oral and poster presentations. The talks were organized into several sessions subdivided into 10 distinct topics. The keynote speaker, Ian Willis, opened the meeting with his presentation entitled \"New Regulators of Signaling to Odd Pols\" and the closing presentation was given by Patrick Cramer with his presentation \"Conservation of the RNA polymerase I, II and III transcription initiation machineries\". Here we present some of the highlights from the meeting using summaries provided by the participants.
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