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Inhibition of pancreatic eZH2 restores progenitor insulin in T1D donor

Signal Transduction and Targeted Therapy 2022年第8期7卷 3045-3053页

作者： keith Al-Hasani Ishant Khurana Lina Mariana Thomas Loudovaris Scott Maxwell K.N.Harikrishnan Jun Okabe Mark eCooper Assam el-Osta Department of Diabetes Central Clinical SchoolMonash UniversityMelbourneVictoria 3004Australia epigenetics in Human Health and Disease Laboratory Central Clinical SchoolMonash UniversityMelbourneVictoria 3004Australia Immunology and Diabetes Unit St Vincent’s Institute of Medical ResearchFitzroyVictoriaAustralia Department of Clinical Pathology The University of MelbourneParkvilleVictoriaAustralia Department of Medicine and Therapeutics The Chinese University of Hong KongSha TinHong Kong SAR Hong Kong Institute of Diabetes and Obesity Prince of Wales HospitalThe Chinese University of Hong Kong3/F Lui Che Woo Clinical Sciences Building30-32 Ngan Shing StreetSha TinHong Kong SAR Li Ka Shing Institute of Health Sciences The Chinese University of Hong KongSha TinHong Kong SAR Faculty of Health Department of TechnologyBiomedical Laboratory ScienceUniversity College CopenhagenCopenhagenDenmark

Type 1 diabetes(T1D)is an autoimmune disease that selectively destroys insulin-producingβ-cells in the *** unmet need in diabetes management,current therapy is focussed on *** the reprogramming of progenitor cells into functional insulin-producingβ-cells has also been proposed this remains controversial and poorly *** challenge is determining why default transcriptional suppression is refractory to exocrine *** the death of a 13-year-old girl with established insulin-dependent T1D,pancreatic cells were harvested in an effort to restore and understand exocrine *** pancreas showed classic silencing ofβ-cell progenitor genes with barely detectable insulin(Ins)***126,a highly selective inhibitor of eZH2 methyltransferase activity influenced H3K27me3 chromatin content and transcriptional control resulting in the expression of coreβ-cell markers and ductal progenitor ***126 also reinstated Ins gene expression despite absoluteβ-cell *** studies show the refractory nature of chromatin characterises exocrine suppression influencingβ-cell *** regeneration studies are warranted to determine if the approach of this n-of-1 study generalises to a broader T1D population.

关键词： eZH2 progenitor donor

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Viscosity and stress autocorrelation function in supercooled water:A molecular dynamics study

Viscosity and stress autocorrelation function in supercooled...

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中国科学院地质与地球物理研究所2002学术年会

作者： keith ReFSON Rutherford Appleton Laboratory ChiltonDidcotOxfordshire OX11 0QXUK

Following our previous study(Guo,G.-*** Zhang,Y.-G,2001,***.,99, 283) which calculates the bulk and shear viscosities of SPC/e water at 30℃and 0.999 g/cm,we performed further molecular dynamics simulations at state points of 0℃,-20℃,-40℃,and -60℃along an approximate isobar with the previous state *** and BACF(stress autocorrelation functions related to shear and bulk viscosities respectively) of high precision are obtained and compared for their similarities and *** and bulk viscosities calculated from them show an increased deviation from real water with decreasing *** correlation functions are then well fitted using a uniform two-step relaxation function including a fast oscillatory Kohlrausch law and a slow straightforward Kohlrausch *** fitting parameters of SACF and BACF are analyzed in detail and several interesting dynamic phenomena are observed, that is,1) The oscillation frequency of SACF(44～48 ps) at short time intervals agree with the stretching mode of hydrogen bonds while that of BACF(7～12 ps) with the bending mode of hydrogen bonds.2) With decreasing temperature,the slow relaxation fraction of BACF increases, while that of SACF keeps constant.3) The exponentsβin Kohlrausch laws with values greater than 1 are obtained for BACF at ambient temperatures.4) With regard to both shear and bulk viscosities, the slow relaxation time largely increases with decreasing temperature,while the fast relaxation time slightly *** phenomena are qualitatively explained and discussed in this paper.

关键词： supercooled water viscosity stress autocorrelation function molecular dynamics

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Two-temperature warm dense hydrogen as a test of quantum protons driven by orbital-free density functional theory electronic forces

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Matter and Radiation at extremes 2020年第6期5卷 48-59页

作者： Dongdong Kang Kai Luo keith Runge S.B.Trickey Department of Physics National University of Defense TechnologyChangshaHunan 410073People’s Republic of China earth and Planets Laboratory Carnegie Institution of Washington5251 Broad Branch Rd.NWWashingtonDC 20015USA Department of Materials Science and engineering University of ArizonaTucsonArizona 85721USA Quantum Theory Project Department of Physics and Department of ChemistryUniversity of FloridaGainesvilleFlorida 32611USA

We consider a steady-state(but transient)situation in which a warm dense aggregate is a two-temperature system with equilibrium electrons at temperature T_(e),ions at T_(i),and T_(e)≠T_(i).Such states are achievable by pump–probe *** warm dense hydrogen in such a twotemperature situation,we investigate nuclear quantum effects(NQes)on structure and thermodynamic properties,thereby delineating the limitations of ordinary ab initio molecular *** use path integral molecular dynamics(PIMD)simulations driven by orbital-free density functional theory(OFDFT)calculations with state-of-the-art noninteracting free-energy and exchange-correlation functionals for the explicit temperature *** calibrate the OFDFT calculations against conventional(explicit orbitals)Kohn–Sham *** find that when the ratio of the ionic thermal de Broglie wavelength to the mean interionic distance is larger than about 0.30,the ionic radial distribution function is meaningfully affected by the inclusion of ***,NQes induce a substantial increase in both the ionic and electronic *** confirms the importance of NQes for highly accurate equation-of-state data on highly driven *** Te>20 kK,increasing Te in the warm dense hydrogen has slight effects on the ionic radial distribution function and equation of state in the range of densities *** addition,we confirm that compared with thermostatted ring-polymer molecular dynamics,the primitive PIMD algorithm overestimates electronic pressures,a consequence of the overly localized ionic description from the primitive scheme.

关键词： orbital quantum electronic

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Hepatic manifestations of non-steroidal inflammatory bowel disease therapy

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World Journal of Hepatology 2015年第27期7卷 2716-2728页

作者： Robert Hirten keith Sultan Ashby Thomas David e Bernstein Division of Gastroenterology North Shore University Hospital--Long Island Jewish Medical Center

Inflammatory bowel disease(IBD) is composed of Crohn's disease and ulcerative colitis and is manifested by both bowel-related and extraintestinal manifestations. Recently the number of therapeutic options available to treat IBD has dramatically increased, with each new medication having its own mechanism of action and side effect profile. A complete understanding of the hepatotoxicity of these medications is important in order to distinguish these complications from the hepatic manifestations of IBD. This review seeks to evaluate the hepatobiliary complications of non-steroid based IBD medications and aide providers in the recognition and management of these side-effects.

关键词： Hepatotoxicity Adverse drug reactions Drug induced

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美国和日本核桃RAPD-PCR反应体系优化

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中南林业科技大学学报 2012年第3期32卷 129-135页

作者：赵鹏 keith e.Woeste 张存旭程飞张硕新蔡靖西北农林科技大学林学院陕西杨凌712100 美国普渡大学森林与自然资源系美国农业部阔叶树种改良与更新中心美国西拉法叶市印第安纳州47907 西北大学生命科学学院西部资源生物与现代生物技术教育部重点实验室陕西西安710069 陕西秦岭森林生态系统国家野外科学观测研究站陕西宁陕711600

核桃属种质资源丰富,其中多数物种木材材质优良,果实可食,营养丰富,为重要的经济树种。以美国白核桃Juglans cinerea、日本核桃Juglans ailantifolia等为材料,通过改良CTAB方法,从嫩芽、新鲜叶片和干叶片中分别提取核桃基因组DNA,并以此... 详细信息

核桃属种质资源丰富,其中多数物种木材材质优良,果实可食,营养丰富,为重要的经济树种。以美国白核桃Juglans cinerea、日本核桃Juglans ailantifolia等为材料,通过改良CTAB方法,从嫩芽、新鲜叶片和干叶片中分别提取核桃基因组DNA,并以此DNA为模板对RAPD-PCR反应体系中的一些重要参数进行摸索和优化试验。结果表明,改良的CTAB法可有效去除细胞内多糖和多酚等杂质对模板DNA的污染,大大提高DNA的数量和质量。优化适合于美国核桃、日本核桃和杂合核桃的RAPD-PCR反应体系为:在20μL的PCR反应体系中,含10 ng模板DNA,0.1 mg/mL牛血清蛋白(BSA),0.25 mmol/L dNTPs,3.5 mmol/L Mg2+,1μL10×Taq DNA聚合酶反应缓冲液,0.5 U Taq聚合酶,5.0 mmol/L RAPD引物。RAPD-PCR反应扩增程序为:92℃变性3 min;93℃变性1 min,35℃复性1 min,72℃延伸1 min,35个循环;72℃后延伸10 min,置4℃保存。

关键词：美国白核桃日本核桃 RAPD 优化

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Three-dimensional reconstruction and comparison of vacuolar membranes in response to viral infection

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Journal of Integrative Plant Biology 2021年第2期63卷 353-364页

作者： Xueting Wang Juncai Ma Xuejiao Jin Ning Yue Peng Gao keith Ka Ki Mai Xian-Bing Wang Dawei Li Byung-Ho Kang Yongliang Zhang State Key Laboratory of Agro-Biotechnology and Ministry of Agriculture Key Laboratory of Soil Microbiology College of Biological SciencesChina Agricultural UniversityBeijing 100193China State Key Laboratory of Agro-Biotechnology School of Life SciencesThe Chinese University of Hong KongHong Kong 999077China

The vacuole is a unique plant organelle that plays an important role in maintaining cellular homeostasis under various environmental stress conditions. However, the effects of biotic stress on vacuole structure has not been examined using three-dimensional(3D) visualization. Here, we performed 3D electron tomography to compare the ultrastructural changes in the vacuole during infection with different viruses. The 3D models revealed that vacuoles are remodeled in cells infected with cucumber mosaic virus(CMV) or tobacco necrosis virus A Chinese isolate(TNV-AC), resulting in the formation of spherules at the periphery of the vacuole. These spherules contain neck-like channels that connect their interior with the cytosol. Confocal microscopy of CMV replication proteins 1 a and 2 a and TNV-AC auxiliary replication protein p23 showed that all of these proteins localize to the *** microscopy revealed that the expression of these replication proteins alone is sufficient to induce spherule formation on the tonoplast, suggesting that these proteins play prominent roles in inducing vacuolar membrane remodeling. This is the first report of the 3D structures of viral replication factories built on the tonoplasts. These findings contribute to our understanding of vacuole biogenesis under normal conditions and during assembly of plant(+) RNA virus replication complexes.

关键词： comparison cucumber mosaic virus electron tomography spherules tobacco necrosis virus A vacuole viral replication

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State of FAIRness in eSFRI Projects

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Data Intelligence 2020年第1期2卷 230-237,316页

作者： Peter Wittenburg Franciska de Jong Dieter van Uytvanck Massimo Cocco keith Jeffery Michael Lautenschlager Hannes Thiemann Margareta Hellstrom Ari Asmi Petr Holub Max Planck Computing and Data Facility Gießenbachstraße 285748 GarchingGermany CLARIN eRIC CLARIN ERIC Drift 10Utrecht 3512 BSThe Netherlands ePOS eRIC Via di Vigna Murata 605Rome 00143Italy keith G Jeffery Consultants FaringdonUK DKRZ Ringgold standard institution Bundesstr.45aHamburgHamburg 20146Germany Department of Physical Geography and ecosystem Ringgold standard institutionLund UniversityScienc Sölvegatan 12Lund 22362Sweden University of Helsinki Ringgold Standard Institution–Institution of Atmospheric and earth System Sciences P.O.Box 64Helsinki 00014Finland BBMRI-eRIC Neue Stiftingtalstrasse 2/B/6 Graz 8010Austria

Since 2009 initiatives that were selected for the roadmap of the european Strategy Forum on Research Infrastructures started working to build research infrastructures for a wide range of research *** important result of the strategic discussions was that distributed infrastructure scenarios were now seen as“complex research facilities”in addition to,for example traditional centralised infrastructures such as *** this paper we look at five typical examples of such distributed infrastructures where many researchers working in different centres are contributing data,tools/services and knowledge and where the major task of the research infrastructure initiative is to create a virtually integrated suite of resources allowing researchers to carry out state-of-the-art *** analysis shows that most of these research infrastructures worked on the Findability,Accessibility,Interoperability and Reusability dimensions before the term“FAIR”was actually *** definition of the FAIR principles and their wide acceptance can be seen as a confirmation of what these initiatives were doing and it gives new impulse to close still existing *** initiatives also seem to be ready to take up the next steps which will emerge from the definition of FAIR maturity *** from these infrastructures should bring in their 10-years’experience in this definition process.

关键词： Infrastructure FAIR Metrics GO FAIR Matrix

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七星瓢虫唇须感器分布和统计特征的雌雄差异(英文)

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昆虫学报 2007年第7期50卷 667-674页

作者： Daniel G.THORNHAM Maureen e.WAKeFIeLD Alison BLACKWeLL Kenneth A.eVANS keith F.A.WALTeRS Central Science Laboratory Sand HuttonYorkYO41 1LZUK Centre for Tropical Veterinary Medicine University of EdinburghEaster Bush Veterinary CentreRoslinMidlothian EH25 9RGUK Scottish Agricultural College West Mains RoadEdinburghEH9 3JGUK

应用扫描电镜观察七星瓢虫Coccinella septempunctata的唇须和附节,以便确认在感应农药残留时起主要作用的化学感受器。研究证明分布在下颚须上的感器类型包括两种锥形感器（兼有机械感受器和化学感受器的功能）和一种钟形感器。同时本... 详细信息

应用扫描电镜观察七星瓢虫Coccinella septempunctata的唇须和附节,以便确认在感应农药残留时起主要作用的化学感受器。研究证明分布在下颚须上的感器类型包括两种锥形感器（兼有机械感受器和化学感受器的功能）和一种钟形感器。同时本文首次报道了对这些感器精确的形态测量,明确了其性二型性。对下颚须的测量表明其左右末节的长度差异与七星瓢虫的性别之间有明显的相关性。文中还记述了下唇须上一种新的钟形感器,其在每个下唇须上的数量大约为12 ~17个。经测量这些机械感受器的平均直径为2.4μm。早期研究中所记述的锥形感器被证实是下唇须上仅有的化学感应器,并且首次证明这些锥形感器的数量与性别相关,雄性平均为18个,雌性平均为16个。附节上也存在性别差异：第2跗节跗垫的宽度在雄性中是从后向前逐渐增大,而在雌性中刚好相反。本文还就这些差异的意义以及新发现感器的功能进行了讨论。

关键词：瓢虫扫描电镜超微结构粘性刚毛形态测量

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Further compatibility tests of the entomopathogenic fungus Lecanicillium muscarium with conventional insecticide products for control of sweetpotato whitefly, Bemisia tabaci on poinsettia plants

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Insect Science 2008年第4期15卷 355-360页

作者： Andrew G. S. Cuthbertson Lisa F. Blackburn Phil Northing Weiqi Luo Raymond J. C. Cannon keith F. A. Waiters Central Science Laboratory Sand Hutton York Y041 1LZ UK

The effect on spore germination of the entomopathogenic fungus Lecanicillium muscarium following direct exposure for 24 h to the insecticides Majestik, Spray Oil, Agri- 50e, Savona and Oberon for the control of both egg and second instar stages of the sweetpotato whitefly, Bemisia tabaci, was determined. exposure to both Agri-50e and Oberon was followed by acceptable spore germination. Infectivity rates ofL. muscarium on poinsettia foliage in the presence of dry residues of the insecticides were also investigated. No significant detrimental effects on the levels of control of B. tabaci were recorded compared with fungus applied to residue-free foliage. Sequential application of the chemicals Savona, Spray Oil and Majestik with the fungus all produced mortalities of second instar B. tabaci above 90%. Incorporation of these chemicals with L. muscarium into integrated control programs for B. tabaci is discussed.

关键词： entomopathogenic fungus integrated pest management insecticidecompatibility Lecanicillium muscarium

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农业知识产权与亚太地区经济利益

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经济资料译丛 2009年第3期 46-63页

作者： keith e. Maskus 周竹南（译）不详东北财经大学国际商务外语学院 116025

一、导言农业经济政策无论在多边层面上还是在不同地区的前沿仍然是国际争论的一个焦点问题。意味深长的农业贸易自由化问题可能是世界贸易组织正在进行的多哈谈判中任何有意义的多边协议的一个必要条件。在亚太地区地区．许多双边协议... 详细信息

一、导言农业经济政策无论在多边层面上还是在不同地区的前沿仍然是国际争论的一个焦点问题。意味深长的农业贸易自由化问题可能是世界贸易组织正在进行的多哈谈判中任何有意义的多边协议的一个必要条件。在亚太地区地区．许多双边协议都在不同程度上涉及到对农业的支持与贸易政策。很显然，日本、韩国及其它东亚国家相对来说仍仅限于食品贸易；而美国，加拿大和澳大利亚对某些农产品的保护力度仍很大。

关键词：农业知识产权亚太地区经济利益农业贸易自由化农业经济政策世界贸易组织焦点问题多边协议

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