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| 1 | A community-derived classification for extant lycophytes and ferns显示文摘发展史长通知了蕨类植物分类。当我们推断进化的树的能力改善了,针对认出生来的组的分类变得逐渐地预兆、稳定。这里,我们为 lycophytes 和蕨纲植物提供一个现代、全面分类,在下面,利用一条基于社区的途径类水平。我们 monophyly 用作主要标准让 taxa,而且目的识别保存两个广泛地被接受的存在 taxa 和界限并且与我们蕨类植物发展史的理解一致。总共,这个分类对待一在 337 个类, 51 个家庭, 14 目,和二个班估计了 11 916 种类。这个分类没在 lycophyte 和蕨纲植物上作为最后的词被打算分类,而是当前的假设的概括陈述,源于最好的可得到的数据并且在问题由熟悉植物的那些大多数塑造了。我们希望它将在蕨类植物上为最近的文学的那些想要的参考用作一个资源发展史和分类,为指导未来调查的一个框架,和推进讲话的刺激。 | Eric Schuettpelz Harald Schneider Alan R. Smith Peter Hovenkamp Jefferson Prado Germinal Rouhan Alexandre Salino Michael Sundue Thafs Elias Almeida Barbara Parris Emily B. Sessa Ashley R. Field Andre Luis de Gasper Carl J. Rothfels Michael D. Windham Marcus Lehnert Benjamin Dauphin Atsushi Ebihara Samuli Lehtonen Pedro Bond Schwartsburd Jordan Metzgar Li-Bing Zhang Li-Yaung Kuo Patrick J. Brownsey Masahiro Kato Marcelo Daniel Arana Francine C. Assis Michael S. Barker David S. Barrington Ho-Ming Chang Yi-Han Chang Yi-Shan Chao Cheng-Wei Chen De-Kui Chen Wen-Liang Chiou Vinicius Antonio de Oliveira Dittrich Yi-Fan Duan Jean-Yves Dubuisson Donald R. Farrar Susan Fawcett Jose Maria Gabriel y Galan Luiz Armando de Araujo Goes-Neto Jason R. Grant Amanda L. Grusz Christopher Haufler Warren Hauk Hai He Sabine Hennequin Regina Yoshie Hirai Layne Huiet Michael Kessler Petra Korall Paulo H. Labiak Anders Larsson Blanca Leen Chun-Xiang Li Fay-Wei Li Melanie Link-Perez Hong-Mei Liu Ngan Thi Lu Esteban I. Meza-Torres Xin-Yuan Miao Robbin Moran Claudine Massi Mynssens Nathalie Nagalingum Benjamin Ollgaard Alison M. Paul Jovani B. de S. Pereira Leon R. Perrie Monica Ponce Tom A. Ranker Christian Schulz Wataru Shinohara Alexander Shmakov Erin M. Sigel Filipe Soares de Souza Lana da Silva Sylvestre Weston Testo Luz Amparo Triana-Moreno Chie Tsutsumi Hanna Tuomisto IvAn A. Valdespino Alejandra Vasco Raquel Stauffer Viveros Alan Weakley Ran Wei Stina Weststrand Paul G. Wolf George Yatskievych Xiao-Gang Xu Yue-Hong Yan Liang Zhang Xian-Chun Zhang Xin-Mao Zhou | 2016 | Journal of Systematics and Evolution2016，54，6： | 44 |
| 2 | LncRNA Dum interacts with Dnmts to regulate Dppa2 expression during myogenic differentiation and muscle regeneration显示文摘新兴的研究在少些在染色质水平,但是相对调整基因表示记录长非编码的 RNA (LncRNAs ) 的角色被知道他们怎么调整 DNA methylation。这里,我们识别 lncRNA, Dum (发展联系 pluripotency 2 (Dppa2 ) 在上游的有约束力的肌肉 lncRNA ) 在骨胳的 myoblast 房间。Dum 的表示动态地在 vitro 并且在 vivo 在 myogenesis 期间被调整。它被在 myoblast 区别之上有约束力的 MyoD transcriptionally 也导致。功能的分析证明它支持 myoblast 区别和导致损坏的肌肉新生。机械学地, Dum 被发现它的附近的基因到沉默, Dppa2,在通过招募的 cis Dnmt1, Dnmt3a 和 Dnmt3b。而且, intrachromosomal 在 Dum 地点和 Dppa2 倡导者之间循环为 Dum/Dppa2 相互作用是必要的。一起,我们识别了与 Dnmts 交往调整 myogenesis 的新奇 lncRNA。 | Lijun Wang Yu Zhao Xichen Bao Xihua Zhu Yvonne Ka-yin Kwok Kun Sun Xiaona Chen Yongheng Huang Ralf Jauch Miguel A Esteban Hao Sun Huating Wang | 2015 | Cell Research2015，25，3： | 34 |
| 3 | 中国婴幼儿接种吸附无细胞百白破灭活脊髓灰质炎和b型流感嗜血杆菌(结合)联合疫苗的安全性和免疫原性研究显示文摘目的比较吸附无细胞百白破灭活脊髓灰质炎和b型流感嗜血杆菌(结合)联合疫苗(DTaP—IPV//PRP~T联合疫苗)与吸附无细胞百白破联合疫苗(DTaP)、b型流感嗜血杆菌结合疫苗(Hib结合疫苗)、注射用灭活脊髓灰质炎疫苗(IPV)的免疫原性和安全性。方法受试者随机分为三组。试验组(A组和B组)分别于2、3、4月龄和3、4、5月龄接种DTaP—IPV//PRP~T联合疫苗,对照组(C组)于3、4、5月龄分别同时接种DTaP、Hib结合疫苗和IPV;3个组均在18~20月龄时加强接种一次。检测每种抗原的抗体滴度,并分别对A、B组与C组的血清保护率/血清转换率进行非劣效性检验。记录每次接种后的安全性数据,并评价疫苗的安全性。结果DTaP.IPV//PRP~T联合疫苗采用2、3、4月龄或者3、4、5月龄接种程序相对于DTaP、Hib结合疫苗和IPV在基础免疫及18~20月龄的加强免疫,对每种抗原的血清保护率/血清转换率均为非劣效;接种DTaP—IPV//PRP~T联合疫苗后安全性良好,并与对照疫苗相似。结论DTaP—IPV//PRP~T联合疫苗对中国婴幼儿具有很高的免疫原性和良好的安全性,并与对照疫苗具有可比性。 | 李艳萍 李凤祥 侯启明 李长贵 李亚南 陈福生 胡学忠 苏文斌 张庶民 方捍华 叶强 曾天德 刘陶宣 李秀必 黄运能 邓曼玲 李荣成 张燕平 Esteban Ortiz | 2011 | 中华流行病学杂志2011，32，8： | 24 |
| 4 | The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters显示文摘最近的研究在众多的生物过程增加了我们长 noncoding RNA (lncRNAs ) 的理解,但是很少在体的房间 reprogramming 检验了他们的角色。通过表示介绍并且功能的屏蔽,我们鉴别了大 intergenic noncoding RNA p21 (lincRNA-p21 ) 损害 reprogramming。尤其是, lincRNA-p21 被 p53 导致,但是不在 reprogramming 支持 apoptosis 或房间老朽。相反, lincRNA-p21 与 H3K9 methyltransferase SETDB1 和维护 DNA methyltransferase DNMT1 联系,它被 RNA 有约束力的蛋白质 HNRNPK 便于。因而, lincRNA-p21 由在 pluripotency 基因倡导者支撑 H3K9me3 或 CpG methylation 阻止 reprogramming。我们的结果在 reprogramming 提供卓见进 lncRNAs 的角色并且建立在 p53 和 heterochromatin 规定之间的一个新奇连接。 | Xichen Bao Haitao Wu Xihua Zhu Xiangpeng Guo Andrew P Hutchins Zhiwei Luo Hong Song Yongqiang Chen Keyu Lai Menghui Yin Lingxiao Xu Liang Zhou Jiekai Chen Dongye Wang Baoming Qin Jon Frampton Hung-Fat Tse Duanqing Pei Huating Wang Biliang Zhang Miguel A Esteban | 2015 | Cell Research2015，25，1： | 21 |
| 5 | Phylogenetic alpha and beta diversity in tropical tree assemblages along regionalscale environmental gradients in northwest South America显示文摘Aims Environmental gradients are drivers of species diversity;however,we know relatively little about the evolutionary processes underlying these relationships.A potentially powerful approach to studying diversity gradients is to quantify the phylogenetic structure within and between assemblages arrayed along broad spatial and environmental gradients.Here,we evaluate the phylogenetic structure of plant assemblages along an environmental gradient with the expectation that the habitat specialization of entire lineages is an important evolutionary pattern influencing the structure of tree communities along environmental gradients.Methods We evaluated the effect of several environmental variables on the phylogenetic structure of plant assemblages in 145 plots distributed in northwestern South America that cover a broad environmental gradient.The phylogenetic alpha diversity was quantified for each plot and the phylogenetic beta diversity between each pair of plots was also quantified.Both the alpha and beta diversity measures were then related to spatial and environmental gradients in the study system.Important Findings We found that gradients in temperature and potential evapotranspiration have a strong relationship with the phylogenetic alpha diversity in our study system,with phylogenetic overdispersion in low temperatures and phylogenetic clustering at higher temperatures.Further,the phylogenetic beta diversity between two plots increases with an increasing difference in temperature,whereas annual precipitation was not a significant predictor of community phylogenetic turnover.We also found that the phylogenetic structure of the plots in our study system was related to the degree of seasonal flooding and seasonality in precipitation.In particular,more stressful environments such as dry forests and flooded forests showed phylogenetic clustering.Finally,in contrast with previous studies,we find that phylogenetic beta diversity was not strongly related to the spatial distance separating two forest plots,which may be the result of the importance of the three independent mountain ranges in our study system,which generate a high degree of environmental variation over very short distances.In conclusion,we found that environmental gradients are important drivers of both phylogenetic alpha and phylogenetic beta diversities in these forests over spatial distance. | Sebastián González-Caro María Natalia Umaña Esteban Álvarez Pablo R.Stevenson Nathan G.Swenson | 2014 | Journal of Plant Ecology2014，7，2： | 17 |
| 6 | Piglets cloned from induced pluripotent stem cells显示文摘 | Nana Fan Jijun Chen Zhouchun Shang Hongwei Dou Guangzhen Ji Qingjian Zou Lu Wu Lixiazi He Fang Wang Kai Liu Na Liu Jianyong Han Qi Zhou Dengke Pan Dongshan Yang Bentian Zhao Zhen Ouyang Zhaoming Liu Yu Zhao Lin Lin Chongming Zhong Quanlei Wang Shouqi Wang Ying Xu Jing Luan Yu Liang Zhenzhen Yang Jing Li Chunxia Lu Gabor Vajta Ziyi Li Hongsheng Ouyang Huayan Wang Yong Wang Yang Yang Zhonghua Liu Hong Wei Zhidong Luan Miguel A Esteban Hongkui Deng Huanming Yang Duanqing Pei Ning Li Gang Pei Lin Liu Yutao Du Lei Xiao Liangxue Lai | 2013 | Cell Research2013，23，1： | 12 |
| 7 | Arabidopsis Squalene Epoxidase 3 (SQE3) Complements SQE1 and Is Important for Embryo Development and Bulk Squalene Epoxidase Activity显示文摘在 mevalonate 小径的 multigenic 家庭的存在为涉及植物甾醇的生合成的小径部件建议分叉的功能的角色。Squalene epoxidases (SQE ) 是这条小径的关键部件,并且 Squalene Epoxidase 1 (SQE1 ) 在这 biosynthetic 步作为基本的酶被识别了。在现在的工作,我们扩大了留下的 SQE 家庭成员的描述,种系发生地在真 SQE 和对 Brassicaceae 独占的象 SQE 一样蛋白质的一个亚科之间解决。真 SQE 家庭成员, Squalene Epoxidase 2 (SQE2 ) 和 Squalene Epoxidase 3 (SQE3 ) 的功能的描述,显示那 SQE3,然而并非 SQE2,在 Arabidopsis 贡献体积 SQE 活动,与积累 squalene 并且显示敏感到 terbinafine 的 sqe3-1 异种。我们遗传上证明 SQE3 似乎在胚胎开发起一个特别地重要的作用。另外, SQE1 和 SQE3 两个都在 endoplasmic 蜂窝胃本地化,并且 SQE3 能机能上地补充 SQE1。因此, SQE1 和 SQE3 似乎是在在 Arabidopsis 的工厂 SQE 活动的提升的二机能上地不相等的冗余的基因。 | Sara Laranjeira Vitor Amorim-Silva Alicia Esteban Monserrat Arro Albert Ferrer Rui Manuel Tavares Miguel Angel Botella Abel Rosado Herlander Azevedo | 2015 | Molecular Plant2015，8，7： | 12 |
| 8 | Taking advantage of the potential of mesenchymal stromal cells in liver regeneration:Cells and extracellular vesicles as therapeutic strategies显示文摘Cell-based therapies for acute and chronic liver diseases are under continuous progress. Mesenchymal stem/stromal cells(MSCs) are multipotent cells able to migrate selectively to damaged tissue and contribute to its healing and regeneration. The MSC pro-regenerative effect occurs due to their immunomodulatory capacity and their ability to produce factors that promote cell protection and survival. Likewise,it has been observed that part of their paracrine effect is mediated by MSC-derived extracellular vesicles(EVs). EVs contain proteins,lipids and nucleic acids(DNA,m RNA,mi RNA,lnc RNA) from the cell of origin,allowing for intercellular communication. Recently,different studies have demonstrated that MSC-derived EVs could reproduce,at least in part,the biological effects obtained by MSCbased therapies. Moreover,due to EVs' stability for long periods of time and easy isolation methods they have become a therapeutic option to MSCs treatments. This review summarizes the latest results achieved in clinical trials using MSCs as cell therapy for liver regeneration,the role of EVs in liver physiopathology and the potential of MSC-derived EVs as intercellular mediators and therapeutic tools in liver diseases. | Esteban Juan Fiore Luciana María Domínguez Juan Bayo Mariana Gabriela García Guillermo Daniel Mazzolini | 2018 | World Journal of Gastroenterology2018，24，23： | 9 |
| 9 | Cerium,manganese and cerium/manganese ceramic monolithic catalysts.Study of VOCs and PM removal显示文摘Ceramic supported cerium, manganese and cerium-manganese catalysts were prepared by direct impregnation of aqueous precursor, and characterized by scanning electron microscopy(SEM), X-ray diffraction(XRD), Brunauer-Emmett-Teller method(BET), temperature programmed reduction(H_2-TPR), X-ray photoelectron spectroscopy(XPS) acidity measurements and electrical conductivity. The catalytic activity was evaluated for volatile organic compounds(VOC)(ethanol, methyl ethyl ketone and toluene) oxidation. Additionally, catalysts were tested in particulate matter(PM) combustion. The characterization results indicated that Ce was in the form of Ce^(4+) and Ce^(3+), and Mn existed in the form of Mn^(4+) and Mn^(3+) on the surface of the Mn/AC sample and in the form of Mn^(4+) in the Ce/Mn/AC monolith. VOC oxidation results revealed that the Ce/Mn/AC sample showed an excellent performance compared with ceramic supported CeO_2(Ce/AC) and MnO_x(Mn/AC) samples. The PM combustion was also higher on Ce/Mn/AC monoliths. The enhanced catalytic activity was mainly attributed to the Ce and Mn interaction which enhanced the acidity, conductivity and the reducibility of the oxides. | COLMAN-LERNER Esteban PELUSO Miguel Andres SAMBETH Jorge THOMAS Horacio | 2016 | Journal of Rare Earths2016，34，7： | 9 |
| 10 | Effects of length and application rate of rice straw mulch on surface runoff and soil loss under laboratory simulated rainfall显示文摘Forest land affected by deforestation yields high soil and water losses.Suitable management practices need to be found that can reduce these losses and achieve ecological and hydrological sustainability of the deforested areas.Mulch has been found to be effective in reducing soil losses;straw mulch is easy to apply,contributes soil organic matter,and is efficient since the day of application.However,the complex effects of rice straw mulch with different application rates and lengths on surface runoff and soil loss have not been clarified in depth.The current paper evaluates the efficiency of rice straw mulch in reducing the hydrological response of a silty clay loam soil under high intensity and low frequency rainfall events(tap water with total depth of 49 mm and intensity of 98 mm/h)simulated in the laboratory.Surface runoff and soil loss at three lengths of the straw(10,30,and 200 mm)and three application rates(1,2,and 3 Mg/ha)were measured in 50 cm(width)×100 cm(length)×10 cm(depth)plots with disturbed soil samples(aggregate soil size<4 mm)collected in a deforested area.Bare soil was used as control experiment.Runoff volume and erosion were significantly(at p<0.05)lower in mulched soils compared to control plots.These reductions were ascribed to the water absorption capacity of the rice straw and the protection cover of the mulch layer.The minimum runoff was observed for a mulch layer of3 Mg/ha of straw with a length of 200 mm.The lowest soil losses were found with straw length of10 mm.The models developed predict runoff and erosion based on simple linear functions of mulch application rate and length,and can be used for a suitable hydrological management of soil.It is concluded that,thanks to rice straw mulch used as an organic soil conditioner,soil erosion and surface runoff are significantly(at p<0.05)reduced,and the mulch protection contributes to reduce the risk of soil degradation.Further research is,however,needed to analyze the upscaling of the hydrological effects of mulching from the plot to the hillslope scale. | Misagh Parhizkar Mahmood Shabanpour Manuel Esteban Lucas-Borja Demetrio Antonio Zema Siyue Li Nobuaki Tanaka Artemio Cerdà | 2021 | International Journal of Sediment Research2021，36，4： | 8 |
| 11 | Interleukin-28B Polymorphism Improves Viral Kinetics and Is the Strongest Pretreatment Predictor of Sustained Virologic Response in Genotype 1 Hepatitis C Virus显示文摘 | Alexander J. Thompson Andrew J. Muir Mark S. Sulkowski Dongliang Ge Jacques Fellay Kevin V. Shianna Thomas Urban Nezam H. Afdhal Ira M. Jacobson Rafael Esteban Fred Poordad Eric J. Lawitz Jonathan McCone Mitchell L. Shiffman Greg W. Galler William M. Lee | 2010 | Gastroenterology2010，，1： | 7 |
| 12 | A transition prediction method for flow over airfoils based on high-order dynamic mode decomposition显示文摘This article presents a novel approach for predicting transition locations over airfoils,which are used to activate turbulence model in a Reynolds-averaged Navier-Stokes flow solver.This approach combines Dynamic Mode Decomposition(DMD)with e^Ncriterion.The core idea is to use a spatial DMD analysis to extract the modes of unstable perturbations from a steady flowfield and substitute the local Linear Stability Theory(LST)analysis to quantify the spatial growth of Tollmien–Schlichting(TS)waves.Transition is assumed to take place at the stream-wise location where the most amplified mode’s N-factor reaches a prescribed threshold and a turbulence model is activated thereafter.To improve robustness,the high-order version of DMD technique(known as HODMD)is employed.A theoretical derivation is conducted to interpret how a spatial highorder DMD analysis can extract the growth rate of the unsteady perturbations.The new method is validated by transition predictions of flows over a low-speed Natural-Laminar-Flow(NLF)airfoil NLF0416 at various angles of attack and a transonic NLF airfoil NPU-LSC-72613.The transition locations predicted by our HODMD/e^Nmethod agree well with experimental data and compare favorably to those obtained by some existing methods■.It is shown that the proposed method is able to predict transition locations for flows over different types of airfoils and offers the potential for application to 3D wings as well as more complex configurations. | Mengmeng WU Zhonghua HAN Han NIE Wenping SONG Soledad Le CLAINCHE Esteban FERRER | 2019 | Chinese Journal of Aeronautics2019，32，11： | 7 |
| 13 | Mechanical and natural ventilation systems in a greenhouse designed using computational fluid dynamics显示文摘The aim of this study was to analyse air exchange and temperature distribution in a greenhouse with combined mechanical and natural ventilation and to design more efficient mechanical ventilation systems.For this purpose,a computational fluid dynamics(CFD)model of the greenhouse was used.Three configurations were considered:Configuration 1(mechanical ventilation and closed roof ventilators),Configurations 2 and 3(mechanical ventilation and roof ventilators open 30%and 100%,respectively).After validation,the CFD model was used to improve the design of the greenhouse mechanical ventilation system in each of the three configurations analyzed.Four greenhouse lengths,28 m,50 m,75 m and 100 m,were used in the simulations.Compared to fan ventilation only,roof ventilation improved the climate of fan-ventilated greenhouses in terms of the air exchange rate(22%)and climate uniformity because the internal air was mixed better than with mechanical ventilation only.As the greenhouse length increased,more advantages were achieved with natural ventilation compared to mechanical ventilation.For most configurations,there was a strong linear correlation between temperature gradient and greenhouse length.The greenhouse whose regression line had the steepest slope was the one with closed roof ventilators.Increasing the fan capacity produced a general reduction in temperature,but the effect was less intense for the greenhouses with open roof ventilators.Compared to box inlet ventilators,an enlarged continuous inlet in the wall opposite the fans increased overall system performance because it eliminated backflow recirculation zones,which are prone to produce high temperatures. | Jorge Flores-Velazquez Juan I.Montero Esteban J.Baeza Juan C.Lopez | 2014 | International Journal of Agricultural and Biological Engineering2014，7，1： | 7 |
| 14 | Characterization of hepatitis B virus X gene quasispecies complexity in mono-infection and hepatitis delta virus superinfection显示文摘Hepatitis delta virus(HDV) seems to strongly suppress hepatitis B virus(HBV)replication, although little is known about the mechanism of this interaction. Both these viruses show a dynamic distribution of mutants, resulting in viral quasispecies. Next-generation sequencing is a viable approach for analyzing the composition of these mutant spectra. As the regulatory hepatitis B X protein(HBx) is essential for HBV replication, determination of HBV X gene(HBX)quasispecies complexity in HBV/HDV infection compared to HBV monoinfection may provide information on the interactions between these two viruses.AIM To compare HBV quasispecies complexity in the HBX 5' region between chronic hepatitis delta(CHD) and chronic HBV mono-infected patients.METHODS Twenty-four untreated patients were included: 7/24(29.2%) with HBeAgnegative chronic HBV infection(CI, previously termed inactive carriers), 8/24(33.3%) with HBeAg-negative chronic hepatitis B(CHB) and 9/24(37.5%) with CHD. A serum sample from each patient was first tested for HBV DNA levels.The HBX 5' region [nucleotides(nt) 1255-1611] was then PCR-amplified for subsequent next-generation sequencing(MiSeq, Illumina, United States). HBV quasispecies complexity in the region analyzed was evaluated using incidencebased indices(number of haplotypes and number of mutations), abundancebased indices(Hill numbers of order 1 and 2), and functional indices(mutation frequency and nucleotide diversity). We also evaluated the pattern of nucleotide changes to investigate which of them could be the cause of the quasispecies complexity.RESULTS CHB patients showed higher median HBV-DNA levels [5.4 logIU/mL,interquartile range(IQR) 3.5-7.9] than CHD(3.4 logIU/mL, IQR 3-7.6)(P = n.s.)or CI(3.2 logIU/mL, IQR 2.3-3.5)(P < 0.01) patients. The incidence and abundance indices indicated that HBV quasispecies complexity was significantly greater in CI than CHB. A similar trend was observed in CHD patients, although only Hill numbers of order 2 showed statistically significant differences(CHB2.81, IQR 1.11-4.57 vs CHD 8.87, 6.56-11.18, P = 0.038). There were no significant differences in the functional indices, but CI and CHD patients also showed a trend towards greater complexity than CHB. No differences were found for any HBV quasispecies complexity indices between CHD and CI patients. G-to-A and C-to-T nucleotide changes, characteristic of APOBEC3 G, were higher in CHD and CI than in CHB in genotype A haplotypes, but not in genotype D. The proportion of nt G-to-A vs A-to-G changes and C-to-T vs T-to-C changes in genotype A and D haplotypes in CHD patients showed no significant differences. In CHB and CI the results of these comparisons were dependent on HBV genotype.CONCLUSION The lower-replication CHD and CI groups show a trend to higher quasispecies complexity than the higher-replication CHB group. The mechanisms associated with this greater complexity require elucidation. | Cristina Godoy David Tabernero Sara Sopena Josep Gregori Maria Francesca Cortese Carolina González Rosario Casillas Mar?al Yll Ariadna Rando Rosa López-Martínez Josep Quer Gloria González-Aseguinolaza Rafael Esteban Mar Riveiro-Barciela Maria Buti Francisco Rodríguez-Frías | 2019 | World Journal of Gastroenterology2019，25，13： | 6 |
| 15 | Detection of hyper-conserved regions in hepatitis B virus X gene potentially useful for gene therapy显示文摘AIM To detect hyper-conserved regions in the hepatitis B virus(HBV) X gene(HBX) 5' region that could be candidates for gene therapy.METHODS The study included 27 chronic hepatitis B treatmentnaive patients in various clinical stages(from chronic infection to cirrhosis and hepatocellular carcinoma, both HBeA g-negative and HBeA g-positive), and infected with HBV genotypes A-F and H. In a serum sample from each patient with viremia > 3.5 log IU/m L, the HBX 5' end region [nucleotide(nt) 1255-1611] was PCRamplified and submitted to next-generation sequencing(NGS). We assessed genotype variants by phylogenetic analysis, and evaluated conservation of this region by calculating the information content of each nucleotide position in a multiple alignment of all unique sequences(haplotypes) obtained by NGS. Conservation at the HBx protein amino acid(aa) level was also analyzed.RESULTS NGS yielded 1333069 sequences from the 27 samples, with a median of 4578 sequences/sample(2487-9279, IQR 2817). In 14/27 patients(51.8%), phylogenetic analysis of viral nucleotide haplotypes showed a complex mixture of genotypic variants. Analysis of the information content in the haplotype multiple alignments detected 2 hyper-conserved nucleotide regions, one in the HBX upstream non-coding region(nt 1255-1286) and the other in the 5' end coding region(nt 1519-1603). This last region coded for a conserved amino acid region(aa 63-76) that partially overlaps a Kunitz-like domain.CONCLUSION Two hyper-conserved regions detected in the HBX 5' end may be of value for targeted gene therapy, regardless of the patients' clinical stage or HBV genotype. | Carolina González David Tabernero Maria Francesca Cortese Josep Gregori Rosario Casillas Mar Riveiro-Barciela Cristina Godoy Sara Sopena Ariadna Rando Marcal Yll Rosa Lopez-Martinez Josep Quer Rafael Esteban Maria Buti Francisco Rodríguez-Frías | 2018 | World Journal of Gastroenterology2018，24，19： | 6 |
| 16 | Direct conversion of human fibroblasts into retinal pigment epithelium-like cells by defined factors显示文摘功能的网膜的颜料上皮(RPE ) 的产生具有到再生药的地的大治疗学的兴趣并且可以为网膜的退化疾病提供可能的痊愈,包括年龄相关的有斑点的退化(AMD ) 。尽管 RPE 房间能从胚胎的干细胞被生产或导致了 pluripotent 干细胞,决定系的抄写因素驾驶的直接房间 reprogramming 提供一条立即的线路给他们的产生。由监视人的 RPE 特定的 Best1::GFP 记者,我们报导进 RPE 系使用的人的成纤维细胞的变换定义抄写因素的集合。我们发现 Best1::GFP 积极房间形成了殖民地并且展出了早阶段 RPE 房间的词法、分子的特征。而且,他们能在 Retinoic 酸(RA ) 和表明小径的声音的刺猬(嘘) 的激活之上获得色素沉着。我们的学习不仅建立了一个理想的平台调查调整 RPE 房间命运决心的 transcriptional 网络,而且提供了其他的策略产生为疾病建模,屏蔽的药,和网膜的退化的房间治疗补充 pluripotent 干细胞的使用的功能的 RPE 房间。 | Kejing Zhang Guang-Hui Liu Fei Yi Nuria Montserrat Tomoaki Hishida Concepcion Rodriguez Esteban Juan Carlos Izpisua Belmonte] | 2014 | Protein & Cell2014，5，1： | 6 |
| 17 | Quasispecies dynamics in main core epitopes of hepatitis B virus by ultra-deep-pyrosequencing显示文摘AIM:To investigate the variability of the main immunodominant motifs of hepatitis B virus(HBV) core gene by ultra-deep-pyrosequencing(UDPS).METHODS:Four samples(2 genotype A and 2 genotype D) from 4 treatment-na ve patients were assessed for baseline variability.Two additional samples from one patient(patient 4,genotype D) were selected for analysis:one sample corresponded to a 36-mo treatment-free period from baseline and the other to the time of viral breakthrough after 18 mo of lamivudine treatment.The HBV region analyzed covered amino acids 40 to 95 of the core gene,and included the two main epitopic regions,Th50-69 and B74-84.UDPS was carried out in the Genome Sequencer FLX system(454 Life Sciences,Roche).After computer filtering of UDPS data based on a Poisson statistical model,122 813 sequences were analyzed.The most conserved position detected by UDPS was analyzed by site-directed mutagenesis and evaluated in cell culture.RESULTS:Positions with highest variability rates were mainly located in the main core epitopes,confirming their role as immune-stimulating regions.In addition,the distribution of variability showed a relationship with HBV genotype.Patient 1(genotype A) presented the lowest variability rates and patient 2(genotype A) had 3 codons with variability higher than 1%.Patient 3 and 4(both genotype D) presented 5 and 8 codons with variability higher than 1%,respectively.The median baseline frequencies showed that genotype A samples had higher variability in epitopic positions than in the other positions analyzed,approaching significance(P = 0.07,sample 1 and P = 0.05,sample 2).In contrast,there were no significant differences in variability between the epitopic and other positions in genotype D cases.Interestingly,patient 1 presented a completely mutated motif from amino acid 64 to 67(E 64 LMT 67),which is commonly recognized by T helper cells.Additionally,the variability observed in all 4 patients was particularly associated with the E 64 LMT 67 motif.Codons 78 and 79 were highly conserved in all samples,in keeping with their involvement in the interaction between the HBV virion capsid and the surface antigens(HBsAg).Of note,codon 76 was even more conserved than codons 78 and 79,suggesting a possible role in HBsAg interactions or even in hepatitis B e antigen conformation.Sequential analysis of samples from patient 4(genotype D) illustrated the dynamism of the HBV quasispecies,with strong selection of one minor baseline variant coinciding with a decrease in core variability during the treatment-free and lamivudinetreated period.The drop in variability seemed to result from a 'steady state' situation of the HBV quasispecies after selection of the variant with greatest fitness.CONCLUSION:Host immune pressure seems to be the main cause of HBV core evolution.UDPS analysis is a useful technique for studying viral quasispecies. | Maria Homs Maria Buti David Tabernero Josep Quer Alex Sanchez Noelia Corral Rafael Esteban Francisco Rodriguez-Frias | 2012 | World Journal of Gastroenterology2012，18，42： | 5 |
| 18 | Analysis of hepatitis B virus preS1 variability and prevalence of the rs2296651 polymorphism in a Spanish population显示文摘AIM To determine the variability/conservation of the domain of hepatitis B virus(HBV) pre S1 region that interacts with sodium-taurocholate cotransporting polypeptide(hereafter, NTCP-interacting domain) and the prevalence of the rs2296651 polymorphism(S267 F, NTCP variant) in a Spanish population. METHODS Serum samples from 246 individuals were included and divided into 3 groups: patients with chronic HBV infection(CHB)(n = 41, 73% Caucasians), patients with resolved HBV infection(n = 100, 100% Caucasians) and an HBV-uninfected control group(n = 105, 100% Caucasians). Variability/conservation of the amino acid(aa) sequences of the NTCPinteracting domain,(aa 2-48 in viral genotype D) and a highly conserved pre S1 domain associated with virion morphogenesis(aa 92-103 in viral genotype D) were analyzed by next-generation sequencing and compared in 18 CHB patients with viremia > 4 log IU/mL. The rs2296651 polymorphism was determined in all individuals in all 3 groups using an in-house real-time PCR melting curve analysis.RESULTS The HBV pre S1 NTCP-interacting domain showed a high degree of conservation among the examined viral genomes especially between aa 9 and 21(in the genotype D consensus sequence). As compared with the virion morphogenesis domain, the NTCPinteracting domain had a smaller proportion of HBV genotype-unrelated changes comprising > 1% of the quasispecies(25.5% vs 31.8%), but a larger proportion of genotype-associated viral polymorphisms(34% vs 27.3%), according to consensus sequences from Gen Bank patterns of HBV genotypes A to H. Variation/conservation in both domains depended on viral genotype, with genotype C being the most highly conserved and genotype E the most variable(limited finding, only 2 genotype E included). Of note, proline residues were highly conserved in both domains, and serine residues showed changes only to threonine or tyrosine in the virion morphogenesis domain. The rs2296651 polymorphism was not detected in any participant.CONCLUSION In our CHB population, the NTCP-interacting domain was highly conserved, particularly the proline residues and essential amino acids related with the NTCP interaction, and the prevalence of rs2296651 was low/null. | Rosario Casillas David Tabernero Josep Gregori Irene Belmonte Maria Francesca Cortese Carolina González Mar Riveiro-Barciela Rosa Maria López Josep Quer Rafael Esteban Maria Buti Francisco Rodríguez-Frías | 2018 | World Journal of Gastroenterology2018，24，6： | 5 |
| 19 | A widely adaptable approach to generate integration-free iPSCs from non-invasively acquired human somatic cells显示文摘 | Zhichao Ding Lina Sui Ruotong Ren Yanjun Liu Xiuling Xu Lina Fu Ruijun Bai Tingting Yuan Ying Hao Weiqi Zhang Huize Pan Wensu Liu Han Yu Concepcion Rodriguez Esteban Xiaobing Yu Ze Yang Jian Li Xiaomin Wang Juan Carlos Izpisua Belmonte Guang-Hui Liu Fei Yi Jing Qu | 2015 | Protein & Cell2015，6，5： | 5 |
| 20 | Biliary cystadenoma显示文摘The diagnosis of cystadenoma is rare, even more so when located in the extrahepatic bile duct.Unspeciflc clinical signs may lead this pathology to be misdiagnosed.The need for pathological anatomy in order to distinguish cystadenomas from simple biliary cysts is crucial.The most usual treatment nowadays is resection of the bile duct, together with cholecystectomy and Roux-en-Y reconstruction. | Miguel A Hernandez Bartolome Sagrario Fuerte Ruiz Israel Manzanedo Romero Beatriz Ramos Lojo Ignacio Rodriguez Prieto Luis Gimenez Alvira Rosario Granados Carreo Manuel Limones Esteban | 2009 | World Journal of Gastroenterology2009，15，28： | 4 |
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