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MicroRNA-regulated viral vectors for gene therapy

World Journal of Experimental Medicine 2016年第2期6卷 37-54页

作者： anja geisler Henry Fechner Department of Applied Bioche-mistry Institute of Biotechnology Technische Universitat Berlin

Safe and effective gene therapy approaches require targeted tissue-specific transfer of a therapeutic *** traditional approaches, such as transcriptional and transductional targeting, micro RNA-dependent posttranscriptional suppression of transgene expression has been emerging as powerful new technology to increase the specificity of vector-mediated transgene expression. Micro RNAs are small non-coding RNAs and often expressed in a tissue-, lineage-, activation- or differentiation-specific pattern. They typically regulate gene expression by binding to imperfectly complementary sequences in the 3' untranslated region(UTR) of the m RNA. To control exogenous transgene expression, tandem repeats of artificial micro RNA target sites are usually incorporated into the 3' UTR of the transgene expression cassette, leading to subsequent degradation of transgene m RNA in cel s expressing the corresponding micro RNA. This targeting strategy, first shown for lentiviral vectors in antigen presenting cells, has now been used for tissue-specific expression of vector-encoded therapeutic transgenes, to reduce immune response against the transgene, to control virus tropism for oncolytic virotherapy, to increase safety of live attenuated virus vaccines and to identify and select cell subsets for pluripotent stem cell therapies, respectively. This review provides an introduction into the technical mechanism underlying micro RNA-regulation, highlights new developments in this field and gives an overview of applications of micro RNA-regulated viral vectors for cardiac, suicide gene cancer and hematopoietic stem cell therapy, as well as for treatment of neurological and eye diseases.

关键词： Micro RNA Micro RNA regulation Micro RNA target sites Viral vectors Adeno-associated virus RNA interference Gene therapy Vector targeting

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Embracing substrate multispecificity in plant ABC transporters

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Molecular Plant 2024年第7期17卷 990-992页

作者： Markus M.geisler Department of Biology University of Fribourg1700 FribourgSwitzerland

By analogy,the first plant ATP-binding cassette(ABC)transporters were identified as vacuolar detoxifiers transporting glutathione conjugates into the vacuole(Martinoia et al.,1993).This somewhat negative image as"unspecific detoxifiers"still clings to plant ABC transporters today,although they have since been described to be involved in completely different programs,including development and defense(Park et al.,2017).In this context,some key plant ABC transporters have been shown to own exceptionally high substrate *** example,the transporter of the native auxin indole-3-acetic acid(IAA),Arabidopsis ABCB1,has been shown to also export the synthetic auxin 1-naphtaleneacetic acid but is even able to distinguish this substrate from its structural isomer,2-naphtaleneacetic acid(geisler et al.,2005).Likewise,ABCG36 and ABCG37,which are known to have a broader substrate portfolio(Park et al.,2017;Aryal et al.,2023),export IBA but do not touch IAA(Aryal et al.,2023).Recently,several reports have challenged our current view on the reported high substrate specificity of plant ABCs,which requires clarification.

关键词： specificity analogy exceptional

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Light-stabilized GIL1 suppresses PIN3 activity to inhibit hypocotyl gravitropism

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Journal of Integrative Plant Biology 2024年第9期66卷 1886-1897页

作者： Xiaolian Wang Yanfang Yuan Laurence Charrier Zhaoguo Deng Markus geisler Xing Wang Deng Haodong Chen Center for Plant Biology School of Life SciencesTsinghua UniversityBeijing 100084China Tsinghua‐Peking Center for Life Sciences Beijing 100084China School of Advanced Agricultural Sciences and School of Life Sciences Peking‐Tsinghua Center for Life SciencesPeking UniversityBeijing 100871China Department of Biology University of FribourgFribourg 1700Switzerland

Light and gravity coordinately regulate the directional growth of *** Gravitropic in the Light 1(GIL1)inhibits the negative gravitropism of hypocotyls in red and far-red light,but the underlying molecular mechanisms remain *** study found that GIL1 is a plasma membrane-localized *** endodermal cells of the upper part of hypocotyls,GIL1 controls the negative gravitropism of ***1 directly interacts with PIN3 and inhibits the auxin transport activity of *** of PIN3 suppresses the abnormal gravitropic response of gil1 *** GIL1 protein is unstable in darkness but it is stabilized by red and far-red ***,our data suggest that light-stabilized GIL1 inhibits the negative gravitropism of hypocotyls by suppressing the activity of the auxin transporter PIN3,thereby enhancing the emergence of young seedlings from the soil.

关键词： GIL1 gravitropism hypocotyls light PIN3

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Driving factors behind multiple populations

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Science China(Physics,Mechanics & Astronomy) 2024年第5期67卷 172-181页

作者： Ruoyun Huang Baitian Tang Chengyuan Li Doug geisler Mario Mateo Ying-Yi Song Holger Baumgardt Julio A.Carballo-Bello Yue Wang Jundan Nie Bruno Dias JoséG.Fernández-Trincado School of Physics and Astronomy Sun Yat-sen UniversityZhuhai 519082China CSST Science Center for the Guangdong-Hong Kong-Macao Greater Bay Area Zhuhai 519082China Departamento de Astronomía Universidad de ConcepcionConcepcionChile Instituto de Investigación Multidisciplinario en Ciencia y Tecnología Universidad de La SerenaLa SerenaChile Departamento de Astronomía Facultad de CienciasUniversidad de La SerenaChile Department of Astronomy University of MichiganAnn Arbor 48109USA David A.Dunlap Department of Astronomy&Astrophysics University of TorontoToronto ON M5S 3H4Canada Dunlap Institute for Astronomy&Astrophysics University of TorontoToronto ON M5S 3H4Canada School of Mathematics and Physics The University of QueenslandSt.Lucia QLD 4072Australia Instituto de Alta Investigación Universidad de TarapacáAricaChile CAS Key Laboratory of Optical Astronomy National Astronomical ObservatoriesChinese Academy of SciencesBeijing 100101China Instituto de Astrofísica Departamento de Ciencias FísicasFacultad de Ciencias ExactasUniversidad Andres BelloSantiagoChile Instituto de Astronomía Universidad Católica del NorteAntofagastaChile

Star clusters were historically considered simple stellar populations,with all stars sharing the same age and initial chemical ***,the presence of chemical anomalies in globular clusters(GCs),called multiple stellar populations(MPs),has challenged star formation theories in dense *** studies show that mass,metallicity,and age are likely controlling parameters for the manifestation of *** the limit between clusters with/without MPs in physical parameter space is crucial to reveal the driving mechanism behind their *** this study,we look for MP signals in Whiting 1,which is traditionally considered a young *** the Magellan telescope,we obtained low-resolution spectra withinλλ=3850-5500?for eight giants of Whiting *** measured the C and N abundances from the CN and CH spectral indices.C and N abundances have variations comparable with their measurement errors(~0.1 dex),suggesting that MPs are absent from Whiting *** these findings with literature studies,we propose a limit in the metallicity *** compactness index parameter space,which relatively clearly separates star clusters with/without MPs(GCs/open clusters).This limit is physically *** a larger scale,the galactic environment determines cluster compactness and metallicity,leading to metal-rich,diffuse,old clusters formed ex *** proposed limit also impacts our understanding of the formation of the Sagittarius dwarf galaxy:star clusters formed after the first starburst(age≤8-10 Gyr).These clusters are simple stellar populations because the enriched galactic environment is no longer suitable for MP formation.

关键词： stellar galactic galaxy

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Angular effects in digital off-axis holography

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Chinese Optics Letters 2009年第12期7卷 1126-1130页

作者：赖国俊申功炘 Reinhard geisler Institute of Fluid Mechanics School of Aeronautic Science and Engineering Beijing University of Aeronautics and Astronautics Institute of Aerodynamics and Flow Technology German Aerospace Center

The relationship between the off-axis angle of the recording setup and the quality of reconstructed particle images in digital off-axis holography is studied. The interference patterns of the same particles in the same plane are recorded at different off-axis angles in horizontal and vertical directions. By means of numerical wave propagation, the particle images are reconstructed so as to evaluate and compare their quality by the numbers of particles picked out and by the signal-to-noise ratio （SNR）. The results provide useful information about the relationship between the off-axis angle and the quality of the reconstructed image.

关键词： Holography

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Tomographic PIV investigation of coherent structures in a turbulent boundary layer flow

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Acta Mechanica Sinica 2012年第3期28卷 572-582页

作者： Zhan-Qi Tang Nan Jiang Andreas Schroder Reinhard geisler Department of Mechanics Tianjin University300072 TianjinChina Tianjin Key Laboratory of Modern Engineering Mechanics 300072 TianjinChina Institute of Aerodynamics and Flow Technology Department of Experimental MethodsBunsenstrasse 1037073 GiSttingenGermany

Tomographic particle image velocimetry was used to quantitatively visualize the three-dimensional co- herent structures in the logarithmic region of the turbulent boundary layer in a water tunnel. The Reynolds number based on momentum thickness is Reo = 2 460. The in- stantaneous velocity fields give evidence of hairpin vortices aligned in the streamwise direction forming very long zones of low speed fluid, which is flanked on either side by high- speed ones. Statistical support for the existence of hairpins is given by conditional averaged eddy within an increasing spanwise width as the distance from the wall increases, and the main vortex characteristic in different wall-normal re- gions can be reflected by comparing the proportion of ejec- tion and its contribution to Reynolds stress with that of sweep event. The pre-multiplied power spectra and two-point cor- relations indicate the presence of large-scale motions in the boundary layer, which are consistent with what have been termed very large scale motions （VLSMs）. The three dimen-sional spatial correlations of three components of veloc- ity further indicate that the elongated low-speed and high- speed regions will be accompanied by a counter-rotating roll modes, as the statistical imprint of hairpin packet structures, all of which together make up the characteristic of coherent structures in the logarithmic region of the turbulent boundary layer （TBL）.

关键词： Tomographic particle image velocimetry Tur-bulent boundary layer Coherent structures Hairpin vortex Very large scale motion

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In situ Raman imaging of high-temperature solid-state reactions in the CaSO4-SiO2 system

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International Journal of Coal Science & Technology 2019年第2期6卷 247-259页

作者： Nadine Bohme Kerstin Hauke Manuela Neuroth Thorsten geisler Institut fiir Geowissenschaften und Meteorologie Universitat Bonn Poppelsdorfer Schloss Meckenheimer Allee 169 53115 Bonn Germany RWE Power AG F und E Kraftwerk NiederauBem Bergheim Germany

The deposition of mineral phases on the heat transfer surfaces of brown coal power plants may have a negative effect on power plant boilers. The paragenesis of these deposits contains information about the actual temperature prevailed during the combustion of lignite, if the temperature-dependences of distinct mineral transformations or reactions are known. Here, we report results of a sintering study (to ?1100℃) with samples containing anhydrite, quartz, and gehlenite, which are typical components of Rhenish lignite ashes. Thermal decompositions and solid-state reactions were analyzed (1) in situ and (2) both in situ and after quenching using confocal hyperspectral Raman imaging. This novel application of confocal Raman spectroscopy provides temperature-and time-resolved, 2-dimensional information about sintering processes with a micrometer-scale resolution. In the course of the sintering experiments with anhydrite and quartz with a weight ratio of 2:1 both polymorphs wollastonite and pseudowollastonite were identified in situ at about 920 and 1000℃, respectively. The formation of pseudowollastonite was thus observed about 120℃ below the phase transition temperature, demonstrating that it can form metastably. In addition,α′L-Ca2SiO4 was identified at about 1100℃. In samples containing equal weight fractions of anhydrite and quartz that were quenched after firing for 9h at about 1100℃,β-Ca2SiO4 (larnite) crystallized as rims around anhydrite grains and in direct contact to wollastonite. We furthermore observed that, depending on the ratio between quartz and anhydrite, wollastonite replaced quartz grains between 920 and 1100℃., i.e., the higher the quartz content, the lower the formation temperature of wollastonite.

关键词： Ash deposition Calcium silicate Calcium sulfate High-temperature Raman imaging

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3D printing of optical materials by processes based on photopolymerization:materials,technologies,and recent advances

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Photonics Research 2022年第6期10卷 1344-1360页

作者： EMMA geisler MAXIME LECOMPèRE OLIVIER SOPPERA Universitéde Haute-Alsace CNRSIS2M UMR 7361F-68100 MulhouseFrance Universitéde Strasbourg F-67000 StrasbourgFrance Essilor International 94000 CréteilFrance

3D printing technologies have expanded beyond the research laboratories where they were used solely for prototyping and have become widely used in several *** production of custom 3D objects has significant potential in optical ***,this necessitates extremely specific material properties,such as transparency,homogeneity,birefringence,and surface ***,the majority of optical objects are manufactured using ***,the 3D printing processes using polymers to produce optical objects have significant advantages,such as limited wastage,short manufacturing time,and easy ***,despite extensive efforts,no technology has achieved the production of objects perfectly suited for optical *** objective of this review is to summarize recent advances in the field of 3D printing for optics,with an emphasis on specific developments for dedicated applications,and to explore new candidate processes.

关键词： printing expanded transparency

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Recognition and Management of Athletic Pubalgia

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中国运动医学杂志 2011年第8期30卷 759-763页

作者： Paul R.geisler Ed.D,ATC Department of Exercise & Sport Sciences Ithaca CollegeNYUSA.

Introduction Whether termed"sports hernias","hockey groin",or"athletic pubalgia",insidious onset and vague groin and hip maladies seem to be on the rise in the last few years,creating much confusion as to the best way... 详细信息

关键词：《中国运动医学杂志》期刊摘要编辑部

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A novel miR167a-OsARF6-OsAUX3 module regulates grain length and weight in rice

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Molecular Plant 2021年第10期14卷 1683-1698页

作者： Jiyue Qiao Hongzhen Jiang Yuqing Lin Lianguang Shang Mei Wang Dongming Li Xiangdong Fu Markus geisler Yanhua Qi Zhenyu Gao Qian Qian Key Laboratory of Herbage&Endemic Crop Biology of Ministry of Education Inner Mongolia Key Laboratory of Herbage&Endemic Crop BiotechnologySchool of Life SciencesInner Mongolia UniversityHohhot 010000China State Key Laboratory of Plant Physiology and Biochemistry College of Life SciencesZhejiang UniversityHangzhou 310058China State Key Laboratory of Rice Biology China National Rice Research InstituteChinese Academy of Agricultural SciencesHangzhou 310006China Shenzhen Branch Guangdong Laboratory of Lingnan Modern AgricultureGenome Analysis Laboratory of the Ministry of Agriculture and Rural AffairsAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518120China State Key Laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental BiologyInnovation Academy for Seed DesignUniversity of Chinese Academy of Sciences100049China Department of Biology University of FribourgRue Albert-Gockel 3CH-1700 FribourgSwitzerland

Grain size is one of the most important factors that control rice yield,as it is associated with grain weight(GW).To date,dozens of rice genes that regulate grain size have been isolated;however,the regulatory mechanism underlying GW control is not fully ***,the quantitative trait locus qGL5 for grain length(GL)and GW was identified in recombinant inbred lines of 9311 and Nipponbare(NPB)and fine mapped to a candidate gene,*** variations between 9311 and NPB in the OsAUX3 promoter and loss of function of OsAUX3 led to higher GL and *** sequencing,gene expression quantification,dual-luciferase reporter assays,chromatin immunoprecipitation-quantitative PCR,and yeast one-hybrid assays demonstrated that OsARF6 is an upstream transcription factor regulating the expression of ***6 binds directly to the auxin response elements of the OsAUX3 promoter,covering a single-nucleotide polymorphism site between 9311 and NPB/Dongjin/Hwayoung,and thereby controls GL by altering longitudinal expansion and auxin distribution/content in glume ***,we showed that miR167a positively regulate GL and GW by directing OsARF6 mRNA *** together,our study reveals that a novel miR167a-OsARF6-OsAUX3 module regulates GL and GW in rice,providing a potential target for the improvement of rice yield.

关键词： grain length grain weight miR167a OsAUX3 OsARF6 rice

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