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Jörg Votteler Elena Iavnilovitch Orit Fingrut Vivian Shemesh Daniel Taglicht Omri Erez Stefan Sörgel Torsten Walther Norbert Bannert Ulrich Schubert Yuval Reiss 《BMC biochemistry》2009,10(1):1-14
Background
The ALG2-interacting protein X (ALIX)/AIP1 is an adaptor protein with multiple functions in intracellular protein trafficking that plays a central role in the biogenesis of enveloped viruses. The ubiquitin E3-ligase POSH (plenty of SH3) augments HIV-1 egress by facilitating the transport of Gag to the cell membrane. Recently, it was reported, that POSH interacts with ALIX and thereby enhances ALIX mediated phenotypes in Drosophila.Results
In this study we identified ALIX as a POSH ubiquitination substrate in human cells: POSH induces the ubiquitination of ALIX that is modified on several lysine residues in vivo and in vitro. This ubiquitination does not destabilize ALIX, suggesting a regulatory function. As it is well established that ALIX rescues virus release of L-domain mutant HIV-1, HIV-1ΔPTAP, we demonstrated that wild type POSH, but not an ubiquitination inactive RING finger mutant (POSHV14A), substantially enhances ALIX-mediated release of infectious virions derived from HIV-1ΔPTAP L-domain mutant (YPXnL-dependent HIV-1). In further agreement with the idea of a cooperative function of POSH and ALIX, mutating the YPXnL-ALIX binding site in Gag completely abrogated augmentation of virus release by overexpression of POSH. However, the effect of the POSH-mediated ubiquitination appears to be auxiliary, but not necessary, as silencing of POSH by RNAi does not disturb ALIX-augmentation of virus release.Conclusion
Thus, the cumulative results identified ALIX as an ubiquitination substrate of POSH and indicate that POSH and ALIX cooperate to facilitate efficient virus release. However, while ALIX is obligatory for the release of YPXnL-dependent HIV-1, POSH, albeit rate-limiting, may be functionally interchangeable. 相似文献14.
Shlomo Margel Ella Cohen Yehudit Dolitzky Orit Sivan 《Journal of polymer science. Part A, Polymer chemistry》1992,30(6):1103-1110
The synthesis and characterization of novel surfaces composed of polyacrolein microspheres covalently bonded onto polyethylene films are described. These surfaces were prepared through a sequence of reactions carried out onto polyethylene films in order to form primary amine groups at the w position. Polyacrolein microspheres in water were then covalently bonded to these modified polyethylene surfaces. The binding between the microspheres and the modified surfaces is due to the interaction between the aldehyde groups of the microspheres and the amine groups of the modified surfaces to form the polyvalent Schiff base bonds. Fourier transform-infrared/attenuated total reflection, electron spectroscopy for chemical analysis, contact angle measurements, and scanning electron microscopy have been used for the characterization of the modified polyethylene surfaces. 相似文献
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Polymeric Nanoparticles with a Glutathione‐Sensitive Heterodimeric Multifunctional Prodrug for In Vivo Drug Monitoring and Synergistic Cancer Therapy 下载免费PDF全文
Dr. Fuwu Zhang Qianqian Ni Dr. Orit Jacobson Siyuan Cheng Arthur Liao Dr. Zhantong Wang Zhimei He Dr. Guocan Yu Dr. Jibin Song Dr. Ying Ma Dr. Gang Niu Dr. Longjiang Zhang Dr. Guizhi Zhu Dr. Xiaoyuan Chen 《Angewandte Chemie (International ed. in English)》2018,57(24):7066-7070
Polymeric micelle‐based drug delivery systems have dramatically improved the delivery of small molecular drugs, yet multiple challenges remain to be overcome. A polymeric nanomedicine has now been engineered that possesses an ultrahigh loading (59 %) of a glutathione (GSH)‐sensitive heterodimeric multifunctional prodrug (HDMP) to effectively co‐deliver two synergistic drugs to tumors. An HDMP comprising of chemotherapeutic camptothecin (CPT) and photosensitizer 2‐(1‐hexyloxyethyl)‐2‐devinyl pyropheophorbide‐α (HPPH) was conjugated via a GSH‐cleavable linkage. The intrinsic fluorogenicity and label‐free radio‐chelation (64Cu) of HPPH enabled direct drug monitoring by fluorescence imaging and positron emission tomography (PET). Through quantitative PET imaging, HDMP significantly improves drug delivery to tumors. The high synergistic therapeutic efficacy of HDMP‐loaded NPs highlights the rational design of HDMP, and presents exciting opportunities for polymer NP‐based drug delivery. 相似文献
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Shauly-Aharonov Michal Barenholz-Goultschin Orit 《Methodology and Computing in Applied Probability》2019,21(3):931-944
Methodology and Computing in Applied Probability - Glycemic control in pregnancies of diabetic women is still suboptimal; birth defects and late miscarriages (i.e., second trimester miscarriages)... 相似文献
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Orit Ravid-Hermesh Naomi Zurgil Yana Shafran Maria Sobolev Moti Galmidi Yoav Badihi Liron Limor Israel Jean Paul Lellouche Emmanuel Lellouche Shulamit Michaeli Mordechai Deutsch 《Analytical and bioanalytical chemistry》2014,406(28):7085-7101
Cell populations represent intrinsically heterogeneous systems with a high level of spatiotemporal complexity. Monitoring and understanding cell-to-cell diversity is essential for the research and application of intra- and interpopulation variations. Optical analysis of live cells is challenging since both adherent and nonadherent cells change their spatial location. However, most currently available single-cell techniques do not facilitate treatment and monitoring of the same live cells over time throughout multistep experiments. An imaging-dish-based live cell array (ID-LCA) has been developed and produced for cell handling, culturing, and imaging of numerous live cells. The dish is composed of an array of pico scale cavities—pico wells (PWs) embossed on its glass bottom. Cells are seeded, cultured, treated, and spatiotemporally measured on the ID-LCA, while each cell or small group of cells are locally constrained in the PWs. Finally, predefined cells can be retrieved for further evaluation. Various types of ID-LCAs were used in this proof-of-principle work, to demonstrate on-ID-LCA transfection of fluorescently tagged chimeric proteins, as well as the detection and kinetic analysis of their induced translocation. High variability was evident within cell populations with regard to protein expression levels as well as the extent and dynamics of protein redistribution. The association of these parameters with cell morphology and functional parameters was examined. Both the new methodology and the device facilitate research of the translocation process at individual cell resolution within large populations and thus, can potentially be used in high-throughput fashion. Graphical Abstract
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Ira Raveh Boris Koichu Irit Peled Orit Zaslavsky 《Research in Mathematics Education》2016,18(1):43-60
In this article we present an integrative framework of knowledge for teaching the standard algorithms of the four basic arithmetic operations. The framework is based on a mathematical analysis of the algorithms, a connectionist perspective on teaching mathematics and an analogy with previous frameworks of knowledge for teaching arithmetic operations with rational numbers. In order to evaluate the potential applicability of the framework to task design, it was used for the design of mathematical learning tasks for teachers. The article includes examples of the tasks, their theoretical analysis, and empirical evidence of the sensitivity of the tasks to variations in teachers’ knowledge of the subject. This evidence is based on a study of 46 primary school teachers. The article concludes with remarks on the applicability of the framework to research and practice, highlighting its potential to encourage teaching the four algorithms with an emphasis on conceptual understanding. 相似文献
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Ortho‐Stabilized 18F‐Azido Click Agents and their Application in PET Imaging with Single‐Stranded DNA Aptamers 下载免费PDF全文
Lu Wang Dr. Orit Jacobson Din Avdic Dr. Benjamin H. Rotstein Dr. Ido D. Weiss Dr. Lee Collier Prof. Dr. Xiaoyuan Chen Prof. Dr. Neil Vasdev Prof. Dr. Steven H. Liang 《Angewandte Chemie (International ed. in English)》2015,54(43):12777-12781
Azido 18F‐arenes are important and versatile building blocks for the radiolabeling of biomolecules via Huisgen cycloaddition (“click chemistry”) for positron emission tomography (PET). However, routine access to such clickable agents is challenged by inefficient and/or poorly defined multistep radiochemical approaches. A high‐yielding direct radiofluorination for azido 18F‐arenes was achieved through the development of an ortho‐oxygen‐stabilized iodonium derivative (OID). This OID strategy addresses an unmet need for a reliable azido 18F‐arene clickable agent for bioconjugation reactions. A ssDNA aptamer was radiolabeled with this agent and visualized in a xenograft mouse model of human colon cancer by PET, which demonstrates that this OID approach is a convenient and highly efficient way of labeling and tracking biomolecules. 相似文献