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  • 1
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    BAX activation is initiated at a novel interaction site (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-10-25
    Description: BAX is a pro-apoptotic protein of the BCL-2 family that is stationed in the cytosol until activated by a diversity of stress stimuli to induce cell death. Anti-apoptotic proteins such as BCL-2 counteract BAX-mediated cell death. Although an interaction site that confers survival functionality has been defined for anti-apoptotic proteins, an activation site has not been identified for BAX, rendering its explicit trigger mechanism unknown. We previously developed stabilized alpha-helix of BCL-2 domains (SAHBs) that directly initiate BAX-mediated mitochondrial apoptosis. Here we demonstrate by NMR analysis that BIM SAHB binds BAX at an interaction site that is distinct from the canonical binding groove characterized for anti-apoptotic proteins. The specificity of the human BIM-SAHB-BAX interaction is highlighted by point mutagenesis that disrupts functional activity, confirming that BAX activation is initiated at this novel structural location. Thus, we have now defined a BAX interaction site for direct activation, establishing a new target for therapeutic modulation of apoptosis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2597110/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2597110/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gavathiotis, Evripidis -- Suzuki, Motoshi -- Davis, Marguerite L -- Pitter, Kenneth -- Bird, Gregory H -- Katz, Samuel G -- Tu, Ho-Chou -- Kim, Hyungjin -- Cheng, Emily H-Y -- Tjandra, Nico -- Walensky, Loren D -- 5P01CA92625/CA/NCI NIH HHS/ -- 5R01CA125562/CA/NCI NIH HHS/ -- 5R01CA50239/CA/NCI NIH HHS/ -- K99 HL095929/HL/NHLBI NIH HHS/ -- K99 HL095929-01A1/HL/NHLBI NIH HHS/ -- K99 HL095929-02/HL/NHLBI NIH HHS/ -- R00 HL095929/HL/NHLBI NIH HHS/ -- R01 CA050239/CA/NCI NIH HHS/ -- R01 CA125562/CA/NCI NIH HHS/ -- R01 CA125562-02/CA/NCI NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2008 Oct 23;455(7216):1076-81. doi: 10.1038/nature07396.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatric Oncology and the Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18948948" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Apoptosis ; Apoptosis Regulatory Proteins/chemistry/metabolism ; BH3 Interacting Domain Death Agonist Protein/metabolism ; Cell Line ; *Gene Expression Regulation ; Humans ; Membrane Proteins/chemistry/metabolism ; Mice ; Mutagenesis, Site-Directed ; Mutation/genetics ; Nuclear Magnetic Resonance, Biomolecular ; Protein Binding ; Proto-Oncogene Proteins/chemistry/metabolism ; Sequence Alignment ; bcl-2-Associated X Protein/chemistry/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    BID, BIM, and PUMA are essential for activation of the BAX- and BAK-dependent cell death program (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-12-04
    Description: Although the proteins BAX and BAK are required for initiation of apoptosis at the mitochondria, how BAX and BAK are activated remains unsettled. We provide in vivo evidence demonstrating an essential role of the proteins BID, BIM, and PUMA in activating BAX and BAK. Bid, Bim, and Puma triple-knockout mice showed the same developmental defects that are associated with deficiency of Bax and Bak, including persistent interdigital webs and imperforate vaginas. Genetic deletion of Bid, Bim, and Puma prevented the homo-oligomerization of BAX and BAK, and thereby cytochrome c-mediated activation of caspases in response to diverse death signals in neurons and T lymphocytes, despite the presence of other BH3-only molecules. Thus, many forms of apoptosis require direct activation of BAX and BAK at the mitochondria by a member of the BID, BIM, or PUMA family of proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163443/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163443/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ren, Decheng -- Tu, Ho-Chou -- Kim, Hyungjin -- Wang, Gary X -- Bean, Gregory R -- Takeuchi, Osamu -- Jeffers, John R -- Zambetti, Gerard P -- Hsieh, James J-D -- Cheng, Emily H-Y -- P30CA21765/CA/NCI NIH HHS/ -- R01 CA125562/CA/NCI NIH HHS/ -- R01 CA125562-02/CA/NCI NIH HHS/ -- R01 CA125562-03/CA/NCI NIH HHS/ -- R01 CA125562-04/CA/NCI NIH HHS/ -- R01CA125562/CA/NCI NIH HHS/ -- R01GM083159/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Dec 3;330(6009):1390-3. doi: 10.1126/science.1190217.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21127253" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Apoptosis Regulatory Proteins/deficiency/genetics/*metabolism ; BH3 Interacting Domain Death Agonist Protein/deficiency/genetics/*metabolism ; Caspases/metabolism ; Cells, Cultured ; Cerebellum/cytology ; Cytochromes c/metabolism ; Intracellular Membranes/metabolism ; Membrane Proteins/deficiency/genetics/*metabolism ; Mice ; Mice, Knockout ; Mitochondria/metabolism ; Models, Biological ; Neurons/*physiology ; Permeability ; Protein Multimerization ; Proto-Oncogene Proteins/deficiency/genetics/*metabolism ; Stress, Physiological ; T-Lymphocytes/physiology ; Tumor Suppressor Proteins/deficiency/genetics/*metabolism ; bcl-2 Homologous Antagonist-Killer Protein/chemistry/genetics/*metabolism ; bcl-2-Associated X Protein/chemistry/genetics/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Corrigendum: Failure to replicate the STAP cell phenomenon (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-12-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉De Los Angeles, Alejandro -- Ferrari, Francesco -- Fujiwara, Yuko -- Mathieu, Ronald -- Lee, Soohyun -- Lee, Semin -- Tu, Ho-Chou -- Ross, Samantha -- Chou, Stephanie -- Nguyen, Minh -- Wu, Zhaoting -- Theunissen, Thorold W -- Powell, Benjamin E -- Imsoonthornruksa, Sumeth -- Chen, Jiekai -- Borkent, Marti -- Krupalnik, Vladislav -- Lujan, Ernesto -- Wernig, Marius -- Hanna, Jacob H -- Hochedlinger, Konrad -- Pei, Duanqing -- Jaenisch, Rudolf -- Deng, Hongkui -- Orkin, Stuart H -- Park, Peter J -- Daley, George Q -- Nature. 2015 Dec 16. doi: 10.1038/nature16479.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26675720" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 4
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    Failure to replicate the STAP cell phenomenon (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-09-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉De Los Angeles, Alejandro -- Ferrari, Francesco -- Fujiwara, Yuko -- Mathieu, Ronald -- Lee, Soohyun -- Lee, Semin -- Tu, Ho-Chou -- Ross, Samantha -- Chou, Stephanie -- Nguyen, Minh -- Wu, Zhaoting -- Theunissen, Thorold W -- Powell, Benjamin E -- Imsoonthornruksa, Sumeth -- Chen, Jiekai -- Borkent, Marti -- Krupalnik, Vladislav -- Lujan, Ernesto -- Wernig, Marius -- Hanna, Jacob H -- Hochedlinger, Konrad -- Pei, Duanqing -- Jaenisch, Rudolf -- Deng, Hongkui -- Orkin, Stuart H -- Park, Peter J -- Daley, George Q -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Sep 24;525(7570):E6-9. doi: 10.1038/nature15513.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stem Cell Transplantation Program, Division of Pediatric Hematology Oncology, Children's Hospital Boston, and Dana-Farber Cancer Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA. ; Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA. ; Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USApeter_park@hms.harvard.edu. ; Children's Hospital &Harvard Stem Cell Institute Flow Cytometry Research Facility, Children's Hospital Boston, Boston, Massachusetts 02115, USA. ; Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA. ; South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. ; Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Boston, Massachusetts 02114, USA. ; Department of Development and Reproduction, Erasmus Medical Center, 3015 CN Rotterdam, Netherlands. ; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. ; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA. ; College of Life Sciences and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26399835" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 5
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    The p53-cathepsin axis cooperates with ROS to activate programmed necrotic death upon DNA damage (2009)
    National Academy of Sciences
    Details
    Publication Date: 2009-01-14
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 6
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    Ultra-multiplexed analysis of single-cell dynamics reveals logic rules in differentiation (2019)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2019
    Description: 〈p〉Dynamical control of cellular microenvironments is highly desirable to study complex processes such as stem cell differentiation and immune signaling. We present an ultra-multiplexed microfluidic system for high-throughput single-cell analysis in precisely defined dynamic signaling environments. Our system delivers combinatorial and time-varying signals to 1500 independently programmable culture chambers in week-long live-cell experiments by performing nearly 10〈sup〉6〈/sup〉 pipetting steps, where single cells, two-dimensional (2D) populations, or 3D neurospheres are chemically stimulated and tracked. Using our system and statistical analysis, we investigated the signaling landscape of neural stem cell differentiation and discovered "cellular logic rules" that revealed the critical role of signal timing and sequence in cell fate decisions. We find synergistic and antagonistic signal interactions and show that differentiation pathways are highly redundant. Our system allows dissection of hidden aspects of cellular dynamics and enables accelerated biological discovery.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 7
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    Planar ring-shaped phononic crystal anchoring boundaries for enhancing the quality factor of Lamb mode resonators (2016)
    American Institute of Physics (AIP)
    Details
    Publication Date: 2016-11-16
    Description: We report the use of planar ring-shaped phononic crystals (PnCs) as anchor boundaries of very-high-frequency band piezoelectric-on-silicon Lamb mode resonators for the purpose of enhancing their quality factor ( Q ). Here, we exploit the acoustic bandgap associated with the PnC anchoring boundaries to reduce acoustic energy leakage out of the micromechanical resonator. The proposed approach provides greater mechanical robustness (by merit of interlocking the cells in a matrix) and the possibility of electrical routing through the PnC cells. We experimentally show enhancements in Q by a factor of three using the proposed approach of hybridizing planar ring-shaped PnCs with micromechanical resonators. The effect of these PnCs on resonator Q is further corroborated by their effects in suppressing transmission when incorporated into a delay line.
    Print ISSN: 0003-6951
    Electronic ISSN: 1077-3118
    Topics: Physics
    Published by American Institute of Physics (AIP)
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  • 8
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    Carbon cloth based on PAN carbon fiber practicability for PEMFC applications (2010)
    Elsevier
    Details
    Publication Date: 2010-04-01
    Print ISSN: 0360-3199
    Electronic ISSN: 1879-3487
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Published by Elsevier
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