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  • 1
    Publication Date: 2018-05-02
    Description: Purpose: No validated biomarkers that could identify the subset of patients with lung adenocarcinoma who might benefit from chemotherapy have yet been well established. This study aimed to explore potential biomarker model predictive of efficacy and survival outcomes after first-line pemetrexed plus platinum doublet based on metabolomics profiling. Experimental Design: In total, 354 consecutive eligible patients were assigned to receive first-line chemotherapy of pemetrexed in combination with either cisplatin or carboplatin. Prospectively collected serum samples before initial treatment were utilized to perform metabolomics profiling analyses under the application of LC/MS-MS. Binary logistic regression analysis was carried out to establish discrimination models. Results: There were 251 cases randomly sorted into discovery set, the rest of 103 cases into validation set. Seven metabolites including hypotaurine, uridine, dodecanoylcarnitine, choline, dimethylglycine, niacinamide, and l -palmitoylcarnitine were identified associated with chemo response. On the basis of the seven-metabolite panel, a discriminant model according to logistic regression values g(z) was established with the receiver operating characteristic curve (AUC) of 0.912 (Discovery set) and 0.909 (Validation set) in differentiating progressive disease (PD) groups from disease control (DC) groups. The median progression-free survival (PFS) after chemotherapy in patients with g(z) ≤0.155 was significantly longer than that in those with g(z) 〉 0.155 (10.3 vs.4.5 months, P 〈 0.001). Conclusions: This study developed an effective and convenient discriminant model that can accurately predict the efficacy and survival outcomes of pemetrexed plus platinum doublet chemotherapy prior to treatment delivery. Clin Cancer Res; 24(9); 2100–9. ©2018 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 2
    Publication Date: 2013-03-23
    Description: Engineering wireframe architectures and scaffolds of increasing complexity is one of the important challenges in nanotechnology. We present a design strategy to create gridiron-like DNA structures. A series of four-arm junctions are used as vertices within a network of double-helical DNA fragments. Deliberate distortion of the junctions from their most relaxed conformations ensures that a scaffold strand can traverse through individual vertices in multiple directions. DNA gridirons were assembled, ranging from two-dimensional arrays with reconfigurability to multilayer and three-dimensional structures and curved objects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, Dongran -- Pal, Suchetan -- Yang, Yang -- Jiang, Shuoxing -- Nangreave, Jeanette -- Liu, Yan -- Yan, Hao -- New York, N.Y. -- Science. 2013 Mar 22;339(6126):1412-5. doi: 10.1126/science.1232252.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA. dongran.han@asu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23520107" target="_blank"〉PubMed〈/a〉
    Keywords: DNA/*chemistry/*ultrastructure ; Models, Molecular ; *Nanostructures ; Nanotechnology/methods ; *Nucleic Acid Conformation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2013-11-29
    Description: N(6)-methyladenosine (m(6)A) is the most prevalent internal (non-cap) modification present in the messenger RNA of all higher eukaryotes. Although essential to cell viability and development, the exact role of m(6)A modification remains to be determined. The recent discovery of two m(6)A demethylases in mammalian cells highlighted the importance of m(6)A in basic biological functions and disease. Here we show that m(6)A is selectively recognized by the human YTH domain family 2 (YTHDF2) 'reader' protein to regulate mRNA degradation. We identified over 3,000 cellular RNA targets of YTHDF2, most of which are mRNAs, but which also include non-coding RNAs, with a conserved core motif of G(m(6)A)C. We further establish the role of YTHDF2 in RNA metabolism, showing that binding of YTHDF2 results in the localization of bound mRNA from the translatable pool to mRNA decay sites, such as processing bodies. The carboxy-terminal domain of YTHDF2 selectively binds to m(6)A-containing mRNA, whereas the amino-terminal domain is responsible for the localization of the YTHDF2-mRNA complex to cellular RNA decay sites. Our results indicate that the dynamic m(6)A modification is recognized by selectively binding proteins to affect the translation status and lifetime of mRNA.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877715/" 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/PMC3877715/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Xiao -- Lu, Zhike -- Gomez, Adrian -- Hon, Gary C -- Yue, Yanan -- Han, Dali -- Fu, Ye -- Parisien, Marc -- Dai, Qing -- Jia, Guifang -- Ren, Bing -- Pan, Tao -- He, Chuan -- GM071440/GM/NIGMS NIH HHS/ -- GM088599/GM/NIGMS NIH HHS/ -- K01 HG006699/HG/NHGRI NIH HHS/ -- R01 GM071440/GM/NIGMS NIH HHS/ -- R01 GM088599/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Jan 2;505(7481):117-20. doi: 10.1038/nature12730. Epub 2013 Nov 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA. ; Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, UCSD Moores Cancer Center and Institute of Genome Medicine, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, California 92093-0653, USA. ; Department of Biochemistry and Molecular Biology and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA. ; 1] Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA [2] Department of Chemical Biology and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24284625" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine/*analogs & derivatives/metabolism/pharmacology ; Base Sequence ; DNA-Binding Proteins/genetics ; HeLa Cells ; Humans ; Nucleotide Motifs ; Organelles/genetics/metabolism ; Protein Binding ; Protein Biosynthesis ; *RNA Stability/drug effects ; RNA Transport ; RNA, Messenger/*chemistry/*metabolism ; RNA, Untranslated/chemistry/metabolism ; RNA-Binding Proteins/chemistry/classification/*metabolism ; Substrate Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2011-04-16
    Description: We present a strategy to design and construct self-assembling DNA nanostructures that define intricate curved surfaces in three-dimensional (3D) space using the DNA origami folding technique. Double-helical DNA is bent to follow the rounded contours of the target object, and potential strand crossovers are subsequently identified. Concentric rings of DNA are used to generate in-plane curvature, constrained to 2D by rationally designed geometries and crossover networks. Out-of-plane curvature is introduced by adjusting the particular position and pattern of crossovers between adjacent DNA double helices, whose conformation often deviates from the natural, B-form twist density. A series of DNA nanostructures with high curvature--such as 2D arrangements of concentric rings and 3D spherical shells, ellipsoidal shells, and a nanoflask--were assembled.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, Dongran -- Pal, Suchetan -- Nangreave, Jeanette -- Deng, Zhengtao -- Liu, Yan -- Yan, Hao -- New York, N.Y. -- Science. 2011 Apr 15;332(6027):342-6. doi: 10.1126/science.1202998.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA. dongran.han@asu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21493857" target="_blank"〉PubMed〈/a〉
    Keywords: DNA/*chemistry ; Models, Molecular ; *Nanostructures ; Nanotechnology ; *Nucleic Acid Conformation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2012-10-09
    Description: The endoplasmic reticulum (ER) is the primary organelle for folding and maturation of secretory and transmembrane proteins. Inability to meet protein-folding demand leads to "ER stress," and activates IRE1alpha, an ER transmembrane kinase-endoribonuclease (RNase). IRE1alpha promotes adaptation through splicing Xbp1 mRNA or apoptosis through incompletely understood mechanisms. Here, we found that sustained IRE1alpha RNase activation caused rapid decay of select microRNAs (miRs -17, -34a, -96, and -125b) that normally repress translation of Caspase-2 mRNA, and thus sharply elevates protein levels of this initiator protease of the mitochondrial apoptotic pathway. In cell-free systems, recombinant IRE1alpha endonucleolytically cleaved microRNA precursors at sites distinct from DICER. Thus, IRE1alpha regulates translation of a proapoptotic protein through terminating microRNA biogenesis, and noncoding RNAs are part of the ER stress response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742121/" 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/PMC3742121/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Upton, John-Paul -- Wang, Likun -- Han, Dan -- Wang, Eric S -- Huskey, Noelle E -- Lim, Lionel -- Truitt, Morgan -- McManus, Michael T -- Ruggero, Davide -- Goga, Andrei -- Papa, Feroz R -- Oakes, Scott A -- DK063720/DK/NIDDK NIH HHS/ -- DP2 OD001925/OD/NIH HHS/ -- DP2OD001925/OD/NIH HHS/ -- GM080783/GM/NIGMS NIH HHS/ -- P30 DK063720/DK/NIDDK NIH HHS/ -- R01 CA136577/CA/NCI NIH HHS/ -- R01 CA136717/CA/NCI NIH HHS/ -- R01 CA140456/CA/NCI NIH HHS/ -- R01 CA154916/CA/NCI NIH HHS/ -- R01 DK080955/DK/NIDDK NIH HHS/ -- R01 GM080783/GM/NIGMS NIH HHS/ -- R01CA136577/CA/NCI NIH HHS/ -- R01CA136717/CA/NCI NIH HHS/ -- R01CA140456/CA/NCI NIH HHS/ -- R01CA154916/CA/NCI NIH HHS/ -- R01DK080955/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Nov 9;338(6108):818-22. doi: 10.1126/science.1226191. Epub 2012 Oct 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23042294" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; Animals ; Apoptosis ; Brefeldin A/pharmacology ; Caspase 2/*genetics/*metabolism ; Cell-Free System ; Cells, Cultured ; Cysteine Endopeptidases/*genetics/*metabolism ; Down-Regulation ; Endoplasmic Reticulum/metabolism ; *Endoplasmic Reticulum Stress ; Endoribonucleases/chemistry/genetics/*metabolism ; Enzyme Activation ; HEK293 Cells ; Humans ; Mice ; Mice, Knockout ; MicroRNAs/*metabolism ; Mutant Proteins ; Protein Biosynthesis ; Protein-Serine-Threonine Kinases/chemistry/genetics/*metabolism ; RNA Stability ; RNA, Messenger/genetics/metabolism ; Up-Regulation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2016-01-30
    Description: Dietary antigens are normally rendered nonimmunogenic through a poorly understood "oral tolerance" mechanism that involves immunosuppressive regulatory T (Treg) cells, especially Treg cells induced from conventional T cells in the periphery (pTreg cells). Although orally introducing nominal protein antigens is known to induce such pTreg cells, whether a typical diet induces a population of pTreg cells under normal conditions thus far has been unknown. By using germ-free mice raised and bred on an elemental diet devoid of dietary antigens, we demonstrated that under normal conditions, the vast majority of the small intestinal pTreg cells are induced by dietary antigens from solid foods. Moreover, these pTreg cells have a limited life span, are distinguishable from microbiota-induced pTreg cells, and repress underlying strong immunity to ingested protein antigens.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Kwang Soon -- Hong, Sung-Wook -- Han, Daehee -- Yi, Jaeu -- Jung, Jisun -- Yang, Bo-Gie -- Lee, Jun Young -- Lee, Minji -- Surh, Charles D -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):858-63. doi: 10.1126/science.aac5560. Epub 2016 Jan 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea. Department of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea. ; Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea. Department of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea. Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26822607" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens/immunology ; Diet ; Dietary Proteins/*immunology ; Dyspepsia/*immunology ; Gastrointestinal Microbiome/*immunology ; Germ-Free Life ; Immune Tolerance ; Immunity, Mucosal ; Intestine, Small/*immunology/*microbiology ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; T-Lymphocytes, Regulatory/*immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2016-02-11
    Description: Gene expression can be regulated post-transcriptionally through dynamic and reversible RNA modifications. A recent noteworthy example is N(6)-methyladenosine (m(6)A), which affects messenger RNA (mRNA) localization, stability, translation and splicing. Here we report on a new mRNA modification, N(1)-methyladenosine (m(1)A), that occurs on thousands of different gene transcripts in eukaryotic cells, from yeast to mammals, at an estimated average transcript stoichiometry of 20% in humans. Employing newly developed sequencing approaches, we show that m(1)A is enriched around the start codon upstream of the first splice site: it preferentially decorates more structured regions around canonical and alternative translation initiation sites, is dynamic in response to physiological conditions, and correlates positively with protein production. These unique features are highly conserved in mouse and human cells, strongly indicating a functional role for m(1)A in promoting translation of methylated mRNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dominissini, Dan -- Nachtergaele, Sigrid -- Moshitch-Moshkovitz, Sharon -- Peer, Eyal -- Kol, Nitzan -- Ben-Haim, Moshe Shay -- Dai, Qing -- Di Segni, Ayelet -- Salmon-Divon, Mali -- Clark, Wesley C -- Zheng, Guanqun -- Pan, Tao -- Solomon, Oz -- Eyal, Eran -- Hershkovitz, Vera -- Han, Dali -- Dore, Louis C -- Amariglio, Ninette -- Rechavi, Gideon -- He, Chuan -- GM113194/GM/NIGMS NIH HHS/ -- GM71440/GM/NIGMS NIH HHS/ -- HG006699/HG/NHGRI NIH HHS/ -- HG008688/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2016 Feb 25;530(7591):441-6. doi: 10.1038/nature16998. Epub 2016 Feb 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA. ; Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA. ; Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel. ; Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. ; Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA. ; The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26863196" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2018-01-12
    Description: We constructed highly oriented and ordered macropores within metal-organic framework (MOF) single crystals, opening up the area of three-dimensional–ordered macro-microporous materials (that is, materials containing both macro- and micropores) in single-crystalline form. Our methodology relies on the strong shaping effects of a polystyrene nanosphere monolith template and a double-solvent–induced heterogeneous nucleation approach. This process synergistically enabled the in situ growth of MOFs within ordered voids, rendering a single crystal with oriented and ordered macro-microporous structure. The improved mass diffusion properties of such hierarchical frameworks, together with their robust single-crystalline nature, endow them with superior catalytic activity and recyclability for bulky-molecule reactions, as compared with conventional, polycrystalline hollow, and disordered macroporous ZIF-8.
    Keywords: Chemistry, Materials Science
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2018-02-27
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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  • 10
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  83. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie; 20120516-20120520; Mainz; DOC12hnod176 /20120404/
    Publication Date: 2012-04-05
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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