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  • 1
    Publication Date: 2018-10-02
    Description: Purpose: Toca 511 is a gammaretroviral replicating vector encoding cytosine deaminase that selectively infects tumor cells and converts the antifungal drug 5-fluorocytosine into the antineoplastic drug 5-fluorouracil, which directly kills tumor cells and stimulates antitumor immune responses. As part of clinical monitoring of phase I clinical trials in recurrent high-grade glioma, we have performed extensive molecular analyses of patient specimens to track vector fate. Patients and Methods: Toca 511 and Toca FC (extended-release 5-fluorocytosine) have been administered to 127 high-grade glioma patients across three phase I studies. We measured Toca 511 RNA and DNA levels in available body fluids and tumor samples from patients to assess tumor specificity. We mapped Toca 511 integration sites and sequenced integrated Toca 511 genomes from patient samples with detectable virus. We measured Toca 511 levels in a diverse set of tissue samples from one patient. Results: Integrated Toca 511 is commonly detected in tumor samples and is only transiently detected in blood in a small fraction of patients. There was no believable evidence for clonal expansion of cells with integrated Toca 511 DNA, or preferential retrieval of integration sites near oncogenes. Toca 511 sequence profiles suggest most mutations are caused by APOBEC cytidine deaminases acting during reverse transcription. Tissue samples from a single whole-body autopsy affirm Toca 511 tumor selectivity. Conclusions: Toca 511 and Toca FC treatment was not associated with inappropriate integration sites and clonal expansion. The vector is tumor-selective and persistent in patients who received Toca 511 injections. Clin Cancer Res; 24(19); 4680–93. ©2018 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 2
    Publication Date: 2018-03-06
    Description: Spike density and processing quality are important traits in modern wheat production and are controlled by multiple gene loci. The associated genes have been intensively studied and new discoveries have been constantly reported during the past few decades. However, no gene playing a significant role in the development of these two traits has been identified. In the current study, a common wheat mutant with extremely compact spikes and good processing quality was isolated and characterized. A new allele ( Q c1 ) of the Q gene (an important domestication gene) responsible for the mutant phenotype was cloned, and the molecular mechanism for the mutant phenotype was studied. Results revealed that Q c1 originated from a point mutation that interferes with the miRNA172-directed cleavage of Q transcripts, leading to its overexpression. It also reduces the longitudinal cell size of rachises, resulting in an increased spike density. Furthermore, Q c1 increases the number of vascular bundles, which suggests a higher efficiency in the transportation of assimilates in the spikes of the mutant than that of wild type. This accounts for the improved processing quality. The effects of Q c1 on spike density and wheat processing quality were confirmed by analyzing nine common wheat mutants possessing four different Q c alleles. These results deepen our understanding of the key roles of Q gene, and provide new insights for the potential application of Q c alleles in wheat quality breeding.
    Electronic ISSN: 2160-1836
    Topics: Biology
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  • 3
    Publication Date: 2018-09-13
    Description: Tailoring the morphology of cobalt–nickel layered double hydroxide (LDH) electrode material was successfully achieved via the process of cathodic electrodeposition by adding different surfactants (hexamethylenetetramine, dodecyltrimethylammonium bromide (DTAB) or cetyltrimethylammonium bromide). The as-prepared Co 0.75 Ni 0.25 (OH) 2 samples with surfactants exhibited wrinkle-like, cauliflower-like or net-like structures that corresponded to better electrochemical performances than the untreated one. In particular, a specific capacitance of 1209.1 F g –1 was found for the cauliflower-like Co 0.75 Ni 0.25 (OH) 2 electrode material using DTAB as the surfactant at a current density of 1 A g –1 , whose structure boosted ion diffusion to present a good rate ability of 64% with a 50-fold increase in current density from 1 A g –1 to 50 A g –1 . Accordingly, the asymmetric supercapacitor assembled by current LDH electrode and activated carbon electrode showed an energy density as high as 21.3 Wh kg –1 at a power density of 3625 W kg –1 . The relationship between surfactant and electrochemical performance of the LDH electrode materials has been discussed.
    Keywords: materials science, energy
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 4
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-12-21
    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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  • 5
    Publication Date: 2011-06-17
    Description: Transforming growth factor (TGF)-beta is stored in the extracellular matrix as a latent complex with its prodomain. Activation of TGF-beta1 requires the binding of alpha(v) integrin to an RGD sequence in the prodomain and exertion of force on this domain, which is held in the extracellular matrix by latent TGF-beta binding proteins. Crystals of dimeric porcine proTGF-beta1 reveal a ring-shaped complex, a novel fold for the prodomain, and show how the prodomain shields the growth factor from recognition by receptors and alters its conformation. Complex formation between alpha(v)beta(6) integrin and the prodomain is insufficient for TGF-beta1 release. Force-dependent activation requires unfastening of a 'straitjacket' that encircles each growth-factor monomer at a position that can be locked by a disulphide bond. Sequences of all 33 TGF-beta family members indicate a similar prodomain fold. The structure provides insights into the regulation of a family of growth and differentiation factors of fundamental importance in morphogenesis and homeostasis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4717672/" 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/PMC4717672/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shi, Minlong -- Zhu, Jianghai -- Wang, Rui -- Chen, Xing -- Mi, Lizhi -- Walz, Thomas -- Springer, Timothy A -- P01 HL103526/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Jun 15;474(7351):343-9. doi: 10.1038/nature10152.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immune Disease Institute, Children's Hospital Boston and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21677751" target="_blank"〉PubMed〈/a〉
    Keywords: Activins/metabolism ; Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Antigens, Neoplasm/chemistry/metabolism ; Camurati-Engelmann Syndrome/genetics ; Cell Line ; Crystallography, X-Ray ; HEK293 Cells ; Humans ; Integrins/chemistry/metabolism ; Latent TGF-beta Binding Proteins/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Multigene Family ; Mutation/genetics ; Oligopeptides/chemistry/metabolism ; Protein Structure, Tertiary ; Receptors, Transforming Growth Factor beta/chemistry/metabolism ; Swine ; Transforming Growth Factor beta1/biosynthesis/*chemistry/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2013-07-05
    Description: The variant antigen Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), which is expressed on the surface of P. falciparum-infected red blood cells, is a critical virulence factor for malaria. Each parasite has 60 antigenically distinct var genes that each code for a different PfEMP1 protein. During infection the clonal parasite population expresses only one gene at a time before switching to the expression of a new variant antigen as an immune-evasion mechanism to avoid the host antibody response. The mechanism by which 59 of the 60 var genes are silenced remains largely unknown. Here we show that knocking out the P. falciparum variant-silencing SET gene (here termed PfSETvs), which encodes an orthologue of Drosophila melanogaster ASH1 and controls histone H3 lysine 36 trimethylation (H3K36me3) on var genes, results in the transcription of virtually all var genes in the single parasite nuclei and their expression as proteins on the surface of individual infected red blood cells. PfSETvs-dependent H3K36me3 is present along the entire gene body, including the transcription start site, to silence var genes. With low occupancy of PfSETvs at both the transcription start site of var genes and the intronic promoter, expression of var genes coincides with transcription of their corresponding antisense long noncoding RNA. These results uncover a previously unknown role of PfSETvs-dependent H3K36me3 in silencing var genes in P. falciparum that might provide a general mechanism by which orthologues of PfSETvs repress gene expression in other eukaryotes. PfSETvs knockout parasites expressing all PfEMP1 proteins may also be applied to the development of a malaria vaccine.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770130/" 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/PMC3770130/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, Lubin -- Mu, Jianbing -- Zhang, Qingfeng -- Ni, Ting -- Srinivasan, Prakash -- Rayavara, Kempaiah -- Yang, Wenjing -- Turner, Louise -- Lavstsen, Thomas -- Theander, Thor G -- Peng, Weiqun -- Wei, Guiying -- Jing, Qingqing -- Wakabayashi, Yoshiyuki -- Bansal, Abhisheka -- Luo, Yan -- Ribeiro, Jose M C -- Scherf, Artur -- Aravind, L -- Zhu, Jun -- Zhao, Keji -- Miller, Louis H -- 250320/European Research Council/International -- Z01 AI000241-27/Intramural NIH HHS/ -- ZIA AI000241-31/Intramural NIH HHS/ -- England -- Nature. 2013 Jul 11;499(7457):223-7. doi: 10.1038/nature12361. Epub 2013 Jul 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Key Laboratory of Molecular Virology & Immunology, Unit of Human Parasite Molecular and Cell Biology, Institut Pasteur of Shanghai, Shanghai 200031, China. lbjiang@ips.ac.cn〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23823717" target="_blank"〉PubMed〈/a〉
    Keywords: DNA-Binding Proteins ; Drosophila Proteins ; Erythrocytes/cytology/metabolism/parasitology ; *Gene Silencing ; Genes, Protozoan/genetics ; Histones/chemistry/*metabolism ; Introns/genetics ; Lysine/metabolism ; Malaria Vaccines/genetics ; Methylation ; Plasmodium falciparum/*genetics/metabolism/*pathogenicity ; Promoter Regions, Genetic/genetics ; Protozoan Proteins/genetics/*metabolism ; RNA, Long Noncoding/genetics ; Transcription Factors ; Transcription Initiation Site ; Virulence/genetics ; Virulence Factors/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2013-05-10
    Description: Most herpes simplex virus 2 (HSV-2) reactivations in humans are subclinical and associated with rapid expansion and containment of virus. Previous studies have shown that CD8(+) T cells persist in genital skin and mucosa at the dermal-epidermal junction (DEJ)--the portal of neuronal release of reactivating virus--for prolonged time periods after herpes lesions are cleared. The phenotype and function of this persistent CD8(+) T-cell population remain unknown. Here, using cell-type-specific laser capture microdissection, transcriptional profiling and T-cell antigen receptor beta-chain (TCRbeta) genotyping on sequential genital skin biopsies, we show that CD8alphaalpha(+) T cells are the dominant resident population of DEJ CD8(+) T cells that persist at the site of previous HSV-2 reactivation. CD8alphaalpha(+) T cells located at the DEJ lack chemokine-receptor expression required for lymphocyte egress and recirculation, express gene signatures of T-cell activation and antiviral activity, and produce cytolytic granules during clinical and virological quiescent time periods. Sequencing of the TCR beta-chain repertoire reveals that the DEJ CD8alphaalpha(+) T cells are oligoclonal with diverse usage of TCR variable-beta genes, which differ from those commonly described for mucosa-associated invariant T cells and natural killer T cells. Dominant clonotypes are shown to overlap among multiple recurrences over a period of two-and-a-half years. Episodes of rapid asymptomatic HSV-2 containment were also associated with a high CD8 effector-to-target ratio and focal enrichment of CD8alphaalpha(+) T cells. These studies indicate that DEJ CD8alphaalpha(+) T cells are tissue-resident cells that seem to have a fundamental role in immune surveillance and in initial containment of HSV-2 reactivation in human peripheral tissue. Elicitation of CD8alphaalpha(+) T cells may be a critical component for developing effective vaccines against skin and mucosal infections.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663925/" 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/PMC3663925/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhu, Jia -- Peng, Tao -- Johnston, Christine -- Phasouk, Khamsone -- Kask, Angela S -- Klock, Alexis -- Jin, Lei -- Diem, Kurt -- Koelle, David M -- Wald, Anna -- Robins, Harlan -- Corey, Lawrence -- P01 AI030731/AI/NIAID NIH HHS/ -- P01AI030731/AI/NIAID NIH HHS/ -- R01 AI042528/AI/NIAID NIH HHS/ -- R01 AI094019/AI/NIAID NIH HHS/ -- R01AI04252815/AI/NIAID NIH HHS/ -- R37 AI042528/AI/NIAID NIH HHS/ -- R37AI042528/AI/NIAID NIH HHS/ -- R56 AI093746/AI/NIAID NIH HHS/ -- R56AI093746/AI/NIAID NIH HHS/ -- England -- Nature. 2013 May 23;497(7450):494-7. doi: 10.1038/nature12110. Epub 2013 May 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Laboratory Medicine, University of Washington, Seattle, Washington 98195, USA. jiazhu@u.washington.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23657257" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; CD8-Positive T-Lymphocytes/cytology/*immunology ; Clone Cells/cytology/immunology ; Herpes Genitalis/*immunology/virology ; Herpesvirus 2, Human/*immunology ; Humans ; Immunologic Memory/immunology ; *Immunologic Surveillance ; Receptors, Antigen, T-Cell, alpha-beta/immunology/metabolism ; Skin/*cytology/*immunology
    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: 2014-07-22
    Description: Extensive genomic characterization of human cancers presents the problem of inference from genomic abnormalities to cancer phenotypes. To address this problem, we analysed proteomes of colon and rectal tumours characterized previously by The Cancer Genome Atlas (TCGA) and perform integrated proteogenomic analyses. Somatic variants displayed reduced protein abundance compared to germline variants. Messenger RNA transcript abundance did not reliably predict protein abundance differences between tumours. Proteomics identified five proteomic subtypes in the TCGA cohort, two of which overlapped with the TCGA 'microsatellite instability/CpG island methylation phenotype' transcriptomic subtype, but had distinct mutation, methylation and protein expression patterns associated with different clinical outcomes. Although copy number alterations showed strong cis- and trans-effects on mRNA abundance, relatively few of these extend to the protein level. Thus, proteomics data enabled prioritization of candidate driver genes. The chromosome 20q amplicon was associated with the largest global changes at both mRNA and protein levels; proteomics data highlighted potential 20q candidates, including HNF4A (hepatocyte nuclear factor 4, alpha), TOMM34 (translocase of outer mitochondrial membrane 34) and SRC (SRC proto-oncogene, non-receptor tyrosine kinase). Integrated proteogenomic analysis provides functional context to interpret genomic abnormalities and affords a new paradigm for understanding cancer biology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249766/" 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/PMC4249766/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Bing -- Wang, Jing -- Wang, Xiaojing -- Zhu, Jing -- Liu, Qi -- Shi, Zhiao -- Chambers, Matthew C -- Zimmerman, Lisa J -- Shaddox, Kent F -- Kim, Sangtae -- Davies, Sherri R -- Wang, Sean -- Wang, Pei -- Kinsinger, Christopher R -- Rivers, Robert C -- Rodriguez, Henry -- Townsend, R Reid -- Ellis, Matthew J C -- Carr, Steven A -- Tabb, David L -- Coffey, Robert J -- Slebos, Robbert J C -- Liebler, Daniel C -- NCI CPTAC -- GM088822/GM/NIGMS NIH HHS/ -- P30 CA068485/CA/NCI NIH HHS/ -- P30 DK058404/DK/NIDDK NIH HHS/ -- P30CA068485/CA/NCI NIH HHS/ -- P50 CA095103/CA/NCI NIH HHS/ -- P50CA095103/CA/NCI NIH HHS/ -- R01 GM088822/GM/NIGMS NIH HHS/ -- U24 CA159988/CA/NCI NIH HHS/ -- U24 CA160019/CA/NCI NIH HHS/ -- U24 CA160034/CA/NCI NIH HHS/ -- U24 CA160035/CA/NCI NIH HHS/ -- U24CA159988/CA/NCI NIH HHS/ -- U24CA160034/CA/NCI NIH HHS/ -- U24CA160035/CA/NCI NIH HHS/ -- U54 HG003079/HG/NHGRI NIH HHS/ -- UL1 TR000448/TR/NCATS NIH HHS/ -- England -- Nature. 2014 Sep 18;513(7518):382-7. doi: 10.1038/nature13438. Epub 2014 Jul 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA [2] Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. ; Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. ; 1] Advanced Computing Center for Research and Education, Vanderbilt University, Nashville, Tennessee 37232, USA [2] Department of Electrical Engineering and Computer Science, Vanderbilt University, Tennessee 37232, USA. ; 1] Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA [2] Jim Ayers Institute for Precancer Detection and Diagnosis, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232, USA. ; Jim Ayers Institute for Precancer Detection and Diagnosis, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232, USA. ; Directorate of Fundamental and Computational Sciences, Pacific Northwest National Laboratory, Richland, Washington 99352, USA. ; Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA. ; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M2-B500, Seattle, Washington 98109, USA. ; Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1498, New York, New York 10029, USA. ; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, Maryland 20892, USA. ; Broad Institute of MIT and Harvard, Cambridge, Maryland 02142, USA. ; Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. ; 1] Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA [2] Jim Ayers Institute for Precancer Detection and Diagnosis, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043054" target="_blank"〉PubMed〈/a〉
    Keywords: Chromosomes, Human, Pair 20/genetics ; Colonic Neoplasms/*genetics/*metabolism ; CpG Islands/genetics ; DNA Copy Number Variations/genetics ; DNA Methylation ; *Genomics ; Hepatocyte Nuclear Factor 4/genetics ; Humans ; Microsatellite Repeats/genetics ; Mitochondrial Membrane Transport Proteins/genetics ; Mutation, Missense/genetics ; Neoplasm Proteins/analysis/genetics/metabolism ; Point Mutation/genetics ; Proteome/analysis/genetics/*metabolism ; Proteomics ; Proto-Oncogene Proteins pp60(c-src)/genetics ; RNA, Messenger/analysis/genetics/metabolism ; RNA, Neoplasm/analysis/genetics/metabolism ; Rectal Neoplasms/*genetics/*metabolism ; Transcriptome/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2014-07-18
    Description: The surface of the cornea consists of a unique type of non-keratinized epithelial cells arranged in an orderly fashion, and this is essential for vision by maintaining transparency for light transmission. Cornea epithelial cells (CECs) undergo continuous renewal from limbal stem or progenitor cells (LSCs), and deficiency in LSCs or corneal epithelium--which turns cornea into a non-transparent, keratinized skin-like epithelium--causes corneal surface disease that leads to blindness in millions of people worldwide. How LSCs are maintained and differentiated into corneal epithelium in healthy individuals and which key molecular events are defective in patients have been largely unknown. Here we report establishment of an in vitro feeder-cell-free LSC expansion and three-dimensional corneal differentiation protocol in which we found that the transcription factors p63 (tumour protein 63) and PAX6 (paired box protein PAX6) act together to specify LSCs, and WNT7A controls corneal epithelium differentiation through PAX6. Loss of WNT7A or PAX6 induces LSCs into skin-like epithelium, a critical defect tightly linked to common human corneal diseases. Notably, transduction of PAX6 in skin epithelial stem cells is sufficient to convert them to LSC-like cells, and upon transplantation onto eyes in a rabbit corneal injury model, these reprogrammed cells are able to replenish CECs and repair damaged corneal surface. These findings suggest a central role of the WNT7A-PAX6 axis in corneal epithelial cell fate determination, and point to a new strategy for treating corneal surface diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4610745/" 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/PMC4610745/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ouyang, Hong -- Xue, Yuanchao -- Lin, Ying -- Zhang, Xiaohui -- Xi, Lei -- Patel, Sherrina -- Cai, Huimin -- Luo, Jing -- Zhang, Meixia -- Zhang, Ming -- Yang, Yang -- Li, Gen -- Li, Hairi -- Jiang, Wei -- Yeh, Emily -- Lin, Jonathan -- Pei, Michelle -- Zhu, Jin -- Cao, Guiqun -- Zhang, Liangfang -- Yu, Benjamin -- Chen, Shaochen -- Fu, Xiang-Dong -- Liu, Yizhi -- Zhang, Kang -- GM049369/GM/NIGMS NIH HHS/ -- R01 EY020846/EY/NEI NIH HHS/ -- R01 EY021374/EY/NEI NIH HHS/ -- England -- Nature. 2014 Jul 17;511(7509):358-61. doi: 10.1038/nature13465. Epub 2014 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [2] Department of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA. ; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92093, USA. ; 1] Department of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing 100730, China (X.Z.); Department of Ophthalmology, Shengjing Hospital of China Medical University, Shenyang 110004, China (Y.Y.). ; Department of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA. ; 1] Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China [2] Guangzhou KangRui Biological Pharmaceutical Technology Company Ltd., Guangzhou 510005, China. ; Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China. ; 1] Department of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Nanoengineering, University of California San Diego, La Jolla, California 92093, USA. ; 1] Department of Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Institute for Genomic Medicine, University of California San Diego, La Jolla, California 92093, USA. ; 1] Department of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92093, USA [3] Institute for Genomic Medicine, University of California San Diego, La Jolla, California 92093, USA. ; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China. ; 1] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [2] Department of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [3] Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China [4] Institute for Genomic Medicine, University of California San Diego, La Jolla, California 92093, USA [5] Veterans Administration Healthcare System, San Diego, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25030175" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Lineage ; Corneal Diseases/*metabolism/*pathology ; Disease Models, Animal ; Epithelium, Corneal/*cytology/*metabolism/pathology ; Eye Proteins/genetics/*metabolism ; Homeodomain Proteins/genetics/*metabolism ; *Homeostasis ; Humans ; Limbus Corneae/cytology/metabolism ; Male ; Paired Box Transcription Factors/genetics/*metabolism ; Rabbits ; Repressor Proteins/genetics/*metabolism ; Signal Transduction ; Skin/cytology/metabolism/pathology ; Stem Cell Transplantation ; Stem Cells/cytology/metabolism ; Transcription Factors/metabolism ; Tumor Suppressor Proteins/metabolism ; Wnt Proteins/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2015-02-06
    Description: The central dogma of gene expression (DNA to RNA to protein) is universal, but in different domains of life there are fundamental mechanistic differences within this pathway. For example, the canonical molecular signals used to initiate protein synthesis in bacteria and eukaryotes are mutually exclusive. However, the core structures and conformational dynamics of ribosomes that are responsible for the translation steps that take place after initiation are ancient and conserved across the domains of life. We wanted to explore whether an undiscovered RNA-based signal might be able to use these conserved features, bypassing mechanisms specific to each domain of life, and initiate protein synthesis in both bacteria and eukaryotes. Although structured internal ribosome entry site (IRES) RNAs can manipulate ribosomes to initiate translation in eukaryotic cells, an analogous RNA structure-based mechanism has not been observed in bacteria. Here we report our discovery that a eukaryotic viral IRES can initiate translation in live bacteria. We solved the crystal structure of this IRES bound to a bacterial ribosome to 3.8 A resolution, revealing that despite differences between bacterial and eukaryotic ribosomes this IRES binds directly to both and occupies the space normally used by transfer RNAs. Initiation in both bacteria and eukaryotes depends on the structure of the IRES RNA, but in bacteria this RNA uses a different mechanism that includes a form of ribosome repositioning after initial recruitment. This IRES RNA bridges billions of years of evolutionary divergence and provides an example of an RNA structure-based translation initiation signal capable of operating in two domains of life.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352134/" 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/PMC4352134/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Colussi, Timothy M -- Costantino, David A -- Zhu, Jianyu -- Donohue, John Paul -- Korostelev, Andrei A -- Jaafar, Zane A -- Plank, Terra-Dawn M -- Noller, Harry F -- Kieft, Jeffrey S -- GM-103105/GM/NIGMS NIH HHS/ -- GM-17129/GM/NIGMS NIH HHS/ -- GM-59140/GM/NIGMS NIH HHS/ -- GM-81346/GM/NIGMS NIH HHS/ -- GM-97333/GM/NIGMS NIH HHS/ -- R01 GM097333/GM/NIGMS NIH HHS/ -- R01 GM106105/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Mar 5;519(7541):110-3. doi: 10.1038/nature14219. Epub 2015 Feb 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA [2] Howard Hughes Medical Institute, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA. ; Center for Molecular Biology of RNA and Department of Molecular, Cell and Developmental Biology, Sinsheimer Labs, University of California at Santa Cruz, Santa Cruz, California 95064, USA. ; Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25652826" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteria/*genetics ; Base Sequence ; Conserved Sequence/genetics ; Crystallography, X-Ray ; Dicistroviridae/genetics ; Eukaryota/*genetics ; Models, Molecular ; *Nucleic Acid Conformation ; Peptide Chain Initiation, Translational/genetics ; Protein Biosynthesis/*genetics ; RNA/*chemistry/*genetics/metabolism ; RNA, Bacterial/chemistry/genetics/metabolism ; RNA, Viral/chemistry/genetics/metabolism ; Ribosomes/chemistry/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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