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  • 1
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    A Phage Tail-Derived Element with Wide Distribution among Both Prokaryotic Domains: A Comparative Genomic and Phylogenetic Study (2014)
    Oxford University Press
    Details
    Publication Date: 2014-07-14
    Description: Prophage sequences became an integral part of bacterial genomes as a consequence of coevolution, encoding fitness or virulence factors. Such roles have been attributed to phage-derived elements identified in several Gram-negative species: The type VI secretion system (T6SS), the R- and F-type pyocins, and the newly discovered Serratia entomophila antifeeding prophage (Afp), and the Photorhabdus luminescens virulence cassette (PVC). In this study, we provide evidence that remarkably conserved gene clusters, homologous to Afp/PVC, are not restricted to Gram-negative bacteria but are widespread throughout all prokaryotes including the Archaea. Even though they are phylogenetically closer to pyocins, they share key characteristics in common with the T6SS, such as the use of a chaperon-type AAA+ ATPase and the lack of a host cell lysis mechanism. We thus suggest that Afp/PVC-like elements could be classified as phage-like-protein-translocation structures (PLTSs) rather than as pyocins. The reconstruction of phylogeny and the conserved gene content suggest that the diversification of prophage sequences to PLTS occurred in bacteria early in evolution and only once, but PLTS clusters have been horizontally transferred to some of the bacterial lineages and to the Archaea. The adaptation of this element in such a wide host range is suggestive of its versatile use in prokaryotes.
    Electronic ISSN: 1759-6653
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Somatic coding mutations in human induced pluripotent stem cells (2011)
    Nature Publishing Group (NPG)
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    Publication Date: 2011-03-04
    Description: Defined transcription factors can induce epigenetic reprogramming of adult mammalian cells into induced pluripotent stem cells. Although DNA factors are integrated during some reprogramming methods, it is unknown whether the genome remains unchanged at the single nucleotide level. Here we show that 22 human induced pluripotent stem (hiPS) cell lines reprogrammed using five different methods each contained an average of five protein-coding point mutations in the regions sampled (an estimated six protein-coding point mutations per exome). The majority of these mutations were non-synonymous, nonsense or splice variants, and were enriched in genes mutated or having causative effects in cancers. At least half of these reprogramming-associated mutations pre-existed in fibroblast progenitors at low frequencies, whereas the rest occurred during or after reprogramming. Thus, hiPS cells acquire genetic modifications in addition to epigenetic modifications. Extensive genetic screening should become a standard procedure to ensure hiPS cell safety before clinical use.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3074107/" 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/PMC3074107/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gore, Athurva -- Li, Zhe -- Fung, Ho-Lim -- Young, Jessica E -- Agarwal, Suneet -- Antosiewicz-Bourget, Jessica -- Canto, Isabel -- Giorgetti, Alessandra -- Israel, Mason A -- Kiskinis, Evangelos -- Lee, Je-Hyuk -- Loh, Yuin-Han -- Manos, Philip D -- Montserrat, Nuria -- Panopoulos, Athanasia D -- Ruiz, Sergio -- Wilbert, Melissa L -- Yu, Junying -- Kirkness, Ewen F -- Izpisua Belmonte, Juan Carlos -- Rossi, Derrick J -- Thomson, James A -- Eggan, Kevin -- Daley, George Q -- Goldstein, Lawrence S B -- Zhang, Kun -- K08 HL089150/HL/NHLBI NIH HHS/ -- R01 HL094963/HL/NHLBI NIH HHS/ -- R01 HL094963-01/HL/NHLBI NIH HHS/ -- T32 GM008666/GM/NIGMS NIH HHS/ -- U01 HL100001/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Mar 3;471(7336):63-7. doi: 10.1038/nature09805.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21368825" target="_blank"〉PubMed〈/a〉
    Keywords: Cells, Cultured ; Cellular Reprogramming/*genetics ; DNA Mutational Analysis ; Epistasis, Genetic/genetics ; Fibroblasts/cytology/metabolism ; Humans ; Induced Pluripotent Stem Cells/cytology/*metabolism ; Male ; Middle Aged ; Models, Genetic ; Mutagenesis/*genetics ; Open Reading Frames/genetics ; Point Mutation/*genetics
    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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  • 3
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    Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-02-25
    Description: Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal human premature ageing disease, characterized by premature arteriosclerosis and degeneration of vascular smooth muscle cells (SMCs). HGPS is caused by a single point mutation in the lamin A (LMNA) gene, resulting in the generation of progerin, a truncated splicing mutant of lamin A. Accumulation of progerin leads to various ageing-associated nuclear defects including disorganization of nuclear lamina and loss of heterochromatin. Here we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS. HGPS-iPSCs show absence of progerin, and more importantly, lack the nuclear envelope and epigenetic alterations normally associated with premature ageing. Upon differentiation of HGPS-iPSCs, progerin and its ageing-associated phenotypic consequences are restored. Specifically, directed differentiation of HGPS-iPSCs to SMCs leads to the appearance of premature senescence phenotypes associated with vascular ageing. Additionally, our studies identify DNA-dependent protein kinase catalytic subunit (DNAPKcs, also known as PRKDC) as a downstream target of progerin. The absence of nuclear DNAPK holoenzyme correlates with premature as well as physiological ageing. Because progerin also accumulates during physiological ageing, our results provide an in vitro iPSC-based model to study the pathogenesis of human premature and physiological vascular ageing.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3088088/" 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/PMC3088088/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Guang-Hui -- Barkho, Basam Z -- Ruiz, Sergio -- Diep, Dinh -- Qu, Jing -- Yang, Sheng-Lian -- Panopoulos, Athanasia D -- Suzuki, Keiichiro -- Kurian, Leo -- Walsh, Christopher -- Thompson, James -- Boue, Stephanie -- Fung, Ho Lim -- Sancho-Martinez, Ignacio -- Zhang, Kun -- Yates, John 3rd -- Izpisua Belmonte, Juan Carlos -- P41 RR011823/RR/NCRR NIH HHS/ -- R01 DA025779/DA/NIDA NIH HHS/ -- R01 DA025779-01/DA/NIDA NIH HHS/ -- R01-DA025779/DA/NIDA NIH HHS/ -- T32 CA009370/CA/NCI NIH HHS/ -- T32 CA009370-25A1/CA/NCI NIH HHS/ -- England -- Nature. 2011 Apr 14;472(7342):221-5. doi: 10.1038/nature09879. Epub 2011 Feb 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21346760" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/metabolism/pathology/physiology ; Aging, Premature/genetics/pathology/physiopathology ; Calcium-Binding Proteins/analysis ; Cell Aging ; Cell Differentiation ; Cell Line ; Cellular Reprogramming ; DNA-Activated Protein Kinase/metabolism ; Epigenesis, Genetic ; Fibroblasts/pathology ; Holoenzymes/metabolism ; Humans ; Induced Pluripotent Stem Cells/metabolism/*pathology ; Lamin Type A ; Microfilament Proteins/analysis ; Models, Biological ; Muscle, Smooth, Vascular/pathology ; Nuclear Envelope/pathology ; Nuclear Proteins/analysis/genetics/metabolism ; Phenotype ; Progeria/genetics/pathology/physiopathology ; Protein Precursors/analysis/genetics/metabolism ; Substrate Specificity
    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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    Analysis of protein-coding mutations in hiPSCs and their possible role during somatic cell reprogramming (2013)
    Springer Nature
    Details
    Publication Date: 2013-01-23
    Description: Analysis of protein-coding mutations in hiPSCs and their possible role during somatic cell reprogramming Nature Communications 4, 1382 (2013). doi:10.1038/ncomms2381 Authors: Sergio Ruiz, Athurva Gore, Zhe Li, Athanasia D. Panopoulos, Nuria Montserrat, Ho-Lim Fung, Alessandra Giorgetti, Josipa Bilic, Erika M. Batchelder, Holm Zaehres, Hans R. Schöler, Kun Zhang & Juan Carlos Izpisua Belmonte
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 5
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    Alternative thermochemical routes for aviation biofuels via alcohols synthesis: Process modeling, techno-economic assessment and comparison (2015)
    Elsevier
    Details
    Publication Date: 2015-01-01
    Print ISSN: 0306-2619
    Electronic ISSN: 1872-9118
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Published by Elsevier
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