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  • 1
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    Insulin staining of ES cell progeny from insulin uptake (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-01-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rajagopal, Jayaraj -- Anderson, William J -- Kume, Shoen -- Martinez, Olga I -- Melton, Douglas A -- New York, N.Y. -- Science. 2003 Jan 17;299(5605):363.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12532008" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies/immunology ; Apoptosis ; Cell Differentiation ; Cell Line ; Embryo, Mammalian/*cytology ; Humans ; Insulin/*analysis/genetics/immunology/*metabolism ; Islets of Langerhans/*cytology/metabolism ; Mice ; Microscopy, Confocal ; RNA, Messenger/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Stem Cells/*cytology/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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  • 2
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    In vivo reprogramming of adult pancreatic exocrine cells to beta-cells (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-08-30
    Description: One goal of regenerative medicine is to instructively convert adult cells into other cell types for tissue repair and regeneration. Although isolated examples of adult cell reprogramming are known, there is no general understanding of how to turn one cell type into another in a controlled manner. Here, using a strategy of re-expressing key developmental regulators in vivo, we identify a specific combination of three transcription factors (Ngn3 (also known as Neurog3) Pdx1 and Mafa) that reprograms differentiated pancreatic exocrine cells in adult mice into cells that closely resemble beta-cells. The induced beta-cells are indistinguishable from endogenous islet beta-cells in size, shape and ultrastructure. They express genes essential for beta-cell function and can ameliorate hyperglycaemia by remodelling local vasculature and secreting insulin. This study provides an example of cellular reprogramming using defined factors in an adult organ and suggests a general paradigm for directing cell reprogramming without reversion to a pluripotent stem cell state.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Qiao -- Brown, Juliana -- Kanarek, Andrew -- Rajagopal, Jayaraj -- Melton, Douglas A -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Oct 2;455(7213):627-32. doi: 10.1038/nature07314. Epub 2008 Aug 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Stem Cell and Regenerative Biology, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18754011" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/physiology ; Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism ; Biomarkers/analysis ; Cell Shape ; Cell Size ; *Cell Transdifferentiation ; Homeodomain Proteins/genetics/metabolism ; Hyperglycemia/metabolism ; Insulin/metabolism ; Insulin-Secreting Cells/*cytology/metabolism/ultrastructure ; Maf Transcription Factors, Large/genetics/metabolism ; Mice ; Neovascularization, Physiologic ; Nerve Tissue Proteins/genetics/metabolism ; Pancreas, Exocrine/*cytology/embryology/secretion ; Regenerative Medicine/methods ; Trans-Activators/genetics/metabolism ; Transcription Factors/genetics/*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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  • 3
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    Pattern formation during animal development (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-04-12
    Description: At the beginning of this century, embryologists defined the central problems of developmental biology that remain today. These questions include how differentiated cells arise and form tissues and organs and how pattern is generated. In short, how does an egg give rise to an adult? In recent years, the application of molecular biology to embryological problems has led to significant advances and recast old problems in molecular and cellular terms. Although not necessarily comprehensive, this idiosyncratic review is intended to highlight selected findings and indicate where there are important gaps in our knowledge for those less than familiar with developmental biology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Melton, D A -- New York, N.Y. -- Science. 1991 Apr 12;252(5003):234-41.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1672778" target="_blank"〉PubMed〈/a〉
    Keywords: Activins ; Animals ; Drosophila melanogaster/embryology ; *Embryonic Development ; Gene Expression ; Genes, Homeobox ; Inhibins/physiology ; *Morphogenesis ; Ovum/ultrastructure ; RNA, Messenger/genetics ; Tretinoin ; Xenopus laevis/embryology
    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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  • 4
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    Induction of mesoderm by a viral oncogene in early Xenopus embryos (1989)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1989-05-19
    Description: During frog embryogenesis, mesoderm is specified in the equatorial region of the early embryo by a signal from the vegetal hemisphere. Prospective ectodermal cells dissected from the animal hemisphere can be respecified to form mesodermal tissues by recombination with vegetal tissue or by treatment with any of several polypeptide growth factors or growth factor-like molecules. Together with the discovery that several developmental mutations in Drosophila are in genes with significant homology to mammalian mitogens and oncogenes, these observations suggest that early developmental signals may use similar transduction pathways to mitogenic signals characterized in cultured mammalian cells. Whether mesoderm can be induced by activation of intracellular signal transduction pathways implicated in mitogenesis and oncogenesis has been investigated with the viral oncogene polyoma middle T. Microinjection of middle T messenger RNA into early embryos results in the respecification of isolated prospective ectodermal tissue to form characteristic mesodermal structures. Middle T in frog blastomeres appears to associate with cellular activities similar to those observed in polyoma-transformed mouse cells, and transformation-defective middle T mutants fail to induce mesoderm. These results suggest that early inductive signals and mitogenic and oncogenic stimuli may share common signal transduction pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Whitman, M -- Melton, D A -- New York, N.Y. -- Science. 1989 May 19;244(4906):803-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2658054" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Polyomavirus Transforming/genetics ; Blastocyst/physiology ; Blastomeres/physiology ; Ectoderm/physiology ; Immunosorbent Techniques ; Mesoderm/*physiology ; Mitosis ; Morphogenesis ; Muscles/embryology ; Mutation ; *Oncogenes ; Protein-Tyrosine Kinases/metabolism ; RNA, Messenger/genetics ; *Signal Transduction ; Transfection ; Transformation, Genetic ; Xenopus/*embryology
    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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  • 5
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    A mouse macrophage factor induces head structures and organizes a body axis in Xenopus (1990)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1990-08-03
    Description: Soluble peptide factors have been implicated as the agents responsible for embryonic inductions in vertebrates. Here, a protein (PIF) secreted by a mouse macrophage cell line is shown to change the developmental fate of Xenopus embryonic cells. Exposure to PIF causes presumptive ectodermal explants to form anterior neural and mesodermal tissues, including brain and eye, instead of ciliated epidermis. In addition, the induced tissues are organized into a rudimentary embryonic axis. These results suggest that PIF or a closely related molecule is involved in inducing anterior structures and organizing the frog body plan.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sokol, S -- Wong, G G -- Melton, D A -- GM 32921/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1990 Aug 3;249(4968):561-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2382134" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastocyst/cytology/drug effects/*physiology ; Cell Differentiation/drug effects ; Embryo, Nonmammalian/cytology/drug effects/*physiology ; Macrophages/*physiology ; Mice ; Molecular Weight ; Organ Culture Techniques ; Proteins/isolation & purification/*pharmacology/secretion ; Xenopus
    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
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    Nuclear reprogramming in cells (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-12-20
    Description: Nuclear reprogramming describes a switch in gene expression of one kind of cell to that of another unrelated cell type. Early studies in frog cloning provided some of the first experimental evidence for reprogramming. Subsequent procedures included mammalian somatic cell nuclear transfer, cell fusion, induction of pluripotency by ectopic gene expression, and direct reprogramming. Through these methods it becomes possible to derive one kind of specialized cell (such as a brain cell) from another, more accessible, tissue (such as skin) in the same individual. This has potential applications for cell replacement without the immunosuppression treatments that are required when cells are transferred between genetically different individuals. This article provides some background to this field, a discussion of mechanisms and efficiency, and comments on prospects for future nuclear reprogramming research.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gurdon, J B -- Melton, D A -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2008 Dec 19;322(5909):1811-5. doi: 10.1126/science.1160810.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Zoology, University of Cambridge, Cambridge CB2 12N, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19095934" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Dedifferentiation ; Cell Differentiation ; Cell Fusion ; Cell Lineage ; *Cellular Reprogramming ; Cloning, Organism ; DNA/metabolism ; DNA-Binding Proteins/metabolism ; Embryonic Stem Cells/cytology/physiology ; Female ; Gene Expression ; Humans ; Male ; Nuclear Transfer Techniques ; Oocytes/cytology ; Pluripotent Stem Cells/cytology/physiology ; Regulatory Sequences, Nucleic Acid ; Transcription Factors/genetics/metabolism
    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
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    Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells (2005)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2005-08-27
    Description: We have explored the use of embryonic stem cells as an alternative to oocytes for reprogramming human somatic nuclei. Human embryonic stem (hES) cells were fused with human fibroblasts, resulting in hybrid cells that maintain a stable tetraploid DNA content and have morphology, growth rate, and antigen expression patterns characteristic of hES cells. Differentiation of hybrid cells in vitro and in vivo yielded cell types from each embryonic germ layer. Analysis of genome-wide transcriptional activity, reporter gene activation, allele-specific gene expression, and DNA methylation showed that the somatic genome was reprogrammed to an embryonic state. These results establish that hES cells can reprogram the transcriptional state of somatic nuclei and provide a system for investigating the underlying mechanisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cowan, Chad A -- Atienza, Jocelyn -- Melton, Douglas A -- Eggan, Kevin -- New York, N.Y. -- Science. 2005 Aug 26;309(5739):1369-73.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Harvard Stem Cell Institute, Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16123299" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Biomarkers/analysis ; Cell Cycle ; Cell Differentiation ; *Cell Fusion ; Cell Line ; Cell Nucleus/*physiology ; Cell Shape ; Cell Transplantation ; Chromosomes, Human/genetics ; Embryo, Mammalian/*cytology ; Epigenesis, Genetic ; Female ; Fibroblasts/cytology/*physiology ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Humans ; Hybrid Cells/cytology/*physiology ; Male ; Mice ; Mice, Nude ; Phenotype ; Pluripotent Stem Cells/cytology/*physiology ; Polyploidy ; Teratoma/pathology ; Transcription, Genetic ; Transcriptional Activation ; Transfection
    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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  • 8
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    Mixer, a homeobox gene required for endoderm development (1998)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1998-07-04
    Description: An expression cloning strategy in Xenopus laevis was used to isolate a homeobox-containing gene, Mixer, that can cause embryonic cells to form endoderm. Mixer transcripts are found specifically in the prospective endoderm of gastrula, which coincides with the time and place that endodermal cells become histologically distinct and irreversibly determined. Loss-of-function studies with a dominant inhibitory mutant demonstrate that Mixer activity is required for endoderm development. In particular, the expression of Sox17alpha and Sox17beta, two previously identified endodermal determinants, require Mixer function. Together, these data suggest that Mixer is an embryonic transcription factor involved in specifying the endodermal germ layer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Henry, G L -- Melton, D A -- New York, N.Y. -- Science. 1998 Jul 3;281(5373):91-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9651252" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastocyst/cytology/physiology ; Cell Lineage ; Cloning, Molecular ; *DNA-Binding Proteins ; *Embryonic Induction ; Endoderm/cytology/*physiology ; Gastrula/cytology/*physiology ; *Gene Expression Regulation, Developmental ; *Genes, Homeobox ; *High Mobility Group Proteins ; Homeodomain Proteins/genetics ; In Situ Hybridization ; Mesoderm/cytology/physiology ; Molecular Sequence Data ; Proteins/genetics ; RNA, Messenger/genetics/metabolism ; SOXF Transcription Factors ; Transcription Factors/genetics/physiology ; *Xenopus Proteins ; Xenopus laevis
    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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  • 9
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    "Stemness": transcriptional profiling of embryonic and adult stem cells (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-09-14
    Description: The transcriptional profiles of mouse embryonic, neural, and hematopoietic stem cells were compared to define a genetic program for stem cells. A total of 216 genes are enriched in all three types of stem cells, and several of these genes are clustered in the genome. When compared to differentiated cell types, stem cells express a significantly higher number of genes (represented by expressed sequence tags) whose functions are unknown. Embryonic and neural stem cells have many similarities at the transcriptional level. These results provide a foundation for a more detailed understanding of stem cell biology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ramalho-Santos, Miguel -- Yoon, Soonsang -- Matsuzaki, Yumi -- Mulligan, Richard C -- Melton, Douglas A -- P60 HL54785/HL/NHLBI NIH HHS/ -- R24 DK56947/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2002 Oct 18;298(5593):597-600. Epub 2002 Sep 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology and Howard Hughes Medical Institute (HHMI), Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12228720" target="_blank"〉PubMed〈/a〉
    Keywords: ATP-Binding Cassette Transporters/genetics/metabolism ; Animals ; Bone Marrow Cells/physiology ; Cell Differentiation ; DNA Helicases/genetics/metabolism ; Embryo, Mammalian/*cytology ; Expressed Sequence Tags ; *Gene Expression ; *Gene Expression Profiling ; Gene Expression Regulation ; Hematopoietic Stem Cells/*physiology ; Lateral Ventricles/cytology ; Mice ; Mice, Inbred C57BL ; Neurons/*cytology ; Oligonucleotide Array Sequence Analysis ; Oxidative Stress ; Reproducibility of Results ; Signal Transduction ; Stem Cells/*physiology ; Transcription, Genetic
    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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  • 10
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    Self-renewal of embryonic-stem-cell-derived progenitors by organ-matched mesenchyme (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-10-09
    Description: One goal of regenerative medicine, to use stem cells to replace cells lost by injury or disease, depends on producing an excess of the relevant cell for study or transplantation. To this end, the stepwise differentiation of stem cells into specialized derivatives has been successful for some cell types, but a major problem remains the inefficient conversion of cells from one stage of differentiation to the next. If specialized cells are to be produced in large numbers it will be necessary to expand progenitor cells, without differentiation, at some steps of the process. Using the pancreatic lineage as a model for embryonic-stem-cell differentiation, we demonstrate that this is a solvable problem. Co-culture with organ-matched mesenchyme permits proliferation and self-renewal of progenitors, without differentiation, and enables an expansion of more than a million-fold for human endodermal cells with full retention of their developmental potential. This effect is specific both to the mesenchymal cell and to the progenitor being amplified. Progenitors that have been serially expanded on mesenchyme give rise to glucose-sensing, insulin-secreting cells when transplanted in vivo. Theoretically, the identification of stage-specific renewal signals can be incorporated into any scheme for the efficient production of large numbers of differentiated cells from stem cells and may therefore have wide application in regenerative biology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sneddon, Julie B -- Borowiak, Malgorzata -- Melton, Douglas A -- 5 U42 RR006042-20/RR/NCRR NIH HHS/ -- K08 DK084206/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Nov 29;491(7426):765-8. doi: 10.1038/nature11463. Epub 2012 Oct 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23041930" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation/drug effects ; Cell Division/drug effects ; Cell Line ; Coculture Techniques/*methods ; Embryonic Stem Cells/*cytology/drug effects/metabolism ; Endoderm/*cytology/drug effects/metabolism ; Glucose/pharmacology ; Humans ; Insulin/metabolism ; Male ; Mesoderm/*cytology ; Mice ; Pancreas/*cytology ; Pluripotent Stem Cells/cytology/drug effects/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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