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  • 1
    ISSN: 0031-9422
    Keywords: Glycine max ; Leguminosae ; environmental effects. ; oil quality ; soybean
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Publication Date: 2013-11-01
    Description: Atopic dermatitis is a chronic inflammatory skin disease that affects 15-30% of children and approximately 5% of adults in industrialized countries. Although the pathogenesis of atopic dermatitis is not fully understood, the disease is mediated by an abnormal immunoglobulin-E immune response in the setting of skin barrier dysfunction. Mast cells contribute to immunoglobulin-E-mediated allergic disorders including atopic dermatitis. Upon activation, mast cells release their membrane-bound cytosolic granules leading to the release of several molecules that are important in the pathogenesis of atopic dermatitis and host defence. More than 90% of patients with atopic dermatitis are colonized with Staphylococcus aureus in the lesional skin whereas most healthy individuals do not harbour the pathogen. Several staphylococcal exotoxins can act as superantigens and/or antigens in models of atopic dermatitis. However, the role of these staphylococcal exotoxins in disease pathogenesis remains unclear. Here we report that culture supernatants of S. aureus contain potent mast-cell degranulation activity. Biochemical analysis identified delta-toxin as the mast cell degranulation-inducing factor produced by S. aureus. Mast cell degranulation induced by delta-toxin depended on phosphoinositide 3-kinase and calcium (Ca(2+)) influx; however, unlike that mediated by immunoglobulin-E crosslinking, it did not require the spleen tyrosine kinase. In addition, immunoglobulin-E enhanced delta-toxin-induced mast cell degranulation in the absence of antigen. Furthermore, S. aureus isolates recovered from patients with atopic dermatitis produced large amounts of delta-toxin. Skin colonization with S. aureus, but not a mutant deficient in delta-toxin, promoted immunoglobulin-E and interleukin-4 production, as well as inflammatory skin disease. Furthermore, enhancement of immunoglobulin-E production and dermatitis by delta-toxin was abrogated in Kit(W-sh/W-sh) mast-cell-deficient mice and restored by mast cell reconstitution. These studies identify delta-toxin as a potent inducer of mast cell degranulation and suggest a mechanistic link between S. aureus colonization and allergic skin disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090780/" 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/PMC4090780/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nakamura, Yuumi -- Oscherwitz, Jon -- Cease, Kemp B -- Chan, Susana M -- Munoz-Planillo, Raul -- Hasegawa, Mizuho -- Villaruz, Amer E -- Cheung, Gordon Y C -- McGavin, Martin J -- Travers, Jeffrey B -- Otto, Michael -- Inohara, Naohiro -- Nunez, Gabriel -- R01 AR059688/AR/NIAMS NIH HHS/ -- R01AR059688/AR/NIAMS NIH HHS/ -- R01HL062996/HL/NHLBI NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2013 Nov 21;503(7476):397-401. doi: 10.1038/nature12655. Epub 2013 Oct 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24172897" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Toxins/*metabolism/pharmacology ; Calcium Signaling/drug effects ; *Cell Degranulation/drug effects ; Culture Media, Conditioned/pharmacology ; Dermatitis, Atopic/immunology/metabolism/*microbiology/pathology ; Female ; Immunoglobulin E/biosynthesis/immunology ; Inflammation/immunology/metabolism/microbiology/pathology ; Interleukin-4/immunology ; Intracellular Signaling Peptides and Proteins/metabolism ; Male ; Mast Cells/*cytology/drug effects ; Mice ; Phosphatidylinositol 3-Kinases/metabolism ; Protein-Tyrosine Kinases/metabolism ; Proto-Oncogene Proteins c-kit/genetics/metabolism ; Staphylococcus aureus/metabolism/*pathogenicity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2011-10-14
    Description: Human induced pluripotent stem cells (iPSCs) represent a unique opportunity for regenerative medicine because they offer the prospect of generating unlimited quantities of cells for autologous transplantation, with potential application in treatments for a broad range of disorders. However, the use of human iPSCs in the context of genetically inherited human disease will require the correction of disease-causing mutations in a manner that is fully compatible with clinical applications. The methods currently available, such as homologous recombination, lack the necessary efficiency and also leave residual sequences in the targeted genome. Therefore, the development of new approaches to edit the mammalian genome is a prerequisite to delivering the clinical promise of human iPSCs. Here we show that a combination of zinc finger nucleases (ZFNs) and piggyBac technology in human iPSCs can achieve biallelic correction of a point mutation (Glu342Lys) in the alpha(1)-antitrypsin (A1AT, also known as SERPINA1) gene that is responsible for alpha(1)-antitrypsin deficiency. Genetic correction of human iPSCs restored the structure and function of A1AT in subsequently derived liver cells in vitro and in vivo. This approach is significantly more efficient than any other gene-targeting technology that is currently available and crucially prevents contamination of the host genome with residual non-human sequences. Our results provide the first proof of principle, to our knowledge, for the potential of combining human iPSCs with genetic correction to generate clinically relevant cells for autologous cell-based therapies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198846/" 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/PMC3198846/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yusa, Kosuke -- Rashid, S Tamir -- Strick-Marchand, Helene -- Varela, Ignacio -- Liu, Pei-Qi -- Paschon, David E -- Miranda, Elena -- Ordonez, Adriana -- Hannan, Nicholas R F -- Rouhani, Foad J -- Darche, Sylvie -- Alexander, Graeme -- Marciniak, Stefan J -- Fusaki, Noemi -- Hasegawa, Mamoru -- Holmes, Michael C -- Di Santo, James P -- Lomas, David A -- Bradley, Allan -- Vallier, Ludovic -- 077187/Wellcome Trust/United Kingdom -- G0601840/Medical Research Council/United Kingdom -- G0701448/Medical Research Council/United Kingdom -- G0800784/Medical Research Council/United Kingdom -- G0901786/Medical Research Council/United Kingdom -- G1000847/Medical Research Council/United Kingdom -- WT077187/Wellcome Trust/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2011 Oct 12;478(7369):391-4. doi: 10.1038/nature10424.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21993621" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; DNA Transposable Elements/genetics ; Hepatocytes/metabolism/transplantation ; Humans ; Induced Pluripotent Stem Cells/*physiology ; Liver/cytology ; Mice ; Serum Albumin/genetics/metabolism ; *Targeted Gene Repair ; Time Factors ; alpha 1-Antitrypsin/*genetics/metabolism ; alpha 1-Antitrypsin Deficiency/*genetics
    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: 2013-03-30
    Description: Based on nuclear and mitochondrial DNA, Hailer et al. (Reports, 20 April 2012, p. 344) suggested early divergence of polar bears from a common ancestor with brown bears and subsequent introgression. Our population genetic analysis that traces each of the genealogies in the independent nuclear loci does not support the evolutionary model proposed by the authors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nakagome, Shigeki -- Mano, Shuhei -- Hasegawa, Masami -- New York, N.Y. -- Science. 2013 Mar 29;339(6127):1522. doi: 10.1126/science.1227339.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Statistical Mathematics, Tachikawa, Tokyo, Japan. nakagome@ism.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23539580" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; *Genome ; *Multilocus Sequence Typing ; Ursidae/*genetics
    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: 2018-03-30
    Description: Background/Aim: The lethal characteristic of pancreatic cancer is metastasis which is recalcitrant to currently-used chemotherapy. Our aim was to understand metastasis at the cellular level. We previously reported that multi-nucleate cells or spindle cells were more prominent in pancreatic cancer metastasis than in the primary tumor. In the present report, we investigated four representative human pancreatic cell lines for differences in cell morphology between the primary tumor and various metastatic organ targets for each cell line. Materials and Methods: Human pancreatic cancer cell lines AsPC-1, Panc-1, KP2 and KP3 were used. Pancreatic cancer cells were injected into spleen of nude mice resulting in experimental metastasis to various organs which were observed at the cellular level when the organs were placed into culture. Results: AsPC-1 and KP2 pancreatic cells formed many experimental liver metastases, in contrast to Panc-1 and KP3. Lung metastasis was only observed for AsPC-1. In the cultures established from the primary and metastatic tumors, multi-nucleate cells were found to be more prominent in the metastasis of the pancreatic cell lines with frequent metastasis, AsPC-1 and KP2. Spindle-like cells were observed prominently in AsPC-1 lung metastasis. Conclusion: Human pancreatic cancer cell lines have differential metastatic characteristics with regard to target organs and cell-morphology changes. Multi-nucleate and spindle cells may play an important role in pancreatic cancer metastasis to the liver and lung, respectively.
    Print ISSN: 0250-7005
    Electronic ISSN: 1791-7530
    Topics: Medicine
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  • 6
    ISSN: 0168-583X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0168-583X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 0168-583X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 0168-583X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0168-583X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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