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  • 1
    Publication Date: 2012-04-13
    Description: The spatial organization of the genome is intimately linked to its biological function, yet our understanding of higher order genomic structure is coarse, fragmented and incomplete. In the nucleus of eukaryotic cells, interphase chromosomes occupy distinct chromosome territories, and numerous models have been proposed for how chromosomes fold within chromosome territories. These models, however, provide only few mechanistic details about the relationship between higher order chromatin structure and genome function. Recent advances in genomic technologies have led to rapid advances in the study of three-dimensional genome organization. In particular, Hi-C has been introduced as a method for identifying higher order chromatin interactions genome wide. Here we investigate the three-dimensional organization of the human and mouse genomes in embryonic stem cells and terminally differentiated cell types at unprecedented resolution. We identify large, megabase-sized local chromatin interaction domains, which we term 'topological domains', as a pervasive structural feature of the genome organization. These domains correlate with regions of the genome that constrain the spread of heterochromatin. The domains are stable across different cell types and highly conserved across species, indicating that topological domains are an inherent property of mammalian genomes. Finally, we find that the boundaries of topological domains are enriched for the insulator binding protein CTCF, housekeeping genes, transfer RNAs and short interspersed element (SINE) retrotransposons, indicating that these factors may have a role in establishing the topological domain structure of the genome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356448/" 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/PMC3356448/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dixon, Jesse R -- Selvaraj, Siddarth -- Yue, Feng -- Kim, Audrey -- Li, Yan -- Shen, Yin -- Hu, Ming -- Liu, Jun S -- Ren, Bing -- R01 HG003991/HG/NHGRI NIH HHS/ -- R01 HG003991-03/HG/NHGRI NIH HHS/ -- R01 HG003991-03S1/HG/NHGRI NIH HHS/ -- R01GH003991/GH/CGH CDC HHS/ -- England -- Nature. 2012 Apr 11;485(7398):376-80. doi: 10.1038/nature11082.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Institute for Cancer Research, 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/22495300" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Cell Differentiation ; Chromatin/chemistry/*genetics/*metabolism ; Chromosomes/chemistry/genetics/metabolism ; Embryonic Stem Cells/metabolism ; Evolution, Molecular ; Female ; Genes, Essential/genetics ; *Genome ; Heterochromatin/chemistry/genetics/metabolism ; Humans ; Male ; Mammals/genetics ; Mice ; RNA, Transfer/genetics ; Repressor Proteins/metabolism ; Short Interspersed Nucleotide Elements/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2015-09-17
    Description: Development of functional nanoparticles can be encumbered by unanticipated material properties and biological events, which can affect nanoparticle effectiveness in complex, physiologically relevant systems. Despite the advances in bottom-up nanoengineering and surface chemistry, reductionist functionalization approaches remain inadequate in replicating the complex interfaces present in nature and cannot avoid exposure of foreign materials. Here we report on the preparation of polymeric nanoparticles enclosed in the plasma membrane of human platelets, which are a unique population of cellular fragments that adhere to a variety of disease-relevant substrates. The resulting nanoparticles possess a right-side-out unilamellar membrane coating functionalized with immunomodulatory and adhesion antigens associated with platelets. Compared to uncoated particles, the platelet membrane-cloaked nanoparticles have reduced cellular uptake by macrophage-like cells and lack particle-induced complement activation in autologous human plasma. The cloaked nanoparticles also display platelet-mimicking properties such as selective adhesion to damaged human and rodent vasculatures as well as enhanced binding to platelet-adhering pathogens. In an experimental rat model of coronary restenosis and a mouse model of systemic bacterial infection, docetaxel and vancomycin, respectively, show enhanced therapeutic efficacy when delivered by the platelet-mimetic nanoparticles. The multifaceted biointerfacing enabled by the platelet membrane cloaking method provides a new approach in developing functional nanoparticles for disease-targeted delivery.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hu, Che-Ming J -- Fang, Ronnie H -- Wang, Kuei-Chun -- Luk, Brian T -- Thamphiwatana, Soracha -- Dehaini, Diana -- Nguyen, Phu -- Angsantikul, Pavimol -- Wen, Cindy H -- Kroll, Ashley V -- Carpenter, Cody -- Ramesh, Manikantan -- Qu, Vivian -- Patel, Sherrina H -- Zhu, Jie -- Shi, William -- Hofman, Florence M -- Chen, Thomas C -- Gao, Weiwei -- Zhang, Kang -- Chien, Shu -- Zhang, Liangfang -- R01DK095168/DK/NIDDK NIH HHS/ -- R01EY25090/EY/NEI NIH HHS/ -- R01HL108735/HL/NHLBI NIH HHS/ -- R25CA153915/CA/NCI NIH HHS/ -- England -- Nature. 2015 Oct 1;526(7571):118-21. doi: 10.1038/nature15373. Epub 2015 Sep 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093, USA. ; Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA. ; Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, USA. ; Institute of Engineering in Medicine, University of California, San Diego, La Jolla, California 92093, USA. ; Shiley Eye Institute, University of California, San Diego, La Jolla, California 92093, USA. ; Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. ; 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/26374997" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/*administration & dosage/pharmacokinetics ; Blood Platelets/*cytology ; Blood Vessels/cytology/metabolism/pathology ; Cell Membrane/*metabolism ; Collagen/chemistry/immunology ; Complement Activation/immunology ; Coronary Restenosis/blood/drug therapy/metabolism ; Disease Models, Animal ; Drug Delivery Systems/*methods ; Humans ; Macrophages/immunology ; Male ; Mice ; Nanoparticles/*administration & dosage/*chemistry ; *Platelet Adhesiveness ; Polymers/chemistry ; Rats ; Rats, Sprague-Dawley ; Staphylococcal Infections/blood/drug therapy/metabolism/microbiology ; Staphylococcus aureus/cytology/metabolism ; Taxoids/administration & dosage/pharmacokinetics ; Unilamellar Liposomes/chemistry ; Vancomycin/administration & dosage/pharmacokinetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Location Call Number Expected Availability
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