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  • 1
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1990-04-06
    Description: Neurons with oscillatory properties are a common feature of the nervous system, but little is known about how neural oscillators shape the behavior of neuronal networks or how network interactions influence the properties of neural oscillators. Mathematical models are used to examine the effect of electrically coupling an oscillatory neuron to a second neuron that is either silent or tonically firing. Models of oscillatory neurons with varying degrees of complexity show that this coupling can either increase or decrease the frequency of an oscillator, depending on its membrane potential wave form, the state of the neuron to which it is coupled, and the strength of the coupling. Thus, electrical coupling provides a flexible mechanism for modifying the behavior of an oscillatory neural network.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kepler, T B -- Marder, E -- Abbott, L F -- NS17813/NS/NINDS NIH HHS/ -- T32NS07292/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1990 Apr 6;248(4951):83-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Brandeis University, Waltham, MA 02254.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2321028" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Biological Clocks ; Electric Conductivity ; Electrophysiology ; Mathematics ; Membrane Potentials ; *Models, Biological ; Neurons/*physiology
    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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  • 2
    Publication Date: 2004-07-13
    Description: The freshwater snail Biomphalaria glabrata possesses a diverse family of fibrinogen-related proteins (FREPs), hemolymph polypeptides that consist of one or two amino-terminal immunoglobulin superfamily (IgSF) domains and a carboxyl-terminal fibrinogen domain. Here, we show that the IgSF1 domain of the FREP3 subfamily is diversified at the genomic level at higher rates than those recorded for control genes. All sequence variants are derived from a small set of nine source sequences by point mutation and recombinatorial processes. Diverse FREP3 transcripts are also produced. We hypothesize a mechanism present in snails that is capable of diversifying molecules involved in internal defense.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Si-Ming -- Adema, Coen M -- Kepler, Thomas B -- Loker, Eric S -- R01AI24340/AI/NIAID NIH HHS/ -- R01AI52363/AI/NIAID NIH HHS/ -- RR-1P20RR18754/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2004 Jul 9;305(5681):251-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of New Mexico, Albuquerque, NM 87131, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15247481" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Base Sequence ; Biomphalaria/embryology/*genetics/immunology ; Blotting, Southern ; Computational Biology ; DNA, Complementary ; Disorders of Sex Development ; Genes, Immunoglobulin ; *Genetic Variation ; Hemocytes ; Immunoglobulins/chemistry/*genetics ; Molecular Sequence Data ; Point Mutation ; Polymerase Chain Reaction ; Protein Structure, Tertiary ; Recombination, 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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  • 3
    Publication Date: 2013-08-24
    Description: The RAG1/RAG2 endonuclease (RAG) initiates the V(D)J recombination reaction that assembles immunoglobulin heavy (IgH) and light (IgL) chain variable region exons from germline gene segments to generate primary antibody repertoires. IgH V(D)J assembly occurs in progenitor (pro-) B cells followed by that of IgL in precursor (pre-) B cells. Expression of IgH mu and IgL (Igkappa or Iglambda) chains generates IgM, which is expressed on immature B cells as the B-cell antigen-binding receptor (BCR). Rag expression can continue in immature B cells, allowing continued Igkappa V(D)J recombination that replaces the initial VkappaJkappa exon with one that generates a new specificity. This 'receptor editing' process, which can also lead to Iglambda V(D)J recombination and expression, provides a mechanism whereby antigen encounter at the Rag-expressing immature B-cell stage helps shape pre-immune BCR repertoires. As the major site of postnatal B-cell development, the bone marrow is the principal location of primary immunoglobulin repertoire diversification in mice. Here we report that early B-cell development also occurs within the mouse intestinal lamina propria (LP), where the associated V(D)J recombination/receptor editing processes modulate primary LP immunoglobulin repertoires. At weanling age in normally housed mice, the LP contains a population of Rag-expressing B-lineage cells that harbour intermediates indicative of ongoing V(D)J recombination and which contain cells with pro-B, pre-B and editing phenotypes. Consistent with LP-specific receptor editing, Rag-expressing LP B-lineage cells have similar VH repertoires, but significantly different Vkappa repertoires, compared to those of Rag2-expressing bone marrow counterparts. Moreover, colonization of germ-free mice leads to an increased ratio of Iglambda-expressing versus Igkappa-expressing B cells specifically in the LP. We conclude that B-cell development occurs in the intestinal mucosa, where it is regulated by extracellular signals from commensal microbes that influence gut immunoglobulin repertoires.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807868/" 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/PMC3807868/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wesemann, Duane R -- Portuguese, Andrew J -- Meyers, Robin M -- Gallagher, Michael P -- Cluff-Jones, Kendra -- Magee, Jennifer M -- Panchakshari, Rohit A -- Rodig, Scott J -- Kepler, Thomas B -- Alt, Frederick W -- AI020047/AI/NIAID NIH HHS/ -- AI89972/AI/NIAID NIH HHS/ -- HHSN272201000053C/PHS HHS/ -- K08 AI089972/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Sep 5;501(7465):112-5. doi: 10.1038/nature12496. Epub 2013 Aug 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Cellular and Molecular Medicine and Department of Medicine, Children's Hospital Boston, Boston, Massachusetts 02115, USA. dwesemann@research.bwh.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23965619" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/*cytology/*immunology/metabolism ; Bone Marrow Cells/cytology/immunology ; *Cell Lineage ; DNA-Binding Proteins/genetics/metabolism ; Gene Rearrangement, B-Lymphocyte/genetics ; Germ-Free Life ; Immunoglobulins/genetics/immunology ; Intestinal Mucosa/*cytology/*immunology ; Mice ; Precursor Cells, B-Lymphoid/cytology/metabolism ; Symbiosis ; Weaning
    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: 2013-04-05
    Description: Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details of their generation could provide a blueprint for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from the time of infection. The mature antibody, CH103, neutralized approximately 55% of HIV-1 isolates, and its co-crystal structure with the HIV-1 envelope protein gp120 revealed a new loop-based mechanism of CD4-binding-site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the unmutated common ancestor of the CH103 lineage avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data determine the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies, and provide insights into strategies to elicit similar antibodies by vaccination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637846/" 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/PMC3637846/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liao, Hua-Xin -- Lynch, Rebecca -- Zhou, Tongqing -- Gao, Feng -- Alam, S Munir -- Boyd, Scott D -- Fire, Andrew Z -- Roskin, Krishna M -- Schramm, Chaim A -- Zhang, Zhenhai -- Zhu, Jiang -- Shapiro, Lawrence -- NISC Comparative Sequencing Program -- Mullikin, James C -- Gnanakaran, S -- Hraber, Peter -- Wiehe, Kevin -- Kelsoe, Garnett -- Yang, Guang -- Xia, Shi-Mao -- Montefiori, David C -- Parks, Robert -- Lloyd, Krissey E -- Scearce, Richard M -- Soderberg, Kelly A -- Cohen, Myron -- Kamanga, Gift -- Louder, Mark K -- Tran, Lillian M -- Chen, Yue -- Cai, Fangping -- Chen, Sheri -- Moquin, Stephanie -- Du, Xiulian -- Joyce, M Gordon -- Srivatsan, Sanjay -- Zhang, Baoshan -- Zheng, Anqi -- Shaw, George M -- Hahn, Beatrice H -- Kepler, Thomas B -- Korber, Bette T M -- Kwong, Peter D -- Mascola, John R -- Haynes, Barton F -- AI067854/AI/NIAID NIH HHS/ -- AI100645/AI/NIAID NIH HHS/ -- P30 AI050410/AI/NIAID NIH HHS/ -- UM1 AI100645/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2013 Apr 25;496(7446):469-76. doi: 10.1038/nature12053. Epub 2013 Apr 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Duke University Human Vaccine Institute, Departments of Medicine and Immunology, Duke University School of Medicine, Durham, North Carolina 27710, USA. hliao@duke.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23552890" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/immunology ; Africa ; Amino Acid Sequence ; Antibodies, Monoclonal/chemistry/genetics/immunology ; Antibodies, Neutralizing/*chemistry/genetics/*immunology ; Antigens, CD4/chemistry/immunology ; Cell Lineage ; Cells, Cultured ; Clone Cells/cytology ; Cross Reactions/immunology ; Crystallography, X-Ray ; Epitopes/chemistry/immunology ; *Evolution, Molecular ; HIV Antibodies/*chemistry/genetics/*immunology ; HIV Envelope Protein gp120/chemistry/genetics/immunology/metabolism ; HIV-1/*chemistry/classification/*immunology ; Humans ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Neutralization Tests ; Phylogeny ; Protein Structure, Tertiary
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2015-08-01
    Description: An HIV-1 DNA prime vaccine, with a recombinant adenovirus type 5 (rAd5) boost, failed to protect from HIV-1 acquisition. We studied the nature of the vaccine-induced antibody (Ab) response to HIV-1 envelope (Env). HIV-1-reactive plasma Ab titers were higher to Env gp41 than to gp120, and repertoire analysis demonstrated that 93% of HIV-1-reactive Abs from memory B cells responded to Env gp41. Vaccine-induced gp41-reactive monoclonal antibodies were non-neutralizing and frequently polyreactive with host and environmental antigens, including intestinal microbiota (IM). Next-generation sequencing of an immunoglobulin heavy chain variable region repertoire before vaccination revealed an Env-IM cross-reactive Ab that was clonally related to a subsequent vaccine-induced gp41-reactive Ab. Thus, HIV-1 Env DNA-rAd5 vaccine induced a dominant IM-polyreactive, non-neutralizing gp41-reactive Ab repertoire response that was associated with no vaccine efficacy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562404/" 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/PMC4562404/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Williams, Wilton B -- Liao, Hua-Xin -- Moody, M Anthony -- Kepler, Thomas B -- Alam, S Munir -- Gao, Feng -- Wiehe, Kevin -- Trama, Ashley M -- Jones, Kathryn -- Zhang, Ruijun -- Song, Hongshuo -- Marshall, Dawn J -- Whitesides, John F -- Sawatzki, Kaitlin -- Hua, Axin -- Liu, Pinghuang -- Tay, Matthew Z -- Seaton, Kelly E -- Shen, Xiaoying -- Foulger, Andrew -- Lloyd, Krissey E -- Parks, Robert -- Pollara, Justin -- Ferrari, Guido -- Yu, Jae-Sung -- Vandergrift, Nathan -- Montefiori, David C -- Sobieszczyk, Magdalena E -- Hammer, Scott -- Karuna, Shelly -- Gilbert, Peter -- Grove, Doug -- Grunenberg, Nicole -- McElrath, M Juliana -- Mascola, John R -- Koup, Richard A -- Corey, Lawrence -- Nabel, Gary J -- Morgan, Cecilia -- Churchyard, Gavin -- Maenza, Janine -- Keefer, Michael -- Graham, Barney S -- Baden, Lindsey R -- Tomaras, Georgia D -- Haynes, Barton F -- P30 AI064518/AI/NIAID NIH HHS/ -- P30-AI-64518/AI/NIAID NIH HHS/ -- U01 AI069412/AI/NIAID NIH HHS/ -- UM1 AI068614/AI/NIAID NIH HHS/ -- UM1 AI068618/AI/NIAID NIH HHS/ -- UM1 AI068635/AI/NIAID NIH HHS/ -- UM1 AI069412/AI/NIAID NIH HHS/ -- UM1 AI069470/AI/NIAID NIH HHS/ -- UM1 AI069481/AI/NIAID NIH HHS/ -- UM1 AI069511/AI/NIAID NIH HHS/ -- UM1 AI100645/AI/NIAID NIH HHS/ -- UM1AI068618/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2015 Aug 14;349(6249):aab1253. doi: 10.1126/science.aab1253. Epub 2015 Jul 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. barton.haynes@duke.edu wilton.williams@duke.edu. ; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. ; Department of Microbiology, Boston University School of Medicine, Boston, MA, USA. ; Department of Medicine, Columbia University Medical Center, New York, NY, USA. ; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. ; The Statistical Center for HIV/AIDS Research and Prevention (SCHARP), Fred Hutchinson Cancer Research Center, Seattle, WA, USA. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ; The Aurum Institute, Johannesburg, South Africa. ; University of Rochester School of Medicine, Rochester, NY, USA. ; Brigham and Women's Hospital, Boston, MA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26229114" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/*immunology ; Adenoviridae ; Antibodies, Monoclonal/genetics/immunology ; Antibody Formation ; Cross Reactions ; HIV Antibodies/genetics/*immunology ; HIV Envelope Protein gp120/immunology ; HIV Envelope Protein gp41/genetics/*immunology ; HIV-1/*immunology ; Humans ; Immunity ; Immunoglobulin Heavy Chains/genetics/immunology ; Immunoglobulin Variable Region/genetics/immunology ; Immunologic Memory ; Intestines/microbiology ; Microbiota/*immunology ; Vaccines, DNA/*immunology
    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
    Publication Date: 2010-04-19
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 7
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  • 10
    Publication Date: 1995-08-29
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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