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  • 1
    Publication Date: 2018-11-21
    Description: A hallmark of biological systems is that particular functions and outcomes are realized in specific contexts, such as when particular signals are received. One mechanism for mediating specificity is described by Fisher’s “lock and key” metaphor, exemplified by enzymes that bind selectively to a particular substrate via specific finely tuned...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2013-11-01
    Description: Human immunodeficiency virus type 1 (HIV-1)-specific monoclonal antibodies with extraordinary potency and breadth have recently been described. In humanized mice, combinations of monoclonal antibodies have been shown to suppress viraemia, but the therapeutic potential of these monoclonal antibodies has not yet been evaluated in primates with an intact immune system. Here we show that administration of a cocktail of HIV-1-specific monoclonal antibodies, as well as the single glycan-dependent monoclonal antibody PGT121, resulted in a rapid and precipitous decline of plasma viraemia to undetectable levels in rhesus monkeys chronically infected with the pathogenic simian-human immunodeficiency virus SHIV-SF162P3. A single monoclonal antibody infusion afforded up to a 3.1 log decline of plasma viral RNA in 7 days and also reduced proviral DNA in peripheral blood, gastrointestinal mucosa and lymph nodes without the development of viral resistance. Moreover, after monoclonal antibody administration, host Gag-specific T-lymphocyte responses showed improved functionality. Virus rebounded in most animals after a median of 56 days when serum monoclonal antibody titres had declined to undetectable levels, although, notably, a subset of animals maintained long-term virological control in the absence of further monoclonal antibody infusions. These data demonstrate a profound therapeutic effect of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys as well as an impact on host immune responses. Our findings strongly encourage the investigation of monoclonal antibody therapy for HIV-1 in humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017780/" 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/PMC4017780/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barouch, Dan H -- Whitney, James B -- Moldt, Brian -- Klein, Florian -- Oliveira, Thiago Y -- Liu, Jinyan -- Stephenson, Kathryn E -- Chang, Hui-Wen -- Shekhar, Karthik -- Gupta, Sanjana -- Nkolola, Joseph P -- Seaman, Michael S -- Smith, Kaitlin M -- Borducchi, Erica N -- Cabral, Crystal -- Smith, Jeffrey Y -- Blackmore, Stephen -- Sanisetty, Srisowmya -- Perry, James R -- Beck, Matthew -- Lewis, Mark G -- Rinaldi, William -- Chakraborty, Arup K -- Poignard, Pascal -- Nussenzweig, Michel C -- Burton, Dennis R -- AI055332/AI/NIAID NIH HHS/ -- AI060354/AI/NIAID NIH HHS/ -- AI078526/AI/NIAID NIH HHS/ -- AI084794/AI/NIAID NIH HHS/ -- AI095985/AI/NIAID NIH HHS/ -- AI096040/AI/NIAID NIH HHS/ -- AI100148/AI/NIAID NIH HHS/ -- AI10063/AI/NIAID NIH HHS/ -- AI100663/AI/NIAID NIH HHS/ -- P01 AI100148/AI/NIAID NIH HHS/ -- P40 OD012217/OD/NIH HHS/ -- P51 RR000168/RR/NCRR NIH HHS/ -- R01 AI084794/AI/NIAID NIH HHS/ -- R37 AI055332/AI/NIAID NIH HHS/ -- R56 AI091514/AI/NIAID NIH HHS/ -- T32 AI007387/AI/NIAID NIH HHS/ -- U19 AI066305/AI/NIAID NIH HHS/ -- U19 AI078526/AI/NIAID NIH HHS/ -- U19 AI095985/AI/NIAID NIH HHS/ -- U19 AI096040/AI/NIAID NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Nov 14;503(7475):224-8. doi: 10.1038/nature12744. Epub 2013 Oct 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA [2] Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24172905" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/*therapeutic use ; Antibodies, Neutralizing/*therapeutic use ; DNA, Viral/blood ; HIV Antibodies/immunology ; HIV-1/*immunology ; Macaca mulatta ; Simian Acquired Immunodeficiency Syndrome/*therapy ; Simian Immunodeficiency Virus/*physiology ; T-Lymphocytes/immunology ; Viremia/therapy
    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: 2016-05-21
    Description: Antiretroviral drugs and antibodies limit HIV-1 infection by interfering with the viral life cycle. In addition, antibodies also have the potential to guide host immune effector cells to kill HIV-1-infected cells. Examination of the kinetics of HIV-1 suppression in infected individuals by passively administered 3BNC117, a broadly neutralizing antibody, suggested that the effects of the antibody are not limited to free viral clearance and blocking new infection but also include acceleration of infected cell clearance. Consistent with these observations, we find that broadly neutralizing antibodies can target CD4(+) T cells infected with patient viruses and can decrease their in vivo half-lives by a mechanism that requires Fcgamma receptor engagement in a humanized mouse model. The results indicate that passive immunotherapy can accelerate elimination of HIV-1-infected cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lu, Ching-Lan -- Murakowski, Dariusz K -- Bournazos, Stylianos -- Schoofs, Till -- Sarkar, Debolina -- Halper-Stromberg, Ariel -- Horwitz, Joshua A -- Nogueira, Lilian -- Golijanin, Jovana -- Gazumyan, Anna -- Ravetch, Jeffrey V -- Caskey, Marina -- Chakraborty, Arup K -- Nussenzweig, Michel C -- 1UM1 AI100663-01/AI/NIAID NIH HHS/ -- 8 UL1 TR000043/TR/NCATS NIH HHS/ -- AI081677-05/AI/NIAID NIH HHS/ -- AI100148-02/AI/NIAID NIH HHS/ -- F31 AI118555-01/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 May 20;352(6288):1001-4. doi: 10.1126/science.aaf1279. Epub 2016 May 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. Weill Cornell Medical College, New York, NY 10065, USA. ; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065, USA. ; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. ; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. nussen@rockefeller.edu arupc@mit.edu. ; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. Howard Hughes Medical Institute. nussen@rockefeller.edu arupc@mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27199430" target="_blank"〉PubMed〈/a〉
    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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  • 4
    Publication Date: 2014-07-06
    Description: Activation of the small guanosine triphosphatase H-Ras by the exchange factor Son of Sevenless (SOS) is an important hub for signal transduction. Multiple layers of regulation, through protein and membrane interactions, govern activity of SOS. We characterized the specific activity of individual SOS molecules catalyzing nucleotide exchange in H-Ras. Single-molecule kinetic traces revealed that SOS samples a broad distribution of turnover rates through stochastic fluctuations between distinct, long-lived (more than 100 seconds), functional states. The expected allosteric activation of SOS by Ras-guanosine triphosphate (GTP) was conspicuously absent in the mean rate. However, fluctuations into highly active states were modulated by Ras-GTP. This reveals a mechanism in which functional output may be determined by the dynamical spectrum of rates sampled by a small number of enzymes, rather than the ensemble average.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255705/" 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/PMC4255705/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Iversen, Lars -- Tu, Hsiung-Lin -- Lin, Wan-Chen -- Christensen, Sune M -- Abel, Steven M -- Iwig, Jeff -- Wu, Hung-Jen -- Gureasko, Jodi -- Rhodes, Christopher -- Petit, Rebecca S -- Hansen, Scott D -- Thill, Peter -- Yu, Cheng-Han -- Stamou, Dimitrios -- Chakraborty, Arup K -- Kuriyan, John -- Groves, Jay T -- P01 AI091580/AI/NIAID NIH HHS/ -- R01 AI104789/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Jul 4;345(6192):50-4. doi: 10.1126/science.1250373.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA. ; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. ; Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. ; Department of Mechanical Engineering, University of California, Berkeley, Berkeley, CA 94720, USA. ; Department of Chemistry, MIT, Cambridge, MA 02139, USA. ; Mechanobiology Institute, National University of Singapore, Singapore. ; Department of Chemistry and Nano-Science Center, University of Copenhagen, Copenhagen, Denmark. ; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA. Department of Chemistry, MIT, Cambridge, MA 02139, USA. Department of Biological Engineering, MIT, Cambridge, MA 02139, USA. Ragon Institute of Massachusetts General Hospital, MIT, and Harvard, Cambridge, MA 02139, USA. Department of Physics, MIT, Cambridge, MA 02139, USA. Institute for Medical Engineering and Science, MIT, Cambridge, MA 02139, USA. ; Howard Hughes Medical Institute, Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA. Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. Physical Biosciences and Materials Sciences Divisions, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. ; Howard Hughes Medical Institute, Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA. Mechanobiology Institute, National University of Singapore, Singapore. Physical Biosciences and Materials Sciences Divisions, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Berkeley Education Alliance for Research in Singapore, 1 Create Way, CREATE tower level 11, University Town, Singapore 138602. jtgroves@lbl.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24994643" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Catalytic Domain ; Crystallography, X-Ray ; Enzyme Activation ; Humans ; Kinetics ; Nucleotides/chemistry ; *Protein Interaction Domains and Motifs ; Proto-Oncogene Proteins p21(ras)/*agonists ; Son of Sevenless Protein, Drosophila/*chemistry/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: 2018-07-03
    Description: Genomic analysis in Juglans (walnuts) is expected to transform the breeding and agricultural production of both nuts and lumber. To that end, we report here the determination of reference sequences for six additional relatives of Juglans regia : Juglans sigillata (also from section Dioscaryon ), Juglans nigra , Juglans microcarpa , Juglans hindsii (from section Rhysocaryon ), Juglans cathayensis (from section Cardiocaryon ), and the closely related Pterocarya stenoptera . While these are ‘draft’ genomes, ranging in size between 640Mbp and 990Mbp, their contiguities and accuracies can support powerful annotations of genomic variation that are often the foundation of new avenues of research and breeding. We annotated nucleotide divergence and synteny by creating complete pairwise alignments of each reference genome to the remaining six. In addition, we have re-sequenced a sample of accessions from four Juglans species (including regia ). The variation discovered in these surveys comprises a critical resource for experimentation and breeding, as well as a solid complementary annotation. To demonstrate the potential of these resources the structural and sequence variation in and around the polyphenol oxidase loci, PPO1 and PPO2 were investigated. As reported for other seed crops variation in this gene is implicated in the domestication of walnuts. The apparently Juglandaceae specific PPO1 duplicate shows accelerated divergence and an excess of amino acid replacement on the lineage leading to accessions of the domesticated nut crop species, Juglans regia and sigillata .
    Electronic ISSN: 2160-1836
    Topics: Biology
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  • 6
    Publication Date: 2018-01-25
    Description: HIV is a highly mutable virus, and over 30 years after its discovery, a vaccine or cure is still not available. The isolation of broadly neutralizing antibodies (bnAbs) from HIV-infected patients has led to renewed hope for a prophylactic vaccine capable of combating the scourge of HIV. A major challenge...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Archiv der Mathematik 63 (1994), S. 509-516 
    ISSN: 1420-8938
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mathematics
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1434-601X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract In this paper the effect of biquadratic exchange on Curie temperature has been discussed on the basis of double-time temperature-dependent Green-function formalism with the utilization of Callen decoupling scheme. Calculation has been done for a spin-1 bcc Heisenberg ferromagnet by the method of Flax and Raich and it has been observed that the variation of Curie temperature with the biquadratic exchange parameter α obeys a law prescribed by the previous authors.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1434-6036
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    The European physical journal 55 (1984), S. 231-234 
    ISSN: 1434-6036
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The statistical mechanics of a spin-one Bethe lattice is discussed. The exact expression for Curie temperature is derived using a Bethe-Peierls approximations. The effect of the inclusion of a single-spin anisotropy to each Ising model of the lattice is also studied. It is seen that under certain situations a first-order phase transition appears.
    Type of Medium: Electronic Resource
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