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  • 1
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    Global and local fMRI signals driven by neurons defined optogenetically by type and wiring (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-05-18
    Description: Despite a rapidly-growing scientific and clinical brain imaging literature based on functional magnetic resonance imaging (fMRI) using blood oxygenation level-dependent (BOLD) signals, it remains controversial whether BOLD signals in a particular region can be caused by activation of local excitatory neurons. This difficult question is central to the interpretation and utility of BOLD, with major significance for fMRI studies in basic research and clinical applications. Using a novel integrated technology unifying optogenetic control of inputs with high-field fMRI signal readouts, we show here that specific stimulation of local CaMKIIalpha-expressing excitatory neurons, either in the neocortex or thalamus, elicits positive BOLD signals at the stimulus location with classical kinetics. We also show that optogenetic fMRI (of MRI) allows visualization of the causal effects of specific cell types defined not only by genetic identity and cell body location, but also by axonal projection target. Finally, we show that of MRI within the living and intact mammalian brain reveals BOLD signals in downstream targets distant from the stimulus, indicating that this approach can be used to map the global effects of controlling a local cell population. In this respect, unlike both conventional fMRI studies based on correlations and fMRI with electrical stimulation that will also directly drive afferent and nearby axons, this of MRI approach provides causal information about the global circuits recruited by defined local neuronal activity patterns. Together these findings provide an empirical foundation for the widely-used fMRI BOLD signal, and the features of of MRI define a potent tool that may be suitable for functional circuit analysis as well as global phenotyping of dysfunctional circuitry.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3177305/" 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/PMC3177305/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Jin Hyung -- Durand, Remy -- Gradinaru, Viviana -- Zhang, Feng -- Goshen, Inbal -- Kim, Dae-Shik -- Fenno, Lief E -- Ramakrishnan, Charu -- Deisseroth, Karl -- 1K99EB008738/EB/NIBIB NIH HHS/ -- R00 EB008738/EB/NIBIB NIH HHS/ -- R00 EB008738-03/EB/NIBIB NIH HHS/ -- England -- Nature. 2010 Jun 10;465(7299):788-92. doi: 10.1038/nature09108.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Electrical Engineering, Psychiatry and Biobehavioral Sciences, Bioengineering, and Radiology, University of California, Los Angeles, California 90095, USA. ljinhy@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20473285" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/radiation effects ; Anesthesia ; Animals ; Brain/anatomy & histology/blood supply/*cytology/*radiation effects ; Cerebrovascular Circulation/radiation effects ; Chlorophyta ; Luminescent Measurements ; Luminescent Proteins/genetics/metabolism ; *Magnetic Resonance Imaging ; Motor Cortex/blood supply/cytology/metabolism/radiation effects ; Neural Pathways/*radiation effects ; Neurons/classification/cytology/*metabolism/*radiation effects ; Oxygen/blood/metabolism ; Photic Stimulation ; Rats ; Rhodopsin/genetics/metabolism/radiation effects ; Thalamus/blood supply/cytology/metabolism/radiation effects
    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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  • 2
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    Green evolution and dynamic adaptations revealed by genomes of the marine picoeukaryotes Micromonas (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-04-11
    Description: Picoeukaryotes are a taxonomically diverse group of organisms less than 2 micrometers in diameter. Photosynthetic marine picoeukaryotes in the genus Micromonas thrive in ecosystems ranging from tropical to polar and could serve as sentinel organisms for biogeochemical fluxes of modern oceans during climate change. These broadly distributed primary producers belong to an anciently diverged sister clade to land plants. Although Micromonas isolates have high 18S ribosomal RNA gene identity, we found that genomes from two isolates shared only 90% of their predicted genes. Their independent evolutionary paths were emphasized by distinct riboswitch arrangements as well as the discovery of intronic repeat elements in one isolate, and in metagenomic data, but not in other genomes. Divergence appears to have been facilitated by selection and acquisition processes that actively shape the repertoire of genes that are mutually exclusive between the two isolates differently than the core genes. Analyses of the Micromonas genomes offer valuable insights into ecological differentiation and the dynamic nature of early plant evolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Worden, Alexandra Z -- Lee, Jae-Hyeok -- Mock, Thomas -- Rouze, Pierre -- Simmons, Melinda P -- Aerts, Andrea L -- Allen, Andrew E -- Cuvelier, Marie L -- Derelle, Evelyne -- Everett, Meredith V -- Foulon, Elodie -- Grimwood, Jane -- Gundlach, Heidrun -- Henrissat, Bernard -- Napoli, Carolyn -- McDonald, Sarah M -- Parker, Micaela S -- Rombauts, Stephane -- Salamov, Aasf -- Von Dassow, Peter -- Badger, Jonathan H -- Coutinho, Pedro M -- Demir, Elif -- Dubchak, Inna -- Gentemann, Chelle -- Eikrem, Wenche -- Gready, Jill E -- John, Uwe -- Lanier, William -- Lindquist, Erika A -- Lucas, Susan -- Mayer, Klaus F X -- Moreau, Herve -- Not, Fabrice -- Otillar, Robert -- Panaud, Olivier -- Pangilinan, Jasmyn -- Paulsen, Ian -- Piegu, Benoit -- Poliakov, Aaron -- Robbens, Steven -- Schmutz, Jeremy -- Toulza, Eve -- Wyss, Tania -- Zelensky, Alexander -- Zhou, Kemin -- Armbrust, E Virginia -- Bhattacharya, Debashish -- Goodenough, Ursula W -- Van de Peer, Yves -- Grigoriev, Igor V -- New York, N.Y. -- Science. 2009 Apr 10;324(5924):268-72. doi: 10.1126/science.1167222.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Monterey Bay Aquarium Research Institute, Moss Landing, CA 95039 USA. azworden@mbari.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19359590" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; *Biological Evolution ; Chlorophyta/classification/cytology/*genetics/physiology ; DNA Transposable Elements ; Ecosystem ; Gene Expression Regulation ; Genes ; Genetic Variation ; *Genome ; Introns ; Meiosis/genetics ; Molecular Sequence Data ; Oceans and Seas ; Photosynthesis/genetics ; Phylogeny ; Phytoplankton/classification/genetics ; Plants/*genetics ; RNA, Untranslated ; Repetitive Sequences, Nucleic Acid ; Sequence Analysis, DNA ; Transcription Factors/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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  • 3
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    Highly conserved protective epitopes on influenza B viruses (2012)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2012-08-11
    Description: Identification of broadly neutralizing antibodies against influenza A viruses has raised hopes for the development of monoclonal antibody-based immunotherapy and "universal" vaccines for influenza. However, a substantial part of the annual flu burden is caused by two cocirculating, antigenically distinct lineages of influenza B viruses. Here, we report human monoclonal antibodies, CR8033, CR8071, and CR9114, that protect mice against lethal challenge from both lineages. Antibodies CR8033 and CR8071 recognize distinct conserved epitopes in the head region of the influenza B hemagglutinin (HA), whereas CR9114 binds a conserved epitope in the HA stem and protects against lethal challenge with influenza A and B viruses. These antibodies may inform on development of monoclonal antibody-based treatments and a universal flu vaccine for all influenza A and B viruses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538841/" 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/PMC3538841/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dreyfus, Cyrille -- Laursen, Nick S -- Kwaks, Ted -- Zuijdgeest, David -- Khayat, Reza -- Ekiert, Damian C -- Lee, Jeong Hyun -- Metlagel, Zoltan -- Bujny, Miriam V -- Jongeneelen, Mandy -- van der Vlugt, Remko -- Lamrani, Mohammed -- Korse, Hans J W M -- Geelen, Eric -- Sahin, Ozcan -- Sieuwerts, Martijn -- Brakenhoff, Just P J -- Vogels, Ronald -- Li, Olive T W -- Poon, Leo L M -- Peiris, Malik -- Koudstaal, Wouter -- Ward, Andrew B -- Wilson, Ian A -- Goudsmit, Jaap -- Friesen, Robert H E -- GM080209/GM/NIGMS NIH HHS/ -- P41RR001209/RR/NCRR NIH HHS/ -- RR017573/RR/NCRR NIH HHS/ -- T32 GM080209/GM/NIGMS NIH HHS/ -- U54 GM094586/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Sep 14;337(6100):1343-8. doi: 10.1126/science.1222908. Epub 2012 Aug 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22878502" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antibodies, Monoclonal/chemistry/*immunology ; Antibodies, Neutralizing/chemistry/immunology ; Conserved Sequence ; Hemagglutinin Glycoproteins, Influenza Virus/*immunology ; Humans ; Immunodominant Epitopes/chemistry/*immunology ; Influenza B virus/*immunology ; Influenza Vaccines/*immunology ; Mice ; Molecular Sequence Data ; Neutralization Tests ; Orthomyxoviridae Infections/*prevention & control ; Protein Conformation
    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
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    Obesity-associated variants within FTO form long-range functional connections with IRX3 (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-03-22
    Description: Genome-wide association studies (GWAS) have reproducibly associated variants within introns of FTO with increased risk for obesity and type 2 diabetes (T2D). Although the molecular mechanisms linking these noncoding variants with obesity are not immediately obvious, subsequent studies in mice demonstrated that FTO expression levels influence body mass and composition phenotypes. However, no direct connection between the obesity-associated variants and FTO expression or function has been made. Here we show that the obesity-associated noncoding sequences within FTO are functionally connected, at megabase distances, with the homeobox gene IRX3. The obesity-associated FTO region directly interacts with the promoters of IRX3 as well as FTO in the human, mouse and zebrafish genomes. Furthermore, long-range enhancers within this region recapitulate aspects of IRX3 expression, suggesting that the obesity-associated interval belongs to the regulatory landscape of IRX3. Consistent with this, obesity-associated single nucleotide polymorphisms are associated with expression of IRX3, but not FTO, in human brains. A direct link between IRX3 expression and regulation of body mass and composition is demonstrated by a reduction in body weight of 25 to 30% in Irx3-deficient mice, primarily through the loss of fat mass and increase in basal metabolic rate with browning of white adipose tissue. Finally, hypothalamic expression of a dominant-negative form of Irx3 reproduces the metabolic phenotypes of Irx3-deficient mice. Our data suggest that IRX3 is a functional long-range target of obesity-associated variants within FTO and represents a novel determinant of body mass and composition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113484/" 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/PMC4113484/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smemo, Scott -- Tena, Juan J -- Kim, Kyoung-Han -- Gamazon, Eric R -- Sakabe, Noboru J -- Gomez-Marin, Carlos -- Aneas, Ivy -- Credidio, Flavia L -- Sobreira, Debora R -- Wasserman, Nora F -- Lee, Ju Hee -- Puviindran, Vijitha -- Tam, Davis -- Shen, Michael -- Son, Joe Eun -- Vakili, Niki Alizadeh -- Sung, Hoon-Ki -- Naranjo, Silvia -- Acemel, Rafael D -- Manzanares, Miguel -- Nagy, Andras -- Cox, Nancy J -- Hui, Chi-Chung -- Gomez-Skarmeta, Jose Luis -- Nobrega, Marcelo A -- DK020595/DK/NIDDK NIH HHS/ -- DK093972/DK/NIDDK NIH HHS/ -- DK20595/DK/NIDDK NIH HHS/ -- HL114010/HL/NHLBI NIH HHS/ -- HL119967/HL/NHLBI NIH HHS/ -- MH090937/MH/NIMH NIH HHS/ -- MH101820/MH/NIMH NIH HHS/ -- P30 DK020595/DK/NIDDK NIH HHS/ -- P60 DK020595/DK/NIDDK NIH HHS/ -- R01 DK093972/DK/NIDDK NIH HHS/ -- R01 HL114010/HL/NHLBI NIH HHS/ -- R01 HL119967/HL/NHLBI NIH HHS/ -- R01 MH090937/MH/NIMH NIH HHS/ -- R01 MH101820/MH/NIMH NIH HHS/ -- T32 HL007381/HL/NHLBI NIH HHS/ -- T32HL007381/HL/NHLBI NIH HHS/ -- U54 AR052646/AR/NIAMS NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2014 Mar 20;507(7492):371-5. doi: 10.1038/nature13138. Epub 2014 Mar 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA [2]. ; 1] Centro Andaluz de Biologia del Desarrollo (CABD), Consejo Superior de Investigaciones Cientificas/Universidad Pablo de Olavide, Carretera de Utrera Km1, Sevilla 41013, Spain [2]. ; 1] Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, and Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada [2]. ; Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA. ; Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA. ; Centro Andaluz de Biologia del Desarrollo (CABD), Consejo Superior de Investigaciones Cientificas/Universidad Pablo de Olavide, Carretera de Utrera Km1, Sevilla 41013, Spain. ; Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, and Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5T 3H7, Canada. ; Cardiovascular Development and Repair Department, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029, Spain. ; 1] Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA [2] Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24646999" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/metabolism ; Animals ; Basal Metabolism/genetics ; Body Mass Index ; Body Weight/genetics ; Brain/metabolism ; Diabetes Mellitus, Type 2/genetics ; Diet ; Genes, Dominant/genetics ; Homeodomain Proteins/*genetics/metabolism ; Humans ; Hypothalamus/metabolism ; Introns/*genetics ; Male ; Mice ; Mixed Function Oxygenases/*genetics ; Obesity/*genetics ; Oxo-Acid-Lyases/*genetics ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; Promoter Regions, Genetic/genetics ; Proteins/*genetics ; Thinness/genetics ; Transcription Factors/deficiency/*genetics/metabolism ; Zebrafish/embryology/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
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    Cross-neutralization of influenza A viruses mediated by a single antibody loop (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-09-18
    Description: Immune recognition of protein antigens relies on the combined interaction of multiple antibody loops, which provide a fairly large footprint and constrain the size and shape of protein surfaces that can be targeted. Single protein loops can mediate extremely high-affinity binding, but it is unclear whether such a mechanism is available to antibodies. Here we report the isolation and characterization of an antibody called C05, which neutralizes strains from multiple subtypes of influenza A virus, including H1, H2 and H3. X-ray and electron microscopy structures show that C05 recognizes conserved elements of the receptor-binding site on the haemagglutinin surface glycoprotein. Recognition of the haemagglutinin receptor-binding site is dominated by a single heavy-chain complementarity-determining region 3 loop, with minor contacts from heavy-chain complementarity-determining region 1, and is sufficient to achieve nanomolar binding with a minimal footprint. Thus, binding predominantly with a single loop can allow antibodies to target small, conserved functional sites on otherwise hypervariable antigens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538848/" 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/PMC3538848/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ekiert, Damian C -- Kashyap, Arun K -- Steel, John -- Rubrum, Adam -- Bhabha, Gira -- Khayat, Reza -- Lee, Jeong Hyun -- Dillon, Michael A -- O'Neil, Ryann E -- Faynboym, Aleksandr M -- Horowitz, Michael -- Horowitz, Lawrence -- Ward, Andrew B -- Palese, Peter -- Webby, Richard -- Lerner, Richard A -- Bhatt, Ramesh R -- Wilson, Ian A -- GM080209/GM/NIGMS NIH HHS/ -- HHSN266200700010C/PHS HHS/ -- P01 AI058113/AI/NIAID NIH HHS/ -- P01AI058113/AI/NIAID NIH HHS/ -- P41 RR017573/RR/NCRR NIH HHS/ -- T32 GM080209/GM/NIGMS NIH HHS/ -- U01 AI070373/AI/NIAID NIH HHS/ -- U01AI070373/AI/NIAID NIH HHS/ -- U54 GM094586/GM/NIGMS NIH HHS/ -- U54-AI057158/AI/NIAID NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Sep 27;489(7417):526-32. doi: 10.1038/nature11414. Epub 2012 Sep 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22982990" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Neutralizing/*chemistry/genetics/*immunology ; Antibodies, Viral/*chemistry/genetics/*immunology ; Antibody Specificity/genetics/*immunology ; Antigens, Viral/chemistry/immunology ; Binding Sites ; Complementarity Determining Regions/chemistry/genetics/immunology ; Conserved Sequence ; Cross Reactions/genetics/immunology ; Crystallography, X-Ray ; Enzyme-Linked Immunosorbent Assay ; Epitopes/chemistry/immunology ; Hemagglutinin Glycoproteins, Influenza Virus/chemistry/immunology ; Influenza A Virus, H1N1 Subtype/chemistry/immunology ; Influenza A Virus, H3N2 Subtype/chemistry/immunology ; Influenza A virus/chemistry/*classification/*immunology ; Influenza Vaccines/immunology ; Mice ; Models, Molecular ; Molecular Sequence Data ; Mutation/genetics ; Orthomyxoviridae Infections/immunology/prevention & control/virology ; Protein Conformation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
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    Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-09-05
    Description: The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration (IC50) 〈50 mug ml(-1). The median IC50 of neutralized viruses was 0.033 mug ml(-1), among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed that it bound to a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current monoclonal-antibody-based approaches to immunotherapies, prophylaxis and vaccine design.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224615/" 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/PMC4224615/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Jinghe -- Kang, Byong H -- Pancera, Marie -- Lee, Jeong Hyun -- Tong, Tommy -- Feng, Yu -- Imamichi, Hiromi -- Georgiev, Ivelin S -- Chuang, Gwo-Yu -- Druz, Aliaksandr -- Doria-Rose, Nicole A -- Laub, Leo -- Sliepen, Kwinten -- van Gils, Marit J -- de la Pena, Alba Torrents -- Derking, Ronald -- Klasse, Per-Johan -- Migueles, Stephen A -- Bailer, Robert T -- Alam, Munir -- Pugach, Pavel -- Haynes, Barton F -- Wyatt, Richard T -- Sanders, Rogier W -- Binley, James M -- Ward, Andrew B -- Mascola, John R -- Kwong, Peter D -- Connors, Mark -- 280829/European Research Council/International -- AI84714/AI/NIAID NIH HHS/ -- AI93278/AI/NIAID NIH HHS/ -- P01 AI082362/AI/NIAID NIH HHS/ -- R01 AI100790/AI/NIAID NIH HHS/ -- UM1 AI100645/AI/NIAID NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- ZIA AI000855-15/Intramural NIH HHS/ -- ZIA AI001090-05/Intramural NIH HHS/ -- England -- Nature. 2014 Nov 6;515(7525):138-42. doi: 10.1038/nature13601. Epub 2014 Sep 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; 1] The Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA [2] International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California 92037, USA. ; San Diego Biomedical Research Institute, San Diego, California 92121, USA. ; International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California 92037, USA. ; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1100 DD, The Netherlands. ; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10065, USA. ; Duke Human Vaccine Institute, Duke University, Durham, North Carolina 27710, USA. ; 1] Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1100 DD, The Netherlands [2] Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25186731" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/chemistry/immunology ; Antibodies, Monoclonal/chemistry/genetics/immunology/pharmacology ; Antibodies, Neutralizing/chemistry/genetics/*immunology/pharmacology ; *Antibody Affinity ; Antibody Specificity ; Antigens, CD4/metabolism ; Cell Line ; Cell Membrane/virology ; Conserved Sequence ; Epitope Mapping ; Epitopes/chemistry/immunology ; HIV Antibodies/chemistry/genetics/*immunology/pharmacology ; HIV Envelope Protein gp120/*chemistry/*immunology ; HIV Envelope Protein gp41/*chemistry/*immunology ; HIV-1/drug effects/immunology ; Humans ; Immunoglobulin Fab Fragments/chemistry/genetics/immunology/ultrastructure ; Inhibitory Concentration 50 ; Leukocytes, Mononuclear ; Models, Molecular ; Molecular Sequence Data ; Receptors, CCR5/metabolism ; Virus Internalization/drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
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    Developmental biology. Mesenchymal progenitor panoply (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-11-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Joo-Hyeon -- Kim, Carla F -- New York, N.Y. -- Science. 2014 Nov 14;346(6211):810-1. doi: 10.1126/science.aaa0609.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Children's Hospital, Harvard Medical School, Boston, MA, USA. ; Children's Hospital, Harvard Medical School, Boston, MA, USA. carla.kim@childrens.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25395521" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Lung/*growth & development ; Mesenchymal Stromal Cells/*physiology ; Stem Cell Niche/*physiology
    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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  • 8
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    Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-03-06
    Description: Sestrins are conserved proteins that accumulate in cells exposed to stress, potentiate adenosine monophosphate-activated protein kinase (AMPK), and inhibit activation of target of rapamycin (TOR). We show that the abundance of Drosophila sestrin (dSesn) is increased upon chronic TOR activation through accumulation of reactive oxygen species that cause activation of c-Jun amino-terminal kinase and transcription factor Forkhead box O (FoxO). Loss of dSesn resulted in age-associated pathologies including triglyceride accumulation, mitochondrial dysfunction, muscle degeneration, and cardiac malfunction, which were prevented by pharmacological activation of AMPK or inhibition of TOR. Hence, dSesn appears to be a negative feedback regulator of TOR that integrates metabolic and stress inputs and prevents pathologies caused by chronic TOR activation that may result from diminished autophagic clearance of damaged mitochondria, protein aggregates, or lipids.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866632/" 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/PMC2866632/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Jun Hee -- Budanov, Andrei V -- Park, Eek Joong -- Birse, Ryan -- Kim, Teddy E -- Perkins, Guy A -- Ocorr, Karen -- Ellisman, Mark H -- Bodmer, Rolf -- Bier, Ethan -- Karin, Michael -- AI070654/AI/NIAID NIH HHS/ -- CA118165/CA/NCI NIH HHS/ -- DK082080/DK/NIDDK NIH HHS/ -- ES006376/ES/NIEHS NIH HHS/ -- NS29870/NS/NINDS NIH HHS/ -- P30 CA023100/CA/NCI NIH HHS/ -- P30-CA23100/CA/NCI NIH HHS/ -- P41-RR004050/RR/NCRR NIH HHS/ -- P42 ES010337/ES/NIEHS NIH HHS/ -- P42 ES010337-10S20010/ES/NIEHS NIH HHS/ -- P42-ES010337/ES/NIEHS NIH HHS/ -- R01 CA118165/CA/NCI NIH HHS/ -- R01 CA118165-04/CA/NCI NIH HHS/ -- R01 ES006376/ES/NIEHS NIH HHS/ -- R01 ES006376-17/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 2010 Mar 5;327(5970):1223-8. doi: 10.1126/science.1182228.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego (UCSD), La Jolla, CA 92093-0723, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20203043" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/metabolism ; *Aging ; Amino Acid Sequence ; Animals ; Autophagy ; Cell Size ; Drosophila Proteins/antagonists & ; inhibitors/chemistry/genetics/metabolism/*physiology ; Drosophila melanogaster/cytology/growth & development/metabolism/*physiology ; Fat Body/metabolism ; Feedback, Physiological ; Forkhead Transcription Factors/metabolism ; Gene Expression Regulation ; Heart/physiology ; Heat-Shock Proteins/chemistry/genetics/*physiology ; JNK Mitogen-Activated Protein Kinases/metabolism ; Mitochondria, Muscle/physiology/ultrastructure ; Models, Animal ; Molecular Sequence Data ; Muscles/physiology ; Oxidative Stress ; Protein Kinases/*metabolism ; Reactive Oxygen Species/metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases ; Transcription, Genetic ; Triglycerides/metabolism ; Wings, Animal/cytology/growth & development/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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  • 9
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    Evolutionarily assembled cis-regulatory module at a human ciliopathy locus (2012)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2012-01-28
    Description: Neighboring genes are often coordinately expressed within cis-regulatory modules, but evidence that nonparalogous genes share functions in mammals is lacking. Here, we report that mutation of either TMEM138 or TMEM216 causes a phenotypically indistinguishable human ciliopathy, Joubert syndrome. Despite a lack of sequence homology, the genes are aligned in a head-to-tail configuration and joined by chromosomal rearrangement at the amphibian-to-reptile evolutionary transition. Expression of the two genes is mediated by a conserved regulatory element in the noncoding intergenic region. Coordinated expression is important for their interdependent cellular role in vesicular transport to primary cilia. Hence, during vertebrate evolution of genes involved in ciliogenesis, nonparalogous genes were arranged to a functional gene cluster with shared regulatory elements.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671610/" 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/PMC3671610/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Jeong Ho -- Silhavy, Jennifer L -- Lee, Ji Eun -- Al-Gazali, Lihadh -- Thomas, Sophie -- Davis, Erica E -- Bielas, Stephanie L -- Hill, Kiley J -- Iannicelli, Miriam -- Brancati, Francesco -- Gabriel, Stacey B -- Russ, Carsten -- Logan, Clare V -- Sharif, Saghira Malik -- Bennett, Christopher P -- Abe, Masumi -- Hildebrandt, Friedhelm -- Diplas, Bill H -- Attie-Bitach, Tania -- Katsanis, Nicholas -- Rajab, Anna -- Koul, Roshan -- Sztriha, Laszlo -- Waters, Elizabeth R -- Ferro-Novick, Susan -- Woods, C Geoffrey -- Johnson, Colin A -- Valente, Enza Maria -- Zaki, Maha S -- Gleeson, Joseph G -- DK068306/DK/NIDDK NIH HHS/ -- DK072301/DK/NIDDK NIH HHS/ -- DK075972/DK/NIDDK NIH HHS/ -- DK090917/DK/NIDDK NIH HHS/ -- EY021872/EY/NEI NIH HHS/ -- G0700073/Medical Research Council/United Kingdom -- GGP08145/Telethon/Italy -- HD042601/HD/NICHD NIH HHS/ -- NS04843/NS/NINDS NIH HHS/ -- NS052455/NS/NINDS NIH HHS/ -- P30 CA023100/CA/NCI NIH HHS/ -- P30NS047101/NS/NINDS NIH HHS/ -- R01 DK068306/DK/NIDDK NIH HHS/ -- R01 DK072301/DK/NIDDK NIH HHS/ -- R01 DK075972/DK/NIDDK NIH HHS/ -- R01 EY021872/EY/NEI NIH HHS/ -- R01 HD042601/HD/NICHD NIH HHS/ -- R01 NS048453/NS/NINDS NIH HHS/ -- R01 NS052455/NS/NINDS NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Feb 24;335(6071):966-9. doi: 10.1126/science.1213506. Epub 2012 Jan 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neurogenetics Laboratory, Howard Hughes Medical Institute (HHMI), Department of Neurosciences, University of California, San Diego, CA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22282472" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell Line ; Cerebellar Diseases/*genetics/metabolism/pathology ; Cilia/metabolism/*ultrastructure ; Conserved Sequence ; DNA, Intergenic ; *Evolution, Molecular ; Eye Abnormalities/*genetics/metabolism/pathology ; Gene Expression Profiling ; *Gene Expression Regulation ; Genetic Heterogeneity ; *Genetic Loci ; Humans ; Kidney Diseases, Cystic/*genetics/metabolism/pathology ; Membrane Proteins/chemistry/*genetics/metabolism ; Molecular Sequence Data ; Multigene Family ; Mutation ; Mutation, Missense ; Phenotype ; Protein Transport ; *Regulatory Sequences, Nucleic Acid ; Retina/abnormalities/metabolism/pathology ; Transport Vesicles/metabolism/ultrastructure
    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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    Regulation of temperature-responsive flowering by MADS-box transcription factor repressors (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-09-14
    Description: Changes in ambient temperature affect flowering time in plants; understanding this phenomenon will be crucial for buffering agricultural systems from the effects of climate change. Here, we show that levels of FLM-beta, an alternatively spliced form of the flowering repressor FLOWERING LOCUS M, increase at lower temperatures, repressing flowering. FLM-beta interacts with SHORT VEGETATIVE PHASE (SVP); SVP is degraded at high temperatures, reducing the abundance of the SVP-FLM-beta repressor complex and, thus, allowing the plant to flower. The svp and flm mutants show temperature-insensitive flowering in different temperature ranges. Control of SVP-FLM-beta repressor complex abundance via transcriptional and splicing regulation of FLM and posttranslational regulation of SVP protein stability provides an efficient, rapid mechanism for plants to respond to ambient temperature changes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Jeong Hwan -- Ryu, Hak-Seung -- Chung, Kyung Sook -- Pose, David -- Kim, Soonkap -- Schmid, Markus -- Ahn, Ji Hoon -- New York, N.Y. -- Science. 2013 Nov 1;342(6158):628-32. doi: 10.1126/science.1241097. Epub 2013 Sep 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Creative Research Initiatives, Department of Life Sciences, Korea University, Seoul 136-701, South Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24030492" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing ; Arabidopsis/genetics/*growth & development/metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Flowers/genetics/*growth & development/metabolism ; Gene Expression Regulation, Plant ; MADS Domain Proteins/genetics/*metabolism ; Molecular Sequence Data ; Mutation ; Repressor Proteins/genetics/*metabolism ; Temperature ; 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
    Published by American Association for the Advancement of Science (AAAS)
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