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  • 1
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    An essential receptor for adeno-associated virus infection (2016)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2016-01-28
    Description: Adeno-associated virus (AAV) vectors are currently the leading candidates for virus-based gene therapies because of their broad tissue tropism, non-pathogenic nature and low immunogenicity. They have been successfully used in clinical trials to treat hereditary diseases such as haemophilia B (ref. 2), and have been approved for treatment of lipoprotein lipase deficiency in Europe. Considerable efforts have been made to engineer AAV variants with novel and biomedically valuable cell tropisms to allow efficacious systemic administration, yet basic aspects of AAV cellular entry are still poorly understood. In particular, the protein receptor(s) required for AAV entry after cell attachment remains unknown. Here we use an unbiased genetic screen to identify proteins essential for AAV serotype 2 (AAV2) infection in a haploid human cell line. The most significantly enriched gene of the screen encodes a previously uncharacterized type I transmembrane protein, KIAA0319L (denoted hereafter as AAV receptor (AAVR)). We characterize AAVR as a protein capable of rapid endocytosis from the plasma membrane and trafficking to the trans-Golgi network. We show that AAVR directly binds to AAV2 particles, and that anti-AAVR antibodies efficiently block AAV2 infection. Moreover, genetic ablation of AAVR renders a wide range of mammalian cell types highly resistant to AAV2 infection. Notably, AAVR serves as a critical host factor for all tested AAV serotypes. The importance of AAVR for in vivo gene delivery is further highlighted by the robust resistance of Aavr(-/-) (also known as Au040320(-/-) and Kiaa0319l(-/-)) mice to AAV infection. Collectively, our data indicate that AAVR is a universal receptor involved in AAV infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pillay, S -- Meyer, N L -- Puschnik, A S -- Davulcu, O -- Diep, J -- Ishikawa, Y -- Jae, L T -- Wosen, J E -- Nagamine, C M -- Chapman, M S -- Carette, J E -- DP2 AI104557/AI/NIAID NIH HHS/ -- R01 GM066875/GM/NIGMS NIH HHS/ -- U19 AI109662/AI/NIAID NIH HHS/ -- England -- Nature. 2016 Feb 4;530(7588):108-12. doi: 10.1038/nature16465. Epub 2016 Jan 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Stanford University School of Medicine, 299 Campus Drive, Stanford, California 94305, USA. ; Department of Biochemistry and Molecular Biology, School of Medicine, Oregon Health &Science University, 3181 Sam Jackson Park Road, Portland, Oregon 97239-3098, USA. ; Shriners Hospital for Children, 3101 Sam Jackson Park Road, Portland, Oregon 97239, USA. ; Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands. ; Department of Comparative Medicine, Stanford University School of Medicine, 287 Campus Drive, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26814968" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies/immunology/pharmacology ; Cell Line ; Dependovirus/classification/drug effects/*physiology ; Endocytosis/drug effects ; Female ; Gene Deletion ; Genetic Therapy/methods ; Host Specificity ; Humans ; Male ; Mice ; Parvoviridae Infections/*metabolism/*virology ; Receptors, Cell Surface/antagonists & inhibitors/deficiency/genetics/*metabolism ; Receptors, Virus/antagonists & inhibitors/deficiency/genetics/*metabolism ; *Viral Tropism/drug effects ; Virus Internalization/drug effects ; trans-Golgi Network/drug 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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    Nuclear DNA sequences from the Middle Pleistocene Sima de los Huesos hominins (2016)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2016-03-16
    Description: A unique assemblage of 28 hominin individuals, found in Sima de los Huesos in the Sierra de Atapuerca in Spain, has recently been dated to approximately 430,000 years ago. An interesting question is how these Middle Pleistocene hominins were related to those who lived in the Late Pleistocene epoch, in particular to Neanderthals in western Eurasia and to Denisovans, a sister group of Neanderthals so far known only from southern Siberia. While the Sima de los Huesos hominins share some derived morphological features with Neanderthals, the mitochondrial genome retrieved from one individual from Sima de los Huesos is more closely related to the mitochondrial DNA of Denisovans than to that of Neanderthals. However, since the mitochondrial DNA does not reveal the full picture of relationships among populations, we have investigated DNA preservation in several individuals found at Sima de los Huesos. Here we recover nuclear DNA sequences from two specimens, which show that the Sima de los Huesos hominins were related to Neanderthals rather than to Denisovans, indicating that the population divergence between Neanderthals and Denisovans predates 430,000 years ago. A mitochondrial DNA recovered from one of the specimens shares the previously described relationship to Denisovan mitochondrial DNAs, suggesting, among other possibilities, that the mitochondrial DNA gene pool of Neanderthals turned over later in their history.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meyer, Matthias -- Arsuaga, Juan-Luis -- de Filippo, Cesare -- Nagel, Sarah -- Aximu-Petri, Ayinuer -- Nickel, Birgit -- Martinez, Ignacio -- Gracia, Ana -- Bermudez de Castro, Jose Maria -- Carbonell, Eudald -- Viola, Bence -- Kelso, Janet -- Prufer, Kay -- Paabo, Svante -- England -- Nature. 2016 Mar 24;531(7595):504-7. doi: 10.1038/nature17405. Epub 2016 Mar 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. ; Centro de Investigacion Sobre la Evolucion y Comportamiento Humanos, Universidad Complutense de Madrid-Instituto de Salud Carlos III, 28029 Madrid, Spain. ; Departamento de Paleontologia, Facultad de Ciencias Geologicas, Universidad Complutense de Madrid, 28040 Madrid, Spain. ; Area de Paleontologia, Departamento de Geografia y Geologia, Universidad de Alcala, Alcala de Henares, 28871 Madrid, Spain. ; Centro Nacional de Investigacion sobre la Evolucion Humana, Paseo Sierra de Atapuerca, 09002 Burgos, Spain. ; Institut Catala de Paleoecologia Humana i Evolucio Social, C/Marcel.li Domingo s/n (Edifici W3), Campus Sescelades, 43007 Tarragona, Spain. ; Area de Prehistoria, Departament d'Historia i Historia de l'Art, Universitat Rovira i Virgili, Facultat de Lletres, Avinguda de Catalunya, 35, 43002 Tarragona, Spain. ; Department of Anthropology, University of Toronto, 19 Russell Street, Toronto, Ontario M5S 2S2, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26976447" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; DNA, Mitochondrial/genetics ; Fossils ; Genome, Mitochondrial/genetics ; Hominidae/classification/*genetics ; Male ; Neanderthals/classification/genetics ; *Phylogeny ; Sequence Alignment ; Spain
    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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  • 3
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    Solar Coronal Jets: Observations, Theory, and Modeling (2016)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: Chromospheric and coronal jets represent important manifestations of ubiquitous solar transients, which may be the source of signicant mass and energy input to the upper solar atmosphere and the solar wind. While the energy involved in a jet-like event is smaller than that of nominal solar ares and Coronal Mass Ejections (CMEs), jets share many common properties with these major phenomena, in particular, the explosive magnetically driven dynamics. Studies of jets could, therefore, provide critical insight for understanding the larger, more complex drivers of the solar activity. On the other side of the size-spectrum, the study of jets could also supply important clues on the physics of transients closeor at the limit of the current spatial resolution such as spicules. Furthermore, jet phenomena may hint to basic process for heating the corona and accelerating the solar wind; consequently their study gives us the opportunity to attack a broadrange of solar-heliospheric problems.
    Keywords: Solar Physics
    Type: GSFC-E-DAA-TN41385 , Space Science Reviews (ISSN 0038-6308) (e-ISSN 1572-9672); 201; 1; 1-53
    Format: application/pdf
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  • 4
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    Solar Coronal Jets: Observations, Theory, and Modeling (2016)
    In:  Other Sources
    Details
    Publication Date: 2019-07-13
    Description: Coronal jets represent important manifestations of ubiquitous solar transients, which may be the source of significant mass and energy input to the upper solar atmosphere and the solar wind. While the energy involved in a jet-like event is smaller than that of "nominal" solar flares and coronal mass ejections (CMEs), jets share many common properties with these phenomena, in particular, the explosive magnetically driven dynamics. Studies of jets could, therefore, provide critical insight for understanding the larger, more complex drivers of the solar activity. On the other side of the size-spectrum, the study of jets could also supply important clues on the physics of transients close or at the limit of the current spatial resolution such as spicules. Furthermore, jet phenomena may hint to basic process for heating the corona and accelerating the solar wind; consequently their study gives us the opportunity to attack a broad range of solar-heliospheric problems.
    Keywords: Solar Physics
    Type: GSFC-E-DAA-TN41210 , Space Science Reviews (ISSN 0038-6308) (e-ISSN 1572-9672); 201; 1; 1-53
    Format: text
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    NASA TECHNICAL REPORTS
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