ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Cell Line  (13)
  • Nature Publishing Group (NPG)  (13)
  • American Geophysical Union (AGU)
  • American Institute of Physics
  • American Institute of Physics (AIP)
  • National Academy of Sciences
Collection
Keywords
Publisher
Years
  • 11
    facet.materialart.
    Unknown
    Cell-to-cell spread of HIV permits ongoing replication despite antiretroviral therapy (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-08-19
    Description: Latency and ongoing replication have both been proposed to explain the drug-insensitive human immunodeficiency virus (HIV) reservoir maintained during antiretroviral therapy. Here we explore a novel mechanism for ongoing HIV replication in the face of antiretroviral drugs. We propose a model whereby multiple infections per cell lead to reduced sensitivity to drugs without requiring drug-resistant mutations, and experimentally validate the model using multiple infections per cell by cell-free HIV in the presence of the drug tenofovir. We then examine the drug sensitivity of cell-to-cell spread of HIV, a mode of HIV transmission that can lead to multiple infection events per target cell. Infections originating from cell-free virus decrease strongly in the presence of antiretrovirals tenofovir and efavirenz whereas infections involving cell-to-cell spread are markedly less sensitive to the drugs. The reduction in sensitivity is sufficient to keep multiple rounds of infection from terminating in the presence of drugs. We examine replication from cell-to-cell spread in the presence of clinical drug concentrations using a stochastic infection model and find that replication is intermittent, without substantial accumulation of mutations. If cell-to-cell spread has the same properties in vivo, it may have adverse consequences for the immune system, lead to therapy failure in individuals with risk factors, and potentially contribute to viral persistence and hence be a barrier to curing HIV infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sigal, Alex -- Kim, Jocelyn T -- Balazs, Alejandro B -- Dekel, Erez -- Mayo, Avi -- Milo, Ron -- Baltimore, David -- HHSN266200500035C/PHS HHS/ -- T32 AI089398/AI/NIAID NIH HHS/ -- England -- Nature. 2011 Aug 17;477(7362):95-8. doi: 10.1038/nature10347.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21849975" target="_blank"〉PubMed〈/a〉
    Keywords: Adenine/analogs & derivatives/pharmacology ; Anti-Retroviral Agents/*pharmacology ; Cell Line ; Drug Resistance, Viral/physiology ; HEK293 Cells ; HIV Infections/transmission/*virology ; HIV-1/drug effects/*physiology ; Humans ; Models, Biological ; Organophosphonates/pharmacology ; Tenofovir ; Virus Replication/drug effects/*physiology
    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)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 12
    facet.materialart.
    Unknown
    X chromosome dosage compensation via enhanced transcriptional elongation in Drosophila (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-03-04
    Description: The evolution of sex chromosomes has resulted in numerous species in which females inherit two X chromosomes but males have a single X, thus requiring dosage compensation. MSL (Male-specific lethal) complex increases transcription on the single X chromosome of Drosophila males to equalize expression of X-linked genes between the sexes. The biochemical mechanisms used for dosage compensation must function over a wide dynamic range of transcription levels and differential expression patterns. It has been proposed that the MSL complex regulates transcriptional elongation to control dosage compensation, a model subsequently supported by mapping of the MSL complex and MSL-dependent histone 4 lysine 16 acetylation to the bodies of X-linked genes in males, with a bias towards 3' ends. However, experimental analysis of MSL function at the mechanistic level has been challenging owing to the small magnitude of the chromosome-wide effect and the lack of an in vitro system for biochemical analysis. Here we use global run-on sequencing (GRO-seq) to examine the specific effect of the MSL complex on RNA Polymerase II (RNAP II) on a genome-wide level. Results indicate that the MSL complex enhances transcription by facilitating the progression of RNAP II across the bodies of active X-linked genes. Improving transcriptional output downstream of typical gene-specific controls may explain how dosage compensation can be imposed on the diverse set of genes along an entire chromosome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076316/" 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/PMC3076316/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Larschan, Erica -- Bishop, Eric P -- Kharchenko, Peter V -- Core, Leighton J -- Lis, John T -- Park, Peter J -- Kuroda, Mitzi I -- GM082798/GM/NIGMS NIH HHS/ -- GM45744/GM/NIGMS NIH HHS/ -- HG4845/HG/NHGRI NIH HHS/ -- R01 HG004845/HG/NHGRI NIH HHS/ -- R01 HG004845-01/HG/NHGRI NIH HHS/ -- R01 HG004845-02/HG/NHGRI NIH HHS/ -- R37 GM045744/GM/NIGMS NIH HHS/ -- England -- Nature. 2011 Mar 3;471(7336):115-8. doi: 10.1038/nature09757.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21368835" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Animals ; Cell Line ; Chromosomes, Insect/*genetics/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Dosage Compensation, Genetic/*genetics ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/enzymology/*genetics ; Genes, Insect/genetics ; Genes, X-Linked/genetics ; Histones/chemistry/metabolism ; Male ; Nuclear Proteins/genetics/metabolism ; RNA Polymerase II/metabolism ; Sequence Analysis, DNA ; Transcription Factors/genetics/metabolism ; *Transcription, Genetic/genetics ; X Chromosome/*genetics/metabolism
    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)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 13
    facet.materialart.
    Unknown
    Exploiting a natural conformational switch to engineer an interleukin-2 'superkine' (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-03-27
    Description: The immunostimulatory cytokine interleukin-2 (IL-2) is a growth factor for a wide range of leukocytes, including T cells and natural killer (NK) cells. Considerable effort has been invested in using IL-2 as a therapeutic agent for a variety of immune disorders ranging from AIDS to cancer. However, adverse effects have limited its use in the clinic. On activated T cells, IL-2 signals through a quaternary 'high affinity' receptor complex consisting of IL-2, IL-2Ralpha (termed CD25), IL-2Rbeta and IL-2Rgamma. Naive T cells express only a low density of IL-2Rbeta and IL-2Rgamma, and are therefore relatively insensitive to IL-2, but acquire sensitivity after CD25 expression, which captures the cytokine and presents it to IL-2Rbeta and IL-2Rgamma. Here, using in vitro evolution, we eliminated the functional requirement of IL-2 for CD25 expression by engineering an IL-2 'superkine' (also called super-2) with increased binding affinity for IL-2Rbeta. Crystal structures of the IL-2 superkine in free and receptor-bound forms showed that the evolved mutations are principally in the core of the cytokine, and molecular dynamics simulations indicated that the evolved mutations stabilized IL-2, reducing the flexibility of a helix in the IL-2Rbeta binding site, into an optimized receptor-binding conformation resembling that when bound to CD25. The evolved mutations in the IL-2 superkine recapitulated the functional role of CD25 by eliciting potent phosphorylation of STAT5 and vigorous proliferation of T cells irrespective of CD25 expression. Compared to IL-2, the IL-2 superkine induced superior expansion of cytotoxic T cells, leading to improved antitumour responses in vivo, and elicited proportionally less expansion of T regulatory cells and reduced pulmonary oedema. Collectively, we show that in vitro evolution has mimicked the functional role of CD25 in enhancing IL-2 potency and regulating target cell specificity, which has implications for immunotherapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338870/" 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/PMC3338870/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Levin, Aron M -- Bates, Darren L -- Ring, Aaron M -- Krieg, Carsten -- Lin, Jack T -- Su, Leon -- Moraga, Ignacio -- Raeber, Miro E -- Bowman, Gregory R -- Novick, Paul -- Pande, Vijay S -- Fathman, C Garrison -- Boyman, Onur -- Garcia, K Christopher -- AR050942/AR/NIAMS NIH HHS/ -- GM07365/GM/NIGMS NIH HHS/ -- R01 AI051321/AI/NIAID NIH HHS/ -- R01 AI051321-05/AI/NIAID NIH HHS/ -- R01 CA065237/CA/NCI NIH HHS/ -- R01-GM062868/GM/NIGMS NIH HHS/ -- R01AI51321/AI/NIAID NIH HHS/ -- R37 AI051321/AI/NIAID NIH HHS/ -- T32 AI007290/AI/NIAID NIH HHS/ -- U01 DK078123/DK/NIDDK NIH HHS/ -- U19 AI 082719/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Mar 25;484(7395):529-33. doi: 10.1038/nature10975.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22446627" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Cell Line ; Cell Proliferation ; Crystallography, X-Ray ; *Directed Molecular Evolution ; Humans ; Immunotherapy ; Interleukin-2/*chemistry/genetics/*immunology/pharmacology ; Interleukin-2 Receptor alpha Subunit/chemistry/deficiency/immunology/metabolism ; Interleukin-2 Receptor beta Subunit/chemistry/metabolism ; Killer Cells, Natural/immunology ; Mice ; Mice, Inbred C57BL ; Models, Molecular ; Molecular Dynamics Simulation ; Mutant Proteins/*chemistry/genetics/*immunology/pharmacology ; Mutation ; Neoplasm Transplantation ; Neoplasms/drug therapy/immunology ; Phosphorylation ; Protein Conformation ; *Protein Engineering ; STAT5 Transcription Factor/metabolism ; Surface Plasmon Resonance ; T-Lymphocytes/cytology/immunology
    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)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...