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  • 1
    Publication Date: 2013-09-13
    Description: Established infections with the human and simian immunodeficiency viruses (HIV and SIV, respectively) are thought to be permanent with even the most effective immune responses and antiretroviral therapies only able to control, but not clear, these infections. Whether the residual virus that maintains these infections is vulnerable to clearance is a question of central importance to the future management of millions of HIV-infected individuals. We recently reported that approximately 50% of rhesus macaques (RM; Macaca mulatta) vaccinated with SIV protein-expressing rhesus cytomegalovirus (RhCMV/SIV) vectors manifest durable, aviraemic control of infection with the highly pathogenic strain SIVmac239 (ref. 5). Here we show that regardless of the route of challenge, RhCMV/SIV vector-elicited immune responses control SIVmac239 after demonstrable lymphatic and haematogenous viral dissemination, and that replication-competent SIV persists in several sites for weeks to months. Over time, however, protected RM lost signs of SIV infection, showing a consistent lack of measurable plasma- or tissue-associated virus using ultrasensitive assays, and a loss of T-cell reactivity to SIV determinants not in the vaccine. Extensive ultrasensitive quantitative PCR and quantitative PCR with reverse transcription analyses of tissues from RhCMV/SIV vector-protected RM necropsied 69-172 weeks after challenge did not detect SIV RNA or DNA sequences above background levels, and replication-competent SIV was not detected in these RM by extensive co-culture analysis of tissues or by adoptive transfer of 60 million haematolymphoid cells to naive RM. These data provide compelling evidence for progressive clearance of a pathogenic lentiviral infection, and suggest that some lentiviral reservoirs may be susceptible to the continuous effector memory T-cell-mediated immune surveillance elicited and maintained by cytomegalovirus vectors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3849456/" 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/PMC3849456/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hansen, Scott G -- Piatak, Michael Jr -- Ventura, Abigail B -- Hughes, Colette M -- Gilbride, Roxanne M -- Ford, Julia C -- Oswald, Kelli -- Shoemaker, Rebecca -- Li, Yuan -- Lewis, Matthew S -- Gilliam, Awbrey N -- Xu, Guangwu -- Whizin, Nathan -- Burwitz, Benjamin J -- Planer, Shannon L -- Turner, John M -- Legasse, Alfred W -- Axthelm, Michael K -- Nelson, Jay A -- Fruh, Klaus -- Sacha, Jonah B -- Estes, Jacob D -- Keele, Brandon F -- Edlefsen, Paul T -- Lifson, Jeffrey D -- Picker, Louis J -- HHSN261200800001E/PHS HHS/ -- P01 AI094417/AI/NIAID NIH HHS/ -- P51OD011092/OD/NIH HHS/ -- R01 AI060392/AI/NIAID NIH HHS/ -- R01 DE021291/DE/NIDCR NIH HHS/ -- R37 AI054292/AI/NIAID NIH HHS/ -- U19 AI095985/AI/NIAID NIH HHS/ -- U19 AI096109/AI/NIAID NIH HHS/ -- U24 OD010850/OD/NIH HHS/ -- U42 OD010426/OD/NIH HHS/ -- England -- Nature. 2013 Oct 3;502(7469):100-4. doi: 10.1038/nature12519. Epub 2013 Sep 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon 97006, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24025770" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cytomegalovirus/genetics/immunology ; Female ; Macaca mulatta ; Male ; Molecular Sequence Data ; SAIDS Vaccines/*immunology ; Simian Acquired Immunodeficiency Syndrome/*prevention & control/virology ; Simian Immunodeficiency Virus/*immunology ; Time Factors ; Vaccines, Attenuated/immunology ; Viral Load ; Virus Replication/physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2012-06-23
    Description: In female (XX) mammals, one of the two X chromosomes is inactivated to ensure an equal dose of X-linked genes with males (XY). X-chromosome inactivation in eutherian mammals is mediated by the non-coding RNA Xist. Xist is not found in metatherians (marsupials), and how X-chromosome inactivation is initiated in these mammals has been the subject of speculation for decades. Using the marsupial Monodelphis domestica, here we identify Rsx (RNA-on-the-silent X), an RNA that has properties consistent with a role in X-chromosome inactivation. Rsx is a large, repeat-rich RNA that is expressed only in females and is transcribed from, and coats, the inactive X chromosome. In female germ cells, in which both X chromosomes are active, Rsx is silenced, linking Rsx expression to X-chromosome inactivation and reactivation. Integration of an Rsx transgene on an autosome in mouse embryonic stem cells leads to gene silencing in cis. Our findings permit comparative studies of X-chromosome inactivation in mammals and pose questions about the mechanisms by which X-chromosome inactivation is achieved in eutherians.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484893/" 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/PMC3484893/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grant, Jennifer -- Mahadevaiah, Shantha K -- Khil, Pavel -- Sangrithi, Mahesh N -- Royo, Helene -- Duckworth, Janine -- McCarrey, John R -- VandeBerg, John L -- Renfree, Marilyn B -- Taylor, Willie -- Elgar, Greg -- Camerini-Otero, R Daniel -- Gilchrist, Mike J -- Turner, James M A -- HD60858/HD/NICHD NIH HHS/ -- MC_U117597137/Medical Research Council/United Kingdom -- MC_U117597141/Medical Research Council/United Kingdom -- U117581331/Medical Research Council/United Kingdom -- U117588498/Medical Research Council/United Kingdom -- U117597137/Medical Research Council/United Kingdom -- U117597141/Medical Research Council/United Kingdom -- Z99 DK999999/Intramural NIH HHS/ -- ZIA DK052035-05/Intramural NIH HHS/ -- England -- Nature. 2012 Jul 12;487(7406):254-8. doi: 10.1038/nature11171.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW71AA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722828" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Gene Expression Regulation ; Gene Silencing ; Mice ; Monodelphis/*genetics/*metabolism ; RNA/*genetics/*metabolism ; Transgenes ; X Chromosome/*genetics/*metabolism ; *X Chromosome Inactivation
    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: 2013-05-25
    Description: CD8(+) T cell responses focus on a small fraction of pathogen- or vaccine-encoded peptides, and for some pathogens, these restricted recognition hierarchies limit the effectiveness of antipathogen immunity. We found that simian immunodeficiency virus (SIV) protein-expressing rhesus cytomegalovirus (RhCMV) vectors elicit SIV-specific CD8(+) T cells that recognize unusual, diverse, and highly promiscuous epitopes, including dominant responses to epitopes restricted by class II major histocompatibility complex (MHC) molecules. Induction of canonical SIV epitope-specific CD8(+) T cell responses is suppressed by the RhCMV-encoded Rh189 gene (corresponding to human CMV US11), and the promiscuous MHC class I- and class II-restricted CD8(+) T cell responses occur only in the absence of the Rh157.5, Rh157.4, and Rh157.6 (human CMV UL128, UL130, and UL131) genes. Thus, CMV vectors can be genetically programmed to achieve distinct patterns of CD8(+) T cell epitope recognition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816976/" 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/PMC3816976/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hansen, Scott G -- Sacha, Jonah B -- Hughes, Colette M -- Ford, Julia C -- Burwitz, Benjamin J -- Scholz, Isabel -- Gilbride, Roxanne M -- Lewis, Matthew S -- Gilliam, Awbrey N -- Ventura, Abigail B -- Malouli, Daniel -- Xu, Guangwu -- Richards, Rebecca -- Whizin, Nathan -- Reed, Jason S -- Hammond, Katherine B -- Fischer, Miranda -- Turner, John M -- Legasse, Alfred W -- Axthelm, Michael K -- Edlefsen, Paul T -- Nelson, Jay A -- Lifson, Jeffrey D -- Fruh, Klaus -- Picker, Louis J -- P01 AI094417/AI/NIAID NIH HHS/ -- P51 OD 011092/OD/NIH HHS/ -- R01 AI059457/AI/NIAID NIH HHS/ -- R01 AI060392/AI/NIAID NIH HHS/ -- U24 OD010850/OD/NIH HHS/ -- New York, N.Y. -- Science. 2013 May 24;340(6135):1237874. doi: 10.1126/science.1237874.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23704576" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD8-Positive T-Lymphocytes/*immunology ; Cytokines/immunology ; Cytomegalovirus/genetics/*immunology ; Epitopes, T-Lymphocyte/*immunology ; Female ; Genetic Vectors/genetics/*immunology ; Histocompatibility Antigens Class II/immunology ; Humans ; Macaca mulatta ; Male ; Membrane Glycoproteins/genetics ; SAIDS Vaccines/administration & dosage/*immunology ; Viral Envelope Proteins/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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  • 4
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 185 (1960), S. 763-764 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Table 1. EFFECT OF CHLOROACETOPHENONE CONCENTRATION ON TRYPTOPHANASE ACTIVITY Chloroacetophenone concentration (M) Tryptophanase activity /*gm. indole/5 min. Percentage 0 0-2 x 10- 0-2 x 10-6 0-4 x 10~5 0-2 x 10-4 0-2 x 10~3 25-5 25-5 24-3 14-3 6-9 0 100 100 95 5627 0 Table 3. EFFECT OF ...
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 179 (1957), S. 155-156 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] In view of recent evidence obtained in this laboratory by Beechey and Happold3 for the exist- Once of a pyridoxamine phosphate transaminase in JSsch, coli which requires magnesium ions for the conversion of pyridoxamine phosphate to the pyri-doxal ester, as well as the effect of monovalent cations ...
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  • 6
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 215 (1967), S. 887-888 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Fig. 1. Effect of the concentration of NAD on the formation of aminoacetone from L-threonine in the presence of 2-oxo acids or malate. Reaction mixtures contained 125 mmolar tris buffer (pH 8.5), 400 mmolar potassium chloride, 25 mmolar L-threonine, 2 mmolar 2-oxc-giutarate (O), oxaloacetate (D) or ...
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 28 (1973), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    ISSN: 0538-8066
    Keywords: Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Quantitative analysis of the products formed in 1,1′-azoisobutane pyrolyses in the temperature range of 553°-602°K has shown that the major reactions of the iso-butyl radical are Analysis of initial rate data gave log10k4/(kc)1/2(cm-3/2.mol 1/2.sec-1/2) = 7.54±0.44 - (136.5 + 4.8) kJ/mol/2.303RT, the Arrhenius parameters obtained being in good agreement with thermodynamic data for reaction (4). Measured values of ka/(kc)1/2 where ka is the rate constant of the reaction iC4H9 + AIB → iC4H10 +. AIB were consistent with published parameters determined by photolysis of 1,1′-azoisobutane. Combination of photolysis and pyrolysis data gave log10 ka/(kc)1/2(cm3/2.mol-1/22.sec-1/2) = 3.68 ± 0.15 - (27.2 ± 1.2) kJ/mol/2.303RT. The crosscombination ratio for methyl and iso-butyl radicals has been found to be 0.25, indicating that the geometric mean rule does not hold for methyl and iso-butyl radicals.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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