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  • 1
    Publication Date: 2015-04-23
    Description: The current outbreak of Ebola virus in West Africa is unprecedented, causing more cases and fatalities than all previous outbreaks combined, and has yet to be controlled. Several post-exposure interventions have been employed under compassionate use to treat patients repatriated to Europe and the United States. However, the in vivo efficacy of these interventions against the new outbreak strain of Ebola virus is unknown. Here we show that lipid-nanoparticle-encapsulated short interfering RNAs (siRNAs) rapidly adapted to target the Makona outbreak strain of Ebola virus are able to protect 100% of rhesus monkeys against lethal challenge when treatment was initiated at 3 days after exposure while animals were viraemic and clinically ill. Although all infected animals showed evidence of advanced disease including abnormal haematology, blood chemistry and coagulopathy, siRNA-treated animals had milder clinical features and fully recovered, while the untreated control animals succumbed to the disease. These results represent the first, to our knowledge, successful demonstration of therapeutic anti-Ebola virus efficacy against the new outbreak strain in nonhuman primates and highlight the rapid development of lipid-nanoparticle-delivered siRNA as a countermeasure against this highly lethal human disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467030/" 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/PMC4467030/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thi, Emily P -- Mire, Chad E -- Lee, Amy C H -- Geisbert, Joan B -- Zhou, Joy Z -- Agans, Krystle N -- Snead, Nicholas M -- Deer, Daniel J -- Barnard, Trisha R -- Fenton, Karla A -- MacLachlan, Ian -- Geisbert, Thomas W -- U19 AI109711/AI/NIAID NIH HHS/ -- U19AI109711/AI/NIAID NIH HHS/ -- England -- Nature. 2015 May 21;521(7552):362-5. doi: 10.1038/nature14442. Epub 2015 Apr 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Tekmira Pharmaceuticals, Burnaby, British Columbia V5J 5J8, Canada. ; 1] Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas 77550, USA [2] Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77550, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25901685" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Disease Models, Animal ; Ebolavirus/classification/*drug effects/*genetics ; Female ; Hemorrhagic Fever, Ebola/pathology/prevention & control/*therapy/*virology ; Humans ; Macaca mulatta/virology ; Male ; Nanoparticles/*administration & dosage ; RNA, Small Interfering/*administration & dosage/pharmacology/*therapeutic use ; Survival Analysis ; Time Factors ; Treatment Outcome ; Viral Load/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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  • 2
    Publication Date: 2011-04-05
    Description: Adult hippocampal neurogenesis is a unique form of neural circuit plasticity that results in the generation of new neurons in the dentate gyrus throughout life. Neurons that arise in adults (adult-born neurons) show heightened synaptic plasticity during their maturation and can account for up to ten per cent of the entire granule cell population. Moreover, levels of adult hippocampal neurogenesis are increased by interventions that are associated with beneficial effects on cognition and mood, such as learning, environmental enrichment, exercise and chronic treatment with antidepressants. Together, these properties of adult neurogenesis indicate that this process could be harnessed to improve hippocampal functions. However, despite a substantial number of studies demonstrating that adult-born neurons are necessary for mediating specific cognitive functions, as well as some of the behavioural effects of antidepressants, it is unknown whether an increase in adult hippocampal neurogenesis is sufficient to improve cognition and mood. Here we show that inducible genetic expansion of the population of adult-born neurons through enhancing their survival improves performance in a specific cognitive task in which two similar contexts need to be distinguished. Mice with increased adult hippocampal neurogenesis show normal object recognition, spatial learning, contextual fear conditioning and extinction learning but are more efficient in differentiating between overlapping contextual representations, which is indicative of enhanced pattern separation. Furthermore, stimulation of adult hippocampal neurogenesis, when combined with an intervention such as voluntary exercise, produces a robust increase in exploratory behaviour. However, increasing adult hippocampal neurogenesis alone does not produce a behavioural response like that induced by anxiolytic agents or antidepressants. Together, our findings suggest that strategies that are designed to increase adult hippocampal neurogenesis specifically, by targeting the cell death of adult-born neurons or by other mechanisms, may have therapeutic potential for reversing impairments in pattern separation and dentate gyrus dysfunction such as those seen during normal ageing.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084370/" 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/PMC3084370/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sahay, Amar -- Scobie, Kimberly N -- Hill, Alexis S -- O'Carroll, Colin M -- Kheirbek, Mazen A -- Burghardt, Nesha S -- Fenton, Andre A -- Dranovsky, Alex -- Hen, Rene -- 1K99MH86615-01/MH/NIMH NIH HHS/ -- K08 MH079088/MH/NIMH NIH HHS/ -- K08 MH079088-01/MH/NIMH NIH HHS/ -- K08 MH079088-02/MH/NIMH NIH HHS/ -- K08 MH079088-03/MH/NIMH NIH HHS/ -- K08 MH079088-03S1/MH/NIMH NIH HHS/ -- K08 MH079088-04/MH/NIMH NIH HHS/ -- K08 MH079088-05/MH/NIMH NIH HHS/ -- K99 MH086615/MH/NIMH NIH HHS/ -- K99 MH086615-02/MH/NIMH NIH HHS/ -- R01 MH068542/MH/NIMH NIH HHS/ -- R01 MH091844/MH/NIMH NIH HHS/ -- R01 MH091844-01/MH/NIMH NIH HHS/ -- R01 MH091844-02/MH/NIMH NIH HHS/ -- R01 MH091844-03/MH/NIMH NIH HHS/ -- T32 HD007430/HD/NICHD NIH HHS/ -- England -- Nature. 2011 Apr 28;472(7344):466-70. doi: 10.1038/nature09817. Epub 2011 Apr 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Columbia University, New York, New York 10032, USA. as2619@columbia.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21460835" target="_blank"〉PubMed〈/a〉
    Keywords: Affect/*physiology ; Aging/drug effects/pathology/*physiology ; Animals ; Antidepressive Agents/pharmacology ; Anxiety/physiopathology/therapy ; Apoptosis/drug effects ; Cell Survival/drug effects ; Cognition/drug effects/*physiology ; Conditioning, Classical/drug effects/physiology ; Dentate Gyrus/cytology/pathology/physiology/physiopathology ; Exploratory Behavior/drug effects/physiology ; Extinction, Psychological/drug effects/physiology ; Fear/physiology/psychology ; Female ; Hippocampus/*cytology/pathology/*physiology/physiopathology ; Learning/drug effects/physiology ; Long-Term Potentiation/drug effects/physiology ; Male ; Memory/drug effects/physiology ; Mice ; Mice, Knockout ; Mice, Transgenic ; *Models, Neurological ; Neural Stem Cells/cytology/drug effects/metabolism ; Neurogenesis/drug effects/*physiology ; Neuronal Plasticity/drug effects/physiology ; Physical Conditioning, Animal/physiology ; Synapses/drug effects/metabolism ; bcl-2-Associated X Protein/deficiency/genetics/metabolism
    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: 2015-04-09
    Description: The family Filoviridae contains three genera, Ebolavirus (EBOV), Marburg virus, and Cuevavirus. Some members of the EBOV genus, including Zaire ebolavirus (ZEBOV), can cause lethal haemorrhagic fever in humans. During 2014 an unprecedented ZEBOV outbreak occurred in West Africa and is still ongoing, resulting in over 10,000 deaths, and causing global concern of uncontrolled disease. To meet this challenge a rapid-acting vaccine is needed. Many vaccine approaches have shown promise in being able to protect nonhuman primates against ZEBOV. In response to the current ZEBOV outbreak several of these vaccines have been fast tracked for human use. However, it is not known whether any of these vaccines can provide protection against the new outbreak Makona strain of ZEBOV. One of these approaches is a first-generation recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing the ZEBOV glycoprotein (GP) (rVSV/ZEBOV). To address safety concerns associated with this vector, we developed two candidate, further-attenuated rVSV/ZEBOV vaccines. Both attenuated vaccines produced an approximately tenfold lower vaccine-associated viraemia compared to the first-generation vaccine and both provided complete, single-dose protection of macaques from lethal challenge with the Makona outbreak strain of ZEBOV.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629916/" 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/PMC4629916/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mire, Chad E -- Matassov, Demetrius -- Geisbert, Joan B -- Latham, Theresa E -- Agans, Krystle N -- Xu, Rong -- Ota-Setlik, Ayuko -- Egan, Michael A -- Fenton, Karla A -- Clarke, David K -- Eldridge, John H -- Geisbert, Thomas W -- R01 AI098817/AI/NIAID NIH HHS/ -- R01AI09881701/AI/NIAID NIH HHS/ -- U19 AI109711/AI/NIAID NIH HHS/ -- England -- Nature. 2015 Apr 30;520(7549):688-91. doi: 10.1038/nature14428. Epub 2015 Apr 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas 77550, USA [2] Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77550, USA. ; Department of Virology and Vaccine Vectors, Profectus BioSciences, Inc., Tarrytown, New York 10591, USA. ; Department of Immunology, Profectus BioSciences, Inc., Tarrytown, New York 10591, USA. ; 1] Department of Virology and Vaccine Vectors, Profectus BioSciences, Inc., Tarrytown, New York 10591, USA [2] Department of Immunology, Profectus BioSciences, Inc., Tarrytown, New York 10591, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25853476" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Western/epidemiology ; Animals ; Antibodies, Viral/immunology ; Democratic Republic of the Congo/epidemiology ; Ebola Vaccines/*administration & dosage/genetics/*immunology ; Ebolavirus/classification/*immunology ; Female ; Genetic Vectors/genetics ; Hemorrhagic Fever, Ebola/immunology/*prevention & control/*virology ; Humans ; Immunoglobulin G/immunology ; Kinetics ; Macaca fascicularis ; Male ; Survival Analysis ; Vaccination ; Vaccines, Attenuated/administration & dosage/genetics/*immunology ; Vesiculovirus/*genetics/growth & development
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2006-08-26
    Description: Analogous to learning and memory storage, long-term potentiation (LTP) is divided into induction and maintenance phases. Testing the hypothesis that the mechanism of LTP maintenance stores information requires reversing this mechanism in vivo and finding out whether long-term stored information is lost. This was not previously possible. Recently however, persistent phosphorylation by the atypical protein kinase C isoform, protein kinase Mzeta (PKMz), has been found to maintain late LTP in hippocampal slices. Here we show that a cell-permeable PKMz inhibitor, injected in the rat hippocampus, both reverses LTP maintenance in vivo and produces persistent loss of 1-day-old spatial information. Thus, the mechanism maintaining LTP sustains spatial memory.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pastalkova, Eva -- Serrano, Peter -- Pinkhasova, Deana -- Wallace, Emma -- Fenton, Andre Antonio -- Sacktor, Todd Charlton -- MH57068/MH/NIMH NIH HHS/ -- R01 MH53576/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2006 Aug 25;313(5790):1141-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Physiology, Pharmacology, and Neurology, Robert F. Furchgott Center for Neural and Behavioral Science, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16931766" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Avoidance Learning ; Conditioning (Psychology) ; Dentate Gyrus/drug effects/physiology ; Electric Stimulation ; Excitatory Postsynaptic Potentials/drug effects ; Heat-Shock Proteins/administration & dosage/pharmacology ; Hippocampus/drug effects/*physiology ; Long-Term Potentiation/drug effects/*physiology ; Male ; Memory/drug effects/*physiology ; Perforant Pathway ; Protein Kinase C/antagonists & inhibitors/metabolism ; Rats ; Rats, Long-Evans ; Staurosporine/pharmacology ; Time Factors
    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
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-02-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fenton, Andre A -- New York, N.Y. -- Science. 2007 Feb 16;315(5814):947-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Pharmacology, Robert F. Furchgott Center for Neural and Behavioral Science, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA. afenton@downstate.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17303741" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dentate Gyrus/physiology ; Hippocampus/*physiology ; Humans ; Neurons/physiology ; Orientation/*physiology ; Rats ; Space Perception/*physiology
    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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  • 6
    Publication Date: 2010-03-20
    Description: The onset of puberty defines a developmental stage when some learning processes are diminished, but the mechanism for this deficit remains unknown. We found that, at puberty, expression of inhibitory alpha4betadelta gamma-aminobutyric acid type A (GABAA) receptors (GABAR) increases perisynaptic to excitatory synapses in CA1 hippocampus. Shunting inhibition via these receptors reduced N-methyl-D-aspartate receptor activation, impairing induction of long-term potentiation (LTP). Pubertal mice also failed to learn a hippocampal, LTP-dependent spatial task that was easily acquired by delta-/- mice. However, the stress steroid THP (3alphaOH-5alpha[beta]-pregnan-20-one), which reduces tonic inhibition at puberty, facilitated learning. Thus, the emergence of alpha4betadelta GABARs at puberty impairs learning, an effect that can be reversed by a stress steroid.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2887350/" 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/PMC2887350/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shen, Hui -- Sabaliauskas, Nicole -- Sherpa, Ang -- Fenton, Andre A -- Stelzer, Armin -- Aoki, Chiye -- Smith, Sheryl S -- AA12958/AA/NIAAA NIH HHS/ -- DA09618/DA/NIDA NIH HHS/ -- R01 AA012958/AA/NIAAA NIH HHS/ -- R01 AA012958-08/AA/NIAAA NIH HHS/ -- R01 AA012958-09/AA/NIAAA NIH HHS/ -- R01 DA009618/DA/NIDA NIH HHS/ -- R01 DA009618-13/DA/NIDA NIH HHS/ -- R01 DA009618-14/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 2010 Mar 19;327(5972):1515-8. doi: 10.1126/science.1184245.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Pharmacology, State University of New York (SUNY) Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20299596" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CA1 Region, Hippocampal/cytology/*metabolism ; Dendrites ; Dendritic Spines/metabolism ; Excitatory Postsynaptic Potentials ; Female ; GABA-A Receptor Antagonists ; *Learning/drug effects ; *Long-Term Potentiation ; Mice ; Mice, Inbred C57BL ; N-Methylaspartate/metabolism ; Neural Inhibition ; Patch-Clamp Techniques ; Pregnanolone/pharmacology ; Pyramidal Cells/metabolism ; Receptors, GABA-A/*metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; *Sexual Maturation ; Spatial Behavior
    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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  • 7
    Publication Date: 2015-09-05
    Description: Infectious diseases often emerge from interactions among multiple species and across nested levels of biological organization. Threats as diverse as Ebola virus, human malaria, and bat white-nose syndrome illustrate the need for a mechanistic understanding of the ecological interactions underlying emerging infections. We describe how recent advances in community ecology can be adopted to address contemporary challenges in disease research. These analytical tools can identify the factors governing complex assemblages of multiple hosts, parasites, and vectors, and reveal how processes link across scales from individual hosts to regions. They can also determine the drivers of heterogeneities among individuals, species, and regions to aid targeting of control strategies. We provide examples where these principles have enhanced disease management and illustrate how they can be further extended.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, Pieter T J -- de Roode, Jacobus C -- Fenton, Andy -- R01GM109499/GM/NIGMS NIH HHS/ -- R01GM109501/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Sep 4;349(6252):1259504. doi: 10.1126/science.1259504.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ecology and Evolutionary Biology, University of Colorado, Boulder, CO 80309, USA. pieter.johnson@colorado.edu. ; Department of Biology, Emory University, Atlanta, GA 30322, USA. ; Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26339035" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biota ; Communicable Disease Control/*methods ; Communicable Diseases/*drug therapy/*epidemiology ; *Host-Parasite Interactions ; Humans ; Symbiosis
    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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  • 8
    Publication Date: 1984-06-08
    Description: Most mitochondrial proteins are encoded in the nucleus and are translated on free cytoplasmic ribosomes as larger precursors containing amino-terminal "leader" sequences, which are removed after the precursors are taken up by mitochondria. We have deduced the complete primary structure of the precursor of a human mitochondrial matrix enzyme, ornithine transcarbamylase (OTC), from the nucleotide sequence of cloned complementary DNA. The amino-terminal leader peptide of OTC is 32 amino acids in length and contains four arginines but no acidic residues. Cleavage of the leader peptide from the "mature" protein occurs between glutamine and asparagine residues. The sequence of mature human OTC resembles that of the subunits of both OTC and aspartate transcarbamylase from Escherichia coli. The biological activity of the cloned OTC complementary DNA was tested by joining it with SV40 (an animal virus) regulatory elements and transfecting cultured HeLa cells, which do not normally express OTC. Both the precursor and mature forms of the OTC subunit were identified; in stable transformants, enzymatic activity was also detected.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Horwich, A L -- Fenton, W A -- Williams, K R -- Kalousek, F -- Kraus, J P -- Doolittle, R F -- Konigsberg, W -- Rosenberg, L E -- AM 09527/AM/NIADDK NIH HHS/ -- AM 12579/AM/NIADDK NIH HHS/ -- GM 31539/GM/NIGMS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1984 Jun 8;224(4653):1068-74.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6372096" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Cloning, Molecular ; DNA/genetics ; DNA, Mitochondrial/*genetics ; DNA, Recombinant/metabolism ; Escherichia coli/enzymology ; HeLa Cells/metabolism ; Humans ; Mitochondria/enzymology ; Ornithine Carbamoyltransferase/*genetics ; Protein Biosynthesis ; Rats
    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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