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  • 1
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    The catalytic cycle for ribonucleotide incorporation by human DNA Pol {lambda} (2012)
    Oxford University Press
    Details
    Publication Date: 2012-08-23
    Description: Although most DNA polymerases discriminate against ribonucleotide triphosphaets (rNTPs) during DNA synthesis, recent studies have shown that large numbers of ribonucleotides are incorporated into the eukaryotic nuclear genome. Here, we investigate how a DNA polymerase can stably incorporate an rNTP. The X-ray crystal structure of a variant of human DNA polymerase reveals that the rNTP occupies the nucleotide binding pocket without distortion of the active site, despite an unfavorable interaction between the 2'-O and Tyr505 backbone carbonyl. This indicates an energetically unstable binding state for the rNTP, stabilized by additional protein–nucleotide interactions. Supporting this idea is the 200-fold lower catalytic efficiency for rNTP relative to deoxyribonucleotide triphosphate (dNTP) incorporation, reflecting a higher apparent Km value for the rNTP. Furthermore, distortion observed in the structure of the post-catalytic product complex suggests that once the bond between the α- and β-phosphates of the rNTP is broken, the unfavorable binding state of the ribonucleotide cannot be maintained. Finally, structural and biochemical evaluation of dNTP insertion onto an ribonucleotide monophosphate (rNMP)-terminated primer indicates that a primer-terminal rNMP does not impede extension. The results are relevant to how ribonucleotides are incorporated into DNA in vivo , during replication and during repair, perhaps especially in non-proliferating cells when rNTP:dNTP ratios are high.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    BvgA regulation of the B. pertussis fim3 promoter [Biochemistry] (2015)
    National Academy of Sciences
    Details
    Publication Date: 2015-02-11
    Description: Two-component systems [sensor kinase/response regulator (RR)] are major tools used by microorganisms to adapt to environmental conditions. RR phosphorylation is typically required for gene activation, but few studies have addressed how and if phosphorylation affects specific steps during transcription initiation. We characterized transcription complexes made with RNA polymerase and the...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 3
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    TAZ couples Hippo/Wnt signalling and insulin sensitivity through Irs1 expression (2019)
    Springer Nature
    Details
    Publication Date: 2019
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 4
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    Estimation of swine movement network at farm level in the US from the Census of Agriculture data (2019)
    Springer Nature
    Details
    Publication Date: 2019
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
    Published by Springer Nature
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  • 5
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    Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-09-03
    Description: The efficacy and safety of biological molecules in cancer therapy, such as peptides and small interfering RNAs (siRNAs), could be markedly increased if high concentrations could be achieved and amplified selectively in tumour tissues versus normal tissues after intravenous administration. This has not been achievable so far in humans. We hypothesized that a poxvirus, which evolved for blood-borne systemic spread in mammals, could be engineered for cancer-selective replication and used as a vehicle for the intravenous delivery and expression of transgenes in tumours. JX-594 is an oncolytic poxvirus engineered for replication, transgene expression and amplification in cancer cells harbouring activation of the epidermal growth factor receptor (EGFR)/Ras pathway, followed by cell lysis and anticancer immunity. Here we show in a clinical trial that JX-594 selectively infects, replicates and expresses transgene products in cancer tissue after intravenous infusion, in a dose-related fashion. Normal tissues were not affected clinically. This platform technology opens up the possibility of multifunctional products that selectively express high concentrations of several complementary therapeutic and imaging molecules in metastatic solid tumours in humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Breitbach, Caroline J -- Burke, James -- Jonker, Derek -- Stephenson, Joe -- Haas, Andrew R -- Chow, Laura Q M -- Nieva, Jorge -- Hwang, Tae-Ho -- Moon, Anne -- Patt, Richard -- Pelusio, Adina -- Le Boeuf, Fabrice -- Burns, Joe -- Evgin, Laura -- De Silva, Naomi -- Cvancic, Sara -- Robertson, Terri -- Je, Ji-Eun -- Lee, Yeon-Sook -- Parato, Kelley -- Diallo, Jean-Simon -- Fenster, Aaron -- Daneshmand, Manijeh -- Bell, John C -- Kirn, David H -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2011 Aug 31;477(7362):99-102. doi: 10.1038/nature10358.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Jennerex Inc., 450 Sansome Street, 16th floor, San Francisco, California 94111, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21886163" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; Aged, 80 and over ; DNA, Viral/blood ; Female ; Gene Expression Regulation, Enzymologic ; Humans ; Infusions, Intravenous ; Male ; Middle Aged ; Neoplasms/pathology/surgery/*therapy/virology ; *Oncolytic Virotherapy ; Oncolytic Viruses/*physiology ; Organisms, Genetically Modified/physiology ; Poxviridae/*physiology ; Transgenes/genetics ; beta-Galactosidase/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)
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  • 6
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    Elimination of established tumors with nanodisc-based combination chemoimmunotherapy (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018-04-19
    Description: Although immune checkpoint blockade has shown initial success for various cancers, only a small subset of patients benefits from this therapy. Some chemotherapeutic drugs have been reported to induce antitumor T cell responses, prompting a number of clinical trials on combination chemoimmunotherapy. However, how to achieve potent immune activation with traditional chemotherapeutics in a manner that is safe, effective, and compatible with immunotherapy remains unclear. We show that high-density lipoprotein–mimicking nanodiscs loaded with doxorubicin (DOX), a widely used chemotherapeutic agent, can potentiate immune checkpoint blockade in murine tumor models. Delivery of DOX via nanodiscs triggered immunogenic cell death of cancer cells and exerted antitumor efficacy without any overt off-target side effects. "Priming" tumors with DOX-carrying nanodiscs elicited robust antitumor CD8 + T cell responses while broadening their epitope recognition to tumor-associated antigens, neoantigens, and intact whole tumor cells. Combination chemoimmunotherapy with nanodiscs plus anti–programmed death 1 therapy induced complete regression of established CT26 and MC38 colon carcinoma tumors in 80 to 88% of animals and protected survivors against tumor recurrence. Our work provides a new, generalizable framework for using nanoparticle-based chemotherapy to initiate antitumor immunity and sensitize tumors to immune checkpoint blockade.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 7
    Electronic Resource
    Electronic Resource
    Study of a laser-heated electron gun (1996)
    [S.l.] : American Institute of Physics (AIP)
    Review of Scientific Instruments 67 (1996), S. 4098-4102 
    Details
    ISSN: 1089-7623
    Source: AIP Digital Archive
    Topics: Physics , Electrical Engineering, Measurement and Control Technology
    Notes: A method of cathode heating using a laser was studied for an electron gun. In order to observe the practicality of the heating system, the characteristics of the laser-heated gun with a dispenser and LaB6 thermionic cathodes have been experimentally investigated. The direct laser irradiation is so efficient that the gun is equipped without heat shielding, a cooling system, or an electrical circuit in the gun chamber for cathode heating. Modeling, based on the experimental data, indicates that the cathode temperature is proportional to one-fourth power of the laser power and that laser power loss and conduction loss of heat in the gun assembly are negligible. An electron beam current density 0.48 A/cm2 was measured with 26 W laser power for a dispenser cathode of 0.06 cm2 emission area. Current density 0.16 A/cm2 with 25 W was recorded for a LaB6 cathode of area 0.12 cm2. Electron beam emittance has been measured by using the typical pepper-pot technique. It was observed that the growth of electron beam emittance was very small in the laser heating. © 1996 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.1147577
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  • 8
    Electronic Resource
    Electronic Resource
    Electron irradiation-induced changes in the surface topography of silicon dioxide (1996)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 80 (1996), S. 4308-4314 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The irradiation of crystalline (α-SiO2) and amorphous (a-SiO2) silicon dioxide with a stationary electron beam produces characteristic changes in the surface topography. The development of these changes has been investigated using cathodoluminescence spectroscopy and microscopy, scanning probe (atomic force) microscopy, and scanning electron microscopy. Electron irradiation produces a permanent volume increase on (crystalline) α-SiO2, while in (amorphous) a-SiO2 an initial small volume increase is followed by volume loss as irradiation continues. The observed changes are consistent with electromigration of oxygen under the influence of the electric field induced by charge trapping at preexisting or irradiation-induced defects. Oxygen enrichment may produce expansion of the surface region due to the formation of peroxy linkage defects. In a-SiO2, charges trapped by defects at grain boundaries produce enhanced electric fields which may result in volume reduction at the surface, when critical field strengths are exceeded. The observed volume reductions may be attributed to electron stimulated desorption of constituents, in particular oxygen mass loss, and densification of the surface region associated with the formation of oxygen-deficient defect centers. © 1996 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.363379
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  • 9
    Electronic Resource
    Electronic Resource
    Thermodynamic Data from Fluorescence Spectra. I. The System Phenol-Acetate1 (1965)
    s.l. : American Chemical Society
    The @journal of physical chemistry 〈Washington, DC〉 69 (1965), S. 2960-2966 
    Details
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/j100893a022
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  • 10
    Electronic Resource
    Electronic Resource
    Activity of sodium nitrate in molten cadmium chloride-sodium nitrate mixtures (1969)
    s.l. : American Chemical Society
    Journal of chemical & engineering data 14 (1969), S. 318-322 
    Details
    ISSN: 1520-5134
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/je60042a015
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