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  • 1
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    Association between mRNA expression and phenotype [Genetics] (2015)
    National Academy of Sciences
    Details
    Publication Date: 2015-04-15
    Description: High-throughput gene expression profiling has revealed substantial leaky and extraneous transcription of eukaryotic genes, challenging the perceptions that transcription is strictly regulated and that changes in transcription have phenotypic consequences. To assess the functional implications of mRNA transcription directly, we analyzed mRNA expression data derived from microarrays, RNA-sequencing, and in...
    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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  • 2
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    Asymptotic patterns of a reaction-diffusion equation with nonlinear-nonlocal functional response (2013)
    Oxford University Press
    Details
    Publication Date: 2013-01-18
    Description: A reaction–diffusion system with nonlinear–nonlocal functional response is considered in this article. We develop the finite delays approximation method combining with the spreading speed and travelling wavefronts theory for semi-flow to discuss the existence of spreading speed c * and travelling wavefronts without the differentiability assumption on the reaction function f . The asymptotic patterns and threshold property for the solutions of the considered system are described clearly according to the threshold parameter c * which is exactly the minimal wave speed as well. Finally, we give an estimate of the spreading speed and minimal wave speed c *.
    Print ISSN: 0272-4960
    Electronic ISSN: 1464-3634
    Topics: Mathematics
    Published by Oxford University Press
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  • 3
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    Bacillus subtilis genome editing using ssDNA with short homology regions (2012)
    Oxford University Press
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    Publication Date: 2012-06-28
    Description: In this study, we developed a simple and efficient Bacillus subtilis genome editing method in which targeted gene(s) could be inactivated by single-stranded PCR product(s) flanked by short homology regions and in-frame deletion could be achieved by incubating the transformants at 42°C. In this process, homologous recombination (HR) was promoted by the lambda beta protein synthesized under the control of promoter P RM in the lambda cI857 P RM –P R promoter system on a temperature sensitive plasmid pWY121. Promoter P R drove the expression of the recombinase gene cre at 42°C for excising the floxed ( lox sites flanked) disruption cassette that contained a bleomycin resistance marker and a heat inducible counter-selectable marker ( hewl , encoding hen egg white lysozyme). Then, we amplified the single-stranded disruption cassette using the primers that carried 70 nt homology extensions corresponding to the regions flanking the target gene. By transforming the respective PCR products into the B. subtilis that harbored pWY121 and incubating the resultant mutants at 42°C, we knocked out multiple genes in the same genetic background with no marker left. This process is simple and efficient and can be widely applied to large-scale genome analysis of recalcitrant Bacillus species.
    Keywords: Targeted inhibition of gene function
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    Oxidation of NADPH on Kv{beta}1 inhibits ball-and-chain type inactivation by restraining the chain [Physiology] (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-04-06
    Description: The Kv1 family voltage-dependent K+ channels assemble with cytosolic β subunits (Kvβ), which are composed of a flexible N terminus followed by a structured core domain. The N terminus of certain Kvβs inactivates the channel by blocking the ion conduction pore, and the core domain is a functional enzyme that uses NADPH as a cofactor. Oxidation of the Kvβ-bound NADPH inhibits inactivation and potentiates channel current, but the mechanism behind this effect is unknown. Here we show that after oxidation, the core domain binds to part of the N terminus, thus restraining it from blocking the channel. The interaction is partially mediated by two negatively charged residues on the core domain and three positively charged ones on the N terminus. These results provide a molecular basis for the coupling between the cellular redox state and channel activity, and establish Kvβ as a target for pharmacological control of Kv1 channels.
    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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  • 5
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    Catalysis under the graphene cover [Chemistry] (2014)
    National Academy of Sciences
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    Publication Date: 2014-12-03
    Description: Graphitic overlayers on metals have commonly been considered as inhibitors for surface reactions due to their chemical inertness and physical blockage of surface active sites. In this work, however, we find that surface reactions, for instance, CO adsorption/desorption and CO oxidation, can take place on Pt(111) surface covered by monolayer...
    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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  • 6
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    Asymptotic stability of diffusive predator-prey model with modified Leslie-Gower and Holling-type II schemes and nonlocal time delays (2014)
    Oxford University Press
    Details
    Publication Date: 2014-03-18
    Description: A diffusive predator–prey model with nonlocal time delays is considered in the present paper. We establish the nonexistence of nonconstant steady states by the use of the auxiliary functions. We also study the convergence of the solution by using the method of upper and lower solutions. The sufficient conditions we obtained are simple and easily verifiable.
    Print ISSN: 0265-0754
    Electronic ISSN: 1471-6887
    Topics: Mathematics
    Published by Oxford University Press
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  • 7
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    Arginine methylation of hnRNPK negatively modulates apoptosis upon DNA damage through local regulation of phosphorylation (2014)
    Oxford University Press
    Details
    Publication Date: 2014-09-02
    Description: Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is an RNA/DNA-binding protein involved in chromatin remodeling, RNA processing and the DNA damage response. In addition, increased hnRNPK expression has been associated with tumor development and progression. A variety of post-translational modifications of hnRNPK have been identified and shown to regulate hnRNPK function, including phosphorylation, ubiquitination, sumoylation and methylation. However, the functional significance of hnRNPK arginine methylation remains unclear. In the present study, we demonstrated that the methylation of two essential arginines, Arg296 and Arg299, on hnRNPK inhibited a nearby Ser302 phosphorylation that was mediated through the pro-apoptotic kinase PKC. Notably, the engineered U2OS cells carrying an Arg296/Arg299 methylation-defective hnRNPK mutant exhibited increased apoptosis upon DNA damage. While such elevated apoptosis can be diminished through addition with wild-type hnRNPK, we further demonstrated that this increased apoptosis occurred through both intrinsic and extrinsic pathways and was p53 independent, at least in part. Here, we provide the first evidence that the arginine methylation of hnRNPK negatively regulates cell apoptosis through PKC-mediated signaling during DNA damage, which is essential for the anti-apoptotic role of hnRNPK in apoptosis and the evasion of apoptosis in cancer cells.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 8
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    Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-03-28
    Description: P-glycoprotein (P-gp) detoxifies cells by exporting hundreds of chemically unrelated toxins but has been implicated in multidrug resistance (MDR) in the treatment of cancers. Substrate promiscuity is a hallmark of P-gp activity, thus a structural description of poly-specific drug-binding is important for the rational design of anticancer drugs and MDR inhibitors. The x-ray structure of apo P-gp at 3.8 angstroms reveals an internal cavity of approximately 6000 angstroms cubed with a 30 angstrom separation of the two nucleotide-binding domains. Two additional P-gp structures with cyclic peptide inhibitors demonstrate distinct drug-binding sites in the internal cavity capable of stereoselectivity that is based on hydrophobic and aromatic interactions. Apo and drug-bound P-gp structures have portals open to the cytoplasm and the inner leaflet of the lipid bilayer for drug entry. The inward-facing conformation represents an initial stage of the transport cycle that is competent for drug binding.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720052/" 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/PMC2720052/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aller, Stephen G -- Yu, Jodie -- Ward, Andrew -- Weng, Yue -- Chittaboina, Srinivas -- Zhuo, Rupeng -- Harrell, Patina M -- Trinh, Yenphuong T -- Zhang, Qinghai -- Urbatsch, Ina L -- Chang, Geoffrey -- F32 GM078914/GM/NIGMS NIH HHS/ -- F32 GM078914-03/GM/NIGMS NIH HHS/ -- GM073197/GM/NIGMS NIH HHS/ -- GM078914/GM/NIGMS NIH HHS/ -- GM61905/GM/NIGMS NIH HHS/ -- P50 GM073197/GM/NIGMS NIH HHS/ -- P50 GM073197-050002/GM/NIGMS NIH HHS/ -- R01 GM061905/GM/NIGMS NIH HHS/ -- R01 GM061905-09/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Mar 27;323(5922):1718-22. doi: 10.1126/science.1168750.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Scripps Research Institute, 10550 North Torrey Pines Road, CB105, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19325113" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Animals ; Apoproteins/chemistry/metabolism ; Binding Sites ; Cell Membrane/chemistry ; Crystallography, X-Ray ; Hydrophobic and Hydrophilic Interactions ; Lipid Bilayers/chemistry ; Mice ; Models, Molecular ; Molecular Sequence Data ; P-Glycoprotein/antagonists & inhibitors/*chemistry/*metabolism ; Peptides, Cyclic/*chemistry/*metabolism ; Protein Binding ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Stereoisomerism ; Verapamil/metabolism/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 9
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    Continuous doping of a cuprate surface: Insights from in situ angle-resolved photoemission (2018)
    American Physical Society (APS)
    Details
    Publication Date: 2018-10-25
    Description: Author(s): Y.-G. Zhong, J.-Y. Guan, X. Shi, J. Zhao, Z.-C. Rao, C.-Y. Tang, H.-J. Liu, Z. Y. Weng, Z. Q. Wang, G. D. Gu, T. Qian, Y.-J. Sun, and H. Ding We report a technique of a continuously doped surface of Bi 2 Sr 2 CaCu 2 O 8 + x through ozone/vacuum annealing and a systematic measurement over the nearly whole superconducting dome on the same sample surface by in situ angle-resolved photoemission spectroscopy. We find that the quasiparticle weight on th... [Phys. Rev. B 98, 140507(R)] Published Wed Oct 24, 2018
    Keywords: Superfluidity and superconductivity
    Print ISSN: 1098-0121
    Electronic ISSN: 1095-3795
    Topics: Physics
    Published by American Physical Society (APS)
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  • 10
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    X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-01-21
    Description: General anaesthetics have enjoyed long and widespread use but their molecular mechanism of action remains poorly understood. There is good evidence that their principal targets are pentameric ligand-gated ion channels (pLGICs) such as inhibitory GABA(A) (gamma-aminobutyric acid) receptors and excitatory nicotinic acetylcholine receptors, which are respectively potentiated and inhibited by general anaesthetics. The bacterial homologue from Gloeobacter violaceus (GLIC), whose X-ray structure was recently solved, is also sensitive to clinical concentrations of general anaesthetics. Here we describe the crystal structures of the complexes propofol/GLIC and desflurane/GLIC. These reveal a common general-anaesthetic binding site, which pre-exists in the apo-structure in the upper part of the transmembrane domain of each protomer. Both molecules establish van der Waals interactions with the protein; propofol binds at the entrance of the cavity whereas the smaller, more flexible, desflurane binds deeper inside. Mutations of some amino acids lining the binding site profoundly alter the ionic response of GLIC to protons, and affect its general-anaesthetic pharmacology. Molecular dynamics simulations, performed on the wild type (WT) and two GLIC mutants, highlight differences in mobility of propofol in its binding site and help to explain these effects. These data provide a novel structural framework for the design of general anaesthetics and of allosteric modulators of brain pLGICs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nury, Hugues -- Van Renterghem, Catherine -- Weng, Yun -- Tran, Alphonso -- Baaden, Marc -- Dufresne, Virginie -- Changeux, Jean-Pierre -- Sonner, James M -- Delarue, Marc -- Corringer, Pierre-Jean -- R01 GM069379/GM/NIGMS NIH HHS/ -- England -- Nature. 2011 Jan 20;469(7330):428-31. doi: 10.1038/nature09647.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut Pasteur, Groupe Recepteurs-Canaux, F-75015 Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21248852" target="_blank"〉PubMed〈/a〉
    Keywords: Anesthetics, General/*chemistry/*metabolism ; Binding Sites/genetics ; Crystallography, X-Ray ; Cyanobacteria/*chemistry ; Electrophysiological Phenomena ; Isoflurane/*analogs & derivatives/chemistry/metabolism ; Ligand-Gated Ion Channels/*chemistry/genetics/*metabolism ; Ligands ; Models, Molecular ; Molecular Dynamics Simulation ; Mutant Proteins/chemistry/genetics/metabolism ; Propofol/*chemistry/metabolism ; Protein Binding ; Protein Structure, Tertiary ; Protons
    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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