GLORIA

GEOMAR Library Ocean Research Information Access

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
  • 1
    facet.materialart.
    Unknown
    Caspase-8 controls the gut response to microbial challenges by Tnf-{alpha}-dependent and independent pathways (2015)
    BMJ Publishing Group
    In: Gut
    Details
    Publication Date: 2015-03-07
    Description: Objectives Intestinal epithelial cells (IEC) express toll-like receptors (TLR) that facilitate microbial recognition. Stimulation of TLR ligands induces a transient increase in epithelial cell shedding, a mechanism that serves the antibacterial and antiviral host defence of the epithelium and promotes elimination of intracellular pathogens. Although activation of the extrinsic apoptosis pathway has been described during inflammatory shedding, its functional involvement is currently unclear. Design We investigated the functional involvement of caspase-8 signalling in microbial-induced intestinal cell shedding by injecting Lipopolysaccharide (LPS) to mimic bacterial pathogens and poly(I:C) as a probe for RNA viruses in vivo. Results TLR stimulation of IEC was associated with a rapid activation of caspase-8 and increased epithelial cell shedding. In mice with an epithelial cell-specific deletion of caspase-8 TLR stimulation caused Rip3-dependent epithelial necroptosis instead of apoptosis. Mortality and tissue damage were more severe in mice in which IECs died by necroptosis than apoptosis. Inhibition of receptor-interacting protein (Rip) kinases rescued the epithelium from TLR-induced gut damage. TLR3-induced necroptosis was directly mediated via TRIF-dependent pathways, independent of Tnf-α and type III interferons, whereas TLR4-induced tissue damage was critically dependent on Tnf-α. Conclusions Together, our data demonstrate an essential role for caspase-8 in maintaining the gut barrier in response to mucosal pathogens by permitting inflammatory shedding and preventing necroptosis of infected cells. These data suggest that therapeutic strategies targeting the cell death machinery represent a promising new option for the treatment of inflammatory and infective enteropathies.
    Keywords: Open access
    Print ISSN: 0017-5749
    Electronic ISSN: 1468-3288
    Topics: Medicine
    Published by BMJ Publishing Group
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 2
    facet.materialart.
    Unknown
    Discovery of Itraconazole with Broad-Spectrum In Vitro Antienterovirus Activity That Targets Nonstructural Protein 3A [Antiviral Agents] (2015)
    The American Society for Microbiology (ASM)
    Details
    Publication Date: 2015-04-11
    Description: There is currently no approved antiviral therapy for the prophylaxis or treatment of enterovirus infections, which remain a substantial threat to public health. To discover inhibitors that can be immediately repurposed for treatment of enterovirus infections, we developed a high-throughput screening assay that measures the cytopathic effect induced by enterovirus 71 (EV71) to screen an FDA-approved drug library. Itraconazole (ITZ), a triazole antifungal agent, was identified as an effective inhibitor of EV71 replication in the low-micromolar range (50% effective concentrations [EC 50 s], 1.15 μM). Besides EV71, the compound also inhibited other enteroviruses, including coxsackievirus A16, coxsackievirus B3, poliovirus 1, and enterovirus 68. Study of the mechanism of action by time-of-addition assay and transient-replicon assay revealed that ITZ targeted a step involved in RNA replication or polyprotein processing. We found that the mutations (G5213U and U5286C) conferring the resistance to the compound were in nonstructural protein 3A, and we confirmed the target amino acid substitutions (3A V51L and 3A V75A) using a reverse genetic approach. Interestingly, posaconazole, a new oral azole with a molecular structure similar to that of ITZ, also exhibited anti-EV71 activity. Moreover, ITZ-resistant viruses do not exhibit cross-resistance to posaconazole or the enviroxime-like compound GW5074, which also targets the 3A region, indicating that they may target a specific site(s) in viral genome. Although the protective activity of ITZ or posaconazole (alone or in combination with other antivirals) remains to be assessed in animal models, our findings may represent an opportunity to develop therapeutic interventions for enterovirus infection.
    Print ISSN: 0066-4804
    Electronic ISSN: 1098-6596
    Topics: Biology , Medicine
    Published by The American Society for Microbiology (ASM)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 3
    facet.materialart.
    Unknown
    PGAM5-mediated programmed necrosis of hepatocytes drives acute liver injury (2017)
    BMJ Publishing Group
    In: Gut
    Details
    Publication Date: 2017-03-12
    Description: Objectives Autoimmune hepatitis (AIH) is a severe necroinflammatory liver disease associated with significant mortality. Although loss of hepatocytes is generally recognised as a key trigger of liver inflammation and liver failure, the regulation of hepatic cell death causing AIH remains poorly understood. The aim of this study was to identify molecular mechanisms that drive hepatocyte cell death in the pathogenesis of acute liver injury. Design Acute liver injury was modelled in mice by intravenous administration of concanavalin A (ConA). Liver injury was demonstrated by serum transaminases and histological assessment of liver sections. PGAM5-deficient mice (PGAM5–/–) were used to determine its role in experimental hepatitis. Mdivi-1 was used as an inhibitor of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission. Mitochondrial fission and the expression of PGAM5 were compared between liver biopsies derived from patients with AIH and control patients. Results PGAM5 was highly expressed in hepatocytes of patients with AIH and in mice with ConA-induced experimental hepatitis. Deficiency of PGAM5 protected mice from ConA-induced hepatocellular death and liver injury. PGAM5 regulated ConA-induced mitochondrial fission in hepatocytes. Administration of the Drp1-inhibitor Mdivi-1 blocked mitochondrial fission, diminished hepatocyte cell death and attenuated liver tissue damage induced by ConA. Conclusions Our data demonstrate for the first time that PGAM5 plays an indispensable role in the pathogenesis of ConA-induced liver injury. Downstream of PGAM5, Drp1-mediated mitochondrial fission is an obligatory step that drives the execution of hepatic necrosis and tissue damage. Our data highlight the PGAM5-Drp1 axis as a potential therapeutic target for acute immune-mediated liver injury.
    Keywords: Hepatitis other
    Print ISSN: 0017-5749
    Electronic ISSN: 1468-3288
    Topics: Medicine
    Published by BMJ Publishing Group
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 4
    facet.materialart.
    Unknown
    Small-Molecule Inhibitors Targeting Protein SUMOylation as Novel Anticancer Compounds [Minireview] (2018)
    The American Society for Pharmacology and Experimental Therapeutics (ASPET)
    Details
    Publication Date: 2018-06-27
    Description: SUMOylation, one of post-translational modifications, is covalently modified on lysine residues of a target protein through an enzymatic cascade reaction similar to protein ubiquitination. Along with identification of many SUMOylated proteins, protein SUMOylation has been proven to regulate multiple biologic activities including transcription, cell cycle, DNA repair, and innate immunity. The dysregulation of protein SUMOylation and deSUMOylation modification is linked with carcinogenesis and tumor progression. The SUMOylation-associated enzymes are usually elevated in various cancers, which function as cancer biomarkers to relate to poor outcomes for patients. Considering the significance of protein SUMOylation in regulating diverse biologic functions in cancer progression, numerous small-molecule inhibitors targeting protein SUMOylation pathway are developed as potentially clinical anticancer therapeutics. Here, we systematically summarize the latest progresses of associations of small ubiquitin-like modifier (SUMO) enzymes with cancers and small-molecular inhibitors against human cancers by targeting SUMOylation enzymes. We also compared the pros and cons of several special anticancer inhibitors targeting SUMO pathway. As more efforts are invested in this field, small-molecule inhibitors targeting the SUMOylation modification pathway are promising for development into novel anticancer drugs.
    Print ISSN: 0026-895X
    Electronic ISSN: 1521-0111
    Topics: Chemistry and Pharmacology , Medicine
    Published by The American Society for Pharmacology and Experimental Therapeutics (ASPET)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 5
    facet.materialart.
    Unknown
    New high-spin structure and possible chirality in $^{109}\mathrm{In}$ (2018)
    American Physical Society (APS)
    Details
    Publication Date: 2018-07-06
    Description: Author(s): M. Wang, Y. Y. Wang, L. H. Zhu, B. H. Sun, G. L. Zhang, L. C. He, W. W. Qu, F. Wang, T. F. Wang, Y. Y. Chen, C. Xiong, J. Zhang, J. M. Zhang, Y. Zheng, C. Y. He, G. S. Li, J. L. Wang, X. G. Wu, S. H. Yao, C. B. Li, H. W. Li, S. P. Hu, and J. J. Liu The high-spin structure of In 109 has been investigated with the Mo 100 ( N 14 , 5 n ) In 109 reaction at a beam energy of 78 MeV using the in-beam γ spectroscopic method. The level scheme of In 109 has been modified considerably and extended by 46 new γ rays to the highest excited state at 8.980 MeV and J π = ( 4... [Phys. Rev. C 98, 014304] Published Thu Jul 05, 2018
    Keywords: Nuclear Structure
    Print ISSN: 0556-2813
    Electronic ISSN: 1089-490X
    Topics: Physics
    Published by American Physical Society (APS)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 6
    facet.materialart.
    Unknown
    Particle identification for a future EIC detector (2018)
    Institute of Physics Publishing (IOP)
    Details
    Publication Date: 2018-03-13
    Description: In its latest Long Range Plan for Nuclear Science Research in the U.S., the Nuclear Science Advisory Committee to the Department of Energy recommended that in regards to new nuclear-physics facilities, the construction of an Electron Ion Collider (EIC) be of the highest priority after the completion of the Facility for Rare Isotope Beams. In order to carry out key aspects of the scientific program of the EIC, the EIC central detector must be capable of hadron particle identification (PID) over a broad momentum range of up to 50 GeV/ c . The goal of the EIC-PID consortium is to develop an integrated program for PID at EIC, which employs several different technologies for imaging Cherenkov detectors. Here we discuss the conceptual designs and the expected PID performance of two of these detectors, as well as the newest results of gain evaluation studies of photon sensors that are good candidates to read out these detectors. Development of a gas-ae...
    Electronic ISSN: 1748-0221
    Topics: Physics
    Published by Institute of Physics Publishing (IOP)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 7
    facet.materialart.
    Unknown
    A helical perylene diimide-based acceptor for non-fullerene organic solar cells: synthesis, morphology and exciton dynamics (2018)
    Royal Society
    Details
    Publication Date: 2018-05-03
    Description: Helical perylene diimide-based (hPDI) acceptors have been established as one of the most promising candidates for non-fullerene organic solar cells (OSCs). In this work, we report a novel hPDI-based molecule, hPDI 2 -CN 2 , as an electron acceptor for OSCs. Combining the hPDI 2 -CN 2 with a low-bandgap polymeric donor (PTB7-Th), the blending film morphology exhibited high sensitivity to various treatments (such as thermal annealing and addition of solvent additives), as evidenced by atomic force microscope studies. The power conversion efficiency (PCE) was improved from 1.42% (as-cast device) to 2.76% after thermal annealing, and a PCE of 3.25% was achieved by further addition of 1,8-diiodooctane (DIO). Femtosecond transient absorption (TA) spectroscopy studies revealed that the improved thin-film morphology was highly beneficial for the charge carrier transport and collection. And a combination of fast exciton diffusion rate and the lowest recombination rate contributed to the best performance of the DIO-treated device. This result further suggests that the molecular conformation needs to be taken into account in the design of perylene diimide-based acceptors for OSCs.
    Keywords: materials science
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 8
    facet.materialart.
    Unknown
    Regression of apoptosis-resistant colorectal tumors by induction of necroptosis in mice (2017)
    Rockefeller University Press
    Details
    Publication Date: 2017-06-06
    Description: Cancer cells often acquire capabilities to evade cell death induced by current chemotherapeutic treatment approaches. Caspase-8, a central initiator of death receptor–mediated apoptosis, for example, is frequently inactivated in human cancers via multiple mechanisms such as mutation. Here, we show an approach to overcome cell death resistance in caspase-8 –deficient colorectal cancer (CRC) by induction of necroptosis. In both a hereditary and a xenograft mouse model of caspase-8 –deficient CRC, second mitochondria-derived activator of caspase (SMAC) mimetic treatment induced massive cell death and led to regression of tumors. We further demonstrate that receptor-interacting protein kinase 3 (RIP3), which is highly expressed in mouse models of CRC and in a subset of human CRC cell lines, is the deciding factor of cancer cell susceptibility to SMAC mimetic–induced necroptosis. Thus, our data implicate that it may be worthwhile to selectively evaluate the efficacy of SMAC mimetic treatment in CRC patients with caspase-8 deficiency in clinical trials for the development of more effective personalized therapy.
    Keywords: Solid Tumors
    Print ISSN: 0022-1007
    Electronic ISSN: 1540-9538
    Topics: Medicine
    Published by Rockefeller University Press
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 9
    facet.materialart.
    Unknown
    Complex formation dynamics in a single-molecule electronic device (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-11-27
    Description: Single-molecule electronic devices offer unique opportunities to investigate the properties of individual molecules that are not accessible in conventional ensemble experiments. However, these investigations remain challenging because they require (i) highly precise device fabrication to incorporate single molecules and (ii) sufficient time resolution to be able to make fast molecular dynamic measurements. We demonstrate a graphene-molecule single-molecule junction that is capable of probing the thermodynamic and kinetic parameters of a host-guest complex. By covalently integrating a conjugated molecular wire with a pendent crown ether into graphene point contacts, we can transduce the physical [2]pseudorotaxane (de)formation processes between the electron-rich crown ether and a dicationic guest into real-time electrical signals. The conductance of the single-molecule junction reveals two-level fluctuations that are highly dependent on temperature and solvent environments, affording a nondestructive means of quantitatively determining the binding and rate constants, as well as the activation energies, for host-guest complexes. The thermodynamic processes reveal the host-guest binding to be enthalpy-driven and are consistent with conventional 1 H nuclear magnetic resonance titration experiments. This electronic device opens up a new route to developing single-molecule dynamics investigations with microsecond resolution for a broad range of chemical and biochemical applications.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 10
    facet.materialart.
    Unknown
    Correlation-Induced Self-Doping in the Iron-Pnictide Superconductor Ba_{2}Ti_{2}Fe_{2}As_{4}O (2015)
    American Physical Society (APS)
    Details
    Publication Date: 2015-01-01
    Description: Author(s): J.-Z. Ma, A. van Roekeghem, P. Richard, Z.-H. Liu, H. Miao, L.-K. Zeng, N. Xu, M. Shi, C. Cao, J.-B. He, G.-F. Chen, Y.-L. Sun, G.-H. Cao, S.-C. Wang, S. Biermann, T. Qian, and H. Ding The electronic structure of the iron-based superconductor Ba 2 Ti 2 Fe 2 As 4 O (T c onset =23.5  K) has been investigated by using angle-resolved photoemission spectroscopy and combined local density approximation and dynamical mean field theory calculations. The electronic states near the Fermi level are dom... [Phys. Rev. Lett. 113, 266407] Published Wed Dec 31, 2014
    Keywords: Condensed Matter: Electronic Properties, etc.
    Print ISSN: 0031-9007
    Electronic ISSN: 1079-7114
    Topics: Physics
    Published by American Physical Society (APS)
    Location Call Number Limitation 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...