@article{ZirkelCecilSchaeferetal.2012,
  author    = {Zirkel, J. and Cecil, A. and Sch{\"a}fer, F. and Rahlfs, S. and Ouedraogo, A. and Xiao, K. and Sawadogo, S. and Coulibaly, B. and Becker, K. and Dandekar, T.},
  title     = {Analyzing Thiol-Dependent Redox Networks in the Presence of Methylene Blue and Other Antimalarial Agents with RT-PCR-Supported in silico Modeling},
  series = {Bioinformatics and Biology Insights},
  volume    = {6},
  journal   = {Bioinformatics and Biology Insights},
  doi       = {10.4137/BBI.S10193},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123751},
  pages     = {287-302},
  year      = {2012},
  abstract  = {BACKGROUND: In the face of growing resistance in malaria parasites to drugs, pharmacological combination therapies are important. There is accumulating evidence that methylene blue (MB) is an effective drug against malaria. Here we explore the biological effects of both MB alone and in combination therapy using modeling and experimental data. RESULTS: We built a model of the central metabolic pathways in P. falciparum. Metabolic flux modes and their changes under MB were calculated by integrating experimental data (RT-PCR data on mRNAs for redox enzymes) as constraints and results from the YANA software package for metabolic pathway calculations. Several different lines of MB attack on Plasmodium redox defense were identified by analysis of the network effects. Next, chloroquine resistance based on pfmdr/and pfcrt transporters, as well as pyrimethamine/sulfadoxine resistance (by mutations in DHF/DHPS), were modeled in silico. Further modeling shows that MB has a favorable synergism on antimalarial network effects with these commonly used antimalarial drugs. CONCLUSIONS: Theoretical and experimental results support that methylene blue should, because of its resistance-breaking potential, be further tested as a key component in drug combination therapy efforts in holoendemic areas.},
  language  = {en}
}
@article{DeaneBrunkCurranetal.2020,
  author    = {Deane, Katrina E. and Brunk, Michael G. K. and Curran, Andrew W. and Zempeltzi, Marina M. and Ma, Jing and Lin, Xiao and Abela, Francesca and Aksit, S{\"u}meyra and Deliano, Matthias and Ohl, Frank W. and Happel, Max F. K.},
  title     = {Ketamine anaesthesia induces gain enhancement via recurrent excitation in granular input layers of the auditory cortex},
  series = {The Journal of Physiology},
  volume    = {598},
  journal   = {The Journal of Physiology},
  number    = {13},
  doi       = {10.1113/JP279705},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216123},
  pages     = {2741 -- 2755},
  year      = {2020},
  abstract  = {Ketamine is commonly used as an anaesthetic agent and has more recently gained attention as an antidepressant. It has been linked to increased stimulus-locked excitability, inhibition of interneurons and modulation of intrinsic neuronal oscillations. However, the functional network mechanisms are still elusive. A better understanding of these anaesthetic network effects may improve upon previous interpretations of seminal studies conducted under anaesthesia and have widespread relevance for neuroscience with awake and anaesthetized subjects as well as in medicine. Here, we investigated the effects of anaesthetic doses of ketamine (15 mg kg\(^{-1}\) h\(^{-1}\)i.p.) on the network activity after pure-tone stimulation within the auditory cortex of male Mongolian gerbils (Meriones unguiculatus). We used laminar current source density (CSD) analysis and subsequent layer-specific continuous wavelet analysis to investigate spatiotemporal response dynamics on cortical columnar processing in awake and ketamine-anaesthetized animals. We found thalamocortical input processing within granular layers III/IV to be significantly increased under ketamine. This layer-dependent gain enhancement under ketamine was not due to changes in cross-trial phase coherence but was rather attributed to a broadband increase in magnitude reflecting an increase in recurrent excitation. A time-frequency analysis was indicative of a prolonged period of stimulus-induced excitation possibly due to a reduced coupling of excitation and inhibition in granular input circuits - in line with the common hypothesis of cortical disinhibition via suppression of GABAergic interneurons.},
  language  = {en}
}
@article{LiuHanBlairetal.2021,
  author    = {Liu, Fengming and Han, Kun and Blair, Robert and Kenst, Kornelia and Qin, Zhongnan and Upcin, Berin and W{\"o}rsd{\"o}rfer, Philipp and Midkiff, Cecily C. and Mudd, Joseph and Belyaeva, Elizaveta and Milligan, Nicholas S. and Rorison, Tyler D. and Wagner, Nicole and Bodem, Jochen and D{\"o}lken, Lars and Aktas, Bertal H. and Vander Heide, Richard S. and Yin, Xiao-Ming and Kolls, Jay K. and Roy, Chad J. and Rappaport, Jay and Erg{\"u}n, S{\"u}leyman and Qin, Xuebin},
  title     = {SARS-CoV-2 Infects Endothelial Cells In Vivo and In Vitro},
  series = {Frontiers in Cellular and Infection Microbiology},
  volume    = {11},
  journal   = {Frontiers in Cellular and Infection Microbiology},
  issn      = {2235-2988},
  doi       = {10.3389/fcimb.2021.701278},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241948},
  year      = {2021},
  abstract  = {SARS-CoV-2 infection can cause fatal inflammatory lung pathology, including thrombosis and increased pulmonary vascular permeability leading to edema and hemorrhage. In addition to the lung, cytokine storm-induced inflammatory cascade also affects other organs. SARS-CoV-2 infection-related vascular inflammation is characterized by endotheliopathy in the lung and other organs. Whether SARS-CoV-2 causes endotheliopathy by directly infecting endothelial cells is not known and is the focus of the present study. We observed 1) the co-localization of SARS-CoV-2 with the endothelial cell marker CD31 in the lungs of SARS-CoV-2-infected mice expressing hACE2 in the lung by intranasal delivery of adenovirus 5-hACE2 (Ad5-hACE2 mice) and non-human primates at both the protein and RNA levels, and 2) SARS-CoV-2 proteins in endothelial cells by immunogold labeling and electron microscopic analysis. We also detected the co-localization of SARS-CoV-2 with CD31 in autopsied lung tissue obtained from patients who died from severe COVID-19. Comparative analysis of RNA sequencing data of the lungs of infected Ad5-hACE2 and Ad5-empty (control) mice revealed upregulated KRAS signaling pathway, a well-known pathway for cellular activation and dysfunction. Further, we showed that SARS-CoV-2 directly infects mature mouse aortic endothelial cells (AoECs) that were activated by performing an aortic sprouting assay prior to exposure to SARS-CoV-2. This was demonstrated by co-localization of SARS-CoV-2 and CD34 by immunostaining and detection of viral particles in electron microscopic studies. Moreover, the activated AoECs became positive for ACE-2 but not quiescent AoECs. Together, our results indicate that in addition to pneumocytes, SARS-CoV-2 also directly infects mature vascular endothelial cells in vivo and ex vivo, which may contribute to cardiovascular complications in SARS-CoV-2 infection, including multipleorgan failure.},
  language  = {en}
}