Carbon monoxide’s role in killing bacterial lung infection: Coverage by Lung Disease News and Digital Journal on “Macrophages sense and kill bacteria through carbon monoxide–dependent inflammasome activation.”
Diet, inflammation, and cancer linked through certain lipids: Coverage by Oncology Nurse Advisor on “Sphingosine-1-phosphate lyase downregulation promotes colon carcinogenesis through STAT3-activated microRNAs.”
Possible new stent to prevent heart attacks: Coverage by Stanford Medical and Health News Digest on "Oxido-reductive regulation of vascular remodeling by receptor tyrosine kinase ROS1."
A new model for JC virus infection: Coverage by Health Canal and University Rochester Medical Center on “Human glial chimeric mice reveal astrocytic dependence of JC virus infection.”
Microbial clearance by eukaryotes relies on complex and coordinated processes that remain poorly understood. The gasotransmitter carbon monoxide (CO) is generated by the stress-responsive enzyme heme oxygenase-1 (HO-1, encoded by
Barbara Wegiel, Rasmus Larsen, David Gallo, Beek Yoke Chin, Clair Harris, Praveen Mannam, Elzbieta Kaczmarek, Patty J. Lee, Brian S. Zuckerbraun, Richard Flavell, Miguel P. Soares, Leo E. Otterbein
Growing evidence supports a link between inflammation and cancer; however, mediators of the transition between inflammation and carcinogenesis remain incompletely understood. Sphingosine-1-phosphate (S1P) lyase (SPL) irreversibly degrades the bioactive sphingolipid S1P and is highly expressed in enterocytes but downregulated in colon cancer. Here, we investigated the role of SPL in colitis-associated cancer (CAC). We generated mice with intestinal epithelium-specific
Emilie Degagné, Ashok Pandurangan, Padmavathi Bandhuvula, Ashok Kumar, Abeer Eltanawy, Meng Zhang, Yuko Yoshinaga, Mikhail Nefedov, Pieter J. de Jong, Loren G. Fong, Stephen G. Young, Robert Bittman, Yasmin Ahmedi, Julie D. Saba
Angioplasty and stenting is the primary treatment for flow-limiting atherosclerosis; however, this strategy is limited by pathological vascular remodeling. Using a systems approach, we identified a role for the network hub gene glutathione peroxidase-1 (
Ziad A. Ali, Vinicio de Jesus Perez, Ke Yuan, Mark Orcholski, Stephen Pan, Wei Qi, Gaurav Chopra, Christopher Adams, Yoko Kojima, Nicholas J. Leeper, Xiumei Qu, Kathia Zaleta-Rivera, Kimihiko Kato, Yoshiji Yamada, Mitsutoshi Oguri, Allan Kuchinsky, Stanley L. Hazen, J. Wouter Jukema, Santhi K. Ganesh, Elizabeth G. Nabel, Keith Channon, Martin B. Leon, Alain Charest, Thomas Quertermous, Euan A. Ashley
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease triggered by infection with the human gliotropic JC virus (JCV). Due to the human-selective nature of the virus, there are no animal models available to investigate JCV pathogenesis. To address this issue, we developed mice with humanized white matter by engrafting human glial progenitor cells (GPCs) into neonatal immunodeficient and myelin-deficient mice. Intracerebral delivery of JCV resulted in infection and subsequent demyelination of these chimeric mice. Human GPCs and astrocytes were infected more readily than oligodendrocytes, and viral replication was noted primarily in human astrocytes and GPCs rather than oligodendrocytes, which instead expressed early viral T antigens and exhibited apoptotic death. Engraftment of human GPCs in normally myelinated and immunodeficient mice resulted in humanized white matter that was chimeric for human astrocytes and GPCs. JCV effectively propagated in these mice, which indicates that astroglial infection is sufficient for JCV spread. Sequencing revealed progressive mutation of the JCV capsid protein VP1 after infection, suggesting that PML may evolve with active infection. These results indicate that the principal CNS targets for JCV infection are astrocytes and GPCs and that infection is associated with progressive mutation, while demyelination is a secondary occurrence, following T antigen–triggered oligodendroglial apoptosis. More broadly, this study provides a model by which to further assess the biology and treatment of human-specific gliotropic viruses.
Yoichi Kondo, Martha S. Windrem, Lisa Zou, Devin Chandler-Militello, Steven J. Schanz, Romane M. Auvergne, Sarah J. Betstadt, Amy R. Harrington, Mahlon Johnson, Alexander Kazarov, Leonid Gorelik, Steven A. Goldman