Cell
-
The 2008 Lasker-Koshland Award will be presented to Stanley Falkow, one of the legendary figures in the history of microbiology research. Falkow's many contributions remade the way we think about bacterial pathogens, antibiotic resistance, and infectious disease.
-
Transient receptor potential vanilloid 1 (TRPV1) is a molecular sensor of noxious heat and capsaicin. Its channel activity can be modulated by several mechanisms. Here we identify a membrane protein, Pirt, as a regulator of TRPV1. ⋯ The PIP2 binding is dependent on the cluster of basic residues in the Pirt C terminus and is crucial for Pirt regulation of TRPV1. Importantly, the enhancement of TRPV1 by PIP2 requires Pirt. Therefore, Pirt is a key component of the TRPV1 complex and positively regulates TRPV1 activity.
-
Acute lung injury (ALI) is a leading cause of death in people infected with H5N1 avian influenza virus or the SARS-coronavirus. Imai et al. (2008) now report that ALI is triggered by the signaling of oxidized phospholipids through Toll-like receptor 4 (TLR4) and the adaptor protein TRIF. These findings provide insight into the molecular pathogenesis of ALI, a condition for which treatment options are currently very limited.
-
Multiple lung pathogens such as chemical agents, H5N1 avian flu, or SARS cause high lethality due to acute respiratory distress syndrome. Here we report that Toll-like receptor 4 (TLR4) mutant mice display natural resistance to acid-induced acute lung injury (ALI). We show that TLR4-TRIF-TRAF6 signaling is a key disease pathway that controls the severity of ALI. ⋯ Loss of TLR4 or TRIF expression protects mice from H5N1-induced ALI. Moreover, deletion of ncf1, which controls ROS production, improves the severity of H5N1-mediated ALI. Our data identify oxidative stress and innate immunity as key lung injury pathways that control the severity of ALI.
-
With new incentives, some governments in Latin America are starting to increase investment in basic and applied research. Although the news is encouraging, scientists in this region still face many challenges ahead.