A two-step target binding and selectivity support vector machines approach for virtual screening of dopamine receptor subtype-selective ligands

10.1371/journal.pone.0039076PLoS ONE76

Evasion by Stealth: Inefficient Immune Activation Underlies Poor T Cell Response and Severe Disease in SARS-CoV-Infected Mice

Severe Acute Respiratory Syndrome caused substantial morbidity and mortality during the 2002–2003 epidemic. Many of the features of the human disease are duplicated in BALB/c mice infected with a mouse-adapted version of the virus (MA15), which develop respiratory disease with high morbidity and mortality. Here, we show that severe disease is correlated with slow kinetics of virus clearance and delayed activation and transit of respiratory dendritic cells (rDC) to the draining lymph nodes (DLN) with a consequent deficient virus-specific T cell response. All of these defects are corrected when mice are treated with liposomes containing clodronate, which deplete alveolar macrophages (AM). Inhibitory AMs are believed to prevent the development of immune responses to environmental antigens and allergic responses by interacting with lung dendritic cells and T cells. The inhibitory effects of AM can also be nullified if mice or AMs are pretreated with poly I:C, which directly activate AMs and rDCs through toll-like receptors 3 (TLR3). Further, adoptive transfer of activated but not resting bone marrow–derived dendritic cells (BMDC) protect mice from lethal MA15 infection. These results may be relevant for SARS in humans, which is also characterized by prolonged virus persistence and delayed development of a SARS-CoV-specific immune response in individuals with severe disease

Enhanced oxygen evolution over dual corner-shared cobalt tetrahedra.

Developing efficient catalysts is of paramount importance to oxygen evolution, a sluggish anodic reaction that provides essential electrons and protons for various electrochemical processes, such as hydrogen generation. Here, we report that the oxygen evolution reaction (OER) can be efficiently catalyzed by cobalt tetrahedra, which are stabilized over the surface of a Swedenborgite-type YBCo4O7 material. We reveal that the surface of YBaCo4O7 possesses strong resilience towards structural amorphization during OER, which originates from its distinctive structural evolution toward electrochemical oxidation. The bulk of YBaCo4O7 composes of corner-sharing only CoO4 tetrahedra, which can flexibly alter their positions to accommodate the insertion of interstitial oxygen ions and mediate the stress during the electrochemical oxidation. The density functional theory calculations demonstrate that the OER is efficiently catalyzed by a binuclear active site of dual corner-shared cobalt tetrahedra, which have a coordination number switching between 3 and 4 during the reaction. We expect that the reported active structural motif of dual corner-shared cobalt tetrahedra in this study could enable further development of compounds for catalyzing the OER