Fluoroketone inhibition of Ca(2+)-independent phospholipase A2 through binding pocket association defined by hydrogen/deuterium exchange and molecular dynamics.

The mechanism of inhibition of group VIA Ca(2+)-independent phospholipase A(2) (iPLA(2)) by fluoroketone (FK) ligands is examined by a combination of deuterium exchange mass spectrometry (DXMS) and molecular dynamics (MD). Models for iPLA(2) were built by homology with the known structure of patatin and equilibrated by extensive MD simulations. Empty pockets were identified during the simulations and studied for their ability to accommodate FK inhibitors. Ligand docking techniques showed that the potent inhibitor 1,1,1,3-tetrafluoro-7-phenylheptan-2-one (PHFK) forms favorable interactions inside an active-site pocket, where it blocks the entrance of phospholipid substrates. The polar fluoroketone headgroup is stabilized by hydrogen bonds with residues Gly486, Gly487, and Ser519. The nonpolar aliphatic chain and aromatic group are stabilized by hydrophobic contacts with Met544, Val548, Phe549, Leu560, and Ala640. The binding mode is supported by DXMS experiments showing an important decrease of deuteration in the contact regions in the presence of the inhibitor. The discovery of the precise binding mode of FK ligands to the iPLA(2) should greatly improve our ability to design new inhibitors with higher potency and selectivity

Case report: VA-ECMO for fulminant myocarditis in an infant with acute COVID-19

Fulminant myocarditis in children was rare during the coronavirus disease 2019 pandemic, but it had the potential for high morbidity and mortality. We describe the clinical course of a previously healthy 9-month-old young male infant who rapidly deteriorated into cardiogenic shock due to coronavirus disease 2019-related fulminant myocarditis. He developed severe heart failure and multiple organ dysfunction syndrome that were treated promptly with central venoarterial extracorporeal membrane oxygenation and continuous venovenous hemofiltration. He made a good recovery without significant morbidity

The Stable Association of Virion with the Triple-geneblockProtein 3-based Complex of Bamboo mosaic virus

The triple-gene-block protein 3 (TGBp3) of Bamboo mosaic virus (BaMV) is an integral endoplasmic reticulum (ER) membraneprotein which is assumed to form a membrane complex to deliver the virus intracellularly. However, the virus entity that isdelivered to plasmodesmata (PD) and its association with TGBp3-based complexes are not known. Results from chemicalextraction and partial proteolysis of TGBp3 in membrane vesicles revealed that TGBp3 has a right-side-out membranetopology; i.e., TGBp3 has its C-terminal tail exposed to the outer surface of ER. Analyses of the TGBp3-specificimmunoprecipitate of Sarkosyl-extracted TGBp3-based complex revealed that TGBp1, TGBp2, TGBp3, capsid protein (CP),replicase and viral RNA are potential constituents of virus movement complex. Substantial co-fractionation of TGBp2, TGBp3and CP, but not TGBp1, in the early eluted gel filtration fractions in which virions were detected after TGBp3-specificimmunoprecipitation suggested that the TGBp2- and TGBp3-based complex is able to stably associate with the virion. Thisnotion was confirmed by immunogold-labeling transmission electron microscopy (TEM) of the purified virions. In addition,mutational and confocal microscopy analyses revealed that TGBp3 plays a key role in virus cell-to-cell movement byenhancing the TGBp2- and TGBp3-dependent PD localization of TGBp1. Taken together, our results suggested that the cellto-cell movement of potexvirus requires stable association of the virion cargo with the TGBp2- and TGBp3-based membranecomplex and recruitment of TGBp1 to the PD by this complex

Near-Infrared H2 and Continuum Survey of Extended Green Objects

The Spitzer GLIMPSE survey has revealed a number of "Extended Green Objects" (EGOs) which display extended emission at 4.5 micron. These EGOs are potential candidates for high mass protostellar outflows. We have used high resolution (< 1") H2 1-0 S(1) line, K, and H-band images from the United Kingdom Infrared Telescope to study 34 EGOs to investigate their nature. We found that 12 EGOs exhibit H2 outflows (two with chains of H2 knotty structures; five with extended H2 bipolar structures; three with extended H2 lobes; two with pairs of H2 knots). In the 12 EGOs with H2 outflows, three of them exhibit similar morphologies between the 4.5 micron and H2 emission. However, the remaining 9 EGOs show that the H2 features are more extended than the continuum features, and the H2 emission is seldom associated with continuum emission. Furthermore, the morphologies of the near-infrared continuum and 4.5 micron emission are similar to each other for those EGOs with K-band emission, implying that at least a part of the IRAC-band continuum emission of EGOs comes from scattered light from the embedded YSOs.Comment: accepted for publication in ApJ

Near-infrared H2 and continuum survey of extended green objects. II. Complete census for the northern Galactic plane

We discuss 94 Extended Green Objects (EGOs) in the northern Galactic plane cataloged by Cyganowski et al., based on near-infrared narrow H2 (2.122 μm) and continuum observations from the United Kingdom Infrared Telescope. This data set is three times larger than the one in our previous study and is unbiased by preselection. As discussed in the previous paper, the morphologies of the 4.5 μm emission generally resemble those of the near-infrared continuum, but are different from those of the H2 emission. Of our sample, only 28% of EGOs with H2 emission show similar morphologies between 4.5 μm and H2 emission. These results suggest that the 4.5 μm emission mainly comes from scattered continuum from the embedded young stellar objects, and partially from H2 emission. About half of EGOs are associated with H2 outflows, if the H 2 outflow incompleteness is considered. The H2 outflow detection rate for EGOs with K-band detections (61%) is significantly higher than for those without K-band detections (36%). This difference may be due to the fact that both H2 and K-band emissions are associated with outflows, i.e., H2 emission and K-band continuum are associated with shocks and outflow cavities, respectively. We also compared the correlation between the H2 outflows and Class I 44 GHz methanol masers from the literature. The methanol masers can be located upstream or downstream of the H2 outflows and some bright H2 spots or outflows are not associated with methanol masers, suggesting that methanol masers and H 2 emission trace different excitation conditions. © 2013. The American Astronomical Society. All rights reserved.