In gram-negative bacteria, the assembly of outer membrane proteins (OMPs) requires a β-barrel assembly machinery (BAM) complex, of which BamA is an essential and evolutionarily conserved component. To elucidate the mechanism of BamA-mediated OMP biogenesis, we determined the crystal structure of the C-terminal transmembrane domain of BamA from Escherichia coli (EcBamA) at 2.6 Å resolution. The structure reveals 2 distinct features. First, a portion of the extracellular side of the β barrel is composed of 5 markedly short β strands, and the loops stemming from these β strands form a potential surface cavity, filled by a portion of the L6 loop that includes the conserved VRGF/Y motif found in the Omp85 family. Second, the 4 extracellular loops L3, L4, L6, and L7 of EcBamA form a dome over the barrel, stabilized by a salt-bridge interaction network. Functional data show that hydrophilic-to-hydrophobic mutations of the potential hydrophilic surface cavity and a single Arg547Ala point mutation that may destabilize the dome severely affect the function of EcBamA. Our structure of the EcBamA β barrel and structure-based mutagenesis studies suggest that the transmembrane β strands of OMP substrates may integrate into the outer membrane at the interface of the first and last β strands of the EcBamA barrel, whereas the soluble loops or domains may be transported out of the cell via the hydrophilic surface cavity on dislocation of the VRGF/Y motif of L6. In addition, the dome over the barrel may play an important role in maintaining the efficiency of OMP biogenesis.
Question: Does remote ischemic conditioning improve neurological function in patients with acute moderate ischemic stroke? Findings: In this randomized clinical trial that included 1893 participants with acute moderate ischemic stroke, excellent neurological function at 90 days in those randomized to remote ischemic conditioning compared with usual care occurred in 67.4% vs 62.0%, a difference that was statistically significant.Meaning: Although remote ischemic conditioning was associated with better neurological function in patients with acute moderate ischemic stroke, this trial requires replication before concluding efficacy for this intervention.
The reaction of the 1,4-diazabutadiene ligand glyoxal bis(2-(methoxymethyl)-4,6-di-tert-butylphenyl)diimine (L) with the platinum complex Pt2Me4(SMe2)2 yields two isomers of
the complex PtMe2
L (2a,b) that have been isolated and characterized. The isomers exhibit
distorted-square-planar coordination geometries about the central Pt(II) ion and differ only
in the relative orientation of the methoxymethyl and tert-butyl substituents with respect to
the coordination plane of the complex. Isomerization between 2a and 2b is promoted by
heating solutions of either form of the complex in benzene or chloroform. Upon prolonged
refluxing in chloroform, 2a,b react with chloroform to yield the methyl chloro derivative
PtMeClL, which is also obtained as syn and anti isomers (3a,b). Cationic solvento complexes
[PtMe(S)L]BF4 (4 and 5, S = MeCN, pyridine) are generated by halide abstraction from 3
using AgBF4. In the presence of selected olefins such as ethylene and acrylonitrile, halide
abstraction from 3 by AgBF4 or methyl group abstraction from 2a and 2b by the strong
Lewis acid B(C6F5)3 yields the cationic α-olefin complexes [PtMe(CH2CHR)L]+ (R = H, CN;
6 and 7 for the BF4 salt, 8 and 9 for the MeB(C6F5)3 salt). All new compounds have been
characterized by IR and NMR spectroscopy. Molecular structures of 2a,b, and 3a were
determined by X-ray single-crystal diffraction.
Novel host−guest/multicomponent energetic materials can be obtained by embedding hydrogen-or nitrogen-containing oxidizing small molecules between the molecules of high-energy explosives, which can improve their explosive energy. To better understand the mechanism of oxidizing small molecules in the reaction and improve the energy, ReaxFF-lg reactive molecular dynamics simulations were performed to investigate the thermal decomposition reaction at different temperatures of the CL-20/H 2 O 2 solvate formed by embedding H 2 O 2 in the cavity of CL-20. We propose an analytical method to investigate the mechanism of H 2 O 2 in the CL-20 reaction by tracing the interactions between the H and O atoms of H 2 O 2 and the C, H, N, and O atoms of CL-20. During thermal decomposition of CL-20/H 2 O 2 , CL-20 and H 2 O 2 first separately decompose, and then, the decomposition products react. The H atoms, O atoms, and hydroxyl (HO) groups generated by H 2 O 2 decomposition connect with the O atoms of nitro groups, leading to N−O bond cleavage. The O atoms generated by H 2 O 2 decomposition connect with C atoms, leading to C−N bond cleavage, which catalyzes destruction of the CL-20 cage structure and increases the CL-20 decomposition rate. Eventually, the H and O atoms of H 2 O 2 mainly bond to the O and C atoms of CL-20, respectively, which causes generation of greater amounts of H 2 O and CO 2 and increases the heat released. These mechanisms increase the detonation velocity and pressure of explosives. The proposed analytical method can be used to investigate the reaction mechanisms of other host−guest/multicomponent energetic materials.
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