A unique strategy towards high dielectric constant and low loss with multiwall carbon nanotubes anchored onto graphene oxide sheets

Multiwall carbon nanotubes (MWNTs) were anchored onto graphene oxide sheets (GOs) via diazonium and C-C coupling reactions and characterized by spectroscopic and electron microscopic techniques. The thus synthesized MWNT-GO hybrid was then melt mixed with 50/50 polyamide6-maleic anhydride-modified acrylonitrile-butadiene-styrene (PA6-mABS) blend to design materials with high dielectric constant (30) and low dielectric loss. The phase morphology was studied by SEM and it was observed that the MWNT-GO hybrid was selectively localized in the PA6 phase of the blend. The 30 scales with the concentration of MWNT-GO in the blends, which interestingly showed a very low dielectric loss (< 0.2) making them potential candidate for capacitors. In addition, the dynamic storage modulus scales with the fraction of MWNT-GO in the blends, demonstrating their reinforcing capability as well.

Inhibition of protein synthesis leading to unfolded protein response is the major event in abrin-mediated apoptosis

Abrin obtained from the plant Abrus precatorius inhibits protein synthesis and also triggers apoptosis in cells. Previous studies from our laboratory suggested a link between these two events. Using an active site mutant of abrin A-chain which exhibits 225-fold lower protein synthesis inhibitory activity than the wild-type abrin A-chain, we demonstrate in this study that inhibition of protein synthesis induced by abrin is the major factor triggering unfolded protein response leading to apoptosis. Since abrin A-chain requires the B-chain for internalization into cells, the wild-type and mutant recombinant abrin A-chains were conjugated to native ricin B-chain to generate hybrid toxins, and the toxic effects of the two conjugates were compared. The rate of inhibition of protein synthesis mediated by the mutant ricin B-rABRA (R167L) conjugate was slower than that of the wild-type ricin B-rABRA conjugate as expected. The mutant conjugate activated p38MAPK and caspase-3 similar to its wild-type counterpart although at later time points. Overall, these results confirm that inhibition of protein synthesis is the major event contributing to abrin-mediated apoptosis.

Sonic hedgehog-Dependent Induction of MicroRNA 31 and MicroRNA 150 Regulates Mycobacterium bovis BCG-Driven Toll-Like Receptor 2 Signaling

Hedgehog (HH) signaling is a significant regulator of cell fate decisions during embryogenesis, development, and perpetuation of various disease conditions. Testing whether pathogen-specific HH signaling promotes unique innate recognition of intracellular bacteria, we demonstrate that among diverse Gram-positive or Gram-negative microbes, Mycobacterium bovis BCG, a vaccine strain, elicits a robust activation of Sonic HH (SHH) signaling in macrophages. Interestingly, sustained tumor necrosis factor alpha (TNF-alpha) secretion by macrophages was essential for robust SHH activation, as TNF-alpha(-/-) macrophages exhibited compromised ability to activate SHH signaling. Neutralization of TNF-alpha or blockade of TNF-alpha receptor signaling significantly reduced the infection-induced SHH signaling activation both in vitro and in vivo. Intriguingly, activated SHH signaling downregulated M. bovis BCG-mediated Toll-like receptor 2 (TLR2) signaling events to regulate a battery of genes associated with divergent functions of M1/M2 macrophages. Genome-wide expression profiling as well as conventional gain-of-function or loss-of-function analysis showed that SHH signaling-responsive microRNA 31 (miR-31) and miR-150 target MyD88, an adaptor protein of TLR2 signaling, thus leading to suppression of TLR2 responses. SHH signaling signatures could be detected in vivo in tuberculosis patients and M. bovis BCG-challenged mice. Collectively, these investigations identify SHH signaling to be what we believe is one of the significant regulators of host-pathogen interactions.

Synthesis and unexpected reactivity of Ru(eta(6)-cymene)Cl-2(PPh2Cl)], leading to Ru(eta(6)-cymene)Cl-2(PPh2H)] and Ru(eta(6)-cymene)Cl-2(PPh2OH)] complexes

The reaction of Ru(eta(6)-cymene)Cl-2](2) and PPh2Cl in the ratio 1:2 gives a stable Ru(h(6)-cymene) Cl-2(PPh2Cl)] complex. Attempts to make the cationic Ru(eta(6)-cymene)Cl(PPh2Cl)(2)]Cl with excess PPh2Cl and higher temperatures led to adventitious hydrolysis and formation of Ru(eta(6)-cymene)Cl-2(PPh2OH)]. Attempts to make a phosphinite complex by reacting Ru(eta(6)-cymene)Cl-2](2) with PPh2Cl in the presence of an alcohol results in the reduction of PPh2Cl to give Ru(eta(6)-cymene)Cl-2(PPh2H)] and the expected phosphinite. The yield of the hydride complex is highest when the alcohol is 1-phenyl-ethane-1,2-diol. All three half-sandwich complexes are characterized by X-ray crystallography. Surprisingly, the conversion of chlorodiphenylphosphine to diphenylphosphine is mediated by 1-phenyl-ethane-1,2-diol even in the absence of the ruthenium half-sandwich precursor.

Insights into the Structural Dynamics of Nucleocytoplasmic Transport of tRNA by Exportin-t

Exportin-t (Xpot) transports mature 5'- and 3'-end processed tRNA from the nucleus to the cytoplasm by associating with a small G-protein Ran (RAs-related nuclear protein), in the nucleus. The release of tRNA in cytoplasm involves RanGTP hydrolysis. Despite the availability of crystal structures of nuclear and cytosolic forms of Xpot, the molecular details regarding the sequential events leading to tRNA release and subsequent conformational changes occurring in Xpot remain unknown. We have performed a combination of classical all-atom and accelerated molecular dynamics simulations on a set of complexes involving Xpot to study a range of features including conformational flexibility of free and cargo-bound Xpot and functionally critical contacts between Xpot and its cargo. The systems investigated include free Xpot and its different complexes, bound either to Ran (GTP/GDP) or tRNA or both. This approach provided a statistically reliable estimate of structural dynamics of Xpot after cargo release. The mechanistic basis for Xpot opening after cargo release has been explained in terms of dynamic structural hinges, about which neighboring region could be displaced to facilitate the nuclear to cytosolic state transition. Post-RanGTP hydrolysis, a cascade of events including local conformational change in RanGTP and loss of critical contacts at Xpot/tRNA interface suggest factors responsible for eventual release of tRNA. The level of flexibility in different Xpot complexes varied depending on the arrangement of individual HEAT repeats. Current study provides one of the most comprehensive and robust analysis carried out on this protein using molecular dynamics schemes.