Myotubularin-related protein 6 is an ion channel-associated pro-leishmanial phosphatase.

Residing obligatorily as amastigotes within the mammalian macrophages, the parasite Leishmania donovani inflicts the potentially fatal, globally re-emerging disease visceral leishmaniasis (VL) by altering intracellular signaling through kinases and phosphatases. Because the phosphatases that modulate the VL outcome in humans remained unknown, we screened a human phosphatase siRNA-library for anti-leishmanial functions in THP-1, a human macrophage-like cell line. Of the 251 phosphatases, the screen identified the Ca++-activated K+-channel-associated phosphatase myotubularin-related protein-6 (MTMR6) as the only phosphatase whose silencing reduced parasite load and IL-10 production in human macrophages. Virulent, but not avirulent, L. donovani infection increased MTMR6 expression in macrophages. As virulent L. donovani parasites expressed higher lipophosphoglycan, a TLR2-ligand, we tested the effect of TLR2 stimulation or blockade on MTMR6 expression. TLR1/TLR2-ligand Pam3CSK4 enhanced, but TLR2 blockade reduced, MTMR6 expression. L. donovani infection of macrophages ex vivo increased, but miltefosine treatment reduced, MTMR6 expression. Corroboratively, compared to endemic controls, untreated VL patients had higher, but miltefosine-treated VL patients had reduced, MTMR6 expression. The phosphatase siRNA-library screening thus identified MTMR6 as the first TLR2-modulated ion channel-associated phosphatase with significant implications in VL patients and anti-leishmanial functions.

Effect of Different Surfactants on the Interfacial Behavior of the n-Hexane-Water System in the Presence of Silica Nanoparticles.

This paper presents the effect of negatively charged silica nanoparticles (NPs) on the interfacial tension of the n-hexane-water system at variable concentrations of four different surfactants, viz., an anionic surfactant, sodium dodecyl sulfate (SDS), a cationic surfactant, cetyltrimethylammonium bromide (CTAB), and two nonionic surfactants, Tween 20 and Triton X-100 (TX-100). The presence of negatively charged silica nanoparticles is found to have a different effect depending on the type of surfactant. In the case of ionic surfactants, SDS and CTAB, silica NPs reduce the interfacial tension of the system. On the contrary, for nonionic surfactants, Tween 20 and TX-100, silica NPs increase the interfacial tension. The increasing/decreasing nature of the interfacial tension in the presence of NPs is well supported by the calculated surface excess concentrations. The diffusion kinetic control (DKC) and statistical rate theory (SRT) models are used to understand the behavior of dynamic interfacial tension of the surfactant-NP-oil-water system. The DKC model is found to describe the studied surfactant-NP-oil-water systems more aptly.