Ultrafast Nano-scale Optical Switching in a Plasmonic Interferometer with Enhanced Tunability

An all-optical switch based on plasmonic metal–insulator–metal (MIM) waveguides and the Mach–Zehnder (MZ) interferometer is designed. In order to realize an all-optical and active switch, a nonlinear material with intensity-dependent refractive index is introduced in one arm. Other than studying a typical MZ structure, we also investigate the asymmetric case where unequal thicknesses and distances for MZ arms are proposed. The finite element method (FEM) with a refined triangle mesh is employed for simulations. Results for ON and OFF states are provided with or without employing the pump field. Investigation of the geometrical dispersion reveals tunability of the structure for specific frequencies in the terahertz region. Finally, we show that introducing asymmetric arms provides better tunability in the designed ultrafast nano-scale switch and suggests its potential applications in integrated optical circuits.

     

Global Analysis of the Evolution and Mechanism of Echinocandin Resistance in Candida glabrata

The evolution of drug resistance has a profound impact on human health. Candida glabrata is a leading human fungal pathogen that can rapidly evolve resistance to echinocandins, which target cell wall biosynthesis and are front-line therapeutics for Candida infections. Here, we provide the first global analysis of mutations accompanying the evolution of fungal drug resistance in a human host utilizing a series of C. glabrata isolates that evolved echinocandin resistance in a patient treated with the echinocandin caspofungin for recurring bloodstream candidemia. Whole genome sequencing identified a mutation in the drug target, FKS2, accompanying a major resistance increase, and 8 additional non-synonymous mutations. The FKS2-T1987C mutation was sufficient for echinocandin resistance, and associated with a fitness cost that was mitigated with further evolution, observed in vitro and in a murine model of systemic candidemia. A CDC6-A511G(K171E) mutation acquired before FKS2-T1987C(S663P), conferred a small resistance increase. Elevated dosage of CDC55, which acquired a C463T(P155S) mutation after FKS2-T1987C(S663P), ameliorated fitness. To discover strategies to abrogate echinocandin resistance, we focused on the molecular chaperone Hsp90 and downstream effector calcineurin. Genetic or pharmacological compromise of Hsp90 or calcineurin function reduced basal tolerance and resistance. Hsp90 and calcineurin were required for caspofungin-dependent FKS2 induction, providing a mechanism governing echinocandin resistance. A mitochondrial respiration-defective petite mutant in the series revealed that the petite phenotype does not confer echinocandin resistance, but renders strains refractory to synergy between echinocandins and Hsp90 or calcineurin inhibitors. The kidneys of mice infected with the petite mutant were sterile, while those infected with the HSP90-repressible strain had reduced fungal burden. We provide the first global view of mutations accompanying the evolution of fungal drug resistance in a human host, implicate the premier compensatory mutation mitigating the cost of echinocandin resistance, and suggest a new mechanism of echinocandin resistance with broad therapeutic potential.     

Promising insights into the kosmotropic effect of magnetic nanoparticles on proteins: The pivotal role of protein corona formation

Increasing concerns about biosafety of nanoparticles (NPs) has raised the need for detailed knowledge of NP interactions with biological molecules especially proteins. Herein, the concentration-dependent effect of magnetic NPs (MNPs) on bovine serum albumin and hen egg white lysozyme was explored. The X-ray diffraction patterns, zeta potential, and dynamic light scattering measurements together with scanning electron microscopy images were employed to characterize MNPs synthesized through coprecipitation method. Then, we studied the behavior of two model proteins with different surface charges and structural properties on interaction with Fe₃O₄. A thorough investigation of protein–MNP interaction by the help of intrinsic fluorescence at different experimental conditions revealed that affinity of proteins for MNPs is strongly affected by the similarity of protein and MNP surface charges. MNPs exerted structure-making kosmotropic effect on both proteins under a concentration threshold; however, binding strength was found to determine the extent of stabilizing effect as well as magnitude of the concentration threshold. Circular dichroism spectra showed that proteins with less resistance to conformational deformations are more prone to secondary structure changes upon adsorption on MNPs. By screening thermal aggregation of proteins in the presence of Fe₃O₄, it was also found that like chemical stability, thermal stability is influenced to a higher extent in more strongly bound proteins. Overall, this report not only provides an integrated picture of protein–MNP interaction but also sheds light on the molecular mechanism underling this process.     

Effect of Piriformospora indica and Sebacina vermifera on plant growth and essential oil yield in Thymus vulgaris in vitro and in vivo experiments

Thymus vulgaris of family Lamiaceae is one of the most plants in pharmacy industries. In this study effect of Piriformospora indica and Sebacina vermifera on growth and development plant, yield and composition of the essential oil in a completely randomized design were evaluated in vitro and in pot culture experiments. Plants were studied by means of plant height, shoot fresh and dry weights, number of shoots, root length, root fresh and dry weights and essential oil analyses. The oil was extracted from the dry matter of shoots by hydro distillation, and their composition was determined by GC/MS. In vitro and in vivo cultures showed that plant height and root length increased in pots inoculated with S. vermifera and P. indica. Maximum fresh and dry weight (shoot and root), number of shoots were observed in pots inoculated with P. indica. In thyme inoculated with S. vermifera and P. indica oil yield increased as compared to non-inoculated control plants. GC and GC/MS revealed that the level of thymol was enhanced as the effect of S. vermifera and P. indica.