Immunoediting role for major vault protein in apoptotic signaling induced by bacterial N-acyl homoserine lactones

The major vault protein (MVP) mediates diverse cellular responses, including cancer cell resistance to chemotherapy and protection against inflammatory responses to Pseudomonas aeruginosa. Here, we report the use of photoactive probes to identify MVP as a target of the N-(3-oxo-dodecanoyl) homoserine lactone (C12), a quorum sensing signal of certain proteobacteria including P. aeruginosa. A treatment of normal and cancer cells with C12 or other N-acyl homoserine lactones (AHLs) results in rapid translocation of MVP into lipid raft (LR) membrane fractions. Like AHLs, inflammatory stimuli also induce LR-localization of MVP, but the C12 stimulation reprograms (functionalizes) bioactivity of the plasma membrane by recruiting death receptors, their apoptotic adaptors, and caspase-8 into LR. These functionalized membranes control AHL-induced signaling processes, in that MVP adjusts the protein kinase p38 pathway to attenuate programmed cell death. Since MVP is the structural core of large particles termed vaults, our findings suggest a mechanism in which MVP vaults act as sentinels that fine-tune inflammation-activated processes such as apoptotic signaling mediated by immunosurveillance cytokines including tumor necrosis factor-related apoptosis inducing ligand (TRAIL).Bio-organic Synthesi

Effects of active anti-methamphetamine vaccination on intravenous self-administration in rats

BACKGROUND: D-methamphetamine (METH) addiction is a serious public health concern for which successful treatment remains elusive. Immunopharmacotherapy has been shown to attenuate locomotor and thermoregulatory effects of METH. The current study investigated whether active vaccination against METH could alter intravenous METH self-administration in rats. METHODS: Male Sprague-Dawley rats (Experiment 1: N=24; Experiment 2: N=18) were vaccinated with either a control keyhole-limpet hemocyanin conjugate vaccine (KLH) or a candidate anti-METH vaccine (MH6-KLH) or. Effects of vaccination on the acquisition of METH self-administration under two dose conditions (0.05, 0.1 mg/kg/inf) and post-acquisition dose-substitution (0, 0.01, 0.05, 0.20 mg/kg/inf, Experiment 1; 0.01, 0.05, 0.10, 0.15 mg/kg/inf, Experiment 2) during steady-state responding were investigated. Plasma METH concentrations were determined 30 min after an acute challenge dose of 3.2 mg/kg METH. RESULTS: Active vaccination inhibited the acquisition of METH self-administration under the 0.1 mg/kg/inf dose condition, with 66% of the MH6-KLH-vaccinated rats compared to 100% of the controls reaching criteria, and produced transient and dose-dependent effects on self-administration during the maintenance phase. Under the 0.05 mg/kg/inf dose condition, MH6-KLH-vaccinated rats initially self-administered more METH than controls, but then self-administration decreased across the acquisition phase relative to controls; a subsequent dose-response assessment confirmed that MH6-KLH-vaccinated rats failed to acquire METH self-administration. Finally, plasma METH concentrations were higher in MH6-KLH-vaccinated rats compared to controls after an acute METH challenge, and these were positively correlated with antibody titers. CONCLUSIONS: These data demonstrate that active immunopharmacotherapy for METH attenuates the acquisition of METH self-administration

Immunoediting role for major vault protein in apoptotic signaling induced by bacterial N-acyl homoserine lactones

© 2021 National Academy of Sciences. All rights reserved.The major vault protein (MVP) mediates diverse cellular responses, including cancer cell resistance to chemotherapy and protection against inflammatory responses to Pseudomonas aeruginosa. Here, we report the use of photoactive probes to identify MVP as a target of the N-(3-oxo-dodecanoyl) homoserine lactone (C12), a quorum sensing signal of certain proteobacteria including P. aeruginosa. A treatment of normal and cancer cells with C12 or other N-acyl homoserine lactones (AHLs) results in rapid translocation of MVP into lipid raft (LR) membrane fractions. Like AHLs, inflammatory stimuli also induce LR-localization of MVP, but the C12 stimulation reprograms (functionalizes) bioactivity of the plasma membrane by recruiting death receptors, their apoptotic adaptors, and caspase-8 into LR. These functionalized membranes control AHL-induced signaling processes, in that MVP adjusts the protein kinase p38 pathway to attenuate programmed cell death. Since MVP is the structural core of large particles termed vaults, our findings suggest a mechanism in which MVP vaults act as sentinels that fine-tune inflammation-activated processes such as apoptotic signaling mediated by immunosurveillance cytokines including tumor necrosis factor-related apoptosis inducing ligand (TRAIL)

Structure and Properties of Nanoparticles Formed by Ion Implantation

This chapter broadly describes the formation, basic microstructure, and fundamental optoelectronic properties of nanocomposites synthesized by ion implantation. It is not meant as a complete literature survey and by no means includes all references on a subject that has seen a considerable amount of research effort in the past 15 years. However, it should be a good starting point for those new to the field and in a concise way summarize the main lines of research by discussing the optical, magnetic, and smart properties of these nanoparticles and the dependence of these properties on the overall microstructure. The chapter concludes with an outlook for the future