Albendazole and antibiotics synergize to deliver short-course anti-Wolbachiacurative treatments in preclinical models of filariasis

Elimination of filariasis requires a macrofilaricide treatment that can be delivered within a 7-day period. Here we have identified a synergy between the anthelmintic albendazole (ABZ) and drugs depleting the filarial endosymbiont Wolbachia, a proven macrofilaricide target, which reduces treatment from several weeks to 7 days in preclinical models. ABZ had negligible effects on Wolbachia but synergized with minocycline or rifampicin (RIF) to deplete symbionts, block embryogenesis, and stop microfilariae production. Greater than 99% Wolbachia depletion following 7-day combination of RIF+ABZ also led to accelerated macrofilaricidal activity. Thus, we provide preclinical proof-of-concept of treatment shortening using antibiotic+ABZ combinations to deliver anti-Wolbachia sterilizing and macrofilaricidal effects. Our data are of immediate public health importance as RIF+ABZ are registered drugs and thus immediately implementable to deliver a 1-wk macrofilaricide. They also suggest that novel, more potent anti-Wolbachia drugs under development may be capable of delivering further treatment shortening, to days rather than weeks, if combined with benzimidazoles

The right to buy a piece of the public sphere: adbusters v. the media

Bibliography: p. 90-94Includes copy of ethics approval. Original copy with original Partial Copyright Licence.This thesis examines public communicative access rights in the public sphere of Canadian television, using the unresolved Adbusters court case as a reference point. This Charier case challenges the right of private and public broadcasters to arbitrarily decide who can and cannot purchase commercial airtime, which Adbusters claims is a violation of its right to freedom of expression in a public space (i.e. the public airwaves). Jn the context of relevant Canadian laws, policies and judicial decisions, the question of 'who should have the right to purchase commercial airtime on publicly owned but privately controlled airwaves?' is examined and compared from a legal perspective and from the theoretical concept of the public sphere. This legal issue raises some significant questions about the inherent relationship between the public sphere, democracy and communication. This thesis investigates the Canadian perspective and discusses some of the underlying tensions and contradictions it reveals

Oxidative Stress Promotes Eating Behavior and Obesity in C. elegans via EGL-4 / DAF-16 Signaling

Oxidative stress is associated with pathophysiological progress of many diseases. The objective of study was to investigate whether increased environmental oxidative stress stimulation can promote excessive eating behavior, a common cause of obesity, and to identify the molecular mechanism.The cGMP-dependent kinase (PKG) activator 8-pCPT-cGMP was applied in worm swimming assay to study behavior shifting between quiescence and foraging in C. elegans. Genetically modified C. elegans (egl-4 loss or gain of function, and daf-16 mutant) were treated with paraquat, an oxidative stress inducer. Worm’s foraging behavior, body fat accumulation and body length were determined. The foxo1::gfp-transfectedHEK293 cells and C. elegans (daf-16::gfpTJ356) were further used to examine the effect of paraquat on PKG expression and FOXO nuclear translocation.A novel swimming assay using PKGactivator stimulation was developed, which allows the rapid and effective study of foraging behavior in C. elegans. Paraquat treatment significantly inhibited quiescence, promoted foraging behavior, increased body fat accumulation and body growth. These responses were associated with diminished PKG expression/activation and increased FOXO (DAF-16) nuclear translocation in both transfected C. elegans and HEK293 cells.Our data suggest that PKG/FOXO signaling may plays an important role in mediating oxidative stress-induced excessive eating behavior and obesity development

Oxidative Stress Promotes Eating Behavior and Obesity in C. elegans via EGL-4 / DAF-16 Signaling

Oxidative stress is associated with pathophysiological progress of many diseases. The objective of study was to investigate whether increased environmental oxidative stress stimulation can promote excessive eating behavior, a common cause of obesity, and to identify the molecular mechanism.The cGMP-dependent kinase (PKG) activator 8-pCPT-cGMP was applied in worm swimming assay to study behavior shifting between quiescence and foraging in C. elegans. Genetically modified C. elegans (egl-4 loss or gain of function, and daf-16 mutant) were treated with paraquat, an oxidative stress inducer. Worm’s foraging behavior, body fat accumulation and body length were determined. The foxo1::gfp-transfectedHEK293 cells and C. elegans (daf-16::gfpTJ356) were further used to examine the effect of paraquat on PKG expression and FOXO nuclear translocation.A novel swimming assay using PKGactivator stimulation was developed, which allows the rapid and effective study of foraging behavior in C. elegans. Paraquat treatment significantly inhibited quiescence, promoted foraging behavior, increased body fat accumulation and body growth. These responses were associated with diminished PKG expression/activation and increased FOXO (DAF-16) nuclear translocation in both transfected C. elegans and HEK293 cells.Our data suggest that PKG/FOXO signaling may plays an important role in mediating oxidative stress-induced excessive eating behavior and obesity development