Fluoroquinolone antibiotics have been known to cause severe, multisystem adverse side effects, termed fluoroquinolone toxicity (FQT). This toxicity syndrome can present with adverse effects that vary from individual to individual, including effects on the musculoskeletal and nervous systems, among others. The mechanism behind FQT in mammals is not known, although various possibilities have been investigated. Among the hypothesized FQT mechanisms, those that could potentially explain multisystem toxicity include off-target mammalian topoisomerase interactions, increased production of reactive oxygen species, oxidative stress, and oxidative damage, as well as metal chelating properties of FQs. This review presents relevant information on fluoroquinolone antibiotics and FQT and explores the mechanisms that have been proposed. A fluoroquinolone-induced increase in reactive oxygen species and subsequent oxidative stress and damage presents the strongest evidence to explain this multisystem toxicity syndrome. Understanding the mechanism of FQT in mammals is important to aid in the prevention and treatment of this condition.
Viral protein U (Vpu) is a type-III integral membrane protein encoded by Human Immunodeficiency Virus-1 (HIV- 1). It is expressed in infected host cells and plays several roles in viral progeny escape from infected cells, including down-regulation of CD4 receptors. But key structure/function questions remain regarding the mechanisms by which the Vpu protein contributes to HIV-1 pathogenesis. Here we describe expression of Vpu in bacteria, its purification and characterization. We report the successful expression of PelB-Vpu in Escherichia coli using the leader peptide pectate lyase B (PelB) from Erwinia carotovora. The protein was detergent extractable and could be isolated in a very pure form. We demonstrate that the PelB signal peptide successfully targets Vpu to the cell membranes and inserts it as a type I membrane protein. PelB-Vpu was biophysically characterized by circular dichroism and dynamic light scattering experiments and was shown to be an excellent candidate for elucidating structural models.
since the late 1990s, with the ultimate goal of improving the multi-threat capabilities of
traditional soft-body armor while significantly improving its protective efficiency - the amount
of layers of armor material required to defeat threats. To create a novel, superior materials
system to reinforce Kevlar armor for the Norica Capstone project, this thesis set out to
synthesize, recover, and characterize zinc oxide nanowire colloids.
The materials synthesized were successfully utilized in the wider Capstone effort to
dramatically enhance the protective abilities of Kevlar, while the data obtained on the 14
hydrothermal synthesis attempts and numerous challenges at recovery provided critical
information on the synthesis parameters involved in the reliable, scalable mass production of the
nanomaterial additive. Additionally, recovery was unconventionally facilitated in the absence of
a vacuum filtration apparatus with nanoscale filters by intentionally inducing electrostatic
agglomeration of the nanowires during standard gravity filtration. The subsequent application of
these nanowires constituted a pioneering use in the production of nanowire-reinforced
STF-based Kevlar coatings, and support the future development and, ultimately, the
commercialization of lighter and more-protective soft armor systems.