2 research outputs found
Oligovalent Amyloid-Binding Agents Reduce SEVI-Mediated Enhancement of HIV-1 Infection
This paper evaluates the use of oligovalent amyloid-binding
molecules
as potential agents that can reduce the enhancement of human immunodeficiency
virus-1 (HIV-1) infection in cells by semen-derived enhancer of virus
infection (SEVI) fibrils. These naturally occurring amyloid fibrils
found in semen have been implicated as mediators that can facilitate
the attachment and internalization of HIV-1 virions to immune cells.
Molecules that are capable of reducing the role of SEVI in HIV-1 infection
may, therefore, represent a novel strategy to reduce the rate of sexual
transmission of HIV-1 in humans. Here, we evaluated a set of synthetic,
oligovalent derivatives of benzothiazole aniline (BTA, a known amyloid-binding
molecule) for their capability to bind cooperatively to aggregated
amyloid peptides and to neutralize the effects of SEVI in HIV-1 infection.
We demonstrate that these BTA derivatives exhibit a general trend
of increased binding to aggregated amyloids as a function of increasing
valence number of the oligomer. Importantly, we find that oligomers
of BTA show improved capability to reduce SEVI-mediated infection
of HIV-1 in cells compared to a BTA monomer, with the pentamer exhibiting
a 65-fold improvement in efficacy compared to a previously reported
monomeric BTA derivative. These results, thus, support the use of
amyloid-targeting molecules as potential supplements for microbicides
to curb the spread of HIV-1 through sexual contact
Investigating the Geochemical Model for Molybdenum Mineralization in the JEB Tailings Management Facility at McClean Lake, Saskatchewan: An X‑ray Absorption Spectroscopy Study
The
geochemical model for Mo mineralization in the JEB Tailings
Management Facility (JEB TMF), operated by AREVA Resources Canada
at McClean Lake, Saskatchewan, was investigated using X-ray Absorption
Near-Edge Spectroscopy (XANES), an elemental-specific technique that
is sensitive to low elemental concentrations. Twenty five samples
collected during the 2013 sampling campaign from various locations
and depths in the TMF were analyzed by XANES. Mo K-edge XANES analysis
indicated that the tailings consisted primarily of Mo<sup>6+</sup> species: powellite (CaMoO<sub>4</sub>), ferrimolybdite (Fe<sub>2</sub>(MoO<sub>4</sub>)<sub>3</sub>·8H<sub>2</sub>O), and molybdate
adsorbed on ferrihydrite (FeÂ(OH)<sub>3</sub> – MoO<sub>4</sub>). A minor concentration of a Mo<sup>4+</sup> species in the form
of molybdenite (MoS<sub>2</sub>) was also present. Changes in the
Mo mineralization over time were inferred by comparing the relative
amounts of the Mo species in the tailings to the independently measured
aqueous Mo pore water concentration. It was found that ferrimolybdite
and molybdate adsorbed on ferrihydrite initially dissolves in the
TMF and precipitates as powellite