13 research outputs found
In the dedicated pursuit of dedicated capital: restoring an indigenous investment ethic to British capitalism
Tony Blair’s landslide electoral victory on May 1 (New Labour Day?) presents the party in power with a rare, perhaps even unprecedented, opportunity to revitalise and modernise Britain’s ailing and antiquated manufacturing economy.* If it is to do so, it must remain true to its long-standing (indeed, historic) commitment to restore an indigenous investment ethic to British capitalism. In this paper we argue that this in turn requires that the party reject the very neo-liberal orthodoxies which it offered to the electorate as evidence of its competence, moderation and ‘modernisation’, which is has internalised, and which it apparently now views as circumscribing the parameters of the politically and economically possible
Single-Quantum-Dot Tracking Reveals Altered Membrane Dynamics of an Attention-Deficit/Hyperactivity-Disorder-Derived Dopamine Transporter Coding Variant
The
presynaptic, cocaine- and amphetamine-sensitive dopamine (DA)
transporter (DAT, <i>SLC6A3</i>) controls the intensity
and duration of synaptic dopamine signals by rapid clearance of DA
back into presynaptic nerve terminals. Abnormalities in DAT-mediated
DA clearance have been linked to a variety of neuropsychiatric disorders,
including addiction, autism, and attention deficit/hyperactivity disorder
(ADHD). Membrane trafficking of DAT appears to be an important, albeit
incompletely understood, post-translational regulatory mechanism;
its dysregulation has been recently proposed as a potential risk determinant
of these disorders. In this study, we demonstrate a link between an
ADHD-associated DAT mutation (Arg615Cys, R615C) and variation on DAT
transporter cell surface dynamics, a combination only previously studied
with ensemble biochemical and optical approaches that featured limited
spatiotemporal resolution. Here, we utilize high-affinity, DAT-specific
antagonist-conjugated quantum dot (QD) probes to establish the dynamic
mobility of wild-type and mutant DATs at the plasma membrane of living
cells. Single DAT-QD complex trajectory analysis revealed that the
DAT 615C variant exhibited increased membrane mobility relative to
DAT 615R, with diffusion rates comparable to those observed after
lipid raft disruption. This phenomenon was accompanied by a loss of
transporter mobilization triggered by amphetamine, a common component
of ADHD medications. Together, our data provides the first dynamic
imaging of single DAT proteins, providing new insights into the relationship
between surface dynamics and trafficking of both wild-type and disease-associated
transporters. Our approach should be generalizable to future studies
that explore the possibilities of perturbed surface DAT dynamics that
may arise as a consequence of genetic alterations, regulatory changes,
and drug use that contribute to the etiology or treatment of neuropsychiatric
disorders