85 research outputs found
3D Brownian Diffusion of Submicron-Sized Particle Clusters
We report on the translation and rotation of particle clusters made through
the combination of spherical building blocks. These clusters present ideal
model systems to study the motion of objects with complex shape. Because they
could be separated into fractions of well-defined configurations on a
sufficient scale and their overall dimensions were below 300 nm, the
translational and rotational diffusion coefficients of particle duplets,
triplets and tetrahedrons could be determined by a combination of polarized
dynamic light scattering (DLS) and depolarized dynamic light scattering (DDLS).
The use of colloidal clusters for DDLS experiments overcomes the limitation of
earlier experiments on the diffusion of complex objects near surfaces because
the true 3D diffusion can be studied. When the exact geometry of the complex
assemblies is known, different hydrodynamic models for calculating the
diffusion coefficient for objects with complex shapes could be applied. Because
hydrodynamic friction must be restricted to the cluster surface the so-called
shell model, in which the surface is represented as a shell of small friction
elements, was most suitable to describe the dynamics. A quantitative comparison
of the predictions from theoretical modeling with the results obtained by DDLS
showed an excellent agreement between experiment and theory
Dysregulation of Macrophage-Secreted Cathepsin B Contributes to HIV-1-Linked Neuronal Apoptosis
Chronic HIV infection leads to the development of cognitive impairments, designated as HIV-associated neurocognitive disorders (HAND). The secretion of soluble neurotoxic factors by HIV-infected macrophages plays a central role in the neuronal dysfunction and cell death associated with HAND. One potentially neurotoxic protein secreted by HIV-1 infected macrophages is cathepsin B. To explore the potential role of cathepsin B in neuronal cell death after HIV infection, we cultured HIV-1ADA infected human monocyte-derived macrophages (MDM) and assayed them for expression and activity of cathepsin B and its inhibitors, cystatins B and C. The neurotoxic activity of the secreted cathepsin B was determined by incubating cells from the neuronal cell line SK-N-SH with MDM conditioned media (MCM) from HIV-1 infected cultures. We found that HIV-1 infected MDM secreted significantly higher levels of cathepsin B than did uninfected cells. Moreover, the activity of secreted cathepsin B was significantly increased in HIV-infected MDM at the peak of viral production. Incubation of neuronal cells with supernatants from HIV-infected MDM resulted in a significant increase in the numbers of apoptotic neurons, and this increase was reversed by the addition of either the cathepsin B inhibitor CA-074 or a monoclonal antibody to cathepsin B. In situ proximity ligation assays indicated that the increased neurotoxic activity of the cathepsin B secreted by HIV-infected MDM resulted from decreased interactions between the enzyme and its inhibitors, cystatins B and C. Furthermore, preliminary in vivo studies of human post-mortem brain tissue suggested an upregulation of cathepsin B immunoreactivity in the hippocampus and basal ganglia in individuals with HAND. Our results demonstrate that HIV-1 infection upregulates cathepsin B in macrophages, increases cathepsin B activity, and reduces cystatin-cathepsin interactions, contributing to neuronal apoptosis. These findings provide new evidence for the role of cathepsin B in neuronal cell death induced by HIV-infected macrophages
Optimal taxation of flow pollutants when firms may also inflict catastrophic environmental damage
Global warming and the evaluation of fuel substitution strategies:on why policy should be left to the politicians
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