Human immunodeficiency virus (HIV) infection of the central nervous system (CNS) can lead to cognitive dysfunction, even in individuals treated with highly active antiretroviral therapy. Using an established simian immunodeficiency virus (SIV)/macaque model of HIV CNS disease, we previously reported that infection shifts the balance of activation of mitogen-activated protein kinase (MAPK) signaling pathways in the brain, resulting in increased activation of the neurodegenerative MAPKs p38 and JNK. Minocycline treatment of SIV-infected macaques reduced the incidence and severity of SIV encephalitis in this model, and suppressed the activation of p38 in the brain. The purpose of this study was to further examine the effects of minocycline on neurodegenerative MAPK signaling. We first demonstrated that minocycline also decreases JNK activation in the brain and levels of the inflammatory mediator nitric oxide (NO). We next used NO to activate these MAPK pathways in vitro, and demonstrated that minocycline suppresses p38 and JNK activation by reducing intracellular levels, and hence, activation of apoptosis signal-regulating kinase 1 (ASK1), a MAPKKK capable of selectively activating both pathways. We then demonstrated that ASK1 activation in the brain during SIV infection is suppressed by minocycline. By suppressing p38 and JNK activation pathways, which are important for the production of and responses to inflammatory mediators, minocycline may interrupt the vicious cycle of inflammation that both results from, and promotes, virus replication in SIV and HIV CNS disease.

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The interface of biology and semiconductor materials has become an important topic of interest as researchers are merging living organisms with microelectromechanical systems (MEMS) in the pursuit of new microfabricated biomedical devices. Biological cells interface with the semiconductor surface through a host of interactions that are mediated by protein adhesion and film formation. To better understand this interface, we have conducted protein adsorption studies of a model system using bovine serum albumin (BSA) and compared it to the adsorption from a complex protein mixture of cell growth serum on uncoated and self-assembled monolayer (SAM) coated silicon wafers. Several characterization techniques -AFM, ellipsometry, water contact angle, and fluorescence microscopy -were used to evaluate the protein-adsorbed layer. An uncoated silicon surface was most attractive to proteins, forming a 70 Å thick film from a solution of BSA at a concentration comparable to that in cell growth serum. Coating with the hydrophobic octadecyltrimethoxysilane (OTMS) SAM reduced protein adhesion by ~15%. In contrast, a hydrophilic N-(triethoxysilylpropyl)-O-polyethyleneoxide urethane (TESP) SAM inhibited protein adhesion by greater than 50%. Protein adhesion studies with cell growth sera containing complex mixtures of proteins paralleled the BSA adsorption studies, clearly identifying the TESP coated surface as a promising biocompatible coating.4

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