HIV-1 Nef is expressed in astrocytes, but a contribution to neuropathogenesis and the development of HIV-associated dementia (HAD) remains uncertain. To determine the neuropathogenic actions of the HIV-1 Nef protein, the brain-derived (YU-2) and blood-derived (NL4-3) Nef proteins were expressed in neural cells using an alphavirus vector, which resulted in astrocyte death (P < 0.001). Supernatants from Nef-expressing astrocytes also caused neuronal death, suggesting the release of neurotoxic molecules by astrocytes. Analysis of pro-inflammatory gene induction in astrocytes expressing Nef revealed increased IP-10 mRNA expression (4000-fold) that was Nef sequence dependent. Recombinant IP-10 caused selective cell death in neurons (P < 0.001) but not astrocytes, and the cytotoxicity of supernatant from astrocytes expressing Nef YU-2 was blocked by an antibody directed against the chemokine receptor CXCR3 (P < 0.001). SCID/NOD mice implanted with a Nef YU-2-expressing vector displayed abnormal motor behavior (P < 0.05), neuroinflammation, and neuronal loss relative to controls. Analysis of mRNA levels in brains from patients with HAD also revealed increased expression of IP-10 (P < 0.05), which was confirmed by immunoreactivity detected principally in astrocytes. Phylogenetic and protein structure analyses of Nef sequences derived from HIV/AIDS patients with and without HAD suggested viral evolution toward a neurotropic Nef protein. These results indicate that HIV-1 Nef contributes to neuropathogenesis by directly causing astrocyte death together with indirect neuronal death through the cytotoxic actions of IP-10 on neurons. Furthermore, Nef molecular diversity was evident in brain tissue among patients with neurological disease and which may influence IP-10 production by astrocytes.

The kinetics of water uptake and redistribution in several soils and their components are studied using NMR relaxometry. Unlike the normal behavior observed in stable porous media, entry into micropores in the soil is a slow process as compared to entry into macro- and mesopores. This indicates that soils air-dried at ambient temperature include gel phases that have collapsed or reoriented, closing micropores, during drying. Wetting must then include the swelling processes that re-open micropores. This can even exhibit temperature dependence giving an "apparent activation energy" comparable to that of a chemical reaction, for example, ester hydrolysis. The processes of micropore opening may play a role in slow uptake of contaminants into soils.

Minocycline has immunomodulatory and neuroprotective activities in vitro and in an animal model of multiple sclerosis (MS). We have previously reported that minocycline decreased gadolinium-enhancing activity over six months in a small trial of patients with active relapsing-remitting MS (RRMS). Here we report the impact of oral minocycline on clinical and magnetic resonance imaging (MRI) outcomes and serum immune molecules in this cohort over 24 months of open-label minocycline treatment. Despite a moderately high pretreatment annualized relapse rate (1.3/year pre-enrolment; 1.2/year during a three-month baseline period) prior to treatment, no relapses occurred between months 6 and 24. Also, despite very active MRI activity pretreatment (19/40 scans had gadolinium-enhancing activity during a three-month run-in), the only patient with gadolinium-enhancing lesions on MRI at 12 and 24 months was on half-dose minocycline. Levels of the p40 subunit of interleukin (IL)-12, which at high levels might antagonize the proinflammatory IL-12 receptor, were elevated over 18 months of treatment, as were levels of soluble vascular cell adhesion molecule-1. The activity of matrix metalloproteinase-9 was decreased by treatment. Thus, clinical and MRI outcomes are supported by systemic immunological changes and call for further investigation of minocycline in MS.

Petroleum-induced water repellency in soils is a problem that has been thought to develop randomly following contamination and then remediation of a site with petroleum. The emergence of the phenomenon can occur within months or years of original contamination and with seemingly no warning. Low-field NMR has been used to study these soils and, specifically, the processes of water uptake that occur in them. Critical aspects in the development of this phenomenon have been identified as well--specifically, a dependence on climatic events in the area and contamination levels that contribute are suggested.

Soil from the Ellerslie site of experimental oil contamination in Alberta developed water repellency some years after initial remediation. The water-repellent soils were compared to clean soils and contaminated but wettable soils by solid-state nuclear magnetic resonance (NMR). The effects of extraction with CH2Cl2 (for petroleum hydrocarbons), NaOH (for natural organic matter), and 2-propanol/ammonia (IPA/NH3) on wettability were evaluated by the molarity of the ethanol droplet (MED) test. Soil extracts and whole soils, after extraction, were examined using NMR and Fourier transform infrared spectroscopy (FTIR). On the basis of the structure--MED correlations, a model of a thin-layer natural organic matter--petroleum products complex formed under strong drying conditions is proposed to account for the development of water repellency. Studies of two similar soils from accidental oil spills are supportive.

Environmental Context.Soil uptake of xenobiotics (e.g. pesticides) can be a complex phenomenon where it is useful to distinguish readily reversible sorption from longer-term retention. A scheme for doing this using fluorescence detection is presented here, along with application to uptake of a model compound in clean and oil-contaminated soils. Both the wetting of the soil and the size of the xenobiotic seem to be important. The present data concern uptake. Desorption is expected to exhibit dependencies on similar factors. The data have implications for understanding persistence. Abstract.Description of sorption of xenobiotics (e.g. pesticides) into soils requires identification of at least two kinetic components. In the present work, the distinction between ‘labile’ (readily reversible) and ‘non-labile’ (not reversible) uptake was extended, introducing a fluorescence-based method using 9-anthracenepropionic acid as a probe molecule. Study of clean, oil-contaminated wettable, and water-repellent oil-contaminated soils has given new perspectives into the role that water plays in xenobiotic uptake. Non-labile uptake is unimportant in the water-repellent soils; however, non-labile components are observed in both clean and wettable oil-contaminated samples, supporting earlier suggestions that water plays a role in non-labile uptake processes. A soil pre-exposed to water exhibited different labile sorption behavior from one where xenobiotic was added simultaneously with water to an air-dried soil. The comparatively rapid non-labile component of uptake (3 days) of 9-anthracenepropanoic acid by a clean soil contrasted with much longer times in earlier studies of 2,4-D and atrazine. This pointed to another factor influencing the sorption phenomenon. Literature data supports a suggestion that the non-labile component of xenobiotic sorption may be more strongly influenced by the size of the xenobiotic than by the structure (e.g. polarity) of the xenobiotic or soil composition.