Absence of aquaporin-4 expression in lesions of neuromyelitis optica but increased expression in multiple sclerosis lesions and normal-appearing white matter.

Aquaporin-4 (AQP4) has recently been implicated in the pathogenesis of neuromyelitis optica(NMO) where it has been identifed as the first defined autoantigen pertinent to an infammatory demyelinating disorder of the human CNS. Furthermore, a recent case report has shown a lack of AQP4 expression in the spinal cord lesions of NMO. However, the pattern of AQP4 expression in multiple sclerosis (MS) tissues has not been well-defned. In the present investigation we have confirmed a lack of expression of AQP4 in optic and spinal cord lesions in NMO which contrasted sharply with the increased levels of AQP4 expression seen in MS lesions. Furthermore a detailed immunohistochemical and semi-quantitative analysis is used to describe the expression pattern of AQP4 on well-characterized tissue microarray samples of MS and control white matter. Anatomically AQP4 was more highly expressed in all categories of MS tissue compared to normal control tissues with the most abundant expression in active lesions. Within active lesions AQP4 expression was significantly correlated with expression of the pro-infammatory cytokine osteopontin. At the cellular level dual-labelling immunofluoresence demonstrated that increased expression of AQP4 was most pronounced at the astrocytic endfeet but was also associated with the cell bodies of astrocytes in the tissue parenchyma. The finding of increased AQP4 expression in MS lesions in contrast to the lack of expression in NMO lesions may suggest different mechanisms of initiation and progression between the two disease states.

‘Ghosts in the Head and Ghost Towns in the Field: Ethnography and the Experience of Presence and Absence’

This article is about an anthropologist coming to terms with the field and fieldwork. In 1995, I left – was evacuated from – my fieldsite as a volcanic eruption started just as my period of fieldwork drew to a close. These eruptions dramatically and instantaneously altered life on the island of Montserrat, a British colony in the Caribbean. While Montserrat the land, and Montserratians the people, migrated and moved on with their lives, Montserrat and Montserratians were preserved in my mind and in my anthropological writings as from “back home.” Revisiting Montserrat several years into the volcano crisis, I drove through the villages and roads leading to the former capital of the island, where I had worked from. My route to this modern-day Pompeii threw up a stark contrast between absence and presence, the imagined past and the experienced present. This is understood, in part, by examining the literary work of two other travelers through Montserrat, Henry Coleridge and Pete McCarthy, both of whom have a very different experience of the place and the people.

Absence of the 7-repeat variant of the DRD4 VNTR is associated with drifting sustained attention in children with ADHD but not in controls

Many genetic studies have demonstrated an association between the 7-repeat (7r) allele of a 48-base pair variable number of tandem repeats (VNTR) in exon 3 of the DRD4 gene and the phenotype of attention deficit hyperactivity disorder (ADHD). Previous studies have shown inconsistent associations between the 7r allele and neurocognitive performance in children with ADHD. We investigated the performance of 128 children with and without ADHD on the Fixed and Random versions of the Sustained Attention to Response Task (SART). We employed timeseries analyses of reaction-time data to allow a fine-grained analysis of reaction time variability, a candidate endophenotype for ADHD. Children were grouped into either the 7r-present group (possessing at least one copy of the 7r allele) or the 7r-absent group. The ADHD group made significantly more commission errors and was significantly more variable in RT in terms of fast moment-to-moment variability than the control group, but no effect of genotype was found on these measures. Children with ADHD without the 7r allele made significantly more omission errors, were significantly more variable in the slow frequency domain and showed less sensitivity to the signal (d') than those children with ADHD the 7r and control children with or without the 7r. These results highlight the utility of time-series analyses of reaction time data for delineating the neuropsychological deficits associated with ADHD and the DRD4 VNTR. Absence of the 7-repeat allele in children with ADHD is associated with a neurocognitive profile of drifting sustained attention that gives rise to variable and inconsistent performance. (c) 2008 Wiley-Liss, Inc.

Dissolved Argon Changes the Rate of Diffusion in Room Temperature Ionic Liquids: Effect of the Presence and Absence of Argon and Nitrogen on the Voltammetry of Ferrocene

This work explores the effects of argon and nitrogen, two electrochemically and chemically inert gases frequently used in sample preparation of room temperature ionic liquid (RTIL) solutions, on the eelectrochemical characterization of ferrocene (Fc) dissolved in the RTIL 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([C(2)mim][NTf2]). Remarkably, chronoamperometrically determined diffusion coefficients of Fc in [C(2)mim][NTf2] are found to increase from 4.8 (+/- 0.2) x 10(-11) m(2) s(-1) under vacuum conditions to 6.6 (+/- 0.5) x 10(-11) m(2) s(-1) in an atmosphere of 1 atm Ar. In contrast, exposing a vacuum-purified sample to an atmosphere of 1 atm N-2 resulted in no significant change in the measured diffusion coefficient of Fc. The effect of dissolved argon on diffusion transport is unexpected and has implications in electrochemistry and elsewhere. Fc was found to volatilize under vacuum conditions. We propose, however, that evacuation of the cell by vacuum prior to electrochemical measurements being carried out is the only way to ensure that no contamination of the sample occurs, and use of an in situ method of determining the diffusion coefficient and concentration of Fc dispells,any ambiguity associated with Fc depletion by vacuum.

Inhibition of Advanced Glycation and Absence of Galectin-3 Prevent Blood-Retinal Barrier Dysfunction during Short-Term Diabetes

Breakdown of the inner blood-retinal barrier (iBRB) occurs early in diabetes and is central to the development of sight-threatening diabetic macular edema (DME) as retinopathy progresses. In the current study, we examined how advanced glycation end products (AGEs) forming early in diabetes could modulate vasopermeability factor expression in the diabetic retina and alter inter-endothelial cell tight junction (TJ) integrity leading to iBRB dysfunction. We also investigated the potential for an AGE inhibitor to prevent this acute pathology and examined a role of the AGE-binding protein galectin-3 (Gal-3) in AGE-mediated cell retinal pathophysiology. Diabetes was induced in C57/BL6 wild-type (WT) mice and in Gal-3(-/-) transgenic mice. Blood glucose was monitored and AGE levels were quantified by ELISA and immunohistochemistry. The diabetic groups were subdivided, and one group was treated with the AGE-inhibitor pyridoxamine (PM) while separate groups of WT and Gal-3(-/-) mice were maintained as nondiabetic controls. iBRB integrity was assessed by Evans blue assay alongside visualisation of TJ protein complexes via occludin-1 immunolocalization in retinal flat mounts. Retinal expression levels of the vasopermeability factor VEGF were quantified using real-time RT-PCR and ELISA. WT diabetic mice showed significant AGE -immunoreactivity in the retinal microvasculature and also showed significant iBRB breakdown (P < .005). These diabetics had higher VEGF mRNA and protein expression in comparison to controls (P < .01). PM-treated diabetics had normal iBRB function and significantly reduced diabetes-mediated VEGF expression. Diabetic retinal vessels showed disrupted TJ integrity when compared to controls, while PM-treated diabetics demonstrated near-normal configuration. Gal-3(-/-) mice showed significantly less diabetes-mediated iBRB dysfunction, junctional disruption, and VEGF expression changes than their WT counterparts. The data suggests an AGE-mediated disruption of iBRB via upregulation of VEGF in the diabetic retina, possibly modulating disruption of TJ integrity, even after acute diabetes. Prevention of AGE formation or genetic deletion of Gal-3 can effectively prevent these acute diabetic retinopathy changes.

The absence of creativity in Feist and the computational process

The decision of the U.S. Supreme Court in 1991 in Feist Publications, Inc. v. Rural Tel. Service Co. affirmed originality as a constitutional requirement for copyright. Originality has a specific sense and is constituted by a minimal degree of creativity and independent creation. The not original is the more developed concept within the decision. It includes the absence of a minimal degree of creativity as a major constituent. Different levels of absence of creativity also are distinguished, from the extreme absence of creativity to insufficient creativity. There is a gestalt effect of analogy between the delineation of the not original and the concept of computability. More specific correlations can be found within the extreme absence of creativity. "[S]o mechanical" in the decision can be correlated with an automatic mechanical procedure and clauses with a historical resonance with understandings of computability as what would naturally be regarded as computable. The routine within the extreme absence of creativity can be regarded as the product of a computational process. The concern of this article is with rigorously establishing an understanding of the extreme absence of creativity, primarily through the correlations with aspects of computability. The understanding established is consistent with the other elements of the not original. It also revealed as testable under real-world conditions. The possibilities for understanding insufficient creativity, a minimal degree of creativity, and originality, from the understanding developed of the extreme absence of creativity, are indicated.