Putting the Text back into Context: A Codicological Approach to Manuscript Transcription

Textual scholars have tended to produce editions which present the text without its manuscript context. Even though digital editions now often present single-witness editions with facsimiles of the manuscripts, nevertheless the text itself is still transcribed and represented as a linguistic object rather than a physical one. Indeed, this is explicitly stated as the theoretical basis for the de facto standard of markup for digital texts: the Guidelines of the Text Encoding Initiative (TEI). These explicitly treat texts as semantic units such as paragraphs, sentences, verses and so on, rather than physical elements such as pages, openings, or surfaces, and some scholars have argued that this is the only viable model for representing texts. In contrast, this chapter presents arguments for considering the document as a physical object in the markup of texts. The theoretical arguments of what constitutes a text are first reviewed, with emphasis on those used by the TEI and other theoreticians of digital markup. A series of cases is then given in which a document-centric approach may be desirable, with both modern and medieval examples. Finally a step forward in this direction is raised, namely the results of the Genetic Edition Working Group in the Manuscript Special Interest Group of the TEI: this includes a proposed standard for documentary markup, whereby aspects of codicology and mise en page can be included in digital editions, putting the text back into its manuscript context

Understanding the role of P2X7 in affective disorders—are glial cells the major players?

Pathophysiology associated with several psychiatric disorders has been linked to inflammatory biomarkers. This has generated a theory of major depressive disorders as an inflammatory disease. The idea of pro-inflammatory cytokines altering behavior is now well accepted however many questions remain. Microglia can produce a plethora of inflammatory cytokines and these cells appear to be critical in the link between inflammatory changes and depressive disorders. Microglia play a known role in sickness behavior which has many components of depressive-like behavior such as social withdrawal, sleep alterations, and anorexia. Numerous candidate genes have been identified for psychiatric disorders in the last decade. Single nucleotide polymorphisms (SNPs) in the human P2X7 gene have been linked to bipolar disorder, depression, and to the severity of depressive symptoms. P2X7 is a ligand-gated cation channel expressed on microglia with lower levels found on astrocytes and on some neuronal populations. In microglia P2X7 is a major regulator of pro-inflammatory cytokines of the interleukin-1 family. Genetic deletion of P2X7 in mice is protective for depressive behavior in addition to inflammatory responses. P2X7−/− mice have been shown to demonstrate anti-depressive-like behavior in forced swim and tail suspension behavioral tests and stressor-induced behavioral responses were blunted. Both neurochemical (norepinephrine, serotonin, and dopamine) and inflammatory changes have been observed in the brains of P2X7−/− mice. This review will discuss the recent evidence for involvement of P2X7 in the pathophysiology of depressive disorders and propose mechanisms by which altered signaling through this ion channel may affect the inflammatory state of the brain

Modulation of TGF-beta signaling by proinflammatory cytokines in articular chondrocytes.

OBJECTIVE: The normal structure and function of articular cartilage are the result of a precisely balanced interaction between anabolic and catabolic processes. The transforming growth factor-beta (TGF-beta) family of growth factors generally exerts an anabolic or repair response; in contrast, proinflammatory cytokines such as interleukin 1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) exert a strong catabolic effect. Recent evidence has shown that IL-1beta, and TNF-alpha, and the TGF-beta signaling pathways share an antagonistic relationship. The aim of this study was to determine whether the modulation of the response of articular chondrocytes to TGF-beta by IL-1beta or TNF-alpha signaling pathways occurs through regulation of activity and availability of mothers against DPP (Drosophila) human homologue (Smad) proteins. METHODS: Human articular chondrocytes isolated from knee joints from patients with osteoarthritis (OA) or normal bovine chondrocytes were cultured in suspension in poly-(2-hydroxyethyl methacrylate)-coated dishes with either 10% fetal bovine serum media or serum-deprived media 6h before treatment with IL-1beta alone, TNF-alpha alone or IL-1beta followed by TGF-beta. Nuclear extracts were examined by electrophoretic mobility-shift assays (EMSA) for nuclear factor-kappa B (NF-kappaB) and Smad3/4 deoxyribonucleic acid (DNA) binding. Nuclear extracts were also subjected to the TranSignal Protein/DNA array (Panomics, Redwood City, CA) enabling the simultaneous semiquantitative assessment of DNA-binding activity of 54 different transcription factors. Nuclear phospho-Smad2/3 and total Smad7 protein expression in whole cell lysates were studied by Western blot. Cytoplasmic Smad7, type II collagen alpha 1 (COL2A1), aggrecan and SRY-related high mobility group-Box gene 9 (SOX-9) mRNA expression were measured by real-time polymerase chain reaction (PCR). RESULTS: The DNA-binding activity of Smad3/4 in the TranSignal Protein/DNA array was downregulated by TNF-alpha (46%) or IL-1beta treatment (42%). EMSA analysis showed a consistent reduction in Smad3/4 DNA-binding activity in human articular chondrocytes treated with IL-1beta or TNF-alpha. TGF-beta-induced Smad3/4 DNA-binding activity and Smad2/3 phosphorylation were also reduced following pretreatment with IL-1beta in human OA and bovine chondrocytes. Real-time PCR and Western blot analysis showed that IL-1beta partially reversed the TGF-beta stimulation of Smad7 mRNA and protein levels in TGF-beta-treated human OA cells. In contrast, TGF-beta-stimulated COL2A1, aggrecan, and SOX-9 mRNA levels were abrogated by IL-1beta. CONCLUSIONS: IL-1beta or TNF-alpha exerted a suppressive effect on Smad3/4 DNA-binding activity in human articular chondrocytes, as well as on TGF-beta-induced stimulation of Smad3/4 DNA-binding activity and Smad2/3 phosphorylation in human OA and bovine articular chondrocytes. IL-1beta partially reversed the increase in TGF-beta-stimulated Smad7 mRNA or protein levels suggesting that Smad7 may not be involved in the suppression of TGF-beta signaling induced by IL-1beta or TNF-alpha in articular chondrocytes. The balance between the IL-1beta or TNF-alpha and the TGF-beta signaling pathways is crucial for maintenance of articular cartilage homeostasis and its disruption likely plays a substantial role in the pathogenesis of OA

ECONOMIC EVALUATION OF INCOME PROTECTION CHOICES FOR WEST TENNESSEE CORN PRODUCERS

Farmers need information about the expected value and variability of net revenues for alternative crop insurance and futures hedging strategies to manage risk. Specifically, the model will determine which risk management strategies are most desirable under various levels of risk aversion. The unstable futures basis relation in the data used in the simulation model contributed to increased variability of net revenues. In general, none of the crop insurance or hedging strategies markedly reduced variability of net revenue and relative riskiness when compared with the cash strategy. Revenue Assurance strategies were the most effective at setting a floor on net revenues. As a result, Revenue Assurance products may perform well for extremely risk averse producers.Marketing, Risk and Uncertainty,

The Vision of Leofric: Manuscript, Text and Context

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The Regius Psalter, Folio 198v: A Reexamination

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King Edgar's Charter for Pershore (AD 972)

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