Ascorbic acid induces an oxidative stress in CCRF cells activating the transcription factors AP-1 and NFRB

We have previously tested the effects of high dose AA supplements on human volunteers in terms of reducing DNA damage, as a possible mechanism of the vitamin’s proposed protective effect against cancer and detected a transient, pro-oxidant effect at high doses (500 mg/day). Herein, we present evidence of a pro-oxidant effect of the vitamin when added to CCRF cells at extracellular concentrations which mimic those present in human serum in vivo (50–150AM). The activation of the transcription factor AP-1 was optimal at 100 AM AA following 3h exposure at 37jC. A minimum dose of 50 AM of AA activated NFnB but there appeared to be no dose-dependent effect. Increases of 2–3 fold were observed for both transcription factors when cells were exposed to 100 AM AA for 3h, comparing well with the pro-oxidant effect of H2O2 at similar concentrations. In parallel experiments the activation of AP-1 (binding to DNA) was potentiated when cells were pre-incubated with AA prior to exposure with H2O2. Cycloheximide pretreatment (10 Ag/ml for 15min) caused a 50% inhibition of AP-1 binding to DNA suggesting that it was due to a combination of increasing the binding of pre-existing Fos and Jun and an increase in their de novo synthesis. Cellular localisation was confirmed by immunocytochemistry using antibodies specific for c-Fos and c-Jun proteins. These results suggest that extracellular AA can elicit an intracellular stress response resulting in the activation of the oxidative stress-responsive transcription factors AP-1 and NFnB. These transcription factors are involved in the induction of genes associated with an oxidative stress response, cell cycle arrest and DNA repair confirmed by our cDNA microarray analysis (Affymetrix). This may explain the abilty for AA to appear to inhibit 8-oxodG, yet simultaneously generate another oxidative stress biomarker, 8-oxo-dA. These results suggest a completely novel DNA repair action for AA. Whether this action is relevant to our in vivo findings will be the subject of our future research.

Online digital special collections in English universities: promoting awareness

Cultural institutions in the UK are repositories of a wealth of historical material. The scholarly importance of such resources is at the basis of the numerous digitisation projects aimed at widening their access worldwide. The lack of national policies has left those institutions alone in engaging in dissemination activities and in raising awareness of their own online material. Of particular interest to the author are the digital special collections hosted in the English Universities. The main activities of these institutions differ from others, such as museums, archives and public libraries, as they do not have the main institutional duties of preserving and the exploiting of their holdings. This article highlights related issues and suggests some of the possible measures to effectively promote and disseminate universities’ online digital special collections.

Online digital special collections in English universities: promoting awareness

Cultural institutions in the UK are repositories of a wealth of historical material. The scholarly importance of such resources is at the basis of the numerous digitisation projects aimed at widening their access worldwide. The lack of national policies has left those institutions alone in engaging in dissemination activities and in raising awareness of their own online material. Of particular interest to the author are the digital special collections hosted in the English Universities. The main activities of these institutions differ from others, such as museums, archives and public libraries, as they do not have the main institutional duties of preserving and the exploiting of their holdings. This article highlights related issues and suggests some of the possible measures to effectively promote and disseminate universities’ online digital special collections.

Pituitary adenylate cyclase-activating polypeptide type 1 receptor (PAC1) gene is suppressed by transglutaminase 2 activation

Pituitary adenylate cyclase-activating polypeptide (PACAP) functions as a neuroprotective factor through the PACAP type 1 receptor, PAC1. In a previous work, we demonstrated that nerve growth factor augmented PAC1 gene expression through the activation of Sp1 via the Ras/MAPK pathway. We also observed that PAC1 expression in Neuro2a cells was transiently suppressed during in vitro ischemic conditions, oxygen-glucose deprivation (OGD). Because endoplasmic reticulum (ER) stress is induced by ischemia, we attempted to clarify how ER stress affects the expression of PAC1. Tunicamycin, which induces ER stress, significantly suppressed PAC1 gene expression, and salubrinal, a selective inhibitor of the protein kinase RNA-like endoplasmic reticulum kinase signaling pathway of ER stress, blocked the suppression. In luciferase reporter assay, we found that two Sp1 sites were involved in suppression of PAC1 gene expression due to tunicamycin or OGD. Immunocytochemical staining demonstrated that OGD-induced transglutaminase 2 (TG2) expression was suppressed by salubrinal or cystamine, a TG activity inhibitor. Further, the OGD-induced accumulation of cross-linked Sp1 in nuclei was suppressed by cystamine or salubrinal. Together with cystamine, R283, TG2-specific inhibitor, and siRNA specific for TG2 also ameliorated OGD-induced attenuation of PAC1 gene expression. These results suggest that Sp1 cross-linking might be crucial in negative regulation of PAC1 gene expression due to TG2 in OGD-induced ER stress. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

Interactive exploration of image collections on mobile devices

Image collections are ever growing and hence visual information is becoming more and more important. Moreover, the classical paradigm of taking pictures has changed, first with the spread of digital cameras and, more recently, with mobile devices equipped with integrated cameras. Clearly, these image repositories need to be managed, and tools for effectively and efficiently searching image databases are highly sought after, especially on mobile devices where more and more images are being stored. In this paper, we present an image browsing system for interactive exploration of image collections on mobile devices. Images are arranged so that visually similar images are grouped together while large image repositories become accessible through a hierarchical, browsable tree structure, arranged on a hexagonal lattice. The developed system provides an intuitive and fast interface for navigating through image databases using a variety of touch gestures. © 2012 Springer-Verlag.

Interactive browsing of image collections on mobile devices

Image collections are growing at a rapid rate and hence visual information is becoming more and more important. Clearly, these image repositories need to be managed, and tools for effectively and efficiently searching image databases are highly sought after, especially on mobile devices where more and more images are being stored. In this paper, we present an image browsing system for interactive exploration of image collections on mobile devices. Images are arranged so that visually similar images are grouped together while large image repositories become accessible through a hierarchical, browsable tree structure, arranged on a hexagonal lattice. The developed system provides an intuitive and fast interface for navigating through image databases using a variety of touch gestures.