Identification of hepatitis a virus mimotopes by phage display, antigenicity and immunogenicity

A phage-displayed peptide approach was used to identify ligands mimicking antigenic determinants of hepatitis A virus (HAV) for the first time. Bacteriophages displaying HAV mimotopes were isolated from a phage-display peptide library by affinity selection on serum antibodies from hepatitis A patients. Selected phage-peptides were screened for reactivity with sera from HAV infected patients and healthy controls. Four cloned peptides with different sequences were identified as mimotopes of HAV; three of them showed similarity in their amino acid sequences with at least one of the VP3 and VP1 antigenic proteins of HAV. One clone was recognised by 92% of the positive sera. The phagotopes competed effectively with HAV for absorption of anti-HAV-specific antibodies in human sera, as determined by ELISA. The four phage clones induced neutralising anti-HAV antibodies in immunised mice. These results demonstrate the potential of this method to elucidate the disease related epitopes of HAV and to use these mimotopes in diagnostic applications or in the development of a mimotope-based hepatitis A vaccine without the necessity of manipulation of the virus

Gene Expression Changes in GABAA Receptors and Cognition Following Chronic Ketamine Administration in Mice

Ketamine is a well-known anesthetic agent and a drug of abuse. Despite its widespread use and abuse, little is known about its long-term effects on the central nervous system. The present study was designed to evaluate the effect of long-term (1- and 3-month) ketamine administration on learning and memory and associated gene expression levels in the brain. The Morris water maze was used to assess spatial memory and gene expression changes were assayed using Affymetrix Genechips; a focus on the expression of GABAA receptors that mediate a tonic inhibition in the brain, was confirmed by quantitative real-time PCR and western blot. Compared with saline controls, there was a decline in learning and memory performance in the ketamine-treated mice. Genechip results showed that 110 genes were up-regulated and 136 genes were down-regulated. An ontology analysis revealed the most significant effects of ketamine were on GABAA receptors. In particular, there was a significant up-regulation of both mRNA and protein levels of the alpha 5 subunit (Gabra5) of the GABAA receptors in the prefrontal cortex. In conclusion, chronic exposure to ketamine impairs working memory in mice, which may be explained at least partly by up-regulation of Gabra5 subunits in the prefrontal cortex

Research through design and digital humanities in practice: What, how and who in an archive research project

This article highlights shared methods, questions, and challenges between Research Through Design (RtD) and Digital Humanities (DH) through the discussion of an archival research project. In DH, debates continue e.g. in (Gold, Debates in the Digital Humanities. University of Minnesota Press, 2012) regarding the impact of digital technologies on epistemology, methodology, and our professional identities as researchers, scholars, academics, and teachers. Our reading of this debate is that there is a tripartite relationship between the kind of work we should call DH (and aspire to produce), the nature of DH knowledge, research and scholarship (particularly regarding the role of artefacts produced), and issues of disciplinary orientation or professional identity. We could phrase these as the what, how, and who of DH and, of course, RtD. The discussion of our project is in no sense intended to provide an exclusive answer to those questions, but to give one snapshot of what DH and RtD may look like when they come together. We emphasize that this relationship can and will be productive for both disciplines and point to the lack of significant discussion hereto

Slow Painting : Works by Kristen Scholfield-Sweet/Works by David Haigh

In separate essays, Gibson notes the various influences in Schofield-Sweet's photo-dependent and Haigh's realist paintings. Includes artist's statements. Biographical notes. 3 bibl. ref

Review of the efficacy and safety of fesoterodine for treating overactive bladder and urgency urinary incontinence in elderly patients

Overactive bladder (OAB) is a common condition, with prevalence rates increasing with advancing age. Symptoms of OAB, including urgency urinary incontinence (UUI), are associated with various co-morbidities in elderly individuals (e.g., falls and fractures, functional impairment, and depression). The current mainstay of pharmacological therapy for OAB is antimuscarinic agents. Until recently, few studies had specifically evaluated the efficacy and safety of antimuscarinics in the treatment of OAB symptoms in elderly patients. This review summarises available evidence from the medical literature on the efficacy and safety of fesoterodine in elderly patients with OAB symptoms, including UUI. The data from unique placebo-controlled fesoterodine trials of elderly and vulnerable elderly patients, together with age-stratified data from post hoc analyses of fesoterodine trials, demonstrate that treatment with fesoterodine 4 or 8 mg results in statistically and clinically significant improvements in OAB symptoms and patient-reported outcomes in many elderly patients.2.610 JCR (2015) Q2, 22/49 Geriatrics & Gerontology, 98/253 Pharmacology & PharmacyUE