Persistent Expression of FLAG-tagged Micro dystrophin in Nonhuman Primates Following Intramuscular and Vascular Delivery

Animal models for Duchenne muscular dystrophy (DMD) have species limitations related to assessing function, immune response, and distribution of micro- or mini-dystrophins. Nonhuman primates (NHPs) provide the ideal model to optimize vector delivery across a vascular barrier and provide accurate dose estimates for widespread transduction. To address vascular delivery and dosing in rhesus macaques, we have generated a fusion construct that encodes an eight amino-acid FLAG epitope at the C-terminus of micro-dystrophin to facilitate translational studies targeting DMD. Intramuscular (IM) injection of AAV8.MCK.micro-dys.FLAG in the tibialis anterior (TA) of macaques demonstrated robust gene expression, with muscle transduction (50–79%) persisting for up to 5 months. Success by IM injection was followed by targeted vascular delivery studies using a fluoroscopy-guided catheter threaded through the femoral artery. Three months after gene transfer, >80% of muscle fibers showed gene expression in the targeted muscle. No cellular immune response to AAV8 capsid, micro-dystrophin, or the FLAG tag was detected by interferon-γ (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) at any time point with either route. In summary, an epitope-tagged micro-dystrophin cassette enhances the ability to evaluate site-specific localization and distribution of gene expression in the NHP in preparation for vascular delivery clinical trials

Starfish diversity in the Wenlock of England

Although their record extends back to the Early Ordovician, the occurrence of fossil starfish (Echinodermata: Asteroidea) is dependent almost exclusively upon horizons of exceptional preservation. Thus, asteroids found in Silurian obrution deposits of the English Midlands and Welsh Borderlands are particularly significant to an understanding of the early diversity of the group. Six species are described here: Hudsonaster? carectum sp. nov. (Hudsonasteridae), from the lower part of the Lower Elton Formation; and, from the Much Wenlock Limestone Formation, the hudsonasterids Doliaster brachyactis gen. et sp. nov. and Siluraster? ketleyi (Spencer, 1916), the lepidasterids Lepidaster grayi Forbes, 1850 and Lepidactis wenlocki Spencer, 1918, and the palasterinid Palasterina orchilocalia sp. nov. Though few in number, they show a diverse range of body morphologies when compared with Ordovician taxa: L. wenlocki had long, slender rays when fully grown whereas D. brachyactis is the first asteroid with the short-rayed body form of extant cushion stars. Most distinctive of all is L. grayi, the earliest multiradiate taxon known, all complete specimens of which have 13 rays. This morphological variety is interpreted as indicating that by the Early Silurian starfish were exploiting a wide range of feeding habits and ecological niches. © 2007 The Palaeontological Association

Culinary Arts Institute Performance Recipe Book

A collection of low-tech performance recipes submitted by national and international women artists for a special event at the 5th Mois de la Performance at La Centrale in 2002. The recipes, or instruction scripts, for a variety of performances reflect the multiple discourses concerning artistic practice, interdisciplinarity, and feminism that contribute to the programming of the gallery. Texts by G. Decamous and S. Cotton in French