Selective expansion of viral variants following experimental transmission of a reconstituted feline immunodeficiency virus quasispecies

Following long-term infection with virus derived from the pathogenic GL8 molecular clone of feline immunodeficiency virus (FIV), a range of viral variants emerged with distinct modes of interaction with the viral receptors CD134 and CXCR4, and sensitivities to neutralizing antibodies. In order to assess whether this viral diversity would be maintained following subsequent transmission, a synthetic quasispecies was reconstituted comprising molecular clones bearing envs from six viral variants and its replicative capacity compared in vivo with a clonal preparation of the parent virus. Infection with either clonal (Group 1) or diverse (Group 2) challenge viruses, resulted in a reduction in CD4+ lymphocytes and an increase in CD8+ lymphocytes. Proviral loads were similar in both study groups, peaking by 10 weeks post-infection, a higher plateau (set-point) being achieved and maintained in study Group 1. Marked differences in the ability of individual viral variants to replicate were noted in Group 2; those most similar to GL8 achieved higher viral loads while variants such as the chimaeras bearing the B14 and B28 Envs grew less well. The defective replication of these variants was not due to suppression by the humoral immune response as virus neutralising antibodies were not elicited within the study period. Similarly, although potent cellular immune responses were detected against determinants in Env, no qualitative differences were revealed between animals infected with either the clonal or the diverse inocula. However, in vitro studies indicated that the reduced replicative capacity of variants B14 and B28 in vivo was associated with altered interactions between the viruses and the viral receptor and co-receptor. The data suggest that viral variants with GL8-like characteristics have an early, replicative advantage and should provide the focus for future vaccine development

Several Interruptions: 15 Years of the Slade Centre for Electronic Media in Fine Art

Seven, sequential solo presentations to celebrate 15 years of the Slade Centre for Electronic Media in Fine Art in 2011. Exhibited: 'Each Long Second' 2006, A0 photocopies, tape. Dimensions: 880 X 850 cms

Modulation of the virus-receptor interaction by mutations in the V5 loop of feline immunodeficiency virus (FIV) following in vivo escape from neutralising antibody

<b>BACKGROUND:</b> In the acute phase of infection with feline immunodeficiency virus (FIV), the virus targets activated CD4+ T cells by utilising CD134 (OX40) as a primary attachment receptor and CXCR4 as a co-receptor. The nature of the virus-receptor interaction varies between isolates; strains such as GL8 and CPGammer recognise a "complex" determinant on CD134 formed by cysteine-rich domains (CRDs) 1 and 2 of the molecule while strains such as PPR and B2542 require a more "simple" determinant comprising CRD1 only for infection. These differences in receptor recognition manifest as variations in sensitivity to receptor antagonists. In this study, we ask whether the nature of the virus-receptor interaction evolves in vivo.<p></p> <b>RESULTS:</b> Following infection with a homogeneous viral population derived from a pathogenic molecular clone, a quasispecies emerged comprising variants with distinct sensitivities to neutralising antibody and displaying evidence of conversion from a "complex" to a "simple" interaction with CD134. Escape from neutralising antibody was mediated primarily by length and sequence polymorphisms in the V5 region of Env, and these alterations in V5 modulated the virus-receptor interaction as indicated by altered sensitivities to antagonism by both anti-CD134 antibody and soluble CD134.<p></p> <b>CONCLUSIONS:</b> The FIV-receptor interaction evolves under the selective pressure of the host humoral immune response, and the V5 loop contributes to the virus-receptor interaction. Our data are consistent with a model whereby viruses with distinct biological properties are present in early versus late infection and with a shift from a "complex" to a "simple" interaction with CD134 with time post-infection.<p></p&gt

Discursive Objects

17-25 October 2015, 11h – 18h Gagelstraat 44, 5616RR, EIndhoven Aldo Bakker, Maarten Baas, David Bernstein, Martin John Callanan, Chmara Rosinke, Sarah Daher & guests, The Grantchester Pottery, Richard Healy, Anton Hjertstedt, Vincent Knopper, Pieteke Korte, Nynke Koster, Pottery Yacht Club, Corinne Mynatt, n-o-m-a-n, Studio Minale Maeda, Superstudio The first exhibition for Work at Home situates art, design, and transdisciplinary practices in the home space. In what might be a likely setting for ‘design’, outside of the white cube it presents an alternate context for how we experience contemporary art today. The presentation of ‘art’ and ‘design’ suggests a mutual inclusion of both devices which we use to frame human experience. Beyond ‘home exhibition’ histories, the structure of the visitor experience is as a lived-in space, and presents potentials of what a contemporary collection of art and design might look like today. Presenting in the home creates a new paradigm that explores the evolving publicisation of our private space

Evolutionary history of the OmpR/IIIA family of signal transduction two component systems in Lactobacillaceae and Leuconostocaceae

<p>Abstract</p> <p>Background</p> <p>Two component systems (TCS) are signal transduction pathways which typically consist of a sensor histidine kinase (HK) and a response regulator (RR). In this study, we have analyzed the evolution of TCS of the OmpR/IIIA family in <it>Lactobacillaceae </it>and <it>Leuconostocaceae</it>, two families belonging to the group of lactic acid bacteria (LAB). LAB colonize nutrient-rich environments such as foodstuffs, plant materials and the gastrointestinal tract of animals thus driving the study of this group of both basic and applied interest.</p> <p>Results</p> <p>The genomes of 19 strains belonging to 16 different species have been analyzed. The number of TCS encoded by the strains considered in this study varied between 4 in <it>Lactobacillus helveticus </it>and 17 in <it>Lactobacillus casei</it>. The OmpR/IIIA family was the most prevalent in <it>Lactobacillaceae </it>accounting for 71% of the TCS present in this group. The phylogenetic analysis shows that no new TCS of this family has recently evolved in these <it>Lactobacillaceae </it>by either lineage-specific gene expansion or domain shuffling. Furthermore, no clear evidence of non-orthologous replacements of either RR or HK partners has been obtained, thus indicating that coevolution of cognate RR and HKs has been prevalent in <it>Lactobacillaceae</it>.</p> <p>Conclusions</p> <p>The results obtained suggest that vertical inheritance of TCS present in the last common ancestor and lineage-specific gene losses appear as the main evolutionary forces involved in their evolution in <it>Lactobacillaceae</it>, although some HGT events cannot be ruled out. This would agree with the genomic analyses of <it>Lactobacillales </it>which show that gene losses have been a major trend in the evolution of this group.</p

Host Specific Diversity in Lactobacillus johnsonii as Evidenced by a Major Chromosomal Inversion and Phage Resistance Mechanisms

Genetic diversity and genomic rearrangements are a driving force in bacterial evolution and niche adaptation. We sequenced and annotated the genome of Lactobacillus johnsonii DPC6026, a strain isolated from the porcine intestinal tract. Although the genome of DPC6026 is similar in size (1.97mbp) and GC content (34.8%) to the sequenced human isolate L. johnsonii NCC 533, a large symmetrical inversion of approximately 750 kb differentiated the two strains. Comparative analysis among 12 other strains of L. johnsonii including 8 porcine, 3 human and 1 poultry isolate indicated that the genome architecture found in DPC6026 is more common within the species than that of NCC 533. Furthermore a number of unique features were annotated in DPC6026, some of which are likely to have been acquired by horizontal gene transfer (HGT) and contribute to protection against phage infection. A putative type III restriction-modification system was identified, as were novel Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) elements. Interestingly, these particular elements are not widely distributed among L. johnsonii strains. Taken together these data suggest intra-species genomic rearrangements and significant genetic diversity within the L. johnsonii species and indicate towards a host-specific divergence of L. johnsonii strains with respect to genome inversion and phage exposure

Integrating Academic and Everyday Learning Through Technology: Issues and Challenges for Researchers, Policy Makers and Practitioners

This paper builds on work undertaken over a number of years by a group of international researchers with an interest in the potential of connecting academic and everyday practices and knowledge. Drawing extensively on literature and our own work, we first discuss the challenges around defining informal learning, concluding that learning is multidimensional and has varying combinations of formal and informal attributes. We then highlight the potential of technology for integrating formal and informal learning attributes and briefly provide some exemplars of good practice. We then discuss in depth the challenges and issues of this approach to supporting learning from the perspective of pedagogy, research, policy and technology. We also provide some recommendations of how these issues may be addressed. We argue that for the learner, integration of formal and informal learning attributes should be an empowering process, enabling the learner to be self-directed, creative and innovative, taking learning to a deeper level. Given the complexity of the learning ecosystem, this demands support from the teacher but also awareness and understanding from others such as parents, family, friends and community members. We present a conceptual model of such an ecosystem to help develop further discussions within and between communities of researchers, policy makers and practitioners