Improvement of the HIV/AIDS vaccine candidate NYVAC-C by deletion of the viral type I IFN inhibitor and/or acquisition of replication competence

Background: Recombinant viruses based on the attenuated vaccinia virus strain NYVAC are promising HIV vaccine candidates as phase I/II clinical trials have shown good safety and immunogenicity profiles. However, this NYVAC strain is non-replicating in most human cell lines and encodes viral inhibitors of the immune system. Methods: With the aim to increase the immune potency of the current NYVAC-C vector (expressing the codon optimized clade C HIV-1 genes encoding gp120 and Gag-Pol-Nef polyprotein), we have generated and characterized three NYVAC-C-based vectors by, 1) deletion of the viral type I IFN inhibitor gene (NYVAC-CdeltaB19R), 2) restoration of virus replication competence in human cells by re-inserting K1L and C7L host range genes (NYVAC-C-KC) and, 3) combination of both strategies (NYVACC- KC-deltaB19R). Results: Insertion of the KC fragment restored the replication competence of the viruses in human cells (HeLa cells and primary dermal fibroblasts and keratinocytes), increased the expression of HIV antigens by more than 3-fold compared to the non-replicating homologs, inhibited apoptosis induced by the parental NYVAC-C and retained attenuation in a newborn mouse model. In adult mice, replication-competent viruses showed a limited capacity to replicate in tissues surrounding the inoculation site (ovaries and lymph nodes). After infection of keratinocytes, PBMCs and dendritic cells these viruses induced differential modulation in specific host cell signal transduction pathways, triggering genes important in immune modulation. Conclusion: We have developed improved NYVAC-C-based vectors with enhanced HIV-1 antigen expression, with the ability to replicate in cultured human cells and partially in some tissues, with an induced expression of cellular genes relevant to immune system activation, and which trigger IFN-dependent and independent signalling pathways, while maintaining a safety phenotype. These new vectors are promising new HIV vaccine candidates. These studies were performed within the Poxvirus Tcell Vaccine Discovery Consortium (PTVDC) which is part of the CAVD program.

Circulating insulin-like growth factor-I in pregnancy and maternal risk of breast cancer.

BACKGROUND: Elevated serum concentrations of insulin-like growth factor (IGF)-1 have been associated with increased risk of breast cancer. Previously, we reported a similar association in samples obtained during pregnancy. The current study was conducted to further characterize the association of IGF-1 during pregnancy with maternal breast cancer risk. METHODS: A case-control study was nested within the Finnish Maternity Cohort. The study was limited to primiparous women less than 40 years of age, who donated blood samples during early (median, 12 weeks) pregnancy and delivered a single child at term. Seven hundred and nineteen women with invasive breast cancer were eligible. Two controls (n = 1,434) were matched to each case on age and date at blood donation. Serum IGF-1 concentration was measured using an Immulite 2000 analyzer. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI).RESULTS: No significant associations were observed between serum IGF-1 concentrations and breast cancer risk in both the overall analysis (OR 1.08 (95% CI 0.80-1.47) and in analyses stratified by histological subtype, lag-time to cancer diagnosis, age at pregnancy or age at diagnosis.CONCLUSIONS: There was no association between IGF-1 and maternal breast cancer risk during early pregnancy in this large nested case-control study.Impact:Serum IGF-1 concentrations during early pregnancy may not be related to maternal risk of breast cancer.

Amphioxus type I keratin cDNA and the evolution of intermediate filament genes

We report the cloning of an intermediate filament (IF) cDNA from the cephalochordate amphioxus that encodes a protein assignable to the type I keratin group. This is the first type I keratin reported from an invertebrate. Molecular phylogenetic analyses reveal that amphioxus also possesses a type II keratin, and that the genes encoding short-rod IF proteins underwent different patterns of duplication in vertebrates and their closest relatives, the cephalochordates. Extensive IF gene duplication and divergence may have facilitated the origin of new specialised cell types in vertebrates.

Food geographies I: relational foodscapes and the busy-ness of being more-than-food

The study of foodscapes has spread throughout geography at the same time as food scholarship has spearheaded post-disciplinary research. This report argues that geographers have taken to post-disciplinarity to explore the ways that food is ‘more-than-food’ through analyses of the visceral nature of eating and politics and the vital (re)materializations of food’s cultural geographies. Visceral food geographies illuminate what I call the ‘contingent relationalities’ of food in the critical evaluation of the indeterminate, situated politics of ‘feeling food’ and those of the embodied collectivities of obesity. Questions remain, however, about how a visceral framework might be deployed for broader critiques within foodscapes and the study of human geography. The study of food’s vital materialisms opens up investigation into the practices of the ‘makings’ of meat, food waste and eating networks. Analysis of affect, embodiment and cultural practices is central to these theorizations and suggests consideration of the multiple materialisms of food, space and eating. There is, I contend, in the more radical, ‘post-relational’ approaches to food, the need for a note of caution. Exuberant claims for the ontological, vital agency of food should be tempered by, or at least run parallel to, critical questions of the real politik of political and practical agency in light of recent struggles over austerity, food poverty and food justice.

Correlation between i.r. spectra and thermal decomposition of cobalt(II), nickel(II), copper(II) and mercury(II) complexes with piperidinedithiocarbamate and pyrrolidinedithiocarbamate

The thermal decomposition of pyrrolidinedithiocarbamate and piperidinedithiocarbamate complexes of CoII, NiII, CuII and HgII have been studied by thermogravimetry and differential scanning calorimetry. The decomposition intermediates and final products were identified by their X-ray diffraction patterns. The i.r. spectra are discussed in terms of the thermal decomposition pathways.

Book Review of <i> Venereal Disease and the Lewis and Clark Expeditioni> by Thomas P. Lowry

Although Lewis and Clark literature has proliferated in the last decade, few works have added scholarly discourse to this field of study. The highly focused Venereal Disease and the Lewis and Clark Expedition, however, will likely stand out on the Lewis and Clark bookshelf as an important contribution.

Book Review of <i> Archaeological Theory and the Politics of Cultural Heritagei> by Laurajane Smith

The passage of the Native American Graves Protection and Repatriation Act (NAGPRA) in 1991 significantly changed the way archaeology would be done in the United States. This act was presaged by growing complaints and resentment directed at the scientific community by Native Americans over the treatment of their ancestral remains. Many of the underlying issues came to a head with the discovery and subsequent court battles over the 9,200-year-old individual commonly known as Kennewick Man. This had a galvanizing effect on the discipline, not only perpetuating the sometimes adversarial relationship between archaeologists and Native Americans, but also creating a rift between those archaeologists who understood Native American concerns and those who saw their ancestral skeletal remains representing the legacy of humankind and thus belonging to everyone. Similar scenarios have emerged in Australia.