A Novel Modular Antigen Delivery System for Immuno Targeting of Human 6-sulfo LacNAc-Positive Blood Dendritic Cells (SlanDCs)

Previously, we identified a major myeloid-derived proinflammatory subpopulation of human blood dendritic cells which we termed slanDCs (e.g. Schäkel et al. (2006) Immunity 24, 767-777). The slan epitope is an O-linked sugar modification (6-sulfo LacNAc, slan) of P-selectin glycoprotein ligand-1 (PSGL-1). As slanDCs can induce neoantigen-specific CD4+ T cells and tumor-reactive CD8+ cytotoxic T cells, they appear as promising targets for an in vivo delivery of antigens for vaccination. However, tools for delivery of antigens to slanDCs were not available until now. Moreover, it is unknown whether or not antigens delivered via the slan epitope can be taken up, properly processed and presented by slanDCs to T cells.Single chain fragment variables were prepared from presently available decavalent monoclonal anti-slan IgM antibodies but failed to bind to slanDCs. Therefore, a novel multivalent anti-slanDC scaffold was developed which consists of two components: (i) a single chain bispecific recombinant diabody (scBsDb) that is directed on the one hand to the slan epitope and on the other hand to a novel peptide epitope tag, and (ii) modular (antigen-containing) linker peptides that are flanked at both their termini with at least one peptide epitope tag. Delivery of a Tetanus Toxin-derived antigen to slanDCs via such a scBsDb/antigen scaffold allowed us to recall autologous Tetanus-specific memory T cells.In summary our data show that (i) the slan epitope can be used for delivery of antigens to this class of human-specific DCs, and (ii) antigens bound to the slan epitope can be taken up by slanDCs, processed and presented to T cells. Consequently, our novel modular scaffold system may be useful for the development of human vaccines

Formal opportunity, informal barriers: black women managers within a local authority

This article examines the equal opportunities policies of a local authority which were intended to improve the representation of black women managers. It reports the types of initiatives and proportions of black women employed in different grades over time; and discusses the organisational context, contrasting the views of personnel and line managers, and EO specialists, with those of black women who had achieved senior positions. These latter accounts illustrated how inequalities were sustained despite, and at times in articulation with, an EO policy which was relatively successful in formal terms. Findings are discussed with reference to two criticisms made of EO policies: inadequate implementation, and a failure to redress the effects of social inequalities or challenge white, male work norms. The article suggests that increasing formal controls or the range of initiatives is insufficient: better ways of understanding and challenging the role of organisational structures, cultures and politics in sustaining inequality is needed

An open resource for non-human primate imaging

Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience. Unfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMatE Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design, and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 25 independent data collections aggregated across 22 sites (total = 217 non-human primates). We also outline the unique pitfalls and challenges that should be considered in the analysis of non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets

Can we measure brain efficiency? An empirical test with common marmosets (Callithrix jacchus)

Various measures of brain size correlate with cognitive performance; however, the fit is not perfect, which bears the question of whether brains also vary in efficiency. Such variation could be expected if a species faces constraints on brain enlargement, for example due to the impossibility of slowing down life history as a consequence of predator pressure, while simultaneously experiencing selective benefits from enhanced cognitive ability related to particular ecological or social conditions. Arguably, this applies to callitrichid monkeys and would lead to the prediction that their relatively small brains are particularly efficient in comparison to their sister taxa, Cebus. This study investigated whether callitrichids' cognitive performance is better than would be expected given their brain size rather than comparing absolute performance between the taxa. As a measure of cognitive performance, we used the reversal learning paradigm, which is reliably and closely associated with brain size across primate taxa, and assessed performance in this paradigm (transfer index) in 14 common marmosets (Callithrix jacchus) as representatives of the callitrichids. These marmosets were found to show higher performance than would be expected for their brain size, and this relative performance was also higher than the relative performance in capuchin monkeys. We outline how these effects may be due to the cooperative breeding system of the callitrichids, particularly the enhancement of behavioural and cognitive propensities associated with shared care and provisioning