Transfer after process-based object-location memory training in healthy older adults

A substantial part of age-related episodic memory decline has been attributed to the decreasing ability of older adults to encode and retrieve associations among simultaneously processed information units from long-term memory. In addition, this ability seems to share unique variance with reasoning. In this study, we therefore examined whether process-based training of the ability to learn and remember associations has the potential to induce transfer effects to untrained episodic memory and reasoning tasks in healthy older adults (60-75 years). For this purpose, the experimental group (n = 36) completed 30 sessions of process-based objectlocation memory training, while the active control group (n = 31) practiced visual perception on the same material. Near (spatial episodic memory), intermediate (verbal episodic memory), and far transfer effects (reasoning) were each assessed with multiple tasks at four measurements (before, midway through, immediately after, and 4 months after training). Linear mixed-effects models revealed transfer effects on spatial episodic memory and reasoning that were still observed 4 months after training. These results provide first empirical evidence that process-based training can enhance healthy older adults' associative memory performance and positively affect untrained episodic memory and reasoning abilities

Space is the Place: European jazz festivals as cultural heritage sites

The JPI-Heritage Plus supported Cultural Heritage and Improvised Music in European Festivals (CHIME) project was established to examine the workings of jazz festivals and their relationship to cultural heritage as discursive practice. Jazz festivals occupy a significant – if undervalued – place in the ecologies of Europe’s cultural heritage, with their dynamic and synergetic relationship to spaces and cultural sites. Drawing on a number of case studies and interviews with members of the Europe Jazz Network, this article presents a typology of European jazz festivals and cultural heritage sites that can be used to inform the different ways in which jazz offers meaning to specific groups and locations. By viewing jazz festivals through the lens of cultural heritage, we can begin to challenge reified presentations of heritage that promote uncomplicated interpretations of nations, people and their associated cultural narratives. Festivals offer meaning to specific groups through acts of remembrance or commemoration, they have the potential to engage with a multitude of voices, and their locations enable people to negotiate a sense of belonging or to (re)consider their place in the world

Does working memory training have to be adaptive?

This study tested the common assumption that, to be most effective, working memory (WM) training should be adaptive (i.e., task difficulty is adjusted to individual performance). Indirect evidence for this assumption stems from studies comparing adaptive training to a condition in which tasks are practiced on the easiest level of difficulty only [cf. Klingberg (Trends Cogn Sci 14:317-324, 2010)], thereby, however, confounding adaptivity and exposure to varying task difficulty. For a more direct test of this hypothesis, we randomly assigned 130 young adults to one of the three WM training procedures (adaptive, randomized, or self-selected change in training task difficulty) or to an active control group. Despite large performance increases in the trained WM tasks, we observed neither transfer to untrained structurally dissimilar WM tasks nor far transfer to reasoning. Surprisingly, neither training nor transfer effects were modulated by training procedure, indicating that exposure to varying levels of task difficulty is sufficient for inducing training gains

Roles for Treg expansion and HMGB1 signaling through the TLR1-2-6 axis in determining the magnitude of the antigen-specific immune response to MVA85A

© 2013 Matsumiya et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedA better understanding of the relationships between vaccine, immunogenicity and protection from disease would greatly facilitate vaccine development. Modified vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis vaccine candidate designed to enhance responses induced by BCG. Antigen-specific interferon-γ (IFN-γ) production is greatly enhanced by MVA85A, however the variability between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression in humans following vaccination with MVA85A and relate these to long-term immunogenicity. Two days post-vaccination, MVA85A induces a strong interferon and inflammatory response. Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders. Additionally, high levels of Toll-like Receptor (TLR) 1 on day of vaccination are associated with an increased response to antigen 85A. In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Rα two days post-vaccination can classify high and low responders with over 80% accuracy. Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A. HMGB1 is released into the supernatant following atimulation with MVA85A and we propose this signal may be the trigger activating the TLR pathway. This study suggests an important role for an endogenous ligand in innate sensing of MVA and demonstrates the importance of pattern recognition receptors and regulatory T cell responses in determining the magnitude of the antigen specific immune response to vaccination with MVA85A in humans.This work was funded by the Wellcome Trust. MM has a Wellcome Trust PhD studentship and HM is a Wellcome Trust Senior Fello

Toward a geography of black internationalism: Bayard Rustin, nonviolence and the promise of Africa

This article charts the trip made by civil rights leader Bayard Rustin to West Africa in 1952, and examines the unpublished ‘Africa Program’ which he subsequently presented to leading American pacifists. I situate Rustin’s writings within the burgeoning literature on black internationalism which, despite its clear geographical registers, geographers themselves have as yet made only a modest contribution towards. The article argues that within this literature there remains a tendency to romanticize cross-cultural connections in lieu of critically interrogating their basic, and often competing, claims. I argue that closer attention to the geographies of black internationalism, however, allows us to shape a more diverse and practiced sense of internationalist encounter and exchange. The article reconstructs the multiplicity of Rustin’s black internationalist geographies which drew eclectically from a range of Pan-African, American and pacifist traditions. Though each of these was profoundly racialized, they conceptualized race in distinctive ways and thereby had differing understandings of what constituted the international as a geographical arena. By blending these forms of internationalism Rustin was able to promote a particular model of civil rights which was characteristically internationalist in outlook, nonviolent in principle and institutional in composition; a model which in selective and uneven ways continues to shape our understanding of the period

Development and Characterization of Synthetic Glucopyranosyl Lipid Adjuvant System as a Vaccine Adjuvant

Innate immune responses to vaccine adjuvants based on lipopolysaccharide (LPS), a component of Gram-negative bacterial cell walls, are driven by Toll-like receptor (TLR) 4 and adaptor proteins including MyD88 and TRIF, leading to the production of inflammatory cytokines, type I interferons, and chemokines. We report here on the characterization of a synthetic hexaacylated lipid A derivative, denoted as glucopyranosyl lipid adjuvant (GLA). We assessed the effects of GLA on murine and human dendritic cells (DC) by combining microarray, mRNA and protein multiplex assays and flow cytometry analyses. We demonstrate that GLA has multifunctional immunomodulatory activity similar to naturally-derived monophosphory lipid A (MPL) on murine DC, including the production of inflammatory cytokines, chemokines, DC maturation and antigen-presenting functions. In contrast, hexaacylated GLA was overall more potent on a molar basis than heterogeneous MPL when tested on human DC and peripheral blood mononuclear cells (PBMC). When administered in vivo, GLA enhanced the immunogenicity of co-administered recombinant antigens, producing strong cell-mediated immunity and a qualitative TH1 response. We conclude that the GLA adjuvant stimulates and directs innate and adaptive immune responses by inducing DC maturation and the concomitant release of pro-inflammatory cytokines and chemokines associated with immune cell trafficking, activities which have important implications for the development of future vaccine adjuvants

The Secreted Lipoprotein, MPT83, of Mycobacterium tuberculosis Is Recognized during Human Tuberculosis and Stimulates Protective Immunity in Mice

The long-term control of tuberculosis (TB) will require the development of more effective anti-TB vaccines, as the only licensed vaccine, Mycobacterium bovis bacille Calmette-Guérin (BCG), has limited protective efficacy against infectious pulmonary TB. Subunit vaccines have an improved safety profile over live, attenuated vaccines, such as BCG, and may be used in immuno-compromised individuals. MPT83 (Rv2873) is a secreted mycobacterial lipoprotein expressed on the surface of Mycobacterium tuberculosis. In this study, we examined whether recombinant MPT83 is recognized during human and murine M. tuberculosis infection. We assessed the immunogenicity and protective efficacy of MPT83 as a protein vaccine, with monophosphyl lipid A (MPLA) in dimethyl-dioctadecyl ammonium bromide (DDA) as adjuvant, or as a DNA vaccine in C57BL/6 mice and mapped the T cell epitopes with peptide scanning. We demonstrated that rMPT83 was recognised by strong proliferative and Interferon (IFN)-γ-secreting T cell responses in peripheral blood mononuclear cells (PBMC) from patients with active TB, but not from healthy, tuberculin skin test-negative control subjects. MPT83 also stimulated strong IFN-γ T cell responses during experimental murine M. tuberculosis infection. Immunization with either rMPT83 in MPLA/DDA or DNA-MPT83 stimulated antigen-specific T cell responses, and we identified MPT83127–135 (PTNAAFDKL) as the dominant H-2b-restricted CD8+ T cell epitope within MPT83. Further, immunization of C57BL/6 mice with rMPT83/MPLA/DDA or DNA-MPT83 stimulated significant levels of protection in the lungs and spleens against aerosol challenge with M. tuberculosis. Interestingly, immunization with rMPT83 in MPLA/DDA primed for stronger IFN-γ T cell responses to the whole protein following challenge, while DNA-MPT83 primed for stronger CD8+ T cell responses to MPT83127–135. Therefore MPT83 is a protective T cell antigen commonly recognized during human M. tuberculosis infection and should be considered for inclusion in future TB subunit vaccines

Vaccines against Tuberculosis: Where Are We and Where Do We Need to Go?

In this review we discuss recent progress in the development, testing, and clinical evaluation of new vaccines against tuberculosis (TB). Over the last 20 years, tremendous progress has been made in TB vaccine research and development: from a pipeline virtually empty of new TB candidate vaccines in the early 1990s, to an era in which a dozen novel TB vaccine candidates have been and are being evaluated in human clinical trials. In addition, innovative approaches are being pursued to further improve existing vaccines, as well as discover new ones. Thus, there is good reason for optimism in the field of TB vaccines that it will be possible to develop better vaccines than BCG, which is still the only vaccine available against TB