Cooperative Stimulation of Dendritic Cells by Cryptococcus neoformans Mannoproteins and CpG Oligodeoxynucleotides

While mannosylation targets antigens to mannose receptors on dendritic cells (DC), the resultant immune response is suboptimal. We hypothesized that the addition of toll-like receptor (TLR) ligands would enhance the DC response to mannosylated antigens. Cryptococcus neoformans mannoproteins (MP) synergized with CpG-containing oligodeoxynucleotides to stimulate enhanced production of proinflammatory cytokines and chemokines from murine conventional and plasmacytoid DC. Synergistic stimulation required the interaction of mannose residues on MP with the macrophage mannose receptor (MR), CD206. Moreover, synergy with MP was observed with other TLR ligands, including tripalmitoylated lipopeptide (Pam3CSK4), polyinosine-polycytidylic acid (pI:C), and imiquimod. Finally, CpG enhanced MP-specific MHC II-restricted CD4+ T-cell responses by a mechanism dependent upon DC expression of CD206 and TLR9. These data suggest a rationale for vaccination strategies that combine mannosylated antigens with TLR ligands and imply that immune responses to naturally mannosylated antigens on pathogens may be greatly augmented if TLR and MR are cooperatively stimulated.National Institutes of Health (RO1 AI25780, RO1 AI37532, K08 AI 53542

Review of research and evaluation on improving adult literacy and numeracy skills

The purposes of this literature review are threefold. First, this review summarises findings of the research from the last decade in six fields identified by the Department for Business, Innovation and Skills (BIS) as critical to its forward planning: (1) the economic, personal and social returns to learning; (2) the quality and effectiveness of provision; (3) the number of learning hours needed for skills gain; (4) learner persistence; (5) the retention and loss of skills over time; (6) the literacy and numeracy skills that are needed. Second, this review assesses this evidence base in terms of its quality and robustness, identifying gaps and recommending ways in which the evidence base can be extended and improved. Thirdly, this review attempts to interpret the evidence base to suggest, where possible, how returns to ALN learning for individuals, employers and wider society might be increased through effective and cost-effective interventions

Direct Inhibition of T-Cell Responses by the Cryptococcus Capsular Polysaccharide Glucuronoxylomannan

The major virulence factor of the pathogenic fungi Cryptococcus neoformans and C. gattii is the capsule. Glucuronoxylomannan (GXM), the major component of the capsule, is a high-molecular-weight polysaccharide that is shed during cryptococcosis and can persist in patients after successful antifungal therapy. Due to the importance of T cells in the anticryptococcal response, we studied the effect of GXM on the ability of dendritic cells (DCs) to initiate a T-cell response. GXM inhibited the activation of cryptococcal mannoprotein-specific hybridoma T cells and the proliferation of OVA-specific OT-II T cells when murine bone marrow-derived DCs were used as antigen-presenting cells. Inhibition of OT-II T-cell proliferation was observed when either OVA protein or OVA323-339 peptide was used as antigen, indicating GXM did not merely prevent antigen uptake or processing. We found that DCs internalize GXM progressively over time; however, the suppressive effect did not require DCs, as GXM directly inhibited T-cell proliferation induced by anti-CD3 antibody, concanavalin A, or phorbol-12-myristate-13-acetate/ionomycin. Analysis of T-cell viability revealed that the reduced proliferation in the presence of GXM was not the result of increased cell death. GXM isolated from each of the four major cryptococcal serotypes inhibited the proliferation of human peripheral blood mononuclear cells stimulated with tetanus toxoid. Thus, we have defined a new mechanism by which GXM can impart virulence: direct inhibition of T-cell proliferation. In patients with cryptococcosis, this could impair optimal cell-mediated immune responses, thereby contributing to the persistence of cryptococcal infections. SynopsisInfections due to the pathogenic yeast Cryptococcus are a significant cause of morbidity and mortality in persons with impaired T-cell functions, particularly those with AIDS. The major virulence factor of Cryptococcus is its capsule, which is composed primarily of the polysaccharide glucuronoxylomannan (GXM). The capsule not only surrounds the organism but also is shed during cryptococcosis. GXM is taken up by macrophages in vitro and in vivo; however, little is known about the interaction between GXM and dendritic cells, which are the most potent cells capable of activating T cells. Because of the importance of T cells in the anticryptococcal response, the authors investigated the effect of GXM on the ability of dendritic cells to initiate a T-cell response. They found the polysaccharide was internalized by dendritic cells and inhibited antigen-specific T-cell responses. Furthermore, GXM had a direct, inhibitory effect on T-cell proliferation, independent of the effect on dendritic cells. These findings may help explain the persistence of cryptococcal infections and suggest that GXM could be therapeutic in situations where suppression of T-cell responses is desired.National Institutes of Health (R01 AI25780, R01 AI066087, R01 AI37532

Porites superfusa mortality and recovery from a bleaching event at Palmyra Atoll, USA.

BackgroundThe demography of a coral colony is not a binary trajectory of life and death. Based on the flexibility afforded by colonial organization, most reef-building corals employ a variety of dynamic survival strategies, including growth and shrinkage. The demographic flexibility affects coral size, shape and reproductive output, among other factors. It is thus critical to quantify the relative importance of key dynamics of recruitment, mortality, growth and shrinkage in changing the overall cover of coral on a reef.MethodsUsing fixed photographic quadrats, we tracked the patterns of change in the cover of one common central Pacific coral, Porites superfusa, before and after the 2009 ENSO event.ResultsCoral colonies suffered both whole and partial colony mortality, although larger colonies were more likely to survive. In subsequent years, recruitment of new colonies and regrowth of surviving colonies both contributed to the modest recovery of P. superfusa.DiscussionThis study is unique in its quantitative comparisons of coral recruitment versus regrowth during periods of areal expansion. Our data suggest that recovery is not limited simply to the long pathway of settlement, recruitment and early growth of new colonies but is accelerated by means of regrowth of already established colonies having suffered partial mortality

Evaluation of the Sustainable Employment in a Green US Economy (SEGUE)

The Rockefeller Foundation's Sustainable Employment in a Green US Economy(SEGUE) initiative has been a central player in green job discussions since 2009, andeven earlier through the Foundation's Campaign for American Workers. In its earliestdevelopmental stages, the initiative sought "to maximize the 'green' growth areas ofthe economy while benefiting low- and moderate-income workers" (RockefellerFoundation, 2009b). SEGUE focused on creating jobs by supporting green economicactivities. Initially, the focus was the building energy-retrofit market in the constructionindustry and, later, on water infrastructure and waste management. The demandfor workers became recognized as the bottleneck that needed to be released, in orderto realize the benefits of the green economy.To document and expand upon the learning and exploration that SEGUE has started,the Rockefeller Foundation provided a grant to the research firm, Abt Associates,Inc., in April 2012, to conduct a short-term, developmental evaluation of SEGUE. Theevaluation focused on three areas: learning for the purposes of determining SEGUE'sfuture direction, documenting SEGUE's grant and non-grant outputs for accountabilityneeds, and providing public knowledge on green jobs and evaluations in general.This report provides the results from the evaluation

Effects of Removing the Time Limit on First and Second Language Intelligence Test Performance

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The Science Behind Learning: Practical Applications of Curiosity, Sociality, and Emotion in Communication Center Consultations

How humans learn is a topic explored by many disciplines.  Eyler (2018) synthesized research from diverse fields such as developmental psychology, anthropology, and cognitive neuroscience to identify themes important for understanding the science behind learning. Three of these principles have important relevance for center work: curiosity, sociality, and emotion. This paper explores practical strategies, based on these three principles, that consultants in communication centers can use to enhance learning and better assist students.Keywords: communication centers, consulting, science of learning, curiosity, sociality, emotio

Bending the Curve: Options for Achieving Savings and Improving Value in Health Spending

Analyzes the potential of fifteen federal health policy options to lower spending over the next ten years and yield higher value on investments in health care

Coordination of Foliar and Wood Anatomical Traits Contributes to Tropical Tree Distributions and Productivity along the Malay-Thai Peninsula

Drought is a critical factor in plant species distributions. Much research points to its relevance even in moist tropical regions. Recent studies have begun to elucidate mechanisms underlying the distributions of tropical tree species with respect to drought; however, how such desiccation tolerance mechanisms correspond with the coordination of hydraulic and photosynthetic traits in determining species distributions with respect to rainfall seasonality deserves attention. In the present study, we used a common garden approach to quantify inherent differences in wood anatomical and foliar physiological traits in 21 tropical tree species with either widespread (occupying both seasonal and aseasonal climates) or southern (restricted to aseasonal forests) distributions with respect to rainfall seasonality. Use of congeneric species pairs and phylogenetically independent contrast analyses allowed examination of this question in a phylogenetic framework. Widespread species opted for wood traits that provide biomechanical support and prevent xylem cavitation and showed associated reductions in canopy productivity and consequently growth rates compared with southern species. These data support the hypothesis that species having broader distributions with respect to climatic variability will be characterized by traits conducive to abiotic stress tolerance. This study highlights the importance of the well-established performance vs. stress tolerance trade-off as a contributor to species distributions at larger scales