Combining in vitro protein detection and in vivo antibody detection identifies potential vaccine targets against Staphylococcus aureus during osteomyelitis

Currently, little is known about the in vivo human immune response against Staphylococcus aureus during a biofilm-associated infection, such as osteomyelitis, and how this relates to protein production in biofilms in vitro. Therefore, we characterized IgG responses in 10 patients with chronic osteomyelitis against 50 proteins of S. aureus, analyzed the presence of these proteins in biofilms of the infecting isolates on polystyrene (PS) and human bone in vitro, and explored the relation between in vivo and in vitro data. IgG levels against 15 different proteins were significantly increased in patients compared to healthy controls. Using a novel competitive Luminex-based assay, eight of these proteins [alpha toxin, Staphylococcus aureus formyl peptide receptor-like 1 inhibitor (FlipR), glucosaminidase, iron-responsive surface determinants A and H, the putative ABC transporter SACOL0688, staphylococcal complement inhibitor (SCIN), and serine–aspartate repeat-containing protein E (SdrE)] were also detected in a majority of the infecting isolates during biofilm formation in vitro. However, 4 other proteins were detected in only a minority of isolates in vitro while, vice versa, 7 proteins were detected in multiple isolates in vitro but not associated with significantly increased IgG levels in patients. Detection of proteins was largely confirmed using a transcriptomic approach. Our data provide further insights into potential therapeutic targets, such as for vaccination, to reduce S. aureus virulence and biofilm formation. At the same time, our data suggest that either in vitro or immunological in vivo data alone should be interpreted cautiously and that combined studies are necessary to identify potential targets

FK506 protects against articular cartilage collagenous extra-cellular matrix degradation

Objective: Osteoarthritis (OA) is a non-rheumatologic joint disease characterized by progressive degeneration of the cartilage extra-cellular matrix (ECM), enhanced subchondral bone remodeling, activation of synovial macrophages and osteophyte growth. Inhibition of calcineurin (Cn) activity through tacrolimus (FK506) in invitro monolayer chondrocytes exerts positive effects on ECM marker expression. This study therefore investigated the effects of FK506 on anabolic and catabolic markers of osteoarthritic chondrocytes in 2D and 3D invitro cultures, and its therapeutic effects in an invivo rat model of OA. Methods: Effects of high and low doses of FK506 on anabolic (QPCR/histochemistry) and catabolic (QPCR) markers were evaluated invitro on isolated (2D) and ECM-embedded chondrocytes (explants, 3D pellets). Severe cartilage damage was induced unilaterally in rat knees using papain injections in combination with a moderate running protocol. Twenty rats were treated with FK506 orally and compared to twenty untreated controls. Subchondral cortical and trabecular bone changes (longitudinal microCT) and macrophage activation (SPECT/CT) were measured. Articular cartilage was analyzed exvivo using contrast enhanced microCT and histology. Results: FK506 treatment of osteoarthritic chondrocytes invitro induced anabolic (mainly collagens) and reduced catabolic ECM marker expression. In line with this, FK506 treatment clearly protected ECM integrity invivo by markedly decreasing subchondral sclerosis, less development of subchondral pores, depletion of synovial macrophage activation and lower osteophyte growth. Conclusion: FK506 protected cartilage matrix integrity invitro and invivo. Additionally, FK506 treatment invivo reduced OA-like responses in different articular joint tissues and thereby makes Cn an interesting target for therapeutic intervention of OA

Forestry for a low carbon future. Integrating forests and wood products in climate change strategies

Following the introduction, Chapter 2 provides an overview of mitigation in the forest sector, addressing the handling of forests under UNFCCC. Chapters 3 to 5 focus on forest-based mitigation options – afforestation, reforestation, REDD+ and forest management – and Chapters 6 and 7 focus on wood-product based options – wood energy and green building and furnishing. The publication describes these activities in the context of UNFCCC rules, assessing their mitigation potential and economic attrac tiveness as well as opportunities and challenges for implementation. Chapter 8 discusses the different considerations involved in choosing the right mix of options as well as some of the instruments and means for implementation. Chapter 8 also highlights the co-benefits generated by forest-based mitigation and emphasizes that economic assessment of mitigation options needs to take these benefits into account. The concluding chapter assesses national commitments under UNFCCC involving forest miti gation and summarizes the challenges and opportunities

Will forests remain in the face of oil palm expansion? Simulating change in Malinau, Indonesia

The severe tensions between conservation and development are illustrated by events in Malinau District (Kalimantan, Indonesia). Conservationists decry proposed plans for logging and conversion of pristine tropical forest to oil palm (Elaeis guineensis). Although the local government is willing to declare the district a “conservation district,” at the same time, it shows interest in oil palm conversion. This article explores the impact of the potential conversion of 500 000 ha of forest to oil palm on forest cover, in-migration, and the local economy in Malinau. The simulation model was developed using STELLA® software, and relies on a combination of empirical data, data from the literature, and stakeholder perceptions. If a company were to clear the forest for timber without planting oil palm (as commonly happens), poverty levels are likely to rise rather than decline over the long term. If large-scale oil palm plantations were to be established, they could yield significant benefits to local authorities. However, such development would induce massive employment-driven migration, with wide-ranging consequences for the current inhabitants of the region. By visualizing and quantifying these trade-offs between conservation and development, the model stimulates debate and information exchange among conservationists, development actors, and district authorities so that well-informed choices can be made