Natural Resources in 2025 - Implications for Development : Opportunity of a trunaround: An expert reassessment

In recent years developing countries have faced highly dynamic changes affecting their natural resource base and their potential for development. Taking into account these changes in the development context, InfoResources initiated a critical reassessment of the results of InfoResources Trends 2005 and again invited experts from around the world to assess trends that least developed countries are likely to be facing by 2025. The unanimous signal conveyed by the international experts for this assessment is alarming: The degradation of natural resources is progressing. By 2025 it will reach a point where livelihoods in least developing countries will be significantly threatened and an increasing number of agro-ecosystems will lose their capacity to deliver important services. Expected positive social trends will not suffice as leverage to reverse the degradation of natural resources and thus alleviate poverty and hunger. However, the present reassessment clearly reveals that a change in thinking and a shift in paradigms have begun to take place. However, a turnaround can only succeed if the emerging awareness of the need to reorient policy-making and the economy is followed by concrete action. It will be crucial that policies and institutions regain regulating power over greedy economic forces. This reassessment does not claim to be comprehensive. However, the present publication, which synthesises the experts’ inputs, aims at providing food for thought and initiating discussions.

Wie klingt reformiert? Arbeiten zu Liturgie und Musik. Gesammelte Aufsätze von Andreas Marti

Die reformierte Kirche gilt weithin als kunst- und musikfeindlich, obschon sie eine reiche musikalische Geschichte und eine dynamische musikalische Gegenwart hat. Diese lässt sich nicht aus einem theologischen Axiom begründen, sondern bedarf der Diskussion. Dabei spielt das von der versammelten Gemeinde gesungene Kirchenlied eine herausragende Rolle. Die in diesem Band vereinigten Aufsätze und Referate von Andreas Marti aus den letzten zwanzig Jahren stellen sich dieser Diskussion aus reformierter Sicht: Dem Kirchenmusiker gelingt es immer wieder, unterschiedliche Perspektiven in eigenständiger und erhellender Weise aufeinander zu beziehen.

CDE links regional research and global efforts for sustainable mountain development

The Centre for Development and Environment (CDE) at the University of Bern has long-standing experience in conducting research in mountain regions around the world. CDE considers mountain regions to be a crucial context for sustainable development. Together with its partners, CDE aims to generate in-depth contextual knowledge about the dynamic social, economic, and ecological processes in mountain regions and elsewhere, with a view to informing development practices, while at the global level it engages in activities that help bring together these regional insights with the goal of informing policy-making. In doing so, CDE addresses the specific challenges of sustainable development—in mountains and elsewhere.

Shaping Institutions for Natural Resource Management

This InfoResources Focus tries to clarify challenges people face when shaping institutions for sustainable NRM and discusses key elements for implementing processes of institutional change. Emphasis is put on local institutions embedded in national, regional and global institutional schemes.

Novel targeted therapies for eosinophil-associated diseases and allergy.

Eosinophil-associated diseases often present with life-threatening manifestations and/or chronic organ damage. Currently available therapeutic options are limited to a few drugs that often have to be prescribed on a lifelong basis to keep eosinophil counts under control. In the past 10 years, treatment options and outcomes in patients with clonal eosinophilic and other eosinophilic disorders have improved substantially. Several new targeted therapies have emerged, addressing different aspects of eosinophil expansion and inflammation. In this review, we discuss available and currently tested agents as well as new strategies and drug targets relevant to both primary and secondary eosinophilic diseases, including allergic disorders.

Toxicity of eosinophil MBP is repressed by intracellular crystallization and promoted by extracellular aggregation.

Eosinophils are white blood cells that function in innate immunity and participate in the pathogenesis of various inflammatory and neoplastic disorders. Their secretory granules contain four cytotoxic proteins, including the eosinophil major basic protein (MBP-1). How MBP-1 toxicity is controlled within the eosinophil itself and activated upon extracellular release is unknown. Here we show how intragranular MBP-1 nanocrystals restrain toxicity, enabling its safe storage, and characterize them with an X-ray-free electron laser. Following eosinophil activation, MBP-1 toxicity is triggered by granule acidification, followed by extracellular aggregation, which mediates the damage to pathogens and host cells. Larger non-toxic amyloid plaques are also present in tissues of eosinophilic patients in a feedback mechanism that likely limits tissue damage under pathological conditions of MBP-1 oversecretion. Our results suggest that MBP-1 aggregation is important for innate immunity and immunopathology mediated by eosinophils and clarify how its polymorphic self-association pathways regulate toxicity intra- and extracellularly.

Active eosinophilic esophagitis is characterized by epithelial barrier defects and eosinophil extracellular trap formation.

BACKGROUND Eosinophilic esophagitis (EoE) exhibits esophageal dysfunction owing to an eosinophil-predominant inflammation. Activated eosinophils generate eosinophil extracellular traps (EETs) able to kill bacteria. There is evidence of an impaired barrier function in EoE that might allow pathogens to invade the esophagus. This study aimed to investigate the presence and distribution of EETs in esophageal tissues from EoE patients and their association with possible epithelial barrier defects. METHODS Anonymized tissue samples from 18 patients with active EoE were analyzed. The presence of DNA nets associated with eosinophil granule proteins forming EETs and the expression of filaggrin, the protease inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI), antimicrobial peptides, and cytokines were evaluated by confocal microscopy following immune fluorescence staining techniques. RESULTS Eosinophil extracellular trap formation occurred frequently and was detected in all EoE samples correlating with the numbers of infiltrating eosinophils. While the expression of both filaggrin and LEKTI was reduced, epithelial antimicrobial peptides (human beta-defensin-2, human beta-defensin-3, cathelicidin LL-37, psoriasin) and cytokines (TSLP, IL-25, IL-32, IL-33) were elevated in EoE as compared to normal esophageal tissues. There was a significant correlation between EET formation and TSLP expression (P = 0.02) as well as psoriasin expression (P = 0.016). On the other hand, a significant negative correlation was found between EET formation and LEKTI expression (P = 0.016). CONCLUSION Active EoE exhibits the presence of EETs. Indications of epithelial barrier defects in association with epithelial cytokines are also present which may have contributed to the activation of eosinophils. The formation of EETs could serve as a firewall against the invasion of pathogens.

Depletion of regulatory T cells augments a vaccine-induced T effector cell response against the liver-stage of malaria but fails to increase memory

Regulatory T cells (T(reg)) have been shown to restrict vaccine-induced T cell responses in different experimental models. In these studies CD4(+)CD25(+) T(reg) were depleted using monoclonal antibodies against CD25, which might also interfere with CD25 on non-regulatory T cell populations and would have no effect on Foxp3(+)CD25(-) T(reg). To obtain more insights in the specific function of T(reg) during vaccination we used mice that are transgenic for a bacterial artificial chromosome expressing a diphtheria toxin (DT) receptor-eGFP fusion protein under the control of the foxp3 gene locus (depletion of regulatory T cell mice; DEREG). As an experimental vaccine-carrier recombinant Bordetella adenylate cyclase toxoid fused with a MHC-class I-restricted epitope of the circumsporozoite protein (ACT-CSP) of Plasmodium berghei (Pb) was used. ACT-CSP was shown by us previously to introduce the CD8+ epitope of Pb-CSP into the MHC class I presentation pathway of professional antigen-presenting cells (APC). Using this system we demonstrate here that the number of CSP-specific T cells increases when T(reg) are depleted during prime but also during boost immunization. Importantly, despite this increase of T effector cells no difference in the number of antigen-specific memory cells was observed.

A novel regulatory macrophage induced by a helminth molecule instructs IL-10 in CD4+ T cells and protects against mucosal inflammation

Immunomodulation is a common feature of chronic helminth infections and mainly attributed to the secretion of bioactive molecules, which target and modify host immune cells. In this study, we show that the helminth immunomodulator AvCystatin, a cysteine protease inhibitor, induces a novel regulatory macrophage (Mreg; AvCystatin-Mreg), which is sufficient to mitigate major parameters of allergic airway inflammation and colitis in mice. A single adoptive transfer of AvCystatin-Mreg before allergen challenge suppressed allergen-specific IgE levels, the influx of eosinophils into the airways, local and systemic Th2 cytokine levels, and mucus production in lung bronchioles of mice, whereas increasing local and systemic IL-10 production by CD4(+) T cells. Moreover, a single administration of AvCystatin-Mreg during experimentally induced colitis strikingly reduced intestinal pathology. Phenotyping of AvCystatin-Mreg revealed increased expression of a distinct group of genes including LIGHT, sphingosine kinase 1, CCL1, arginase-1, and costimulatory molecules, CD16/32, ICAM-1, as well as PD-L1 and PD-L2. In cocultures with dendritic cells and CD4(+) T cells, AvCystatin-Mreg strongly induced the production of IL-10 in a cell-contact-independent manner. Collectively, our data identify a specific suppressive macrophage population induced by a single parasite immunomodulator, which protects against mucosal inflammation.