Septischer Schock: Molekulare Pathophysiologie und therapeutische Ansaetze. Teilprojekt B1: Isolierung und strukturelle Charakterisierung von Endotoxin-Antagonisten Ein Beitrag zur Untersuchung der Struktur-Funktionsweise von Lipoid A/LPS Strukturen mit antagonistischem Potential. Schlussbericht

A new method has been developed to isolate and investigate lipid A and lipid A-part structures resulting in high purity (>95%) and excellent yield (35-40%). A preparation protocol has been elaborated to prepare polar and charged glycolipids suitable for mass spectrometric analysis (MALDI-TOF). In addition, non-invasive NMR-spectroscopy has been used and investigated in several organic and aqueous solution, allowing the lipid A-preparation to be investigated, thus giving access to study identical preparations by both ways chemically and biologically. This approach has to the best of our knowledge not been described so far. A new endotoxin-antagonist has been described for the first time, and its structure was completely elucidated and biologically characterised with respect to induce or inhibit proinflammatory cytokines in human monocytes (hMNC). The antagonist was identified as a tetraacylated lipid A part-structure expressing identical antagonistic activty as compared to the well characterised synthetic compound 406. The physicochemical properties of this new antagonist are in agreement with the model postulating that bioactivity of LPS (or lipid A) is related not directly to its primary structure, but rather to its physicochemical and supramolecular properties ('endotoxic conformation'). (orig.)SIGLEAvailable from TIB Hannover: F99B46 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

Exploring the relationship between plural values of nature, human well‐being, and conservation and development intervention: Why it matters and how to do it?

Publication status: PublishedFunder: Alexander von Humboldt‐Stiftung; doi: http://dx.doi.org/10.13039/100005156Funder: Consortium of International Agricultural Research Centers: FTAFunder: Direktion für Entwicklung und Zusammenarbeit; doi: http://dx.doi.org/10.13039/100009131Funder: Frank Jackson Foundation; doi: http://dx.doi.org/10.13039/501100015683Funder: Science for Nature and People Partnership; doi: http://dx.doi.org/10.13039/100014606Globally, land and seascapes across the bioculturally diverse tropics are in transition. Impacted by the demands of distant consumers, the processes of global environmental change and numerous interventions seeking climate, conservation and development goals, these transitions have the potential to impact the relationships and plurality of values held between people and place. This paper is a Synthesis of seven empirical studies within the Special Feature (SF): ‘What is lost in transition? Capturing the impacts of conservation and development interventions on relational values and human wellbeing in the tropics’. Through two Open Forum workshops, and critical review, contributing authors explored emergent properties across the papers of the SF. Six core themes were identified and are subsumed within broad categories of: (i) the problem of reconciling scale and complexity, (ii) key challenges to be overcome for more plural understanding of social dimensions of landscape change and (iii) ways forward: the potential of an environmental justice framework, and a practical overview of methods available to do so. The Synthesis interprets disparate fields and complex academic work on relational values, human well‐being and de‐colonial approaches in impact appraisal. It offers a practical and actionable catalogue of methods for plural valuation in the field, and reflects on their combinations, strengths and weaknesses. The research contribution is policy relevant because it builds the case for why a more plural approach in intervention design and evaluation is essential for achieving more just and sustainable futures, and highlights some of the key actions points deemed necessary to achieve such a transition to conventional practice. Read the free Plain Language Summary for this article on the Journal blog

Co-producing Knowledge for Sustainable Development in Telecoupled Land Systems

Land is at the core of our planet’s sustainable development challenges. Different actors have contesting claims on ecosystem services provided by local land systems. Land-use changes therefore always entail trade-offs in terms of ecosystem service provision. The United Nations’ 2030 Agenda for Sustainable Development offers a normative frame for land system science to produce relevant knowledge for transformation. Such knowledge should include an understanding of social-ecological systems from a systemic as well as a power perspective. Telecoupled interactions between distant systems present an additional challenge to knowledge production requiring methodological innovation. To co-produce evidence for navigating trade-offs inherent to land-use changes, we need to embrace the three knowledge dimensions of systems, target, and transformation knowledge and make use of inter- and transdisciplinary research approaches

Directing the Immune System with Chemical Compounds

Agonists of immune cell receptors direct innate and adaptive immunity. These agonists range in size and complexity from small molecules to large macromolecules. Here, agonists of a class of immune cell receptors known as the Toll-like receptors (TLRs) are highlighted focusing on the distinctive molecular moieties that pertain to receptor binding and activation. How the structure and combined chemical signals translate into a variety of immune responses remain major questions in the field. In this structure-focused review, we outline potential areas where the tools of chemical biology could help decipher the emerging molecular codes that direct immune stimulation