Microbiota colonization tunes the antigen threshold of microbiota-specific T cell activation in the gut

Harnessing the potential of commensal bacteria for immunomodulatory therapy in the gut requires the identification of conditions that modulate immune activation towards incoming colonizing bacteria. In this study, we used the commensal Bacteroides thetaiotaomicron (B.theta) and combined it with B.theta-specific transgenic T cells, in the context of defined colonization of gnotobiotic and immunodeficiency mouse models, to probe the factors modulating bacteria-specific T cell activation against newly colonizing bacteria. After colonizing germ-free (GF) and conventionally raised (SPF) mice with B.theta, we only observed proliferation of B.theta-specific T cells in GF mice. Using simple gnotobiotic communities we could further demonstrate that T-cell activation against newly colonizing gut bacteria is restricted by previous bacteria colonization in GF mice. However, this restriction requires a functional adaptive immune system as Rag1$^{-/-}$ allowed B.theta-specific T cell proliferation even after previous colonization. Interestingly, this phenomenon seems to be dependent on the type of TCR-transgenic model used. B.theta-specific transgenic T cells also proliferated after gut colonization with an E.coli strain carrying the B.theta-specific epitope. However, this was not the case for the SM-1 transgenic T cells as they did not proliferate after similar gut colonization with an E.coli strain expressing the cognate epitope. In summary, we found that activation of T cells towards incoming bacteria in the gut is modulated by the influence of colonizing bacteria on the adaptive immune system of the host

An optimised assay for quantitative, high-throughput analysis of polysialyltransferase activity

YesThe polysialyltransferases are biologically important glycosyltransferase enzymes responsible for the biosynthesis of polysialic acid, a carbohydrate polymer that plays a critical role in the progression of several diseases, notably cancer. Having improved the chemical synthesis and purification of the fluorescently-labelled DMB-DP3 acceptor, we report optimisation and validation of a highly sensitive cell-free high-throughput HPLC-based assay for assessment of human polysialyltransferase activity

Manager- und transaktionsspezifische Determinanten der Performance von Arbitrage CLOs

Der vorliegende Beitrag untersucht die Determinanten der Performance europäischer Arbitrage Collateralized Loan Obligations für das Jahr 2009. Der Fokus liegt dabei auf der Bedeutung der performanceabhängigen Vergütung des CLO-Managers, den Eigenschaften des CLO-Managers und der Transaktionscharakteristika als mögliche Einflussfaktoren der Rating Performance. Es wird gezeigt, dass Transaktionen, bei denen dem CLO-Manager eine Incentive Management Fee gewährt wird, mit einer höheren Wahrscheinlichkeit herabgestuft werden als Transaktionen ohne Incentive Fee. Dieser Befund bestätigt die Hypothese, dass durch die Incentive Fee Risikoanreize für CLO-Manager geschaffen werden. Des Weiteren wird ein positiver Zusammenhang zwischen der Erfahrung bzw. der Größe eines CLO-Managers und der Rating Performance festgestellt. Der Einfluss des Managers auf die Performance einer CLO-Transaktion wird auch an den weiteren in der Studie herangezogenen managerspezifischen Charakteristika wie Typ und Unternehmenssitz bestätigt. Für die Transaktionscharakteristika wird hingegen im betrachteten Untersuchungszeitraum kein signifikanter Einfluss auf die Rating Performance nachgewiesen

The changing culture of silviculture

Changing climates are altering the structural and functional components of forest ecosystems at an unprecedented rate. Simultaneously, we are seeing a diversification of public expectations on the broader sustainable use of forest resources beyond timber production. As a result, the science and art of silviculture needs to adapt to these changing realities. In this piece, we argue that silviculturists are gradually shifting from the application of empirically derived silvicultural scenarios to new sets of approaches, methods and practices, a process that calls for broadening our conception of silviculture as a scientific discipline. We propose a holistic view of silviculture revolving around three key themes: observe, anticipate and adapt. In observe, we present how recent advances in remote sensing now enable silviculturists to observe forest structural, compositional and functional attributes in near-real-time, which in turn facilitates the deployment of efficient, targeted silvicultural measures in practice that are adapted to rapidly changing constraints. In anticipate, we highlight the importance of developing state-of-the-art models designed to take into account the effects of changing environmental conditions on forest growth and dynamics. In adapt, we discuss the need to provide spatially explicit guidance for the implementation of adaptive silvicultural actions that are efficient, cost-effective and socially acceptable. We conclude by presenting key steps towards the development of new tools and practical knowledge that will ensure meeting societal demands in rapidly changing environmental conditions. We classify these actions into three main categories: reexamining existing silvicultural trials to identify key stand attributes associated with the resistance and resilience of forests to multiple stressors, developing technological workflows and infrastructures to allow for continuous forest inventory updating frameworks, and implementing bold, innovative silvicultural trials in consultation with the relevant communities where a range of adaptive silvicultural strategies are tested. In this holistic perspective, silviculture can be defined as the science of observing forest condition and anticipating its development to apply tending and regeneration treatments adapted to a multiplicity of desired outcomes in rapidly changing realities

The changing culture of silviculture

Changing climates are altering the structural and functional components of forest ecosystems at an unprecedented rate. Simultaneously, we are seeing a diversification of public expectations on the broader sustainable use of forest resources beyond timber production. As a result, the science and art of silviculture needs to adapt to these changing realities. In this piece, we argue that silviculturists are gradually shifting from the application of empirically derived silvicultural scenarios to new sets of approaches, methods and practices, a process that calls for broadening our conception of silviculture as a scientific discipline. We propose a holistic view of silviculture revolving around three key themes: observe, anticipate and adapt. In observe, we present how recent advances in remote sensing now enable silviculturists to observe forest structural, compositional and functional attributes in near-real-time, which in turn facilitates the deployment of efficient, targeted silvicultural measures in practice that are adapted to rapidly changing constraints. In anticipate, we highlight the importance of developing state-of-the-art models designed to take into account the effects of changing environmental conditions on forest growth and dynamics. In adapt, we discuss the need to provide spatially explicit guidance for the implementation of adaptive silvicultural actions that are efficient, cost-effective and socially acceptable. We conclude by presenting key steps towards the development of new tools and practical knowledge that will ensure meeting societal demands in rapidly changing environmental conditions. We classify these actions into three main categories: re-examining existing silvicultural trials to identify key stand attributes associated with the resistance and resilience of forests to multiple stressors, developing technological workflows and infrastructures to allow for continuous forest inventory updating frameworks, and implementing bold, innovative silvicultural trials in consultation with the relevant communities where a range of adaptive silvicultural strategies are tested. In this holistic perspective, silviculture can be defined as the science of observing forest condition and anticipating its development to apply tending and regeneration treatments adapted to a multiplicity of desired outcomes in rapidly changing realities

Measuring emotional and social wellbeing in Aboriginal and Torres Strait Islander populations: an analysis of a Negative Life Events Scale

Aboriginal and Torres Strait Islander Australians experience widespread socioeconomic disadvantage and health inequality. In an attempt to make Indigenous health research more culturally-appropriate, Aboriginal and Torres Strait Islander Australians have called for more attention to the concept of emotional and social wellbeing (ESWB). Although it has been widely recognised that ESWB is of crucial importance to the health of Aboriginal and Torres Strait Islander peoples, there is little consensus on how to measure in Indigenous populations, hampering efforts to better understand and improve the psychosocial determinants of health. This paper explores the policy and political context to this situation, and suggests ways to move forward. The second part of the paper explores how scales can be evaluated in a health research setting, including assessments of endorsement, discrimination, internal and external reliability

Trees, forests and water: Cool insights for a hot world

Forest-driven water and energy cycles are poorly integrated into regional, national, continental and global decision-making on climate change adaptation, mitigation, land use and water management. This constrains humanity’s ability to protect our planet’s climate and life-sustaining functions. The substantial body of research we review reveals that forest, water and energy interactions provide the foundations for carbon storage, for cooling terrestrial surfaces and for distributing water resources. Forests and trees must be recognized as prime regulators within the water, energy and carbon cycles. If these functions are ignored, planners will be unable to assess, adapt to or mitigate the impacts of changing land cover and climate. Our call to action targets a reversal of paradigms, from a carbon-centric model to one that treats the hydrologic and climate-cooling effects of trees and forests as the first order of priority. For reasons of sustainability, carbon storage must remain a secondary, though valuable, by-product. The effects of tree cover on climate at local, regional and continental scales offer benefits that demand wider recognition. The forest- and tree-centered research insights we review and analyze provide a knowledge-base for improving plans, policies and actions. Our understanding of how trees and forests influence water, energy and carbon cycles has important implications, both for the structure of planning, management and governance institutions, as well as for how trees and forests might be used to improve sustainability, adaptation and mitigation efforts

Sarcopenia and cachexia: the adaptations of negative regulators of skeletal muscle mass

Recent advances in our understanding of the biology of muscle, and how anabolic and catabolic stimuli interact to control muscle mass and function, have led to new interest in the pharmacological treatment of muscle wasting. Loss of muscle occurs as a consequence of several chronic diseases (cachexia) as well as normal aging (sarcopenia). Although many negative regulators [Atrogin-1, muscle ring finger-1, nuclear factor-kappaB (NF-κB), myostatin, etc.] have been proposed to enhance protein degradation during both sarcopenia and cachexia, the adaptation of mediators markedly differs among these conditions. Sarcopenic and cachectic muscles have been demonstrated to be abundant in myostatin- and apoptosis-linked molecules. The ubiquitin–proteasome system (UPS) is activated during many different types of cachexia (cancer cachexia, cardiac heart failure, chronic obstructive pulmonary disease), but not many mediators of the UPS change during sarcopenia. NF-κB signaling is activated in cachectic, but not in sarcopenic, muscle. Some studies have indicated a change of autophagic signaling during both sarcopenia and cachexia, but the adaptation remains to be elucidated. This review provides an overview of the adaptive changes in negative regulators of muscle mass in both sarcopenia and cachexia

Distinct Argonaute-mediated 22G-RNA pathways direct genome surveillance in the C. elegans germline

Endogenous small RNAs (endo-siRNAs) interact with Argonaute (AGO) proteins to mediate sequence-specific regulation of diverse biological processes. Here, we combine deep-sequencing and genetic approaches to explore the biogenesis and function of endo-siRNAs in C. elegans. We describe conditional alleles of the dicer-related helicase, drh-3, that abrogate both RNA interference and the biogenesis of endo-siRNAs, called 22G-RNAs. DRH-3 is a core component of RNA-dependent RNA polymerase (RdRP) complexes essential for several distinct 22G-RNA systems. We show that in the germ-line, one system is dependent on worm-specific AGOs, including WAGO-1, which localizes to germ-line nuage structures called P-granules. WAGO-1 silences certain genes, transposons, pseudogenes and cryptic loci. Finally, we demonstrate that components of the nonsense-mediated decay pathway function in at least one WAGO-mediated surveillance pathway. These findings broaden our understanding of the biogenesis and diversity of 22G-RNAs and suggest novel regulatory functions for small RNAs