Handelt mit Luft!

Die Arbeit „Handelt mit Luft!“ geht der Frage nach, worin die fundamentalen Ursachen im Scheitern bei der Überwindung des Klimaproblems liegen. Sie zeigt, dass individuell rationales Verhalten im Kollektiv zu einer weiteren Belastung der Atmosphäre führt. Der Schlüssel zur Lösung liegt demnach in einer ordnungsethischen Konzeption, die moralisches Verhalten nicht beim Individuum, sondern in einer Rahmenordnung verortet. Als konkrete Ausgestaltung einer solchen Ordnung untersucht der Autor einen um individuelle Akteure erweiterten Emissionszertifikatehandel auf seine Wirksamkeit, seine Effizienz und seine gerechtigkeitsrelevanten Aspekte im Hinblick auf die politisch geforderte Reduktion von CO2 Emissionen. Er wendet dazu philosophische, ökonomische und politische Theorieressourcen an, analysiert damit den konkreten ordnungspolitischen Lösungsansatz und reflektiert die zugrunde gelegten ethischen Prämissen. Ausgehend von der Annahme rational handelnder Individuen untersucht er die vorherrschenden Interaktionsstrukturen und plädiert für einen persönlichen Emissionshandel als Institution zur Überwindung von Dilemmastrukturen im Klimaschutz

Handelt mit Luft!

Die Arbeit „Handelt mit Luft!“ geht der Frage nach, worin die fundamentalen Ursachen im Scheitern bei der Überwindung des Klimaproblems liegen. Sie zeigt, dass individuell rationales Verhalten im Kollektiv zu einer weiteren Belastung der Atmosphäre führt. Der Schlüssel zur Lösung liegt demnach in einer ordnungsethischen Konzeption, die moralisches Verhalten nicht beim Individuum, sondern in einer Rahmenordnung verortet. Als konkrete Ausgestaltung einer solchen Ordnung untersucht der Autor einen um individuelle Akteure erweiterten Emissionszertifikatehandel auf seine Wirksamkeit, seine Effizienz und seine gerechtigkeitsrelevanten Aspekte im Hinblick auf die politisch geforderte Reduktion von CO2 Emissionen. Er wendet dazu philosophische, ökonomische und politische Theorieressourcen an, analysiert damit den konkreten ordnungspolitischen Lösungsansatz und reflektiert die zugrunde gelegten ethischen Prämissen. Ausgehend von der Annahme rational handelnder Individuen untersucht er die vorherrschenden Interaktionsstrukturen und plädiert für einen persönlichen Emissionshandel als Institution zur Überwindung von Dilemmastrukturen im Klimaschutz

Immunopeptidomics for next-generation bacterial vaccine development

Antimicrobial resistance is an increasing global threat and alternative treatments substituting failing antibiotics are urgently needed. Vaccines are recognized as highly effective tools to mitigate antimicrobial resistance; however, the selection of bacterial antigens as vaccine candidates remains challenging. In recent years, advances in mass spectrometry-based proteomics have led to the development of so-called immunopeptidomics approaches that allow the untargeted discovery of bacterial epitopes that are presented on the surface of infected cells. Especially for intracellular bacterial pathogens, immunopeptidomics holds great promise to uncover antigens that can be encoded in viral vector- or nucleic acid-based vaccines. This review provides an overview of immunopeptidomics studies on intracellular bacterial pathogens and considers future directions and challenges in advancing towards next-generation vaccines

Influence of RNA structural stability on the RNA chaperone activity of the Escherichia coli protein StpA

Proteins with RNA chaperone activity are able to promote folding of RNA molecules by loosening their structure. This RNA unfolding activity is beneficial when resolving misfolded RNA conformations, but could be detrimental to RNAs with low thermodynamic stability. In order to test this idea, we constructed various RNAs with different structural stabilities derived from the thymidylate synthase (td) group I intron and measured the effect of StpA, an Escherichia coli protein with RNA chaperone activity, on their splicing activity in vivo and in vitro. While StpA promotes splicing of the wild-type td intron and of mutants with wild-type-like stability, splicing of mutants with a lower structural stability is reduced in the presence of StpA. In contrast, splicing of an intron mutant, which is not destabilized but which displays a reduced population of correctly folded RNAs, is promoted by StpA. The sensitivity of an RNA towards StpA correlates with its structural stability. By lowering the temperature to 25°C, a temperature at which the structure of these mutants becomes more stable, StpA is again able to stimulate splicing. These observations clearly suggest that the structural stability of an RNA determines whether the RNA chaperone activity of StpA is beneficial to folding

The WD40 domain of ATG16L1 is required for its non-canonical role in lipidation of LC3 at single membranes

A hallmark of macroautophagy is the covalent lipidation of LC3 and insertion into the double-membrane phagophore, which is driven by the ATG16L1/ATG5-ATG12 complex. In contrast, non-canonical autophagy is a pathway through which LC3 is lipidated and inserted into single membranes, particularly endolysosomal vacuoles during cell engulfment events such as LC3-associated phagocytosis. Factors controlling the targeting of ATG16L1 to phagophores are dispensable for non-canonical autophagy, for which the mechanism of ATG16L1 recruitment is unknown. Here we show that the WD repeat containing C-terminal domain (WD40 CTD) of ATG16L1 is essential for LC3 recruitment to endolysosomal membranes during non-canonical autophagy, but dispensable for canonical autophagy. Using this strategy to inhibit non-canonical autophagy specifically we show a reduction of MHC class II antigen presentation in dendritic cells from mice lacking the WD40 CTD. Further, we demonstrate activation of non-canonical autophagy dependent on the WD40 CTD during influenza A virus infection. This suggests dependence on WD40 CTD distinguishes between macroautophagy and non-canonical use of autophagy machinery.This research was supported by the Cambridge NIHR BRC Cell Phenotyping Hub. This work was funded by Cancer Research UK (C47718/A16337, O.F.), the Medical Research Council (RG89611, R.B.) and the BBSRC Institute Strategic Programme Gut Health and Food Safety (BB/J004529/1)

ATP13A3 is a major component of the enigmatic mammalian polyamine transport system

Polyamines, such as putrescine, spermidine, and spermine, are physiologically important polycations, but the transporters responsible for their uptake in mammalian cells remain poorly characterized. Here, we reveal a new component of the mammalian polyamine transport system using CHO-MG cells, a widely used model to study alternative polyamine uptake routes and characterize polyamine transport inhibitors for therapy. CHO-MG cells present polyamine uptake deficiency and resistance to a toxic polyamine biosynthesis inhibitor methylglyoxal bis-(guanylhydrazone) (MGBG), but the molecular defects responsible for these cellular characteristics remain unknown. By genome sequencing of CHO-MG cells, we identified mutations in an unexplored gene, ATP13A3, and found disturbed mRNA and protein expression. ATP13A3 encodes for an orphan P5B-ATPase (ATP13A3), a P-type transport ATPase that represents a candidate polyamine transporter. Interestingly, ATP13A3 complemented the putrescine transport deficiency and MGBG resistance of CHO-MG cells, whereas its knockdown in WT cells induced a CHO-MG phenotype demonstrated as a decrease in putrescine uptake and MGBG sensitivity. Taken together, our findings identify ATP13A3, which has been previously genetically linked with pulmonary arterial hypertension, as a major component of the mammalian polyamine transport system that confers sensitivity to MGBG

Revealing the community within: valuing the role of local community structures within evidence-based school intervention programmes

Schools and the families they serve are sometimes perceived as deficient and in need of fixing. One response has been the implementation of evidence-based family intervention programmes, which may be highly regulated and prescriptive as a condition of their (often philanthropic) funding. This article seeks to explore and bring to the foreground the often hidden role of the pre-existing, informal community networks with a view to more authentic evaluation of these externally imposed programmes. The article draws on a range of qualitative data reflecting the lived experiences of participants—including parents and other community members—in a family and parenting programme at an English primary school. The analysis uses the work of Tönnies as a theoretical lens. It suggests that while there are tensions caused by the rigid requirements of external programmes, these are overcome in many cases by the highly effective, but often unacknowledged, contributions of the informal aspects of community. It is argued that these operate within and complement the formal programme. Far from subverting the more overt procedures, they actually enable it to function successfully, leading to additional, unanticipated transformations among participants. The article concludes that these organic, often invisible connections need to be identified, documented and nurtured if their full potential is to be recognised and realised when evaluating similar interventions

Follicular helper T cell signature in type 1 diabetes

The strong genetic association between particular HLA alleles and type 1 diabetes (T1D) indicates a key role for CD4+ T cells in disease; however, the differentiation state of the responsible T cells is unclear. T cell differentiation originally was considered a dichotomy between Th1 and Th2 cells, with Th1 cells deemed culpable for autoimmune islet destruction. Now, multiple additional T cell differentiation fates are recognized with distinct roles. Here, we used a transgenic mouse model of diabetes to probe the gene expression profile of islet-specific T cells by microarray and identified a clear follicular helper T (Tfh) cell differentiation signature. Introduction of T cells with a Tfh cell phenotype from diabetic animals efficiently transferred diabetes to recipient animals. Furthermore, memory T cells from patients with T1D expressed elevated levels of Tfh cell markers, including CXCR5, ICOS, PDCD1, BCL6, and IL21. Defects in the IL-2 pathway are associated with T1D, and IL-2 inhibits Tfh cell differentiation in mice. Consistent with these previous observations, we found that IL-2 inhibited human Tfh cell differentiation and identified a relationship between IL-2 sensitivity in T cells from patients with T1D and acquisition of a Tfh cell phenotype. Together, these findings identify a Tfh cell signature in autoimmune diabetes and suggest that this population could be used as a biomarker and potentially targeted for T1D interventions.This work was funded by an MRC Senior Fellowship (to L.S.K. Walker), a project grant from JDRF (to L.S.K. Walker and P. Narendran), and a studentship from Diabetes UK (to L.S.K. Walker and P. Narendran). L. Wardzinski and A. Kogimtzis were supported by a Wellcome Trust project grant (to L.S.K. Walker). M. Ono is a BBSRC David Philips fellow.Published versio

Galaxy morphology, kinematics and clustering in a hydrodynamic simulation of a LambdaCDM universe

We explore galaxy properties and their link with environment and clustering using a population of ~1000 galaxies formed in a high resolution hydrodynamic simulation of the Lambda CDM cosmology. At the redshift we concentrate on, z=1, the spatial resolution is 1.4 proper kpc/h and Milky-way sized disk galaxies contain ~10^5 particles within their virial radii. We include supermassive black hole accretion and feedback as well as a multiphase model for star formation. We find that a number of familiar qualitative relationships hold approximately between galaxy properties, for example, galaxies lie between two broad extremes of type, where ``late'' types tend to be smaller in size, have lower circular velocities, younger stars, higher star formation rates, larger disk to bulge ratios and lower Sersic indices than ``early types''. As in previous studies the stellar component of disk galaxies is not as rotationally supported as in observations. Bulges contain too much of the stellar mass, although disks do have scale lengths compatible with observations. The addition of black hole physics to the simulations does not appear to have an impact on the angular momentum results, nor do we find that it is affected in an identical simulation with significantly lower mass resolution. Despite this, we can profitably use the rank order of either disk to total ratio, Sersic index, or galaxy age to separate galaxies into morphological classes and examine the density-morphology relation and morphology dependence of clustering. We find that while at redshift z=0, the well known preponderance of early types in dense environments is seen, at z=1 the density-morphology relation becomes flatter and late type galaxies are even seen to have a higher clustering amplitude than early types (abridged).Comment: 25 pages, 15 figures, submitted to MNRA