Spaceflight modulates gene expression in the whole blood of astronauts

Astronauts are exposed to a unique combination of stressors during spaceflight, which leads to alterations in their physiology and potentially increases their susceptibility to disease, including infectious diseases. To evaluate the potential impact of the spaceflight environment on the regulation of molecular pathways mediating cellular stress responses, we performed a first-of-its-kind pilot study to assess spaceflight-related gene-expression changes in the whole blood of astronauts. Using an array comprised of 234 well-characterized stress-response genes, we profiled transcriptomic changes in six astronauts (four men and two women) from blood preserved before and immediately following the spaceflight. Differentially regulated transcripts included those important for DNA repair, oxidative stress, and protein folding/degradation, including HSP90AB1, HSP27, GPX1, XRCC1, BAG-1, HHR23A, FAP48, and C-FOS. No gender-specific differences or relationship to number of missions flown was observed. This study provides a first assessment of transcriptomic changes occurring in the whole blood of astronauts in response to spaceflight

Coproducing flood risk management through citizen involvement: insights from cross-country comparison in Europe

Across Europe, citizens are increasingly expected to participate in the implementation of flood risk management (FRM), by engaging in voluntary-based activities to enhance preparedness, implementing property-level measures, etc. While citizen participation in FRM decision-making is widely addressed in academic literature, citizens' involvement in the delivery of FRM measures is comparatively understudied. Drawing from public administration literature, this paper adopts the notion of 'co-production' as an analytical framework for studying the interaction between citizens and public authorities, from the decision making process through to the implementation of FRM in practice. The paper considers to what extent co-production is evident in selected EU Member States, drawing from research conducted within the EU project 'STAR-FLOOD'. On the basis of a cross-country comparison between Flanders (Belgium), England (UK), France, the Netherlands and Poland, this research highlights the varied forms of co-production and reflects on how these have been established within divergent settings. Co-production is most outspoken in discourse and practice in England, and is emergent in France and Flanders. By contrast, FRM in the Netherlands and Poland remains almost exclusively reliant on governmental protection measures and thereby consultation-based forms of co-production. Analysis reveals how these actions are motivated by different underlying rationales, which in turn shape the type of approaches and degree of institutionalization of co-production. In the Netherlands, co-production is primarily encouraged to increase societal resilience, while public authorities in the other countries use it as well to improve cost-efficiency and redistribute responsibilities to its beneficiaries

RhIR-regulated acyl-homoserine lactone quorum sensing in a cystic fibrosis isolate of Pseudomonas aeruginosa

The opportunistic pathogen Pseudomonas aeruginosa is a leading cause of airway infection in cystic fibrosis (CF) patients. P. aeruginosa employs several hierarchically arranged and interconnected quorum sensing (QS) regulatory circuits to produce a battery of virulence factors such as elastase, phenazines, and rhamnolipids. The QS transcription factor LasR sits atop this hierarchy and activates the transcription of dozens of genes, including that encoding the QS regulator RhIR. Paradoxically, inactivating lasR mutations are frequently observed in isolates from CF patients with chronic P. aeruginosa infections. In contrast, mutations in rh1R are rare. We have recently shown that in CF isolates, the QS circuitry is often rewired such that RhIR acts in a LasR-independent manner. To begin understanding how QS activity differs in this rewired background, we characterized QS activation and RhIR-regulated gene expression in P. aeruginosa E90, a LasR-null, RhIR-active chronic infection isolate. In this isolate, RhIR activates the expression of 53 genes in response to increasing cell density. The genes regulated by RhIR include several that encode virulence factors. Some, but not all, of these genes are present in the QS regulon described in the well-studied laboratory strain PAO1. We also demonstrate that E90 produces virulence factors at similar concentrations as PAO1, and in E90, RhIR plays a significant role in mediating cytotoxicity in a three-dimensional lung epithelium cell model. These data illuminate a rewired LasR-independent RhIR regulon in chronic infection isolates and suggest further investigation of RhIR as a possible target for therapeutic development in chronic infections. IMPORTANCE Pseudomonas aeruginosa is a prominent cystic fibrosis (CF) pathogen that uses quorum sensing (QS) to regulate virulence. In laboratory strains, the key QS regulator is LasR. Many isolates from patients with chronic CF infections appear to use an alternate QS circuitry in which another transcriptional regulator, RhIR, mediates QS. We show that a LasR-null CF clinical isolate engages in QS through RhIR and remains capable of inducing cell death in an in vivo-like lung epithelium cell model. Our findings support the notion that LasR-null clinical isolates can engage in RhIR QS and highlight the centrality of RhIR in chronic P. aeruginosa infections

Three-dimensional organotypic co-culture model of intestinal epithelial cells and macrophages to study Salmonella enterica colonization patterns

Three-dimensional models of human intestinal epithelium mimic the differentiated form and function of parental tissues often not exhibited by two-dimensional monolayers and respond to Salmonella in key ways that reflect in vivo infections. To further enhance the physiological relevance of three-dimensional models to more closely approximate in vivo intestinal microenvironments encountered by Salmonella, we developed and validated a novel three-dimensional co-culture infection model of colonic epithelial cells and macrophages using the NASA Rotating Wall Vessel bioreactor. First, U937 cells were activated upon collagen-coated scaffolds. HT-29 epithelial cells were then added and the three-dimensional model was cultured in the bioreactor until optimal differentiation was reached, as assessed by immunohistochemical profiling and bead uptake assays. The new co-culture model exhibited in vivo-like structural and phenotypic characteristics, including three-dimensional architecture, apical-basolateral polarity, well-formed tight/adherens junctions, mucin, multiple epithelial cell types, and functional macrophages. Phagocytic activity of macrophages was confirmed by uptake of inert, bacteria-sized beads. Contribution of macrophages to infection was assessed by colonization studies of Salmonella pathovars with different host adaptations and disease phenotypes (Typhimurium ST19 strain SL1344 and ST313 strain D23580; Typhi Ty2). In addition, Salmonella were cultured aerobically or microaerobically, recapitulating environments encountered prior to and during intestinal infection, respectively. All Salmonella strains exhibited decreased colonization in co-culture (HT-29-U937) relative to epithelial (HT-29) models, indicating antimicrobial function of macrophages. Interestingly, D23580 exhibited enhanced replication/survival in both models following invasion. Pathovar-specific differences in colonization and intracellular co-localization patterns were observed. These findings emphasize the power of incorporating a series of related three-dimensional models within a study to identify microenvironmental factors important for regulating infection

Metabolite profiling of Dioscorea (yam) species reveals underutilised biodiversity and renewable sources for high-value compounds

Yams (Dioscorea spp.) are a multispecies crop with production in over 50 countries generating ~50 MT of edible tubers annually. The long-term storage potential of these tubers is vital for food security in developing countries. Furthermore, many species are important sources of pharmaceutical precursors. Despite these attributes as staple food crops and sources of high-value chemicals, Dioscorea spp. remain largely neglected in comparison to other staple tuber crops of tropical agricultural systems such as cassava (Manihot esculenta) and sweet potato (Ipomoea batatas). To date, studies have focussed on the tubers or rhizomes of Dioscorea, neglecting the foliage as waste. In the present study metabolite profiling procedures, using GC-MS approaches, have been established to assess biochemical diversity across species. The robustness of the procedures was shown using material from the phylogenetic clades. The resultant data allowed separation of the genotypes into clades, species and morphological traits with a putative geographical origin. Additionally, we show the potential of foliage material as a renewable source of high-value compounds

Governance strategies for improving flood resilience in the face of climate change

Flooding is the most common of all natural disasters and accounts for large numbers of casualties and a high amount of economic damage worldwide. To be ‘flood resilient’, countries should have sufficient capacity to resist, the capacity to absorb and recover, and the capacity to transform and adapt. Based on international comparative research, we conclude that six key governance strategies will enhance ‘flood resilience’ and will secure the necessary capacities. These strategies pertain to: (i) the diversification of flood risk management approaches; (ii) the alignment of flood risk management approaches to overcome fragmentation; (iii) the involvement, cooperation, and alignment of both public and private actors in flood risk management; (iv) the presence of adequate formal rules that balance legal certainty and flexibility; (v) the assurance of sufficient financial and other types of resources; (vi) the adoption of normative principles that adequately deal with distributional effects. These governance strategies appear to be relevant across different physical and institutional contexts. The findings may also hold valuable lessons for the governance of climate adaptation more generally

To what extent are land resource managers preparing for high-end climate change in Scotland?

We explore the individual and institutional conditions and the climate information used to underpin decision-making for adaptation to high-end climate change (HECC) scenarios in a land resource management context. HECC refers to extreme projections with global annual temperature increases of over 4 °C. We analyse whether HECC scenarios are used in the adaptation decision-making of stakeholders who will tackle the potential problem. We also explore whether the adaptation actions being considered are pertinent only to future climate change or whether other drivers and information types are used in decision-making (including non-climate drivers). We also address the role of knowledge uncertainty in adaptation decision-making. Decision-makers perceive HECC as having a low probability of occurrence and so they do not directly account for HECC within existing actions to address climate change. Such actions focus on incremental rather than transformative solutions in which non-climate drivers are at least as important, and in many cases more important, than climate change alone. This reflects the need to accommodate multiple concerns and low risk options (i.e. incremental change). Uncertainty in climate change information is not a significant barrier to decision-making and stakeholders indicated little need for more climate information in support of adaptation decision-making. There is, however, an identified need for more information about the implications of particular sectoral and cross-sectoral impacts under HECC scenarios. The outcomes of this study provide evidence to assist in contextualising climate change information by creating usable, cross-sectoral, decision-centred information

Social Participation and Disaster Risk Reduction Behaviors in Tsunami Prone Areas

This paper examines the relationships between social participation and disaster risk reduction actions. A survey of 557 households in tsunami prone areas in Phang Nga, Thailand was conducted following the 2012 Indian Ocean earthquakes. We use a multivariate probit model to jointly estimate the likelihood of undertaking three responses to earthquake and tsunami hazards (namely, (1) following disaster-related news closely, (2) preparing emergency kits and/or having a family emergency plan, and (3) having an intention to migrate) and community participation.We find that those who experienced losses from the 2004 tsunami are more likely to participate in community activities and respond to earthquake hazards. Compared to men, women are more likely to prepare emergency kits and/or have an emergency plan and have a greater intention to migrate. Living in a community with a higher proportion of women with tertiary education increases the probability of engaging in community activities and carrying out disaster risk reduction measures. Individuals who participate in village-based activities are 5.2% more likely to undertake all three risk reduction actions compared to those not engaging in community activities. This implies that encouraging participation in community activities can have positive externalities in disaster mitigation

Phenotyping progenies for complex architectural traits: a strategy for 1-year-old apple trees (Malus x domestica Borkh.)

International audienceThe aim of this study was to define a methodology for describing architectural traits in a quantitative way on tree descendants. Our strategy was to collect traits related to both tree structural organization, resulting from growth and branching, and tree form and then to select among these traits relevant descriptors on the basis of their genetic parameters. Because the complexity of tree architecture increases with tree age, we chose to describe the trees in the early stages of development. The study was carried out on a 1-year-old apple progeny derived from two parent cultivars with contrasted architecture. A large number of variables were collected at different positions and scales within the trees. Broad-sense heritability and genetic correlations were estimated and the within tree variability was analyzed for variables measured on long sylleptic axillary shoots (LSAS). These results were combined to select heritable and not correlated variables. Finally, the selection of variables proposed combines topological with geometric traits measured on both trunks and LSAS: (1) on the trunk, mean internode length, and number of sylleptic axillary shoots; (2) on axillary shoots, conicity, bending, and number of sylleptic axillary shoots born at order 3. The trees of the progeny were partitioned on the basis of these variables. The putative agronomic interest of the selected variables with respect to the subsequent tree development is discussed