Roadmap for an early gene therapy for cystic fibrosis airway disease

Gene therapy provides a mutation-independent approach to treat or even cure CF airway disease. To develop a clinical candidate for CF gene therapy, a thorough examination of preclinical efficacy in relevant cell and animal models is a prerequisite. For a long time, the CF field was struggling with a lack of appropriate animal models for CF airway pathology. Since 2008, many different and complementary animal models have been generated that develop hallmarks of CF airway disease, including the CF pig, ferret, and rat. With this, a new era has arisen that allows investigating the efficacy of gene therapy beyond molecular and electrophysiological end-points. Successful gene therapy most likely requires an appropriate time window. CF lung pathology progresses with age and therefore an early treatment would be beneficial to prevent irreversible damage. In that regard, newborn screening programs and prenatal diagnosis already provide a basis to facilitate future preventive gene-based treatment. If successful, gene therapy for CF airway disease would markedly reduce the treatment burden and improve life quality and life expectancy of CF patients.     

Tritium and Cl as constraints on fast fracture flow and percolation flux in the unsaturated zone at Yucca Mountain

An analysis of tritium and ³⁶Cl data collected at Yucca Mountain, Nevada suggests that fracture flow may occur at high velocities through the thick unsaturated zone. The mechanisms and extent of this “fast flow” in fractures at Yucca Mountain are investigated with data analysis, mixing models and several one-dimensional modeling scenarios. The model results and data analysis provide evidence substantiating the weeps model [Gauthier, J.H., Wilson, M.L., Lauffer, F.C., 1992. Proceedings of the Third Annual International High-level Radioactive Waste Management Conference, vol. 1, Las Vegas, NV. American Nuclear Society, La Grange Park, IL, pp. 891–989] and suggest that fast flow in fractures with minimal fracture–matrix interaction may comprise a substantial proportion of the total infiltration through Yucca Mountain. Mixing calculations suggest that bomb-pulse tritium measurements, in general, represent the tail end of travel times for thermonuclear-test-era (bomb-pulse) infiltration. The data analysis shows that bomb-pulse tritium and ³⁶Cl measurements are correlated with discrete features such as horizontal fractures and areas where lateral flow may occur. The results presented here imply that fast flow in fractures may be ubiquitous at Yucca Mountain, occurring when transient infiltration (storms) generates flow in the connected fracture network.     

Three beetles—three concepts. Different defensive strategies of congeneric myrmecophilous beetles

Myrmecophiles, i.e., organisms associated with ants live in a variety of ecological niches in the vicinity or inside ant colonies and employ different strategies to survive ant encounters. Because different niches are characterized by different encounter rates with host ants, strategies used to avoid ant aggressions should depend on these niches. This hypothesis was studied with three rove beetle species of the genus Pella, which are myrmecophiles of the ant Lasius fuliginosus and the non-myrmecophilous relative Drusilla canaliculata. Behavioral tests in the field revealed that Pella species are better adapted to interactions with ants than D. canaliculata, but that they use species-specific strategies in ant interactions. Pella cognata and Pella funesta avoid encounters with ants by swift movements. Chemical analyses of the defensive tergal gland secretions showed that P. cognata has replaced the aggression inducing undecane by the behaviorally neutral tridecane. P. funesta repels the ants by releasing the panic alarm pheromone sulcatone from its tergal gland resulting in an “ant free space” around the beetles. Finally, Pella laticollis uses a specific and unique appeasing behavior. Behavioral and chemical data did not reveal any indication for the mimicry of the ants' cuticular hydrocarbon profiles by any of the beetle species. It is discussed that the employed strategies correlate with the ecological niches of the beetles. P. cognata and P. funesta are living along ant trails with ample space to escape and the employed strategies are probably sufficient to escape from dangerous conflicts. In contrast, P. laticollis lives in refuse areas of ant nests with frequent ant encounters, and its appeasement strategy allows it to stay at the encounter site.     

Sustainable development in four Swedish communities priorities, responsibility, empowerment

The aims were to identify sustainable development priorities and perceived responsibility of sustainable development issues. Differences in opinions between politicians, officials, environmental representatives and the public in four Swedish municipalities were analysed. Sustainable development issues were perceived as more important on the global level than on the municipal and family levels. Among the most important issues on both the global and family levels were clean air, fresh water, and health, whereas decision-making, co-operation, and participation were considered most important on the municipal level. The highest responsibility for sustainable development issues was placed on governments and global organizations and the lowest on the individual. The public felt less individual responsibility and less possibility to influence than did the other groups. The correlation between importance and responsible on municipal and world levels was high but low on the individual level. The responsibility for the most important issue on the family level (clean air) was placed on governments and global organizations. An attitude change is needed to increase responsibility for issues ranked low on individual responsibility. To further raise the awareness of global sustainable development issues, an increased concentration on locally based international co-operation projects is suggested.     

Demonstration of sex pheromones in the predaceous diving beetle Rhantus suturalis (MacLeay 1825) (Dytiscidae)

Sex pheromones are used by a wide variety of species in terrestrial ecosystems. Much less is known about these pheromones in aquatic systems e.g., for diving beetles. To test the use of pheromones and visual signals for mate finding by the diving beetle Rhantus suturalis (MacLeay 1825), behavioral experiments were performed using three different types of vessels containing conspecific. In experiments with non-permeable glass flasks, which did not allow the diffusion of chemical substances, males and females did not stimulate any reaction by conspecific of either sex. In experiments with opaque but water permeable vessels, and in experiments with vessels made of finely woven steel, which allowed the perception of chemical as well as optical cues, male diving beetles were significantly attracted to females. Females were attracted to other females only in the last experiment, when simultaneously perceiving chemical and optical cues. These results indicate that R. suturalis females release sex pheromones to attract mating partners, which is the first experimental demonstration of pheromones in the Dytiscidae.     

Levels and trends of persistent organic pollutants in ringed seals (Phoca hispida) from Central West Greenland, with particular focus on polybrominated diphenyl ethers (PBDEs)

Polybrominated diphenyl ethers (PBDEs) and the organochlorine compounds polychlorinated biphenyls (PCBs), DDTs, HCB, chlordane-related pesticides, HCH and toxaphene were analysed in blubber of juvenile ringed seals from Central West Greenland collected between 1982 and 2006. The longest time series could be established for PBDEs, partly based on archived material, while PCBs and DDTs covered a study period from 1994-2006. All organochlorines showed decreasing trends, most pronounced for DDT and HCH with an annual change of 8%. BDE-47 had a significantly increasing trend of 5% annually. It was the only BDE congener consistently above the detection limit, with annual median concentrations between 0.78 ng/g lw to 3.54 ng/g lw, i.e. about 10 times lower than values from East Greenland observed in a similar time trend study on ringed seal blubber [Rigét F, Vorkamp K, Dietz R, Rastogi SC. Temporal trend studies on polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) in ringed seals from East Greenland. J Environ Monit 2006; 8: 1000-5]. A clear East>West difference was also found for PCBs and DDTs, but not for chlordanes, toxaphene or HCHs. Sigma 10-PCB, Sigma DDT and Sigma Chlordanes had similar annual median concentrations, typically exceeding SigmaPBDE by two orders of magnitude. The concentrations of HCH and toxaphene were in an intermediate group, with highest annual median concentrations of 135 ng/g lw and 20 ng/g lw, respectively. For most compound groups, the circumpolar trend previously established under for example the Arctic Monitoring and Assessment Programme was confirmed, but apparently, more data are needed for chlordane-related compounds and toxaphene. Statistical analyses of the compound patterns in the ringed seal samples revealed significantly greater differences between seals from East and West than between different sampling years. Higher proportions of PCBs and DDTs and lower proportions of chlordanes and HCHs were found in seals from East Greenland than in those from West Greenland. Based on principal component analysis of individual congener and compounds, seals from East Greenland were found to contain higher proportions of the higher chlorinated CB congeners. Varying patterns between sampling locations may be caused by different exposure situations related to contaminant emissions and transport, but different feeding habits may also affect the contaminant composition.     

Sea-level rise in Indonesia: on adaptation priorities in the agricultural sector

Adaptation to climate-change impacts requires understanding of where impacts are to be expected and what their magnitude may be. Adaptation funds are only a limited resource for helping affected parties in coping with climate-change impacts. The application of suitable methods helps to determine the recipients of adaptation aid. A quantification of impacts based on different impact analyses can aid in taking on various perspectives on the same problem in order to identify the appropriate perspective for the given decision-making context or for identifying impact patterns. Once executed, this prioritizes adaptation needs and finding a suitable allocation rule, given the policy makers perception of the decision-making context. The study introduces a set of methods of spatially explicit, sub-national (province level), and country-wide impact analyses regarding inundation impacts on agricultural areas for four important food crops in Indonesia. These methods are applied to a 1 and 2 m sea-level rise scenario and include a novel approach for impact analyses, data envelopment analysis, which is not widely used in environmental studies as of yet. Based on the given case study, the paper demonstrates the applicability of these methods and identifies impact patterns.