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The mature palm forest of the Vallée de Mai, a UNESCO World Heritage Site, on the Seychelles island of Praslin, is a unique ecosystem containing many endemic species, including the iconic coco de mer palm Lodoicea maldivica. In 2009, the invasive yellow crazy ant Anoplolepis gracilipes was recorded for the first time within the palm forest, raising concern about its potential impacts on the endemic fauna. This research aimed to: (1) assess the current distribution and spread of A. gracilipes within the palm forest; (2) identify environmental variables that are linked to A. gracilipes distribution; and (3) compare endemic species richness and abundance in A. gracilipes invaded and uninvaded areas. Anoplolepis gracilipes was confined to the north-east of the site and remained almost stationary between April 2010 and December 2012, with isolated outbreaks into the forest. Infested areas had significantly higher temperature and humidity and lower canopy cover. Abundance and species richness of the endemic arboreal fauna were lower in the A. gracilipes invaded area. Molluscs were absent from the invaded area. The current restricted distribution of A. gracilipes in this ecosystem, combined with lower abundance of endemic fauna in the invaded area, highlight the need for further research to assess control measures and the possible role of biotic resistance to the invasion of the palm forest by A. gracilipes.
In the last few decades, the abundance and importance of invasive alien species have grown continuously due to the undiminished growth of global trade. In most cases, arthropod introductions were unintended and occurred as hitchhikers or contaminants. Alien arthropods can have significant environmental impacts and can be economically costly. To measure these impacts, we expand a generic impact scoring system initially developed for mammals and birds, and applied it to terrestrial arthropods. It consists of six environmental impact categories and six economic impact categories, each with five impact levels. Information on impact was derived from an intensive analysis of published scientific literature. The scoring of the 77 most widely distributed arthropod species alien to Europe revealed the mite Varroa destructor as the most harmful species, followed by the Chinese longhorn beetle Anoplophora chinensis and the Argentine ant Linepithema humile. The highest environmental impact is through herbivory, disease transmission, and ecosystem impacts. The highest economic impact is on agriculture and human infrastructure and administration. The generic impact scoring system allows the impact scores of vertebrates and arthropods to be compared, thus serving as a background for the decision making processes of policy makers and stakeholders.
Invasions by non-native species are a threat to biodiversity because invaders can impact native populations, communities and entire ecosystems. To manage this threat, it is necessary to have a strong mechanistic understanding of how non-native species affect local species and communities. We reviewed 259 published papers (1972–2012) that described field experiments quantifying the impact of aquatic nonnative species, to examine whether various types of study biases are limiting this understanding. Our review revealed that invasion impacts had been experimentally quantified for 101 aquatic non-native species, in all major freshwater and marine habitats, on all continents except Antarctica and for most higher taxonomic groupings. Over one-quarter (26%) of studies included tests for impacts on local biodiversity. However, despite this extensive research effort, certain taxa, habitats and regions remain poorly studied. For example, of the over one hundred species examined in previous studies, only one was a marine fish and only six were herbivores. Furthermore, over half (53%) of the studies were from the USA and two-thirds (66%) were from experiments conducted in temperate latitudes. By contrast, only 3% of studies were from Africa and <2% from high latitudes. We also found that one-fifth (20%) of studies were conducted in estuaries, but only 1% from coral reefs. Finally, we note that the standard procedure of pooling or not reporting non-significant treatments and responses is likely to limit future synthetic advancement by biasing meta-analysis and severely limiting our ability to identify non-native species with none or negligible ecological impacts. In conclusion, a future focus on poorly-studied taxa, habitats and regions, and enhanced reporting of results, should improve our understanding and management of impacts associated with aquatic non-native species.
To understand what makes some species successful invaders, it is critical to quantify performance differences between native and introduced regions, and among populations occupying a broad range of environmental conditions within each region. However, these data are not available even for the world’s most notorious invasive species. Here we introduce the Global Garlic Mustard Field Survey, a coordinated distributed field survey to collect performance data and germplasm from a single invasive species: garlic mustard (Alliaria petiolata) across its entire distribution using minimal resources. We chose this species for its ecological impacts, prominence in ecological studies of invasion success, simple life history, and several genetic and life history attributes that make it amenable to experimental study. We developed a standardised field survey protocol to estimate population size (area) and density, age structure, plant size and fecundity, as well as damage by herbivores and pathogens in each population, and to collect representative seed samples. Across four years and with contributions from 164 academic and non-academic participants from 16 countries in North America and Europe thus far, we have collected 45,788 measurements and counts of 137,811 plants from 383 populations and seeds from over 5,000 plants. All field data and seed resources will be curated for release to the scientific community. Our goal is to establish A. petiolata as a model species for plant invasion biology and to encourage large collaborative studies of other invasive species.
The cattle egret (Bubulcus ibis) has recently colonized Brazil. This process offers an excellent opportunity for the study of colonization and dispersal patterns across extensive areas by non-native birds. The aims of the present investigation were a) to determine the genetic diversity of the cattle egret in Brazil and Africa, b) evaluate genetic differentiation between populations in different regions of Brazil and Africa, and c) detect genetic signs of demographic expansion in these two areas. Mitochondrial DNA (mtDNA) Control Region (CR) sequences were obtained from 112 cattle egrets in four Brazilian and four African (Kenya, Ghana and Nigeria) populations. Genetic diversity (H, h, θ) and population structure (AMOVA, Fst) were assessed and the populations were tested for signs of recent demographic expansion. A total of 35 haplotypes were found: 22 exclusive to Africa, 10 exclusive to Brazil and three shared by both samples. The degree of genetic diversity, determined by mtDNA analysis, was similar between Brazil and Africa, demonstrating that the successful colonization of the non-native area occurred with no significant loss of diversity. The pairwise Fst values among the Brazilian and African populations were all significantly different. The population in southern Brazilian exhibited the lowest degree of differentiation with respect to the African population, followed by the southeastern and northeastern populations of the country. The genetic differentiation data suggest that the colonization of Brazil by the cattle egret began in the southern region and expanded to the southeastern and northeastern regions of the country. This genetic differentiation pattern is in accordance with the higher number of cattle per grazing area in southern Brazil, which may have favored the onset of the successful establishment of the species. The findings indicate that mtDNA genetic diversity was retained during the colonization process and colonization began in the southern region of the country. Moreover, signs of demographic expansion were detected in the African sample.
Wrack burial reduces germination and establishment of the invasive cordgrass Spartina densiflora
(2014)
Germination and emergence of halophytes may decrease significantly by seed burial in dead plant material, or wrack, which is common and abundant in tidal marshes. The effects of plant debris (wrack) burial on seed germination and seedling establishment of Spartina densiflora, an invasive cordgrass, were studied under greenhouse conditions and compared with field observations. Five wrack burial depths were applied: control without wrack, 1 cm (1235 ± 92 g DW wrack m-2), 2 cm (3266 ± 13 g DW m-2), 4 cm (4213 ± 277 g DW m-2), and 8 cm (6138 ± 227 g DW m-2). Sediment pH, electrical conductivity, redox potential and temperature were recorded. Quiescence increased with wrack load up to ~20% at 8 cm deep. Germination decreased with wrack load from 96% to 14%, which could be related with anoxic conditions under the debris since sediment redox potential was as low as -83 ± 7 mV at 8 cm. Germination percentage increased and quiescent and dormant percentages decreased at higher daily sediment temperatures and with higher daily temperature fluctuations, conditions that were recorded without or under low loads of wrack. Spartina densiflora did not show primary dormancy, but its seeds entered into a non-deep physiological dormancy below 1 cm deep in plant debris. The establishment of S. densiflora seedlings was also greatly reduced by wrack burial since only 6 seedlings (11 ± 5 % of germinated seeds) emerged above plant debris from 1 cm and all seedlings died from deeper than 1 cm. S. densiflora seedling development was also reduced by wrack burial. The inverse relationship between germination and emergence of S. densiflora with wrack burial recorded in our study is useful to predict its invasion dynamics and to plan the management of invaded marshes.
Halting biological invasions in Europe : from data to decisions ; a message from NEOBIOTA 2012
(2014)
The NEOBIOTA conferences initiated by the European Group on Biological Invasions represents a forum for exchange of ideas and discussion of topics related to biological invasions as well as an interface between science, application and policies (Kowarik and Starfinger 2009). The 7th NEOBIOTA conference (http://neobiota2012.blogspot.com.es/), held in Pontevedra (Spain) from 12–14 September 2012, brought together 288 participants (ecologists, conservationists, representatives of governmental agencies and stake-holders), from 24 European countries and 9 non-European ones (namely, Australia, Brazil, Canada, Chile, Colombia, New Zealand, South Africa, United States and Venezuela).
The success of invasive species has been explained by two contrasting but non-exclusive views: (i) intrinsic factors make some species inherently good invaders; (ii) species become invasive as a result of extrinsic ecological and genetic influences such as release from natural enemies, hybridization or other novel ecological and evolutionary interactions. These viewpoints are rarely distinguished but hinge on distinct mechanisms leading to different management scenarios. To improve tests of these hypotheses of invasion success we introduce a simple mathematical framework to quantify the invasiveness of species along two axes: (i) interspecific differences in performance among native and introduced species within a region, and (ii) intraspecific differences between populations of a species in its native and introduced ranges. Applying these equations to a sample dataset of occurrences of 1,416 plant species across Europe, Argentina, and South Africa, we found that many species are common in their native range but become rare following introduction; only a few introduced species become more common. Biogeographical factors limiting spread (e.g. biotic resistance, time of invasion) therefore appear more common than those promoting invasion (e.g. enemy release). Invasiveness, as measured by occurrence data, is better explained by inter-specific variation in invasion potential than biogeographical changes in performance. We discuss how applying these comparisons to more detailed performance data would improve hypothesis testing in invasion biology and potentially lead to more efficient management strategies.
Saccharum spontaneum L. is an invasive grass that has spread extensively in disturbed areas throughout the Panama Canal watershed (PCW), where it has created a fire hazard and inhibited reforestation efforts. Currently physical removal of aboveground biomass is the primary means of controlling this weed, which is largely ineffective and does little to inhibit spread of the species. Little is known about reproduction of this species, although it is both rhizomatous and produces abundant seed. Here we report a series of studies looking at some of the basic reproductive mechanisms and strategies utilised by S. spontaneum to provide information to support development of better targeted management strategies. We found that seed produced between September and November was germinable both in the lab and in situ. Genetic diversity of mature stands was assessed using microsatellite markers and found to be high, even at small scales. Studies of vegetative reproduction showed that buds on stems that had been dried for up to six weeks were still capable of sprouting. Separate experiments showed that stem fragments could sprout when left on the surface or buried shallowly and that larger pieces sprouted more readily than smaller pieces. Collectively these results demonstrate that S. spontaneum in the PCW has the capability to produce many propagules that can successfully recruit and it is likely that seed dispersal drives the spread of the species. Timing of management actions to reduce flowering would significantly reduce the seed load into the environment and help to prevent spread to new sites. Similarly, where biomass is cut, cutting stems into smaller pieces will allow the stems to dry out and reduce the ability of buds to sprout. Additionally, attention should be paid to prevent accidental transport to new sites on machinery.
Smut fungi are well-suited to investigate the ecology and evolution of plant pathogens, as they are strictly biotrophic, yet cultivable on media. Here we report the genome sequence of Melanopsichium pennsylvanicum, closely related to Ustilago maydis and other Poaceae-infecting smuts, but parasitic to a dicot plant. To explore the evolutionary patterns resulting from host adaptation after this huge host jump, the genome of M. pennsylvanicum was sequenced and compared to the genomes of Ustilago maydis, Sporisorium reilianum, and Ustilago hordei. While all four genomes had a similar completeness in CEGMA analyses, gene absence was highest in M. pennsylvanicum, and most pronounced in putative secreted proteins, which are often considered as effector candidates. In contrast, the amount of private genes was similar among the species, highlighting that gene loss rather than gene gain is the hallmark of adaptation after the host jump to the dicot host. Our analyses revealed a trend of putative effectors to be next to another putative effector, but the majority of these are not in clusters and thus the focus on pathogenicity clusters might not be appropriate for all smut genomes. Positive selection studies revealed that M. pennsylvanicum has the highest number and proportion of genes under positive selection. In general, putative effectors showed a higher proportion of positively selected genes than non-effector candidates. The 248 putative secreted effectors found in all four smut genomes might constitute a core set needed for pathogenicity, while those 92 that are found in all grass-parasitic smuts, but have no ortholog in M. pennsylvanicum might constitute a set of effectors important for successful colonization of grass hosts.
Obesity and associated lifestyle in a large sample of multi-morbid German primary care attendees
(2014)
Background: Obesity and the accompanying increased morbidity and mortality risk is highly prevalent among older adults. As obese elderly might benefit from intentional weight reduction, it is necessary to determine associated and potentially modifiable factors on senior obesity. This cross-sectional study focuses on multi-morbid patients which make up the majority in primary care. It reports on the prevalence of senior obesity and its associations with lifestyle behaviors.
Methods: A total of 3,189 non-demented, multi-morbid participants aged 65–85 years were recruited in primary care within the German MultiCare-study. Physical activity, smoking, alcohol consumption and quantity and quality of nutritional intake were classified as relevant lifestyle factors. Body Mass Index (BMI, general obesity) and waist circumference (WC, abdominal obesity) were used as outcome measures and regression analyses were conducted.
Results: About one third of all patients were classified as obese according to BMI. The prevalence of abdominal obesity was 73.5%. Adjusted for socio-demographic variables and objective and subjective disease burden, participants with low physical activity had a 1.6 kg/m2 higher BMI as well as a higher WC (4.9 cm, p<0.001). Current smoking and high alcohol consumption were associated with a lower BMI and WC. In multivariate logistic regression, using elevated WC and BMI as categorical outcomes, the same pattern in lifestyle factors was observed. Only for WC, not current but former smoking was associated with a higher probability for elevated WC. Dietary intake in quantity and quality was not associated with BMI or WC in either model.
Conclusions: Further research is needed to clarify if the huge prevalence discrepancy between BMI and WC also reflects a difference in obesity-related morbidity and mortality. Yet, age-specific thresholds for the BMI are needed likewise. Encouraging and promoting physical activity in older adults might a starting point for weight reduction efforts.
Introduction: Multimorbidity is a major concern in primary care. Nevertheless, evidence of prevalence and patterns of multimorbidity, and their determinants, are scarce. The aim of this study is to systematically review studies of the prevalence, patterns and determinants of multimorbidity in primary care.
Methods: Systematic review of literature published between 1961 and 2013 and indexed in Ovid (CINAHL, PsychINFO, Medline and Embase) and Web of Knowledge. Studies were selected according to eligibility criteria of addressing prevalence, determinants, and patterns of multimorbidity and using a pretested proforma in primary care. The quality and risk of bias were assessed using STROBE criteria. Two researchers assessed the eligibility of studies for inclusion (Kappa = 0.86).
Results: We identified 39 eligible publications describing studies that included a total of 70,057,611 patients in 12 countries. The number of health conditions analysed per study ranged from 5 to 335, with multimorbidity prevalence ranging from 12.9% to 95.1%. All studies observed a significant positive association between multimorbidity and age (odds ratio [OR], 1.26 to 227.46), and lower socioeconomic status (OR, 1.20 to 1.91). Positive associations with female gender and mental disorders were also observed. The most frequent patterns of multimorbidity included osteoarthritis together with cardiovascular and/or metabolic conditions.
Conclusions: Well-established determinants of multimorbidity include age, lower socioeconomic status and gender. The most prevalent conditions shape the patterns of multimorbidity. However, the limitations of the current evidence base means that further and better designed studies are needed to inform policy, research and clinical practice, with the goal of improving health-related quality of life for patients with multimorbidity. Standardization of the definition and assessment of multimorbidity is essential in order to better understand this phenomenon, and is a necessary immediate step.
Gene transfer vectors such as lentiviral vectors offer versatile possibilities to express transgenic antigens for vaccination purposes. However, viral vaccines leading to broad transduction and transgene expression in vivo, are undesirable. Therefore, strategies capable of directing gene transfer only to professional antigen-presenting cells would increase the specific activity and safety of genetic vaccines. A lentiviral vector pseudotype specific for murine major histocompatibilty complex class II (LV-MHCII) was recently developed and the present study aims to characterize the in vivo biodistribution profile and immunization potential of this vector in mice. Whereas the systemic administration of a vector pseudotyped with a ubiquitously-interacting envelope led to prominent detection of vector copies in the liver of animals, the injection of an equivalent amount of LV-MHCII resulted in a more specific biodistribution of vector and transgene. Copies of LV-MHCII were found only in secondary lymphoid organs, essentially in CD11c+ dendritic cells expressing the transgene whereas B cells were not efficiently targeted in vivo, contrary to expectations based on in vitro testing. Upon a single injection of LV-MHCII, naive mice mounted specific effector CD4 and CD8 T cell responses against the intracelllular transgene product with the generation of Th1 cytokines, development of in vivo cytotoxic activity and establishment of T cell immune memory. The targeting of dendritic cells by recombinant viral vaccines must therefore be assessed in vivo but this strategy is feasible, effective for immunization and cross-presentation and constitutes a potentially safe alternative to limit off-target gene expression in gene-based vaccination strategies with integrative vectors.
Background: Autotaxin (ATX) and its product lysophosphatidic acid (LPA) are considered to be involved in the development of liver fibrosis and elevated levels of serum ATX have been found in patients with hepatitis C virus associated liver fibrosis. However, the clinical role of systemic ATX in the stages of liver cirrhosis was unknown. Here we investigated the relation of ATX serum levels and severity of cirrhosis as well as prognosis of cirrhotic patients.
Methods: Patients with liver cirrhosis were prospectively enrolled and followed until death, liver transplantation or last contact. Blood samples drawn at the day of inclusion in the study were assessed for ATX content by an enzyme-linked immunosorbent assay. ATX levels were correlated with the stage as well as complications of cirrhosis. The prognostic value of ATX was investigated by uni- and multivariate Cox regression analyses. LPA concentration was determined by liquid chromatography-tandem mass spectrometry.
Results: 270 patients were enrolled. Subjects with liver cirrhosis showed elevated serum levels of ATX as compared to healthy subjects (0.814±0.42 mg/l vs. 0.258±0.40 mg/l, P<0.001). Serum ATX levels correlated with the Child-Pugh stage and the MELD (model of end stage liver disease) score and LPA levels (r = 0.493, P = 0.027). Patients with hepatic encephalopathy (P = 0.006), esophageal varices (P = 0.002) and portal hypertensive gastropathy (P = 0.008) had higher ATX levels than patients without these complications. Low ATX levels were a parameter independently associated with longer overall survival (hazard ratio 0.575, 95% confidence interval 0.365–0.905, P = 0.017).
Conclusion: Serum ATX is an indicator for the severity of liver disease and the prognosis of cirrhotic patients.
Global-scale assessments of freshwater fluxes and storages by hydrological models under historic climate conditions are subject to a variety of uncertainties. Using the global hydrological model WaterGAP 2.2, we investigated the sensitivity of simulated freshwater fluxes and water storage variations to five major sources of uncertainty: climate forcing, land cover input, model structure, consideration of human water use and calibration (or no calibration). In a modelling experiment, five variants of the standard version of WaterGAP 2.2 were generated that differed from the standard version only regarding the investigated source of uncertainty. Sensitivity was analyzed by comparing water fluxes and water storage variations computed by the variants to those of the standard version, considering both global averages and grid cell values for the time period 1971–2000. The basin-specific calibration approach for WaterGAP, which forces simulated mean annual river discharge to be equal to observed values at 1319 gauging stations (representing 54% of global land area except Antarctica and Greenland), has the highest effect on modelled water fluxes and leads to the best fit of modelled to observed monthly and seasonal river discharge. Alternative state-of-the-art climate forcings rank second regarding the impact on grid cell specific fluxes and water storage variations, and their impact is ubiquitous and stronger than that of alternative land cover inputs. The diverse model refinements during the last decade lead to an improved fit to observed discharge, and affect globally averaged fluxes and storage values (the latter mainly due to modelling of groundwater depletion) but only affect a relatively small number of grid cells. Considering human water use is important for the global water storage trend (in particular in the groundwater compartment) but impacts on water fluxes are rather local and only important where water use is high. The best fit to observed time series of monthly river discharge (Nash–Sutcliffe criterion) or discharge seasonality is obtained with the standard WaterGAP 2.2 model version which is calibrated and driven by a sequence of two time series of daily observation-based climate forcings, WFD/WFDEI. Discharge computed by a calibrated model version using monthly CRU 3.2 and GPCC v6 climate input reduced the fit to observed discharge for most stations. Taking into account the investigated uncertainties of climate and land cover data, we estimate that the global 1971–2000 discharge into oceans and inland sinks is between 40 000 and 42 000 km3 yr−1. The range is mainly due differences in precipitation data that affect discharge in uncalibrated river basins. Actual evapotranspiration, with approximately 70 000 km3 yr−1, is rather unaffected by climate and land cover in global sum but differs spatially. Human water use is calculated to reduce river discharge by approximately 1000 km3 yr−1. Thus, global renewable water resources are estimated to range between 41 000 and 43 000 km3 yr−1. The climate data sets WFD (available until 2001) and WFDEI (starting in 1979) were found to be inconsistent with respect to short wave radiation data, resulting in strongly different potential evapotranspiration. Global assessments of freshwater fluxes and storages would therefore benefit from the development of a global data set of consistent daily climate forcing from 1900 to current.
MicroRNAs (miRNAs, miRs) emerged as key regulators of gene expression. Germline hemizygous deletion of the gene that encodes the miR-17~92 miRNA cluster was associated with microcephaly, short stature and digital abnormalities in humans. Mice deficient for the miR-17~92 cluster phenocopy several features such as growth and skeletal development defects and exhibit impaired B cell development. However, the individual contribution of miR-17~92 cluster members to this phenotype is unknown. Here we show that germline deletion of miR-92a in mice is not affecting heart development and does not reduce circulating or bone marrow-derived hematopoietic cells, but induces skeletal defects. MiR-92a−/− mice are born at a reduced Mendelian ratio, but surviving mice are viable and fertile. However, body weight of miR-92a−/− mice was reduced during embryonic and postnatal development and adulthood. A significantly reduced body and skull length was observed in miR-92a−/− mice compared to wild type littermates. µCT analysis revealed that the length of the 5th mesophalanx to 5th metacarpal bone of the forelimbs was significantly reduced, but bones of the hindlimbs were not altered. Bone density was not affected. These findings demonstrate that deletion of miR-92a is sufficient to induce a developmental skeletal defect.
Knowledge of factors influencing the timing of reproduction is important for animal conservation and management. Brown bears (Ursus arctos) are able to vary the birth date of their cubs in response to their fat stores, but little information is available about the timing of implantation and parturition in free-ranging brown bears. Body temperature and activity of pregnant brown bears is higher during the gestation period than during the rest of hibernation and drops at parturition. We compared mean daily body temperature and activity levels of pregnant and nonpregnant females during preimplantation, gestation, and lactation. Additionally we tested whether age, litter size, primiparity, environmental conditions, and the start of hibernation influence the timing of parturition. The mean date of implantation was 1 December (SD = 12), the mean date of parturition was 26 January (SD = 12), and the mean duration of the gestation period was 56 days (SD = 2). The body temperature of pregnant females was higher during the gestation and lactation periods than that of nonpregnant bears. The body temperature of pregnant females decreased during the gestation period. Activity recordings were also used to determine the date of parturition. The parturition dates calculated with activity and body temperature data did not differ significantly and were the same in 50% of the females. Older females started hibernation earlier. The start of hibernation was earlier during years with favorable environmental conditions. Dates of parturition were later during years with good environmental conditions which was unexpected. We suggest that free-ranging pregnant brown bears in areas with high levels of human activities at the beginning of the denning period, as in our study area, might prioritize investing energy in early denning than in early parturition during years with favorable environmental conditions, as a strategy to prevent disturbances caused by human.
Sanctions placed upon airlines and other operators transporting persons without the required paperwork are called ‘carrier sanctions’. They constitute a key example of how border control mechanisms are currently being outsourced, privatized, delegated, and moved from the border itself to new physical locations. These practices can lead to a phenomenon referred to in this paper as ‘hidden coercion’. This paper argues that, while hidden coercion is commonplace in the reality of migration policy in most states, it is so far neglected in theoretical discussions of state coercion. Moreover, the discussion of carrier sanctions demonstrates that this neglect is problematic, since hidden coercion is not justifiable even within a framework that legitimizes state border coercion.
Cytochrome P450 (CYP) epoxygenases generate bioactive lipid epoxides which can be further metabolized to supposedly less active diols by the soluble epoxide hydrolase (sEH). As the role of epoxides and diols in angiogenesis is unclear, we compared retinal vasculature development in wild-type and sEH−/− mice. Deletion of the sEH significantly delayed angiogenesis, tip cell, and filopodia formation, a phenomenon associated with activation of the Notch signaling pathway. In the retina, sEH was localized in Müller glia cells, and Müller cell–specific sEH deletion reproduced the sEH−/− retinal phenotype. Lipid profiling revealed that sEH deletion decreased retinal and Müller cell levels of 19,20–dihydroxydocosapentaenoic acid (DHDP), a diol of docosahexenoic acid (DHA). 19,20-DHDP suppressed endothelial Notch signaling in vitro via inhibition of the γ-secretase and the redistribution of presenilin 1 from lipid rafts. Moreover, 19,20-DHDP, but not the parent epoxide, was able to rescue the defective angiogenesis in sEH−/− mice as well as in animals lacking the Fbxw7 ubiquitin ligase, which demonstrate strong basal activity of the Notch signaling cascade. These studies demonstrate that retinal angiogenesis is regulated by a novel form of neuroretina–vascular interaction involving the sEH-dependent generation of a diol of DHA in Müller cells.
Alternative polyadenylation (APA) is a widespread mechanism that contributes to the sophisticated dynamics of gene regulation. Approximately 50% of all protein-coding human genes harbor multiple polyadenylation (PA) sites; their selective and combinatorial use gives rise to transcript variants with differing length of their 3' untranslated region (3'UTR). Shortened variants escape UTR-mediated regulation by microRNAs (miRNAs), especially in cancer, where global 3'UTR shortening accelerates disease progression, dedifferentiation and proliferation. Here we present APADB, a database of vertebrate PA sites determined by 3' end sequencing, using massive analysis of complementary DNA ends. APADB provides (A)PA sites for coding and non-coding transcripts of human, mouse and chicken genes. For human and mouse, several tissue types, including different cancer specimens, are available. APADB records the loss of predicted miRNA binding sites and visualizes next-generation sequencing reads that support each PA site in a genome browser. The database tables can either be browsed according to organism and tissue or alternatively searched for a gene of interest. APADB is the largest database of APA in human, chicken and mouse. The stored information provides experimental evidence for thousands of PA sites and APA events. APADB combines 3' end sequencing data with prediction algorithms of miRNA binding sites, allowing to further improve prediction algorithms. Current databases lack correct information about 3'UTR lengths, especially for chicken, and APADB provides necessary information to close this gap. Database URL: http://tools.genxpro.net/apadb/