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Distribution and abundance of exotic earthworms within a boreal forest system in southcentral Alaska
(2016)
Little is known about exotic earthworms (Oligochaeta: Lumbricidae) in Alaska outside its southeastern panhandle. This study documents the distribution of exotic earthworms in the relatively undisturbed Kenai National Wildlife Refuge (KNWR), a large, primarily wilderness refuge in southcentral Alaska. We sampled 69 sites near boat launches, along road corridors, and in low human impact areas > 5 km from the road, finding three species of earthworms (Dendrobaena octaedra, Dendrodrilus rubidus, and Lumbricus terrestris). Most road sites (90%) and boat launches (80%) contained earthworms; half (50%) of low human impact sites contained earthworms. Distance to roads was the only significant factor in predicting earthworm occurrence; soil pH, soil moisture, leaf litter depth, and vegetation cover were not. The disparate distributions of these three species suggest that within the KNWR road construction and vehicle traffic played a role in dispersal of the widespread, abundant Dendrobaena octaedra and uncommon Dendrodrilus rubidus; bait abandonment appeared to be the primary method of introduction of Lumbricus terrestris. While the distribution of harmful anecic earthworms in KNWR is currently limited, the prohibition of Lumbricus spp. as bait within conservation units in Alaska may be warranted.
Trichopsis vittata (Cuvier, 1831) is a small, freshwater gourami (Fam: Osphronemidae) native to southeast Asia. It was first detected in Florida in the 1970s and seems to have persisted for decades in a small area. In this study, we documented T. vittata’s ecophysiological tolerances (salinity and low-temperature) and qualitatively compared them to published values for other sympatric non-native species that have successfully invaded much of the Florida peninsula. Trichopsis vittata survived acute salinity shifts to 16 psu and was able to survive up to 20 psu when salinity was raised more slowly (5 psu per week). In a cold-tolerance experiment, temperature was lowered from 24 °C at 1 °C hr-1 until fish died. Mean temperature at death (i.e., lower lethal limit) was 7.2 °C. Trichopsis vittata seems as tolerant or more tolerant than many other sympatric non-native fishes for the variables we examined. However, T. vittata is the only species that has not dispersed since its introduction. Species other than T. vittata have broadly invaded ranges, many of which include the entire lower third of the Florida peninsula. It is possible that tolerance to environmental parameters serves as a filter for establishment, wherein candidate species must possess the ability to survive abiotic extremes as a first step. However, a species’ ability to expand its geographic range may ultimately rely on a secondary set of criteria including biotic interactions and life-history variables.
Established populations of non-natives may collapse without a clear causal mechanism. Hypothetically, fluctuations in habitat structural complexity may influence dynamics of invaders and the biotic resistance offered by predators. Herein I report observations of the collapse of a reproducing population of the nonnative African jewelfish (Hemichromis letourneuxi) in a Florida lake concurrent with an unusual low-water period. I test the hypothesis that predation may have played a key role in the collapse using a combination of field surveys of habitat and fish abundance and predator-prey experiments. Habitat complexity was high before and after the low water period but virtually nonexistent during low water. The abundance of African jewelfish and native juvenile bluegill (Lepomis macrochirus) and eastern mosquitofish (Gambusia holbrooki) declined concurrently with decreasing complexity but the native species rebounded when lake levels increased. Large-bodied natives such as largemouth bass (Micropterus salmoides) and adult bluegill showed no pattern of fluctuation related to habitat complexity. African jewelfish survival was 1.6 times greater at high versus low complexity and over 7 times higher versus no complexity in the presence of largemouth bass. Conversely, eastern mosquitofish, a species that exerts strong effects on small-bodied fishes in structurally complex habitats had no effect on African jewelfish survival. Predation effects on susceptible non-natives should be considered as a potential control action. Population collapse is understudied but may provide insights into long-term dynamics of invaders and information useful for management of problematic species.
We argue that human-mediated invasions are part of the spectrum of species movements, not a unique phenomenon, because species self-dispersing into novel environments are subject to the same barriers of survival, reproduction, dispersal and further range expansion as those assisted by people. Species changing their distributions by human-mediated and non-human mediated modes should be of identical scientific interest to invasion ecology and ecology. Distinctions between human-mediated invasions and natural colonisations are very valid for management and policy, but we argue that these are value-laden distinctions and not necessarily an appropriate division for science, which instead should focus on distinctions based on processes and mechanisms. We propose an all-encompassing framework of species range expansion. This does not detract from the importance of invasion biology as a discipline, but instead will help bring together research being conducted on multiple taxa, and by multiple disciplines, including epidemiology, that are often focused on an identical phenomenon: colonisation.
This study investigated laypersons’ perception of invasive alien plant species (IAPS) and attitudes towards their management with the help of a written questionnaire in the cities of Zurich, Geneva, and Lugano, Switzerland. Survey participants (n = 720) judged attractiveness from certain species on visual contact (eight IAPS were shown as photographs). Trachycarpus fortunei and Ludwigia grandiflora were liked most, while Ambrosia artemisiifolia was clearly disliked most. With the exception of Trachycarpus fortunei, all plant species were perceived as rather ordinary, familiar and native to Switzerland, and feelings of ordinariness, familiarity and nativeness were positively correlated. Few participants could correctly identify the species depicted. Knowledge of an IAPS (ability to identify it) and desire to have it around were negatively correlated. Participants agreed most with the eradication of IAPS that cause serious costs and problems. However, people were rather unwilling to remove Buddleja davidii, Solidago canadensis, and Trachycarpus fortunei which are already widely established ornamentals in settlement areas or gardens. Overall, willingness to remove an IAPS and to report it to the authorities decreased with increasing desirability (and thus beauty) of a species.
Acacia mearnsii De Wilde is on the top 100 of the world’s most invasive alien species and has successfully invaded many areas around the world. However, its distribution and expansion is seldom reported in China. This study for the first time conducted a survey on the new distribution of A. mearnsii at the Kunming Changshui Airport (Yunnan Province, China), through monitoring on population characteristics (number, density, height and ground diameter) and spatial distribution (spread distance). Our survey results show that A. mearnsii has spread rapidly across the airport. This study discusses three factors of environmental factors, human disturbance and weed characteristics behind this successful invasion. The species invasion has a strong potential to change the local vegetation structure, enhances the probability of bird strikes at the airport, and is vulnerable to invade new biogeographic regions if it is not controlled. Currently, eradication combined with mechanical control is considered to be the best option for control. Our study helps improve awareness about the potential risk of A. mearnsii invasion in other airports around China and the world.
Halting the loss of grassland biodiversity and restoring degraded ecosystems are high priority tasks in the EU Biodiversity Strategy. Sowing low-diversity seed mixtures is widely used in grassland restoration because of its high predictability and fast, promising results. Generally, the sown perennial grasses establish within a few years and form a dense sward, which effectively suppresses weeds. Unfortunately, these grasslands are often species-poor because the sown grasses hamper the colonisation of target grassland forbs. Our aim was to test a novel approach to increase the diversity of species-poor grasslands. We selected eight 8-year-old grasslands restored by low-diversity seed sowing where we created 32 establishment gaps by breaking up the grass sward and sowing a high-diversity seed mixture (35 native species). Altogether, we established three grazed gaps (1m × 1m, 2m × 2m and 4m × 4m) and one fenced gap (4m × 4m) per site and monitored the presence and abundance of sown and non-sown species within a time frame of two years. We asked the following questions: (1) Which target species establish most successfully? (2) What is the effect of establishment gap size on the establishment success of target species and weeds? (3) What is the effect of management (grazed versus not managed) on the species composition of the establishment gaps? Our results showed that by creating establishment gaps and sowing diverse seed mixtures, we were able to overcome microsite and propagule limitation, successfully introducing target species into the species-poor grasslands. We found that all sown species established in the gaps, and the majority of the species maintained or even increased their first-year cover in the second year. Smaller gaps were characterised by lower cover of sown species and a quite stochastic development compared to the larger ones. Weed cover was moderate in the first year and decreased significantly in the second year, regardless of gap size. Therefore, in restoration practice, the use of larger establishment gaps is recommended. We found that the cover of sown species and weeds were similar in the grazed and unmanaged gaps during our study. However, management by extensive grazing might be crucial in the long-term because livestock can disperse target species propagules and create microsites. Our study shows that establishment gaps can serve as biodiversity hotspots. Further studies need to clarify to what extent they can improve the restoration success across the entire grassland.
Inland sand vegetation, in our case steppic sandy grassland on base-rich soils, is highly endangered in Europe and therefore in the focus of restoration ecology. While there are studies which deal with short-term restoration success, results for an extended time are rare. We were able to analyse the success of a three-step restoration measure for 10 years.
The experiment was established on an exarable field in the Upper Rhine valley, Hesse, Germany. The three-step restoration approach comprised 1) abiotic restoration by deep-sand deposition, 2) inoculation with raked/mown plant material from two different donor sites with well-developed Koelerion glaucae/Allio-Stipetum vegetation and 3) low-intensity grazing by donkeys. The vegetation of the restoration and donor sites (also serving as reference sites to assess restoration success) was sampled on six permanent plots, respectively. Data analyses included ordination, classification and target-species ratios (TSR: relation of target species to all species).
Detrended correspondence analysis revealed a continuous succession of the restoration plots towards the corresponding reference plots: open soil decreased, ruderal species declined and target species increased. While speed of succession decreased, there was still a further improvement in the tenth year. The qualitative TSR (number of target species) reached a plateau after the sixth year with values only slightly lower than at the reference sites. The quantitative TSR (cover of target species) showed a steady improvement and even excelled one reference site. Koelerion glaucae species were present with constancy 17–67% since the 3rd year, with 33–100% since the 7th year. It does not completely resemble either reference site due to a mixture of propagules of both donor sites (e.g. by wind and donkeys) and input from the surroundings. Already in the first year, three Red-list species established themselves, since the 8th year 23 Red-list/near-threatened species have been present. Some ruderal species colonised the restoration site and occurred permanently.
Additionally, we studied the establishment of the highly threatened species Bassia laniflora after inoculation for 6–12 years on three further plots adjacent to the other ones. One of these plots was located on a former sandy field without abiotic restoration; two other plots represented typical Koelerion glaucae vegetation on a newer deep-sand deposition. Bassia laniflora established itself well on all plots. We conclude that restoration of steppic sandy grassland, including highly threatened species, was not only permanently, but increasingly successful over a time span of 10 years. Management by grazing, however, will remain essential to suppress ruderalisation.
Semi-dry grasslands were once widely distributed communities, but today they represent some of the most vulnerable habitats in Central Europe. European and national legislation and non-governmental organizations have managed to protect some of the remaining fragments. However, despite their status as Natura 2000 habitats, they are often endangered due to improper management, fragmentation and edge effects from adjacent croplands. By using a sample of 44 semi-dry hay meadows in the south-eastern Alpine Foreland of Styria, we investigated how species-richness and trait composition of semi-dry grassland species respond to variation in patch size, connectivity, abiotic site factors and management regimes. We used linear regression models to identify the most important drivers for richness of typical semi-dry grassland species and thus conservation value. The number of typical semi-dry grassland species was highest in well-connected fragments, i.e. units that shared two or more borders with neighbouring species-rich grasslands. Furthermore, large semi-dry grasslands (> 8000 m²) had highest numbers of semi-dry grassland species and highest relevance for conservation; no difference was found among smaller fragment sizes. Unregular management was associated with increased presence of competitive species which replaced stress-tolerant specialists. Our study indicates that under eutrophication, small fragment size and isolation, only large semi-dry grasslands can sustain a high number of species with high conservation value. The conservation value of smaller semi-dry grassland fragments could be improved by buffer zones, adapted mowing treatments and periodical sheep grazing.
The degradation of species-rich mountain meadows has been observed in many parts of Central Europe in the last few decades. It is reflected in decreasing species numbers and changes in the proportions of plant species in the aboveground vegetation. Some species are increasing in abundance and eventually dominate the meadow vegetation. There is still a lack of studies explaining how this process is reflected in the soil seed bank. Therefore, the goal of the current study was to test whether expansive species that degrade aboveground vegetation of mountain meadows also influence, quantitatively and qualitatively, seed rain and seed bank. Soil samples were taken from 14 plots in degraded patches and another 14 plots in non-degraded patches. Nearly the same numbers of seedlings were recorded in both meadow types. In both cases, low similarities between aboveground vegetation and soil seed rain and seed bank were observed. Expansive species causing meadow degradation (Calamagrostis epigejos, Festuca rubra, Deschampsia cespitosa and Lupinus polyphyllus) reached cover values of 60–83% in the aboveground vegetation, and a share of up to 36% in the seed rain and seed bank. The mean species richness in the aboveground vegetation and the soil of degraded meadows was lower than in the non-degraded plots. However, the seed bank may buffer degradation to some extent since the degradation of aboveground vegetation was faster than impoverishment of seed bank. Consequently, seed rain and seed bank of degraded meadows still contained typical mesic meadow species in similar proportions as non-degraded meadows. This indicates that seed rain and seed bank may contribute to the restoration of degraded meadows after the removal of expansive species from the aboveground vegetation.
This paper is the continuation of a survey of the scree vegetation in alpine landscapes of western Pamir-Alai Mts in Tajikistan. In total, 105 phytosociological relevés were collected in the colline and montane belt in 2012‒2014, applying the Braun-Blanquet method. Phytocoenoses inhabiting mobile or fairly stabilised screes of different sizes of rock particles in the montane and colline zone are herein described. A hierarchical syntaxonomic synopsis of scree communities in the western Pamir Alai Mts is provided. The collected vegetation samples represent the majority of the variations among the phytocoenoses of gravel, pebble, cobble and rock block slides and screes. As a result of field survey and numerical analyses, eight associations ‒ Cousinietum corymbosae, Eremostachyetum tadschikistanicae, Cousinietum refractae, Caccinietum dubiae, Eremuretum sogdiani (with two subassociations: E. s. typicum and E. s. delphinietosum decolorati), Feruletum kuhistanicae, Zygophylletum atriplicoidis and Corydalidetum kashgaricae ‒ have been described. Because of their floristic composition, all of these communities have been assigned to a new alliance Alceion nudiflorae within the Sileno brahuicae-Scutellarietalia intermediae order and Artemisio santolinifoliae-Berberidetea sibiricae class. The main factors determining the species composition of the classified associations seem to be scree mobility, rock particle size, elevation above sea level and slope inclination. Saxicolous vegetation in Tajikistan reveal an extraordinary diversity and richness in terms of species composition and beta diversity along the main environmental gradients in this mountaionous areas. A further geobotanical survey is needed, especially in eastern Pamir and adjacent areas to fully recognize the chasmophytic plant communities of this rocky land.
Dry open rocky grassland vegetation on shallow ultramafic soils in the Central Balkans represents typical secondary grasslands, which have developed mainly in the zone of thermophilous mixed deciduous broadleaved and pine forests. Although all relevant national and regional syntaxonomic reviews classify these rocky grasslands within the distinct order Halacsyetalia sendtneri, the syntaxonomic position of the order in different systems of classification has varied in the past. Considering this as well as the fact that there have been no synoptic works on this specific vegetation type, we gathered all available data on the order Halacsyetalia sendtnerii from the serpentinites of the Western and Central Balkan Peninsula for its critical evaluation. The results obtained in our analyses allowed us to propose a new syntaxonomic concept, which is partly in accordance with previously published syntaxonomic schemes. Two alliances can be distinguished: Centaureo kosaninii-Bromion fibrosi and Potentillion visianii, for which the diagnoses, diagnostic and constant taxa are given. Furthermore, we discussed the syntaxonomic position of the order Halacsyetalia sendtneri with respect to the classes Festuco-Brometea and Koelerio-Corynephoretea, as within the analysed associations, many taxa diagnostic for the class Koelerio-Corynephoretea were registered. The thermophytic pioneer grasslands and therophyte sward communities included in the alliance Thymion jankae nomen. inval., characterised by the absence of typical species of the order Halascyetalia sendtneri and presence of taxa diagnostic for the class Koelerio-Corynephoretea, are temporarily left within the order Halacsyetalia sendtneri. Finally, we provided nomenclatural adjustments for the analysed associations when necessary, although a conclusive judgement regarding all the associations currently included within the analysed order can only be made after more detailed field surveys including data on cryptogams as well as joint analyses including all floristically and ecologically similar syntaxa (e.g. Astragalo-Potentilletalia, Festucetalia valesiacae).
In many regions of Central Europe, semi-natural grasslands have experienced severe vegetation changes, e.g. compositional change and overall species loss, because of land use changes, atmospheric nitrogen input and also climate change. Here we analysed the vegetation change in a dry grassland complex (Gabower Hänge) in the Biosphere Reserve Schorfheide-Chorin (NE Brandenburg, Germany), one of the driest regions of the country. We resampled four 10 m² plots of each of four typical alliances (Festucion valesiacae, Koelerion glaucae, Armerion elongatae, Arrhenatherion elatioris) about 20 years after their original sampling with a recovery accuracy of approx. 10 m. The cover of vascular plants, bryophytes and lichens was recorded in both samplings. The overall compositional change was analysed with a detrended correpondence analysis (DCA). To interpret this change, we calculated unweighted mean Ellenberg indicator values for old and new plots. Furthermore we tested differences in constancy of individual species between old and new plots as well as differences in species richness, cover of herb and cryptogam layer, ecological indicator values and unweighted proportion of species groups (vascular plants, bryophytes, lichens), floristic status (native or not), life forms, CSR-strategy types and Red List species. The results of the ordination indicated no significant vegetation change, but revealed tendencies towards more nutrient-rich conditions. Ellenberg indicator values for nutrients and soil reaction were significantly correlated with the axes of the ordination. There were 28 species exclu-sively found in the new plots and 45 species of the old plots missing. While no species decreased signif-icantly, there were seven species that increased significantly. Mean species richness was significantly increased in the new plots. There were no significant differences in mean Ellenberg indicator values. Proportions of vascular plants, neophytes, hemicryptophytes and CS-strategists decreased. We conclude that overall vegetation changes are small, indicating that the dry grassland complex at the Gabower Hänge is still in a good state and of high conservation value. This relative stability over time compared to the situation in many other dry grasslands throughout temperate Europe is likely attributable to low nitrogen deposition and the dryness of the local climate. However, the detected tendency towards more nutrient-rich conditions should be taken into account in future management.
The majority of studies investigating plant functional traits have used species average trait values, and assumed that average values were sufficiently representative of each species considered. Although this approach has proven valuable in community ecology studies, plant functional traits can significant-ly vary at different scales, i.e. between but also within populations. The study of species functional trait variability can facilitate increasingly accurate studies in community ecology. Nevertheless, the current extent of within-site plant trait variability has been poorly addressed in the literature. Calcareous grass-lands are ecosystems well-suited to study plant trait variation at small spatial scales. Many species are present on heterogeneous calcareous sites, with significant differences in hydric status due to variations in soil depth, soil moisture, aspect, and slope. This study assesses the extent of intra-population func-tional trait variability and tests the hypothesis that this variability can be explained by within-site envi-ronmental heterogeneity. Three functional traits (SLA-specific leaf area, LDMC-leaf dry matter con-tent, and plant vegetative height) were assessed in three populations of four calcareous grassland spe-cies totalling 950 individuals. The heterogeneity in soil depth and potential direct incident radiation was also quantified and related to plant functional trait variability. The intra-population functional trait variability was compared to the inter-population variability of collected data and global inter-population variability data obtained from the worldwide TRY functional traits database. The results showed that SLA, LDMC, and plant height are characterized by considerable intra-population variation (SLA: 72–95%, LDMC: 78–100% and vegetative height: 70–94% of trait variability). The results also indicate higher plant height and larger SLA for individuals located in plots with deeper soils or lower potential direct incident radiation, on gentle slopes or north-facing slopes. Our findings additionally support the concept that higher plant height, higher SLA, and lower LDMC are related to higher availability of soil water. Individuals on shallow soils or in more exposed areas are better equipped to cope with environ-mental stress. Our results indicate plasticity or local adaptation in individuals to environmental hetero-geneity. This study suggests that detailed analyses involving plant functional traits require measure-ments in situ from a large number of individuals, as the degree of individual response strongly depends on an individual’s location and its micro-environmental conditions. Neglecting intra-population trait variability may be critical, as intraspecific variation can be very high at the population scale, and is likely to be driven by local environmental heterogeneity.
Plant diversity change for cities and their surroundings is well documented. For rural areas such studies are difficult as literature data are mostly insufficient. We reconstructed phytodiversity change in the Feldatal community (Germany, Hesse) by comparison of historical herbarium collections (1945–1976, Hans Hupke) with a recent floristic survey (2012). The study area is a rural area typical for Central Europe, dominated by agriculture and forestry and with a stable human population. Floristic diversity decreased (683 to 497 species; 31% of the total flora), principally by disappearance of species of unimproved grassland, fields and villages. The small number of newly documented species (33 spp.; 5% of total flora) comprises mostly naturalized ornamentals and salt tolerant species along roads. Plant diversity change of the last decades in rural landscapes in Central Europe was mainly dependent on the intensification of agriculture.
In Italy most of the habitats hosting terricolous lichens are found in the Alps and along the coasts, but some lichen-rich plant communities are also present in the Po Plain. We report a study of terrico-lous lichen communities found in dry grasslands attributed to Spergulo vernalis-Corynephoretum canescentis in the western Po Plain (Northern Italy), in accordance with the Braun-Blanquet approach. Relevés (138) were carried out in several developmental stages of the Corynephorus grassland. They were sorted manually and analyzed using ANOSIM, non-parametric MANOVA and PCA. Indicator species of the groups were found by means of INDVAL and SIMPER analyses and literature. Seven lichen vegetation types were distinguished. These were attributable to 4 described associations: Stere-ocauletum condensati, Cladonietum foliaceae (in which we found 3 subassociations: typicum, cladonietosum furcatae and cladonietosum subrangiformis), Cladonietum mitis and Cladonietum rei, and to one impoverished community (Cetraria aculeata community). Ordination of floristic variables showed several overlaps between communities, underlining the depleted floristic conditions found in the study area, where several species occur in many communities and other species are very rare, and thus play a minor role in the differentiation of the lichen vegetation types. Overlaps are also referable to intermediate conditions between one community and another, reflecting dynamic relationships, with Stereocauletum condensati, Cetraria aculeata community and Cladonietum foliaceae typicum having the most distinct pioneer character and Cladonietum mitis being the most evolved. Ordination of eco-logical variables based on the indices of substrate pH, light and humidity requirements and tolerance to eutrophication showed several overlaps between the communities, found to be from acidophytic to subneutrophytic, from rather to very photophytic, from mesophytic to rather xerophytic and from anitrophytic to slightly nitrophytic. Rarity in Italy and conservation needs are discussed in detail, also in comparison with the situation of the same communities in central European Corynephorus grasslands. These grasslands and their typical lichen communities are rare in Italy and, though somewhat depleted, they are the habitat of several threatened lichen species at the southern margin of their distribution range. Therefore management plans should always consider both the cryptogamic and the vascular plant communities.
This paper compares the floodplain forests from Romania to those described from Central and Southeastern Europe from syntaxonomical and ecological perspectives and proposes a clear and ade-quate vegetation classification system that was needed for the Romanian floodplain forests. We performed a syntaxonomical analysis and classification of 473 vegetation relevés published from all nine Romanian provinces, between the years 1968 and 2015. The plant communities, established on the basis of character and differential species, were grouped within the alliance Alnion incanae Pawłowski 1928, according to current phytosociological consensus. The floristic structure of each syntaxon is presented in a synoptic table with species constancy expressed as a percentage. Since plant communi-ties specific to intramontane river floodplains are notably different from those in the plains, we grouped the associations within two different suballiances. Within the suballiance Alnenion glutinosae-incanae Oberdorfer 1953, we included the associations Stellario nemorum-Alnetum glutionosae Lohmeyer 1957, Telekio speciosae-Alnetum incanae Coldea 1990, and Carici remotae-Fraxinetum excelsioris Koch ex Faber 1936. In the suballiance Ulmenion Oberdorfer 1953, we included the associations Fraxino pannonicae-Ulmetum glabrae Aszód 1935 corr. Soó 1963, Ulmo campestris-Fraxinetum holotrichae Borza ex Sanda 1970 and Fraxino pallisae-Quercetum pedunculiflorae Oprea 1997. In order to show the distribution of these associations within the territory of Romania, we have generated two maps displaying the provenance of the analyzed relevés. The proposed classification system will facilitate the phytosociological and ecological investigation of floodplain forests and support the activities aiming at their conservation.
Elevational gradients in high mountain ranges are particularly suitable to study and understand patterns and drivers of plant community diversity and composition, yet there are only few studies that explicitly addressed this topic for the European Alps. Here we analysed an elevational gradient in grasslands of the Gran Paradiso National Park (NW Italy) from c. 1,700 to 3,100 m a.s.l. We recorded vascular plant species composition in 13 100-m² plots, each with two series of nested subplots from 0.0001 to 10 m², as well as a set of environmental parameters (topography, soil). Beta-diversity was assessed via the z-values of power-law species-area relationships, both across all plot sizes and from one plot size to the next bigger one. Diversity-environment relationships were assessed with multi-model inference based on Akaike information criterion (AIC), while scale dependence in z-values across plot sizes was analysed with an ANOVA. Life forms and three major functional traits (specific leaf area = SLA, canopy height, seed mass) were derived from trait databases to calculate fractions of life forms and community-weighted means for the metric traits. Species richness on 100 m² ranged from 17 to 65, with a mean of 43.5. The z-values were within a typical range known for European grasslands (mean: 0.227), with non-significant scale dependence. The importance of environmental factors for richness changed across grain sizes, with inclination (positive effect), mean soil depth and soil skeleton content (both: negative effect) being most influential at grain sizes of 0.0001–1 m². By contrast, soil pH was most important (with a unimodal relationship) for 10 and 100 m². After account-ing for the other environmental factors, elevation showed a moderate unimodal relationship only for the two largest grain sizes. By contrast, functional composition showed strong and mostly significant rela-tionships with elevation: hemicryptophytes and geophytes became rarer and chamaephytes more fre-quent, while community-weighted means of SLA, canopy height and seed mass decreased. Our findings highlight the scale dependence of biodiversity patterns, thus pointing to the need of multi-scale sampling to reach comprehensive understanding. Further, we could provide one of the first documentations of biodiversity and functional composition along an elevational gradient in the Alps, some in agreement with expectations, others not. This suggests that more extensive studies with a similar design in this and other regions of the Alps could be a valuable contribution to the understanding of how environmental factors drive components of biodiversity as well a functional community assembly.
The intensification of agricultural practices has led to a severe decrease in grassland biodiversity. Although there is strong evidence that organic farming can reduce the negative impacts of land use, knowledge regarding the most beneficial management system for species richness on organic grasslands is still scarce. This study examines differences in the biodiversity of plants and butterflies on rotationally and continuously grazed pastures as well as on meadows cut twice per year on two large organic suckler cow farms in NE Germany. Vegetation and flower abundance, as factors likely to influence butterfly abundance and diversity, were compared and used to explain the differences. The data attained by vegetation assessments and monthly transect inspections from May to August were analyzed using descriptive statistics and nonparametric methods. The abiotic site conditions of the studied plots had more influence on plant species numbers than the management method. Dry and nutrient-poor areas (mainly poor types of Cynosurion) and undrained wet fens (Calthion) were important for phytodiversity, measured by the absolute number of species, indicator species for ecologically valuable grasslands and the Shannon Index. Meadows tended to have more indicator species than pastures, where small-scale special sites such as wet depressions were crucial for plant diversity. Butterfly diversity was very low, and 90% of the recorded butterflies were individuals of the generalist species Pieris napi. Butterfly abundance depended mainly on occurrence of specific habitat types and specific larval host plants. Supply of flowers was crucial only in certain time periods. Differences in butterfly abundance between the management systems could be explained by the site conditions of the studied grasslands. We conclude that meadows are more favorable to support ecologically valuable plant species; however, their extension is contradictory to the organic farming method of suckler cows maintained outside of stables. Rotationally grazed pastures could be a compromise that would enhance the temporal heterogeneity of flower abundance and vegetation structure. The plant diversity on pastures should be improved by less intensive grazing on special sites and plant species enrichment by means of hay transfer. For enhancing butterfly diversity we suggest to reduce land use intensity especially on poor soils. Considering the economic perspective of the farms, small parts of the agricultural area could be sufficient if connectivity to other suitable habitats is assured. Flower abundance and diversity of larval host plants could be promoted by high diversity of farming practices as well as pre-serving small uncut strips of meadows.
Orange lily Lilium bulbiferum subsp. bulbiferum occurs in the mountains of Western and Central Europe. Within almost the entire area of distribution, it is considered to be rare and endangered. The main purpose of the present study is to analyse the variability of environmental conditions of sites of the orange lily that are considered natural on its north-eastern border of occurrence. Using vegetation databases from Poland, the Czech Republic and Slovakia and our material collected during field work in the Western Carpathians and the Sudetes, we analysed the variability of species composition within communities with the occurrence of L. bulbiferum subsp. bulbiferum. The classification was performed using a modified TWINSPAN algorithm in the JUICE software. Ecological analysis was performed on the basis of Ellenberg indicator values with a Zelený-Schaffers modified permutation test. In general, the findings indicate that in the study area there are at least seven plant communities, within three separate classes, with the occurrence of the orange lily. All vegetation units distinguished here are semi-natural communities, which are maintained through extensive and traditional agricultural practices. Microclimatic conditions, which indicate a narrow ecological tolerance of the species to light availability and temperature, may have a crucial effect on the distribution of L. bulbiferum subsp. bulbiferum on the north-eastern border of its range in Europe. These factors significantly reduce the possibility of penetration of the species into forest or scrub communities. On the other hand, owing to far wider ranges of tolerance to moisture conditions and soil reaction than previously considered typical of the species, the orange lily can occur in different light-demanding communities, from acidic pastures up to calcareous thermophilous grasslands. An almost exclusive presence of L. bulbiferum subsp. bulbiferum in semi-natural habitats suggests that active management and protection are crucial to protect its full genetic variation on the European continent.
Despite the high significance of the Western Siberian grain belt for crop production in Russia, its weed communities are largely unknown. In this region spring wheat is grown on fertile Chernozem soils with large field sizes but land-use intensity per area is low compared to Central Europe. By using a randomized sampling design we studied arable weed assemblages in the northern forest-steppe zone of Tyumen region on 99 within-field sampling plots of 100 m² size. Surprisingly, with average of 9.8 ± 3.8 species 100 m-2 species richness was low when compared with low-input farming in Central Europe and did not differ between areas of different land-use intensity. Against expectations species composition was not predominantly controlled by soil characteristics and climate, most likely due to short natural gradients. Instead, management factors such as fertilization and tillage intensity seemed to be important factors. Except for two species the Tyumen weed flora consisted mainly of species that are widespread throughout the temperate zone. We found only 10 species with an origin or core area in North Asia or Eastern Europe. The species pool was generally small and with 26% the proportion of non-native species (archaeophytes) was low, when compared to Central European weed communities. Given that weed communities with higher species richness are described from neighboring Bashkiria, we conclude that arable land-use intensity in Tyumen region is high enough to reduce community species richness within arable fields estimated by a randomized sampling design. Since measured soil nutrient values did not affect species richness, herbicide use is most likely the crucial management factor. Furthermore, species-richness was vitally restricted by the small species pool. The low proportion of thermophilous arable weed species that originate from the Mediterranean or Middle-Eastern area and contribute signif-icantly to the Central European weed diversity indicate that climatic dispersal limitations may be re-sponsible for the small number of weed species in the Tyumen flora. An additional constraint was the short history of arable farming in Western Siberia, where considerable arable land use was started only by the end of the 17th century.
Gastric cancer is one of the most common malignancies and a leading cause of cancer death worldwide. The prognosis of stomach cancer is generally poor as this cancer is not very sensitive to commonly used chemotherapies. Epigenetic modifications play a key role in gastric cancer and contribute to the development and progression of this malignancy. In order to explore new treatment options in this target area we have screened a library of epigenetic inhibitors against gastric cancer cell lines and identified inhibitors for the BET family of bromodomains as potent inhibitors of gastric cancer cell proliferations. Here we show that both the pan-BET inhibitor (+)-JQ1 as well as a newly developed specific isoxazole inhibitor, PNZ5, showed potent inhibition of gastric cancer cell growth. Intriguingly, we found differences in the antiproliferative response between gastric cancer cells tested derived from Brazilian patients as compared to those from Asian patients, the latter being largely resistant to BET inhibition. As BET inhibitors are entering clinical trials these findings provide the first starting point for future therapies targeting gastric cancer.
Latent transforming growth factor beta binding protein 4 (LTBP4) belongs to the fibrillin/LTBP family of proteins and plays an important role as a structural component of extracellular matrix (ECM) and local regulator of TGFβ signaling. We have previously reported that Ltbp4S knock out mice (Ltbp4S −/−) develop centrilobular emphysema reminiscent of late stage COPD, which could be partially rescued by inactivating the antioxidant protein Sestrin 2 (Sesn2). More recent studies showed that Sesn2 knock out mice upregulate Pdgfrβ-controlled alveolar maintenance programs that protect against cigarette smoke induced pulmonary emphysema. Based on this, we hypothesized that the emphysema of Ltbp4S −/− mice is primarily caused by defective Pdgfrβ signaling. Here we show that LTBP4 induces Pdgfrβ signaling by inhibiting the antioxidant Nrf2/Keap1 pathway in a TGFβ-dependent manner. Overall, our data identified Ltbp4 as a major player in lung remodeling and injury repair.
Sequence type 131 (ST131) is one of the predominant Escherichia coli lineages among extraintestinal pathogenic E. coli (ExPEC) that causes a variety of diseases in humans and animals and frequently shows multidrug resistance. Here, we report the first genome sequence of an ST131-ExPEC strain from poultry carrying the plasmid-encoded colistin resistance gene mcr-1.
Many oncogenic mutants of the tumor suppressor p53 are conformationally unstable, including the frequently occurring Y220C mutant. We have previously developed several small-molecule stabilizers of this mutant. One of these molecules, PhiKan083, 1-(9-ethyl-9H-carbazole-3-yl)-N-methylmethanamine, binds to a mutation-induced surface crevice with a KD = 150 μM, thereby increasing the melting temperature of the protein and slowing its rate of aggregation. Incorporation of fluorine atoms into small molecule ligands can substantially improve binding affinity to their protein targets. We have, therefore, harnessed fluorine–protein interactions to improve the affinity of this ligand. Step-wise introduction of fluorines at the carbazole ethyl anchor, which is deeply buried within the binding site in the Y220C–PhiKan083 complex, led to a 5-fold increase in affinity for a 2,2,2-trifluoroethyl anchor (ligand efficiency of 0.3 kcal mol–1 atom–1). High-resolution crystal structures of the Y220C–ligand complexes combined with quantum chemical calculations revealed favorable interactions of the fluorines with protein backbone carbonyl groups (Leu145 and Trp146) and the sulfur of Cys220 at the mutation site. Affinity gains were, however, only achieved upon trifluorination, despite favorable interactions of the mono- and difluorinated anchors with the binding pocket, indicating a trade-off between energetically favorable protein–fluorine interactions and increased desolvation penalties. Taken together, the optimized carbazole scaffold provides a promising starting point for the development of high-affinity ligands to reactivate the tumor suppressor function of the p53 mutant Y220C in cancer cells.
Methanogenic archaea share one ion gradient forming reaction in their energy metabolism catalyzed by the membrane-spanning multisubunit complex N5-methyl-tetrahydromethanopterin: coenzyme M methyltransferase (MtrABCDEFGH or simply Mtr). In this reaction the methyl group transfer from methyl-tetrahydromethanopterin to coenzyme M mediated by cobalamin is coupled with the vectorial translocation of Na+ across the cytoplasmic membrane. No detailed structural and mechanistic data are reported about this process. In the present work we describe a procedure to provide a highly pure and homogenous Mtr complex on the basis of a selective removal of the only soluble subunit MtrH with the membrane perturbing agent dimethyl maleic anhydride and a subsequent two-step chromatographic purification. A molecular mass determination of the Mtr complex by laser induced liquid bead ion desorption mass spectrometry (LILBID-MS) and size exclusion chromatography coupled with multi-angle light scattering (SEC-MALS) resulted in a (MtrABCDEFG)3 heterotrimeric complex of ca. 430 kDa with both techniques. Taking into account that the membrane protein complex contains various firmly bound small molecules, predominantly detergent molecules, the stoichiometry of the subunits is most likely 1:1. A schematic model for the subunit arrangement within the MtrABCDEFG protomer was deduced from the mass of Mtr subcomplexes obtained by harsh IR-laser LILBID-MS.
Background: Cancer screening participation rates in Germany differ depending on patients’ gender. International studies have found that patient–physician gender concordance fosters recommendation and conducting of cancer screening, and especially cancer screening for women.
Objectives: We aimed to ascertain whether gender concordance influences general practitioners' (GPs’) rating of the usefulness of cancer screening, as well as their recommendations and readiness to conduct cancer screening in general practice in Germany.
Methods: For an exploratory cross-sectional survey, 500 randomly selected GPs from all over Germany were asked to fill in a questionnaire on cancer screening in general practice between March and June 2015. We asked them to rate the usefulness of each cancer screening examination, how frequently they recommended and conducted them and whether they viewed GPs or specialists as responsible for carrying them out. We used multiple logistic regression to analyse gender effect size by calculating odds ratios.
Results: Our study sample consisted of 139 GPs of which 65% were male. Male and female GPs did not differ significantly in their rating of the general usefulness of any of the specified cancer screening examinations. Male GPs were 2.9 to 6.8 times as likely to consider GPs responsible for recommending and conducting PSA testing and digital rectal examinations and were 3.7 to 7.9 times as likely to recommend and conduct these examinations on a regular basis.
Conclusion: Patient–physician gender concordance made it more likely that male-specific cancer screenings would be recommended and conducted, but not female-specific screenings.
The assessment of water balance components using global hydrological models is subject to climate forcing uncertainty as well as to an increasing intensity of human water use within the 20th century. The uncertainty of five state-of-the-art climate forcings and the resulting range of cell runoff that is simulated by the global hydrological model WaterGAP is presented. On the global land surface, about 62 % of precipitation evapotranspires, whereas 38 % discharges into oceans and inland sinks. During 1971–2000, evapotranspiration due to human water use amounted to almost 1 % of precipitation, while this anthropogenic water flow increased by a factor of approximately 5 between 1901 and 2010. Deviation of estimated global discharge from the ensemble mean due to climate forcing uncertainty is approximately 4 %. Precipitation uncertainty is the most important reason for the uncertainty of discharge and evapotranspiration, followed by shortwave downward radiation. At continental levels, deviations of water balance components due to uncertain climate forcing are higher, with the highest discharge deviations occurring for river discharge in Africa (−6 to 11 % from the ensemble mean). Uncertain climate forcings also affect the estimation of irrigation water use and thus the estimated human impact of river discharge. The uncertainty range of global irrigation water consumption amounts to approximately 50 % of the global sum of water consumption in the other water use sector.
Congenital sensory deprivation can lead to reorganization of the deprived cortical regions by another sensory system. Such cross-modal reorganization may either compete with or complement the “original“ inputs to the deprived area after sensory restoration and can thus be either adverse or beneficial for sensory restoration. In congenital deafness, a previous inactivation study documented that supranormal visual behavior was mediated by higher-order auditory fields in congenitally deaf cats (CDCs). However, both the auditory responsiveness of “deaf” higher-order fields and interactions between the reorganized and the original sensory input remain unknown. Here, we studied a higher-order auditory field responsible for the supranormal visual function in CDCs, the auditory dorsal zone (DZ). Hearing cats and visual cortical areas served as a control. Using mapping with microelectrode arrays, we demonstrate spatially scattered visual (cross-modal) responsiveness in the DZ, but show that this did not interfere substantially with robust auditory responsiveness elicited through cochlear implants. Visually responsive and auditory-responsive neurons in the deaf auditory cortex formed two distinct populations that did not show bimodal interactions. Therefore, cross-modal plasticity in the deaf higher-order auditory cortex had limited effects on auditory inputs. The moderate number of scattered cross-modally responsive neurons could be the consequence of exuberant connections formed during development that were not pruned postnatally in deaf cats. Although juvenile brain circuits are modified extensively by experience, the main driving input to the cross-modally (visually) reorganized higher-order auditory cortex remained auditory in congenital deafness.
Periods of rhythmic slow-wave activity during physiological slow-wave sleep or induced by anesthesia are characterized by a waxing and waning of spontaneous neuronal firing coordinated between cortex and thalamus. This activity is generated in the cortex but influences neuronal excitability and stimulus–response properties of neuronal networks throughout the brain (Steriade et al., 1993; Stroh et al., 2013; McGinley et al., 2015b). The corresponding low-frequency component of field potential recordings reflects alternating active states, in which cells are depolarized and synaptic activity is high, and silent states with hyperpolarized membrane potentials and low synaptic activity (Steriade et al., 2001; Timofeev et al., 2001). In contrast, waking is generally associated with continuous depolarization of cortical neurons, resulting in persistent activity (Destexhe et al., 2007; Sheroziya and Timofeev, 2015) and suppression of silent states (Steriade et al., 2001; McGinley et al., 2015b). In their recent study, Sheroziya and Timofeev (2015) demonstrated that moderate cortical cooling (to 29–31°C) of lightly ketamine/xylazin (ket/xyl) anesthetized or non-anesthetized mice reversibly diminished silent states and induced a persistent active state of the cortex. Mild heating (to 39–40°C), in contrast, increased rhythmicity of slow waves. Under deep ket/xyl anesthesia, cortical cooling disrupted slow waves and promoted bursts of activity correlated with thalamic firing. Local cooling of somatosensory cortex was shown to be sufficient to induce a shift from slow-wave to wide-spread persistent cortical activity, extending to the thalamus as well as the contralateral hemisphere. These results suggest that cortical temperature change can be used as a bidirectional and reversible tool for investigating global brain state fluctuations, and provide evidence that the thalamocortical network rapidly reacts upon local depolarization of a small neuronal population with wide-spread shifts of brain state. ...
Background: Cytokine-induced-killer (CIK) cells are a promising immunotherapeutic approach for impending relapse following hematopoietic stem cell transplantation (HSCT). However, there is a high risk for treatment failure associated with severe graft versus host disease (GvHD) necessitating pharmaceutical intervention post-transplant. Whether immunosuppression with mycophenolate mofetil (MMF) or Ciclosporin A (CsA) influences the cytotoxic effect of CIK cell immunotherapy is still an open issue.
Methods: CIK cells were generated from PBMC as previously described followed by co-incubation with mycophenolic acid (MPA) or CsA. Proliferation, cytotoxicity and receptor expression were investigated following short- (24 h), intermediate- (3 days) and long-term (7 days) MPA incubation with the intention to simulate the in vivo situation when CIK cells were given to a patient with relevant MPA/CsA plasma levels.
Results: Short-term MPA treatment led to unchanged proliferation capacity and barely had any effect on viability and cytotoxic capability in vitro. The composition of CIK cells with respect to T-, NK-like T- and NK cells remained stable. Intermediate MPA treatment lacked effects on NKG2D, FasL and TRAIL receptor expression, while an influence on proliferation and viability was detectable. Furthermore, long-term treatment significantly impaired proliferation, restricted viability and drastically reduced migration-relevant receptors accompanied by an alteration in the CD4/CD8 ratio. CD3+CD56+ cells upregulated receptors relevant for CIK cell killing and migration, whereas T cells showed the most interference through significant reductions in receptor expression. Interestingly, CsA treatment had no significant influence on CIK cell viability and the cytotoxic potential against K562.
Conclusions: Our data indicate that if immunosuppressant therapy is indispensable, efficacy of CIK cells is maintained at least short-term, although more frequent dosing might be necessary.
Ecological networks are more sensitive to plant than to animal extinction under climate change
(2016)
Impacts of climate change on individual species are increasingly well documented, but we lack understanding of how these effects propagate through ecological communities. Here we combine species distribution models with ecological network analyses to test potential impacts of climate change on >700 plant and animal species in pollination and seed-dispersal networks from central Europe. We discover that animal species that interact with a low diversity of plant species have narrow climatic niches and are most vulnerable to climate change. In contrast, biotic specialization of plants is not related to climatic niche breadth and vulnerability. A simulation model incorporating different scenarios of species coextinction and capacities for partner switches shows that projected plant extinctions under climate change are more likely to trigger animal coextinctions than vice versa. This result demonstrates that impacts of climate change on biodiversity can be amplified via extinction cascades from plants to animals in ecological networks.
Ligand stimulation of CD95 induces activation of Plk3 followed by phosphorylation of caspase-8
(2016)
Upon interaction of the CD95 receptor with its ligand, sequential association of the adaptor molecule FADD (MORT1), pro-forms of caspases-8/10, and the caspase-8/10 regulator c-FLIP leads to the formation of a death-inducing signaling complex. Here, we identify polo-like kinase (Plk) 3 as a new interaction partner of the death receptor CD95. The enzymatic activity of Plk3 increases following interaction of the CD95 receptor with its ligand. Knockout (KO) or knockdown of caspase-8, CD95 or FADD prevents activation of Plk3 upon CD95 stimulation, suggesting a requirement of a functional DISC for Plk3 activation. Furthermore, we identify caspase-8 as a new substrate for Plk3. Phosphorylation occurs on T273 and results in stimulation of caspase-8 proapoptotic function. Stimulation of CD95 in cells expressing a non-phosphorylatable caspase-8-T273A mutant in a rescue experiment or in Plk3-KO cells generated by CRISPR/Cas9 reduces the processing of caspase-8 prominently. Low T273 phosphorylation correlates significantly with low Plk3 expression in a cohort of 95 anal tumor patients. Our data suggest a novel mechanism of kinase activation within the Plk family and propose a new model for the stimulation of the extrinsic death pathway in tumors with high Plk3 expression.
The Hydrogen Dependent Carbon dioxide Reductase (HDCR) from Acetobacterium woodii presents a promising solution to the issue of H2 storage by reversibly coupling H2 oxidation to CO2 reduction. We here report on the electrocatalytic properties of the hydrogenase (Hase) module in the intact complex, including (an)aerobic oxidation, CO inhibition and the first systematic analysis of the catalytic bias (CB) of a Hase. CB depends on pH, regardless of the H2 concentration, despite a higher affinity for H2 than other FeFe-Hases. Remarkably, CO inhibition is fully reversible under all oxidation states of the active site, making HDCR the first "syngas-friendly" FeFe-Hase.
Objectives: This study aimed to analyse and compare differences in occupational stress, depressive symptoms, work ability and working environment among residents working in various medical specialties.
Methods: 435 German hospital residents in medical training working in 6 different medical specialties participated in a cross-sectional survey study. Physicians were asked about their working conditions and aspects of mental health and work ability. The Copenhagen Psychosocial Questionnaire, the Work Ability Index, the ICD-10 Symptom Rating and the Perceived Stress Questionnaire were used to measure working conditions, mental health and work ability.
Results: Results show that up to 17% of the physicians reported high levels of occupational distress and 9% reported high levels of depressive symptoms. 11% of the hospital physicians scored low in work ability. Significant differences between medical specialties were demonstrated for occupational distress, depressive symptoms, work ability, job demands and job resources. Surgeons showed consistently the highest levels of perceived distress but also the highest levels of work ability and lowest scores for depression. Depressive symptoms were rated with the highest levels by anaesthesiologists. Significant associations between physicians’ working conditions, occupational distress and mental health-related aspects are illustrated.
Conclusions: Study results demonstrated significant differences in specific job stressors, demands and resources. Relevant relations between work factors and physicians' health and work ability are discussed. These findings should be reinvestigated in further studies, especially with a longitudinal study design. This work suggests that to ensure physicians' health, hospital management should plan and implement suitable mental health promotion strategies. In addition, operational efficiency through resource planning optimisation and work process improvements should be focused by hospital management.
Pirinixic acid derivatives, a new class of drug candidates for a range of diseases, interfere with targets including PPARα, PPARγ, 5-lipoxygenase (5-LO), and microsomal prostaglandin and E2 synthase-1 (mPGES1). Since 5-LO, mPGES1, PPARα, and PPARγ represent potential anti-cancer drug targets, we here investigated the effects of 39 pirinixic acid derivatives on prostate cancer (PC-3) and neuroblastoma (UKF-NB-3) cell viability and, subsequently, the effects of selected compounds on drug-resistant neuroblastoma cells. Few compounds affected cancer cell viability in low micromolar concentrations but there was no correlation between the anti-cancer effects and the effects on 5-LO, mPGES1, PPARα, or PPARγ. Most strikingly, pirinixic acid derivatives interfered with drug transport by the ATP-binding cassette (ABC) transporter ABCB1 in a drug-specific fashion. LP117, the compound that exerted the strongest effect on ABCB1, interfered in the investigated concentrations of up to 2μM with the ABCB1-mediated transport of vincristine, vinorelbine, actinomycin D, paclitaxel, and calcein-AM but not of doxorubicin, rhodamine 123, or JC-1. In silico docking studies identified differences in the interaction profiles of the investigated ABCB1 substrates with the known ABCB1 binding sites that may explain the substrate-specific effects of LP117. Thus, pirinixic acid derivatives may offer potential as drug-specific modulators of ABCB1-mediated drug transport.
Purpose: The PELICAN trial evaluates for the first time efficacy and safety of pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line treatment of metastatic breast cancer (MBC).
Methods: This randomized, phase III, open-label, multicenter trial enrolled first-line MBC patients who were ineligible for endocrine or trastuzumab therapy. Cumulative adjuvant anthracyclines of 360 mg/m2 doxorubicin or equivalent were allowed. Left ventricular ejection fraction of >50 % was required. Patients received PLD 50 mg/m2 every 28 days or capecitabine 1250 mg/m2 twice daily for 14 days every 21 days. The primary endpoint was time-to-disease progression (TTP).
Results: 210 patients were randomized (n = 105, PLD and n = 105, capecitabine). Adjuvant anthracyclines were given to 37 % (PLD) and 36 % (capecitabine) of patients. No significant difference was observed in TTP [HR = 1.21 (95 % confidence interval, 0.838–1.750)]. Median TTP was 6.0 months for both PLD and capecitabine. Comparing patients with or without prior anthracyclines, no significant difference in TTP was observed in the PLD arm (log-rank P = 0.64). For PLD versus capecitabine, respectively, overall survival (median, 23.3 months vs. 26.8 months) and time-to-treatment failure (median, 4.6 months vs. 3.7 months) were not statistically significantly different. Compared to PLD, patients on capecitabine experienced more serious adverse events (P = 0.015) and more cardiac events among patients who had prior anthracycline exposure (18 vs. 8 %; P = 0.31).
Conclusion: Both PLD and capecitabine are effective first-line agents for MBC.
Loss of HIF-1α in macrophages attenuates AhR/ARNT-mediated tumorigenesis in a PAH-driven tumor model
(2016)
Activation of hypoxia-inducible factor (HIF) and macrophage infiltration of solid tumors independently promote tumor progression. As little is known how myeloid HIF affects tumor development, we injected the polycyclic aromatic hydrocarbon (PAH) and procarcinogen 3-methylcholanthrene (MCA; 100 μg/100 μl) subcutaneously into myeloid-specific Hif-1α and Hif-2α knockout mice (C57BL/6J) to induce fibrosarcomas (n = 16). Deletion of Hif-1α but not Hif-2α in macrophages diminished tumor outgrowth in the MCA-model. While analysis of the tumor initiation phase showed comparable inflammation after MCA-injection, metabolism of MCA was impaired in the absence of Hif-1α. An ex vivo macrophage/fibroblast coculture recapitulated reduced DNA damage after MCA-stimulation in fibroblasts of cocultures with Hif-1α LysM-/- macrophages compared to wild type macrophages. A loss of myeloid Hif-1α decreased RNA levels of arylhydrocarbon receptor (AhR)/arylhydrocarbon receptor nuclear translocator (ARNT) targets such as Cyp1a1 because of reduced Arnt but unchanged Ahr expression. Cocultures using Hif-1α LysM-/- macrophages stimulated with the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA; 2 μg/ml) also attenuated a DNA damage response in fibroblasts, while the DNA damage-inducing metabolite DMBA-trans-3,4-dihydrodiol remained effective in the absence of Hif-1α. In chemical-induced carcinogenesis, HIF-1α in macrophages maintains ARNT expression to facilitate PAH-biotransformation. This implies a metabolic activation of PAHs in stromal cells, i.e. myeloid-derived cells, to be crucial for tumor initiation.
A chiral analog of the bicyclic guanidine TBD : synthesis, structure and Brønsted base catalysis
(2016)
Starting from (S)-β-phenylalanine, easily accessible by lipase-catalyzed kinetic resolution, a chiral triamine was assembled by a reductive amination and finally cyclized to form the title compound 10. In the crystals of the guanidinium benzoate salt the six membered rings of 10 adopt conformations close to an envelope with the phenyl substituents in pseudo-axial positions. The unprotonated guanidine 10 catalyzes Diels–Alder reactions of anthrones and maleimides (25–30% ee). It also promotes as a strong Brønsted base the retro-aldol reaction of some cycloadducts with kinetic resolution of the enantiomers. In three cases, the retro-aldol products (48–83% ee) could be recrystallized to high enantiopurity (≥95% ee). The absolute configuration of several compounds is supported by anomalous X-ray diffraction and by chemical correlation.
Evaluation of radiation components in a global freshwater model with station-based observations
(2016)
In many hydrological models, the amount of evapotranspired water is calculated using the potential evapotranspiration (PET) approach. The main driver of several PET approaches is net radiation, whose downward components are usually obtained from meteorological input data, whereas the upward components are calculated by the model itself. Thus, uncertainties can be large due to both the input data and model assumptions. In this study, we compare the radiation components of the WaterGAP Global Hydrology Model, driven by two meteorological input datasets and two radiation setups from ERA-Interim reanalysis. We assess the performance with respect to monthly observations provided by the Baseline Surface Radiation Network (BSRN) and the Global Energy Balance Archive (GEBA). The assessment is done for the global land area and specifically for energy/water limited regions. The results indicate that there is no optimal radiation input throughout the model variants, but standard meteorological input datasets perform better than those directly obtained by ERA-Interim reanalysis for the key variable net radiation. The low number of observations for some radiation components, as well as the scale mismatch between station observations and 0.5° × 0.5° grid cell size, limits the assessment.
Super-resolution fluorescence microscopy revolutionizes cell biology research and provides novel insights on how proteins are organized at the nanoscale and in the cellular context. In order to extract a maximum of information, specialized tools for image analysis are necessary. Here, we introduce the LocAlization Microscopy Analyzer (LAMA), a comprehensive software tool that extracts quantitative information from single-molecule super-resolution imaging data. LAMA allows characterizing cellular structures by their size, shape, intensity, distribution, as well as the degree of colocalization with other structures. LAMA is freely available, platform-independent and designed to provide direct access to individual analysis of super-resolution data.
Shrew-1, also called AJAP1, is a transmembrane protein associated with E-cadherin-mediated adherence junctions and a putative tumor suppressor. Apart from its interaction with β-catenin and involvement in E-cadherin internalization, little structure or function information exists. Here we explored shrew-1 expression during postnatal differentiation of mammary gland as a model system. Immunohistological analyses with antibodies against either the extracellular or the cytoplasmic domains of shrew-1 consistently revealed the expression of full-length shrew-1 in myoepithelial cells, but only part of it in luminal cells. While shrew-1 localization remained unaltered in myoepithelial cells, nuclear localization occurred in luminal cells during lactation. Based on these observations, we identified two unknown shrew-1 transcript variants encoding N-terminally truncated proteins. The smallest shrew-1 protein lacks the extracellular domain and is most likely the only variant present in luminal cells. RNA analyses of human tissues confirmed that the novel transcript variants of shrew-1 exist in vivo and exhibit a differential tissue expression profile. We conclude that our findings are essential for the understanding and interpretation of future functional and interactome analyses of shrew-1 variants.
Motion analysis in the field of dentistry : a kinematic comparison of dentists and orthodontists
(2016)
Objectives: To conduct a kinematic comparison of occupational posture in orthodontists and dentists in their workplace.
Design: Observational study.
Setting: Dentist surgeries and departments of orthodontics at university medical centres in Germany.
Participants: A representative sample of 21 (10 female, 11 male) dentists (group G1) and 21 (13 female, 8 male) orthodontists (G2) with one male dropout in G2.
Outcome measures: The CUELA (computer-assisted acquisition and long-term analysis of musculoskeletal loads) system was used to analyse occupational posture. Parallel to the recording through the CUELA system, a software-supported analysis of the activities performed (I: treatment; II: office; III: other activities) was carried out. In line with ergonomic standards the measured body angles are categorised into neutral, moderate and awkward postures. Activities between the aforementioned groups are compared using the stratified van Elteren U test and the Wilcoxon–Mann–Whitney U test. All p values are subject to the Bonferroni–Holm correction. The level of significance is set at 5%.
Results: The percentage of time spent on activities in categories I–II–III was as follows: dentists 41%–23%–36% and orthodontists 28%–37%–35%. The posture analysis of both groups showed, for all percentiles (P5–95), angle values primarily in the neutral or moderate range. However, depending on the activity performed, between 5% and 25% of working hours were spent in unfavourable postures, especially in the head-and-neck area. Orthodontists have a greater tendency than dentists to perform treatment activities with the head and torso in unfavourable positions. The statistically significant differences between the two groups with regard to the duration and the relevance of the activities performed confirm this assumption for all three categories (p<0.01, p<0.05).
Conclusions: Generally, both groups perform treatment activities in postures that are in the neutral or medium range; however, dentists had slightly more unfavourable postures during treatment for a greater share of their work day.
The acoustic startle response (ASR) and its modulation by non-startling prepulses, presented shortly before the startle-eliciting stimulus, is a broadly applied test paradigm to determine changes in neural processing related to auditory or psychiatric disorders. Modulation by a gap in background noise as a prepulse is especially used for tinnitus assessment. However, the timing and frequency-related aspects of prepulses are not fully understood. The present study aims to investigate temporal and spectral characteristics of acoustic stimuli that modulate the ASR in rats and gerbils. For noise-burst prepulses, inhibition was frequency-independent in gerbils in the test range between 4 and 18 kHz. Prepulse inhibition (PPI) by noise-bursts in rats was constant in a comparable range (8–22 kHz), but lower outside this range. Purely temporal aspects of prepulse–startle-interactions were investigated for gap-prepulses focusing mainly on gap duration. While very short gaps had no (rats) or slightly facilitatory (gerbils) influence on the ASR, longer gaps always had a strong inhibitory effect. Inhibition increased with durations up to 75 ms and remained at a high level of inhibition for durations up to 1000 ms for both, rats and gerbils. Determining spectral influences on gap-prepulse inhibition (gap-PPI) revealed that gerbils were unaffected in the limited frequency range tested (4–18 kHz). The more detailed analysis in rats revealed a variety of frequency-dependent effects. Gaps in pure-tone background elicited constant and high inhibition (around 75%) over a broad frequency range (4–32 kHz). For gaps in noise-bands, on the other hand, a clear frequency-dependency was found: inhibition was around 50% at lower frequencies (6–14 kHz) and around 70% at high frequencies (16–20 kHz). This pattern of frequency-dependency in rats was specifically resulting from the inhibitory effect by the gaps, as revealed by detailed analysis of the underlying startle amplitudes. An interaction of temporal and spectral influences, finally, resulted in higher inhibition for 500 ms gaps than for 75 ms gaps at all frequencies tested. Improved prepulse paradigms based on these results are well suited to quantify the consequences of central processing disorders.
The chloroplast phosphorylation network is important for posttranslational regulation of photosynthetic complexes, gene expression and metabolic pathways. In mass-spectrometric analyses a lot of putative phosphorylation targets have been found but these data need to be confirmed and brought into a physiological context. Here, we present a current protocol to quantify the phosphorylation state of thylakoid proteins and an in situ method to verify putative substrates for thylakoid associated kinases.
One hallmark of MLL-r leukemia is the highly specific gene expression signature indicative for commonly deregulated target genes. An usual read-out for this transcriptional deregulation is the HOXA gene cluster, where upregulated HOXA genes are detected in MLL-r AML and ALL patients. In case of t(4;11) leukemia, this simple picture becomes challenged, because these patients separate into HOXAhi- and HOXAlo-patients. HOXAlo-patients showed a reduced HOXA gene transcription, but instead overexpressed the homeobox gene IRX1. This transcriptional pattern was associated with a higher relapse rate and worse outcome. Here, we demonstrate that IRX1 binds to the MLL-AF4 complex at target gene promotors and counteract its promotor activating function. In addition, IRX1 induces transcription of HOXB4 and EGR family members. HOXB4 is usually a downstream target of c-KIT, WNT and TPO signaling pathways and necessary for maintaining and expanding in hematopoietic stem cells. EGR proteins control a p21-dependent quiescence program for hematopoietic stem cells. Both IRX1-dependend actions may help t(4;11) leukemia cells to establish a stem cell compartment. We also demonstrate that HDACi administration is functionally interfering with IRX1 and MLL-AF4, a finding which could help to improve new treatment options for t(4;11) patients.
The Asian tiger mosquito, Aedes albopictus (Diptera: Culicidae, SKUSE), is an important threat to public health due to its rapid spread and its potential as a vector. The eggs of Ae. albopictus are the most cold resistant life stage and thus, the cold hardiness of eggs is used to predict the future occurrence of the species in distribution models. However, the mechanism of cold hardiness has yet to be revealed. To address this question, we analyzed the layers of diapausing and cold acclimatized eggs of a temperate population of Ae. albopictus in a full factorial test design using transmission electron microscopy. We reviewed the hypotheses that a thickened wax layer or chorion is the cause of cold hardiness but found no evidence. As a result of the induced diapause, the thickness of the dark endochorion as a layer of high electron density and thus an assumed location for waxes was decreasing. We therefore hypothesized a qualitative alteration of the wax layer due to compaction. Cold acclimation was causing an increase in the thickness of the middle serosa cuticle indicating a detachment of serosa membrane from the endochorion as a potential adaptation strategy to isolate inoculating ice formations in the inter-membranous space.
Endometriosis and its global research architecture : an in-depth density-equalizing mapping analysis
(2016)
Background: Endometriosis is one of the most common gynecological diseases. It is still a chameleon in many aspects and urges intense research activities in the fields of diagnosis, therapy and prevention. Despite the need to foster research in this area, no in-depth analysis of the global architecture of endometriosis research exists yet.
Methods: We here used the NewQIS platform to conduct a density equalizing mapping study, using the Web of Science as database with endometriosis related entries between 1900 and 2009. Density equalizing maps of global endometriosis research encompassing country-specific publication activities, and semi-qualitative indices such as country specific citations, citation rates, h-Indices were created.
Results: In total, 11,056 entries related to endometriosis were found. The USA was leading the field with 3705 publications followed by the United Kingdom (952) and Japan (846). Concerning overall citations and country-specific h-Indices, the USA again was the leading nation with 74,592 citations and a modified h-Index of 103, followed by the UK with 15,175 citations (h-Index 57). Regarding the citation rate, Sweden and Belgium were at top positions with rates of 22.46 and 22.26, respectively. Concerning collaborative studies, there was a steep increase in numbers present; analysis of the chronological evolution indicated a strong increase in international collaborations in the past 10 years.
Conclusions: This study is the first analysis that illustrates the global endometriosis research architecture. It shows that endometriosis research is constantly gaining importance but also underlines the need for further efforts and investments to foster research and ultimately improve endometriosis management on a global scale.
Allostery is a phenomenon observed in many proteins where binding of a macromolecular partner or a small-molecule ligand at one location leads to specific perturbations at a site not in direct contact with the region where the binding occurs. The list of proteins under allosteric regulation includes AGC protein kinases. AGC kinases have a conserved allosteric site, the phosphoinositide-dependent protein kinase 1 (PDK1)-interacting fragment (PIF) pocket, which regulates protein ATP-binding, activity, and interaction with substrates. In this study, we identify small molecules that bind to the ATP-binding site and affect the PIF pocket of AGC kinase family members, PDK1 and Aurora kinase. We describe the mechanistic details and show that although PDK1 and Aurora kinase inhibitors bind to the conserved ATP-binding site, they differentially modulate physiological interactions at the PIF-pocket site. Our work outlines a strategy for developing bidirectional small-molecule allosteric modulators of protein kinases and other signaling proteins.
In the cochlea of the mustached bat, cochlear resonance produces extremely sharp frequency tuning to the dominant frequency of the echolocation calls, around 61 kHz. Such high frequency resolution in the cochlea is accomplished at the expense of losing temporal resolution because of cochlear ringing, an effect that is observable not only in the cochlea but also in the cochlear nucleus. In the midbrain, the duration of sounds is thought to be analyzed by duration-tuned neurons, which are selective to both stimulus duration and frequency. We recorded from 57 DTNs in the auditory midbrain of the mustached bat to assess if a spectral-temporal trade-off is present. Such spectral-temporal trade-off is known to occur as sharp tuning in the frequency domain which results in poorer resolution in the time domain, and vice versa. We found that a specialized sub-population of midbrain DTNs tuned to the bat’s mechanical cochlear resonance frequency escape the cochlear spectral-temporal trade-off. We also show evidence that points towards an underlying neuronal inhibition that appears to be specific only at the resonance frequency.