Differential expression of the receptor tyrosine kinase EphB4 and its ligand Ephrin-B2 during human placental development

Normal placentation involves the development of an utero-placental circulation following the migration of the extravillous cytotrophoblasts into the decidua and invasion of the spiral arteries, which are thereby transformed into large vessels of low resistance. Given the documented role of the receptor tyrosine kinase EphB4 and its ligand ephrin-B2 in the establishment of the embryonal vascular network, we hypothesized that these molecules are also instrumental in the development of the human placenta. Monitoring the expression during placental development revealed that in first trimester and term placentae both molecules are equally expressed at the RNA level. In contrast, the protein levels were significantly reduced during gestation. Immunohistochemistry revealed a distinct localization of the EphB4 and ephrin-B2 proteins. EphB4 was predominantly expressed in the villous syncytial trophoblast layer and in a subset of intravillous capillaries. Prominent expression was also observed in the extravillous cytotrophoblast giant cells. In contrast, ephrin-B2 expression was detected in the villous cytotrophoblast and syncytial trophoblast cell layers, as well as initially in all intravillous capillaries. Strong expression was also observed in extravillous anchoring cytotrophoblast cells. Hypoxia is a major inducer of placental development. In vitro studies employing trophoblast-derived cell lines revealed that predominantly ephrin-B2 expression is induced by hypoxia, however, in an Hif-1alpha independent manner. These experiments suggest that EphB4 and ephrin-B2 are instrumental in the establishment of a functional placental structure and of the utero-placental circulation.

Variability of in vivo fish acute toxicity data

The variability of toxicity data contained within databases was investigated using the widely used US EPA ECOTOX database as an example. Fish acute lethality (LC50) values for 44 compounds (for which at least 10 data entries existed) were extracted from the ECOTOX database yielding a total of 4654 test records. Significant variability of LC50 test results was observed, exceeding several orders of magnitude. In an attempt to systematically explore potential causes of the data variability, the influence of biological factors (such as test species or life stages) and physical factors (such as water temperature, pH or water hardness) were examined. Even after eliminating the influence of these inherent factors, considerable data variability remained, suggesting an important role of factors relating to technical and measurement procedures. The analysis, however, was limited by pronounced gaps in the test documentation. Of the 4654 extracted test reports, 66.5% provided no information on the fish life stage used for testing. Likewise, water temperature, hardness or pH were not recorded in 19.6%, 48.2% and 41.2% of the data entries, respectively. From these findings, we recommend the rigorous control of data entries ensuring complete recording of testing conditions. A more consistent database will help to better discriminate between technical and natural variability of the test data, which is of importance in ecological risk assessment for extrapolation from laboratory tests to the field, and also might help to develop correction factors that account for systematic differences in test results caused by species, life stage or test conditions.

Observations of the northern seasonal polar cap on Mars III: CRISM/HiRISE observations of spring sublimation

We analyze a series of targeted CRISM and HiRISE observations of seven regions of interest at high latitudes in the Northern polar regions of Mars. These data allow us to investigate the temporal evolution of the composition of the seasonal ice cap during spring, with a special emphasis on peculiar phenomena occurring in the dune fields and in the vicinity of the scarps of the North Polar Layered Deposits (NPLDs). The strength of the spectral signature of CO2 ice continuously decreases during spring whereas the one of H2O ice first shows a strong increase until Ls = 50°. This evolution is consistent with a scenario previously established from analysis of OMEGA data, in which a thin layer of pure H2O ice progressively develops at the surface of the volatile layer. During early spring (Ls < 10°), widespread jet activity is observed by HiRISE while strong spectral signatures of CO2 ice are detected by CRISM. Later, around Ls = 20-40°, activity concentrates at the dune fields where CRISM also detects a spectral enrichment in CO2 ice, consistent with "Kieffer's model" (Kieffer, H.H. [2007]. J. Geophys. Res. 112, E08005. doi:10.1029/2006JE002816) for jet activity. Effects of wind are prominent across the dune fields and seem to strongly influence the sublimation of the volatile layer. Strong winds blowing down the scarps could also be responsible for the significant spatial and temporal variability of the surface ice composition observed close to the NPLD.

The Anomalous Merging of the African and North Atlantic Jet Streams during the Northern Hemisphere Winter of 2010

The North Atlantic jet stream during winter 2010 was unusually zonal, so the typically separated Atlantic and African jets were merged into one zonal jet. Moreover, the latitude–height structure and temporal variability of the North Atlantic jet during this winter were more characteristic of the North Pacific. This work examines the possibility of a flow regime change from an eddy-driven to a mixed eddy–thermally driven jet. A monthly jet zonality index is defined, which shows that a persistent merged jet state has occurred in the past, both at the end of the 1960s and during a few sporadic months. The anomalously zonal jet is found to be associated with anomalous tropical Pacific diabatic heating and eddy anomalies similar to those found during a negative North Atlantic Oscillation (NAO) state. A Lagrangian back-trajectory diagnosis of eight winters suggests the tropical Pacific is a source of momentum to the Atlantic and African jets and that this source was stronger during the winter of 2010. The results suggest that the combination of weak eddy variance and fluxes in the North Atlantic, along with strong tropical heating, act to push the jet toward a merged eddy–thermally driven state. The authors also find significant SST anomalies in the North Atlantic, which reinforce the anomalous zonal winds, particularly in the eastern Atlantic.

A stratigraphic framework for abrupt climatic changes during the Last Glacial period based on three synchronized Greenland ice-core records: refining and extending the INTIMATE event stratigraphy

Due to their outstanding resolution and well-constrained chronologies, Greenland ice-core records provide a master record of past climatic changes throughout the Last Interglacial–Glacial cycle in the North Atlantic region. As part of the INTIMATE (INTegration of Ice-core, MArine and TErrestrial records) project, protocols have been proposed to ensure consistent and robust correlation between different records of past climate. A key element of these protocols has been the formal definition and ordinal numbering of the sequence of Greenland Stadials (GS) and Greenland Interstadials (GI) within the most recent glacial period. The GS and GI periods are the Greenland expressions of the characteristic Dansgaard–Oeschger events that represent cold and warm phases of the North Atlantic region, respectively. We present here a more detailed and extended GS/GI template for the whole of the Last Glacial period. It is based on a synchronization of the NGRIP, GRIP, and GISP2 ice-core records that allows the parallel analysis of all three records on a common time scale. The boundaries of the GS and GI periods are defined based on a combination of stable-oxygen isotope ratios of the ice (δ18O, reflecting mainly local temperature) and calcium ion concentrations (reflecting mainly atmospheric dust loading) measured in the ice. The data not only resolve the well-known sequence of Dansgaard–Oeschger events that were first defined and numbered in the ice-core records more than two decades ago, but also better resolve a number of short-lived climatic oscillations, some defined here for the first time. Using this revised scheme, we propose a consistent approach for discriminating and naming all the significant abrupt climatic events of the Last Glacial period that are represented in the Greenland ice records. The final product constitutes an extended and better resolved Greenland stratotype sequence, against which other proxy records can be compared and correlated. It also provides a more secure basis for investigating the dynamics and fundamental causes of these climatic perturbations.

Echinococcus P29 antigen: molecular characterization and implication on post-surgery follow-up of CE patients infected with different species of the Echinococcus granulosus complex.

The protein P29 is a potential serological marker for post-treatment monitoring of cystic echinococcosis (CE) especially in young patients. We now have demonstrated that P29 is encoded in the Echinococcus genus by a single gene consisting of 7 exons spanning 1.2 kb of DNA. Variability of the p29 gene at inter- and intra-species level was assessed with 50 cDNA and 280 genomic DNA clones isolated from different E. granulosus s.l. isolates (E. granulosus sensu stricto (G1), E. equinus (G4), E. ortleppi (G5), E. canadensis (G6), E. canadensis (G7) and E. canadensis (G10)) as well as four E. multilocularis isolates. Scarce interspecies polymorphism at the p29 locus was observed and affected predominantly E. granulosus s.s. (G1), where we identified two alleles (A1 and A2) coding for identical P29 proteins and yielding in three genotypes (A1/A1, A2/A2 and A1/A2). Genotypic frequencies expected under Hardy-Weinberg equilibrium revealed a high rate of heterozygosity (47%) that strongly supports the hypothesis that E. granulosus s.s. (G1) is predominantly outbreeding. Comparative sequence analyses of the complete p29 gene showed that phylogenetic relationships within the genus Echinococcus were in agreement with those of previous nuclear gene studies. At the protein level, the deduced P29 amino acid (AA) sequences exhibited a high level of conservation, ranging from 97.9% AA sequence identity among the whole E. granulosus s.l. group to 99.58% identity among E. multilocularis isolates. We showed that P29 proteins of these two species differ by three AA substitutions without implication for antigenicity. In Western-blot analyses, serum antibodies from a human CE patient infected with E. canadensis (G6) strongly reacted with recombinant P29 from E. granulosus s.s. (G1) (recEg(G1)P29). In the same line, human anti-Eg(G1)P29 antibodies bound to recEcnd(G6)P29. Thus, minor AA sequence variations appear not to impair the prognostic serological use of P29.

Clinical Outcomes According to Diabetic Status in Patients Treated With Biodegradable Polymer Sirolimus-Eluting Stents Versus Durable Polymer Everolimus-Eluting Stents: Prespecified Subgroup Analysis of the BIOSCIENCE Trial.

BACKGROUND Ultrathin strut biodegradable polymer sirolimus-eluting stents (BP-SES) proved noninferior to durable polymer everolimus-eluting stents (DP-EES) for a composite clinical end point in a population with minimal exclusion criteria. We performed a prespecified subgroup analysis of the Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent for Percutaneous Coronary Revascularisation (BIOSCIENCE) trial to compare the performance of BP-SES and DP-EES in patients with diabetes mellitus. METHODS AND RESULTS BIOSCIENCE trial was an investigator-initiated, single-blind, multicentre, randomized, noninferiority trial comparing BP-SES versus DP-EES. The primary end point, target lesion failure, was a composite of cardiac death, target-vessel myocardial infarction, and clinically indicated target lesion revascularization within 12 months. Among a total of 2119 patients enrolled between February 2012 and May 2013, 486 (22.9%) had diabetes mellitus. Overall diabetic patients experienced a significantly higher risk of target lesion failure compared with patients without diabetes mellitus (10.1% versus 5.7%; hazard ratio [HR], 1.80; 95% confidence interval [CI], 1.27-2.56; P=0.001). At 1 year, there were no differences between BP-SES versus DP-EES in terms of the primary end point in both diabetic (10.9% versus 9.3%; HR, 1.19; 95% CI, 0.67-2.10; P=0.56) and nondiabetic patients (5.3% versus 6.0%; HR, 0.88; 95% CI, 0.58-1.33; P=0.55). Similarly, no significant differences in the risk of definite or probable stent thrombosis were recorded according to treatment arm in both study groups (4.0% versus 3.1%; HR, 1.30; 95% CI, 0.49-3.41; P=0.60 for diabetic patients and 2.4% versus 3.4%; HR, 0.70; 95% CI, 0.39-1.25; P=0.23, in nondiabetics). CONCLUSIONS In the prespecified subgroup analysis of the BIOSCIENCE trial, clinical outcomes among diabetic patients treated with BP-SES or DP-EES were comparable at 1 year. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01443104.

Temporal variability of damage potential on roads as a conceptual contribution towards a short-term avalanche risk simulation

The fatality risk caused by avalanches on road networks can be analysed using a long-term approach, resulting in a mean value of risk, and with emphasis on short-term fluctuations due to the temporal variability of both, the hazard potential and the damage potential. In this study, the approach for analysing the long-term fatality risk has been adapted by modelling the highly variable short-term risk. The emphasis was on the temporal variability of the damage potential and the related risk peaks. For defined hazard scenarios resulting from classified amounts of snow accumulation, the fatality risk was calculated by modelling the hazard potential and observing the traffic volume. The avalanche occurrence probability was calculated using a statistical relationship between new snow height and observed avalanche releases. The number of persons at risk was determined from the recorded traffic density. The method resulted in a value for the fatality risk within the observed time frame for the studied road segment. The long-term fatality risk due to snow avalanches as well as the short-term fatality risk was compared to the average fatality risk due to traffic accidents. The application of the method had shown that the long-term avalanche risk is lower than the fatality risk due to traffic accidents. The analyses of short-term avalanche-induced fatality risk provided risk peaks that were 50 times higher than the statistical accident risk. Apart from situations with high hazard level and high traffic density, risk peaks result from both, a high hazard level combined with a low traffic density and a high traffic density combined with a low hazard level. This provided evidence for the importance of the temporal variability of the damage potential for risk simulations on road networks. The assumed dependence of the risk calculation on the sum of precipitation within three days is a simplified model. Thus, further research is needed for an improved determination of the diurnal avalanche probability. Nevertheless, the presented approach may contribute as a conceptual step towards a risk-based decision-making in risk management.

Pinus nigra (European black pine) as the dominant species of the last glacial pinewoods in south-western to central Iberia: a morphological study of modern and fossil pollen

Aim Our aim was to discriminate different species of Pinus via pollen analysis in order to assess the responses of particular pine species to orbital and millennial-scale climate changes, particularly during the last glacial period. Location Modern pollen grains were collected from current pine populations along transects from the Pyrenees to southern Iberia and the Balearic Islands. Fossil pine pollen was recovered from the south-western Iberian margin core MD95-2042. Methods We measured a set of morphological traits of modern pollen from the Iberian pine species Pinus nigra, P. sylvestris, P. halepensis, P. pinea and P. pinaster and of fossil pine pollen from selected samples of the last glacial period and the early to mid-Holocene. Classification and regression tree (CART) analysis was used to establish a model from the modern dataset that discriminates pollen from the different pine species and allows identification of fossil pine pollen at the species level. Results The CART model was effective in separating pollen of P. nigra and P. sylvestris from that of the Mediterranean pine group (P. halepensis, P. pinea and P. pinaster). The pollen of Pinus nigra diverged from that of P. sylvestris by having a more flattened corpus. Predictions using this model suggested that fossil pine pollen is mainly from P. nigra in all the samples analysed. Pinus sylvestris was more abundant in samples from Greenland stadials than Heinrich stadials, whereas Mediterranean pines increased in samples from Greenland interstadials and during the early to mid-Holocene. Main conclusions Morphological parameters can be successfully used to increase the taxonomic resolution of fossil pine pollen at the species level for the highland pines (P. nigra and P. sylvestris) and at the group of species level for the Mediterranean pines. Our study indicates that P. nigra was the dominant component of the last glacial south-western/central Iberian pinewoods, although the species composition of these woodlands varied in response to abrupt climate changes.

Stable oxygen isotope composition of benthic foraminifera from sediments of the Skagerrak, North Sea

Benthic foraminiferal tests of a sediment core from southwestern Skagerrak (northeastern North Sea, 420 m water depth) were investigated for their ratio of stable oxygen isotopes. During modern times sudden drops in temperature and salinity of Skagerrak deep waters point to advection-induced cascades of colder and denser central North Sea waters entering the Skagerrak. These temperature drops, which are recorded in benthic foraminiferal tests via the stable oxygen isotopic composition, were used to reconstruct deep-water renewal in the Skagerrak. In a second step we will show that, at least during the last 1200 years, Skagerrak deep-water renewal is triggered by the negative phase of the North Atlantic Oscillation (NAO). The NAO exerts a strong influence on the climate of northwestern Europe. It is currently under debate if the long-term variability of the NAO is capable of influencing Northern Hemisphere climate on long timescales. The data presented here cannot reinforce these speculations. Our data show that most of the 'Little Ice Age' was dominated by comparably warm deep-water temperatures. However, we did find extraordinary strong temperature differences between central North Sea waters and North Atlantic water masses during this time interval.

Revised age models and foraminiferal records obtained for the Last Interglacial period in six marine sediment cores

The dataset contains the revised age models and foraminiferal records obtained for the Last Interglacial period in six marine sediment cores: - the Southern Ocean core MD02-2488 (age model, sea surface temperatures, benthic d18O and d13C for the period 136-108 ka), - the North Atlantic core MD95-2042 (age model, planktic d18O, benthic d18O and d13C for the period 135-110 ka), - the North Atlantic core ODP 980 (age model, planktic d18O, sea surface temperatures, seawater d18O, benthic d18O and d13C, ice-rafted detritus for the period 135-110 ka), - the North Atlantic core CH69-K09 (age model, planktic d18O, sea surface temperatures, seawater d18O, benthic d18O and d13C, ice-rafted detritus for the period 135-110 ka), - the Norwegian Sea core MD95-2010 (age model, percentage of Neogloboquadrina pachyderma sinistral, sea surface temperatures, benthic d18O, ice-rafted detritus for the period 134-110 ka), - the Labrador Sea core EW9302-JPC2 (age model, percentage of Neogloboquadrina pachyderma sinistral, sea surface temperatures, benthic d18O for the period 134-110 ka).

Distribution of planktonic foraminifera in Pleistocene sediments of the New Jersey margin, NW Atlantic Ocean

Abundance records of planktonic foraminifera (>150 µm) from the upper 520 m of ODP Site 1073 (Hole 1073A, Leg 174A, 639 m water depth) have been integrated with SPECMAP-derived isotope stratigraphy, percentage of calcium carbonate, and coarse sediment fraction data in order to investigate the Pleistocene climatic history of the New Jersey margin. Six planktonic taxonomic groups dominate the foraminiferal assemblage at Site 1073: Neogloboquadrina pachyderma (d) (mean 33.8%), Turborotalita quinqueloba (18.5%), N. pachyderma (s) (18.4%), Globigerina bulloides group (11.4%), Globorotalia inflata group (9.4%), and Globigerinita glutinata (4.1%). Based on the distributions of these six foraminiferal groups, the Pleistocene section can be divided into three paleoclimatic intervals: Interval I (intermediate) corresponds to the Quaternary sediments from sequence boundary pp1 to the seafloor (79.5-0 mbsf; Emiliania huxleyi acme [85 ka] at 72 mbsf); Interval II (warm) occurs between sequence boundaries pp3 and pp1 (325-79.5 mbsf; last occurrence of Pseudoemiliania lacunosa [460 ka] at 330 mbsf); and Interval III (coldest) occurs between sequence boundaries pp4 and pp3 (520-325 mbsf; Calcareous nannofossils and dinocysts in proximity to pp4 indicate that the sedimentary record for 0.9-1.7 Ma is either missing altogether or highly condensed within the basal few meters of the section). Neogloboquadrina pachyderma (d) displays eight peaks of abundance which correlate, for the most part, with depleted delta18O values, increases in calcium carbonate percentages, low coarse fraction percentages, increased planktonic fragmentation (greater dissolution), and low N. pachyderma (s) abundances. These intervals are interpreted as representing warmer/interglacial conditions. Neogloboquadrina pachyderma (s) displays seven peaks of abundance which correlate, for the most part, with delta18O increases, decreases in calcium carbonate percentages, increases in coarse fraction percentages, and low N. pachyderma (d) abundances. These intervals are interpreted as representing cooler/glacial conditions. In Interval III, a faunal response to relative changes in sea-surface temperature is reflected by abundance peaks in Neogloboquadrina pachyderma (d), followed by Turborotalita quinqueloba and then N. pachyderma (s) (proceeding from warmest to coolest, respectively). This tripartite response is consistent with the oxygen isotope record and, although not as clear, also occurs in Intervals I and II. Six peaks/peak intervals of Globigerina bulloides abundance are closely matched by peaks in Globigerinita glutinata and occur within oxygen isotope stage (OIS) 2 (latter part) 3, 4, 5, 8, 9, 13(?), 14(?), and 15(?). We speculate that these intervals reflect increased upwelling and nutrient levels during both glacials and interglacials. Eight peak intervals of Globorotalia inflata show a general inverse correlation with G. bulloides and may reflect lowered nutrient and warmer surface waters.

Reconstruction of sea surface temperature and salinity of the Arabian Sea

High-frequency suborbital variations (Dansgaard-Oeschger cycles) characterize the climatic history of the Northern Hemisphere as observed in Greenland ice cores, deep-sea sediments of the North Atlantic, the Californian borderland, the Arabian Sea, the South China Sea, and the Chinese loess area. Paleoceanographic data from core KL126 from the Bay of Bengal in combination with data from the other Asian monsoonal areas indicate that the feedback processes involving snow and dust of the Tibetan Plateau vary the summer monsoon capacity to transport moisture into central South Asia and into the atmosphere. We postulate that the summer monsoon initiates, amplifies, and terminates these cycles in the Northern Hemisphere.