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Ca2+ and cAMP signalling pathways interact in a complex manner at multiple sites. This crosstalk fine-tunes the spatiotemporal patterns of Ca2+ and cAMP signals. In salivary glands of the blowfly Calliphora vicina fluid secretion is stimulated by serotonin (5-hydroxytryptamine, 5-HT) via activation of two different 5-HT receptors coupled to the InsP(3)/Ca2+ (Cv5-HT2 alpha) or the cAMP pathway (Cv5-HT7), respectively. We have shown recently in permeabilized gland cells that cAMP sensitizes InsP(3)-induced Ca2+ release to InsP(3). Here we study the effects of the CAMP signalling pathway on 5-HT-induced oscillations in transepithelial potential (TEP) and in intracellular [Ca2+]. We show: (1) Blocking the activation of the cAMP pathway by cinanserin suppresses the generation of TEP and Ca2+ oscillations, (2) application of 8-CPT-cAMP in the presence of cinanserin restores 5-HT-induced TEP and Ca2+ oscillations, (3) 8-CPT-cAMP sensitizes the InsP(3)/Ca2+ signalling pathway to 5-HT and the Cv5-HT2 alpha, receptor agonist 5-MeOT, (4) 8-CPT-cAMP induces Ca2+ oscillations in cells loaded with subthreshold concentrations of InsP(3), (5) inhibition of protein kinase A by H-89 abolishes 5-HT-induced TEP and Ca2+ spiking and mimics the effect of cinanserin. These results suggest that activation of the cyclic AMP pathway promotes the generation of 5-HT-induced Ca2+ oscillations in blowfly salivary glands.
The northern part of the Pamir orogen is the preeminent example of an active intracontinental subduction zone in the early stages of continent-continent collision. Such zones are the least understood type of plate boundaries because modern examples are few and of limited access, and ancient analogs have been extensively overprinted by subsequent tectonic and erosion processes. In the Pamir, it has been assumed that most of the plate convergence was accommodated by overthrusting along the plate-bounding Main Pamir Thrust (MPT), which forms the principal northern mountain and deformation front of the Pamir. However, the synopsis of our new and previously published thermochronologic data from this region shows that the hanging wall of the MPT experienced relatively minor amounts of late Cenozoic exhumation. The Pamir orogen as a whole is an integral part of the overriding plate in a subduction system, while the remnant basin to the north constitutes the downgoing plate, with the bulk of the convergence accommodated by underthrusting. Herein, we demonstrate that the observed deformation of the upper and lower plates within the Pamir-Alai convergence zone resembles highly arcuate oceanic subduction systems characterized by slab rollback, subduction erosion, subduction accretion, and marginal slab-tear faults. We suggest that the curvature of the North Pamir is genetically linked to the short width and rollback of the south-dipping Alai slab; northward motion (indentation) of the Pamir is accommodated by crustal processes related to this rollback. The onset of south-dipping subduction is tentatively linked to intense Pamir contraction following break-off of the north-dipping Indian slab beneath the Karakoram.
Cratons with their thick lithospheric roots can influence the thermal structure, and thus the convective flow, in the surrounding mantle. As mantle temperatures are hard to measure directly, depth variations in the mantle transition zone (MTZ) discontinuities are often employed as a proxy. Here, we use a large new data set of P-receiver functions to map the 410 km and 660 km discontinuities beneath the western edge of the East European Craton and adjacent Phanerozoic Europe across the most fundamental lithospheric boundary in Europe, the Trans-European Suture Zone (TESZ). We observe significantly shorter travel times for conversions from both MTZ discontinuities within the craton, caused by the high velocities of the cratonic root. By contrast, the differential travel time across the MTZ is normal to only slightly raised. This implies that any insulating effect of the cratonic keel does not reach the MTZ. In contrast to earlier observations in Siberia, we do not find any trace of a discontinuity at 520 km depth, which indicates a rather dry MTZ beneath the western edge of the craton. Within most of covered Phanerozoic Europe, the MTZ differential travel time is remarkably uniform and in agreement with standard Earth models. No widespread thermal effects of the various episodes of Caledonian and Variscan subduction that took place during the amalgamation of the continent remain. Only more recent tectonic events, related to Alpine subduction and Quarternary volcanism in the Eifel area, can be traced. While the East European craton shows no distinct imprint into the MTZ, we discover the signature of the TESZ in the MTZ in the form of a linear region of about 350 km width with a 1.5 s increase in differential travel time, which could either be caused by high water content or decreased temperature. Taking into account results of recent S-wave tomographies, raised water content in the MTZ cannot be the main cause for this observation. Accordingly, we explain the increase, equivalent to a 15 km thicker MTZ, by a temperature decrease of about 80 K. We discuss two alternative models for this temperature reduction, either a remnant of subduction or an indication of downwelling due to small-scale, edge-driven convection caused by the contrast in lithospheric thickness across the TESZ. Any subducted lithosphere found in the MTZ at this location is unlikely to be related to Variscan subduction along the TESZ, though, as Eurasia has moved significantly northward since the Variscan orogeny.
Novosphingobium fuchskuhlense sp nov., isolated from the north-east basin of Lake Grosse Fuchskuhle
(2013)
A yellow pigmented, Gram-negative, rod-shaped bacterium designated FNE08-7(T) was isolated from subsurface water of the north-east basin of the bog lake Grosse Fuchskuhle (Brandenburg, Germany). A first analysis of the nearly full-length 16S rRNA gene sequence analysis including environmental 16S rRNA gene sequences derived from freshwater ecosystems showed that strain FNE08-7(T) is the first cultured representative, to our knowledge, of the freshwater tribe Novo-A2. Further analysis indicates highest 16S rRNA gene sequence similarities to the type strains of Novosphingobium stygium (98.0%) and Novosphingobium taihuense (97.4%) and between 94.0% and 96.9% sequence similarity to other members of the genus Novosphingobium. Reconstruction of phylogenetic trees showed that strain FNE08-7(T) formed a distinct cluster with the type strains of N. stygium and N. taihuense supported by high bootstrap values. DNA DNA hybridization of strain FNE08-7(T) with N. stygium SMCC B0712(T) and N. taihuense DSM 17507(T) revealed low similarity values of 18.4% (reciprocal: 11.4%) and 23.1% (reciprocal: 54.2%), respectively. The predominant fatty acid of the isolate is C-18:1 omega 7c (56.4%) and two characteristic 2-hydroxy fatty acids, C-14:0 2-OH (16.5%) and C-15:0 2-OH (3.3%) occur. Ubiquinone Q-10 is the major respiratory quinone. The predominant polar lipids are phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylglycerol, sphingoglycolipid, phosphatidylcholine and minor amounts of diphosphatidylglycerol. Spermidine is the predominant polyamine. Characterization by genotypic, chemotaxonomic and phenotypic analysis indicate that strain FNE08-7(T) represents a novel species of the genus Novosphingobium within the Alphaproteobacteria. Therefore, we propose the species Novosphingobium fuchskuhlense sp. nov., with FNE08-7(T) (=DSM 25065(T)=CCM 7978(T)=CCUG 61508(T)) as the type strain.
An increasing number of OB stars have been shown to possess magnetic fields. Although the sample remains small, it is surprising that the magnetic and X-ray properties of these stars appear to be far less correlated than expected. This contradicts model predictions, which generally indicate that the X-rays from magnetic stars are harder and more luminous than their non-magnetic counterparts. Instead, the X-ray properties of magnetic OB stars are quite diverse.
tau Sco is one example where the expectations are better met. This bright main-sequence, early B star has been studied extensively in a variety of wavebands. It has a surface magnetic field of around 500 G, and Zeeman Doppler tomography has revealed an unusual field configuration. Furthermore, tau Sco displays an unusually hard X-ray spectrum, much harder than similar, non-magnetic OB stars. In addition, the profiles of its UV P Cygni wind lines have long been known to possess a peculiar morphology.
Recently, two stars, HD 66665 and HD 63425, whose spectral types and UV wind line profiles are similar to those of tau Sco, have also been determined to be magnetic. In the hope of establishing a magnetic field - X-ray connection for at least a subset of the magnetic stars, we obtained XMM-Newton European Photon Imaging Camera spectra of these two objects. Our results for HD 66665 are somewhat inconclusive. No especially strong hard component is detected; however, the number of source counts is insufficient to rule out hard emission. Longer exposure is needed to assess the nature of the X-rays from this star. On the other hand, we do find that HD 63425 has a substantial hard X-ray component, thereby bolstering its close similarity to tau Sco.
Programmers make many changes to the program to eventually find a good solution for a given task. In this course of change, every intermediate development state can of value, when, for example, a promising ideas suddenly turn out inappropriate or the interplay of objects turns out more complex than initially expected before making changes. Programmers would benefit from tool support that provides immediate access to source code and run-time of previous development states of interest. We present IDE extensions, implemented for Squeak/Smalltalk, to preserve, retrieve, and work with this information. With such tool support, programmers can work without worries because they can rely on tools that help them with whatever their explorations will reveal. They no longer have to follow certain best practices only to avoid undesired consequences of changing code.
The coexistence of fast and slowly rotating cool stars in ZAMS clusters - forming distinct sequences in the color vs. rotation period plane - is providing clues to differences in their pre main-sequence angular momentum evolution. This Cool Stars 17 splinter was dedicated to a discussion of new observational and theoretical results that may help discriminate between proposed mechanisms for early angular momentum regulation and help us explain the observed ZAMS dichotomy.
We easily recover the causal properties of visual events, enabling us to understand and predict changes in the physical world. We see a tennis racket hitting a ball and sense that it caused the ball to fly over the net; we may also have an eerie but equally compelling experience of causality if the streetlights turn on just as we slam our car's door. Both perceptual [1] and cognitive [2] processes have been proposed to explain these spontaneous inferences, but without decisive evidence one way or the other, the question remains wide open [3-8]. Here, we address this long-standing debate using visual adaptation-a powerful tool to uncover neural populations that specialize in the analysis of specific visual features [9-12]. After prolonged viewing of causal collision events called "launches" [1], subsequently viewed events were judged more often as noncausal. These negative aftereffects of exposure to collisions are spatially localized in retinotopic coordinates, the reference frame shared by the retina and visual cortex. They are not explained by adaptation to other stimulus features and reveal visual routines in retinotopic cortex that detect and adapt to cause and effect in simple collision stimuli.
The spatial magnetic properties (Through-Space NMR Shieldings-TSNMRS) of already synthesized dehydro[n]annulenes of various ring size (from C-12 to C-20) have been computed, visualized as Isochemical Shielding Surfaces (ICSS) of various size and direction, and were examined subject to present (anti)aromaticity. For this purpose the thus quantified ring current effect of the macro cycles on proximate protons in proton NMR spectra was employed.
In order to unravel the intricate interplay between disorder effects, molecular reorganization, and charge carrier localization, a comprehensive study was conducted on hole transport in a series of conjugated alternating phenanthrene indenofluorene copolymers. Each polymer in the series contained one further comonomer comprising monoamines, diamines, or amine-free structures, whose influence on the electronic, optical, and charge transport properties was studied. The series covered a wide range of highest occupied molecular orbital (HOMO) energies as determined by cyclovoltammetry. The mobility, inferred from time-of-flight (ToF) experiments as a function of temperature and electric field, was found to depend exponentially on the HOMO energy. Since possible origins for this effect include energetic disorder, polaronic effects, and wave function localization, the relevant parameters were determined using a range of methods. Disorder and molecular reorganization were established first by an analysis of absorption and emission measurements and second by an analysis of the ToF measurements. In addition, density functional theory calculations were carried out to determine how localized or delocalized holes on a polymer chain are and to compare calculated reorganization energies with those that have been inferred from optical spectra. In summary, we conclude that molecular reorganization has little effect on the hole mobility in this system while both disorder effects and hole localization in systems with low-lying HOMOs are predominant. In particular, as the energetic disorder is comparable for the copolymers, the absolute value of the hole mobility at room temperature is determined by the hole localization associated with the triarylamine moieties.
Functional evaluation of candidate ice structuring proteins using
cell-free expression systems
(2013)
Ice structuring proteins (ISPs) protect organisms from damage or death by freezing. They depress the non-equilibrium freezing point of water and prevent recrystallization, probably by binding to the surface of ice crystals. Many ISPs have been described and it is likely that many more exist in nature that have not yet been identified. ISPs come in many forms and thus cannot be reliably identified by their structure or consensus ice-binding motifs. Recombinant protein expression is the gold standard for proving the activity of a candidate ISP. Among existing expression systems, cell-free protein expression is the simplest and gives the fastest access to the protein of interest, but selection of the appropriate cell-free expression system is crucial for functionality. Here we describe cell-free expression methods for three ISPs that differ widely in structure and glycosylation status from three organisms: a fish (Macrozoarces americanus), an insect (Dendroides canadensis) and an alga (Chlamydomonas sp. CCMP681). We use both prokaryotic and eukaryotic expression systems for the production of ISPs. An ice recrystallization inhibition assay is used to test functionality. The techniques described here should improve the success of cell-free expression of ISPs in future applications. (C) 2012 Elsevier B.V. All rights reserved.
We report the discovery of TeV gamma-ray emission coincident with the shell-type radio supernova remnant (SNR) CTA 1 using the VERITAS gamma-ray observatory. The source, VER J0006+729, was detected as a 6.5 standard deviation excess over background and shows an extended morphology, approximated by a two-dimensional Gaussian of semimajor (semiminor) axis 0.degrees 30 (0.degrees 24) and a centroid 5’ from the Fermi gamma-ray pulsar PSR J0007+7303 and its X-ray pulsar wind nebula (PWN). The photon spectrum is well described by a power-law dN/dE = N-0(E/3 TeV)(-Gamma), with a differential spectral index of Gamma = 2.2 +/- 0.2(stat) +/- 0.3(sys), and normalization N-0 = (9.1 +/- 1.3(stat) +/- 1.7(sys)) x 10(-14) cm(-2) s(-1) TeV-1. The integral flux, F-gamma = 4.0 x 10(-12) erg cm(-2) s(-1) above 1 TeV, corresponds to 0.2% of the pulsar spin-down power at 1.4 kpc. The energetics, colocation with the SNR, and the relatively small extent of the TeV emission strongly argue for the PWN origin of the TeV photons. We consider the origin of the TeV emission in CTA 1.
Contamination of soil with toxic heavy metals poses a major threat to the environment and human health. Anthropogenic sources include smelting of ores, municipal wastes, fertilizers, and pesticides. In assessing soil quality and the environmental and ecological risk of contamination with heavy metals, often homogeneous contamination of the soil is assumed. However, soils are very heterogeneous environments. Consequently, both contamination and the response of soil organisms can be assumed to be heterogeneous. This might have consequences for the exposure of soil organisms and for the extrapolation of risk from the individual to the population level. Therefore, to explore how soil contamination of different spatial heterogeneity affects population dynamics of soil invertebrates, we developed a spatially explicit individual-based model of the springtail, Folsomia candida, a standard test species for ecotoxicological risk assessment. In the model, individuals were assumed to sense and avoid contaminated habitat with a certain probability that depends on contamination level. Avoidance of contaminated areas thus influenced the individuals' movement and feeding, their exposure, and in turn all other biological processes underlying population dynamics. Model rules and parameters were based on data from the literature, or were determined via pattern-oriented modelling. The model correctly predicted several patterns that were not used for model design and calibration. Simulation results showed that the ability of the individuals to detect and avoid the toxicant, combined with the presence of clean habitat patches which act as "refuges", made equilibrium population size due to toxic effects less sensitive to increases in toxicant concentration. Additionally, the level of heterogeneity among patches of soil (i.e. the difference in concentration) was important: at the same average concentration, a homogeneously contaminated scenario was the least favourable habitat, while higher levels of heterogeneity corresponded to higher population growth rate and equilibrium size. Our model can thus be used as a tool for extrapolating from short-term effects at the individual level to long-term effects at the population level under more realistic conditions. It can thus be used to develop and extrapolate from standard ecotoxicological tests in the laboratory to ecological risk assessments.
Induction of apoptosis mediated by the inhibition of ceramidases has been shown to enhance the efficacy of conventional chemotherapy in several cancer models. Among the inhibitors of ceramidases reported in the literature, B-13 is considered as a lead compound having good in vitro potency towards acid ceramidase. Furthermore, owing to the poor activity of B-13 on lysosoamal acid ceramidase in living cells, LCL-464 a modified derivative of B-13 containing a basic omega-amino group at the fatty acid was reported to have higher potency towards lysosomal acid ceramidase in living cells. In a search for more potent inhibitors of ceramidases, we have designed a series of compounds with structural modifications of B-13 and LCL-464. In this study, we show that the efficacy of B-13 in vitro as well as in intact cells can be enhanced by suitable modification of functional groups. Furthermore, a detailed SAR investigation on LCL-464 analogues revealed novel promising inhibitors of aCDase and nCDase. In cell culture studies using the breast cancer cell line MDA-MB-231, some of the newly developed compounds elevated endogenous ceramide levels and in parallel, also induced apoptotic cell death. In summary, this study shows that structural modification of the known ceramidase inhibitors B-13 and LCL-464 generates more potent ceramidase inhibitors that are active in intact cells and not only elevates the cellular ceramide levels, but also enhances cell death.
The electromagnetic force on a polarizable particle is calculated in a covariant framework. Local equilibrium temperatures for the electromagnetic field and the particle's dipole moment are assumed, using a relativistic formulation of the fluctuation-dissipation theorem. Two examples illustrate radiative friction forces: a particle moving through a homogeneous radiation background and above a planar interface. Previous results for arbitrary relative velocities are recovered in a compact way.
Multi-proxy dating of Holocene maar lakes and Pleistocene dry maar sediments in the Eifel, Germany
(2013)
During the last twelve years the ELSA Project (Eifel Laminated Sediment Archive) at Mainz University has drilled a total of about 52 cores from 27 maar lakes and filled-in maar basins in the Eifel/Germany. Dating has been completed for the Holocene cores using 6 different methods (Pb-210 and Cs-137 activities, palynostratigraphy, event markers, varve counting, C-14) In general, the different methods consistently complement one another within error margins. Event correlation was used for relating typical lithological changes with historically known events such as the two major Holocene flood events at 1342 AD and ca 800 BC. Dating of MIS2-MIS3 core sections is based on greyscale tuning, radiocarbon and OSL dating, magnetostratigraphy and tephrochronology. The lithological changes in the sediment cores demonstrate a sequence of events similar to the North Atlantic rapid climate variability of the Last Glacial Cycle. The warmest of the MIS3 interstadials was GI14, when a forest with abundant spruce covered the Eifel area from 55 to 48 ka BP, i.e. during a time when also other climate archives in Europe suggested very warm conditions. The forest of this "Early Stage 3 warm phase" developed subsequently into a steppe with scattered birch and pine, and finally into a glacial desert at around 25 ka BP. Evidence for Mono Lake and Laschamp geomagnetic excursions is found in two long cores. Several large eruptions during Middle and Late Pleistocene (Ulmener Maar - 11,000 varve years BP, Laacher See - 12,900 varve years BP, Mosenberg volcanoes/Meerfelder Maar 41-45 cal ka BP, Dumpel Maar 116 ka BP, Glees Maar - 151 ka BP) produced distinct ash-layers crucial for inter-core and inter-site correlations. The oldest investigated maar of the Eifel is Ar-40/Ar-39 dated to the time older than 520 ka BP.
The 12 January 2010 M-w 7.0 Haiti earthquake occurred in a complex deformation zone at the boundary between the North American and Caribbean plates. Combined geodetic, geological and seismological data posited that surface deformation was driven by rupture on the Leogane blind thrust fault, while part of the rupture occurred as deep lateral slip on the Enriquillo-Plantain Garden Fault (EPGF). The earthquake triggered >4490 landslides, mainly shallow, disrupted rock falls, debris-soil falls and slides, and a few lateral spreads, over an area of similar to 2150 km(2). The regional distribution of these slope failures defies those of most similar earthquake-triggered landslide episodes reported previously. Most of the coseismic landslides did not proliferate in the hanging wall of the main rupture, but clustered instead at the junction of the blind Leogane and EPGF ruptures, where topographic relief and hillslope steepness are above average. Also, low-relief areas subjected to high coseismic uplift were prone to lesser hanging wall slope instability than previous studies would suggest. We argue that a combined effect of complex rupture dynamics and topography primarily control this previously rarely documented landslide pattern. Compared to recent thrust fault-earthquakes of similar magnitudes elsewhere, we conclude that lower static stress drop, mean fault displacement, and blind ruptures of the 2010 Haiti earthquake resulted in fewer, smaller, and more symmetrically distributed landslides than previous studies would suggest. Our findings caution against overly relying on across-the-board models of slope stability response to seismic ground shaking. (C) 2012 Elsevier B.V. All rights reserved.
The reaction of pharmacological active protic ionic liquid tris-(2-hydroxyethyl)ammonium 4-chlorophenylsulfanylacetate H+N(CH2CH2OH)(3) center dot (-OOCCH2SC6H4Cl-4) (1) with zinc or nickel chloride in a ratio of 2:1 affords stable at room temperature powder-like adducts [H+N(CH2CH2OH)(3)](2) center dot [M(OOCCH2SC6H4Cl-4)(2)Cl-2](2-), M = Zn (2), Ni (3). By recrystallization from aqueous alcohol compound 2 unexpectedly gives Zn(OOCCH2SC6H4Cl-4)(2) center dot 2H(2)O (4). Unlike 2, compound 3 gives crystals [N(CH2CH2OH)(3)](2)Ni2+ center dot [-OOCCH2SC6H4Cl-4](2) (5), which have a structure of metallated ionic liquid. The structure of 5 has been proved by X-ray diffraction analysis. It is the first example of the conversion of a protic ionic liquid into potentially biological active metallated ionic liquid (1 -> 3 -> 5).
The Escherichia coli L-cysteine desulfurase IscS mobilizes sulfur from L-cysteine for the synthesis of several biomolecules such as iron-sulfur (FeS) clusters, molybdopterin, thiamin, lipoic acid, biotin, and the thiolation of tRNAs. The sulfur transfer from IscS to various biomolecules is mediated by different interaction partners (e.g. TusA for thiomodification of tRNAs, IscU for FeS cluster biogenesis, and ThiI for thiamine biosynthesis/tRNA thiolation), which bind at different sites of IscS. Transcriptomic and proteomic studies of a Delta tusA strain showed that the expression of genes of the moaABCDE operon coding for proteins involved in molybdenum cofactor biosynthesis is increased under aerobic and anaerobic conditions. Additionally, under anaerobic conditions the expression of genes encoding hydrogenase 3 and several molybdoenzymes such as nitrate reductase were also increased. On the contrary, the activity of all molydoenzymes analyzed was significantly reduced in the Delta tusA mutant. Characterization of the Delta tusA strain under aerobic conditions showed an overall low molybdopterin content and an accumulation of cyclic pyranopterin monophosphate. Under anaerobic conditions the activity of nitrate reductase was reduced by only 50%, showing that TusA is not essential for molybdenum cofactor biosynthesis. We present a model in which we propose that the direction of sulfur transfer for each sulfur-containing biomolecule is regulated by the availability of the interaction partner of IscS. We propose that in the absence of TusA, more IscS is available for FeS cluster biosynthesis and that the overproduction of FeS clusters leads to a modified expression of several genes.
Aqueous mixtures of a coumarin-labeled non-ionic thermoresponsive copolymer and a cationic polythiophene exhibit marked changes in their fluorescence properties upon heating. At room temperature, emission from the label is significantly quenched due to energy transfer to the conjugated polyelectrolyte. Heating the mixture reduces the energy-transfer efficiency markedly, resulting in a clearly visible change of the emission color. Although the two macromolecules associate strongly at room temperature, the number of interacting sites is largely reduced upon the phase transition. Crucially, the intermolecular association does not suppress the responsiveness of the smart polymer, meaning that this concept should be applicable to chemo- or bioresponsive polymers with optical read-out, for example, as a sensor device.