bluuebunny/crossref_metadata_2025 huggingface dataset:
The base of the global Dapingian Stage (Ordovician) in Baltoscandia: conodonts, graptolites and unconformities
Authors: Bergström Stig M. , Löfgren Anita
Published: November 2009

In the recently completed and formally ratified new series and stage classification of the Ordovician System, the base of the Middle Ordovician Series coincides with the base of the global Dapingian Stage. In the Global Stratotype Section and Point (GSSP) of this stage, which is located at Huanghuachang in southern China, the base of the Dapingian Stage is defined as the level of first appearance of the conodont Baltoniodus triangularis. The fact that this species, along with some other taxa present at the Dapingian GSSP, occurs in many sections in Baltoscandia makes it possible to recognise with considerable precision the level of this global stage boundary in Sweden, Estonia, northwestern Russia, and Denmark. In several, but not all, regions, especially in the East Baltic, the global stage boundary coincides with the base of the regional Volkhov Stage and can be tied to the base of the Megistaspis polyphemus Trilobite Zone. The regionally somewhat different relationships between the position of the global stage boundary and a very widespread hardground complex are probably due to the occurrence of local and/or regional unconformities in the upper Floian–lower Dapingian interval. Although biostratigraphically important graptolites are present in the study interval in some Baltoscandic sections, the precise graptolite correlation of the base of the Dapingian Stage remains somewhat unclear, although it appears to be near, or at, the base of the Isograptus victoriae victoriae Zone (Ca 2).
A reactive assimilation model for regional-scale cordierite-bearing granitoids: geochemical evidence from the Late Variscan granites of the Central Iberian Zone, Spain
Authors: Ugidos J. M. , Stephens W. E. , Carnicero A. , Ellam R. M.
Published: November 2009

Regional scale biotite and cordierite-bearing granites (s.l.) in the Variscan of the Central Iberian Zone (CIZ) are spatially closely associated with cordierite-rich nebulites and cordierite-bearing two-mica granites, and with cordierite-rich high grade hornfelses and cordieritites (>60% cordierite) that are relatively common in the aureoles of these granites. Building on published field evidence, petrological data are presented which, combined with new chemical and isotopic (Sr–Nd) modelling, indicate that the cordierite-bearing granites cannot be derived by simple anatexis of regional sedimentary protoliths; but the data are consistent with a process of reactive assimilation that involves the interaction of biotite granite magma with high-grade host rocks ranging from cordierite nebulites to andalusite-bearing cordieritites. The contribution of the postulated cordierite-rich contaminants to the diversity of cordierite granite compositions is modelled using the compositions of regional Lower Cambrian–Upper Neoproterozoic metasedimentary rocks that are generally chemically mature (CaO very rarely exceeds 1·4%). These rocks include specific horizons in which extreme chemical alteration is attributable to sediment reworking during eustatic falls in sea level. Such compositions may account for the presence of the high concentrations in Al that later produced cordieritites. Fractional crystallisation is also important, particularly in generating the more evolved cordierite granite and cordierite biotite muscovite granite compositions. Although assimilation in situ is normally regarded as a minor contributor volumetrically to evolving plutons, in this instance the emplacement of large volumes of granite magma into a high-T–low-P environment significantly increased the potential for reactive assimilation.
Semantically Clustered Words Are Stored With Integrated Context
Authors: Bröder Arndt
Published: November 2009

Source memory (i.e., memory for context) has been studied with recognition tasks almost exclusively. However, encoding context affects recall stronger than recognition, presumably because of more complex retrieval strategies in the former task. An extension of Batchelder and Riefer (1980) pair-clustering model is proposed which is intended to measure the storage and retrieval of clusterable word pairs as well as the memory for the sources in which these were presented. In two experiments, the construct validity of the central model parameters is demonstrated. Furthermore, there was a strong stochastic dependency between recalling the sources of the first and the second word of a clustered pair, respectively, suggesting that not only semantic but also contextual features are bound together in clustered pairs. Advantages of using recall tests in source monitoring research are discussed.
Confirmatory Factor Analysis of the Long and Short Forms of the Worry Domains Questionnaire
Authors: Nuevo Roberto , Losada Andrés , Márquez-González María , Peñacoba Cecilia
Published: November 2009

The Worry Domains Questionnaire was proposed as a measure of both pathological and nonpathological worry, and assesses the frequency of worrying about five different domains: relationships, lack of confidence, aimless future, work, and financial. The present study analyzed the factor structure of the long and short forms of the WDQ (WDQ and WDQ-SF, respectively) through confirmatory factor analysis in a sample of 262 students (M age = 21.8; SD = 2.6; 86.3% females). While the goodness-of-fit indices did not provide support for the WDQ, good fit indices were found for the WDQ-SF. Furthermore, no source of misspecification was identified, thus, supporting the factorial validity of the WDQ-SF scale. Significant positive correlations between the WDQ-SF and its subscales with worry (PSWQ), anxiety (STAI-T), and depression (BDI) were found. The internal consistency was good for the total scale and for the subscales. This work provides support for the use of the WDQ-SF, and potential uses for research and clinical purposes are discussed.
A German Validation of the UPPS Impulsive Behavior Scale
Authors: Kämpfe Nicole , Mitte Kristin
Published: November 2009

The present research broadens the understanding of the multidimensional nature of impulsivity by investigating the validity of a German adaptation of the UPPS scale of impulsivity ( Whiteside & Lynam, 2001 ). Two studies utilizing paper-pencil and computerized administration replicated the internal structure of the UPPS, provided evidence for convergent and discriminant validity utilizing self- and peer-reports, demonstrated incremental validity for the UPPS scale over the respective personality facets, and investigated the relationships between self-reported impulsivity and behavioral measures including perceptual speed and response latencies. Taken together, results not only confirm the reliability and validity of the German UPPS scale but also prove its benefit in predicting relevant criteria beyond well-established personality questionnaires. Significant but weak correlations with behavioral measures of cognitive aspects of impulsivity were particularly observed for (lack of) Premeditation and (lack of) Perseverance.
Measuring Interpersonal Stress with the Bergen Social Relationships Scale
Authors: Bancila Delia , Mittelmark Maurice B.
Published: November 2009

This study assessed the equivalence of the Bergen Social Relationships Scale (BSRS) across three countries. The six-item BSRS was developed to measure interpersonal stress in close relationships and is grounded in Festinger’s cognitive dissonance theory. In this context, interpersonal stress refers to perceived troubled relationships with significant others who cause stress even when they do not mean to (e.g., inept social support attempts, criticism, demands that are too high). Interpersonal stress is of considerable concern because community-based research indicates that levels of anxiety, depressive symptomatology, and loneliness are significantly associated with levels of interpersonal stress. Structural equation models were used to assess the equivalence of the BSRS linguistic versions used in community-based samples in Norway (n = 328), Romania (n = 581), and Russia (n = 665). Results indicate that the BSRS has satisfactory internal consistency and that the factor structure is invariant across all three linguistic adaptations. This study provides evidence that the BSRS is equivalent across countries and suitable for the assessment of interpersonal stress, both to compare population levels of interpersonal stress and to explore structural relationships with other constructs in analytical models of psychological debilitation. The BSRS is brief enough for use in survey research applications.
Development and Validation of the Work Effort Scale
Authors: De Cooman Rein , De Gieter Sara , Pepermans Roland , Jegers Marc , Van Acker Frederik
Published: November 2009

In the current article, the development and validation of the Work Effort Scale (WESC), a self-report 10-item scale, is described. Data from several samples are used. The three-factor structure (persistence, direction, and intensity) of the WESC is confirmed by confirmatory factor analysis and reliability is well documented. In accordance with our expectations, we found positive correlations between self-rated performance and global job satisfaction scales and work effort.
Global warming, convective threshold and false thermostats
Authors: Williams Ian N. , Pierrehumbert Raymond T. , Huber Matthew
Published: November 2009

We demonstrate a theoretically expected behavior of the tropical sea surface temperature probability density function (PDF) in future and past (Eocene) greenhouse climate simulations. To first order this consists of a shift to warmer temperatures as climate warms, without change of shape of the PDF. The behavior is tied to a shift of the temperature for deep convection onset. Consequently, the threshold for appearance of high clouds and associated radiative forcing shifts along with temperature. An excess entropy coordinate provides a reference to which the onset of deep convection is invariant, and gives a compact description of SST changes and cloud feedbacks suitable for diagnostics and as a basis for simplified climate models. The results underscore that the typically skewed appearance of tropical SST histograms, with a sharp drop‐off above some threshold value, should not be taken as evidence for tropical thermostats.
Source analysis of the Memorial Day explosion, Kimchaek, North Korea
Authors: Ford Sean R. , Dreger Douglas S. , Walter William R.
Published: November 2009

A series of source inversions are performed for the 25 May 2009 (Memorial Day) North Korean seismic event using intermediate period (10–50 s) complete waveform modeling. An earthquake source is inconsistent with the data and the best‐fit full seismic moment tensor is dominantly explosive (∼60%) with a moment magnitude (MW) of 4.5. A pure explosion solution yields a scalar seismic moment of 1.8 × 1022 dyne‐cm (MW4.1) and fits the data almost as well as the full solution. The difference between the full and explosion solutions is the predicted fit to observed tangential displacement, which requires some type of non‐isotropic (non‐explosive) radiation. Possible causes of the tangential displacement are additional tectonic sources, tensile failure at depth, and anisotropic wave propagation. Similar displacements may be hidden in the noise of the 2006 event. Future analyses of this type could be used to identify and characterize non‐earthquake events such as explosions and mine collapses.
On seasonality of stratomesospheric CO above midlatitudes: New insight from solar FTIR spectrometry at Zugspitze and Garmisch
Authors: Borsdorff Tobias , Sussmann Ralf
Published: November 2009

A significant seasonality in stratomesospheric CO (24–100 km) above mid‐latitudes is derived from FTIR via a new regularization scheme. Half hourly means from the Zugspitze (47.42°N, 10.98°E, 2964 m a.s.l.) and nearby Garmisch (745 m a.s.l.) measurements show excellent agreement (R = 0.94, slope 0.91, standard deviation 12%). Mean seasonality of the Zugspitze series (1999–2008) shows a November–April enhancement (February maximum 3.63 × 1016 cm−2) and a summer background (1.64 × 1016 cm−2) which agrees with the WACCM model. Measured monthly means reveal a year‐to‐year variability of up to 32% (1‐sigma) in winter not reproduced by WACCM (R = −0.13). Frequency distributions of daily means are right skewed in winter due to enhancements by vortex air transport (1–3 days duration) which typically reflect CO levels of the vortex border and may even reach vortex‐center levels (≈300% of the multi‐annual monthly median).
Self‐consistent evolution of auroral downward‐current region ion outflow and moving double layer
Authors: Hwang K.‐J. , Ergun R. E. , Newman D. L. , Tao J.‐B. , Andersson L.
Published: November 2009

Vlasov simulations have been performed to investigate the development and evolution of the parallel potential drop, often structured as a localized double layer (DL), electron phase‐space holes, and ion perpendicular heating, resulting in ion outflow in the auroral downward‐current region. We focus on the feedback between a moving DL and heated ions, suggesting a self‐consistent model: the heated ions regulate the evolution of the DL which controls the level of ion heating and, consequently, the outflow rate. Strongly heated ions forming conics are found in agreement with in‐situ observations. The intensification and widening of the DL develops with time, and the DL eventually weakens due to a reduction in the background population resulting from excessive ion heating.
Is the airborne fraction of anthropogenic CO2 emissions increasing?
Authors: Knorr Wolfgang
Published: November 2009

Several recent studies have highlighted the possibility that the oceans and terrestrial ecosystems have started loosing part of their ability to sequester a large proportion of the anthropogenic CO2 emissions. This is an important claim, because so far only about 40% of those emissions have stayed in the atmosphere, which has prevented additional climate change. This study re‐examines the available atmospheric CO2 and emissions data including their uncertainties. It is shown that with those uncertainties, the trend in the airborne fraction since 1850 has been 0.7 ± 1.4% per decade, i.e. close to and not significantly different from zero. The analysis further shows that the statistical model of a constant airborne fraction agrees best with the available data if emissions from land use change are scaled down to 82% or less of their original estimates. Despite the predictions of coupled climate‐carbon cycle models, no trend in the airborne fraction can be found.
Ocean climate change fingerprints attenuated by salt fingering?
Authors: Johnson Gregory C. , Kearney Kelly A.
Published: November 2009

Intensified double diffusive mixing may attenuate changes in ocean temperature and salinity patterns from global‐warming induced increases in the Earth's hydrological cycle. Increasingly fresher Antarctic Intermediate Water and saltier subtropical waters would tend to increase destabilizing vertical salinity stratification compared to the stabilizing temperature stratification. Destabilization would increase salinity (and temperature) fluxes through double‐diffusive salt fingering. These fluxes could in turn act to reduce widely recognized climate change fingerprints, potentially leading to underestimates of ocean changes in climate studies that do not account for double‐diffusive mixing. Data from a subtropical trans‐Indian Ocean survey occupied in 1987, 1995, 2002, and 2009 are used to investigate temperature‐salinity changes and to estimate the variations of double diffusive mixing driven by these changes.
West Antarctic Rift System in the Antarctic Peninsula
Authors: Eagles Graeme , Larter Robert D. , Gohl Karsten , Vaughan Alan P. M.
Published: November 2009

Decades after the recognition of the West Antarctic Rift System, and in spite of its global importance, the location and nature of the plate boundary it formed at are unknown east of the Byrd Subglacial Basin. Alternative constructions of the circuit of South Pacific plate boundaries suggest the presence of either a transcurrent plate boundary or a continuation of the extensional rift system. We identify George VI Sound, a curved depression separating Alexander Island from Palmer Land, as the easternmost basin of a rift system that terminated at a triple junction with the Antarctic Peninsula subduction zone. The history of the triple junction's third, transform, arm suggests extension started around 33.5–30 Ma. A more speculatively identified basin further west may have formed earlier during the same episode of rifting, starting around 43 Ma. Proposals of earlier Cenozoic relative motion between East and West Antarctica cannot be verified from this region.
Analysis on 29 March 2006 eclipse effect on the ionosphere over Ilorin, Nigeria
Authors: Adeniyi J. O. , Oladipo O. A. , Radicella S. M. , Adimula I. A. , Olawepo A. O.
Published: November 2009

Ionospheric measurements obtained during the 29 March 2006 eclipse period over Ilorin, Nigeria (longitude 4.57°E, latitude 8.53°N, dip 4.1°S), an equatorial station, are used for this study. The data are used in the determination of photoionisation rates (q) and loss coefficients at various heights. It was found that the transition height between the regions where the linear (β) and quadratic (α) loss coefficients hold is around 200 km. Some form of validations of the parameters q and α were carried out. A comparison of the results of production rates, vertical velocities and loss coefficients obtained for the F region from our study with those obtained at high solar activity for a previous eclipse at a station close to Ilorin indicates solar activity effects.
Storm‐enhanced plasma density features, daytime polar cap plasma enhancements, and their underlying plasma flows investigated during superstorms
Authors: Horvath Ildiko , Lovell Brian C.
Published: November 2009

This study investigates the effects of November superstorms on the daytime‐evening northern topside ionosphere. We utilize multi‐instrument interplanetary and geomagnetic data to analyze the interplanetary shock/electric (E) field events. To assess their impact, field‐aligned DMSP (Defense Meteorological Satellite Program) passes are employed. We tracked evening storm‐enhanced density (SED) features and daytime polar plasma enhancements occurring regularly that allowed us to learn about the basic mechanisms responsible for their development. Results show that large vertical downward plasma flows supplied the plasma building up the SED features and polar plasma enhancements detected. These plasma formations occurred during the main phase with the forward superfountain and during a substorm with the reverse fountain. These provide observational evidence that primary downward plasma flows, triggered by detachment processes caused by the westward subauroral polarization stream (SAPS) E‐fields, existed and became transported sunward. At SED latitudes, these primary downward plasma flows were intensified by the forward superfountain when its upward plasma flow spilled over into the equatorial anomaly and cascaded down the magnetic field lines. When the reverse fountain was active, such intensification was not available to the primary downward plasma flows at SED latitudes. As the downward streaming plasma found its way to the polar cap, it resulted in the development of daytime polar plasma enhancements. Statistically, daytime polar plasma enhancements occurred at all longitudes contradicting the myth that the North American region is better suited for the development of large plasma enhancements in the polar cap.
Observations of a Kenai Eddy and a Sitka Eddy in the Northern Gulf of Alaska
Authors: Rovegno P. S. , Edwards C. A. , Bruland K. W.
Published: November 2009

Mesoscale eddies in the Gulf of Alaska are thought to contribute to the shelf‐slope exchange of nutrients and plankton, enhancing biological production. We report on a study of two anticyclonic mesoscale eddies in this region observed through in situ sampling during August and September 2007. Both eddies exhibited in their cores θ‐S profiles with warmer, fresher water relative to the properties of the ambient basin water between 150‐ and 300‐m depths. Hydrographic properties and satellite altimetry data were analyzed to identify likely formation regions for each feature. One eddy, sampled near Yakutat, Alaska, originated in the Sitka formation region (221–223°E); the second eddy, sampled south of Kodiak Island, originated near the Kenai Peninsula, southeast of the Kennedy and Stevenson entrances to Cook Inlet, an area not previously studied as a formation region. Subsequent analysis of 16 years of satellite altimeter data (from 1992 to 2008) with an algorithm designed to identify and track eddies revealed approximately six Kenai eddies that have formed in this region. Although this number constitutes only 3.2% of the 188 eddies identified by the algorithm during this period, it represents 15.4% of the 39 eddies that formed in or propagated westward into the Alaskan Stream.
Estimating the effective energy transfer velocity at air‐sea interface
Authors: Hwang Paul A.
Published: November 2009

An analytical expression of the effective energy transfer velocity relating surface wind stress and energy dissipation is derived from the parameterization functions of wave energy dissipation and ocean surface friction coefficient. The equation is applied to analyses from two field experiments at very different stages of wave development. Discussions on relevant issues such as the effect of wind field steadiness, scaling, and spectral resolution are presented. A key result from this investigation is that the effective energy transfer velocity is confined in a narrow range, with the majority of data points within 1.5 and 3 m/s, over a wide range of wind speed (5–16 m/s) and dimensionless frequency (0.8–4.2) of the wavefield. A sharp increase in the energy transfer coefficient and effective energy transfer velocity occurs at a wind speed near 6 or 7 m/s. Data points that deviated significantly from the parameterization prediction appear to be associated with wind field unsteadiness, which is not accounted for in the formulation of parameterization function. The breaking process is local in space or time as well as in wave number or frequency. Global (mean) quantities such as dominant wave speed and wind friction velocity are not the proper scaling factor for the breaking velocity or energy transfer coefficient. The scaling factor should reflect the local characteristics (steepness, acceleration, or orbital velocity) of the wavefield that lead to waveform instability.
IKK/NF‐κB and STAT3 pathways: central signalling hubs in inflammation‐mediated tumour promotion and metastasis
Authors: Bollrath Julia , Greten Florian R.
Published: November 2009

Our understanding of the molecular mechanisms that link inflammation and cancer has significantly increased in recent years. Here, we analyse genetic evidence indicating that the transcription factors nuclear factor‐κB (NF‐κB) and signal transducer and activator of transcription 3 (STAT3) have a central role in this context by regulating distinct functions in cancer cells and surrounding non‐tumorigenic cells. In immune cells, NF‐κB induces the transcription of genes that encode pro‐inflammatory cytokines, which can act in a paracrine manner on initiated cells. By contrast, in tumorigenic cells, both NF‐κB and STAT3 control apoptosis, and STAT3 can also enhance proliferation. Consequently, inflammation should be considered as a valuable target for cancer prevention and therapy.
Evaluating near infrared spectroscopy for field prediction of soil properties
Authors: Minasny Budiman , McBratney Alex B. , Pichon Leo , Sun Wei , Short Michael G.
Published: November 2009

This paper demonstrates the application of near infrared diffuse reflectance spectroscopy (NIR-DRS) measurements as part of digital soil mapping. We also investigate whether calibration functions developed from a spectral library can be used for rapid characterisation of soil properties in the field. Soil samples were collected along 24 toposequences in the Pokolbin irrigation district, ~7 km2 of predominantly agricultural land in the Hunter Valley, NSW, Australia. Soil samples at 2 depths: 0–0.10 and 0.40–0.50 m were collected. The soil samples were scanned using NIR under 3 different conditions: field condition, dried unground, and dried ground. A separate spectral library containing soil laboratory measurements was used to develop functions to predict 3 main soil properties from NIR spectra (total C content, clay content, and sum of exchangeable cations). The absorbance spectra were found to be different for the 3 soil conditions. The field spectra appear to have higher absorbance, followed by dried unground samples and then dried ground samples. Although most spectral signatures or peaks were similar for the 3 soil conditions, field samples appear to have higher absorbance, particularly at 1400 nm and 1900 nm. The convex hull of the first 2 principal components of the soil spectra is an easy tool to evaluate the similarity of spectra from a calibration set to an observation. For field prediction, samples need to be calibrated using field samples. Finally, this study shows that NIR-DRS measurement is a useful part of digital soil mapping.
Soil structure changes: aggregate size and soil texture effects on hydraulic conductivity under different saline and sodic conditions
Authors: Ben-Hur M. , Yolcu G. , Uysal H. , Lado M. , Paz A.
Published: November 2009

Hydraulic conductivity of soil is strongly dependent on soil structure, which can be degraded during wetting and leaching. It was hypothesised that this structural degradation is dependent on initial aggregate size distribution and soil texture. The general aim of this study was to investigate the effects of aggregate sizes and soil textures, and their interactions, on the structural degradation and saturated hydraulic conductivity (Ks) of smectitic soils under different saline and sodic conditions. The studied soils were clay and loamy sand soils with low (~4.5) or high (~10) exchangeable sodium percentages (ESP), and with aggregate sizes in the ranges: (i) <1 mm (small aggregates); or (ii) 2–4 mm (large aggregates). The Ks values of the samples in a column after slow or fast pre-wetting were determined by means of a constant head device. Different wetting rates and leaching under various saline and sodic conditions had no effect on the Ks of the loamy sand; however, the Ks values of this soil with large aggregates were an order of magnitude greater than those of the soil with small aggregates. In contrast, in the clay soil with large aggregates, the Ks values after fast pre-wetting were significantly smaller than those after slow pre-wetting, probably because of aggregate slaking. No significant effects of the wetting rates on Ks were found in clay soil with small aggregates. An increase in the ESP in the clay soil decreased the Ks by a factor of 1.5 for the large aggregates and by an order of magnitude for the small aggregates, mainly as a result of increased clay swelling. Leaching the clay soil with deionised water significantly decreased the Ks values, partly because of clay dispersion. Although significant structural degradation of the clay soil occurred during leaching, the Ks values were smaller in the soils with small aggregates than in those with large aggregates, indicating the importance of the initial aggregate size on Ks even in soils that are prone to structural damage.
Knowledge and innovation relationships in the shrimp industry in Thailand and Mexico
Authors: Lebel Louis , Garden Po , Luers Amy , Manuel-Navarrete David , Giap Dao Huy
Published: November 2009

Experts, government officials, and industry leaders concerned about the sustainability of shrimp aquaculture believe they know what farmers need to know and should be doing. They have framed sustainability as a technical problem that, at the farm level, is to be solved by better shrimp and management of ponds and businesses. Codes of conduct, standards, and regulations are expected to bring deviant practices into line. Shrimp farmers are often cornered in a challenging game of knowledge in which their livelihoods are at stake. In the commodity chain there are multiple relations with both suppliers and buyers, not all of which are trustworthy. The social networks shrimp farmers belong to are crucial for sifting out misinformation and multiplying insights from personal experience in learning by doing. Successful farmers become part of a learning culture through seminars, workshops, and clubs in which knowledge and practices are continually re-evaluated. The combination of vertical and horizontal relationships creates a set of alternative arenas that together are critical to bridging knowledge and action gaps for shrimp farmers. Government and industry initiatives for improving links between knowledge and practice for sustainability have largely succeeded when incentives are aligned: shrimp grow better in healthy environments, and using fewer resources means higher profits.
The selective antagonist EPPTB reveals TAAR1-mediated regulatory mechanisms in dopaminergic neurons of the mesolimbic system
Authors: Bradaia Amyaouch , Trube Gerhard , Stalder Henri , Norcross Roger D. , Ozmen Laurence , Wettstein Joseph G. , Pinard Audrée , Buchy Danièle , Gassmann Martin , Hoener Marius C. , Bettler Bernhard
Published: November 2009

Trace amine-associated receptor 1 (TAAR1) is a G protein-coupled receptor (GPCR) that is nonselectively activated by endogenous metabolites of amino acids. TAAR1 is considered a promising drug target for the treatment of psychiatric and neurodegenerative disorders. However, no selective ligand to identify TAAR1-specific signaling mechanisms is available yet. Here we report a selective TAAR1 antagonist, EPPTB, and characterize its physiological effects at dopamine (DA) neurons of the ventral tegmental area (VTA). We show that EPPTB prevents the reduction of the firing frequency of DA neurons induced by
p
-tyramine (
p
-tyr), a nonselective TAAR1 agonist. When applied alone, EPPTB increases the firing frequency of DA neurons, suggesting that TAAR1 either exhibits constitutive activity or is tonically activated by ambient levels of endogenous agonist(s). We further show that EPPTB blocks the TAAR1-mediated activation of an inwardly rectifying K
+
current. When applied alone, EPPTB induces an apparent inward current, suggesting the closure of tonically activated K
+
channels. Importantly, these EPPTB effects were absent in
Taar1
knockout mice, ruling out off-target effects. We additionally found that both the acute application of EPPTB and the constitutive genetic lack of TAAR1 increase the potency of DA at D2 receptors in DA neurons. In summary, our data support that TAAR1 tonically activates inwardly rectifying K
+
channels, which reduces the basal firing frequency of DA neurons in the VTA. We hypothesize that the EPPTB-induced increase in the potency of DA at D2 receptors is part of a homeostatic feedback mechanism compensating for the lack of inhibitory TAAR1 tone.
PD-118057 contacts the pore helix of hERG1 channels to attenuate inactivation and enhance K
+
conductance
Authors: Perry Matthew , Sachse Frank B. , Abbruzzese Jennifer , Sanguinetti Michael C.
Published: November 2009

Human
ether-a-go-go-related
gene 1 (hERG1) K
+
channels mediate repolarization of cardiac action potentials. Unintended block of hERG1 channels by some drugs can prolong the QT interval and induce arrhythmia. Recently, hERG1 channel agonists were discovered and, based on their mechanisms of action can be classified into two types. RPR260243 [(3
R
,4
R
)-4-[3-(6-methoxy-quinolin-4-yl)-3-oxo-propyl]-1-[3-(2,3,5 trifluorophenyl)-prop-2-ynyl]-piperidine-3-carboxylic acid], a type 1 agonist, binds to residues located near the intracellular end of S5 and S6 transmembrane segments and activates hERG1 channels by a dual mechanism of slowed deactivation and attenuated P-type inactivation. As defined here, type 2 agonists such as PD-118057 [2-(4-[2-(3,4-dichloro-phenyl)-ethyl]-phenylamino)-benzoic acid] attenuate inactivation but do not slow deactivation. At 10 μM, PD-118057 shifted the half-point for inactivation of wild-type hERG1 channels by +19 mV and increased peak outward current by 136%. Scanning mutagenesis and functional characterization of 44 mutant channels expressed in
Xenopus
oocytes was used to identify the major structural determinants of the binding site for PD-118057. Single mutations of residues in the pore helix (F619) or the S6 segment (L646) of hERG1 eliminated agonist activity. Mutation of a nearby residues in the S6 segment (C643, M645) enhanced drug activity, presumably by reducing steric hindrance for drug binding. Molecular modeling indicates that PD-118057 binds to a hydrophobic pocket formed by L646 of one hERG1 subunit and F619 of an adjacent subunit. We conclude that direct interaction of PD-118057 with the pore helix attenuates fast P-type inactivation and increases open probability of hERG1 channels.
Local maternal control of seed size by
KLUH
/
CYP78A5
-dependent growth signaling
Authors: Adamski Nikolai M. , Anastasiou Elena , Eriksson Sven , O'Neill Carmel M. , Lenhard Michael
Published: November 2009

Seed development in plants involves the coordinated growth of the embryo, endosperm, and maternal tissue. Several genes have been identified that influence seed size by acting maternally, such as
AUXIN RESPONSE FACTOR2
,
APETALA2
, and
DA1
. However, given the lack of gain-of-function effects of these genes on seed size, it is unclear whether their activity levels are limiting in WT plants and whether they could thus be used to regulate seed size in development or evolution. Also, whether the altered seed sizes reflect local gene activity or global physiological changes is unknown. Here, we demonstrate that the cytochrome P450 KLUH (KLU) regulates seed size.
KLU
acts locally in developing flowers to promote seed growth, and its activity level is limiting for seed growth in WT.
KLU
is expressed in the inner integument of developing ovules, where it non-cell autonomously stimulates cell proliferation, thus determining the growth potential of the seed coat and seed. A
KLU
-induced increase in seed size leads to larger seedlings and higher relative oil content of the seeds. Genetic analyses indicate that
KLU
acts independently of other tested maternal factors that influence integument cell proliferation. Thus, the level of
KLU
-dependent growth factor signaling determines size in ovules and seeds, suggesting this pathway as a target for crop improvement.
Successful immunotherapy with IL-2/anti-CD40 induces the chemokine-mediated mitigation of an immunosuppressive tumor microenvironment
Authors: Weiss Jonathan M. , Back Timothy C. , Scarzello Anthony J. , Subleski Jeff J. , Hall Veronica L. , Stauffer Jimmy K. , Chen Xin , Micic Dejan , Alderson Kory , Murphy William J. , Wiltrout Robert H.
Published: November 2009

Treatment of mice bearing orthotopic, metastatic tumors with anti-CD40 antibody resulted in only partial, transient anti-tumor effects whereas combined treatment with IL-2/anti-CD40, induced tumor regression. The mechanisms for these divergent anti-tumor responses were examined by profiling tumor-infiltrating leukocyte subsets and chemokine expression within the tumor microenvironment after immunotherapy. IL-2/anti-CD40, but not anti-CD40 alone, induced significant infiltration of established tumors by NK and CD8+T cells. To further define the role of chemokines in leukocyte recruitment into tumors, we evaluated anti-tumor responses in mice lacking the chemokine receptor, CCR2. The anti-tumor effects and leukocyte recruitment mediated by anti-CD40 alone, were completely abolished in CCR2−/−mice. In contrast, IL-2/anti-CD40-mediated leukocyte recruitment and reductions in primary tumors and metastases were maintained in CCR2−/−mice. Treatment of mice with IL-2/anti-CD40, but not anti-CD40 alone, also caused an IFN-γ-dependent increase in the expression of multiple Th1 chemokines within the tumor microenvironment. Interestingly, although IL-2/anti-CD40 treatment increased Tregs in the spleen, it also caused a coincident IFN-γ-dependent reduction in CD4+/FoxP3+Tregs, myeloid-derived suppressor cells and Th2 chemokine expression specifically within the tumor microenvironment that was not observed after treatment with anti-CD40 alone. Similar effects were observed using IL-15 in combination with anti-CD40. Taken together, our data demonstrate that IL-2/anti-CD40, but not anti-CD40 alone, can preferentially reduce the overall immunosuppressive milieu within the tumor microenvironment. These results suggest that the use of anti-CD40 in combination with IL-2 or IL-15 may hold substantially more promise for clinical cancer treatment than anti-CD40 alone.
Stabilization of Ca
2+
-permeable AMPA receptors at perisynaptic sites by GluR1-S845 phosphorylation
Authors: He Kaiwen , Song Lihua , Cummings Laurel W. , Goldman Jonathan , Huganir Richard L. , Lee Hey-Kyoung
Published: November 2009

AMPA receptor (AMPAR) channel properties and function are regulated by its subunit composition and phosphorylation. Certain types of neural activity can recruit Ca
2+
-permeable (CP) AMPARs, such as GluR1 homomers, to synapses likely via lateral diffusion from extrasynaptic sites. Here we show that GluR1-S845 phosphorylation can alter the subunit composition of perisynaptic AMPARs by providing stability to GluR1 homomers. Using mice specifically lacking phosphorylation of the GluR1-S845 site (GluR1-S845A mutants), we demonstrate that this site is necessary for maintaining CP-AMPARs. Specifically, in the GluR1-S845A mutants, CP-AMPARs were absent from perisynaptic locations mainly due to lysosomal degradation. This regulation was mimicked by acute desphosphorylation of the GluR1-S845 site in wild-type mice by NMDA application. Furthermore, long-term depression (LTD) was associated with a reduction in perisynaptic CP-AMPAR levels. Our findings suggest that GluR1-S845 is necessary for maintaining CP-AMPARs on the surface, especially at perisynaptic sites, and suggest that the regulation of these receptors is involved in synaptic plasticity.
Ceramide kinase regulates phospholipase C and phosphatidylinositol 4, 5, bisphosphate in phototransduction
Authors: Dasgupta Ujjaini , Bamba Takeshi , Chiantia Salvatore , Karim Pusha , Tayoun Ahmad N. Abou , Yonamine Ikuko , Rawat Satinder S. , Rao Raghavendra Pralhada , Nagashima Kunio , Fukusaki Eiichiro , Puri Vishwajeet , Dolph Patrick J. , Schwille Petra , Acharya Jairaj K. , Acharya Usha
Published: November 2009

Phosphoinositide-specific phospholipase C (PLC) is a central effector for many biological responses regulated by G-protein–coupled receptors including
Drosophila
phototransduction where light sensitive channels are activated downstream of NORPA, a PLCβ homolog. Here we show that the sphingolipid biosynthetic enzyme, ceramide kinase, is a novel regulator of PLC signaling and photoreceptor homeostasis. A mutation in ceramide kinase specifically leads to proteolysis of NORPA, consequent loss of PLC activity, and failure in light signal transduction. The mutant photoreceptors also undergo activity-dependent degeneration. Furthermore, we show that a significant increase in ceramide, resulting from lack of ceramide kinase, perturbs the membrane microenvironment of phosphatidylinositol 4, 5, bisphosphate (PIP
2
), altering its distribution. Fluorescence image correlation spectroscopic studies on model membranes suggest that an increase in ceramide decreases clustering of PIP
2
and its partitioning into ordered membrane domains. Thus ceramide kinase–mediated maintenance of ceramide level is important for the local regulation of PIP
2
and PLC during phototransduction.
Ethanolic Extract of Propolis Augments TRAIL‐Induced Apoptotic Death in Prostate Cancer Cells
Authors: Szliszka Ewelina , Czuba Zenon P. , Bronikowska Joanna , Mertas Anna , Paradysz Andrzej , Krol Wojciech
Published: November 2009

Prostate cancer is a commonly diagnosed cancer in men. The ethanolic extract of propolis (EEP) and its phenolic compounds possess immunomodulatory, chemopreventive and antitumor effects. Tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL/APO2L) is a naturally occurring anticancer agent that preferentially induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effects of EEP and phenolic compounds isolated from propolis in combination with TRAIL on two prostate cancer cell lines, hormone‐sensitivity LNCaP and hormone‐refractory DU145. The cytotoxicity was evaluated by MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V‐FITC/propidium iodide. The prostate cancer cell lines were proved to be resistant to TRAIL‐induced apoptosis. Our study demonstrated that EEP and its components significantly sensitize to TRAIL‐induced death in prostate cancer cells. The percentage of the apoptotic cells after cotreatment with 50 μg mL−1 EEP and 100 ng mL−1 TRAIL increased to 74.9 ± 0.7% for LNCaP and 57.4 ± 0.7% for DU145 cells. The strongest cytotoxic effect on LNCaP cells was exhibited by apigenin, kaempferid, galangin and caffeic acid phenylethyl ester (CAPE) in combination with TRAIL (53.51 ± 0.68–66.06 ± 0.62% death cells). In this work, we showed that EEP markedly augmented TRAIL‐mediated apoptosis in prostate cancer cells and suggested the significant role of propolis in chemoprevention of prostate cancer.
Poly(amidoamine) dendrimer-supported organoplatinum antitumour agents
Authors: Howell B. A. , Fan D.
Published: November 2009

While numerous water-soluble biocompatible polymers have been utilized for the construction of drug conjugates that offer significant advantages for drug delivery, poly(amidoamine) (PAMAM) dendrimers are superior in many ways for this purpose. They display nanoscale size, uniform shape, excellent water solubility, low toxicity and high surface functionality. In an attempt to circumvent the toxic side effects associated with the administration of organoplatinum drugs, a polymeric prodrug has been prepared from the treatment of a generation 4.5 PAMAM dendrimer with diaquo(1,2-diaminocyclohexane)platinum(II). A well-defined dendrimer–platinum conjugate containing 40 (1,2-diaminocyclohexane)platinum(II) units coordinated to the dendrimer surface
via
carboxylate groups is formed. This adduct is well behaved, water soluble, contains a high loading of platinum moieties and displays sustained release of active platinum species over a 24 h period under physiological conditions.
Apoptosis in Candida biofilms exposed to amphotericin B
Authors: Al-Dhaheri Rawya S. , Douglas L. Julia
Published: November 2009

Candidabiofilms are resistant to a range of antifungal agents in current clinical use. The basis of this drug resistance is not clear, but in some cases it could be due to the presence of a small number of drug-tolerant or persister cells. In this study, specific staining methods were used to investigate the existence of persisters and apoptosis inCandidabiofilms subjected to different concentrations of amphotericin B. Fluorescein diacetate staining revealed the presence of persisters in biofilms of one of two strains ofCandida albicanstested, and in biofilms ofCandida kruseiandCandida parapsilosis.Caspase activity, indicative of apoptosis, was detected with SR-FLICA and (aspartyl)2-rhodamine 110 fluorochrome-based staining reagents in all of these biofilms. The general inhibitor of mammalian caspases, Z-VAD-FMK, when used at a low concentration (2.5 μM), increased the viability of drug-treated biofilms up to 11.5-fold (P<0.001 %). Seven specific caspase inhibitors had different effects onC. albicansbiofilm viability, but inhibitors of caspases-1, −9, −5, −3 and −2 all significantly increased cell survival (40-fold, 8-fold, 3.5-fold, 1.9-fold and 1.7-fold, respectively). However, histone deacetylase (HDA) inhibitors enhanced the activity of amphotericin B for biofilms of all threeCandidaspecies. Sodium butyrate and sodium valproate, for example, when added concurrently with amphotericin B, completely eliminated biofilm populations ofC. albicans. Overall, our results demonstrate an apoptotic process in amphotericin-treated biofilms of threeCandidaspecies. They also indicate that HDA inhibitors can enhance the action of the drug and in some cases even eradicate persister subpopulations, suggesting that histone acetylation might activate apoptosis in these cells.
Genome diversity in the genera Fructobacillus, Leuconostoc and Weissella determined by physical and genetic mapping
Authors: Chelo Ivo M. , Zé-Zé Líbia , Tenreiro Rogério
Published: November 2009

Pulsed-field gel electrophoresis analysis of chromosomal single and double restriction profiles of 17 strains belonging to three genera of ‘Leuconostocaceae’ was done, resulting in physical and genetic maps for three Fructobacillus, six Leuconostoc and four Weissella strains. AscI, I-CeuI, NotI and SfiI restriction enzymes were used together with Southern hybridization of selected probes to provide an assessment of genomic organization in different species. Estimated genome sizes varied from 1408 kb to 1547 kb in Fructobacillus, from 1644 kb to 2133 kb in Leuconostoc and from 1371 kb to 2197 kb in Weissella. Other genomic characteristics of interest were analysed, such as oriC and terC localization and rrn operon organization. The latter seems markedly different in Weissella, in both number and disposition in the chromosome. Comparisons of intra- and intergeneric features are discussed in the light of chromosome rearrangements and genomic evolution.
Differences in adherence and virulence gene expression between two outbreak strains of enterohaemorrhagic Escherichia coli O157 : H7
Authors: Abu-Ali Galeb S. , Ouellette Lindsey M. , Henderson Scott T. , Whittam Thomas S. , Manning Shannon D.
Published: November 2009

The Escherichia coli O157 : H7 TW14359 strain was implicated in a multi-state outbreak in North America in 2006, which resulted in high rates of severe disease. Similarly, the O157 : H7 RIMD0509952 (Sakai) strain caused the largest O157 : H7 outbreak to date. Both strains were shown to represent divergent phylogenetic lineages. Here we compared global gene expression patterns before and after epithelial cell exposure, as well as the ability to adhere to and invade epithelial cells, between the two outbreak strains. Epithelial cell assays demonstrated a 2.5-fold greater adherence of the TW14359 strain relative to Sakai, while whole-genome microarrays detected significant differential expression of 914 genes, 206 of which had a fold change ≥1.5. Interestingly, most locus of enterocyte effacement (LEE) genes were upregulated in TW14359, whereas flagellar and chemotaxis genes were primarily upregulated in Sakai, suggesting discordant expression of these genes between the two strains. The Shiga toxin 2 genes were also upregulated in the TW14359 strain, as were several pO157-encoded genes that promote adherence, including type II secretion genes and their effectors stcE and adfO. Quantitative RT-PCR confirmed the expression differences detected in the microarray analysis, and expression levels were lower for a subset of LEE genes before versus after exposure to epithelial cells. In all, this study demonstrated the upregulation of major and ancillary virulence genes in TW14359 and of flagellar and chemotaxis genes in Sakai, under conditions that precede intimate bacterial attachment to epithelial cells. Differences in the level of adherence to epithelial cells were also observed, implying that these two phylogenetically divergent O157 : H7 outbreak strains vary in their ability to colonize, or initiate the disease process.