bluuebunny/crossref_metadata_2025 huggingface dataset:
Decadal‐scale changes in meridional heat transport across 24°N in the Pacific Ocean
Authors: Kawai Yoshimi , Doi Toshimasa , Tomita Hiroyuki , Sasaki Hideharu
Published: August 2008

We investigated the long‐term variability of the meridional heat transport across 24°N in the Pacific Ocean in two ways: (1) by adding the surface net heat flux to the temporal change rate of the ocean heat content (OHC) north of 24°N and (2) by integrating the product of meridional velocity and potential temperature over the 24°N section in numerical models. Decadal‐scale changes with amplitudes of approximately 0.1–0.2 PW were detected consistently in the 5‐year running means of the meridional heat transport in the 1980s and 1990s from these different analyses. The heat transport increased during the 1980s, which is closely linked with the change in the OHC. While both the Ekman and Kuroshio transports were responsible for the change in the 1980s, the contribution of the former was dominant. On the other hand, the variation in the Kuroshio temperature transport dominated meridional heat transport in the 1990s. The air‐sea net heat fluxes of the atmospheric reanalysis data sets integrated north of 24°N increased in the 1990s, which indicates that the increase of the lateral heat transport was distributed mainly to the atmosphere, particularly in the Kuroshio and Kuroshio‐Oyashio Extension (KOE) regions. However, there are also large discrepancies in the surface heat flux among the data sets. To reveal the impact of the decadal‐scale changes in meridional heat transport on the atmosphere, it is crucial to obtain more accurate values for the air‐sea heat exchange and OHC by using a sustainable observing system and numerical models.
Modeling feedbacks between a boreal forest and the planetary boundary layer
Authors: Hill T. C. , Williams M. , Moncrieff J. B.
Published: August 2008

The atmosphere and biosphere interact strongly in the planetary boundary layer. Understanding the mechanisms controlling the coupled atmosphere‐biosphere system allows improved scaling between observations at the stand scale (e.g., flux towers) and those at larger scales, e.g., airborne or satellite measurements. Simulation of the joint atmosphere‐biosphere system permits the study of feedbacks occurring within the coupled system. In this paper, two well‐tested models, one a process‐based biosphere model (SPA) and the other a planetary boundary layer model (CAPS), were coupled to allow simulation of atmosphere‐biosphere feedbacks and interactions with a focus on ecological controls. As part of the validation process, the biosphere model was tested using eddy covariance, surface meteorology, and soil data collected during a 120 day period at a boreal black spruce site during the 1994 BOREAS field campaign. The coupled atmosphere‐biosphere model was also validated with radiosonde data above the black spruce site, demonstrating that atmosphere and biosphere models can be coherently combined. We show that negative feedbacks at the black spruce site have strong moderating effects. The feedbacks reduce the mean impact of LAI changes on the atmospheric surface layer by 21% for latent energy, 64% for air temperature, and 44% for water mixing ratio. We show that both radiative and hydraulic limitations imposed by the vegetation structure strongly affected the interactions within the atmosphere‐biosphere system, while the impact of the canopy roughness length was weak.
An assessment of the land surface parameters on the simulated regional climate circulations: The 1997 and 1998 east Asian summer monsoon cases
Authors: Kang Hyun‐Suk , Hong Song‐You
Published: August 2008

In atmospheric modeling, the treatment of land surface processes is a critical component to the success of seasonal climate simulation. The purpose of this study is to assess the importance of the surface parameters of the land surface model in regional climate simulations for the 1997 and 1998 east Asian summer monsoon (EASM) cases. In order to reach this end, three ensemble experiments were conducted using the National Centers for Environmental Prediction Regional Spectral Model with different vegetation type data set, which leads to differences in surface albedo and roughness length. These two parameters which are mainly dependent on vegetation type are obtained from the corresponding climatological data sets externally during the model integration. As a result, it is found that the specification of surface albedo and roughness length for a given vegetation type is more crucial than either the number of classification types for vegetation and soil or the horizontal resolutions. It is concluded that the geographical uniqueness of the EASM region is also a major factor to be emphasized, as it causes dynamically driven impacts in association with the thermodynamical effects arising from the values in surface parameters.
Intercomparison and harmonization of UV Index measurements from multiband filter radiometers
Authors: Johnsen Bjørn , Kjeldstad Berit , Aalerud Tommy Nakken , Nilsen Lill Tove , Schreder Josef , Blumthaler Mario , Bernhard Germar , Topaloglou Chrysanthi , Meinander Outi , Bagheri Asadollah , Slusser James R. , Davis John
Published: August 2008

Multiband filter radiometers (MBFRs) are extensively used in national measurement networks for UV climate monitoring and for informing the public about potential health risks from excessive solar UV exposure. Results from the first international intercomparison of MBFRs, arranged in Oslo in 2005, are presented. Forty‐three radiometers of type GUV, NILU‐UV, and UVMFR‐7 were assembled, representing monitoring stations on several continents. The first objective was to conduct a blind intercomparison of Global UV Index (UVI) processed by the instrument owners. Eleven independent data sets were compared, eight of which agreed with the reference to within ±5% and ten to within ±10%. The second objective was to provide a harmonized calibration scale for all instruments. When this scale was applied, the UVI agreed to within ±5% (2‐sigma) for solar zenith angles (SZAs) up to 90°. The results demonstrate that MBFRs provide accurate UVI measurements for realistic sky conditions and a wide range of SZAs, provided the calibration functions are optimized. The harmonized UVI scale is traceable to the European QASUME reference spectroradiometer.
Spatial variability of methane emissions from rice fields and implications for experimental design
Authors: Khalil M. A. K. , Butenhoff Christopher L.
Published: August 2008

It is observed that side by side plots in rice fields, managed by the same practices, produce methane emissions that are often different by factors of 2 to 4. Similarly on a given day when many plots are sampled, the emissions from one plot may differ from another by factors of 3–4 on average. These large variations must be taken into account if these data are extrapolated to larger scales such as countries or the world. In this paper we analyze and delineate the nature of this variability. We distinguish temporal and spatial variability and examine the effects of both on the observed seasonal average emission rates. While temporal variability is managed well in most experiments because frequent measurements are taken, the spatial variability remains a potential major uncertainty in many experiments. Using the characteristics of the observed variability we use simulations to show that with a proper and realistic sampling strategy, it is possible to get to within 15%–20% of the true flux for most cases of interest. We calculate how many plots are needed and how often they should be sampled during the growing season to obtain a seasonal average flux within prescribed limits relative to the true flux.
Global plate motion frames: Toward a unified model
Authors: Torsvik Trond H. , Müller R. Dietmar , Van der Voo Rob , Steinberger Bernhard , Gaina Carmen
Published: August 2008

Plate tectonics constitutes our primary framework for understanding how the Earth works over geological timescales. High‐resolution mapping of relative plate motions based on marine geophysical data has followed the discovery of geomagnetic reversals, mid‐ocean ridges, transform faults, and seafloor spreading, cementing the plate tectonic paradigm. However, so‐called “absolute plate motions,” describing how the fragments of the outer shell of the Earth have moved relative to a reference system such as the Earth's mantle, are still poorly understood. Accurate absolute plate motion models are essential surface boundary conditions for mantle convection models as well as for understanding past ocean circulation and climate as continent‐ocean distributions change with time. A fundamental problem with deciphering absolute plate motions is that the Earth's rotation axis and the averaged magnetic dipole axis are not necessarily fixed to the mantle reference system. Absolute plate motion models based on volcanic hot spot tracks are largely confined to the last 130 Ma and ideally would require knowledge about the motions within the convecting mantle. In contrast, models based on paleomagnetic data reflect plate motion relative to the magnetic dipole axis for most of Earth's history but cannot provide paleolongitudes because of the axial symmetry of the Earth's magnetic dipole field. We analyze four different reference frames (paleomagnetic, African fixed hot spot, African moving hot spot, and global moving hot spot), discuss their uncertainties, and develop a unifying approach for connecting a hot spot track system and a paleomagnetic absolute plate reference system into a “hybrid” model for the time period from the assembly of Pangea (∼320 Ma) to the present. For the last 100 Ma we use a moving hot spot reference frame that takes mantle convection into account, and we connect this to a pre–100 Ma global paleomagnetic frame adjusted 5° in longitude to smooth the reference frame transition. Using plate driving force arguments and the mapping of reconstructed large igneous provinces to core–mantle boundary topography, we argue that continental paleolongitudes can be constrained with reasonable confidence.
Leaky modes at backward endfire on periodic printed structures
Authors: Baccarelli Paolo , Paulotto Simone , Jackson David R. , Oliner Arthur A.
Published: August 2008

In this work, the transition at backward endfire between bound (nonleaky) and leaky modes on one‐dimensional periodic structures printed on a grounded dielectric substrate is examined. This mode evolution has been characterized for a class of structures with a finite‐width cross section. Such structures support leakage into surface waves as well as into space due to the presence of the substrate. The solutions in this transition region are calculated using an accurate full‐wave moment‐method approach that allows for the determination of both physical and nonphysical solutions, both of which play an important role in the transition region.
Regional methods for trend detection: Assessing field significance and regional consistency
Authors: Renard B. , Lang M. , Bois P. , Dupeyrat A. , Mestre O. , Niel H. , Sauquet E. , Prudhomme C. , Parey S. , Paquet E. , Neppel L. , Gailhard J.
Published: August 2008

This paper describes regional methods for assessing field significance and regional consistency for trend detection in hydrological extremes. Four procedures for assessing field significance are compared on the basis of Monte Carlo simulations. Then three regional tests, based on a regional variable, on the regional average Mann‐Kendall test, and a new semiparametric approach, are tested. The latter was found to be the most adequate to detect consistent changes within homogeneous hydro‐climatic regions. Finally, these procedures are applied to France, using daily discharge data arising from 195 gauging stations. No generalized change was found at the national scale on the basis of the field significance assessment of at‐site results. Hydro‐climatic regions were then defined, and the semiparametric procedure applied. Most of the regions showed no consistent change, but three exceptions were found: in the northeast flood peaks were found to increase, in the Pyrenees high and low flows showed decreasing trends, and in the Alps, earlier snowmelt‐related floods were detected, along with less severe drought and increasing runoff due to glacier melting. The trend affecting floods in the northeast was compared to changes in rainfall, using rainfall‐runoff simulation. The results showed flood trends consistent with the observed rainfall.
Small‐scale upper mantle convection and crustal dynamics in southern California
Authors: Fay N. P. , Bennett R. A. , Spinler J. C. , Humphreys E. D.
Published: August 2008

We present numerical modeling of the forces acting on the base of the crust caused by small‐scale convection of the upper mantle in southern California. Three‐dimensional upper mantle shear wave velocity structure is mapped to three‐dimensional density structure that is used to load a finite element model of instantaneous upper mantle flow with respect to a rigid crust, providing an estimate of the tractions acting on the base of the crust. Upwelling beneath the southern Walker Lane Belt and Salton Trough region and downwelling beneath the southern Great Valley and eastern and western Transverse Ranges dominate the upper mantle flow and resulting crustal tractions. Divergent horizontal and upward directed vertical tractions create a tensional to transtensional crustal stress state in the Walker Lane Belt and Salton Trough, consistent with transtensional tectonics in these areas. Convergent horizontal and downward directed vertical tractions in the Transverse Ranges cause approximately N–S crustal compression, consistent with active shortening and transpressional deformation near the “Big Bend” of the San Andreas fault. Model predictions of crustal dilatation and the forces acting on the Mojave block compare favorably with observations suggesting that small‐scale upper mantle convection provides an important contribution to the sum of forces driving transpressional crustal deformation in southern California. Accordingly, the obliquity of the San Andreas fault with respect to plate motions may be considered a consequence, rather than a cause, of contractional deformation in the Transverse Ranges, itself driven by downwelling in the upper mantle superimposed on shear deformation caused by relative Pacific–North American plate motion.
Simultaneous THEMIS in situ and auroral observations of a small substorm
Authors: Donovan E. , Liu W. , Liang J. , Spanswick E. , Voronkov I. , Connors M. , Syrjäsuo M. , Baker G. , Jackel B. , Trondsen T. , Greffen M. , Angelopoulos V. , Russell C. T. , Mende S. B. , Frey H. U. , Keiling A. , Carlson C. W. , McFadden J. P. , Glassmeier K.‐H. , Auster U. , Hayashi K. , Sakaguchi K. , Shiokawa K. , Wild J. A. , Rae I. J.
Published: August 2008

We present ground‐based and in situ observations from March 13, 2007. The THEMIS satellites were in the evening sector conjugate to THEMIS ground‐based imagers. At ∼0507 UT there was an optical onset on inner CPS field lines. This involved near‐simultaneous brightening of 1 MLT hour longitudinal segment of the onset arc. The part of the arc that brightened was that closest to the equatorward boundary of the diffuse (proton) aurora. Within one minute, a dipolarization front moved across four THEMIS satellites. Based on their locations, the order in which they detected the dipolarization front, and the auroral evolution, we assert that the expansion phase began earthward of the four satellites and evolved radially outwards. We conclude that this onset occurred in an azimuthally localized region of highly stretched field lines.
Sub‐basin scale dust source geomorphology detected using MODIS
Authors: Bullard Joanna , Baddock Matthew , McTainsh Grant , Leys John
Published: August 2008

The spatial and temporal variability of dust emissions from different surfaces in the Lake Eyre Basin, Australia is determined using MODIS data. For 2003–6 the sources of 529 dust plumes were classified: overall 37% of plumes originated in areas of aeolian deposits, 30% from alluvial deposits and floodplains and 29% from ephemeral lakes or playas. At this sub‐basin scale, the relative importance of different dust source geomorphologies varied primarily in response to sediment supply and availability and was not related to aeolian transport capacity, suggesting the Lake Eyre Basin is a supply‐limited system.
Tropical methane emissions: A revised view from SCIAMACHY onboard ENVISAT
Authors: Frankenberg Christian , Bergamaschi Peter , Butz André , Houweling Sander , Meirink Jan Fokke , Notholt Justus , Petersen Anna Katinka , Schrijver Hans , Warneke Thorsten , Aben Ilse
Published: August 2008

Methane retrievals from near‐infrared spectra recorded by the SCIAMACHY instrument onboard ENVISAT hitherto suggested unexpectedly large tropical emissions. Even though recent studies confirm substantial tropical emissions, there were indications for an unresolved error in the satellite retrievals. Here we identify a retrieval error related to inaccuracies in water vapor spectroscopic parameters, causing a substantial overestimation of methane correlated with high water vapor abundances. We report on the overall implications of an update in water spectroscopy on methane retrievals with special focus on the tropics where the impact is largest. The new retrievals are applied in a four‐dimensional variational (4D‐VAR) data assimilation system to derive a first estimate of the impact on tropical CH4 sources. Compared to inversions based on previous SCIAMACHY retrievals, annual tropical emission estimates are reduced from 260 to about 201 Tg CH4 but still remain higher than previously anticipated.
On the role of transient currents in the global electric circuit
Authors: Mareev E. A. , Yashunin S. A. , Davydenko S. S. , Marshall T. C. , Stolzenburg M. , Maggio C. R.
Published: August 2008

This study examines the way in which different types of lightning, both cloud‐to‐ground (CG) and intracloud (IC) flashes, drive current in the global circuit. A numerical model of the transient electric field due to CG and IC flashes and their Maxwell relaxation (slow transients) is developed. The electric field (E) and current distributions, the decay time of E, and the total charge transferred to the ionosphere and the ground are calculated. Because of the slow transients, only a portion of the charge neutralized by a flash contributes to the global circuit, with the efficiency depending on the altitudes of the lightning charges. Typical CG flashes have efficiencies of 55–75%, and typical IC flashes have 5–15%. An example from balloon E data has been used to verify the theory. Total current estimations of the combined CG and IC slow transient processes in the global electric circuit range from 50–400 A.
Ocean physical and biogeochemical responses to the passage of Typhoon Meari in the East China Sea observed from Argo float and multiplatform satellites
Authors: Siswanto Eko , Ishizaka Joji , Morimoto Akihiko , Tanaka Katsuhisa , Okamura Kazumaro , Kristijono Agus , Saino Toshiro
Published: August 2008

We elucidated ocean physical and biogeochemical responses to slow‐moving Typhoon Meari using a new method combining Argo float and satellite observations. Meari‐driven upwelling brought colder, nutrient‐rich deep water to the surface layer, causing sea surface cooling (3–6°C) and threefold enhancement of primary production (PP). Maximum surface cooling (and hence nutrient injection) and peak PP enhancement lagged Meari's passage by 1 and 3 days, respectively, implying that remarkable PP enhancement was attributed to new production (NP). This NP accounted for approximately 3.8% of annual carbon export in the East China Sea (ECS) outer shelf, suggesting that typhoon‐driven upwelling is important for biogeochemical processes in the ECS. Given the wide coverage of Argo float and satellite data, our new approach may prompt comparative studies in other basins and advance the understanding of the role of tropical cyclones in the global ocean biogeochemical cycle.
Statistical validation of a solar wind propagation model from 1 to 10 AU
Authors: Zieger Bertalan , Hansen Kenneth C.
Published: August 2008

A one‐dimensional (1‐D) numerical magnetohydrodynamic (MHD) code is applied to propagate the solar wind from 1 AU through 10 AU, i.e., beyond the heliocentric distance of Saturn's orbit, in a non‐rotating frame of reference. The time‐varying boundary conditions at 1 AU are obtained from hourly solar wind data observed near the Earth. Although similar MHD simulations have been carried out and used by several authors, very little work has been done to validate the statistical accuracy of such solar wind predictions. In this paper, we present an extensive analysis of the prediction efficiency, using 12 selected years of solar wind data from the major heliospheric missions Pioneer, Voyager, and Ulysses. We map the numerical solution to each spacecraft in space and time, and validate the simulation, comparing the propagated solar wind parameters with in‐situ observations. We do not restrict our statistical analysis to the times of spacecraft alignment, as most of the earlier case studies do. Our superposed epoch analysis suggests that the prediction efficiency is significantly higher during periods with high recurrence index of solar wind speed, typically in the late declining phase of the solar cycle. Among the solar wind variables, the solar wind speed can be predicted to the highest accuracy, with a linear correlation of 0.75 on average close to the time of opposition. We estimate the accuracy of shock arrival times to be as high as 10–15 hours within ±75 d from apparent opposition during years with high recurrence index. During solar activity maximum, there is a clear bias for the model to predicted shocks arriving later than observed in the data, suggesting that during these periods, there is an additional acceleration mechanism in the solar wind that is not included in the model.
Plasma probes for the lunar surface
Authors: Wang Xu , Horányi Mihály , Robertson Scott
Published: August 2008

Dust particles on the lunar surface, or on any other airless planetary surface, can be directly exposed to solar wind plasma and ultraviolet radiation, resulting in electrostatic charging and possible subsequent mobilization and transport. Although there are several independent observations indicating dust levitation and transport on the Moon, these processes are still poorly understood, and the development of specialized plasma and dust diagnostic tools will be necessary for future missions. Here we discuss a measurement technique that could characterize the near surface lunar plasma environment. We report on laboratory experiments using an asymmetric double probe with vastly different collection areas to characterize the sheath above a photoemissive surface in a vacuum chamber. The approach could form the basis of a future in situ experiment that probes the photoelectron layer on the lunar surface.
Defining a fire year for reporting and analysis of global interannual fire variability
Authors: Boschetti Luigi , Roy David P.
Published: August 2008

The interannual variability of fire activity has been studied without an explicit investigation of a suitable starting month for yearly calculations. Sensitivity analysis of 37 months of global MODIS active fire detections indicates that a 1‐month change in the start of the fire year definition can lead, in the worst case, to a difference of over 6% and over 45% in global and subcontinental scale annual fire totals, respectively. Optimal starting months for analyses of global and subcontinental fire interannual variability are described. The research indicates that a fire year starting in March provides an optimal definition for annual global fire activity.
Anti‐inflammatory effects of dimemorfan on inflammatory cells and LPS‐induced endotoxin shock in mice
Authors: Wang Y‐H , Shen Y‐C , Liao J‐F , Lee C‐H , Chou C‐Y , Liou K‐T , Chou Y‐C
Published: August 2008

British Journal of Pharmacology (2008) 154, 1702; doi:10.1038/bjp.2008.282
Inhibitory activity of the novel CB2receptor agonist, GW833972A, on guinea‐pig and human sensory nerve function in the airways
Authors: Belvisi M G , Patel H J , Freund‐Michel V , Hele D J , Crispino N , Birrell M A
Published: August 2008

Background and purpose:

Sensory nerves regulate central and local reflexes such as airway plasma protein leakage, bronchoconstriction and cough. Sensory nerve activity may be enhanced during inflammation such that these protective effects become exacerbated and deleterious. Cannabinoids are known to inhibit airway sensory nerve function. However, there is still controversy surrounding which receptor is involved in eliciting these effects.

Experimental approach:

We have adopted a pharmacological approach, including using a novel, more selective CB2receptor agonist, GW 833972A (1000‐fold selective CB2/CB1), and receptor selective antagonists to investigate the inhibitory activity of cannabinoids on sensory nerve activityin vitroandin vivoin guinea‐pig models of cough and plasma extravasation.

Key results:

GW 833972A inhibited capsaicin‐induced depolarization of the human and guinea‐pig and prostaglandin E2(PGE2) and hypertonic saline‐induced depolarization of the guinea‐pig isolated vagus nervein vitro.GW 833972A also inhibited citric acid‐induced cough but not plasma extravasation in the guinea‐pig and this effect was blocked by a CB2receptor antagonist.

Conclusions and implications:

This confirms and extends previous studies highlighting the role of CB2receptors in the modulation of sensory nerve activity elicited both by the exogenous ligands capsaicin and hypertonic saline but also by endogenous modulators such as PGE2and low pH stimuli. These data establish the CB2receptor as an interesting target for the treatment of chronic cough.

British Journal of Pharmacology(2008)155, 547–557; doi:10.1038/bjp.2008.298; published online 11 August 2008
Effects of genistein aglycone in osteoporotic, ovariectomized rats: a comparison with alendronate, raloxifene and oestradiol
Authors: Bitto A , Burnett B P , Polito F , Marini H , Levy R M , Armbruster M A , Minutoli L , Di Stefano V , Irrera N , Antoci S , Granese R , Squadrito F , Altavilla D
Published: August 2008

Background and purpose:

Genistein aglycone positively affects bone loss in postmenopausal women, but bone quality data are still lacking. To clarify this, we investigated the effects of genistein compared with alendronate, raloxifene and oestradiol in an animal model of established osteoporosis.

Experimental approach:

Six months after ovariectomy, 96 ovariectomized (OVX) rats were divided into 8 equal groups, randomized to treatments (genistein aglycone (1 and 10 mg kg−1s.c.); alendronate (0.003 and 0.03 mg kg−1s.c.); raloxifene hydrochloride (0.05 and 0.5 mg kg−1s.c.); 17‐α‐ethinyl oestradiol (0.003 and 0.03 mg kg−1s.c.)) for 12 weeks. Untreated OVX (n=12) and sham OVX (n=12) were used as controls. At the beginning and end of treatment, bone mineral density (BMD) and bone mineral content (BMC) were assessed. At the end of the experiment, calcium, phosphorus, bone‐alkaline phosphatase (b‐ALP), collagen C‐telopeptide (CTX), osteoprotegerin (OPG) and soluble receptor activator of nuclear factor‐κB ligand (sRANKL) were assayed. Femurs were removed and tested for breaking strength and histology.

Key results:

Genistein (10 mg kg−1) showed a greater increase in both BMD (P<0.0001 vs OVX) and BMC than all the other treatments. Moreover, genistein significantly increased breaking strength, bone quality, b‐ALP (P<0.0001 vs OVX) and OPG, and reduced CTX and sRANKL compared with the other treatments at all dose levels.

Conclusions and implications:

The results strongly suggest that the genistein aglycone might be a new therapy for the management of postmenopausal osteoporosis in humans.

British Journal of Pharmacology(2008)155, 896–905; doi:10.1038/bjp.2008.305; published online 11 August 2008
Novel interactions between the 5‐HT transporter, 5‐HT1B receptors and Rho kinase in vivo and in pulmonary fibroblasts
Authors: Mair K M , MacLean M R , Morecroft I , Dempsie Y , Palmer T M
Published: August 2008

Background and purpose:

While the 5‐HT and Rho‐kinase (ROCK) pathways have been implicated in the development of pulmonary arterial hypertension (PAH), the nature of any interactions between them remain unclear. This study investigated a role for ROCK in 5‐HT‐regulated proliferative responses in lung fibroblasts in vivo and in vitro.

Experimental approach:

PAH was examined in mice over‐expressing human 5‐HT transporters (SERT+), from which pulmonary artery fibroblasts (PFs) were isolated to assess ROCK expression. In vitro analysis of 5‐HT signalling employed CCL39 hamster lung fibroblasts.

Key results:

ROCK inhibition ablated increased pulmonary remodelling and hypertension observed in SERT+ mice, and ROCK1/2 protein levels were elevated in SERT+ PFs. ROCK inhibition also reduced 5‐HT‐stimulated proliferation by suppressing MEK‐stimulated ERK phosphorylation. While optimal 5‐HT‐stimulated proliferation required 5‐HT1B and 5‐HT2A receptors and SERT, receptor sensitivity to Y27632 was restricted to the 5‐HT1B receptor. Also, while hypoxia‐induced pulmonary vascular remodelling and hypertension were sensitive to Y27632 in WT and SERT+ animals, the proportions sensitive to ROCK inhibition were increased by SERT over‐expression.

Conclusions and implications:

SERT over‐expression increased ROCK‐dependent pulmonary remodelling in normoxia and hypoxia and SERT over‐expression was associated with elevated ROCK1/2 levels. ROCK also potentiated 5‐HT1B receptor‐stimulated ERK activation and proliferation in vitro by facilitating MEK‐ERK interaction.

British Journal of Pharmacology (2008) 155, 606–616; doi:10.1038/bjp.2008.310; published online 11 August 2008
Novel role of curcumin in the prevention of cytokine‐induced islet death in vitro and diabetogenesis in vivo
Authors: Kanitkar M , Gokhale K , Galande S , Bhonde R R
Published: August 2008

Background and purpose:

Oxidative stress caused by cytokine exposure is a major cause of pancreatic islet death in vitro and of diabetogenesis. Antioxidant compounds may prevent cytokine‐induced damage to islet cells. Hence, we studied the potential of curcumin, an antioxidant and anti‐inflammatory compound, in vitro to protect islets against pro‐inflammatory cytokines and in vivo to prevent the progression of diabetes induced by multiple low doses of streptozotocin (MLD‐STZ).

Experimental approach:

Pancreatic islets from C57/BL6J mice were pretreated with curcumin (10 μM) and then exposed to a combination of cytokines. Islet viability, reactive oxygen species (ROS), NO, inducible NO synthase and NF‐κB translocation were studied. Curcumin pretreated (7.5 mg kg−1 day−1) C57/BL6J mice were given MLD‐STZ (40 mg kg−1), and various parameters of diabetes induction and progression were monitored.

Key results:

Curcumin protected islets from cytokine‐induced islet death in vitro by scavenging ROS and normalized cytokine‐induced NF‐κB translocation by inhibiting phosphorylation of inhibitor of kappa B alpha (IκBα). In vivo, curcumin also prevented MLD‐STZ, as revealed by sustained normoglycaemia, normal glucose clearance and maintained pancreatic GLUT2 levels. Pro‐inflammatory cytokine concentrations in the serum and pancreas were raised in STZ‐treated animals, but not in animals pretreated with curcumin before STZ.

Conclusions and implications:

Here, we have demonstrated for the first time that curcumin in vitro protects pancreatic islets against cytokine‐induced death and dysfunction and in vivo prevents STZ‐induced diabetes.

British Journal of Pharmacology (2008) 155, 702–713; doi:10.1038/bjp.2008.311; published online 11 August 2008
cGMP‐independent anti‐tumour actions of the inhibitor of soluble guanylyl cyclase, ODQ, in prostate cancer cell lines
Authors: Haramis G , Zhou Z , Pyriochou A , Koutsilieris M , Roussos C , Papapetropoulos A
Published: August 2008

Background and purpose:

Soluble guanylyl cyclase (sGC) is a receptor for nitric oxide that generates cGMP. This second messenger molecule has established roles in cellular physiology; however, less is known about its effects in tumour cells.

Experimental approach:

The effects of 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ) and 4H‐8‐bromo‐1,2,4‐oxadiazolo(3,4‐d)benz(b)(1,4)oxazin‐1‐one (NS2028), both selective sGC inhibitors on proliferation, death and migration were determined in prostate cancer cell lines.

Key results:

Western blot analysis confirmed the presence of α1 and β1 subunits of sGC in LNCaP and PC‐3 cells. Sodium nitroprusside (SNP) increased cGMP accumulation in LNCaP and PC‐3, but not DU‐145 cells. SNP‐stimulated cGMP production in LNCaP cells was dose‐dependently reduced by ODQ, with more than 90% inhibition being observed at 0.1 μM. ODQ activated caspase‐3 in all three cell lines, but not in normal prostate epithelial cells, at concentrations over 10 μM. High concentrations of ODQ also promoted DNA fragmentation and nucleosome accumulation in the cytosol of LNCaP cells. Interestingly, the chemically related inhibitor, NS2028 was without effect on caspase‐3. In addition, ODQ inhibited LNCaP, Du145 and PC‐3 cell growth. Finally, although fibroblast growth factor‐2 did not enhance cGMP levels in LNCaP cells, its ability to stimulate LNCaP motility was abolished by ODQ.

Conclusions and implications:

These observations taken together suggest that the action of ODQ in LNCaP cells did not reflect sGC inhibition. We conclude that ODQ promotes cell death and inhibits growth and migration of prostate cancer cells and that these actions are independent of its effects on GMP levels.

British Journal of Pharmacology(2008)155, 804–813; doi:10.1038/bjp.2008.312; published online 11 August 2008
A ketolide antibiotic, telithromycin, inhibits vascular adrenergic neurotransmission in the rat mesenteric vascular bed
Authors: Hatanaka Y , Zamami Y , Koyama T , Hobara N , Jin X , Kitamura Y , Kawasaki H
Published: August 2008

Background and purpose:

A ketolide antibiotic, telithromycin, has side effects including temporary loss of consciousness in clinical use, but the underlying mechanisms remain unclear. This study investigated the effects of telithromycin on perivascular nerve function in rat mesenteric arteries, in comparison with those of macrolide (erythromycin and clarithromycin) and new quinolone antibiotics (levofloxacin and gatifloxacin).

Experimental approach:

In vitro, vascular responses and release of noradrenaline induced by periarterial nerve stimulation (PNS) of rat perfused mesenteric vascular beds were measured in the presence of each antibiotic.In vivoblood pressure measurement was performed in Wistar rats.

Key results:

In mesenteric preparations with resting tone, telithromycin (10 nM–10 μM) markedly inhibited PNS (4–12 Hz)‐induced adrenergic nerve‐ and exogenous noradrenaline‐mediated vasoconstriction, whereas the other antibiotics slightly inhibited PNS‐induced responses without affecting noradrenaline‐induced responses. Telithromycin significantly reduced PNS (12 Hz)‐evoked noradrenaline release in the perfusate. In pre‐constricted preparations with or without endothelium, telithromycin (0.1 nM–10 μM) caused a concentration‐dependent vasodilation. Telithromycin (10 nM) inhibited calcium‐induced vasoconstriction in high KCl and calcium‐free medium. None of the antibiotics used affected PNS (0.5–2 Hz)‐induced calcitonin gene‐related peptide (CGRP) nerve‐ and exogenous CGRP‐mediated vasodilation. Intravenous injection of telithromycin significantly lowered blood pressure in anaesthetized rats.

Conclusions and implications:

These results suggest that telithromycin causes not only strong inhibition of perivascular adrenergic neurotransmission but also a vasodilator action in mesenteric vascular beds and hypotension. It is thus possible that telithromycin increases visceral blood flow, consequently reducing cerebral blood flow and resulting in a temporary loss of consciousness.

British Journal of Pharmacology(2008)155, 826–836; doi:10.1038/bjp.2008.313; published online 11 August 2008
Cannabinoids reduce granuloma‐associated angiogenesis in rats by controlling transcription and expression of mast cell protease‐5
Authors: De Filippis D , Russo A , D'Amico A , Esposito G , Pietropaolo C , Cinelli M , Russo G , Iuvone T
Published: August 2008

British Journal of Pharmacology (2008) 154, 1701; doi:10.1038/bjp.2008.314
Lack of effects of acemetacin on signalling pathways for leukocyte adherence may explain its gastrointestinal safety
Authors: Chávez‐Piña A E , Vong L , McKnight W , Dicay M , Zanardo R C O , Ortiz M I , Castañeda‐Hernández G , Wallace J L
Published: August 2008

Background and purpose:

Acemetacin is a non‐steroidal anti‐inflammatory drug which is rapidly bioconverted to indomethacin, but produces significantly less gastric damage than indomethacin. This study was performed to investigate several possible mechanisms that could account for the gastrointestinal tolerability of acemetacin.

Experimental approach:

The gastric and intestinal damaging effects of acemetacin and indomethacin were examined in the rat. Effects of the drugs on blood levels of leukotriene B4 and thromboxane B2, on leukocyte‐endothelial adherence in post‐capillary mesenteric venules, and on gastric expression of tumour necrosis factor‐α (TNF‐α) were determined. The two drugs were also compared for gastric toxicity in rats pretreated with inhibitors of COX‐2 and NOS.

Key results:

Acemetacin induced significantly less gastric and intestinal damage than indomethacin, despite markedly suppressing COX activity. Indomethacin, but not acemetacin, significantly increased leukocyte adherence within mesenteric venules, and gastric expression of TNF‐α. Pretreatment with L‐nitro‐arginine methyl ester or lumiracoxib increased the severity of indomethacin‐induced gastric damage, but this was not the case with acemetacin.

Conclusions and implications:

The increased gastric and intestinal tolerability of acemetacin may be related to the lack of induction of leukocyte–endothelial adherence. This may be attributable to the reduced ability of acemetacin to elevate leukotriene‐B4 synthesis and TNF‐α expression, compared to indomethacin, despite the fact that acemetacin is rapidly bioconverted to indomethacin after its absorption.

British Journal of Pharmacology (2008) 155, 857–864; doi:10.1038/bjp.2008.316; published online 11 August 2008
(Pro3)GIP[mPEG]: novel, long‐acting, mPEGylated antagonist of gastric inhibitory polypeptide for obesity‐diabetes (diabesity) therapy
Authors: McClean P L , Irwin N , Hunter K , Gault V A , Flatt P R
Published: August 2008

Background and purpose:

Antagonism of the gastric inhibitory polypeptide (GIP) receptor with daily injection of proline‐3 gastric inhibitory polypeptide ((Pro3)GIP) can reverse or prevent many of the metabolic abnormalities associated with diet‐induced obesity‐diabetes (diabesity). This study has examined the ability of a novel and longer‐acting form of (Pro3)GIP, (Pro3)GIP mini‐polyethylene glycol ((Pro3)GIP[mPEG]), to counter diet‐induced diabesity in mice, using a daily and intermittent dosing regime.

Experimental approach:

We studied the actions of (Pro3)GIP[mPEG] at the GIP receptor in vitro and in vivo in both dietary and genetic diabesity.

Key results:

(Pro3)GIP[mPEG] was completely resistant to degradation by dipeptidyl peptidase IV. (Pro3)GIP[mPEG] inhibited GIP‐induced cAMP and insulin production in vitro. A greater and prolonged antagonism of GIP‐induced glucose‐lowering action was followed (Pro3)GIP[mPEG] administration, compared with (Pro3)GIP. In contrast with (Pro3)GIP, mice injected once every 3 days for 48 days with (Pro3)GIP[mPEG] displayed reduced body weight gain and hyperinsulinemia with improved glucose tolerance and insulin secretory responses, compared with high‐fat‐fed controls. Daily i.p. injection of (Pro3)GIP, (Pro3)GIP[mPEG] or (Pro3)GIP b.i.d. for 21 days also decreased body weight, circulating plasma insulin levels and improved glucose tolerance, compared with high‐fat controls. Plasma triglycerides were decreased by (Pro3)GIP[mPEG] and (Pro3)GIP b.i.d. treatment groups. The observed changes were accompanied by enhancement of insulin sensitivity in all treatment regimes. (Pro3)GIP[mPEG] was also effective over 16 days treatment of genetically obese‐diabetic ob/ob mice.

Conclusions and implications:

These data demonstrate the utility of GIP receptor antagonism for the treatment of diabesity and the potential offered by (Pro3)GIP[mPEG] as a long‐acting stable GIP receptor antagonist.

British Journal of Pharmacology (2008) 155, 690–701; doi:10.1038/bjp.2008.317; published online 11 August 2008
Native profiles of α1A‐adrenoceptor phenotypes in rabbit prostate
Authors: Su T‐H , Morishima S , Suzuki F , Yoshiki H , Anisuzzaman A S M , Tanaka T , Cheng J‐T , Muramatsu I
Published: August 2008

Background and purpose:

α1‐Adrenoceptors in the rabbit prostate have been studied because of their controversial pharmacological profiles in functional and radioligand binding studies. The purpose of the present study is to determine the native profiles of α1‐adrenoceptor phenotypes and to clarify their relationship.

Experimental approach:

Binding experiments with [3H]‐silodosin and [3H]‐prazosin were performed using intact tissue segments and crude membrane preparations of rabbit prostate and the results were compared with α1‐adrenoceptor‐mediated prostate contraction.

Key results:

[3H]‐Silodosin at subnanomolar concentrations bound specifically to intact tissue segments of rabbit prostate. However, [3H]‐prazosin at the same range of concentrations failed to bind to α1‐adrenoceptors of intact segments. Binding sites of [3H]‐silodosin in intact segments were composed of α1Lphenotype with low affinities for prazosin (pKi=7.1), 5‐methyurapidil andN‐[2‐(2‐cyclopropylmethoxyphenoxy)ethyl]‐5‐chloro‐α,α‐dimethyl‐1H‐indole‐3‐ethamine hydrochloride (RS‐17053), and α1A‐like phenotype with moderate affinity for prazosin (pKi=8.8) but high affinity for 5‐methyurapidil and RS‐17053. In contrast, both radioligands bound to a single population of α1‐adrenoceptors in the membrane preparations at the same density with a subnanomolar affinity, showing a typical profile of ‘classical’ α1A‐adrenoceptors (pKi for prazosin=9.8). The pharmacological profile of α1‐adrenoceptor‐mediated prostate contraction was in accord with the α1Lphenotype observed by intact segment binding approach.

Conclusions and implications:

Three distinct phenotypes (α1Land α1A‐like phenotypes in the intact segments and a classical α1Aphenotype in the membranes) with different affinities for prazosin were detected in rabbit prostate. It appears that the three phenotypes are phenotypic subtypes of α1A‐adrenoceptors, but are not genetically different subtypes.

British Journal of Pharmacology(2008)155, 906–912; doi:10.1038/bjp.2008.318; published online 11 August 2008
Kallikrein inhibitors limit kinin B2antagonist‐induced progression of oedematous to haemorrhagic pancreatitis in rats
Authors: Griesbacher T , Rainer I , Tiran B , Peskar B A
Published: August 2008

Background and purpose:

Exocrine hyperstimulation with caerulein is an established model for oedematous acute pancreatitis. Prevention of oedema formation by bradykinin B2receptor antagonists induces a progression to a haemorrhagic course in this model. We have investigated whether increased kallikrein activity in the pancreas is responsible for vascular damage and whether this could be prevented by selective kallikrein inhibitors.

Experimental approach:

Caerulein was infused i.v. and vascular damage was assessed by histological evaluation and determination of haemoglobin accumulation in the tissue. In addition, oedema formation, tissue and plasma kallikrein (PK) activities and the endogenous kallikrein inhibitors α1‐antitrypsin (α1‐AT) and α2‐macroglobulin (α2‐M) were measured.

Key results:

Haemorrhagic lesions induced by icatibant in caerulein‐induced pancreatitis were associated with a reduction in α1‐AT and α2‐M in the pancreas and a concomitant augmentation of tissue kallikrein (TK) activity. The TK inhibitor VA999024 (previously FE999024), or its combination with the PK inhibitor VA999026 (previously FE999026), inhibited oedema formation to the same extent but did not induce vascular damage. Furthermore, VA999024 inhibited TK activity. When icatibant was combined with VA999024 and VA999026, progression from oedematous to haemorrhagic pancreatitis was abolished.

Conclusions and implications:

Reduced oedema formation by B2antagonists prevented influx of endogenous kallikrein inhibitors and led to an excessive activity of kallikrein in the pancreas leading to vascular damage. This can be prevented by a combined inhibition of both tissue‐type and plasma‐type kallikrein. Kallikrein inhibitors thus should be further evaluated for their therapeutic potential in preventing haemorrhagic lesions in acute pancreatitis.

British Journal of Pharmacology(2008)155, 865–874; doi:10.1038/bjp.2008.321; published online 11 August 2008
Modulation of the anti‐nociceptive effects of 2‐arachidonoyl glycerol by peripherally administered FAAH and MGL inhibitors in a neuropathic pain model
Authors: Desroches J , Guindon J , Lambert C , Beaulieu P
Published: August 2008

Background and purpose:

There are limited options for the treatment of neuropathic pain. Endocannabinoids, such as anandamide and 2‐arachidonoyl glycerol (2‐AG), are promising pain modulators and there is recent evidence of interactions between anandamide and 2‐AG biosynthesis and metabolism. It has been clearly demonstrated that 2‐AG degradation is mainly catalysed not only by monoacylglycerol lipase (MGL) but also by a fatty acid amide hydrolase (FAAH). Inhibitors specifically targeting these two enzymes have also been described: URB602 and URB597, respectively. However, the anti‐nociceptive effects of the combination of peripherally injected 2‐AG, URB602 and URB597 in a neuropathic pain model have not yet been determined. This was performed in the presence or absence of cannabinoid CB1(AM251) and CB2(AM630) receptor antagonists.

Experimental approach:

Mechanical allodynia and thermal hyperalgesia were evaluated in 213 male Wistar rats allocated to 32 different groups. Drugs were injected subcutaneously in the dorsal surface of the hind paw (50 μL) 15 min before pain tests.

Key results:

2‐AG, URB602 and URB597 significantly decreased mechanical allodynia and thermal hyperalgesia with ED50 of 1.6±1.5 and 127±83 μg for 2‐AG and URB602, respectively. These effects were mediated locally and were mostly inhibited by the two cannabinoid antagonists.

Conclusions and implications:

The combination of the three compounds did not produce any greater anti‐allodynic or anti‐hyperalgesic effects, suggesting that FAAH inhibition could reduce or limit the anti‐nociceptive effects of 2‐AG. Peripheral administration of endocannabinoids or MGL/FAAH inhibitors is a promising analgesic approach requiring further investigation.

British Journal of Pharmacology(2008)155, 913–924; doi:10.1038/bjp.2008.322; published online 11 August 2008