bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating air‐sea fluxes of heat, freshwater, and momentum through global ocean data assimilation
Authors: Stammer D. , Ueyoshi K. , Köhl A. , Large W. G. , Josey S. A. , Wunsch C.
Published: May 2004

ECCO state estimation results from 10 years during the World Ocean Circulation Experiment are used to assess the quality of surface flux adjustments made to the initial NCEP re‐analysis‐1 products. During the state estimation procedure, surface fluxes are adjusted together with initial temperature and salinity conditions so that the model simulation becomes consistent with ocean observations. Independent estimates of the adjustments from bulk formula and regional field observations are also employed to evaluate the results. Buoyancy flux adjustments are found to be within the crude prior error bars on these fields. Outside the boundary current regions, they are consistent with known large‐scale deficiencies in the NCEP products. Wind stress adjustments are also everywhere within the prior error bars, but exhibit regional small‐scale features that reflect ocean model failures to resolve intense boundary currents. On large scales, the inferred adjustments to NCEP wind stress fields are consistent with inferences made from satellite wind stress measurements. Further improvements in the surface flux estimates obtained through state estimation procedures are anticipated as the estimation procedure becomes more complete by including the use of improved prior error covariance information, and as the ocean model becomes more skillful, for example, in simulating boundary currents by increasing its resolution.
Chemical transport model ozone simulations for spring 2001 over the western Pacific: Regional ozone production and its global impacts
Authors: Wild Oliver , Prather Michael J. , Akimoto Hajime , Sundet Jostein K. , Isaksen Ivar S. A. , Crawford James H. , Davis Douglas D. , Avery Melody A. , Kondo Yutaka , Sachse Glen W. , Sandholm Scott T.
Published: May 2004

The spatial and temporal variation in ozone production over major source regions in East Asia during the NASA Transport and Chemical Evolution over the Pacific (TRACE‐P) measurement campaign in spring 2001 is assessed using a global chemical transport model. There is a strong latitudinal gradient in ozone production in springtime, driven by regional photochemistry, which rapidly diminishes as the season progresses. The great variability in meteorological conditions characteristic of East Asia in springtime leads to large daily variability in regional ozone formation, but we find that it has relatively little impact on the total global production. We note that transport processes effectively modulate and thus stabilize total ozone production through their influence over its location. However, the impact on the global ozone burden, important for assessing the effects of precursor emissions on tropospheric oxidizing capacity and climate, is sensitive to local meteorology through the effects of location on chemical lifetime. Stagnant, anticyclonic conditions conducive to substantial boundary layer ozone production typically allow little lifting of precursors into the free troposphere where greater ozone production could occur, and the consequent shorter chemical lifetime for ozone leads to relatively small impacts on global ozone. Conversely, cyclonic conditions with heavy cloud cover suppressing regional ozone production are often associated with substantial cloud convection, enhancing subsequent production in the free troposphere where chemical lifetimes are longer, and the impacts on global ozone are correspondingly greater. We find that ozone formation in the boundary layer and free troposphere outside the region of precursor emissions dominates total gross production from these sources in springtime, and that it makes a big contribution to the long range transport of ozone, which is greatest in this season.
Microphysical modeling of the 1999–2000 Arctic winter: 3. Impact of homogeneous freezing on polar stratospheric clouds
Authors: Drdla K. , Browell E. V.
Published: May 2004

Simulations of the 1999–2000 winter have tested the effect on polar stratospheric clouds (PSCs) of the homogeneous freezing of liquid ternary solutions into nitric acid trihydrate (NAT) and nitric acid dihydrate (NAD). Proposed laboratory‐derived volume‐based and surface‐based homogeneous freezing rates have both been examined, including different assumptions about the extrapolation of laboratory measurements to atmospheric conditions. Widespread PSC formation and denitrification are possible in several of the scenarios examined. However, the simulations are all unable to explain the solid‐phase PSCs observed early in the 1999–2000 winter and are unable to reproduce the measured extent of vortex denitrification. These problems can both be attributed to the relatively cold temperatures, more than 5 K below the NAT condensation point, necessary for homogeneous freezing to be effective at producing solid‐phase PSCs. Therefore synoptic‐scale homogeneous freezing appears unlikely to be the primary mechanism responsible for solid‐phase PSC formation.
Simplification of a dust emission scheme and comparison with data
Authors: Shao Yaping
Published: May 2004

A simplification of a dust emission scheme is proposed, which takes into account of saltation bombardment and aggregates disintegration. The statement of the scheme is that dust emission is proportional to streamwise saltation flux, but the proportionality depends on soil texture and soil plastic pressure p. For small p values (loose soils), dust emission rate is proportional to u*4 (u* is friction velocity) but not necessarily so in general. The dust emission predictions using the scheme are compared with several data sets published in the literature. The comparison enables the estimate of a model parameter and soil plastic pressure for various soils. While more data are needed for further verification, a general guideline for choosing model parameters is recommended.
Factors regulating Shasta Lake (California) cold water accumulation, a resource for endangered salmon conservation
Authors: Nickel D. K. , Brett M. T. , Jassby A. D.
Published: May 2004

Shasta Lake, in northern California, has recently experienced reduced cold water storage, making it difficult to meet downstream temperature objectives for endangered winter‐run chinook salmon spawning habitat. This study used a novel form of time series analysis to examine the causes, timing, and predictability of cold water storage in Shasta Lake. This analysis detected two independent modes of variability in Shasta Lake cold water storage. The first mode, representing variability during February–July and describing 64% of the overall variability in cold water storage, was negatively correlated with both the preceding year's late summer hypolimnetic discharges and that spring's air temperatures. A second mode, representing December–January and describing an additional 24% of variability, was negatively correlated with Shasta Lake fall water temperatures and winter air temperatures and positively correlated with winter inflows. These results suggest hypolimnetic discharges, air and water temperatures, and inflows act in concert to determine cold water storage in Shasta Lake. These results also suggest water column mixing should be promoted during the cold midwinter period and thermal stratification should be promoted the remainder of the year to minimize surface warming of the entire water column.
Seasonal and successional streamflow response to forest cutting and regrowth in the northwest and eastern United States
Authors: Jones Julia A. , Post David A.
Published: May 2004

This study examined daily streamflow response over up to four decades in northwest conifer forest and eastern deciduous forest sites in the United States. We used novel methods to analyze daily observations of climate and streamflow spanning more than 900 basin years of record at 14 treated/control basin pairs where forest removal and regrowth experiments were underway in the period 1930–2002. In the 1 to 5‐year period after forest removal, maximum daily increases ranged from 2 to 3 mm at deciduous forest sites, to 6 to 8 mm at conifer forest sites. Significant spring surpluses persisted for up to 35 years in conifer forest basins, but winter and spring streamflow deficits appeared after 10 to 15 years of forest regrowth in eastern deciduous forest basins. In all 5‐yr posttreatment periods, absolute changes in daily streamflow were significantly more likely during moist, warm seasons, or during snowmelt seasons, but relative changes were more likely during warm seasons irrespective of moisture status. Both relative and absolute streamflow changes in the 1 to 5 and 15 to 25‐year periods after forest removal were significantly positively related to the age of the forest at the time it was cut. Eastern deciduous forests had been disturbed by logging or hurricane 12 to 56 years prior to forest removal, while Pacific Northwest conifer forests had been not experienced logging or wildfire for 90 to 450 years. Paired basin experiments provide a continuous, and continuously changing, record of vegetation structure, composition, and climate, and their effects on streamflow.
Low‐frequency variability of the statistical moments of sea surface winds
Authors: Monahan Adam Hugh
Published: May 2004

Low‐frequency variability of the mean, standard deviation, and skewness of 6‐hourly zonal sea surface wind (u) is considered. It is found that, in general, the standard deviation of u decreases as the magnitude of the mean of u increases. Throughout most of the extratropics, the skewness of u decreases as the mean of u increases; in the tropics, the skewness of u is generally an increasing function of the mean. These relationships are explained using a simple stochastic boundary‐layer model with a nonlinear drag law.
Contemporaneous convective and collapsing eruptive dynamics: The transitional regime of explosive eruptions
Authors: Di Muro A. , Neri A. , Rosi M.
Published: May 2004

Two contrasting eruptive regimes have been classically postulated to describe the behavior of explosive eruptions: convective and collapsing. Early studies have recognized that many eruptions evolve from the first to the second regime and have assumed the existence of a sharp boundary between them. Consequently, the dynamics of such transition has never been investigated in detail. Here, we present results of integrated deposit analyses and numerical simulations which demonstrate univocally that both dynamics can, and often do, coexist for hours in a new intermediate transitional regime of explosive eruptions. The study elucidates the features of the new regime in terms of mass partitioning, pyroclastic current dynamics and interplay among convective and collapsing styles.
‘Reemergence’ areas of winter sea surface temperature anomalies in the world's oceans
Authors: Hanawa Kimio , Sugimoto Shusaku
Published: May 2004

Using datasets of sea surface temperature (SST), surface heat flux, upper ocean thermal data, and climatological temperature and salinity profiles, we try to detect ‘reemergence’ areas of winter SST anomalies in the world's oceans, and describe characteristics of these areas in terms of mixed layer depth (MLD), annual mean heat flux and properties of waters formed in winter mixed layer. Eventually, seven reemergence areas are found: four in the Northern Hemisphere and three in the southern Hemisphere. All areas have a large seasonal variation of MLD, and are the regions where annual mean heat fluxes are relatively small except for two regions in the Northern Hemisphere. In the viewpoint of water properties, it is found that these areas correspond to the mode water formation regions: subtropical mode waters of the Indian Ocean, South Pacific, South Atlantic, North Pacific and North Atlantic, and North Pacific central and North Atlantic subpolar mode waters.
Glacial deposits on the rim of a Hesperian‐Amazonian outflow channel source trough: Mangala Valles, Mars
Authors: Head James W. , Marchant David R. , Ghatan Gil J.
Published: May 2004

Mangala Valles, located in tropical regions of Mars, is interpreted to have formed by dike‐induced cracking of the cryosphere to produce a linear graben and catastrophic release of groundwater sequestered under hydrostatic pressure. Outpouring of water and downcutting led to erosion and widening of the graben to produce a trough. Patterns of ridges and lobes along the outer rims of the trough are interpreted to have formed primarily by local accumulations of snow and ice on the graben rim (derived from exposed ponded groundwater in the graben), and glacial‐like outward flow of ice lobes resulting in development of moraines and tills along the north and south rims of the trough. These observations and interpretations support the concept that the climate of Mars was a hyper‐arid cold polar‐like desert similar to today in the Late Hesperian‐Early Amazonian period.
Expression of Concern: Carrageenan‐induced mouse paw oedema is biphasic, age‐weight dependent and displays differential nitric oxide cyclooxygenase‐2 expression
Authors: Posadas Inmaculada , Bucci Mariarosaria , Roviezzo Fiorentina , Rossi Antonietta , Parente Luca , Sautebin Lidia , Cirino Giuseppe
Published: May 2004

Injection of carrageenan 1% (50 μl) in the mouse paw causes a biphasic response: an early inflammatory response that lasts 6 h and a second late response that peaks at 72 h, declining at 96 h. Only mice 7‐ or 8‐week old, weighing 32–34 g, displayed a consistent response in both phases.

In 8‐week‐old mice, myeloperoxidase (MPO) levels are significantly elevated in the early phase at 6 h and reach their maximum at 24 h to decline to basal value at 48 h. Nitrate+nitrite (NOx) levels in the paw are maximal after 2 h and slowly decline thereafter in contrast to prostaglandin E2 levels that peak in the second phase at the 72 h point.

Western blot analysis showed that inducible nitric oxide synthase (iNOS) is detectable at 6 h and cyclooxygenase 2 (COX‐2) at 24 h point, respectively. Analysis of endothelial nitric oxide synthase (eNOS), iNOS and COX‐2 expression at 6 and 24 h in 3–8‐week‐old mice demonstrated that both eNOS and iNOS expressions are dependent upon the age–weight of mice, as opposite to COX‐2 that is present only in the second phase of the oedema and is not linked to mouse age–weight.

Subplantar injection of carrageenan to C57BL/6J causes a biphasic oedema that is significantly reduced by about 20% when compared to CD1 mice. Interestingly, in these mice, iNOS expression is absent up to 6 h, as opposite to CD1, and becomes detectable at the 24 h point. Cyclooxygenase (COX‐1) expression is upregulated between 4 and 24 h after carrageenan injection, whereas in CD1 mice COX‐1 remains unchanged after irritant agent injection. MPO levels are maximal at the 24 h point and they are significantly lower, at 6 h point, than MPO levels detected in CD1 mice.

In conclusion, mouse paw oedema is biphasic and age‐weight dependent. The present results are the first report on the differential expressions of eNOS, iNOS, COX‐1 and COX‐2 in response to carrageenan injection in the two phases of the mouse paw oedema.

British Journal of Pharmacology (2004) 142, 331–338. doi:10.1038/sj.bjp.0705650
Methylamine, but not ammonia, is hypophagic in mouse by interaction with brain Kv1.6 channel subtype
Authors: Pirisino Renato , Ghelardini Carla , Pacini Alessandra , Galeotti Nicoletta , Raimondi Laura
Published: May 2004

Ammonia and methylamine (MET) are endogenous compounds increased during liver and renal failure, Alzheimer's disease, vascular dementia and diabetes, where they alter some neurobehavioural functions probably acting as potassium channel blockers.

We have already described that potassium channel blockers including tetraethylammonium (TEA), ammonia and MET are hypophagic in mice. Antisense oligonucleotides (aODNs) against Shaker‐like Kv1.1 gene abolished the effect of TEA but not of ammonia and MET.

The central effects elicited in fasted mice by ammonia and MET were further studied. For MET, an ED50 value 71.4±1.8 nmol mouse−1 was calculated. The slope of the dose–response curves for these two compounds and the partial hypophagic effect elicited by ammonia indicated a different action mechanism for these amines.

The aODNs pretreatments capable of temporarily reducing the expression of all seven known subtypes of Shaker‐like gene or to inactivate specifically the Kv1.6 subtype abolished the hypophagic effect of MET but not that of ammonia.

Reverse transcription–polymerase chain reaction, Western blot and immunohistochemical results indicate that a full expression in the brain of Kv1.6 is required only for the activity of MET, and confirms the different action mechanism of ammonia and MET.

British Journal of Pharmacology (2004) 142, 381–389. doi:10.1038/sj.bjp.0705740
Schaffer collateral and perforant path inputs activate different subtypes of NMDA receptors on the same CA1 pyramidal cell
Authors: Arrigoni Elda , Greene Robert W
Published: May 2004

The two major inputs to CA1 pyramidal neurons, the perforant pathway (PP) that terminates on distal dendrites and the Schaffer collaterals (SCH) that terminate on proximal dendrites, activate both AMPA and N‐methyl‐D‐aspartate (NMDA) receptors.

In an in vitro slice preparation, the pharmacologically isolated NMDA receptor‐mediated excitatory postsynaptic currents (EPSCs) (NMDA‐EPSCs) of either pathway can be selectively activated onto a single CA1 pyramidal neuron.

Analysis of the decay phase of PP and SCH NMDA‐EPSCs revealed no significant difference in their time constants, suggesting no apparent different distribution in NR2‐subunit composition in the NMDA receptors (NMDAR) activated by the two synaptic inputs.

However, application of the NR2B‐selective antagonist, ifenprodil, differently affected the NMDA‐EPSCs activated by the PP and SCH inputs. The reduction of the PP responses was only 30% compared to 75% for the SCH responses.

In addition, for both pathways, the ifenprodil‐insensitive component of the NMDA‐EPSCs had significantly more rapid decay kinetics than those prior to application of ifenprodil.

Our results show a greater NR2B subunit contribution to the NMDA component of the SCH EPSC, compared to the NMDA component of the PP EPSC and that in single CA1 pyramidal neurons NMDA composition is anatomically specific to the afferent input.

British Journal of Pharmacology (2004) 142, 317–322. doi:10.1038/sj.bjp.0705744
Simultaneous central nervous system distribution and pharmacokinetic–pharmacodynamic modelling of the electroencephalogram effect of norfloxacin administered at a convulsant dose in rats
Authors: Chenel Marylore , Marchand Sandrine , Dupuis Antoine , Lamarche Isabelle , Paquereau Joël , Pariat Claudine , Couet William
Published: May 2004

The objective of this study was to investigate the contribution of norfloxacin blood–brain barrier (BBB) transport to its delayed electroencephalogram (EEG) effect in rats.

Norfloxacin was injected as a bolus dose of 150 mg kg−1. Blood samples were collected for total norfloxacin plasma concentration measurements. The corresponding unbound levels were determined in brain extracellular fluid (ECF) using microdialysis. Quantitative EEG recording was conducted during 9 h post‐dose.

Brain ECF norfloxacin concentrations were much lower than plasma levels (AUC ratio=9.7±2.8%) but peaked very early, and concentration versus time profiles were parallel in both biological fluids. The best pharmacokinetic (PK) modelling was obtained by considering that ECF concentrations were part of the central compartment, with a proportionality factor. The peak of EEG effect was delayed and the effect versus plasma concentration curves exhibited a dramatic hysteresis. A PK–pharmacodynamic (PD) effect compartment model with a spline function to describe the relationship between effect and concentration at the effect site successfully described the data.

Comparisons of PK–PD parameters estimated from plasma and ECF concentrations show that most of the delayed norfloxacin EEG effect is not due to BBB transport, but also that PD parameters derived from plasma data must be carefully interpreted when drug distribution at the effect site is restricted, as may often be the case for centrally acting drugs.

British Journal of Pharmacology (2004) 142, 323–330. doi:10.1038/sj.bjp.0705748
Involvement of histamine H4 and H1 receptors in scratching induced by histamine receptor agonists in BalbC mice
Authors: Bell J K , McQueen D S , Rees J L
Published: May 2004

The role of histamine H1, H2, H3 and H4 receptors in acute itch induced by histamine was investigated in female BalbC mice. Scratching was induced by intradermal injections of pruritogen into the back of the neck and ‘itch’ assessed by quantifying the scratching evoked.

Histamine (0.03–80 μmol), histamine‐trifluoromethyl‐toluidine (HTMT, H1 agonist, 0.002–2 μmol), clobenpropit (H4 agonist, H3 antagonist, 0.002–0.6 μmol) and to a lesser extent imetit (H3/H4 agonist, 0.03–3 μmol) all induced dose‐dependent scratching. Dimaprit (H2 agonist, 0.04–40 μmol) did not cause scratching.

Mepyramine (H1 antagonist, 20 mg kg−1, i.p.) reduced scratching evoked by histamine and HTMT, but not that caused by H3 or H4 agonists. Thioperamide (H3/H4 antagonist, 20 mg kg−1, i.p.) reduced scratching induced by histamine, H3 and H4 agonists, but not that caused by HTMT. The non‐sedating H1 antagonist, terfenadine, also significantly reduced the scratching induced by the H1 agonist, HTMT. Cimetidine (H2 antagonist, 20 mg kg−1, i.p.) did not affect histamine‐induced scratching.

These results indicate that activation of histamine H4 receptors causes itch in mice, in addition to the previously recognised role for H1 receptors in evoking itch. Histamine H4 receptor antagonists therefore merit investigation as antipruritic agents.

British Journal of Pharmacology (2004) 142, 374–380. doi:10.1038/sj.bjp.0705754
Differential regulation of calcium homeostasis in adenocarcinoma cell line A549 and its Taxol‐resistant subclone
Authors: Padar Shanthala , Van Breemen Cornelis , Thomas David W , Uchizono James A , Livesey John C , Rahimian Roshanak
Published: May 2004

Drug resistance is a fundamental problem in cancer chemotherapy. Intracellular calcium concentration ([Ca2+]i) may play a role in the development of chemoresistance. We investigated the regulatory role of [Ca2+]i in Taxol resistance in the non‐small‐cell lung cancer cell line A549 and its chemoresistant subclone A549‐T24.

Measurement of cytosolic calcium ([Ca2+]c) in single cells and cell populations revealed similar levels of basal calcium in the two cell lines. However, a reduced response to thapsigargin (a sarcoplasmic/endoplasmic reticulum Ca2+‐ATPase (SERCA) inhibitor) in A549‐T24 cells compared to the parent cell line suggested a lower ER Ca2+ content in these cells.

mRNA expression of SERCA2b and SERCA3, major Ca2+ pumps involved in ER Ca2+ homeostasis, did not significantly differ between the two cell lines, as revealed by RT–PCR.

An altered calcium influx pathway in the Taxol‐resistant cell line was observed. Modulation of the ER calcium pools using CMC (4‐chloro‐m‐cresol) and ATP revealed lower ryanodine receptor (RyR) and IP3 receptor (IP3R)‐sensitive Ca2+ stores in the chemoresistant cell line.

Western blot and RT–PCR studies suggested that A549‐T24 cells expressed higher levels of the antiapoptotic protein Bcl‐2 and the calcium‐binding protein sorcin, respectively, in comparison to the parent cell line. Both of these proteins have been previously implicated in chemoresistance, in part, due to their ability to modulate [Ca2+]i.

These results suggest that altered intracellular calcium homeostasis may contribute to the Taxol‐resistant phenotype.

British Journal of Pharmacology (2004) 142, 305–316. doi:10.1038/sj.bjp.0705755
Pharmacological characterization of canine bradykinin receptors in prostatic culture and in isolated prostate
Authors: Srinivasan Dinesh , Burbach Leah R , Daniels Donald V , Ford Anthony P D W , Bhattacharya Anindya
Published: May 2004

The objective of this study was to characterize pharmacologically bradykinin (Arg‐Pro‐Pro‐Gly‐Phe‐Ser‐Pro‐Phe‐Arg, BK) receptors in the canine prostate.

Primary cultures of canine prostate stromal (PS) and epithelial cells (PE) were established and then characterized using cell‐specific antibodies (actin, vimentin and cytokeratin). Cultured cells were assayed for BK receptors using fluorometric imaging plate reader assays. In addition, isolated strips of the canine prostate were studied for BK‐induced isometric contraction.

PS cells were labeled only with anti‐actin and ‐vimentin antibodies, while the anti‐cytokeratin antibodies labeled only the PE cells.

In cultured prostate cells, the BK receptor 2 (B2)‐preferring agonist BK induced mobilization of intracellular Ca2+ in a concentration‐dependent manner with potencies (log[EC50]∣PE, pEC50) of 8.72±0.12 in PS and 8.75±0.06 in PE cells. In contrast, the BK receptor 1 (B1)‐selective agonist [des‐Arg9]BK (Arg‐Pro‐Pro‐Gly‐Phe‐Ser‐Pro‐Phe) did not elicit any significant effect (pEC50<5) on Ca2+ responses.

BK agonism (10 nM) was inhibited by HOE‐140 (D‐arginyl‐L‐arginyl‐L‐prolyl‐trans‐4‐hydroxy‐L‐prolylglycyl‐3‐(2‐thienyl)‐L‐alanyl‐L‐seryl‐D‐1,2,3,4‐tetrahhydro‐3‐isoquinolinecarbonyl‐L‐(2a,3b,7ab)‐octahydro‐1H‐indole‐2‐carbonyl‐L‐arginine), a B2‐selective antagonist, with a log[IC50] (pIC50) of 8.11±0.19 and 9.23±0.20 in PS and PE cells, respectively. [des‐Arg10]HOE‐140 (D‐arginyl‐L‐arginlyl‐L‐prolyl‐trans‐4‐hydroxy‐L‐prolylglycyl‐3‐(2‐thienyl)‐L‐alanyl‐L‐seryl‐D‐1,2,3,4‐tetrahydro‐3‐isoquinolinecarbonyl‐L‐(2a, 3b,7ab)‐octahydro‐1H‐indole‐2‐carbonyl), a B1‐selective antagonist, displayed weak antagonism with pIC50 values of 4.87±0.23 and 6.38±0.16 in PS and PE cells, respectively.

Isolated tissue strips of the canine prostate contracted to BK (10 μM) but not to [des‐Arg9]BK (10 μM). BK‐induced contractility was attenuated by HOE‐140 (1 μM).

In conclusion, canine prostates express functional B2 receptors, with no apparent B1 receptor subtypes.

British Journal of Pharmacology (2004) 142, 297–304. doi:10.1038/sj.bjp.0705757
Correlation between brain bradykinin receptor binding sites and cardiovascular function in young and adult spontaneously hypertensive rats
Authors: Cloutier Frank , Ongali Brice , Campos Maria M , Thibault Gaétan , Neugebauer Witold , Couture Réjean
Published: May 2004

Intracerebroventricular (i.c.v.) effects of bradykinin (BK) B1and B2receptor agonists and antagonists were assessed on mean arterial blood pressure (MAP) and heart rate (HR) in awake unrestrained spontaneously hypertensive rats (SHR, aged of 8 and 16 weeks) and age‐matched Wistar Kyoto rats (WKY). Quantitativein vitroautoradiographic studies were also performed on the brain of both strains with specific radioligands for B2receptors [125I]HPP‐Hoe 140 and B1receptors [125I]HPP‐des‐Arg10and Hoe140.

MAP increased linearly with doses of BK (81–8100 pmol) and the amplitudes were significantly greater in SHR, particularly at 16 weeks. While BK evoked a negative linear trend on HR (bradycardia) in WKY, a positive one (tachycardia) was observed in adult SHR. In both strains, BK‐induced pressor response was blocked by equimolar doses of B2receptor antagonist,D‐Arg‐[Hyp3, Thi5,D‐Tic7, Oic8]‐BK (Hoe 140), but not by B1receptor antagonist, AcLys[D‐βNal7, Ile8]des‐Arg9‐BK (R‐715).

B1receptor agonists (Sar‐[D‐Phe8]‐des‐Arg9‐BK, des‐Arg9‐BK, des‐Arg10‐Kallidin) and antagonist (R‐715 alone or with Hoe 140) had no or marginal effect on MAP and HR at doses up to 8100 pmol in SHR and WKY.

Higher densities of specific [125I]HPP‐Hoe 140 labelling were found in discrete brain areas of SHR, especially in regions associated with cardiovascular function. Low levels of [125I]HPP‐[des‐Arg10]‐Hoe140 binding sites were seen in WKY and SHR, yet densities were significantly greater in midbrain and cortical regions of SHR aged of 16 weeks. Contrary to SHR, ageing caused a downregulation of B2and B1receptor binding sites in specific brain nuclei in WKY.

It is concluded that the hypersensitivity of the pressor response to i.c.v. BK in SHR occurs during both the early and established phases of hypertension in parallel with the enhancement of B2receptor binding sites in various cardiovascular brain centres. In contrast, brain B1receptors do not seem to participate in the central pressor effects of kinins nor in the maintenance of hypertension in SHR.

British Journal of Pharmacology(2004)142, 285–296. doi:10.1038/sj.bjp.0705759
Left regional cardiac perfusion in vitro with platelet‐activating factor, norepinephrine and K+ reveals that ischaemic arrhythmias are caused by independent effects of endogenous ‘mediators’ facilitated by interactions, and moderated by paradoxical antagonism
Authors: Baker Kathryn E , Curtis Michael J
Published: May 2004

Various putative drug targets for suppression of ischaemia‐induced ventricular fibrillation (VF) have been proposed, but therapeutic success in the suppression of sudden cardiac death (SCD) has been disappointing. Platelet‐activating factor (PAF) is a known component of the ischaemic milieu. We examined its arrhythmogenic activity, and its interaction with two other putative mediators, norepinephrine and K+, using an ischaemia‐free in vitro heart bioassay, and a specific PAF antagonist (BN‐50739).

PAF (0.1–100 nmol) was administered selectively to the left coronary bed of rat isolated hearts using a specially designed catheter. In some hearts, PAF was administered to the left coronary bed during concomitant regional perfusion with norepinephrine and/or K+. In separate studies, PAF accumulation in the perfused cardiac tissue was evaluated using 3H‐PAF.

PAF evoked ventricular arrhythmias concentration‐dependently (P<0.05). It also widened QT interval and reduced coronary flow selectively in the PAF‐exposed left coronary bed (both P<0.05). Two exposures of hearts to PAF were necessary to evoke the QT and rhythm effects.

The PAF‐induced arrhythmias and coronary vasoconstriction were partially suppressed by the PAF antagonist BN‐50739 (10 μM), although BN‐50739 itself widened QT interval.

K+ (8 and 15 mM) unexpectedly antagonised the arrhythmogenic effects of PAF without itself eliciting arrhythmias (P<0.05). Norepinephrine (0.1 μM) had little or no effect on the actions of PAF, while failing to evoke arrhythmias itself. Nevertheless, the combination of 15 mM K+ and 0.1 μM norepinephrine evoked arrhythmias of a severity similar to arrhythmias evoked by PAF alone, without adding to or diminishing the arrhythmogenic effects of PAF.

3H‐PAF accumulated in the cardiac tissue, with 43±5% still present 5 min after bolus administration, accounting for the need for two exposures of the heart to PAF for evocation of arrhythmias.

Thus, PAF, by activating specific receptors in the ventricle, can be expected to contribute to arrhythmogenesis during ischaemia. However, its interaction with other components of the ischaemic milieu is complex, and selective block of its actions (or its accumulation) in the ischaemic milieu is alone unlikely to reduce VF/SCD.

British Journal of Pharmacology (2004) 142, 352–366. doi:10.1038/sj.bjp.0705767
Measuring reactive species and oxidative damagein vivoand in cell culture: how should you do it and what do the results mean?
Authors: Halliwell Barry , Whiteman Matthew
Published: May 2004

Free radicals and other reactive species (RS) are thought to play an important role in many human diseases. Establishing their precise role requires the ability to measure them and the oxidative damage that they cause.

This article first reviews what is meant by the terms free radical, RS, antioxidant, oxidative damage and oxidative stress.

It then critically examines methods used to trap RS, including spin trapping and aromatic hydroxylation, with a particular emphasis on those methods applicable to human studies.

Methods used to measure oxidative damage to DNA, lipids and proteins and methods used to detect RS in cell culture, especially the various fluorescent ‘probes’ of RS, are also critically reviewed.

The emphasis throughout is on the caution that is needed in applying these methods in view of possible errors and artifacts in interpreting the results.

British Journal of Pharmacology(2004)142, 231–255. doi:10.1038/sj.bjp.0705776
Cannabinoid receptor‐independent actions of the aminoalkylindole WIN 55,212‐2 on trigeminal sensory neurons
Authors: Price Theodore J , Patwardhan Amol , Akopian Armen N , Hargreaves Kenneth M , Flores Christopher M
Published: May 2004

The prototypical aminoalkylindole cannabinoid WIN 55,212‐2 (WIN‐2) has been shown to produce antihyperalgesia through a peripheral mechanism of action. However, it is not known whether WIN‐2 exerts this action directly via cannabinoid receptors located on primary afferents or if other, perhaps indirect or noncannabinoid, mechanisms are involved. To address this question, we have examined the specific actions of WIN‐2 on trigeminal ganglion (TG) neurons in vitro by quantifying its ability to modulate the evoked secretion of the proinflammatory neuropeptide CGRP as well as the inflammatory mediator‐induced generation of cAMP.

WIN‐2 evoked CGRP release from TG neurons in vitro (EC50=26 μM) in a concentration‐ and calcium‐dependent manner, which was mimicked by the cannabinoid receptor‐inactive enantiomer WIN 55,212‐3 (WIN‐3). Moreover, WIN‐2‐evoked CGRP release was attenuated by the nonselective cation channel blocker ruthenium red but not by the vanilloid receptor type 1 (TRPV1) antagonist capsazepine, suggesting that, unlike certain endogenous and synthetic cannabinoids, WIN‐2 is not a TRPV1 agonist but rather acts at an as yet unidentified cation channel.

The inhibitory effects of WIN‐2 on TG neurons were also examined. WIN‐2 neither inhibited capsaicin‐evoked CGRP release nor did it inhibit forskolin‐, isoproteranol‐ or prostaglandin E2‐stimulated cAMP accumulation.

On the other hand, WIN‐2 significantly inhibited (EC50=1.7 μM) 50 mM K+‐evoked CGRP release by approximately 70%. WIN‐2 inhibition of 50 mM K+‐evoked CGRP release was not reversed by antagonists of cannabinoid type 1 (CB1) receptor, but was mimicked in magnitude and potency (EC50=2.7 μM) by its cannabinoid‐inactive enantiomer WIN‐3.

These findings indicate that WIN‐2 exerts both excitatory and inhibitory effects on TG neurons, neither of which appear to be mediated by CB1, CB2 or TRPV1 receptors, but by a novel calcium‐dependent mechanism. The ramifications of these results are discussed in relation to our current understanding of cannabinoid/vanilloid interactions with primary sensory neurons.

British Journal of Pharmacology (2004) 142, 257–266. doi:10.1038/sj.bjp.0705778
Selective modulation of noradrenaline release by α2‐adrenoceptor blockade in the rat‐tail artery in vitro
Authors: Brock James A , Tan Joy H C
Published: May 2004

The effects of blocking α2‐adrenoceptors on noradrenaline (NA) and adenosine 5′‐triphosphate (ATP) release from postganglionic sympathetic nerves have been investigated in rat‐tail artery in vitro. Continuous amperometry was used to measure NA release and intracellularly recorded excitatory junction potentials (e.j.p.'s) were used to measure ATP release.

Application of the α2‐adrenoceptor antagonist, idazoxan (1 μM), increased the amplitude of NA‐induced oxidation currents evoked by trains of 10 stimuli at 1 and 10 Hz.

In cells deep in the media, idazoxan (1 μM) had no effect on the amplitude of e.j.p.'s evoked by trains of 10 stimuli at 1 and 10 Hz. In cells close to the adventitial – medial border, idazoxan produced a small increase in the amplitude of e.j.p.'s evoked at the end of trains of 10 stimuli at 1 Hz.

In tissues pretreated with the neuronal NA uptake inhibitor, desmethylimpramine (0.3 μM), idazoxan (1 μM) markedly increased the amplitude of e.j.p.'s in cells deep in the media.

The α2‐adrenoceptor agonist, clonidine (0.5 μM), produced similar reductions in the amplitudes of both NA‐induced oxidation currents and e.j.p.'s evoked by 10 stimuli at 1 Hz. These effects of clonidine were reversed by the subsequent addition of idazoxan (1 μM).

The release of both NA and ATP is inhibited to a similar extent by activation of prejunctional α2‐adrenoceptors by clonidine. In contrast, endogenously released NA more markedly inhibits NA release. These findings provide further support for the differential modulation of NA and ATP release.

British Journal of Pharmacology (2004) 142, 267–274. doi:10.1038/sj.bjp.0705779
A Pivot-Based Routine for Improved Parent-Finding in Hybrid MDS
Authors: Morrison Alistair , Chalmers Matthew
Published: May 2004

The problem of exploring or visualising data of high dimensionality is central to many tools for information visualisation. Through representing a data set in terms of inter-object proximities, multidimensional scaling may be employed to generate a configuration of objects in low-dimensional space in such a way as to preserve high-dimensional relationships. An algorithm is presented here for a heuristic hybrid model for the generation of such configurations. Building on a model introduced in 2002, the algorithm functions by means of sampling, spring model and interpolation phases. The most computationally complex stage of the original algorithm involved the execution of a series of nearest-neighbour searches. In this paper, we describe how the complexity of this phase has been reduced by treating all high-dimensional relationships as a set of discretised distances to a constant number of randomly selected items: pivots. In improving this computational bottle-neck, the algorithmic complexity is reduced from O( N√N) to O( N5/4). As well as documenting this improvement, the paper describes evaluation with a data set of 108,000 13-dimensional items and a set of 23,141 17-dimensional items. Results illustrate that the reduction in complexity is reflected in significantly improved run times and that no negative impact is made upon the quality of layout produced.
Integrated modeling of clinical and gene expression information for personalized prediction of disease outcomes
Authors: Pittman Jennifer , Huang Erich , Dressman Holly , Horng Cheng-Fang , Cheng Skye H. , Tsou Mei-Hua , Chen Chii-Ming , Bild Andrea , Iversen Edwin S. , Huang Andrew T. , Nevins Joseph R. , West Mike
Published: May 2004

We describe a comprehensive modeling approach to combining genomic and clinical data for personalized prediction in disease outcome studies. This integrated clinicogenomic modeling framework is based on statistical classification tree models that evaluate the contributions of multiple forms of data, both clinical and genomic, to define interactions of multiple risk factors that associate with the clinical outcome and derive predictions customized to the individual patient level. Gene expression data from DNA microarrays is represented by multiple, summary measures that we term metagenes; each metagene characterizes the dominant common expression pattern within a cluster of genes. A case study of primary breast cancer recurrence demonstrates that models using multiple metagenes combined with traditional clinical risk factors improve prediction accuracy at the individual patient level, delivering predictions more accurate than those made by using a single genomic predictor or clinical data alone. The analysis also highlights issues of communicating uncertainty in prediction and identifies combinations of clinical and genomic risk factors playing predictive roles. Implicated metagenes identify gene subsets with the potential to aid biological interpretation. This framework will extend to incorporate any form of data, including emerging forms of genomic data, and provides a platform for development of models for personalized prognosis.
The statistical structure of natural light patterns determines perceived light intensity
Authors: Yang Zhiyong , Purves Dale
Published: May 2004

The same target luminance in different contexts can elicit markedly different perceptions of brightness, a fact that has long puzzled vision scientists. Here we test the proposal that the visual system encodes not luminance as such but rather the statistical relationship of a particular luminance to all possible luminance values experienced in natural contexts during evolution. This statistical conception of vision was validated by using a database of natural scenes in which we could determine the probability distribution functions of co-occurring target and contextual luminance values. The distribution functions obtained in this way predict target brightness in response to a variety of challenging stimuli, thus explaining these otherwise puzzling percepts. That brightness is determined by the statistics of natural light patterns implies that the relevant neural circuitry is specifically organized to generate these probabilistic responses.
Neuroprotectin D1: A docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress
Authors: Mukherjee Pranab K. , Marcheselli Victor L. , Serhan Charles N. , Bazan Nicolas G.
Published: May 2004

Docosahexaenoic acid (DHA) is a lipid peroxidation target in oxidative injury to retinal pigment epithelium (RPE) and retina. Photoreceptor and synaptic membranes share the highest content of DHA of all cell membranes. This fatty acid is required for RPE functional integrity; however, it is not known whether specific mediators generated from DHA contribute to its biological significance. We used human ARPE-19 cells and demonstrated the synthesis of 10,17S-docosatriene [neuroprotectin D1 (NPD1)]. This synthesis was enhanced by the calcium ionophore A-23187, by IL-1β, or by supplying DHA. Under these conditions, there is a time-dependent release of endogenous free DHA followed by NPD1 formation, suggesting that phospholipase A2releases the mediator's precursor. Added NPD1 potently counteracted H2O2/tumor necrosis factor α oxidative-stress-triggered apoptotic RPE DNA damage. NPD1 also up-regulated the antiapoptotic proteins Bcl-2 and Bcl-xLand decreased proapoptotic Bax and Bad expression. Moreover, NPD1 (50 nM) inhibited oxidative-stress-induced caspase-3 activation. NPD1 also inhibited IL-1β-stimulated expression of cyclooxygenase 2 promoter transfected into ARPE-19 cells. Overall, NPD1 protected RPE cells from oxidative-stress-induced apoptosis, and we predict that it will similarly protect neurons. This lipid mediator therefore may indirectly contribute to photoreceptor cell survival as well. Because both RPE and photoreceptor cells die in retinal degenerations, our findings contribute to the understanding of retinal cell survival signaling and potentially to the development of new therapeutic strategies.
Lack of intraspecific biological variation between two geographical populations of Oomyzus sokolowskii (Hymenoptera: Eulophidae), a gregarious larval–pupal parasitioid of Plutella xylostella (Lepidoptera: Plutellidae)
Authors: Mahmood A.R. , Liu S.S. , Shi Z.H. , Song X.H. , Zalucki M.P.
Published: May 2004

The chalcid, Oomyzus sokolowskii Kurdjumov has been recorded in many parts of the world as a major larval–pupal, gregarious endoparasitoid of the diamondback moth, Plutella xylostella (Linnaeus), a serious pest of brassica vegetable crops worldwide. This study investigated intraspecific variation between two populations of O. sokiolowskii, one from Cape Verde Islands, West Africa and the other from Hangzhou, China. In all crosses and backcrosses between the two geographical populations, the numbers of progeny and sex ratio of progeny were similar to those obtained within each of the populations, demonstrating complete reproductive compatibility between the two populations. The two populations showed similar responses to temperature with respect to development time and survival of immature stages. Observations on the interactions between the two O. sokolowskii populations and Cotesia plutellae (Kurdjumov), another major parasitoid of P. xylostella, showed that neither population could achieve successful parasitism of P. xylostella larvae already parasitized by C. plutellae. However, both O. sokolowskii populations could achieve hyperparasitism by ovipositing into a mid-late stage larva of C. plutellae developing inside the primary host. Contrary to earlier reports, no evidence of intraspecific variations in ability to hyperparasitize between these two populations of O. sokolowskii was found.
Recent advances in transgenic arthropod technology
Authors: Kramer M.G.
Published: May 2004

The ability to insert foreign genes into arthropod genomes has led to a diverse set of potential applications for transgenic arthropods, many of which are designed to advance public health or improve agricultural production. New techniques for expressing foreign genes in arthropods have now been successfully used in at least 18 different genera. However, advances in field biology are lagging far behind those in the laboratory, and considerable work is needed before deployment in nature can be a reality. A mechanism to drive the gene of interest though a natural population must be developed and thoroughly evaluated before any field release, but progress in this area has been limited. Likewise, serious consideration of potential risks associated with deployment in nature has been lacking. This review gives an overview of the most promising techniques for expressing foreign genes in arthropods, considers the potential risks associated with their deployment, and highlights the areas of research that are most urgently needed for the field to advance out of the laboratory and into practice.
An aerial netting study of insects migrating at high altitude over England
Authors: Chapman J.W. , Reynolds D.R. , Smith A.D. , Smith E.T. , Woiwod I.P.
Published: May 2004

Day and night sampling of windborne arthropods at a height of 200 m above ground was undertaken at Cardington, Bedfordshire, UK, during July 1999, 2000 and 2002, using a net supported by a tethered balloon. The results from this study are compared with those from the classic aerial sampling programmes carried out by Hardy, Freeman and colleagues over the UK and North Sea in the 1930s. In the present study, aerial netting was undertaken at night as well as daytime, and so the diel periodicity of migration could be investigated, and comparisons made with the results from Lewis and Taylor’s extensive survey of flight periodicity near ground level. In some taxa with day-time emigration, quite large populations could continue in high-altitude flight after dark, perhaps to a previously underrated extent, and this would greatly increase their potential migratory range. Any trend towards increases in night temperatures, associated with global warming, would facilitate movements of this type in the UK. Observations on the windborne migration of a variety of species, particularly those of economic significance or of radar-detectable size, are briefly discussed.