bluuebunny/crossref_metadata_2025 huggingface dataset:
Perspectives on changes in early Roman Gaul
Authors: Wells Peter S.
Published: August 2008

Jan Slofstra and Greg Woolf have written very stimulating papers about the changing character of societies, and especially of their elites, in Interior Gaul and on the Rhine frontier. The contrast between these two regions provides a valuable arena for considering larger questions of change in Gaul, with emphasis on development of civic society in Central Gaul and of a militarised society on the frontier. I shall first comment on a few of the important issues that these papers raise, then suggest some additional and alternative ways of thinking about the problems. Woolf's discussion of cultural practice shows how this approach can help to focus future research on subjects related directly to the actual changes. His review of expressions of status differences in earlier circumstances, back into the early Iron Age, provides a useful long-term context for considering the changes that accompanied and followed the Roman conquest. The distinction he draws between the mainly public display of elite status in late Iron Age contexts, and more private displays in the Roman period, is important and merits further investigation. In Slofstra's paper, I find the discussion of the relationships between structure and agency very useful in this context. His emphasis on the interplay between the categories power, culture, and identity is highly pertinent. His explication of the differences in Roman policy and native reaction between pre-Augustan and post-Augustan times is instructive. The contrasting patterns he outlines between changes in Central Gaul and those on the Rhine frontier, and the three-level interpretation he presents for understanding the Batavian revolt, are valuable models for formulating future research strategies.
Making the most of historical Roman archaeology
Authors: Woolf Greg
Published: August 2008

Archaeological dialogues are not always genteel affairs. I have been very fortunate in the care with which the commentators have read my paper and the generosity with which they have responded to it. Collectively, their remarks raise more issues than I can adequately respond to in my turn.
Crossing boundaries
Authors: Laneri Nicola
Published: August 2008

Archaeology is not just about writing reports and interpreting ancient societies and their social structures, but it is also a process which should aim at the creation of a clear communicative message to the general public. Thus, archaeologists should be aware of every possible medium of communication – verbal, written, visual, sound – to express re-constructions of ancient pasts. In this essay I express some ideas about how archaeologists could collaborate with experts, for example theatre directors, in defining artistic way of communicating the past. Finally, I focus on the relationship between academia and fringe archaeology and I look into the political role of archaeologists in modern society.
The Invention Of Hunter-Gatherers in Seventeenth Century Europe? A Comment on Mark Pluciennik
Authors: Zvelebil Marek
Published: August 2008

Mark Pluciennik has presented us with an excellent and original piece of research. His conclusion that the current categorisation of pre-industrial societies into hunter-gatherers and farmers is, effectively, a modern invention represents a continuation of his earlier investigations into this subject (1998; 2001). He supports this conclusion with very convincing arguments, and offers a historically contingent explanation in terms of the coalescence of several ideological and economic ‘currents’ which, in the course of the seventeenth and eighteenth centuries, led to the establishment of a categorical distinction between ‘savage hunter-gatherers’ and ‘civilised farmers’. In my comment, I would like to focus on two issues, broadly following the structure of his paper: (1) in general terms, are we really dealing with yet another ‘invented tradition’, spawned by the need for an ideological justification for the supremacy of western capitalist ideology and economic order? (2) How do we categorise early farming, fishing, hunting and gathering communities in the past, if at all?
Enlightened Views of the Transition to Agriculture
Authors: Bogucki Peter
Published: August 2008

Mark Pluciennik has correctly pointed out that many of our current views of social and economic development in prehistory have their roots in the intellectual movement known as the Enlightenment during the seventeenth and eighteenth centuries. His critique focuses on the assignment of primacy to subsistence change as a way of dividing pre-state societies into meaningful categories. Although he and I probably approach archaeology from very different theoretical positions, I must confess that I have also marveled (privately) from time to time at the amount of attention that archaeologists pay to food-getting and consumption. This may be a bit surprising to the reader, since my research has been focused on early farming societies and my analytical specialty is the study of animal bones. Thus, it would be fair to conclude that I must have some intellectual stake in maintaining the conceptual distinction between foragers and farmers.
History Matters: A Reply
Authors: Pluciennik Mark
Published: August 2008

First of all let me wholeheartedly thank all those who have responded for their helpful comments and careful readings. In this reply I would like first to discuss points dealing with the history of concepts related to ‘hunter-gatherers’, before pursuing the implications for contemporary prehistories. One preliminary note: van de Velde and Bogucki both point to the many advantages of Enlightenment thought (or reason). There are many political and scientific reasons to concur. I certainly have no desire to throw out the baby with the bathwater and return to metaphysical speculation as a substitute for archaeological and historical practice. I would also like to respond directly to van de Velde's comments about Adam Kuper (1988). Kuper's book, though also a work of critical anthropological history, is concerned with the later nineteenth century onwards and the idea of ‘primitive society’ characterised by certain forms of social and religious organisation, rather than subsistence (Kuper 1988, 5–7). I have argued elsewhere (Pluciennik 2001, 744–746) that this is typical of certain nineteenth-century European anthropologists and highlights a moment of divergence between ethnologists and archaeologists. Van de Velde also queries the omission of the ‘noble savage’ strand of Enlightenment thought from the paper. Certainly the recognition that there could be markedly different societies was sometimes used to critique the perceived excesses and artifices of the writer's society or of ‘civilisation’ more generally (Berkhofer 1978, 72–80; Carey 1998). However I would argue generally that the ‘noble savage’ has tended to be a minority construct adopted for strategic rhetorical and literary purposes (even if there was a revival from the 1960s with the ecologically noble savage: Buege 1996). Indeed Ellingson (2001) has recently proposed that even the trope of the noble savage was largely a 19th century invention, a myth constructed by racists to provide a stick with which to beat ‘liberals’. I disagree, in that the image of ‘Others’ supposedly without the corruption and vices of modern civilisation has long been utilised to construct alternatives to contemporary conditions and to progressive social evolutionary scenarios, with foragers supplying ‘evidence’ of an Edenic place, a Golden Age past, or degenerative human histories.
Presentism and the LAW
Authors: Bernbeck Reinhard , Pollock Susan
Published: August 2008

We welcome the Lampeter Archaeology Workshop's (LAW) attempt to clarify the ways in which they understand relativism in post-processual archaeology and especially their distinctions among several kinds of relativism. We would like to comment on links between epistemological relativism and a particular view of history (or, more generally, the past) that the LAW's discussion raises. In particular, we draw attention to several implications of their positions, including the relative emphasis placed on the past and/or the present in archaeological interpretations, different ways of linking past and present, and the political implications of such links
Bringen Scherben Glück?
Authors: Bonani M. , Frei P. , Glaab R. , Lenzlinger M.
Published: August 2008

Eine 56-jährige Patientin stellte sich aufgrund einer plötzlich aufgetretenen Schwellung am Oberschenkel vor. Klinisch fand sich eine druckdolente Schwellung, aspektmässig einem Hämatom entsprechend. Ein Trauma wurde verneint. Sonographisch kam eine hyperechogene Struktur zur Darstellung, welche sich in der Computertomographie als intramuskulär liegender Fremdkörper herausstellte. Der intraoperative Befund bestätigte die Verdachtsdiagnose einer sekundären Dislokation eines Glasfremdkörpers. Glasfremdkörper können mittels Röntgenaufnahmen mit einer hohen Sensitivität erkannt werden, sodass die Indikation zur radiologischen Fremdkörpersuche bei entsprechendem Unfallmechanismus grosszügig gestellt werden sollte.
Interannual variations in continental‐scale net carbon exchange and sensitivity to observing networks estimated from atmospheric CO2 inversions for the period 1980 to 2005
Authors: Gurney Kevin R. , Baker David , Rayner Peter , Denning Scott
Published: August 2008

Interannually varying net carbon exchange fluxes from the TransCom 3 Level 2 Atmospheric Inversion Intercomparison Experiment are presented for the 1980 to 2005 time period. The fluxes represent the model mean, net carbon exchange for 11 land and 11 ocean regions after subtraction of fossil fuel CO2 emissions. Both aggregated regional totals and the individual regional estimates are accompanied by a model uncertainty and model spread. We find that interannual variability is larger on the land than the ocean, with total land exchange correlated to the timing of both El Niño/Southern Oscillation (ENSO) as well as the eruption of Mt. Pinatubo. The post‐Pinatubo negative flux anomaly is evident across much of the tropical and northern extratropical land regions. In the oceans, the tropics tend to exhibit the greatest level of interannual variability, while on land, the interannual variability is slightly greater in the tropics and northern extratropics. The interannual variation in carbon flux estimates aggregated by land and ocean across latitudinal bands remains consistent across eight different CO2 observing networks. The interannual variation in carbon flux estimates for individual flux regions remains mostly consistent across the individual observing networks. At all scales, there is considerable consistency in the interannual variations among the 13 participating model groups. Finally, consistent with other studies using different techniques, we find a considerable positive net carbon flux anomaly in the tropical land during the period of the large ENSO in 1997/1998 which is evident in the Tropical Asia, Temperate Asia, Northern African, and Southern Africa land regions. Negative anomalies are estimated for the East Pacific Ocean and South Pacific Ocean regions. Earlier ENSO events of the 1980s are most evident in southern land positive flux anomalies.
Polar cap convection and PC index during sudden changes in solar wind dynamic pressure
Authors: Stauning P. , Troshichev O. A.
Published: August 2008

The polar cap (PC) index derived from polar magnetic variations is primarily a measure of the intensity of the transpolar ionospheric currents generated by the solar wind interaction with the Earth's magnetosphere. We have examined the influence of the solar wind dynamic pressure on the PC index in cases of global sudden impulses (SI) or storm sudden commencement (SSC) magnetic impulses. Such events usually give rise to a sequence of a negative preliminary reverse impulse (PRI) followed by a positive main impulse (MI) in the PC index. Sudden decreases in the solar wind dynamic pressure generate the corresponding sequence of pulses with inverted polarity. These pulses have amplitudes of typically 0.5 in the PC index and a total duration of 10–30 min. Using magnetic recordings from a network of observatories in the polar cap we have examined in detail the development in the polar ionospheric convection following sudden solar wind dynamic pressure changes. The PRI impulses are related to the occurrence of a pair of transient dayside reverse convection vortices at cusp latitudes. We conclude that the short negative PRI pulses in the PC index following sudden changes in solar wind dynamic pressure are caused by the diversion of magnetopause currents along cusp field lines to the polar cap ionosphere as the pressure front sweeps over the magnetosphere. The more extended positive MI main impulses are related to the formation of a pair of forward convection vortices in the dayside auroral oval supported by enhanced Region 1 (R1) field‐aligned currents flowing to and from the auroral ionosphere.
Eruption‐fed particle plumes and volcaniclastic deposits at a submarine volcano: NW Rota‐1, Mariana Arc
Authors: Walker Sharon L. , Baker Edward T. , Resing Joseph A. , Chadwick William W. , Lebon Geoffrey T. , Lupton John E. , Merle Susan G.
Published: August 2008

NW Rota‐1 is an active submarine volcano in the Mariana Arc with a summit depth of 517 m and an explosively erupting volcanic vent southwest of the summit at a depth of 530–560 m. During a period of ongoing explosive eruptions, particle plumes surrounded the volcano and at least 3.3 × 107 m3 of volcaniclastic material was deposited on the southern flank. Particle plumes over the summit were magmatic‐hydrothermal in origin characterized by 3He enrichment, hydrothermal precipitates, and low pH values. Plumes at multiple depths below the summit surrounded the volcano and were composed overwhelmingly of fresh, glassy shards of basalt. Rare anhydrite particles were present, but there was a complete absence of other hydrothermal components in the deep plume samples. These short‐lived anhydrite particles indicate the source of the deep plumes is from within or very near the eruptive vent, and the mechanism for transport down the flanks of the volcano must be far faster than settling of individual particles. The deep plumes most likely originated from sediment gravity flows generated by explosive eruptions or slope failure and landslides of unstable materials that had accumulated near the eruptive vent. Suspended sediments detach from the volcano slopes at multiple depths and are transported laterally up to tens of kilometers where they contribute to fall‐out deposits in distal sediments. These observations link mechanisms for the transport of volcanic ash in the submarine environment to the types of deposits common in volcaniclastic aprons and fine ash layers in distal sediments.
Vertical propagation of extratropical Rossby waves during the 1997–1998 El Niño off the west coast of South America in a medium‐resolution OGCM simulation
Authors: Ramos Marcel , Dewitte Boris , Pizarro Oscar , Garric Gilles
Published: August 2008

A medium‐resolution ocean general circulation model (OGCM) simulation is used to investigate the subthermocline interannual variability in the eastern South Pacific. The focus is on isotherm vertical displacement variability associated with extratropical Rossby waves (ETRW) and their connection with equatorial Kelvin waves (EKW). The WKB theory is used to interpret the modeled subsurface variability. The analysis reveals vertical propagation of energy associated with the 1997–1998 El Niño near the coast at various latitudes. Consistent with theory, WKB raypaths are steeper southward and do not extend more than ∼600 km from the coast at ∼2000 m depth. A vertical mode decomposition of model variability showed that vertical propagation mostly involves the first three baroclinic modes. The vertical isotherm displacements along the raypaths, associated with the downwelling EKW of the 1997–1998 El Niño, are negative (rising isotherms) and peak (minimum isotherm) as El Niño reverses to La Niña conditions. The relationship between vertical propagation of ETRW and equatorial variability is interpreted in the light of EKW sequence. The evolution of the vertical isotherm displacements along the raypath at extratropical latitudes is controlled by the vertical structure of the EKW. As El Niño develops, high‐order baroclinic mode contributions to the EKW progressively increase, leading to the dominance of finer vertical scales of variability along the coast, triggering the vertical propagation of ETRW. This mechanism of connection between equatorial variability and subsurface variability at the extratropical latitudes illustrates how sensitive the ETRW characteristics in the eastern South Pacific are to equatorial forcing.
Space‐time variability of equatorial Kelvin waves and intraseasonal oscillations around the tropical tropopause
Authors: Suzuki Junko , Shiotani Masato
Published: August 2008

Using the ECMWF 40‐year reanalysis data, large‐scale variations of temperature and zonal wind around the tropical tropopause are investigated. From the space‐time spectral analysis, two dominant spectral regions in the eastward propagating domain are found: one for Kelvin waves and the other for intraseasonal oscillations (ISOs). To investigate activities of Kelvin waves and ISOs we reconstructed the grid data for the two spectral windows and calculated the square amplitude at each grid point. Kelvin wave activities in zonal wind are vigorous during two seasons around February and July in the upper troposphere up to 100 hPa. However, the longitudinal maxima are found in the Eastern Hemisphere at 100 hPa and in the Western Hemisphere at 150 hPa and below. Activities calculated from the outgoing longwave radiation data for the Kelvin wave spectral window are different from those in zonal wind about their maximum longitudes and seasons. As the climatological background zonal wind in the upper troposphere is easterly in the Eastern Hemisphere and westerly in the Western Hemisphere, it seems that the difference of Kelvin wave activities between 100 hPa and 150 hPa is closely related to the background wind field affecting Kelvin wave propagation and dissipation. ISO activities in zonal wind at 100 hPa are vigorous in the western Pacific during northern winter, and we may find relation to those in OLR. This indicates that the eastward moving disturbance with the ISO time scale is coupled with the organized convective system such as the Madden‐Julian oscillation.
Short‐term response of methane fluxes and methanogen activity to water table and soil warming manipulations in an Alaskan peatland
Authors: Turetsky M. R. , Treat C. C. , Waldrop M. P. , Waddington J. M. , Harden J. W. , McGuire A. D.
Published: August 2008

Growing season CH4 fluxes were monitored over a two year period following the start of ecosystem‐scale manipulations of water table position and surface soil temperatures in a moderate rich fen in interior Alaska. The largest CH4 fluxes occurred in plots that received both flooding (raised water table position) and soil warming, while the lowest fluxes occurred in unwarmed plots in the lowered water table treatment. A combination of treatment and soil hydroclimate variables explained more than 70% of the variation in ln‐transformed CH4 fluxes, with mean daily water table position representing the strongest predictor. We used quantitative PCR of the α‐subunit of mcr operon to explore the influence of soil climate manipulations on methanogen abundances. Methanogen abundances were greatest in warmed plots, and showed a positive relationship with mean daily CH4 fluxes. Our results show that water table manipulations that led to soil inundation (flooding) had a stronger effect on CH4 fluxes than water table drawdown. Seasonal CH4 fluxes increased by 80–300% under the combined wetter and warmer soil climate treatments. Thus, while warming is expected to increase CH4 emissions from Alaskan wetlands, higher water table positions caused by increases in precipitation or disturbances such as permafrost thaw that lead to thermokarst and flooding in wetlands will stimulate CH4 emissions beyond the effects of soil warming alone. Consequently, we argue that modeling the effects of climate change on Alaskan wetland CH4 emissions needs to consider the interactive effects of soil warming and water table position on CH4 production and transport.
Modeling U(VI) biomineralization in single‐ and dual‐porosity porous media
Authors: Rotter B. E. , Barry D. A. , Gerhard J. I. , Small J. S.
Published: August 2008

Uranium extraction, processing, and storage have resulted in a legacy of uranium‐contaminated groundwater aquifers worldwide. An emerging remediation technology for such sites is the in situ immobilization of uranium via biostimulation of dissimilatory metal‐reducing bacteria (DMRB). While this approach has been successfully demonstrated in experimental studies, advances in understanding and optimization of the technique are needed. The motivation of this work was to understand better how dual‐porosity (DP) porous media may affect immobilization efficiency via interactions with the dominant geochemical and microbial processes. A biogeochemical reactive transport model was developed for uranium immobilization by DMRB in both single‐ and dual‐porosity porous media. The impact that microbial residence location has on the success of biostimulated U(VI) immobilization in DP porous media was explored under various porosity and mass transfer conditions. Simulations suggest that DP media are likely to show delayed U(VI) immobilization relative to single‐porosity systems. U(VI) immobilization is predicted to be less when microbial activity is restricted to diffusion‐dominant regions but not when restricted to advective‐dominant regions. The results further highlight the importance of characterizing the bioresidency status of field sites if biogeochemical models are to predict accurately remediation schemes in physically heterogeneous media.
Steady state lateral water flow through unsaturated soil layers
Authors: Warrick A. W. , Hinnell A. C. , Ferré T. P. A. , Knight J. H.
Published: August 2008

The effects of gravity on flow through variably saturated soil layers are investigated quantitatively using two new analytical solutions and a numerical model. In all cases, steady state flow occurs laterally through a tilted, rectangular layer of soil with a constant hydraulic head on either end. The first solution is for gravity‐driven flow through a tilted layer with sublayering parallel to the slope. As intuitively suggested by earlier investigators, flow occurs parallel to the floor of the layer and the pressure head is a simple function of the normal distance from the floor of the layer. The second analytical solution is for a tilted soil layer described by a Gardner soil model with both gravity and pressure head gradients. Flow velocities remain parallel to the layer floor, which is confirmed by numerical simulations. This is in contrast with chosen non‐Gardner examples for which the flow does not necessarily remain parallel to the floor.
Seismicity on volcanoes generated by gas slug ascent
Authors: O'Brien G. S. , Bean C. J.
Published: August 2008

Very long period (VLP) signals provide a unique insight into the source process of seismic signals recorded on active or restless volcanoes. This is due to the large wavelengths that may allow the structural heterogeneity to be ignored hence source inversions can be calculated. The source process involved in such events is thought to be related to magma transport, gas slug ascent or dike resonance initiated by a fluid driven process. Numerical modelling of gas slug ascent (constrained by results from published laboratory experiments) shows that this process is capable of generating long period and VLP like signals. Inputting the fluid dynamic derived forces into an elastic medium, with volcano like topography, VLP signals are reproduced. A moment tensor inversion is performed on these synthetic VLP signals retrieving the correct input source mechanism (a pipe structure).
Annual amphidromes observed in the atmosphere with remote sensing data
Authors: Zhang Caiyun , Chen Ge , Qiu Fang
Published: August 2008

Annual cycle, one of the principle modes in the variability of the air‐sea system, can be analyzed using tide analysis tools for extending the concept of oceanic tidal amphidromes to the atmosphere. In this paper, the annual phase‐amplitude characteristics of two variables, sea‐level pressure (SLP) and precipitation, were investigated to explore the annual atmospheric amphidromes on a global scale. For SLP, around a dozen annual amphidromic points were successfully identified. These points are distinguished by large‐scale rotary phase propagations around them. For global precipitation, we identified a substantial amount of annual rainfall amphidromic points, with many of them appearing as pairs close to each other and less developed. Further examinations illustrate that these rainfall amphidromes tend to occur in narrow bands or small regions with low annual amplitudes and phase structures opposite to their surroundings. This suggests that precipitation amphidromes tend to appear as quasi‐amphidromic lines or quasi‐amphidromic zones. The occurrence of El Niño/La Niña events does not affect the formation and stability of SLP and precipitation amphidromes, although it can modify the annual variations in terms of amplitude and phase changes.
A case study of the mesospheric 6.5‐day wave observed by radar systems
Authors: Jiang G. , Xu Jiyao , Xiong J. , Ma R. , Ning B. , Murayama Y. , Thorsen D. , Gurubaran S. , Vincent R. A. , Reid I. , Franke S. J.
Published: August 2008

In this paper, analysis of wind data detected by six ground‐based radar systems located in equatorial and midlatitude belts shows that a strong mesospheric 6.5‐day wave event occurred during April–May 2003. We compared the global distribution of the observed 6.5‐day wave event with the theoretical wave structure (Rossby normal mode (s, n) = (1, −2)). Additionally, we investigated several important wave characteristics to understand the mesospheric 6.5‐day wave event, i.e., wave period, vertical structure, relationship with background wind, propagating direction, and the zonal wave number. Our results are summarized into three points: (1) the latitudinal structure of the mesospheric 6.5‐day wave during April–May 2003 is basically in agreement with the theoretical Rossby mode (s, n) = (1, −2), although the wave amplitude of zonal wind peaked at the subequatorial latitude of Northern Hemisphere but not at the theoretical place, equatorial region; (2) the main wave periods and the altitude distribution of large amplitude of this wave event varied with latitude; (3) the downward propagating wave phases indicated that this wave event originated in the lower atmosphere and propagated upward to the upper region.
Venus Express observations of atmospheric oxygen escape during the passage of several coronal mass ejections
Authors: Luhmann J. G. , Fedorov A. , Barabash S. , Carlsson E. , Futaana Y. , Zhang T. L. , Russell C. T. , Lyon J. G. , Ledvina S. A. , Brain D. A.
Published: August 2008

The solar wind interaction contributes to the loss of Venus atmospheric constituents, especially oxygen, by direct antisunward acceleration of planetary ions and possibly by related sputtering of neutrals. Both comet‐like “ion pickup” and related sputtering processes may have played a key role in Venus' atmosphere evolution, but the significance of their effects, as well as other proposed escape mechanisms, is still uncertain. In particular, recent reports of only modest ion escape rates measured on Venus Express (VEX) during the current low‐activity phase of the solar cycle make it important to reconsider the evidence seen in both Pioneer Venus Orbiter and VEX observations suggesting significantly enhanced escaping O+ ion fluxes during periods of disturbed interplanetary conditions. At present, the most extreme interplanetary conditions result from the effects of coronal mass ejections (CME), which may have been more prevalent in the first 1–2 billion years of the Sun's history. The Analyser of Space Plasmas and Energetic Atoms 4 (ASPERA‐4) Ion Mass Analyzer and Magnetometer on Venus Express have now made detailed measurements during several periods when CME disturbances encountered Venus. The observations and models described in this report provide further insights into the possible response of oxygen ion escape to solar activity. In particular, they illustrate nuances of in situ sampling of large‐gyroradius pickup ions, related to the atmospheric source properties, spacecraft orbit geometry, and the prevailing interplanetary conditions, that make the estimation of the variable global escape fluxes due to that process particularly challenging. In three of the four cases examined in some detail, ionospheric oxygen ions were either unobservable or below the limit of detectability for passes well within interplanetary coronal mass ejection (ICME) intervals. In the fourth example, where ionospheric ions were observed as expected from the model, O+ pickup ions were observed in greater abundance than is typical in undisturbed solar wind. Other escape processes are not considered here, although it is assumed the source population for the modeled pickup ions is a preaccelerated upper atmosphere component. Analysis of many more ICME events, expected to be obtained as the Sun becomes more active in future years, are necessary to resolve the question of the importance of ICME to Venus oxygen escape.
Cultured CD4T cells and primary human lymphocytes express hOATPs: intracellular accumulation of saquinavir and lopinavir
Authors: Janneh O , Hartkoorn R C , Jones E , Owen A , Ward S A , Davey R , Back D J , Khoo S H
Published: August 2008

Background and purpose:

Drug efflux tranporters (P‐glycoprotein (P‐gp), multidrug resistance‐associated protein (MRP)) limit the cellular uptake of human immunodeficiency virus protease inhibitors but the contribution of influx transporters in cells that (over)express P‐gp or MRP is less clear. Here, we studied the expression of one influx transporter system, human organic anion‐transporting polypeptide (hOATP), in some T‐cell lines (CEM, CEMVBL, CEME1000) and in peripheral blood mononuclear cells (PBMCs) and examined the effects of manipulation of influx/efflux transporters on the uptake of saquinavir and lopinavir.

Experimental approach:

The expression of hOATPs was studied by PCR. We used hOATP substrate or inhibitor (estrone‐3‐sulphate (E‐3‐S) or montelukast, respectively) and inhibitors of P‐gp (XR9576) and MRP (MK571 and frusemide) to study functional interactions between influx and efflux transporters in the uptake of saquinavir and lopinavir. Lipophilicity of the drugs was measured by octanol/saline partition coefficient.

Key results:

CEM cells, their variants and PBMCs express various hOATP isoforms, with OATP3A1 detected in all of the cells. MK571, XR9576 and frusemide increased the uptake of saquinavir and lopinavir. E‐3‐S and montelukast reduced the uptake of saquinavir and lopinavir in some, but not all, of the cells. Pretreatment of the cells with MK571, XR9576 or frusemide, followed by E‐3‐S co‐incubation reduced the cellular accumulation of saquinavir and lopinavir. Lopinavir is much more lipophilic than saquinavir.

Conclusions and implications:

Human OATPs, MRP, P‐gp and lipophilicity determine the cellular uptake and retention of saquinavir and lopinavir. These data may have important implications for drug–drug interactions, drug safety and efficacy.

British Journal of Pharmacology(2008)155, 875–883; doi:10.1038/bjp.2008.320; published online 18 August 2008
Pharmacology of the short QT syndrome N588K‐hERG K+channel mutation: differential impact on selected class I and class III antiarrhythmic drugs
Authors: McPate M J , Duncan R S , Hancox J C , Witchel H J
Published: August 2008

Background and purpose:

The short QT syndrome (SQTS) is associated with cardiac arrhythmias and sudden death. The SQT1 form of SQTS results from an inactivation‐attenuated, gain‐of‐function mutation (N588K) to thehuman ether‐à‐go‐go‐related gene(hERG) potassium channel. Pharmacological blockade of this mutated hERG channel may have therapeutic value. However, hERG‐blocking potencies of canonical inhibitors such as E‐4031 andD‐sotalol are significantly reduced for N588K‐hERG. Here, five hERG‐blocking drugs were compared to determine their relative potencies for inhibiting N588K channels, and two other inactivation‐attenuated mutant channels were tested to investigate the association between impaired inactivation and altered drug potency.

Experimental approach:

Whole‐cell patch clamp measurements of hERG current (IhERG) mediated by wild‐type and mutant (N588K, S631A and N588K/S631A) channels were made at 37 °C CHO cells.

Key results:

The N588K mutation attenuatedIhERGinhibition in the following order: E‐4031>amiodarone>quinidine>propafenone>disopyramide. Comparing the three inactivation mutants, the two single mutations, although occurring in different modules of the channel, attenuated inactivation to a nearly identical degree, whereas the double mutant caused considerably greater attenuation, permitting the titration of inactivation. Attenuation of channel inhibition was similar between the single mutants for each drug, and was significantly greater with the double mutant.

Conclusions and implications:

The degree of drug inhibition of hERG channels may vary based on the level of channel inactivation. Drugs previously identified as useful for treating SQT1 have the least dependence on hERG inactivation. In addition, our findings indicate that amiodarone may warrant further investigation as a potential treatment for SQT1.

British Journal of Pharmacology(2008)155, 957–966; doi:10.1038/bjp.2008.325; published online 25 August 2008
Diabetic state, high plasma insulin and angiotensin II combine to augment endothelin‐1‐induced vasoconstriction via ETAreceptors and ERK
Authors: Kobayashi T , Nogami T , Taguchi K , Matsumoto T , Kamata K
Published: August 2008

Background and purpose:

Mechanisms associated with the enhanced contractile response to endothelin‐1 in hyperinsulinaemic diabetes have been examined using the rat aorta. Functions for angiotensin II, endothelin‐1 receptor expression and extracellular signal‐regulated kinase (ERK) have been investigated.

Experimental approach:

Streptozotocin‐induced diabetic rats were infused with angiotensin II or, following insulin treatment, were treated with losartan, an angiotensin II receptor antagonist. Contractions of aortic strips with or without endothelium, in response to endothelin‐1 and angiotensin II, were examinedin vitro. Aortic ETAreceptors and ERK/MEK expression were measured by western blotting.

Key results:

Insulin‐treated diabetic rats exhibited increases in plasma insulin, angiotensin II and endothelin‐1. The systolic blood pressure and endothelin‐1‐induced contractile responses in aortaein vitrowere enhanced in insulin‐treated diabetic rats and blunted by chronic losartan administration. LY294002 (phosphatidylinositol 3‐kinase inhibitor) and/or PD98059 (MEK inhibitor) diminished the enhanced contractile response to endothelin‐1 in aortae from insulin‐treated diabetic rats. ETAand ETBreceptors, ERK‐1/2 and MEK‐1/2 protein expression and endothelin‐1‐stimulated ERK phosphorylation were all increased in aortae from insulin‐treated diabetic rats. Such increases were blunted by chronic losartan administration. Endothelin‐1‐induced contraction was significantly higher in aortae from angiotensin II‐infused diabetic rats. angiotensin II‐infusion increased ERK phosphorylation, but the expression of endothelin receptors and ERK/MEK proteins remained unchanged.

Conclusions and implications:

These results suggest that the combination of high plasma angiotensin II and insulin with a diabetic state induced enhancement of endothelin‐1‐induced vasoconstriction, ETAreceptor expression and ERK expression/activity in the aorta. Losartan improved both the diabetes‐related abnormalites and the diabetic hypertension.

British Journal of Pharmacology(2008)155, 974–983; doi:10.1038/bjp.2008.327; published online 18 August 2008
Treating lung inflammation with agonists of the adenosine A2Areceptor: promises, problems and potential solutions
Authors: Trevethick M A , Mantell S J , Stuart E F , Barnard A , Wright K N , Yeadon M
Published: August 2008

Adenosine A2Areceptor agonists may be important regulators of inflammation. Such conclusions have come from studies demonstrating that, (i) adenosine A2Aagonists exhibit anti‐inflammatory propertiesin vitroandin vivo, (ii) selective A2Aantagonists enhance inflammationin vivoand, (iii) knock outs of this receptor aggravate inflammation in a wide variety ofin vivomodels. Inflammation is a hallmark of asthma and COPD and adenosine has long been suggested to be involved in disease pathology. Two recent publications, however, suggested that an inhaled adenosine A2Areceptor agonist (GW328267X) did not affect either the early and late asthmatic response or symptoms associated with allergic rhinitis suggesting that the rationale for treating inflammation with an adenosine A2Areceptor agonist may be incorrect. A barrier to fully investigating the role of adenosine A2Areceptor agonists as anti‐inflammatory agents in the lung is the side effect profile due to systemic exposure, even with inhalation. Unless strategies can be evolved to limit the systemic exposure of inhaled adenosine A2Areceptor agonists, the promise of treating lung inflammation with such agents may never be fully explored. Using strategies similar to that devised to improve the therapeutic index of inhaled corticosteroids, UK371,104 was identified as a selective agonist of the adenosine A2Areceptor that has a lung focus of pharmacological activity following delivery to the lung in a pre clinicalin vivomodel of lung function. Lung‐focussed agents such as UK371,104 may be suitable for assessing the anti‐inflammatory potential of inhaled adenosine A2Areceptor agonists.

British Journal of Pharmacology(2008)155, 463–474; doi:10.1038/bjp.2008.329; published online 1 September 2008
Effects of excitatory and inhibitory neurotransmission on motor patterns of human sigmoid colonin vitro
Authors: Aulí M , Martínez E , Gallego D , Opazo A , Espín F , Martí‐Gallostra M , Jiménez M , Clavé P
Published: August 2008

Background and purpose:

To characterize thein vitromotor patterns and the neurotransmitters released by enteric motor neurons (EMNs) in the human sigmoid colon.

Experimental approach:

Sigmoid circular strips were studied in organ baths. EMNs were stimulated by electrical field stimulation (EFS) and through nicotinic ACh receptors.

Key results:

Strips developed weak spontaneous rhythmic contractions (3.67±0.49 g, 2.54±0.15 min) unaffected by the neurotoxin tetrodotoxin (TTX; 1 μM). EFS induced strong contractions during (on, 56%) or after electrical stimulus (off, 44%), both abolished by TTX. Nicotine (1–100 μM) inhibited spontaneous contractions. Latency of off‐contractions and nicotine responses were reduced byNG‐nitro‐L‐arginine (1 mM) and blocked after further addition of apamin (1 μM) or the P2Y1receptor antagonist MRS 2179 (10 μM) and were unaffected by the P2X antagonist NF279 (10 μM) or α‐chymotrypsin (10 U mL−1). Amplitude ofon‐and off‐contractions was reduced by atropine (1 μM) and the selective NK2receptor antagonist Bz‐Ala‐Ala‐D‐Trp‐Phe‐D‐Pro‐Pro‐Nle‐NH2(1 μM). MRS 2179 reduced the amplitude of EFS on‐ and off‐contractions without altering direct muscular contractions induced by ACh (1 nM–1 mM) or substance P (1 nM–10 μM).

Conclusions and implications:

Latency of EFS‐induced off‐contractions and inhibition of spontaneous motility by nicotine are caused by stimulation of inhibitory EMNs coreleasing NO and a purine acting at muscular P2Y1receptors through apamin‐sensitive K+channels. EFS‐induced on‐ and off‐contractions are caused by stimulation of excitatory EMNs coreleasing ACh and tachykinins acting on muscular muscarinic and NK2receptors. Prejunctional P2Y1receptors might modulate the activity of excitatory EMNs. P2Y1and NK2receptors might be therapeutic targets for colonic motor disorders.

British Journal of Pharmacology(2008)155, 1043–1055; doi:10.1038/bjp.2008.332; published online 1 September 2008
Etomidate reduces glutamate uptake in rat cultured glial cells: involvement of PKA
Authors: Räth M , Föhr K J , Weigt H U , Gauss A , Engele J , Georgieff M , Köster S , Adolph O
Published: August 2008

Background and purpose:

Glutamate is the main excitatory neurotransmitter in the vertebrate CNS. Removal of the transmitter from the synaptic cleft by glial and neuronal glutamate transporters (GLTs) has an important function in terminating glutamatergic neurotransmission and neurological disorders. Five distinct excitatory amino‐acid transporters have been characterized, among which the glial transporters excitatory amino‐acid transporter 1 (EAAT1) (glutamate aspartate transporter) and EAAT2 (GLT1) are most important for the removal of extracellular glutamate. The purpose of this study was to describe the effect of the commonly used anaesthetic etomidate on glutamate uptake in cultures of glial cells.

Experimental approach:

The activity of the transporters was determined electrophysiologically using the whole cell configuration of the patch‐clamp recording technique.

Key results:

Glutamate uptake was suppressed by etomidate (3–100 μM) in a time‐ and concentration‐dependent manner with a half‐maximum effect occurring at 2.4±0.6 μM. Maximum inhibition was approximately 50% with respect to the control. Etomidate led to a significant decrease ofVmaxwhereas theKmof the transporter was unaffected. In all cases, suppression of glutamate uptake was reversible within a few minutes upon washout. Furthermore, both GF 109203X, a nonselective inhibitor of PKs, and H89, a selective blocker of PKA, completely abolished the inhibitory effect of etomidate.

Conclusion and implications:

Inhibition of glutamate uptake by etomidate at clinically relevant concentrations may affect glutamatergic neurotransmission by increasing the glutamate concentration in the synaptic cleft and may compromise patients suffering from acute or chronic neurological disorders such as CNS trauma or epilepsy.

British Journal of Pharmacology(2008)155, 925–933; doi:10.1038/bjp.2008.336; published online 18 August 2008
The antioxidant activity of chondroitin‐4‐sulphate, in carbon tetrachloride‐induced acute hepatitis in mice, involves NF‐κB and caspase activation
Authors: Campo G M , Avenoso A , Campo S , Nastasi G , Traina P , D'Ascola A , Rugolo C A , Calatroni A
Published: August 2008

Background and purpose:

Reactive oxygen species (ROC) are the main causes of carbon tetrachloride (CCl4)‐induced acute liver injury. Chondroitin‐4‐sulphate (C4S) is known to inhibit lipid peroxidation through antioxidant mechanisms. Activation of nuclear factor (NF)‐κB and caspases may strongly intensify inflammation and cell damage, in addition to that directly exerted by ROS. We investigated whether treatment with C4S, besides exerting antioxidant activity, was able to modulate NF‐κB and apoptosis activation in CCl4‐induced liver injury in mice.

Experimental approach:

Acute hepatitis was induced in mice by an i.p. injection of CCl4. Varying doses of C4S were administered i.p. 1 h before, 6 and 12 h after CCl4 injection. 24 h after CCl4 injection, the mice were killed for biochemical and histological analysis.

Key results:

CCl4 injection produced: marked elevation of alanine aminotransferase and aspartate aminotransferase; hepatic membrane lipid peroxidation, assayed by 8‐isoprostane levels; and depletion of reduced glutathione and superoxide dismutase. CCl4 also decreased NF‐κB translocation and IkBα, and increased gene expression of mRNA and protein of metalloproteases (MMP)‐2 and ‐9, and of pro‐ and cleaved forms of caspases‐3 and ‐7. There was also increased liver polymorphonuclear infiltration, evaluated by elastase assay, and hepatic cell disruption.

C4S treatment inhibited lipid peroxidation; blocked NF‐κB activation and IkBα protein loss; decreased mRNA and proteins for MMPs and caspases; restored endogenous antioxidants; limited hepatic polymorphonuclear accumulation and tissue damage.

Conclusions and implications:

As antioxidants may inhibit NF‐κB and caspase activation, we hypothesize that treatment with C4S was able to inhibit NF‐κB and apoptosis activation in hepatic injury.

British Journal of Pharmacology (2008) 155, 945–956; doi:10.1038/bjp.2008.338; published online 25 August 2008
MDA7: a novel selective agonist for CB2receptors that prevents allodynia in rat neuropathic pain models
Authors: Naguib M , Diaz P , Xu J J , Astruc‐Diaz F , Craig S , Vivas‐Mejia P , Brown D L
Published: August 2008

Background and purpose:

There is growing interest in using cannabinoid type 2 (CB2) receptor agonists for the treatment of neuropathic pain. In this report, we describe the pharmacological characteristics of MDA7 (1‐[(3‐benzyl‐3‐methyl‐2,3‐dihydro‐1‐benzofuran‐6‐yl)carbonyl]piperidine), a novel CB2receptor agonist.

Experimental approach:

We characterized the pharmacological profile of MDA7 by using radioligand‐binding assays andin vitrofunctional assays at human cannabinoid type 1 (CB1) and CB2receptors.In vitrofunctional assays were performed at rat CB1and CB2receptors. The effects of MDA7 in reversing neuropathic pain were assessed in spinal nerve ligation and paclitaxel‐induced neuropathy models in rats.

Key results:

MDA7 exhibited selectivity and agonist affinity at human and rat CB2receptors. MDA7 treatment attenuated tactile allodynia produced by spinal nerve ligation or by paclitaxel in a dose‐related manner. These effects were selectively antagonized by a CB2receptor antagonist but not by CB1or opioid receptor antagonists. MDA7 did not affect rat locomotor activity.

Conclusion and implications:

MDA7, a novel selective CB2agonist, was effective in suppressing neuropathic nociception in two rat models without affecting locomotor behaviour. These results confirm the potential for CB2agonists in the treatment of neuropathic pain.

British Journal of Pharmacology(2008)155, 1104–1116; doi:10.1038/bjp.2008.340; published online 1 September 2008
Pleiotropic action(s) of the bradycardic agent ivabradine: cardiovascular protection beyond heart rate reduction
Authors: Heusch G
Published: August 2008

The bradycardic agent ivabradine has proved to be of benefit in experimental models with the end points of ischaemic myocardial blood flow and contractile function, infarct size, post‐infarct remodelling and atherosclerosis. The benefits to ischaemic myocardial blood flow and contractile function are strictly heart rate dependent; those on infarct size are partly heart rate independent. The heart rate dependency of ivabradine's benefit for atherosclerotic vascular function is contradictory, and that on post‐infarct remodelling is entirely unclear.

British Journal of Pharmacology (2008) 155, 970–971; doi:10.1038/bjp.2008.347; published online 1 September 2008