bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond Colonial Law: Indigenous Litigation and the Contestation of Property in the Mayor's Court in Late Eighteenth-Century Madras
Authors: Brimnes Niels
Published: July 2003

An important branch in recent debates on the nature of the judiciary in colonial south India has focused on the extent
to which the judicial institutions—and the social transformations mediated through them—were controlled by the colonial state. This debate is of interest not only from the point of legal history. From the broader perspective of social and cultural history the debate is important because it draws attention to issues such as indigenous agency, conceptual negotiation and the hybrid nature of institutions under colonial rule. It is these issues I intend to address through an analysis of indigenous litigation in the Mayor's Court in late eighteenth-century Madras. The analysis falls in two parts. First, I analyse how indigenous agents availed themselves of the court, despite an official colonial policy of excluding disputes between Indians from its jurisdiction. In the second part, I focus on the ways in which the nature of property was contested and negotiated in complex dialogues between indigenous litigants and representatives of the colonial judiciary. Both parts of the analysis indicate that important aspects of the litigation in the Mayor's Court were largely beyond the control of the colonial authorities.
The PRC's Relationship with the ASEAN Regional Forum
Authors: Evans Thammy
Published: July 2003

Ever since the discovery of China by Western nations the West has continually tried to gain access to China, and sometime even to understand her. Conversely, many Eastern nations who came within China's reach have preferred to keep her at arms length. This dichotomy continues today, although the East/West division is less clear. The People's Republic of China's sheer geographical size, its location in the heart of Asia, its huge population and thus its potential as an economic and miitary superpower instils fear in many. Will the PRC become a ‘responsible power’, an irresponsible hegemon, or collapse into political disorder and chaos? In anticipation of the coming changes in the PRC, the foreign policy of those nations concerned with the PRC has oscillated between engagement and containment of China.
The carer careers of son and daughter primary carers of their very old parents in Norway
Authors: ROMOREN TOR INGE
Published: July 2003

The purpose of this article is to analyse with longitudinal data from Norway the caring activities of sons and daughters who were the primary care-giver to a parent aged 80 or more years. The study sample consists of the 227 offspring care-givers in the Larvik study, which examined the illnesses and disabilities and the informal and formal care received until their deaths of all those aged 80 or more years in the town's population in 1981. Prospective and retrospective data were collected from that year about the health, functional losses and formal service utilisation of the older people. After the death of an older person in the study, the next-of-kin was interviewed about the informal care provided by relatives and friends during the same time span. The sequences and content of the care-giving activities differed little for son or daughter care-givers, except during a short escalation phase. The average duration of informal home care was shorter for sons than for daughters, primarily because a minority of the daughters had very long care-giving careers. The duration of the care recipients' stays in acute or long-term care institutions before death did not differ by the gender of the carer. Compared with many earlier studies, few gender differences in offspring care-giving activities were found. The findings suggest that the potential of sons to provide informal care to frail older parents is underestimated in modern societies.
Why International Relations theorists should stop reading Thucydides
Authors: Welch David A.
Published: July 2003

Many regard Thucydides as the first genuine International Relations theorist and a writer of continuing, even timeless importance. His history of the Peloponnesian War is certainly a remarkable work that obviously has had an enormous influence on the development of the field. Its influence, however, is largely pernicious. This article explores why.
Humanitarian responsibilities and interventionist claims in international society
Authors: Bellamy Alex J.
Published: July 2003

This article calls for a widening of the debate about humanitarian intervention to incorporate insights from constructivism, ‘Welsh School’; Critical Security Studies, and critical approaches to Third World International Relations. After identifying a series of problems with the contemporary debate, which is dominated by the English School, it calls for a broadening of the concept of intervention and suggests a need to rethink the meaning of humanitarianism and terms such as the ‘supreme humanitarian emergency’.
Odd man out: rethinking British policy on European monetary integration
Authors: Aspinwall Mark
Published: July 2003

This article examines British preferences on European monetary integration. It challenges dominant theories of preference formation, suggesting an alternative explanation focusing on governmental majority. Empirical evidence is presented on both UK economic behaviour and the views of domestic economic interests, as well as government majority. The article also analyses first and second-hand accounts of the main players involved in three cases: the decision not to join the Exchange Rate Mechanism in 1979, the decision to join the ERM in 1990, and the decision to opt out of stage 3 of Economic and Monetary Union.
Negotiating international cooperation: global public goods and fairness
Authors: Albin Cecilia
Published: July 2003

Global public goods (GPGs) are vital to human welfare and security worldwide. Yet often they suffer from under-provision and free-riding, and are not accessible or beneficial to everyone. They illustrate starkly problems of collective action. This article examines multilateral negotiations in which countries seek agreement on the terms for collaboration in providing GPGs. It argues that common obstacles to an effective agreement concern justice and fairness issues, which arise from the earliest phase when the agenda is set to the final stage of securing implementation and compliance. Drawing on recent negotiation practice, it proposes a framework and a set of strategies for how such issues could be tackled.
The English School vs. American Realism: a meeting of minds or divided by a common language?
Authors: Little Richard
Published: July 2003

This Forum has two main aims. First and foremost, it is designed to assess the relevance of American realism in the wake of developments that are considered to have transformed international relations over the past decade. A second aim, but one that is central to my contribution, is to assess whether or not the resurgent English School provides the foundations for an approach that can account more effectively for developments in the post-Cold War world than American realism.
Serious Fun: Berlin Dada's Tactical Engagement with German National Narration
Authors: CLEMONS LEIGH
Published: July 2003

German Dada, particularly the Berlin performance practices of George Grosz and Richard Hülsenbeck, shifted the ‘eternal’ history of the German Reich into the immediacy and annihilation of the postwar Berlin environment. These practitioners formed their social and political opinions into Dada's own German national narrative. The Weimar government responded by classifying ‘Dada’ as obscene, putting its members on trial, and judging its practices to be detrimental to the reforming German nation. The issues raised by Berlin Dada's performance practices formed the basis for Berlin Dada's future historical treatment by its own members, who sought to establish the German cell's primacy as both the singular heir to Hugo Ball's Cabaret Voltaire and the only legitimate mode of Dada expression in Weimar Germany.
The Making of a Martyr: The Legend of Meyerhold's Last Public Appearance
Authors: SENELICK LAURENCE
Published: July 2003

The disappearance of Meyerhold into the Soviet prison system in 1939 fostered
legends, which contributed to his rehabilitation as a martyr. A primary contribution to this
process was a fictional account of his defiant speech at the All-Soviet Directors'
Conference a few days before his arrest. The speech, made up out of whole cloth by
the émigré musician Yury Elagin in 1951, gained considerable currency
and was circulated as Cold War propaganda. It was not wholly discredited until the 1990s, when
the publication of the stenographic transcript of the Conference proceedings
revealed Meyerhold's actual capitulation to Stalinist artistic policy and his poor
showing on the podium.

As I was going up the stair

I met a man who wasn't there.

He wasn't there again today.

I wish, I wish he'd stay away.

Hughes Mearns
Finding a Home on Stage: A Place for Romania in Europe?
Authors: SZEMAN IOANA
Published: July 2003

Home, a pioneering theatrical production in post-communist Romania, cast homeless/orphaned youth in the Youth Theatre in Bucharest. The ‘orphan problem’ has been one of the most covered topics on Romania in western media, and one of the signs of Romania's ‘backwardness’, while neglect and indifference have characterized local press coverage. The significance of the production in changing the Romanian public's perception of these young people, many of whom are from the Roma ethnic group, is analysed, as are much wider political implications. Emma Nicholson, the European Parliament rapporteur for Romania, saw Home and afterwards expressed her support for Romania's acceptance into the European Union. The production and its reception permit a tracing of the historical relationship between the performance of Romanian marginality and national identity in relation to Europe.
EDITORIAL
Authors: Landy Leigh
Published: July 2003

This issue of Organised Sound is about interactivity, a theme that the journal has often visited in the past. What makes this visit to this very important subject special is that it has been chosen as the first theme within our annual collaboration with the International Computer Music Association (ICMA). The ICMA President, Mary Simoni, has joined the Editors this year as ICMA representative and Mara Helmuth, currently the ICMA's editor of Array, has kindly taken on the role of Guest Editor for this issue. The journal Editors would like to welcome the ICMA and thank those ICMA members, and Mara in particular, who helped to make this issue possible. We look forward to further developing this collaborotion.
Approaches to creating interactivated spaces, from intimate to inhabited interfaces
Authors: Harris Yolande , Bongers Bert
Published: July 2003

In contemporary music and arts practices the previously distinct roles of author, composer and performer have become increasingly conflated, catalysed by the use of computer technology. Newly combined roles of composer and performer that are assumed by one or more people or computer systems are identified and described, as well as actions including preparation, organisation and presentation. In this paper the interface is described as an ‘interactivated space’ to encompass both the intimate scale of a performer manipulating the materials through an on-body interface, and the larger in-space interface where the work is shared with the performers and audience. Two examples of projects the authors are involved in are described, which form the basis for further discussion. The two interfaces that manifest themselves in the processes, the instrument and the score are discussed in more detail with a focus on their changed appearance and role.
The habitable zone of Earth-mass planets around 47 UMa: results for land and water worlds
Authors: Franck S. , Cuntz M. , von Bloh W. , Bounama C.
Published: July 2003

In a previous paper, we showed that Earth-type habitable planets around 47 UMa are in principle possible if a distinct set of conditions is warranted. These conditions include that the Earth-type planets have successfully formed and are orbitally stable and, in addition, that the 47 UMa star–planet system is relatively young ([lsim ]6 Gyr). We now extend this study by considering Earth-like planets with different land/ocean coverages. This study is again based on the so-called integrated system approach, which describes the photosynthetic biomass production taking into account a variety of climatological, biogeochemical and geodynamical processes. This approach implies a special characterization of the habitable zone defined for a distinct type of planet. We show that the likelihood of finding a habitable Earth-like planet on a stable orbit around 47 UMa critically depends on the percentage of the planetary land/ocean coverage. The likelihood is significantly increased for planets with a very high percentage of ocean surface (‘water worlds’).
The Work–Life Balance in Social Practice
Authors: Kay Tess
Published: July 2003

This article examines the extent to which the growing attention being paid at EU and national level to issues related to work–life balance is reflected in families' lived experience. It identifies the demands facing families in balancing paid work with other activities, the strategies they adopt to meet them, and the role played by policy interventions. Attention is drawn to diversity in family structures and labour market participation throughout Europe, to differences in the issues encountered by families in achieving a satisfactory work–life balance, and to the contribution of policy to their strategies.
Informationaler Stimmungseinfluss und mentale Anstrengung:
Authors: Gendolla Guido H. E.
Published: June 2003

Zusammenfassung. Die Vorhersagen des Mood-Behavior-Models ( Gendolla, 2000 ) zur Wirkung von Stimmungen auf die Anstrengungsmobilisierung bei mentaler Beanspruchung werden dargestellt und die Ergebnisse einer hierauf bezogenen Serie von Experimenten werden diskutiert. Anstrengung wurde als kardiovaskuläre (KV) Reaktivität operationalisiert. Die Studien stützen die theoretischen Vorhersagen und demonstrieren, dass (1) Stimmungen an sich keine anstrengungsmobilisierende Funktion haben, (2) Stimmungen pragmatisch als Information für Anforderungsbewertungen genutzt werden, (3) stimmungskongruente Anforderungsbewertungen anstrengungsbezogene KV Reaktivität bestimmen, und (4) leistungskontingente Anreize hierbei die Höhe maximal gerechtfertigter Anstrengung festlegen. Die Befunde spezifizieren und erweitern Annahmen anderer Ansätze und haben gesundheitspsychologische Implikationen.
CO2 exchange between air and water in an Arctic Alaskan and midlatitude Swiss lake: Importance of convective mixing
Authors: Eugster Werner , Kling George , Jonas Tobias , McFadden Joseph P. , Wüest Alfred , MacIntyre Sally , Chapin F. Stuart
Published: June 2003

CO2 exchange between lake water and the atmosphere was investigated at Toolik Lake (Alaska) and Soppensee (Switzerland) employing the eddy covariance (EC) method. The results obtained from three field campaigns at the two sites indicate the importance of convection in the lake in driving gas flux across the water‐air interface. Measurements were performed during short (1–3 day) periods with observed diurnal changes between stratified and convective conditions in the lakes. Over Toolik Lake the EC net CO2 efflux was 114 ± 33 mg C m−2 d−1, which compares well with the 131 ± 2 mg C m−2 d−1 estimated by a boundary layer model (BLM) and the 153 ± 3 mg C m−2 d−1 obtained with a surface renewal model (SRM). Floating chamber measurements, however, indicated a net efflux of 365 ± 61 mg C m−2 d−1, which is more than double the EC fluxes measured at the corresponding times (150 ± 78 mg C m−2 d−1). The differences between continous (EC, SRM, and BLM) and episodic (chamber) flux determination indicate that the chamber measurements might be biased depending on the chosen sampling interval. Significantly smaller fluxes (p < 0.06) were found during stratified periods (51 ± 42 mg C m−2 d−1) than were found during convective periods (150 ± 45 mg C m−2 d−1) by the EC method, but not by the BLM. However, the congruence between average values obtained by the models and EC supports the use of both methods, but EC measurements and the SRM provide more insight into the physical‐biological processes affecting gas flux. Over Soppensee, the daily net efflux from the lake was 289 ± 153 mg C m−2 d−1 during the measuring period. Flux differences were significant (p < 0.002) between stratified periods (240 ± 82 mg C m−2 d−1) and periods with penetrative convection (1117 ± 236 mg C m−2 d−1) but insignificant if convection in the lake was weak and nonpenetrative. Our data indicate the importance of periods of heat loss and convective mixing to the process of gas exchange across the water surface, and calculations of gas transfer velocity using the surface renewal model support our observations. Future studies should employ the EC method in order to obtain essential data for process‐scale investigations. Measurements should be extended to cover the full season from thaw to freeze, thereby integrating data over stratified and convective periods. Thus the statistical confidence in the seasonal budgets of CO2 and other trace gases that are exchanged across lake surfaces could be increased considerably.
Seasonal behavior of the semidiurnal and diurnal tides, and mean flows at 95 km, based on measurements from the High Resolution Doppler Imager (HRDI) on the Upper Atmosphere Research Satellite (UARS)
Authors: Huang Frank T. , Reber Carl A.
Published: June 2003

Derived results from the High Resolution Doppler Imager (HRDI) on UARS have provided an enormous amount of new and invaluable information, including insight into the large global seasonal variability of atmospheric tides. These and other results have given added impetus to theoretical modeling efforts, including a focus on wave‐wave and wave‐mean‐flow interactions and the resulting momentum and energy exchanges. We have extended previous analyses, and provide new results for HRDI data at 95 km using an algorithm that simultaneously generates the diurnal and semidiurnal tidal variations and the mean flows. The diurnal variations with season are quite different from those of the semidiurnal components, showing evidence of possible strong damping around the solstices, especially in the meridional winds. The mean zonal winds are eastward at equatorial latitudes, while the annual component of the mean meridional wind generally flows from the summer to the winter hemisphere. We compare our results with earlier results from HRDI and from selected models.
Saharan dust storms and indirect aerosol effects on clouds: CRYSTAL‐FACE results
Authors: Sassen Kenneth , DeMott Paul J. , Prospero Joseph M. , Poellot Michael R.
Published: June 2003

A recent field experiment in southern Florida using aircraft and polarization lidar shows that mineral dust particles transported from Saharan Africa are effective ice nuclei, apparently capable of glaciating a mildly supercooled (−5.2° to −8.8°C) altocumulus cloud. These results are similar to those from Asian dust storm particles observed over the western US, suggesting that in the northern hemisphere major dust storms play a role in modulating climate through the indirect aerosol effect on cloud properties. If this is true of desert dusts in general, then even minor aeolian emissions could have an effect on regional weather and climate.
Nest site selection and predation driven despotic distribution of breeding long‐eared owls Asio otus
Authors: Tome Davorin
Published: July 2003

Long‐eared owls Asio otus do not build their own nests. They occupy old corvid nests in either coniferous or deciduous trees. In my study area owls favoured coniferous over deciduous trees for nesting and occupied nest sites in that order. Comparing overall breeding output, I found no difference between the two kinds of nest sites, but among early nests there was a higher proportion of unsuccessful nests in deciduous trees. This difference was due to differences in predation rate, indicating that the owls' pattern of nest site occupation followed predictions from the ideal despotic distribution model. I also show that, due to a seasonal change in habitat quality, predator driven despotism, although present, can be well masked and hence difficult to detect.
Sex allocation in black‐capped chickadees Poecile atricapilla
Authors: Ramsay Scott M. , Mennill Daniel J. , Otter Ken A. , Ratcliffe Laurene M. , Boag Peter T.
Published: July 2003

Optimal sex allocation for individuals can be predicted from a number of different hypotheses. Fisherian models of sex allocation predict equal investment in males and females up to the end of parental care and predict brood compositions based on the relative costs of producing males and females. The Trivers‐Willard hypothesis predicts that individual females should alter the sex ratio of their broods based on their own condition if it has a differential impact on the lifetime reproductive success of their sons and daughters. The Charnov model of sex allocation predicts that females should alter sex allocation based on paternal attributes that may differentially benefit sons versus daughters. Because females are the heterogametic sex in birds, many recent studies have focussed on primary sex ratio biases. In black‐capped chickadees Poecile atricapilla, males are larger than females suggesting they may be more costly to raise than females. Female condition affects competitive ability in contests for mates, and thus may be related to variance in fecundity. Females prefer high‐ranking males as both social and extrapair partners. These observations suggest that females might vary the sex ratio of their broods based on the predictions of any of the above models. Here, we report on the results of PCR based sex determination of 1093 nestlings in 175 broods sampled from 1992 to 2001. Population‐wide, we found a mean brood sex ratio of 0.525±0.016, with no significant deviation from a predicted binomial distribution. We found no effect of clutch size, female condition, hatch date, parental rank or paternity. Our results reject the idea that female black‐capped chickadees systematically vary sex allocation in their broods.
Phylogeography of Sula: the role of physical barriers to gene flow in the diversification of tropical seabirds
Authors: Steeves Tammy E. , Anderson David J. , McNally Heather , Kim Michael H. , Friesen Vicki L.
Published: July 2003

We examined mitochondrial cytochrome b sequence variation in masked Sula dactylatra, red‐footed S. sula, and brown S. leucogaster boobies sampled from islands in the central and eastern Pacific Ocean and in the Caribbean Sea. Each species showed a different phylogeographic pattern. Whereas haplotypes in masked and red‐footed boobies were shared across the central and eastern Pacific (i.e., across the Eastern Pacific Basin), brown booby haplotypes were not shared across the Eastern Pacific Basin. Although most masked booby haplotypes from the Pacific were distinct from those in the Caribbean, one haplotype was shared across the Isthmus of Panama. Red‐footed and brown boobies, however, did not share haplotypes across the Isthmus of Panama. We estimate that divergence of these regional populations occurred within the last 560,000 years. Thus, the Isthmus of Panama and the Eastern Pacific Basin (albeit to a lesser degree) appear to have played a role in the diversification of these species.
Properties of NO‐activated guanylyl cyclases expressed in cells
Authors: Gibb Barry J , Wykes Victoria , Garthwaite John
Published: July 2003

Physiological nitric oxide (NO) signal transduction occurs through activation of guanylyl cyclase (GC)‐coupled receptors, resulting in cGMP accumulation. There are five possible receptors: four heterodimers (α1β1, α2β1, α1β2, α2β2) and a presumed homodimer (νβ2). The present study investigated the kinetic and pharmacological properties of all these putative receptors expressed in COS‐7 (or HeLa) cells.

All exhibited NO‐activated GC activity, that of α1β1 and α2β1 being much higher than that of the β2‐containing heterodimers or νβ2. All were highly sensitive NO detectors. Using clamped NO concentrations, EC50 values were 1 nM for α1β1 and 2 nM for α2β1. With α1β2, α2β2 and νβ2, the EC50 was estimated to be lower, about 8 nM.

All the GCs displayed a marked desensitising profile of activity. Consistent with this property, the concentration–response curves were bell‐shaped, particularly those of the β2 heterodimers and νβ2.

Confocal microscopy of cells transfected with the fluorescently tagged β2 subunit suggested targeting to the endoplasmic reticulum through its isoprenylation sequence, but no associated particulate GC activity was detected.

The NO‐stimulated GC activity of all heterodimers and νβ2 was inhibited by 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one and, except for νβ2, was enhanced by the allosteric activator YC‐1.

It is concluded that all the four possible heterodimers, as well as the putative νβ2 homodimer, can function as high‐affinity GC‐coupled NO receptors when expressed in cells. They exhibit differences in NO potency, maximal GC activity, desensitisation kinetics and possibly subcellular location but, except for νβ2, cannot be differentiated using existing pharmacological agents.

British Journal of Pharmacology (2003) 139, 1032–1040. doi:10.1038/sj.bjp.0705318
Modulation of ATP‐induced currents by zinc in acutely isolated hypothalamic neurons of the rat
Authors: Vorobjev Vladimir S , Sharonova Irina N , Sergeeva Olga A , Haas Helmut L
Published: July 2003

Whole‐cell patch‐clamp and fast perfusion were used to study the effects of zinc on adenosine 5′‐triphosphate (ATP)‐induced responses of histaminergic neurons.

At 10–30 μM ATP, Zn2+ had biphasic effects on ATP responses. Zn2+ at 3–100 μM increased the ATP‐induced currents, but inhibited them at higher concentrations.

At 300 μM ATP, Zn2+ predominantly but incompletely inhibited the currents.

At 5 and 50 μM, Zn2+ shifted to the left the concentration–response curve for ATP‐induced currents, without changing the maximal response. At 1 mM, Zn2+ inhibited ATP‐induced currents in a noncompetitive way, reducing the maximal response by 58%.

Zn2+ increased the decay time of ATP‐evoked currents nine fold with an EC50 of 63 μM. Upon removal of high concentrations of Zn2+, there was a rapid increase of the current followed by a slow decline towards the response amplitude seen with ATP alone. The appearance of a tail current is consistent with a Zn2+‐induced increase of ATP affinity and an inhibition of its efficacy.

Thus, Zn2+ acts as a bidirectional modulator of ATP receptor channels in tuberomamillary neurons, which possess functional P2X2 receptors. The data are consistent with the existence of two distinct modulatory sites on the P2X receptor, which can be occupied by Zn2+.

Our data suggest that zinc‐induced potentiation of ATP‐mediated currents is caused by the slowing of ATP dissociation from the receptor, while inhibition of ATP‐induced currents is related to the suppression of ATP receptor gating.

British Journal of Pharmacology (2003) 139, 919–926. doi:10.1038/sj.bjp.0705321
Endothelin‐1 inhibits TNFα‐induced iNOS expression in 3T3‐F442A adipocytes
Authors: Mérial‐Kieny Christelle , Lonchampt Michel , Cogé Francis , Verwaerde Patrick , Galizzi Jean‐Pierre , Boutin Jean A , Lafontan Max , Levens Nigel , Galitzky Jean , Félétou Michel
Published: July 2003

Endothelin‐1 (ET‐1) and tumor necrosis factor α (TNFα) by their action on adipocytes have been independently linked to the pathogenesis of insulino‐resistance. In isolated adipocytes, TNFα induces the expression of the inducible nitric oxide synthase (iNOS). The purpose of the present work was, in the 3T3‐F442A adipocyte cell line, to characterise TNFα‐induced iNOS expression and to determine whether or not ET‐1 could influence TNFα‐induced iNOS expression and NO production.

In differentiated 3T3‐F442A, treatment with TNFα (20 ng ml−1) induced the expression of a functional iNOS as demonstrated by nitrite assay, Western blot, reverse transcription–polymerase chain reaction and Northern blot analysis. TNFα‐induced iNOS expression requires nuclear factor κB activation, but does not necessitate the activation of the PI‐3 kinase/Akt and P38–MAP kinase pathways.

ET‐1, but not ET‐3, inhibited the TNFα‐induced expression of iNOS protein and mRNA as well as nitrite production. The effects of ET‐1 were blocked by a specific ETA (BQ123, pA2 7.4) but not by a specific ETB receptor antagonist (BQ788). 3T3‐F442A adipocytes express the mRNAs for prepro‐ET‐1 and the ET‐A receptor subtype, but not for the ET‐B subtype.

The inhibitory effect of ET‐1 was not affected by bisindolylmaleimide, SB 203580 or indomethacin, inhibitors of protein kinase C, p38‐MAP kinase and cyclooxygenase, respectively, and was not associated with cAMP production. However, the effect of ET‐1 was partially reversed by wortmannin, suggesting the involvement of PI3 kinase in the transduction signal of ET‐1.

Differentiated 3T3‐F442A adipocytes did not release ET‐1 with or without exposure to TNFα, although the mRNA for preproET‐1 was detected in both pre‐ and differentiated adipocytes.

Thus, these results confirm that adipocytes are a target for circulating ET‐1 and demonstrate that the activation of the ETA receptor subtype can prevent TNFα‐induced iNOS expression.

British Journal of Pharmacology (2003) 139, 935–944. doi:10.1038/sj.bjp.0705325
Docosahexaenoic acid and arachidonic acid release in rat brain astrocytes is mediated by two separate isoforms of phospholipase A2 and is differently regulated by cyclic AMP and Ca2+
Authors: Strokin Mikhail , Sergeeva Marina , Reiser Georg
Published: July 2003

Docosahexaenoic acid (DHA) and arachidonic acid (AA), polyunsaturated fatty acids (PUFAs), are important for central nervous system function during development and in various pathological states. Astrocytes are involved in the biosynthesis of PUFAs in neuronal tissue. Here, we investigated the mechanism of DHA and AA release in cultured rat brain astrocytes.

Primary astrocytes were cultured under standard conditions and prelabeled with [14C]DHA or with [3H]AA. Adenosine 5′‐triphosphate (ATP) (20 μM applied for 15 min), the P2Y receptor agonist, stimulates release of both DHA (289% of control) and AA (266% of control) from astrocytes. DHA release stimulated by ATP is mediated by Ca2+‐independent phospholipase A2 (iPLA2), since it is blocked by the selective iPLA2 inhibitor 4‐bromoenol lactone (BEL, 5 μM) and is not affected either by removal of Ca2+ from extracellular medium or by suppression of intracellular Ca2+ release through PLC inhibitor (U73122, 5 μM).

AA release, on the other hand, which is stimulated by ATP, is attributed to Ca2+‐dependent cytosolic PLA2 (cPLA2). AA release is abolished by U73122 and, by removal of extracellular Ca2+, is insensitive to BEL and can be selectively suppressed by methyl arachidonyl fluorophosphonate (3 μM), a general inhibitor of intracellular PLA2 s.

Western blot analysis confirms the presence in rat brain astrocytes of 85 kDa cPLA2 and 40 kDa protein reactive to iPLA2 antibodies.

The influence of cAMP on regulation of PUFA release was investigated. Release of DHA is strongly amplified by the adenylyl cyclase activator forskolin (10 μM), and by the protein kinase A (PKA) activator dibutyryl‐cAMP (1 mM). In contrast, release of AA is not affected by forskolin or dibutyryl‐cAMP, but is almost completely blocked by 2,3‐dideoxyadenosine (20 μM) and inhibited by 34% by H89 (10 μM), inhibitors of adenylyl cyclase and PKA, respectively.

Other neuromediators, such as bradykinin, glutamate and thrombin, stimulate release of DHA and AA, which is comparable to the release stimulated by ATP.

Different sensitivities of iPLA2 and cPLA2 to Ca2+ and cAMP reveal new pathways for the regulation of fatty acid release and reflect the significance of astrocytes in control of DHA and AA metabolism under normal and pathological conditions in brain.

British Journal of Pharmacology (2003) 139, 1014–1022. doi:10.1038/sj.bjp.0705326
Pharmacological profile of store‐operated channels in cerebral arteriolar smooth muscle cells
Authors: Flemming R , Xu S Z , Beech D J
Published: July 2003

In this study, we determined a pharmacological profile of store‐operated channels (SOCs) in smooth muscle cells of rabbit pial arterioles. Ca2+‐indicator dyes, fura‐PE3 or fluo‐4, were used to track [Ca2+]i and 10 μM methoxyverapamil (D600) was present in all experiments on SOCs to prevent voltage‐dependent Ca2+ entry. Store depletion was induced using thapsigargin or cyclopiazonic acid.

SOC‐mediated Ca2+ entry was inhibited concentration dependently by Gd3+ (IC50 101 nM). It was also inhibited by 10 μM La3+ (70% inhibition, N=5), 100 μM Ni2+ (57% inhibition, N=5), 75 μM 2‐aminoethoxydiphenylborate (66% inhibition, N=4), 100 μM capsaicin (12% inhibition, N=3) or preincubation with 10 μM wortmannin (76% inhibition, N=4). It was completely resistant to 1 μM nifedipine (N=5), 10 μM SKF96365 (N=6), 10 μM LOE908 (N=14), 10–100 μM ruthenium red (N=1+2), 100 μM sulindac (N=4), 0.5 mM streptomycin (N=3) or 1 : 10,000 dilution Grammostolla spatulata venom (N=4).

RT–PCR experiments on isolated arteriolar fragments showed expression of mRNA species for TRPC1, 3, 4, 5 and 6.

The pharmacological profile of SOC‐mediated Ca2+ entry in arterioles supports the hypothesis that these SOCs are distinct from tonically active background channels and several store‐operated and other nonselective cation channels described in other cells. Similarities with the pharmacology of TRPC1 support the hypothesis that TRPC1 is a subunit of the arteriolar smooth muscle SOC.>

British Journal of Pharmacology (2003) 139, 955–965. doi:10.1038/sj.bjp.0705327
Lipid‐lowering properties of TAK‐475, a squalene synthase inhibitor, in vivo and in vitro
Authors: Nishimoto Tomoyuki , Amano Yuichiro , Tozawa Ryuichi , Ishikawa Eiichiro , Imura Yoshimi , Yukimasa Hidefumi , Sugiyama Yasuo
Published: July 2003

Squalene synthase is the enzyme that converts farnesyl pyrophosphate to squalene in the cholesterol biosynthesis pathway. We examined the lipid‐lowering properties of 1‐[[(3R,5S)‐1‐(3‐acetoxy‐2,2‐dimethylpropyl)‐7‐chloro‐5‐(2,3‐dimethoxyphenyl)‐2‐oxo‐1,2,3,5‐tetrahydro‐4,1‐benzoxazepin‐3‐yl]acetyl]piperidine‐4‐acetic acid (TAK‐475), a novel squalene synthase inhibitor.

TAK‐475 inhibited hepatic cholesterol biosynthesis in rats (ED50, 2.9 mg kg−1) and showed lipid‐lowering effects in beagle dogs, marmosets, cynomolgus monkeys and Wistar fatty rats.

In marmosets, TAK‐475 (30, 100 mg kg−1, p.o., for 4 days) lowered both plasma non‐high‐density lipoprotein (HDL) cholesterol and triglyceride, but did not affect plasma HDL cholesterol. On the other hand, atorvastatin (10, 30 mg kg−1, p.o., for 4 days) lowered the levels of all these lipids. A correlation between decrease in triglyceride and increase in HDL cholesterol was observed, and TAK‐475 increased HDL cholesterol with a smaller decrease in triglyceride than did atorvastatin.

TAK‐475 (60 mg kg−1, p.o., for 15 days) suppressed the rate of triglyceride secretion from the liver in hypertriglyceridemic Wistar fatty rats, which show an enhanced triglyceride secretion rate from the liver compared with their lean littermates.

In HepG2 cells, TAK‐475 and its pharmacologically active metabolite, T‐91485, increased the binding of 125I‐low‐density lipoprotein (LDL) to LDL receptors.

6 These results suggest that TAK‐475 has clear hypolipidemic effects in animals via inhibition of hepatic triglyceride secretion and upregulation of LDL receptors, and that TAK‐475 might increase HDL cholesterol by decreasing triglyceride. Thus, TAK‐475 is expected to be useful for the treatment of dyslipidemia.

British Journal of Pharmacology (2003) 139, 911–918. doi:10.1038/sj.bjp.0705332
On the estimation variance for the specific Euler–Poincaré characteristic of random networks
Authors: Tscheschel A. , Stoyan D.
Published: July 2003

The specific Euler number is an important topological characteristic in many applications. It is considered here for the case of random networks, which may appear in microscopy either as primary objects of investigation or as secondary objects describing in an approximate way other structures such as, for example, porous media. For random networks there is a simple and natural estimator of the specific Euler number. For its estimation variance, a simple Poisson approximation is given. It is based on the general exact formula for the estimation variance. In two examples of quite different nature and topology application of the formulas is demonstrated.
Measurement of the electric field distribution and potentials on the object surface in an emission electron microscope without restriction of the electron beams
Authors: Nepijko S. A. , Gloskovskii A. , Sedov N. N. , Schönhense G.
Published: July 2003

An emission electron microscope without restriction of the electron beams was used to visualize and measure the distribution of electric fields and potentials on the surface under study. Investigations of this kind can be performed in an emission electron microscope without any aperture diaphragm. The potentialities of this method have been demonstrated using measurements with a silicon p–n junction to which a voltage has been applied in the reverse direction. The quantitative analysis becomes more complicated if the specimen is characterized by a heterogeneous intensity distribution of the electron emission from different areas of its surface. In the latter case two images obtained at different accelerating voltages (i.e. different voltages of the microscope extractor) provide the information necessary for an analysis of electric field and potential distributions.
The maintenance and preservation of keratinophilic fungi and related dermatophytes
Authors: Deshmukh S. K.
Published: July 2003

A total of 239 fungi belonging to nine genera and 23 species were maintained on agar slopes in a refrigerator at +8 ± 1 °C and in sterile distilled water, under liquid paraffin, dried on silica gel, in sterile soil at room temperature. A limited number has been stored by freeze‐drying between 1985 and 1998. It is recommended that each isolate should be maintained by at least two of these methods. The choice of the method will depend to a large extent on the equipment and facilities available in the laboratory. It is reported that simple methods can be used for preservation of keratinophilic fungi and related dermatophytes.
An epidemiological and clinical study of untreated patients with tinea pedis within a company in Japan
Authors: Maruyama R , Hiruma M , Yamauchi K , Teraguchi S , Yamaguchi H
Published: July 2003

In this study, we investigated epidemiological and clinical aspects of dermatophyte foot infections among employees of one dairy product company located in Kanagawa prefecture in central Japan. Sixty‐nine of 377 subjects were reported having “athlete's foot” in response to a simple questionnaire. A subsequent mycological examination revealed 41 untreated patients with tinea pedis and/or tinea unguium (89% of subjects examined) and the overall prevalence was estimated at 18%. Comparing severity scores of five clinical symptoms (itching, erythema, vesicles/pustules, erosion/maceration, and scales) between those untreated patients within the subjects and another group of patients who spontaneously attended dermatological clinics to treat tinea pedis, itching, erythema, and total score were significantly higher in the latter group.
Subcutaneous phaeohyphomycosis on face caused by Cladophialophora bantiana
Authors: Jain S. K. , Agrawal S. C. , Jain P. C.
Published: July 2003

We report the case of a patient suffering from subcutaneous phaeohyphomycosis caused by Cladophialophora bantiana. The face of the upper site was involved with small, stellate, pyogranulomatous foci and low inflammation. The patient was treated by topical and systemic corticosteriod and amphotericin B. After 3 months of treatment, the patient showed good response.
Sialic acids are absent from the dermatophytes Trichophyton mentagrophytes and Trichophyton rubrum
Authors: Esquenazi D. , Rozental S. , Alviano C. S. , Travassos L. R. , Schauer R.
Published: July 2003

Summary Experiments were performed to determine whether sialic acids are expressed in two dermatophytes: Trichophyton rubrum and T. mentagrophytes, similarly to other fungal pathogens. Chemical extraction of mycelia and microconidia followed by high‐performance thin‐layer chromatography and colorimetric assays were all negative for sialic acid. Incubation of dermatophytes in the presence of Limax flavus agglutinin, specific for sialic acid, was negative in a fluorescence staining test. We have also used other lectins that bind to sialic acid and/or other sugar residues, and these ligands coupled to fluorescein strongly stained these fungi. Such fluorescence staining was not abolished or reduced when fungi were pretreated with sialidase. Different strains of influenza virus which recognize sialic acid residues were also used, but no agglutination of the dermatophytes was observed. Based on these methods, which successfully revealed the presence of sialic acids in other fungal pathogens, we show that these monosaccharides do not occur in both dermatophyte species. Thus, sialic acids do not seem to play a role in the pathogenicity of these fungi.
What is the significance of an isolated positive cryptococcal antigen in the cerebrospinal fluid of cancer patients?
Authors: Kontoyiannis Dimitrios P.
Published: July 2003

We evaluated the significance of an isolated positive cryptococcal antigen titer in the cerebrospinal fluid (CSF) of 12 cancer patients. In most of the cases, the test had a low titer, was frequently associated with an intracranial malignancy and was considered to represent a false‐positive result. Hence, an isolated cryptococcal antigen in the CSF has an unclear clinical value and must be interpreted with caution.
Salivary Gland Progenitor Cells Induced by Duct Ligation Differentiate Into Hepatic and Pancreatic Lineages
Authors: Okumura Kenji , Nakamura Kimitoshi , Hisatomi Yuichiro , Nagano Koji , Tanaka Yasuhiko , Terada Kunihiko , Sugiyama Toshihiro , Umeyama Kazuhiro , Matsumoto Kozo , Yamamoto Tetsuro , Endo Fumio
Published: June 2003

Tissue damage can be assessed based on regenerative responses, including progenitor cell proliferation. In the salivary gland, tissue damage induced by ligation of main ducts leads to the disappearance of acinar cells and to marked proliferation of ductal cells. Reopening of the ducts leads to repopulation of acinar cells within 1 to 2 weeks, which suggests activation of tissue progenitor cells in a damaged state. Because submandibular glands derive from the endoderm and ectoderm, we investigated the possibility of the presence of endodermal progenitor cells. We cultured cells obtained from the ligated salivary gland and identified colonies of epithelium–like cells. We singled out and purified the cells by limited dilution, and one of the cells designated SGP–1 was used for further experiments. The SGP–1 expresses both α6β1 integrin and cytoplasmic laminin. The hematopoietic stem cell marker CD34 and hepatic oval cell markers such as albumin, α–fetoprotein (AFP), and cytokeratin 19 are all negative. However, when SGP–1 cells were transplanted into the liver via the portal vein, these cells were integrated into hepatic trabecula and produced albumin. When SGP–1 cells formed clusters on type I collagen–coated dishes, they differentiated into endodermal lineage and 2 major types of clusters appeared: one contained cells positive for AFP and/or albumin (hepatic cluster) and the other positive for glucagon and/or insulin (pancreatic cluster). On laminin–coated dishes, SGP–1 selectively differentiated into hepatic–type cells. In conclusion, the multipotent progenitor cells isolated from the rat salivary gland have characteristics of tissue stem cells and can differentiate into cells of endodermal lineages.
A Highly Efficient, Stable, and Rapid Approach For Ex Vivo Human Liver Gene Therapy Via A Flap Lentiviral Vector
Authors: Giannini Carlo , Morosan Serban , Tralhao Guilherme J. , Guidotti Jacques Emmanuel , Battaglia Serena , Mollier Karine , Hannoun Laurent , Kremsdorf Dina , Gilgenkrantz Helene , Charneau Pierre
Published: June 2003

Allogenic hepatocyte transplantation or autologous transplantation of genetically modified hepatocytes has been used successfully to correct congenital or acquired liver diseases and can be considered as an alternative to orthotopic liver transplantation. However, hepatocytes are neither easily maintained in culture nor efficiently genetically modified and are very sensitive to dissociation before their reimplantation into the recipient. These difficulties have greatly limited the use of an ex vivo approach in clinical trials. In the present study, we have shown that primary human and rat hepatocytes can be efficiently transduced with a FLAP lentiviral vector without the need for plating and culture. Efficient transduction of nonadherent primary hepatocytes was achieved with a short period of contact with vector particles, without modifying hepatocyte viability, and using reduced amounts of vector. We also showed that the presence of the DNA FLAP in the vector construct was essential to reach high levels of transduction. Moreover, transplanted into uPA/SCID mouse liver, lentivirally transduced primary human hepatocytes extensively repopulated their liver and maintained a differentiated and functional phenotype as assessed by the stable detection of human albumin and antitrypsin in the serum of the animals for months. In conclusion, the use of FLAP lentiviral vectors allows, in a short period of time, a high transduction efficiency of human functional and reimplantable hepatocytes. This work therefore opens new perspectives for the development of human clinical trials based on liver–directed ex vivo gene therapy.
Interleukin 6/Gp130–Dependent Pathways Are Protective During Chronic Liver Diseases
Authors: Streetz Konrad L. , Tacke Frank , Leifeld Ludger , Wüstefeld Torsten , Graw Andrea , Klein Christian , Kamino Kenjii , Spengler Ulrich , Kreipe Hans , Kubicka Stefan , Müller Werner , Manns Michael P. , Trautwein Christian
Published: June 2003

The contribution of the acute phase inducer interleukin 6 (IL–6) in the pathogenesis of liver diseases is yet unclear. Our analysis showed enhanced expression of IL–6 in livers derived from patients with acute and chronic liver diseases. Additionally, IL–6 plasma levels were significantly increased in patients with chronic liver diseases and showed an inverse correlation with biochemical markers of liver function and a positive correlation with inflammatory markers, signs of portal hypertension, and the degree of liver fibrosis. To prove the relevance of these clinical findings, we applied the tetrachlorcarbonide (CCl4) model to conditional knockout animals (Cre/loxP system) for gp130, the common signal transducer of IL–6 family cytokines. Cre recombinases were expressed through a hepatocyte (AlfpCre) and a ubiquitous (MxCre) control element. Gp130 deleted mice had a totally abolished STAT3 activation and acute phase response induction, but gp130 deletion had no effect on the degree of acute liver injury and subsequent hepatocyte proliferation. In contrast, during chronic liver injury induced by biweekly application of CCl4, deletion of the gp130 receptor in nonparenchymal liver cells and not hepatocytes resulted in fibrosis progression. In conclusion, our experiments indicate an involvement of IL–6 in the pathogenesis of liver diseases and suggest a protective role of IL–6/gp130–dependent pathways in nonparenchymal liver cells during fibrosis progression in chronic liver diseases.