bluuebunny/crossref_metadata_2025 huggingface dataset:
Investment Scale as a Signal in Industrial Assistance Schemes with Employment Objectives
Authors: Wren Colin
Published: May 2003

The paper examines the implications of asymmetric information for the existence and efficiency of automatic industrial assistance schemes with employment objectives, based on UK regional policy experience. Firms differ in productivities and factor intensities, about which the government is uninformed. The more capital‐intensive firms generate few jobs but implement larger project scales, and the use of this signal for the design of efficient assistance contracts is analysed. The fixed‐rate investment grant used in UK regional policy is found to be poor performing, and is welfare‐dominated by contracts in the grant amount. Assistance contracts specifying both the grant amount and rate may be preferred.
The Covariance Structure of Earnings in Great Britain, 1991–1999
Authors: Ramos Xavier
Published: May 2003

I analyse the dynamic structure of earnings in Great Britain for the period 1991–99 by decomposing the earnings covariance structure into its permanent and transitory components. According to the British Household Panel Study data, earnings inequality of male full‐time employees increases over the 1990s. However, earnings mobility may have also increased. That is, for this period earnings persistence falls. This evidence is at odds with previous literature on earnings dynamics both for Britain and other OECD countries. Moreover, human capital and job related characteristics account for nearly all persistent earnings differences and the transitory component is highly persistent.
On Measuring Deprivation and the Standard of Living in a Multidimensional Framework on the Basis of Aggregate Data
Authors: Dutta Indranil , Pattanaik Prasanta K. , Xu Yongsheng
Published: May 2003

In measuring social deprivation in a multidimensional framework, ideally one should first measure each individual's overall deprivation, and then aggregate the overall deprivation levels of all individuals. However, given only aggregate data, one is often forced to measure social deprivation in terms of each attribute separately and then to aggregate them so as to get the overall social deprivation. This paper shows that it is only under extremely stringent conditions that this procedure would always yield the same result as the conceptually sound procedure referred to earlier. A similar difficulty also arises in measuring a society's standard of living.
Efficiency Pricing, Tenancy Rent Control and Monopolistic Landlords
Authors: Basu Kaushik , Emerson Patrick M.
Published: May 2003

This paper presents a model of ‘tenancy rent control’ where rent increases on, and evictions of, sitting tenants are prohibited but nominal rents for new tenants are unrestricted. If there is any inflation, landlords prefer to take short‐staying tenants. If there is no way for landlords to tell a tenant's type, an adverse selection problem arises. If landlords have monoply power, then they may prefer not to raise the rent even when there is excess demand for housing. These ‘efficiency rents’ show that tenancy rent control can give rise to equilibria that look as if there were a flat ceiling on rents.
Fixed or Flexible? Wage‐setting in Search Equilibrium
Authors: Ellingsen Tore , Rosén ÅSa
Published: May 2003

Why do some vacancies offer a posted wage whereas others offer a negotiable wage? The paper endogenizes the choice of wage policy in a standard sequential search model with heterogeneous workers. In particular, we identify circumstances such that there exists an equilibrium in which all firms negotiate wages. We find that this equilibrium exists if and only if the labour market is sufficiently tight and worker heterogeneity is sufficiently large.
Wage‐setting under Different Monetary Regimes
Authors: Holden Steinar
Published: May 2003

In an economy with large wage‐setters (like industry unions), the monetary regime affects the trade‐off between consumer real wages and employment and profits faced by the wage‐setters. This paper shows that an exchange rate target, including participation in a monetary union, is likely to involve lower wages in the traded sector, and higher wages in the non‐traded sector, than does a price target. An exchange rate target also involves higher prices on non‐traded goods relative to on traded goods. Overall welfare is likely to be higher under a price target.
Effects on Employment of Trade and Technical Change: Evidence from Norway
Authors: Salvanes Kjell G. , Førre Svein Erik
Published: May 2003

Trade and technology‐related explanations for the change in plant‐level skill composition in Norway are examined by exploiting matched employer–employee data. The results show that the changes are taking place mainly through a reallocation of labour resources between plants within sectors, leading to greater dispersion of skills across establishments. Results from estimating plant‐level dynamic demand functions support skill‐biased technological change via a positive gross job creation effect. A strong impact from trade is also found along the gross job destruction margin for low‐ and medium‐educated workers in sectors exposed to increased competition from abroad. Highly educated workers are insulated from negative trade effects.
Reflections on International Criminal Justice
Authors: Cassese Antonio
Published: May 2003

Judge Cassese presents arguments in favour of the use of international courts in order to punish war crimes. He argues that the application of justice through a court is better in certain circumstances than amnesties. He examines the merits of international courts rather than national courts, but acknowledges that at present there are several major stumbling blocks to an effective international criminal justice system.
Legal Irritants: Good Faith in British Law or How Unifying Law Ends Up in New Divergencies
Authors: Teubner Gunther
Published: May 2003

Legal transplant is an unsatisfactory metaphor for describing the transfer of legal rules from one legal system to another. Instead, the metaphor of legal irritant better describes the impact on the legal system, and then a distinction between tight and loose coupling between law and its social context better explains the trajectory of social effects. The example of the importation of the civil law concept of good faith into British law illustrates the co‐evolving trajectories of the legal system and tightly coupled social systems which instead of furthering harmonisation of laws produces new divergences as their unintended consequences.
Choice of Law in Tort—Blending in with the Landscape of the Conflict of Laws?
Authors: Harris Jonathan
Published: May 2003

The reformed choice of law in tort rules contained in the Private International Law (Miscellaneous Provisions) Act 1995 have proved a source of great controversy. This piece attempts to show that there are wider concerns fuelled by the Act. It seeks to demonstrate that one can not reform one area of the Conflict of Laws (such as choice of law in tort) in isolation from other areas (such as jurisdiction in tortious matters and choice of law in contract) and to illustrate the unsatisfactory state that the statutory reforms have had on these other areas. The analysis of the problems generated by the Act may be used as a model for a far more fundamental proposition: namely that the tendency to regard choice of law and jurisdiction as separate areas throughout the Conflict of Laws, rather than as combining to form a coherent law of international litigation, is a critical shortcoming of the study of the subject.
Sex Equality as Substantive Justice
Authors: Hervey Tamara K.
Published: May 2003

Books reviewed in this article:

Sandra Fredman, Women and the Law

Aileen McColgan, Just Wages for Women
Limited Liability: Large Company Theory and Small Firms
Authors: Freedman Judith
Published: May 2003

Current enthusiasm for the ‘enterprise culture’ results in strong support for easy access to limited liability forms of business organisation. This has manifested itself in the creation of new limited liability vehicles such as the LLC and the LLP. The UK Company Law Review is examining ways of enhancing the attractiveness of the limited liability company to small business owners. This article examines the claims made for the ‘efficiency’ of limited liability and the applicability of these claims to small firms. It raises the importance of taking into account public policy issues beyond economic efficiency when considering the degree of risk taking and shifting to be encouraged. The article concludes that, although it is difficult to find rational methods of restricting access to limited liability, it does not follow that limited liability should be positively encouraged for all small firms. It is important to signal the limitations of limited liability.
Share Capital and Creditor Protection: Efficient Rules for a Modern Company Law
Authors: Armour John
Published: May 2003

This article examines the case for rules of company law which regulate the raising and maintenance of share capital by companies. The enquiry has practical relevance because the content of company law is currently under review, and the rules relating to share capital have been singled out for particular attention. The existing rules, which apply generally, are commonly rationalised as a means of protecting corporate creditors. The analysis considers whether such rules can be understood as responses to failures in the markets for corporate credit. It suggests that whilst the current rules are unlikely, on the whole, to be justified in terms of efficiency, a case may be made for a framework within which companies may ‘opt in’ to customised restrictions on dealings in their share capital.
International Promises and Domestic Pragmatism: To What Extent will the Employment Relations Act 1999 Implement International Labour Standards Relating to Freedom of Association
Authors: Novitz Tonia
Published: May 2003

This paper explores the rhetoric and reality surrounding implementation of international labour standards in the Employment Relations Act 1999. It focuses on UK commitments relating to freedom of association and considers whether the new legislation goes any significant way towards their fulfilment. The paper begins by outlining obligations which arise from a state's membership of the International Labour Organisation (ILO) and ratification of ILO Conventions. It then goes on to examine indications that, since the change of government in 1997, there has been a significant shift in UK policy relating to such international obligations. The remainder of the paper examines reforms made by the Employment Relations Act to trade union recognition, protection of strikers from dismissal and prevention of anti‐union discrimination. It emerges that the Third Way proposed by the present Labour Government entails a complicated detour from the path of full compliance with ILO standards.
Children of Misfortune: Parallels in the Cases of Child Murderers Thompson and Venables, Barratt and Bradley
Authors: Rowbotham Judith , Stevenson Kim , Pegg Samantha
Published: May 2003

Were Victorian attitudes towards child murderers harsher than those now? Theparallel cases of the notorious Bulger and Burgess murders, 1993 and 1861,demonstrate any such assumption is simplistic. Reactions from the public and legalsystem to these disturbingly similar murderers are explored, including significantlydiffering responses to the trial reportage, pointing up the debate over ‘fair’ trials and themedia's role in that process. Though newspapers present such subject matter‘sensationally’, contextual examination of the coverage demonstrates they are reactingto, not creating, public reactions. Differences in public attitudes between the two arehighlighted, suggesting disquieting reasons for modern responses.
Women Behind Bars: Explanations and Implications
Authors: Deakin Jo , Spencer Jon
Published: May 2003

Increases in the women's prison population in the UK, in line with many other industrialised countries, is occurring at an alarming rate and yet the types of offences for which women are imprisoned and the lengths of sentences they receive suggest that most present little risk to society. However, the personal and social costs to these women and their families of being imprisoned, and the economic costs to society, can be immense. Through an analysis of official statistics, this article explores some possible explanations for the growth in female imprisonment set within the framework of effective practice with a particular emphasis on the actuarial approach to managing offenders.
Privatisation and Innovation — Rhetoric and Reality: The Development of a Therapeutic Community Prison
Authors: Genders Elaine
Published: May 2003

Privatisation is here to stay, albeit under the rhetorical guise of public‐private partnership. All new prisons are now provided by means of competition. The recent issuing to potential contractors of the invitation to tender, and award of contract to Premier Prisons, for the DCMF (design, construction, management and finance) of the first purpose built therapeutic community prison HMP Dovegate (opened in November 2001) illustrates well some of the advantages and disadvantages inherent in the private as opposed to public mode of provision of innovative regimes.
In Denial of Murder: No Parole
Authors: Samuels Alec
Published: May 2003

The mandatory lifer who denies guilt is likely to be refused parole, or given only delayed parole, because it is said that his attitude is all wrong and he represents a continuing danger to the public. When it comes to parole, better to be guilty than innocent.
Probation, Punishment and Restorative Justice: Should Al Turism be Engaged in Punishment?
Authors: Duff R. A.
Published: May 2003

The argument of this article is that we should understand probation as a mode of punishment: not as the kind of ‘merely punitive’ punishment which is all too familiar in our existing penal systems, but as a mode of constructive punishment which seeks to bring offenders to face up to the effects and implications of their crimes, to rehabilitate them, and to secure the kinds of goal — reparation and reconciliation — that are emphasised by advocates of restorative justice. To support this argument, I sketch a conception of punishment as a communicative enterprise in which probation officers would play a crucial role — not merely in administering sentences, but as mediators between offenders, victims and the wider community.
‘It's No Time or High Time’: Young Offenders' Experiences of Time and Drug Use in Prison
Authors: Cope Nina
Published: May 2003

Article: This article explores perspectives of time amongst young male inmates in prison and reflects on their cannabis use as a strategy that enabled them to manage their long sentences. The article considers the theoretical foundations of time and its association with punishment and prison, arguing that prison time is conceptually distinct from experiences of time outside prison. The overt external control over inmates' time and the limited resources available to make time ‘flow’ means time is experienced consciously in prison. This experience of time influenced the significance and function of the inmates' cannabis use, which helped them to control and manipulate the passing of their sentence.
Legislative—Executive Relations in the EU
Authors: Crum Ben
Published: May 2003

This article outlines and evaluates competing views of the future organization of legislative—executive relationships in the European Union (EU). It argues that the organization of legislative—executive relations faces three challenges: to streamline the organization of powers, to convey democratic accountability, and to accommodate diversity between Member States' interests. By systematically analysing member governments' contributions to the debate on the Future of the EU, three main positions are identified: a federal, an intergovernmental and a ‘federation of nation‐states’ position. For each of these positions an internally coherent account is reconstructed, including their respective answers to the three challenges outlined.
Cutting the Bank Down to Size: Efficient and Legitimate Decision‐making in the European Central Bank After Enlargement
Authors: Heisenberg Dorothee
Published: May 2003

This article examines the problems enlargement poses for one specific supranational organization, the European Central Bank (ECB). The article synthesizes three different literatures, on enlargement, ECB transparency and legitimacy, and effective monetary policy‐making, which up until now have not been linked. The three issues are related, and ought to be considered together when policy choices regarding institution‐building are made, because the choices in one issue constrain those in the others. Specifically, the argument is that transparency in the decision‐making process is key to allowing the denationalization of decision‐making to make it more effective. The more transparent the policy‐making process is, the easier it is to have a rotation of votes. Conversely, if the policy‐making process is opaque, a system of combining regions into one voting entity is better because the citizenry is represented in every vote, even if in a highly diluted fashion. The proposed ECB reform does not adequately address legitimate concerns on the part of the public as to how the decisions are made within the Governing Council.
Deficit Targeting Strategies: Fiscal Consolidation and the Probability Distribution of Deficits under the Stability Pact
Authors: Hughes Hallett A.J. , McAdam Peter
Published: May 2003

Using stochastic simulations, this article analyses the probability distribution of a country's deficit ratio under fixed exchange rates and a variety of monetary and fiscal policy rules. The purpose is to show how the probability of an ‘excessive deficit’, defined by Europe's Stability Pact as a deficit to GDP ratio above 3 per cent, varies with different deficit targets and policy rules. Using a macro model, we find that when subject to historically consistent shocks, these fiscal ratios typically have a wide distribution, with fat tails and significantly longer tails on the upper side. That means fiscal targets may have to be country‐specific and conservative, and that fiscal policy has to be forward‐looking to keep the probability of excessive deficits below acceptable limits.
The Creation, Interpretation and Contestation of Institutions — Revisiting Historical Institutionalism
Authors: Lindner Johannes , Rittberger Berthold
Published: May 2003

One shortcoming of much of the historical institutionalist literature is its alleged lack of testable propositions and the elusive notion of ‘unintended consequences’ of initial institutional choices. This article, which offers an historical institutionalist explanation of institutional creation and operation, aims to overcome these shortcomings. We develop a set of propositions and demonstrate their plausibility by exploring the creation of the European Community's budgetary treaty in 1970 and the operation of the enacted treaty provisions. We demonstrate that, under specific conditions, actors may be doomed to opt for ‘dysfunctional’ institutions at the moment of their creation. Furthermore, we show that the notion of ‘unintended consequences’ does not necessarily help us to understand the reason for the contestation of treaty provisions.
European Integration: Between Micro‐Regionalism and Globalism
Authors: Longo Michael
Published: May 2003

With the Convention on the Future of the European Union (EU) now in progress, it is opportune to examine the processes and forces currently shaping the EU's constitutional development and impacting on governmental arrangements. For some time, debate on the constitutionalization of the EU has focused on whether the EU needs a constitution and, if so, what kind of constitution. It is argued that analysis of these core issues cannot be conducted in isolation from the processes and forces currently shaping the EU, chief among which are micro‐regionalization, Europeanization and globalization. Moreover, a comprehensive understanding of the nature and degree of interaction between these processes and forces is required to inform theory and guide constitutional practice.
Costs, Commitment and Compliance: The Impact of EU Democratic Conditionality on Latvia, Slovakia and Turkey
Authors: Schimmelfennig Frank , Engert Stefan , Knobel Heiko
Published: May 2003

‘Democratic conditionality’ is the core strategy of the EU to induce candidate states to comply with its human rights and democracy standards. How does it work and when is it effective? This article reports findings of a comparative study of ‘hard cases’: Slovakia under Meciar; Turkey; and Latvia. We argue that EU democratic conditionality is a strategy of ’reinforcement by reward’ which works through intergovernmental material bargaining. Its efficacy depends on the candidate governments' domestic political costs of compliance. By contrast, social influence and transnational mobilization have proved ineffective.
Price Insurance Aspects of Monetary Union
Authors: VON FURSTENBERG GEORGE M.
Published: May 2003

Omitted from traditional optimal currency area criteria, price effects are important because regional monetary union protects from pricing risks and contributes to greater uniformity and efficiency in price‐setting. Among member countries it reduces price dispersion in tradeables in part by irrevocably fixing the internal exchange rate and in part by facilitating arbitrage. The larger integrated market of the euro area also encourages outside producers to engage in more ‘pricing to market’ within it. With inflation differentials in tradeables reduced throughout the euro area, systematic national inflation differentials are likely to be limited to those attributable to productivity differentials that cause differences in the inflation rate of non‐tradeables.
Democratic Deficits in Comparison: Best (and Worst) Practices in European, US and Swiss Merger Regulation
Authors: Zweifel Thomas D.
Published: May 2003

Policy‐makers and scholars continue to express concerns that the EU suffers from a ‘democratic deficit’. But most democratic deficit arguments are not based on recent empirical research; and seeing the EU as sui generis, they fail to compare the EU to other polities. This article compares the European ‘regulatory state’ with two federal democracies, the United States and Switzerland, in recent merger regulation. Its main finding is that European merger regulation is less democratic than American, but more democratic than Swiss regulation. If the EU suffers from a democratic deficit, it is hardly alone.
Sailing Through Troubled Waters: Palestinian Christians in the Holy Land
Authors: Raheb Mitri
Published: May 2003

For many people the names “Arab Christians” and “Palestinian Christians” seem to be oxymoronic. Christianity was, however, born in the Middle East, in a little town called Bethlehem. This article explores the ways in which Palestinian Christians, a minority group in both Palestine and Israel, relate to both Jews and Muslims in Palestine and Israel. Though there is no covert persecution of Palestinian Christians, they face the same trials as other Arabs and Muslims in Palestine, due to the current policies and actions of the Israeli government and to the current “war on terrorism.” In fact, Christians in Palestine become easy targets for both those enraged by and supportive of the US declaration of war. At the same time, they offer the world an example of healthy Christian–Muslim relations. Perhaps too, Palestinian Christians can be the bridge between the Jewish and Muslim communities in the Holy Land.
September 11 and the Role of the Theologian
Authors: Chinnici Rosemary
Published: May 2003

As is the case with all “disasters” the nation is experiencing the various psychological stages to the September 11, 2001 disaster: threat, warning, impact, inventory, heroism, honeymoon, disillusionment, and reconstruction. In order for healing to occur from and within the religious community, theologians, pastors, and religiously–minded people must enter into these different stages of disaster and suffer–with the community. Instead of explaining September 11 from an abstract, removed stance, we ought to reveal our concerns and uncertainties about God in this situation and wonder with the rest of the community of grievers, “How has this happened?” From this place, true healing and reconstruction of the community will be possible.
A tetradic analysis of GIS and society using McLuhan's law of the media
Authors: Sui Daniel Z. , Goodchild Michael F.
Published: May 2003

The social implications of GIS have been debated over the past five years among scholars in several disciplines. GIS have been either conceived by practitioners as value‐free, neutral tools for problem‐solving or castigated by critical social theorists as socially biased technologies serving only corporate and state interests. Neither of these polarized views is very helpful in understanding the complex relationship between GIS and society. This paper argues that GIS are increasingly becoming media for communicating various crucial social and environmental information to the general public. By reconceptualizing GIS as media, the paper conducts a detailed tetradic analysis on the social implications of GIS using Marshall McLuhan's law of media. The analysis reveals the paradoxical and ambivalent nature of GIS technology. To make GIS fulfill democratic ideals in society, this paper calls for a shift of perspective, from viewing them as instruments for problem‐solving to viewing them as media for communication. This shift from instrumental to communicative rationality enables us to examine more critically and holistically how space, people and environment have been represented, manipulated and visualized in GIS and thus promotes a more critical and democratic GIS practice.
Geolibraries: geographers, librarians and spatial collaboration
Authors: Boxall James
Published: May 2003

Geography, GIS and GIScience are closely aligned with the emergence of ‘geolibraries’. Geolibraries are also coincident with the metaphor of ‘Digital Earth’. The growth in these areas of research and practice can be traced to collaborations among multiple disciplines. Geography and library science stand out as interesting partners. At first glance it may seem that it would be difficult to find common ground for such collaboration. The reality is that the two communities have been closer for longer than most may think. Such collaboration does, however, face unique challenges in a Canadian context, and collaborations thus far have been more successful in the United States. This paper reviews issues at the intersection of GIS and libraries and offers suggestions for further spatial collaboration in Canada within the context of geolibraries and GIScience.
Developing geographic information infrastructures for local government: the role of trust
Authors: Harvey Francis
Published: May 2003

The United States's National Spatial Data Infrastructure (NSDI) model presumes that the local government agencies of counties and municipalities will share their geographic information freely with government agencies of regions, states and federal agencies. This article takes up the issue of local government involvement in the NSDI by asking the question: why should local governments involve themselves in the NSDI? This question is informed by considering the social and technological imbrication of the NSDI.

One of the oldest spatial data infrastructure projects, the NSDI offers insights into the complexity of implementing infrastructure in federal models of shared governance. This article focuses on the political and financial dimensions of developing infrastructure among local governments. Trust is quintessential at this level of government. Local government agency activities experience an inherently closer coupling with political representatives and with different agencies in both intramunicipal and intermunicipal activities. Building the NSDI is fundamentally an interagency act and thus a matter of trust. Trust is a key issue in the development of the NSDI, as the results of a study of Kentucky local government agencies indicate.
The true cost of spatial data in Canada
Authors: Klinkenberg Brian
Published: May 2003

The evolution of the Information Age, in Canada, has meant an unheralded parallel social evolution—the development of a class structure, if you will, that is tied to data accessibility. While other countries have made data freely available for use by industry, education and the public, Canada has opted to follow a restrictive data policy under which data are essentially available to a select few—those who can afford the prices. While anyone can purchase the data, not everyone can pay the price.

The implications of this in our society are immense and are felt throughout our social structures. One obvious example of this is the lack of quality, high‐resolution Canadian data freely available for use in the Canadian education system, particularly in the university classes in which students today are usually introduced to GIS, visualization and data interpretation. Our students have data to work with, but often they are the freely available American data. They learn from examples derived in the mountains of Wyoming or the forests of Washington.

How did this Canadian data restriction happen? In this paper, the evolution of GIS classicism is explored through examination of the evolution in Canada of GIS itself. The data situation elsewhere in the world is reviewed, the feasibility of ‘freeing’ data is discussed and a call for a radical change in the way data/information are handled in Canada is presented.
Public participation geographic information systems across borders
Authors: Sieber R.E.
Published: May 2003

Geographic information systems (GIS) technology is increasingly being used by nongovernmental organizations, grassroots organizations and other activist groups involved in transforming social, economic and environmental policy in multiple countries. The use of GIS represents a response to the fact that environmental problems are multidimensional and refuse to acknowledge political borders. It also represents a growing awareness that, for activism to compete in an era of globalization, it must utilize tools that scale from a local to a multinational level.

A research field called public participation GIS (PPGIS) has emerged to investigate the use and value of GIS by marginalized peoples and communities engaged in social change. It has yet to formally examine cross‐border and multinational applications. This paper makes a substantial contribution to moving the PPGIS research agenda forward to pace existing nonprofit activities. The paper considers the critical aspects of PPGIS being used across borders and in scaling up nonprofit organizations. The paper briefly reviews the PPGIS literature on issues of resources and data access and the role of GIS expertise. It then analyzes the use of PPGIS across borders as a function of building organizational capacity. Theory is reinforced with examples of nonprofits currently using GIS in multiple countries. A transnational PPGIS is framed, which can serve as a base for further investigation and discussion.
The open black box: the role of the end‐user in GIS integration
Authors: Poore Barbara S.
Published: May 2003

Formalist theories of knowledge that underpin GIS scholarship on integration neglect the importance and creativity of end‐users in knowledge construction. This has practical consequences for the success of large distributed databases that contribute to spatial‐data infrastructures. Spatial‐data infrastructures depend on participation at local levels, such as counties and watersheds, and they must be developed to support feedback from local users. Looking carefully at the work of scientists in a watershed in Puget Sound, Washington, USA during the salmon crisis reveals that the work of these end‐users articulates different worlds of knowledge. This view of the user is consonant with recent work in science and technology studies and research into computer‐supported cooperative work. GIS theory will be enhanced when it makes room for these users and supports their practical work.
Exercise but not Prostanoids Enhance Levels of Vascular Endothelial Growth Factor and other Proliferative Agents in Human Skeletal Muscle Interstitium
Authors: Höffner Lotte , Nielsen Jens Jung , Langberg Henning , Hellsten Ylva
Published: May 2003

In the present study we examined whether exercise and prostanoids have an effect on the muscle interstitial concentration of vascular endothelial growth factor (VEGF) and on the proliferative effect of muscle interstitial fluid. Dialysate from resting and exercising human skeletal muscle, obtained either during control conditions or during cyclooxygenase inhibition, was examined for its content of VEGF and for its effect on endothelial cell proliferation. Microdialysis probes with high (960 kDa) and low (5 kDa) molecular‐mass cut‐off membranes were placed in the vastus lateralis muscle of healthy young males. The subjects performed one‐legged knee extensions (20 W). The concentration of VEGF in the 960 kDa dialysate was greater (P < 0.05) during exercise compared to at rest (67 ± 28 vs. 230 ± 22 pg ml−1). The rate of endothelial cell proliferation was 2.7‐fold higher (P < 0.05) with the 960 kDa dialysate from resting muscle than with perfusate and was 5.8‐fold higher (P < 0.05) than the perfusate value with dialysate from exercising muscle. VEGF was not enhanced with exercise in the 5 kDa dialysate, yet the exercise dialysate induced a 1.9‐fold higher (P < 0.05) proliferation than the resting dialysate. Cyclooxygenase inhibition did not affect the VEGF concentration or the proliferating effect of the dialysates (P > 0.05). This study demonstrates for the first time that VEGF is present in the interstitium of human skeletal muscle and that exercise enhances the interstitial concentration of VEGF and of other, as yet unidentified, angiogenic compounds. Products of cyclooxygenase do not appear to have an effect on the release of VEGF or other proliferative agents in human skeletal muscle.
Five ADNFLE Mutations Reduce the Ca2+ Dependence of the Mammalian α4β2 Acetylcholine Response
Authors: Rodrigues‐Pinguet Nivalda , Jia Li , Li Maureen , Figl Antonio , Klaassen Alwin , Truong Anthony , Lester Henry A. , Cohen Bruce N.
Published: May 2003

Five nicotinic acetylcholine receptor (nAChR) mutations are currently linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). The similarity of their clinical symptoms suggests that a common functional anomaly of the mutations underlies ADNFLE seizures. To identify this anomaly, we constructed rat orthologues (S252F, +L264, S256L, V262L, V262M) of the human ADNFLE mutations, expressed them in Xenopus oocytes with the appropriate wild‐type (WT) subunit (α4 or β2), and studied the Ca2+ dependence of their ACh responses. All the mutations significantly reduced 2 mM Ca2+‐induced increases in the 30 μM ACh response (P < 0.05). Consistent with a dominant mode of inheritance, this reduction persisted in oocytes injected with a 1:1 mixture of mutant and WT cRNA. BAPTA injections showed that the reduction was not due to a decrease in the secondary activation of Ca2+‐activated Cl− currents. The S256L mutation also abolished 2 mM Ba2+ potentiation of the ACh response. The S256L, V262L and V262M mutations had complex effects on the ACh concentration‐response relationship but all three mutations shifted the concentration‐response relationship to the left at [ACh]⩾ 30 μM. Co‐expression of the V262M mutation with a mutation (E180Q) that abolished Ca2+ potentiation resulted in 2 mM Ca2+ block, rather than potentiation, of the 30 μM ACh response, suggesting that the ADNFLE mutations reduce Ca2+ potentiation by enhancing Ca2+ block of the α4β2 nAChR. Ca2+ modulation may prevent presynaptic α4β2 nAChRs from overstimulating glutamate release at central excitatory synapses during bouts of synchronous, repetitive activity. Reducing the Ca2+ dependence of the ACh response could trigger seizures by increasing α4β2‐mediated glutamate release during such bouts.
Interaction between sympathetic nerve activation and muscle fibre contraction in resistance vessels of hamster retractor muscle
Authors: VanTeeffelen Jurgen W. G. E. , Segal Steven S.
Published: May 2003

The interaction between skeletal muscle contraction and sympathetic nerve activation (SNA) on blood flow during exercise has remained ambiguous due to indirect estimates of vasomotor control. In the hamster retractor muscle (n= 54), interactions between three levels of SNA (∼3, 6 and 12 Hz) and of contractile activity (2.5, 10 and 20 % duty cycle) were studied in feed arteries (FA) and first‐ (1A), second‐ (2A), and third‐order (3A) arterioles using intravital microscopy. During functional dilatation with rhythmic muscle contractions, sympathetic vasoconstriction was sustained in FA and 1A but impaired in 2A and 3A (P< 0.05), where vessels ‘escaped’ from responding to SNA. To account for changes in baseline diameter and blood flow during contractions, vasodilatation was induced passively (2–3 levels) in resting muscles with papaverine or sodium nitroprusside. Compared to functional dilatation, the range of passive dilatation was similar in 3A and progressively greater in 2A, 1A and FA. With passive dilatation, SNA responses were sustained in 2A and increased with baseline diameter in 3A. Blood flow through FA (rest, ∼20 nl s−1) increased ∼5‐fold during contractile activity and ∼10‐fold during passive dilatation. Absolute flow reductions (nl s−1) with SNA increased during contractile activity and during passive dilatation; relative flow reductions were impaired during functional dilatation (P< 0.05) and remained constant during passive dilatation. Thus, SNA can restrict blood flow to exercising muscle by constricting FA and 1A while dilatation prevails in 2A and 3A. Such concerted interaction will promote oxygen extraction when blood flow is restricted to maintain arterial pressure.
Facilitation of Ca2+‐dependent exocytosis by Rac1‐GTPase in bovine chromaffin cells
Authors: Li Quanwen , Ho Chi S. , Marinescu Vlad , Bhatti Humaa , Bokoch Gary M. , Ernst Stephen A. , Holz Ronald W. , Stuenkel Edward L.
Published: May 2003

Rho family GTPases are primary mediators of cytoskeletal reorganization, although they have also been reported to regulate cell secretion. Yet, the extent to which Rho family GTPases are activated by secretory stimuli in neural and neuroendocrine cells remains unknown. In bovine adrenal chromaffin cells, we found Rac1, but not Cdc42, to be rapidly and selectively activated by secretory stimuli using an assay selective for the activated GTPases. To examine effects of activated Rac1 on secretion, constitutively active mutants of Rac1 (Rac1‐V12, Rac1‐L61) were transiently expressed in adrenal chromaffin cells. These mutants facilitated secretory responses elicited from populations of intact and digitonin‐permeabilized cells as well as from cells under whole cell patch clamp. A dominant negative Rac1 mutant (Rac1‐N17) produced no effect on secretion. Expression of RhoGDI, a negative regulator of Rac1, inhibited secretory responses while overexpression of effectors of Rac1, notably, p21‐activated kinase (Pak1) and actin depolymerization factor (ADF) promoted evoked secretion. In addition, expression of effector domain mutants of Rac1‐V12 that exhibit reduced activation of the cytoskeletal regulators Pak1 and Partner of Rac1 (POR1) resulted in a loss of Rac1‐V12‐mediated enhancement of evoked secretion. These findings suggest that Rac1, in part, functions to modulate secretion through actions on the cytoskeleton. Consistent with this hypothesis, the actin modifying drugs phalloidin and jasplakinolide enhanced secretion, while latrunculin‐A inhibited secretion and eliminated the secretory effects of Rac1‐V12. In summary, Rac1 was activated by secretory stimuli and modulated the secretory pathway downstream of Ca2+ influx, partly through regulation of cytoskeletal organization.
Development of Rat CA1 Neurones in Acute Versus Organotypic Slices: Role of Experience in Synaptic Morphology and Activity
Authors: De Simoni Anna , Griesinger Claudius B. , Edwards Frances A.
Published: May 2003

Despite their wide use, the physiological relevance of organotypic slices remains controversial. Such cultures are prepared at 5 days postnatal. Although some local circuitry remains intact, they develop subsequently in isolation from the animal and hence without plasticity due to experience. Development of synaptic connectivity and morphology might be expected to proceed differently under these conditions than in a behaving animal. To address these questions, patch‐clamp techniques and confocal microscopy were used in the CA1 region of the rat hippocampus to compare acute slices from the third postnatal week with various stages of organotypic slices. Acute slices prepared at postnatal days (P) 14, 17 and 21 were found to be developmentally equivalent to organotypic slices cultured for 1, 2 and 3 weeks, respectively, in terms of development of synaptic transmission and dendritic morphology. The frequency of inhibitory and excitatory miniature synaptic currents increased in parallel. Development of dendritic length and primary branching as well as spine density and proportions of different spine types were also similar in both preparations, at these corresponding stages. The most notable difference between organotypic and acute slices was a four‐ to five‐fold increase in the absolute frequency of glutamatergic (but not GABAergic) miniature postsynaptic currents in organotypic slices. This was probably related to an increase in complexity of higher order dendritic branching in organotypic slices, as measured by fractal analysis, resulting in an increased total synapse number. Both increased excitatory miniature synaptic current frequency and dendritic complexity were already established during the first week in culture. The level of complexity then stayed constant in both preparations over subsequent stages, with synaptic frequency increasing in parallel. Thus, although connectivity was greater in organotypic slices, once this was established, development continued in both preparations at a remarkably similar rate. We conclude that, for the parameters studied, changes seem to be preprogrammed by 5 days and their subsequent development is largely independent of environment.
Aquaporin‐1 and HCO3−‐Cl−transporter‐mediated transport of CO2across the human erythrocyte membrane
Authors: Blank Michael E. , Ehmke Heimo
Published: May 2003

Recent studies have suggested that aquaporin‐1 (AQP1) as well as the HCO3−‐Cl−transporter may be involved in CO2transport across biological membranes, but the physiological importance of this route of gas transport remained unknown. We studied CO2transport in human red blood cell ghosts at physiological temperatures (37 °C). Replacement of inert with CO2‐containing gas above a stirred cell suspension caused an outside‐to‐inside directed CO2gradient and generated a rapid biphasic intracellular acidification. The gradient of the acidifying gas was kept small to favour high affinity entry of CO2passing the membrane. All rates of acidification except that of the approach to physicochemical equilibrium of the uncatalysed reaction were restricted to the intracellular environment. Inhibition of carbonic anhydrase (CA) demonstrated that CO2‐induced acidification required the catalytic activity of CA. Blockade of the function of either AQP1 (by HgCl2at 65 μM) or the HCO3−‐Cl−transporter (by DIDS at 15 μM) completely prevented fast acidification. These data indicate that, at low chemical gradients for CO2, nearly the entire CO2transport across the red cell membrane is mediated by AQP1 and the HCO3−‐Cl−transporter. Therefore, these proteins may function as high affinity sites for CO2transport across the erythrocyte membrane.
Methylmercury Differentially Affects GABAA Receptor‐Mediated Spontaneous IPSCs in Purkinje and Granule Cells of Rat Cerebellar Slices
Authors: Yuan Yukun , Atchison William D.
Published: May 2003

Using whole‐cell recording techniques we compared effects of the environmental cerebellar neurotoxicant methylmercury (MeHg) on spontaneous IPSCs (sIPSCs) of both Purkinje and granule cells in cerebellar slices of the rat. In Purkinje cells, bath application of 10, 20 or 100 μM MeHg initially increased then suppressed the frequency of sIPSCs to zero. In granule cells, the initial increase in frequency was not observed in ≈50 % of cells examined, but suppression of sIPSCs by MeHg occurred in every cell tested. For both cells, time to onset of effects of MeHg was inversely related to the concentration; moreover, the pattern of changes in mIPSCs induced by MeHg in the presence of tetrodotoxin was similar to that in sIPSCs. For each concentration of MeHg, it took 2–3 times longer to block sIPSCs in Purkinje cells than it did in granule cells. MeHg also initially increased then decreased amplitudes of sIPSCs to block in both cells; again the response was more variable in granule cells. In most Purkinje and some granule cells, MeHg induced a giant, slow inward current during the late stages of exposure. Appearance of this current appeared to be MeHg concentration dependent, and the direction of current flow was reversed by changing the holding potentials. Reduction of the [Cl−] in the internal solution caused inwardly directed, but not outwardly directed giant currents to disappear, suggesting that this current is a Cl−‐mediated response. However, bicuculline and picrotoxin failed to block it. MeHg apparently acts at both presynaptic and postsynaptic sites to alter GABAA receptor‐mediated inhibitory synaptic transmission. GABAA receptors in granule cells appear to be more sensitive to block by MeHg than are those in Purkinje cells, although the general patterns of effects on the two cells are similar.
Lucifer Yellow Slows Voltage‐Gated Na+ Current Inactivation in a Light‐Dependent Manner in Mice
Authors: Higure Yoko , Katayama Yoshimi , Takeuchi Keita , Ohtubo Yoshitaka , Yoshii Kiyonori
Published: May 2003

Lucifer Yellow CH (LY), a membrane‐impermeant fluorescent dye, has been used in electrophysiological studies to visualize cell morphology, with little concern about its pharmacological effects. We investigated its effects on TTX‐sensitive voltage‐gated Na+ channels in mouse taste bud cells and hippocampal neurons under voltage‐clamp conditions. LY applied inside cells irreversibly slowed the inactivation of Na+ currents upon exposure to light of usual intensities. The inactivation time constant of Na+ currents elicited by a depolarization to −15 mV was increased by fourfold after a 5 min exposure to halogen light of 3200 lx at source (3200 lx light), and sevenfold after a 1‐min exposure to 12 000 lx light. A fraction of the Na+ current became non‐inactivating following the exposure. The non‐inactivating current was ≈ 20 % of the peak total Na+ current after a 5 min exposure to 3200 lx light, and ≈ 30 % after a 1 min exposure to 12 000 lx light. Light‐exposed LY shifted slightly the current‐voltage relationship of the peak Na+ current and of the steady‐state inactivation curve, in the depolarizing direction. A similar light‐dependent decrease in kinetics occurred in whole‐cell Na+ currents of cultured mouse hippocampal neurones. Single‐channel recordings showed that exposure to 6500 lx light for 3 min increased the mean open time of Na+ channels from 1.4 ms to 2.4 ms without changing the elementary conductance. The pre‐incubation of taste bud cells with 1 mM dithiothreitol, a scavenger of radical species, blocked these LY effects. These results suggest that light‐exposed LY yields radical species that modify Na+ channels.