bluuebunny/crossref_metadata_2025 huggingface dataset:
Transport Taxes with Multiple Trip Purposes
Authors: Van Dender Kurt
Published: June 2003

A congestible urban transport system is considered in which cars and buses are used for commuting and non‐commuting trips. Commuting is a strict complement to taxable labour supply. The optimal tax structure for raising a given amount of government revenue is examined for the cases where differentiation of transport tolls between trip purposes is and is not possible. An application to Belgian urban environments shows that optimal toll differentiation produces significant efficiency improvements. Without differentiation, reforming transport taxes generates substantial gains only when the labour tax can be reduced.
The Repo Auctions of the European Central Bank and the Vanishing Quota Puzzle*
Authors: Nautz Dieter , Oechssler Jörg
Published: June 2003

Until June 2000 the European Central Bank (ECB) used fixed rate tenders for its weekly repo auctions. A switch to variable rate tenders became necessary due to massive overbidding by banks. In this paper we introduce a stylized game among banks to investigate this overbidding phenomenon. Our results confirm the weakness of the fixed rate tender format and indicate that the ECB's liquidity management has significantly improved since the switch to the variable rate system. Yet recent episodes of rate cut expectations suggest that the ECB's practice of setting a minimum bid rate should be abandoned in favor of a more symmetric interest rate target.
Monetary Policy Rules and Business Cycles
Authors: Kim Soyoung
Published: June 2003

Basic features of business cycle properties under both exogenous and endogenous monetary policy rules are examined in calibrated dynamic stochastic general equilibrium models with nominal rigidities (the nominal wage contract model, the monopolistic competition model with price adjustment costs and a combination of these models). The experiments show that the difference in business cycle features under exogenous and endogenous monetary policy rules is as large as the change generated by introducing nominal rigidities (and monetary disturbances). This result suggests that, for monetary business cycle research, developing a proper way to incorporate endogenous monetary policy rules may be as important as developing new transmission mechanisms of monetary policy disturbances.
How High is the Private Gain from Wage Indexation?
Authors: Laséen Stefan
Published: June 2003

The effects of firm‐specific shocks on the gain from writing state‐contingent wage contracts are examine in an extension of the model in Gottfries (1992). It is shown that the introduction of firm‐specific uncertainty increases the gain from indexation to prices only moderately. Moreover, nominal wage contracts should be more prevalent when unemployment benefits are high or unemployment spells are short.
Firm Size Distribution and Growth*
Authors: Pagano Patrizio , Schivardi Fabiano
Published: June 2003

Abstract Empirical documentation of the sectoral distribution of firm size for a set of European countries reveals substantial differences. We study the relationship between productivity growth at the industry level and size structure. A positive and robust relation is found between average firm size and growth. We ask why size should matter for growth by considering the role of innovation to construct a test based on the differential effect of size on growth according to various indicators of R&D intensity. Our results indicate that larger size fosters productivity growth because it allows firms to take advantage of all the increasing returns associated with R&D. We argue that our test can be interpreted as a test of reverse causality, which lends support to the view that firm size has a causal impact on growth.
Risk Preferences, Production Risk and Firm Heterogeneity*
Authors: Kumbhakar Subal C. , Tveterås Ragnar
Published: June 2003

A new technique is proposed for deriving the risk preference function under production risk and expected utility of profit maximization. The derivation depends on neither a specific parametric form of the utility function nor any distribution of the error term representing production risk. The proposed risk preference function is flexible enough to test different types of risk behavior and symmetry of the output distribution. Furthermore, our production risk specification allows for inputs with positive and negative marginal risk. The econometric model accommodates production risk, risk preferences and firm heterogeneity simultaneously. Norwegian salmon farming data are used as an application.
Echo's Lament: Teaching, Mentoring, and the Danger of Narcissistic Pedagogy
Authors: Hess Carol Lakey
Published: June 2003

In this essay, I explore “narcissistic pedagogy,” a pedagogy that centers disproportionately on the needs of the teacher – especially the need for admiration. I engage psychological discussions of narcissistic patterns, and I retell the ancient myth of Narcissus. The core of narcissistic pedagogy is that the teacher experiences students not as centers of their own activity but as part of the teacher's self. All educational situations are vulnerable to narcissistic dynamics, and I will consider strongly narcissistic pedagogy as well as milder narcissistic dangers. I will, additionally, explore healthy narcissism. I pose “conversational education” as an alternative to narcissistic patterns.
Theological Education with Hispanic Persons: Teaching Distinctiveness
Authors: Pazmiño Robert W.
Published: June 2003

The article explores the distinctiveness of Hispanic or Latino/a persons and implications for teaching practice in theological education. It reports on findings from a workshop for non‐Hispanic faculty that was conducted at the Hispanic Summer Program in 1901. The content is broadly defined, and the context and persons of theological education are considered in addressing the particular learning characteristics that can typify Hispanic persons. The work draws upon the pioneering work of Dr. Eldin Villafañe (The Liberating Spirit) who identifies cultural distinctiveness among Hispanic persons in the United States. Suggestions related to each of those characteristics are proposed for teaching practice with the expectation that transformation in practice can foster greater inclusion of Hispanic persons in theological education.
The Tensile Core: Theological Pedagogy in a New Context
Authors: Ricciuti Gail A.
Published: June 2003

Older, second‐career and non‐traditional students in seminaries present challenges for theological curricula and teaching in situations where theological study and the actual practice of ministry are no longer sequential but simultaneous. The author proposes a threefold response to these challenges, combining scholarly excellence and compassionate pedagogy with an eye toward seamless integration of study, formation, and life. The axis connecting past and future within this trinity is compassionate pedagogy: an approach to teaching in which passionate mutual participation yields creative contextualizing of academics and practice, guiding students toward a comprehension of their lives and work as the central arena of theological inquiry.
Transformational Travel for Seminarians: Reading James in Haiti
Authors: Grieb A. Katherine
Published: June 2003

How will we teach the Bible in the twenty‐first century? This essay is intended to contribute to that larger discussion in three ways: after a brief introduction, I will, first, state some general working assumptions about the present situation of the church and about teaching the New Testament in the context of a seminary or divinity school; second, I will describe the course “Reading James in Haiti” which I designed and taught in the Spring of 1902; finally, and much more briefly, I will comment on the implications of transformational travel experiences like this one for the ability of seminarians to understand New Testament texts more deeply than the classroom setting allows.
Doing It Differently: Unleashing Student Creativity
Authors: O'Donovan Theresa
Published: June 2003

Student assignments and assessment – is there life beyond the ten‐page essay? Drawing on the theory of multiple intelligences and experience with an assignment in which students were asked to address course content in anything but an essay, the author considers the challenges and virtues of a creative format that does not rely exclusively on linguistic intelligence. The process, presentations, and evaluative approach employed in an assignment that called upon student creativity in a “Women and the Bible” course are described, and pedagogical and practical considerations explored. The analysis of a particularly memorable student submission reveals layers of complexity seldom achieved in a conventional essay format.
Facilitating the Academic Success of International Students
Authors: Spencer Amy
Published: June 2003

International seminarians seeking an education at academic institutions located in the United States often face a host of learning challenges. Seminary faculty that teach in these institutions are often confronted with a need to adjust their teaching methods to facilitate learning by international students. This essay outlines specific strategies to facilitate academic success of international seminarians by offering specific teaching methods for faculty and learning strategies for international students. Topics include training faculty in how to respond to diverse learning styles, expanding learning environments beyond the classroom, methods for enhancing student participation, and development of assignments. Strategies for student success include developing skills in how to improve note taking, critical reading, and writing.
Teaching Music in the Seminary
Authors: Yardley Anne Bagnall
Published: June 2003

Teaching music in certain seminary contexts poses particular challenges for teaching and learning. The theme of disjuncture between teacher and student in courses that aim to incorporate music in the seminary curriculum are more vital than ever before because of the extreme cultural diversity of our population and integral nature of music in the worship life of religious communities. This essay tackles the difficulties associated with teaching worship music in seminaries where there are a plurality of religious traditions represented and a host of expectations held by diverse student bodies about what connotes worship music. Topics addressed include issues concerning terminology, repertoire, pedagogical methods for teaching worship music, and current issues in church music.
The Virtue of Heaven: From Calvin to Cyber‐Talk and Back
Authors: Morse Christopher
Published: June 2003

Protestant theology at the beginning of the twentieth century, as represented by such influential figures as Johannes Weiss, Albert Schweitzer, Franz Over‐beck, and later Rudolf Bultmann, asked what was no longer believable in the Gospel talk of heaven given the modern frame of reference. A century later the opposite question invites at least equal attention: what is no longer believable in the modern frame of reference given the Gospel talk of heaven? Calvin’s references to the real (or true) presence of Christ's heavenly life as "virtus" invite a conversation with computer talk of virtuality that illumines by contrast the current task of dogmatic theology in addressing what is heard today in the Gospel message as "the real world".
Divine Energies or Divine Personhood: Vladimir Lossky and John Zizioulas on conceiving the transcendent and immanent God
Authors: Papanikolaou Aristotle
Published: June 2003

This essay explores a debate between two contemporary Orthodox theolo‐gians, Vladimir Lossky and John Zizioulas, over how to adequately conceive the doctrine of the Trinity as an expression of the realism of divine‐human communion, and hence, of the God who is transcendent and immanent. The essay critically analyzes the implications of Zizioulas’s reworking of the patristic category of hypostasis. Zizioulas's theology is suggesting a paradigm shift in contemporary Eastern Orthodox theology insofar as it prioritizes hypostasis over energies for expressing the realism of divine‐human communion. The implications of this study also extend to debates within contemporary trinitarian theologies over the adequacy of the concept of "person" for conceptualizing the Trinity.
Unknow Thyself: Apophaticism, Deconstruction, and Theology after Ontotheology
Authors: Rubenstein Mary‐Jane
Published: June 2003

This essay investigates the relationship between post‐structuralist thought and apophaticism, arguing via Pseudo‐Dionysius and Meister Eckhart that theology at its most negative eludes logocentric determinations by disabling the two lynchpins of ontotheology. These are the self‐determined "self" and the conceptually domesticated "God"; by unhinging the self as epistemologically constituted, the apophatic voyage destroys the mutually‐reinforcing cogito and causa sui. It is ultimately suggested that the complete abandonment of "self" and "God", prefigured by negative theology and now provoked by post‐structuralist critique, might enable their transformed restoration as relational, conditioning the possibility of an anti‐ontotheological theology.
The Regulation of Media Markets in selected EU Accession States in Central and Eastern Europe
Authors: Harcourt Alison
Published: June 2003

Abstract:  This article examines the phenomenon of policy transfer in the EU accession countries of the Czech Republic, Hungary, Poland and Slovenia. When formulating media laws in the early 1990s, these countries were presented with models put forth by advisors from the US and EU Member States. Advisors proposed models based upon their own domestic policy and/or organisation agendas. A resulting ‘battle of the models’ can be observed with different experts and actors lobbying for the adoption of contrasting regulatory models. Underlying this were often political, economic and trade interests. In particular, ‘Western’ governments were interested in guaranteeing the opening of new markets, and the stability of these new media markets for Western capital investment, as well as wider political concerns of consolidating democracy in Europe. Interest groups and NGOs wished to transfer their ideas to Eastern Europe often in advocacy of their own agendas in an enlarged Europe.
The Regulation of Telecommunications in the Czech Republic
Authors: Skudder Andrew
Published: June 2003

Abstract:  Since the fundamental upheaval of the political, social, and economic climate of the Czech Republic in 1989 successive governments have striven hard to develop a functioning market economy in which investors, both domestic and foreign, enjoy sufficient stability and legal certainty in which to thrive. The rapid development of the telecommunications sector was to act as a catalyst for the general improvement of the entire national economy, whilst at the same time helping the country to meet its policy goal of creating the conditions precedent to its successful integration into the European Union. The purpose of this article is to trace the progress of the Czech telecommunications market to date and to assess the regulatory framework adopted by the Czech government in light of its stated policy goals. After giving a brief history of the development of the market and the corresponding development of a regulatory régime this article shall turn to examine the current legal position after the adoption of the recent Law on which came into force on 1 July 2000. As well as suggesting necessary modifications and amendments due to certain flaws or omissions in the Act, modifications arising from the adoption by the EU of its new regulatory framework for communications shall also be suggested.
Constitutionalising Enlargement, Enlarging Constitutionalism
Authors: Walker Neil
Published: June 2003

Abstract:  The relationship between the present enlargement and the development of an active constitutional discourse in the EU is a complex one. On the one hand, it may appear that the pre‐existence and the current extension of the constitutional acquis threatens to confront the enlargement countries, many of whom are understandably jealous of their recently won constitutional autonomy, with a fait accompli whereby their membership of the club is conditional upon acceptance of an already mature constitutional doctrine and culture. On the other hand, EU constitutional discourse is by no means a closed book, or one which systematically favours old members over new. Rather, it remains an open‐textured and provisional affair which is bound to address certain deep‐rooted and urgent tensions over institutional design and fundamental values and which may do so in a manner that combats rather than accentuates the possibility of discrimination against the new members. In this regard, the current Convention on the Future of Europe and the Intergovernmental Conference to which it is directed represent a key episode in the ongoing development of the EU's constitutional identity.
A Proposed Monetary Regime for Small Commodity Exporters: Peg the Export Price (‘PEP’)
Authors: Frankel Jeffrey
Published: June 2003

On the one hand, the big selling points of floating exchange rates – monetary independence and accommodation of terms of trade shocks – have not lived up to their promise. On the other hand, proposals for credible institutional monetary commitments to nominal anchors have each run aground on their own peculiar shoals. Rigid pegs to the dollar are dangerous when the dollar appreciates. Money targeting does not work when there is a velocity shock. CPI targeting is not viable when there is a large import price shock. And the gold standard fails when there are large fluctuations in the world gold market. This paper advances a new proposal called PEP: peg the export price. Most applicable for countries that are specialized in the production of a particular mineral or agricultural product, the proposal calls on them to commit to fix the price of that commodity in terms of domestic currency. A series of simulations shows how such a proposal would have worked for oil producers over the period 1970–2000. The paths of real oil prices, exports, and debt are simulated under alternative regimes. An illustrative finding is that countries that suffered a declining world market in oil or other export commodities in the late 1990s would under the PEP proposal have automatically experienced a depreciation and a boost to exports when it was most needed. The argument for PEP is that it simultaneously delivers automatic accommodation to terms of trade shocks, as floating exchange rates are supposed to do, while retaining the credibility‐enhancing advantages of a nominal anchor, as dollar pegs are supposed to do.
Sovereign Debt Restructurings – The Market Knows Best
Authors: Galvis Sergio J.
Published: June 2003

Books reviewed in this article:

Jeremy Bulow, First World Governments and Third World Debt

Jeffrey Sachs, Resolving the Debt Crisis of Low‐Income Countries

Michelle J. White, Sovereigns in Distress: Do They Need Bankruptcy?

Nouriel Roubini, Do We Need a New Bankruptcy Regime?

Hal S. Scott, How Would a Bankruptcy Regime Help?

Edwin M. Truman, Debt Restructuring: Evolution or Revolution?
Intervention and Exchange Rate Stabilization Policy in Developing Countries
Authors: Hutchison Michael M.
Published: June 2003

Recent evidence based on event studies demonstrates the short‐run effectiveness of sterilized (non‐monetary) intervention to stabilize exchange rates. This role is especially important for developing economies where currency volatility is frequently tied to unstable market expectations, herding behaviour and contagion, rather than ‘fundamental’ macroeconomic imbalances. Intervention coordinated with several governments is more likely to succeed in moving exchange rates in the desired direction. The Chiang Mai Initiative (CMI) is a step towards greater cooperation on exchange rate management in Asia, but its main component is a limited US dollar swap agreement between Japan and developing economies and is conditional on an IMF financial package. A much stronger political, as well as economic, commitment to intervene in exchange markets than currently embodied in the CMI would be needed to reduce exchange rate volatility in the region and to ward off future speculative attacks. Greater currency stability, in turn, would give developing economies more flexibility to use monetary and fiscal policy to pursue domestic stabilization policy objectives.
Business Cycles and Macroeconomic Policy in Emerging Market Economies
Authors: Lane Philip R.
Published: June 2003

This paper argues that significant structural differences exist between industrial and emerging market economies. Cyclical fluctuations have been more extreme for the latter group and exacerbated by inappropriately pro‐cyclical macroeconomic policies. However, we argue that effective stabilization policies remain feasible for the emerging market economies, so long as these invest in developing a robust domestic institutional infrastructure.
Financial Centres and the Geography of Capital Flows
Authors: Warnock Francis E. , Cleaver Chad
Published: June 2003

A geographical mismatch is evident in portfolio flows data. Because the data collection system was designed to measure cross‐border transactions with foreign counterparties who are often intermediaries, the majority of flows are attributed to financial centres. We quantify this geographical mismatch by using the bilateral capital flows data to estimate bilateral debt and equity positions between the USA and over 40 countries and comparing those estimates with data from benchmark surveys. Our findings have implications for researchers and policy makers who use capital flows data or flows‐based positions estimates.
Is Business Cycle Volatility Costly? Evidence from Surveys of Subjective Well‐Being
Authors: Wolfers Justin
Published: June 2003

This paper analyses the effects of business cycle volatility on measures of subjective well‐being, including self‐reported happiness and life satisfaction. I find robust evidence that high inflation and, to a greater extent, unemployment lower perceived well‐being. Greater macroeconomic volatility also undermines well‐being. These effects are moderate but important: eliminating unemployment volatility would raise well‐being by an amount roughly equal to that from lowering the average level of unemployment by a quarter of a percentage point. The effects of inflation volatility on well‐being are less easy to detect and are likely smaller.
Schooling, Literacy, Numeracy and Labour Market Success
Authors: Chiswick Barry R. , Lee Yew Liang , Miller Paul W.
Published: June 2003

The present paper uses data from the 1996 Australian Aspects of Literacy survey to examine the effects on labour market outcomes of literacy, numeracy and schooling. The survey includes a range of literacy and numeracy variables that are highly intercorrelated. A ‘general to specific’ approach identifies the most relevant literacy and numeracy variables. Including the others adds little explanatory power. Among males and females separately, approximately half of the total effect of schooling on labour force participation and on unemployment can be attributed to literacy and numeracy (the indirect effect) and approximately half to the direct effect of schooling. There is apparently no indirect effect of labour market experience through literacy and numeracy on participation or unemployment. The direct and total effects of experience are the same. Similarly, the direct and total effects of literacy and numeracy are reasonably similar to each other.
Inflation and Capacity Constraints in Australian Manufacturing Industry
Authors: Shepherd David , Driver Ciaran
Published: June 2003

In the present paper we estimate a model of price‐cost inflation for Australia using business survey responses of firms in the manufacturing sector. The data allow us to circumvent a number of key statistical problems, related in particular to the measurement of costs and structural changes in the model. Equally important, the data allow a new and more detailed perspective on the nature of supply constraints affecting inflation in the manufacturing sector. A new finding is that capital constraints have been more important in generating inflationary pressure than labour constraints or general indicators of capacity utilisation.
Reliance on Income Support in Australia: Prevalence and Persistence
Authors: Tseng Yi‐Ping , Wilkins Roger
Published: June 2003

Welfare dependence or reliance is widely regarded to have adverse consequences for both the community and welfare recipients, yet there have been few studies of the extent and nature of welfare reliance. Indeed, the concept of welfare reliance does not seem to be well defined. In the present paper, we clarify the meaning of the concept and derive reliance measures consistent with this concept. These measures are applied to describe the extent and nature of reliance on income support payments in Australia of persons aged 15–64 years, using Australian Bureau of Statistics income survey data and Australian government administrative data for income support payments.
Within‐Breath Control of Genioglossal Muscle Activation in Humans: Effect of Sleep‐Wake State
Authors: Fogel Robert B. , Trinder John , Malhotra Atul , Stanchina Michael , Edwards Jill K. , Schory Karen E. , White David P.
Published: June 2003

Pharyngeal dilator muscles are clearly important in the pathogenesis of obstructive sleep apnoea syndrome. Substantial data support the role of a local negative pressure reflex in modifying genioglossal activation across inspiration during wakefulness. Using a model of passive negative pressure ventilation, we have previously reported a tight relationship between varying intrapharyngeal negative pressures and genioglossal muscle activation (GGEMG) during wakefulness. In this study, we used this model to examine the slope of the relationship between epiglottic pressure (Pepi) and GGEMG, during stable NREM sleep and the transition from wakefulness to sleep. We found that there was a constant relationship between negative epiglottic pressure and GGEMG during both basal breathing (BB) and negative pressure ventilation (NPV) during wakefulness (slope GGEMG/Pepi 1.86 ± 0.3 vs. 1.79 ± 0.3 arbitrary units (a.u.) cmH2O−1). However, while this relationship remained stable during NREM sleep during BB, it was markedly reduced during NPV during sleep (2.27 ± 0.4 vs. 0.58 ± 0.1 a.u. cmH2O−1). This was associated with a markedly higher pharyngeal airflow resistance during sleep during NPV. At the transition from wakefulness to sleep there was also a greater reduction in peak GGEMG seen during NPV than during BB. These data suggest that while the negative pressure reflex is able to maintain GGEMG during passive NPV during wakefulness, this reflex is unable to do so during sleep. The loss of this protective mechanism during sleep suggests that an airway dependent upon such mechanisms (as in the patient with sleep apnoea) will be prone to collapse during sleep.
Slow excitatory synaptic transmission mediated by P2Y1 receptors in the guinea‐pig enteric nervous system
Authors: Hu H.‐Z. , Gao N. , Zhu M. X. , Liu S. , Ren J. , Gao C. , Xia Y. , Wood J. D.
Published: June 2003

Electrophysiological recording was used to study a type of slow excitatory postsynaptic potential (slow EPSP) that was mediated by release of ATP and its action at P2Y1 receptors on morphologically identified neurones in the submucosal plexus of guinea‐pig small intestine. MRS2179, a selective P2Y1 purinergic receptor antagonist, blocked both the slow EPSP and mimicry of the EPSP by exogenously applied ATP. Increased conductance accounted for the depolarization phase of the EPSP, which occurred exclusively in neurones with S‐type electrophysiological behaviour and uniaxonal morphology. The purinergic excitatory input to the submucosal neurones came from neighbouring neurones in the same plexus, from neurones in the myenteric plexus and from sympathetic postganglionic neurones. ATP‐mediated EPSPs occurred coincident with fast nicotinic synaptic potentials evoked by the myenteric projections and with noradrenergic IPSPs evoked by sympathetic fibres that innervated the same neurones. The P2Y1 receptor on the neurones was identified as a metabotropic receptor linked to activation of phospholipase C, synthesis of inositol 1,4,5‐trisphosphate and mobilization of Ca2+ from intracellular stores.
Properties and Modulation of the G Protein‐Coupled K+ Channel in Rat Cerebellar Granule Neurons: ATP Versus Phosphatidylinositol 4,5‐Bisphosphate
Authors: Han Jaehee , Kang Dawon , Kim Donghee
Published: June 2003

Cerebellar granule (CG) neurons express a G protein‐gated K+ current (GIRK) that is involved in the neurotransmitter regulation of the excitatory input to the Purkinje fibres of the cerebellum. Here, we characterized the single‐channel behaviour of GIRK in CG neurons, and examined the effects of several known modulators of GIRK and their putative physiological roles. Whole‐cell GIRKs were activated by baclofen, a GABAB receptor agonist. In cell‐attached patches, baclofen activated GIRK with a single‐channel conductance of 34 pS and a mean open time of 0.5 ms. In inside‐out patches, application of GTPγS to the cytoplasmic side activated GIRK with similar kinetic properties. Addition of 2 mm ATP resulted in a marked increase in GIRK activity and induced longer‐lived openings with a mean open time of 2.3 ms (ATP‐dependent gating). Brain cytosolic fraction or free fatty acids inhibited this effect of ATP, and this was reversed by addition of purified recombinant brain fatty acid binding protein. Applying phosphatidylinositol 4,5‐bisphosphate (PIP2) to inside‐out patches in place of ATP also increased GIRK activity; however, only an increase in the frequency of opening was observed. The stimulatory effect of PIP2 on GIRK activity was not inhibited by the cytosolic fraction. Following maximal activation by PIP2, ATP caused an additional 2.2‐fold increase in GIRK activity. These results show that GIRKs in CG neurons are regulated by positive and negative modulators that affect frequency as well as open time duration. The net effect is that the ligand‐activated GIRK is in the ‘low activity’ state associated with short‐lived openings, mainly due to strong action of the cytosolic inhibitor of ATP‐dependent gating. Our results also show that intracellular ATP modulates GIRK via pathways different from that of PIP2 in CG neurons.
GABA Depolarizes Neuronal Progenitors of the Postnatal Subventricular Zone Via GABAA Receptor Activation
Authors: Wang D. D. , Krueger D. D. , Bordey A.
Published: June 2003

Previous studies have reported the presence of migrating and dividing neuronal progenitors in the subventricular zone (SVZ) and rostral migratory stream (RMS) of the postnatal mammalian brain. Although the behaviour of these progenitors is thought to be influenced by local signals, the nature and mode of action of the local signals are largely unknown. One of the signalling molecules known to affect the behaviour of embryonic neurons is the neurotransmitter GABA. In order to determine whether GABA affects neuronal progenitors via the activation of specific receptors, we performed cell‐attached, whole‐cell and gramicidin perforated patch‐clamp recordings of progenitors in postnatal mouse brain slices containing either the SVZ or the RMS. Recorded cells displayed a morphology typical of migrating neuronal progenitors had depolarized zero‐current resting potentials, and lacked action potentials. A subset of progenitors contained GABA and stained positive for glutamic acid decarboxylase 67 (GAD‐67) as shown by immunohistochemistry. In addition, every neuronal progenitor responded to GABA via picrotoxin‐sensitive GABAA receptor (GABAAR) activation. GABAARs displayed an ATP‐dependent rundown and a low sensitivity to Zn2+. GABA responses were sensitive to benzodiazepine agonists, an inverse agonist, as well as a barbiturate agonist. While GABA was hyperpolarizing at the zero‐current resting potentials, it was depolarizing at the cell resting potentials estimated from the reversal potential of K+ currents through a cell‐attached patch. Thus, our study demonstrates that neuronal progenitors of the SVZ/RMS contain GABA and are depolarized by GABA, which may constitute the basis for a paracrine signal among neuronal progenitors to dynamically regulate their proliferation and/or migration.
Differential Modulation of Intracortical Inhibition in Human Motor Cortex during Selective Activation of an Intrinsic Hand Muscle
Authors: Zoghi Maryam , Pearce Sophie L. , Nordstrom Michael A.
Published: June 2003

Paired‐pulse transcranial magnetic stimulation (TMS) was used to assess the effectiveness of intracortical inhibition (ICI) acting on corticospinal neurons controlling three intrinsic hand muscles in humans. We hypothesised that the suppression of ICI with selective activation of a muscle would be restricted to corticospinal neurons controlling the muscle targeted for activation. Surface EMG was recorded from abductor pollicis brevis (APB), first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles of the left hand. Subjects were tested at rest and during weak selective activation of APB or ADM, while they attempted to keep the other muscles relaxed using visual feedback. Paired‐pulse TMS was applied with a circular coil oriented to produce antero‐posterior (AP) current flow in the right motor cortex (to preferentially evoke I3 waves in corticospinal neurons) and with postero‐anterior (PA) currents (to preferentially evoke I1 waves). Paired‐pulse TMS was less effective in suppressing the muscle evoked potential (MEP) when the muscle was targeted for selective activation, with both AP and PA stimulation. The mechanism for this includes effects on late I waves, as it was evident with a weak AP test TMS pulse that elicited negligible I1 waves in corticospinal neurons. ICI circuits activated by TMS, which exert their effects on late I waves but do not affect I1 waves, are strongly implicated in this modulation. With AP stimulation, paired‐pulse inhibition was not significantly altered for corticospinal neurons controlling other muscles of the same hand which were required to be inactive during the selective activation task. This differential modulation was not seen with PA stimulation, which preferentially activates I1 waves and evokes a MEP that is less influenced by ICI. The observations with AP stimulation suggest that selective activation of a hand muscle is accompanied by a selective suppression of ICI effects on the corticospinal neurons controlling that muscle. The pattern of differential modulation of ICI effectiveness with voluntary activation suggests that the ICI circuits assist the corticospinal system in producing fractionated activity of intrinsic hand muscles.
Resting Membrane Potential Regulates Na+–Ca2+ Exchange‐Mediated Ca2+ Overload during Hypoxia–Reoxygenation in Rat Ventricular Myocytes
Authors: Baczkó István , Giles Wayne R. , Light Peter E.
Published: June 2003

In the heart, reperfusion following an ischaemic episode can result in a marked increase in [Ca2+]i and cause myocyte dysfunction and death. Although the Na+–Ca2+ exchanger has been implicated in this response, the ionic mechanisms that are responsible have not been identified. In this study, the hypothesis that the diastolic membrane potential can influence Na+–Ca2+ exchange and Ca2+ homeostasis during chemically induced hypoxia–reoxygenation has been tested using right ventricular myocytes isolated from adult rat hearts. Superfusion with selected [K+]o of 0.5, 2.5, 5, 7, 10 and 15 mm yielded the following resting membrane potentials: −27.6 ± 1.63 mV, −102.2 ± 1.89, −86.5 ± 1.03, −80.1 ± 1.25, −73.6 ± 1.02 and −66.4 ± 1.03, respectively. In a second set of experiments myocytes were subjected to chemically induced hypoxia–reoxygenation at these different [K+]o, while [Ca2+]i was monitored using fura‐2. These results demonstrated that after chemically induced hypoxia–reoxygenation had caused a marked increase in [Ca2+]i, hyperpolarization of myocytes with 2.5 mm[K+]o significantly reduced [Ca2+]i (7.5 ± 0.32 vs. 16.9 ± 0.55 %); while depolarization (with either 0.5 or 15 mm[K+]o) significantly increased [Ca2+]i (31.8 ± 3.21 and 20.8 ± 0.36 vs. 16.9 ± 0.55 %, respectively). As expected, at depolarized membrane potentials myocyte hypercontracture and death increased in parallel with Ca2+ overload. The involvement of the Na+–Ca2+ exchanger in Ca2+ homeostasis was evaluated using the Na+–Ca2+ exchanger inhibitor KB‐R7943. During reoxygenation KB‐R7943 (5 μm) almost completely prevented the increase in [Ca2+]i both in control conditions (in 5 mm[K+]o: 2.2 ± 0.40 vs. 10.8 ± 0.14 %) and in depolarized myocytes (in 15 mm[K+]o: −2.1 ± 0.51 vs. 11.3 ± 0.05 %). These findings demonstrate that the resting membrane potential of ventricular myocytes is a critical determinant of [Ca2+]i during hypoxia–reoxygenation. This appears to be due mainly to an effect of diastolic membrane potential on the Na+–Ca2+ exchanger, since at depolarized potentials this exchanger mechanism operates in the reverse mode, causing a significant Ca2+ influx.
T‐ and L‐type Ca2+ Currents in Freshly Dispersed Smooth Muscle Cells from the Human Proximal Urethra
Authors: Hollywood M. A. , Woolsey Siobhan , Walsh I. K. , Keane P. F. , McHale N. G. , Thornbury K. D.
Published: June 2003

The purpose of the present study was to characterise Ca2+ currents in smooth muscle cells isolated from biopsy samples taken from the proximal urethra of patients undergoing surgery for bladder or prostate cancer. Cells were studied at 37 °C using the amphotericin B perforated‐patch configuration of the patch‐clamp technique. Currents were recorded using Cs+‐rich pipette solutions to block K+ currents. Two components of current, with electrophysiological and pharmacological properties typical of T‐ and L‐type Ca2+ currents, were present in these cells. When steady‐state inactivation curves for the L current were fitted with a Boltzmann equation, this yielded a V1/2 of −45 ± 5 mV. In contrast, the T current inactivated with a V1/2 of −80 ± 3 mV. The L currents were reduced in a concentration‐dependent manner by nifedipine (ED50= 159 ± 54 nm) and Ni2+ (ED50= 65 ± 16 μm) but were enhanced when external Ca2+ was substituted with Ba2+. The T current was little affected by TTX, reduction in external Na+, application of nifedipine at concentrations below 300 nm or substitution of external Ca2+ with Ba2+, but was reduced by Ni2+ with an ED50 of 6 ± 1 μm. When cells were stepped from −100 to −30 mV in Ca2+‐free conditions, small inward currents could be detected. These were enhanced 40‐fold in divalent‐cation‐free solution and blocked in a concentration‐dependent manner by Mg2+ with an ED50 of 32 ± 16 μm. These data support the idea that human urethral myocytes possess currents with electrophysiological and pharmacological properties typical of T‐ and L‐type Ca2+ currents.
C Terminus L‐type Ca2+ Channel Calmodulin‐Binding Domains are ‘Auto‐Agonist’ Ligands in Rabbit Ventricular Myocytes
Authors: Dzhura Igor , Wu Yuejin , Zhang Rong , Colbran Roger J. , Hamilton Susan L. , Anderson Mark E.
Published: June 2003

L‐type Ca2+ channel C terminus calmodulin (CaM)‐binding domains are molecular determinants for Ca2+–CaM‐dependent increases in L‐type Ca2+ current (ICa), and a CaM‐binding IQ domain mimetic peptide (IQmp) increases L‐type Ca2+ channel current by promoting a gating mode with prolonged openings (mode 2), suggesting the intriguing possibility that CaM‐binding domains are ‘auto‐agonist’ signalling molecules. In order to test the breadth of this concept, we studied the effect of a second C terminus CaM‐binding domain (CB) mp (CBmp), in conjunction with IQmp, on single L‐type Ca2+ channel currents in excised cell membrane patches from rabbit ventricular myocytes. Here we show that both CBmp and IQmp are agonist ligands that non‐additively increase L‐type Ca2+ channel opening probability (Po) by inducing mode 2 gating. CBmp and IQmp agonist effects were lost under conditions favouring calcification of CaM (Ca2+–CaM, 150 nm free Ca2+ and 10–20 μm CaM), but persisted in the presence of CaM (0–20 μm) under conditions adverse to Ca2+–CaM (20 mm BAPTA), indicating that CaM‐binding domains increase L‐type Ca2+ channel Po by a low Ca2+–CaM activity mechanism. Increasing Ca2+–CaM in the bath (cytosol) reduced the efficacy of CBmp and IQmp signals with Ba2+ as charge carrier, suggesting that CaM binding motifs target a site outside of the pore region. We measured the combined effects of CBmp and Ca2+–CaM‐dependent protein kinase II (CaMKII) on L‐type Ca2+ channels by using an engineered Ca2+–CaM‐independent form of CaMKII that remains active under low Ca2+–CaM conditions, permissive for CBmp signalling. CBmp and CaMKII increased L‐type Ca2+ channel Po in a non‐additive manner, suggesting that low and high Ca2+–CaM‐dependent L‐type Ca2+ channel facilitation pathways converge upon a common signalling mechanism.
Na+‐Ca2+ Exchange Function Underlying Contraction Frequency Inotropy in the Cat Myocardium
Authors: Petroff Martín G. Vila , Palomeque Julieta , Mattiazzi Alicia R.
Published: June 2003

In most mammalian species, an increase in stimulation frequency (ISF) produces an increase in contractility (treppe phenomenon), which results from larger Ca2+ transients at higher frequencies, due to an increase in sarcoplasmic reticulum Ca2+ load and release. The present study attempts to elucidate the contribution of the Na+‐Ca2+ exchanger (NCX) to this phenomenon. Isolated cat ventricular myocytes, loaded with [Ca2+]i‐ and [Na+]i‐sensitive probes, were used to determine whether the contribution of the NCX to the positive inotropic effect of ISF is due to an increase in Ca2+ influx (reverse mode) and/or a decrease in Ca2+ efflux (forward mode) via the NCX, due to frequency‐induced [Na+]i elevation, or whether it was due to the reduced time for the NCX to extrude Ca2+. The results showed that the positive intropic effect produced by ISF was temporally dissociated from the increase in [Na+]i and was not modified by KB‐R7943 (1 or 5 μm), a specific blocker of the reverse mode of the NCX. Whereas the ISF from 10 to 30 beats min−1 (bpm) did not affect the forward mode of the NCX (assessed by the time to half‐relaxation of the caffeine‐induced Ca2+ transient), the ISF to 50 bpm produced a significant reduction of the activity of the forward mode of the NCX, which occurred in association with an increase in [Na+]i (from 4.33 ± 0.40 to 7.25 ± 0.50 mm). However, both changes became significant well after the maximal positive inotropic effect had been reached. In contrast, the positive inotropic effect produced by ISF from 10 to 50 bpm was associated with an increase in diastolic [Ca2+]i, which occurred in spite of a significant increase in the relaxation rate and at a time at which no increases in [Na+]i were detected. The contribution of the NCX to stimulus frequency inotropy would therefore depend on a decrease in NCX‐mediated Ca2+ efflux due to the reduced diastolic interval between beats and not on [Na+]i‐dependent mechanisms.
Cellular and Network Mechanisms Underlying Spontaneous Sharp Wave–Ripple Complexes in Mouse Hippocampal Slices
Authors: Maier Nikolaus , Nimmrich Volker , Draguhn Andreas
Published: June 2003

The mammalian hippocampus displays a peculiar pattern of fast (≈200 Hz) network oscillations superimposed on slower sharp waves. Such sharp wave–ripple complexes (SPW–R) have been implicated in memory consolidation. We have recently described a novel and unique method for studying SPW–R in naive slices of murine hippocampus. Here, we used this model to analyse network and cellular mechanisms of this type of network activity. SPW–R are usually generated within area CA3 but can also originate within the isolated CA1 region. Cellular synchronisation during SPW–R requires both excitatory and inhibitory synaptic transmission as well as electrical coupling, the latter being particularly important for the high‐frequency component. Extracellular and intracellular recordings revealed a surprisingly strong inhibition of most CA1 pyramidal cells during SPW–R. A minority of active cells, however, increases action potential frequency and fires in strict synchrony with the field ripples. This strong separation between members and non‐members of the network may serve to ensure a high signal‐to‐noise ratio in information processing during sharp wave–ripple complexes.
EEG oscillations at 600 Hz are macroscopic markers for cortical spike bursts
Authors: Baker Stuart N. , Gabriel Curio , Lemon Roger N.
Published: June 2003

The human electroencephalogram (EEG) is generated predominantly by synchronised cortical excitatory postsynaptic potentials oscillating at frequencies <100 Hz. Unusually, EEG responses to electrical nerve stimulation contain brief bursts of high‐frequency (600 Hz) wavelets. Here we show, in awake monkeys, that a subset of primary somatosensory cortex single units consistently fires both bursts and single spikes phase‐locked to EEG wavelets. Spike bursts were also evoked by tactile stimuli, proving that this is a natural response mode. EEG wavelets at 600 Hz may therefore permit non‐invasive assessment of population spike timing in human cortex.
Glacial Refugia: Hotspots But Not Melting Pots of Genetic Diversity
Authors: Petit Rémy J. , Aguinagalde Itziar , de Beaulieu Jacques-Louis , Bittkau Christiane , Brewer Simon , Cheddadi Rachid , Ennos Richard , Fineschi Silvia , Grivet Delphine , Lascoux Martin , Mohanty Aparajita , Müller-Starck Gerhard , Demesure-Musch Brigitte , Palmé Anna , Martín Juan Pedro , Rendell Sarah , Vendramin Giovanni G.
Published: June 2003

Glacial refuge areas are expected to harbor a large fraction of the intraspecific biodiversity of the temperate biota. To test this hypothesis, we studied chloroplast DNA variation in 22 widespread European trees and shrubs sampled in the same forests. Most species had genetically divergent populations in Mediterranean regions, especially those with low seed dispersal abilities. However, the genetically most diverse populations were not located in the south but at intermediate latitudes, a likely consequence of the admixture of divergent lineages colonizing the continent from separate refugia.
Sensing DNA Damage Through ATRIP Recognition of RPA-ssDNA Complexes
Authors: Zou Lee , Elledge Stephen J.
Published: June 2003

The function of the ATR (ataxia-telangiectasia mutated– and Rad3-related)–ATRIP (ATR-interacting protein) protein kinase complex is crucial for the cellular response to replication stress and DNA damage. Here, we show that replication protein A (RPA), a protein complex that associates with single-stranded DNA (ssDNA), is required for the recruitment of ATR to sites of DNA damage and for ATR-mediated Chk1 activation in human cells. In vitro, RPA stimulates the binding of ATRIP to ssDNA. The binding of ATRIP to RPA-coated ssDNA enables the ATR-ATRIP complex to associate with DNA and stimulates phosphorylation of the Rad17 protein that is bound to DNA. Furthermore, Ddc2, the budding yeast homolog of ATRIP, is specifically recruited to double-strand DNA breaks in an RPA-dependent manner. A checkpoint-deficient mutant of RPA,
rfa1-t11
, is defective for recruiting Ddc2 to ssDNA both in vivo and in vitro. Our data suggest that RPA-coated ssDNA is the critical structure at sites of DNA damage that recruits the ATR-ATRIP complex and facilitates its recognition of substrates for phosphorylation and the initiation of checkpoint signaling.
Seismic Evidence for Water Deep in Earth's Upper Mantle
Authors: van der Meijde Mark , Marone Federica , Giardini Domenico , van der Lee Suzan
Published: June 2003

Water in the deep upper mantle can influence the properties of seismic discontinuities in the mantle transition zone. Observations of converted seismic waves provide evidence of a 20- to 35-kilometer-thick discontinuity near a depth of 410 kilometers, most likely explained by as much as 700 parts per million of water by weight.