bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Oil Hinder Democracy?
Authors: Ross Michael L.
Published: February 2007

Some scholars suggest that the Middle East's oil wealth helps explain its failure to democratize. This article examines three aspects of this “oil impedes democracy” claim. First, is it true? Does oil have a consistendy antidemocratic effect on states, once other factors are accounted for? Second, can this claim be generalized? Is it true only in the Middle East or elsewhere as well? Is it true for other types of mineral wealth and other types of commodity wealth or only for oil? Finally, if oil does have antidemocratic properties, what is the causal mechanism?

The author uses pooled time-series cross-national data from 113 states between 1971 and 1997 to show that oil exports are strongly associated with authoritarian rule; that this effect is not limited to the Middle East; and that other types of mineral exports have a similar antidemocratic effect, while other types of commodity exports do not.

The author also tests three explanations for this pattern: a “rentier effect,” which suggests that resource-rich governments use low tax rates and patronage to dampen democratic pressures; a “repression effect,” which holds that resource wealth enables governments to strengthen their internal security forces and hence repress popular movements; and a “modernization effect,” which implies that growth that is based on the export of oil and minerals will fail to bring about die social and cultural changes that tend to produce democratic government. He finds at least limited support for all three effects.
Ethnic Conflict and Civil Society: India and Beyond
Authors: Varshney Ashutosh
Published: February 2007

Scholars have worked either on civil society or on ethnic conflict, but no systematic attempt has yet been made to connect the two. In an attempt to explore the possible links, this article makes two interconnected arguments. First,interethnicandintraethnicnetworks of civic engagement play very different roles in ethnic conflict. Because they build bridges and manage tensions, interethnic networks are agents of peace. But if communities are organized only along intraethnic lines and the interconnections with other communities are very weak (or do not exist), ethnic violence is then quite likely. Second, civic networks, both intra- and interethnic, can also be broken down into two other types:associational forms of engagementandeveryday forms of engagement. This distinction is based on whether civic interaction is formal or not. Both forms of engagement, if robust, promote peace: contrariwise, their absence or weakness opens up space for ethnic violence. Of the two, however, the associational forms turn out to be sturdier than everyday engagement, especially when confronted with attempts by politicians to polarize the people along ethnic lines. Both arguments have significance for theories of ethnic conflict and social capital.
Globalization, Domestic Politics, and Social Spending in Latin America: A Time-Series Cross-Section Analysis, 1973–97
Authors: Kaufman Robert R. , Segura-Ubiergo Alex
Published: February 2007

This study examines the effects of globalization, democratization, and partisanship on social spending in fourteen Latin American countries from 1973 to 1997, using a pooled time-series error-correction model. The authors examine three sets of issues. First, following debates in the literature on OECD countries, they want to know whether social spending has been encouraged or constrained by integration into global markets. Within this context, they examine the extent to which such outcomes might be influenced by two additional sets of domestic political and institutional factors discussed in work on developed countries: the electoral pressures of democratic institutions and whether or not popularly based governments are in power.

The authors show that trade integration has a consistently negative effect on aggregate social spending and that this is compounded by openness to capital markets. This is the strongest and most robust finding in the study. Neither democratic nor popularly based governments consistently affect overall social spending. The authors then disaggregate spending into social security transfers and expenditures on health and education. They find that popularly based governments tend to protect social security transfers, which tend toflowdisproportionately to their unionized constituencies; but they have a negative impact on health and education spending. Conversely, a shift to democracy leads to increases in health and education spending, which reaches a larger segment of the population. The authors conclude by emphasizing the contrasting political log-ics of the different types of social spending.
The Benefits of Ethnic War: Understanding Eurasia's Unrecognized States
Authors: King Charles
Published: February 2007

Within international relations, discussions about how civil wars end have focused mainly on the qualities of the belligerents (ethnicity, commitment to the cause) or on the strategic environment of decision making (security dilemmas). Work in sociology and development economics, however, has highlighted the importance of war economies and the functional role of violence. This article combines these approaches by examining the mechanisms through which the chaos of war becomes transformed into networks of profit, and through which these in turn become hardened into the institutions of quasi states. The first section offers a brief overview of current research on civil war endings. The second section outlines the course of four Eurasian wars and identifies the de facto states that have arisen after them: the republic of Nagorno-Karabakh (in Azerbaijan), the Dnestr Moldovan republic (in Moldova), and the republics of Abkhazia and South Ossetia (in Georgia). The third section analyzes the pillars of state building in each case: the political economy of weak states, the role of external actors, the mythologizing function of cultural and educational institutions, and the complicity of central governments. The concluding section suggests lessons that these cases might hold for further study of intrastate violence.
Wage-Setting Measures: A Survey and Assessment
Authors: Kenworthy Lane
Published: February 2007

Wage setting has been one of the most heavily studied institutions in the field of comparative political economy over the past two decades, and quantitative measures of wage-setting arrangements have played a major role in this research. Yet the proliferation of such measures in recent years presents researchers with a sizable array from which to choose. In addition, some scholars are rather skeptical about the validity and/or reliability of these measures. This article offers a survey and assessment of fifteen wage-setting measures. It attempts to answer questions about (1) how these indicators differ from one another in conceptualization and measurement strategy; (2) which are the most valid and reliable; (3) the strengths and weaknesses of measures of wage centralization versus those of wage coordination; (4) particular countries or time periods for which there are noteworthy discrepancies in scoring; (5) how sensitive empirical findings are to the choice of wage-setting measure.
Organization and Labor-Based Party Adaptation: The Transformation of Argentine Peronism in Comparative Perspective
Authors: Levitsky Steven
Published: February 2007

This article examines the capacity of Latin American labor-based parties to adapt to the challenges of economic liberalization and working class decline. It presents an organizational approach to explaining party change, highlighting the ways in which informal and weakly institutionalized structures may contribute to party adaptation. It argues that loosely structured labor-based parties, such as many mass populist parties, possess a distinctive advantage in adapting to environmental change. Though a source of inefficiency and even internal chaos, populist legacies such as fluid internal structures, nonbureaucratic hierarchies, and centralized leaderships yield a high degree of strategic flexibility. The argument is applied to the case of the Argentine Justicialista Party (PJ), a mass populist party that adapted with striking success to the socioeconomic changes of the 1980s and 1990s. The weakly institutionalized nature of Peronism's party-union linkage facilitated the dismantling of traditional mechanisms of labor participation, which resulted in the Pj's rapid transformation from a labor-based party into a predominantly patronage-based party. At the same time, the Pj's nonbureaucratic hierarchy and weakly institutionalized leadership bodies provided President Carlos Menem with substantial room for maneuver in developing and carrying out a radical neoliberal strategy that, while at odds with Peronism's traditional program, was critical to its survival as a major political force. The conclusion places the Peronist case in comparative perspective by examining the cases of five other Latin American labor-based parties.
Autonomy as a Source of Conflict: Caucasian Conflicts in Theoretical Perspective
Authors: Cornell Svante E.
Published: February 2007

The granting of autonomous status to minority populations has gained support among academics and practitioners alike as a way to solve, manage, and even preempt ethnic conflict. In spite of the enthusiasm for ethnofederalism, however, the provision of autonomy to minorities may actually increase rather than decrease the likelihood of conflict. Under certain political conditions, autonomy promotes the separate identity of the minority and increases its motivation and capacity to seek separation from the central state. This article presents a rudimentary theoretical framework identifying which qualities of autonomy solutions increase the likelihood of conflict. It discusses how autonomy relates to other factors conducive to conflict by studying minorities in the South Caucasus and examines the case of Georgia. In Georgia, there were five ethnic minority populations, two of whom—the Abkhaz and the South Ossetians—enjoyed autonomous status and were the only minorities to engage in armed conflict with the Georgian government. This article shows how autonomy, by empowering ethnic elites with control of statelike institutions and by enhancing factors such as leadership, economic viability, and external support, played a crucial role in the escalation of the conflicts in Abkhazia and South Ossetia. Conversely, the absence of autonomy mitigated separatist and secessionist sentiments among two of Georgia's other minority groups—Javakheti's Armenian and Kvemo Kartli's Azeri populations.
Fiscal Games and Public Employment: A Theory with Evidence from Russia
Authors: Gimpelson Vladimir , Treisman Daniel
Published: February 2007

Why do some governments—both in different countries and in regions within those countries—employ more workers than others? Existing theories focus on the level of economic development, political redistribution, and social insurance. But they raise additional puzzles and do not account for all evidence or for a global trend toward decentralization of public employment. The authors propose a new theory, inspired by Russia's recent experience, that locates one motive for subnational public employment growth in a political and fiscal game between central and subnational governments. In countries with weak legal systems, local and regional officials may deliberately set their employment levels beyond their fiscal capacity, prompting bailouts from the central government, which fears the political cost to it if wage arrears accumulate and provoke strikes. The authors model the logic of such brinkmanship, derive several propositions, and show that they—and the model's assumptions—fit empirical evidence from Russia in the 1990s. Deficiencies of that country's overstaffed, underequipped, irregularly paid, ineffective, and strikeprone public sector appear to result in part from a system of dysfunctional incentives created by the interaction of electoral pressures with the system of fiscal federalism. The authors suggest parallels with Latin American countries such as Argentina and Brazil.
Translating Social Cleavages into Party Systems: The Significance of New Democracies
Authors: Zielinski Jakub
Published: February 2007

This article focuses on new democracies in Eastern Europe and addresses two questions about the translation of social cleavages into political oppositions. The first question concerns the translation of preexisting cleavages: does the evolution of new party systems influence the politicization of social conflicts? The second question concerns the translation of new social cleavages, that is, cleavages that emerge once a party system freezes: can a new social cleavage be politicized? To answer these questions, the article integrates a formalization of social cleavage theory with a game-theoretic model of a new party system. The first result is that translation of preexisting cleavages depends on which parties survive the early rounds of electoral competition. In fact, depending on which parties survive, the axis of political conflict can shift by 90 degrees. This implies that party systems in new democracies should be seen as important founding moments, during which political actors determine the long-term axes of political conflict. The second result is that once a party system freezes, the politicization of a new social cleavage is difficult. Indeed, it is possible that a new social cleavage will remain politically dormant. In the context of Eastern Europe, this result suggests that political salience of class conflict is likely to be low because competitive elections and political parties predate the entrenchment of propertyowning classes.
“Reform and Openness”: Why China's Economic Reforms Have Delayed Democracy
Authors: Gallagher Mary E.
Published: February 2007

Most theories that seek to explain democratization look to changes in the economy as the precursor to significant political liberalization, locating the main causal factor in either severe economic crisis or rapid economic growth. In the Chinese context, by contrast, the Communist Party has extricated itself from the socialist social contract with the urban working class without losing its grip on political power. Moreover, China has maintained a rapid pace of economic growth for over twenty-five years without significant political liberalization. Comparative analysis of China's post-1978 reform policies yields insights both across types of socialist transition, comparing China with Eastern Europe and Russia, and across time, comparing China with other high-growth East Asian economies. A key factor in China's ability to reform the economy without sacrificing political control is the timing and sequencing of its foreign direct investment (FDl) liberalization. There are two key variables that are important to this comparative analysis: China's pattern of ownership diversification and China's mode of integration into the global economy. The article relates these two variables to the success of economic change without political liberalization, in particular, how FDI liberalization has affected relations between workers and the ruling Communist Party. “Reform and openness” in this context resulted in a strengthened Chinese state, a weakened civil society (especially labor), and a delay in political liberalization.
Are Smart Sanctions Feasible?
Authors: Tostensen Arne , Bull Beate
Published: February 2007

This article reviews the literature on the “smart sanctions” approach developed in the late 1990s in response to the failure of conventional sanctions and questions the efficacy of this instrument. Smart sanctions modify the conventional sanctions tool by targeting the culpable political elites by means of arms embargoes, financial sanctions, and travel restrictions and by cushioning vulnerable groups (children, women, the infirm, and the elderly) by exempting specified commodities such as food and medical supplies from embargoes. This two-pronged sanctions approach is designed to hit the real perpetrators directly and spare potential innocent victims, thus leading to the speedier change of sanctionee behavior. Although the special design of smart sanctions may seem logically compelling and politically attractive, this article argues that the numerous operational problems involved, combined with the intricacies of the political processes of the UN Security Council, will make a smart sanctions regime difficult to establish and enforce effectively.
Political Bias in Policy Convergence: Privatization Choices in Latin America
Authors: Murillo M. Victoria
Published: February 2007

Since the early 1980s privatization has spread in Latin America under both right-wing rulers and populist presidents. This regional convergence toward privatization seemed to announce the end of partisan policy-making. However, not all governments implement privatization in the same way even in the context of policy convergence. Technocrats propose similar policy options in countries where capital dearth creates pressures for convergence. Yet politicians build the electoral and government coalitions that make these policies possible, and their preferences shape the institutions chosen at implementation. The “bias” introduced by politicians depends on their prior beliefs and constituencies, which shape their institutional preferences. Beliefs about economic nationalism and state intervention influence the selection of regulations at the time of privatization, whereas coalition buildingwith political constituencies shapes the definition of selling conditions in privatized companies. This “political bias,” which is contingent on the privatizing government, explains that the regional policy convergence toward privatization did not extend to its implementation. That is, although politicians may be losing influence about whether to privatize, they still have a say in the choice of how to privatize. This article analyzes the impact of this “political bias” by focusing on the choice of regulatory institutions and selling conditions in five cases of privatization of electricity and telecommunications in Latin America.
Islam and Authoritarianism
Authors: Fish M. Steven
Published: February 2007

Are predominantly Muslim societies distinctly disadvantaged in democratization? If so, why? The article presents a straightforward cross-national examination of the link between Islam and political regime. The evidence strongly suggests that Muslim countries are in fact democratic underachievers. The nature of the causal connection between Islam and political regime is investigated. Many conventional assumptions about Islam and politics do not withstand scrutiny. But one factor does help explain the dearth of democracy in the Muslim world: the treatment of women and girls. The rudiments of a provisional theory linking the treatment of females and regime type are offered and the implications of the findings for democracy, both in Muslim societies and elsewhere, are discussed.
Beyond the Policy Frontier: Canada, Mexico, and the Ideological Origins of NAFTA
Authors: Golob Stephanie R.
Published: February 2007

Why are certain foreign policy options considered taboo or simply kept off the agenda as necessarily unthinkable or self-destructive? And under what conditions can governments transcend such “policy frontiers”? This article seeks to answer these questions by examining the circumstances that brought about Canada's and Mexico's entry into the North American Free Trade Agreement (NAFTA)—a move that constituted a surprising reversal of historic prohibitions on formalizing bilateral economic integration that had long been entrenched in these two nations' foreign policies. Policy frontiers develop as certain elements of the “national interest”—sovereignty, security, and identity—become equated with the legitimation of state elites. When these leaders defend the policy frontier (ostensibly to defend the nation), they are also defending their own political power. These barriers are constructed in a path-dependent fashion, through a critical juncture that first establishes the frontier, and then are maintained over time by institutional and ideological mechanisms of reproduction. For the frontier to be transcended, a critical juncture combining an exogenous shock with an internal legitimacy crisis must undermine, and then reconfigure, both mechanisms of reproduction. The origins of NAFTA in the Canadian and Mexican embrace of the once-forbidden bilateral free-trade option in 1985 and 1990, respectively, illustrate this dynamic, while the individual cases offer variations on the policy frontier model that can provide insights into the analysis of other cases of historically resisted foreign policy change.
Political Manipulations and Market Reforms Failures
Authors: Manzetti Luigi
Published: February 2007

Economists have recently underscored that the failure of market reforms in producing sustained growth in emerging markets is the result of poor advice from the International Monetary Fund, as well as of erroneous macroeconomic policies of domestic decision makers. This article proposes a complementary hypothesis. If market reforms are enacted in a political system with weak accountability institutions, then one should expect the executive to manipulate such reforms in pursuit of such old-fashioned practices as collusion between government and business, political patronage, and corruption. This, in turn, ends up depriving a given economy of potential advantages that could have accrued had the reforms promoted true competition rather than i reallocating monopolistic rents and squandering a large amount of resources.
Endogenous Democratization
Authors: Boix Carles , Stokes Susan C.
Published: February 2007

The authors show that economic development increases the probability that a country will undergo a transition to democracy. These results contradict the finding of Przeworski and his associates, that development causes democracy to last but not to come into existence in the first place. By dealing adequately with problems of sample selection and model specification, the authors discover that economic growth does cause nondemocracies to democratize. They show that the effect of economic development on the probability of a transition to democracy in the hundred years between the mid-nineteenth century and World War II was substantial, indeed, even stronger than its effect on democratic stability. They also show that, in more recent decades, some countries that developed but remained dictatorships would, because of their development, be expected to democratize in as few as three years after achieving a per capita income of $12,000 per capita.
Transnational Civil Society and Advocacy in World Politics
Authors: Price Richard
Published: February 2007

This article takes stock of a plethora of recent works examining the flowering of transnational civil society activism in world politics. The author argues that this work contributes to a progressive research agenda that responds to a succession of criticisms from alternative perspectives. As the research program has advanced, new areas of inquiry have been opened up, including the need for a central place for normative international theory. The author also contends that the focus of this research on the transnationalization of civil society provides a trenchant response to an important puzzle concerning the leverage of civil society vis-à-vis the contemporary state in an era of globalization. Further, the liberal variant of transnational advocacy research constitutes a powerful theoretical counter not only to other nonliberal theories that privilege other agents or structures but also to other varieties of contemporary liberal international theory, such as those privileging preexisting domestic preference formation or state centric versions of liberal constructivism.
Translating Media: Why We Should Rethink Textuality
Authors: Hayles N. Katherine
Published: February 2007

Literary criticism is filled with assumptions specific to print. As print materials are increasingly translated into electronic documents, these unrecognized assumptions tend to be overlaid onto electronic materials without thinking through how textuality must change when texts are electronic. Arguing that an electronic text should properly be considered a process rather than an object, this essay revisits definitions of work, text, and document. Two central premises need to be rethought: that work and text are disembodied, and that "work" is a convergent ideal construct. The essay proposes instead that both work and text be considered embodied and media-specific, and that "work" be thought of as an Assemblage rather than a convergent ideal.
Political scientists on the functions of personal pronouns in their writing: An interview-based study of ‘I’ and ‘we’
Authors: Harwood Nigel
Published: February 2007

In contrast to the numerous corpus-based studies of pronouns in academic writing, this paper uses qualitative interviews in an attempt to account for academic writers' motivations for using the pronouns ‘I’ and ‘we’ and to describe the textual effects that each case of ‘I’ and ‘we’ helps to create. Five political scientists took part in the research, commenting upon their pronoun use in one of their own journal articles and also in the other informants' texts. Seven textual effects that ‘I’ and ‘we’ help to construct are identified and described. ‘I’ and ‘we’ are said to help (i) make the readership feel included and involved in the writers' argument; (ii) make the text more accessible; (iii) convey a tentative tone and hedge writers' claims; (iv) explicate the writers' logic or method regarding their arguments or procedures; (v) signal writers' intentions and arguments; (vi) indicate the contribution and newsworthiness of the research; and (vii) allow the writer to inject a personal tenor into the text. The insights and implications of the study are discussed and the paper closes by proposing that similar interview-based studies could be used for pedagogical purposes in English for academic purposes (EAP) contexts.
Enabling talk: How the facilitator shapes a focus group
Authors: Myers Greg
Published: February 2007

Contemporary democratic politics involves, not just constitutions, elections, and representative bodies, but complex processes of more direct consultation with the public. The value of these processes depends on their openness to voices, topics, and styles of expression that might be excluded from other forums. In this paper I analyze focus group discussions, one of the genres used for public consultation, and the ways that discussions are framed by facilitators. The facilitators' turns are seldom in the form of free-standing questions or statements requiring a response from the participants. Instead, the kinds of interventions they make—probes, prompts, formulations, and metacomments—can be understood in terms of what Sacks (1992) called second-speaker tying rules; that is, they construct coherence by presenting the facilitators' turns as following from what has already been said by a participant. These turns signal that participants are entitled to speak and the facilitator is listening; they also signal the kind of additional response that is wanted. These additional responses call for wider range, greater specificity and personal context, or further reflection on the wording or form of the statement. I argue that a forum does not extend consultation with the public just by removing institutional constraints to allow opinions to be spoken; it should also enable talk that would not otherwise have had an occasion to happen.
Complex advice acceptance as a resource for managing asymmetries
Authors: Waring Hansun Zhang
Published: February 2007

Hutchby (1995: 221) calls advice giving ‘an activity which assumes or establishes an asymmetry between the participants’. The problematic nature of such asymmetry has been convincingly demonstrated by conversation analysts, especially in contexts where advice is uninvited (e.g., Jeerson and Lee 1992). This study turns to a context where advice is expected, but due to competence concerns, asymmetry remains problematic. On the basis of a detailed analysis of 10 graduate peer tutoring sessions, I show how two complex advice acceptance methods can be used by the advice recipient to reconfigure the asymmetrical role relations into less asymmetrical ones: (i)
Estrogen Regulates Bcl-w and Bim Expression: Role in Protection against β-Amyloid Peptide-Induced Neuronal Death
Authors: Yao Mingzhong , Nguyen Thuy-Vi V. , Pike Christian J.
Published: February 2007

Estrogen is neuroprotective against a variety of insults, including β-amyloid peptide (Aβ); however, the underlying mechanism(s) is not fully understood. Here, we report that 17β-estradiol (E2) selectively regulates neuronal expression of the Bcl-2 family (bcl-2,bcl-x,bcl-w,bax,bak,bad,bik,bnip3,bid, andbim). In primary cerebrocortical neuron cultures under basal conditions, we observe that E2 upregulates expression of antiapoptotic Bcl-w and downregulates expression of proapoptotic Bim in an estrogen receptor (ER)-dependent manner. In the presence of toxic levels of Aβ, we observe that E2 attenuates indices of neuronal apoptosis: c-Jun N-terminal kinase (JNK)-dependent downregulation of Bcl-w and upregulation of Bim, mitochondrial release of cytochromecand Smac, and cell death. These neuroprotective effects of E2 against Aβ-induced apoptosis are mimicked by the JNK inhibitor SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one). In addition, E2 attenuates Aβ-induced JNK phosphorylation in an ER-dependent manner, but does not affect basal levels of JNK phosphorylation. These results suggest that E2 may reduce Aβ-induced neuronal apoptosis at least in part by two complementary pathways: (1) ER-dependent, JNK-independent upregulation of Bcl-w and downregulation of Bim under basal conditions, and (2) ER-dependent inhibition of Aβ-induced JNK activation and subsequent JNK-dependent downregulation of Bcl-w and upregulation of Bim, resulting in mitochondrial release of cytochromecand Smac and eventual cell death. These data provide new understanding into the mechanisms contributing to estrogen neuroprotection, a neural function with potential therapeutic relevance to Alzheimer's disease.
Regional Gray Matter Growth, Sexual Dimorphism, and Cerebral Asymmetry in the Neonatal Brain
Authors: Gilmore John H. , Lin Weili , Prastawa Marcel W. , Looney Christopher B. , Vetsa Y. Sampath K. , Knickmeyer Rebecca C. , Evans Dianne D. , Smith J. Keith , Hamer Robert M. , Lieberman Jeffrey A. , Gerig Guido
Published: February 2007

Although there has been recent interest in the study of childhood and adolescent brain development, very little is known about normal brain development in the first few months of life. In older children, there are regional differences in cortical gray matter development, whereas cortical gray and white matter growth after birth has not been studied to a great extent. The adult human brain is also characterized by cerebral asymmetries and sexual dimorphisms, although very little is known about how these asymmetries and dimorphisms develop. We used magnetic resonance imaging and an automatic segmentation methodology to study brain structure in 74 neonates in the first few weeks after birth. We found robust cortical gray matter growth compared with white matter growth, with occipital regions growing much faster than prefrontal regions. Sexual dimorphism is present at birth, with males having larger total brain cortical gray and white matter volumes than females. In contrast to adults and older children, the left hemisphere is larger than the right hemisphere, and the normal pattern of fronto-occipital asymmetry described in older children and adults is not present. Regional differences in cortical gray matter growth are likely related to differential maturation of sensory and motor systems compared with prefrontal executive function after birth. These findings also indicate that whereas some adult patterns of sexual dimorphism and cerebral asymmetries are present at birth, others develop after birth.
Sphingosine 1-Phosphate (S1P) Signaling Is Required for Maintenance of Hair Cells Mainly via Activation of S1P2
Authors: Herr Deron R. , Grillet Nicolas , Schwander Martin , Rivera Richard , Müller Ulrich , Chun Jerold
Published: February 2007

Hearing requires the transduction of vibrational forces by specialized epithelial cells in the cochlea known as hair cells. The human ear contains a finite number of terminally differentiated hair cells that, once lost by noise-induced damage or toxic insult, can never be regenerated. We report here that sphingosine 1-phosphate (S1P) signaling, mainly via activation of its cognate receptor S1P2, is required for the maintenance of vestibular and cochlear hair cellsin vivo. Two S1P receptors, S1P2and S1P3, were found to be expressed in the cochlea by reverse transcription-PCR andin situhybridization. Mice that are null for both these receptors uniformly display progressive cochlear and vestibular defects with hair cell loss, resulting in complete deafness by 4 weeks of age and, with complete penetrance, balance defects of increasing severity. This study reveals the previously unknown role of S1P signaling in the maintenance of cochlear and vestibular integrity and suggests a means for therapeutic intervention in degenerative hearing loss.
Spike Timing-Dependent Synaptic Depression in theIn VivoBarrel Cortex of the Rat
Authors: Jacob Vincent , Brasier Daniel J. , Erchova Irina , Feldman Dan , Shulz Daniel E.
Published: February 2007

Spike timing-dependent plasticity (STDP) is a computationally powerful form of plasticity in which synapses are strengthened or weakened according to the temporal order and precise millisecond-scale delay between presynaptic and postsynaptic spiking activity. STDP is readily observedin vitro, but evidence for STDPin vivois scarce. Here, we studied spike timing-dependent synaptic depression in single putative pyramidal neurons of the rat primary somatosensory cortex (S1)in vivo, using two techniques. First, we recorded extracellularly from layer 2/3 (L2/3) and L5 neurons, and paired spontaneous action potentials (postsynaptic spikes) with subsequent subthreshold deflection of one whisker (to drive presynaptic afferents to the recorded neuron) to produce “post-leading-pre” spike pairings at known delays. Short delay pairings (<17 ms) resulted in a significant decrease of the extracellular spiking response specific to the paired whisker, consistent with spike timing-dependent synaptic depression. Second, in whole-cell recordings from neurons in L2/3, we paired postsynaptic spikes elicited by direct-current injection with subthreshold whisker deflection to drive presynaptic afferents to the recorded neuron at precise temporal delays. Post-leading-pre pairing (<33 ms delay) decreased the slope and amplitude of the PSP evoked by the paired whisker, whereas “pre-leading-post” delays failed to produce depression, and sometimes produced potentiation of whisker-evoked PSPs. These results demonstrate that spike timing-dependent synaptic depression occurs in S1in vivo, and is therefore a plausible plasticity mechanism in the sensory cortex.
The Nociceptin/Orphanin FQ Receptor Antagonist J-113397 and l-DOPA Additively Attenuate Experimental Parkinsonism through Overinhibition of the Nigrothalamic Pathway
Authors: Marti Matteo , Trapella Claudio , Viaro Riccardo , Morari Michele
Published: February 2007

By using a battery of behavioral tests, we showed that nociceptin/orphanin FQ receptor (NOP receptor) antagonists attenuated parkinsonian-like symptoms in 6-hydroxydopamine hemilesioned rats (Marti et al., 2005). We now present evidence that coadministration of the NOP receptor antagonist 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2Hbenzimidazol-2-one (J-113397) andl-DOPA to 6-hydroxydopamine hemilesioned rats produced an additive attenuation of parkinsonism. To investigate the neurobiological substrates underlying this interaction,in vivomicrodialysis was used in combination with behavioral measurements (bar test). J-113397 andl-DOPA alone reduced the time on bars (i.e., attenuated akinesia) and elevated GABA release selectively in the lesioned substantia nigra reticulata. J-113397 also reduced nigral glutamate levels, whereasl-DOPA was ineffective. J-113397 andl-DOPA coadministration produced additive antiakinetic effect, which was associated with additive increase in nigral GABA release but no additional reductions in glutamate levels. To investigate whether the increase in nigral GABA release could translate to changes in nigrothalamic transmission, GABA release was monitored in the ventromedial thalamus (one of the main target areas of the nigrothalamic projections). J-113397 andl-DOPA decreased thalamic GABA release and attenuated akinesia, their combination resulting in a more profound effect. These actions were prevented by perfusing the voltage-dependent Na+channel blocker tetrodotoxin or the GABAAreceptor antagonist bicuculline in the substantia nigra reticulata. These data demonstrate that J-113397 andl-DOPA exert their antiparkinsonian action through overinhibition of nigrothalamic transmission and suggest that NOP receptor antagonists may be useful as an adjunct tol-DOPA therapy for Parkinson's disease.
Presynaptic α-Synuclein Aggregates, Not Lewy Bodies, Cause Neurodegeneration in Dementia with Lewy Bodies
Authors: Kramer Michael L. , Schulz-Schaeffer Walter J.
Published: February 2007

Lewy bodies, the pathological hallmark of dementia with Lewy bodies (DLB), are large juxtanuclear inclusions of aggregated α-synuclein. However, the small number of cortical Lewy bodies relative to the total neuron count does not correlate with the extent of cognitive impairment. In contrast to dopaminergic neurons in Parkinson's disease, nerve cell loss is usually less prevalent in the cortex of DLB, suggesting a different mechanism of neurodegeneration.

Because antibodies used for immunodetection per se do not generally differentiate the aggregated from the physiological and monomeric isoform of α-synuclein, we developed the paraffin-embedded tissue (PET) blot and the protein aggregate filtration (PAF) assay for the sensitive and selective detection of α-synuclein aggregates in tissue slides and brain homogenates, respectively.

In contrast to common immunohistochemistry, the PET blot detected an enormous number of small α-synuclein aggregates, which, in contrast to the few Lewy bodies, may explain the cognitive impairment in DLB. Using the PAF assay, we demonstrate that the absolute majority of α-synuclein aggregates are located at presynaptic terminals, suggesting a severe pathological impact on synaptic function. Indeed, parallel to the massive presynaptic accumulation of α-synuclein aggregates, we observed significant synaptic pathology with almost complete loss of dendritic spines at the postsynaptic area.

Our results provide strong evidence for a novel concept of neurodegeneration for DLB in which synaptic dysfunction is caused by presynaptic accumulation of α-synuclein aggregates. This concept may also be valid for Parkinson's disease.
The Spatial Organization of Long-Term Synaptic Plasticity at the Input Stage of Cerebellum
Authors: Mapelli Jonathan , D'Angelo Egidio
Published: February 2007

The spatial organization of long-term synaptic plasticity [long-term potentiation (LTP) and long-term depression (LTD)] is supposed to play a critical role for distributed signal processing in neuronal networks, but its nature remains undetermined in most central circuits. By using multielectrode array recordings, we have reconstructed activation maps of the granular layer in cerebellar slices. LTP and LTD induced by theta-burst stimulation appeared in patches organized in such a way that, on average, LTP was surrounded by LTD. The sign of long-term synaptic plasticity in a given granular layer region was directly correlated with excitation and inversely correlated with inhibition: the most active areas tended to generate LTP, whereas the least active areas tended to generate LTD. Plasticity was almost entirely prevented by application of the NMDA receptor blocker, APV. This suggests that synaptic inhibition, through a control of membrane depolarization, effectively regulates NMDA channel unblock, postsynaptic calcium entry, and the induction of bidirectional synaptic plasticity at the mossy fiber–granule cell relay (Gall et al., 2005). By this mechanism, LTP and LTD could regulate the geometry and contrast of network computations, preprocessing the mossy fiber input to be conveyed to Purkinje cells and molecular layer interneurons.
p19Ink4dand p21Cip1Collaborate to Maintain the Postmitotic State of Auditory Hair Cells, Their Codeletion Leading to DNA Damage and p53-Mediated Apoptosis
Authors: Laine Heidi , Doetzlhofer Angelika , Mantela Johanna , Ylikoski Jukka , Laiho Marikki , Roussel Martine F. , Segil Neil , Pirvola Ulla
Published: February 2007

Sensory hair cells of the auditory organ are generated during embryogenesis and remain postmitotic throughout life. Previous work has shown that inactivation of the cyclin-dependent kinase inhibitor (CKI)p19Ink4dleads to progressive hearing loss attributable to inappropriate DNA replication and subsequent apoptosis of hair cells. Here we show the synergistic action of another CKI,p21Cip1, on cell cycle reactivation. The codeletion ofp19Ink4dandp21Cip1triggered profuse S-phase entry of auditory hair cells during a restricted period in early postnatal life, leading to the transient appearance of supernumerary hair cells. In addition, we show that aberrant cell cycle reentry leads to activation of a DNA damage response pathway in these cells, followed by p53-mediated apoptosis. The majority of hair cells were absent in adult cochleas. These data, together with the demonstration of changing expression patterns of multipleCKIsin auditory hair cells during the stages of early postnatal maturation, show that the maintenance of the postmitotic state is an active, tissue-specific process, cooperatively regulated by several CKIs, and is critical for the lifelong survival of these sensory cells.
Age-Related Differences in Neuromagnetic Brain Activity Underlying Concurrent Sound Perception
Authors: Alain Claude , McDonald Kelly L.
Published: February 2007

Deficits in parsing concurrent auditory events are believed to contribute to older adults' difficulties in understanding speech in adverse listening conditions (e.g., cocktail party). To explore the level at which aging impairs sound segregation, we measured auditory evoked fields (AEFs) using magnetoencephalography while young, middle-aged, and older adults were presented with complex sounds that either had all of their harmonics in tune or had the third harmonic mistuned by 4 or 16% of its original value. During the recording, participants were asked to ignore the stimuli and watch a muted subtitled movie of their choice. For each participant, the AEFs were modeled with a pair of dipoles in the superior temporal plane, and the effects of age and mistuning were examined on the amplitude and latency of the resulting source waveforms. Mistuned stimuli generated an early positivity (60–100 ms), an object-related negativity (ORN) (140–180 ms) that overlapped the N1 and P2 waves, and a positive displacement that peaked at ∼230 ms (P230) after sound onset. The early mistuning-related enhancement was similar in all three age groups, whereas the subsequent modulations (ORN and P230) were reduced in older adults. These age differences in auditory cortical activity were associated with a reduced likelihood of hearing two sounds as a function of mistuning. The results reveal that inharmonicity is rapidly and automatically registered in all three age groups but that the perception of concurrent sounds declines with age.
Growth hormone-binding protein is directly and IGFBP-3 is inversely associated with risk of female breast cancer
Authors: Pazaitou-Panayiotou Kalliopi , Kelesidis Theodore , Kelesidis Iosif , Kaprara Athina , Blakeman Jennifer , Vainas Iraklis , Mpousoulegas Aris , Williams Catherine J , Mantzoros Christos
Published: February 2007

Objective: Several components of the GH and IGF systems have been implicated in the development of malignancies. All components of these hormonal systems have never been jointly evaluated in female breast cancer, and previous studies have not examined the role of IGF-binding proteins (IGFBP-4, IGFBP-6) or GH-binding protein (GHBP).

Design: Hospital-based case–control study.

Methods: In this sample of primarily postmenopausal women, we obtained serum measures of IGF-I, IGF-II, and binding proteins IGFBP-1, IGFBP-3, IGFBP-4, IGFBP-6, as well as GHBP, insulin, and leptin from 74 breast cancer cases and 76 control subjects.

Results: In crude analyses, we found lower age-standardized mean IGF-I, IGFBP-3, IGFBP-4, IGFBP-6, and higher IGFBP-1 and GHBP in breast cancer cases when compared with controls. Multivariate models mutually adjusted for other GH–IGF system components and classical breast cancer risk factors demonstrated an inverse association between IGFBP-3 and risk of breast cancer (odds ratio (OR) = 0.2, P < 0.01) and a direct association between GHBP and disease risk (OR = 3.3, P < 0.01). No significant associations were detected in multivariate analyses among IGF-I, IGF-II or IGFBP-1, IGFBP-4, IGFBP-6 with risk of breast cancer, indicating that these factors may not have effects independent of and/or comparable with IGFBP-3 and GHBP.

Conclusions: These results support a protective role of IGFBP-3 and demonstrate for the first time an increased risk of breast cancer with higher GHBP, after accounting for variation in IGFs, IGFBPs, and classical breast cancer risk factors.
Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry
Authors: Saeger Wolfgang , Lüdecke Dieter K , Buchfelder Michael , Fahlbusch Rudolf , Quabbe Hans-Jürgen , Petersenn Stephan
Published: February 2007

In 1996, the German Registry of Pituitary Tumors was founded by the Pituitary Section of the German Society of Endocrinology as a reference center for collection and consultant pathohistological studies of pituitary tumors. The experiences of the first 10 years of this registry based on 4122 cases will herein be reported. The data supplement former collections of the years 1970–1995 with 3480 surgically removed tumors or lesions of the pituitary region. The cases were studied using histology, immunostainings and in some cases also molecular pathology or electron microscopy. The adenomas were classified according to the current World Health Organization classification in the version of 2004. From 1996 on 3489 adenomas (84.6%), 5 pituitary carcinomas (0.12%), 133 craniophar-yngiomas (3.2%), 39 meningiomas (0.94%), 25 metastases (0.6%), 22 chordomas (0.5%), 115 cystic non-neoplastic lesions (2.8%), and 46 inflammatory lesions (1.1%, 248 other lesions or normal tissue (6.0%)) were collected by us. The adenomas (100%) were classified into densely granulated GH cell adenomas (9.2%), sparsely granulated GH cell adenomas (6.3%), sparsely granulated prolactin (PRL) cell adenomas (8.9%), densely granulated PRL cell adenomas (0.3%), mixed GH/PRL cell adenomas (5.2%), mammosomatotropic adenomas (1.1%), acidophilic stem cell adenomas (0.2%), densely granulated ACTH cell adenomas (7.2%), sparsely granulated ACTH cell adenomas (7.9%), Crooke cell adenomas (0.03%), TSH cell adenomas (1.5%), FSH/LH cell adenomas (24.8%), null cell adenomas (19.3%), null cell adenoma, oncocytic variant (5.8%), and plurihormonal adenomas (1.3%). Following the WHO classification of 2004, the new entity ‘atypical adenoma’ was found in 12 cases in 2005. Various prognostic parameters and clinical implications are discussed.