bluuebunny/crossref_metadata_2025 huggingface dataset:
Synaptic organization and input‐specific short‐term plasticity in anterior cingulate cortical neurons with intact thalamic inputs
Authors: Lee Chia‐Ming , Chang Wei‐Chih , Chang Kung‐Bo , Shyu Bai‐Chuang
Published: June 2007

The absence of a slice preparation with intact thalamocortical pathways has held back elucidation of the cellular and synaptic mechanisms by which thalamic signals are differentially transmitted to and processed in the anterior cingulate cortex (ACC). In this report we introduce an innovative mouse brain slice preparation in which it is possible to explore the electrophysiological properties of ACC neurons with intact long‐distance inputs from medial thalamic (MT) nuclei by intracellular recordings; this MT–ACC neuronal pathway plays an integral role in information transmission. Biocytin‐labeled fibers in a functional slice could be traced anterogradely or retrogradely from the MT via the reticular thalamic nuclei, striatum and corpus callosum to the cingulate cortical areas. Eighty‐seven cells downstream of the thalamic projections in 49 slices were recorded intracellularly. Intracellular recordings in the ACC showed that thalamocingulate transmission involves both α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA)/kainate and N‐methyl‐d‐aspartate (NMDA) subtypes of glutamate receptors. Thalamus‐evoked responses recorded extracellularly in the ACC were activated and progressed along a deep–superficial–deep trajectory loop across the ACC layers. We observed enhanced paired‐pulse facilitation and tetanic potentiation of thalamocingulate synapses, suggestive of input‐specific ACC plasticity and selective processing of information relayed by thalamocingulate pathways. Furthermore, we observed differential responses of ACC neurons to thalamic burst stimulation, which underscores the importance of MT afferents in relaying sensory information to the ACC. This new slice preparation enables the contribution of MT‐evoked ACC synaptic transmission to short‐term plasticity in the neuronal circuitry underlying sensory information processing to be examined in detail.
Directing neurotransmitter identity of neurones derived from expanded adult neural stem cells
Authors: Berninger Benedikt , Guillemot François , Götz Magdalena
Published: June 2007

In‐vitro expanded neural stem cells (NSCs) of the adult subependymal zone (SEZ) may serve as a source for replacing degenerating neurones in disease and trauma. Crucial for the viability of this approach is the ability to selectively generate specific types of neurones from these cells. Here we show that NSCs derived from the adult mouse SEZ and expanded in vitro as neurosphere cells lose their in‐vivo specification and generate a mixture of progeny comprising both GABAergic and also, surprisingly, glutamatergic neurones. When forced to express the pro‐neural transcription factor neurogenin 2, virtually all progeny of in‐vitro expanded adult NSCs acquire a glutamatergic identity, whereas only GABAergic neurones are generated upon expression of the transcription factor Mash1. Respecification of expanded NSCs from the adult SEZ by neurogenin 2 was accompanied by upregulation of the T‐box transcription factor Tbr1, suggesting that their progeny had acquired a dorsal telencephalic identity. Thus, in‐vitro expanded adult NSCs have the competence to become directed towards distinct functional neurotransmitter phenotypes when the appropriate transcriptional cues are provided.
Ferroportin1 and hephaestin are involved in the nigral iron accumulation of 6‐OHDA‐lesioned rats
Authors: Wang Jun , Jiang Hong , Xie Jun‐Xia
Published: June 2007

Elevated iron levels in the substantia nigra (SN) participate in neuronal death in Parkinson's disease (PD). While the mechanisms underlying the increased iron are still unknown, some iron transport proteins may be involved. The nigral iron accumulation could be a result of either increased import or decreased export. The mechanisms of iron import have received considerable attention, but little is known about iron export mechanisms. Ferroportin1 (FP1) and hephaestin (HP), two newly discovered iron export proteins, cooperate in the iron export in the gut. Here, we investigated their expression in the SN of rats lesioned by 6‐hydroxydopamine (6‐OHDA). Using immunofluorescence, we showed that FP1 and HP were both expressed on astrocytes, microglia, oligodendrocytes and neurons in the SN. By immunohistochemistry, we showed that 1 day after 6‐OHDA lesion, the expression of the two proteins decreased compared with the control. When rats began showing rotation behaviour induced by apomorphine, usually 6 weeks after 6‐OHDA lesion, they are considered PD models. In these PD models, a further decrease in the two proteins was observed. Reverse transcriptase‐polymerase chain reaction showed that the mRNA levels of FP1 and HP decreased 1 day after 6‐OHDA lesion compared with the control, and further decrease was also observed in the PD model rats. These results show for the first time that FP1 and HP co‐localize in the rat brain, and suggest that decreased expression of these transporters in the SN can account for the increased iron levels.
EphB1 null mice exhibit neuronal loss in substantia nigra pars reticulata and spontaneous locomotor hyperactivity
Authors: Richards A. Brent , Scheel Tracy A. , Wang Kan , Henkemeyer Mark , Kromer Lawrence F.
Published: June 2007

The molecular mechanisms that regulate basal ganglia development are largely unknown. Eph receptor tyrosine kinases are potential participants in this process as they regulate development of other CNS regions and are expressed in basal ganglia nuclei, such as the substantia nigra (SN) and striatum. To address the role of Eph receptors in the development of these nuclei, we analysed anatomical changes in the SN and striatum of mice with null mutations for EphB1. These mice express β‐galactosidase as a marker for cells normally expressing EphB1. In situ hybridization data and a direct comparison of SN neurons expressing tyrosine hydroxylase (TH) and/or the β‐gal marker for EphB1 revealed that EphB1 is not expressed in TH+ neurons of pars compacta (SNc), but is restricted to neurons in pars reticulata (SNr). Consistent with this, we find that EphB1 null mice exhibit a significant decrease in the volume and number of neurons (40% decrease) in SNr, whereas the volume and number of TH+ neurons in SNc is not significantly affected nor are there changes in the distribution of nigrostriatal dopamine neurons. Although EphB1 is expressed in the striatum, EphB1–/– mice exhibit no significant changes in striatal volume and TH fiber density, and have no obvious alterations in striatal patch/matrix organization. Behavioral evaluation of EphB1 null mice in an open‐field environment revealed that these mice exhibited spontaneous locomotor hyperactivity. These results suggest that EphB1 is necessary for the proper formation of SNr, and that neuronal loss in SNr is associated with altered locomotor functions.
Desensitization and binding properties determine distinct α1β2γ2 and α3β2γ2 GABAA receptor‐channel kinetic behavior
Authors: Barberis Andrea , Mozrzymas Jerzy W. , Ortinski Pavel I. , Vicini Stefano
Published: June 2007

GABAA receptor subtypes comprising the α1 and α3 subunits change with development and have a specific anatomical localization in the adult brain. These receptor subtypes have been previously demonstrated to greatly differ in deactivation kinetics but the underlying gating mechanisms have not been fully elucidated. Therefore, we expressed rat α1β2γ2 and α3β2γ2 receptors in human embryonic kidney 293 cells and recorded current responses to ultrafast GABA applications at macroscopic and single‐channel levels. We found that the slow deactivation of α3β2γ2‐mediated currents is associated with a relatively small rate and extent of apparent desensitization. In contrast, responses mediated by α1β2γ2 receptors had faster deactivation and stronger desensitization. α3β2γ2 receptors had faster recovery in the paired‐pulse agonist applications than α1β2γ2 channels. The onset of currents mediated by α3β2γ2 receptors was slower than that of α1β2γ2 for a wide range of GABA concentrations. Single‐channel analysis did not reveal differences in the opening/closing kinetics of α1β2γ2 and α3β2γ2 channels but burst durations were longer in α3β2γ2 receptors. Simulation with a previously reported kinetic model was used to explore the differences in respective rate constants. Reproduction of major kinetic differences required a smaller desensitization rate as well as smaller binding and unbinding rates in α3β2γ2 compared with α1β2γ2 receptors. Our work describes the mechanisms underlying the kinetic differences between two major GABAA receptor subtypes and provides a framework to interpret data from native GABA receptors.
LTP‐like changes induced by paired associative stimulation of the primary somatosensory cortex in humans: source analysis and associated changes in behaviour
Authors: Litvak Vladimir , Zeller Daniel , Oostenveld Robert , Maris Eric , Cohen Ayala , Schramm Axel , Gentner Reinhard , Zaaroor Menashe , Pratt Hillel , Classen Joseph
Published: June 2007

Paired associative stimulation (PAS), which combines repetitive peripheral nerve stimulation with transcranial magnetic stimulation (TMS), may induce neuroplastic changes in somatosensory cortex (S1), possibly by long‐term potentiation‐like mechanisms. We used multichannel median nerve somatosensory evoked potential (MN‐SSEP) recordings and two‐point tactile discrimination testing to examine the location and behavioural significance of these changes. When TMS was applied to S1 near‐synchronously to an afferent signal containing mechanoreceptive information, MN‐SSEP changes (significant at 21–31 ms) could be explained by a change in a tangential source located in Brodmann area 3b, with their timing and polarity suggesting modification of upper cortical layers. PAS‐induced MN‐SSEP changes between 28 and 32 ms were linearly correlated with changes in tactile discrimination. Conversely, when the near‐synchronous afferent signal contained predominantly proprioceptive information, PAS‐induced MN‐SSEP changes (20–29 ms) were shifted medially, and tactile performance remained stable. With near‐synchronous mechanoreceptive stimulation subtle differences in the timing of the two interacting signals tended to influence the direction of tactile performance changes. PAS performed with TMS delivered asynchronously to the afferent pulse did not change MN‐SSEPs. Hebbian interaction of mechanoreceptive afferent signals with TMS‐evoked activity may modify synaptic efficacy in superficial cortical layers of Brodmann area 3b and is associated with timing‐dependent and qualitatively congruent behavioural changes.
How does a short history of spinal cord injury affect movement‐related brain potentials?
Authors: Castro Antonio , Díaz Fernando , Van Boxtel Geert J. M.
Published: June 2007

Brain plasticity following spinal cord injury (SCI) has been studied by a wide range of neurofunctional techniques, which tend to have low temporal resolution or overlook cognitive preparatory processes. This study tried to overcome both limitations by recording the movement‐related brain potentials using an experimental task somewhat similar to the contingent negative variation paradigm. The aim was to look for amplitude or topographic distribution changes at an early stage of the SCI. Hence, the brain electrical activity of patients who had a clinical history of less than 6 months of paraplegia was recorded and compared with that of two groups of healthy volunteers. None of the patients was able to move their toes, but they were asked to prepare to carry out this movement and to try to execute it in the same way as one of the control groups. The other control group was instructed to prepare to conduct the same movement but not to execute it. Results did not show significant differences in the readiness potential between patients with paraplegia and both controls. However, the readiness potential topography observed in patients was more similar to that of healthy participants who conducted the movement, whereas a greater similarity was found in the motor potential between patients and healthy participants who did not carry out the movement. These findings suggest that neurofunctional changes that take place in the brain after a SCI may be shown earlier by the motor potential than by the readiness potential.
Synaptic activation of GABAB receptors regulates neuronal network activity and entrainment
Authors: Brown Jon T. , Davies Ceri H. , Randall Andrew D.
Published: June 2007

In the mammalian central nervous system, GABAB receptors mediate slow pre‐ and postsynaptic inhibition. Using rat hippocampal slices we investigated the role of synaptic GABAB receptors in regulating kainate‐induced subthreshold neuronal network oscillations in the gamma frequency range (25–80 Hz). The GABAB receptor agonist baclofen largely eliminated gamma oscillations. The GABAB receptor antagonist CGP55845 reversed this action of baclofen but alone did not alter the power or frequency of ongoing oscillations. To examine the role of synaptically released GABA on network activity, we electrically stimulated stratum radiatum of CA3 whilst recording gamma oscillations from stratum pyramidale. Single stimuli produced a pronounced transient (up to 1 s in duration) inhibition of gamma frequency oscillations. This stimulus‐induced shutdown of network activity was enhanced by the GABA uptake inhibitor tiagabine and largely inhibited by CGP55845. Multiple stimuli delivered at frequencies of 1–3 Hz resulted in an activity‐dependent fatigue of the inhibition of gamma activity, such that, after a number of stimuli, oscillations could be detected tens of milliseconds after the stimulus. Interestingly, this activity‐dependent fatigue of inhibition uncovered a stimulus‐dependent temporal entrainment of the gamma oscillations. Furthermore, the amount of repetitive synaptic input that was required to cause this entrainment was dramatically reduced by GABAB receptor antagonism such that it was evident within just a few stimuli. These data suggest that convergent afferent synaptic activity can alter the precise temporal arrangement of neuronal network activity. Furthermore, the flow of such information into a functioning neuronal network is highly regulated by GABAB receptor‐mediated synaptic inhibition.
Shedding light on circadian clock resetting by dark exposure: differential effects between diurnal and nocturnal rodents
Authors: Mendoza Jorge , Revel Florent G. , Pévet Paul , Challet Etienne
Published: June 2007

The master circadian clock in mammals, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, is entrained by light and behavioural stimulation. In addition, the SCN can be reset by dark pulses in nocturnal rodents under constant light conditions. Here, the shifting effects of a dark pulse on the SCN clock were detailed at both a behavioural and molecular level in a nocturnal rodent (Syrian hamster), and were compared to those of a diurnal rodent (Arvicanthis ansorgei). Four‐hour dark pulses led to phase advances in the circadian rhythm of locomotor activity from subjective midday to dusk in hamsters, but from subjective dusk to midnight in Arvicanthis. Moreover, dark pulses had no resetting effect during the middle of the subjective night in hamsters, while such a dead shifting zone occurred during most of the subjective day in Arvicanthis. The behavioural phase advances in both hamsters and Arvicanthis were most often accompanied by marked downregulation of the clock genes Per1 and/or Per2 in the SCN, and also by changes in the transforming growth factor‐α expression, a neuropeptide that suppresses daytime activity in nocturnal mammals. Despite that both hamsters and Arvicanthis showed dark‐induced phase advances at circadian time‐12, Per1 gene and its protein PER1 were downregulated in Arvicanthis but not in hamsters. Altogether these results show that dark resetting of the SCN is always associated with downregulation of Per1 and/or Per2 expression, and mostly occurs during resting. Thus, the circadian window of sensitivity to dark differs between nocturnal and diurnal rodents.
Dexterity is impaired at both hands following unilateral subcortical middle cerebral artery stroke
Authors: Nowak Dennis A. , Grefkes Christian , Dafotakis Manuel , Küst Jutta , Karbe Hans , Fink Gereon R.
Published: June 2007

Dexterity was investigated in right‐handed subjects in the subacute phase of a first unilateral subcortical middle cerebral artery stroke affecting the left or right hemisphere and right‐handed healthy subjects. Dexterity was quantified at both hands by kinematic recordings of finger and hand tapping, a reach‐to‐grasp movement, quantitative analysis of grip forces in a grasp‐lift task and clinical rating scales. Stroke subjects exhibited significant deficits in timing and coordination of tapping movements at both the contralesional and ipsilesional hands, irrespective of the hemisphere affected. Likely for the reach‐to‐grasp and grasp‐lift movements a bilateral impairment was found in stroke subjects. In particular, slowing of hand transport towards the object, deficient timing and scaling of grasp formation, discoordination between grip and lift forces and inefficient scaling of grip forces were observed. The severity of impairment was independent of the hemisphere affected and evident for both the reach (involving more proximal muscles of the arm) and grasp (involving more distal muscles of the arm and hand) components of the task. Strong correlations were found between clinical scores of hand function and loss of sensibility with the deficits in timing, coordination and efficiency of movement of the contralesional and ipsilesional hand. These data provide evidence that dexterity is impaired at both hands after subcortical middle cerebral artery stroke.
A novel mechanism for evoked responses in the human brain
Authors: Nikulin Vadim V. , Linkenkaer‐Hansen Klaus , Nolte Guido , Lemm Steven , Müller Klaus R. , Ilmoniemi Risto J. , Curio Gabriel
Published: June 2007

Magnetoencephalographic and electroencephalographic evoked responses are primary real‐time objective measures of cognitive and perceptual processes in the human brain. Two mechanisms (additive activity and phase reset) have been debated and considered as the only possible explanations for evoked responses. Here we present theoretical and empirical evidence of a third mechanism contributing to the generation of evoked responses. Interestingly, this mechanism can be deduced entirely from the characteristics of spontaneous oscillations in the absence of stimuli. We show that the amplitude fluctuations of neuronal α oscillations at rest are associated with changes in the mean value of ongoing activity in magnetoencephalography, a phenomenon that we term baseline shifts associated with α oscillations. When stimuli modulate the amplitude of α oscillations, baseline shifts become the basis of a novel mechanism for the generation of evoked responses; the averaging of several trials leads to a cancellation of the oscillatory component but the baseline shift remains, which gives rise to an evoked response. We propose that the presence of baseline shifts associated with α oscillations can be explained by the asymmetric flow of inward and outward neuronal currents related to the generation of α oscillations. Our findings are relevant to the vast majority of electroencephalographic and magnetoencephalographic studies involving perceptual, cognitive and motor activity.
Assembly of two distinct dimers and higher‐order oligomers from full‐length tau
Authors: Sahara Naruhiko , Maeda Sumihiro , Murayama Miyuki , Suzuki Takehiro , Dohmae Naoshi , Yen Shu‐Hui , Takashima Akihiko
Published: June 2007

Abnormal accumulation of tau as filamentous structures is a neuropathological hallmark of neurodegenerative diseases referred to as tauopathies. Little is known about the role of native cysteine residues in tau assembly because their substitution with other amino acids has no effect on tau filament morphology. To understand the process involved in tau oligomerization, we analysed both heparin‐induced assembly of different forms of recombinant human tau and assembly of tau from COS‐7 cells transiently expressing different human tau constructs. Here, we demonstrated that tau assembly involves two distinct dimers (cysteine‐dependent and cysteine‐independent) that differ in resistance to reduction. During assembly, an increase of cysteine‐dependent tau oligomer was observed prior to detection of increased thioflavin T fluorescence signals. The latter event was accompanied by an increase of cysteine‐independent dimer. Fewer higher‐order oligomers and aggregates were assembled from four‐repeat tau containing two amino‐terminus inserts that have either the C291A/C322A mutation (cysless‐4R2N) or a hexapeptide deletion at residues 306–311 (ΔPHF6–4R2N) compared with those assembled from wild‐type tau. Assembly of distinct types of dimers was also observed in lysates from COS‐7 cells expressing wild‐type 4R2N and brain extracts from mice expressing P301L mutant tau. In contrast, COS‐7 cells expressing cysless‐ or ΔPHF6–4R2N tau contained very little cysteine‐dependent dimer. Together, the results indicate that intermolecular disulfide crosslinking along with PHF6 hexapeptide facilitates tau oligomerization and that this event is accompanied by cysteine‐independent intermolecular bridging of microtubule‐binding domain, leading to assembly of higher‐order oligomers. The levels of these dimers may be used to gauge the potential for tau assembly.
5‐HT2Creceptor activation inhibits appetitive and consummatory components of feeding and increases brain c‐fosimmunoreactivity in mice
Authors: Somerville Elizabeth M. , Horwood Julia M. , Lee Michelle D. , Kennett Guy A. , Clifton Peter G.
Published: June 2007

5‐Hydroxytryptamine (5‐HT)2Cand 5‐HT1Breceptors are implicated in the inhibitory modulation of feeding behaviour. However, their respective, and possibly different, roles have not been clearly identified because of a lack of selective 5‐HT2Creceptor agonists. Here, using the putative, selective 5‐HT2Creceptor agonist VER23779, we show that its effects on feeding are fully reversed by pretreatment with a selective 5‐HT2Creceptor antagonist, but unaffected by pretreatment with either a 5‐HT1Bor a 5‐HT2Areceptor antagonist. In mice eating a palatable mash, feeding ends earlier, inactivity is increased but the behavioural satiety sequence is preserved. In a second‐order schedule of reinforcement with an initial, non‐food‐reinforced appetitive phase, VER23779 produces a much greater relative reduction in appetitive responding than the 5‐HT1Breceptor agonist CP‐94,253. Increased c‐fosimmunoreactivity patterns following VER23779 also differ from those described for CP‐94,253, in particular showing strong activation of the basolateral amygdala. The different behavioural consequences of 5‐HT2Cand 5‐HT1Breceptor activation may relate to the patterns of c‐fosimmunoreactivity. In particular, the basolateral amygdala may have a role in maintaining response in the appetitive phase of the second‐order schedule and also be susceptible to serotonergic modulation through activation of 5‐HT2Creceptors.
Synaptic plasticity of the CA3 commissural projection in epileptic rats: an in vivo electrophysiological study
Authors: Queiroz Claudio M. T. , Mello Luiz Eugênio
Published: June 2007

The hippocampal commissural system has recently been found to participate in the generation of mirror foci after kainate‐induced epileptiform discharges. In the present study we have evaluated the electrophysiological alterations in the ventral commissural hippocampal system that originates in the pyramidal CA3 cells and connects to the contralateral CA3 pyramidal cells. The recordings were performed in epileptic rats 24 h after an early behavioural spontaneous seizure between 5 and 21 days after pilocarpine‐induced status epilepticus. Epileptic animals presented a marked increase in neuronal excitability after contralateral CA3 stimulation, characterized by a shift to the left in the input–output curve and the clear appearance of a population spike. Input–output curves showed that maximum population excitatory postsynaptic potential (pEPSP) amplitude was decreased by 30%, which could be related to cell death in these regions. Using paired‐pulse protocols to evaluate a fast form of synaptic plasticity (i.e. paired‐pulse facilitation) we observed that, despite the similar pEPSP amplitude between control and experimental groups, only epileptic animals showed strong paired‐pulse population spike facilitation up to 500 ms interstimulus intervals. Despite increased excitability and pyramidal cell death, epileptic animals presented a more robust potentiation after high‐frequency stimulation than controls, a protocol used to evaluate a slow form of synaptic plasticity (i.e. long‐term potentiation). The increased excitability in CA3 pyramidal neurons enhanced the probability of burst activity in these neurons; this could lead to greater CA1 synchronization. The present results might have relevance for the understanding of epileptogenesis and of learning and memory deficits seen in temporal lobe epilepsy.
Proteasome‐dependent and ‐independent mechanisms for FosB destabilization: identification of FosB degron domains and implications for ΔFosB stability
Authors: Carle Tiffany L. , Ohnishi Yoshinori N. , Ohnishi Yoko H. , Alibhai Imran N. , Wilkinson Matthew B. , Kumar Arvind , Nestler Eric J.
Published: June 2007

The transcription factor ΔFosB (Delta FosB) accumulates in a region‐specific manner in the brain during chronic exposure to stress, drugs of abuse or other chronic stimuli. Once induced, ΔFosB persists in the brain for at least several weeks following cessation of the chronic stimulus. The biochemical basis of the persistent expression of ΔFosB has remained unknown. Here, we show that the FosB C‐terminus, absent in ΔFosB as a result of alternative splicing, contains two degron domains. Pulse‐chase experiments of C‐terminal truncation mutants of full‐length FosB indicate that removal of its most C‐terminal degron increases its half‐life ∼ fourfold, and prevents its proteasome‐mediated degradation and ubiquitylation, properties similar to ΔFosB. In addition, removal of a second degron domain, which generates ΔFosB, further stabilizes FosB ∼ twofold, but in a proteasome‐independent manner. These data indicate that alternative splicing specifically removes two destabilizing elements from FosB in order to generate a longer‐lived transcription factor, ΔFosB, in response to chronic perturbations to the brain.
Testing the impact of climate variability on European plant diversity: 320 000 years of water–energy dynamics and its long‐term influence on plant taxonomic richness
Authors: Willis Katherine J. , Kleczkowski Adam , New Mark , Whittaker Robert J.
Published: June 2007

Models examining the present‐day relationship between macro‐scale patterns in terrestrial species richness and variables of water and energy demonstrate that a combined water–energy model is a good predictor of richness in mid‐to‐high latitude regions. However, the power of the individual water and energy variables to explain this richness through time has never been explored. Here, we assess how well energy and water can predict long‐term variations in plant richness using a 320 000‐year fossil pollen data set from Hungary. Results demonstrate that a combined water–energy model best explains the variation in plant diversity through time. However, this long temporal record also demonstrates that amplitude of energy variation appears to be a strong determinant of richness. Decreased richness correlates with increased climate variability and certain species appear to be more susceptible according to their ecological traits. These findings have important implications for predicting richness at times of increasing climate variability.
Landscape heterogeneity shapes predation in a newly restored predator–prey system
Authors: Kauffman Matthew J. , Varley Nathan , Smith Douglas W. , Stahler Daniel R. , MacNulty Daniel R. , Boyce Mark S.
Published: June 2007

Because some native ungulates have lived without top predators for generations, it has been uncertain whether runaway predation would occur when predators are newly restored to these systems. We show that landscape features and vegetation, which influence predator detection and capture of prey, shape large‐scale patterns of predation in a newly restored predator–prey system. We analysed the spatial distribution of wolf (Canis lupus) predation on elk (Cervus elaphus) on the Northern Range of Yellowstone National Park over 10 consecutive winters. The influence of wolf distribution on kill sites diminished over the course of this study, a result that was likely caused by territorial constraints on wolf distribution. In contrast, landscape factors strongly influenced kill sites, creating distinct hunting grounds and prey refugia. Elk in this newly restored predator–prey system should be able to mediate their risk of predation by movement and habitat selection across a heterogeneous risk landscape.
A Circumplex Model of Interpersonal Attributes in Middle Childhood
Authors: Di Blas Lisa
Published: June 2007

ABSTRACT
This article presents evidence for the validity of the circumplex model to represent how parents and teachers organize interpersonal attributes in children. Study 1 showed that the ratings of adults using interpersonal adjectives to describe 4‐ to 10‐year‐old children conformed to a circumplex structure. Eight scales—labeled Interpersonal Adjective Scales for Children (IAS‐C)—were developed to represent the circular sequence of children's interpersonal attributes, as ordered around the reference axes of Extraversion and Social Appropriateness. The continuum of interpersonal variables substantially corresponded to Schaefer's model for social and emotional behavior, as follows: Warm‐Agreeable, Sociable‐Cheerful, Exuberant‐Dominant, Impulsive‐Aggressive, Egocentric‐Irritable, Fearful‐Insecure, Shy‐Silent, and Mild‐Placid. Study 2 demonstrated cross‐validity for the IAS‐C and how they are related to Big Five measures. Study 3 used data from Studies 1 and 2 in a confirmatory approach to test the circumplex IAS‐C structure. Findings are discussed in relation to the adult circumplex model and suggest that the child circumplex has distinctive features that must be kept in due consideration when attempting to assess interpersonal qualities in children validly.
RELATIVE FACTOR PRICES IN THE PERIPHERY DURING THE FIRST GLOBAL CENTURY: ANY LESSONS FOR TODAY?
Authors: Williamson Jeffrey G.
Published: June 2007

Globalisation before 1939 had profound effects on factor prices and income distribution, especially between the industrialising core economies and the economies of periphery. Jeffrey Williamson reflects briefly on: the impact of globalisation on relative factor price convergence; the interaction between commodity market convergence and convergence in labour and capital markets; and whether the nineteenth history of the periphery was a different history from that of the industrialising European core. Williamson concludes with observations on why the blacklash against globalisation is less severe today than it was during the first global century.
ARE MOVERS STILL THE SAME? CHARACTERISTICS OF INTERREGIONAL MIGRANTS IN SWEDEN 1970–2001
Authors: LUNDHOLM EMMA
Published: June 2007

The purpose of this study is to investigate interregional migration in Sweden during the last three decades and to discuss the effects that changes on the labour market and in household structures have had on migration patterns. The empirical data consists of all interregional migrants in Sweden from 1970 to 2001. The results indicate that the pattern of labour market‐related migration has changed as more migrants today migrate at an age prior to having become established on the labour market. The increase in interregional migration is to a large extent an effect of increased student migration. The study further shows that changed household structures have also had an impact on migration patterns during the studied period. Interregional migration among families has become rarer as dual income households have become the norm.
PORT COMPETITION BETWEEN LOS ANGELES and LONG BEACH: AN INSTITUTIONAL ANALYSIS
Authors: JACOBS WOUTER
Published: June 2007

This paper focuses on the process of institutional change at the leading ports of the United States: Los Angeles and Long Beach. In order to do so, it makes use of the structure of provision‐approach and the concept of regime politics which allows for a systematic analysis and comparison. Key questions are: how are both ports institutionally structured? How do they evolve in relation to each other? And what is the role of agency in this process? The paper reveals how both ports remain institutionally different in spite of competition. This persistent institutional diversity can be explained by that fact that institutions represent territorially rooted structures of power in which competitive performance will not always be the decisive interest.
GEOPOLITICS OF THE SATELLITE INDUSTRY
Authors: WARF BARNEY
Published: June 2007

This paper situates the international satellite industry within three lines of contemporary geographic thought. Second, it reviews the industry's Cold War origins. Third, it explains changing international regulatory structures of satellites, particularly Intelsat, which control access to and use of the technology. Fourth, it summarises the changing role of satellites in the post‐Cold War era, including the impacts of deregulation, rising competition between Intelsat and national and commercial providers, and the heated rivalry between satellites and fibre optic carriers. Throughout, it emphasises the ways in which terrestrial power relations alter access and applications to this sector.
A EUROPEAN CULTURAL IDENTITY? HERITAGE and SHARED HISTORIES IN THE EUROPEAN UNION
Authors: VAN GORP BOUKE , RENES HANS
Published: June 2007

Do the people in the European Union share a cultural identity? One important aspect of cultural identity is shared histories or common memories. Such histories can be presented by heritage. Heritage is those traces of the past a society chooses to preserve. Heritage is therefore also a way of defining oneself. To this day, the European Union has not yet compiled its own list of heritage. This paper analyses the World Heritage Sites of EU member states: sites that are considered to be of universal value. When taken together, what image of European history do these sites represent?
Lotteries, Group Size, and Public Good Provision
Authors: PECORINO PAUL , TEMIMI AKRAM
Published: June 2007

We analyze the effect of group size on public good provision under theMorgan (2000)lottery mechanism. For a pure public good, the lottery performs quite well as public good provision is found to increase in group size, even when the lottery prize is held constant. By contrast, for fully rival public goods, per capita provision is found to decrease in group size, even when the lottery prize is proportional to group size. Further, the per capita level of provision will approach zero when group size is sufficiently large.
Help the Low Skilled or Let the Hardworking Thrive? A Study of Fairness in Optimal Income Taxation
Authors: FLEURBAEY MARC , MANIQUET FRANÇOIS
Published: June 2007

In a model where agents have unequal wages and heterogeneous preferences, we study the optimal redistribution via an income tax, when the social objective is based on a combination of efficiency and fairness principles, and when incentive issues are taken into account. We show how some fairness principles entail specific features for the optimal taxes, such as progressivity or tax exemption for incomes below the minimum wage.
Analysing and Assessing Accountability: A Conceptual Framework1
Authors: Bovens Mark
Published: June 2007

Abstract:  It has been argued that the EU suffers from serious accountability deficits. But how can we establish the existence of accountability deficits? This article tries to get to grips with the appealing but elusive concept of accountability by asking three types of questions. First a conceptual one: what exactly is meant by accountability? In this article the concept of accountability is used in a rather narrow sense: a relationship between an actor and a forum, in which the actor has an obligation to explain and to justify his or her conduct, the forum can pose questions and pass judgement, and the actor may face consequences. The second question is analytical: what types of accountability are involved? A series of dimensions of accountability are discerned that can be used to describe the various accountability relations and arrangements that can be found in the different domains of European governance. The third question is evaluative: how should we assess these accountability arrangements? The article provides three evaluative perspectives: a democratic, a constitutional and a learning perspective. Each of these perspectives may produce different types of accountability deficits.
Longitudinal changes in serum lipids among HIV‐infected men on highly active antiretroviral therapy
Authors: Riddler SA , Li X , Chu H , Kingsley LA , Dobs A , Evans R , Palella F , Visscher B , Chmiel JS , Sharrett AR
Published: June 2007

Objective

The aim of the study was to describe longitudinal changes in serum lipids among HIV‐infected men receiving highly active antiretroviral therapy (HAART) with long‐term follow‐up.

Methods

A total of 304 HIV‐infected men who initiated HAART and who had serum lipid measurements prior to and for up to 7 years after HAART initiation were identified from the Multicenter AIDS Cohort Study (MACS). Mean levels of total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C) and low‐density lipoprotein cholesterol (LDL‐C) were examined at biannual time‐points.

Results

Significant lipid changes were seen within 0.5 years of HAART initiation but increases in TC (+1.09 mmol/L), LDL‐C (+0.57 mmol/L), HDL‐C (+0.16 mmol/L) and non‐HDL‐C (+0.91 mmol/L) reached peak levels 2–3 years after HAART initiation. Declines in serum TC, LDL‐C and non‐HDL‐C in subsequent years occurred concurrently with a substantial increase in use of lipid‐lowering medications (from 1% usage pre‐HAART to 43% 6–7 years after HAART initiation) but the proportion of men who either were treated with cholesterol‐lowering medication or had elevated cholesterol levels (>5.18 mmol/L) did not change during the 2–7‐year interval after HAART. Mean HDL‐C also decreased after 2–3 years and was low (<1.04 mmol/L) in 55% of HIV‐infected men 6–7 years after HAART initiation.

Conclusions

Atherogenic serum lipids increased early after the initiation of HAART, peaked at 2–3 years and remained high or required treatment thereafter. Low HDL‐C levels persisted in the majority of men. The long‐term effects of lipid abnormalities on cardiovascular risk and the effectiveness and toxicity of prolonged use of lipid‐lowering medications in combination with HAART are not known.
The significance of Epstein–Barr virus detected in the cerebrospinal fluid of people with HIV infection
Authors: Wang J , Ozzard A , Nathan M , Atkins M , Nelson M , Gazzard B , Bower M
Published: June 2007

Introduction

Epstein–Barr virus (EBV) is detected in the cerebrospinal fluid (CSF) in people with HIV infection who develop primary cerebral lymphoma (PCL). However, EBV may also be detected in the CSF of patients without PCL, and here the significance is uncertain.

Methods

Ninety‐eight HIV‐positive patients had lumbar punctures performed and polymerase chain reaction (PCR) for EBV was undertaken on the CSF. Thirty‐eight patients had non‐Hodgkin's lymphoma (NHL), including four with PCL. Sixty patients had a CSF examination for other indications. The clinicopathological details, symptoms, diagnosis, CSF and neuroimaging findings and therapy at time of CSF were recorded and correlated with CSF EBV PCR results.

Results

EBV was detected in the CSF in three of four patients (75%) with PCL, one of three (33%) with systemic lymphoma and meningeal involvement, and four of 31 (13%) with systemic lymphoma and no meningeal disease. Seven of 60 patients (12%) without lymphoma were CSF EBV‐positive. There were no differences in immunological, clinical, biochemical or radiological parameters between patients with and without EBV in the CSF. After a median follow‐up time of 30 weeks (maximum 102 weeks), none of the seven CSF EBV‐positive patients has developed PCL.

Conclusion

EBV was detected in up to 12% of patients with neurological symptoms but without lymphoma. A positive result did not correlate with more advanced immunosuppression or a particular neurological diagnosis. Patients with EBV in their CSF did not appear to be at increased risk of developing PCL in the short term.
Eye movement disorders in vitamin B12 deficiency: two new cases and a review of the literature
Authors: Akdal G. , Yener G. G. , Ada E. , Halmagyi G. M.
Published: June 2007

Eye movement disorders are rarely reported in vitamin B12 deficiency. We describe two cases with eye movement disorder and vitamin B12 deficiency; one with bilateral internuclear ophthalmoplegia and the other with downbeat nystagmus. Both of the patients received replacement therapy but their eye movement disorders did not respond to treatment. We also review the nine previously reported cases.
Effect of deep brain stimulation of the posterior hypothalamic area on the cardiovascular system in chronic cluster headache patients
Authors: Cortelli P. , Guaraldi P. , Leone M. , Pierangeli G. , Barletta G. , Grimaldi D. , Cevoli S. , Bussone G. , Baruzzi A. , Montagna P.
Published: June 2007

The objective of this study was to determine the cardiovascular effects of chronic stimulation of the posterior hypothalamic area (PHA) in cluster headache (CH) patients. Systolic and diastolic blood pressure (SBP, DBP), cardiac output, total peripheral resistance (TPR), heart rate (HR) and breathing were monitored at supine rest and during head‐up tilt test (HUTT), Valsalva manoeuvre, deep breathing, cold face test and isometric handgrip in eight drug‐resistant chronic CH patients who underwent monolateral electrode implantation in the PHA for therapeutic purposes. Autoregressive power spectral analysis (PSA) of HR variability (HRV) was calculated at rest and during HUTT. Each subject was studied before surgery (condition A) and after chronic deep brain stimulation (DBS) of PHA (condition B). Baseline SBP, DBP, HR and cardiovascular reflexes were normal and similar in both conditions. With respect to condition A, DBP, TPR and the LF/HF obtained from the PSA of HRV were significantly (P < 0.05) increased during HUTT in condition B. In conclusion, chronic DBS of the PHA in chronic CH patients is associated with an enhanced sympathoexcitatory drive on the cardiovascular system during HUTT.
The Value‐relevance of Earnings and Book Value, Ownership Structure, and Business Group Affiliation: Evidence From Korean Business Groups
Authors: Bae Kee‐Hong , Jeong Seok Woo
Published: June 2007

Abstract:  We investigate the quality of two primary accounting summary measures, i.e., earnings and book value, provided by firms belonging to Korean business groups (chaebols). We find that the value‐relevance of earnings and book value is significantly smaller for firms affiliated with business groups. We also find that cross‐equity ownership (a proxy for the agency problem between controlling and minority shareholders) negatively affects value‐relevance, while foreign equity ownership (a proxy for the monitoring effect) positively affects value‐relevance. This evidence is consistent with the view that the poor quality of earnings and book value provided by chaebol‐affiliated firms is due to the inherently poor governance structure of chaebols.
Regulation and execution of molecular disassembly and catabolism during senescence
Authors: Hopkins Marianne , Taylor Catherine , Liu Zhongda , Ma Fengshan , McNamara Linda , Wang Tzann‐Wei , Thompson John E.
Published: June 2007

Contents

Summary
201

I.
Introduction
202

II.
Role of signaling cascades in the initiation of senescence
202

III.
Senescence transcriptome
203

IV.
Execution of senescence
203

V.
Conclusions and outlook
210

Acknowledgements
210

References
211
Enhancement of α‐secretase cleavage of amyloid precursor protein by a metalloendopeptidase nardilysin
Authors: Hiraoka Yoshinori , Ohno Mikiko , Yoshida Kazuhiro , Okawa Katsuya , Tomimoto Hidekazu , Kita Toru , Nishi Eiichiro
Published: June 2007

Amyloid‐β (Aβ) peptide, the principal component of senile plaques in the brains of patients with Alzheimer’s disease, is derived from proteolytic cleavage of amyloid precursor protein (APP) by β‐ and γ‐secretases. Alternative cleavage of APP by α‐secretase occurs within the Aβ domain and precludes generation of Aβ peptide. Three members of the ADAM (a disintegrin and metalloprotease) family of proteases, ADAM9, 10 and 17, are the main candidates for α‐secretases. However, the mechanism that regulates α‐secretase activity remains unclear. We have recently demonstrated that nardilysin (EC 3.4.24.61, N‐arginine dibasic convertase; NRDc) enhances ectodomain shedding of heparin‐binding epidermal growth factor‐like growth factor through activation of ADAM17. In this study, we show that NRDc enhances the α‐secretase activity of ADAMs, which results in a decrease in the amount of Aβ generated. When expressed with ADAMs in cells, NRDc dramatically increased the secretion of α‐secretase‐cleaved soluble APP and reduced the amount of Aβ peptide generated. A peptide cleavage assay in vitro also showed that recombinant NRDc enhances ADAM17‐induced cleavage of the peptide substrate corresponding to the α‐secretase cleavage site of APP. A reduction of endogenous NRDc by RNA interference was accompanied by a decrease in the cleavage by α‐secretase of APP and increase in the amount of Aβ generated. Notably, NRDc is clearly expressed in cortical neurons in human brain. Our results indicate that NRDc is involved in the metabolism of APP through regulation of the α‐secretase activity of ADAMs, which may be a novel target for the treatment of Alzheimer’s disease.
Rapid down‐regulation of Ret following exposure of dopaminergic neurons to neurotoxins
Authors: Hirata Yoko , Kiuchi Kazutoshi
Published: June 2007

The survival and functional maintenance of vertebrate neurons depends on the availability of specific neurotrophic factors. We studied the influence of neurotrophic support on responses of dopaminergic neurons to 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine, a neurotoxin known to damage the nigrostriatal dopaminergic pathway in humans and other mammals. Treatment of mice with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine caused decreases in levels of Ret, a tyrosine kinase receptor for glial cell line‐derived neurotrophic factor (GDNF) in the striatum, under the condition in which tyrosine hydroxylase was moderately decreased and the GDNF family receptor α1, another receptor of GDNF that is the ligand‐binding subunit, were unaffected. Down‐regulation of Ret was also observed in dopamine‐producing PC12 cells undergoing apoptosis induced by rotenone, another toxic substance for dopaminergic neurons, while other cellular components were not affected. Ret was also extremely vulnerable to other apoptotic inducing conditions. Taken together, these results indicate that Ret, an important signal molecule in dopaminergic neurons, may be down‐regulated in the early stages of neuronal degeneration caused by various neurotoxic substances, and may lead to reduced neurotrophic influences.