bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unilateral cochlear ablation produces greater loss of inhibition in the contralateral inferior colliculus
Authors: Vale Carmen , Juíz José M. , Moore David R. , Sanes Dan H. 
Published: September 2004

AbstractBilateral cochlear ablation leads to a profound weakening of synaptic inhibition within the inferior colliculus (IC) of gerbils [Vale & Sanes (2000) J. Neurosci., 20, 1912–1921]. To examine whether unilateral deafening leads to similar functional alterations, we studied the effect of unilateral cochlear ablation on inhibitory synaptic properties both ipsilateral and contralateral to the deafened ear. Lateral lemniscal and commissure of the IC‐evoked inhibitory postsynaptic currents (IPSCs) were recorded in an IC brain slice preparation using whole‐cell and gramicidin perforated‐patch electrodes in the presence of kynurenic acid. Unilateral cochlear ablation led to a 23 mV depolarizing shift in the IPSC equilibrium potential for IC neurons contralateral to the deafened ear, but only a 10 mV depolarization in the ipsilateral IC. Lateral lemniscal‐evoked inhibitory synaptic conductance declined significantly in the ipsilateral and contralateral IC, whereas commissural‐evoked inhibitory synaptic conductance declined only contralateral to the ablated cochlea. An analysis of paired‐pulse facilitation showed that inhibitory transmitter release was more affected ipsilateral to the ablated cochlea. Thus, unilateral cochlear ablation modifies inhibitory synapses in the inferior colliculus, but these changes appear to be dominated by postsynaptic alterations in the contralateral IC, and by presynaptic changes in the ipsilateral IC.
The β‐amyloid precursor protein controls a store‐operated Ca2+ entry in cortical neurons
Authors: Bouron Alexandre , Mbebi Corinne , Loeffler Jean‐Philippe , De Waard Michel 
Published: September 2004

AbstractA polyclonal antibody (APP‐Ab) raised against the extracellular domain of the beta‐amyloid precursor protein (APP) triggers a marked neuronal cell death preceded by activation of Ca2+‐dependent enzymes, neurite degeneration, oxidative stress and nuclear condensation [Mbebi et al. (2002) J. Biol. Chem., 277, 20979–20990]. We have investigated whether activation of APP by this antibody could promote cell death through cellular Ca2+ homeostasis alteration. We carried out time‐lapse recordings of intracellular Ca2+ signals in cultured mice cortical neurons by means of a scanning confocal microscope. When applied in the presence of 2 mm external Ca2+, APP‐Ab elicited a long‐lasting elevation of the intracellular concentration of Ca2+ ([Ca2+]i). Experiments performed in the absence of external Ca2+ showed that APP‐Ab triggers the release of Ca2+ from intracellular stores. The re‐admission of external Ca2+ provides an additional rise of Ca2+ most likely through store‐operated channels. A pretreatment of the cells with pertussis toxin, to inhibit the activity of Gi/Go proteins, or with the phospholipase C inhibitor, 3‐nitrocoumarin, prevented both the APP‐dependent elevation of Ca2+ as well as the APP‐Ab‐mediated cell death. Similarly, the store‐operated channel inhibitors, 2‐APB or SKF‐96365 block both the APP‐Ab‐dependent Ca2+ entry and the APP‐Ab‐mediated cell death. Altogether, our data provide functional evidence that APP can perturb intracellular Ca2+ homeostasis by emptying intracellular Ca2+ stores and triggering Ca2+ entry through store‐operated channels. In response to APP activation, the long‐lasting elevation of [Ca2+]i due to an entry of Ca2+ via store‐operated channels appears as a major event that leads to neuronal cell death.
Bone morphogenetic proteins regulate ionotropic glutamate receptors in human retina
Authors: Shen Wen , Finnegan Sarah , Lein Pamela , Sullivan Susan , Slaughter Malcolm , Higgins Dennis 
Published: September 2004

AbstractBone morphogenetic proteins (BMPs) are required for the development of retina, but their role in the mature eye is unknown. We therefore examined the expression of BMP‐7 in adult human retina and assessed its effects on horizontal cells cultured from adult human retina. BMP‐7 expression was detected in all retinal layers, with high levels of expression being present in the inner and outer nuclear layers. Human horizontal cells, found in the inner nuclear layer, possess both AMPA and kainate receptors, and glutamatergic agonists that activate these receptors induce prominent inward currents. Exposure to BMP‐7 suppresses the kainate receptor current but enhances the AMPA receptor current. BMP‐6, activin, and cartilage‐derived morphogenic protein‐2 (CDMP‐2) have similar effects to BMP‐7 and act just as rapidly (< 1 s). In contrast BMP‐2 and transforming growth factor‐β2 are inactive. The actions of BMP‐7 on both AMPA and kainate receptors were blocked by the nonselective kinase inhibitor, staurosporine. In contrast, the serine/threonine kinase inhibitors blocked only the effects of BMP‐7 on the AMPA current. Thus, BMPs rapidly and differentially regulate two ionotropic glutamate receptors through distinct pathways, neither of which involves nuclear regulatory activity. These observations suggest that BMPs might modify synaptic function in the mature nervous system.
Multiple GABAA receptor subtypes regulate hippocampal ripple oscillations
Authors: Ponomarenko A. A. , Korotkova T. M. , Sergeeva O. A. , Haas H. L. 
Published: September 2004

AbstractHigh‐frequency oscillations (140–200 Hz) were recorded in behaving rats from the CA1 area of the hippocampus. As generation of these synchronous patterns is assumed to depend on coordinated interneuronal inhibition, we studied the interference of benzodiazepines with the fine structure and occurrence of ripple oscillations. The nonselective GABAA receptor α‐subunit agonist, diazepam, lowered the frequency of ripple oscillations and reduced their occurrence, amplitude and duration. Zolpidem, an α1‐subunit selective benzodiazepine elevated ripple duration but acted similar to diazepam in other respects. The nonselective α‐subunit benzodiazepine antagonist, flumazenil, reduced ripple numbers, amplitude and duration. Wavelet based analysis of the dynamics of intraripple frequency revealed a dramatic decay within a ripple. Only diazepam (1 mg/kg) accelerated this intraripple frequency accommodation. The effects were not due to increased behavioural activity and alertness as evident from vigilance state control. The results suggest a differential role of GABAA receptor subtype specific inhibitory mechanisms in the mediation and fine‐tuning of the network synchronization during ≈200 Hz hippocampal oscillations.
Benzodiazepine impairment of perirhinal cortical plasticity and recognition memory
Authors: Wan H. , Warburton E. C. , Zhu X. O. , Koder T. J. , Park Y. , Aggleton J. P. , Cho K. , Bashir Z. I. , Brown M. W. 
Published: September 2004

AbstractBenzodiazepines, including lorazepam, are widely used in human medicine as anxiolytics or sedatives, and at higher doses can produce amnesia. Here we demonstrate that in rats lorazepam impairs both recognition memory and synaptic plastic processes (long‐term depression and long‐term potentiation). Both impairments are produced by actions in perirhinal cortex. The findings thus establish a mechanism by means of which benzodiazepines impair recognition memory. The findings also strengthen the hypotheses that the familiarity discrimination component of recognition memory is dependent on reductions in perirhinal neuronal responses when stimuli are repeated and that these response reductions are due to a plastic mechanism also used in long‐term depression.
Why Subsidise Private Health Insurance?
Authors: Frech H. E. , Hopkins Sandra 
Published: September 2004

AbstractWhat are the economic rationales for the public subsidy of private health insurance? Inducing more people to purchase private cover has the potential to create a positive fiscal externality, as it frees up the limited public beds and other public resources for people who cannot afford private health insurance. Investigating this quantitatively, based on short‐run demand estimates, we find that the subsidy cannot be justified on the basis of this externality effect alone. We estimate that the optimal subsidy is actually negative, that is, a tax on private health insurance premiums. On the other hand, the externality does finance some of the costs. We then consider a long‐run dynamic version, consistent with the government's stated rationales for the reforms. In this context, the subsidy might be justified, or at least largely offset, by the fiscal externality. We then discuss other rationales for a subsidy and implementation issues.
A Critique of the Private Health Insurance Regulations
Authors: Vaithianathan Rhema 
Published: September 2004

AbstractThe private health insurance sector is one of the most regulated sectors in Australia. The Private Health Insurance Incentives Scheme, along with community rating, is intended to make private insurance equitable, profitable and popular. We argue that the subsidy to health insurance ought to be a very effective tool for increasing insurance–but it was ineffective because community rating was ineffective. Using data from the Household Expenditure Survey we find that despite community rating rules which prohibit age‐adjusted premiums, young adults paid considerably less for their insurance than older adults. We conclude that insurers circumvented community rating through plan design, screening older consumers into more expensive plans. We also find that the penalty of 2 per cent per year for delaying insurance, introduced as part of the lifetime cover plan, is too low to be effective. We reflect on the New Zealand experience, where a completely deregulated insurance industry continues to be profitable and enjoys similar rates of coverage to those of Australia, and we ask whether Australia too could not benefit from complete deregulation.
Combining Work and Family in Two Welfare State Contexts: A Discourse Analytical Perspective
Authors: Repo Katja 
Published: September 2004

AbstractThis paper describes and compares the way in which British and Finnish mothers of dual‐career families construct discourses on the work and family interplay. Through this comparison, the paper also considers the presence or visibility of larger welfare state frameworks at the level of the discourse of mothers. The paper argues that, despite the many structural and ideological differences between the British and the Finnish welfare states, mothers living in them often construct their daily lives by using similar discursive frameworks. These discourses are, however, contextualized and interpreted differently. This level of contextualization and interpretation of the discourses is argued to be the stage where the structures and gender constructs of welfare states step in.
Family Commitments under Negotiation: Dual Carers in Finland and Italy
Authors: Zechner Minna 
Published: September 2004

AbstractThis paper makes a comparison between Finnish and Italian working dual carers. Dual carers have responsibilities simultaneously at two different fronts. The selected Finnish and Italian samples of carers are doing similar care work in different settings. They negotiate care with a variety of actors and under differing circumstances. A care life story has been constructed for each participant. Then these care life stories have been compared with each other, especially at points where the need for negotiation has been evident, at life's various turning points. There are many individual similarities in negotiations performed in Finland and in Italy. However, their divergent contexts create considerable variation.
Managing the Family: Productivity, Scheduling and the Male Veto
Authors: Baldock John , Hadlow Jan 
Published: September 2004

AbstractThis paper argues that research, analysis and policy innovations focused on how households combine paid work with care responsibilities are driven to too great a degree by preconceptions of “the problem” that do not take sufficient account of how families themselves understand their work and care roles and the choices they are making. The evidence of 246 SOCCARE interviews across five European countries (Finland, France, Italy, Portugal and the UK) is that the variables that are conventionally accepted as having fundamental significance (family‐friendly policies and generous care services, flexible working hours, women's work–life preferences, family type, national labour markets, cultural differences) are less important than is often suggested. More important are time pressures and the idiosyncratic factors that constrain the work and care timetables that families are able to construct. We characterize these as “scheduling problems”. They occupied a large part of the accounts of their lives provided by our respondents and are a primary dimension within which their combinations of paid work and care responsibilities need to be understood. The difficulties our respondents faced in coordinating the work and care activities of their families bear a striking similarity to the problems described in the operations research literature on small businesses. Within the context of these scheduling problems a second important factor emerged: the preferences and behaviour of men who played a critical, though often passive, part in the construction of work and care timetables of the families. We characterize this effect as the “the male veto”.
Has the National Minimum Wage Reduced UK Wage Inequality?
Authors: Dickens Richard , Manning Alan 
Published: September 2004

SummaryThe paper investigates the effect on the wage distribution of the introduction, in April 1999, of the national minimum wage (NMW) in the UK. Because of the structure of UK earnings statistics, it is not straightforward to investigate this and various methods for adjusting the published statistics are discussed. The main conclusions are that the NMW does have a detectable effect on the wage distribution and that compliance with the NMW is widespread but the effect is limited because the NMW has been set at a level such that only 6–7% of workers are directly affected and the NMW has had virtually no effect on the pay of workers who are not directly affected. Furthermore, virtually all the changes occurred within 2 months of the introduction in April 1999 and its effect declined over time from April 1999 to September 2001 as the minimum wage was not uprated in line with the increase in average earnings. The more substantial increase in the NMW in October 2001 partially, but not wholly, restored some of this decline in impact.
New Routes to the PhD: Cause for Concern?
Authors: Johnston Bill , Murray Rowena 
Published: September 2004

AbstractRecent developments suggest that the PhD is at a turning point. Professional groups have criticised the so‐called ‘traditional PhD’. New routes to the PhD are proposed by several bodies and endorsed by one funding council. In light of these developments, it is appropriate to ask what the implications are for the PhD and for the academy. A focus group was used to gather student responses to these developments. The findings show qualified support: students agree that the PhD should cater for different careers but challenge what they see as a simplistic channelling of PhD routes. This paper demonstrates apparent consensus on the need for change in the PhD and reveals movement beyond reconceptualisation towards reconstruction. However, we argue that there is cause for concern in the lack of attention paid to student views and the continuing neglect of quality issues in the PhD.
Selecting Undergraduate Students: What can the UK Learn from the American SAT?
Authors: West Anne , Gibbs Rebecca 
Published: September 2004

AbstractThis short paper explores the contribution or otherwise that could be made by using a test akin to the American Scholastic Assessment Test or SAT to select students for undergraduate degrees in the UK. It examines the political context to the debate about the potential value of such a test, before outlining how SAT results in America vary along dimensions related to social background and how American universities have adapted their admissions procedures in response to these differences. From the research examined it cannot be assumed that the introduction of a test such as the SAT would be any more equitable then the current use of public examinations in England. It is suggested that profiling students along the lines used by some American universities may assist with making access ‘fairer’.
Anatomical substrates for the discriminative stimulus effects of methamphetamine in rats
Authors: Nakajima Akira , Yamada Kiyofumi , He Jue , Zeng Nan , Nitta Atsumi , Nabeshima Toshitaka 
Published: September 2004

AbstractMethamphetamine is a psychostimulant drug acting on central monoaminergic neurons to produce both acute psychomotor stimulation and long‐lasting behavioral effects including addiction and psychosis. Drug discrimination procedures have been particularly useful in characterizing subjective effects of addictive drugs. In the present study, to identify potential anatomical substrates for the discriminative stimulus effects of methamphetamine, we investigated the drug discrimination‐associated Fos expression in Sprague–Dawley rats trained to discriminate methamphetamine from saline under a two‐lever fixed ratio 20 (FR‐20) schedule of food reinforcement. The rats that fulfilled the criteria for learning the discrimination were anesthetized and perfused 2 h after the drug discrimination test, and Fos immunoreactivity was examined in 15 brain regions. Fos expression in the brains of rats that discriminate methamphetamine from saline was significantly increased in the nucleus accumbens (NAc) and the ventral tegmental area (VTA), but not in other areas including the cerebral cortex, caudate putamen, substantia nigra, hippocampus, amygdala and habenulla, as compared with the expression in control rats that were maintained under the FR‐20 schedule. The present findings suggest a role for the VTA and NAc as possible neuronal substrates in the discriminative stimulus effects of methamphetamine.
1‐trichloromethyl‐1,2,3,4‐tetrahydro‐β‐carboline‐induced apoptosis in the human neuroblastoma cell line SK‐N‐SH
Authors: Akundi Ravi Shankar , Macho Antonio , Muñoz Eduardo , Lieb Klaus , Bringmann Gerhard , Clement Hans‐Willi , Hüll Michael , Fiebich Bernd L. 
Published: September 2004

AbstractTrichloroethylene, a common industrial solvent and a metabolic precursor of chloral hydrate, occurs widely in the environment. Chloral hydrate, which is also used as a hypnotic, has been found to condense spontaneously with tryptamine, in vivo, to give rise to a highly unpolar 1‐trichloromethyl‐1,2,3,4‐tetrahydro‐β‐carboline (TaClo) that has a structural analogy to the dopaminergic neurotoxin N‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). Earlier studies have revealed the relative permeability of the molecule through the blood–brain barrier and its ability to induce Parkinson‐like symptoms in rats. In this study, we report that TaClo induces an apoptotic pathway in the human neuroblastoma cell line, SK‐N‐SH, involving the translocation of mitochondrial cytochrome c to the cytosol and activation of caspase 3. TaClo‐induced apoptosis shows considerable differences from that mediated by other Parkinson‐inducing agents such as MPTP, rotenone and manganese. Although it is not clear if the clinically administered dosage of chloral hydrate or the relatively high environmental levels of trichloroethylene could lead to an onset of Parkinson's disease, the spontaneous in vivo formation of TaClo and its pro‐apoptotic properties, as shown in this report, should be considered.
Amphetamine‐evoked gene expression in striatopallidal neurons: regulation by corticostriatal afferents and the ERK/MAPK signaling cascade
Authors: Ferguson Susan M. , Robinson Terry E. 
Published: September 2004

AbstractThe environmental context in which psychostimulant drugs are experienced influences their ability to induce immediate early genes (IEGs) in the striatum. When given in the home cage amphetamine induces IEGs predominately in striatonigral neurons, but when given in a novel test environment amphetamine also induces IEGs in striatopallidal neurons. The source of the striatopetal projections that regulate the ability of amphetamine to differentially engage these two striatofugal circuits has never been described. We report that transection of corticostriatal afferents selectively blocks, whereas enhancement of cortical activity with an ampakine selectively augments, the number of amphetamine‐evoked c‐fos‐positive striatopallidal (but not striatonigral) neurons. In addition, blockade of the extracellular signal‐regulated kinase (ERK)/mitogen‐activated protein kinase (MAPK) signaling cascade preferentially inhibits the number of amphetamine‐evoked c‐fos‐positive striatopallidal neurons. These results suggest that glutamate released from corticostriatal afferents modulates the ability of amphetamine to engage striatopallidal neurons through an ERK/MAPK signaling‐dependent mechanism. We speculate that this may be one mechanism by which environmental context facilitates some forms of drug experience‐dependent plasticity, such as psychomotor sensitization.
U‐box protein carboxyl terminus of Hsc70‐interacting protein (CHIP) mediates poly‐ubiquitylation preferentially on four‐repeat Tau and is involved in neurodegeneration of tauopathy
Authors: Hatakeyama Shigetsugu , Matsumoto Masaki , Kamura Takumi , Murayama Miyuki , Chui Du‐Hua , Planel Emmanuel , Takahashi Ryosuke , Nakayama Keiichi I. , Takashima Akihiko 
Published: September 2004

AbstractNeurofibrillary tangles (NFTs), which are composed of hyperphosphorylated and ubiquitylated tau, are exhibited at regions where neuronal loss occurs in neurodegenerative diseases; however, the mechanisms of NFT formation remain unknown. Molecular studies of frontotemporal dementia with parkinsonism‐17 demonstrated that increasing the ratio of tau with exon 10 insertion induced fibrillar tau accumulation. Here, we show that carboxyl terminus of Hsc70‐interacting protein (CHIP), a U‐box protein, recognizes the microtubule‐binding repeat region of tau and preferentially ubiquitylates four‐repeat tau compared with three‐repeat tau. Overexpression of CHIP induced the prompt degradation of tau, reduced the formation of detergent‐insoluble tau and inhibited proteasome inhibitor‐induced cell death. NFT bearing neurons in progressive supranuclear palsy, in which four‐repeat tau is a component, showed the accumulation of CHIP. Thus, CHIP is a ubiquitin ligase for four‐repeat tau and maintains neuronal survival by regulating the quality control of tau in neurons.