bluuebunny/crossref_metadata_2025_split huggingface dataset:
Behavioural correlates of an altered balance between synaptic and extrasynaptic GABAAergic inhibition in a mouse model
Authors: Sinkkonen Saku T. , Vekovischeva Olga Y. , Möykkynen Tommi , Ogris Waltraud , Sieghart Werner , Wisden William , Korpi Esa R. 
Published: September 2004

AbstractGABAA receptors mediate fast phasic inhibitory postsynaptic potentials and participate in slower tonic extrasynaptic inhibition. Thy1α6 mice with ectopic forebrain expression of GABAA receptor α6 subunits exhibit increased extrasynaptic GABAA receptor‐mediated background conductance and reduced synaptic GABAA receptor currents in hippocampal CA1 neurons [W. Wisden et al. (2002) Neuropharmacology 43, 530–549]. Here we demonstrate that isolated CA1 neurons of these mice showed furosemide‐sensitivity of GABA‐evoked currents, confirming the functional expression of α6 subunit. In addition, receptor autoradiography of the CA1 region of Thy1α6 brain sections revealed pharmacological features that are unique for α6βγ2 and α6β receptors. The existence of atypical α6β receptors was confirmed after completely eliminating GABAA receptors containing γ1, γ2, γ3 or δ subunits using serial immunoaffinity chromatography on subunit‐specific GABAA receptor antibodies. Behaviourally, the Thy1α6 mice showed normal features with slightly enhanced startle reflex and struggle‐escape behaviours. However, they were more sensitive to GABAA antagonists DMCM (shorter latency to writhing clonus) and picrotoxinin (shorter latency to generalized convulsions). Tiagabine, an antiepileptic GABA‐uptake inhibitor that increases brain GABA levels, delayed picrotoxinin‐induced convulsions at a low dose of 3.2 mg/kg in Thy1α6 mice, but not in control mice; however, the overall effect of higher tiagabine doses on the convulsion latency remained smaller in the Thy1α6 mice. Altered balance between extrasynaptic and synaptic receptors thus affects seizure sensitivity to GABAergic convulsants. Importantly, the increased extrasynaptic inhibition, even when facilitated in the presence of tiagabine, was not able fully to counteract enhanced seizure induction by GABAA antagonists.
Astroglial processes show spontaneous motility at active synaptic terminals in situ
Authors: Hirrlinger Johannes , Hülsmann Swen , Kirchhoff Frank 
Published: September 2004

AbstractWithin the tripartite structure of vertebrate synapses, enwrapping astroglial processes regulate synaptic transmission by transmitter uptake and by direct transmitter release. We applied confocal and two‐photon laser scanning microscopy to acutely isolated slices prepared from the brainstem of transgenic TgN(GFAP‐EGFP) mice. In transversal sections fluorescently labelled astrocytes are evenly distributed throughout the tissue. Astroglial processes contacted neuronal somata and enwrapped active synaptic terminals as visualized using FM1‐43 staining in situ. Here, at these synaptic regions astroglial process endings displayed a high degree of dynamic morphological changes. Two defined modes of spontaneous motility could be distinguished: (i) gliding of thin lamellipodia‐like membrane protrusions along neuronal surfaces and (ii) transient extensions of filopodia‐like processes into the neuronal environment. Our observations highlight the active role of astrocytes in direct modulation of synaptic transmission.
Managing Work and Care: A Difficult Challenge for Immigrant Families
Authors: Wall Karin , José José São 
Published: September 2004

AbstractThis paper explores the strategies used by immigrant families to reconcile work and care for young children in Finland, France, Italy and Portugal. Drawing upon interviews with couples or lone parents who have children below age ten, it shows that immigrant families rely on a diversity of work/care strategies. These strategies include extensive delegation of care (mostly to formal or non‐familial informal care), negotiation of care within the nuclear family (both partners sharing the care responsibilities as well as older child care), mother‐centredness (mothers cutting back on working hours), child negligence (leaving children alone) and the superimposition of care upon work (taking children to work). Almost all immigrant families, but especially first‐generation ones, suffer from the absence of close kin networks to support childcare, strong pressure to work and from work (long or atypical hours) and various integration problems such as social isolation, lack of information on services, and problems with housing. However, our findings show that migration patterns, among other factors, have a significant impact on work/care strategies. Highly qualified “professional migration” is more associated with extensive paid delegation (often private and high‐cost), “marriage migration” with mother‐centredness, and “unskilled worker migration” with low‐cost solutions supplemented by workplace care, older child care and negligence. First‐generation unskilled worker migrant families are more exposed to occupational and residential segregation, atypical working hours, low earnings and difficulties in managing work and care for young children. Findings point to the still weak regulatory function of the different welfare states in the protection of these families.
Work and Care Strategies of European Families: Similarities or National Differences?
Authors: Larsen Trine P. 
Published: September 2004

AbstractThis paper examines the work and care strategies chosen by full‐time working families with children in Finland, Italy, Portugal and the UK. It asks whether European families in different countries, facing the same problems of balancing employment and childcare responsibilities, respond to their situations in similar ways. An increase in dual‐earner families where both parents work full‐time represents a general employment trend in today's Europe. Also, within families with children, such employment patterns are now more common than they were previously. National differences may therefore not any longer be as marked as often indicated by country‐based surveys. The qualitative data from the SOCCARE Project offer a way to examine this issue. The focal point of the paper is to make a comparative analysis of couples in similar work and care situations. Using their working hours as the common denominator, this paper analyses their daily childcare arrangements and how these are impacted by gender roles, working schedules, flexibility of workplace, income levels, parents’ educational background and availability of care facilities. The paper concludes that European families’ work and care strategies have many similarities whereby national differences may not be as marked as often indicated by contemporary research.
Caregiving in Transition in Southern Europe: Neither Complete Altruists nor Free‐riders
Authors: Simoni Simonetta , Trifiletti Rossana 
Published: September 2004

AbstractIn the framework of the SOCCARE Project, focusing on families dealing with a double front of care for children and frail elderly people, similarities can be found in Italy, France and Portugal beyond their different welfare regimes. The comparison of family histories and caregiving strategies, by the methodology of case‐matching, gives an interesting overview of the relationship between the debate on social care and that on the intergenerational contract. The paper aims to understand which are the available combinations of family, informal and institutional resources making a heavy burden of care “acceptable and still normal”: this focuses both typical situations of each country and common features through the countries. The results show how changes in the representations of obligation and duty in the intergenerational pact produce different outcomes and demands in welfare systems. The analysis of shifting boundaries between the public and private spheres in care provides useful policy recommendations, aimed at improving choices and “sustainable” responsibilities of individuals, families and social networks. Sustainable policies seem to be more dependent on family and structural types and resources of networks than on different welfare and services support.
Bayesian Binary Segmentation Procedure for Detecting Streakiness in Sports
Authors: Yang Tae Young 
Published: September 2004

SummaryWhen an individual player or team enjoys periods of good form, and when these occur, is a widely observed phenomenon typically called ‘streakiness’. It is interesting to assess which team is a streaky team, or who is a streaky player in sports. Such competitors might have a large number of successes during some periods and few or no successes during other periods. Thus, their success rate is not constant over time. We provide a Bayesian binary segmentation procedure for locating changepoints and the associated success rates simultaneously for these competitors. The procedure is based on a series of nested hypothesis tests each using the Bayes factor or the Bayesian information criterion. At each stage, we only need to compare a model with one changepoint with a model based on a constant success rate. Thus, the method circumvents the computational complexity that we would normally face in problems with an unknown number of changepoints. We apply the procedure to data corresponding to sports teams and players from basketball, golf and baseball.
A Comparison of Univariate and Multivariate Multilevel Models for Repeated Measures of use of Antenatal Care in Uttar Pradesh
Authors: Griffiths Paula L. , Brown James J. , Smith Peter W. F. 
Published: September 2004

SummaryWe compare two different multilevel modelling approaches to the analysis of repeated measures data to assess the effect of mother level characteristics on women’s use of prenatal care services in Uttar Pradesh, India. We apply univariate multilevel models to our data and find that the model assumptions are severely violated and the parameter estimates are not stable, particularly for the mother level random effect. To overcome this we apply a multivariate multilevel model. The correlation structure shows that, once the decision has been made regarding use of antenatal care by the mother for her first observed birth in the data, she does not tend to change this decision for higher order births.
The Sensitivity of Estimates of the Change in Population Behaviour to Realistic Changes in Bias in Repeated Surveys
Authors: Copas Andrew J. , Farewell Vern T. , Mercer Catherine H. , Yao Guiqing 
Published: September 2004

SummaryThe first British National Survey of Sexual Attitudes and Lifestyles (NATSAL) was conducted in 1990–1991 and the second in 1999–2001. When surveys are repeated, the changes in population parameters are of interest and are generally estimated from a comparison of the data between surveys. However, since all surveys may be subject to bias, such comparisons may partly reflect a change in bias. Typically limited external data are available to estimate the change in bias directly. However, one approach, which is often possible, is to define in each survey a sample of participants who are eligible for both surveys, and then to compare the reporting of selected events that occurred before the earlier survey time point. A difference in reporting suggests a change in overall survey bias between time points, although other explanations are possible. In NATSAL, changes in bias are likely to be similar for groups of sexual experiences. The grouping of experiences allows the information that is derived from the selected events to be incorporated into inference concerning population changes in other sexual experiences. We use generalized estimating equations, which incorporate weighting for differential probabilities of sampling and non-response in a relatively straightforward manner. The results, combined with estimates of the change in reporting, are used to derive minimum established population changes, based on NATSAL data. For some key population parameters, the change in reporting is seen to be consistent with a change in bias alone. Recommendations are made for the design of future surveys.
Modelling the Evolution of Distributions: An Application to Major League Baseball
Authors: Koop Gary 
Published: September 2004

SummaryWe develop Bayesian techniques for modelling the evolution of entire distributions over time and apply them to the distribution of team performance in Major League baseball for the period 1901–2000. Such models offer insight into many key issues (e.g. competitive balance) in a way that regression-based models cannot. The models involve discretizing the distribution and then modelling the evolution of the bins over time through transition probability matrices. We allow for these matrices to vary over time and across teams. We find that, with one exception, the transition probability matrices (and, hence, competitive balance) have been remarkably constant across time and over teams. The one exception is the Yankees, who have outperformed all other teams.
Governance of Higher Education in Britain: The Significance of the Research Assessment Exercises for the Funding Council Model
Authors: Tapper Ted , Salter Brian 
Published: September 2004

AbstractThis article uses the political struggles that have enveloped the research assessment exercises (RAEs) to interpret the UK's current funding council model of governance. Ironically, the apparently widespread improvement in the research performance of British universities, as demonstrated by RAE 2001, has made it more difficult to distribute research income selectively, which was supposedly the central objective of the whole evaluative process. Whilst enhanced research ratings may be seen as a cause for celebration in the universities, the failure to anticipate this outcome and, more significantly, to plan for its financial implications is seen in political circles as a failure of higher education management. The article explores the alternative models of governance that are likely to emerge as a consequence of this crisis and, in particular, whether the funding councils can have much freedom of action, given the tighter political control of policy goals and their critical dependence upon the academic profession for the conduct of the evaluative process.
A Challenge to Established Assessment Practice
Authors: Elton Lewis 
Published: September 2004

AbstractThe article looks back 35 years to a challenge on examination practices, based on common assumptions at the time. It notes that many – although not all – of these assumptions are still accepted in much of current practice, although some have been examined by researchers and found wanting extensively in the intervening time. The particular assumptions investigated relate to the distribution, recording and use of examination results, the demand for uniformity of treatment, the comparability of degrees, the assessment of imponderables and the use and value of external examiners.
Intraischaemic hypothermia reduces free radical production and protects against ischaemic insults in cultured hippocampal slices
Authors: McManus Terence , Sadgrove Matthew , Pringle Ashley K. , Chad John E. , Sundstrom Lars E. 
Published: September 2004

AbstractHypothermia has been demonstrated to be an effective neuroprotective strategy in a number of models of ischaemic and excitotoxic neurodegeneration in vitro and in vivo. Reduced glutamate release and free radical production have been postulated as potential mechanisms underlying this effect but no definitive mechanism has yet been reported. In the current study, we have used oxygen–glucose deprivation in organotypic hippocampal slice cultures as an in vitro model of cerebral ischaemia. When assessed by propidium iodide fluorescence, reducing the temperature during oxygen–glucose deprivation to 31–33°C was significantly neuroprotective but this effect was lost if the initiation of hypothermia was delayed until the post‐insult recovery period. The neuroprotective effects of hypothermia were associated with a significant decrease in both nitric oxide production, as assessed by 3‐amino‐4‐aminomethyl‐2′,7′‐difluorofluorescein fluorescence, and superoxide formation. Further, hypothermia significantly attenuated NMDA‐induced nitric oxide formation in the absence of hypoxia/hypoglycaemia. We conclude that the neuroprotective effects of hypothermia are mediated through a reduction in nitric oxide and superoxide formation and that this effect is likely to be downstream of NMDA receptor activation.
Co‐transplantation of carotid body and ventral mesencephalic cells as an alternative approach towards functional restoration in 6‐hydroxydopamine‐lesioned rats: implications for Parkinson's disease
Authors: Shukla S. , Agrawal A. K. , Chaturvedi R. K. , Seth K. , Srivastava N. , Sinha C. , Shukla Y. , Khanna V. K. , Seth P. K. 
Published: September 2004

AbstractExogenous administration of various neurotrophic factors has been shown to protect neurons in animal model of Parkinson's disease (PD). Several attempts are being made to search a tissue source simultaneously expressing many of these neurotrophic factors. Carotid body (CB) contains oxygen‐sensitive glomus cells rich in dopamine (DA) and expresses glial cell line‐derived neurotrophic factor, brain‐derived neurotrophic factor and neurotrophin‐3. We have attempted to study the functional restoration following co‐transplantation of CB cells and ventral mesencephalic cells (VMC) in a 6‐hydroxydopamine‐lesioned rat model of PD. A significant recovery (p < 0.001) in d‐amphetamine‐induced circling behavior (80%) and spontaneous locomotor activity (85%) was evident in co‐transplanted animals at 12 weeks post‐transplantation as compared to lesioned animals. Similarly, a significant (p < 0.001) restoration was observed in DA‐D2 receptor binding (77%), striatal DA (87%) and 3,4‐dihydroxyphenylacetic acid (DOPAC) (85%) levels and nigral DA (75%) and DOPAC (74%) levels. Functional recovery was accompanied by tyrosine hydroxylase (TH) expression and quantification of TH‐positive cells by image analysis revealed a significant restoration in TH‐immunoreactive (IR) fiber density in striatum, as well as TH‐IR neurons in substantia nigra pars compacta in co‐transplanted animals over VMC‐transplanted animals. The result suggests that co‐transplantation of CB cells along with VMC provides better and long‐term functional restoration in the rat model of PD, possibly by supporting the survival of newly grafted cells as well as remaining host DA neurons.
Involvement of cytochrome P450 2E1 in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐induced mouse model of Parkinson's disease
Authors: Vaglini Francesca , Pardini Carla , Viaggi Cristina , Bartoli Cristina , Dinucci Dinuccio , Corsini Giovanni Umberto 
Published: September 2004

AbstractElucidation of the biochemical steps leading to the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced degeneration of the nigrostriatal dopamine (DA) pathway has provided new clues to the pathophysiology of Parkinson's disease. In line with the enhancement of MPTP toxicity by diethyldithiocarbamate (DDC), here we demonstrate how other cytochrome P450 (CYP) 2E1 inhibitors, such as diallyl sulphide (DAS) and phenylethylisothiocyanate (PIC), also potentiate the selective DA neurone degeneration in C57/bl mice. In addition, we show that CYP 2E1 is present in the brain and in the basal ganglia of this mouse strain, as measured by RT–PCR, western blot analysis and immunohistochemistry. A kinetic analysis of MPTP and its metabolites, by means of the microdialysis technique in the striatum, indicates that no detoxification metabolic pathway is affected by any of these inhibitors. This does not rule out, however, that an undetected detoxification pathway involving CYP 2E1 is operating. In order to provide direct evidence for this isozyme involvement, CYP 2E1 knockout mice were challenged with MPTP or the combined treatment. Here we show that these transgenic mice have a low sensitivity to MPTP alone, similar to their wild‐type counterparts, suggesting that it is likely that transgenic mice compensate for the missing enzyme. However, DDC pretreatment completely fails to enhance MPTP toxicity in CYP 2E1 knockout mice, whereas this enhancement is regularly present in wild‐type animals. This study indicates that the occurrence of CYP 2E1 in C57/bl mouse brain is relevant to MPTP toxicity, and suggests that this isozyme may have a detoxificant role related to the efflux transporter of the toxin.
Identification of tyrosine hydroxylase as a physiological substrate for Cdk5
Authors: Kansy Janice W. , Daubner S. Colette , Nishi Akinori , Sotogaku Naoki , Lloyd Michael D. , Nguyen Chan , Lu Lin , Haycock John W. , Hope Bruce T. , Fitzpatrick Paul F. , Bibb James A. 
Published: September 2004

AbstractCyclin‐dependent kinase 5 (Cdk5) is emerging as a neuronal protein kinase involved in multiple aspects of neurotransmission in both post‐ and presynaptic compartments. Within the reward/motor circuitry of the basal ganglia, Cdk5 regulates dopamine neurotransmission via phosphorylation of the postsynaptic signal transduction pathway integrator, DARPP‐32 (dopamine‐ and cyclic AMP‐regulated phosphoprotein, Mr 32 000). Cdk5 has also been implicated in regulating various steps in the presynaptic vesicle cycle. Here we report that Cdk5 phosphorylates tyrosine hydroxylase (TH), the key enzyme for synthesis of dopamine. Using phosphopeptide mapping, site‐directed mutagenesis, and phosphorylation state‐specific antibodies, the site was identified as Ser31, a previously defined extracellular signal‐regulated kinases 1/2 (ERK1/2) site. The phosphorylation of Ser31 by Cdk5 versus ERK1/2 was investigated in intact mouse striatal tissue using a pharmacological approach. The results indicated that Cdk5 phosphorylates TH directly and also regulates ERK1/2‐dependent phosphorylation of TH through the phosphorylation of mitogen‐activated protein kinase kinase 1 (MEK1). Finally, phospho‐Ser31 TH levels were increased in dopaminergic neurons of rats trained to chronically self‐administer cocaine. These results demonstrate direct and indirect regulation of the phosphorylation state of a Cdk5/ERK1/2 site on TH and suggest a role for these pathways in the neuroadaptive changes associated with chronic cocaine exposure.
Cystamine increases l‐cysteine levels in Huntington's disease transgenic mouse brain and in a PC12 model of polyglutamine aggregation
Authors: Fox Jonathan H. , Barber David S. , Singh Bhupinder , Zucker Birgit , Swindell Mary K. , Norflus Fran , Buzescu Rodica , Chopra Raman , Ferrante Robert J. , Kazantsev Aleksey , Hersch Steven M. 
Published: September 2004

AbstractCystamine, a small disulfide‐containing chemical, is neuroprotective in a transgenic mouse and a Drosophila model of Huntington's disease (HD) and decreases huntingtin aggregates in an in vitro model of HD. The mechanism of action of cystamine in these models is widely thought to involve inhibition of transglutaminase mediated cross‐linking of mutant huntingtin in the process of aggregate formation/stabilization. In this study we show that cystamine, both in vitro and in a transgenic mouse model of HD (R6/2), increases levels of the cellular antioxidant l‐cysteine. Several oxidative stress markers increase in HD brain. We provide further evidence of oxidative stress in mouse HD by demonstrating compensatory responses in R6/2 HD brains. We found age‐dependent increases in forebrain glutathione (GSH), and increased levels of transcripts coding for proteins involved in GSH synthesis and detoxification pathways, as revealed by quantitative PCR analysis. Given the general importance of oxidative stress as a mediator of neurodegeneration we propose that an increase in brain l‐cysteine levels could be protective in HD. Furthermore, cystamine was dramatically protective against 3‐nitropropionic acid‐induced striatal injury in mice. We suggest that cystamine's neuroprotective effect in HD transgenic mice results from pleiotropic effects that include transglutaminase inhibition and antioxidant activity.