bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reversible modulation of GABAA receptor‐mediated currents by light is dependent on the redox state of the receptor
Authors: Leszkiewicz Daniel N. , Aizenman Elias 
Published: May 2003

AbstractLight has recently been shown to be a physical modulator of GABAA receptor activity. Here, we further characterize the effects of light on a native cortical and retinal population of GABAA receptors, and identify a possible mechanism for light induced potentiation using recombinant receptors. GABA‐induced currents in cortical neurons were observed to be rapidly and reversibly potentiated following exposure to a brief flash of light (0.5–2 s; > 280 nm) directed via an optical fibre (50 µm i.d.). GABAA receptor‐mediated responses in retinal ganglion cells were also enhanced by light, while glycine‐induced currents in these cells were unaffected by the same stimulus. We also determined that physiological levels of light, that is, those that would normally reach the retina, also enhanced GABA‐induced currents. Finally, we observed that chemical reduction of recombinant α1β2 and α1β2γ2S GABAA receptors by dithiothreitol substantially attenuated the effects of light. These results suggest that GABAA receptors can be reversibly modified by a brief pulse of light via an allosteric mechanism that is intimately linked to redox modulation.
Expression and functional role of mGluR3 and mGluR5 in human astrocytes and glioma cells: opposite regulation of glutamate transporter proteins
Authors: Aronica Eleonora , Gorter Jan A. , Ijlst‐Keizers Helen , Rozemuller Annemieke J. , Yankaya Bulent , Leenstra Sieger , Troost Dirk 
Published: May 2003

AbstractWe examined the regulation of glutamate transporter protein expression after stimulation with selective metabotropic glutamate receptor (mGluR) agonists in cultured human glial cells. mGluR3 and mGluR5 are expressed in human astrocytes and in human glioma cells in vivo as well as in vitro, as shown by either RT‐PCR or western blot analysis. The selective group I agonist (S)‐3,5‐dihydroxyphenylglycine produced a significant down‐regulation of both GLAST and GLT‐1 protein expression in astrocytes cultured in the presence of growth factors. This condition mimics the morphology of reactive glial cells in vivo including an increased expression of mGluR5 protein (observed in pathological conditions). In contrast, (2S,2′R,3′R)‐2‐(2′,3′‐dicarboxycyclopropyl)glycine, a selective agonist of group II metabotropic glutamate receptors, positively modulates the expression of GLAST and GLT‐1 proteins. A similar opposite effect of (S)‐3,5‐dihydroxyphenylglycine and (2S,2′R,3′R)‐2‐(2′,3′‐dicarboxycyclopropyl)glycine was observed for the expression of EAAT3 protein in U373 glioblastoma cell line. Selective group I and II antagonists prevented these effects. Pharmacological inhibition of mitogen‐activated protein kinase and phosphatidylinositol‐3‐K pathways reduces the induction of GLT‐1 observed in response to the group II metabotropic glutamate receptor agonist (2S,2′R,3′R)‐2‐(2′,3′‐dicarboxycyclopropyl)glycine. Thus, mGluR3 and mGluR5 can critically and differentially modulate the expression of glutamate transporters and may represent interesting pharmacological targets to regulate the extracellular levels of glutamate in pathological conditions.
Influence of regular voluntary exercise on spontaneous and social stress‐affected sleep in mice
Authors: Lancel Marike , Droste Susanne K. , Sommer Susanne , Reul Johannes M. H. M. 
Published: May 2003

AbstractTo investigate the impact of regular physical exercise on sleep, we assessed sleep–wake behaviour in male C57BL/6N mice with and without long‐term access (i.e. 4 weeks) to a running wheel. We studied sleep–wake behaviour during undisturbed conditions as well as after social stress. The exercising mice ran approximately 4 km/day, which affected their physical constitution, their spontaneous sleep–wake pattern and their endocrine and sleep responses to stress. When compared with the control mice, exercising animals had more muscle substance, less body fat and heavier adrenal glands. At baseline, exercising mice showed fewer, but longer‐lasting, sleep episodes (indicating improved sleep consolidation) and less rapid‐eye‐movement sleep. In both control and exercising mice, mild social stress (elicited by a 15‐min social conflict) evoked elevated plasma levels of adrenocorticotrophic hormone and corticosterone, an increase in non‐rapid‐eye‐movement sleep, an enhancement of low‐frequency activity in the electroencephalogram within non‐rapid‐eye‐movement sleep (indicating increased sleep intensity) and a decrease in wakefulness. However, as compared with the control animals, exercising mice responded to social stress with higher corticosterone levels, but not adrenocorticotrophic hormone levels, suggesting an increased sensitivity of their adrenal glands to adrenocorticotrophic hormone. Moreover, in control mice, social stress increased rapid‐eye‐movement sleep in parallel to non‐rapid‐eye‐movement sleep, whereas this stressor selectively decreased rapid‐eye‐movement sleep in exercising animals. Corticosterone is known to decrease rapid‐eye‐movement sleep. Therefore, changes in the regulation of the hypothalamic‐pituitary‐adrenocortical axis as a result of the long‐term exercise may contribute to the observed differences in spontaneous and social stress‐affected sleep. In conclusion, regular exercise appears to increase sleep quality and reverses the effects of mild social stress on rapid‐eye‐movement sleep.
Stress‐mediated heart rate dynamics after deletion of the gene encoding corticotropin‐releasing factor receptor 2
Authors: Stiedl Oliver , Meyer Michael , Kishimoto Toshimitsu , Rosenfeld Michael G. , Spiess Joachim 
Published: May 2003

AbstractThe objective of the present study was to investigate the potential role of corticotropin‐releasing factor receptor subtype 2 (CRFR2) in autonomic regulation of heart rate and heart rate variability under physiological conditions in conscious mice. Heart rate dynamics during novelty exposure and auditory fear conditioning were assessed by radiotelemetry. Heart rate responses and heart rate variability values were not different in CRFR2+/+ and CRFR2−/− mice during novelty exposure, which was associated with similar locomotor activity exhibited by both genotypes. The heart rate responses during retention of conditioned auditory fear were similar and the exponential relationship between heart rate and heart rate variability was independent of genotype. Pharmacological stimulation of the peripheral CRFR2β by intraperitoneal injection of 200 ng human/rat corticotropin‐releasing factor yielded a sustained tachycardia in wildtype control (CRFR2+/+) mice which was absent in CRFR2‐deficient (CRFR2−/−) mice. Similarly, the tachycardia was effectively blocked by preinjection of the CRFR2 antagonist antisauvagine‐30. In conclusion, the results indicate the involvement of CRFR2 in heart rate dynamics upon pharmacological stimulation but demonstrate that CRFR2 is not involved in baseline heart rate regulation and stress‐mediated modulation of heart rate responses.
Removal of PSA from NCAM affects the survival of magnocellular vasopressin‐ and oxytocin‐producing neurons in organotypic cultures of the paraventricular nucleus
Authors: Vutskits L. , Gascon E. , Kiss J. Z. 
Published: May 2003

AbstractThe expression of the polysialic acid neural cell adhesion molecule (PSA‐NCAM) in the hypothalamo‐neurohypophyseal system has been correlated with morphofunctional plasticity. In this study, we investigated the role of PSA‐NCAM in the survival of oxytocin (OT)‐ and vasopressin (VP)‐producing magnocellular cells of this system. We used a recently developed organotypic slice culture model of the rat hypothalamic paraventricular nucleus (PVN) in which ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) are potent survival factors for magnocellular neurons. We demonstrate by means of confocal microscopy that cultured magnocellular VP and OT neurons express strong immunoreactivity for PSA‐NCAM. Removal of PSA from NCAM by the enzyme Endo N leads to a significant loss of both VP and OT neurons in the presence of low concentrations of CNTF. Endo N treatment did not change cell survival in the presence of LIF. These results suggest that, in addition to its role in neuro‐glial plasticity, PSA‐NCAM might also influence the trophic factor responsiveness of hypothalamic VP and OT neurosecretory cells.
Pleiotrophin exhibits a trophic effect on survival of dopaminergic neurons in vitro
Authors: Hida Hideki , Jung Cha‐Gyun , Wu Chen‐Zhen , Kim Hye‐Jung , Kodama Yuji , Masuda Tadashi , Nishino Hitoo 
Published: May 2003

AbstractTo understand what kind of trophic factors are up‐regulated in dopamine (DA)‐depleted striatum, we first analysed the up‐regulation of mRNAs using a DNA microarray in DA‐depleted striatum where DAergic inputs were denervated by 6‐OHDA. We then investigated whether or not such trophic factors had an effect on cultured dopaminergic neurons. The microarray analysis revealed that pleiotrophin (PTN), glial‐derived neurotopic factor (GDNF) and others were up‐regulated in DA‐depleted striatum. As PTN has been reported to have a wide range of trophic effects on neurons, we focused on the functional role of PTN in the present study. The increase in PTN mRNA was confirmed by Northern blotting at 1–3 weeks after the lesion, reaching a peak at 1 week. In embryonic day 15 mesencephalic neuron culture, PTN increased the number of tyrosine hydroxylase (TH) ‐positive neurons in a dose‐dependent manner (125.2 ± 2.0% of the control at 50 ng/mL), while a family protein, midkine (10 ng/mL) did not show any trophic effect (99.3 ± 0.7%). In addition, the PTN effect on DAergic neurons was additive to the GDNF effect. As PTN did not increase the number of microtubule‐associated protein‐2 (MAP 2)‐positive neurons or promote the proliferation of dopaminergic progenitors in a bromodeoxyuridine (BrdU) labelling study, the effect appeared to enhance the specific survival of dopaminergic neurons. Expression of PTN receptors (syndecan‐3, PTP‐ζ) was detected on the cultured mesencephalic neurons, and also up‐regulated in DA‐depleted striatum. The data indicate that PTN is up‐regulated in DA‐depleted striatum and exhibits a trophic effect specifically on the survival of cultured dopaminergic neurons.
Synaptic changes characterize early behavioural signs in the ME7 model of murine prion disease
Authors: Cunningham C. , Deacon R. , Wells H. , Boche D. , Waters S. , Diniz C. Picanco , Scott H. , Rawlins J. N. P. , Perry V. H. 
Published: May 2003

AbstractPrion diseases are fatal, chronic neurodegenerative diseases of mammals, characterized by amyloid deposition, astrogliosis, microglial activation, tissue vacuolation and neuronal loss. In the ME7 model of prion disease in the C57BL/6 J mouse, we have shown previously that these animals display behavioural changes that indicate the onset of neuronal dysfunction. The current study examines the neuropathological correlates of these early behavioural changes. After injection of ME7‐infected homogenate into the dorsal hippocampus, we found statistically significant impairment of burrowing, nesting and glucose consumption, and increased open field activity at 13 weeks. At this time, microglia activation and PrPSc deposition was visible selectively throughout the limbic system, including the hippocampus, entorhinal cortex, medial and lateral septum, mamillary bodies, dorsal thalamus and, to a lesser degree, in regions of the brainstem. No increase in apoptosis or neuronal cell loss was detectable at this time, while in animals at 19 weeks postinjection there was 40% neuronal loss from CA1. There was a statistically significant reduction in synaptophysin staining in the stratum radiatum of the CA1 at 13 weeks indicating loss of presynaptic terminals. Damage to the dorsal hippocampus is known to disrupt burrowing and nesting behaviour. We have demonstrated a neuropathological correlate of an early behavioural deficit in prion disease and suggest that this should allow insights into the first steps of the neuropathogenesis of prion diseases.
Effect of lidocaine and NMDA injections into the medial pontobulbar reticular formation on mastication evoked by cortical stimulation in anaesthetized rabbits
Authors: Scott G. , Westberg K. G. , Vrentzos N. , Kolta A. , Lund J. P. 
Published: May 2003

AbstractNeurons of the dorsal nucleus reticularis pontis caudalis (nPontc) fire rhythmically during fictive mastication, while neurons of the ventral half tend to fire tonically (Westberg et al., 2001). This paper describes the changes in the pattern of rhythmical mastication elicited by stimulation of the sensorimotor cortex during inhibition or excitation of neurons in this nucleus and adjacent parts of nucleus reticularis gigantocellularis (Rgc) in the anaesthetized rabbit. Masticatory movements and electromyographic (EMG) activity of the masseter and digastric muscles produced by cortical stimulation were recorded before, during and after injections of a local anaesthetic (lidocaine) or excitatory amino acid N‐methyl‐d‐aspartate (NMDA) into nPontc and Rgc through a microsyringe with attached microelectrode to record neuronal activity. Lidocaine inhibited local neurons and modified the motor program, and the effects varied with the site of injection. Most injections into the ventral half of nPontc increased cycle duration, digastric burst duration and burst area. The action of lidocaine in dorsal nPontc was more variable, although burst duration and area were often decreased. The effects on the muscle activity were always bilateral. Lidocaine block of the rostromedial part of Rgc had no effect on movements or on EMGs. Injections of NMDA excited local neurons and when injected into ventral nPontc, it completely blocked mastication. Dorsal injections either had no effect or increased cycle frequency, while decreasing burst duration and area. No increases in EMG burst duration or area were observed with NMDA. Our findings suggest that neurons of ventral nPontc tonically inhibit other parts of the central pattern generator during mastication, while dorsal neurons have mixed effects. We incorporated these findings into a new model of the masticatory central pattern generator.
Gene expression of neuropeptide Y in the nucleus of the solitary tract is activated in rats under restricted daily feeding but not under 48‐h food deprivation
Authors: Ishizaki Kouji , Honma Sato , Katsuno Yumiko , Abe Hiroshi , Masubuchi Satoru , Namihira Masakazu , Honma Ken‐ichi 
Published: May 2003

AbstractThe two neuropeptide Y (NPY) systems innervating the hypothalamic paraventrivular nucleus were examined regarding their roles in the prefeeding corticosterone peak developed under restricted daily feeding (RF). Protein and mRNA levels of NPY were measured in the arcuate nucleus (ARC) and the nucleus of the solitary tract (NST) in rats under 48‐h food deprivation (48‐hFD), RF, and 72‐h food deprivation imposed after RF (post‐RF 72‐hFD) with 7 days of ad libitum feeding in between. NPY protein and mRNA levels in the ARC significantly increased with 48‐hFD and decreased with re‐feeding, whereas those in the NST were not changed by 48‐hFD. When rats had RF imposed with free access to food from 10.00 to 12.00 h (lights on from 06.00 to 18.00 h) for 3 weeks, NPY concentrations in the ARC increased at 10.00 h, just prior to the daily meal, but those in the NST did not change significantly throughout the period examined. On the other hand, NPY mRNA levels in both the ARC and NST increased before the meal supply and remained high for 4 h after feeding. Under post‐RF 72‐hFD, the prefeeding peak of NPY mRNA was detected in the NST, but NPY mRNA levels in the ARC were continuously high throughout the 24‐h period. These findings indicate that the NPY neurons from the NST are specifically activated by RF, whereas those from the ARC are generally stimulated by an increased food demand.
The impact of diabetes‐related complications on healthcare costs: results from the United Kingdom Prospective Diabetes Study (UKPDS Study No. 65)
Authors: Clarke P. , Gray A. , Legood R. , Briggs A. , Holman R. 
Published: May 2003

AbstractAims To develop a model for estimating the immediate and long‐term healthcare costs associated with seven diabetes‐related complications in patients with Type 2 diabetes participating in the UK Prospective Diabetes Study (UKPDS).Methods The costs associated with some major complications were estimated using data on 5102 UKPDS patients (mean age 52.4 years at diagnosis). In‐patient and out‐patient costs were estimated using multiple regression analysis based on costs calculated from the length of admission multiplied by the average specialty cost and a survey of 3488 UKPDS patients’ healthcare usage conducted in 1996–1997.Results Using the model, the estimate of the cost of first complications were as follows: amputation £8459 (95% confidence interval £5295, £13 200); non‐fatal myocardial infarction £4070 (£3580, £4722); fatal myocardial infarction £1152 (£941, £1396); fatal stroke £3383 (£1935, £5431); non‐fatal stroke £2367 (£1599, £3274); ischaemic heart disease £1959 (£1467, £2541); heart failure £2221 (£1690, £2896); cataract extraction £1553 (£1320, £1855); and blindness in one eye £872 (£526, £1299). The annual average in‐patient cost of events in subsequent years ranged from £631 (£403, £896) for heart failure to £105 (£80, £142) for cataract extraction. Non‐in‐patient costs for macrovascular complications were £315 (£247, £394) and for microvascular complications were £273 (£215, £343) in the year of the event. In each subsequent year the costs were, respectively, £258 (£228, £297) and £204 (£181, £255).Conclusions These results provide estimates of the immediate and long‐term healthcare costs associated with seven diabetes‐related complications.Diabet. Med. 20, 442–450 (2003)
Ethical Codes in Humanitarian Emergencies: From Practice to Research?
Authors: Black Richard 
Published: May 2003

Notable strides have been made in recent years to develop codes of conduct for humanitarian intervention in conflicts on the part of international NGOs and UN organisations. Yet engagement by the academic and broader research communities with humanitarian crises and ongoing complex political emergencies remains relatively ad hoc and unregulated beyond the basic ethical guidelines and norms developed within universities for research in general, and within the governing and representative bodies of particular academic disciplines.This paper draws on a case study of research on humanitarian assistance to Liberia during that country's civil war from 1989 to 1996. The difficulties faced by humanitarian agencies in Liberia led to the development of two key sets of ethical guidelines for humanitarian intervention: the Joint Policy of Operations (JPO) and Principles and Policies of Humanitarian Operations (PPHO). This paper seeks to address what lessons, if any, these ethical guidelines, together with different experiences of conducting research in war‐torn Liberia, can provide in terms of the role of academic researchers — and research itself — in humanitarian crises.
The 1998 Flood in Bangladesh: Is Different Targeting Needed During Emergencies and Recovery to Tackle Malnutrition?
Authors: Hossain S.M. Moazzem , Kolsteren Patrick 
Published: May 2003

Bangladesh suffered the century's worst flood during July–October 1998 and appealed for assistance. To provide information for appropriate interventions to tackle nutritional problems, a rapid assessment survey was conducted to look at the nutritional situation, problems encountered by the community, their coping mechanisms and rehabilitation priorities in six rural areas. The survey was repeated after four months to measure the outcome of activities during the flood and the necessity for future assistance. There were 3,048 children measured in both surveys (1,597 and 1,451). The sample of most interest was a sub‐group of 180 children present in two previous independent surveys.The analysis found that while moving from the crisis period to post‐flood phase there was evidence of a ‘crossover phenomenon’ in the recovery pattern of nutritional status. Sixty‐eight per cent of the children who were malnourished (WHZ <‐2SD) during the crisis period (18 per cent) recovered enough to cross the cut‐off point and became normal after four months. Another 8 per cent of children (9 per cent of all normal) who were normal during the crisis period, after four months had deteriorated to be malnourished. Thus, despite there being a shift in the overall distribution of nutritional status, there has been another shift that reduced the net effect. Subsequent episodes of diarrhoea, access to food and loan burden had also influenced the recovery pattern of the children's nutritional status as evident from the statistically significant associations. These findings raise questions about targeting acute malnutrition during emergencies, and using the same criteria during both the crisis and rehabilitation phases.
No Credit for Transition: European Institutions and German Unemployment
Authors: Driffill John , Miller Marcus 
Published: June 2003

Abstract The Stability and Growth Pact, adopted by members of the European Union,imposes tight limits on government deficits. But since the collapse of Communism,Europe has been faced with the problems of economies in transition: and reunifiedGermany—the leading economy of the EU—combines a prosperous western stateand an eastern economy in the process of transition. In a model where unions play akey role in wage bargaining and transition imposes a substantial burden on thenational budget, we analyze the implications of balancing the budget for the path ofunemployment. Where high but temporary costs are financed by raising taxes onemployment to satisfy the Stability and Growth Pact, then the title is a misnomer:relative to a policy of `tax smoothing', the pact increases unemployment and slowsgrowth. In designing fiscal rules for Europe, the benefits of tax smoothing must beweighed in the balance along with the virtues of fiscal discipline.
Single or double bounded contingent valuation? A Bayesian test
Authors: León Roberto , León Carmelo J. 
Published: June 2003

AbstractThis paper evaluates the performance of asymptotic approximations of the Bayes factor to appraise the relative likelihoods of the bivariate and the restricted double bounded models for contingent valuation. The performance of the Bayes factor test is studied by Monte Carlo simulation showing that it correctly chooses the bivariate model when appropriate, but tends to over predict the double bounded model when the correlation coefficient is not estimated accurately. However, the quadratic error in estimating willingness to pay is reduced if the model preferred by the test is chosen. In addition, we consider the effect of averaging the estimates of WTP from both models, weighting each model with its posterior probability. The results show that ‘model averaging’ across the competing hypothesis further reduces the squared error. The applications with two data sets on National Parks show that the test rejects the restricted double bounded hypotheses against the bivariate model.
Crop Genetic Diversity, Productivity and Stability of Agroecosystems. A Theoretical and Empirical Investigation
Authors: Di Falco Salvatore , Perrings Charles 
Published: June 2003

AbstractThis paper purports a model of farmers' crop choices in an uncertain environment. The model shows that profit maximizing farmers will choose a crop mix characterised by greater crop diversity if diversity is positively related to productivity and negatively correlated with production and income variability. An application using data from a Vavilov megadiversity spot, southern Italy, from 1970 up to 1993 is provided to test model hypotheses. It is found that interspecies crop genetic diversity is positively related to mean income and negatively related to the variance of income.