bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intraocular delivery of BDNF following visual cortex lesion upregulates cytosolic branched chain aminotransferase (BCATc) in the rat dorsal lateral geniculate nucleus
Authors: Madeddu Federico , Naska Sibel , Menna Elisabetta , Chiellini Chiara , Sweatt Andrew J. , Hutson Susan M. , Benzi Luca , Maffei Margherita , Maffei Lamberto , Bozzi Yuri 
Published: July 2004

AbstractVisual cortex ablation in newborn rats determines the almost complete degeneration of neurons in the dorsal lateral geniculate nucleus (dLGN), as a consequence of the axotomy of the geniculo‐cortical fibres. Death of dLGN neurons is massive and rapid, and occurs by apoptosis. We recently showed that exogenous administration of the neurotrophin brain‐derived neurotrophic factor (BDNF) in the eye prevents the degeneration of dLGN neurons occurring after visual cortex lesion in newborn rats. To elucidate the molecular mechanisms of BDNF‐mediated neuroprotection, we sought to identify novel genes regulated by BDNF in the rat dLGN after visual cortex lesion. By using mRNA fingerprinting, we isolated a cDNA fragment upregulated in the dLGN of lesioned rats treated with BDNF. This cDNA fragment shared 100% homology with the rat cytosolic branched chain aminotransferase (BCATc), a key enzyme of glutamate metabolism. Quantitative reverse transcription‐polymerase chain reaction and in situ hybridization confirmed that BCATc mRNA is markedly overexpressed by exogenous supply of BDNF to axotomized dLGNs. Immunohistochemical analysis showed that upregulation of BCATc in the dLGN of lesioned rats treated with BDNF takes place in astrocytes. These results suggest that modulation of glutamate metabolism by astrocytes might play an important role in BDNF‐mediated survival of axotomized dLGN neurons.
Inhibition of tyrosine kinase receptor type B synthesis blocks axogenic effect of estradiol on rat hypothalamic neurones in vitro
Authors: Brito V. I. , Carrer H. F. , Cambiasso M. J. 
Published: July 2004

Abstract17‐β‐estradiol (E2) increases axonal growth and tyrosine kinase receptor (Trk)B levels of male‐derived hypothalamic neurones in vitro. To investigate whether the axogenic response depends on the upregulation of TrkB, we analysed neuritic growth and neuronal polarization in cultures treated with an antisense oligonucleotide against TrkB mRNA. In cultures without E2, treatment with 7.5 or 10 µm antisense reduced TrkB levels and the percentage of neurones showing an identifiable axon; the number and length of minor processes were increased. In cultures treated with 5 µm antisense, morphometric parameters were normal although total TrkB levels were reduced. The same dose prevented the E2‐dependent increase of TrkB levels and suppressed the axogenic effect of E2. These results indicate that TrkB is necessary for normal neuronal growth and maturation and further suggest that an increase in TrkB is necessary for E2 to exert its axogenic effect in male‐derived neurones.
Glutamatergic‐receptors blockade does not regularize the slow wave sleep bursty pattern of subthalamic neurons
Authors: Urbain Nadia , Vautrelle Nicolas , Dahan Lionel , Savasta Marc , Chouvet Guy 
Published: July 2004

AbstractThe subthalamic nucleus (STN) has been implicated in movement disorders observed in Parkinson's disease because of its pathological mixed burst firing mode and hyperactivity. In physiological conditions, STN bursty pattern has been shown to be dependent on slow wave cortical activity. Indeed, cortical ablation abolished STN bursting activity in urethane‐anaesthetized intact or dopamine depleted rats. Thus, glutamate afferents might be involved in STN bursting activity during slow wave sleep (SWS) when thalamic and cortical cells oscillate in a low‐frequency range. The present work was aimed to test, on non‐anaesthetized rats, if it was possible to regularize the SWS STN bursty pattern by microiontophoresis of kynurenate, a broad‐spectrum glutamate ionotropic receptors antagonist. As glutamatergic effects might be masked by GABAergic inputs arriving tonically and during the entire sleep‐wake cycle on STN neurons, kynurenate was also co‐iontophoresed with bicuculline, a GABAA receptors antagonist. Kynurenate iontophoretic applications had a weak inhibitory effect on the discharge rate of STN neurons whatever the vigilance state, and did not regularize the SWS STN bursty pattern. But, the robust bursty bicuculline‐induced pattern was impaired by kynurenate, which elicited the emergence of single spikes between remaining bursts. These data indicate that the bursty pattern exhibited by STN neurons specifically in SWS, does not seem to exclusively depend on glutamatergic inputs to STN cells. Furthermore, GABAA receptors may play a critical role in regulating the influence of excitatory inputs on STN cells.
Intravenous heroin self‐administration decreases GABA efflux in the ventral pallidum: an in vivo microdialysis study in rats
Authors: Caillé Stéphanie , Parsons Loren H. 
Published: July 2004

AbstractSeveral lines of evidence suggest that opiate‐induced disinhibition of the ventral pallidum participates in the mediation of opiate reward, though direct in vivo evidence to support this hypothesis has been lacking. The present experiment tested this hypothesis by investigating alterations in ventral pallidal amino acid efflux using in vivo microdialysis during ongoing intravenous heroin self‐administration in rats. Concentrations of the inhibitory amino acid GABA in ventral pallidal dialysates were significantly reduced within the first 10 min of heroin self‐administration (0.02 mg per infusion; FR‐1), and remained ≈ 65% of presession baseline levels for the remainder of the 3‐h self‐administration session. Dialysate glutamate levels were unaltered during the first hour of heroin intake but significantly increased to a stable level of ≈ 120% presession values during the subsequent 2 h of self‐administration. Thus, heroin self‐administration is associated with both decreased GABA efflux and a late phase increase in glutamate efflux in the ventral pallidum. These observations are consistent with the hypothesis that heroin self‐administration results in a disinhibition and/or excitation of the ventral pallidum.
NMDA receptors are essential for the acquisition, but not expression, of conditional fear and associative spike firing in the lateral amygdala
Authors: Goosens Ki A. , Maren Stephen 
Published: July 2004

AbstractWe examined the contribution ofN‐methyl‐D‐aspartate (NMDA) receptors (NMDARs) to the acquisition and expression of amygdaloid plasticity and Pavlovian fear conditioning using single‐unit recording techniques in behaving rats. We demonstrate that NMDARs are essential for the acquisition of both behavioral and neuronal correlates of conditional fear, but play a comparatively limited role in their expression. Administration of the competitive NMDAR antagonist ±‐3‐(2‐carboxypiperazin‐4‐yl) propyl‐1‐phosphonic acid (CPP) prior to auditory fear conditioning completely abolished the acquisition of conditional freezing and conditional single‐unit activity in the lateral amygdala (LA). In contrast, CPP given prior to extinction testing did not affect the expression of conditional single‐unit activity in LA, despite producing deficits in conditional freezing. Administration of CPP also blocked the induction of long‐term potentiation in the amygdala. Together, these data suggest that NMDARs are essential for the acquisition of conditioning‐related plasticity in the amygdala, and that NMDARs are more critical for regulating synaptic plasticity and learning than routine synaptic transmission in the circuitry supporting fear conditioning.
Fear memories induce a switch in stimulus response and signaling mechanisms for long‐term potentiation in the lateral amygdala
Authors: Schroeder Bradley W. , Shinnick‐Gallagher Patricia 
Published: July 2004

AbstractActivity‐dependent modification of synapses is fundamental for information storage in the brain and underlies behavioral learning. Fear conditioning is a model of emotional memory and anxiety that is expressed as an enduring increase in synaptic strength in the lateral amygdala (LA). Here we analysed synaptic plasticity in the rat cortico‐LA pathway during maintenance of fear memory. We show for the first time that the stimulus frequency for synaptic potentiation is switched during maintenance of fear memory, and the underlying signaling mechanisms are altered in the cortico‐LA pathway. In slices from fear‐conditioned animals, high‐frequency stimulation‐induced (HFS) long‐term potentiation (LTP) was attenuated, whereas low‐frequency stimulation (LFS) elicited a long‐lasting potentiation. HFS generates robust LTP that is dependent onN‐methyl‐d‐aspartate receptor (NMDAR) andL‐type voltage‐gated calcium channel (VGCC) activation in control animals, whereas in fear‐conditioned animals HFS LTP is NMDAR‐ and VGCC‐independent. LFS‐LTP is partially NMDAR‐dependent, but VGCCs are necessary for potentiation in fear memory. Collectively, these results show that during maintenance of fear memory the stimulus requirements for amygdala afferents and critical signaling mechanisms for amygdala synaptic potentiation are altered, suggesting that cue‐engaged synaptic mechanisms in the amygdala are dramatically affected as a result of emotional learning.
Representations of Wales and the Welsh during the civil wars and Interregnum
Authors: Bowen Lloyd 
Published: July 2004

Abstract
This article examines how Wales and the Welsh were represented in the pamphlet literature of the civil war and early Interregnum. It considers the historical construction of the Welsh image in English minds, and traces how this image came to be politicized by Welsh support for Charles I during the sixteen-forties. An examination of the public controversies surrounding the state-sponsored evangelization programme in Wales during the early sixteen-fifties shows how the contested image of Wales in the public sphere interacted with high politics at the centre. This study contributes to our understanding of the interplay between ethnicity, identity and politics during the sixteen-forties and fifties, and demonstrates how imagery and representation informed political discourse in the mid seventeenth century.
The mobilization of manpower for Britain's mid-eighteenth-century wars
Authors: Conway Stephen 
Published: July 2004

Abstract
This article seeks to assess the size and social composition of the armed forces from Britain and Ireland employed in the wars of 1739–63. The number of men serving in a military or naval capacity was larger than is usually recognized – especially during the Seven Years' War – and the background of such men was much more varied than most general accounts suggest. The ‘middling’ and artisan contribution was far from insignificant, especially in unofficial volunteer formations, but even in the regular armed forces.
‘No-one telling us what to do’: anarchist schools in Britain, 1890–1916
Authors: Thomas Matthew 
Published: July 2004

Abstract
This article seeks to analyse the intentions of anarchists in organizing schools in London and Liverpool between 1890 and 1916. It will also address the various teaching practices and methods of management adopted, and the experience of the children within the schools. Although they formulated many original ideas, the anarchist educators failed to break out of their own milieu and influence a wider community. The experiments in counter-education, meant to be a starting point for an alternative culture, embraced mostly foreign children who had already been brought up within an anarchist sub-culture. This was despite the fact that the libertarian schools belonged to a wider tradition of independent, working-class education that at times was in tune with anarchist thinking.
Regulation of RANTES/CCL5 expression in human astrocytes by interleukin‐1 and interferon‐β
Authors: Kim Mee‐Ohk , Suh Hyeon‐Sook , Brosnan Celia F. , Lee Sunhee C. 
Published: July 2004

AbstractIn the CNS, astrocytes are significant sources of RANTES/CCL5 (regulated upon activation, normal T cell expressed and secreted), a CC‐chemokine with important biological function. Astrocyte RANTES/CCL5 has been shown to be induced by interleukin‐1 (IL‐1), with interferon‐γ (IFNγ) as a primer, but whether type I interferons play any role in the expression of RANTES/CCL5 is not known. In this report, we studied the detailed mechanism of RANTES/CCL5 induction in primary human astrocytes activated with IL‐1 and IFNβ. Ribonuclease protection assay and ELISA showed that IFNβ, although not effective alone, increased IL‐1‐induced RANTES/CCL5 expression, but did not antagonize IFNγ. IL‐1 or IL‐1/IFNβ‐induced RANTES/CCL5 expression was inhibited by the super‐repressor IκBα or inhibitors of p38 or c‐Jun N‐terminal kinase (JNK) MAPKs (mitogen‐activated protein kinases), but not by extracellular signal regulated kinases (ERK) inhibitors. IFNβ enhanced IL‐1‐induced phosphorylation of p38 MAPK, but was not effective alone. Transfection with mutated RANTES/CCL5 promoter‐reporter constructs revealed that κB, interferon‐stimulated response element (ISRE) and CAATT‐enhancer binding protein‐β (C/EBPβ) sites all contributed to IL‐1/IFNβ‐induced RANTES/CCL5 transcription. IFNβ synergized with IL‐1 to induce nuclear accumulation of C/EBPβ protein. They also synergized to form nuclear ISRE complexes with Stat1, Stat2 and interferon regulatory factor‐1 (IRF‐1) proteins. Together, our results demonstrate that IFNβ plays a positive regulatory role in the expression of RANTES/CCL5 in human astrocytes through several distinct mechanisms.
Shift in the localization of sites of hydrogen peroxide production in brain mitochondria by mitochondrial stress
Authors: Gyulkhandanyan Armen V. , Pennefather Peter S. 
Published: July 2004

AbstractWe have determined the underlying sites of H2O2generation by isolated rat brain mitochondria and how these can shift depending on the presence of respiratory substrates, electron transport chain modulators and exposure to stressors. H2O2production was determined using the fluorogenic Amplex red and peroxidase system. H2O2production was higher when succinate was used as a respiratory substrate than with another FAD‐dependent substrate, α‐glycerophosphate, or with the NAD‐dependent substrates, glutamate/malate. Depolarization by the uncouplerp‐trifluoromethoxyphenylhydrazone decreased H2O2production stimulated by all respiratory substrates. H2O2production supported by succinate during reverse transfer of electrons was decreased by inhibitors of complex I (rotenone and diphenyleneiodonium) whereas in glutamate/malate‐oxidizing mitochondria diphenyleneiodonium decreased while rotenone increased H2O2generation. The complex III inhibitors antimycin and myxothiazol decreased succinate‐induced H2O2production but stimulated H2O2production in glutamate/malate‐oxidizing mitochondria. Antimycin and myxothiazol also increased H2O2production in mitochondria using α‐glycerophosphate as a respiratory substrate. In substrate/inhibitor experiments maximal stimulation of H2O2production by complex I was observed with the α‐glycerophosphate/antimycin combination. In addition, three forms ofin vitromitochondrial stress were studied: Ca2+overload, cold storage for more than 24 h and cytochromecdepletion. In each case we observed (i) a decrease in succinate‐supported H2O2production by complex I and an increase in succinate‐supported H2O2production by complex III, (ii) increased glutamate/malate‐induced H2O2generation by complex I and (iii) increased α‐glycerophosphate‐supported H2O2generation by complex III. Our results suggest that all three forms of mitochondrial stress resulted in similar shifts in the localization of sites of H2O2generation and that, in both normal and stressed states, the level and location of H2O2production depend on the predominant energetic substrate.
Modulation of feeding‐related peptide/protein signals by the blood–brain barrier
Authors: Pan Weihong , Akerstrom Victoria , Zhang Jian , Pejovic Vojislav , Kastin Abba J. 
Published: July 2004

AbstractThe peptide urocortin is a member of the corticotropin‐releasing factor (CRF) family and a potent satiety signal to the brain. Urocortin in blood does not reach the brain significantly by itself, but its permeation across the blood–brain barrier (BBB) can be enhanced by leptin. How leptin facilitates the influx of urocortin has not been elucidated. In this study, we tested the hypothesis that leptin activates receptor‐mediated endocytosis of urocortin. We measured the kinetics of permeation of radioactively labeled urocortin across the mouse BBB and determined the specific effects of leptin and receptor antibodies. The results show that the influx transfer constant of urocortin was enhanced in the presence of leptin and mediated by CRF‐2β, the specific receptor for urocortin. To determine the specificity of this modulation, the effect of leptin was compared with that of TNFα. Both TNFα and leptin independently facilitated receptor‐mediated transport of urocortin across the BBB. Even though TNFα and leptin have similar effects on urocortin transport, leptin did not significantly affect the influx of TNFα across the BBB. The results indicate that permeation of ingestive peptides and cytokines across the BBB can be acutely modulated, consistent with a role of BBB in regulating feeding behavior. Thus, sites of action of leptin, urocortin, and TNFα exist not only in the brain but also at the BBB where they each control the flow of other ingestive signals to CNS targets.
Substitution of conserved glycine residue by alanine in natural and synthetic neuropeptide ligands causes partial agonism at the stomoxytachykinin receptor
Authors: Poels Jeroen , Van Loy Tom , Franssens Vanessa , Detheux Michel , Nachman Ronald J. , Oonk Hendrica B. , Åkerman Karl E. , Vassart Gilbert , Parmentier Marc , De Loof Arnold , Torfs Herbert , Broeck Jozef Vanden 
Published: July 2004

AbstractA few naturally occurring insect tachykinin‐related peptides, such as stomoxytachykinin (Stc‐TK), contain an Ala‐residue instead of the highly conserved Gly‐residue that is present in most other members of this peptide family. Stc‐TK is a potent, partial agonist of the stable fly (Stomoxys calcitrans) tachykinin receptor, STKR. By means of synthetic analogues, the Gly/Ala exchange, representing the addition of a single methyl group in the active core region of these peptides, was shown to be fully responsible for the generation of this partial agonism, which was also accompanied by an increase in agonistic potency. Surprisingly, this Ala‐dependent reduction in maximal response levels was only observed for the agonist‐induced cellular calcium rise. Stomoxytachykinin, Stc‐TK, did not display partial agonism for the STKR‐mediated cyclic AMP response. A possible explanation for this differential partial agonism is that the Gly‐containing and Ala‐replaced peptides recognize and stabilize active receptor conformations that differ in their functional coupling efficacies towards these response pathways. Drosotachykinins, Drm‐TK, tachykinin‐like peptides encoded in the fruit fly genome, were shown to be STKR‐agonists. Interestingly, one of these peptides, which contains an Ala‐residue instead of the conserved Gly‐residue, also proved to be a potent, partial agonist for STKR.
Composition of the early Oligocene ocean from coral stable isotope and elemental chemistry
Authors: IVANY LINDA C. , PETERS STEPHEN C. , WILKINSON BRUCE H. , LOHMANN KYGER C. , REIMER BETH A. 
Published: July 2004

ABSTRACTA sectioned and polished specimen of the coral Archohelia vicksburgensis from the early Oligocene Byram Formation (∼30 Ma) near Vicksburg, Mississippi, reveals 12 prominent annual growth bands. Stable oxygen isotopic compositions of 77 growth‐band‐parallel microsamples of original aragonite exhibit well‐constrained fluctuations that range between −2.0 and −4.8. Variation in δ18O of coral carbonate reflects seasonal variation in temperature ranging from 12 to 24 °C about a mean of 18 °C. These values are consistent with those derived from a bivalve and a fish otolith from the same unit, each using independently derived palaeotemperature equations. Mg/Ca and Sr/Ca ratios were determined for 40 additional samples spanning five of the 12 annual bands. Palaeotemperatures calculated using elemental‐ratio thermometers calibrated on modern corals are consistently lower; mean temperature from Mg/Ca ratios are 12.5 ± 1 °C while those from Sr/Ca are 5.8 ± 2.2 °C. Assuming that δ18O‐derived temperatures are correct, relationships between temperature and elemental ratio for corals growing in today's ocean can be used to estimate Oligocene palaeoseawater Mg/Ca and Sr/Ca ratios. Calculations indicate that early Oligocene seawater Mg/Ca was ∼81% (4.2 mol mol−1) and Sr/Ca ∼109% (9.9 mmol mol−1) of modern values. Oligocene seawater with this degree of Mg depletion and Sr enrichment is in good agreement with that expected during the Palaeogene transition from ‘calcite’ to ‘aragonite’ seas. Lower Oligocene Mg/Ca probably reflects a decrease toward the present day in sea‐floor hydrothermal activity and concomitant decrease in scavenging of magnesium from seawater. Elevated Sr/Ca ratio may record lesser amounts of Oligocene aragonite precipitation and a correspondingly lower flux of strontium into the sedimentary carbonate reservoir than today.
Acute effects of smoking on left ventricular function and neuro‐humoral responses in patients with known or suspected ischaemic heart disease
Authors: Høilund‐Carlsen Poul Flemming , Marving Jens , Gadsbøll Niels , Rasmussen Sten , Lønborg‐Jensen Harald , Nielsen Meta Damkjær , Christensen Niels Juel , Jensen Birte Hjort 
Published: July 2004

SummarySystolic left ventricular function was examined by radionuclide ventriculography in 12 habitual smokers with known or suspected ischaemic heart disease, aged 33–69 years, before, during, and after smoking of two cigarettes in a row and was repeated on a non‐smoking control day. Plasma concentrations of adrenaline, noradrenaline, renin, and angiotensin II were determined on the smoking day, before and immediately after smoking. During smoking, there were significant increases in heart rate (+27%), rate‐pressure product (+23%), and cardiac output (+14%) in the face of a significant increase in left ventricular end‐systolic volume (+5%) and significant decreases in ejection fraction (−6%) and stroke volume (−8%). Blood pressure was virtually unchanged, and total peripheral resistance remained constant. Plasma adrenaline increased by 100%, renin decreased by 21%, and noradrenaline and angiotensin II did not change. The humoral changes were not correlated to changes in any of the haemodynamic variables. Areas of myocardial hypokinesis emerged or widened during smoking in 11 of 12 patients. Thus, in patients with known or suspected ischaemic heart disease, smoking was associated with an acute decrease in systolic ventricular function and development of widespread hypokinesis despite adrenaline stimulation.