bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ectopic activity in cutaneous regenerating afferent nerve fibers following nerve lesion in the rat
Authors: Gorodetskaya Natalia , Constantin Cristina , Jänig Wilfrid 
Published: November 2003

AbstractSpontaneous activity, and mechanical and thermal sensitivity were investigated in regenerating afferent nerve fibers within 4–21 days post sural nerve lesion (crush or transection and resuturing) in anaesthetized rats. About 33–40% of the myelinated (A) and 22–27% of the unmyelinated (C) fibers excited by electrical nerve stimulation exhibited at least one of these ectopic discharge properties. In total 177 A‐ and 169 C‐fibers with ectopic activity were analysed. Most A‐fibers (161/177) were mechanosensitive. Spontaneous activity (median 1 imp/s) was present in 23/177 and thermosensitivity in 14/177 A‐fibers (13 of them being activated by heat stimuli). Almost all A‐fibers (159/177) exhibited only one type of ectopic discharge property. Most C‐fibers (94/169) were thermosensitive responding either to cold (n = 45) or to heat stimuli (n = 33) or to both (n = 16). Eighty‐four of 169 C‐fibers were spontaneously active (median 0.3 imp/s) and 75/169 C‐fibers were mechanosensitive. Both the proportion and the discharge rate of spontaneously active C‐fibers were significantly higher after crush than after section and resuturing of the nerve. About 60% of the C‐fibers (101/169) had only one ectopic discharge property and 40% two or three. In conclusion, regenerating cutaneous afferent A‐ and C‐fibers may develop mechano‐ and/or thermosensitivity as well as spontaneous activity. We suggest that spontaneous and evoked ectopic activity in regenerating cutaneous afferents are a function of the intrinsic functional properties of these neurons and of the interaction between the regenerating nerve fibers and non‐neural cells during Wallerian degeneration in the nerve distal to the nerve lesion.
Direct evidence for the up‐regulation of spinal µ‐opioid receptor function after repeated stimulation of κ‐opioid receptors in the mouse
Authors: Narita Minoru , Khotib Junaidi , Mizoguchi Hirokazu , Suzuki Masami , Ozaki Satoru , Yajima Yoshinori , Tseng Leon F. , Suzuki Tsutomu 
Published: November 2003

AbstractThe present study was designed to investigate the possible change in spinal µ‐opioid receptor function after repeated administration of a selective κ‐opioid receptor agonist (1S‐trans)‐3,4‐dichloro‐N‐methyl‐N‐[2‐(1‐pyrrolidinyl) cyclohexyl]‐benzeneacetamide hydrochloride [(−)U‐50,488H] in the ICR mouse. A single s.c. or i.t. injection of (−)U‐50,488H produced a dose‐dependent antinociception. Repeated s.c. or i.t. administration of (−)U‐50,488H resulted in the development of tolerance to (−)U‐50,488H‐induced antinociception. Under these conditions, we demonstrated here that repeated s.c. injection of (−)U‐50,488H significantly enhanced the antinociceptive effect induced by the i.t. administration of a selective µ‐opioid receptor agonist [d‐Ala2,N‐Me‐Phe4,Gly5‐ol] enkephalin (DAMGO). Using the guanosine‐5′‐o‐(3‐[35S]thio) triphosphate ([35S]GTPγS) binding assay, we found that (−)U‐50,488H was able to produce a dose‐dependent increase in [35S]GTPγS binding to membranes of the mouse spinal cord. Repeated administration of (−)U‐50,488H caused a significant reduction in the (−)U‐50,488H‐stimulated [35S]GTPγS binding in this region, whereas repeated treatment with (−)U‐50,488H exhibited an increase in the DAMGO‐stimulated [35S]GTPγS binding in membranes of the spinal cord. Using a receptor binding assay, repeated treatment with (−)U‐50,488H significantly increased the density of [3H]DAMGO binding sites in membranes of the mouse spinal cord. In contrast, the expression of µ‐opioid receptor was not affected after repeated treatment with (−)U‐50,488H. These results suggest that repeated stimulation of κ‐opioid receptors leads to the up‐regulation of µ‐opioid receptor functions in the spinal cord, which may be associated with an increase in the number of functional µ‐opioid receptors in the mouse spinal cord.
Erythropoietin protects the in vitro blood–brain barrier against VEGF‐induced permeability
Authors: Martínez‐Estrada Ofelia María , Rodríguez‐Millán Elisabeth , González‐de Vicente Esther , Reina Manuel , Vilaró Senén , Fabre Myriam 
Published: November 2003

AbstractThe blood–brain barrier (BBB) ensures the homeostasis of the brain microenvironment, mostly through complex tight junctions between brain endothelial cells that prevent the passage of hydrophilic molecules from blood to brain and vice versa. A recent study has shown in vivo that systemic administration of erythropoietin (Epo) protects against brain injury. Using an in vitro model of the bovine BBB, we observed that the expression of the Epo receptor is modulated by its ligand and hypoxic stimuli such as vascular endothelial growth factor (VEGF) treatment. In addition, Epo protects against the VEGF‐induced permeability of the BBB, decreases the levels of endothelial nitric oxide synthase and restores junction proteins. The kinetic transport experiments revealed the capacity of Epo to cross the in vitro BBB in a saturable and specific way. Our results suggest a new mechanism for Epo‐induced neuroprotection, in which circulating Epo controls and maintains the BBB through an Epo receptor signalling pathway and the re‐establishment of cell junctions.
Catecholamine‐independent transient expression of tyrosine hydroxylase in primary auditory neurons is coincident with the onset of hearing in the rat cochlea
Authors: Trigueiros‐Cunha Nuno , Renard Nicole , Humbert Ghislaine , Tavares Maria Amélia , Eybalin Michel 
Published: November 2003

AbstractDuring the last stages of neuronal maturation, tyrosine hydroxylase is transiently expressed in the absence of the other catecholamine‐synthesizing enzymes. We show here that it is expressed in rat spiral ganglion neurons between postnatal days 8 and 20, with a peak of expression at postnatal day 12. These tyrosine hydroxylase‐immunoreactive neurons did not display aromatic amino acid decarboxylase‐ or dopamine‐β‐hydroxylase‐immunoreactivities, ruling out the possibilities of dopamine or noradrenaline synthesis. They also did not display peripherin‐ or intense neurofilament 200‐kDa‐immunoreactivities, two indicators of type II primary auditory neurons. Tyrosine hydroxylase‐immunoreactive dendrites were seen in synaptic contact with the inner hair cells and expressed the GluR2 subunit of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptors, further confirming the type I nature of the neurons transiently expressing the enzyme. The end of the tyrosine hydroxylase expression was not due to cell death because the immunoreactive neurons did not show TUNEL‐labelled nuclei. Finally, all the type I neurons expressed the tyrosine hydroxylase mRNA at postnatal day 12, suggesting that the expression of the enzyme is a maturational step common to all these neurons and that the expression of the protein is not synchronized. Because the period of transient expression of tyrosine hydroxylase in type I neurons parallels the periods of maturation of evoked exocytosis in inner hair cells and of appearance and maturation of the cochlear potentials, we propose that the expression of the enzyme indicates the onset of hearing in individual type I primary auditory neurons. This enzyme expression could rely on a Ca2+ activation of its encoding gene subsequent to a sudden and massive Ca2+ entry through voltage‐activated Ca2+ channels.
Cerebellar contribution to spatial event processing: do spatial procedures contribute to formation of spatial declarative knowledge?
Authors: Mandolesi L. , Leggio M. G. , Spirito F. , Petrosini L. 
Published: November 2003

AbstractSpatial knowledge of an environment involves two distinct competencies: declarative spatial knowledge, linked to where environmental cues are and where the subject is with respect to the cues, and, at the same time, procedural spatial knowledge, linked to how to move into the environment. It has been previously demonstrated that hemicerebellectomized (HCbed) rats are impaired in developing efficient exploration strategies, but not in building spatial maps or in utilizing localizing cues. The aim of the present study was to analyse the relationships between spatial procedural and declarative knowledge by using the open field test. HCbed rats have been tested in two different protocols of the open field task. The results indicate that HCbed animals succeeded in moving inside the arena, in contacting the objects and in habituating to the new environment. However, HCbed animals did not react to environmental changes, when their impaired explorative pattern was inappropriate to the environment, suggesting that they were not able to represent a new environment because they were not able to explore it appropriately. Nevertheless, when their altered procedures were favoured by object arrangement, they detected environmental changes as efficiently as did normal rats. This finding suggests that no declarative spatial learning is possible without appropriate procedural spatial learning.
Insulin induces cobalt uptake in a subpopulation of rat cultured primary sensory neurons
Authors: Sathianathan Vivian , Avelino António , Charrua Ana , Santha Peter , Matesz Klara , Cruz Francisco , Nagy Istvan 
Published: November 2003

AbstractPrevious findings show that both the vanilloid receptor 1 and the insulin receptor are expressed on small primary sensory neurons. As insulin evokes activity in second messengers which could induce opening of the vanilloid receptor 1, we examined, by using the cobalt‐uptake technique, whether or not insulin can activate cultured rat primary sensory neurons through activating the vanilloid receptor 1. Capsaicin (50, 100 and 500 nm) induced concentration‐dependent labelling in primary sensory neurons. Preincubation of cells in insulin (10 µm) for 10 min followed by a 2‐min wash did not produce significant change in the capsaicin‐induced labelling. Coapplication of insulin (10 µm) with capsaicin, however, potentiated the 50 and 100 nm capsaicin‐evoked staining. Insulin itself also produced cobalt labelling in a concentration‐dependent manner. The size–frequency distributions of neurons showing capsaicin‐ or insulin‐induced cobalt accumulation were similar. The insulin‐induced cobalt labelling was significantly reduced by the tyrosine kinase inhibitor, tyrphostin AG1024, the vanilloid receptor 1 antagonists, ruthenium red and capsazepine, the protein kinase inhibitor, staurosporine and the phospholipase C inhibitor neomycin. Double immunostaining of cultured primary sensory neurons and sections from dorsal root ganglia revealed that about one‐third of the cells coexpress the insulin receptor and vanilloid receptor 1. These findings suggest that insulin activates a subpopulation of primary sensory neurons, probably through phosphorylation‐ and/or phosphatidylinositol(4,5)biphosphate hydrolysis‐evoked activation of the vanilloid receptor 1. Although the insulin‐induced activation of vanilloid receptor 1 seems to be a short‐lived effect in vitro, in vivo it might play a role in the development of burning pain sensation in hyperinsulinism.
Blockade of noradrenergic receptors in the basolateral amygdala impairs taste memory
Authors: Miranda M. I. , LaLumiere R. T. , Buen T. V. , Bermudez‐Rattoni F. , McGaugh J. L. 
Published: November 2003

AbstractIn conditioned taste aversion (CTA), a subject learns to associate a novel taste (conditioned stimulus, CS) with visceral malaise (unconditioned stimulus, US). Considerable evidence indicates that the noradrenergic system in the amygdala plays an important role in memory consolidation for emotionally arousing experiences. The specific aim of the present set of experiments was to determine the involvement of noradrenergic activity in the basolateral amygdala (BLA) during the US presentation and consolidation of CTA as well as during the consolidation of a nonaversive/incidental gustatory memory. Selective bilateral microinfusions of the β‐adrenergic antagonist propranolol administered into the BLA immediately before intraperitoneal (i.p.) lithium chloride (LiCl) injections disrupted CTA memory. Additionally, propranolol infused into the BLA immediately after a pre‐exposure to the saccharin (CS) significantly attenuated latent inhibition. The present findings indicating that alterations in noradrenergic function in the BLA affect taste memory formation, provide additional evidence that the BLA plays a critical role in modulating the consolidation of memory and that the influence is mediated by interactions with other brain regions that support memory for different kinds of experiences.
Scrg1, a novel protein of the CNS is targeted to the large dense‐core vesicles in neuronal cells
Authors: Dandoy‐Dron Françoise , Griffond Bernadette , Mishal Zohar , Tovey Michael G. , Dron Michel 
Published: November 2003

AbstractScrapie responsive gene one (Scrg1) is a novel transcript discovered through identification of the genes associated with or responsible for the neurodegenerative changes observed in transmissible spongiform encephalopathies. Scrg1 mRNA is distributed principally in the central nervous system and the cDNA sequence predicts a small cysteine‐rich protein 98 amino acids in length, with a N‐terminal signal peptide. In this study, we have generated antibodies against the predicted protein and revealed expression of a predominant immunoreactive protein of 10 kDa in mouse brain by Western blot analysis. We have established CAD neuronal cell lines stably expressing Scrg1 to determine its subcellular localization. Several lines of evidence show that the protein is targeted to dense‐core vesicles in these cells. (i) Scrg1 is detected by immunocytochemistry as very punctate signals especially in the Golgi apparatus and tips of neurites, suggesting a vesicular localization for the protein. Moreover, Scrg1 exhibits a high degree of colocalization with secretogranin II, a dense‐core vesicle marker and a very limited colocalization with markers for small synaptic vesicles. (ii) Scrg1 immunoreactivity is associated with large secretory granules/dense‐core vesicles, as indicated by immuno‐electron microscopy. (iii) Scrg1 is enriched in fractions of sucrose density gradient where synaptotagmin V, a dense‐core vesicle‐associated protein, is also enriched. The characteristic punctate immunostaining of Scrg1 is observed in N2A cells transfected with Scrg1 and for the endogenous protein in cultured primary neurons, attesting to the generality of the observations. Our findings strongly suggest that Scrg1 is associated with the secretory pathway of neuronal cells.
First‐generation SNP/InDel markers tagging loci for pathogen resistance in the potato genome
Authors: Rickert Andreas M. , Kim Jeong H. , Meyer Svenja , Nagel Axel , Ballvora Agim , Oefner Peter J. , Gebhardt Christiane 
Published: November 2003

SummaryA panel of 17 tetraploid and 11 diploid potato genotypes was screened by comparative sequence analysis of polymerase chain reaction (PCR) products for single nucleotide polymorphisms (SNPs) and insertion‐deletion polymorphisms (InDels), in regions of the potato genome where genes for qualitative and/or quantitative resistance to different pathogens have been localized. Most SNP and InDel markers were derived from bacterial artificial chromosome (BAC) insertions that contain sequences similar to the family of plant genes for pathogen resistance having nucleotide‐binding‐site and leucine‐rich‐repeat domains (NBS‐LRR‐type genes). Forty‐four such NBS‐LRR‐type genes containing BAC‐insertions were mapped to 14 loci, which tag most known resistance quantitative trait loci (QTL) in potato. Resistance QTL not linked to known resistance‐gene‐like (RGL) sequences were tagged with other markers. In total, 78 genomic DNA fragments with an overall length of 31 kb were comparatively sequenced in the panel of 28 genotypes. 1498 SNPs and 127 InDels were identified, which corresponded, on average, to one SNP every 21 base pairs and one InDel every 243 base pairs. The nucleotide diversity of the tetraploid genotypes (π = 0.72 × 10−3) was lower when compared with diploid genotypes (π = 2.31 × 10−3). RGL sequences showed higher nucleotide diversity when compared with other sequences, suggesting evolution by divergent selection. Information on sequences, sequence similarities, SNPs and InDels is provided in a database that can be queried via the Internet.
Foreign gene products can be enhanced by introduction into low storage protein mutants
Authors: Tada Yoshifumi , Utsumi Shigeru , Takaiwa Fumio 
Published: November 2003

SummaryTransgenic rice expressing soybean glycinin in its endosperm was crossed with two types of low‐glutelin mutants to determine how much storage the protein mutants can contribute to increases in glycinin accumulation. The glycinin level (102 µg/100 mg seed) in the parental transgenic line was enhanced to ≈ 224–237 µg/100 mg seed within a genetic background deficient in glutelin (i.e. of low glutelins). The enrichment of this foreign gene product was compensated by a decrease in the expression of other endogenous prolamine and globulin storage proteins, resulting in an almost equivalent total amount of seed storage proteins. These results show that low storage protein mutants can provide potentially useful hosts for the expression of foreign genes, allowing a higher‐level accumulation, because they can provide wider space for the accumulation of foreign gene products than in the normal host plant.
Monoclonal C5‐1 antibody produced in transgenic alfalfa plants exhibits a N‐glycosylation that is homogenous and suitable for glyco‐engineering into human‐compatible structures
Authors: Bardor Muriel , Loutelier‐Bourhis Corinne , Paccalet Thomas , Cosette Pascal , Fitchette Anne‐Catherine , Vézina Louis‐P. , Trépanier Sonia , Dargis Michèle , Lemieux Réal , Lange Catherine , Faye Loïc , Lerouge Patrice 
Published: November 2003

SummaryStructural analysis of the N‐glycosylation of alfalfa proteins was investigated in order to evaluate the capacity of this plant to perform this biologically important post‐translational modification. We show that, in alfalfa, N‐linked glycans are processed into a large variety of mature oligosaccharides having core‐xylose and core α(1,3)‐fucose, as well as terminal Lewisa epitopes. In contrast, expression of the C5‐1 monoclonal antibody in alfalfa plants results in the production of plant‐derived IgG1 which is N‐glycosylated by a predominant glycan having a α(1,3)‐fucose and a β(1,2)‐xylose attached to a GlcNAc2Man3GlcNAc2 core. Since this core is common to plant and mammal N‐linked glycans, it therefore appears that alfalfa plants have the ability to produce recombinant IgG1 having a N‐glycosylation that is suitable for in vitro or in vivo glycan remodelling into a human‐compatible plantibody. For instance, as proof of concept, in vitro galactosylation of the alfalfa‐derived C5‐1 mAb resulted in a homogenous plantibody harbouring terminal β(1,4)‐galactose residues as observed in the mammalian IgG.
Transcriptional regulation of a pineapple polyphenol oxidase gene and its relationship to blackheart
Authors: Zhou Yuchan , O'Hare Tim J. , Jobin‐Decor Marcelle , Underhill Steven J. R. , Wills Ron B. H. , Graham Michael W. 
Published: November 2003

SummaryTwo genes encoding polyphenol oxidase (PPO) were isolated from pineapple (Ananas comosus[L.] Merr. cv. Smooth Cayenne). Sequence analyses showed that both contained a single intron and encoded typical chloroplast‐localized PPO proteins, the sequences of which corresponded to two pineapple PPO cDNAs, PINPPO1 and PINPPO2, recently described by Stewart et al. (2001). Southern blot analyses suggested that pineapple contained only two PPO genes. Analysis of expression of PINPPO1 promoter GUS fusion constructs showed this promoter had a low basal activity and was cold‐ and wound‐inducible, consistent with known mRNA expression profiles. Striking homologies to gibberellin response complexes (GARC) were observed in sequences of both the PINPPO1 and PINPPO2 promoters. Transient assays in mature pineapple fruit and stable expression in transgenic tobacco showed that PINPPO1 promoter‐GUS fusions were indeed gibberellin (GA) responsive. A role for the element within the putative GARCs in mediating GA‐responsiveness of the PINPPO1 promoter was confirmed by mutational analysis. PINPPO2 was also shown to be GA‐responsive by RT‐PCR analysis. Mutant PINPPO1 promoter–GUS fusion constructs, which were no longer GA‐inducible, showed a delayed response to cold induction in pineapple fruit in transient assays, suggesting a role for GA in blackheart development. This was supported by observations that exogenous GA3 treatment induced blackheart in the absence of chilling. Sequences showing homology to GARCs are also present in some PPO promoters in tomato, suggesting that GA regulates PPO expression in diverse species.
Quasi‐markets in British Health Policy: A Longue Durée Perspective
Authors: Powell Martin 
Published: November 2003

Abstract Quasi‐markets in health care are generally associated with the period 1991–7 in the later years of office of the British Conservative Party. This paper aims to place such claims in a wider framework by exploring definitions of and conditions of success for quasi‐markets over a longer timescale, beginning in the 1930s and ending with the current New Labour government. It suggests a typology of quasi‐markets based on hard versus soft, direct versus indirect and internal versus external forms. It applies these categories and the conditions for success for quasi‐markets to seven historical periods. Both the typologies and the conditions for success of quasi‐markets varied over time, defying a simple linear development, suggesting a more nuanced historical narrative than simple continuity or discontinuity accounts of recent developments provide. Covering such a large topic over a long sweep of time, with the absence of clear evidence for much of the period, necessarily means that verdicts tend to be impressionistic. However, even at this level, the tentative conclusions provide important contextual elements in the debate on quasi‐markets.
Support for Carers of Older People: The Roles of the Public and Voluntary Sectors in Sweden
Authors: Jegermalm Magnus 
Published: November 2003

Abstract This study examines the support services offered to informal caregivers, whether directly or indirectly, in Sweden over the period of a special investment initiative between 1999 and 2001. Data were collected in a Swedish county using two separate mail questionnaires in 1999 and 2001. The first questionnaire was addressed to each municipality in the region. The second questionnaire was sent to a random sample of voluntary organizations in the area. The findings showed that only the municipalities provided direct forms of relief service, day care and financial support. The voluntary organizations’ support for carers focused on support groups and training as well as services for older care users themselves. There was a significant increase between 1999 and 2001 in the number of municipalities providing information material and training for carers and using professional caregiver consultants. On the one hand, the Swedish public social care system appears to be following the international pattern in paying more attention to informal caregivers and investing in support services for them. On the other hand the findings did not show any growth in support provided by the voluntary organizations. Here Swedish welfare is dissimilar to other European countries, where it is increasingly common for voluntary organizations to play an important role as providers of support for carers.