bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anatomical Remodelling of the Supraoptic Nucleus: Changes in Synaptic and Extrasynaptic Transmission
Authors: Oliet S. H. R. , Piet R. 
Published: April 2004

AbstractThe adult hypothalamic‐neurohypophysial system undergoes activity‐dependent morphological plasticity that modifies the astrocytic enwrapping of its magnocellular neurones. For a long time, the functional consequences of such changes have remained hypothetical. Modifications in the glial environment of neurones are expected to have important physiological repercussions in view of the various functions played by astrocytes in the central nervous system. In particular, glial cells are essential for uptake of neurotransmitters, including glutamate, and for physically and functionally restricting diffusion of neuroactive substances within the extracellular space. Recent studies performed in the supraoptic nucleus of lactating and chronically dehydrated animals, in conditions where astrocytic coverage of neurones is reduced, have revealed a significant impairment of glutamate clearance. The resulting accumulation of the excitatory amino acid in the extracellular space around glutamatergic inputs causes an enhanced activation of presynaptic metabotropic glutamate receptors that inhibit transmitter release. In the supraoptic nucleus of lactating rats, neuroglial remodelling is accompanied by modification of the geometry, size and diffusion properties of the extracellular space. The latter observations suggest that, in the activated supraoptic nucleus, the range of action and the concentration of released neuroactive substances may be significantly enhanced. Overall, our observations indicate that the glial environment of supraoptic neurones influences synaptic glutamatergic transmission, as well as extrasynaptic forms of communication.
The Discovery of Novel Vasopressin V1b Receptor Ligands for Pharmacological, Functional and Structural Investigations
Authors: Guillon G. , Derick S. , Pena A. , Cheng L. L. , Stoev S. , Seyer R. , Morgat J. L. , Barberis C. , Gal C. Serradeil‐Le , Wagnon J. , Manning M. 
Published: April 2004

AbstractUntil recently, pharmacological studies dealing with vasopressin receptor isoforms were severely hampered by the lack of selective agonists or antagonists that recognize the pituitary V1b vasopressin receptor. By contrast, many selective vasopressin‐related compounds are available for characterization of the vasopressor (V1a) or antidiuretic (V2) vasopressin receptor subtypes. Recently, SSR149415, a selective nonpeptide molecule, was discovered with nanomolar affinity for mammalian V1b receptors and good selectivity for the other vasopressin and oxytocin receptor isoforms. This molecule exhibits potent antagonist properties both in vitro and in vivo. We also designed synthetic peptides derived from [deaminocysteine1,arginine8]vasopressin (dAVP), modified in position 4 by various amino acid residues. Some of these, d[cyclohexylalanine4]AVP or d[lysine4]AVP, have a high affinity and an excellent selectivity for the human V1b receptor subtype. However, they exhibit a mixed V1b/V2 pharmacological profile for the rat vasopressin receptor isoforms. Whatever the species considered, these peptides behave as agonists both in bioassays performed in vitro and in vivo. The d[cyclohexylalanine4]AVP was tritiated and represents the first selective radiolabelled ligand available for studying the human V1b receptors. The discovery of these new selective V1b agonists and V1b antagonist allows an accurate pharmacological characterization of all the vasopressin receptor isoforms. As emphasized in this review, attention to the vasopressin and oxytocin receptor species differences is of critical importance in studies with all vasopressin and oxytocin ligands.
Assessment of Spike Activity in the Supraoptic Nucleus
Authors: Bhumbra G. S. , Inyushkin A. N. , Dyball R. E. J. 
Published: April 2004

AbstractNovel approaches to the characterization of coding carried by spike trains are discussed. Measuring firing frequency alone may only partially reflect spike patterning, and can only quantify changes of the most obvious kind. We have devised a method that combines probabilistic and information approaches to quantify the variability of the interspike intervals in a way that is independent of spike frequency. To illustrate the technique, the firing of an oxytocin cell and a vasopressin cell were compared before and after osmotic stimulation. A bimodal lognormal function was fitted to the interspike interval histograms. The entropy of the log interval histogram was used to measure the variability of intervals and to reflect the coding capacity of the cell per spike. A perfect metronome shows no variability in interval and thus has no greater coding capacity than is conveyed by its frequency, whereas the variability of intervals of magnocellular neurones means that their irregular activity has greater potential for coding. While the mean spike frequency increased in both the oxytocin and vasopressin cells in response to osmotic stimulation, the changes in their irregularity showed differences. Osmotic stimulation reduced the entropy of the oxytocin cell, reflecting an increase in the regularity of its spike activity. Conversely, osmotic stimulation had little effect on the entropy of the vasopressin cell. Such differences are not evident from a simple inspection of ratemeter activity. The comparison highlights the limitations of mean spike frequency as a measure of spike coding. Parameters based on the interspike intervals constitute informative measures of spike activity that allow objective comparisons to be made between the activity under different physiological conditions.
Subcellular Vasopressin mRNA Trafficking and Local Translation in Dendrites
Authors: Mohr E. , Richter D. 
Published: April 2004

AbstractVasopressin mRNA is delivered to axons and dendrites of rat hypothalamic magnocellular neurones. Subcellular localization of mRNAs requires sequences (cis‐acting elements) within the RNA and proteins (trans‐acting factors), which together mediate nucleic acid transport along the cytoskeleton to specific cytoplasmic destinations. In cultured neurones, vasopressin mRNA transcribed from a microinjected eukaryotic expression vector is sorted to dendrites. Detailed analyses revealed the presence of a complex cis‐acting element, called dendritic localizer sequence (DLS), within part of the coding‐ and the 3′‐untranslated region of vasopressin mRNA. Biochemical investigations have shown a specific interaction of poly(A)‐binding protein (PABP) with the DLS. PABP is implicated in translation, translational control, RNA stability and RNA transport. Hence, PABP could be a component of a probably multifactor complex regulating transport and local translation of vasopressin mRNA. Dendrites are capable of translation. Local synthesis of the vasopressin precursor in dendrites of in vitro cultured neurones was demonstrated by microinjecting a vector encoding a mutant vasopressin polyprotein that is unable to leave the rough endoplasmic reticulum. Expression of this construct revealed that the nondiffusable protein is only detectable in dendrites harbouring vasopressin mRNA whereas dendrites devoid of this transcript lack the mutant vasopressin precursor.
Pathological Role of Aquaporin‐2 in Impaired Water Excretion and Hyponatremia
Authors: Ishikawa S. , Saito T. , Kasono K. 
Published: April 2004

AbstractIn the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), inappropriately elevated secretion of vasopressin can result in a reduction of antidiuretic efficacy: a phenomenon known as ‘vasopressin escape’. We compared experimental SIADH with 1‐deamino‐8‐d‐arginine vasopressin (dDAVP)‐excess rats, where both groups received continuous subcutaneous administration of dDAVP by osmotic minipump but the SIADH rats also received a liquid diet that induced hyponatraemia. The SIADH rats, but not the dDAVP excess rats, showed a marked attenuation of urinary concentrating ability. Vasopressin V2 receptor binding capacity and mRNA expression were similar between the two groups, but the SIADH rats showed a diminished up‐regulation of aquaporin‐2 (AQP‐2) mRNA and protein expression. These findings indicate the presence of tonicity‐response regions in the AQP‐2 promoter gene, and that either hypervolemia or hypotonicity may attenuate the postreceptor signalling of vasopressin in renal collecting duct cells in SIADH rats.
Novel G‐Protein Coupled Receptor Ligands and Neurohypophysial Hormones
Authors: Ueta Y. , Ozaki Y. , Saito J. 
Published: April 2004

AbstractRecently, novel peptides have been identified as unknown ligands of orphan G‐protein coupled receptors. In the paraventicular (PVN) and supraoptic nuclei (SON), the expression of the G‐protein genes are abundant. In this review, we focus on the physiological role of neuromedin U and galanin‐like peptide, which were recently identified as ligands of G‐protein coupled receptors, in the regulation of neurohypophysial hormones. Intracerebroventricular (i.c.v) administration of neuromedin U induced the expression of c‐fos mRNA in both the magnocellular and parvocellular division of the PVN and throughout the SON. Administration of i.c.v. neuromedin U caused a significant increase in plasma concentrations of vasopressin and oxytocin as well as adrenocorticotropic hormone. The expression of galanin‐like peptide mRNA was observed in the pituicytes of rat posterior pituitary gland. The expression of galanin‐like peptide mRNA in the posterior pituitary gland was markedly increased after dehydration, salt loading and intraperitoneal administration of lipopolysaccaride, challenges that stimulate the secretion of vasopressin and oxytocin, and which activate the hypothalamic‐pituitary adrenal axis. These results suggest that neuromedin U and galanin‐like peptide may have an important role in the regulation of both the hypothalamic‐neurohypophysial system and the hypothalamic‐adrenohypophysial system.
Homo‐ and Hetero‐Dimeric Complex Formations of the Human Oxytocin Receptor
Authors: Devost D. , Zingg H. H. 
Published: April 2004

AbstractUsing two different coimmunoprecipitation strategies as well as bioluminescence resonance energy transfer (BRET) techniques, we determined that the human oxytocin receptor forms dimeric and oligomeric complexes in vivo in intact living cells, and that these complexes exist at the cell surface level. Using a BRET‐based assay, we found that oligomers can form between oxytocin receptors themselves (homo‐oligomers) as well as, with a reduced affinity, between the oxytocin receptor and related members of the vasopressin receptor family (V1a and V2 receptors), but not with the more remotely related bradykinin receptor. The existence of oxytocin receptor oligomers at the level of the cell surface was demonstrated by a coimmunoprecipitation approach involving direct antibody exposure of intact living cells. Furthermore, this approach demonstrated that cell surface oxytocin receptor oligomerization is ligand independent. However, agonist addition led to an apparent rapid decrease in receptor oligomerization, as assessed by the coimmunoprecipitation approach, indicating that agonist exposure may modulate the oligomerization status. It remains to be determined to what extent oxytocin receptor oligomerization impacts on signal transduction.
Imagining Ukraine: Regional Differences and the Emergence of an Integrated State Identity, 1926–1994
Authors: Liber George O. 
Published: April 2004

Abstract. When Ukraine gained its independence in 1991, it did not possess an integrated Ukrainian state identity. Serious differences between those regions which entered the Russian empire and the Soviet Union before 1939 and those annexed since 1939 hampered the creation of a post‐Soviet state identity.Just as the Ukrainian and Russian languages dominate in different regions in Ukraine, attitudes towards economic reform also vary by region. Russian‐speaking areas are more conservative in regard to economic reforms than Ukrainian‐speaking ones. But despite these regional differences, Ukraine is not on the verge of civil war. Two public opinion polls taken in 1991 and 1994 in Lviv (in Western Ukraine) and in Donetsk (in Eastern Ukraine) document that the citizens of Ukraine possess a common desire for peace and stability. This desire overshadows Ukraine's regional differences and will help create the new post‐Soviet Ukrainian state identity.
Explaining Third‐Party Intervention in Ethnic Conflict: Theory and Evidence
Authors: Garment David , James Patrick 
Published: April 2004

Abstract.One of the most challenging developments for students of international relations is the resurgence of ethnic strife, including secessionism and irredentism. Basic questions are only beginning to be addressed in the post‐Cold War era. Why are some states more likely than others to intervene in ethnic conflicts? How can international norms about third‐party intervention in ethnic conflicts be evaded or ignored by some states but respected by others? Why are some states inclined to use force rather than mediation to resolve ethnic strife? In short, what accounts for the emergence of adventurous and belligerent foreign policies with respect to internal ethnic conflicts? These questions are of increasing importance to students of international politics, yet the dynamics and internationalisation of ethnic conflict are far from fully understood.This study focuses on the dynamics of third‐party intervention in ethnic strife and implications for peaceful resolution. The first section presents a model that identifies the general conditions under which ethnic strife is most likely to lead to intervention by third‐party states. The second uses four cases to illustrate, within the context of the model, different processes with respect to internationalisation of ethnic conflict. The third and final stage identifies implications for policy and theory, along with directions for future research.
Review Article: Nationalisms, National Identities and Nation States: Gendered Perspectives
Authors: Al‐Ali Nadje 
Published: April 2004

Books reviewed in this article:Nira Yuval‐Davis, Gender & NationLois West (ed.), Feminist NationalismRick Wilford and Robert L. Miller (eds.), Women, Ethnicity and Nationalism: The Politics of TransitionCynthia Cockburn, The Space Between Us: Negotiating Gender and National Identities in Conflict
Clearing the cervical spine in unconscious polytrauma victims, balancing risks and effective screening
Authors: Morris C. G. T. , McCoy É. 
Published: April 2004

SummaryCervical spine injury occurs in 5–10% of cases of blunt polytrauma. A missed or delayed diagnosis of cervical spine injury may be associated with permanent neurological sequelae. However, there is no consensus about the ideal evaluation and management of the potentially injured cervical spine and, despite the publication of numerous clinical guidelines, this issue remains controversial. In addition, many studies are limited in their application to the obtunded or unconscious trauma victim. This review will provide the clinician managing unconscious trauma victims with an assessment of the actual performance of clinical examination and imaging modalities in detecting cervical spine and isolated ligamentous injury, a review of existing guidelines in light of the available evidence, relative risk estimates and a proposed management scheme.
Hydraulic requirements of stream communities: a case study on invertebrates
Authors: Mérigoux S. , Dolédec S. 
Published: April 2004

Summary1. We relate invertebrate assemblages to direct measurements of near‐bed hydraulic conditions that integrate the complex three‐dimensional structure of flow close to the bottom.2. We sampled invertebrate taxa from a Mediterranean River along a spatial gradient of increasing shear stress in two seasons (spring and autumn) with different hydrological conditions. We used a recently described ordination technique, Outlying Mean Index (OMI) analysis, to study the response of stream invertebrates to near‐bed hydraulic parameters.3. The distribution of nearly 70% of the taxa collected was significantly related to the hydraulic parameters assessed. In both seasons, shear stress and Froude number were the most important hydraulic parameters whereas substratum particle size and bed roughness had less influence. Most of the 31 taxa collected in both seasons had a higher OMI (an index showing the deviation between the mean environmental conditions used by a taxon and the mean environmental conditions used by a theoretical taxon uniformly distributed across the studied gradient) in autumn (when flow was greater) and were found in samples with high shear stress and high Froude number. This suggests that benthic invertebrates changed their preferences according to flow conditions.4. Taxon richness declined with increased shear stress during lower flow in spring. Finally, and agreeing with previous results, the proportion of filter feeders and collector‐gatherers was inversely related to shear stress.5. Our results are a first step towards better habitat suitability models that could inform management decisions.
Autoreactive responses to an environmental factor. 2. Phthalate‐induced anti‐DNA specificity is downregulated by autoreactive cytotoxic T cells
Authors: Lim So‐Yon , Ghosh Swapan K. 
Published: April 2004

SummaryAn environmental factor (phthalate) was shown, in our previous study, to induce serum anti‐DNA responses in BALB/c, NZB and lupus‐prone NZB/W F1 mice. Out of such anti‐phthalate responses, cross‐reactive populations were identified that strongly bind phthalate, DNA, or both. A phthalate‐specific BALB/c monoclonal antibody, 2C3‐Ig (γ1,κ), showed considerable affinity for DNA and had extensive sequence homology with the heavy and light chain variable regions of a known anti‐DNA immunoglobulin, BV04‐01, from lupus‐prone NZB/W F1 mice. This study was initiated to address how BALB/c mice, but not NZB/W F1 mice, are protected from these adverse autoreactive B cells. Using 2C3 hybridoma cells as the prototype autoreactive BALB/c B cell, we determined whether its DNA‐binding monoclonal antibody would induce any regulatory cell‐mediated immune responses. Synthetic idiopeptides corresponding to the heavy and light chain variable regions of 2C3‐Ig were found to be effective at inducing specific effector cells in BALB/c mice, but not in lupus‐prone F1 mice. The splenocytes from BALB/c mice incubated in vitro with the idiopeptides, particularly the complementarity‐determining region 1 (VL1) of the 2C3‐Ig light chain, showed significant proliferative and cytolytic responses. A CD8+ cytotoxic T‐lymphocyte (CTL) response was elicited that recognized the VL1 peptide presented by the Kd allele, and affected the growth of 2C3 cells. In vivo depletion of CD8+ T cells in BALB/c mice significantly decreased this CTL activity but increased the anti‐DNA humoral response. These results suggest that autoreactive CTLs are induced in non‐autoimmune prone mice as a mechanism to downregulate self‐reactive B cells.
Importance of the inducible costimulator molecule for the induction of allergic immune responses and its decreased expression on T helper cells after venom immunotherapy
Authors: Bellinghausen Iris , Klostermann Bettina , Böttcher Ingo , Knop Jürgen , Saloga Joachim 
Published: April 2004

SummaryThe inducible costimulator (ICOS), a newly identified member of the CD28 receptor family that is induced after T‐cell activation, and its ligand (ICOSL), being expressed on activated monocytes and dendritic cells play a key role in T‐cell‐mediated immune responses. As ICOS costimulation also seems to regulate T helper 2 effector cells, the aim of this study was to analyse the function of this molecule in allergic immune responses and their specific therapy, mainly venom immunotherapy (VIT). CD4+ T cells from grass pollen‐, or bee or wasp venom‐allergic donors were stimulated in the presence of autologous mature dendritic cells, which were pulsed with different allergen doses. In this system, costimulation of ICOS strongly enhanced the production of the T helper 2 cytokines interleukin (IL)‐4, IL‐5 and IL‐10 and, to a lesser extent, secretion of the T helper 1 cytokine, interferon‐γ. Expression of ICOS on CD4+ T cells was induced, in a dose‐dependent manner, after a few days of stimulation with allergen‐pulsed dendritic cells, reaching a peak on day 6. The upregulation of ICOS after stimulation with venom allergens was significantly reduced after VIT. Addition of exogenous IL‐10 (which is induced during VIT) to the co‐cultures before VIT also led to an inhibition of ICOS expression, while blocking of IL‐10 in co‐cultures after VIT partially restored the expression of ICOS. These data indicate that the inhibition of T cells after immunotherapy also involves decreased induction of the costimulatory molecule ICOS, which, in turn, seems to be dependent on the presence of IL‐10, also associated with the inhibited status of T cells after VIT. This makes the ICOS–ICOSL pathway a potential target for therapeutic intervention in T helper 2‐mediated diseases, such as allergic diseases.
Murine CD8 lymphocyte expansion in vitro by artificial antigen‐presenting cells expressing CD137L (4‐1BBL) is superior to CD28, and CD137L expressed on neuroblastoma expands CD8 tumour‐reactive effector cells in vivo
Authors: Yan Xiaocai , Johnson Bryon D. , Orentas Rimas J. 
Published: April 2004

SummaryThe ability to expand tumour‐infiltrating lymphocytes in vitro has been greatly enhanced by the use of antigen‐independent mechanisms of immune cell costimulation. We have produced human, using the K562 cell line, and murine, using YAC‐1 cells, artificial antigen presenting cells (aAPC) and demonstrate that these cell types stimulate murine lymphocyte populations in distinct ways. Using aAPC that have been transfected with CD137L (4‐1BBL) and CD32 (FcRγII), as a means to bind anti‐CD3 and anti‐CD28 antibody, we found that CD4 cells preferentially expanded in vitro with K562 aAPC, while CD8 cells expanded with both K562 and YAC‐1 aAPC. Co‐stimulation mediated by CD137L on aAPC was superior to that mediated by anti‐CD28 antibody. This was seen in both long and short‐term expansion assays, and by the rapid induction of a CD8+ DX5+ population. DX5 serves, under these in vitro conditions, as a general marker for lymphocyte activation. In vivo, the superiority of CD137L was demonstrated by the induction of T helper 1 effectors seen in freshly isolated splenocytes from mice immunized with CD137L‐expressing neuroblastoma tumour vaccines. The ability to stimulate a strong CD8 CTL response in vivo correlated with the induction of a DX5+ cell population in splenocytes with a memory‐effector phenotype. The presence of this unique DX5+ cell population, phenotypically distinct with regards to CD69 and CD62L expression from DX5+ cells induced by aAPC in vitro, may be associated with the ability of CD137L to induce strong anti‐tumour immunity.