bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linking Rights and Standards: The Process of Developing ‘Rights‐based’ Minimum Standards on Food Security, Nutrition and Food Aid
Authors: Young Helen , Taylor Anna , Way Sally‐Anne , Leaning Jennifer 
Published: June 2004

This article examines the recent revision of the Sphere Minimum Standards in disaster response relating to food security, nutrition and food aid. It describes how the revision attempted to incorporate the principles of the Humanitarian Charter, as well as relevant human rights principles and values into the Sphere Minimum Standards. The initial aim of the revision was to ensure that the Sphere Minimum Standards better reflected the principles embodied in the Humanitarian Charter. This was later broadened to ensure that key legal standards and principles from human rights and humanitarian law were considered and also incorporated, in part to fill the ‘protection gap’ within the existing standards. In relation to the food security, nutrition and food aid standards, it was agreed by participants in the process that the human right to adequate food and freedom from hunger should be incorporated. In relation to more general principles underlying the Humanitarian Charter, itself drawn largely from human rights and humanitarian law, it was agreed that there was a need to strengthen ‘protection’ elements within the standards and a need to incorporate the basic principles of the right to life with dignity, non‐discrimination, impartiality and participation, as well as to explore the relevance of the concept of the progressive realisation of the right to food.The questions raised in linking rights to operational standards required thought, on the one hand, about whether the technical standards reflected a deep understanding of the values expressed within the legal instruments, and whether the existing standards were adequate in relation to those legal rights. On the other hand, it also required reflection on how operational standards like Sphere could give concrete content to human rights, such as the right to food and the right to be free from hunger. However, there remain challenges in examining what a rights‐based approach will mean in terms of the role of humanitarian agencies as duty‐bearers of rights, given that the primary responsibility rests with state governments. It will also require reflection on the modes and mechanisms of accountability that are brought to bear in ensuring the implementation of the Minimum Standards.
The United Nations' Humanitarian Pillar: Refocusing the UN's Disaster and Emergency Roles and Responsibilities
Authors: Kent Randolph C. 
Published: June 2004

Changes in the nature of humanitarian crises and in the ways that the international community responds to such crises demand a radically overhauled role for the United Nations system. At a time when the UN and its member states are pursuing reform of some of that institution's most fundamental peace and security functions, this paper suggests that reform, too, is required to meet humanitarian crises of the future. This paper proposes a new type of operational role for the UN, while at the same time arguing that the UN has to place itself in the vanguard of humanitarian assistance as ‘the standard‐bearer’.The article draws many of its conclusions and recommendations from a recently completed study, requested by the Inter‐Agency Standing Committee, concerning the effect for the UN system of changes in humanitarian financing.
Regional expression of RGS4 mRNA in human brain†
Authors: Erdely Holly A. , Lahti Robert A. , Lopez Mary B. , Myers Carol S. , Roberts Rosalinda C. , Tamminga Carol A. , Vogel Michael W. 
Published: June 2004

AbstractRegulators of G‐protein signalling (RGS) proteins are a recently discovered class of proteins that modulate G‐protein activity. More than 20 RGS proteins have been identified and are expressed throughout the body and brain. In particular, RGS4 appears to regulate dopamine receptor function and has been implicated in several dopamine related diseases, including schizophrenia. This study presents an extensive examination of the regional distribution of RGS4 mRNA in postmortem human brain. Using in situ hybridization, the expression levels of RGS4 mRNA were determined in human hemicoronal (Talairach sections +8 and −20) brain sections. In the rostral slice (Talairach +8) highest levels were found in the inferior frontal cortex, the superior frontal, and the cingulate cortex. Slightly lower levels were found in the insular cortex and inferior temporal cortex. The caudate, putamen and nucleus accumbens had lower levels. In the caudal slice (−20), the cortical layers showed the highest levels, with moderate levels observed in the parahippocampal gyrus, low levels in the CA‐pyramidal region, and almost undetectable levels in the thalamus. In the frontal cortex a dense band was apparent near one of the inner layers of the cortex. In conclusion, RGS4 mRNA distribution in human postmortem tissue from normal persons was very dense in most cortical layers examined, with lower density in the basal ganglia and thalamus.
Development of the mouse hypothalamo‐neurohypophysial system in the munc18–1 null mutant that lacks regulated secretion
Authors: Korteweg Niki , Maia Ascanio S. , Verhage Matthijs , Burbach J. Peter H. 
Published: June 2004

AbstractThe hypothalamo‐neurohypophysial system (HNS) is composed of hypothalamic magnocellular neurons and neural lobe pituicytes that accommodate the nerve terminals. Here we have investigated if the communication of the peptidergic neurons of the HNS with neighbouring cells plays a role in the development and assembly of the HNS. We employed munc18–1‐deficient mice, which completely lack neurotransmitter secretion. Morphological and immunohistological analysis of the HNS in these mutant embryos during brain development showed that this peptidergic system was formed normally during early embryogenesis. However, the development arrested at embryonal day 14.5, the stage when terminal differentiation has to take place. The peptidergic neurons targeted axons in the correct direction, but few arrived at their final location and the neurons were not maintained in later stages. The pituicytes in the neural lobe of the pituitary were generated, but failed to organize normally. Our results indicate that peptide gene expression, axon outgrowth and migration are intrinsic developmental events in these peptidergic neurons, that are initiated in the munc18–1 null mutant. The further expansion and the integration of outgrowing axon terminals with neural lobe pituicytes requires munc18–1‐dependent processes, probably exocytosis, at multiple levels. Firstly, to maintain and propagate neuronal outgrowth and guidance, and secondly, to control the cellular organization of the pituicytes. Thus, the communication between the outgrowing neurons and the pituicytes could serve to integrate these two cell types to constitute a functional peptidergic system.
The therapeutic window after spinal cord injury can accommodate T cell‐based vaccination and methylprednisolone in rats
Authors: Ibarra Antonio , Hauben Ehud , Butovsky Oleg , Schwartz Michal 
Published: June 2004

AbstractImmune system activity has traditionally been considered harmful for recovery after spinal cord injury (SCI). Recent evidence suggests, however, that immune activity – and specifically autoimmune activity − is evoked by the insult, is beneficial if properly regulated and is amenable to boosting. Thus, for example, vaccination with an altered peptide ligand derived from myelin basic protein reduces the progressive degeneration of neurons that escaped the initial insult, thereby promoting recovery after SCI. As the steroid drug methylprednisolone (MP) is currently the only treatment available for patients with SCI, our purpose in the present study was to examine the mutual compatibility of the two treatments within the post‐traumatic therapeutic window. We show, using rats of two different strains, that if MP is injected concomitantly with the therapeutic vaccination, the beneficial effect of the vaccination is diminished. However, if MP is given immediately after the insult and the vaccination 48 h later, MP does not detract from the beneficial effect of the vaccination. These results demonstrate that the therapeutic window after SCI can accommodate immediate administration of MP plus a delayed therapeutic vaccination.
Irreversible loss of a subpopulation of cortical interneurons in the absence of glutamatergic network activity
Authors: De Lima Ana Dolabela , Opitz Thoralf , Voigt Thomas 
Published: June 2004

AbstractIn the cerebral cortex of mammals, γ‐aminobutyric acid (GABA)ergic neurons represent 15–25% of all neurons, depending on the species and area being examined. Because converging evidence suggests that activity may play an important role in the neuritic maturation and synaptic function of GABAergic neurons, it is feasible that activity plays a role in the regulation of the proportion of GABAergic neurons. Here we provide direct evidence that early in cortical development activity blockade may deplete the network of a subpopulation of GABA immunoreactive neurons characterized by their small size and late generation in vitro. In a period of time coinciding with the emergence of synchronous network activity, the survival and morphological differentiation of GABAergic neurons was influenced by long‐term blockade of synaptic activity. While GABAA receptor antagonists had a minor promoting effect on interneuronal survival during the second week in vitro, antagonists of ionotropic glutamate receptors strongly impaired survival and differentiation of immature GABAergic interneurons. Interneuronal loss was more severe when N‐methyl‐d‐aspartate receptors were blocked than after blockade of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐proprionic acid (AMPA)/kainate receptors. The decrease in the density of GABAergic neurons was irreversible, but could be prevented by the simultaneous addition of brain‐derived neurotrophic factor (BDNF). These results suggest that there is a narrow time window during neocortical development when glutamatergic activity, and specially NMDA receptor stimulation, is crucial to assure survival and maturation of a subpopulation of late developing GABAergic interneurons.
Phasic bursts in rat magnocellular neurosecretory cells are not intrinsically regenerative in vivo
Authors: Brown Colin H. , Bull Philip M. , Bourque Charles W. 
Published: June 2004

AbstractVasopressinergic hypothalamic magnocellular neurosecretory cells fire in phasic bursts. Burst initiation involves summation of postsynaptic potentials to generate action potentials. Action potentials are each followed by a nonsynaptic depolarizing after‐potential that summates temporally to generate a plateau potential and so sustain activity throughout the burst. It is unknown whether this plateau potential exceeds spike threshold in vivo to cause intrinsic regenerative firing or simply approaches threshold to increase the probability that excitatory postsynaptic potentials will trigger further action potentials. Here we show that pharmacological blockade of ionotropic glutamatergic transmission by microdialysis application of kynurenic acid into the supraoptic nucleus of anaesthetized rats prevents spontaneous bursts and bursts (after‐discharge) evoked by short trains of antidromically stimulated action potentials in magnocellular neurosecretory cells. Even during prolonged depolarization induced by 1 m NaCl infusion, kynurenic acid microdialysis application still blocked after‐discharge. The ability of kynurenic acid to block after‐discharge during osmotic stimulation was not caused by an unmasking of inhibitory postsynaptic potentials as kynurenic acid was equally effective in the presence of the ionotropic γ‐aminobutyric acid receptor antagonist, bicuculline, nor did it result from inhibition of plateau potential amplitude as this was unaffected by kynurenic acid and bicuculline in vitro, as was after‐discharge evoked in vitro. We conclude that phasic bursts are nonregenerative in vivo but rather require continued excitatory synaptic input activity superimposed upon a subthreshold plateau potential to sustain burst activity.
Absence of phosphoglucose isomerase‐1 in retinal photoreceptor, pigment epithelium and Muller cells
Authors: Archer Simon N. , Ahuja Poonam , Caffé Romeo , Mikol Catherine , Foster Russell G. , Van Veen Theo , Von Schantz Malcolm 
Published: June 2004

AbstractMacroarray analysis was used to compare equal amounts of cDNA from wild‐type and rd/rd (retinal degeneration) mice, collected at P90 when photoreceptor degeneration is virtually complete. A stronger signal for the glycolytic enzyme phosphoglucose isomerase (Gpi1) was observed in the rd/rd sample. Extracellularly, Gpi1 may act as a cytokine, independently described as neuroleukin and autocrine motility factor. Retinal Gpi1 expression was investigated by Northern and Western blot analysis and immunohistochemistry. Double‐labelling was performed with antibodies against Gpi1 and calbindin‐D, glutamine synthetase, RPE65, calretinin and ultraviolet opsin in order to provide positive cell type identification. Northern and Western blots showed double expression levels per microgram of RNA and protein, respectively, in the rd/rd retina compared with wild‐type. However, the total amount of Gpi1 protein per retina was indistinguishable. Gpi1 immunoreactivity was found in ganglion, amacrine, horizontal and bipolar cells, but not in rods, cones, pigment epithelium and Muller cells. This distribution explains why the absolute amounts of Gpi1 protein were not appreciably different between wild‐type and the rd/rd phenotype, where rods and cones are absent, whilst the relative contribution of Gpi1 to the total protein and RNA pools differed. Some extracellular immunoreactivity was observed in the photoreceptor matrix around cones in freshly fixed tissue only, which could possibly reflect a role as a cytokine. We propose that glycolysis in Gpi1‐negative cells proceeds entirely through the pentose phosphate pathway, creating NADPH at the cost of organic carbon. We hypothesize that the unique metabolic needs of photoreceptors justify this trade‐off.
Postnatal emergence of mature release properties in terminals of rat fast‐ and slow‐twitch muscles
Authors: Bewick Guy S. , Reid Brian , Jawaid Sabiha , Hatcher Tina , Shanley Lynne 
Published: June 2004

AbstractMotor nerve terminals in adult mammalian slow‐twitch muscles have lower levels of spontaneous and evoked neurotransmitter release than terminals in fast‐twitch muscles. These reflect adaptive differences, allowing terminals in slow (postural) muscles to sustain release during the prolonged firing trains experienced in vivo. Here we ask whether these differences in terminal release properties in Sprague–Dawley rat extensor digitorum longus (EDL, fast) and soleus (slow) muscles reflect their early cytodifferentiation in the embryo or whether they might be adaptations to their distinct mature activity patterns, which emerge around two weeks postnatally. We find that the mature pattern of differences in release arise through co‐ordinated increases in presynaptically dependent release properties (quantal content, spontaneous release frequency and evoked potential amplitude), beginning at three weeks, which are particularly substantial in EDL. In contrast, other synaptic properties are either consistently greater in the same muscle throughout development (evoked potential kinetics, muscle fibre diameter) or display no systematic muscle type‐dependent differences (terminal area, input resistance, spontaneous release amplitude). Thus, the emergence of adaptive differences in terminal release properties correlates with the differentiation of locomotor activity patterns in postnatal rat hindlimb muscles.
Glutamate‐induced elevations in intracellular chloride concentration in hippocampal cell cultures derived from EYFP‐expressing mice
Authors: Slemmer Jennifer E. , Matsushita Shinichi , De Zeeuw Chris I. , Weber John T. , Knöpfel Thomas 
Published: June 2004

AbstractThe homeostasis of intracellular Cl− concentration ([Cl−]i) is critical for neuronal function, including γ‐aminobutyric acid (GABA)ergic synaptic transmission. Here, we investigated activity‐dependent changes in [Cl−]i using a transgenetically expressed Cl−‐sensitive enhanced yellow‐fluorescent protein (EYFP) in cultures of mouse hippocampal neurons. Application of glutamate (100 µm for 3 min) in a bath perfusion to cell cultures of various days in vitro (DIV) revealed a decrease in EYFP fluorescence. The EYFP signal increased in amplitude with increasing DIV, reaching a maximal response after 7 DIV. Glutamate application resulted in a slight neuronal acidification. Although EYFP fluorescence is sensitive to pH, EYFP signals were virtually abolished in Cl−‐free solution, demonstrating that the EYFP signal represented an increase in [Cl−]i. Similar to glutamate, a rise in [Cl−]i was also induced by specific ionotropic glutamate receptor agonists and by increasing extracellular [K+], indicating that an increase in driving force for Cl− suffices to increase [Cl−]i. To elucidate the membrane mechanisms mediating the Cl− influx, a series of blockers of ion channels and transporters were tested. The glutamate‐induced increase in [Cl−]i was resistant to furosemide, bumetanide and 4,4′‐diisothiocyanato‐stilbene‐2,2′‐disulphonic acid (DIDS), was reduced by bicuculline to about 80% of control responses, and was antagonized by niflumic acid (NFA) and 5‐nitro‐2‐(3‐phenylpropylamino)benzoic acid (NPPB). We conclude that membrane depolarization increases [Cl−]i via several pathways involving NFA‐ and NPPB‐sensitive anion channels and GABAA receptors, but not through furosemide‐, bumetanide‐ or DIDS‐sensitive Cl− transporters. The present study highlights the vulnerability of [Cl−]i homeostasis after membrane depolarization in neurons.
Behavioral training interferes with the ability of gonadal hormones to increase CA1 spine synapse density in ovariectomized female rats
Authors: Frick Karyn M. , Fernandez Stephanie M. , Bennett Jennifer C. , Prange‐Kiel Janine , MacLusky Neil J. , Leranth Csaba 
Published: June 2004

AbstractEstradiol benzoate (EB) has repeatedly been shown to increase hippocampal CA1 spine synapse density in ovariectomized female rats. Although this increase has been assumed to enhance memory, a direct link between increased spine synapse density and memory has not been demonstrated. Furthermore, while androgens, such as testosterone propionate (TP) and dihydrotestosterone (DHT), also increase spine synapse density in females, their effects on memory have yet to be investigated. In the present study, ovariectomized female rats were given two injections, 24 h apart, of sesame oil (control), 10 µg EB, 500 µg TP or 500 µg DHT. Forty‐eight hours after the second injection, rats were tested in a 1‐day spatial Morris water maze task and then immediately perfused for analysis of CA1 spine synapse density (using electron microscopy and unbiased stereology). In the spatial acquisition phase of testing, EB, but not TP or DHT, significantly impaired memory relative to controls. Hormone treatment did not affect spatial retention or performance in the non‐spatial phase of testing. In contrast to previous work, spine synapse density was not increased by EB, TP or DHT. We therefore examined a new set of EB‐treated females, only half of which were water maze tested. Consistent with previous work, EB significantly increased spine synapse density among behaviorally naïve females. In contrast, spine synapse densities did not differ among behaviorally tested control and EB females, although they were higher than behaviorally naïve controls. These data indicate that 1‐day water maze testing can eliminate the hormone‐induced increases in CA1 spine synapse density typically observed in behaviorally naïve females.
Endocannabinoid transport tightly controls 2‐arachidonoyl glycerol actions in the hippocampus: effects of low temperature and the transport inhibitor AM404
Authors: Hájos Norbert , Kathuria Satish , Dinh Thien , Piomelli Daniele , Freund Tamás F. 
Published: June 2004

AbstractThe control of endocannabinoid actions on cortical neurons by a putative carrier‐mediated uptake is still poorly understood at the level of synaptic transmission. We investigated the effect of an endocannabinoid, 2‐arachidonoyl glycerol (2‐AG), on inhibitory postsynaptic currents (IPSCs) in hippocampal slices under physiological conditions, and when uptake was altered by a selective blocker or lower temperature. Bath application of 2‐AG (20 µm) caused a 40% reduction in the amplitude of IPSCs evoked in the perisomatic region of CA1 pyramidal neurons at room temperature; this effect could be blocked by a specific CB1 receptor antagonist, AM251. By contrast, a smaller (20%) but significant suppression of inhibitory transmission was found by 2‐AG at 33–35 °C. This reduced blocking effect at physiological temperature could be brought back to 40% by coapplying the endocannabinoid uptake blocker, AM404 (10 or 20 µm) with 2‐AG. In parallel experiments, we measured [3H]2‐AG uptake at different temperatures in primary cultures prepared from cortical neurons. These data confirmed a striking inhibition of [3H]2‐AG uptake at room temperature compared with values observed at 37 °C. Uptake could be significantly modified by anandamide, 2‐AG and AM404, suggesting a common transporter for the two endocannabinoids. These findings together demonstrate the presence of an effective endocannabinoid uptake in cortical neurons, which could considerably alter the spatial and temporal constraints of endocannabinoid signalling at physiological temperature, and which may critically change the interpretation of findings at room temperature.
DREAM ablation selectively alters THC place aversion and analgesia but leaves intact the motivational and analgesic effects of morphine
Authors: Cheng Hai‐Ying M. , Laviolette Steven R. , Van Der Kooy Derek , Penninger Josef M. 
Published: June 2004

AbstractDREAM (downstream regulatory element antagonistic modulator) is a novel transcriptional repressor for the prodynorphin gene, and genetic deletion of DREAM in mice results in a phenotype of ongoing analgesia by virtue of its effect on opioid gene expression. In the present study, we evaluated the motivational effects of opioids (morphine), cannabinoids [Δ9‐tetrahydrocannabinol (THC)] and cocaine in mice lacking the dream gene (dream−/−). The aversive effects of THC were potentiated in dream−/− mice in a κ‐opioid receptor‐dependent fashion, whereas morphine reward and the aversive effects of morphine withdrawal remained intact. The rewarding and aversive effects of cocaine were likewise unperturbed in dream−/− mice. Moreover, the aversive properties of lithium chloride and naloxone were unaffected by the absence of DREAM, indicating that the effect of DREAM on THC‐induced dysphoria is not due to a general involvement in the behavioral response to aversive stimuli. Additionally, physical dependence to morphine and the locomotor‐sensitizing effects of cocaine were unaltered in these animals. Finally, whereas the absence of DREAM reduced the analgesic efficacy of THC, morphine analgesia was unaffected in dream−/− mice.