bluuebunny/crossref_metadata_2025 huggingface dataset:
Migration and differentiation of neural progenitor cells from two different regions of embryonic central nervous system after transplantation into the intact spinal cord
Authors: Enomoto Mitsuhiro , Shinomiya Kenichi , Okabe Shigeo
Published: December 2004

Transplantation of in vitro‐expanded neural stem cells (NSCs) is a potentially powerful tool to repair functions of the injured spinal cord. A prerequisite for the successful transplantation therapy is identification of optimized experimental parameters that can promote maximal survival, extensive migration and selective differentiation of the transplanted NSC population in the spinal cord. To this end, we evaluated the basic characteristics of NSC‐like cells from two different donor sources, the embryonic hippocampus and spinal cord, after transplantation into the neonatal spinal cord. Proliferation and differentiation phenotypes of both NSC‐like cells can be controlled by the concentration of fibroblast growth factor‐2 (FGF‐2) in vitro. Both NSC‐like cells can survive within the environment of the intact neonatal spinal cord and showed extensive migratory behaviour shortly after transplantation. However, quantitative analysis revealed preferential migration of hippocampus‐derived cells in the dorsal white matter. Both NSC‐like cells showed restricted phenotype toward the oligodendroglial lineage after transplantation. Transplantation of the mixture of two cell types revealed selective survival of hippocampus‐derived NSC‐like cells. This study indicates the possibility of transplanting hippocampus‐derived NSCs to supply the cell source for immature oligodendrocytes, which are thought to be essential for both the myelination and trophic support of regenerating axons in the dorsal white matter of the spinal cord.
Extra‐cellular dopamine increases in the paraventricular nucleus of male rats during sexual activity
Authors: Melis Maria Rosaria , Succu Salvatora , Mascia Maria Stefania , Cortis Luca , Argiolas Antonio
Published: December 2004

Dopamine and 3,4‐dihydroxyphenylacetic acid (DOPAC) concentrations were measured in the dialysate obtained with vertical microdialysis probes implanted into the paraventricular nucleus of the hypothalamus of sexually potent male rats. Animals showed noncontact erections when put in the presence of, and copulated with a receptive (ovarietomized oestrogen and progesterone primed) female rat. Dopamine and DOPAC concentrations in the paraventricular dialysate increased 140% and 19%, respectively, above baseline values during exposure to the receptive female and 280% and 31%, respectively, during copulation. No changes in dopamine and DOPAC concentrations were detected in the paraventricular dialysate when sexually potent male rats were exposed to nonreceptive (ovariectomized not oestrogen plus progesterone primed) female rats. These results confirm the involvement of the paraventricular nucleus in control of erectile function and copulatory behaviour and show for the first time that dopamine neurotransmission is increased in this hypothalamic nucleus when erection occurs in physiological contexts.
Perinatal maturation of the mouse respiratory rhythm‐generator: in vivo and in vitro studies
Authors: Viemari Jean‐Charles , Burnet Henri , Bévengut Michelle , Hilaire Gérard
Published: December 2004

In vivo (plethysmography) and in vitro (en bloc preparations) experiments were performed from embryonic day 16 (E16) to postnatal day 9 (P9) in order to analyse the perinatal maturation of the respiratory rhythm‐generator in mice. At E16, delivered foetuses did not ventilate and survive but at E18 they breathed at about 110 cycles/min with respiratory cycles of variable individual duration. From E18 to P0–P2, the respiratory cycles stabilised without changes in the breathing parameters. However, these increased several‐fold during the next days. Hypoxia increased breathing frequency from E18–P5 and only significantly affected ventilation from P3 onwards. At E16, in vitro medullary preparations (pons resection) produced rhythmic phrenic bursts at a low frequency (about 5 cycles/min) with variable cycle duration. At E18, their frequency doubled but cycle duration remained variable. After birth, the frequency did not change although cycle duration stabilised. At E18 and P0–P2, the in vitro frequency decreased by around 50% under hypoxia, increased by 40–50% under noradrenaline or substance P and was permanently depressed by the pontine A5 areas. At E16 however, hypoxia had no effects, both noradrenaline and substance P drastically increased the frequency and area A5 inhibition was not expressed at this time. At E18 and P0–P2, electrical stimulation and electrolytic lesion of the rostral ventrolateral medulla affected the in vitro rhythm but failed to induce convincing effects at E16. Thus, a major maturational step in respiratory rhythmogenesis occurs between E16–E18, in agreement with the concept of multiple rhythmogenic mechanisms.
Serotonin inhibits glutamate‐ but not PACAP‐induced per gene expression in the rat suprachiasmatic nucleus at night
Authors: Sanggaard K. M. , Hannibal J. , Fahrenkrug J.
Published: December 2004

Circadian rhythms of physiology and behaviour generated by the brain's biological clock located in the suprachiasmatic nucleus are entrained by light via the retinohypothalamic tract. Two neurotransmitters, glutamate and pituitary adenylate cyclase‐activating polypeptide (PACAP), found in this monosynaptic pathway mediate the effects of light to the clock. It is well known that not only light entrains the clock. Nonphotic cues mediated by neurotransmitters such as serotonin reaching the suprachiasmatic nucleus from the midbrain raphe nucleus modulate light‐induced phase shifts at night. Two clock genes, per1 and per2, have been attributed a role in light‐induced phase shift. In the present study, using an in vitro brain slice model and quantitative in situ hybridization for per1 and per2, we have shown that serotonin induces per1 gene expression at late subjective night but not at early night. Furthermore, serotonin application before glutamate or PACAP blocked glutamate‐induced per1 expression at early night and per2 gene expression at late night. In contrast, serotonin did not influence PACAP‐induced per gene expression at late night. Triple antigen immunohistochemistry and confocal microscopy supported both a pre‐ and post‐synaptic interaction of retinohypothalamic tract (PACAP‐immunoreactive) and serotonin projections on vasoactive intestinal peptide‐ and gastrin‐releasing peptide‐containing cell bodies in the ventro‐lateral suprachiasmatic nucleus. Our findings suggest that the per genes could be the molecular target for the modulatory effects of serotonin on light signalling to the clock.
Altered hemispheric asymmetry of auditory P100m in dyslexia
Authors: Heim Sabine , Eulitz Carsten , Elbert Thomas
Published: December 2004

In various studies, deviances of hemispheric laterality in the organization of the perisylvian region in dyslexia have been suggested. Although associated with impaired language functioning, the clinical significance of atypical cerebral lateralization remains unclear. The present study examined interhemispheric source differences of magnetic responses to the German synthetic syllable [ba:] in the auditory cortex of 14 dyslexic children and 12 normally literate controls aged 8–15 years. In all subjects, two main deflections, P100m and N260m, were evident in the responses over each hemisphere. While in the control group the right P100m dipole was located more anterior than the corresponding dipole of the left hemisphere, the dyslexic group displayed a rather symmetrical source configuration between the hemispheres. This symmetry reflected a deviance in the right perisylvian region for the dyslexic subjects' P100m, which was generated ≈1 cm more posterior than the response in controls. The deviation was also obvious relative to the source location of the later component, N260m, which did not systematically differ between the participant groups. Our results suggest that the altered hemispheric asymmetry reflects an atypical organization of the right hemisphere in children and adolescents with dyslexia.
Potentiation of parkinsonian symptoms by depletion of locus coeruleus noradrenaline in 6‐hydroxydopamine‐induced partial degeneration of substantia nigra in rats
Authors: Srinivasan J. , Schmidt W. J.
Published: December 2004

Parkinson's disease is characterized not only by a progressive loss of dopaminergic neurons in the substantia nigra but also by a degeneration of locus coeruleus noradrenergic neurons. The present study addresses the question of whether a partial neurodegeneration of dopaminergic neurons using 6‐hydroxydopamine in rat, not sufficient to produce motor disturbances, is potentiated by prior selective denervation of locus coeruleus noradrenergic terminal fields using N‐ethyl‐2‐bromobenzylamine. Two types of denervations, one causing dopamine deficiency alone and the other causing noradrenaline and dopamine deficiency, were performed. Noradrenaline, 5‐hydroxytryptamine, 5‐hydroxyindole acetic acid, dopamine and its metabolites were analysed in various brain regions. Behaviour was evaluated by catalepsy tests and activity box. N‐ethyl‐2‐bromobenzylamine selectively depleted noradrenaline from neurons of locus coeruleus origin. Decreased dopamine content in the striatum, substantia nigra and pre‐frontal cortex was observed after dopaminergic lesion with 6‐hydroxydopamine (42.9%). Additional locus coeruleus noradrenaline depletion with N‐ethyl‐2‐bromobenzylamine aggravated the dopamine depletion (61.2%). The lesion in the noradrenergic and dopaminergic neurodegenerated group was not sufficient to induce consistent catalepsy and akinesia. However, after a subthreshold dose of haloperidol (0.1 mg/kg), the expression of catalepsy and akinesia was strong in the dual‐lesioned group and less in the 6‐hydroxydopamine‐lesioned group. These results indicate that denervation of locus coeruleus noradrenergic terminals with N‐ethyl‐2‐bromobenzylamine potentiates the 6‐hydroxydopamine‐induced partial dopaminergic neurodegeneration and parkinsonian symptoms. Based on the present findings and existing reports, it can be concluded that noradrenergic neurons of locus coeruleus have neuromodulatory and neuroprotective properties on the dopaminergic neurons of basal ganglia and that noradrenergic degeneration may contribute to the aetiology and pathophysiology of Parkinson's disease.
Long‐term potentiation in freely moving rats reveals asymmetries in thalamic and cortical inputs to the lateral amygdala
Authors: Doyère Valérie , Schafe Glenn E. , Sigurdsson Torfi , LeDoux Joseph E.
Published: December 2004

Long‐term memory underlying Pavlovian fear conditioning is believed to involve plasticity at sensory input synapses in the lateral nucleus of the amygdala (LA). A useful physiological model for studying synaptic plasticity is long‐term potentiation (LTP). LTP in the LA has been studied only in vitro or in anaesthetized rats. Here, we tested whether LTP can be induced in auditory input pathways to the LA in awake rats, and if so, whether it persists over days. In chronically implanted rats, extracellular field potentials evoked in the LA by stimulation of the auditory thalamus and the auditory association cortex, using test simulations and input/output (I/O) curves, were compared in the same animals after tetanization of either pathway alone or after combined tetanization. For both pathways, LTP was input‐specific and long lasting. LTP at cortical inputs exhibited the largest change at early time points (24 h) but faded within 3 days. In contrast, LTP at thalamic inputs, though smaller initially than cortical LTP, remained stable until at least 6 days. Comparisons of I/O curves indicated that the two pathways may rely on different mechanisms for the maintenance of LTP and may benefit differently from their coactivation. This is the first report of LTP at sensory inputs to the LA in awake animals. The results reveal important characteristics of synaptic plasticity in neuronal circuits of fear memory that could not have been revealed with in vitro preparations, and suggest a differential role of thalamic and cortical auditory afferents in long‐term memory of fear conditioning.
Long‐term potentiation recruits a trisynaptic excitatory associative network within the mouse dentate gyrus
Authors: Kleschevnikov Alexander M. , Routtenberg Aryeh
Published: December 2004

Granule cells of the hippocampal dentate gyrus receive two powerful excitatory inputs: the perforant path, originating from the entorhinal cortex, and the associational pathway, originating from mossy cells, the principal neurons of the dentate gyrus hilus. We examined the electrophysiological properties of the less well‐studied associational pathway and its interaction with the perforant path in the intact mouse hippocampus and then tested homosynaptic, trans‐synaptic and associative long‐term potentiation of these pathways. The associational pathway was either monosynaptically activated by stimulation within the inner molecular layer or trisynaptically activated after stimulation of the perforant path. Laminar profiles of extracellularly recorded associational pathway field potentials demonstrated a bell‐shaped curve with a peak in the inner molecular layer. Tetanization of the perforant path induced not only homosynaptic potentiation of the perforant path (162.4 ± 6.7% at 0.5–1.5 h after tetanus) but also heterosynaptic potentiation of the associational pathway (115.7 ± 4.9%). Direct tetanization of the associational pathway within the inner molecular layer was ineffective in either the septo‐temporal (97.2 ± 4.5%) or temporal‐septal (104.4 ± 4.6%) direction. In contrast, conjoint tetanization of the associational pathway with the perforant path potentiated the associational pathway responses in both the septo‐temporal (123.4 ± 5.8%) and the temporal‐septal (124.8 ± 7.3%) directions. Paired‐pulse facilitation was attenuated by long‐term potentiation in the perforant path and the associational pathway, suggesting pre‐synaptic involvement. These results demonstrate that long‐term potentiation of the associational pathway and the perforant path is a product of the network properties of the dentate gyrus rather than of each monosynaptic input alone. The architecture of this neural network may be designed for flexible dynamic associations of the afferent perforant path inputs to configure encoded information within hippocampal neuronal ensembles.
The role of CD36 in peripheral nerve remyelination after crush injury
Authors: Eto Masaki , Yoshikawa Hiroo , Fujimura Harutoshi , Naba Ichiro , Sumi‐Akamaru Hisae , Takayasu Satoshi , Itabe Hiroyuki , Sakoda Saburo
Published: December 2004

We previously demonstrated that the deficiency of class A macrophage scavenger receptor type I/II was involved in the delayed phagocytosis of degraded myelin by macrophages in class A macrophage scavenger receptor type I/II knockout mice after crush injury of the sciatic nerve [Naba et al. (2000) Exp. Neurol., 166, 83–89]. In order to elucidate the role of CD36, one of the scavenger receptors, here we inflicted crush injury to the sciatic nerves of CD36 knockout mice and investigated the remyelination after crush injury in comparison with that of class A macrophage scavenger receptor type I/II knockout mice. Although we previously reported a lot of onion‐bulbs in class A macrophage scavenger receptor type I/II knockout mice at 3 weeks, the number of onion‐bulbs was limited both in CD36 knockout mice and wild‐type mice. In the morphometry, the remyelination was seriously delayed, and the infiltrating macrophages into the nerve fascicles were quite frequent in CD36 knockout mice compared with wild‐type mice at 3 and 6 weeks postinjury. The immunohistochemistry with the monoclonal antibody reacted with oxidized phosphatidylcholine and oil red O staining were positive in wild‐type mice, but were negative in CD36 knockout mice, suggesting that the oxidation of phosphatidylcholine and the generation of neutral lipids in macrophages were disturbed in CD36 knockout mice. We hypothesize that the delayed phagocytosis by macrophages and the defect in reuse of lipids from degraded myelin are related to seriously delayed remyelination and a small number of onion‐bulbs in CD36 knockout mice.
Anterograde delivery of brain‐derived neurotrophic factor to striatum via nigral transduction of recombinant adeno‐associated virus increases neuronal death but promotes neurogenic response following stroke
Authors: Gustafsson Elin , Andsberg Gunnar , Darsalia Vladimer , Mohapel Paul , Mandel Ronald J. , Kirik Deniz , Lindvall Olle , Kokaia Zaal
Published: December 2004

To explore the role of brain‐derived neurotrophic factor for survival and generation of striatal neurons after stroke, recombinant adeno‐associated viral vectors carrying brain‐derived neurotrophic factor or green fluorescent protein genes were injected into right rat substantia nigra 4–5 weeks prior to 30 min ipsilateral of middle cerebral artery occlusion. The brain‐derived neurotrophic factor–recombinant adeno‐associated viral transduction markedly increased the production of brain‐derived neurotrophic factor protein by nigral cells. Brain‐derived neurotrophic factor was transported anterogradely to the striatum and released in biologically active form, as revealed by the hypertrophic response of striatal neuropeptide Y‐positive interneurons. Animals transduced with brain‐derived neurotrophic factor‐recombinant adeno‐associated virus also exhibited abnormalities in body posture and movements, including tilted body to the right, choreiform movements of left forelimb and head, and spontaneous, so‐called ‘barrel’ rotation along their long axis. The continuous delivery of brain‐derived neurotrophic factor had no effect on the survival of striatal projection neurons after stroke, but exaggerated the loss of cholinergic, and parvalbumin‐ and neuropeptide Y‐positive, γ‐aminobutyric acid‐ergic interneurons. The high brain‐derived neurotrophic factor levels in the animals subjected to stroke also gave rise to an increased number of striatal cells expressing doublecortin, a marker for migrating neuroblasts, and cells double‐labelled with the mitotic marker, 5‐bromo‐2′‐deoxyuridine‐5′monophosphate, and early neuronal (Hu) or striatal neuronal (Meis2) markers. Our findings indicate that long‐term anterograde delivery of high levels of brain‐derived neurotrophic factor increases the vulnerability of striatal interneurons to stroke‐induced damage. Concomitantly, brain‐derived neurotrophic factor potentiates the stroke‐induced neurogenic response, at least at early stages.
Distinct functions of Rac1 and Cdc42 during axon guidance and growth cone morphogenesis in Drosophila
Authors: Matsuura Ryouta , Tanaka Hideaki , Go Masahiro J.
Published: December 2004

Rho family small GTPases are thought to be key molecules in the regulation of cytoskeletal organization, especially for actin filaments. In order to examine the functions of Rac1 and Cdc42 in axon guidance at the midline of the central nervous system in Drosophila embryos, we either activated or inactivated Rac1 and Cdc42 in all postmitotic neurons. We found that the phenotypes of Cdc42 activation and Rac1 inactivation were similar to those of roundabout mutants, in that many extra axons crossed the midline. We also found that Rac1 inactivation is dominant over Roundabout receptor activation. Our observations indicate that Rac1 and Cdc42 have distinct functions in downstream signalling events triggered by Roundabout receptors. In order to further examine the functional difference between Rac1 and Cdc42 in the growth cone morphogenesis, we used primary embryonic cultures to closely observe neurite formation. We showed that activation of Rac1 and Cdc42 has distinct effects on neurite formation, particularly on growth cone morphology and the actin filaments within. Both Rac1 and Cdc42 activation induced large growth cones and long filopodia, but Cdc42 did so more efficiently than Rac1. Only Rac1 activation, however, induced thick actin bundles in the filopodia. We also found a clear difference between Rac1 and Cdc42 in terms of the response to an inhibitor of actin polymerization. Our results suggest that Cdc42 is specifically involved in the regulation of actin filaments in growth cones, whereas Rac1 is involved in additional functions.
Two oceans, two taxa and one mode of development: latitudinal diversity patterns of South American crabs and test for possible causal processes
Authors: Astorga Anna , Fernández Miriam , Boschi Enrique E. , Lagos Nelson
Published: December 2004

The latitudinal gradient of species diversity is a widely recognized but poorly understood phenomenon. In marine systems, differences in dispersal abilities among species may pose an additional problem in identifying the processes that affect diversity. We compared latitudinal diversity gradients along two parallel continental coasts, the east and west coasts of South America, of two groups of Crustacea (Brachyura and Anomura), which exclusively exhibit planktonic development. We also evaluated the species‐area and the energy‐input hypotheses. Diversity decreased with increasing latitude for both groups in both oceans. Results suggest that the spatial structure of sea surface temperature (SST) explains diversity of both groups at large, but not small (< 5°), scales. Range size and latitude were not correlated. We hypothesize that SST differentially affects taxa with contrasting modes of development, influencing patterns of diversity. We suggest that developmental modes of marine organisms should be considered in future diversity analyses.
Parameter drift stabilizes long‐range extinction forecasts
Authors: Halley J. M.
Published: December 2004

Estimates of the reliability of population viability analysis (PVA), accounting for uncertainties in model parameters, often arrive at confidence intervals for extinction probability so wide as to be almost meaningless. This lack of precision is a consequence of extreme sensitivity to average linear growth rate, when predicting to a distant time horizon. Longer‐term trends or drift in parameter values (a form of ‘reddened’ environmental variability) will also affect the accuracy of such forecasts. This letter reports how, contrary to intuition, introducing such a component of variability may improve the precision of extinction forecasts. The paradoxical result arises because the dependence of extinction probability on growth rate is weakened, and shifted onto other parameters (e.g. diffusion strength) where dependence is less sensitive. This offers hope that, with reasonable knowledge of environmental stochasticity, it may still be meaningful to carry out longer range PVAs.
The role of host sex in parasite dynamics: field experiments on the yellow‐necked mouseApodemus flavicollis
Authors: Ferrari Nicola , Cattadori Isabella M. , Nespereira Javier , Rizzoli Annapaola , Hudson Peter J.
Published: December 2004

We investigated the role of host sex in parasite transmission and questioned: ‘Is host sex important in influencing the dynamics of infection in free living animal populations?’ We experimentally reduced the helminth community of either males or females in a yellow‐necked mice (Apodemus flavicollis) population using an anthelmintic, in replicated trapping areas, and subsequently monitored the prevalence and intensity of macroparasites in the untreated sex. We focussed on the dominant parasiteHeligmosomoides polygyrusand found that reducing parasites in males caused a consistent reduction of parasitic intensity in females, estimated through faecal egg counts, but the removal of parasites in females had no significant influence on the parasites in males. This finding suggests that males are responsible for driving the parasite infection in the host population and females may play a relatively trivial role. The possible mechanisms promoting such patterns are discussed.
Social life‐history response to individual immune challenge of workers of Bombus terrestris L.: a possible new cooperative phenomenon
Authors: Moret Yannick , Schmid‐Hempel Paul
Published: December 2004

Parasites typically reduce host survival or fecundity. To minimize fitness loss, hosts can make temporal adjustments of their reproductive effort. To date such plastic shifts of life‐history traits in response to parasitism are only known from solitary organisms where infected individuals can react by themselves. In the case of social insects, where brood care and reproductive effort is shared between reproductive individuals (typically the queen) and workers, adjustments of the reproductive effort would depend on collective decision‐making. We tested for this possibility by experimentally activating the immune response of individual workers in colonies of the bumblebee, Bombus terrestris L. This induction resulted, in combination with environmental conditions, in a reduction of fitness of the social unity (i.e. colony success, measured by number and biomass of offspring) and a collective response towards earlier reproduction. As both phenomena are expressed at the level of the colony, the result suggests that key elements of the use of immune defence have been maintained through the evolutionary transition to sociality.
Are viruses driving microbial diversification and diversity?
Authors: Weinbauer Markus G. , Rassoulzadegan Fereidoun
Published: December 2004

Viruses can influence the genetic diversity of prokaryotes in various ways. They can affect the community composition of prokaryotes by ‘killing the winner’ and keeping in check competitive dominants. This may sustain species richness and the amount of information encoded in genomes. Viruses can also transfer (viral and host) genes between species. Such mechanisms have probably influenced the speciation of prokaryotes. Whole‐genome sequencing has clearly revealed the importance of (virus‐mediated) gene transfer. However, its significance for the ecological performance of aquatic microbial communities is only poorly studied, although the few available reports indicate a large potential. Here, we present data supporting the hypothesis that viral genes and viral activity generate genetic variability of prokaryotes and are a driving force for ecological functioning and evolutionary change.
Functional gene diversity analysis in BTEX contaminated soils by means of PCR‐SSCP DNA fingerprinting: comparative diversity assessment against bacterial isolates and PCR‐DNA clone libraries
Authors: Junca Howard , Pieper Dietmar H.
Published: December 2004

Developments in molecular biology based techniques have led to rapid and reliable tools to characterize microbial community structures and to monitor their dynamics under in situ conditions. However, there has been a distinct lack of emphasis on monitoring the functional diversity in the environment. Genes encoding catechol 2,3‐dioxygenases (C23O), as key enzymes of various aerobic aromatic degradation pathways, were used as functional targets to assess the catabolic gene diversity in differentially BTEX contaminated environments by polymerase chain reaction‐single‐strand conformation polymorphism (PCR‐SSCP). Site specific PCR‐SSCP fingerprints were obtained, showing that gene diversity experienced shifts correlated to temporal changes and levels of contamination. PCR‐SSCP enabled the recovery of predominant gene polymorphs, and results closely matched with the information retrieved from random sequencing of PCR‐DNA clone libraries. A new method for isolating strains capable of growing on BTEX compounds was developed to diminish preselection or enrichment bias and to assess the function of predominant gene polymorphs. C23O abundance in isolates correlated with the levels of BTEX pollution in the soil samples analysed. Isolates harbouring C23O genes, identical to the gene polymorph predominant in all contaminated sites analysed, showed an unexpected benzene but not toluene mineralizing phenotype whereas isolates harbouring a C23O gene variant differing by a single point mutation and observed in highly polluted sites only, were capable, among some other isolates, to mineralize benzene and toluene, indicating a catabolically determined sharing of carbon sources on‐site. The PCR‐SSCP technique is thus a powerful tool for assessing the diversity of functional genes and the identification of predominant gene polymorphs in environmental samples as a prerequisite to understand the functioning of microbial communities.
Physiological and molecular genetic evaluation of the dechlorination agent, pyridine‐2,6‐bis(monothiocarboxylic acid) (PDTC) as a secondary siderophore of Pseudomonas
Authors: Lewis Thomas A. , Leach Lynne , Morales Sergio , Austin Paula R. , Hartwell Hadley J. , Kaplan Benjamin , Forker Cynthia , Meyer Jean‐Marie
Published: December 2004

The bacterial metabolite and transition metal chelator pyridine‐2,6‐dithiocarboxylic acid (PDTC), promotes a novel and effective means of dechlorination of the toxic and carcinogenic pollutant, carbon tetrachloride. Pyridine‐2,6‐dithiocarboxylic acid has been presumed to act as a siderophore in the Pseudomonas strains known to produce it. To explore further the physiological function of PDTC production, we have examined its regulation, the phenotype of PDTC‐negative (pdt) mutants, and envelope proteins associated with PDTC in P. putida strain DSM 3601. Aspects of the regulation of PDTC production and outer membrane protein composition were consistent with siderophore function. Pyridine‐2,6‐dithiocarboxylic acid production was coordinated with production of the well‐characterized siderophore pyoverdine; exogenously added pyoverdine led to decreased PDTC production, and added PDTC led to decreased pyoverdine production. Positive regulation of a chromosomal pdtI‐xylE transcriptional fusion, and of a 66 kDa outer membrane protein (IROMP), was seen in response to exogenous PDTC. Tests with transition metal chelators indicated that PDTC could provide a benefit under conditions of metal limitation; the loss of PDTC biosynthetic capacity caused by a pdtI transposon insertion resulted in increased sensitivity to 1,10‐phenanthroline, a chelator that has high affinity for a range of divalent transition metals (e.g. Fe2+, Cu2+, Zn2+). Exogenously added PDTC could also suppress a phenotype of pyoverdine‐negative (Pvd–) mutants, that of sensitivity to EDDHA, a chelator with higher affinity and specificity for Fe3+. Measurement of 59Fe incorporation showed uptake from 59Fe:PDTC by DSM 3601 grown in low‐iron medium, but not by cells grown in high iron medium, or by the pdtI mutant, which did not show expression of the 66 kDa envelope protein. These data verified a siderophore function for PDTC, and have implicated it in the uptake of transition metals in addition to iron.
Functional improvement in cerebral palsy patients treated with botulinum toxin A injections – preliminary results
Authors: Sławek J. , Klimont L.
Published: December 2004

Authors report the preliminary results of an open‐label, prospective study to evaluate a functional benefit of botulinum toxin type A injections in diparetic cerebral palsy patients, using gross motor function measure (GMFM) score. In a group of 14 children (mean age 3.9 years, range 2–6) treated with Dysport 30 IU/kg, a statistically significant improvement (P < 0.05) was noticed in both simple measurements (Modified Ashworth Scale, Selective Motor Control, Passive Range of Movements, Physician Rating Scale and parental Clinical Global Impression) and complex functions (GMFM dimensions D and E) after 1 and 3 months. However, the simple measurement scores decreased (but not to the baseline) after 3 months; surprisingly, GMFM scores were still increasing (7.7% change after 3 months and 11.3% change after 6 months in nine patients). These results are in concordance with a few other data published to date. The study may support the concept of persistent functional gain in long‐term treatment of spasticity caused by cerebral palsy with botulinum toxin type A.
Expectations of wheelchair‐dependency in recently diagnosed patients with multiple sclerosis and their partners
Authors: Janssens A. C. J. W. , De Boer J. B. , Van Doorn P. A. , Van Der Ploeg H. M. , Van Der Meché F. G. A. , Passchier J. , Hintzen R. Q.
Published: December 2004

The aim of the present paper was to quantify expectations of wheelchair‐dependency in patients recently diagnosed with MS (n = 101) and their partners (n = 78). Expectations focused on the risk and seriousness of becoming wheelchair‐dependent in 2 years, 10 years or lifetime. Expectations were compared with natural history data, compared between patients and their partners, and related to clinical characteristics. Our results show that patients overestimated their 2‐year and 10‐year risks of wheelchair‐dependency, but underestimated their lifetime risks. A large number of patients were uncertain about their 2‐year risk, even those with no or only minimal disability [Expanded Disability Status Scale (EDSS) <3.0]. One‐third of the patients perceived the 10‐year and lifetime risk to be 50%, which, as they explained in the interviews, reflected their uncertainty: they did not know what to expect – it might happen or not. Patients with more functional limitations had higher perceptions of risk, but lower perceptions of seriousness. Concordance in perceived risk and seriousness between patients and partners was moderate. The overestimation of the short‐term risks and the substantial differences in expectations within couples warrant further research on the impact of expectations on their treatment decisions and psychological well‐being.
Interactions Between Oxcarbazepine and Conventional Antiepileptic Drugs in the Maximal Electroshock Test in Mice: An Isobolographic Analysis
Authors: Luszczki Jarogniew J. , Borowicz Kinga K. , Swiader Mariusz , Czuczwar Stanislaw J.
Published: December 2004

Summary:  Purpose: The aim of this study was to determine the types of interactions between oxcarbazepine (OCBZ) and conventional antiepileptic drugs (AEDs) against maximal electroshock‐induced seizures (MES test) in mice, by using a method of isobolographic analysis.

Methods: Adverse effects of combinations were evaluated in the chimney test (motor performance), also using the isobolographic method, which allowed determination of the median toxic dose (TD50) values for individual combinations; thus the protective indices could be determined.

Results: OCBZ and phenytoin (PHT) at the fixed‐ratio combination of 1:1 were significantly infraadditive (antagonistic) with respect to the antiseizure protection against MES and simultaneously additive in terms of side effects in the chimney test. Interestingly, combinations between OCBZ and clonazepam (CZP) in the MES test proved antagonistic or synergistic, depending on the proportion of both AEDs in the mixture. Low doses of OCBZ with high doses of CZP exerted antagonism. Conversely, high doses of OCBZ combined with low doses of CZP resulted in a synergistic interaction. Remaining combinations between OCBZ and phenobarbital, valproate, or carbamazepine were purely additive, either as regards the anticonvulsant activity against MES or in terms of motor impairment in the chimney test.

Conclusions: The results of this study indicate that interaction of OCBZ and CZP at fixed‐ratio combination of 1:1 might be profitable from a clinical point of view. Conversely, combinations of OCBZ with PHT may not be clinically efficient.
Pentylenetetrazol‐induced Seizures in Immature Rats Provoke Long‐term Changes in Adult Hippocampal Cholinergic Excitability
Authors: Meilleur Sébastien , Aznavour Nicolas , Descarries Laurent , Carmant Lionel , Mamer Orval A. , Psarropoulou Caterina
Published: December 2004

Summary:  Purpose: We previously demonstrated that the anticholinesterase eserine provokes interictal‐like discharges in the CA3 area of hippocampal slices from rats in which generalized seizures had been induced by pentylenetetrazol (PTZ) when immature. In this study, we investigated several factors as the possible mechanism for this effect, including age at convulsions.

Methods: Rats were injected with PTZ on postnatal day (P) 18–20 or >P60, and neuronal activity was recorded intra‐ and extracellularly from CA3 5–10 or >40 days later. In additional experiments, convulsions were triggered by kainate or were blocked by pentobarbital. Hippocampal (a) acetylcholine (ACh) innervation density was measured by immunocytochemistry, and ACh and γ‐aminobutyric acid (GABA) contents were determined by high‐performance liquid chromatography (HPLC)‐electrospray ionization.

Results: The excitatory effect of eserine was the most consistent in slices from rats PTZ‐treated when immature and after the long interval, whereas the reverse was true in rats treated as adults. This effect was dependent on the occurrence of a seizure and was less prevalent when the seizure had been provoked by kainate. Adult animals PTZ‐treated at P20 did not differ from control in (a) poly‐ or monosynaptic GABAA and GABAB CA3 inhibitory postsynaptic potentials (IPSPs); (b) density of ACh innervation; or (c) tissue content of ACh and GABA.

Conclusions: A PTZ‐induced generalized seizure in immature rat provokes endogenous ACh‐induced interictal‐like discharges in adult hippocampal CA3. This effect is only transiently observed if the seizure was induced in adult. It does not appear to be related to a change in GABAergic inhibition, in density of ACh innervation, or in ACh or GABA content.
Sudden Cardiac Death: Exploring the Limits of Our Knowledge
Authors: MYERBURG ROBERT J.
Published: December 2004

Sudden Cardiac Death. Despite progress in epidemiology, clinical profiling, and interventions, sudden cardiac death remains a major clinical and public health problem. There remain important unresolved issues that are challenges for future progress. Among these are a better understanding of the magnitude of the problem and methods of profiling risk for individuals, the etiology and mechanisms of cardiac arrest in individuals with and without previously identified structural heart disease, clinical strategies for primary and secondary prevention of sudden cardiac death, and further development of community programs for improving cardiac arrest survival in the out‐ofhospital environment. Each of these areas of endeavor and potential progress are reviewed and discussed.
Behavioral alterations induced by repeated testing in C57BL/6J and 129S2/Sv mice: implications for phenotyping screens
Authors: Võikar V. , Vasar E. , Rauvala H.
Published: December 2004

The C57BL/6JOlaHsd and 129S2/SvHsd mice were tested in a battery designed for behavioral phenotyping of genetically modified mice. The study was performed in order to reveal the effect of training history on the behavior by comparison with the experimentally naïve mice in the same tests. Significant strain differences were obtained in all experiments. Previous handling and testing reduced exploratory activity and emotionality significantly in the mice. The coordination ability was better and nociceptive sensitivity was increased in the trained mice. The contextual fear was reduced whereas the cued fear was enhanced in the experienced mice. The training history did not alter initial learning in the water maze. However, after reversal learning the naïve mice displayed significant preference for both old and new platform locations, whereas the battery animals did not exhibit preference to the old location. The experienced mice appeared to be less active in the forced swimming test and exhibited decreased conditioned taste aversion. The influence of test history was strain‐dependent in certain cases. Therefore, the experience has substantial consequences on the behavior, mainly by reducing exploratory activity, and the previous experience of the animals has always to be considered in the analysis of genetically modified mice.
Cooperation between Drosophila flies in searching behavior
Authors: Tinette S. , Zhang L. , Robichon A.
Published: December 2004

In Drosophila melanogaster food search behaviour, groups of flies swarm around and aggregate on patches of food. We wondered whether flies explore their environment in a cooperative way as interactions between individual flies within a population might influence the flies' ability to locate food sources. We have shown that the food search behavior in the fruit fly Drosophila is a two‐step process. Firstly, ‘primer’ flies search the environment and randomly land on different food patches. Secondly, the remaining group of flies move to the most favorable food source and aggregate there. We call this a ‘search–aggregation’ cycle. Our data demonstrate that flies do not individually assess all available food resources. Rather, social interactions between flies appear to affect their choice of a specific food patch. A genetic analysis of this ‘search–aggregation’ behavior shows that flies carrying mutations in specific genes (for example, the dunce (dnc) gene which codes for a phosphodiesterase) were defective in this search–aggregation behavior when compared to normal flies. Future investigations of the neuronal signaling involved in this behavior will help us to understand the complexities of this aspect of Drosophila social behaviour.
Tooth loss and caries prevalence in very old Swedish people: the relationship to cognitive function and functional ability
Authors: Avlund Kirsten , Holm‐Pedersen Poul , Morse Douglas E. , Viitanen Matti , Winblad Bengt
Published: December 2004

Objective:  To analyse whether cognitive function and functional ability are related to oral health among community‐dwelling older people over the age of 80 years.

Background:  This cross‐sectional study is based on the Kungsholmen Elders Oral Health Survey (KEOHS). The study included oral examinations carried out in two local clinics by standardised examiners and interviews using structured questionnaires.

Materials and Methods:  Altogether 159 individuals were included in this study. Coronal caries and root caries were assessed using the National Institute of Dental and Craniofacial Research (NIDCR) diagnostic criteria. Cognitive function was assessed by the Mini‐Mental State Examination (MMSE) index and functional ability was assessed by a global measure of self‐reported changes.

Results:  Older adults with a low MMSE score (≤23) tended to have a higher risk of coronal caries than those with higher scores. Participants with mild cognitive decline (MMSE = 24–26) and with a decrease in functional ability had a significantly higher risk of root caries. These associations changed little when adjusted by the covariates. In addition, people with a low MMSE (0–23) had a four times higher risk of not using dental services regularly. This result was unchanged after adjusting for the variables studied.

Conclusions:  This study revealed associations between the cognitive and functional status of the individual and aspects of oral health, that may contribute to a deeper understanding of the background of oral health status in older adults.
Triple-Shock-Wave Intersections
Authors: Sternberg Joseph
Published: December 2004

In the Mach reflection of weak shock waves, there has been a wide difference between theory and experiment for the shock wave angles at the triple point. Using the electric tank analogy in the hodograph to obtain the shock patterns it is found that the shock waves are so strongly curved near the intersection that the triple point angles cannot be observed in the laboratory. However, it is shown that the visible shock patterns are apparently inconsistent with the hodograph boundaries specified by the existing triple point theory. The effect of shock wave thickness on the boundary conditions at the triple point is then examined. It is shown that at the intersection there must be a non-Rankine-Hugoniot shock wave zone separating the three R-H shock waves. It follows that for weak shock waves where the shock curvatures → ∞ at the triple point, the simple boundary conditions of equal pressure and direction are invalid for a real fluid. A semiquantitative description is then given of a real fluid model which is consistent with the experimental data and with the Navier-Stokes equations. The examination of this model reveals the formidable difficulties in the way of obtaining a detailed mathematical description of a triple shock wave intersection in a real fluid. The question of the solution for the limiting case as μ → 0 is also discussed.
On the Inertial-Electrostatic Confinement of a Plasma
Authors: Elmore William C. , Tuck James L. , Watson Kenneth M.
Published: December 2004

A system in which electrons are projected radially inwards from a spherical surface, has been proposed for the confinement of a plasma at thermonuclear temperatures. The equilibrium, economics, and stability of such a system are discussed theoretically.

Although we conclude that it is of doubtful utility as a thermonuclear reactor, it may be possible to produce in this way small regions of thermonuclear plasma for study. The device appears to be unstable at economic densities. The stability is discussed in terms of a virial, which turns out to be mathematically tractable in this geometry.
Characteristic Manifolds in Three-Dimensional Unsteady Magnetohydrodynamics
Authors: Ong Rudi S.
Published: December 2004

The technique developed in the general theory of discontinuities is applied to the basic equations of unsteady magnetohydrodynamics in order to find the conditions to be satisfied by the discontinuities in the derivatives of the significant flow and magnetic field parameters. In the formulation of the basic equations use is made of the ``magnetohydrodynamic approximation.'' This amounts to the assumption that the magnetic energy is very large compared with the electric energy, or physically, that the displacement current is negligible. The fluid itself is considered to be infinitely conductive, inviscid, and compressible. With the aid of the relations satisfied by the jumps in the derivatives of the parameters the various characteristic manifolds are found. Finally, it is shown that these manifolds are hypersurfaces along which small disturbances and weak shocks are propagated.
Fluctuation Measurements in a Supersonic Turbulent Boundary Layer
Authors: Kistler Alan L.
Published: December 2004

Hot-wire measurements of the fluctuations in turbulent, constant-pressure boundary layers have been made at Mach numbers of 1.72, 3.56, and 4.76 and a Reynolds number based on momentum thickness of about 30 000. The distribution of the static-temperature fluctuation levels through the boundary layer is approximately similar at the various Mach numbers, and the levels are proportional to the mean static-temperature difference across the boundary layer. A decrease of the velocity fluctuation levels is observed as the Mach number is increased. There is a high negative correlation between the velocity and temperature fluctuations at all Mach numbers.
Combined Forced and Free Convection in a Boundary Layer Flow
Authors: Sparrow E. M. , Eichhorn R. , Gregg J. L.
Published: December 2004

Consideration is given to the combined forced and free convection flow and heat transfer about a nonisothermal body subjected to a nonuniform free stream velocity. Similar solutions for the laminar boundary layer equations are found to exist when the free stream velocity and surface temperature vary respectively as xm and x2m−1. The parameter controlling the relative importance of the free and forced convection is Gr/Re2. A flow separation phenomenon may occur when the forced and free convection act in opposite directions. Extensive numerical solutions of the transformed boundary layer equations have been carried out for the cases of uniform wall temperature and uniform wall heat flux for a Prandtl number of 0.7 (gases) over a wide range of values of Gr/Re2. Results are reported for the heat transfer, shear stress, and velocity and temperature fields. Criteria are given for cataloging flows as purely forced, purely free, and mixed.