bluuebunny/crossref_metadata_2025 huggingface dataset:
Generalized Tuberculosis in Llamas (Lama glama) Due toMycobacterium microti
Authors: Oevermann A. , Pfyffer G. E. , Zanolari P. , Meylan M. , Robert N.
Published: April 2004

Necropsy of two llamas revealed numerous caseous nodules containing abundant acid-fast bacilli (AFB) in various organs. The AFB were identified by spoligotyping asMycobacterium microti, vole type. Infection caused byM. microtishould be considered in the differential diagnosis of debilitating diseases in New World camelids.
Analyse du flux de Poiseuille bidimensionnel via l'équation de Boltzmann
Authors: Sabbane M , Tij M
Published: April 2004

The two-dimensional Poiseuille flow induced by an external force is analysed in the framework of BoltzmannMaxwell kinetic theory. In the limit of small Knudsen numbers (Kn [Formula: see text] 0.1), Boltzmann's nonlinear equation, written in terms of moments, is solved using perturbation theory. In our results, the hydrodynamic variable profiles are determined up to the fourth order in the perturbation parameter. Nonetheless, the method of solution remains valid to obtain all physical quantities of a gas undergoing Poiseuille flow. The major conclusion of our analysis has two elements. First, the profiles of hydrodynamic variables in two dimensions differ quantitatively (and sometimes qualitatively) from those in plane geometry. Thus, the Poiseuille flow representation in a cylindrical pipe is more accurate than in a canal between two parallel planes. Second, a critical comparaison between the theoretical predictions of the kinetic theory and those of NavierStokes shows that the two theories agree only up to the first order of perturbation. Starting at the second order, the difference between the two increases. Thus, within the limit of validity of the present study, the description by NavierStokes remains insufficient to predict the correct profiles for the hydrodynamic variables in the Poisseuille flow. [Journal translation]
Stabilized jellium model and structural relaxation effects on the fragmentation energies of ionized silver clusters
Authors: Payami M
Published: April 2004

Using the stabilized jellium model (SJM) in two schemes of "relaxed" and "rigid", we calculate the dissociation energies and the fission-barrier heights for the binary fragmentations of singly-ionized and doubly-ionized Ag clusters. In the calculations, we assume spherical geometries for the clusters. Comparison of the fragmentation energies in the two schemes show differences that are significant. This result reveals the advantages of the relaxed SJM over the rigid SJM in dynamical processes such as fragmentation. Comparing the relaxed SJM results and experimental data on fragmentation energies, it is possible to predict the sizes of the clusters just before their fragmentations. PACS Nos.: 36.40.Qv, 36.40.c, 36.40.Wa
Effects of charge non-neutrality and finite beta on the electron temperature gradient modes in Tokamaks
Authors: Hirose A , Liu D Z , Livingstone S , Hirose A
Published: April 2004

Local kinetic analysis of the electron temperature gradient (ETG) mode in Tokamaks indicates that the effects of charge non-neutrality are significant in the parameter regime of Tokamaks. The maximum growth rate occurs at (k/kDe)2 [Formula: see text] 0.5 when the electron temperature and density are varied over a wide range. The growth rate becomes dependent on the β factor even though the ETG mode is predominantly electrostatic. Finite β stabilization of the ETG mode requires a large ballooning parameter so as to cause an effective drift reversal. Mixing length estimate yields an electron thermal diffusivity χe [Formula: see text] qνTe (c/ωpe)2 [Formula: see text] / Ln where c/ωpe is the electron skin depth.

PACS Nos.: 52.65.Tt, 52.55.Fa, 52.35.Py
EXPERIMENTS WITH LEARNING OPENING STRATEGY IN THE GAME OF GO
Authors: HUANG TIMOTHY , CONNELL GRAEME , McQUADE BRYAN
Published: April 2004

We present an experimental methodology and results for a machine learning approach to learning opening strategy in the game of Go, a game for which the best computer programs play only at the level of an advanced beginning human player. While the evaluation function in most computer Go programs consists of a carefully crafted combination of pattern matchers, expert rules, and selective search, we employ a neural network trained by self-play using temporal difference learning. Our focus is on the sequence of moves made at the beginning of the game. Experimental results indicate that our approach is effective for learning opening strategy, that including higher-level features of the game can improve the quality of the learned evaluation function, and that different input representations of higher-level information can substantially affect performance.
INTELLIGENT PROTOCOL ADAPTATION IN A MEDICAL E-COLLABORATION ENVIRONMENT
Authors: GHINEA GHEORGHITA , MAGOULAS GEORGE D. , FRANK ANDREW O.
Published: April 2004

Distributed multimedia e-health applications have a set of specific requirements which must be taken into account if effective use is to be made of the limited resources provided by public telecommunication networks. Moreover, there is an architectural gap between the provision of network-level Quality of Service (QoS) and user requirements of e-health applications. In this paper, we address the problem of bridging this gap from a multi-criteria decision-making perspective in the context of a remote collaborative environment for back pain treatment. We propose adaptable data transport mechanisms, capable of responding to evolving networking, application and user requirements. To this end we present a framework which allows for not only construction of tailored multimedia communication protocols, but also for the inclusion of user requirements in such protocols. This is achieved by equipping our protocol adaptation mechanism with multi-criteria decision making based techniques that can be used to allocate resources according to their ratio-scale priorities in response to detection of system degradation or evolving user preferences. The applicability of our approach is illustrated in three usage scenarios.
Mitochondrial autophagy and injury in the liver in α1-antitrypsin deficiency
Authors: Teckman Jeffrey H. , An Jae-Koo , Blomenkamp Keith , Schmidt Bela , Perlmutter David
Published: April 2004

Homozygous, PIZZ α1-antitrypsin (α1-AT) deficiency is associated with chronic liver disease and hepatocellular carcinoma resulting from the toxic effects of mutant α1-anti-trypsin Z (α1-ATZ) protein retained in the endoplasmic reticulum (ER) of hepatocytes. However, the exact mechanism(s) by which retention of this aggregated mutant protein leads to cellular injury are still unknown. Previous studies have shown that retention of mutant α1-ATZ in the ER induces an intense autophagic response in hepatocytes. In this study, we present evidence that the autophagic response induced by ER retention of α1-ATZ also involves the mitochondria, with specific patterns of both mitochondrial autophagy and mitochondrial injury seen in cell culture models of α1-AT deficiency, in PiZ transgenic mouse liver, and in liver from α1-AT-deficient patients. Evidence for a unique pattern of caspase activation was also detected. Administration of cyclosporin A, an inhibitor of mitochondrial permeability transition, to PiZ mice was associated with a reduction in mitochondrial autophagy and injury and reduced mortality during experimental stress. These results provide evidence for the novel concept that mitochondrial damage and caspase activation play a role in the mechanism of liver cell injury in α1-AT deficiency and suggest the possibility of mechanism-based therapeutic interventions.
Proximal airway mucous cells of ovalbumin-sensitized and -challenged Brown Norway rats accumulate the neuropeptide calcitonin gene-related peptide
Authors: Larson Shawnessy D. , Plopper Charles G. , Baker Greg , Tarkington Brian K. , Decile Kendra C. , Pinkerton Kent , Mansoor James K. , Hyde Dallas M. , Schelegle Edward S.
Published: April 2004

Mucous cell hypersecretion and increased neuropeptide production play a role in the exacerbation of symptoms associated with asthma. The source of these neuropeptides have been confined to the contributions of small afferent nerves or possibly neuroendocrine cells. We tested the hypothesis that repeated exposure to allergen would alter the sources and abundance of neuropeptides in airways. Right middle lobes from rats (8 wk old) exposed to 2.5% ovalbumin (OVA) for five episodes (30 min each) or filtered air were inflation fixed with paraformaldehyde. The lobes were dissected to expose the airway tree, permeabilized with DMSO, and incubated in antibody to rat calcitonin gene-related peptide (CGRP), followed with a fluorochrome-labeled second antibody. CGRP-positive structures were imaged via confocal microscopy. Airways were later embedded in plastic and sectioned for cell identification. In animals challenged with OVA, CGRP-positive cells, not neuroendocrine or neuronal in origin (confirmed by a lack of protein gene product 9.5 signal), were recorded along the axial path. In section, this fluorescent signal was localized to granules within epithelial cells. Alcian blue/periodic acid-Schiff staining of these same sections positively identify these cells as mucous cells. Mucous cells of animals not challenged with OVA were not positive for CGRP. We conclude that episodic allergen exposure results in the accumulation of CGRP within mucous cells, creating a new source for the release of this neuropeptide within the airway.
Pressor responses to platelet-activating factor and thromboxane are mediated by Rho-kinase
Authors: Martin C. , Göggel R. , Ressmeyer A.-R. , Uhlig S.
Published: April 2004

Platelet-activating factor (PAF) contracts smooth muscle of airways and vessels primarily via release of thromboxane. Contraction of smooth muscle is thought to be mediated either by calcium and inositol trisphosphate (IP3)-dependent activation of the myosin light chain kinase or, alternatively, via the recently discovered Rho-kinase pathway. Here we investigated the contribution of these two pathways to PAF and thromboxane receptor-mediated broncho- and vasoconstriction in two different rat models: the isolated perfused lung (IPL) and precision-cut lung slices. Inhibition of the IP3receptor (1–10 μM xestospongin C) or inhibition of phosphatidylinositol-specific PLC (30 μM L-108) did not affect bronchoconstriction but attenuated the sustained vasoconstriction by PAF. Inhibition of myosin light chain kinase (35 μM ML-7) or of calmodulin kinase kinase (26 μM STO609), which regulates the phosphorylation of the myosin light chain, had only a small effect on PAF- or thromboxane-induced pressor responses. Similarly, calmidazolium (10 μM), which inhibits calmodulin-dependent proteins, only weakly reduced the airway responses. In contrast, Y-27632 (10 μM), a Rho-kinase inhibitor, attenuated the thromboxane release triggered by PAF and provided partial or complete inhibition against PAF- and thromboxane-induced pressor responses, respectively. Together, our data indicate that PAF- and thus thromboxane receptor-mediated smooth muscle contraction depends largely on the Rho-kinase pathway.
Biotelemetry transmitter implantation in rodents: impact on growth and circadian rhythms
Authors: Leon Lisa R. , Walker Larry D. , DuBose David A. , Stephenson Lou A.
Published: April 2004

The implantation of a biotelemetry transmitter for core body temperature (Tc) and motor activity (MA) measurements is hypothesized to have effects on growth and circadian rhythmicity depending on animal body-to-transmitter (B:T) size ratio. This study examined the impact of transmitter implantation (TM) on body weight, food intake (FI), water intake (WI), and circadian Tc and MA rhythms in mice (23.8 ± 0.04 g) and rats (311.5 ± 5.1 g) receiving no treatment (NT), anesthesia, laparotomy (LAP), and TM. The B:T size ratio was 6:1 and 84:1 for mice and rats, respectively. In mice, body weight required 14 days to recover to presurgical levels and never attained the level of the other groups. FI recovered in 3 days, whereas WI never reached presurgical levels. Rat body weight did not decrease below presurgical levels. FI and WI recovered to presurgical levels in rats by day 2 postsurgery. Anesthesia decreased mouse body weight for 1 wk, but was without effect in rats. LAP significantly decreased body weight for 5 days in mice and 1 day in rats, showing a significant effect of the surgical procedure in the absence of TM in both species. Circadian Tc and MA rhythms were evident within the first week in both species, indicating dissociation between circadian rhythmicity and recovery of growth variables. Cosinor analysis showed a TM effect on Tc min, Tc max, mesor, amplitude, and period of mice, whereas only the amplitude of the rhythm was affected in rats. These data indicate that a large B:T size ratio is associated with minimization of the adverse effects of surgical implantation. We recommend that B:T size ratio, recovery of presurgical body weight, and display of a robust circadian Tc and MA rhythm be established before collection of biotelemetry data collection under an experimental paradigm.
Bed rest attenuates sympathetic and pressor responses to isometric exercise in antigravity leg muscles in humans
Authors: Kamiya Atsunori , Michikami Daisaku , Shiozawa Tomoki , Iwase Satoshi , Hayano Junichiro , Kawada Toru , Sunagawa Kenji , Mano Tadaaki
Published: April 2004

Although spaceflight and bed rest are known to cause muscular atrophy in the antigravity muscles of the legs, the changes in sympathetic and cardiovascular responses to exercises using the atrophied muscles remain unknown. We hypothesized that bed rest would augment sympathetic responses to isometric exercise using antigravity leg muscles in humans. Ten healthy male volunteers were subjected to 14-day 6° head-down bed rest. Before and after bed rest, they performed isometric exercises using leg (plantar flexion) and forearm (handgrip) muscles, followed by 2-min postexercise muscle ischemia (PEMI) that continues to stimulate the muscle metaboreflex. These exercises were sustained to fatigue. We measured muscle sympathetic nerve activity (MSNA) in the contralateral resting leg by microneurography. In both pre- and post-bed-rest exercise tests, exercise intensities were set at 30 and 70% of the maximum voluntary force measured before bed rest. Bed rest attenuated the increase in MSNA in response to fatiguing plantar flexion by ∼70% at both exercise intensities (both P < 0.05 vs. before bed rest) and reduced the maximal voluntary force of plantar flexion by 15%. In contrast, bed rest did not alter the increase in MSNA response to fatiguing handgrip and had no effects on the maximal voluntary force of handgrip. Although PEMI sustained MSNA activation before bed rest in all trials, bed rest entirely eliminated the PEMI-induced increase in MSNA in leg exercises but partially attenuated it in forearm exercises. These results do not support our hypothesis but indicate that bed rest causes a reduction in isometric exercise-induced sympathetic activation in (probably atrophied) antigravity leg muscles.
NMDA receptor blockade attenuates CCK-induced reduction of real feeding but not sham feeding
Authors: Covasa Mihai , Ritter Robert C. , Burns Gilbert A.
Published: April 2004

Systemic injection of MK-801, a noncompetitive antagonist of N-methyl-d-aspartate (NMDA) receptor ion channels, increases meal size and delays satiation. We examined whether MK-801 increases food intake by directly interfering with actions of cholecystokinin (CCK). Prior administration of MK-801 (100 μg/kg ip) reversed the inhibitory effects of CCK-8 (2 and 4 μg/kg ip) on real feeding of both liquid and solid foods. MK-801 alone did not alter 30-min sham intake of 15% sucrose compared with intake after saline. Furthermore, while CCK-8 (2 or 4 μg/kg ip) reduced sham intake, this reduction was not attenuated by MK-801 pretreatment. To ascertain whether MK-801 attenuation of CCK-induced reduction of real feeding was associated with attenuated inhibition of gastric emptying, we tested the effect of MK-801 pretreatment on CCK-induced inhibition of gastric emptying of 5-ml saline loads. Ten-minute gastric emptying was accelerated after MK-801 (3.9 ± 0.2 ml) compared with saline vehicle (2.72 ± 0.2 ml). CCK-8 (0.5 μg/kg ip) reduced 10-min emptying to 1.36 ± 0.3 ml. Pretreatment with MK-801 did not significantly attenuate CCK-8-induced reduction of gastric emptying (0.9 ± 0.4 ml). This series of experiments demonstrates that blockade of NMDA ion channels reverses inhibition of real feeding by CCK. However, neither inhibition of sham feeding nor inhibition of gastric emptying by CCK is attenuated by MK-801. Therefore, increased food intake after NMDA receptor blockade is not caused by a direct interference with CCK-induced satiation. Rather, increased real feeding, either in the presence or absence of CCK, depends on blockade of NMDA receptor participation in other postoral feedback signals such as gastric sensation or gastric tone.
ANG II-induced excitation of paraventricular nucleus magnocellular neurons: a role for glutamate interneurons
Authors: Latchford K. J. , Ferguson A. V.
Published: April 2004

The hypothalamic paraventricular nucleus (PVN) plays a critical role in cardiovascular and neuroendocrine regulation. ANG II (ANG) acts throughout the periphery in the maintenance of fluid-electrolyte homeostasis and has also been demonstrated to act as a neurotransmitter in PVN exerting considerable influence on neuronal excitability in this nucleus. The mechanisms underlying the ANG-mediated excitation of PVN magnocellular neurons have yet to be determined. We have used whole cell patch-clamp techniques in hypothalamic slices to examine the effects of ANG on magnocellular neurons. Application of ANG resulted in a depolarization of magnocellular neurons, a response that was abolished in TTX, suggesting an indirect mechanism of action. Interestingly, ANG also increased the frequency of excitatory postsynaptic potentials/currents in magnocellular neurons, an effect that was abolished after application of the glutamate antagonist kynurenic acid. ANG was without effect on the amplitude of excitatory postsynaptic currents, suggesting a presynaptic action on an excitatory interneuron within PVN. The ANG-induced depolarization was shown to be sensitive to kynurenic acid, revealing the requisite role of glutamate in mediating the ANG-induced excitation of magnocellular neurons. These observations indicate that the ANGergic excitation of magnocellular PVN neurons are dependent on an increase in glutamatergic input and thus highlight the importance of a glutamate interneuron in mediating the effects of this neurotransmitter.
Activation of 5-HT1A receptors in raphe pallidus inhibits leptin-evoked increases in brown adipose tissue thermogenesis
Authors: Morrison Shaun F.
Published: April 2004

To elucidate the central neural pathways contributing to the thermogenic component of the autonomic response to intravenous administration of leptin, experiments were conducted in urethane-chloralose-anesthetized, ventilated rats to address 1) the role of neurons in the rostral ventromedial medulla, including raphe pallidus (RPa), in the leptin-evoked stimulation of brown adipose tissue (BAT) sympathetic nerve activity (SNA); and 2) the potential thermolytic effect of 5-hydroxytryptamine1A (5-HT1A) receptors on RPa neurons that influence BAT thermogenesis. Leptin (1 mg/kg) administration increased BAT SNA by 1,219% of control, BAT temperature by 2.8°C, expired CO2 by 1.8%, heart rate by 90 beats/min, and mean arterial pressure by 12 mmHg. Microinjection of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into RPa resulted in a prompt and sustained reversal of the leptin-evoked stimulation of BAT SNA, BAT thermogenesis, and heart rate, with these variables returning to their pre-leptin control levels. Subsequent microinjection of the selective 5-HT1A receptor antagonist WAY-100635 into RPa reversed the BAT thermolytic effects of 8-OH-DPAT, returning BAT SNA and BAT temperature to the elevated levels after leptin. In conclusion, activation of neurons in RPa, possibly BAT sympathetic premotor neurons, is essential for the increases in BAT SNA, BAT thermogenesis, and heart rate stimulated by intravenous administration of leptin. Neurons in RPa express 5-HT1A receptors whose activation leads to reversal of the BAT thermogenic and the cardiovascular responses to intravenous leptin, possibly through hyperpolarization of local sympathetic premotor neurons. These results contribute to our understanding of central neural substrates for the augmented energy expenditure stimulated by leptin.
Hindlimb unloading depresses corneal epithelial wound healing in mice
Authors: Li Zhijie , Rivera Chantal A. , Burns Alan R. , Smith C. Wayne
Published: April 2004

C57BL/6 mice were subjected to hindlimb unloading (HU) for a period of 3 wk to determine the possible effects on epithelial wound healing. A standardized corneal epithelial wound was performed, and parameters of the inflammatory response and reepithelialization were analyzed over an observation period of 96 h. Wound closure was significantly retarded in mice during HU with reepithelialization being delayed by ∼12 h. Both epithelial migration and cell division were significantly depressed and delayed. The inflammatory response to epithelial wounding was also significantly altered during HU. Neutrophils, as detected by the Gr-1 marker, were initially elevated above normal levels before wounding and during the first few hours afterward, but there was a significant reduction in neutrophil response to wounding at times where neutrophil influx and migration in controls were vigorous. A similar pattern was seen with CD11b+CD11c+ cells (monocyte lineage). Langerhans cells are normally resident within the peripheral corneal epithelium. They respond to injury by initially leaving the epithelial site within 6 h and returning to normal levels by 96 h, 2 days after reepithelialization is complete. During HU, this pattern is distinctly different, with Langerhans cell numbers slowly diminishing, reaching a nadir at 96 h, which is significantly below normal. Evidence for systemic effects of HU is provided by findings that collagen deposition within subcutaneous sponges was significantly reduced during HU. In conclusion, HU, a ground-based model simulating some physiological aspects of spaceflight, impairs wound repair of corneas. Multiple factors, both local and systemic, likely contribute to this delayed wound healing.
Impact of controlling shear rate on flow-mediated dilation responses in the brachial artery of humans
Authors: Pyke Kyra E. , Dwyer Erin M. , Tschakovsky Michael E.
Published: April 2004

The reactive hyperemia test (RHtest) evokes a transient increase in shear stress as a stimulus for endothelial-dependent flow-mediated vasodilation (EDFMD). We developed a noninvasive method to create controlled elevations in brachial artery (BA) shear rate (SR, estimate of shear stress), controlled hyperemia test (CHtest), and assessed the impact of this vs. the RHtest approach on EDFMD. Eight healthy subjects participated in two trials of each test on 3 separate days. For the CHtest, SR was step increased from 8 to 50 s−1, created by controlled release of BA compression during forearm heating. For the RHtest, transient increases in SR were achieved after 5 min of forearm occlusion. BA diameter and blood flow velocity (ultrasound) were measured upstream of compression and occlusion sites. Both tests elicited significant dilation (RHtest: 6.33 ± 3.12%; CHtest: 3.00 ± 1.05%). The CHtest resulted in 1) reduced between-subject SR and EDFMD variability vs. the RHtest [SR coefficient of variation (CV): 4.9% vs. 36.6%; EDFMD CV: 36.16% vs. 51.80%] and 2) virtual elimination of the impact of BA diameter on the peak EDFMD response (peak EDFMD vs. baseline diameter for RHtest, r2 = 0.64, P < 0.01, vs. CHtest, r2 = 0.14, P < 0.01). Normalization of the RHtest EDFMD response to the magnitude of the SR stimulus eliminated test differences in between-subject response variability. Reductions in trial-to-trial and day-to-day SR variability with the CHtest did not reduce EDFMD variability. Between-subject SR variability contributes to EDFMD variability with the RHtest. SR controls with the CHtest or RHtest response normalization are essential for examining EDFMD between groups differing in baseline arterial diameter.
Short-Term Synchronization Between Motor Units in Different Functional Subdivisions of the Human Flexor Digitorum Profundus Muscle
Authors: Reilly Karen T. , Nordstrom Michael A. , Schieber Marc H.
Published: April 2004

The ability to independently move the digits is limited by peripheral as well as central factors. A central limitation to independent finger movements might arise from the inability of the human nervous system to activate motor units (MUs) that exert force on one finger without also activating MUs that exert force on adjacent fingers. Short-term synchronization between MU pairs is thought to be the result of the two motoneurons receiving common input from last-order neuronal projections. The human flexor digitorum profundus (FDP) muscle contains four subdivisions, one for each of the fingers. We hypothesized that the distribution of MU synchrony within and between subdivisions of FDP might parallel the ability to selectively activate different functional subdivisions within FDP, and the ability to flex one digit independently of another. We found that the degree of MU synchrony indeed was not uniform among the different functional subdivisions of FDP; MUs acting on ulnar digits (d5, d4) were more synchronized than MUs acting on radial digits (d2, d3). Furthermore, synchrony was observed between MU pairs where each unit acted on a different digit and was highest when both units of a pair acted on the least-independent digits (d4, d5). This indicates that the CNS does not exert completely independent control over the different functional subdivisions of FDP. The strength of synchrony appears related to the inability to produce completely independent forces or movements with the digits. These observations reflect widespread divergence of last-order inputs within the FDP motoneuron pool, and we suggest that the organization of the CNS drive to this muscle contributes to the limited ability of humans to flex one digit in isolation from other digits.
Modulation of Single Channels Underlying Hippocampal L-Type Current Enhancement by Agonists Depends on the Permeant Ion
Authors: Tavalin Steven J. , Shepherd Dawn , Cloues Robin K. , Bowden Sarah E. H. , Marrion Neil V.
Published: April 2004

The influx of calcium (Ca2+) ions through L-type channels underlies many cellular processes, ranging from initiation of gene transcription to activation of Ca2+-activated potassium channels. L-type channels possess a diagnostic pharmacology, being enhanced by the dihydropyridine BAY K 8644 and benzoylpyrrole FPL 64176. It is assumed that the action of these compounds is independent of the ion conducted through the channel. In contrast to this assumption, modulation of L-type channel activity in acutely dissociated rat CA1 hippocampal neurons depended on the divalent ion identity. BAY K 8644 and FPL 64176 substantially increased single-channel open time only when barium (Ba2+) was the permeant ion. BAY K 8644 increased single-channel conductance when either Ba2+ or Ca2+ ions were the charge carrier, an effect not observed with FPL 64176. BAY K 8644 enhanced the whole cell L-type channel Ca2+- or Ba2+-carried current without a change in deactivation tail kinetics. In contrast, enhancement by FPL 64176 was associated with a dramatic slowing of deactivation kinetics only when Ba2+ and not Ca2+ was the charge carrier. Current activation was slowed by FPL 64176 with either charge carrier, an effect arising from a clustering of agonist-modified long-duration openings toward the end of the voltage step. These data indicate that agonists enhanced L-type current by distinct mechanisms dependent on the permeant ion, indicating that care must be considered when used as diagnostic tools.
Galanin Inhibits Gut-Related Vagal Neurons in Rats
Authors: Tan Zhenjun , Fogel Ronald , Jiang Chunhui , Zhang Xueguo
Published: April 2004

Galanin plays an important role in the regulation of food intake, energy balance, and body weight. Many galanin-positive fibers as well as galanin-positive neurons were seen in the dorsal vagal complex, suggesting that galanin produces its effects by actions involving vagal neurons. In the present experiment, we used tract-tracing and neurophysiological techniques to evaluate the origin of the galaninergic fibers and the effect of galanin on neurons in the dorsal vagal complex. Our results reveal that the nucleus of the solitary tract is the major source of the galanin terminals in the dorsal vagal complex. In vivo experiments demonstrated that galanin inhibited the majority of gut-related neurons in the dorsal motor nucleus of the vagus. In vitro experiments demonstrated that galanin inhibited the majority of stomach-projecting neurons in the dorsal motor nucleus of the vagus by suppressing spontaneous activity and/or producing a fully reversible dose-dependent membrane hyperpolarization and outward current. The galanin-induced hyperpolarization and outward current persisted after synaptic input was blocked, suggesting that galanin acts directly on receptors of neurons in the dorsal motor nucleus of the vagus. The reversal potential induced by galanin was close to the potassium ion potentials of the Nernst equation and was prevented by the potassium channel blocker tetraethylammonium, indicating that the inhibitory effect of galanin was mediated by a potassium channel. These results indicate that the dorsal motor nucleus of the vagus is inhibited by galanin derived predominantly from neurons in the nucleus of the solitary tract projecting to the dorsal motor nucleus of the vagus nerve. Galanin is one of the neurotransmitters involved in the vago-vagal reflex.
Forskolin-Induced LTP in the CA1 Hippocampal Region Is NMDA Receptor Dependent
Authors: Otmakhov Nikolai , Khibnik Lena , Otmakhova Nonna , Carpenter Stephen , Riahi Shervin , Asrican Brent , Lisman John
Published: April 2004

Chemically induced long-term potentiation (cLTP) could potentially work by directly stimulating the biochemical machinery that underlies synaptic plasticity, bypassing the need for synaptic activation. Previous reports suggested that agents that raise cAMP concentration might have this capability. We examined the cLTP induced in acute slices by application of Sp-cAMPS or a combination of the adenylyl cyclase activator, forskolin, and the phosphodiesterase inhibitor, rolipram. Under our conditions, cLTP was induced but only if inhibition was reduced. We found that this form of cLTP was blocked by a N-methyl-d-aspartate receptor (NMDAR) antagonist and required the low-frequency test stimulation typically used to monitor the strength of synapses. Interestingly, similar LTP could be induced by lowering the Mg2+concentration of the ACSF during forskolin/rolipram or Sp-cAMPS application or even by just lowering Mg2+concentration alone. This LTP was also NMDAR dependent and required only a few (∼5) low-frequency stimuli for its induction. The finding that even low-frequency synaptic stimulation was sufficient for LTP induction indicates that a highly sensitized plasticity state was generated. The fact that some stimulation was required means that potentiation is probably restricted to the stimulated axons, limiting the usefulness of this form of cLTP. However, when similar experiments were conducted using slice cultures, potentiation occurred without test stimuli, probably because the CA3–CA1 connections are extensive and because presynaptic spontaneous activity is sufficient to fulfill the activity requirement. As in acute slices, the potentiation was blocked by an NMDAR antagonist. Our general conclusion is that the induction of LTP caused by elevating cAMP requires presynaptic activity and NMDA channel opening. The method of inducing cLTP in slice cultures will be useful when it is desirable to produce NMDAR-dependent LTP in a large fraction of synapses.
Localized IP3-Evoked Ca2+Release Activates a K+Current in Primary Vagal Sensory Neurons
Authors: Hoesch Robert E. , Weinreich Daniel , Kao Joseph P. Y.
Published: April 2004

Electrophysiological and microfluorimetric techniques were used to determine whether intracellular photorelease of caged IP3, and the consequent release of Ca2+, could trigger a Ca2+-activated K+current ( IIP3). Photorelease of caged IP3evoked an IIP3that averaged 2.36 ± 0.35 (SE) pA/pF in 24 of 28 rabbit primary vagal sensory neurons (nodose ganglion neurons, NGNs) voltage-clamped at –50 mV. IIP3was abolished by intracellular BAPTA (2 mM), a Ca2+chelator. Changing the K+equilibrium potential by increasing extracellular K+ion concentration caused a predicted Nernstian shift in the reversal potential of IIP3. These results indicated that IIP3was a Ca2+-dependent K+current. IIP3was unaffected by three common antagonists of Ca2+-activated K+currents: bath-applied iberiotoxin (50 nM) or apamin (100 nM), and intracellular 8-Br-cAMP (100 μM) included in the patch pipette. We have previously demonstrated that both IP3-evoked Ca2+release and Ca2+-induced Ca2+release (CICR) are co-expressed in NGNs and that CICR can trigger a Ca2+-activated K+current. In the present study, using caffeine, a CICR agonist, to selectively attenuate intracellular Ca2+stores, we showed that IP3-evoked Ca2+release occurs independently of CICR, but interestingly, that a component of IIP3requires CICR. These data suggest that IP3-evoked Ca2+release activates a K+current that is pharmacologically distinct from other Ca2+-activated K+currents in NGNs. We describe several models that explain our results based on Ca2+signaling microdomains in NGNs.
Enhancing Encoding of a Motor Memory in the Primary Motor Cortex By Cortical Stimulation
Authors: Bütefisch Cathrin M. , Khurana Vikram , Kopylev Leonid , Cohen Leonardo G.
Published: April 2004

Motor training results in encoding of motor memories, a form of use-dependent plasticity. Here we tested the hypothesis that transcranial magnetic stimulation (TMS) synchronously applied to a motor cortex engaged in a motor training task could enhance this plastic process. Healthy volunteers were studied in four sessions: training consisting of performance of directionally specific voluntary thumb movements ( Train alone), training with TMS delivered during the execution of the training movement in a strictly temporal relationship to the motor cortex contralateral ( Train+ TMS synchronouscontra) and ipsilateral ( Train+ TMS synchronousipsi) to the training hand, and training with TMS delivered asynchronous to the training movement to the motor cortex contralateral to the training hand ( Train+ TMS asynchronouscontra). Train alone, Train+ TMS synchronouscontra, and Train+ TMS asynchronouscontra but not Train+ TMS synchronousipsi elicited a clear motor memory. The longevity of the encoded memory was significantly enhanced by Train+ TMS synchronouscontra when compared with Train alone and Train+ TMS asynchronouscontra. Therefore use-dependent encoding of a motor memory can be enhanced by synchronous Hebbian stimulation of the motor cortex that drives the training task and reduced by stimulation of the homologous ipsilateral motor cortex, a result relevant for studies of cognitive and physical rehabilitation.
Multiple Spontaneous Rhythmic Activity Patterns Generated by the Embryonic Mouse Spinal Cord Occur Within a Specific Developmental Time Window
Authors: Yvert Blaise , Branchereau Pascal , Meyrand Pierre
Published: April 2004

Spontaneous rhythmic activity is a ubiquitous phenomenon in developing neural networks and is assumed to play an important role in the elaboration of mature circuitry. Here we describe the day-by-day evolution of spontaneous activity in the embryonic mouse spinal cord and show that, at a specific developmental stage, 2 distinct rhythms coexist. On embryonic days E12.5 and E13.5, we observed a single type of regularly recurring short spike-episodes synchronized across cervical, thoracic, and lumbar levels. By E14.5, in addition to this motor rhythm, another type of spontaneous synchronous activity appeared, characterized by much longer lasting episodes separated by longer time intervals. On E15.5, these long episodes disappeared. Short episodes were less numerous and more irregular except at the cervical level where a rhythm was occasionally observed. By E16.5, this cervical rhythm became more robust, whereas the lumbar level fell almost silent. Surprisingly, at E17.5, spontaneous activity resumed at caudal levels, now characterized by numerous erratic short episodes. A striking ontogenetic feature of spontaneous activity was the occurrence of long episodes only at E14.5. Although concomitant at all levels of the spinal cord, long episodes displayed different patterns along the spinal cord, with tonic firing at the thoracic level and rhythmic discharge with occasional sequences of left/right alternation at the lumbar level. Thus at E14.5, the originally synchronized network has started to segregate into more specialized subnetworks. In conclusion, this work suggests that ongoing spontaneous rhythms do not follow a smooth evolution during maturation, but rather undergo profound changes at very specific stages.
Ambiguities in Sound-Duration Selectivity by Neurons in the Inferior Colliculus of the Bat Molossus molossus From Cuba
Authors: Mora Emanuel C. , Kössl Manfred
Published: April 2004

This study examines duration selectivity in auditory neurons of the inferior colliculus of the bat Molossus molossus (Molossidae, Chiroptera) from Cuba. Three main types of duration selectivity, short-, band-, and long-pass, as previously described in other species, are present in M. molossus. The range of best durations in the inferior colliculus of this species approximates the durations of their echolocation calls, suggesting that, as has been shown in other species of bats and frogs, the filter mechanism that produces duration tuning is selective for species-specific sounds relevant to behavior. Duration coding in M. molossus is not unambiguous because ∼30% of the short- and band-pass neurons respond best to two different stimulus durations. This bimodal duration selectivity could be explained by time delayed excitatory inputs that coincide with an inhibitory rebound. In addition, the effect of stimulus intensity on duration selectivity was tested. For most of the neurons (78%), duration selectivity was affected by absolute sound pressure level and/or small changes of sound pressure. In this respect, the processing of stimulus duration by collicular neurons seems to be more complex in M. molossus than in other species studied so far.
Spontaneous Waves in the Ventricular Zone of Developing Mammalian Retina
Authors: Syed Mohsin Md. , Lee Seunghoon , He Shigang , Zhou Z. Jimmy
Published: April 2004

Spontaneous rhythmic waves in the developing mammalian retina are thought to propagate among differentiated neurons in the inner retina (IR) and play an important role in activity-dependent visual development. Here we report a new form of rhythmic Ca2+wave in the ventricular zone (VZ) of the developing rabbit retina. Ca2+imaging from two-photon optical sections near the ventricular surface of the whole-mount retina showed rhythmic Ca2+transients propagating laterally as waves. The VZ waves had a distinctively slow Ca2+dynamics (lasting ∼20 s) but shared a similar frequency and propagation speed with the IR waves. Simultaneous Ca2+imaging in VZ and multi-electrode array recording in the ganglion cell layer (GCL) revealed close spatiotemporal correlation between spontaneous VZ and IR waves, suggesting a common source of initiation and/or regulation of the two waves. Pharmacological studies further showed that all drugs that blocked IR waves also blocked VZ waves. However, the muscarinic antagonist atropine selectively blocked VZ but not IR waves at this developmental stage, indicating that IR waves were not dependent on VZ waves, but VZ waves likely relied on the initiation of IR waves. Eliciting IR waves with puffs of nicotinic or non- N-methyl-d-aspartate agonists in GCL produced atropine-sensitive waves in the VZ, demonstrating a unique, retrograde signaling pathway from IR to VZ. Thus differentiated neurons in the IR use spontaneous, rhythmic waves to send both forward signals to the central visual targets and retrograde messages to the developing cells in the VZ.
Evidence That Phospholipase D Activation Prevents Group I mGluR-Induced Persistent Prolongation of Epileptiform Bursts
Authors: Rico Marjorie J. , Merlin Lisa R.
Published: April 2004

Selective activation of group I metabotropic glutamate receptors (mGluRs) with ( S)-3,5-dihydroxyphenylglycine (DHPG) in guinea pig hippocampal slices converts 275- to 475-ms picrotoxin-induced interictal bursts into persistent seizure-length discharges typically over 1 s in duration. Here we report that l-cysteine sulfinic acid (CSA), a sulfur-containing amino acid, prevented the induction of this persistent group I mGluR-mediated epileptiform burst prolongation. However, CSA had no effect on baseline interictal bursting activity and failed to suppress the expression of the group I mGluR-induced persistent prolonged bursts once they were fully induced. (2 R,1′ S,2′ R,3′ S)-2-(2′-carboxy-3′-phenylcyclopropyl)glycine (PCCG-13), a selective antagonist at the phospholipase D (PLD)-coupled mGluR, had no effect of its own on DHPG-induced burst prolongation; however, CSA applied in the presence of PCCG-13 could no longer fully block the burst prolongation induced by DHPG, suggesting that CSA's antiepileptogenic effect is mediated by agonist action at this PLD-coupled receptor. These data parallel our previous data revealing that protein synthesis inhibitors prevent induction but not expression of group I mGluR-mediated persistent seizure-length discharges. Hence, PLD activation with CSA may prevent the synthesis of a protein critical for the induction of group I mGluR-mediated epileptogenesis.
Frequency-Specific Effects on Cochlear Responses During Activation of the Inferior Colliculus in the Guinea Pig
Authors: Ota Y. , Oliver D. L. , Dolan D. F.
Published: April 2004

The inferior colliculus (IC) is a major processing center in the ascending auditory pathway. The role of the IC in the descending efferent auditory system is less clear. Although the IC central nucleus (ICC) is the major relay station for the ascending auditory pathways, the IC's cortex receives its main input from the neocortex and nonauditory sources. The goal of this study was to determine if the IC subdivisions had different functions in the descending efferent auditory system. IC subdivisions were identified by their tuning curves evoked by tone stimulation, and the effects of localized electrical stimulation on the cochlear whole-nerve action potential (CAP). Sharp tuning curves were obtained from ICC in contrast to broad tuning curves from the lateral, external cortex. Electrical stimulation within the central nucleus had a sharply tuned effect on the CAP. The frequency region affected within the cochlea closely matched the best frequency of local cells within the central nucleus. The effect of electrical stimulation within the lateral, external cortex on the CAP was smaller in comparison to central nucleus stimulation. Similar to the broad tuning of cells within the lateral cortex, electrical stimulation had a broad frequency effect on CAP thresholds.
Adaptive changes of duodenal iron transport proteins in celiac disease
Authors: Barisani Donatella , Parafioriti Antonina , Bardella Maria Teresa , Zoller Heinz , Conte Dario , Armiraglio Elisabetta , Trovato Cristina , Koch Robert O. , Weiss Günter
Published: April 2004

Iron deficiency is a manifestation of celiac disease (CD) usually attributed to a decreased absorptive surface, although no data on the regulation of iron transport under these conditions are currently available. Our aim was to evaluate divalent metal transporter 1 (DMT1), duodenal cytochrome b (Dcytb), ferroportin 1 (FP1), hephaestin, and transferrin receptor 1 (TfR1) expression, as well as iron regulatory protein (IRP) activity in duodenal biopsies from control, anemic, and CD patients. We studied 10 subjects with dyspepsia, 6 with iron-deficiency anemia, and 25 with CD. mRNA levels were determined by real-time PCR, protein expression by Western blotting or immunohistochemistry, and IRP activity by gel shift assay. Our results showed that DMT1, FP1, hephaestin, and TfR1 mRNA levels were significantly increased in CD patients with reduced body iron stores compared with controls, similar to what was observed in anemic patients. Protein expression paralleled the mRNAs changes. DMT1 protein expression was localized in differentiated enterocytes at the villi tips in controls, whereas with iron deficiency it was observed throughout the villi. FP1 expression was localized on the basolateral membrane of enterocytes and increased with low iron stores. TfR1 was localized in the crypts in controls but also in the villi with iron deficiency. These changes were paralleled by IRP activity, which increased in all iron-deficient subjects. We conclude that duodenal DMT1, FP1, hephaestin, and TfR1 expression and IRP activity, thus the iron absorption capacity, are upregulated in CD patients as a consequence of iron deficiency, whereas the increased enterocyte proliferation observed in CD has no effect on iron uptake regulation.
Endogenous Diadenosine Tetraphosphate, Diadenosine Pentaphosphate, and Diadenosine Hexaphosphate in Human Myocardial Tissue
Authors: Luo Jiankai , Jankowski Vera , Güngär Nihayrt , Neumann Joachim , Schmitz Wilhelm , Zidek Walter , Schlüter Hartmut , Jankowski Joachim
Published: April 2004

Diadenosine polyphosphates have been characterized as extracellular mediators controlling numerous physiological effects. In this study, diadenosine tetraphosphate, diadenosine pentaphosphate, and diadenosine hexaphosphate were isolated and identified in human myocardial tissue. Human myocardial tissue was homogenized and fractionated by affinity chromatography, displacement chromatography, anion-exchange chromatography, and reversed-phase chromatography. In fractions purified to homogeneity, diadenosine tetraphosphate, diadenosine pentaphosphate, and diadenosine hexaphosphate were revealed by matrix-assisted laser desorption/ionization mass spectrometry and ultraviolet spectroscopy. These diadenosine polyphosphates were further identified by enzymatic analysis, which demonstrated an interconnection of the phosphate groups with the adenosines in the 5′ positions of the riboses. Furthermore, diadenosine tetraphosphate, diadenosine pentaphosphate, and diadenosine hexaphosphate were found in human cardiac-specific granules, and the amount of diadenosine tetraphosphate, diadenosine pentaphosphate, and diadenosine hexaphosphate was estimated in the range of ≈500 μmol/L. In conclusion, the experiments show that the diadenosine polyphosphates with 2 and 3 phosphate groups occur in human myocardial tissue, and so do the diadenosine polyphosphates with 4 to 6 phosphate groups. After being released by cholinergic stimulation, which is known to affect diadenosine polyphosphate release from secretory granules, diadenosine tetraphosphate, diadenosine pentaphosphate, and diadenosine hexaphosphate activate P2X purinoceptors in vascular smooth muscle; hence, they can act as vasoconstrictors. It may be inferred that the differential action of both predominantly vasodilator and vasoconstrictor diadenosine polyphosphates allow a fine-tuning of myocardial blood flow by locally released diadenosine polyphosphates.