bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Gesture on Speech Production and Comprehension
Authors: Driskell James E. , Radtke Paul H.
Published: March 2004

Hand gestures are ubiquitous in communication. However, there is considerable debate regarding the fundamental role that gesture plays in communication and, subsequently, regarding the value of gesture for telecommunications. Controversy exists regarding whether gesture has a primarily communicative function (enhancing listener comprehension) or a primarily noncommunicative function (enhancing speech production). Moreover, some have argued that gesture seems to enhance listener comprehension only because of the effect gesture has on speech production. The purpose of this study was to examine the extent to which gesture enhances listener comprehension and the extent to which the effect of gesture on listener comprehension is mediated by the effects of gesture on speech production. Results indicated that gesture enhanced both listener comprehension and speech production. When the effects of gesture on speech production were controlled, the relationship between gesture and listener comprehension was reduced but still remained significant. These results suggest that gesture aids the listener as well as the speaker and that gesture has a direct effect on listener comprehension, independent of the effects gesture has on speech production. Implications for understanding the value of gestural information in telecommunications are discussed. Potential applications of this research include the design of computer-mediated communication systems and displays in which the visibility of gestures may be beneficial.
Metabotropic Glutamate Receptor Activation Regulates Fragile X Mental Retardation Protein andFmr1mRNA Localization Differentially in Dendrites and at Synapses
Authors: Antar Laura N. , Afroz Rownak , Dictenberg Jason B. , Carroll Reed C. , Bassell Gary J.
Published: March 2004

Fragile X syndrome is caused by the absence of the mRNA-binding protein Fragile X mental retardation protein (FMRP), which may play a role in activity-regulated localization and translation of mRNA in dendrites and at synapses. We investigated whether neuronal activity and glutamatergic signals regulate trafficking of FMRP and its encodingFmr1mRNA into dendrites or at synapses. Using high-resolution fluorescence and digital imaging microscopy in cultured hippocampal neurons, FMRP andFmr1mRNA were localized in granules throughout dendrites and within spines. KCl depolarization rapidly increased FMRP andFmr1mRNA levels in dendrites. Metabotropic glutamate receptor (mGluR) activation, in particular mGluR5 activation, was necessary for localization of FMRP into dendrites. Blockade of either PKC or internal calcium prevented mGluR-dependent localization of both FMRP andFmr1mRNA in dendrites. The activity-dependent localization of FMRP was not dependent on protein synthesis. Fluorescence recovery after photobleaching analysis of live neurons transfected with enhanced green fluorescent protein–FMRP revealed increased granule trafficking in response to KCl depolarization. In contrast to its dendritic localization, mGluR activation diminished FMRP, but notFmr1mRNA, localization at synapses. These results demonstrate regulation of FMRP andFmr1mRNA trafficking in dendrites and synapses in response to specific glutamatergic signals.
Neural Stem Cells Show Bidirectional Experience-Dependent Plasticity in the Perinatal Mammalian Brain
Authors: Kippin Tod E. , Cain Sean W. , Masum Zahra , Ralph Martin R.
Published: March 2004

Many of the effects of prenatal stress on the endocrine function, brain morphology, and behavior in mammals can be reversed by brief sessions of postnatal separation and handling. We have tested the hypothesis that the effects of both the prenatal and postnatal experiences are mediated by negative and positive regulation of neural stem cell (NSC) number during critical stages in neurodevelopment. We used thein vitroclonal neurosphere assay to quantify NSCs in hamsters that had experienced prenatal stress (maternal restraint stress for 2 hr per day, for the last 7 d of gestation), postnatal handling (maternal–offspring separation for 15 min per day during postnatal days 1–21), orboth. Prenatal stress reduced the number of NSCs derived from the subependyma of the lateral ventricle. The effect was already present at postnatal day 1 and persisted into adulthood (at least 14 months of age). Similarly, prenatal stress reducedin vivoproliferation in the adult subependyma of the lateral ventricle. Conversely, postnatal handling increased NSC number and reversed the effect of prenatal stress. The effects of prenatal stress on NSCs and proliferation and the effect of postnatal handling on NSCs did not differ between male and females. The findings demonstrate that environmental factors can produce changes in NSC number that are present at birth and endure into late adulthood. These changes may underlie some of the behavioral effects produced by prenatal stress and postnatal handling.
Changes in Excitability of Ascending and Descending Inputs to Cerebellar Climbing Fibers during Locomotion
Authors: Pardoe Joanne , Edgley Stephen A. , Drew Trevor , Apps Richard
Published: March 2004

The inferior olive climbing fiber projection plays a central role in all major theories of cerebellar function. Therefore, mechanisms that control the ability of climbing fibers to forward information to the cerebellum are of considerable interest. We examined changes in transmission in cerebro-olivocerebellar pathways (COCPs) and spino-olivocerebellar pathways (SOCPs) during locomotion in awake cats (n= 4) using low-intensity electrical stimuli delivered to the contralateral cerebral peduncle or the ipsilateral superficial radial nerve to set up volleys in COCPs and SOCPs, respectively. The responses were recorded as evoked extracellular climbing fiber field potentials within the C1 or C3 zones in the paravermal cerebellar cortex (lobule Va–Vc). At most C1 and C3 zone sites, the largest COCP responses occurred during the stance phase, and the smallest responses occurred during the swing phase of the ipsilateral forelimb step cycle. In marked contrast, SOCP responses recorded at the same sites were usually largest during the swing phase and smallest during the stance phase. Because substantial climbing fiber responses could be evoked in all phases of the step cycle, the results imply that olivary neurons remain excitable throughout, and that the differences between SOCPs and COCPs in their pattern of step-related modulation are unlikely to have arisen solely through inhibition at the level of the inferior olive (e.g., by activity in the inhibitory cerebellar nucleo-olivary pathway). The different patterns of modulation also suggest that climbing fiber signals conveyed by COCPs and SOCPs are likely to affect information processing within the cerebellar cortical C1 and C3 zones at different times during locomotion.
Vesicular Glutamate Transporter-Dependent Glutamate Release from Astrocytes
Authors: Montana Vedrana , Ni Yingchun , Sunjara Vice , Hua Xue , Parpura Vladimir
Published: March 2004

Astrocytes exhibit excitability based on variations of their intracellular Ca2+concentrations, which leads to glutamate release, that in turn can signal to adjacent neurons. This glutamate-mediated astrocyte–neuron signaling occurs at physiological intracellular Ca2+levels in astrocytes and includes modulation of synaptic transmission. The mechanism underlying Ca2+-dependent glutamate release from astrocytes is most likely exocytosis, because astrocytes express the protein components of the solubleN-ethyl maleimide-sensitive fusion protein attachment protein receptors complex, including synaptobrevin 2, syntaxin, and synaptosome-associated protein of 23 kDa. Although these proteins mediate Ca2+-dependent glutamate release from astrocytes, it is not well understood whether astrocytes express functional vesicular glutamate transporters (VGLUTs) that are critical for vesicle refilling. Here, we find in cultured and freshly isolated astrocytes the presence of brain-specific Na+-dependent inorganic phosphate cotransporter and differentiation-associated Na+-dependent inorganic phosphate cotransporter that have recently been identified as VGLUTs 1 and 2. Indirect immunocytochemistry showed a punctate pattern of VGLUT immunoreactivity throughout the entire cell body and processes, whereas pharmacological inhibition of VGLUTs abolished mechanically and agonist-evoked Ca2+-dependent glutamate release from astrocytes. Taken together, these data indicate that VGLUTs play a functional role in exocytotic glutamate release from astrocytes.
Nitric Oxide Inhibits the Rate and Strength of Cardiac Contractions in the LobsterHomarus americanusby Acting on the Cardiac Ganglion
Authors: Mahadevan Anand , Lappé Jason , Rhyne Randall T. , Cruz-Bermúdez Nelson D. , Marder Eve , Goy Michael F.
Published: March 2004

The lobster heart is synaptically driven by the cardiac ganglion, a spontaneously bursting neural network residing within the cardiac lumen. Here, we present evidence that nitric oxide (NO) plays an inhibitory role in lobster cardiac physiology. (1) NO decreases heartbeat frequency and amplitude. Decreased frequency is a direct consequence of a decreased ganglionic burst rate. Decreased amplitude is an indirect consequence of decreased burst frequency, attributable to the highly facilitating nature of the synapses between cardiac ganglion neurons and muscle fibers (although, during prolonged exposure to NO, amplitude recovers to the original level by a frequency-independent adaptation mechanism). NO does not alter burst duration, spikes per burst, heart muscle contractility, or amplitudes of synaptic potentials evoked by stimulating postganglionic motor nerves. Thus, NO acts on the ganglion, but not on heart muscle. (2) Two observations suggest that NO is produced within the lobster heart. First, immunoblot analysis shows that nitric oxide synthase (NOS) is strongly expressed in heart muscle relative to other muscles. Second,l-nitroarginine (l-NA), an NOS inhibitor, increases the rate of the heartbeat (opposite to the effects of NO). In contrast, the isolated ganglion is insensitive tol-NA, suggesting that heart muscle (but not the ganglion) produces endogenous NO. Basal heart rate varies from animal to animal, andl-NA has the greatest effect on the slowest hearts, presumably because these hearts are producing the most NO. Thus, because the musculature is a site of NOS expression, whereas the ganglion is the only intracardiac target of NO, we hypothesize that NO serves as an inhibitory retrograde transmitter.
A Novel p75 Neurotrophin Receptor-Related Protein, NRH2, Regulates Nerve Growth Factor Binding to the TrkA Receptor
Authors: Murray Simon S. , Perez Pilar , Lee Ramee , Hempstead Barbara L. , Chao Moses V.
Published: March 2004

Nerve growth factor (NGF) functions as a ligand for two receptors, the TrkA tyrosine kinase receptor and the p75 neurotrophin receptor (p75NTR). The Ig-like domains of Trk receptors and the cysteine-rich repeats of p75NTRare involved in binding to the neurotrophins. Recently, a closely related gene to p75NTRcalled neurotrophin receptor homolog-2 (NRH2) was identified; however, the function of NRH2 and its relevance to neurotrophin signaling are unclear. NRH2 contains a similar transmembrane and intracellular domain as p75NTRbut lacks the characteristic cysteine-rich repeats in the extracellular domain. Here we show that NRH2 is expressed in several neuronal populations that also express p75NTRand Trk receptors. NRH2 does not bind to NGF; however, coimmunoprecipitation experiments demonstrate that NRH2 is capable of interacting with TrkA receptors. Coexpression of NRH2 with TrkA receptors resulted in the formation of high-affinity binding sites for NGF. These results indicate that a transmembrane protein related to p75NTRis capable of modulating Trk receptor binding properties.
Neurochemical and Behavioral Alterations in Glucocorticoid Receptor-Impaired Transgenic Mice after Chronic Mild Stress
Authors: Froger Nicolas , Palazzo Enza , Boni Claudette , Hanoun Naïma , Saurini Françoise , Joubert Chantal , Dutriez-Casteloot Isabelle , Enache Michaela , Maccari Stefania , Barden Nicholas , Cohen-Salmon Charles , Hamon Michel , Lanfumey Laurence
Published: March 2004

Mice (GR-i) bearing a transgene encoding a glucocorticoid receptor (GR) antisense RNA under the control of a neuron-specific neurofilament promoter were used to investigate the effects of a 4 week chronic mild stress (CMS) on the hypothalamo–pituitary–adrenocortical (HPA) axis and the serotoninergic system in a transgenic model of vulnerability to affective disorders. GR-i mice showed a decrease in both GR-specific binding (hippocampus and cerebral cortex) and GR mRNA levels [hippocampus, cerebral cortex, and dorsal raphe nucleus (DRN)] as well as a deficit in HPA axis feedback control (dexamethasone test) compared with paired wild-type (WT) mice. In the latter animals, CMS exposure caused a significant decrease in both GR mRNA levels and the density of cytosolic GR binding sites in the hippocampus, whereas, in the DRN, GR mRNA levels tended to increase. In contrast, in stressed GR-i mice, both GR mRNA levels and the density of GR binding sites were significantly increased in the hippocampus, cerebral cortex, and DRN. Electrophysiological recordings in brainstem slices and [γ-35S]GTP-S binding measurements to assess 5-HT1Areceptor functioning showed that CMS exposure produced a desensitization of DRN 5-HT1Aautoreceptors in WT, but not in GR-i, mice. In addition, CMS was found to facilitate choice behavior of WT, but not GR-i, mice in a decision-making task derived from an alternation paradigm. These results demonstrate that impaired GR functioning affects normal adaptive responses of the HPA axis and 5-HT system to CMS and alters stress-related consequences on decision-making behaviors.
Aberrant Cellular Behavior of Mutant TorsinA Implicates Nuclear Envelope Dysfunction in DYT1 Dystonia
Authors: Gonzalez-Alegre Pedro , Paulson Henry L.
Published: March 2004

Torsion dystonia-1 (DYT1) dystonia, the most common inherited form of dystonia, is caused by a three base pair deletion that eliminates a single amino acid from the disease protein, torsinA. TorsinA is an “AAA” protein thought to reside in the endoplasmic reticulum (ER), yet both its cellular function and the basis for neuronal dysfunction in DYT1 remain unknown. A clue to disease pathogenesis is the fact that mutant, but not wild-type, torsinA forms membranous inclusions in cell culture. To explore the pathobiology of DYT1 dystonia, we generated PC12 neural cell lines that inducibly express wild-type or mutant torsinA. Although in this model torsinA displays some properties consistent with ER localization, mutant torsinA also accumulates in the nuclear envelope (NE), a structure contiguous with cytoplasmic ER. Consistent with this, membranous inclusions formed by mutant torsinA are shown to derive not from the ER, as thought previously, but from the NE. We demonstrate further that torsinA forms different disulfide-linked complexes that may be linked functionally to subcellular localization in the NE versus cytoplasmic ER. Despite mutant TA accumulation in NE structures, nucleocytoplasmic transport of a reporter protein was unaffected. These findings, together with parallel studies failing to demonstrate perturbation of ER function, implicate the NE as a primary site of dysfunction in DYT1. DYT1 dystonia can be added to the growing list of inherited neurological disorders involving the NE.
Interleukin-1β Induces a Reactive Astroglial Phenotype via Deactivation of the Rho GTPase–Rock Axis
Authors: John Gareth R. , Chen Lanfen , Rivieccio Mark A. , Melendez-Vasquez Carmen V. , Hartley Adam , Brosnan Celia F.
Published: March 2004

The cytokine interleukin-1β (IL-1β) is critical to the formation of an astrocytic scar after CNS injury, but the mechanisms by which it induces a reactive phenotype remain unresolved. Here, we show that IL-1β regulates the phenotype of astrocytes via deactivation of the Rho GTPase–Rho kinase (ROCK) pathway, which governs cellular morphology and migration via effects on F-actin and its interactions with focal adhesions, nonmuscle myosin, and microvillar adapter proteins of the ezrin–radixin–moesin (ERM) family. We found that IL-1β induced cortical reorganization of F-actin and dephosphorylation of focal adhesion kinase, myosin light chain 2, and myosin phosphatase targeting subunit 1 in primary human astrocytes, and that all of these effects were mimicked by Rho-ROCK pathway blockade. We also found that IL-1β conversely potentiated ERM phosphorylation, and that this effect was mediated via a Rho–ROCK-independent mechanism. Next, we used a rhotekin pulldown assay to confirm directly that IL-1β deactivates Rho, and further demonstrated that a constitutively active Rho construct rescued astrocytes from developing an IL-1β-induced reactive phenotype. These data implicate cytokine regulation of the Rho–ROCK pathway in the generation of a reactive astrogliosis, and we suggest that interventions targeted at this level may facilitate manipulation of the glial scar in inflammatory disorders of the human CNS.
Constitutive Spinal Cyclooxygenase-2 Participates in the Initiation of Tissue Injury-Induced Hyperalgesia
Authors: Ghilardi Joseph R. , Svensson Camilla I. , Rogers Scott D. , Yaksh Tony L. , Mantyh Patrick W.
Published: March 2004

Inhibitors of the isozyme cyclooxygenase-2 (COX-2) represent an important advance in pain management, although where and when these inhibitors can exert their antihyperalgesic actions are not completely understood. Here we show that unlike many peripheral tissues in which COX-2 is only expressed in physiologically significant levels after tissue injury, in the normal rat lumbar spinal cord, the majority of neurons and radial glia constitutively express high levels of COX-2 protein. Immediately after peripheral tissue injury and before any measurable upregulation of COX-2 protein in peripheral tissue or spinal cord, inhibition of constitutively expressed spinal COX-2 reduced injury-induced activation of primary afferent neurons, activation of spinal neurons, and the mechanical and thermal hyperalgesia that normally occurs after peripheral tissue injury. The present data demonstrate that constitutively expressed spinal COX-2 plays an important role in the initial hyperalgesia that follows peripheral tissue injury. These results suggest that blocking constitutive spinal COX-2 before tissue injury may reduce the initial peripheral and central sensitization that occurs after tissue injury.
Evidence for Gaze Feedback to the Cat Superior Colliculus: Discharges Reflect Gaze Trajectory Perturbations
Authors: Matsuo Satoshi , Bergeron André , Guitton Daniel
Published: March 2004

Rapid coordinated eye–head movements, called saccadic gaze shifts, displace the line of sight from one location to another. A critical structure in the gaze control circuitry is the superior colliculus (SC) of the midbrain, which drives gaze saccades by relaying cortical commands to brainstem eye and head motor circuits. We proposed that the SC lies within a gaze feedback loop and generates an error signal specifying gaze position error (GPE), the distance between target and current gaze positions. We investigated this feedback hypothesis in cats by briefly stopping head motion during large (≈50°) gaze saccades made in the dark. This maneuver interrupted intended gaze saccades and briefly immobilized gaze (a plateau). After brake release, a corrective gaze saccade brought the gaze on goal. In the caudal SC, the firing frequency of a cell gradually increased to a maximum that just preceded the optimal gaze saccade encoded by the position of the cell and then declined back to zero near gaze saccade end. In brake trials, the activity level just preceding a brake-induced plateau continued steadily during the plateau and waned to zero only near the end of the corrective saccade. The duration of neural activity was stretched to reflect the increased time to target acquisition, and firing frequency during a plateau was proportional to the GPE of the plateau. In comparison, in the rostral SC, the duration of saccade-related pauses in fixation cell activity increased as plateau duration increased. The data show that the cat's SC lies in a gaze feedback loop and that it encodes GPE.
Carbonic Anhydrase Isoform VII Acts as a Molecular Switch in the Development of Synchronous Gamma-Frequency Firing of Hippocampal CA1 Pyramidal Cells
Authors: Ruusuvuori Eva , Li Hong , Huttu Kristiina , Palva J. Matias , Smirnov Sergei , Rivera Claudio , Kaila Kai , Voipio Juha
Published: March 2004

Identification of the molecular mechanisms that enable synchronous firing of CA1 pyramidal neurons is central to the understanding of the functional properties of this major hippocampal output pathway. Using microfluorescence measurements of intraneuronal pH,in situhybridization, as well as intracellular, extracellular, and K+-sensitive microelectrode recordings, we show now that the capability for synchronous gamma-frequency (20–80 Hz) firing in response to high-frequency stimulation (HFS) emerges abruptly in the rat hippocampus at approximately postnatal day 12. This was attributable to a steep developmental upregulation of intrapyramidal carbonic anhydrase isoform VII, which acts as a key molecule in the generation of HFS-induced tonic GABAergic excitation. These results point to a crucial role for the developmental expression of intrapyramidal carbonic anhydrase VII activity in shaping integrative functions, long-term plasticity and susceptibility to epileptogenesis.
Enantioselectivity of Projection Neurons Innervating Identified Olfactory Glomeruli
Authors: Reisenman Carolina E. , Christensen Thomas A. , Francke Wittko , Hildebrand John G.
Published: March 2004

Projection neurons (PNs) with arborizations in the sexually dimorphic “lateral large female glomerulus” (latLFG) in the antennal lobe (AL) of the mothManduca sextapreviously were shown to respond preferentially to antennal stimulation with (±)linalool, a volatile compound commonly emitted by plants. In the present study, using intracellular recording and staining techniques, we examined the responsiveness of latLFG-PNs to the enantiomers, (+)linalool and (–)linalool and found that (1) latLFG-PNs are more responsive to antennal stimulation with (+)linalool than with (–)linalool, (2) PNs with arborizations in a glomerulus adjacent to the latLFG are preferentially responsive to (–)linalool, and (3) PNs with arborizations confined to other glomeruli near the latLFG are equally responsive to both enantiomers of linalool. Structure-activity studies showed that the hydroxyl group in this tertiary terpene alcohol is the key feature of the molecule determining the response of enantioselective PNs to linalool. In contrast, the responses of non-enantioselective PNs are less dependent on the alcoholic functionality of linalool. Our findings show that PNs innervating a uniquely identifiable glomerulus respond preferentially to a particular enantiomer of an odor substance. Moreover, PNs with arborizations in a glomerulus adjacent to the latLFG, although less sensitive than latLFG-PNs to linalool, respond preferentially to the opposite enantiomer, demonstrating that information about stimulus-absolute configuration can be encoded in different olfactory glomeruli.
Spinal G-Protein-Gated K+Channels Formed by GIRK1 and GIRK2 Subunits Modulate Thermal Nociception and Contribute to Morphine Analgesia
Authors: Marker Cheryl L. , Stoffel Markus , Wickman Kevin
Published: March 2004

G-protein-gated potassium (K+) channels are found throughout the CNS in which they contribute to the inhibitory effects of neurotransmitters and drugs of abuse. Recent studies have implicated G-protein-gated K+channels in thermal nociception and the analgesic action of morphine and other agents. Because nociception is subject to complex spinal and supraspinal modulation, however, the relevant locations of G-protein-gated K+channels are unknown. In this study, we sought to clarify the expression pattern and subunit composition of G-protein-gated K+channels in the spinal cord and to assess directly their contribution to thermal nociception and morphine analgesia. We detected GIRK1 (G-protein-gated inwardly rectifying K+channel subunit 1) and GIRK2 subunits, but not GIRK3, in the superficial layers of the dorsal horn. Lack of either GIRK1 or GIRK2 was correlated with significantly lower expression of the other, suggesting that a functional and physical interaction occurs between these two subunits. Consistent with these findings, GIRK1 knock-out and GIRK2 knock-out mice exhibited hyperalgesia in the tail-flick test of thermal nociception. Furthermore, GIRK1 knock-out and GIRK2 knock-out mice displayed decreased analgesic responses after the spinal administration of higher morphine doses, whereas responses to lower morphine doses were preserved. Qualitatively similar data were obtained with wild-type mice after administration of the G-protein-gated K+channel blocker tertiapin. We conclude that spinal G-protein-gated K+channels consisting primarily of GIRK1/GIRK2 complexes modulate thermal nociception and mediate a significant component of the analgesia evoked by intrathecal administration of high morphine doses.
Electroconvulsive Seizures Regulate Gene Expression of Distinct Neurotrophic Signaling Pathways
Authors: Altar C. Anthony , Laeng Pascal , Jurata Linda W. , Brockman Jeffrey A. , Lemire Andrew , Bullard Jeffrey , Bukhman Yury V. , Young Theresa A. , Charles Vinod , Palfreyman Michael G.
Published: March 2004

Electroconvulsive therapy (ECT) remains the treatment of choice for drug-resistant patients with depressive disorders, yet the mechanism for its efficacy remains unknown. Gene transcription changes were measured in the frontal cortex and hippocampus of rats subjected to sham seizures or to 1 or 10 electroconvulsive seizures (ECS), a model of ECT. Among the 3500–4400 RNA sequences detected in each sample, ECS increased by 1.5- to 11-fold or decreased by at least 34% the expression of 120 unique genes. The hippocampus produced more than three times the number of gene changes seen in the cortex, and many hippocampal gene changes persisted with chronic ECS, unlike in the cortex. Among the 120 genes, 77 have not been reported in previous studies of ECS or seizure responses, and 39 were confirmed among 59 studied by quantitative real time PCR. Another 19 genes, 10 previously unreported, changed by <1.5-fold but with very high significance. Multiple genes were identified within distinct pathways, including the BDNF–MAP kinase–cAMP–cAMP response element-binding protein pathway (15 genes), the arachidonic acid pathway (5 genes), and more than 10 genes in each of the immediate-early gene, neurogenesis, and exercise response gene groups. Neurogenesis, neurite outgrowth, and neuronal plasticity associated with BDNF, glutamate, and cAMP–protein kinase A signaling pathways may mediate the antidepressant effects of ECT in humans. These genes, and others that increase only with chronic ECS such as neuropeptide Y and thyrotropin-releasing hormone, may provide novel ways to select drugs for the treatment of depression and mimic the rapid effectiveness of ECT.
Expression of Cannabinoid CB1 Receptors by Vagal Afferent Neurons Is Inhibited by Cholecystokinin
Authors: Burdyga Galina , Lal Simon , Varro Andrea , Dimaline Rod , Thompson David G. , Dockray Graham J.
Published: March 2004

Both inhibitory (satiety) and stimulatory (orexigenic) factors from the gastrointestinal tract regulate food intake. In the case of the satiety hormone cholecystokinin (CCK), these effects are mediated via vagal afferent neurons. We now report that vagal afferent neurons expressing the CCK-1 receptor also express cannabinoid CB1 receptors. Retrograde tracing established that these neurons project to the stomach and duodenum. The expression of CB1 receptors determined by RT-PCR, immunohistochemistry andin situhybridization in rat nodose ganglia was increased by withdrawal of food for ≥12 hr. After refeeding of fasted rats there was a rapid loss of CB1 receptor expression identified by immunohistochemistry andin situhybridization. These effects were blocked by administration of the CCK-1 receptor antagonist lorglumide and mimicked by administration of CCK to fasted rats. Because CCK is a satiety factor that acts via the vagus nerve and CB1 agonists stimulate food intake, the data suggest a new mechanism modulating the effect on food intake of satiety signals from the gastrointestinal tract.
Ischemic Preconditioning: Neuronal Survival in the Face of Caspase-3 Activation
Authors: Tanaka Hidenobu , Yokota Hidenori , Jover Teresa , Cappuccio Irene , Calderone Agata , Simionescu Monica , Bennett Michael V. L. , Zukin R. Suzanne
Published: March 2004

Apoptosis is an evolutionarily conserved process critical to tissue development and tissue homeostasis in eukaryotic organisms and, when dysregulated, causes inappropriate cell death. Global ischemia is a neuronal insult that induces delayed cell death with many features of apoptosis. Ischemic preconditioning affords robust protection of CA1 neurons against a subsequent severe ischemic challenge. The molecular mechanisms underlying ischemic tolerance are unclear. Here we show that ischemia induces pronounced caspase-3 activity in naive neurons that die and in preconditioned neurons that survive. Preconditioning intervenes downstream of proteolytic processing and activation of caspase-3 (a protease implicated in the execution of apoptosis) and upstream of the caspase-3 target caspase-activated DNase (CAD, a deoxyribonuclease that catalyzes DNA fragmentation) to arrest neuronal death. We further show that global ischemia promotes expression of the pro-survival inhibitor-of-apoptosis (IAP) family member cIAP, but unleashes Smac/DIABLO (second mitochondria-derived activator of caspases/direct IAP-binding protein with low pI), a factor that neutralizes the protective actions of IAPs and promotes neuronal death. Preconditioning blocks the mitochondrial release of Smac/DIABLO, but not the ischemia-induced upregulation of IAPs. In the absence of Smac/DIABLO, cIAP halts the caspase death cascade and arrests neuronal death. These findings suggest that preconditioning preserves the integrity of the mitochondrial membrane, enabling neurons to survive in the face of caspase activation.
Origins of Cortical Interneuron Subtypes
Authors: Xu Qing , Cobos Inma , De La Cruz Estanislao , Rubenstein John L. , Anderson Stewart A.
Published: March 2004

Cerebral cortical functions are conducted by two general classes of neurons: glutamatergic projection neurons and GABAergic interneurons. Distinct interneuron subtypes serve distinct roles in modulating cortical activity and can be differentially affected in cortical diseases, but little is known about the mechanisms for generating their diversity. Recent evidence suggests that many cortical interneurons originate within the subcortical telencephalon and then migrate tangentially into the overlying cortex. To test the hypothesis that distinct interneuron subtypes are derived from distinct telencephalic subdivisions, we have used anin vitroassay to assess the developmental potential of subregions of the telencephalic proliferative zone (PZ) to give rise to neurochemically defined interneuron subgroups. PZ cells from GFP+donor mouse embryos were transplanted onto neonatal cortical feeder cells and assessed for their ability to generate specific interneuron subtypes. Our results suggest that the parvalbumin- and the somatostatin-expressing interneuron subgroups originate primarily within the medial ganglionic eminence (MGE) of the subcortical telencephalon, whereas the calretinin-expressing interneurons appear to derive mainly from the caudal ganglionic eminence (CGE). These results are supported by findings from primary cultures of cortex fromNkx2.1mutants, in which normal MGE fails to form but in which the CGE is less affected. In these cultures, parvalbumin- and somatostatin-expressing cells are absent, although calretinin-expressing interneurons are present. Interestingly, calretinin-expressing bipolar interneurons were nearly absent from cortical cultures ofDlx1/2mutants. By establishing spatial differences in the origins of interneuron subtypes, these studies lay the groundwork for elucidating the molecular bases for their distinct differentiation pathways.
3′ Untranslated Region in a Light Neurofilament (NF-L) mRNA Triggers Aggregation of NF-L and Mutant Superoxide Dismutase 1 Proteins in Neuronal Cells
Authors: Lin Hong , Zhai Jinbin , Cañete-Soler Rafaela , Schlaepfer William W.
Published: March 2004

The pathogenesis of neurodegenerative diseases is believed to involve abnormal aggregation of proteins, but the mechanisms initiating protein aggregation are unclear. Here we report a novel phenomenon that could be instrumental in triggering protein aggregation in neurodegenerative diseases. We show that the 3′ untranslated region (3′UTR) of a light neurofilament (NF-L) transcript enhances the reactivity of its own translated product and leads to loss of solubility and aggregation of NF-L protein and to coaggregation of mutant superoxide dismutase 1 (SOD1) protein. Full-length mouse NF-L cDNAs, with and without NF-L 3′UTR, were fused to the C terminus of a green fluorescent protein (GFP) reporter gene, and the GFP-tagged NF-L proteins were examined in transfected Neuro2a cells. The GFP-tagged NF-L protein expressed from the transgene containing NF-L 3′UTR, but not from the transgene lacking NF-L 3′UTR, colocalizes with endogenous heavy neurofilament protein and, at high-level expression, leads to loss of solubility and aggregation of GFP-tagged NF-L protein. Aggregation of GFP-tagged NF-L protein triggers coaggregation and loss of solubility of coexpressed DsRed-tagged mutant (G93A) SOD1 protein but not wild-type SOD1 protein. Deletional mutagenesis maps the RNA sequence causing aggregation of GFP-tagged NF-L protein to the proximal 45 nucleotides of NF-L 3′UTR. This is the site of a major destabilizing element in NF-L RNA and binding site for RNA-binding proteins. Our findings support a working model whereby NF-L RNA, or cognate RNA-binding factors, enhances the reactivity of NF-L protein and provides a triggering mechanism leading to aggregation of NF-L and other proteins in neurodegenerative diseases.
Social and cultural issues in urban communities
Authors: Rogers Elice E. , Hansman Catherine A.
Published: March 2004

To better understand the world of adult learners, we must remove ourselves from our ivory towers, classrooms,
and offices and engage in the practice of adult education programs in urban settings.
Gangsta rap and adult education
Authors: Guy Talmadge C.
Published: March 2004

Adult education instructors and administrators, who typically are not members of the hip‐hop
generation, have little or no background, sensitivity, or understanding of the influence and significance of
black popular culture and music for young African American and white adult learners.
New directions for urban adult education
Authors: Martin Larry G. , Rogers Elice E.
Published: March 2004

In this volume several themes have emerged regarding the role of urban adult education in assisting residents
of inner‐city communities to traverse the social, structural, economic, cultural, and technological
borders that disconnect them from the more affluent communities in urban areas. These themes also suggest,
however, several challenges that remain to be addressed.
Origins and development of biomedical engineering within chemical engineering
Authors: Peppas Nicholas A. , Langer Robert
Published: March 2004

Over the past 45 years, the field of biomedical engineering has found a welcome home in academic chemical engineering departments and in companies working with artificial organs, medical devices, and pharmaceutical formulations. The contributions of chemical engineers to the definition and the growth of the field have been important and at times seminal. The development and early contributions in the biomedical field with special emphasis on the contributions of chemical engineers is examined. © 2004 American Institute of Chemical Engineers AIChE J, 50: 536–546, 2004
Effective and coupled thermal conductivities of isotropic open‐cellular foams
Authors: Fourie J. G. , Du Plessis J. P.
Published: March 2004

The effective and the coupled thermal conductivity of the solid microstructure of open‐cellular foams and an accompanying saturation fluid are defined in a conceptual representation of conductive heat transfer in a two‐phase system of which the phases are in a thermal nonequilibrium state. The effective and coupled thermal conductivities were determined from a close observation of the relationship between microscopic and macroscopic temperature distributions. Temperature distributions were obtained from the numerical solution of the three‐dimensional (3‐D) conduction equation in a representative geometrical model of the foam solid microstructure and the fluid pores. Empirical correlations are provided for the effective and coupled thermal conductivities in terms of the solid and the fluid thermal conductivity and foam porosity. Thermal radiation was not considered in the energy transfer process. © 2004 American Institute of Chemical Engineers AIChE J, 50: 547–556, 2004
Simulating aggregation and reaction: New Hounslow DPB and four‐parameter summary
Authors: Wynn E. J. W.
Published: March 2004

A new formulation is developed of the popular Discretized Population Balance due to Hounslow and co‐workers. This new formulation is simpler and permits some variations in the method; three variations are put forward and tested. It also allows more flexibility in the choice of discretization, so that detail can be added at small sizes. The method is applied to the case of free‐molecular aggregation of SiO2 molecules in flames. The SiO2 is in equilibrium with SiO, which is assumed not to participate in aggregation; SiO2 molecules are, therefore, continuously created during aggregation. This source term complicates the resulting particle‐size distributions compared to the self‐preserving size distribution. Four parameters are used to summarize the PSDs, and their rates of change are found by approximations. This summarized model, a quasi‐self‐preserving size distribution, matches the detailed simulations very well. The cause of the stiffness of the differential equations is shown to be collisions between small and large particles. © 2004 American Institute of Chemical Engineers AIChE J, 50:578–588, 2004
Predicting packed‐bed breakthrough behavior from PFG NMR diffusion data
Authors: Rittig Frank , Farris Thomas S. , Zielinski John M.
Published: March 2004

Pulsed field gradient (PFG) NMR measurements have been conducted to measure self‐diffusion coefficients of gases within porous media. Analysis of these microscopic data with the use of a previously developed long‐range diffusion model has enabled us to accurately predict breakthrough curves for transport through packed‐bed adsorption columns, and the length of unused bed (LUB). This methodology enables the evaluation of mass‐transfer coefficients without the complications associated with transient sorption experiments, that is, heat effects, and thereby offers a reasonable alternative to conventional breakthrough experimentation for the evaluation of mass‐transfer coefficients, and LUB for large‐scale unit operations. 2004 American Institute of Chemical Engineers AIChE J, 50:589–595, 2004)
Detailed study of Tröger's base separation by SMB process
Authors: Mihlbachler Kathleen , Seidel‐Morgenstern Andreas , Guiochon Georges
Published: March 2004

This investigation of the separation of Tröger's base by the SMB process demonstrates: (1) the major importance of a proper modeling of the separation in order to determine the optimal operating conditions; (2) the need of an accurate modeling of the adsorption isotherms of the feed components. The adsorption of Tröger's base onto the stationary phase ChiralPak AD was successfully described by multilayer adsorption isotherm models. Due to the complexity of these models, the region of suitable operating parameters cannot be determined algebraically by the equilibrium theory. As an alternative, the equilibrium‐dispersive model, and a reliable numerical algorithm were used to scan a wide operating region, and to define this separation area. To verify the results of these calculations, the separation area was also experimentally detected by performing measurements of product purity and production rate for selected operating points. The combination of a UV detector and a polarimeter allows the accurate monitoring of the internal concentration profiles of both enantiomers. These profiles were compared to the profiles calculated using the multilayer adsorption isotherm models. In addition, the influence of the heterogeneity of the column set on the performance of the SMB process, is studied. Even under strongly nonlinear conditions, excellent agreements between calculated and experimental profiles were obtained. © 2004 American Institute of Chemical Engineers AIChE J, 50: 611–624, 2004
Experimental assessment of powerfeed chromatography
Authors: Zhang Ziyang , Morbidelli Massimo , Mazzotti Marco
Published: March 2004

The PowerFeed process is a modification of the simulated moving bed (SMB) technique, where the flow rates in the unit are allowed to change during a switching period following a predefined pattern. Through multiobjective optimization, using a genetic algorithm, it is shown that PowerFeed achieves better performances than SMB in several cases of interest for applications. Moreover, its experimental feasibility and effectiveness is assessed by running and comparing SMB and PowerFeed separations of the enantiomers of α‐ionone, on a cyclodextrin based chiral stationary phase. © 2004 American Institute of Chemical Engineers AIChE J, 50: 625–632, 2004
Interaction of separation and reactive stages on ETBE reactive distillation columns
Authors: Bisowarno Budi H. , Tian Yu‐Chu , Tadé Moses O.
Published: March 2004

Reactive distillation is a favorable alternative to conventional series of reactor‐distillation processes for ether productions. However, the design of such columns is complicated due to the interaction between vapor‐liquid equilibrium and reaction rates. There are conflicting reports on whether adding excessive separation stages degrade the column performance. A comparison is made of several designs of single and double feed reactive distillation columns for ETBE production to investigate the effects of separation and reaction stages on the overall performance. The explanations are presented using simulation results, whose mathematical models are written in the Aspen Plus environment. The results confirm that a conservative approach by adding extra separation and reaction stages can be applied to reactive distillation design. However, output multiplicity may be observed for longer column and should be considered in the early design phase. © 2004 American Institute of Chemical Engineers AIChE J, 50: 646–653, 2004
Control of polymer molecular weight using near infrared spectroscopy
Authors: Othman Nida Sheibat , Févotte Gilles , Peycelon Dominique , Egraz Jean‐Bernard , Suau Jean‐Marc
Published: March 2004

Near Infrared spectroscopy is used to control a polymerization reactor in order to produce solution polymers with well‐defined molecular weight. A model for the monitoring of both the average polymer molecular weight, and the concentration of monomer in the reactor is developed with the partial least‐squares calibration technique applied to the NIR spectra.On the basis of a process model, a nonlinear input–output linearizing geometric approach is then applied to control the polymer molecular weight by manipulating the inlet flow rate of the monomer. The control strategy is then validated on‐line during the solution polymerization of acrylic acid in an industrial pilot scale reactor. © 2004 American Institute of Chemical Engineers AIChE J, 50:654–664, 2004
Methylphosphonic acid oxidation kinetics in supercritical water
Authors: Sullivan Patricia A , Tester Jefferson W.
Published: March 2004

Oxidation and hydrolysis rates of the model organophosphorus compound, methylphosphonic acid (MPA), were measured in supercritical water. The effects of MPA concentration (0.5 to 1.0 mM), oxygen concentration (1.0 to 3.8 mM), temperature (478 to 572°C) and pressure (138 to 277 bar) on oxidation rates were determined for residence times ranging from 3.0 to 9.5 s. The MPA oxidation rate was dependent on both oxygen concentration and pressure (or water density), but was relatively independent of initial MPA concentration. The only phosphorus‐containing product was phosphoric acid, while the primary carbon‐containing products included carbon monoxide, methane, and carbon dioxide. Data were regressed to an empirical global rate law with a pre‐exponential factor of 1014.0±1.6 (s−1 M−1.47), an activation energy of 228±22 kJ/mol, a first‐order MPA dependence, an oxygen order of 0.30±0.18, and a water order of 1.17±0.30 (all parameters to 95% confidence). A macroscopic model was also developed to estimate reaction rate constants and oxygen dependences of the major identified reaction pathways. © 2004 American Institute of Chemical Engineers AIChE J, 50: 673–683, 2004
Multiscale hybrid modeling of film deposition within porous substrates
Authors: Gummalla M. , Tsapatsis M. , Watkins J. J. , Vlachos D. G.
Published: March 2004

A multiscale, hybrid computational framework for the deposition of films within porous substrates, is developed and applied to a prototype deposition reaction in the opposed reactant flow geometry. The developed model captures transport of reactants through the pores, homogeneous reaction of reagents producing an intermediate species, nucleation, and growth of the film as a moving boundary problem. The pore evolution is described using a capillary model. Adaptive mesh refinement is used to resolve length scales varying from nanometers to one millimeter. Nucleation is treated stochastically at the finest level, whereas transport and reaction at coarser levels are treated deterministically. Transport parameters chosen for these simulations correspond to the deposition of Pd films in porous alumina under supercritical CO2 conditions. The numerical results provide insight into the strategies that could be used to control their thickness, including confining thin films within substrates. For example, it has been found that the location of the deposit within the porous substrate is essentially determined by the relative concentrations of reagents on either side of the porous substrate, and the startup of the process. In addition, it is shown that the interplay of nucleation and growth kinetics determines the morphology and roughness of the deposit at short time scales. © 2004 American Institute of Chemical Engineers AIChE J, 50: 684–695, 2004
Structure and oxygen permeability of Ag‐doped SrCo0.8Fe0.2O3‐δ oxides
Authors: Tan Liang , Yang Li , Gu Xuehong , Jin Wanqin , Zhang Lixiong , Xu Nanping
Published: March 2004

The powders of SrCo0.8Fe0.2O3‐δ (SCF) and SCF doped with a different amount of Ag cation are synthesized by a solid‐state reaction method and the corresponding membranes are prepared. XRD results show that the doped Ag promotes the formation of a perovskite structure. The dissolution of Ag2O into the SCF matrix results in a decreasing lattice constant with the increasing Ag content. The doping of Ag can increase the surface exchange rate and decrease the activation energy of the SCF membrane. The oxygen permeability of the Ag‐doped SCF membrane is mainly influenced by both the reduction of the oxygen vacancy concentration and the improvement of the surface exchange, which depend on the content of the doped Ag and the operation temperature. The highest oxygen permeation flux is obtained when the mole ratio of Ag to SCF is 5%. © 2004 American Institute of Chemical Engineers AIChE J, 50: 701–707, 2004