bluuebunny/crossref_metadata_2025 huggingface dataset:
The Conserved Ig Superfamily Member Turtle Mediates Axonal Tiling in Drosophila
Authors: Ferguson Kerry , Long Hong , Cameron Scott , Chang Wen-Tzu , Rao Yong
Published: November 2009

Restriction of adjacent same-type axons/dendrites to separate single columns for specific neuronal connections is commonly observed in vertebrates and invertebrates, and is necessary for proper processing of sensory information. Columnar restriction is conceptually similar to tiling, a phenomenon referring to the avoidance of neurites from adjacent same-type neurons. The molecular mechanism underlying the establishment of columnar restriction or axonal/dendritic tiling remains largely undefined. Here, we identify Turtle (Tutl), a member of the conserved Tutl/Dasm1/IgSF9 subfamily of the Ig superfamily, as a key player in regulating the tiling pattern of R7 photoreceptor terminals inDrosophila. Tutl functions to prevent fusion between two adjacent R7 terminals, and acts in parallel to the Activin pathway. Tutl mediates homophilic cell–cell interactions. We propose that extrinsic terminal–terminal recognition mediated by Tutl, acts in concert with intrinsic Activin-dependent control of terminal growth, to restrict the connection made by each R7 axon to a single column.
Adding Insult to Injury: Cochlear Nerve Degeneration after “Temporary” Noise-Induced Hearing Loss
Authors: Kujawa Sharon G. , Liberman M. Charles
Published: November 2009

Overexposure to intense sound can cause temporary or permanent hearing loss. Postexposure recovery of threshold sensitivity has been assumed to indicate reversal of damage to delicate mechano-sensory and neural structures of the inner ear and no persistent or delayed consequences for auditory function. Here, we show, using cochlear functional assays and confocal imaging of the inner ear in mouse, that acoustic overexposures causing moderate, but completely reversible, threshold elevation leave cochlear sensory cells intact, but cause acute loss of afferent nerve terminals and delayed degeneration of the cochlear nerve. Results suggest that noise-induced damage to the ear has progressive consequences that are considerably more widespread than are revealed by conventional threshold testing. This primary neurodegeneration should add to difficulties hearing in noisy environments, and could contribute to tinnitus, hyperacusis, and other perceptual anomalies commonly associated with inner ear damage.
Local and Large-Range Inhibition in Feature Detection
Authors: Bolzon Douglas M. , Nordström Karin , O'Carroll David C.
Published: November 2009

Lateral inhibition is perhaps the most ubiquitous of neuronal mechanisms, having been demonstrated in early stages of processing in many different sensory pathways of both mammals and invertebrates. Recent work challenges the long-standing view that assumes that similar mechanisms operate to tune neuronal responses to higher order properties. Scant evidence for lateral inhibition exists beyond the level of the most peripheral stages of visual processing, leading to suggestions that many features of the tuning of higher order visual neurons can be accounted for by the receptive field and other intrinsic coding properties of visual neurons. Using insect target neurons as a model, we present unequivocal evidence that feature tuning is shaped not by intrinsic properties but by potent spatial lateral inhibition operating well beyond the first stages of visual processing. In addition, we present evidence for a second form of higher-order spatial inhibition—a long-range interocular transfer of information that we argue serves a role in establishing interocular rivalry and thus potentially a neural substrate for directing attention to single targets in the presence of distracters. In so doing, we demonstrate not just one, but two levels of spatial inhibition acting beyond the level of peripheral processing.
Overexpressing Temperature-Sensitive Dynamin Decelerates Phototransduction and Bundles Microtubules in Drosophila Photoreceptors
Authors: Gonzalez-Bellido Paloma T. , Wardill Trevor J. , Kostyleva Ripsik , Meinertzhagen Ian A. , Juusola Mikko
Published: November 2009

shibirets1, a temperature-sensitive mutation of theDrosophilagene encoding a Dynamin orthologue, blocks vesicle endocytosis and thus synaptic transmission, at elevated, or restrictive temperatures. By targeted Gal4 expression, UAS-shibirets1has been used to dissect neuronal circuits. We investigated the effects of UAS-shibirets1overexpression inDrosophilaphotoreceptors at permissive (19°C) and restrictive (31°C) temperatures. At 19°C, overexpression of UAS-shits1causes decelerated phototransduction and reduced neurotransmitter release. This phenotype is exacerbated with dark adaptation, age and inwhitemutants. Photoreceptors overexpressing UAS-shibirets1contain terminals with widespread vacuolated mitochondria, reduced numbers of vesicles and bundled microtubules. Immuno-electron microscopy reveals that the latter are dynamin coated. Further, the microtubule phenotype is not restricted to photoreceptors, as UAS-shibirets1overexpression in lamina cells also bundles microtubules. We conclude that dynamin has multiple functions that are interrupted by UAS-shibirets1overexpression inDrosophilaphotoreceptors, destabilizing their neural communication irreversibly at previously reported permissive temperatures.
A Novel, Nongenomic Mechanism Underlies Retinoic Acid-Induced Growth Cone Turning
Authors: Farrar Nathan R. , Dmetrichuk Jennifer M. , Carlone Robert L. , Spencer Gaynor E.
Published: November 2009

The vitamin A metabolite, retinoic acid (RA), is well known for its roles in neural development and regeneration. We have previously shown that RA can induce positive growth cone turning in regenerating neuronsin vitro. In this study, we address the subcellular mechanisms underlying this chemo-attractive response, using identified central neurons from the adult mollusc,Lymnaea stagnalis. We show that the RA-induced positive growth cone turning was maintained in the presence of the transcriptional inhibitor, actinomycin D. We also physically transected the neurites from the cell body and showed that isolated growth cones retain the capacity to turn toward a gradient of RA. Moreover, this attractive turning is dependent onde novolocal protein synthesis and Ca2+influx. Most of RA's actions during neurite outgrowth and regeneration require gene transcription, although these data show for the first time in any species, that the chemotropic action of RA in guiding neurite outgrowth, involves a novel, nongenomic mechanism.
Representation of Cross-Frequency Spatial Phase Relationships in Human Visual Cortex
Authors: Henriksson Linda , Hyvärinen Aapo , Vanni Simo
Published: November 2009

An image patch can be locally decomposed into sinusoidal waves of different orientations, spatial frequencies, amplitudes, and phases. The local phase information is essential for perception, because important visual features like edges emerge at locations of maximal local phase coherence. Detection of phase coherence requires integration of spatial frequency information across multiple spatial scales. Models of early visual processing suggest that the visual system should implement phase-sensitive pooling of spatial frequency information in the identification of broadband edges. We used functional magnetic resonance imaging (fMRI) adaptation to look for phase-sensitive neural responses in the human visual cortex. We found sensitivity to the phase difference between spatial frequency components in all studied visual areas, including the primary visual cortex (V1). Control experiments demonstrated that these results were not explained by differences in contrast or position. Next, we compared fMRI responses for broadband compound grating stimuli with congruent and random phase structures. All studied visual areas showed stronger responses for the stimuli with congruent phase structure. In addition, selectivity to phase congruency increased from V1 to higher-level visual areas along both the ventral and dorsal streams. We conclude that human V1 already shows phase-sensitive pooling of spatial frequencies, but only higher-level visual areas might be capable of pooling spatial frequency information across spatial scales typical for broadband natural images.
NOS2Gene Deficiency Protects from Sepsis-Induced Long-Term Cognitive Deficits
Authors: Weberpals Marc , Hermes Michael , Hermann S. , Kummer Markus P. , Terwel Dick , Semmler Alexander , Berger Meike , Schäfers Michael , Heneka Michael T.
Published: November 2009

To date, long-term consequences of septic encephalopathy on cerebral metabolism, cognition, learning, and memory capabilities and factors involved are poorly understood. In this study, we used a murine sepsis model to demonstrate that bacterial lipopolysaccharide (LPS) causes long-term cognitive deficits in mice. Two months after LPS treatment, wild-type mice committed more working and reference memory errors than controls. The behavioral impairment was independent of the cerebral glucose uptake as evidenced by18F-Fluordeoxyglucose small animal positron emission tomography. In contrast, mice deficient for the inducible nitric oxide synthase gene (NOS2−/−) did not show any cognitive changes when challenged with LPS. Immunohistochemical analysis demonstrated that LPS did not lead to neuronal cell death but caused sustained microglial activation in wild-type as compared toNOS2−/− mice. Expression analysis showed that LPS-treatedNOS2−/− mice had lower brain mRNA levels for proinflammatory factors compared with wild-type mice. Expression analysis demonstrated distinct changes in the content of synaptic proteins in wild-type mice, which were not observed in theNOS2−/− mice. Together, this data set outlines the importance of the NOS2 activation for long-term cerebral changes after severe sepsis.
Musical Experience Limits the Degradative Effects of Background Noise on the Neural Processing of Sound
Authors: Parbery-Clark Alexandra , Skoe Erika , Kraus Nina
Published: November 2009

Musicians have lifelong experience parsing melodies from background harmonies, which can be considered a process analogous to speech perception in noise. To investigate the effect of musical experience on the neural representation of speech-in-noise, we compared subcortical neurophysiological responses to speech in quiet and noise in a group of highly trained musicians and nonmusician controls. Musicians were found to have a more robust subcortical representation of the acoustic stimulus in the presence of noise. Specifically, musicians demonstrated faster neural timing, enhanced representation of speech harmonics, and less degraded response morphology in noise. Neural measures were associated with better behavioral performance on the Hearing in Noise Test (HINT) for which musicians outperformed the nonmusician controls. These findings suggest that musical experience limits the negative effects of competing background noise, thereby providing the first biological evidence for musicians' perceptual advantage for speech-in-noise.
The Spinothalamic System Targets Motor and Sensory Areas in the Cerebral Cortex of Monkeys
Authors: Dum Richard P. , Levinthal David J. , Strick Peter L.
Published: November 2009

Classically, the spinothalamic (ST) system has been viewed as the major pathway for transmitting nociceptive and thermoceptive information to the cerebral cortex. There is a long-standing controversy about the cortical targets of this system. We used anterograde transneuronal transport of the H129 strain of herpes simplex virus type 1 in the Cebus monkey to label the cortical areas that receive ST input. We found that the ST system reaches multiple cortical areas located in the contralateral hemisphere. The major targets are granular insular cortex, secondary somatosensory cortex and several cortical areas in the cingulate sulcus. It is noteworthy that comparable cortical regions in humans consistently display activation when subjects are acutely exposed to painful stimuli. We next combined anterograde transneuronal transport of virus with injections of a conventional tracer into the ventral premotor area (PMv). We used the PMv injection to identify the cingulate motor areas on the medial wall of the hemisphere. This combined approach demonstrated that each of the cingulate motor areas receives ST input. Our meta-analysis of imaging studies indicates that the human equivalents of the three cingulate motor areas also correspond to sites of pain-related activation. The cingulate motor areas in the monkey project directly to the primary motor cortex and to the spinal cord. Thus, the substrate exists for the ST system to have an important influence on the cortical control of movement.
Local Changes in the Excitability of the Cerebellar Cortex Produce Spatially Restricted Changes in Complex Spike Synchrony
Authors: Marshall Sarah P. , Lang Eric J.
Published: November 2009

Complex spike (CS) synchrony patterns are modulated by the release of GABA within the inferior olive (IO). The GABAergic projection to most of the IO arises from the cerebellar nuclei, which are themselves subject to strong inhibitory control by Purkinje cells in the overlying cortex. Moreover, the connections between the IO and cerebellum are precisely aligned, raising the possibility that each cortical region controls its own CS synchrony distribution. This possibility was tested using multielectrode recordings of CSs and simple spikes (SSs) in crus 2a of anesthetized rats. Picrotoxin or muscimol was applied to the cerebellar cortex at the borders of the recording array. These drugs induced significant changes in CS synchrony and in CS and SS firing rates and changes in post-CS pauses and modulation of SS activity. The level of CS synchrony was correlated with SS firing rate in control, and application of picrotoxin increased both. In contrast, muscimol decreased CS synchrony. Furthermore, when picrotoxin was applied only at the lateral edge of the array, changes in CS synchrony occurred sequentially across the recording array, with cells located in the lateral half of the array having earlier and larger changes in CS synchrony than cells in the medial half. The results indicate that a double-inhibitory feedback circuit from Purkinje cells to the IO provides a mechanism by which SS activity may regulate CS synchrony. Thus, CS synchrony may be a physiologically controlled parameter of cerebellar activity, with the cerebellum and IO comprising a series of self-updating circuits.
Regulation of Radial Glial Motility by Visual Experience
Authors: Tremblay Marc , Fugère Vincent , Tsui Jennifer , Schohl Anne , Tavakoli Aydin , Travençolo Bruno A. N. , Costa Luciano da F. , Ruthazer Edward S.
Published: November 2009

Radial glia in the developing optic tectum express the key guidance molecules responsible for topographic targeting of retinal axons. However, the extent to which the radial glia are themselves influenced by retinal inputs and visual experience remains unknown. Using multiphoton live imaging of radial glia in the optic tectum of intactXenopus laevistadpoles in conjunction with manipulations of neural activity and sensory stimuli, radial glia were observed to exhibit spontaneous calcium transients that were modulated by visual stimulation. Structurally, radial glia extended and retracted many filopodial processes within the tectal neuropil over minutes. These processes interacted with retinotectal synapses and their motility was modulated by nitric oxide (NO) signaling downstream of neuronal NMDA receptor (NMDAR) activation and visual stimulation. These findings provide the firstin vivodemonstration that radial glia actively respond both structurally and functionally to neural activity, via NMDAR-dependent NO release during the period of retinal axon ingrowth.
Glucocorticoid Effects on Memory Consolidation Depend on Functional Interactions between the Medial Prefrontal Cortex and Basolateral Amygdala
Authors: Roozendaal Benno , McReynolds Jayme R. , Van der Zee Eddy A. , Lee Sangkwan , McGaugh James L. , McIntyre Christa K.
Published: November 2009

Considerable evidence indicates that the basolateral complex of the amygdala (BLA) interacts with efferent brain regions in mediating glucocorticoid effects on memory consolidation. Here, we investigated whether glucocorticoid influences on the consolidation of memory for emotionally arousing training depend on functional interactions between the BLA and the medial prefrontal cortex (mPFC), a brain region involved in higher-order cognitive and affective processing. The glucocorticoid receptor (GR) agonist 11β,17β-dihydroxy-6,21-dimethyl-17α-pregna-4,6-trien-20yn-3-one (RU 28362) administered unilaterally into the left mPFC of male Sprague Dawley rats immediately after inhibitory avoidance training enhanced 48 h retention performance. An ipsilateral, but not contralateral, lesion of the BLA blocked the memory enhancement. In a second experiment, RU 28362 infused into the mPFC after inhibitory avoidance training increased BLA levels of phosphorylated extracellular signal-regulated kinase 1/2 (pErk1/2). Blockade of this pErk1/2 activity in the BLA with the mitogen-activated protein kinase kinase inhibitor PD98059 [2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one] prevented the memory enhancement, suggesting that GR agonist administration into the mPFC enhances memory consolidation via modulation of BLA activity. Conversely, GR agonist infusions administered into the BLA posttraining increased pErk1/2 levels in the mPFC in regulating memory consolidation. Moreover, as assessed with a two-phase inhibitory avoidance procedure designed to separate modulatory influences on memory of context and footshock, posttraining GR agonist infusions into either the BLA or mPFC enhanced memory of the contextual as well as aversive information acquired during inhibitory avoidance training. These findings indicate that glucocorticoid effects on memory consolidation depend on bidirectional interactions between the BLA and mPFC.
Surviving Hilar Somatostatin Interneurons Enlarge, Sprout Axons, and Form New Synapses with Granule Cells in a Mouse Model of Temporal Lobe Epilepsy
Authors: Zhang Wei , Yamawaki Ruth , Wen Xiling , Uhl Justin , Diaz Jessica , Prince David A. , Buckmaster Paul S.
Published: November 2009

In temporal lobe epilepsy, seizures initiate in or near the hippocampus, which frequently displays loss of neurons, including inhibitory interneurons. It is unclear whether surviving interneurons function normally, are impaired, or develop compensatory mechanisms. We evaluated GABAergic interneurons in the hilus of the dentate gyrus of epileptic pilocarpine-treated GIN mice, specifically a subpopulation of somatostatin interneurons that expresses enhanced green fluorescence protein (GFP). GFP-immunocytochemistry and stereological analyses revealed substantial loss of GFP-positive hilar neurons (GPHNs) but increased GFP-positive axon length per dentate gyrus in epileptic mice. Individual biocytin-labeled GPHNs in hippocampal slices from epileptic mice also had larger somata, more axon in the molecular layer, and longer dendrites than controls. Dual whole-cell patch recording was used to test for monosynaptic connections from hilar GPHNs to granule cells. Unitary IPSCs (uIPSCs) recorded in control and epileptic mice had similar average rise times, amplitudes, charge transfers, and decay times. However, the probability of finding monosynaptically connected pairs and evoking uIPSCs was 2.6 times higher in epileptic mice compared to controls. Together, these findings suggest that surviving hilar somatostatin interneurons enlarge, extend dendrites, sprout axon collaterals in the molecular layer, and form new synapses with granule cells. These epilepsy-related changes in cellular morphology and connectivity may be mechanisms for surviving hilar interneurons to inhibit more granule cells and compensate for the loss of vulnerable interneurons.
Ghrelin Promotes and Protects Nigrostriatal Dopamine Function via a UCP2-Dependent Mitochondrial Mechanism
Authors: Andrews Zane B. , Erion Derek , Beiler Rudolph , Liu Zhong-Wu , Abizaid Alfonso , Zigman Jeffrey , Elsworth John D. , Savitt Joseph M. , DiMarchi Richard , Tschöp Matthias , Roth Robert H. , Gao Xiao-Bing , Horvath Tamas L.
Published: November 2009

Ghrelin targets the hypothalamus to regulate food intake and adiposity. Endogenous ghrelin receptors [growth hormone secretagogue receptor (GHSR)] are also present in extrahypothalamic sites where they promote circuit activity associated with learning and memory, and reward seeking behavior. Here, we show that the substantia nigra pars compacta (SNpc), a brain region where dopamine (DA) cell degeneration leads to Parkinson's disease (PD), expresses GHSR. Ghrelin binds to SNpc cells, electrically activates SNpc DA neurons, increases tyrosine hydroxylase mRNA and increases DA concentration in the dorsal striatum. Exogenous ghrelin administration decreased SNpc DA cell loss and restricted striatal dopamine loss after 1-methyl-4-phenyl-1,2,5,6 tetrahydropyridine (MPTP) treatment. Genetic ablation of ghrelin or the ghrelin receptor (GHSR) increased SNpc DA cell loss and lowered striatal dopamine levels after MPTP treatment, an effect that was reversed by selective reactivation of GHSR in catecholaminergic neurons. Ghrelin-induced neuroprotection was dependent on the mitochondrial redox state via uncoupling protein 2 (UCP2)-dependent alterations in mitochondrial respiration, reactive oxygen species production, and biogenesis. Together, our data reveal that peripheral ghrelin plays an important role in the maintenance and protection of normal nigrostriatal dopamine function by activating UCP2-dependent mitochondrial mechanisms. These studies support ghrelin as a novel therapeutic strategy to combat neurodegeneration, loss of appetite and body weight associated with PD. Finally, we discuss the potential implications of these studies on the link between obesity and neurodegeneration.
A Selective Allosteric Potentiator of the M1Muscarinic Acetylcholine Receptor Increases Activity of Medial Prefrontal Cortical Neurons and Restores Impairments in Reversal Learning
Authors: Shirey Jana K. , Brady Ashley E. , Jones Paulianda J. , Davis Albert A. , Bridges Thomas M. , Kennedy J. Phillip , Jadhav Satyawan B. , Menon Usha N. , Xiang Zixiu , Watson Mona L. , Christian Edward P. , Doherty James J. , Quirk Michael C. , Snyder Dean H. , Lah James J. , Levey Allan I. , Nicolle Michelle M. , Lindsley Craig W. , Conn P. Jeffrey
Published: November 2009

M1muscarinic acetylcholine receptors (mAChRs) may represent a viable target for treatment of disorders involving impaired cognitive function. However, a major limitation to testing this hypothesis has been a lack of highly selective ligands for individual mAChR subtypes. We now report the rigorous molecular characterization of a novel compound, benzylquinolone carboxylic acid (BQCA), which acts as a potent, highly selective positive allosteric modulator (PAM) of the rat M1receptor. This compound does not directly activate the receptor, but acts at an allosteric site to increase functional responses to orthosteric agonists. Radioligand binding studies revealed that BQCA increases M1receptor affinity for acetylcholine. We found that activation of the M1receptor by BQCA induces a robust inward current and increases spontaneous EPSCs in medial prefrontal cortex (mPFC) pyramidal cells, effects which are absent in acute slices from M1receptor knock-out mice. Furthermore, to determine the effect of BQCA on intact and functioning brain circuits, multiple single-unit recordings were obtained from the mPFC of rats that showed BQCA increases firing of mPFC pyramidal cellsin vivo. BQCA also restored discrimination reversal learning in a transgenic mouse model of Alzheimer's disease and was found to regulate non-amyloidogenic APP processingin vitro, suggesting that M1receptor PAMs have the potential to provide both symptomatic and disease modifying effects in Alzheimer's disease patients. Together, these studies provide compelling evidence that M1receptor activation induces a dramatic excitation of PFC neurons and suggest that selectively activating the M1mAChR subtype may ameliorate impairments in cognitive function.
Robo-2 Controls the Segregation of a Portion of Basal Vomeronasal Sensory Neuron Axons to the Posterior Region of the Accessory Olfactory Bulb
Authors: Prince Janet E. A. , Cho Jin Hyung , Dumontier Emilie , Andrews William , Cutforth Tyler , Tessier-Lavigne Marc , Parnavelas John , Cloutier Jean-François
Published: November 2009

The ability of sensory systems to detect and process information from the environment relies on the elaboration of precise connections between sensory neurons in the periphery and second order neurons in the CNS. In mice, the accessory olfactory system is thought to regulate a wide variety of social and sexual behaviors. The expression of the Slit receptors Robo-1 and Robo-2 in vomeronasal sensory neurons (VSNs) suggests they may direct the stereotypic targeting of their axons to the accessory olfactory bulb (AOB). Here, we have examined the roles of Robo-1 and Robo-2 in the formation of connections by VSN axons within the AOB. While Robo-1 is not necessary for the segregation of VSN axons within the anterior and posterior regions of the AOB, Robo-2 is required for the targeting of some basal VSN axons to the posterior region of the AOB but is dispensable for the fasciculation of VSN axons. Furthermore, the specific ablation of Robo-2 expression in VSNs leads to mistargeting of a portion of basal VSN axons to the anterior region of the AOB, indicating that Robo-2 expression is required on projecting VSN axons. Together, these results identify Robo-2 as a receptor that controls the targeting of basal VSN axons to the posterior AOB.
Trafficking of Membrane Proteins to Cone But Not Rod Outer Segments Is Dependent on Heterotrimeric Kinesin-II
Authors: Avasthi Prachee , Watt Carl B. , Williams David S. , Le Yun Z. , Li Sha , Chen Ching-Kang , Marc Robert E. , Frederick Jeanne M. , Baehr Wolfgang
Published: November 2009

Heterotrimeric kinesin-II is a molecular motor localized to the inner segment, connecting cilium and axoneme of mammalian photoreceptors. Our purpose was to identify the role of kinesin-II in anterograde intraflagellar transport by photoreceptor-specific deletions of kinesin family member 3A (KIF3A), its obligatory motor subunit. In cones lacking KIF3A, membrane proteins involved in phototransduction did not traffic to the outer segments resulting in complete absence of a photopic electroretinogram and progressive cone degeneration. Rod photoreceptors lacking KIF3A degenerated rapidly between 2 and 4 weeks postnatally, but the phototransduction components including rhodopsin trafficked to the outer segments during the course of degeneration. Furthermore, KIF3A deletion did not affect synaptic anterograde trafficking. The results indicate that trafficking of membrane proteins to the outer segment is dependent on kinesin-II in cone, but not rod photoreceptors, even though rods and cones share similar structures, and closely related phototransduction polypeptides.
Polar Residues in the Second Transmembrane Domain of the Rat P2X2 Receptor That Affect Spontaneous Gating, Unitary Conductance, and Rectification
Authors: Cao Lishuang , Broomhead Helen E. , Young Mark T. , North R. Alan
Published: November 2009

Membrane ion channels activated by extracellular ATP (P2X receptors) are widely distributed in the nervous system. Their molecular architecture is fundamentally distinct from that of the nicotinic or glutamate receptor families. We have measured single-channel currents, spontaneous gating, and rectification of rat P2X2 receptor in which polar and charged residues of the second transmembrane domain (TM2) were systematically probed by mutagenesis. The results suggest that Asn333and Asp349lie respectively in external and internal vestibules. Substitutions at Asn333, Thr336, and Ser340were particularly likely to cause spontaneously active channels. At Thr336, Thr339, and Ser340, the introduction of positive charge (Arg, Lys, or His, or Cys followed by treatment with 2-aminoethyl methanethiosulphonate) greatly enhanced outward currents, suggesting that side-chains of these three residues are exposed in the permeation pathway of the open channel. These functional findings are interpreted in the context of the recently reported 3.1 Å crystal structure of the zebrafish P2X4.1 receptor in the closed state. They imply that the gate is formed by residues Asn333to Thr339and that channel opening involves a counter-clockwise rotation and separation of the TM2 helices.
Medieninformatik in Studium und Lehre
Authors: Boll Susanne
Published: November 2009

Medieninformatik ist ein junges dynamisches Fachgebiet der Informatik, das in den vergangenen Jahren auch mehr und mehr in Studium und Lehre vertreten ist. Universitäten und Fachhochschulen haben eigene Studiengänge eingerichtet oder Schwerpunkte und Vertiefungsgebiete in den Informatikstudiengängen etabliert. Dieser Artikel trägt Ansichten zu den geeigneten Lehrinhalten für ein Curriculum der Medieninformatik zusammen. Er wirft einen Blick auf die unterschiedlichen Ausgestaltungen der Studienangebote auch mit der Fragestellung des konkreten Berufsbildes für die zukünftigen Medieninformatikerinnen und Medieninformatiker.
Medienkunst oder die Kunst die Medien zu erforschen
Authors: Beckhaus Steffi
Published: November 2009

Die Möglichkeiten und Wirkungsweisen von Medien lassen sich mit künstlerischen Projekten frei von Anforderungen an das Ergebnis oder ein Anwendungsziel entdecken und erforschen. Bereits in den 60er Jahren untersuchten sowohl Künstler als auch Ingenieure das Medium Computer künstlerisch und kreativ, um Einblicke in die Möglichkeiten des Computers zu bekommen. Ein aktuelles interaktives Beispiel, das die Fähigkeiten heutiger Computer nutzt und mit Hilfe des Computers als Medium tatsächliche prompte Interaktion zwischen Menschen ermöglicht, ist SoundVision, eine interaktive und kooperative audiovisuelle Installation. An verschiedenen vernetzten Stationen können mit unterschiedlichen Eingabegeräten “Klangbilder” erzeugt werden. Gespielte Musik erzeugt dabei ein Bild und Bilder aus Zeichnungen und Videos werden zusätzlich vertont. Zusammen ergeben sie jeweils einzelne TonBild-Stücke, die auf einer gemeinsamen Fläche kooperativ angeordnet werden können und dort ein gemeinsames TonBild entstehen lassen. Im Sinne einer Konversation arbeiten verschiedene Teilnehmer an verschiedenen Stationen gleichzeitig an einem gemeinsamen Werk. Das Werk materialisiert sich flüchtig im Sinne eines Konzerts. Es bleibt die notwendigerweise zuvor selbst entwickelte eigene Sprache der Teilnehmer ebenso wie das gegebenenfalls neu gewonnene Verständnis über BildTon Zusammenhänge und deren Ästhetik, über Kommunikation und das eingesetzte Medium als Solches — es entsteht Erfahrung, vielleicht sogar Erkenntnis über das Medium, das Medium wird erforscht. Diese Art Erfahrungen und Erkenntnisse aus künstlerisch motivierten Projekten lassen sich gewinnbringend auch in die Informatikforschung einbringen, auch wenn Ergebnisse daraus zunächst nicht quantifizierbar oder bewertbar sind. Experimentelle, spielerische, künstlerische Methoden haben einen wichtigen Anteil am Entstehen von Innovation und es wird motiviert, dass diese Methoden auch ihren Stellenwert und Raum in unserer Forschung erhalten.
Emotional Sensitivity in Human-Computer Interaction
Authors: Kim Jonghwa , Wagner Johannes , Vogt Thurid , André Elisabeth , Jung Frank , Rehm Matthias
Published: November 2009

Human conversational partners usually try to interpret the speaker´s or listener´s affective cues and respond to them accordingly. Recently, the modelling and simulation of such behaviours has been recognized as an essential factor for more natural man-machine communication. The implicit emotion channels of human communication such as speech, facial expression, gesture, and physiological responses are used in general to extract emotion-relevant features for the computational perception of emotion. So far, research on emotion recognition has mostly dealt with offline analysis of recorded emotion corpora, and online processing (in realtime or near realtime) has hardly been addressed. Online processing is, however, a necessary prerequisite for the realization of human-computer interfaces that analyze and respond to the user´s emotions while he or she is interacting with an application. In this paper, we first describe how we recognize emotions from various modalities including speech, gestures and biosignals. We then present Smart Sensor Integration (SSI), a framework which we developed to meet the specific requirements of online emotion recognition.
Tangible, Embedded, and Reality-Based Interaction
Authors: Döring Tanja , Krüger Antonio , Schmidt Albrecht , Schöning Johannes
Published: November 2009

Tangible, embedded, and reality-based interaction are among novel concepts of interaction design that will change our usage of computers and be part of our daily life in coming years. In this article, we present an overview of the research area of tangible, embedded, and reality-based interaction as an area of media informatics. Potentials and challenges are demonstrated with four selected case studies from our research work.
Mobile Digital Media: Challenges and Opportunities
Authors: Aras Hidir , Feige Sebastian , Malaka Rainer , Walther-Franks Benjamin , Wenig Dirk
Published: November 2009

The use of digital media in mobile surroundings has a massive influence on the type of content consumed and produced, its presentation form and how interactive access is guaranteed in such mobile contexts. To fully leverage the possibilities that digital media offer in mobile use, it is necessary to understand this influence and approach it with appropriate concepts. This article gives an overview of the impact of novel devices, diverse contexts of use, and changed demands on digital content and the interaction with it. Works of the authors and others are presented as examples for how possibilities are created and used to produce digital media optimised for mobile use.
Modellbasierte Bildmodifikation
Authors: Blanz Volker
Published: November 2009

Die Verwendung realer Bild- und 3D Scandaten in digitalen Medien ermöglicht es, photorealistische Inhalte effizient zu generieren. Um die Daten einbinden und modifizieren zu können, ist jedoch aufwändige Technologie erforderlich. Der Artikel beschreibt einen statistischen, lernbasierten Ansatz, der menschliche Gesichter rekonstruieren, modifizieren, animieren und in Bildern austauschen kann.
Medieninformatik NXG — Die nächste Generation: Wie Kinder und Jugendliche heute die Medien von morgen erlernen können
Authors: Herczeg Michael
Published: November 2009

Die Medieninformatik ist eines der jüngsten Teilgebiete der Informatik. Seit etwa 1990 werden Begriffsdefinitionen, Hochschul-Curricula und Forschungsagendas entwickelt und umgesetzt, um dieses interdisziplinäre Gebiet zu klären und nachhaltig zu entwickeln. In diesem Beitrag soll die Frage gestellt werden, welche Rolle die Medieninformatik für die Generation spielen kann, die gerade in der Schule auf Studium und Beruf vorbereitet wird. Dazu soll dargestellt und diskutiert werden, wie schon heute Kinder und Jugendliche auf diese moderne, interdisziplinäre Form der Informatik eingestimmt, vorbereitet und motiviert werden können. Anstatt sich auf Algorithmen und Datenstrukturen sowie auf mathematische Grundlagen zu beschränken, sollte diese Generation bereits heute mit den interaktiven Medien von morgen umzugehen lernen. Seit 2001 wird an deutschen Schulen und Vorschulen im Rahmen der Forschungs- und Transferinitiative KiMM (Kids in Media and Motion) ein dieser Zielsetzung entsprechender projektorientierter Unterricht durchgeführt, der Kindern und Jugendlichen vor allem neue körper- und raumbezogene digitale Medien nahe bringt, indem sie interaktive mediale Systeme selbst entwickeln und anwenden. Der Unterricht findet unter Berücksichtigung der vorhandenen schulischen Curricula in praktisch allen Schulfächern meist fachübergreifend statt und macht die Medieninformatik und damit auch die Informatik in der Schule zu einer neuen Querschnittsdisziplin.
DFG Research Training Group 722 Use of Information Technologies for Precision Crop Protection
Authors: Oerke Erich-Christian , Gerhards Roland
Published: November 2009

In an interdisciplinary approach Research Training Group 722 investigates methods and technologies for a site-specific and efficient control of weeds, pathogens, and nematodes in agricultural crops. By utilizing and developing innovative sensor techniques, geo-information systems, data processing and control techniques, pest control measures are applied only if, when and where economically needed. The spatial and temporal heterogeneity of incidence and distribution of pests in the field is assessed using remote sensing techniques and global positioning systems. For on-line and off-line applications these data are analysed in decision support systems considering a spatial component. Spatially and temporally precise pest control is achieved by using sensor-guided equipment. The short-term effects, i. e., the efficacy of control of weeds and diseases, and long-term effects of site-specific control strategies on the incidence and distribution of pests in the field are monitored by using technical sensors again. The documentation of all steps in these pest management systems may contribute to develop new production standards and to demonstrate the ecologic benefits of this crop protection strategy. The generation and management of information on the incidence of pests with high spatial resolution and its implementation in precise control systems will enable a targeted and resource-preserving integrated pest management system under high productivity conditions, which is economically successful, environmentally sound and socially acceptable.
Elektronische Verhandlungssysteme und ihre Rolle in der betrieblichen Kommunikation — Eine explorative Untersuchung der Beschaffungsauktion
Authors: Köhne Frank
Published: November 2009

Die Arbeit untersucht die Rolle von elektronischen Beschaffungsauktionen anhand von branchenübergreifenden, narrativen Interviews. Defizite in Bezug auf interorganisationale Kommunikation werden mit Mitteln der Language Action Perspective (LAP) sowie der Spieltheorie aufgedeckt und analysiert.
Lower early morning plasma cortisol levels are associated with thyroid autoimmunity in the elderly
Authors: Terzidis K , Panoutsopoulos A , Mantzou A , Tourli P , Papageorgiou G , Saltiki K , Mara C , Alevizaki M
Published: November 2009

Objectives

Thyroid autoimmunity decreases in the very old. We investigated whether glucocorticoid (GC) activity, which increases in old age, is involved in this process.

Subjects and methods

A total of 321 ambulatory subjects (age 51–95 years, median 71, 207 female) were studied. Thyroid function tests, cortisol, glucose, insulin and biochemical parameters were measured. A modified overnight dexamethasone suppression test (0.25 mg) was performed as an index of GC sensitivity.

Results

Forty subjects had positive anti-thyroid peroxidase antibodies and 36 had positive anti-thyroglobulin antibodies, while 57 had either one or the other or both thyroid autoantibodies (ThAbs) positive. Mean basal cortisol levels were significantly lower in the ThAbs (+) groups (320±125 vs 378±128 nmol/l, P=0.002). Triiodothyronine, free thyroxine, post-dexamethasone cortisol levels, C-reactive protein, homeostasis model assessment-insulin-resistance-index and body mass index did not differ between these two groups. Mean age of ThAbs (+) subjects was lower compared to the ThAbs (−) group (67.38±7.38 vs 71.64±8.57 years, P=0.001).

Conclusions

Reduced GC activity is associated with an increased prevalence of ThAbs positivity in older ambulatory subjects. Subjects without ThAbs in this population sample are relatively older. It is not known whether this is related to increasing GC activity with age.
Trough serum testosterone predicts the development of polycythemia in hypogonadal men treated for up to 21 years with subcutaneous testosterone pellets
Authors: Ip Flora F , di Pierro Irene , Brown Ross , Cunningham Ilona , Handelsman David J , Liu Peter Y
Published: November 2009

Objectives

Testosterone formulations that have more steady-state pharmacokinetics, such as subcutaneously implanted testosterone pellets, may cause less erythrocytosis than i.m. injections of shorter acting androgen esters. We, therefore, sought to define the prevalence, predictors, and proximate basis (role of erythropoietin) for polycythemia (hematocrit >0.50) in hypogonadal men receiving testosterone implants long term.

Design

A cross-sectional study was conducted in an academic andrology center with a longitudinal subgroup analysis.

Patients

A total of 158 hypogonadal men aged 14–84 years (mean age 46.7 years) treated on average for 8 years (range 0–21 years).

Measurements

Trough blood testosterone and hematocrit. Serial serum erythropoietin concentrations were measured in 16 volunteers.

Results

Positive univariate associations between polycythemia (hematocrit >0.50) and log(testosterone) (odds ratio (OR) 24.7, 95% confidence interval (CI): 4.3, 141.2, P<0.01) and age (OR 1.1, 95% CI: 1.0, 1.1, P=0.03) and a borderline relationship with current smoking (OR 4.2, 95% CI: 0.9, 20.0, P=0.08) were unveiled. A sensitivity analysis using alternate definitions of polycythemia was performed to capture all potential covariants. Multivariate regression analysis incorporating all potential covariants disclosed the independent OR of developing polycythemia (after adjusting for smoking and age) for log(testosterone) to be 15.0 (95% CI: 2.5, 90.8). Duration of testosterone therapy did not alter the risk of polycythemia. A direct relationship between testosterone and erythropoietin was observed (P=0.05).

Conclusions

Higher trough serum testosterone concentrations but not duration of treatment predict the development of polycythemia in men receiving long-acting depot testosterone treatment.
Bevacizumab plus capecitabine as a salvage therapy in advanced adrenocortical carcinoma
Authors: Wortmann Sebastian , Quinkler Marcus , Ritter Christian , Kroiss Matthias , Johanssen Sarah , Hahner Stefanie , Allolio Bruno , Fassnacht Martin
Published: November 2009

Objective

No standard therapy for advanced adrenocortical carcinoma (ACC) is established by any randomized trial but a consensus conference 2003 recommended mitotane as monotherapy or combined with etoposide, doxorubicin and cisplatin or with streptozotocin as first-line systemic therapy. However, there is no evidence for any therapy beneficial in patients failing these therapies. Therefore, we evaluated the effects of the anti-VEGF antibody bevacizumab plus capecitabine as salvage therapy in ACC.

Methods

Patients registered with the German ACC Registry with refractory ACC progressing after cytotoxic therapies were offered treatment with bevacizumab (5 mg/kg body weight i.v. every 21 days) and oral capecitabine (950 mg/m2 twice daily for 14 days followed by 7 days of rest) in 2006–2008. Evaluation of tumour response was performed by imaging according to response evaluation criteria in solid tumours every 12 weeks.

Results

Ten patients were treated with bevacizumab plus capecitabine. None of them experienced any objective response or stable disease. Two patients had to stop therapy after few weeks due to hand-foot syndrome, and three patients died on progressive disease within 12 weeks. Other adverse events were mild (grade I–II). Median survival after treatment initiation was 124 days.

Conclusions

Bevacizumab plus capecitabine has no activity in patients with very advanced ACC. Hence, this regimen cannot be recommended as a salvage therapy.
Clinical relevance of thyroid dysfunction in human haematopoiesis: biochemical and molecular studies
Authors: Kawa Miłosz Piotr , Grymuła Katarzyna , Paczkowska Edyta , Baśkiewicz-Masiuk Magdalena , Dąbkowska Elżbieta , Koziołek Monika , Tarnowski Maciej , Kłos Patrycja , Dziedziejko Violetta , Kucia Magdalena , Syrenicz Anhelli , Machaliński Bogusław
Published: November 2009

Objective

Abnormalities in haematological parameters have been noted in patients with thyroid diseases. Nevertheless, the exact mechanism of thyroid hormones' (THs) action on human haematopoiesis is still not entirely clear.

Design

The influence of THs through TH receptors (TRα-1 and TRβ-1) on haematopoiesis in patients with hypo- and hyperthyroidism was analysed.

Methods

TR gene expression at the mRNA and protein levels in human CD34+-enriched haematopoietic progenitor cells (HPCs) obtained from the peripheral blood of patients with thyroid disorders and healthy volunteers was analysed. The cell populations were also investigated for clonogenic growth of granulocyte macrophage-colony forming units and erythrocyte-burst forming units (BFU-E). The level of apoptosis was determined by annexin V/propidium iodide staining and quantitative RT-PCR.

Results

The studies revealed that hypo- and hyperthyroidism modify TR gene expression in HPCs in vivo. TH deficiency resulted in a decrease in total blood counts and clonogenic potential of BFU-E. In contrast, hyperthyroid patients presented increased clonogenic growth and BFU-E number and significantly higher expressions of cell cycle-regulating genes such as those for PCNA and cyclin D1. Finally, an increase in the frequency of apoptotic CD34+-enriched HPCs in hypo- and hyperthyroidism with a modulation of apoptosis-related genes was detected.

Conclusions

The following conclusions were derived: i) TR expression in human haematopoietic cells depends on TH status, ii) both hypo- and hyperthyroidism significantly influence clonogenicity and induce apoptosis in CD34+-enriched HPCs and iii) the molecular mechanism by which THs influence haematopoiesis might provide a basis for designing novel therapeutic interventions in thyroid diseases.
Hypothalamic–pituitary–adrenal axis response to the severity of illness in non-critically ill patients: does relative corticosteroid insufficiency exist?
Authors: Michalaki M , Margeli T , Tsekouras A , Gogos C H , Vagenakis A G , Kyriazopoulou V
Published: November 2009

Objective

Relative corticosteroid insufficiency may be common in critically ill patients and is associated with a poor outcome; however, the response of the hypothalamic–pituitary–adrenal (HPA) axis in nursed patients is not known. Our aim was to evaluate the response of HPA axis to the severity of illness in non-critically ill nursed (NCIN) patients and the clinical outcome.

Subjects and methods

Fifty-six nursed patients who were divided into four groups (stroke, mild disease, sepsis and severe sepsis) as well as a control group (n=15) were studied. At admission (day 1), cortisol and ACTH were measured and a low-dose (1 μg) corticotrophin test was performed, followed 2 h later by a standard-dose (250 μg) corticotrophin test. Diurnal variation of cortisol was obtained on day 2. A second identical set of low-dose and standard-dose corticotrophin tests were performed on day 5 or 6 (recovery phase).

Results

In patients with stroke and severe sepsis, cortisol had the highest values and its diurnal variation was abolished. Dissociation of ACTH and cortisol was found in all patients.

The Δmax of cortisol after the 1-μg corticotrophin test did not differ among the groups, while after the 250-μg corticotrophin test, it was borderline higher in controls. The ratio of responders (Δmax of cortisol ≥9 μg/dl) to non-responders after 1- or 250-μg corticotrophin test did not differ among patients and controls. All patients had a good outcome without glucocorticoid treatment.

Conclusions

Depending on the severity of illness, mild alterations in the HPA axis occurred. However, relative corticosteroid insufficiency was not confirmed in NCIN patients.