bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Deficiencies in Fragile X Neurons Derived from Human Embryonic Stem Cells
Authors: Telias Michael , Kuznitsov-Yanovsky Liron , Segal Menahem , Ben-Yosef Dalit 
Published: November 2015

Fragile X syndrome (FXS), the most common form of inherited mental retardation, is a neurodevelopmental disorder caused by silencing of the FMR1 gene, which in FXS becomes inactivated during human embryonic development. We have shown recently that this process is recapitulated byin vitroneural differentiation of FX human embryonic stem cells (FX-hESCs), derived from FXS blastocysts. In the present study, we analyzed morphological and functional properties of neurons generated from FX-hESCs. Human FX neurons can fire single action potentials (APs) to depolarizing current commands, but are unable to discharge trains of APs. Their APs are of a reduced amplitudes and longer durations than controls. These are reflected in reduced inward Na+and outward K+currents. In addition, human FX neurons contain fewer synaptic vesicles and lack spontaneous synaptic activity. Notably, synaptic activity in these neurons can be restored by coculturing them with normal rat hippocampal neurons, demonstrating a critical role for synaptic mechanisms in FXS pathology. This is the first extensive functional analysis of human FX neurons derivedin vitrofrom hESCs that provides a convenient tool for studying molecular mechanisms underlying the impaired neuronal functions in FXS.SIGNIFICANCE STATEMENTFragile X syndrome (FXS), the most common form of inherited mental retardation, is caused by silencing of the FMR1 gene. In this study, we describe for the first time the properties of neurons developed from human embryonic stem cells (hESCs) that carry the FMR1 mutation and are grown in culture for extended periods. These neurons are retarded compared with controls in several morphological and functional properties.In vitroneural differentiation of FX hESCs can thus serve as a most relevant system for the analysis of molecular mechanisms underlying the impaired neuronal functions in FXS.
Head-Directional Tuning and Theta Modulation of Anatomically Identified Neurons in the Presubiculum
Authors: Tukker John J. , Tang Qiusong , Burgalossi Andrea , Brecht Michael 
Published: November 2015

The presubiculum provides a major input to the medial entorhinal cortex (MEC) and contains cells that encode for the animal's head direction (HD), as well as other cells likely to be important for navigation and memory, including grid cells. To understand the mechanisms underlying HD cell firing and its effects on other parts of the circuit, it is important to determine the anatomical identity of these functionally defined cells. Therefore, we juxtacellularly recorded single cells in the presubiculum in freely moving rats, finding two classes of cells based on firing patterns and juxtacellular labeling (of a subset). Regular-firing cells had the anatomical characteristics of pyramidal cells and included most recorded HD cells. Therefore, HD cells are likely to be excitatory pyramidal cells. For one HD cell, we could follow an axon projecting directly to the MEC. Fast-spiking (FS) cells had the anatomical characteristics of interneurons and displayed weak HD tuning. Furthermore, FS cells displayed a surprising lack of theta-rhythmic firing, in strong contrast to the FS cells that we recorded in the MEC. Overall, we show that HD cells in the presubiculum are pyramidal cells, with FS interneurons only showing weak HD tuning; therefore, MEC may receive an excitatory HD input, as previously assumed by many models. The lack of theta rhythmicity in FS interneurons suggests that different mechanisms may underlie theta in different parts of the hippocampal formation.SIGNIFICANCE STATEMENTIn freely moving rats, we recorded and labeled single neurons in the presubiculum, an area providing one of the major inputs to the medial entorhinal cortex and part of a network involved in spatial navigation and memory.Post hocidentification of labeled cells showed that (fast-spiking, FS) interneurons and pyramidal cells in the presubiculum can be distinguished based on physiological criteria. We found that both moderately and strongly tuned head-direction (HD) cells are pyramidal cells and therefore likely to provide an excitatory HD input to the entorhinal cortex. FS interneurons were weakly head directional and, surprisingly, showed no theta-rhythmic firing. Therefore, the presubiculum appears to encode HD information via excitatory pyramidal cells, possibly also involving FS interneurons, without using a theta-rhythmic temporal code.
Astroglial Connexin 43 Hemichannels Modulate Olfactory Bulb Slow Oscillations
Authors: Roux Lisa , Madar Antoine , Lacroix Marie Masako , Yi Chenju , Benchenane Karim , Giaume Christian 
Published: November 2015

An emergent concept in neurosciences consists in considering brain functions as the product of dynamic interactions between neurons and glial cells, particularly astrocytes. Although the role played by astrocytes in synaptic transmission and plasticity is now largely documented, their contribution to neuronal network activity is only beginning to be appreciated. In mouse olfactory bulb slices, we observed that the membrane potential of mitral cells oscillates between UP and DOWN states at a low frequency (<1 Hz). Such slow oscillations are correlated with glomerular local field potentials, indicating spontaneous local network activity. Using a combination of genetic and pharmacological tools, we showed that the activity of astroglial connexin 43 hemichannels, opened in an activity-dependent manner, increases UP state amplitude and impacts mitral cell firing rate. This effect requires functional adenosine A1 receptors, in line with the observation that ATP is released via connexin 43 hemichannels. These results highlight a new mechanism of neuroglial interaction in the olfactory bulb, where astrocyte connexin hemichannels are both targets and modulators of neuronal circuit function.SIGNIFICANCE STATEMENTAn emergent concept in neuroscience consists in considering brain function as the product of dynamic interactions between neurons and glial cells, particularly astrocytes. A typical feature of astrocytes is their high expression level of connexins, the molecular constituents of gap junction channels and hemichannels. Although hemichannels represent a powerful medium for intercellular communication between astrocytes and neurons, their function in physiological conditions remains largely unexplored. Our results show that in the olfactory bulb, connexin 43 hemichannel function is promoted by neuronal activity and, in turn, modulates neuronal network slow oscillations. This novel mechanism of neuroglial interaction could influence olfactory information processing by directly impacting the output of the olfactory bulb.
Layer-Specific fMRI Responses to Excitatory and Inhibitory Neuronal Activities in the Olfactory Bulb
Authors: Poplawsky Alexander John , Fukuda Mitsuhiro , Murphy Matthew , Kim Seong-Gi 
Published: November 2015

High-resolution functional magnetic resonance imaging (fMRI) detects localized neuronal activity via the hemodynamic response, but it is unclear whether it accurately identifies neuronal activity specific to individual layers. To address this issue, we preferentially evoked neuronal activity in superficial, middle, and deep layers of the rat olfactory bulb: the glomerular layer by odor (5% amyl acetate), the external plexiform layer by electrical stimulation of the lateral olfactory tract (LOT), and the granule cell layer by electrical stimulation of the anterior commissure (AC), respectively. Electrophysiology, laser-Doppler flowmetry of cerebral blood flow (CBF), and blood oxygenation level-dependent (BOLD) and cerebral blood volume-weighted (CBV) fMRI at 9.4 T were performed independently. We found that excitation of inhibitory granule cells by stimulating LOT and AC decreased the spontaneous multi-unit activities of excitatory mitral cells and subsequently increased CBF, CBV, and BOLD signals. Odor stimulation also increased the hemodynamic responses. Furthermore, the greatest CBV fMRI responses were discretely separated into the same layers as the evoked neuronal activities for all three stimuli, whereas BOLD was poorly localized with some exception to the poststimulus undershoot. In addition, the temporal dynamics of the fMRI responses varied depending on the stimulation pathway, even within the same layer. These results indicate that the vasculature is regulated within individual layers and CBV fMRI has a higher fidelity to the evoked neuronal activity compared with BOLD. Our findings are significant for understanding the neuronal origin and spatial specificity of hemodynamic responses, especially for the interpretation of laminar-resolution fMRI.SIGNIFICANCE STATEMENTFunctional magnetic resonance imaging (fMRI) is a noninvasive,in vivotechnique widely used to map function of the entire brain, including deep structures, in animals and humans. However, it measures neuronal activity indirectly by way of the vascular response. It is currently unclear how finely the hemodynamic response is regulated within single cortical layers and whether increased inhibitory neuronal activities affect fMRI signal changes. Both laminar specificity and the neural origins of fMRI are important to interpret functional maps properly, which we investigated by activating discrete rat olfactory bulb circuits.
Amperometric Monitoring of Sensory-Evoked Dopamine Release in Awake Larval Zebrafish
Authors: Shang Chun-feng , Li Xiao-quan , Yin Chen , Liu Bing , Wang Yu-fan , Zhou Zhuan , Du Jiu-lin 
Published: November 2015

Dopamine plays crucial roles in a broad spectrum of brain functions, and neural circuit mechanisms underlying dopaminergic regulation have been intensively studied in the past decade. As larval zebrafish have relatively simple and highly conserved dopaminergic systems, it can serve as an ideal vertebrate animal model to tackle this issue at a whole-brain scale. For this purpose, it is important to develop methods for monitoring endogenous dopamine release in intact larval zebrafish. Here, we developed a real-time method to monitor dopamine release at high spatiotemporal resolution in the brain of awake larval zebrafish using carbon fiber microelectrodes. As an example for application, we combined this method with genetic tools andin vivocalcium imaging and found that food extract can activate pretectal dopaminergic neurons, which in turn release dopamine at the visual center through their projection, providing a dopaminergic circuit mechanism for olfactory modulation of visual functions. Thus, our study demonstrates, for the first time, the utility of carbon fiber microelectrodes for monitoring sensory-evoked dopamine release in the brain of an awake small organism.SIGNIFICANCE STATEMENTWith carbon fiber microelectrodes, we have succeeded in monitoring sensory-evoked dopamine release in the brain of an awake small organism for the first time. By elucidating the circuitry origin of the dopamine release, we illustrated the potential application of this method in dissection of the neural circuitry mechanisms underlying dopaminergic neuromodulation.
Comprehensive Corticospinal Labeling withmu-crystallinTransgene Reveals Axon Regeneration after Spinal Cord Trauma inngr1−/−Mice
Authors: Fink Kathren L. , Strittmatter Stephen M. , Cafferty William B.J. 
Published: November 2015

Spinal cord injury interrupts descending motor tracts and creates persistent functional deficits due to the absence of spontaneous axon regeneration. Of descending pathways, the corticospinal tract (CST) is thought to be the most critical for voluntary function in primates. Even with multiple tracer injections and genetic tools, the CST is visualized to only a minor degree in experimental studies. Here, we identify and validate the mu-crystallin (crym) gene as a high-fidelity marker of the CST. In transgenic mice expressing green fluorescent protein (GFP) undercrymregulatory elements (crym-GFP), comprehensive and near complete CST labeling is achieved throughout the spinal cord. Bilateral pyramidotomy eliminated the 17,000 GFP-positive CST axons that were reproducibly labeled in brainstem from the spinal cord. We show that CST tracing withcrym-GFP is 10-fold more efficient than tracing with biotinylated dextran amine (BDA). Usingcrym-GFP, we reevaluated the CST in mice lacking nogo receptor 1 (NgR1), a protein implicated in limiting neural repair. The number and trajectory of CST axons inngr1−/−mice without injury was indistinguishable fromngr1+/+mice. After dorsal hemisection in the midthoracic cord, CST axons did not significantly regenerate inngr1+/+mice, but an average of 162 of the 6000 labeled thoracic CST axons (2.68%) regenerated >100 μm past the lesion site incrym-GFPngr1−/−mice. Although traditional BDA tracing cannot reliably visualize regeneratingngr1−/−CST axons, their regenerative course is clear withcrym-GFP. Therefore thecrym-GFP transgenic mouse is a useful tool for studies of CST anatomy in experimental studies of motor pathways.SIGNIFICANCE STATEMENTAxon regeneration fails in the adult CNS, resulting in permanent functional deficits. Traditionally, inefficient extrinsic tracers such a biotinylated dextran amine (BDA) are used to label regenerating fibers after therapeutic intervention. We introducecrym-green fluorescent protein (GFP) transgenic mice as a comprehensive and specific tool with which to study the primary descending motor tract, the corticospinal tract (CST). CST labeling withcrym-GFP is 10 times more efficient compared with BDA. The enhanced sensitivity afforded bycrym-GFP revealed significant CST regeneration in NgR1 knock-out mice. Therefore,crym-GFP can be used as a standardized tool for future CST spinal cord injury studies.
Automatic and Controlled Semantic Retrieval: TMS Reveals Distinct Contributions of Posterior Middle Temporal Gyrus and Angular Gyrus
Authors: Davey James , Cornelissen Piers L. , Thompson Hannah E. , Sonkusare Saurabh , Hallam Glyn , Smallwood Jonathan , Jefferies Elizabeth 
Published: November 2015

Semantic retrieval involves both (1) automatic spreading activation between highly related concepts and (2) executive control processes that tailor this activation to suit the current context or goals. Two structures in left temporoparietal cortex, angular gyrus (AG) and posterior middle temporal gyrus (pMTG), are thought to be crucial to semantic retrieval and are often recruited together during semantic tasks; however, they show strikingly different patterns of functional connectivity at rest (coupling with the “default mode network” and “frontoparietal control system,” respectively). Here, transcranial magnetic stimulation (TMS) was used to establish a causal yet dissociable role for these sites in semantic cognition in human volunteers. TMS to AG disrupted thematic judgments particularly when the link between probe and target was strong (e.g., a picture of an Alsatian with a bone), and impaired the identification of objects at a specific but not a superordinate level (for the verbal label “Alsatian” not “animal”). In contrast, TMS to pMTG disrupted thematic judgments for weak but not strong associations (e.g., a picture of an Alsatian with razor wire), and impaired identity matching for both superordinate and specific-level labels. Thus, stimulation to AG interfered with the automatic retrieval of specific concepts from the semantic store while stimulation of pMTG impaired semantic cognition when there was a requirement to flexibly shape conceptual activation in line with the task requirements. These results demonstrate that AG and pMTG make a dissociable contribution to automatic and controlled aspects of semantic retrieval.SIGNIFICANCE STATEMENTWe demonstrate a novel functional dissociation between the angular gyrus (AG) and posterior middle temporal gyrus (pMTG) in conceptual processing. These sites are often coactivated during neuroimaging studies using semantic tasks, but their individual contributions are unclear. Using transcranial magnetic stimulation and tasks designed to assess different aspects of semantics (item identity and thematic matching), we tested two alternative theoretical accounts. Neither site showed the pattern expected for a “thematic hub” (i.e., a site storing associations between concepts) since stimulation disrupted both tasks. Instead, the data indicated that pMTG contributes to the controlled retrieval of conceptual knowledge, while AG is critical for the efficient automatic retrieval of specific semantic information.
Predictive value of various Doppler-derived parameters of atrial conduction time for successful atrial fibrillation ablation
Authors: Shanks Miriam , Valtuille Lucas , Choy Jonathan B. , Becher Harald 
Published: November 2015

Abstract
Various Doppler-derived parameters of left atrial electrical remodeling have been demonstrated to predict recurrence of atrial fibrillation (AF) after AF ablation. The aim of this study was to compare three Doppler-derived measures of atrial conduction time in patients undergoing AF ablation, and to investigate their predictive value for successful procedure. In 32 prospectively enrolled patients undergoing the first AF ablation, atrial conduction time was estimated by measuring the time delay between the onset of P-wave on the surface ECG to the peak of the a′-wave on the pulsed-wave Doppler and color-coded tissue Doppler imaging of the left atrial lateral wall, and to the peak of the A-wave on the pulsed-wave Doppler of the mitral inflow. There was a significant difference in the baseline atrial conduction time measured by different echocardiographic techniques. Most (88%) patients had normal or only mildly dilated left atrium. At 6 months, 12 patients (38%) had recurrent AF/atrial tachycardia. The duration of history of AF was the only predictor of AF/atrial tachycardia recurrence following the first AF ablation (P=0.024; OR 1.023, CI 1.003–1.044). A combination of normal left atrial volume and history of paroxysmal AF of ≤48 months was associated with the best outcome. Predictive value of the Doppler derived parameters of atrial conduction time may be reduced in the early stages of left atrial remodeling. Future studies may determine which echocardiographic parameter correlates best with the extent of left atrial remodeling and is most predictive of successful AF ablation.
Messung kaniner und feliner PankreaslipaseImmunreaktivität – analytischer Vergleich neuer kommerzieller Tests mit etablierten Assays
Authors: Höfel E. , Suchodolski J. S. , Steiner J. M. , Burke K. , Rieker T. 
Published: November 2015

ZusammenfassungGegenstand und Ziel: Zur Messung der kaninen und felinen Pankreaslipase-Immunreaktivität gibt es seit mehreren Jahren kommerzielle Tests (Spec cPL®, Spec fPL®). Ziel der Studie war, neu verfügbare, bisher in der Literatur nicht validierte Assays mit den etablierten Assays zu vergleichen. Material und Methoden: Überschüssige Serumproben des GI-Labors der Texas A&M University wurden basierend auf verschiedenen Parametern (z. B. gute Probenqualität, hämolytische, lipämische, ikterische Proben) gesammelt und mit randomisierten ID-Nummern gekennzeichnet. Nach Durchführung der Tests Spec cPL® bzw. Spec fPL® wurden die Proben auf Trockeneis an die Kleintierklinik am Hochberg (Deutschland) versandt. Von dort ging ein Teil jeder Probe zur Untersuchung mit den neuen Assays verblindet an das Diagnostiklabor Laboklin (Deutschland). Ein weiterer Teil jeder Probe wurde zur erneuten Testung an das GI-Labor zurückgeschickt, um transportbedingte Veränderungen ausschließen zu können. Die Ergebnisse wurden mittels Wilcoxon-Vorzeichen-Rang-Tests, Rangkorrelationskoeffizienten, Bias Plots, Regressionsgleichung und Konkordanzkoeffizienten statistisch ausgewertet. Ergebnisse: Die Resultate des Spec cPL® und Spec fPL® im GI-Labor vor bzw. nach dem Transport differierten nicht signifikant (Wilcoxon-Rangsummentest: p = 0,581 bzw. 0,712). Zwischen den Ergebnissen der neuen Assays und der etablierten Assays bestanden signifikante Unterschiede (p = 0,0004 bzw. 0,025). Es zeigte sich zwar eine signifikante Assoziation zwischen den neuen und den etablierten Assays (Spearman r: 0,775 und 0,739), doch wurden signifikante systematische Abweichungen für die neuen Assays festgestellt. Konkordanzkoeffizienten der neuen Assays im Vergleich zu den etablierten Assays erwiesen sich als schwach (0,539 bzw. 0,465). Die klinische Interpretation der cPLund fPL-Ergebnisse stimmte in vielen Fällen nicht überein. Schlussfolgerung und klinische Relevanz: Die neuen Assays zur Bestimmung der cPL und fPL weisen statistisch signifikante Ungenauigkeiten auf und ergeben teilweise andere klinische Interpretationen. Deshalb sind weitere Studien zur Validierung der Tests nötig, bevor sie für den klinischen Gebrauch empfohlen werden können.
Computertomographische Untersuchungen mit computerassistierter Detektion von pulmonalen Rundherden bei Hund und Katze
Authors: Piesnack S. , Köhler C. , Ludewig E. , Alef M. , Kiefer I. , Niesterok C. 
Published: November 2015

ZusammenfassungZiel war, den diagnostischen Wert der computerassistierten Detektion (CAD) von pulmonalen Rundherden in der Tiermedizin zu überprüfen. Hierzu wurde die Detektionsrate der computerassistierten Methode mit der Detektionsrate zweier unabhängiger Untersucher in Bezug auf die Sensitivität und die Rate falsch positiver Befunde verglichen. Material und Methoden: In die Studie wurden 51 Hunde und 16 Katzen einbezogen, bei denen zuvor mittels computertomographischer Untersuchung pulmonale Rundherde diagnostiziert worden waren. Zwei unabhängige Untersucher erfassten bei jedem Patienten die Anzahl der Rundherde ≥ 3 mm und setzten anschließend das Programm zur automatischen Rundherddetektion ein. Im letzten Schritt wurde ein Konsensus der beiden Untersucher unter Kenntnis der CAD-Ergebnisse getroffen. Zur Rundherdauswertung diente ein kommerziell erhältliches Programm zur computerassistierten Detektion. Ergebnisse: Insgesamt wurden 586 pulmonale Rundherde diagnostiziert. Für Untersucher 1 ergab sich eine Sensitivität von 89,2%, für Untersucher 2 betrug sie 87,4%. Die CAD erreichte eine Sensitivität von 69,4%. Mithilfe der CAD ließ die Sensitivität von Untersucher 1 auf 94,7% und die Sensitivität von Untersucher 2 auf 90,8% steigern. Schlussfolgerung und klinische Relevanz: Das verwendete CAD-System wies eine moderate Sensitivität von 69,4% auf. Trotz gewichtiger Limitationen wie einer hohen Anzahl an falsch positiven und falsch negativen Befunden konnte die CAD die Sensitivität beider Untersucher erhöhen, sodass sie zumindest eine unterstützende Funktion besitzt.
Establecimiento de tres especies arbóreas en la cuenca del río Magdalena, México
Authors: Castillo-Argüero Silvia , Martínez-Orea Yuriana , Barajas-Guzmán Guadalupe 
Published: November 2015

Se evaluó la supervivencia y crecimiento de tres especies arbóreas bajo diferentes tratamientos de micorrización ( Quercus rugosa ), y cobertura vegetal ( Abies religiosa y Pinus hartwegii ) con el objetivo de recomendar los tratamientos para la restauración y manejo del bosque en la cuenca del río Magdalena. La supervivencia, la altura y el diámetro del tallo se evaluaron a lo largo de un año, de agosto de 2006 a agosto de 2007. Los porcentajes de supervivencia más bajos se registraron tanto en Abies religiosa como en Pinus hartwegii en el tratamiento sin vegetación. En el caso Quercus rugosa en el tratamiento con micorrizas fue donde se presentó mayor supervivencia. Asimismo las plantas de Quercus rugosa con micorrizas alcanzaron significativamente un mayor crecimiento en altura que las no inoculadas. Los tratamientos utilizados fueron exitosos para las tres especies arbóreas por lo que se recomienda reforestar adecuadamente con estas especies para un mejor manejo de cada tipo de vegetación dentro de la cuenca del río Magdalena.