bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ökonometrische Analyse der Entscheidungspraxis des Bundeskartellamtes / Econometric Analysis of the Decisions of the German Federal Cartel Office
Authors: Lauk Martina 
Published: April 2016

Zusammenfassung
Die Arbeit untersucht Entscheidungen des Bundeskartellamtes in den Bereichen „Missbrauchsaufsicht" und „Wettbewerbsbeschränkende Vereinbarungen". Die hier interessierende Frage ist, inwieweit die Entscheidungen der Kartellbehörde durch Kenntnis des Vorwurfs und einiger beobachtbarer Marktstrukturmerkmale erklärt werden können. Für die ökonometrische Analyse wurde in 196 Kartell- und Missbrauchsfällen der Jahre 1985-2000 recherchiert. Ergebnis der Analyse ist, dass Marktstrukturmerkmale einen signifikanten Einfluss auf die Entscheidungen des BKartA haben. Ca. 75 % der Entscheidungen können mit Kenntnis einiger beobachtbarer Marktstrukturmerkmale und dem kartellbehördlichen Vorwurf erklärt werden.
GluD2 Endows Parallel Fiber–Purkinje Cell Synapses with a High Regenerative Capacity
Authors: Ichikawa Ryoichi , Sakimura Kenji , Watanabe Masahiko 
Published: April 2016

Although injured axons usually do not regenerate in the adult CNS, parallel fibers (PFs) regenerate synaptic connections onto cerebellar Purkinje cells (PCs). In this study, we investigated the role of GluD2 in this regenerative process after PF transection using GluD2-knock-out (KO) mice. All dendritic spines on distal dendrites were innervated by PFs in sham-operated wild-type controls, whereas one-third were devoid of innervation in GluD2-KO mice. In both genotypes, a steep drop in the number of PF synapses occurred with a reciprocal surge in the number of free spines on postlesion day 1, when the PF territory aberrantly expanded toward the proximal dendrites. In wild-type mice, the territory and number of PF synapses were nearly fully restored to normal on postlesion day 7, although PF density remained low. Moreover, presynaptic and postsynaptic elements were markedly enlarged, and the PF terminal-to-PC spine contact ratio increased from 1:1 to 1:2 at most synapses. On postlesion day 30, the size and contact ratio of PF synapses returned to sham-operated control values and PF density recovered through the sprouting and elongation of PF collaterals. However, GluD2-KO mice showed neither a hypertrophic response nor territorial restoration 7 d postlesion, nor the recovery of PF axons or synapses on postlesion day 30. This suggests that PF wiring regenerates initially by inducing hypertrophic responses in surviving synaptic elements (hypertrophic phase), followed by collateral formation by PF axons and retraction of PF synapses (remodeling phase). Without GluD2, no transition to these regenerative phases occurs.SIGNIFICANCE STATEMENTThe glutamate receptor GluD2 expressed at parallel fiber (PF)–Purkinje cell (PC) synapses regulates the formation and maintenance of the synapses. To investigate the role of GluD2 in their extraordinarily high regenerative capacity, the process after surgical transection of PFs was compared between wild-type and GluD2-knock-out mice. We discovered that, in wild-type mice, PF synapses regenerate initially by inducing hypertrophic responses in surviving synaptic elements, and then by sprouting and elongation of PF collaterals. Subsequently, hypertrophied PF synapses remodel into compact synapses. In GluD2-knock-out mice, PF wiring remains in the degenerative phase, showing neither a hypertrophic response nor recovery of PF axons or synapses. Our finding thus highlights that synaptic connection in the adult brain can regenerate with aid of GluD2.
Task-Related Dynamic Division of Labor Between Anterior Temporal and Lateral Occipital Cortices in Representing Object Size
Authors: Chiou Rocco , Lambon Ralph Matthew A. 
Published: April 2016

Object size is represented by functionally distinct sectors along the ventral visual pathway. The early visual cortex encodes objects' sensory-retinal size. Subsequently, the occipitotemporal cortex computes objects' canonical size based on statistical regularities of visual features. Although the neurocomputation of size has been studied in a “bottom-up” sensory-driven framework, little is known about how perceptual size information is transformed into conceptual knowledge and how this computation is modulated by “top-down” goal-driven signals. Using continuous theta burst stimulation, we demonstrated that behavioral goal shapes the neurocognitive network underpinning object size. We manipulated the congruency of perceptual versus conceptual object size, which provides a robust behavioral probe reflecting implicit size knowledge. Neurostimulation was targeted at the lateral occipital cortex (LOC), a key region for object perception, or the anterior temporal lobe (ATL), a “hub” of supramodal conceptual processing. We observed striking contextual modulation of the neurocognitive architecture: when human participants judged perceptual size, the congruency effect was significantly attenuated by LOC stimulation but stayed resilient to ATL stimulation. By contrast, when they judged conceptual size, both LOC and ATL stimulation eradicated the otherwise robust effect. Our findings demonstrate disparate functional profiles of the LOC and ATL, providing the first evidence of a malleable network adaptively altering its division of labor with top-down states. The LOC, regardless of task demand, automatically represents “bottom-up” statistical regularities of visual conformation (reflecting typical object size), whereas the ATL contributes to this computation when the context requires semantically based linkage of visual attributes to object recognition.SIGNIFICANCE STATEMENTIn the present study, we provide compelling evidence that the “top-down” cognitive state of an observer changes the dynamic interaction between different subregions of the ventral temporal cortex. Using inhibitory neurostimulation combined with a novel paradigm, we demonstrate a flexible division of labor in the neurocognitive architecture that underpins size knowledge: the lateral occipital cortex codes perceptually based aspects (statistical visual configuration of small/large objects), whereas the anterior temporal lobe represents semantically based aspects (object identity), with their involvement interactively weighted by task demand. The interactive nature of the ventral temporal cortex highlights how top-down modulation constrains and shapes neural representations in the visual system.
Epac Signaling Is Required for Cocaine-Induced Change in AMPA Receptor Subunit Composition in the Ventral Tegmental Area
Authors: Liu Xiaojie , Chen Yao , Tong Jiaqing , Reynolds Ashley M. , Proudfoot Sarah C. , Qi Jinshun , Penzes Peter , Lu Youming , Liu Qing-song 
Published: April 2016

Exchange protein directly activated by cAMP (Epac) and protein kinase A (PKA) are intracellular receptors for cAMP. Although PKA and its downstream effectors have been studied extensively in the context of drug addiction, whether and how Epac regulates cellular and behavioral effects of drugs of abuse remain essentially unknown. Epac is known to regulate AMPA receptor (AMPAR) trafficking. Previous studies have shown that a single cocaine exposurein vivoleads to an increase in GluA2-lacking AMPARs in dopamine neurons of the ventral tegmental area (VTA). We tested the hypothesis that Epac mediates cocaine-induced changes in AMPAR subunit composition in the VTA. We report that a single cocaine injectionin vivoin wild-type mice leads to inward rectification of EPSCs and renders EPSCs sensitive to a GluA2-lacking AMPAR blocker in VTA dopamine neurons. The cocaine-induced increase in GluA2-lacking AMPARs was absent in Epac2-deficient mice but not in Epac1-deficient mice. In addition, activation of Epac with the selective Epac agonist 8-CPT-2Me-cAMP (8-CPT) recapitulated the cocaine-induced increase in GluA2-lacking AMPARs, and the effects of 8-CPT were mediated by Epac2. We also show that conditioned place preference to cocaine was impaired in Epac2-deficient mice and in mice in which Epac2 was knocked down in the VTA but was not significantly altered in Epac1-deficient mice. Together, these results suggest that Epac2 is critically involved in the cocaine-induced change in AMPAR subunit composition and drug-cue associative learning.SIGNIFICANCE STATEMENTAddictive drugs, such as cocaine, induce long-lasting adaptions in the reward circuits of the brain. A single intraperitoneal injection of cocaine leads to changes in the composition and property of the AMPAR that carries excitatory inputs to dopamine neurons. Here, we provide evidence that exchange protein directly activated by cAMP (Epac), a cAMP sensor protein, is required for the cocaine-induced changes of the AMPAR. We found that the effects of cocaine were mimicked by activation of Epac but were blocked by genetic deletion of Epac. Furthermore, cocaine-cue associative learning was impaired in mice lacking Epac. These findings uncovered a critical role of Epac in regulating the cellular and behavioral actions of cocaine.
Neurotrophin-3 Regulates Synapse Development by Modulating TrkC-PTPσ Synaptic Adhesion and Intracellular Signaling Pathways
Authors: Han Kyung Ah , Woo Doyeon , Kim Seungjoon , Choii Gayoung , Jeon Sangmin , Won Seoung Youn , Kim Ho Min , Heo Won Do , Um Ji Won , Ko Jaewon 
Published: April 2016

Neurotrophin-3 (NT-3) is a secreted neurotrophic factor that binds neurotrophin receptor tyrosine kinase C (TrkC), which in turn binds to presynaptic protein tyrosine phosphatase σ (PTPσ) to govern excitatory synapse development. However, whether and how NT-3 cooperates with the TrkC-PTPσ synaptic adhesion pathway and TrkC-mediated intracellular signaling pathways in rat cultured neurons has remained unclear. Here, we report that NT-3 enhances TrkC binding affinity for PTPσ. Strikingly, NT-3 treatment bidirectionally regulates the synaptogenic activity of TrkC: at concentrations of 10–25 ng/ml, NT-3 further enhanced the increase in synapse density induced by TrkC overexpression, whereas at higher concentrations, NT-3 abrogated TrkC-induced increases in synapse density. Semiquantitative immunoblotting and optogenetics-based imaging showed that 25 ng/ml NT-3 or light stimulation at a power that produced a comparable level of NT-3 (6.25 μW) activated only extracellular signal-regulated kinase (ERK) and Akt, whereas 100 ng/ml NT-3 (light intensity, 25 μW) further triggered the activation of phospholipase C-γ1 and CREB independently of PTPσ. Notably, disruption of TrkC intracellular signaling pathways, extracellular ligand binding, or kinase activity by point mutations compromised TrkC-induced increases in synapse density. Furthermore, only sparse, but not global, TrkC knock-down in cultured rat neurons significantly decreased synapse density, suggesting that intercellular differences in TrkC expression level are critical for its synapse-promoting action. Together, our data demonstrate that NT-3 is a key factor in excitatory synapse development that may direct higher-order assembly of the TrkC/PTPσ complex and activate distinct intracellular signaling cascades in a concentration-dependent manner to promote competition-based synapse development processes.SIGNIFICANCE STATEMENTIn this study, we present several lines of experimental evidences to support the conclusion that neurotrophin-3 (NT-3) modulates the synaptic adhesion pathway involving neurotrophin receptor tyrosine kinase C (TrkC) and presynaptic protein tyrosine phosphatase σ (PTPσ) in a bidirectional manner at excitatory synapses. NT-3 acts in concentration-independent manner to facilitate TrkC-mediated presynaptic differentiation, whereas it acts in a concentration-dependent manner to exert differential effects on TrkC-mediated organization of postsynaptic development. We further investigated TrkC extracellular ligand binding, intracellular signaling pathways, and kinase activity in NT-3-induced synapse development. Last, we found that interneuronal differences in TrkC levels regulate the synapse number. Overall, these results suggest that NT-3 functions as a positive modulator of synaptogenesis involving TrkC and PTPσ.
Knockdown of Dyslexia-GeneDcdc2Interferes with Speech Sound Discrimination in Continuous Streams
Authors: Centanni Tracy Michelle , Booker Anne B. , Chen Fuyi , Sloan Andrew M. , Carraway Ryan S. , Rennaker Robert L. , LoTurco Joseph J. , Kilgard Michael P. 
Published: April 2016

Dyslexia is the most common developmental language disorder and is marked by deficits in reading and phonological awareness. One theory of dyslexia suggests that the phonological awareness deficit is due to abnormal auditory processing of speech sounds. Variants inDCDC2and several other neural migration genes are associated with dyslexia and may contribute to auditory processing deficits. In the current study, we tested the hypothesis that RNAi suppression ofDcdc2in rats causes abnormal cortical responses to sound and impaired speech sound discrimination. In the current study, rats were subjectedin uteroto RNA interference targeting of the geneDcdc2or a scrambled sequence. Primary auditory cortex (A1) responses were acquired from 11 rats (5 withDcdc2RNAi; DC−) before any behavioral training. A separate group of 8 rats (3 DC−) were trained on a variety of speech sound discrimination tasks, and auditory cortex responses were acquired following training.Dcdc2RNAi nearly eliminated the ability of rats to identify specific speech sounds from a continuous train of speech sounds but did not impair performance during discrimination of isolated speech sounds. The neural responses to speech sounds in A1 were not degraded as a function of presentation rate before training. These results suggest that A1 is not directly involved in the impaired speech discrimination caused byDcdc2RNAi. This result contrasts earlier results usingKiaa0319RNAi and suggests that different dyslexia genes may cause different deficits in the speech processing circuitry, which may explain differential responses to therapy.SIGNIFICANCE STATEMENTAlthough dyslexia is diagnosed through reading difficulty, there is a great deal of variation in the phenotypes of these individuals. The underlying neural and genetic mechanisms causing these differences are still widely debated. In the current study, we demonstrate that suppression of a candidate-dyslexia gene causes deficits on tasks of rapid stimulus processing. These animals also exhibited abnormal neural plasticity after training, which may be a mechanism for why some children with dyslexia do not respond to intervention. These results are in stark contrast to our previous work with a different candidate gene, which caused a different set of deficits. Our results shed some light on possible neural and genetic mechanisms causing heterogeneity in the dyslexic population.
Maternal Loss ofUbe3aImpairs Experience-Driven Dendritic Spine Maintenance in the Developing Visual Cortex
Authors: Kim Hyojin , Kunz Portia A. , Mooney Richard , Philpot Benjamin D. , Smith Spencer L. 
Published: April 2016

Dendritic spines are a morphological feature of the majority of excitatory synapses in the mammalian neocortex and are motile structures with shapes and lifetimes that change throughout development. Proper cortical development and function, including cortical contributions to learning and memory formation, require appropriate experience-dependent dendritic spine remodeling. Dendritic spine abnormalities have been reported for many neurodevelopmental disorders, including Angelman syndrome (AS), which is caused by the loss of the maternally inheritedUBE3Aallele (encoding ubiquitin protein ligase E3A). Prior studies revealed that UBE3A protein loss leads to reductions in dendritic spine density and diminished excitatory synaptic transmission. However, the decrease in spine density could come from either a reduction in spine formation or an increase in spine elimination. Here, we used acute and longitudinalin vivotwo-photon microscopy to investigate developmental and experience-dependent changes in the numbers, dynamics, and morphology of layer 5 pyramidal neuron apical dendritic spines in the primary visual cortex of control and AS model mice (Ube3am−/p+mice). We found that neurons in AS model mice undergo a greater elimination of dendritic spines than wild-type mice during the end of the first postnatal month. However, when raised in darkness, spine density and dynamics were indistinguishable between control and AS model mice, which indicates that decreased spine density in AS model mice reflects impaired experience-driven spine maintenance. Our data thus demonstrate an experience-dependent anatomical substrate by which the loss of UBE3A reduces dendritic spine density and disrupts cortical circuitry.SIGNIFICANCE STATEMENTReduced dendritic spine densities are common in the neurodevelopmental disorder Angelman syndrome (AS). Because prior reports were based on postmortem tissue, it was unknown whether this anatomical deficit arises from decreased spine formation and/or increased spine elimination. Here, we usedin vivotwo-photon imaging to track spines over multiple days in a mouse model of AS. We found that spine formation is normal, but experience-dependent spine maintenance is reduced in the visual cortex of AS model mice. Our data pinpoint the anatomical process underlying the loss of dendritic spines, which can account for the decreased excitatory synaptic connectivity associated with AS. Therefore, normalizing spine maintenance is a potential therapeutic strategy.
Management of Acute Severe Colitis in Children With Ulcerative Colitis in the Biologics Era
Authors: Romano Claudio , Syed Sana , Valenti Simona , Kugathasan Subra 
Published: April 2016

BACKGROUND AND OBJECTIVE:Approximately one-third of children with ulcerative colitis will experience at least 1 attack of acute severe colitis (ASC) before 15 years of age. Severe disease can be defined in children when Pediatric Ulcerative Colitis Activity Index is &gt;65 and/or ≥6 bloody stools per day, and/or 1 of the following: tachycardia, fever, anemia, and elevated erythrocyte sedimentation rate with or without systemic toxicity. Our aim was to provide practical suggestions on the management of ASC in children. The goal of medical therapy is to avoid colectomy while preventing complications of disease, side effects of medications, and mortality.METHODS:A systematic search was carried out through Medline via PubMed to identify all articles published in English to date, based on the following keywords “ulcerative colitis,” “pediatric ulcerative colitis,” “biological therapy,” and “acute severe colitis.” Multidisciplinary clinical evaluation is recommended to identify early nonresponders to conventional treatment with intravenous corticosteroids, and to start, if indicated, second-line therapy or “rescue therapy,” such as calcineurin inhibitors (cyclosporine, tacrolimus) and anti–tumor necrosis factor molecules (infliximab).RESULTS:Pediatric Ulcerative Colitis Activity Index is a valid predictive tool that can guide clinicians in evaluating response to therapy. Surgery should be considered in the case of complications or rapid clinical deterioration during medical treatment.CONCLUSIONS:Several pitfalls may be present in the management of ASC, and a correct clinical and therapeutic approach is recommended to reduce surgical risk.
New light on the 1824 William Smith Northumberland County map: A joint work by Smith and Phillips
Authors: Pedley Martyn 
Published: April 2016

Smith's geological map of Northumberland probably was the most challenging of his 21 county maps to complete. It combined at least two earlier sets of data together with additional fieldwork in 1821 by his nephew John Phillips. This account focuses on two extant pre-publication maps and relates them to the published version. The earliest is a Smith field map drawn onto an Andrew Armstrong base map dated 1769 and the other is a pre-publication map drawn by an unknown hand onto a John Cary 1821 base map, possibly for use by Phillips as a reference map during his 1821 field work. There were significant gaps in the compilation of field data into a final master map caused by misfortunes ranging from Smith's wife's deteriorating mental state, his debt problems, brief incarceration, and a devastating fire at the Cary print works. Advancing old age also encouraged Smith to increasingly draw on the assistance of John Phillips for the final Northumberland field work. This was Phillips' first important piece of solo field mapping and was carried out late in 1821. His itinerary was designed in liaison with Smith who was concurrently working in Cumbria. Unfortunately, Phillips' field reference map misinterpreted Smith's inland Whin Sill outcrops drawn on the 1769 Armstrong base map. Consequently, Phillips in1821 did not recognise their significance and failed to include them in the 1824 published map.
Nevertheless, Phillips did solve Smith's geological problems in the southwest of the county where the Hartley Burn (Midgeholme) coalfield appeared to be out of sequence along its unexposed southern margins. This was correctly interpreted as a major fault contact and was indicated by a dashed line on the 1824 published map. This is believed to be the first fault line to be drawn on any Smith map and fits closely to the northern master fault of the Alston Block now known as the Stublick Fault. Phillips also identified the northerly extension of the Burtreeford Disturbance into the area. This is also marked by a bold dashed north-south line along the valley of the River East Allen. A third (unnamed) fault-line with a northwest-southeast trend in the West Allen valley was identified on the basis of truncated mineralisation within deep mines in the High Chapel area.
Co‐adsorption of Trichloroethylene and Arsenate by Iron‐Impregnated Granular Activated Carbon
Authors: Deng Baolin , Kim Eun‐Sik 
Published: April 2016

ABSTRACT: Co‐adsorption of trichloroethylene (TCE) and arsenate [As(V)] was investigated using modified granular activated carbons (GAC): untreated, sodium hypochlorite‐treated (NaClO‐GAC), and NaClO with iron‐treated GAC (NaClO/Fe‐GAC). Batch experiments of single‐ [TCE or As(V)] and binary‐ [TCE and As(V)] components solutions are evaluated through Langmuir and Freundlich isotherm models and adsorption kinetic tests. In the single‐component system, the adsorption capacity of As(V) was increased by the NaClO‐GAC and the NaClO/Fe‐GAC. The untreated GAC showed a low adsorption capacity for As(V). Adsorption of TCE by the NaClO/Fe‐GAC was maximized, with an increased Freundlich constant. Removal of TCE in the binary‐component system was decreased 15% by the untreated GAC, and NaClO‐ and NaClO/Fe‐GAC showed similar efficiency to the single‐component system because of the different chemical status of the GAC surfaces. Results of the adsorption isotherms of As(V) in the binary‐component system were similar to adsorption isotherms of the single‐component system. The adsorption affinities of single‐ and binary‐component systems corresponded with electron transfer, competitive adsorption, and physicochemical properties.