bluuebunny/crossref_metadata_2025 huggingface dataset:
Mismatch Negativity in Patients with Schizophrenia
Authors: Urban Aleš , Kremláček Jan , Libiger Jan
Published: April 2018

Cognitive deficit is considered to be a part of core dysfuncions in schizophrenia. It is associated with social impairment and influences the long-term course of the disorder. In addition to neuropsychological methods, event-related potentials can be used to study cognitive functions. In patients with schizophrenia an association was found between amplitude changes in slow negative component of evoked responses and infrequent deviations in a series of uniform stimuli. This amplitude change is known as „mismatch negativity“ (MMN). It is supposed to be independent of the focused attention and effort that otherwise interfere with neuropsychological testing. Recently accumulated knowledge on MMN as a possible preattentive measure of cognition supports its potential significance for neuropsychological assessment. It may be helpful in more precise diagnosis and functional evaluation of schizophrenia.
Essential PTX3 Biology (not only) for Cardiologists and Cardiac Surgeons
Authors: Kuneš Pavel , Lonský Vladimír , Manďák Jiří , Brtko Miroslav , Koláčková Martina , Andrýs Ctirad , Kudlová Manuela , Krejsek Jan
Published: April 2018

Inflammation has been recognized to form an integral part of the atherosclerotic process. Much consideration has been given lately to the role played in atherogenesis by C-reactive protein (CRP). Although not accepted unequivocally, CRP appears to be not only a marker, but also an active mediator of the atherosclerotic process. Pentraxin 3 (PTX3) is a newly identified acute phase reactant which shares some structural and some functional properties with CRP. On the other hand, pentraxin 3 displays unique biological properties of its own, including a possible role in the pathogenesis of cardiovascular diseases and in processes accompanying the natural evolution of surgical wounds. This review article discusses recent information concerning basic pentraxin 3 biology in inflammation and in innate immunity reactions as viewed by a cardiologist in the context of acute coronary events and by a surgeon in patients struck with multiple wounds who are at the same time menaced by bacterial infections.
Differentiation of Neural Stem Cells Into Cells of Oligodendroglial Lineage
Authors: Mokrý Jaroslav , Karbanová Jana , Čížková Dana , Pazour Jan , Filip Stanislav , Österreicher Jan
Published: April 2018

We described three different conditions that induce differentiation of dissociated neural stem cells derived from mouse embryonic CNS. In the first set of experiments, where the cell differentiation was triggered by cell adhesion, removal of growth factors and serum-supplemented medium, only sporadic neuronal and astroglial cells survived longer than two weeks and the latter formed a monolayer. When differentiation was induced in serum-free medium supplemented with retinoic acid, rapid and massive cell death occurred. A prolonged survival was observed in cultivation medium supplemented with serum and growth factors EGF plus FGF-2. One third of the cells did not express cell differentiation markers and were responsible for an increase in cell numbers. The remaining cells differentiated and formed the astrocytic monolayer on which occasional neuronal cells grew. One third of the differentiated phenotypes were represented by cells of oligodendroglial lineage. Differentiation of oligodendroglial cells occurred in a stepwise mechanism because the culture contained all successive developmental stages, including oligodendrocyte progenitors, preoligodendrocytes and immature and mature oligodendrocytes. Maturing oligodendrocytes displayed immunocytochemical and morphological features characteristic of cells that undergo physiological development. The cultivation conditions that supported growth and differentiation of neural stem cells were optimal for in vitro developmental studies and the production of oligodendroglial cells.
Depletion of ATP and Oxidative Stress Underlie Zinc-Induced Cell Injury
Authors: Rudolf Emil
Published: April 2018

The mechanisms of cell injury resulting in a special type of cell death combining the features of apoptosis and necrosis were examined in Hep-2 cells exposed to 300 μM zinc sulfate during 24h. Acute exposure to zinc induced a rapid rise in metallothionein levels and increased oxidative stress occurring in the absence of a significant early ATP depletion. Accentuated ATP loss and elevated levels of superoxide at later treatment intervals (12h and longer) were present along with increased DNA damage. Manipulation with ATP production and inhibition of NADPH oxidase had a positive effect on zinc-related increase in oxidative stress and influenced the observed type of cell death. These results suggest that Hep-2 cells acutely exposed to zinc increase intracellular labile zinc stores and over express metalothioneins. Elevated production of peroxides in zinc-treated cells is at later treatment intervals accompanied by an increase in superoxide levels, possibly by activation of NADPH oxidase, DNA damage and severe ATP loss. Prevention of critical ATP depletion and, in particular, inhibition of oxidative stress attenuates zinc-mediated cell injury and stimulates apoptosis-like phenotype in exposed cells.
NT-proBNP and Echocardiographic Parameters in Patients with Acute Heart Failure
Authors: Pudil Radek , Tichý Miloš , Praus Rudolf , Bláha Václav , Vojáček Jan
Published: April 2018

Aim. The aim of this study was to analyse the relation between clinical, haemodynamic and X-ray parameters and plasma NT-proBNP level in pts with symptoms of left ventricular dysfunction. Methods. The plasma NT-proBNP levels, chest x-ray, transthoracic 2-d and Doppler echocardiography were performed at the time of admission in a group of 96 consecutive patients (mean age 68 ± 11 years) with symptoms of acute heart failure. NT-proBNP levels were assessed with the use of commercial tests (Roche Diagnostics). Results. All patients have significant increase in NT-proBNP (8 000 ± 9 000 pg/mL vs. controls 90 ± 80 pg/mL, p < 0.001). The group of all patients has shown a significant increase in cardiothoracic ratio (CTR, 0.6 ± 0.1, vs. 0.4 ± 0.1, p <0.001), left atrium diameter (LAD, 4.4 ± 0.8 cm, vs.3.5 ± 0.4 cm, p <0.01). Left ventricular ejection fraction (LVEF) was decreased (37 ± 15%, vs. 64 ± 5%, p <0.001). In patients with acute heart failure, NT-proBNP significantly correlated with end-systolic and end-diastolic left ventricle diameters, ejection fraction, vena cava inferior diameter and plasma creatinine levels. Conclusion. Increased plasma NT-proBNP level is influenced by the clinical severity of acute heart failure and correlates with LVEF and IVCD. NT-proBNP can serve as a marker for the clinical severity of the disease.
Portal Hypertension Due to Echinococcus Alveolaris: A Case Report
Authors: Poyrazoğlu Orhan Kürşat , Ataseven Hüseyin , Bektas Sevim , Aydin Ayse , Yalniz Mehmet , Çelebı Selman , Bahçecıoğlu Ibrahim Halil
Published: April 2018

Infection of the liver with Echinococcus alveolaris (EA) contemplates with a fatal course though it is a rare condition. We present herein a patient with upper gastrointestinal bleeding due to portal hypertension caused by the involvement of the liver with EA.
A survey of the vulnerable Cuvier’s gazelle (Gazella cuvieri) in the mountains of Ait Tamlil and Anghomar, Central High Atlas of Morocco
Authors: El Alami Abderrazak
Published: April 2018

This article reports data on the distribution of the Cuvier’s gazelle in the mountains of Ait Tamlil and Anghomar, Central High Atlas. In this study, a combination of standardized interviews combined with a field survey to gather information about gazelles in the region was used. Results confirm the presence of the Cuvier’s gazelle in the high summits of the region limited by the villages of Tikhfist, Megdaz and the lake of Tamda n’Anghomar. The species is threatened by overhunting and habitat destruction. The conservation of Gazella cuvieri is required to increase habitat protection, to enforce the law against capturing gazelles and to raise the awareness of local people about the conservation of this mammal.
Crystal structure of 1,1′-((1E,1′E)-(((ethane-1,2-diylbis(oxy))bis(2,1-phenylene))bis(azanylylidene))bis(methanylylidene))bis(naphthalen-2-olato)cobalt(II), C36H26N2O4Co
Authors: Li Guo Qiang , Zhao Yan Ling , Jiang Yong Sen , Yu Yun Chun , Fang Jun Ran , Xu Qiang
Published: April 2018

C36H26N2O4Co, monolinic, C2/c (no. 15), a = 43.230(14) Å, b = 17.100(6) Å, c = 11.275(4) Å, β = 103.112(4)°, V = 8118(5) Å3, Z = 12, R
gt(F) = 0.0370, wR
ref(F
2) = 0.0931, T = 100(2) K.
Crystal structure of dimethanol-(μ2-squarato-κ2
O:O′)-tetrakis(tri-p-tolylphosphane-κP)disilver(I) – methanol (1/2), C92H98Ag2O8P4
Authors: Liu Kuanguan , Nie Jing
Published: April 2018

C92H98Ag2O8P4, triclinic, P1̄ (no. 2), a = 11.179(3) Å, b = 12.623(3) Å, c = 15.656(4) Å, α = 83.607(8)°, β = 78.636(9)°, γ = 83.128(9)°, V = 2141.6(10) Å3, Z = 2, R
gt(F) = 0.0398, wR
ref(F
2) = 0.1034, T = 294(2) K.
Crystal structure of aqua(1-(2-pyridyl)ethanone oxime-κ2
N,N′)(1-(2-pyridyl)ethanone oximato-κ2
N,N′) nitrate monohydrate, C14H19N5O7Cu
Authors: Zuo Jian
Published: April 2018

C14H19N5O7Cu, triclinic, P1̅ (no. 2), a = 10.8164(15) Å, b = 11.4831(17) Å, c = 15.423(2) Å, α = 101.035(3)°, β = 100.538(2)°, γ = 101.708(2)°, V = 1791.5(4) Å3, Z = 4, R
gt(F) = 0.0416, wR
ref(F
2) = 0.1131, T = 298(2) K.
Crystal structure of 3,5-bis(trifluoromethyl)benzyl(Z)-N-(adamantan-1-yl)morpholine-4-carbothioimidate, C24H28F6N2OS
Authors: Al-Wahaibi Lamya H. , Hassan Hanan M. , Ghabbour Hazem A. , El-Emam Ali A.
Published: April 2018

C24H28F6N2OS, monoclinic, P21/n (no. 14), a = 17.4112(7) Å, b = 8.3694(3) Å, c = 17.6728(7) Å, β = 104.612(2)°, V = 2492.01(17) Å3, Z = 4, R
gt(F) = 0.0603, wR(F
2) = 0.1704, T = 293(2) K.
Synthesis and crystal structure of 6-carboxy-1-(3,5-dicarboxyphenyl)-1H-benzo[d]imidazol-3-ium-5-carboxylate dihydrate, C18H12N2O8
Authors: Yun Meng , Dong Xiu-Yan
Published: April 2018

C18H12N2O8, triclinic, P1̄ (no. 2), a = 8.4592(10) Å, b = 9.8442(11) Å, c = 11.2565(12) Å, α = 66.892(3)°, β = 86.069(3)°, γ = 81.658(4)°, V = 852.97(17) Å3, Z = 2, R
gt(F) = 0.0609, wR
ref(F
2) = 0.1557, T = 153(2) K.
Crystal structure and molecular packing of O-ethyl (2-chlorophenyl)carbamothioate, C9H10ClNOS
Authors: Yeo Chien Ing , Tiekink Edward R.T.
Published: April 2018

C9H10ClNOS, triclinic, P1̄ (no. 2), a = 7.2277(3) Å, b = 9.9791(3) Å, c = 14.7725(7) Å, α = 81.007(3)°, β = 82.268(4)°, γ = 73.210(3)°, V = 1003.01(7) Å3, Z = 4, R
gt(F) = 0.0364, wR
ref(F
2) = 0.0828, T = 100(2) K.
Religious Diversity, Social Cohesion, and the Role of Interfaith Cooperation in Resilient Global Cities
Authors: Banout Tony , Henderson Brad
Published: April 2018

The city of the future will have to come to terms with astronomical population growth comprised of individuals and communities that differ on matters of fundamental beliefs living in increasingly close proximity. The test will be whether religious diversity increasingly leads to clashing parochialisms or unlocks possibilities for human flourishing. With 7.5 billion people urbanized by 2050, cities simply must include attention to religious diversity, and the science of social capital and interfaith cooperation can inform the discourse of resiliency as humanity prepares. Ample sociological research supports the conclusion that societies thrive where and when they are able to build trusting relationships across lines of deep difference. The inverse failure to do so is a direct danger to civil peace. This article charts a path forward to building and sustaining those relationships in an urban setting.
Fe3+-bis-ethylenediamine complex bridged periodic mesoporous organosilica for the efficient removal of arsenate and chromate
Authors: Parambadath Surendran , Mathew Aneesh , Kim Su Yeon , Park Sung Soo , Ha Chang-Sik
Published: April 2018

The direct removal of arsenate (AsO4
3−) and chromate (CrO4
2−) from water were achieved using a Fe3+-bis-ethylenediamine complex-bridged periodic mesoporous organosilica with a 20% organosilane content (Fe-EDPMO-20). The bridged Fe3+-bis-ethylenediamine complex was introduced to the pore wall of the PMO by combining the pre-complexation and co-condensation processes. N,N′-bis[3-(triethoxysilyl)propyl]ethylenediamine (TESEN) and tetramethyl orthosilicate (TMOS) as silica precursors were used with cetyltrimethylammonium bromide (CTABr) as a surfactant under basic conditions for the preparation of highly ordered Fe-EDPMO-20. Transmission electron microscopy, X-ray diffraction, and N2 adsorption-desorption measurements confirmed that the Fe-EDPMO-20 had an ordered hexagonal p6mm mesostructure. The material had a Brunauer-Emmett-Teller surface area of 734 m2 g−1, pore diameter of 2.6 nm, and pore volume of 0.61 cm3 g−1. UV-vis and X-ray photoelectron spectroscopy confirmed that Fe3+ was embedded in the coordination site by the nitrogen atoms from ethylenediamine. The adsorption efficiencies of arsenate and chromate ions by Fe-EDPMO-20 were examined as a function of pH, stirring time, amount of adsorbent, and initial concentration of metal ion solution. The maximum adsorption for arsenate and chromate were 156 and 102 mg g−1 within 6 and 24 h, respectively, at pH 4.
Design of smart tools to support pre- and intra-operative use of surgical navigation systems
Authors: Gieseler Oliver , Alvarez-Gomez Julio C. , Roth Hubert , Wahrburg Jürgen
Published: April 2018

In this paper we present novel solutions to support the application of computer assisted surgical interventions in which optical surgical navigation systems based on stereo cameras are used. The objective is to improve both the pre-operative setup and the intra-operative use of the navigation system. Following a short introduction describing the potential for improvements of existing navigation systems new approaches and the components to implement them are described. The pre-operative alignment of the stereo camera is made easier by attaching a small graphic display to its tripod which can show how much of the operating area is covered by the measurement volume of the camera. The intra-operative application is improved by a mechanism for motorized camera motions in order to follow the position of surgical instruments. Furthermore a small display can be attached to a surgical instrument which clearly indicates to the surgeon how to guide the instrument in order to stay on the planned trajectory.
Individualisierung von Religion?
Authors: Lienau Detlef
Published: April 2018

Am Beispiel des Pilgerns wird die Annahme einer Individualisierung von Religion erörtert. Ergebnisse einer qualitativ-empirischen Studie zur religiösen Erfahrung von Pilgern werden in die für Individualisierung relevanten theoretischen Konzepte Subjektivität, Sozialität und Autonomie eingebracht. Religion wird als selbst gemachte Erfahrung, also subjektiviert, sichtbar. Autonomie wird zwar gegenüber sozialen Ansprüchen behauptet, zugleich aber aufgehoben im Sich-Ausliefern an und Aufgehen in den Dingen und Eindrücken. Die soziologischen Konzepte zu Privatisierung und Entscheidungscharakter von Religion bestätigen sich im Pilgern nicht. Die Frage nach der Individualisierung von Religion ist für das Pilgern mithin differenziert zu beantworten: Religion ereignet sich im je einzelnen Subjekt, das sich hinsichtlich der sozialen Einbindung pragmatisch verhält, während es eine gewissheitsstiftende ent-individualisierende Einbindung in scheinbar vorsoziale Dinge wie Natur und den eigenen Leib sucht.
The Medium is the Messenger?
Authors: Roth Mirko
Published: April 2018

In diesem Aufsatz wird eine kommunikations- und medientheoretische Untersuchung ausgewählter Divinationspraktiken unternommen. Im Zentrum stehen hierbei das Giftorakel der zentralafrikanischen Zande sowie die arabisch-islamische Geomantie. Dieses Unternehmen hat den Zweck, drei Thesen bezüglich Medien religiöser Kommunikation zu erproben, die sich dem Autor aus der Auseinandersetzung mit Ritualen und speziell Divinationsformen aus unterschiedlichen soziokulturellen Kontexten ergeben haben:1) Divinationsmedien unterscheiden sich in frappierender Weise von Medien der Alltagskommunikation; 2) diese besonderen Medien ermöglichen eine Kommunikation zwischen Wirklichkeitsbereichen (i. S. der Strukturen der Lebenswelt [Schütz/Luckmann]) und verkörpern damit ein fundamentales „Dazwischen“; 3) von einer Innenperspektive betrachtet, werden Divinationsmedien oft als aktive Kommunikationspartner konzipiert und wahrgenommen – selbst wenn diese aus einer Beobachterperspektive unbelebte Paraphernalia sind.Um eine Grundlage für die Plausibilisierung dieser Thesen zu schaffen, ist anfänglich von Kommunikation und Medien sowie den Besonderheiten religiöser Kommunikation und Medien religiöser Kommunikation die Rede. Auf die detaillierte Beschreibung der Divinationspraktiken folgen ihre kommunikationstheoretische Analyse sowie eine zeichen- und medientheoretische Deutung dieser Ergebnisse.Das Ziel dieses Aufsatzes liegt neben der Plausibilisierung seiner Thesen auch darin, Impulse für die religionswissenschaftliche Debatte um Medien, Materialität und Performanz zu liefern. Gerade in den Ergebnissen der Divinationsforschung sieht David Morgan, wie er jüngst in Material religion schrieb, ein ertragreiches Feld.
Theory and Empiricism of Religious Evolution (THERE): Foundation of a Research Program. Part 1
Authors: Krech Volkhard
Published: April 2018

This two-part article presents the research program for a theory and empirical analysis of religious evolution. It is assumed that religion isprimarilya co-evolution to societal evolution, which in turn is a co-evolution to mental, organic, and physical evolution. The theory of evolution is triangulated with the systems theory and the semiotically informed theory of communication, so that knowledge can be gained that would not be acquired by only one of the three theories: The differentiation between religion and its environment can be reconstructed based on the theory of evolution. The elements of the theory of evolution can be understood as the formation of systems. The semiotically informed theory of communication clarifies the conditions of the combination of both the systems theory and the theory of evolution as well as its objects. In turn, the combination of the systems theory and the theory of evolution can describe how communication – including religion and science – evolves and is structured.
The Mahā Kumbh Melā in Allahabad 2013
Authors: Gäbel Cora
Published: April 2018

The following article deals with the Mahā Kumbh Melā1in Allahabad (Uttar Pradesh, northern India) and the practices of Hindu world renouncers2during this festival. In 2013, the year under study, approximately 120 million renouncers and lay pilgrims attended the festival. After a brief overview of the academic discussion on Hindu renunciation, the article proceeds to outline the mythology, history, and meaning of the Kumbh Melā. Subsequently, it presents the festival from the renouncers’ point of view. This section of the article summarizes the functions of the festival, describes two particular forms of meals (bhaṇḍārāsandannakṣetras), and outlines the daily routine of the participants. Finally, the article discusses the inner-worldly asceticism of lay pilgrims, the main participants, as well as the ritual bathing during the festival, a crucial part of the Kumbh Melā for all participants.
Kompetenzen islamischer Religionslehrkräfte – eine empirische Studie
Authors: Kamcili-Yildiz Naciye
Published: April 2018

Das Forschungsprojekt „fachwissenschaftliche und fachdidaktische Kompetenzen von muslimischen Religionslehrkräften“ ist eine empirische Arbeit, in der die fachwissenschaftlichen und fachdidaktischen Kompetenzen muslimischer Lehrkräfte überprüft werden. Auf der Grundlage des entwickelten Kompetenzmodells wurde unter Beteiligung der islamischen Theologie und Religionspädagogik ein Fragebogen mit Items entwickelt, womit die Kompetenzen der derzeit eingesetzten Religionslehrkräfte in der Sekundarstufe I erfasst werden. Die Bewertung der Ergebnisse soll insbesondere dazu dienen, systematische Empfehlungen für die Aus- und Weiterbildung zu geben.
Förderung interreligiöser Dialog- und Kooperationskompetenz in der Hochschuldidaktik. Empirische Analyse eines kooperativen Seminarkonzepts
Authors: Kürzinger Kathrin S. , Schneider Sibylle
Published: April 2018

Aufgrund der steigenden Bedeutung interreligiösen Lernens, das zunehmend auch strukturell bei der Konzeption von Religionsunterricht eine Rolle spielt, müssen angehende Lehrkräfte adäquat ausgebildet werden. Um ihnen den Erwerb interreligiöser Dialog- und Kooperationskompetenz sowie eigene Kooperationserfahrungen beim Lernen und Lehren bereits während der Ausbildung an der Universität zu ermöglichen, wurde ein hochschuldidaktisches Seminarkonzept entwickelt, das mittels eines Fragebogens evaluiert wird. Die Ergebnisse des Pretests von Seminarkonzeption und Fragebogeninstrument werden im Beitrag vorgestellt.
Das Kamishibai als erzählgenerierender Eingangsstimulus für narrative Interviews mit Kindern
Authors: Ulfat Fahimah
Published: April 2018

Narrationen sind für die Erforschung von lebensweltlichen Erfahrungen von Kindern zentral. Dazu bedarf es qualitativer Methoden, die es ermöglichen, Narrationen anzuregen. Solche Erhebungsmethoden erfordern einen Stimulus, der sowohl breit als auch spezifisch formuliert ist. Auf diese Weise wird den Interviewten einerseits Raum für ihre eigenen „Relevanzsysteme“ eröffnet, andererseits der gewünschte Erfahrungsbereich angesteuert. Gerade in Interviews mit Kindern stellt sich die Frage, wie ein Stimulus gestaltet sein muss, der die interviewten Kinder zum Erzählen anregen und eine offene Kommunikation ermöglichen soll. Der Fokus des folgenden Beitrags liegt auf der Vorstellung des Erzähltheaters Kamishibai als einer möglichen Option, Narrationen bei Kindern anzuregen und so Zugang zu den lebensweltlichen Erfahrungen als auch den Orientierungen von Kindern zu erhalten.
Gymnasien in kirchlicher Trägerschaft zwischen christlicher Profilierung und exzellentem Leistungsanspruch – Schulleiter- und Schülerperspektiven
Authors: Niemann Mareke
Published: April 2018

Gymnasien in kirchlicher Trägerschaft bewegen sich zwischen einem exzellenten Leistungsanspruch und dem Ideal einer christlichen Vergemeinschaftung. Diese Gymnasien können aufgrund ihrer selektiven Zulassungsverfahren und ihres besonderen Profils als exklusive Schulen definiert werden. Der Beitrag bietet anhand von qualitativen Rekonstruktionen des Datenmaterials zweier konfessioneller Gymnasien Einblicke in das Verhältnis einer christlichen Profilierung und der schulischen Leistungslogik. Insbesondere werden Erkenntnisse über die Deutungen der schulischen Akteure möglich. Es zeigt sich ein Spannungsfeld, für das sich auf der institutionellen Ebene für die beiden Schulen unterschiedliche Umgangsformen abstrahieren lassen. Außerdem unterscheidet sich die Wahrnehmung in der institutionellen und schülerbiographischen Perspektive.
„Da fließt etwas zusammen!“ Über die Wirksamkeit biografisch entwickelter Bildungslogiken von Fachkräften aus Religions- und Gemeindepädagogik
Authors: Schulz Claudia , Rehm-Kordesee Maria
Published: April 2018

Der Beitrag bietet einen Überblick über zentrale Ergebnisse einer Studie zum lebenslangen Lernen von Fachkräften in der Religions- und Gemeindepädagogik. In dieser Studie werden auf der Basis von autobiografisch-narrativen Interviews Bildungslogiken von DiakonInnen und PfarrerInnen rekonstruiert. Anhand der biografisch verankerten Bildungslogiken lässt sich zeigen, mit welchen unterschiedlichen Verständnissen von beruflicher Bildung und dem Zusammenhang von eigener Person und Religiosität, beruflicher Tätigkeit und Weiterentwicklung die Fachkräfte ihre berufliche Weiterbildung gestalten. Die Ergebnisse lassen sich zu konkreten Fragen der Fort- und Weiterbildung sowie Personalentwicklung in den Berufsgruppen in Bezug setzen.
Distinct Synaptic and Extrasynaptic NMDA Receptors in Developing Cerebellar Granule Neurons
Authors: Rumbaugh Gavin , Vicini Stefano
Published: April 2018

In rat cerebellar granule neurons, mRNA and protein levels of the NR2A and NR2C subunits of the NMDA receptor increase during the second postnatal week. At this time, mRNA and protein levels of the NR2B subunit begin to fall. To investigate targeting of NMDA receptor subunits, we performed whole-cell recordings from rat cerebellar granule neurons at different times during development and investigated the pharmacological and biophysical properties of mossy fiber-evoked NMDA EPSCs. Isolated NMDA EPSCs from newly formed synapses in the first postnatal week exhibited partial block by the NR2B subunit-specific antagonist (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol (CP 101,606). By the end of the second postnatal week, NMDA EPSCs were virtually unaffected by the NR2B antagonist. In parallel, NMDA EPSC decay times decreased over a similar developmental time course. We compared properties of synaptic NMDA receptors with extrasynaptic receptors that are present on the cell body with rapid application of glutamate to excised nucleated patches. Deactivation of patch responses accelerated with development and closely resembled evoked NMDA EPSCs in rats of the same age. However, patch responses were highly sensitive to CP 101,606 through the second postnatal week, and sensitivity was seen in some neurons up to the fourth postnatal week. Spermine potentiated peak NMDA patch responses from postnatal days 10–14 rats but had little effect on evoked NMDA EPSCs. Our data suggest selective targeting of a distinct NMDA receptor subtype to synaptic receptor populations in cerebellar granule neurons. Later in development, similar changes occur in the extrasynaptic receptor population.
Probing of NMDA Channels with Fast Blockers
Authors: Sobolevsky Alexander I. , Koshelev Sergey G. , Khodorov Boris I.
Published: April 2018

Using whole-cell patch-clamp techniques, we studied the interaction of open NMDA channels with tetraalkylammonium compounds: tetraethylammonium (TEA), tetrapropylammonium (TPA), tetrabutylammonium (TBA), and tetrapentylammonium (TPentA). Analysis of the blocking kinetics, concentration, and agonist dependencies using a set of kinetic models allowed us to create the criteria distinguishing the effects of these blockers on the channel closure, desensitization, and agonist dissociation. Thus, it was found that TPentA prohibited, TBA partly prevented, and TPA and TEA did not prevent either the channel closure or the agonist dissociation. TPentA and TBA prohibited, TPA slightly prevented, and TEA did not affect the channel desensitization. These data along with the voltage dependence of the stationary current inhibition led us to hypothesize that: (1) there are activation and desensitization gates in the NMDA channel; (2) these gates are distinct structures located in the external channel vestibule, the desensitization gate being located deeper than the activation gate. The size of the blocker plays a key role in its interaction with the NMDA channel gating machinery: small blockers (TEA and TPA) bind in the depth of the channel pore and permit the closure of both gates, whereas larger blockers (TBA) allow the closure of the activation gate but prohibit the closure of the desensitization gate; finally, the largest blockers (TPentA) prohibit the closure of both activation and desensitization gates. The mean diameter of the NMDA channel pore in the region of the activation gate localization was estimated to be ∼11 Å.
The General Anesthetic Propofol Slows Deactivation and Desensitization of GABAAReceptors
Authors: Bai Donglin , Pennefather Peter S. , MacDonald John F. , Orser Beverley A.
Published: April 2018

Propofol (2,6-di-isopropylphenol) has multiple actions on GABAAreceptor function that act in concert to potentiate GABA-evoked currents. To understand how propofol influences inhibitory IPSCs, we examined the effects of propofol on responses to brief applications of saturating concentrations of GABA (1–30 mm). GABA was applied using a fast perfusion system to nucleated patches excised from hippocampal neurons. In this preparation, propofol (10 μm) had no detectable agonist effect but slowed the decay, increased the charge transfer (62%), and enhanced the peak amplitude (8%) of currents induced by brief pulses (3 msec) of GABA. Longer pulses (500 msec) of GABA induced responses that desensitized with fast (τf= 1.5–4.5 msec) and slow (τs= 1–3 sec) components and, after the removal of GABA, deactivated exponentially (τd= 151 msec). Propofol prolonged this deactivation (τd= 255 msec) and reduced the development of both fast and slow desensitization. Recovery from fast desensitization, assessed using pairs of brief pulses of GABA, paralleled the time course of deactivation, indicating that fast desensitization traps GABA on the receptor. With repetitive applications of pulses of GABA (0.33 Hz), the charge transfer per pulse declined exponentially (τ ≈ 15 sec) to a steady-state value equal to ∼40% of the initial response. Despite the increased charge transfer per pulse with propofol, the time course of the decline was unchanged. These experimental data were interpreted using computer simulations and a kinetic model that assumed fast and slow desensitization, as well as channel opening developed in parallel from a pre-open state. Our results suggest that propofol stabilizes the doubly liganded pre-open state without affecting the isomerization rate constants to and from the open state. Also, the rate constants for agonist dissociation and entry into the fast and slow desensitization states were reduced by propofol. The recovery rate constant from fast desensitization was slowed, whereas that from slow desensitization appeared to be unchanged. Taken together, the effects of propofol on GABAAreceptors enhance channel opening, particularly under conditions that promote desensitization.
Long-Term Depression of Excitatory Synaptic Transmission in the Rat Amygdala
Authors: Wang Su-Jane , Gean Po-Wu
Published: April 2018

In view of the fact that both kindling and fear-potentiated startle are expressed by long-term enhancement of synaptic transmission in the amygdala, synaptic plasticity in this area of the brain is of particular importance. Here, we show for the first time that low-frequency stimulation of the lateral nucleus at 1 Hz for 15 min elicited a long-term depression (LTD) in the basolateral amygdala (BLA) neurons. LTD is expressed specifically at the lateral–BLA synapses but not at ventral endopyriform nucleus–BLA synapses. The induction of LTD requires activation of both NMDA and metabotropic glutamate receptors. Loading cells with a Ca2+chelator BAPTA or extracellular superfusion with protein phosphatase inhibitors prevents LTD, suggesting that LTD may result from dephosphorylation of AMPA receptors. The same stimulating protocol could not elicit LTD in neurons from kindled animals, whereas neurons from sham-operated or age-matched control rats were able to exhibit LTD. Together, this study characterizes the properties of LTD in the naı̈ve amygdala slices for the first time and demonstrates that epileptogenesisin vivoinduces disruption of LTD in thein vitropreparation.
Heterogeneity of Synaptic Plasticity at Unitary CA3–CA1 and CA3–CA3 Connections in Rat Hippocampal Slice Cultures
Authors: Debanne Dominique , Gähwiler Beat H. , Thompson Scott M.
Published: April 2018

Long-term potentiation (LTP) of unitary EPSPs, generated by pairs of monosynaptically connected CA3 and CA1 pyramidal cells, was compared with LTP of extracellularly evoked, multi-unitary EPSPs in rat hippocampal slice cultures. LTP was induced by repeated, synchronous pairing of low-frequency presynaptic and postsynaptic activity. Three differences were observed. First, LTP of multi-unitary EPSPs displayed two phases: transient (<5 min) and sustained. Potentiation of unitary EPSPs displayed both phases in 42% of experiments; the remainder showed sustained potentiation only. Unitary EPSPs displaying transient-sustained and only sustained potentiation could be recorded from single postsynaptic cells, indicating that excitatory synapses on a given cell are heterogeneous with respect to short-term plasticity. Second, whereas LTP of multi-unitary EPSPs never resulted in greater than twofold increases in amplitude (mean potentiation of 175% of control), maximal LTP of unitary EPSPs was as great as 13-fold (mean potentiation of 250%). Third, LTP could not be induced in 24% of unitary EPSPs. We provide here the first evidence for the coexistence of potentiatable and nonpotentiatable synapses on individual postsynaptic neurons. Thirty-seven percent of connections not displaying LTP exhibited long-term depression (LTD), suggesting that the connections were already maximally potentiated. In the remaining 63% of these pairs, neither LTP nor LTD could be induced, despite the existence of a pharmacologically identified, NMDA receptor-mediated EPSP component. In conclusion, there is considerable heterogeneity in the amplitude and time course of LTP expression at different synaptic connections. A substantial proportion of apparently nonplastic synapses probably accounts for the weaker potentiation displayed by compound EPSPs.
XenopusEmbryonic Spinal Neurons Express Potassium Channel Kvβ Subunits
Authors: Lazaroff Meredith A. , Hofmann Alison D. , Ribera Angeles B.
Published: April 2018

Developmental regulation of voltage-dependent delayed rectifier potassium current (IKv) ofXenopusprimary spinal neurons regulates the waveform of the action potential.IKvundergoes a tripling in density and acceleration of it activation kinetics during the initial day of its appearance. Another voltage-dependent potassium current, the A current, is acquired during the subsequent day and contributes to further shortening of the impulse duration. To decipher the molecular mechanisms underlying this functional differentiation, we are identifying potassium channel genes expressed in the embryonic amphibian nervous system. Potassium channels consist of pore-forming (α) as well as auxiliary (β) subunits. Here, we report the primary sequence, developmental localization, and functional properties of twoXenopusKvβ genes. On the basis of primary sequence, one of these (xKvβ2) is highly conserved with Kvβ2 genes identified in other species, whereas the other (xKvβ4) appears to identify a new member of the Kvβ family. Both are expressed in developing spinal neurons during the period of impulse maturation but in different neuronal populations. In a heterologous system, coexpression of xKvβ subunits modulates properties of potassium current that are developmentally regulated in the endogenousIKv. Consistent with xKvβ4's unique primary sequence, the repertoire of functional effects it has on coexpressed Kv1α subunits is novel. Taken together, the results implicate auxiliary subunits in regulation of potassium current function and action potential waveforms in subpopulations of embryonic primary spinal neurons.
Sustained Plateau Activity Precedes and Can Generate Ictal-Like Discharges in Low-Cl−Medium in Slices from Rat Piriform Cortex
Authors: Demir Rezan , Haberly Lewis B. , Jackson Meyer B.
Published: April 2018

Interictal and ictal discharges represent two different forms of abnormal brain activity associated with epilepsy. Ictal discharges closely parallel seizure activity, but depending on the form of epilepsy, interictal discharges may or may not be correlated with the frequency, severity, and location of seizures. Recent voltage-imaging studies in slices of piriform cortex indicated that interictal-like discharges are generated in a two-stage process. The first stage consists of a sustained, low-amplitude depolarization (plateau activity) lasting the entire latent period prior to discharge onset. Plateau activity takes place at a site distinct from the site of discharge onset and serves to sustain and amplify activity initiated by an electrical stimulus. In the second stage a rapidly accelerating depolarization begins at the onset site and then spreads over a wide region. Here, we asked whether ictal-like discharges can be generated in a similar two-stage process. As with interictal-like activity, the first sign of an impending ictal-like discharge is a sustained depolarization with a plateau-like time course. The rapidly accelerating depolarization that signals the start of the actual discharge develops later at a separate onset site. As found previously with interictal-like discharges, local application of kynurenic acid to the plateau site blocked ictal-like discharges throughout the entire slice. However, in marked contrast to interictal-like activity, blockade of synaptic transmission at the onset site failed to block the ictal-like discharge. This indicates that interictal- and ictal-like discharges share a common pathway in the earliest stage of their generation and that their mechanisms subsequently diverge.
Compromised Glutamate Transport in Human Glioma Cells: Reduction–Mislocalization of Sodium-Dependent Glutamate Transporters and Enhanced Activity of Cystine–Glutamate Exchange
Authors: Ye Zu-Cheng , Rothstein Jeffrey D. , Sontheimer Harald
Published: April 2018

Elevated levels of extracellular glutamate ([Glu]o) can induce seizures and cause excitotoxic neuronal cell death. This is normally prevented by astrocytic glutamate uptake. Neoplastic transformation of human astrocytes causes malignant gliomas, which are often associated with seizures and neuronal necrosis. Here, we show that Na+-dependent glutamate uptake in glioma cell lines derived from human tumors (STTG-1, D-54MG, D-65MG, U-373MG, U-251MG, U-138MG, and CH-235MG) is up to 100-fold lower than in astrocytes. Immunohistochemistry and subcellular fractionation show very low expression levels of the astrocytic glutamate transporter GLT-1 but normal expression levels of another glial glutamate transporter, GLAST. However, in glioma cells, essentially all GLAST protein was found in cell nuclei rather than the plasma membrane. Similarly, brain tissues from glioblastoma patients also display reduction of GLT-1 and mislocalization of GLAST. In glioma cell lines, over 50% of glutamate transport was Na+-independent and mediated by a cystine–glutamate exchanger (system xc−). Extracellularl-cystine dose-dependently induced glutamate release from glioma cells. Glutamate release was enhanced by extracellular glutamine and inhibited by (S)-4-carboxyphenylglycine, which blocked cystine–glutamate exchange. These data suggest that the unusual release of glutamate from glioma cells is caused by reduction–mislocalization of Na+-dependent glutamate transporters in conjunction with upregulation of cystine–glutamate exchange. The resulting glutamate release from glioma cells may contribute to tumor-associated necrosis and possibly to seizures in peritumoral brain tissue.
Opposing Effects of Excitatory Amino Acids on Chick Embryo Spinal Cord Motoneurons: Excitotoxic Degeneration or Prevention of Programmed Cell Death
Authors: Lladó Jerònia , Calderó Jordi , Ribera Joan , Tarabal Olga , Oppenheim Ronald W. , Esquerda Josep E.
Published: April 2018

Acute administration of a single dose of NMDA on embryonic day (E) 7 or later induces a marked excitotoxic injury in the chick spinal cord, including massive necrotic motoneuron (MN) death. When the same treatment was performed before E7, little, if any, excitotoxic response was observed. Chronic treatment with NMDA starting on E5 prevents the excitotoxic response produced by a later “acute” administration of NMDA. Additionally, chronic NMDA treatment also prevents the later excitotoxic injury induced by non-NMDA glutamate receptor agonists, such as kainate or AMPA. Chronic NMDA treatment also reduces normal MN death when treatment is maintained during the period of naturally occurring programmed cell death (PCD) of MNs and rescues MNs from PCD induced by early peripheral target deprivation. The trophic action of chronic NMDA treatment appears to involve a downregulation of glutamate receptors as shown by both a reduction in the obligatory NR1 subunit protein of the NMDA receptor and a decrease in the kainate-induced Co2+uptake in MNs. Both tolerance to excitotoxicity and trophic effects of chronic NMDA treatment are prevented by the NMDA receptor antagonist MK-801. Additionally, administration of MK-801 alone results in an increase in MN PCD. These data indicate for the first time that early activation of NMDA receptors in developing avian MNsin vivohas a trophic, survival-promoting effect, inhibiting PCD by a target-independent mechanism that involves NMDA receptor downregulation.
Synaptic Density in Geniculocortical Afferents Remains Constant after Monocular Deprivation in the Cat
Authors: Silver Michael A. , Stryker Michael P.
Published: April 2018

Monocular eyelid closure in cats during a critical period in development produces both physiological plasticity, as indicated by a loss of responsiveness of primary visual cortical neurons to deprived eye stimulation, and morphological plasticity, as demonstrated by a decrease in the total length of individual geniculocortical arbors representing the deprived eye. Although the physiological plasticity appears maximal after 2 d of monocular deprivation (MD), the shrinkage of deprived-eye geniculocortical arbors is less than half-maximal at 4 d and is not maximal until 7 d of deprivation, at which time the deprived arbors are approximately half their previous size. To study this form of plasticity at the level of individual thalamocortical synapses rather than arbors, we developed a new double-label colocalization technique. First, geniculocortical afferent arbors serving either the deprived or nondeprived eye were labeled by injection of the anterograde tracerPhaseolus vulgarisleucoagglutinin into lamina A of the lateral geniculate nucleus. Then, using antibodies to synaptic vesicle proteins, we identified presynaptic terminals within the labeled arbors in layer IV of the primary visual cortex. Analysis of serial optical sections obtained using confocal microscopy allowed measurement of the numerical density of presynaptic sites and the relative amounts of synaptic vesicle protein in geniculocortical afferents after both 2 and 7 d of MD. We found that the density of synapses in geniculocortical axons was similar for deprived and nondeprived afferents, suggesting that this feature of the afferents is conserved even during periods in which synapse number is reduced by half in deprived-eye arbors. These results are not consistent with the hypothesis that a rapid loss of deprived-eye geniculocortical presynaptic sites is responsible for the prompt physiological effects of MD.
Amygdala–Hippocampal Involvement in Human Aversive Trace Conditioning Revealed through Event-Related Functional Magnetic Resonance Imaging
Authors: Büchel Christian , Dolan Raymond J. , Armony Jorge L. , Friston Karl J.
Published: April 2018

Previous functional neuroimaging studies have characterized brain systems mediating associative learning using classical delay conditioning paradigms. In the present study, we used event-related functional magnetic resonance imaging to characterize neuronal responses mediating aversive trace conditioning. During conditioning, neutral auditory tones were paired with an aversive sound [unconditioned stimulus (US)]. We compared neuronal responses evoked by conditioned (CS+) and nonconditioned (CS−) stimuli in which a 50% pairing of CS+ and the US enabled us to limit our analysis to responses evoked by the CS+ alone. Differential responses (CS+ vs CS−), related to conditioning, were observed in anterior cingulate and anterior insula, regions previously implicated in delay fear conditioning. Differential responses were also observed in the amygdala and hippocampus that were best characterized with a time × stimulus interaction, indicating rapid adaptation of CS+-specific responses in medial temporal lobe. These results are strikingly similar to those obtained with a previous delay conditioning experiment and are in accord with a preferential role for medial temporal lobe structures during the early phase of conditioning. However, an additional activation of anterior hippocampus in the present experiment supports a view that its role in trace conditioning is to maintain a memory trace between the offset of the CS+ and the delayed onset of the US to enable associative learning in trace conditioning.
Graded and Areal Expression Patterns of Regulatory Genes and Cadherins in Embryonic Neocortex Independent of Thalamocortical Input
Authors: Nakagawa Yasushi , Johnson Jane E. , O'Leary Dennis D. M.
Published: April 2018

The differentiation of areas of the mammalian neocortex has been hypothesized to be controlled by intrinsic genetic programs and extrinsic influences such as those mediated by thalamocortical afferents (TCAs). To address the interplay between these intrinsic and extrinsic mechanisms in the process of arealization, we have analyzed the requirement of TCAs in establishing or maintaining graded or areal patterns of gene expression in the developing mouse neocortex. We describe the differential expression ofLhx2,SCIP, andEmx1, representatives of three different classes of transcription factors, and the type II classical cadherinsCad6,Cad8, andCad11, which are expressed in graded or areal patterns, as well as layer-specific patterns, in the cortical plate. The differential expression ofLhx2,SCIP,Emx1,andCad8in the cortical plate is not evident until after TCAs reach the cortex, whereasCad6andCad11show subtle graded patterns of expression before the arrival of TCAs, which later become stronger. We find that these genes exhibit normal-appearing graded or areal expression patterns inMash-1mutant mice that fail to develop a TCA projection. These findings show that TCAs are not required for the establishment or maintenance of the graded and areal expression patterns of these genes and strongly suggest that their regulation is intrinsic to the developing neocortex.
Cerebral Microvascular Obstruction by Fibrin is Associated with Upregulation of PAI-1 Acutely after Onset of Focal Embolic Ischemia in Rats
Authors: Zhang Zheng Gang , Chopp Michael , Goussev Anton , Lu Dunyue , Morris Daniel , Tsang Wayne , Powers Cecylia , Ho Khang-Loon
Published: April 2018

The mechanisms underlying cerebral microvascular perfusion deficit resulting from occlusion of the middle cerebral artery (MCA) require elucidation. We, therefore, tested the hypothesis that intravascular fibrin depositionin situdirectly obstructs cerebral microcirculation and that local changes in type 1 plasminogen activator inhibitor (PAI-1) gene expression contribute to intravascular fibrin deposition after embolic MCA occlusion. Using laser-scanning confocal microscopy (LSCM) in combination with immunofluorescent staining, we simultaneously measured in three dimensions the distribution of microvascular plasma perfusion deficit and fibrin(ogen) immunoreactivity in a rat model of focal cerebral embolic ischemia (n= 12). In addition, usingin situhybridization and immunostaining, we analyzed expression of PAI-1 in ischemic brain (n= 13). A significant (p< 0.05) reduction of cerebral microvascular plasma perfusion accompanied a significant (p< 0.05) increase of intravascular and extravascular fibrin deposition in the ischemic lesion. Microvascular plasma perfusion deficit and fibrin deposition expanded concomitantly from the subcortex to the cortex during 1 and 4 hr of embolic MCA occlusion. Three-dimensional analysis revealed that intravascular fibrin deposition directly blocks microvascular plasma perfusion. Vascular plugs contained erythrocytes, polymorphonuclear leukocytes, and platelets enmeshed in fibrin.In situhybridization demonstrated induction of PAI-1 mRNA in vascular endothelial cells in the ischemic region at 1 hr of ischemia. PAI-1 mRNA significantly increased at 4 hr of ischemia. Immunohistochemical staining showed the same pattern of increased PAI-1 antigen in the endothelial cells. These data demonstrate, for the first time, that progressive intravascular fibrin deposition directly blocks cerebral microvascular plasma perfusion in the ischemic region during acute focal cerebral embolic ischemia, and upregulation of the PAI-1 gene in the ischemic lesion may foster fibrin deposition through suppression of fibrinolysis.