bluuebunny/crossref_metadata_2025 huggingface dataset:
Generating and repairing genetically programmed DNA breaks during immunoglobulin class switch recombination
Authors: Nicolas Laura , Cols Montserrat , Choi Jee Eun , Chaudhuri Jayanta , Vuong Bao
Published: April 2018

Adaptive immune responses require the generation of a diverse repertoire of immunoglobulins (Igs) that can recognize and neutralize a seemingly infinite number of antigens. V(D)J recombination creates the primary Ig repertoire, which subsequently is modified by somatic hypermutation (SHM) and class switch recombination (CSR). SHM promotes Ig affinity maturation whereas CSR alters the effector function of the Ig. Both SHM and CSR require activation-induced cytidine deaminase (AID) to produce dU:dG mismatches in the Ig locus that are transformed into untemplated mutations in variable coding segments during SHM or DNA double-strand breaks (DSBs) in switch regions during CSR. Within the Ig locus, DNA repair pathways are diverted from their canonical role in maintaining genomic integrity to permit AID-directed mutation and deletion of gene coding segments. Recently identified proteins, genes, and regulatory networks have provided new insights into the temporally and spatially coordinated molecular interactions that control the formation and repair of DSBs within the Ig locus. Unravelling the genetic program that allows B cells to selectively alter the Ig coding regions while protecting non-Ig genes from DNA damage advances our understanding of the molecular processes that maintain genomic integrity as well as humoral immunity.
Construction of Belonging to Surfaces One-Dimensional Contours by Mapping Them to a Plane
Authors: Иванов Геннадий , Ivanov Gennadiy
Published: April 2018

As is known, differential geometry studies the properties of curve lines (tangent, curvature, torsion), surfaces (bending, first and second basic quadratic forms) and their families in small, that is, in the neighborhood of the point by means of differential calculus. Algebraic geometry studies properties of algebraic curves, surfaces, and algebraic varieties in general [1; 17]: order, class, genre, existence of singular points and lines, curves and surfaces family intersections (sheaves, bundles, congruences, complexes and their characteristics). Rational curves and surfaces occupy a special place among them: • their design by bi-rational (Cremona) transformations [10; 21]; • investigation of their properties by mapping to lines and planes [9; 21; 22]; • construction of smooth contours from arcs of rational curves belonging to surfaces [10]. It seems that the main results obtained in this direction by mathematicians in the second half of the 19th century by structural and geometric methods should be the theoretical support for the design of technical forms that meet a number of pre-set requirements using modern computational tools and information technologies. It is obvious that application of Cremona transformations’ powerful apparatus is useful when designing, for example, pipes of complex geometry according to set of streamlines, thin-walled shells for a given mesh manifold of curvature lines etc. Apparently, this stage should precede computer graphics’ calculation procedures. However, in Russian publications on applied (engineering) geometry, only a little attention is paid to the study of surfaces in general. The author knows nothing about the use of this approach for solving of these applied problems. In this regard, the aims of this paper are: • illustration of method for mapping a surface to a plane to study its properties in general by the example of construction a flat model for a hyperboloid of one sheet; • constructive approach to the construction of smooth one-dimensional contours on rational surfaces.
Six-Measured Epure Nomogram in Four Oktant Measurement
Authors: Левкин Ю. , Levkin Yu.
Published: April 2018

A graphic construction of six-measured nomogram with its subsequent decomposition on four cell-like three-dimensional spatial axonometries with their physiographic analysis is offered in this work. Compact construction of the six-measured nomogram allows obtain fully a graphic illustration for the current experiment and explicitly characterize its physical entity by means of parametric link. A qualitatively new illustrative model graphically connects all experimental cycle of operating parameters by means of projective dependence for Cartesian coordinate system taking into account the materialization of spot measurements. In the course of receiving geometrical images in the form of straight lines’ segments, curves, planes and surfaces during construction of the six-measured nomogram a question about obtaining of each geometrical image’s physical characteristics is set. Regularity of parameters layout on the epure six-measured nomogram’s planes should define physical evolution or its absence in the experiment. In case of construction a graphic dependence between parameters the applicate axis, certainly, is resultant or functional one and all remaining axes are arguments or variables. Geometrical images, such as horizontal planes of level, are involved in the work, and each of these planes expresses the spot measurement of all projective parameters. Horizontally projecting surfaces have been presented by intersection of generatrixes with directing lines that are the transition link of conformance points between two-phase flow’s phases. The compliance axiom is given that is the graphic confirmation for what has been said.
Orthodox symbolism in the history of Russian literature
Authors: Волосков Игорь , Voloskov Igor
Published: April 2018

The monograph examines the history of Russian literature from the perspective of the development of Orthodox tradition and symbolism. The symbols are analyzed in the context of literary tradition, change of different literary trends, genre features.
A General theory of upbringing
Authors: Темина Светлана , Temina Svetlana
Published: April 2018

The book presents the theory of education from the perspective of various scientific approaches implemented in modern psychological and pedagogical research. The problems of education are considered in the context of current trends and important ideas of philosophy, anthropology, genetics, psychology, pedagogics.
For bachelors in psychological and pedagogical areas of training, as well as undergraduates, graduate students and professors.
Emancypacja etniczno-kulturowa Białorusinów na skrzyżowaniu epok i kultur (druga połowa XIX – początek XX wieku)
Authors: Kachanouski Alaksandr
Published: April 2018

Alexander G. Kokhanovsky, Ethnocultural Emancipation of the Belarusians on the Border of the Epochs and Cultures (Second Half of the XIX – Beginning of the XX Century)

The article deals with the analysis of the sociocultural changes in the Belarusian society in the second half of the XIX – beginning of the XX century, when Belarus stood at the crossroads of the different civilizations and cultures. The author pays special attention to the processes of the widening of literacy among the Belarusians, formation of the intellectual elites and premises of the ethnocultural emancipation of the Belarusians in the conditions when the society had just taken first steps from the traditional culture towards modernity. The special features that distinguish the development of the mentioned processes on the territory of Belarus were emphasized.
»Lean« und »agil« im Büro
Authors: Boes Andreas , Kämpf Tobias , Langes Barbara , Lühr Thomas
Published: April 2018

In der gegenwärtigen digitalen Transformation wird auch die Büroarbeit komplett neu organisiert. Eine zentrale Rolle spielen dabei Konzepte wie »Lean Production« und »agile Methoden«. Das Buch zeigt die Folgen dieser Entwicklung für die Arbeitswelt von Angestellten anhand von Fallstudien aus den Bereichen Software-Entwicklung, Maschinenbau, Metall- und Elektroindustrie. Erkennbar wird ein grundlegender Umbruch in der Angestelltenarbeit mit ungewissem Ausgang. Kommt die Büroarbeit am digitalen Fließband oder ein Aufbruch in eine neue Humanisierung der Arbeitswelt? Das Buch liefert Antworten auf diese Fragen und zeigt: Das Ergebnis der Entwicklung hängt von unserer bewussten Gestaltung ab.
Are Heavy Pirates also Heavy Buyers?: A Case of the Video Game Industry in Japan
Authors: Fukugawa Nobuya
Published: April 2018

Purpose

This study aims to examine how piracy via peer-to-peer (P2P) network affects sales of original version in the video game industry.

Design/methodology/approach

This study conducted an online questionnaire survey in 2009 with a focus on 9970 users of portable video game platforms, and collected information of how familiar respondents were with techniques for downloading pirated video games via P2P network and how this knowledge affected their purchase behavior of original video games.

Findings

First, 38% of the respondents know how to download pirated video games via P2P network. Younger male respondents with greater enthusiasm for video games are exposed to greater opportunities to learn to pirate. Second, different respondents employ different channels to learn about piracy. Third, 95% of the respondents who knew how to pirate did not download any pirated video game. Once involved in piracy, jobless respondents with less enthusiasm for video games who were informed about piracy by their friends tend to download pirated video games more intensively. Fourth, there is no significantly negative relationship between the number of pirated video games respondents downloaded and the number of original video games they purchased. Fifth, respondents who downloaded pirated video games also purchased original video games of which pirated version they have downloaded.

Originality/value

This study clarified that heavy pirates are also heavy buyers not only at the aggregate level, but also at the individual level, and interpreted the results from the viewpoint of peculiarities of video games as a cultural product, making piracy harmless to sales of original version.
Die globale Dichtung des Orlando Furioso
Authors: Italiano Federico
Published: April 2018

The epic poem of Ludovico Ariosto, Orlando Furioso (1516–1532), oneof the most influential texts of Renaissance writing, shows not only a precisecognition of early modern cartographic knowledge, as Alexandre Doroszlaï hasillustrated it in Ptolemée et l’hippogriffe (1998), but also performs a complextransmedial translation of cartographic depictions. The journeys around the globeof the Christian paladins Ruggiero and Astolfo narrated by Ariosto are, in fact,performative negotiations between literary and cartographic processes. Riding theHippograph, the hybrid vehicle par excellence, Ruggiero and Astolfo fly over theEarth as if they were flying over a map. Their journeys do not merely transmediallytranslate the course to the West pursued by Early Modern Europe. Rather, bytranslating the map Ariosto performs a new geopoetics that turns away from thesymbolic dominance of the East (or “Ent-Ostung”, as Peter Sloterdijk has usefullycalled it) and offers us one of the first poetic versions of modern globalization.
Lässig – subtil – lakonischAbgesehen von den Anmerkungen und wenigen kleineren Modifikationen entspricht der folgende Text demjenigen der Antrittsvorlesung, die ich zur Übernahme meines Lehrstuhls für Vergleichende Literaturwissenschaft (SoSe 2010) am 25. Mai 2011 an der Rheinischen Friedrich-Wilhelms-Universität Bonn gehalten habe. Der Charakter des Vortrags (für ein nicht nur akademisches Publikum) wurde nach Möglichkeit gewahrt. Die Hinweise auf Forschungsliteratur beschränken sich auf ein Minimum.
Authors: Mainberger Sabine
Published: April 2018

The concept of grace is as complex as it is wide-ranging: it is relevant to social history and the history of religion, to mythology, theology, law, ethics, social aesthetics, art theory, and the theory of culture. The Three Graces embody a structure of giving, receiving, and returning, i.e., actions that form part of the discourse on exchanging goods and gifts, – one that is normally quite distinct from the discourse on aesthetics and art theory. The question arises: how can aspects of the grace-discourse be reformulated by means of the gift-discourse? How can we form a conceptual configuration of gift, social interaction, and art? From a wide array of possible examples, some are singled out here for closer inspection: Castiglione’s sixteenth-century model of courtly society, the connection between the social aesthetic use of the concepts of grazia and sprezzatura, and their role in art theory, as well as the enhanced meaning of these concepts in the combined discourses on love, art, and (theological) grace that are to be found in the friendship between Michelangelo and the poet Vittoria Colonna; examples from the eighteenth to the twentieth century include Schiller’s considerations on grace and Charis, giving and being gifted, as well as Nietzsche’s new morality associated with lightness and self-giving. The essay is framed by Pliny the Elder’s anecdote about the competition between Apelles, the master of charis, and his fellow painter Protogenes, and by Pasternak’s modern version of it: a short story about two rival writers and their antagonistic exchange of gifts.
Goethes Wahlverwandtschaften
Authors: Pignotti Sandro
Published: April 2018

This literary critique of Goethe’s “Elective Affinities” combines three approaches. First, it follows the Italian Germanists Ladislao Mittner and Giuliano Baioni who showed the importance of Edmund Burke’s treatise “A Philosophical Enquiry into the Origin of Our Ideas of the Sublime and Beautiful” (1757) for Goethe’s poetry. Second, it explores Walter Benjamin’s essay and some thoughts of Hermann Cohen. They show the significance story “Die Wunderlichen Nachbarskinder” for the novel as a whole, the philosophical sense banning images, and the relation between the halacha and aggadah in literature. Finally, this essay studies the differences between the spoken and the written word in Goethe’s novel, as well as in Jewish traditions and media theories.
Jean Pauls Titan als metaenzyklopädischer Roman
Authors: Schmitz-Emans Monika
Published: April 2018

In a programmatic way, Jean Paul’s novel “Titan” illustrates in how far novels are inclined to become ‘encyclopaedias’. First, it is based on abundant knowledge resources that are linked together in a complex way and may be regarded as ‘encyclopaedic’. On the intradiegetic level, the different kinds of knowledge are partially represented by single characters. Secondly, Jean Paul’s “Titan” reflects upon different strategies of creating orders of knowledge as well as of representing and mediating knowledge. Thirdly, it can be regarded as an encyclopaedic arrangement that reflects different novelistic genres. In order to cope with the complexity of encyclopaedic dimensions characteristic of this literary text, it appears to be helpful to present the multiple aspects concerned in alphabetical order.
Parables and Uses of a Stumbling Stone
Authors: Suvin Darko
Published: April 2018

Parallels are discussed between the Biblical (Jewish and then Christian) use of ‘stumbling stone’ and Shklovsky’s thisworldly notion of estrangement – ‘making the stone stony.’ To Shklovsky’s esthetic salvation through estranged perception, Brecht adds value criteria from salvational politics, using, for example, in The Caucasian Chalk Circle a Marxist figuralism, which rationalizes the sensual body. However, estrangement as a formal device which doubts the present norms is ideologico-politically ambiguous: in the Brecht or Marxist wing it is ‘critical,’ but in other hands it may be ‘mythical’: Hamsun, Jünger, Pound, and the Iranian Ta’ziyeh play use it with a lay or religious proto-fascist horizon. The final section follows Timpanaro’s insistence on biological death as not fully reducible to politics in the usual sense, and juxtaposes stumbling, death, and creative eros as politics. In spite of Hegel’s insistence on death as a powerful negative, it is a blind spot in canonical Marxism. Even Ernst Bloch, positing hope as the central principle, does not fully engage with it, though I mention some initial useful leads from him, Brecht, and Jameson. We are left with the Freudian topology pitting eros against thanatos, and the essay closes on a discussion of Marvell’s To His Coy Mistress.
Sialylated isoforms of apolipoprotein C-III and plasma lipids in subjects with coronary artery disease
Authors: Olivieri Oliviero , Chiariello Carmela , Martinelli Nicola , Castagna Annalisa , Speziali Giulia , Girelli Domenico , Pizzolo Francesca , Bassi Antonella , Cecconi Daniela , Robotti Elisa , Manfredi Marcello , Conte Eleonora , Marengo Emilio
Published: April 2018

Background:

Apolipoprotein C-III (ApoC-III), a key regulator of plasma triglyceride (TG), is present in three isoforms, i.e. non-sialylated (ApoC-III0), monosialylated (ApoC-III1) and disialylated (ApoC-III2). We aimed at quantifying the distribution of the ApoC-III glycoforms in patients with angiographically demonstrated coronary artery disease (CAD) according to levels of total ApoC-III plasma concentration.

Methods:

ApoC-III glycoforms were quantified by a specifically developed, high-resolution, mass spectrometry method in unrelated CAD patients. Lipoprotein lipase (LPL) activity was estimated by a fluorescence-based method.

Results:

In 101 statin-treated CAD patients, the absolute concentrations of the three glycoforms similarly increased across ApoC-III quartiles, but the proportion of ApoC-III1 rose whereas that of ApoC-III0 decreased progressively by increasing total ApoC-III concentrations. The proportion of ApoC-III2 was quite constant throughout the whole range of total ApoC-III. A higher proportion of ApoC-III1 reflected an unfavorable lipid profile characterized by high levels of TG, total and low density lipoprotein cholesterol, ApoE and reduced ApoA-I. The correlations between ApoC-III glycoforms and TG were confirmed in 50 statin-free CAD patients. High concentration of total ApoC-III was associated with low LPL activity, while no correlation was found for the relative proportion of glycoforms.

Conclusions:

Specific patterns of ApoC-III glycoforms are present across different total ApoC-III concentrations in CAD patients. The inhibitory effect of ApoC-III on LPL appears related to total ApoC-III concentration, but not to the relative proportion of ApoC-III glycoforms.
Japanese pronoun hon-nin
Authors: Hatakeyama Yuji , Honda Kensuke , Tanaka Kosuke
Published: April 2018

This paper investigates the Japanese pronoun hon-nin, which has so far been paid little attention to, and proposes the binding condition to the effect that hon-nin must not be bound by the subject NP. We further show that the Japanese reflexive zibun and the Japanese pronoun hon-nin show complementary distribution just as the English reflexive (himself, etc.) and the English pronoun (him, etc.) do so.
ZnO-CeO2 nanocomposite: efficient catalyst for the preparation of thieno[2,3-d]pyrimidin-4(3H)-one derivatives
Authors: Ghayour Farzaneh , Mohammad Shafiee Mohammad Reza , Ghashang Majid
Published: April 2018

The Zinc oxide-cerium oxide (ZnO-CeO2) nanocomposite was prepared by a coprecipitation method and characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), and particle size distribution analysis. The XRD pattern shows the cubic phase of cerium oxide as the dominant phase. The FE-SEM images show the homogeneity distribution of zinc and cerium oxides in the sample. The mean particle size of the nanocomposite determined by dynamic light scattering technique was 58 nm. The catalytic activity of ZnO-CeO2nanocomposite was examined on the synthesis of thieno[2,3-d]pyrimidin-4(3H)-one derivatives. In all cases, the products were obtained in good to excellent yields.
Hopf-Pitchfork Bifurcation in a Symmetrically Conservative Two-Mass System with Delay
Authors: Sun Ye , Zhang Chunrui , Cai Yuting
Published: April 2018

A symmetrically conservative two-mass system with time delay is considered here. We analyse the influence of interaction coefficient and time delay on the Hopf-pitchfork bifurcation. The bifurcation diagrams and phase portraits are then obtained by computing the normal forms for the system in which, particularly, the unfolding form for case III is seldom given in delayed differential equations. Furthermore, we also find some interesting dynamical behaviours of the original system, such as the coexistence of two stable non-trivial equilibria and a pair of stable periodic orbits, which are verified both theoretically and numerically.
Comparison of Static and Dynamic Balance at Different Levels of Sport Competition in Professional and Junior Elite Soccer Players
Authors: Jadczak Łukasz , Grygorowicz Monika , Dzudziński Witold , Śliwowski Robert
Published: April 2018

Jadczak, Ł, Grygorowicz, M, Dzudziński, W, and Śliwowski, R. Comparison of static and dynamic balance at different levels of sport competition in professional and junior elite soccer players. J Strength Cond Res 33(12): 3384–3391, 2019—The purpose of this study was to compare body balance control and balance recovery strategies of professional football players, representing various sports levels in static (eyes open, eyes closed) and dynamic conditions, both on the dominant and nondominant leg. Three groups of professional and junior elite soccer players were investigated: a PRO group (n = 52), a U-21 group (n = 55), and a U-19 group (n = 47). The study of body balance control was performed using a Delos Postural Proprioceptive System measurement tool. The analysis of the results showed an effect of group (p < 0.01) and leg significance (p < 0.95) in the dynamic test. Three-way analysis of variance (3 [group] × 2 [leg] × 2 [eyes]) of static test data showed that the main effect of eyes (p < 0.0001), group (p < 0.0001), and leg (p = 0.0092) and the 2-way interaction of eyes × group (p = 0.0003) were significant. To represent statistical significance, the cutoff value was set to be p ≤ 0.005 for all measures. Our results indicate the importance of evaluation and monitoring of dynamic and static balance on both legs, which allows for a comprehensive comparison of body balance control and the balance recovery strategy depending on the represented sport level. Our study indicates that the higher the sport level of football players (the PRO group), the better their balance, which may indirectly contribute to the prevention of injuries and more effective performance of any actions directly related to the game.
Determinants of Excitability at Transition Zones in Kv1.1-Deficient Myelinated Nerves
Authors: Zhou Lei , Messing Albee , Chiu Shing Yan
Published: April 2018

This study examines the role of K channel segregation and fiber geometry at transition zones of mammalian nerve terminals in the peripheral nervous system. Mutant mice that are deficient in Kv1.1, a fast Shaker K channel normally localized beneath the myelin sheath, display three types of cooling-induced abnormal hyperexcitability localized to regions before the transition zones of myelinated nerves. The first type is stimulus-evoked nerve backfiring that is absent at birth, peaks at postnatal day 17 (P17), and subsides in adults. The second type is spontaneous activity that has a more delayed onset, peaks at P30, and also disappears in older mice (>P60). TEA greatly amplifies this spontaneous activity with an effective dosage of ∼0.7 mm, and can induce its reappearance in older mutant mice (>P100). These first two types of hyperexcitability occur only in homozygous mutants that are completely devoid of Kv1.1. The third type occurs in heterozygotes and represents a synergism between a TEA-sensitive channel and Kv1.1. Heterozygotes exposed to TEA display no overt phenotype until a single stimulation is given, which is then followed by an indefinite phase of repetitive discharge. Computer modeling suggests that the excitability of the transition zone near the nerve terminal has at least two major determinants: the preterminal internodal shortening and axonal slow K channels. We suggest that variations in fiber geometry create sites of inherent instability that is normally stabilized by a synergism between myelin-concealed Kv1.1 and a slow, TEA-sensitive K channel.
Ca2+-Permeable AMPA Receptors Induce Phosphorylation of cAMP Response Element-Binding Protein through a Phosphatidylinositol 3-Kinase-Dependent Stimulation of the Mitogen-Activated Protein Kinase Signaling Cascade in Neurons
Authors: Perkinton Michael S. , Sihra Talvinder S. , Williams Robert J.
Published: April 2018

Ca2+-permeable AMPA receptors may play a key role during developmental neuroplasticity, learning and memory, and neuronal loss in a number of neuropathologies. However, the intracellular signaling pathways used by AMPA receptors during such processes are not fully understood. The mitogen-activated protein kinase (MAPK) cascade is an attractive target because it has been shown to be involved in gene expression, synaptic plasticity, and neuronal stress. Using primary cultures of mouse striatal neurons and a phosphospecific MAPK antibody we addressed whether AMPA receptors can activate the MAPK cascade. We found that in the presence of cyclothiazide, AMPA caused a robust and direct (no involvement of NMDA receptors or L-type voltage-sensitive Ca2+channels) Ca2+-dependent activation of MAPK through MAPK kinase (MEK). This activation was blocked by GYKI 53655, a noncompetitive selective antagonist of AMPA receptors. Probing the mechanism of this activation revealed an essential role for phosphatidylinositol 3-kinase (PI 3-kinase) and the involvement of a pertussis toxin (PTX)-sensitive G-protein, a Src family protein tyrosine kinase, and Ca2+/calmodulin-dependent kinase II. Similarly, kainate activated MAPK in a PI 3-kinase-dependent manner. AMPA receptor-evoked neuronal death and arachidonic acid mobilization did not appear to involve signaling through the MAPK pathway. However, AMPA receptor stimulation led to a Ca2+-dependent phosphorylation of the nuclear transcription factor CREB, which could be prevented by inhibitors of MEK or PI 3-kinase. Our results indicate that Ca2+-permeable AMPA receptors transduce signals from the cell surface to the nucleus of neurons through a PI 3-kinase-dependent activation of MAPK. This novel pathway may play a pivotal role in regulating synaptic plasticity in the striatum.
Illusory Arm Movements Activate Cortical Motor Areas: A Positron Emission Tomography Study
Authors: Naito Eiichi , Ehrsson H. Henrik , Geyer Stefan , Zilles Karl , Roland Per E.
Published: April 2018

Vibration at ∼70 Hz on the biceps tendon elicits a vivid illusory arm extension. Nobody has examined which areas in the brain are activated when subjects perceive this kinesthetic illusion. The illusion was hypothesized to originate from activations of somatosensory areas normally engaged in kinesthesia. The locations of the microstructurally defined cytoarchitectonic areas of the primary motor (4a and 4p) and primary somatosensory cortex (3a, 3b, and 1) were obtained from population maps of these areas in standard anatomical format. The regional cerebral blood flow (rCBF) was measured with15O-butanol and positron emission tomography in nine subjects. The left biceps tendon was vibrated at 10 Hz (LOW), at 70 or 80 Hz (ILLUSION), or at 220 or 240 Hz (HIGH). A REST condition with eyes closed was included in addition. Only the 70 and 80 Hz vibrations elicited strong illusory arm extensions in all subjects without any electromyographic activity in the arm muscles. When the rCBF of the ILLUSION condition was contrasted to the LOW and HIGH conditions, we found two clusters of activations, one in the supplementary motor area (SMA) extending into the caudal cingulate motor area (CMAc) and the other in area 4a extending into the dorsal premotor cortex (PMd) and area 4p. When LOW, HIGH, and ILLUSION were contrasted to REST, giving the main effect of vibration, areas 4p, 3b, and 1, the frontal and parietal operculum, and the insular cortex were activated. Thus, with the exception of area 4p, the effects of vibration and illusion were associated with disparate cortical areas. This indicates that the SMA, CMAc, PMd, and area 4a were activated associated with the kinesthetic illusion. Thus, against our expectations, motor areas rather than somatosensory areas seem to convey the illusion of limb movement.
Neural Correlates of Perceived Brightness in the Retina, Lateral Geniculate Nucleus, and Striate Cortex
Authors: Rossi Andrew F. , Paradiso Michael A.
Published: April 2018

Brightness changes can be induced in a static gray field by modulating the luminance of surrounding areas. We used this induction phenomenon to investigate the neural representation of perceived brightness. Extracellular recordings were made in striate cortex, the lateral geniculate nucleus (LGN), and the optic tract of anesthetized cats using stimuli that produced brightness induction. While a cell’s receptive field (RF) was covered by uniform gray illumination, the luminance of rectangular flanking regions was modulated sinusoidally in time, inducing brightness changes in the RF. We looked for a correspondence between the modulation of a cell’s response and stimulus conditions that did or did not produce perceptual changes in brightness. We found that the responses of retinal ganglion cell axons in the optic tract were never correlated with brightness. On the other hand, many neurons in striate cortex and a small fraction in the LGN responded in a phase-locked manner at the temporal frequency of the flank modulation, even though the flanks were 3–7° beyond the edges of the RF. Only in striate cortex were cells found that had responses correlated with brightness under all stimulus conditions. These findings suggest that brightness information is explicitly represented in the responses of neurons in striate cortex as part of a neural representation of object surfaces.
Addiction-Prone Lewis But Not Fischer Rats Develop Compulsive Running that Coincides with Downregulation of Nerve Growth Factor Inducible-B and Neuron-Derived Orphan Receptor 1
Authors: Werme Martin , Thorén Peter , Olson Lars , Brené Stefan
Published: April 2018

We have examined the effects of chronic voluntary running for 30 d on the levels of nerve growth factor inducilble-B (NGFI-B) and neuron-derived orphan receptor 1 (NOR1) mRNAs in Fischer and Lewis rats. The aim was to compare the addiction-prone Lewis rat strain to the Fischer strain in a plausible model for natural reward. The Lewis strain ran markedly more than the Fischer strain, as indicated by the length of running per day when given free access to running wheels. Both strains progressively increased their amount of daily running. By day 14, Lewis rats had reached a maximal level corresponding to 10 km/d, which slowly decreased to ∼8 km/d. Fischer rats ran considerably less, averaging ∼1.5 km/d by day 30. After 30 d of running, levels of mRNA encoding NGFI-B and Nor1 were decreased in cerebral cortex in Lewis but not Fischer rats. The downregulation of NGFI-B mRNA in Lewis rats could not be attenuated by the opioid receptor antagonist naloxone. Instead, naloxone by itself downregulated NGFI-B in striatum and cerebral cortex in both strains. In contrast, naloxone had no effect on Nor1 mRNA levels, although the running-induced downregulation of Nor1 was, in most cases, attenuated by naloxone. Data from the present study suggest that the same genetic factors contributing to the drug addiction-prone behavior of Lewis rats also control the excessive running behavior and that this coincides with downregulation of transcription factors of the NGFI-B family.
Interactions between Hippocampus and Medial Septum during Sharp Waves and Theta Oscillation in the Behaving Rat
Authors: Dragoi George , Carpi Daniel , Recce Michael , Csicsvari Jozsef , Buzsáki György
Published: April 2018

The medial septal region and the hippocampus are connected reciprocally via GABAergic neurons, but the physiological role of this loop is still not well understood. In an attempt to reveal the physiological effects of the hippocamposeptal GABAergic projection, we cross-correlated hippocampal sharp wave (SPW) ripples or theta activity and extracellular units recorded in the medial septum and diagonal band of Broca (MSDB) in freely moving rats. The majority of single MSDB cells (60%) were significantly suppressed during SPWs. Most cells inhibited during SPW (80%) fired rhythmically and phase-locked to the negative peak of the CA1 pyramidal layer theta waves. Because both SPW and the negative peak of local theta waves correspond to the maximum discharge probability of CA1 pyramidal cells and interneuron classes, the findings indicate that the activity of medial septal neurons can be negatively (during SPW) or positively (during theta waves) correlated with the activity of hippocampal interneurons. We hypothesize that the functional coupling between medial septal neurons and hippocampal interneurons varies in a state-dependent manner.
Serotonin Enhances Central Olfactory Neuron Responses to Female Sex Pheromone in the Male Sphinx MothManduca sexta
Authors: Kloppenburg Peter , Ferns Donald , Mercer Alison R.
Published: April 2018

In the brain of the sphinx mothManduca sexta, sex-pheromonal information is processed in a prominent male-specific area of the antennal lobe called the macroglomerular complex (MGC). Whole-cell patch-clamp recordings from identified projection (output) neurons in the MGC have shown that serotonin [5-hydroxytryptamine (5-HT)] increases both the excitability of MGC projection neurons and their responses to stimulation with pheromone. At least two types of voltage-activated potassium currents in these cells are modulated by 5-HT. 5-HT decreases the maximal conductance of a transient potassium current (IA) and shifts its voltage for half-maximal inactivation to more negative potentials without affecting the half-maximal voltage for activation. This reduces the “window current” between the voltage activation and inactivation curves, decreasing the tonically activeIAnear the resting potential and causing the cell to depolarize. 5-HT’s effect in this case is to decrease both the transient and resting K+conductance by modulating the same channel (IA). 5-HT also decreases the maximal conductance of a sustained potassium current [IK(V)] without affecting its voltage dependence. Using HPLC, we show also that levels of 5-HT in the antennal lobes fluctuate significantly over a 24 hr period. Interestingly, 5-HT levels are highest at times when the moths are most active. We suggest that by controlling the responsiveness of antennal-lobe projection neurons to olfactory stimuli, 5-HT will have significant impact on the performance of odor-dependent behaviors.
Characterization of an NGF–P-TrkA Retrograde-Signaling Complex and Age-Dependent Regulation of TrkA Phosphorylation in Sympathetic Neurons
Authors: Tsui-Pierchala Brian A. , Ginty David D.
Published: April 2018

Nerve growth factor (NGF) is a target-derived trophic factor for developing sympathetic and cutaneous sensory neurons. NGF promotes growth and survival of neurons via activation of the receptor tyrosine kinase TrkA. We used compartmentalized cultures of sympathetic neurons to address the mechanism of NGF signaling from distal axons and terminals to proximal axons and cell bodies. Our results demonstrate that an NGF–phospho-TrkA (NGF–P-TrkA)–signaling complex forms in distal axons and is retrogradely transported as a complex to cell bodies of sympathetic neurons. Although a minor fraction of both NGF and TrkA is retrogradely transported, a large fraction of the NGF that is retrogradely transported is found complexed with retrogradely transported TrkA. Interestingly, the metabolism of the P-TrkA complex is dramatically different in young, NGF-dependent sympathetic neurons as compared to older, NGF-independent sympathetic neurons. After withdrawal of NGF from distal axons of young neurons, P-TrkA within distal axons, as well as within proximal axons and cell bodies, dephosphorylates rapidly. In contrast, after withdrawal of NGF from distal axons of older neurons, P-TrkA within distal axons dephosphorylates completely, although more slowly than that in young neurons, whereas dephosphorylation of P-TrkA within proximal axons and cell bodies occurs markedly more slowly, with at least one-half of the level of P-TrkA remaining 2 d after NGF withdrawal. Thus, P-TrkA within the cell bodies of young, NGF-dependent sympathetic neurons is derived from distal axons. A more stable P-TrkA complex within cell bodies of mature sympathetic neurons may contribute to the acquisition of NGF independence for survival of mature sympathetic neurons.
Heteromeric Kainate Receptors Formed by the Coassembly of GluR5, GluR6, and GluR7
Authors: Cui Changhai , Mayer Mark L.
Published: April 2018

In the CNS kainate subtype glutamate receptors (GluRs) are likely to be heteromeric assemblies containing multiple gene products. However, although recombinant kainate receptors from the GluR5–GluR7 gene family have been studied extensively in their homomeric forms, there have been no tests to determine whether these subunits can coassemble with each other. We used the GluR5 selective agonists (RS)-2-amino-3-(3-hydroxy-5-tertbutylisoxazol-4-yl)propanoic acid (ATPA) and (S)-5-iodowillardiine (I-will) to test for the coassembly of GluR5 with GluR6 and GluR7 by measuring changes in rectification that occur for heteromeric receptors containing both edited and unedited Q/R site subunits. Birectifying ATPA and I-will responses resulting from polyamine block for homomeric GluR5(Q) became outwardly rectifying when GluR6(R) was coexpressed with GluR5(Q), although GluR6 was not activated by ATPA or I-will, indicating the formation of heteromeric receptors. Similar approaches showed the coassembly of GluR7 with GluR6 and GluR5. Heteromeric kainate receptors containing both GluR5 and GluR6 subunits exhibited novel functional properties, including reduced desensitization and faster recovery from desensitization than those recorded for homomeric GluR5. Coexpression of GluR6 with GluR5 also enhanced the magnitude of responses to GluR5 selective agonists. In contrast, the coassembly of GluR7 with GluR6 markedly decreased the amplitude of agonist responses. Our results indicate that, similar to AMPA receptors, the kainate receptor subunits GluR5–GluR7 exhibit promiscuous coassembly. The formation of heteromeric kainate receptors may help to explain why the functional properties of native kainate receptors differ from those that have been reported for recombinant kainate receptors.
Optic Nerve Crush: Axonal Responses in Wild-Type and bcl-2 Transgenic Mice
Authors: Chierzi Sabrina , Strettoi Enrica , Cenni Maria Cristina , Maffei Lamberto
Published: April 2018

Retinal ganglion cells of transgenic mice overexpressing the anti-apoptotic protein Bcl-2 in neurons show a dramatic increase of survival rate after axotomy. We used this experimental system to test the regenerative potentials of central neurons after reduction of nonpermissive environmental factors. Survival of retinal ganglion cells 1 month after intracranial crush of the optic nerve was found to be 100% in adult bcl-2 mice and 44% in matched wild-type (wt) mice. In the optic nerve, and particularly at the crush site, fibers regrowing spontaneously or simply sprouting were absent in both wt and bcl-2 mice. We attempted to stimulate regeneration implanting in the crushed nerves hybridoma cells secreting antibodies that neutralize central myelin proteins, shown to inhibit regeneration (IN-1 antibodies) (Caroni and Schwab, 1988). Again, we found that regeneration of fibers beyond the site of crush was virtually absent in the optic nerves of both wt and bcl-2 mice. However, in bcl-2 animals treated with IN-1 antibodies, fibers showed sprouting in the proximity of the hybridoma implant. These results suggest that neurons overexpressing bcl-2 are capable of surviving axotomy and sprout when faced with an environment in which inhibition of regeneration has been reduced. Nevertheless, extensive regeneration does not occur, possibly because other factors act by preventing it.
Calcium Entry Related to Active Zones and Differences in Transmitter Release at Phasic and Tonic Synapses
Authors: Msghina M. , Millar A. G. , Charlton M. P. , Govind C. K. , Atwood H. L.
Published: April 2018

Synaptic functional differentiation of crayfish phasic and tonic motor neurons is large. For one impulse, quantal release of neurotransmitter is typically 100–1000 times higher for phasic synapses. We tested the hypothesis that differences in synaptic strength are determined by differences in synaptic calcium entry. Calcium signals were measured with the injected calcium indicator dyes Calcium Green-1 and fura-2. Estimated Ca2+entry increased almost linearly with frequency for both axons and was two to three times larger in phasic terminals. Tonic terminal Ca2+at 10 Hz exceeded phasic terminal Ca2+at 1 Hz, yet transmitter release was much higher for phasic terminals at these frequencies. Freeze-fracture images of synapses revealed on average similar numbers of prominent presynaptic active zone particles (putative ion channels) for both neurons and a two- to fourfold phasic/tonic ratio of active zones per terminal volume. This can account for the larger calcium signals seen in phasic terminals. Thus, differences in synaptic strength are less closely linked to differences in synaptic channel properties and calcium entry than to differences in calcium sensitivity of transmitter release.
The Neuronal Architecture ofXenopusRetinal Ganglion Cells Is Sculpted by Rho-Family GTPasesIn Vivo
Authors: Ruchhoeft Maureen L. , Ohnuma Shin-ichi , McNeill Lisa , Holt Christine E. , Harris William A.
Published: April 2018

Dendritogenesis, axonogenesis, pathfinding, and target recognition are all affected in distinct ways whenXenopusretinal ganglion cells (RGCs) are transfected with constitutively active (ca), wild-type (wt), and dominant negative (dn) Rho-family GTPasesin vivo. Dendritogenesis required Rac1 and Cdc42 activity. Moreover, ca-Rac1 caused dendrite hyperproliferation. Axonogenesis, in contrast, was inhibited by ca-Rac1. This phenotype was partially rescued by the coexpression of dn cyclin-dependent kinase (Cdk5), a proposed effector of Rac1, suggesting that Rac1 activity must be regulated tightly for normal axonogenesis. Growth cone morphology was particularly sensitive to dn-RhoA and wt-Cdc42 constructs. These also caused targeting errors, such as tectal bypass, suggesting that cytoskeletal rearrangements are involved in target recognition and are transduced by these pathways.
Matrix Metalloproteinase-9/Gelatinase B Is Required for Process Outgrowth by Oligodendrocytes
Authors: Oh Luke Y. S. , Larsen Peter H. , Krekoski Craig A. , Edwards Dylan R. , Donovan Frances , Werb Zena , Yong V. Wee
Published: April 2018

Oligodendrocytes (OLs) extend processes to contact axons as a prerequisite step in myelin formation. As the OL processes migrate toward their axonal targets, they modify adhesion to their substrate, an event that may be regulated by matrix metalloproteinases (MMPs). In the mouse optic nerve, MMP-9/gelatinase B increases during myelin formation. Although tissue inhibitor of metalloproteinase (TIMP)-3 also increases in parallel, the developing optic nerve has focally active MMPs demonstrable byin situzymography. The distribution of proteolytic activity is similar to that of myelin basic protein, a marker of myelin formation. OLs in culture secrete MMP-9 and express active cell-associated metalloproteinases at the growing tips of their processes. TIMP-1 and a function-perturbing anti-MMP-9 antibody attenuate outgrowth of processes by OLs, indicating a requirement for MMP-9 in process outgrowth. Process reformation is retarded significantly in OLs cultured from MMP-9 null mice, as compared with controls, providing genetic evidence that MMP-9 is necessary for process outgrowth. These data show that MMP-9 facilitates process outgrowth by OLsin vivoand in culture.
Relief of G-Protein Inhibition of Calcium Channels and Short-Term Synaptic Facilitation in Cultured Hippocampal Neurons
Authors: Brody David L. , Yue David T.
Published: April 2018

G-protein inhibition of voltage-gated calcium channels can be transiently relieved by repetitive physiological stimuli. Here, we provide evidence that such relief of inhibition contributes to short-term synaptic plasticity in microisland-cultured hippocampal neurons. With G-protein inhibition induced by the GABABreceptor agonist baclofen or the adenosine A1 receptor agonist 2-chloroadenosine, short-term synaptic facilitation emerged during action potential trains. The facilitation decayed with a time constant of ∼100 msec. However, addition of the calcium channel inhibitor Cd2+at 2–3 μmhad no such effect and did not alter baseline synaptic depression. As expected of facilitation from relief of channel inhibition, analysis of miniature EPSCs implicated presynaptic modulation, and elevating presynaptic Ca2+entry blunted the facilitation. Most telling was the near occlusion of synaptic facilitation after selective blockade of P/Q- but not N-type calcium channels. This was as predicted from experiments using recombinant calcium channels expressed in human embryonic kidney (HEK) 293 cells; we found significantly stronger relief of G-protein inhibition in recombinant P/Q- versus N-type channels during action potential trains. G-protein inhibition in HEK 293 cells was induced via recombinant M2 muscarinic acetylcholine receptors activated by carbachol, an acetylcholine analog. Thus, relief of G-protein inhibition appears to produce a novel form of short-term synaptic facilitation in cultured neurons. Similar short-term synaptic plasticity may be present at a wide variety of synapses, as it could occur during autoreceptor inhibition by glutamate or GABA, heterosynaptic inhibition by GABA, tonic adenosine inhibition, and in many other instances.
Local Control of Acetylcholinesterase Gene Expression in Multinucleated Skeletal Muscle Fibers: Individual Nuclei Respond to Signals from the Overlying Plasma Membrane
Authors: Rossi Susana G. , Vazquez Ana E. , Rotundo Richard L.
Published: April 2018

Nuclei in multinucleated skeletal muscle fibers are capable of expressing different sets of muscle-specific genes depending on their locations within the fiber. Here we test the hypothesis that each nucleus can behave autonomously and responds to signals generated locally on the plasma membrane. We used acetylcholinesterase (AChE) as a marker because its transcripts and protein are concentrated at the neuromuscular and myotendenous junctions. First, we show that tetrodotoxin (TTX) reversibly suppresses accumulation of cell surface AChE clusters, whereas veratridine or scorpion venom (ScVn) increase them. AChE mRNA levels are also regulated by membrane depolarization. We then designed chambered cultures that allow application of sodium channel agonists or antagonists to restricted regions of the myotube surface. When a segment of myotube is exposed to TTX, AChE cluster formation is suppressed only on that region. Conversely, ScVn increases AChE cluster formation only where in contact with the muscle surface. Likewise, both the synthesis and secretion of AChE are shown to be locally regulated. Moreover, usingin situhybridization, we show that the perinuclear accumulation of AChE transcripts also depends on signals that each nucleus receives locally. Thus AChE can be up- and downregulated in adjacent regions of the same myotubes. These results indicate that individual nuclei are responding to locally generated signals for cues regulating gene expression.