bluuebunny/crossref_metadata_2025 huggingface dataset:
How to Do Things with Literature: Blasphemous Speech Acts, Satanic Intentions, and the Uncommunicativeness of Verses
Authors: Allington Daniel
Published: September 2008

Literature has at times been theorized in terms of a message passing from author to reader, and this has often been done by reference to general theories of language use: the work is the vehicle of intentions that are realized (or not) in the reader's responses; the work is a “speech act” that operates on the reader and causes his or her responses. Although this article argues that such theorizations mistake the role of communication in literature, it suggests that they nonetheless reflect prevalent ways of talking about literary texts, which should be investigated as tactically useful techniques employed in discourse between readers (and nonreaders) of those texts. Drawing on the work of a range of thinkers, notably Quentin Skinner and Jerome McGann, this article then proposes an alternative application of the concepts of authorial intention and speech act to the genesis of literary works. This is followed by a study of early contributions to the public controversy over The Satanic Verses, in which Lena Jayyusi's analysis of moral action descriptions is used to draw attention to commentators' ideological attempts to structure this novel as a speech-like action carried out by its author Salman Rushdie.
Love's Hologram: Shakespeare, Ricoeur, and the Equivocations of Erotic Identity
Authors: Deitch Judith A.
Published: September 2008

Holograms are three-dimensional visual records capable of transmitting peculiar and arresting special effects. A number of Shakespeare's sonnets reveal particular holographic effects, in which scenes of looking and speaking are enhanced by the lyric “I's” creation of distorted composite images. These holograms of self and other provide visual signals which correspond to Paul Ricoeur's philosophy of “oneself as another.” The crisis of selfhood prompted by entanglement with the other— something established in both Shakespeare's poetry and Ricoeur's philosophy—is explored and clarified by reading these holographic sonnets through the application of three basic tenets: (1) the dialectic of idem-self and ipse-self, (2) temporality as a primary trait of the self, and (3) the dialectic of possession and dispossession. The implications of such a reading are wide-ranging, affecting how we understand the peculiar interiority of the sonnets as well as the radical challenge of Ricoeur's thinking.
Refoundation as Survival
Authors: Kristeva Julia
Published: September 2008

This guest column suggests that we should follow Hannah Arendt in resisting the urge to expound doctrines or systems and, instead, should disclose the processes of our thought as they are “in motion.” While we should not hesitate to express judgments, our aim in intellectual work should be to occasion (and experience) surprise. Like Arendt, we should candidly express “the bliss of thought” as we think and write. On this basis, the political arena can become “a space for self-analysis and (by analogy with psychoanalysis) continuous rebirth.” And it is only on this basis, Kristeva argues, that reconstruction, after a century of unprecedented destruction, be accomplished without our succumbing to nostalgia. Efforts at reconstruction must be undertaken, as Arendt undertook them, “in light of the history of nihilism” and “in the name of sheer survival.” Kristeva joins Arendt in advising against a return to foundationalism while at the same time urging the development of a kind of “re-foundationalism.” Kristeva concludes by showing how, in these attitudes, Arendt's thinking was—despite her notorious dismissal of psychoanalysis—in tune with those of Freud.
The Case of “THE Yellow Notebook”
Authors: Ostashevsky Eugene
Published: September 2008

“The Case of `The Yellow Notebook'” contains reminiscences of Wittgenstein's conversations with the philosopher Tatiana Gornshteyn (1904-80) on his visit to Leningrad in 1935. The reminiscences are contained in a document written by her daughter Ludmila. It records a story about a “Yellow Notebook” of his work (in the genre of his so-called Blue and Brown Books)—a notebook that, it is claimed, Wittgenstein gave to Tatiana and was subsequently lost. Attempts have been made to find it in Russia and all have failed. Biographical and historical context is provided in an introductory essay by the translator.
Introduction: From Scratch
Authors: Tamen Miguel , Andersen Wayne , Rao Velcheru Narayana , Subrahmanyam Sanjay , Rowland Ingrid D. , Hunter J. Paul , Wong Yoke-Sum
Published: September 2008

The essay discusses the presumption of one's singularity, the uniqueness of one's time, the picturesqueness of one actions, and the capacity of human beings, whether corporately or individually, to begin everything or indeed anything again from scratch. Such presumptions are indeed present in some varieties of contemporary fanaticism, but, more to the point, it is suggested that the feeling of doing something for the first time is the oldest feeling in the world.
AN ELEGY FOR Nīti
Authors: Rao Velcheru Narayana , Subrahmanyam Sanjay
Published: September 2008

The essay reflects in an elegiac mode on a now largely forgotten (or effaced) body of literature from precolonial India regarding the art and business of politics. This body, known as nīti, has classical roots in Sanskrit but came in particular to be popular in peninsular India between the thirteenth and the eighteenth centuries in vernacular languages such as Telugu, Kannada, and Marathi. Secular and this-worldly in orientation, it can be broadly contrasted to the far better known body of texts on dharma, which are concerned to preserve a normative, ritually and religiously sanctioned, order based on strict adherence to caste and gender roles. We first trace the classical roots of the tension between dharma and nīti and then set out how these two bodies of texts came to play distinct and evolving roles in medieval and early modern south India. We argue further that under the early phase of colonial rule, East India Company officials misunderstood the nature of nīti texts and that this has led to a persistently erroneous view of their role and content. We conclude by noting, however, that some astute modern observers of and participants in Indian politics, such as B. R. Ambedkar, have understood the part that nīti might play for the development of a secular language of politics in modern India.
Missing Years
Authors: Hunter J. Paul
Published: September 2008

The third of a century between the late 1680s and the early 1720s—a time when a vast number of prolific poets flourished—is almost completely overlooked in literary history, perhaps because there was no single poetic leader and no dominant direction in the poetry. But it was a very fertile period in poetry, with many talented poets and many potential directions that did not develop into dominant trends. Because literary history almost inevitably looks at dominant directions, it tends to pass over not only individual poets who don't quite fit, but also poetic kinds and directions that don't turn out to be the winning ones. One valuable poetic mode in this period is what we might call the fallen, or disappointed, or misdirected lyric—exemplified most notably by Matthew Prior but also created by a host of other poets (Egerton, Chudleigh, Dixon, Hill, and Swift, for example). “Lost” years between distinct eras or directions also raise larger questions about the premises and practices of literary history itself.
A new perturbation estimator in a sliding mode control system with application to robot control
Authors: Choi S-B , Ham J H , Nguyen V Q , Lee Y S , Han M S
Published: September 2008

In this work, a new perturbation estimator associated with a sliding mode controller is proposed to enhance control performance of linear or non-linear systems under perturbations such as parameter uncertainties and extraneous disturbances. The estimator is designed by adopting an integrated average value of the imposed perturbation over a certain sampling period. Subsequently, in order to improve control performance, a so-called perturbation filtering condition (PFC) is introduced for the estimator. By applying the PFC in which useful components of the imposed perturbations are kept, control performance can be substantially improved without additional control input. Some benefits of the proposed methodology are demonstrated on a two-link planar robotic manipulator. The position tracking control performances of the manipulator are evaluated in the time domain and a comparative work between the proposed methodology and conventional scheme for the perturbation estimation is undertaken.
Particle filtering for state estimation in industrial robotic systems
Authors: Rigatos G G
Published: September 2008

State estimation is a major problem in industrial systems. To this end, Gaussian and non-parametric filters have been developed. In this paper the extended Kalman filter which assumes Gaussian measurement noise is compared to the particle filter which does not make any assumption on the measurement noise distribution. As a case study the estimation of the state vector of an industrial robot is used, when measurements are available from an accelerometer mounted on the end-effector of the robotic manipulator and from the encoders of the joint motors. It is shown that in this kind of sensor fusion problem the particle filter outperforms the extended Kalman filter, at the cost of more demanding computations.
Control design and stabilization analysis of non-linear systems using angular representations
Authors: Sangelaji Z , Banks S P
Published: September 2008

The stabilization of non-linear systems using the angular method are considered in this paper. Using the angular method, the system is converted into two subsystems. One is a non-linear equation on a sphere and the other is a radial differential equation. The control is designed by considering the radial subsystem. The radial control can be continuous or discontinuous depending on the structure of the input map. Whenever the input map of the radial subsystem is zero, the radial control is not accessible. In this paper methods for removing this obstacle are presented.
Fuzzy-scheduling control of a linear permanent magnet synchronous motor with payload variations
Authors: Chang Y-H , Lin H-W , Hu Y-H , Lee J-H
Published: September 2008

This paper presents a fuzzy-scheduling control scheme, including the feedback of states and the integral of tracking errors, for a linear permanent magnet synchronous motor (LPMSM). First, a parameter-dependent system model of the LPMSM is addressed. With the consideration of payload variations, a perturbed system model is described for further robustness investigation. In this paper, a Takagi—Sugeno (T-S) model is adopted to deal with the regional quadratic stability, where sufficient conditions for ensuring the performance of concern are derived in the form of linear matrix inequalities. A digital signal processor (DSP)/field programmable gate array (FPGA)-based control platform is completed to evaluate the feasibility of the proposed works. Experimental results, associated with different payload conditions, illustrate that the proposed system has satisfactory controlled responses.
Robust performance margins and robust controller design for systems with uncertain parameters
Authors: Bozorg M
Published: September 2008

The control of linear systems with uncertain parameters is considered and a method is presented for the computation of allowable parameter perturbations to maintain stability and performance conditions. Frequency bounds are placed on the sensitivity and the complementary sensitivity functions of the system in order to guarantee desired performance specifications such as input tracking and sensor noise attenuation. The algorithm makes use of Neimark's D-decomposition results on robust stability and extends the results to the case of robust performance. Explicit formulae are provided for performance measures that need to be minimized in a frequency range to compute the robust performance margin. The algorithm is then used in a controller synthesis procedure to design robust controllers in order to meet both stability and performance requirements. The details of the implementation of the procedure are illustrated through case studies.
Modelling and control of a small-scale unmanned helicopter
Authors: Du J F , Kondak K , Zhang Y O , Lu T S
Published: September 2008

The dynamical model of a toy helicopter considered as two rigid bodies is deduced using Kane's equation. Another model is presented that considers the helicopter as a single rigid body. It is shown that the response of the rotational dynamics modelled as two rigid bodies is cosine while that modelled as one rigid body is linear. In addition, a flight controller is presented that is based on dynamic inversion and model predictive control (MPC). In order to decrease the online computational effort associated with a conventional model predictive controller, an explicit MPC algorithm is introduced, which converts the online computations to offline computations to solve the real-time problem. Experimental results show that the controller is able to operate in real-time and can closely track the trajectory without overshoot.
Removing the algebraic loops of a bond graph model
Authors: Gonzalez G , Galindo R
Published: September 2008

A general straightforward procedure solving the problem of algebraic loops in a bond graph model of a linear time invariant (LTI) multi-input multi-output (MIMO) system is presented. This procedure is based on a proposed junction structure and an R-field. This junction structure allows interactions only between the state variables and the dissipation field and inputs, and between the dissipation field and the co-energy variables. This junction structure decouples the elements of the dissipation field, thereby removing the algebraic loops. The outputs are only functions of the co-energy variables and the inputs. In order to obtain a physical meaning for the proposed bond graph model, the initial R-field of this bond graph is transformed to a dissipative field of 1-port resistors, transformers, and gyrators. The proposed bond graph does not have algebraic loops and allows predefined integral (BGI) or derivative (BGD) causality assignments to be realized.
Theoretical simulation of ripples for different leading-side groove volumes on manifolds in fixed-displacement axial-piston pump
Authors: Mandal N P , Saha R , Sanyal D
Published: September 2008

For many hydraulic systems, fixed-displacement axial-piston pumps often employ swash plate. The design challenge for such a pump is to minimize the pressure and flow ripples and the consequent noises. Although the use of grooves at the leading and trailing sides of the pump manifolds has been adopted by several manufacturers as a remedy to this problem, theoretical modelling and analysis of the effects of these silencing grooves are very limited. This study presents a model that puts special emphasis on analysing the effect of volume variation of the silencing grooves. All the non-linear dynamic and algebraic equations developed during modelling have been solved in a Matlab/Simulink framework. The analysis has been carried out for a pump with leading-side manifolds, since experimental results for such a pump were available. Through a constant-speed parametric analysis at fixed load, optimal dimensions for these grooves have been indicated. The major contribution of the present work is the development of a mathematical model that attempts an explicit solution of pressure within each silencing groove. The model has been presented in the analysis as an effective design analysis tool for minimizing the pressure and flow ripples.
MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis
Authors: Yan Li-Xu , Huang Xiu-Fang , Shao Qiong , Huang MA-Yan , Deng Ling , Wu Qiu-Liang , Zeng Yi-Xin , Shao Jian-Yong
Published: September 2008

To investigate the global expression profile of miRNAs in primary breast cancer (BC) and normal adjacent tumor tissues (NATs) and its potential relevance to clinicopathological characteristics and patient survival, the genome-wide expression profiling of miRNAs in BC was investigated using a microarray containing 435 mature human miRNA oligonucleotide probes. Nine miRNAs of hsa-miR-21, hsa-miR-365, hsa-miR-181b, hsa-let-7f, hsa-miR-155, hsa-miR-29b, hsa-miR-181d, hsa-miR-98, and hsa-miR-29c were observed to be up-regulated greater than twofold in BC compared with NAT, whereas seven miRNAs of hsa-miR-497, hsa-miR-31, hsa-miR-355, hsa-miR-320, rno-mir-140, hsa-miR-127 and hsa-miR-30a-3p were observed to be down-regulated greater than twofold. The most significantly up-regulated miRNAs, hsa-mir-21 (miR-21), was quantitatively analyzed by TaqMan real-time PCR in 113 BC tumors. Interestingly, among the 113 BC cases, high level expression of miR-21 was significantly correlated with advanced clinical stage (P = 0.006, Fisher's exact text), lymph node metastasis (P = 0.007, Fisher's exact text), and shortened survival of the patients (hazard ratio [HR]=5.476, P < 0.001). Multivariate Cox regression analysis revealed this prognostic impact (HR=4.133, P = 0.001) to be independent of disease stage (HR=2.226, P = 0.013) and histological grade (HR=3.681, P = 0.033). This study could identify the differentiated miRNAs expression profile in BC and reveal that miR-21 overexpression was correlated with specific breast cancer biopathologic features, such as advanced tumor stage, lymph node metastasis, and poor survival of the patients, indicating that miR-21 may serve as a molecular prognostic marker for BC and disease progression.
Crystal structure of Escherichia coli PNPase: Central channel residues are involved in processive RNA degradation
Authors: Shi Zhonghao , Yang Wei-Zen , Lin-Chao Sue , Chak Kin-Fu , Yuan Hanna S.
Published: September 2008

Bacterial polynucleotide phosphorylase (PNPase) plays a major role in mRNA turnover by the degradation of RNA from the 3′- to 5′-ends. Here, we determined the crystal structures of the wild-type and a C-terminal KH/S1 domain-truncated mutant (ΔKH/S1) of Escherichia coli PNPase at resolutions of 2.6 Å and 2.8 Å, respectively. The six RNase PH domains of the trimeric PNPase assemble into a ring-like structure containing a central channel. The truncated mutant ΔKH/S1 bound and cleaved RNA less efficiently with an eightfold reduced binding affinity. Thermal melting and acid-induced trimer dissociation studies, analyzed by circular dichroism and dynamic light scattering, further showed that ΔKH/S1 formed a less stable trimer than the full-length PNPase. The crystal structure of ΔKH/S1 is more expanded, containing a slightly wider central channel than that of the wild-type PNPase, suggesting that the KH/S1 domain helps PNPase to assemble into a more compact trimer, and it regulates the channel size allosterically. Moreover, site-directed mutagenesis of several arginine residues in the channel neck regions produced defective PNPases that either bound and cleaved RNA less efficiently or generated longer cleaved oligonucleotide products, indicating that these arginines were involved in RNA binding and processive degradation. Taking these results together, we conclude that the constricted central channel and the basic-charged residues in the channel necks of PNPase play crucial roles in trapping RNA for processive exonucleolytic degradation.
Absence of 2-Hydroxylated Sphingolipids Is Compatible with Normal Neural Development But Causes Late-Onset Axon and Myelin Sheath Degeneration
Authors: Zöller Inge , Meixner Marion , Hartmann Dieter , Büssow Heinrich , Meyer Rainer , Gieselmann Volkmar , Eckhardt Matthias
Published: September 2008

Sphingolipids containing 2-hydroxylated fatty acids are among the most abundant lipid components of the myelin sheath and therefore are thought to play an important role in formation and function of myelin. To prove this hypothesis, we generated mice lacking a functional fatty acid 2-hydroxylase (FA2H) gene. FA2H-deficient (FA2H−/−) mice lacked 2-hydroxylated sphingolipids in the brain and in peripheral nerves. In contrast, nonhydroxylated galactosylceramide was increased inFA2H−/−mice. However, oligodendrocyte differentiation examined byin situhybridization with cRNA probes for proteolipid protein and PDGFα receptor and the time course of myelin formation were not altered inFA2H−/−mice compared with wild-type littermates. Nerve conduction velocity measurements of sciatic nerves revealed no significant differences betweenFA2H−/−and wild-type mice. Moreover, myelin ofFA2H−/−mice up to 5 months of age appeared normal at the ultrastructural level, in the CNS and peripheral nervous system. Myelin thickness and g-ratios were normal inFA2H−/−mice. Aged (18-month-old)FA2H−/−mice, however, exhibited scattered axonal and myelin sheath degeneration in the spinal cord and an even more pronounced loss of stainability of myelin sheaths in sciatic nerves. These results show that structurally and functionally normal myelin can be formed in the absence of 2-hydroxylated sphingolipids but that its long-term maintenance is strikingly impaired. Because axon degeneration appear to start rather early with respect to myelin degenerations, these lipids might be required for glial support of axon function.
The Glycine Transporter GlyT2 Controls the Dynamics of Synaptic Vesicle Refilling in Inhibitory Spinal Cord Neurons
Authors: Rousseau France , Aubrey Karin R. , Supplisson Stéphane
Published: September 2008

At inhibitory synapses, glycine and GABA are accumulated into synaptic vesicles by the same vesicular transporter VGAT/VIAAT (vesicular GABA transporter/vesicular inhibitory amino acid transporter), enabling a continuum of glycine, GABA, and mixed phenotypes. Many fundamental aspects of the presynaptic contribution to the inhibitory phenotypes remain unclear. The neuronal transporter GlyT2 is one of the critical presynaptic factors, because glycinergic transmission is impaired in knock-outGlyT2−/−mice and mutations in the human GlyT2 gene slc6a5 are sufficient to cause hyperekplexia. Here, we establish that GlyT2-mediated uptake is directly coupled to the accumulation of glycine into recycling synaptic vesicles using cultured spinal cord neurons derived from GlyT2–enhanced green fluorescent protein transgenic mice. Membrane expression of GlyT2 was confirmed by recording glycine-evoked transporter current. We show that GlyT2 inhibition induces a switch from a predominantly glycine to a predominantly GABA phenotype. This effect was mediated by a reduction of glycinergic quantal size after cytosolic depletion of glycine and was entirely reversed by glycine resupply, illustrating that the filling of empty synaptic vesicles is tightly coupled to GlyT2-mediated uptake. Interestingly, high-frequency trains of stimuli elicit two phases of vesicle release with distinct kinetic requirements for glycine refilling. Thus, our results demonstrate the central role played by GlyT2 in determining inhibitory phenotype and therefore in the physiology and pathology of inhibitory circuits.
TIMELESS Is an Important Mediator of CK2 Effects on Circadian Clock FunctionIn Vivo
Authors: Meissner Rose-Anne , Kilman Valerie L. , Lin Jui-Ming , Allada Ravi
Published: September 2008

Circadian oscillations in clock components are central to generation of self-sustained 24-h periodicity. In theDrosophilamolecular clock, accumulation, phosphorylation, and degradation of PERIOD (PER) and TIMELESS (TIM) proteins govern period length. Yet little is known about the kinases that phosphorylate TIMin vivo. It has been shown previously that the protein kinase CK2 phosphorylates TIMin vitro. Here, we identify a role for CK2 in TIM regulationin vivo. Induction of a dominant-negativeCK2α,CK2αTik(Tik), increases TIM protein andtimtranscript levels, reduces oscillation amplitude, and results in persistent cytoplasmic TIM localization. Exposure to light and subsequent TIM degradation results in an increase in the fraction of the transcriptional repressor PER that is nuclear and suppression ofperandtimRNA levels. TIM protein, but nottimtranscript, levels are elevated inTikmutants in aper01background. In contrast,Tikeffects on PER are undetectable in atim01background, suggesting that TIM is required for CK2 effects on PER. To identify potential CK2 target sites, we assayed TIM phosphorylation rhythms in a deletion mutant that removes a conserved serine-rich domain and found that TIM protein does not show robust rhythmic changes in mobility by Western blotting, a hallmark of rhythmic phosphorylation. The period lengthening effects inTikheterozygotes are reduced in atimULmutant that disrupts a putative CK2 phosphorylation site. Together, these data indicate that TIM is an important mediator of CK2 effects on circadian rhythms.
Activating Parabrachial Cannabinoid CB1Receptors Selectively Stimulates Feeding of Palatable Foods in Rats
Authors: DiPatrizio Nicholas V. , Simansky Kenny J.
Published: September 2008

The endocannabinoid system is emerging as an integral component in central and peripheral regulation of feeding and energy balance. Our investigation analyzed behavioral roles for cannabinoid mechanisms of the pontine parabrachial nucleus (PBN) in modulating intake of presumably palatable foods containing fat and/or sugar. The PBN serves to gate neurotransmission associated with, but not limited to, the gustatory properties of food. Immunofluorescence andin vitro[35S]GTPγS autoradiography of rat tissue sections containing the PBN revealed the presence of cannabinoid receptors and their functional capability to couple to their G-proteins after incubation with the endocannabinoid 2-arachidonoyl glycerol (2-AG). The selective cannabinoid 1 receptor (CB1R) antagonist AM251 [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide] prevented the response, demonstrating CB1R mediation of 2-AG-induced coupling. Microinfusions of 2-AG into the PBN in behaving rats robustly stimulated feeding of pellets high in content of fat and sucrose (HFS), pure sucrose, and pure fat (Crisco), during the first 30 min after infusion. In contrast, 2-AG failed to increase consumption of standard chow, even when the feeding regimen was manipulated to match baseline intakes of HFS. Orexigenic responses to 2-AG were attenuated by AM251, again indicating CB1R mediation of 2-AG actions. Furthermore, responses were regionally specific, because 2-AG failed to alter intake when infused into sites ∼500 μm caudal to infusions that successfully stimulated feeding. Our data suggest that hedonically positive sensory properties of food enable endocannabinoids at PBN CB1Rs to initiate increases in eating, and, more generally, these pathways may serve a larger role in brain functions controlling behavioral responses for natural reward.
Facilitatory Mechanisms Underlying Selectivity for the Direction and Rate of Frequency Modulated Sweeps in the Auditory Cortex
Authors: Razak Khaleel A. , Fuzessery Zoltan M.
Published: September 2008

Neurons selective for frequency modulated (FM) sweeps are common in auditory systems across different vertebrate groups and may underlie representation of species-specific vocalizations. Studies on mechanisms of FM sweep selectivity have primarily focused on sideband inhibition. Here, we present the first evidence for facilitatory mechanisms of FM sweep selectivity. Facilitatory interactions were found in 46 of 264 (17%) neurons tuned in the echolocation range (25–60 kHz) in the auditory cortex of the pallid bat. These neurons respond poorly to individual tones but are facilitated by combinations of tones with specific spectral and temporal intervals. Facilitation neurons show remarkable sensitivity to sub-millisecond differences in time delays between the two tones. Interestingly, the range of delays eliciting facilitation is not fixed but varies systematically with frequency difference between the two tones. Properties of facilitation strongly predict selectivity for the direction and rate of FM sweeps. Together with previous studies, there appear to be at least three mechanisms underlying FM rate and direction selectivity: sideband inhibition, duration tuning, and facilitation. Interestingly, similar mechanisms underlie direction and velocity tuning in the visual system, suggesting the evolution of similar computations across sensory systems to process dynamic sensory stimuli.
Function and Structure of the Right Inferior Frontal Cortex Predict Individual Differences in Response Inhibition: A Model-Based Approach
Authors: Forstmann Birte U. , Jahfari Sara , Scholte H. Steven , Wolfensteller Uta , van den Wildenberg Wery P. M. , Ridderinkhof K. Richard
Published: September 2008

The ability to suppress one's impulses and actions constitutes a fundamental mechanism of cognitive control, thought to be subserved by the right inferior frontal cortex (rIFC). The neural bases of more selective inhibitory control when selecting between two actions have thus far remained articulated with less precision. Selective inhibition can be explored in detail by extracting parameters from response time (RT) distributions as derived from performance in the Simon task. Individual differences in RT distribution parameters not only can be used to probe the efficiency and temporal dynamics of selective response inhibition, but also allow a more detailed analysis of functional neuroimaging data. Such model-based analyses, which capitalize on individual differences, have demonstrated that selective response inhibition is subserved by the rIFC. The aim of the present study was to specify the relationship between model parameters of response inhibition and their functional and structural underpinnings in the brain. Functional magnetic resonance imaging (fMRI) data were obtained from healthy participants while performing a Simon task in which irrelevant information can activate incorrect responses that should be selectively inhibited in favor of selecting the correct response. In addition, structural data on the density of coherency of white matter tracts were obtained using diffusion tensor imaging (DTI). The analyses aimed at quantifying the extent to which RT distribution measures of response inhibition are associated with individual differences in both rIFC function and structure. The results revealed a strong correlation between the model parameters and both fMRI and DTI characteristics of the rIFC. In general, our results reveal that individual differences in inhibition are accompanied by differences in both brain function and structure.
Numbers, Densities, and Colocalization of AMPA- and NMDA-Type Glutamate Receptors at Individual Synapses in the Superficial Spinal Dorsal Horn of Rats
Authors: Antal Miklós , Fukazawa Yugo , Eördögh Mária , Muszil Dóra , Molnár Elek , Itakura Makoto , Takahashi Masami , Shigemoto Ryuichi
Published: September 2008

Ionotropic glutamate receptors play important roles in spinal processing of nociceptive sensory signals and induction of central sensitization in chronic pain. Here we applied highly sensitive freeze-fracture replica labeling to laminae I–II of the spinal dorsal horn of rats and investigated the numbers, densities, and colocalization of AMPA- and NMDA-type glutamate receptors at individual postsynaptic membrane specializations with a high resolution. All glutamatergic postsynaptic membranes in laminae I–II expressed AMPA receptors, and most of them (96%) were also immunoreactive for the NR1 subunit of NMDA receptors. The numbers of gold particles for AMPA and NMDA receptors at individual postsynaptic membranes showed a linear correlation with the size of postsynaptic membrane specializations and varied in the range of 8–214 and 5–232 with median values of 37 and 28, whereas their densities varied in the range of 325–3365/μm2and 102–2263/μm2with median values of 1115/μm2and 777/μm2, respectively. Virtually all (99%) glutamatergic postsynaptic membranes expressed GluR2, and most of them (87%) were also immunoreactive for GluR1. The numbers of gold particles for pan-AMPA, NR1, and GluR2 subunits showed a linear correlation with the size of postsynaptic surface areas. Concerning GluR1, there may be two populations of synapses with high and low GluR1 densities. In synapses larger than 0.1 μm2, GluR1 subunits were recovered in very low numbers. Differential expression of GluR1 and GluR2 subunits suggests regulation of AMPA receptor subunit composition by presynaptic mechanism.
Driver or Coincidence Detector: Modal Switch of a Corticothalamic Giant Synapse Controlled by Spontaneous Activity and Short-Term Depression
Authors: Groh Alexander , de Kock Christiaan P. J. , Wimmer Verena C. , Sakmann Bert , Kuner Thomas
Published: September 2008

Giant synapses between layer 5B (L5B) neurons of somatosensory (barrel) cortex and neurons of the posteromedial nucleus (POm) of thalamus reside in a key position of the cortico-thalamo-cortical (CTC) loop, yet their synaptic properties and contribution to CTC information processing remain poorly understood. Fluorescence-guided local stimulation of terminals were combined with postsynaptic whole-cell recordings in thalamus to study synaptic transmission at an identified giant synapse. We found large EPSCs mediated by Ca2+-permeable AMPA and NMDA receptors. A single presynaptic electrical stimulus evoked a train of postsynaptic action potentials, indicating that a single L5B input can effectively drive the thalamic neuron. Repetitive stimulation caused strong short-term depression (STD) with fast recovery. To examine how these synaptic properties affect information transfer, spontaneous and evoked activity of L5B neurons was recordedin vivoand played back to giant terminalsin vitro. We found that suprathreshold synaptic transmission was suppressed because of spontaneous activity causing strong STD of the L5B–POm giant synapse. Thalamic neurons only spiked after intervals of presynaptic silence or when costimulating two giant terminals. Therefore, STD caused by spontaneous activity of L5B neurons can switch the synapse from a “driver mode” to a “coincidence mode.” Mechanisms decreasing spontaneous activity in L5B neurons and inputs synchronized by a sensory stimulus may thus gate the cortico-thalamo-cortical loop.
Connexin45-Containing Neuronal Gap Junctions in Rodent Retina Also Contain Connexin36 in Both Apposing Hemiplaques, Forming Bihomotypic Gap Junctions, with Scaffolding Contributed by Zonula Occludens-1
Authors: Li Xinbo , Kamasawa Naomi , Ciolofan Cristina , Olson Carl O. , Lu Shijun , Davidson Kimberly G. V. , Yasumura Thomas , Shigemoto Ryuichi , Rash John E. , Nagy James I.
Published: September 2008

Mammalian retinas contain abundant neuronal gap junctions, particularly in the inner plexiform layer (IPL), where the two principal neuronal connexin proteins are Cx36 and Cx45. Currently undetermined are coupling relationships between these connexins and whether both are expressed together or separately in a neuronal subtype-specific manner. Although Cx45-expressing neurons strongly couple with Cx36-expressing neurons, possibly via heterotypic gap junctions, Cx45 and Cx36 failed to form functional heterotypic channelsin vitro. We now show that Cx36 and Cx45 coexpressed in HeLa cells were colocalized in immunofluorescent puncta between contacting cells, demonstrating targeting/scaffolding competence for both connexinsin vitro. However, Cx36 and Cx45 expressed separately did not form immunofluorescent puncta containing both connexins, supporting lack of heterotypic coupling competence. In IPL, 87% of Cx45-immunofluorescent puncta were colocalized with Cx36, supporting either widespread heterotypic coupling or bihomotypic coupling. Ultrastructurally, Cx45 was detected in 9% of IPL gap junction hemiplaques, 90–100% of which also contained Cx36, demonstrating connexin coexpression and cotargeting in virtually all IPL neurons that express Cx45. Moreover, double replicas revealed both connexins in separate domains mirrored on both sides of matched hemiplaques. With previous evidence that Cx36 interacts with PDZ1 domain of zonula occludens-1 (ZO-1), we show that Cx45 interacts with PDZ2 domain of ZO-1, and that Cx36, Cx45, and ZO-1 coimmunoprecipitate, suggesting that ZO-1 provides for coscaffolding of Cx45 with Cx36. These data document that in Cx45-expressing neurons of IPL, Cx45 is almost always accompanied by Cx36, forming “bihomotypic” gap junctions, with Cx45 structurally coupling to Cx45 and Cx36 coupling to Cx36.
Critical Role of the Prefrontal Cortex in the Regulation of Hippocampus–Accumbens Information Flow
Authors: Belujon Pauline , Grace Anthony A.
Published: September 2008

The nucleus accumbens (NAc) is an integral part of limbic circuits proposed to play a central role in the pathophysiology of schizophrenia, and is positioned to integrate information from limbic and cortical regions, including the medial prefrontal cortex (mPFC) and the hippocampus. The ventral subiculum (vSub) of the hippocampus, in particular, is proposed to gate information flow within the NAc, a factor that is disrupted in models of schizophrenia. Usingin vivoextracellular recordings in anesthetized rats, we examined the response of NAc neurons to vSub stimulation and how this is modulated by the mPFC. We found that inactivation of mPFC by tetrodotoxin attenuates the ability of the vSub to drive spike firing in the NAc. Thus, a contribution of the mPFC is required for the activation of NAc by the vSub. However, when long-term potentiation is induced in the vSub–NAc pathway, the vSub is now capable of driving the NAc without the participation of the mPFC. Moreover, this interaction is dependent on activation of dopaminergic D2receptors in the NAc.

This work demonstrates the critical role of the mPFC in the ability of vSub to drive NAc neurons in normal anesthetized animals. One model of schizophrenia posits that vSub hyperactivity may underlie both the hyperdopaminergic state and disruption of information flow in this circuit in schizophrenia. Therefore, inactivation of the mPFC, as would occur with mPFC leukotomy in schizophrenia, may prevent the abnormal vSub drive of the NAc.
Schwann Cells Promote Synaptogenesis at the Neuromuscular Junction via Transforming Growth Factor-β1
Authors: Feng Zhihua , Ko Chien-Ping
Published: September 2008

Recent studies suggest that glial cells actively participate in the formation, function, maintenance, and repair of the chemical synapse. However, the molecular mechanisms of glia–synapse interactions are largely unknown. We have shown previously that Schwann cell-conditioned medium (SC-CM) promotes synaptogenesis inXenopusnerve–muscle cocultures. The present study aimed to identify the synaptogenic molecules in SC-CM. Combining biochemical approaches andin vitrobioassays, we found that SC-CM contains transforming growth factor (TGF)-β1, which is expressed in Schwann cells bothin vivoandin vitro. Similar to SC-CM, TGF-β1 doubled the size of acetylcholine receptor (AChR) clusters at nerve–muscle contacts and significantly increased the percentage of nerve–muscle contacts that show AChR clusters to ∼60%, compared with ∼20% seen in control cultures. The synaptogenic effects of SC-CM were abolished if SC-CM was immunodepleted of TGF-β1 or if the latency-associated protein or a TGF-β1 receptor kinase inhibitor was added to block the bioactivity of TGF-β1. Similar to frog SC-CM, mammalian SC-CM also showed synaptogenic effects, which were prevented by immunodepletion of TGF-β1. TGF-β1 upregulated agrin expression in spinal neurons, which could explain the increase in AChR clusters in cultures treated with SC-CM. These results suggest that Schwann cells express TGF-β1, which is both sufficient and necessary for mediating the synapse-promoting effects of Schwann cells at the developing neuromuscular junction. Schwann cell-derived TGF-β1 thus joins other astrocyte-derived synaptogenic factors in further strengthening the emerging concept that glial cells contribute to synaptogenesis in both the PNS and the CNS.
Increased Vesicular Monoamine Transporter Binding during Early Abstinence In Human Methamphetamine Users: Is VMAT2 a Stable Dopamine Neuron Biomarker?
Authors: Boileau Isabelle , Rusjan Pablo , Houle Sylvain , Wilkins Diana , Tong Junchao , Selby Peter , Guttman Mark , Saint-Cyr Jean A. , Wilson Alan A. , Kish Stephen J.
Published: September 2008

Animal data indicate that methamphetamine can damage striatal dopamine terminals. Efforts to document dopamine neuron damage in living brain of methamphetamine users have focused on the binding of [11C]dihydrotetrabenazine (DTBZ), a vesicular monoamine transporter (VMAT2) positron emission tomography (PET) radioligand, as a stable dopamine neuron biomarker. Previous PET data report a slight decrease in striatal [11C]DTBZ binding in human methamphetamine users after prolonged (mean, 3 years) abstinence, suggesting that the reduction would likely be substantial in early abstinence. We measured striatal VMAT2 binding in 16 recently withdrawn (mean, 19 d; range, 1–90 d) methamphetamine users and in 14 healthy matched-control subjects during a PET scan with (+)[11C]DTBZ. Unexpectedly, striatal (+)[11C]DTBZ binding was increased in methamphetamine users relative to controls (+22%, caudate; +12%, putamen; +11%, ventral striatum). Increased (+)[11C]DTBZ binding in caudate was most marked in methamphetamine users abstinent for 1–3 d (+41%), relative to the 7–21 d (+15%) and >21 d (+9%) groups. Above-normal VMAT2 binding in some drug users suggests that any toxic effect of methamphetamine on dopamine neurons might be masked by an increased (+)[11C]DTBZ binding and that VMAT2 radioligand binding might not be, as is generally assumed, a “stable” index of dopamine neuron integrityin vivo. One potential explanation for increased (+)[11C]DTBZ binding is that VMAT2 binding is sensitive to changes in vesicular dopamine storage levels, presumably low in drug users. If correct, (+)[11C]DTBZ might be a useful imaging probe to correlate changes in brain dopamine stores and behavior in users of methamphetamine.
Dysregulation of Gene Expression in Primary Neuron Models of Huntington's Disease Shows That Polyglutamine-Related Effects on the Striatal Transcriptome May Not Be Dependent on Brain Circuitry
Authors: Runne Heike , Régulier Etienne , Kuhn Alexandre , Zala Diana , Gokce Ozgun , Perrin Valérie , Sick Beate , Aebischer Patrick , Déglon Nicole , Luthi-Carter Ruth
Published: September 2008

Gene expression changes are a hallmark of the neuropathology of Huntington's disease (HD), but the exact molecular mechanisms of this effect remain uncertain. Here, we report thatin vitromodels of disease comprised of primary striatal neurons expressing N-terminal fragments of mutant huntingtin (via lentiviral gene delivery) faithfully reproduce the gene expression changes seen in human HD. Neither viral infection nor unrelated (enhanced green fluorescent protein) transgene expression had a major effect on resultant RNA profiles. Expression of a wild-type fragment of huntingtin [htt171-18Q] also caused only a small number of RNA changes. The disease-related signal in htt171-82Q versus htt171-18Q comparisons was far greater, resulting in the differential detection of 20% of all mRNA probe sets. Transcriptomic effects of mutated htt171 are time- and polyglutamine-length dependent and occur in parallel with other manifestations of polyglutamine toxicity over 4–8 weeks. Specific RNA changes in htt171-82Q-expressing striatal cells accurately recapitulated those observed in human HD caudate and included decreases in PENK (proenkephalin), RGS4 (regulator of G-protein signaling 4), dopamine D1receptor (DRD1), DRD2, CNR1 (cannabinoid CB1receptor), and DARPP-32 (dopamine- and cAMP-regulated phosphoprotein-32; also known as PPP1R1B) mRNAs. HD-related transcriptomic changes were also observed in primary neurons expressing a longer fragment of mutant huntingtin (htt853-82Q). The gene expression changes observed in cultured striatal neurons are not secondary to abnormalities of neuronal firing or glutamatergic, dopaminergic, or brain-derived neurotrophic factor signaling, thereby demonstrating that HD-induced dysregulation of the striatal transcriptome might be attributed to intrinsic effects of mutant huntingtin.
Attenuation of Neural Responses in Primary Visual Cortex during the Attentional Blink
Authors: Williams Mark A. , Visser Troy A. W. , Cunnington Ross , Mattingley Jason B.
Published: September 2008

Information-processing bottlenecks are characteristic of many cognitive and neural systems. One such bottleneck is revealed by tasks in which rapidly successive stimulus events must be reported. Here, observers missed the second of two visual targets if it occurred within 700 ms of the first [an “attentional blink” (AB)], even though this second target could be reported accurately when the first item was ignored. Isolating neural responses to such rapid events has proven difficult because current magnetic resonance imaging methods rely on relatively sluggish changes in the brain's physiological response to sensory inputs. Here, we overcame this limitation by presenting successive visual targets at different spatial locations, thereby exploiting the retinotopic organization of early cortical visual areas to distinguish neural activity associated with successive target events. We show that neural activity in primary visual cortex is significantly modulated during the AB, and that this activity mirrors behavioral measures of target identification accuracy. The findings suggest that the neural signature of perceptual suppression during processing of rapidly successive stimuli is evident at the earliest stages of cortical sensory processing.
The Neurotrophin-Inducible GeneVgfRegulates Hippocampal Function and Behavior through a Brain-Derived Neurotrophic Factor-Dependent Mechanism
Authors: Bozdagi Ozlem , Rich Erin , Tronel Sophie , Sadahiro Masato , Patterson Kamara , Shapiro Matthew L. , Alberini Cristina M. , Huntley George W. , Salton Stephen R. J.
Published: September 2008

VGF is a neurotrophin-inducible, activity-regulated gene product that is expressed in CNS and PNS neurons, in which it is processed into peptides and secreted. VGF synthesis is stimulated by BDNF, a critical regulator of hippocampal development and function, and two VGF C-terminal peptides increase synaptic activity in cultured hippocampal neurons. To assess VGF function in the hippocampus, we tested heterozygous and homozygous VGF knock-out mice in two different learning tasks, assessed long-term potentiation (LTP) and depression (LTD) in hippocampal slices from VGF mutant mice, and investigated how VGF C-terminal peptides modulate synaptic plasticity. Treatment of rat hippocampal slices with the VGF-derived peptide TLQP62 resulted in transient potentiation through a mechanism that was selectively blocked by the BDNF scavenger TrkB–Fc, the Trk tyrosine kinase inhibitor K252a (100 nm), and tPA STOP, an inhibitor of tissue plasminogen activator (tPA), an enzyme involved in pro-BDNF cleavage to BDNF, but was not blocked by the NMDA receptor antagonist APV, anti-p75NTRfunction-blocking antiserum, or previous tetanic stimulation. Although LTP was normal in slices from VGF knock-out mice, LTD could not be induced, and VGF mutant mice were impaired in hippocampal-dependent spatial learning and contextual fear conditioning tasks. Our studies indicate that the VGF C-terminal peptide TLQP62 modulates hippocampal synaptic transmission through a BDNF-dependent mechanism and that VGF deficiency in mice impacts synaptic plasticity and memory in addition to depressive behavior.