bluuebunny/crossref_metadata_2025 huggingface dataset:
Steffen Diefenbach, Römische Erinnerungsräume. Heiligenmemoria und kollektive Identitäten im Rom des 3. bis 5. Jahrhunderts n. Chr.
Authors: Lambrecht Ulrich
Published: May 2009

For a long time historians took it for granted that the history of memorial culture from Late Antiquity to the early Middle Ages was characterized by a clear continuity. As a historian of Antiquity, but drawing upon the latest theoretical achievements in the interdisciplinary field of memory and identity studies, Steffen Diefenbach now challenges this view by pointing to significant transformations that went along with the transition of eras. In a series of five case studies on various aspects of the memory of saints and ancient Roman history between 250 and 500 A.D. Diefenbach analyzes the ways in which the social fabric of ancient life was deeply transformed between the 3rd and 6th centuries and how it became dissolved into something new. This process affected not only the topography of the city but also the life and mentality of its inhabitants. New references of memory triggered an accelerating change that eventually lead to the historical end of the ancient city. Diefenbach offers convincing results in regard to various topics and manages to turn them into general insights into a continuous process of transformation.
Carl Schmidt und kein Ende. Aus großer Zeit der Koptologie an der Berliner Akademie und der Theologischen Fakultät der Universität
Authors: Markschies Christoph
Published: May 2009

This article presents the life and work of the Berlin coptologist Carl Schmidt (1868-1938) in the light of new sources, among them the correspondence between Schmidt and his mentor Adolf Harnack. Due to Carl Schmidt's continuous purchase of newly discovered texts and their preparation for critical editions changed the image of Ancient Christianity, partly in a radical sense. This is especially the case for the Manichaean and other Gnostic texts, but even for some apocrypha he discovered during his numerous expeditions to Egypt. The efforts of preparing critical editions of these newly found documents last until today. Thus first as an assistant of the “Berliner Kirchenväteredition”, then as an initially adjunct professor of Church History, who also gave lectures at the Berlin Faculty of Theology, Carl Schmidt gave support to his lifetime mentor Harnack.
Die Forschung am Thomasevangelium im Berliner Arbeitskreis für koptisch-gnostische Schriften. Beobachtungen anhand von Logion 58 (NHC II, p. 43,7-9)
Authors: Schröter Jens
Published: May 2009

Starting with some reflections on the history of the “Berliner Arbeitskreis” this article discusses characteristics of the German translation of the Gospel of Thomas which was produced by this group and published in the 15th edition of the “Synopsis Quattuor Evangeliorum” as well as in “Nag Hammadi Deutsch”. Thereby Logion 58, the motto for he Symposium honoring Hans-Gebhard Bethge, was chosen as an example. A comparison with the first German translation, done by Johannes Leipoldt and published in 1958, gives an insight into philological and textual decisions made by the „Berliner Arbeitskreis” during the work on the Gospel of Thomas.
Die Eschatologie des Thomasevangeliums
Authors: Pokorný Petr
Published: May 2009

The Gospel of Thomas with its spiritual eschatology is a timeless Platonic interpretation of the Early Christian faith. Nevertheless in its inner structure this interpretation may have been an intentional attempt to restore and re-present the realized eschatology mediated by the Holy Spirit as it was at the beginning. This was an experience that did not yet acknowledge the splitting of the Christian eschatology into the first and second coming of Jesus as the Messiah. The Thomasine group considered this early experience to be the most authentic expression of faith and tried to express it by means of a Platonic project.
„Perlen vor die Säue“ – Mt 7,6 im Licht von EvThom 93
Authors: Plisch Uwe-Karsten
Published: May 2009

The essay discusses the two-part rule in Mt 7,6 in light of its parallel in Gospel of Thomas 93. This often ignored parallel, even though the closest parallel to Mt 7,6 in terms of history of religion, has a more simple structure than the text of Mt 7,6. This simple structure (rule 1 followed by its rationale, then rule 2 followed by its rationale) makes a strong argument for the interpretation of the text of Mt 7,6 as chiastic. In light of Gospel of Thomas 93, most of the common German and English translations of Mt 7,6 seem to be mistranslated.
Sethianer?
Authors: Luttikhuizen Gerard P.
Published: May 2009

In two seminal articles Hans Martin Schenke and his “Berliner Arbeitskreis” proposed the designation “Sethianism” for an allegedly distinctive body of Gnostic texts. His proposal was adopted and elaborated by several scholars. Focusing on the Apocryphon of John, the present essay discusses some aspects of the Sethian thesis: what is the role played by Seth and the Sethians in this important mythological text, is it correct to assume that its teachings are essentially pre-Christian Jewish?
Der Begriff μετάνoια in gnostischen Schriften
Authors: Brankaer Johanna
Published: May 2009

This paper explores the use and meaning of the concept of μετάνoια in Gnostic texts. It is found with regard to Sophia, Sabaoth and the soul. It expresses their avertion from the created order and its demiurge and their conversion to the real God. The main characteristics of the μετάνoια are: it starts off as an avertion, some kind of negative knowledge about reality; it involves some public display of culpability and regret; it is a demand to a graceful deity who allows for an eschatological liberation of everything that belongs to the order of creation; before this return to the pleromatic origin takes places, the repentent often stays in a place called the μετάνoια. Typical for the Gnostic μετάνoια is the fact that it has an epistemic value: it is the condition for true knowledge.
Warum und inwiefern ist Judas ein „Daimon“? Überlegungen zum Evangelium des Judas (Codex Tchacos 44,21)
Authors: Petersen Silke
Published: May 2009

The recently published Gospel of Judas has rapidly become a disputed text. Whilst some scholars welcome the depiction of a “good Judas”, which they believe can be found in this text, others believe that Judas is here portrayed as negatively as ever – even not more so. That Jesus calls Judas a “demon” seems to support the latter opinion. This article explores the use of the term “demon” in a range of ancient texts – the New Testament, the Nag Hammadi writings, and the Platonic tradition – discussing which might shed light on the Judas figure in the Gospel of Judas. It concludes that the question of whether Judas is presented as good or bad is misleading: Judas is neither good nor bad, but a middle figure with the ability of receiving and communicating revelation.
Erste Annäherung einer Hermeneutik des in alttestamentlichen Schriften mit Überlegungen zur Rezeption dieses Begriffes in den neutestamentlichen Evangelien
Authors: Brix Katrine
Published: May 2009

Compared to the frequent use of the word παραβoλή in the Septuagint and the Synoptic Gospels the absence of this term in the Gospel of John prompted this investigation of the hermeneutic of the Hebrew I in accordance with its Greek translation in the Septuagint as παραβoλή and παρoιμíα respectively. Etymologically I has several meanings: “proverb”, “byword”, “reproach” and “parable”. Despite these different meanings coherence can still be found within the hermeneutical setting of the word, where it seems to signify either a positive or negative relationship between Yahweh and Israel. In the negative sense of the word it appears as “proverb”, “byword” or “reproach” indicating a broken relationship between Yahweh and Israel caused by disobedience to the Word of the Covenant. In the positive sense of the word it indicates a manifest and unique relationship between Yahweh and the one speaking the , i.e. an elect individual such as a prophet or king of Israel.

Only in Ezekiel (Ez 17,2; 21,5; 24,3) the word appears in the sense of parable in accordance with the Synoptic use of the word as expressing exhortation in riddles. Where the needs a human being as medium and thus never goes forth directly from the mouth of Yahweh, the revelation of the Will of Yahweh is not expressed in , but in דבד,אמד, in Septuagint λóγoς or ῥῆμα. Though the Synoptic παραβoλή is commonly understood as a riddle or simile it is remarkable that these riddles do not appear without exhortation, which may require a reconsideration of the definition of the Synoptic παραβoλή. This in turn leads to further questions concerning the consequences of a παραβoλή-speaking Christ for the Christology. If this argument is accepted it might be possible to draw a tentative conclusion to the absence of the word παραβoλή in the Gospel of John, where the divine λóγoς is not transformed into /παραβoλή through the flesh of Jesus or by his act of speaking, but remains λóγoς, ῥῆμα and related to the positive sense of as παρoιμíα. Thus, Jesus not only gains a higher status as a prophet, but the words he speaks are more than exhortations to the Word of Yahweh, they are the Words of Yahweh.
Hermes Trismegistos, die Gnosis und der „Berliner Arbeitskreis für koptisch-gnostische Schriften“ – Ein Rückblick
Authors: Tröger Karl-Wolfgang
Published: May 2009

Since 40 years the „Berliner Arbeitskreis für koptisch-gnostische Schriften“ deals with the translation and interpretation of the writings of Nag Hammadi. In this time, numerous international meetings and close cooperation occured, visible in several publications. The East-West-conflict meant heavy difficulties for this, but common scientific work and personal friendship made it possible. The highly specialized research founded by Hans-Martin Schenke († 2002) is successfully continued by Hans-Gebhard Bethge and several young scholars.
The Mammalian Molecular Clockwork Controls Rhythmic Expression of Its Own Input Pathway Components
Authors: Pfeffer Martina , Müller Christian M. , Mordel Jérôme , Meissl Hilmar , Ansari Nariman , Deller Thomas , Korf Horst-Werner , von Gall Charlotte
Published: May 2009

The core molecular clockwork in the suprachiasmatic nucleus (SCN) is based on autoregulatory feedback loops of transcriptional activators (CLOCK/NPAS2 and BMAL1) and inhibitors (mPER1–2 and mCRY1–2). To synchronize the phase of the molecular clockwork to the environmental day and night condition, light at dusk and dawn increasesmPerexpression. However, the signal transduction pathways differ remarkably between the day/night and the night/day transition. Light during early night leads to intracellular Ca2+release by neuronal ryanodine receptors (RyRs), resulting in phase delays. Light during late night triggers an increase in guanylyl cyclase activity, resulting in phase advances. To date, it is still unknown how the core molecular clockwork regulates the availability of the respective input pathway components. Therefore, we examined light resetting mechanisms in mice with an impaired molecular clockwork (BMAL1−/−) and the corresponding wild type (BMAL1+/+) usingin situhybridization, real-time PCR, immunohistochemistry, and a luciferase reporter system. In addition, intracellular calcium concentrations (Ca2+i) were measured in SCN slices using two-photon microscopy. In the SCN ofBMAL1−/−miceRyrmRNA and RyR protein levels were reduced, and light-inducedmPerexpression was selectively impaired during early night. Transcription assays with NIH3T3 fibroblasts showed thatRyrexpression was activated by CLOCK::BMAL1 and inhibited by mCRY1. The Ca2+iresponse of SCN cells to the RyR agonist caffeine was reduced inBMAL1−/−compared withBMAL1+/+mice. Our findings provide the first evidence that the mammalian molecular clockwork influencesRyrexpression and thus controls its own photic input pathway components.
Inadvertent Contralateral Activity during a Sustained Unilateral Contraction Reflects the Direction of Target Movement
Authors: Post Marijn , Bakels Rob , Zijdewind Inge
Published: May 2009

Strong unilateral contractions are accompanied by excitatory effects to the ipsilateral cortex. This activity can even result in overt contractions of muscles in the contralateral limb. We used this inadvertent, associated activity to study whether the cortical presentation of movements is organized in a directional-related or a muscle-related reference frame. We assessed the contralateral activation for the left index finger during a sustained maximal abduction of the right index finger. In the first experiment, both hands were held vertically in a symmetrical orientation, and in the second experiment the hands were in an asymmetrical orientation (left hand, palm downward; right hand, vertical). In both experiments, the direction of the contralateral associated contraction was upward, i.e., in the symmetrical hand orientation the contralateral force increased mainly in abduction direction, whereas in the asymmetrical hand orientation the contralateral force increased in the extension direction. Thus, the contralateral contractions reflected the direction of the target movement rather than simply the activity of the muscles activated on the target side. These observations provide strong evidence that motor commands are organized in an extrinsic, direction-related reference frame, as opposed to an internal muscle-related reference frame.
Increased Dependence of Action Selection on Recent Motor History in Parkinson's Disease
Authors: Helmich Rick C. , Aarts Esther , de Lange Floris P. , Bloem Bastiaan R. , Toni Ivan
Published: May 2009

It is well known that the basal ganglia are involved in switching between movement sequences. Here we test the hypothesis that this contribution is an instance of a more general role of the basal ganglia in selecting actions that deviate from the context defined by the recent motor history, even when there is no sequential structure to learn or implement. We investigated the effect of striatal dopamine depletion [in Parkinson's disease (PD)] on the ability to switch between independent action plans. PD patients with markedly lateralized signs performed a hand laterality judgment task that involved action selection of their most and least affected hand. Trials where patients selected the same (repeat) or the alternative (switch) hand as in a previous trial were compared, and this was done separately for the most and least affected hand. Behaviorally, PD patients showed switch-costs that were specific to the most affected hand and that increased with disease severity. Functional magnetic resonance imaging (fMRI) showed that this behavioral effect was related to the state of the frontostriatal system: as disease severity increased, contributions of the basal ganglia to the selection process and their effective connectivity with the medial frontal cortex (MFC) decreased, whereas involvement of the MFC increased. We conclude that the basal ganglia are important for rapidly switching toward novel motor plans even when there is no sequential structure to learn or implement. The enhanced MFC activity may result either from reduced focusing abilities of the basal ganglia or from compensatory processes.
Signal Propagation inDrosophilaCentral Neurons
Authors: Gouwens Nathan W. , Wilson Rachel I.
Published: May 2009

Drosophilais an important model organism for investigating neural development, neural morphology, neurophysiology, and neural correlates of behaviors. However, almost nothing is known about how electrical signals propagate inDrosophilaneurons. Here, we address these issues in antennal lobe projection neurons, one of the most well studied classes ofDrosophilaneurons. We use morphological and electrophysiological data to deduce the passive membrane properties of these neurons and to build a compartmental model of their electrotonic structure. We find that these neurons are electrotonically extensive and that a somatic recording electrode can only imperfectly control the voltage in the rest of the cell. Simulations predict that action potentials initiate at a location distant from the soma, in the proximal portion of the axon. Simulated synaptic input to a single dendritic branch propagates poorly to the rest of the cell and cannot match the size of real unitary synaptic events, but we can obtain a good fit to data when we model unitary input synapses as dozens of release sites distributed across many dendritic branches. We also show that the true resting potential of these neurons is more hyperpolarized than previously thought, attributable to the experimental error introduced by the electrode seal conductance. A leak sodium conductance also contributes to the resting potential. Together, these findings have fundamental implications for how these neurons integrate their synaptic inputs. Our results also have important consequences for the design and interpretation of experiments aimed at understandingDrosophilaneurons and neural circuits.
Alternatively Spliced Isoforms of TRIP8b Differentially Control h Channel Trafficking and Function
Authors: Lewis Alan S. , Schwartz Emily , Savio Chan C. , Noam Yoav , Shin Minyoung , Wadman Wytse J. , James Surmeier D. , Baram Tallie Z. , Macdonald Robert L. , Chetkovich Dane M.
Published: May 2009

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels (h channels) are the molecular basis for the current,Ih, which contributes crucially to intrinsic neuronal excitability. The subcellular localization and biophysical properties of h channels govern their function, but the mechanisms controlling these characteristics, and especially the potential role of auxiliary subunits or other binding proteins, remain unclear. We focused on TRIP8b, an h channel-interacting protein that colocalizes with HCN1 in cortical and hippocampal pyramidal neuron dendrites, and found that it exists in multiple alternative splice variants with distinct effects on h channel trafficking and function. The developmentally regulated splice variants of TRIP8b all shared dual, C terminus-located interaction sites with HCN1. When coexpressed with HCN1 in heterologous cells individual TRIP8b isoforms similarly modulated gating ofIh, causing a hyperpolarizing shift in voltage dependence of channel activation, but differentially upregulated or downregulatedIhcurrent density and HCN1 surface expression. In hippocampal neurons, coexpression of TRIP8b isoforms with HCN1 produced isoform-specific changes of HCN1 localization. Interestingly, the TRIP8b isoforms most abundant in the brain are those predicted to enhance h channel surface expression. Indeed, shRNA knockdown of TRIP8b in hippocampal neurons significantly reduced nativeIh. Thus, although TRIP8b exists in multiple splice isoforms, our data suggest that the predominant role of this protein in brain is to promote h channel surface expression and enhanceIh. BecauseIhexpression is altered in models of several diseases, including temporal lobe epilepsy, TRIP8b may play a role in both normal neuronal function and in aberrant neuronal excitability associated with neurological disease.
TRPC1 and TRPC6 Channels Cooperate with TRPV4 to Mediate Mechanical Hyperalgesia and Nociceptor Sensitization
Authors: Alessandri-Haber Nicole , Dina Olayinka A. , Chen Xiaoje , Levine Jon D.
Published: May 2009

The transient receptor potential vanilloid 4 (TRPV4) contributes to mechanical hyperalgesia of diverse etiologies, presumably as part of a mechanoreceptor signaling complex (Alessandri-Haber et al., 2008). To investigate the hypothesis that a functional interaction between TRPV4 and stretch-activated ion channels (SACs) is involved in this mechanical transduction mechanism, we used a selective SACs inhibitor, GsMTx-4. Intradermal injection of GsMTx-4 in the rat hindpaw reversed the mechanical hyperalgesia induced by intradermal injection of inflammatory mediators.In vivosingle fiber recordings showed that GsMTx-4 reversed inflammatory mediator-induced decrease in mechanical threshold in half of sensitized C-fibers. Furthermore, GsMTx-4 reduced hyperalgesia to both mechanical and hypotonic stimuli in different models of inflammatory and neuropathic pain, although it had no effect on baseline mechanical nociceptive thresholds.

TRPC1 and TRPC6, two GsMTx-4-sensitive SACs, are expressed in dorsal root ganglion (DRG) neurons. Single-cell reverse transcription-PCR showed that messenger RNAs for TRPV4, TRPC1, and TRPC6 are frequently coexpressed in DRG neurons. Spinal intrathecal administration of oligodeoxynucleotides antisense to TRPC1 and TRPC6, like that to TRPV4, reversed the hyperalgesia to mechanical and hypotonic stimuli induced by inflammatory mediators without affecting baseline mechanical nociceptive threshold. However, antisense to TRPC6, but not to TRPC1, reversed the mechanical hyperalgesia induced by a thermal injury or the TRPV4-selective agonist 4α-PDD (4 α-phorbol 12,13-didecanoate). We conclude that TRPC1 and TRPC6 channels cooperate with TRPV4 channels to mediate mechanical hyperalgesia and primary afferent nociceptor sensitization, although they may have distinctive roles.
Immunization with Amyloid-β Attenuates Inclusion Body Myositis-Like Myopathology and Motor Impairment in a Transgenic Mouse Model
Authors: Kitazawa Masashi , Vasilevko Vitaly , Cribbs David H. , LaFerla Frank M.
Published: May 2009

Inclusion body myositis (IBM), the most common muscle disease to afflict the elderly, causes slow but progressive degeneration of skeletal muscle and ultimately paralysis. Hallmark pathological features include T-cell mediated inflammatory infiltrates and aberrant accumulations of proteins, including amyloid-β (Aβ), tau, ubiquitinated-proteins, apolipoprotein E, and α-synuclein in skeletal muscle. A large body of work indicates that aberrant Aβ accumulation contributes to the myodegeneration. Here, we investigated whether active immunization to promote clearance of Aβ from affected skeletal muscle fibers mitigates the IBM-like myopathological features as well as motor impairment in a transgenic mouse model. We report that active immunization markedly reduces intracellular Aβ deposits and attenuates the motor impairment compared with untreated mice. Results from our current study indicate that Aβ oligomers contribute to the myopathy process as they were significantly reduced in the affected skeletal muscle from immunized mice. In addition, the anti-Aβ antibodies produced in the immunized mice blocked the toxicity of the Aβ oligomersin vitro, providing a possible key mechanism for the functional recovery. These findings provide support for the hypothesis that Aβ is one of the key pathogenic components in IBM pathology and subsequent skeletal muscle degeneration.
Preserving Information in Neural Transmission
Authors: Sincich Lawrence C. , Horton Jonathan C. , Sharpee Tatyana O.
Published: May 2009

Along most neural pathways, the spike trains transmitted from one neuron to the next are altered. In the process, neurons can either achieve a more efficient stimulus representation, or extract some biologically important stimulus parameter, or succeed at both. We recorded the inputs from single retinal ganglion cells and the outputs from connected lateral geniculate neurons in the macaque to examine how visual signals are relayed from retina to cortex. We found that geniculate neurons re-encoded multiple temporal stimulus features to yield output spikes that carried more information about stimuli than was available in each input spike. The coding transformation of some relay neurons occurred with no decrement in information rate, despite output spike rates that averaged half the input spike rates. This preservation of transmitted information was achieved by the short-term summation of inputs that geniculate neurons require to spike. A reduced model of the retinal and geniculate visual responses, based on two stimulus features and their associated nonlinearities, could account for >85% of the total information available in the spike trains and the preserved information transmission. These results apply to neurons operating on a single time-varying input, suggesting that synaptic temporal integration can alter the temporal receptive field properties to create a more efficient representation of visual signals in the thalamus than the retina.
Activity Level-Dependent Synapse-Specific AMPA Receptor Trafficking Regulates Transmission Kinetics
Authors: Zhu J. Julius
Published: May 2009

Central glutamatergic synapses may express AMPA-sensitive glutamate receptors (AMPA-Rs) with distinct gating properties and exhibit different transmission dynamics, which are important for computing various synaptic inputs received at different populations of synapses. However, how glutamatergic synapses acquire AMPA-Rs with distinct kinetics to influence synaptic integration remains poorly understood. Here I report synapse-specific trafficking of distinct AMPA-Rs in rat cortical layer 4 stellate and layer 5 pyramidal neurons. The analysis indicates that in single layer 4 stellate neurons thalamocortical synapses generate faster synaptic responses than intracortical synapses. Moreover, GluR1-containing AMPA-Rs traffic selectively into intracortical synapses, and this process requires sensory experience-dependent activity and slows down transmission kinetics. GluR4-containing AMPA-Rs traffic more heavily into thalamocortical synapses than intracortical synapses, and this process requires spontaneous synaptic activity and speeds up transmission kinetics. GluR2-containing AMPA-Rs traffic equally into both thalamocortical and intracortical synapses, and this process requires no synaptic activity and resets transmission kinetics. Notably, synaptic trafficking of distinct AMPA-Rs differentially regulates synaptic integration. Thus, synapse-specific AMPA-R trafficking coarsely sets and synaptic activity finely tunes transmission kinetics and integration properties at different synapses in central neurons.
Medial Prefrontal Cortex Activity Is Predictive for Hyperalgesia and Pharmacological Antihyperalgesia
Authors: Seifert Frank , Bschorer Kathrin , De Col Roberto , Filitz Jörg , Peltz Elena , Koppert Wolfgang , Maihöfner Christian
Published: May 2009

Sodium channel blockers are known for reducing pain and hyperalgesia. In the present study we investigated changes in cerebral processing of secondary mechanical hyperalgesia induced by pharmacological modulation with systemic lidocaine. An experimental electrical pain model was used in combination with functional magnetic resonance imaging. After induction of pin-prick hyperalgesia lidocaine or placebo was administered systemically using a double-blinded design. A 2 × 2 factorial analysis was performed. The factors were (1) sensitization to pain (levels: pin-prick hyperalgesia and normal pin-prick pain) and (2) pharmacological modulation (levels: lidocaine and placebo). A main effect of (1) sensitization was found in bilateral secondary somatosensory cortex (S2), insula, anterior cingulate gyrus (ACC), medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex (dlPFC), parietal association cortex (PA), thalamus and contralateral midbrain. A main effect of (2) pharmacological modulation was found in bilateral S2, insula, ACC, mPFC, dlPFC, PA, midbrain and contralateral primary motor cortex, and thalamus. Interaction of pharmacological modulation and sensitization to pin-prick pain with activity increase during hyperalgesia and placebo was found in mPFC, posterior cingulate gyrus and thalamus. However, only activity in mPFC was inversely correlated to area of hyperalgesia during placebo and antihyperalgesic treatment effect. Furthermore, the difference of mPFC activity during hyperalgesia and placebo versus hyperalgesia and lidocaine correlated inversely with the change of the weighted hyperalgesic area (as a factor of area and rated pain intensity). We conclude that activity in mPFC correlates inversely with individual extent of central hyperalgesia and predicts individual pharmacological antihyperalgesic treatment response.
Short-Latency Activation of Striatal Spiny Neurons via Subcortical Visual Pathways
Authors: Schulz Jan M. , Redgrave Peter , Mehring Carsten , Aertsen Ad , Clements Koreen M. , Wickens Jeff R. , Reynolds John N. J.
Published: May 2009

The striatum is a site of integration of neural pathways involved in reinforcement learning. Traditionally, inputs from cerebral cortex are thought to be reinforced by dopaminergic afferents signaling the occurrence of biologically salient sensory events. Here, we detail an alternative route for short-latency sensory-evoked input to the striatum requiring neither dopamine nor the cortex. Using intracellular recording techniques, we measured subthreshold inputs to spiny projection neurons (SPNs) in urethane-anesthetized rats. Contralateral whole-field light flashes evoked weak membrane potential responses in approximately two-thirds of neurons. However, after local disinhibitory injections of the GABAAantagonist bicuculline into the deep layers of the superior colliculus (SC), but not the overlying visual cortex, strong, light-evoked, depolarizations to the up state emerged at short latency (115 ± 14 ms) in all neurons tested. Dopamine depletion using α-methyl-para-tyrosine had no detectable effect on striatal visual responses during SC disinhibition. In contrast, local inhibitory injections of GABA agonists, muscimol and baclofen, into the parafascicular nucleus of the thalamus blocked the early, visual-evoked up-state transitions in SPNs. Comparable muscimol-induced inhibition of the visual cortex failed to suppress the visual responsiveness of SPNs induced by SC disinhibition. Together, these results suggest that short-latency, preattentive visual input can reach the striatum not only via the tecto-nigro-striatal route but also through tecto-thalamo-striatal projections. Thus, after the onset of a biologically significant visual event, closely timed short-latency thalamostriatal (glutamate) and nigrostriatal (dopamine) inputs are likely to converge on striatal SPNs, providing depolarizing and neuromodulator signals necessary for synaptic plasticity mechanisms.
A New Role for FGF2 as an Endogenous Inhibitor of Anxiety
Authors: Perez Javier A. , Clinton Sarah M. , Turner Cortney A. , Watson Stanley J. , Akil Huda
Published: May 2009

Human postmortem studies have demonstrated that fibroblast growth factor-2 (FGF2) expression is decreased in the brain of depressed individuals. It remained unclear, however, whether this is a consequence of the illness or whether FGF2 plays a primary role in the control of mood and emotions. In this series of studies, we first ask whether endogenous FGF2 expression correlates with spontaneous anxiety, a trait associated with vulnerability to severe mood disorders in humans. This is tested in two genetically distinct groups of rats selectively bred to differ dramatically in their response to novelty and anxiety-provoking conditions (HRs = low anxiety/high response to novelty vs LRs = high anxiety/low response to novelty). We demonstrate that high-anxiety LRs have significantly lower levels of hippocampal FGF2 mRNA relative to low-anxiety HRs. We then demonstrate that FGF2 expression is modifiable by environmental factors that alter anxiety—thus, environmental complexity reduces anxiety behavior and induces FGF2 expression in hippocampus, particularly in high-anxiety LRs. Finally, we directly test the role of FGF2 as an anxiolytic and show that a 3 week treatment regimen of peripherally administered FGF2 is highly effective at blunting anxiety behavior, specifically in high-anxiety LRs. This treatment is accompanied by an increase in survival of adult-born hippocampal cells, both neurons and astrocytes, most clearly in LRs. These findings implicate hippocampal FGF2 as a central integrator of genetic and environmental factors that modify anxiety, point to hippocampal neurogenesis and gliogenesis as key in this modulation, and underscore FGF2's potential as a new target for treatment of depression and anxiety disorders.
Identification of BLyS (B Lymphocyte Stimulator), a Non-Myelin-Associated Protein, as a Functional Ligand for Nogo-66 Receptor
Authors: Zhang Lei , Zheng Sushuang , Wu Haitao , Wu Yan , Liu Shuhong , Fan Ming , Zhang Jian
Published: May 2009

B lymphocyte stimulator (BLyS), a tumor necrosis factor family protein essential for B cell development, was previously shown to be expressed at an elevated level in the CNS of multiple sclerosis patients. Although it may be involved in CNS diseases, its exact functions in CNS remain unknown. We hypothesize that BLyS may be a negative regulator for neuronal functions. Here Nogo-66 receptor (NgR) is identified as a high affinity receptor for BLyS, which inhibits dorsal root ganglion outgrowth in culture. The inhibition by BLyS can be reversed by a truncated NgR or by removal of glycosylphosphatidylinositol-linked proteins from neurons. More importantly, the inhibitory effect by BLyS is significantly diminished for neurons isolated from NgR−/−mice. Furthermore, expressions of BLyS and NgR are also found to be associated with astrocytes and macrophages/microglial cells at spinal cord injury sites. Thus, BLyS can function independently of myelin-associated inhibitors and likely serves as a redundant NgR ligand that negatively influences axonal outgrowth in CNS.
Cue-Induced Dopamine Release Predicts Cocaine Preference: Positron Emission Tomography Studies in Freely Moving Rodents
Authors: Schiffer Wynne K. , Liebling Courtney N. B. , Reiszel Corinne , Hooker Jacob M. , Brodie Jonathan D. , Dewey Stephen L.
Published: May 2009

Positron emission tomography studies in drug-addicted patients have shown that exposure to drug-related cues increases striatal dopamine, which displaces binding of the D2ligand, [11C]-raclopride. However, it is not known if animals will also show cue-induced displacement of [11C]-raclopride binding. In this study, we use [11C]-raclopride imaging in awake rodents to capture cue-induced changes in dopamine release associated with the conditioned place preference model of drug craving. Ten animals were conditioned to receive cocaine in a contextually distinct environment from where they received saline. Following conditioning, each animal was tested for preference and then received two separate [11C]-raclopride scans. For each scan, animals were confined to the cocaine and/or the saline-paired environment for the first 25 min of uptake, after which they were anesthetized and scanned. [11C]-raclopride uptake in the saline-paired environment served as a within-animal control for uptake in the cocaine-paired environment. Cocaine produced a significant place preference (p= 0.004) and exposure to the cocaine-paired environment decreased [11C]-raclopride binding relative to the saline-paired environment in both the dorsal (20%;p< 0.002) and ventral striatum (22%;p< 0.05). The change in [11C]-raclopride binding correlated with preference in the ventral striatum (R2= −0.87;p= 0.003). In this region, animals who showed little or no preference exhibited little or no change in [11C]-raclopride binding in the cocaine-paired environment. This noninvasive procedure of monitoring neurochemical events in freely moving, behaving animals advances preclinical molecular imaging by interrogating the degree to which animal models reflect the human condition on multiple dimensions, both biological and behavioral.
Prenatal Cocaine Reduces AMPA Receptor Synaptic Expression through Hyperphosphorylation of the Synaptic Anchoring Protein GRIP
Authors: Bakshi Kalindi , Gennaro Serena , Chan Christopher Y. , Kosciuk Mary , Liu JingJing , Stucky Andres , Trenkner Ekkehart , Friedman Eitan , Nagele Robert G. , Wang Hoau-Yan
Published: May 2009

Prenatal cocaine exposure produces sustained neurobehavioral and brain synaptic changes closely resembling those of animals with defective AMPA receptors (AMPARs). We hypothesized that prenatal cocaine exposure attenuates AMPAR signaling by interfering with AMPAR synaptic targeting. AMPAR function is governed by receptor cycling on and off the synaptic membrane through its interaction with glutamate receptor-interacting protein (GRIP), a PDZ domain protein that is regulated by reversible phosphorylation. Our results show that prenatal cocaine exposure markedly reduces AMPAR synaptic targeting and attenuates AMPAR-mediated synaptic long-term depression in the frontal cortex of 21-d-old rats. This cocaine effect is the result of reduced GRIP–AMPAR interaction caused by persistent phosphorylation of GRIP by protein kinase C (PKC) and Src tyrosine kinase. These data support the restoration of AMPAR activation via suppressing excessive PKC-mediated GRIP phosphorylation as a novel therapeutic approach to treat the neurobehavioral consequences of prenatal cocaine.
Lateral Gain Control in the Outer Retina Leads to Potentiation of Center Responses of Retinal Neurons
Authors: VanLeeuwen Marjelle , Fahrenfort Iris , Sjoerdsma Trijntje , Numan Robert , Kamermans Maarten
Published: May 2009

The retina can function under a variety of adaptation conditions and stimulus paradigms. To adapt to these various conditions, modifications in the phototransduction cascade and at the synaptic and network levels occur. In this paper, we focus on the properties and function of a gain control mechanism in the cone synapse. We show that horizontal cells, in addition to inhibiting cones via a “lateral inhibitory pathway,” also modulate the synaptic gain of the photoreceptor via a “lateral gain control mechanism.” The combination of lateral inhibition and lateral gain control generates a highly efficient transformation. Horizontal cells estimate the mean activity of cones. This mean activity is subtracted from the actual activity of the center cone and amplified by the lateral gain modulation system, ensuring that the deviation of the activity of a cone from the mean activity of the surrounding cones is transmitted to the inner retina with high fidelity. Sustained surround illumination leads to an enhancement of the responses of transient ON/OFF ganglion cells to a flickering center spot. Blocking feedback from horizontal cells not only blocks the lateral gain control mechanism in the outer retina, but it also blocks the surround enhancement in transient ON/OFF ganglion cells. This suggests that the effects of the outer retinal lateral gain control mechanism are visible in the responses of ganglion cells. Functionally speaking, this result illustrates that horizontal cells are not purely inhibitory neurons but have a role in response enhancement as well.
Motor Cortex Bilateral Motor Representation Depends on Subcortical and Interhemispheric Interactions
Authors: Brus-Ramer Marcel , Carmel Jason B. , Martin John H.
Published: May 2009

The corticospinal tract is a predominantly crossed pathway. Nevertheless, the primary motor cortex (M1) is activated bilaterally during unilateral movements and several animal studies showed that M1 has a bilateral motor representation. A better understanding of the uncrossed corticospinal system is especially important for elucidating its role in recovery of limb control after unilateral injury. We used intracortical microstimulation (ICMS) to determine the representation of contralateral and ipsilateral forelimb joints at single M1 sites in the rat. Most sites representing an ipsilateral joint corepresented the same joint contralaterally. We next determined whether ipsilateral responses evoked in one hemisphere depended on the function of M1 in the opposite hemisphere using reversible inactivation and pyramidal tract lesion. Ipsilateral responses were eliminated when the homotopic forelimb area of M1 in the opposite hemisphere was inactivated or when the pyramidal tract on the nonstimulated side was sectioned. To determine the role of transfer between M1 in each hemisphere we sectioned the corpus callosum, which produced a 33% increase in ipsilateral ICMS thresholds. Neither M1 inactivation nor callosal section changed contralateral response thresholds, indicating the absence of tonic excitatory or inhibitory drive to the opposite M1. Finally, ipsilateral responses following M1 inactivation and pyramidal tract lesion could be evoked after systemic administration of the K+channel blocker 4-aminopyridine, suggesting the presence of latent connections. Our findings show important interactions between the corticospinal systems from each side, especially at the spinal level. This has important implications for recruiting the ipsilateral corticospinal system after injury.
ZO-1 and the Spatial Organization of Gap Junctions and Glutamate Receptors in the Outer Plexiform Layer of the Mammalian Retina
Authors: Puller Christian , de Sevilla Müller Luis Pérez , Janssen-Bienhold Ulrike , Haverkamp Silke
Published: May 2009

Information processing in the retina starts at the first synaptic layer, where photoreceptors and second-order neurons exhibit a complex architecture of glutamatergic and electrical synapses. To investigate the composition of this highly organized synaptic network, we determined the spatial relationship of zonula occludens-1 (ZO-1) with different connexins (Cx) and glutamate receptor (GluR) subunits in the outer plexiform layer (OPL) of rabbit, mouse, and monkey retinas. ZO-1 is well known as an intracellular component of tight and adherens junctions, but also interacts with various connexins at gap junctions. We found ZO-1 closely associated with Cx50 on dendrites of A-type horizontal cells in rabbit, and with Cx57 at dendro-dendritic gap junctions of mouse horizontal cells. The spatial arrangement of ZO-1 at the giant gap-junctional plaques in rabbit was particularly striking. ZO-1 formed a clear margin around the large Cx50 plaques instead of being colocalized with the connexin staining. Our finding suggests the involvement of ZO-1 in the composition of tight or adherens junctions around gap-junctional plaques instead of interacting with connexins directly. Furthermore, gap junctions were found to be clustered in close proximity to GluRs at the level of desmosome-like junctions, where horizontal cell dendrites converge before invaginating the cone pedicle. Based on this distinct spatial organization of gap junctions and GluRs, it is tempting to speculate that glutamate released from the photoreceptors may play a role in modulating the conductance of electrical synapses in the OPL.
Validação e reprodutibilidade da Escala de Evaluación de Insatisfación Corporal para Adolescentes
Authors: Conti Maria Aparecida , Slater Betzabeth , Latorre Maria do Rosário Dias de Oliveira
Published: May 2009

OBJETIVO:Validar escala de insatisfação corporal para adolescentes. MÉTODOS: Participaram do estudo 386 adolescentes, de ambos os sexos, entre dez e 17 anos de idade, de uma escola particular de ensino fundamental e médio, de São Bernardo do Campo, SP, em 2006. Foram realizadas tradução e adaptação cultural da "Escala de Evaluación de Insatisfación Corporal para Adolescentes" para o português. Foram avaliadas consistência interna por meio do coeficiente alfa de Cronbach, análise fatorial pelo método Varimax e validade discriminante pelas diferenças entre médias de estado nutricional, utilizando-se o teste de Kruskal-Wallis. Na validação concorrente, calculou-se o coeficiente de correlação de Spearman entre a escala e o índice de massa corporal, a razão circunferência quadril e a circunferência da cintura. Para reprodutibilidade, foram utilizados o teste de Wilcoxon, o coeficiente de correlação intra-classe. RESULTADOS: A escala traduzida não apresentou discordâncias significativas com a original. A escala apresentou consistência interna satisfatória para todos os subgrupos estudados (fases inicial e intermediária de adolescência, ambos os sexos) e foi capaz de discriminar os adolescentes segundo o estado nutricional. Na análise concorrente, as três medidas corporais foram correlacionadas, exceto adolescentes do sexo masculino em fase inicial, e sua reprodutibilidade foi confirmada. CONCLUSÕES: A Escala de Avaliação da Insatisfação Corporal para Adolescentes está traduzida e adaptada para o português e apresentou resultados satisfatórios, sendo recomendada para avaliação do aspecto atitudinal da imagem corporal de adolescentes.
Mother-child transmission of Chagas disease: could coinfection with human immunodeficiency virus increase the risk?
Authors: Scapellato Pablo Gustavo , Bottaro Edgardo Gabriel , Rodríguez-Brieschke María Teresa
Published: May 2009

A study was conducted on all newborns from mothers with Chagas disease who were attended at Hospital Donación F. Santojanni between January 1, 2001, and August 31, 2007. Each child was investigated for the presence of Trypanosoma cruzi parasitemia through direct examination of blood under the microscope using the buffy coat method on three occasions during the first six months of life. Serological tests were then performed. Ninety-four children born to mothers infected with Trypanosoma cruzi were attended over the study period. Three of these children were born to mothers coinfected with the human immunodeficiency virus. Vertical transmission of Chagas disease was diagnosed in 13 children, in all cases by identifying parasitemia. The overall Chagas disease transmission rate was 13.8% (13/94). It was 100% (3/3) among the children born to mothers with HIV infection and 10.9% (10/91) among children born to mothers without HIV [Difference = 0.89; CI95 = 0.82-0.95; p = 0.0021]. We concluded that coinfection with HIV could increase the risk of vertical transmission of Chagas disease.
Clima e epidemias de dengue no Estado do Rio de Janeiro
Authors: Câmara Fernando Portela , Gomes Adriana Fagundes , Santos Gualberto Teixeira dos , Câmara Daniel Cardoso Portela
Published: May 2009

As temperaturas dos primeiros trimestres do período de 1986-2003, especialmente as mínimas, mostraram-se significativamente mais altas nos anos em que as epidemias de dengue tiveram início na Cidade do Rio de Janeiro. Não houve relação significativa com o total das precipitações pluviométricas para os mesmos trimestres, contudo, as epidemias foram mais freqüentes nos anos em que o volume de chuvas no verão foi pequeno (abaixo de 200mm).
Prevalência de Staphylococcus spp resistentes à meticilina isolados em uma maternidade escola da Cidade de Natal, Estado do Rio Grande do Norte
Authors: Sousa Junior Francisco Canindé de , Nunes Éderson William de Figueiredo , Nascimento Ermeton Duarte do , Oliveira Solange Maria de , Melo Maria Celeste Nunes de , Fernandes Maria José de Britto Costa
Published: May 2009

Com o objetivo de determinar a prevalência de Staphylococcus spp resistentes à meticilina isolados na Maternidade Escola Januário Cicco, Natal, RN, no período de 2002 a 2003, analisou-se 1.576 materiais clínicos de pacientes hospitalizados. As amostras foram coletadas, processadas e identificadas conforme procedimento padrão para cada espécime clínico. O perfil de susceptibilidade in vitro foi realizado pelo método de Kirby-Bauer. Isolou-se 188 cepas de Staphylococcus spp, das quais 105 foram identificadas como Staphylococcus aureus e 83 como Staphylococcus coagulase negativos. Staphylococcus aureus foi isolado com mais freqüência em secreções enquanto Staphylococcus coagulase negativos foram mais prevalentes em hemoculturas. A elevada (41,5%) prevalência dos Staphylococcus spp resistentes à meticilina demonstra a necessidade de medidas profiláticas imediatas com o objetivo de impedir a disseminação desse fenômeno.
Aedes aegypti e fauna associada em área rural de Manaus, na Amazônia brasileira
Authors: Barbosa Maria Graças Vale , Fé Nelson Ferreira , Jesus Rossicleide Dias Barbosa de , Rodriguez Iria Cabral , Monteiro Wuelton Marcelo , Mourão Maria Paula Gomes , Guerra Jorge Augusto de Oliveira
Published: May 2009

Após detectar larvas de Aedes aegypti em área rural de Manaus, realizou-se durante dois anos consecutivos um trabalho de notificação da ocorrência dessa espécie naquela área, através da vigilância entomológica, ferramenta que representa um importante papel entre as medidas preventivas contra doenças de transmissão por insetos em particular as arboviroses.