bluuebunny/crossref_metadata_2025 huggingface dataset:
Dazwischen: Medea. Zu einer transgressiven Figur(ation) bei Euripides
Authors: Pister David
Published: April 2018

Medea kills. But why? For her murders, mythological sources provide plenty of explanations: She kills as an abandoned wife, as a vengeful princess, as an insane melancholic person, or as a hurt woman. Yet, these attempts to locate her motivation in a social, political, psychological, or even biological sphere don’t do Medea justice at all. Instead of locating her motivation in one of these categories, I will develop Medea as a transgressive figuration of the in-between, that is: a figuration that cannot be located in one category or the other and I will consider the murders of Euripides’ Medea as a catalyst that is capable of setting this figuration in motion. Whenever Medea kills, she can indeed be located in a category. Yet, as soon as each murder makes the process of localization possible, the figuration of Medea has already moved into another in-between.
Mythologies identitaires et « idéologie (auto)biographique » dans l’écriture mémorielle du post-totalitarisme roumain
Authors: Crihană Alina
Published: April 2018

Having survived an age in which legitimizing political narratives have smothered personal histories, Romanian writers are now increasingly interested in personal memoirs. The identity myths of post-war writing surface in the life stories published after 1989, emerging in a context that favors “the return of the repressed.” The mythology of “resistance via culture” is conditioned by an (auto)biographical ideology. It is latent in the personal writings of the “East-Ethic revisionists” and manifest in publications that advocate political dissidence via the aesthetic. The resultant myth-laden histories perform a therapeutic function in the authors’ profound inner identity reconstruction and a restorative function concerning their public image.
„Much book, little know“ – Enzyklopädie als Lederstrumpf
Authors: Richter Jörg Thomas
Published: April 2018

Though James Fenimore Cooper’s five Leatherstocking-Tales (1823–1841) seem unlikely candidates for an encyclopaedic poetics, they encompass frontier life in an extensive scope, integrating a wide range of sources as well as using immense descriptive detail that often enough overgrows their plot. Even more to the point is the often voiced scepticism towards academic knowledge. By taking the tales as a test case for the ‘encyclopaedic novel‘, I explore how encyclopaedic reference shifts in the genesis of these five novels. In addition, a survey of contemporary publishing shows a similar fluidity in the various bearings that encyclopaedic forms could take on at the time. Given the double flexibility of the status and formation of encyclopaedic knowledge, both in the Leatherstocking tales and in contemporary discourse, the article suggests a less strict, more profane and popularly grounded, as well as more historically relative notion of what constitutes an encyclopaedic narrative. As to the Leatherstocking tales, I suggest that they occupy an epistemic space that was then only recently given up by academic encyclopaedic thought, and that they do so by claiming an encyclopaedic function of their own.
From Staged to Disguised Self-Translation: Heine and Celan in France
Authors: Weissmann Dirk
Published: April 2018

Heinrich Heine and Paul Celan have often been compared, mainly because of their shared Parisian exile and Jewish identity. Yet we should add another dimension to this comparison, by examining the authors’ relationship to the French versions of their texts. In fact, although Heine and Celan have always considered themselves as German-speaking writers, their perfect bilingualism and active participation in French literary circles made it possible for them to exert an early and considerable influence upon their own reception in France. This particularly affected the translation of their works, which were intensely managed and controlled by both poets. However, their influence took very different forms: Heine alleged to be the author of the French version of his writings, hiding the work of the translator, whereas Celan never wanted to appear as a self-translator, even if he played a key role in the development of the French translations of his works. Thus Heine’s French works appear to be staged self-translations, produced mostly by French translators, while many of the French translations of Celan are actually very close to disguised self-translation. In both cases the original connection between the author and his text is upheld and the movement of estrangement and disappropriation, inherent in translation, is impeded or even stopped.
Von dem Trauma des anderen und der Sehnsucht nach Behausung in Lutz Seilers Roman Kruso (2014)
Authors: Wennerscheid Sophie
Published: April 2018

Drawing on Sara Ahmed’s concept of the ‘body not at home’ on the one hand and on the concept of the disturbing ‘foreign body’ (Fremdkörper) as deployed in various trauma studies on the other, this article explores how the traumatized body is to be understood as a disoriented and unstable body. Trauma, however, is not only something that leaves one restless. It also connects one with the trauma of another and leads to mutual understanding. Having been affected by the wound of another, a certain kind of communication among the wounded emerges, which makes traumatic memory accessible. How such an affective impact may look can be shown by examining Lutz Seiler’s award-winning novel Kruso (2014). Set on the isle of Hiddensee shortly before the fall of the Berlin Wall in 1989, Seiler tells the story of two men, Kruso and Ed, both traumatized by the loss of a loved one. As both are East German castaways and equally affected by their loss, they develop an intimate relationship, one not void of suppressed desire, mistrust, and aggression. Only years after Kruso’s death is Ed able to come to terms with the past and find a place for burying the vanished dead.
Development of conditional imperatives in Japanese: A diachronic constructional approach
Authors: Kikuta Chiharu Uda
Published: April 2018

This paper proposes a diachronic construction grammar analysis of the conditional imperative in Japanese to demonstrate that a constructional approach provides an effective model for language change. The Japanese conditional imperative comprises two types with distinct properties, but no study to date has successfully analyzed how the two types appeared and are related to each other. In diachronic construction grammar, language change is situated in the context of a construction as well as in relation to other constructions linked in a network. This perspective makes it a particularly beneficial model for accommodating the case in question. The construction developed in two steps, exemplifying different types of language change, both of which, however, are motivated by analogy between different constructions. Adopting the multiple inheritance analysis, I contend that the construction first emerged as a result of the reanalysis of a sequence of an imperative sentence and a subsequent sentence as a type of the conditional construction. A later development reflected another case of construction-based analogy: the daughter construction inherited the host-class expansion that occurred in the parent, and the new type emerged as a result of coercion to accommodate the expansion. Thus the development of the Japanese conditional imperative not only finds a consistent analysis in this framework, but provides valuable insight into the workings of the construction network. This paper also addresses the issues of the inheritance model, and suggests the present case argues for a model with default inheritance at the construction level, which runs counter to previous studies which have restricted the overrides of default inheritance to the level of construct.
La nécessité des traductions. Translating legislation in a young parliamentary regime. The case of Belgium (1830–1895)
Authors: Nouws Bieke , Meylaerts Reine
Published: April 2018

In order to better understand the features and purposes of translation in multilingual states, this study looks at nineteenth-century translation policies in Belgium, a young state (founded in 1830) with liberal ambitions and a multilingual population. More specifically, it deals with the parliamentary debates on the translation into Flemish of the Bulletin des Arrêtés, Bulletin Officiel and Moniteur belge, the consecutive official journals for the publication of new legislation. Until now, language history and language policy researchers have paid too little attention to the key role played by translation and the many aspects of translation policies to consider (such as spelling, timing, translators … ), matters that go to the heart of identity issues in politics and that, consequently, aroused great emotion in some Members of Parliament (MPs).
Language, translation and interpreting policies in prisons: Protecting the rights of speakers of non-official languages
Authors: Martínez-Gómez Aída
Published: April 2018

Despite the human rights principle of no discrimination, the growing numbers of imprisoned linguistic minorities around the world face multiple inequalities related to communication barriers: from cultural and social isolation to lack of equal access to facilities and services. This international survey of prison language policies shows that, in general terms, the protection of prisoners’ language rights responds to non-binding international provisions and scarce broadly-defined national ones. At the individual level, however, prison systems can be grouped according to two distinctive factors: (a) the comprehensiveness of their prison language policies, and (b) the type of policy instruments used to provide for language issues. This article describes the content and extent of language, translation and interpreting policies in forty prison systems around the world, placing a final focus on California and England and Wales, which emerge as examples of good practice that could potentially inspire other systems.
Psychological deictic–te kurucompared to passive: The case of victims’ stories in Japanese
Authors: Minagawa Harumi
Published: April 2018

Japanese is often said to be stronger than English in construing an event and reporting it from the subjective position. While the auxiliary verb–te kuru‘COME’ is one of the deictic devices that reports an event from a subjective perspective, very limited attention has been given to the use of–te kuruwhen it denotes ‘psychological deixis’ (Sawada 2000). Using on-line postings of sexual harassment victims, this study examines how the psychological–te kuruexpresses the victims’ experience subjectively particularly in comparison with the much-studied passive structure. While showing that the two syntactic structures would often be interchangeable in the data, the study reveals that when the victim feels powerless and subdued by the offender’s act upon her/him, only the passive is used, while if the victim has a sufficient sense of power to feel anger,–te kurutends to be used. The study argues that the semantic traits of the passive [associated with the perfective aspect] and–te kuru[which is interpreted as ‘psychological inchoative’ in this study] are reflected in the choices made in the victims’ narratives.
On the grammaticalization of Japanese verbal negative marker
Authors: Kishimoto Hideki
Published: April 2018

In Japanese, the verbal negative markernaiappears in both negated verbs (as a sentential negator) and compound negative adjectives (as an affix). Negativenaiused as a sentential negator is a syntactically independent word devoid of adjectival properties despite its adjectival inflection, whereas negativenaiappearing in negative adjectives is a derivational affix. On the basis of idiomatic expressions, the present article argues that the lexical wordnai‘null, empty’ has developed into the affixnaiwhile retaining its lexical properties via morphologization. On the other hand, the functional negatornaiis argued to have emerged from the same lexical wordnaivia decategorialization, which induces a shift from a lexical to a functional category. The analysis taking the two uses ofnaito trace back to the common source of the lexical negative adjective wordnaiprovides a natural account for whynaihas these two totally different uses.
Glycated hemoglobin A1c as a screening test for detecting type 2 diabetes mellitus in obese children and adolescents
Authors: Yoon Jong Seo , So Cheol Hwan , Lee Hae Sang , Hwang Jin Soon
Published: April 2018

Background:

The diagnostic cutoff points for indicators of type 2 diabetes mellitus (T2DM) in the pediatric population have not been defined thus far.

Methods:

A retrospective, single-center study was conducted from April 2003 to May 2016. We enrolled 236 overweight or obese children and adolescents aged 4–17 years. Thirty-nine (26.9%) of 145 patients had T2DM according to the oral glucose tolerance test results.

Results:

A glycated hemoglobin (HbA1c) level of 6.5% had a sensitivity and specificity of 87.2% and 98.5%, respectively, for detecting T2DM. The optimal HbA1c cutoff level for T2DM was >6.2% (94.7% sensitivity, 95.5% specificity).

Conclusions:

We observed that the use of an HbA1c level of 6.5% had a lower sensitivity for detecting T2DM than an HbA1c level of >6.2%.
Still too little, too late? Ten years of growth hormone therapy baseline data from the NordiNet® International Outcome Study
Authors: Polak Michel , Konrad Daniel , Tønnes Pedersen Birgitte , Puras Gediminas , Šnajderová Marta
Published: April 2018

Background:

We investigated time trends in age, gender, growth hormone (GH) dose and height standard deviation score (SDS) in children with GH deficiency (GHD), born small for gestational age (SGA) or with Turner syndrome (TS) starting GH treatment.

Methods:

Data were obtained from children enrolled in the NordiNet® International Outcome Study (IOS) between 2006 and 2015 in the Czech Republic, France, Germany, Serbia and Montenegro (all indications), and Switzerland and the UK (GHD only). Trends were analyzed by linear regression. Patients were divided by age into early-, medium- or late-start groups in three different time periods.

Results:

Approximately one-third of children starting treatment for GHD were girls, with no apparent increase in proportion over time. The mean baseline age for starting treatment decreased significantly (p<0.001) for both GHD and SGA in the Czech Republic and Germany. In the other countries studied, over 40% of children started treatment for GHD and SGA late (girls >10, boys >11 years) between 2013 and 2015. The mean baseline GH doses were largely within recommended ranges for GHD and SGA, but below the lowest recommended starting dose for TS in almost every year since 2011 except in France.

Conclusions:

Approximately one-third of children starting treatment for GHD were girls. Between 2013 and 2015, more than 40% of children started treatment for GHD and SGA late except in Germany and the Czech Republic. TS patients received below-recommended doses. These results highlight the need for earlier identification of short stature in children, particularly girls, and for dose optimization in TS.
Crystal structure of acetonitrile{bis(2-benzimidazolylmethyl)amine-κ3
N,N′,N′′}-{maleato-κO}zinc(II) perchlorate - acetonitrile (1/1), C24H24ClN7O8Zn
Authors: Chen Jiang-Li , Wang Chen , Su Guo-Hua , Nie Feng-Mei
Published: April 2018

C24H24ClN7O8Zn, triclinic, P1̅ (no. 2), a = 10.0834(7) Å, b = 10.8269(7) Å, c = 13.1958(8) Å, α = 77.658(5)°, β = 77.135(5)°, γ = 87.797(5)°, V = 1371.93(15) Å3, Z = 2, R
gt(F) = 0.0410, wR
ref(F
2) = 0.1015, T = 105.6 K.
A new disodium hafnium borate Na2Hf(BO3)2: synthesis, crystal structure, DFT calculations and luminescent properties
Authors: Shi Jian-Chao , Zhao Dan , Ma Zhao , Zhang Rui-Juan , Xue Ya-Li , Liu Bao-Zhong
Published: April 2018

A ternary borate Na2Hf(BO3)2 has been prepared using a high temperature molten salt method and structurally determined by single crystal X-ray diffraction analysis. It crystallizes in dolomite-type structure with trigonal space group R3̅, and features a layer structure containing [Hf(BO3)2] layers and Na atom layers perpendicular to the c-axis. Band structure calculation using the density functional theory (DFT) method indicates that Na2Hf(BO3)2 has an indirect bond gap of about 4.76 eV. The photoluminescence excitation and emission spectra, decay curve, and the color coordinates of Na2Hf(BO3)2 were investigated. The results show that it can be efficiently excited by UV light (302 nm) and presents blue-green emission (centred at 480 nm), which may be attributed to the lattice defect emission.
Coupled Plasmon Resonances and Gap Modes in Laterally Assembled Gold Nanorod Arrays
Authors: Kumar Jatish , Wei Xingzhan , Barrow Steven J. , Funston Alison M. , Thomas K. George , Mulvaney Paul
Published: April 2018

The assembly of metal nanocrystals offers a flexible method for creating new materials with tunable, size-dependent optical properties. Here we study the lateral assembly of gold nanorods into arrays, which leads to strong colour changes due to surface plasmon coupling. We also demonstrate the first example of gap modes in colloid systems, an optical mode in which light waves propagate in the channels between the gold rods. Such modes resonate at wavelengths which strongly depend on the gap width and length.
Subcellular Localization of Full-Length and Truncated Trk Receptor Isoforms in Polarized Neurons and Epithelial Cells
Authors: Kryl David , Yacoubian Talene , Haapasalo Annakaisa , Castren Eero , Lo Donald , Barker Philip A.
Published: April 2018

Neurotrophins affect neuronal development and plasticity via spatially localized effects, yet little is known about the subcellular distribution of the Trk neurotrophin receptors and the impact of this distribution on neurotrophin action. To address this, we examined the subcellular location of full-length TrkB and TrkC tyrosine kinase receptors and truncated TrkB isoforms after transfection of Madin–Darby canine kidney (MDCK) cells, dissociated primary hippocampal neurons, and cortical neurons within intact brain slices. Myc-, herpes virus glycoprotein (HVG)-, or FLAG-derived epitope–tagged receptor isoforms were created to allow their unambiguous identification and localization after transfection. All tagged receptors were appropriately synthesized, and full-length myc-TrkB and myc-TrkC mediated appropriate neurotrophin-signaling events. We found that full-length TrkB receptors were excluded from the apical domain of MDCK cells but that TrkC receptors were present in both apical and basolateral domains. Full-length TrkB and TrkC were found throughout transfected primary cultured hippocampal neurons and transfected neurons in neocortical brain slices and showed no evidence of vectorial sorting. Truncated forms of TrkB were also homogeneously distributed in MDCK cells, dissociated hippocampal neurons, and cortical neurons within slice preparations. Levels of full-length and truncated TrkB were examined in postsynaptic densities; both receptor isoforms were present but only moderately enriched in these structures. Together, these findings suggest that Trk receptors are uniformly distributed in both axonal and dendritic compartments and that local neurotrophin responses are controlled by other mechanisms.
Rabphilin Knock-Out Mice Reveal That Rabphilin Is Not Required for Rab3 Function in Regulating Neurotransmitter Release
Authors: Schlüter Oliver M. , Schnell Eric , Verhage Matthijs , Tzonopoulos Thanos , Nicoll Roger A. , Janz Roger , Malenka Robert C. , Geppert Martin , Südhof Thomas C.
Published: April 2018

Rab3A and rab3C are GTP-binding proteins of synaptic vesicles that regulate vesicle exocytosis. Rabphilin is a candidate rab3 effector at the synapse because it binds to rab3s in a GTP-dependent manner, it is co-localized with rab3s on synaptic vesicles, and it dissociates with rab3s from the vesicles during exocytosis. Rabphilin contains two C2domains, which could function as Ca2+sensors in exocytosis and is phosphorylated as a function of stimulation. However, it is unknown what essential function, if any, rabphilin performs. One controversial question regards the respective roles of rab3s and rabphilin in localizing each other to synaptic vesicles: although rabphilin is mislocalized in rab3A knock-out mice, purified synaptic vesicles were shown to require rabphilin for binding of rab3A but not rab3A for binding of rabphilin. To test whether rabphilin is involved in localizing rab3s to synaptic vesicles and to explore the functions of rabphilin in regulating exocytosis, we have now analyzed knock-out mice for rabphilin. Mice that lack rabphilin are viable and fertile without obvious physiological impairments. In rabphilin-deficient mice, rab3A is targeted to synaptic vesicles normally, whereas in rab3A-deficient mice, rabphilin transport to synapses is impaired. These results show that rabphilin binds to vesicles via rab3s, consistent with an effector function of rabphilin for a synaptic rab3-signal. Surprisingly, however, no abnormalities in synaptic transmission or plasticity were observed in rabphilin-deficient mice; synaptic properties that are impaired in rab3A knock-out mice were unchanged in rabphilin knock-out mice. Our data thus demonstrate that rabphilin is endowed with the properties of a rab3 effector but is not essential for the regulatory functions of rab3 in synaptic transmission.
The Stoned Proteins Regulate Synaptic Vesicle Recycling in the Presynaptic Terminal
Authors: Fergestad Tim , Davis Warren S. , Broadie Kendal
Published: April 2018

TheDrosophila stonedlocus was identified 25 years ago on the basis of stress-sensitive behavioral mutants (Grigliatti et al., 1973). The locus is dicistronic and encodes two distinct proteins, stoned A and stoned B, which are expressed specifically in presynaptic terminals at central and peripheral synapses. Severalstonedmutant alleles cause embryonic lethality, suggesting that these proteins are essential for synaptic function. Physiological analyses at thestonedsynapse reveal severe neurotransmission defects, including reduced and asynchronous neurotransmitter release and rapid fatigue after repetitive stimulation. At the EM level,stonedsynapses show a depletion of synaptic vesicles and a concomitant increase in membrane-recycling intermediates. Mutant terminals also display a specific mislocalization of the synaptic vesicle protein synaptotagmin. These results suggest that the stoned proteins are essential for the recycling of synaptic vesicle membrane and are required for the proper sorting of synaptotagmin during endocytosis.
Overexpression of Brain-Derived Neurotrophic Factor Enhances Sensory Innervation and Selectively Increases Neuron Number
Authors: LeMaster Ann M. , Krimm Robin F. , Davis Brian M. , Noel Teresa , Forbes Mary E. , Johnson James E. , Albers Kathryn M.
Published: April 2018

Target-derived neurotrophin growth factors have significant effects on the development and maintenance of the mammalian somatosensory system. Studies of transgenic mice that overexpress neurotrophins NGF and neurotrophin 3 (NT-3) at high levels in skin have shown increased sensory neuron number and enhanced innervation of specific sensory ending types. The effects of two other members of this family, BDNF and NT-4, on sensory neuron development are less clear. This study examined the role of brain-derived neurotrophic factor (BDNF) using transgenic mice that overexpress BDNF in epithelial target tissues of sensory neurons. BDNF transgenic mice had an increase in peripheral innervation density and showed selective effects on neuron survival. Neuron number in trigeminal ganglia, DRG, and SCG were unchanged, although a 38% increase in neurons comprising the placode-derived nodose–petrosal complex occurred. BDNF transgenic skin showed notable enhancement of innervation to hair follicles as detected by PGP9.5 immunolabeling. In nonhairy plantar skin, Meissner corpuscle sensory endings were larger, and the number of Merkel cells with associated innervation was increased. In trigeminal ganglia, neurons expressing trkB receptor were increased threefold, whereas trkA-positive neurons doubled. Analysis of trkB by Northern, reverse transcription-PCR, and Western assays indicated a modest increase in the expression of the T1 truncated receptor and preferential distribution to the periphery. These data indicate that skin-derived BDNF does not enhance survival of cutaneous sensory neurons, although it does promote neurite innervation of specific sites and sensory end organs of the skin.
Stimulation of Neonatal and Adult Brain Neurogenesis by Subcutaneous Injection of Basic Fibroblast Growth Factor
Authors: Wagner Joseph P. , Black Ira B. , DiCicco-Bloom Emanuel
Published: April 2018

Mounting evidence indicates that extracellular factors exert proliferative effects on neurogenetic precursorsin vivo. Recently we found that systemic levels of basic fibroblast growth factor (bFGF) regulate neurogenesis in the brain of newborn rats, with factors apparently crossing the blood–brain barrier (BBB) to stimulate mitosis. To determine whether peripheral bFGF affects proliferation during adulthood, we focused on regions in which neurogenesis persists into maturity, the hippocampus and the forebrain subventricular zone (SVZ). In postnatal day 1 (P1) rats, 8 hr after subcutaneous injection (5 ng/gm body weight), bFGF increased [3H]thymidine incorporation 70% in hippocampal and SVZ homogenates and elicited twofold increases in mitotic nuclei in the dentate gyrus and the dorsolateral SVZ, detected by bromodeoxyuridine immunohistochemistry. Because ∼25% of proliferating hippocampal cells stimulatedin vivoexpressed neuronal traits in culture, bFGF-induced mitosis may reflect increased neurogenesis. bFGF effects were not restricted to the perinatal period; hippocampal DNA synthesis was stimulated by peripheral factor in older animals (P7–P21), indicating the persistence of bFGF-responsive cells and activity of peripheral bFGF into late development. To begin defining underlying mechanisms, pharmacokinetic studies were performed in P28 rats; bFGF transferred from plasma to CSF rapidly, levels rising in both compartments in parallel, indicating that peripheral factor crosses the BBB during maturity. Consequently, we tested bFGF in adults; peripheral bFGF increased the number of mitotic nuclei threefold in the SVZ and olfactory tract, regions exhibiting persistent neurogenesis. Our observations suggest that bFGF regulates ongoing neurogenesis via a unique, endocrine-like pathway, potentially coordinating neuron number and body growth, and potentially providing new approaches for treating damaged brain during development and adulthood.
Migration Defects ofcdk5−/−Neurons in the Developing Cerebellum is Cell Autonomous
Authors: Ohshima Toshio , Gilmore Edward C. , Longenecker Glenn , Jacobowitz David M. , Brady Roscoe O. , Herrup Karl , Kulkarni Ashok B.
Published: April 2018

Cyclin-dependent kinase 5 (Cdk5) is a member of the family of cell cycle-related kinases. Previous neuropathological analysis ofcdk5−/−mice showed significant changes in CNS development in regions from cerebral cortex to brainstem. Among the defects in these animals, a disruption of the normal pattern of cell migrations in cerebellum was particularly apparent, including a pronounced abnormality in the location of cerebellar Purkinje cells. Complete analysis of this brain region is hampered in the mutant because most of cerebellar morphogenesis occurs after birth and thecdk5−/−mice die in the perinatal period. To overcome this disadvantage, we have generated chimeric mice by injection ofcdk5−/−embryonic stem cells into host blastocysts. Analysis of the cerebellum from the resultingcdk5−/−↔cdk5+/+chimeric mice shows that the abnormal location of the mutant Purkinje cells is a cell-autonomous defect. In addition, significant numbers of granule cells remain located in the molecular layer, suggesting a failure to complete migration from the external to the internal granule cell layer. In contrast to the Purkinje and granule cell populations, all three of the deep cerebellar nuclear cell groupings form correctly and are composed of cells of both mutant and wild-type genotypes. Despite similarities of thecdk5−/−phenotype to that reported inreelerandmdab-1−/−(scrambler/yotari) mutant brains,reelinanddisabled-1mRNA were found to be normal incdk5−/−brain. Together, the data further support the hypothesis that Cdk5 activity is required for specific components of neuronal migration that are differentially required by different neuronal cell types and by even a single neuronal cell type at different developmental stages.
Effects of the Sodium Channel Blocker Tetrodotoxin on Acute White Matter Pathology After Experimental Contusive Spinal Cord Injury
Authors: Rosenberg Lisa J. , Teng Yang D. , Wrathall Jean R.
Published: April 2018

Focal microinjection of tetrodotoxin (TTX), a potent voltage-gated sodium channel blocker, reduces neurological deficits and tissue loss after spinal cord injury (SCI). Significant sparing of white matter (WM) is seen at 8 weeks after injury and is correlated to a reduction in functional deficits. To determine whether TTX exerts an acute effect on WM pathology, Sprague Dawley rats were subjected to a standardized weight-drop contusion at T8 (10 gm × 2.5 cm). TTX (0.15 nmol) or vehicle solution was injected into the injury site 5 or 15 min later. At 4 and 24 hr, ventromedial WM from the injury epicenter was compared by light and electron microscopy and immunohistochemistry. By 4 hr after SCI, axonal counts revealed reduced numbers of axons and significant loss of large (≥5 μm)-diameter axons. TTX treatment significantly reduced the loss of large-diameter axons. In addition, TTX significantly attenuated axoplasmic pathology at both 4 and 24 hr after injury. In particular, the development of extensive periaxonal spaces in the large-diameter axons was reduced with TTX treatment. In contrast, there was no significant effect of TTX on the loss of WM glia after SCI. Thus, the long-term effects of TTX in reducing WM loss after spinal cord injury appear to be caused by the reduction of acute axonal pathology. These results support the hypothesis that TTX-sensitive sodium channels at axonal nodes of Ranvier play a significant role in the secondary injury of WM after SCI.
Cellular and Molecular Mechanisms of Glial Scarring and Progressive Cavitation:In VivoandIn VitroAnalysis of Inflammation-Induced Secondary Injury after CNS Trauma
Authors: Fitch Michael T. , Doller Catherine , Combs Colin K. , Landreth Gary E. , Silver Jerry
Published: April 2018

Post-traumatic cystic cavitation, in which the size and severity of a CNS injury progress from a small area of direct trauma to a greatly enlarged secondary injury surrounded by glial scar tissue, is a poorly understood complication of damage to the brain and spinal cord. Using minimally invasive techniques to avoid primary physical injury, this study demonstratesin vivothat inflammatory processes alone initiate a cascade of secondary tissue damage, progressive cavitation, and glial scarring in the CNS. Anin vitromodel allowed us to test the hypothesis that specific molecules that stimulate macrophage inflammatory activation are an important step in initiating secondary neuropathology. Time-lapse video analyses of inflammation-induced cavitation in ourin vitromodel revealed that this process occurs primarily via a previously undescribed cellular mechanism involving dramatic astrocyte morphological changes and rapid migration. The physical process of cavitation leads to astrocyte abandonment of neuronal processes, neurite stretching, and secondary injury. The macrophage mannose receptor and the complement receptor type 3 β2-integrin are implicated in the cascade that induces cavity and scar formation. We also demonstrate that anti-inflammatory agents modulating transcription via the nuclear hormone receptor peroxisome proliferator–activated receptor-γ may be therapeutic in preventing progressive cavitation by limiting inflammation and subsequent secondary damage after CNS injury.
Stability and Secretion of Acetylcholinesterase Forms in Skeletal Muscle Cells
Authors: Legay Claire , Mankal Fawzi A. , Massoulié Jean , Jasmin Bernard J.
Published: April 2018

Muscle cells express a distinct splice variant of acetylcholinesterase (AChET), but the specific mechanisms governing this restricted expression remain unclear. In these cells, a fraction of AChE subunits is associated with a triple helical collagen, ColQ, each strand of which can recruit a tetramer of AChET. In the present study, we examined the expression of the various splice variants of AChE by transfection in the mouse C2C12 myogenic cellsin vitro,as well asin vivoby injecting plasmid DNA directly into tibialis anterior muscles of mice and rats. Surprisingly, we found that transfection with an ACHEHcDNA, generating a glycophosphatidylinositol-anchored enzyme species, produced much more activity than transfection with AChETcDNA in both C2C12 cells andin vivo. This indicates that the exclusive expression of AChETin mature muscle is governed by specific splicing. Interaction of AChETsubunits with the complete collagen tail ColQ increased enzyme activity in cultured cells, as well as in muscle fibersin vivo. Truncated ColQ subunits, presenting more or less extensive C-terminal deletions, also increased AChE activity and secretion in C2C12 cells, although the triple helix could not form in the case of the larger deletion. This suggests that heteromeric associations are stabilized compared with isolated AChETsubunits. Coinjections of AChETand ColQ resulted in the production and secretion of asymmetric forms, indicating that assembly, processing, and externalization of these molecules can occur outside the junctional region of muscle fibers and hence does not require the specialized junctional Golgi apparatus.
The Inwardly Rectifying K+Channel Subunit GIRK1 Rescues the GIRK2weaverPhenotype
Authors: Hou Ping , Yan Shuizhong , Tang Weijen , Nelson Deborah J.
Published: April 2018

Theweaver(wv) gene has been identified as a glycine to serine substitution at residue 156 in the H5 region of inwardly rectifying K+channel, GIRK2. The mutation is permissive for the expression of homotetrameric channels that are nonselective for cations and G-protein-independent. Coexpression of GIRK2wvwith GIRK1, GIRK2, or GIRK3 inXenopusoocytes along with expression of subunit combinations linked as dimers and tetramers was used to investigate the effects of the pore mutation on channel selectivity and gating as a function of relative subunit position and number within a heterotetrameric complex. GIRK1 formed functional, K+selective channels with GIRK2 and GIRK3. Coexpression of GIRK2wvwith GIRK1 gave rise to a component of K+-selective, G-protein-dependent current. Currents resulting from coexpression of GIRK2wvwith GIRK2 or GIRK3 wereweaver-like. Current from dimers of GIRK1-GIRK2wv, GIRK2-GIRK2wv, and GIRK3-GIRK2wvwas phenotypically similar to that obtained from coexpression of monomers. Linked tetramers containing GIRK1 and GIRK2wvin an alternating array gave rise to wild-type, K+-selective currents. When two mutant subunits were arranged adjacently in a tetramer, currents wereweaver-like. These results support the hypothesis that in specific channel stoichiometries, GIRK1 rescues theweaverphenotype and suggests a basis for the selective neuronal vulnerability that is observed in theweavermouse.
White Matter of the CNS Supports or Inhibits Neurite OutgrowthIn VitroDepending on Geometry
Authors: Pettigrew David B. , Crutcher Keith A.
Published: April 2018

Axonal regeneration is normally limited within myelinated fiber tracts in the CNS of higher vertebrates. Numerous studies suggest that CNS myelin contains inhibitors that may contribute to abortive axonal growth. In contrast to the evidence of myelin-associated neurite inhibitors, embryonic neurons transplanted into the CNS can regenerate extensively within myelinated tractsin vivo. It has been speculated that embryonic neurons do not yet express the appropriate receptors for myelin-associated inhibitors. Recently, however, extensive regeneration from transplanted adult neurons has also been reported within myelinated tracts of the CNS, casting doubt on the role myelin-associated inhibitors play in abortive regeneration. The present study reexamined the potential of white matter to support neurite growthin vitro. By the use of Neurobasal medium, neurons were cultured onto unfixed cryostat sections of mature rat CNS tissue. As documented previously, robust neuronal attachment and neurite outgrowth occurred on gray matter but these neurites were sharply inhibited by white matter. In addition, however, increased rates of neuronal attachment directly to white matter occurred with neurite outgrowth comparable in length with that on gray matter but limited to directions parallel to the fiber tract. Frequently, the same section of white matter was found to inhibit neurite outgrowth from neurons on gray matter while supporting parallel neurite outgrowth from neurons on white matter. These results suggest that whether white matter supports or inhibits axonal growth depends on the geometric relationship between the axon and the fiber tract; more specifically, white matter supports parallel growth but inhibits nonparallel growth.
An Empirical Explanation of the Cornsweet Effect
Authors: Purves Dale , Shimpi Amita , Lotto R. Beau
Published: April 2018

A long-standing puzzle in vision is the assignment of illusory brightness values to visual territories based on the characteristics of their edges (the Craik–O’Brien–Cornsweet effect). Here we show that the perception of the equiluminant territories flanking the Cornsweet edge varies according to whether these regions are more likely to be similarly illuminated surfaces having the same material properties or unequally illuminated surfaces with different properties. Thus, if the likelihood is increased that these territories are surfaces with similar reflectance properties under the same illuminant, the Craik–O’Brien–Cornsweet effect is diminished; conversely, if the likelihood is increased that the adjoining territories are differently reflective surfaces receiving different amounts of illumination, the effect is enhanced. These findings indicate that the Craik–O’Brien–Cornsweet effect is determined by the relative probabilities of the possible sources of the luminance profiles in the stimulus.
High Corticosterone Levels in Prenatally Stressed Rats Predict Persistent Paradoxical Sleep Alterations
Authors: Dugovic C. , Maccari S. , Weibel L. , Turek F. W. , Van Reeth and O.
Published: April 2018

Prenatal stress predisposes rats to long-lasting disturbances that persist throughout adulthood (e.g., high anxiety, dysfunction of the hypothalamo–pituitary–adrenal axis, and abnormal circadian timing). These disturbances parallel to a large extent those found in depressed patients, in which hypercortisolemia and sleep alterations may be related to stress-inducing events. We studied sleep–wake parameters in control and prenatally stressed adult rats (3–4 months old) and examined possible relationships with their corticosterone levels (determined at 2 months of age). Under baseline conditions, prenatally stressed rats showed increased amounts of paradoxical sleep, positively correlated to plasma corticosterone levels. Other changes include increased sleep fragmentation, total light slow-wave sleep time, and a slight decrease in the percentage of deep slow-wave sleep relative to total sleep time. During recovery sleep from acute restraint stress, all sleep changes persisted and were correlated with stress-induced corticosterone secretion. High corticosterone levels under baseline conditions as well as an acute stress challenge may thus predict long-term sleep–wake alterations in rats. Taken together with other behavioral and hormonal abnormalities in prenatally stressed animals, the pronounced changes in sleep–wake parameters that are similar to those found in depressed patients suggest that prenatal stress may be a useful animal model of depression.
Conductive Hearing Loss Produces a Reversible Binaural Hearing Impairment
Authors: Moore David R. , Hine Jemma E. , Jiang Ze Dong , Matsuda Hiroaki , Parsons Carl H. , King Andrew J.
Published: April 2018

Conductive hearing loss, produced by otitis media with effusion, is widespread in young children. However, little is known about its short- or long-term effects on hearing or the brain. To study the consequences of a conductive loss for the perception and processing of sounds, we plugged the left ear canal of ferrets for 7–15 months during either infancy or adulthood. Before or during plugging, the ferrets were trained to perform a binaural task requiring the detection of a 500 Hz tone, positioned 90° to the right, that was masked by two sources of broad-band noise. In one condition (“control”), both noise sources were 90° right and, in the second condition (“bilateral”), one noise source was moved to 90° left. Normal ferrets showed binaural unmasking: tone detection thresholds were lower (mean 10.1 dB) for the bilateral condition than for the control condition. Both groups of ear-plugged ferrets had reduced unmasking; the mean residual unmasking was 2.3 dB for the infant and 0.7 dB for the adult ear-plugged animals. After unplugging, unmasking increased in both groups (infant, 7.1 dB; adult, 6.9 dB) but not to normal levels. Repeated testing during the 22 months after unplugging revealed a gradual return to normal levels of unmasking. These results show that a unilateral conductive hearing loss, in either infancy or adulthood, impairs binaural hearing both during and after the hearing loss. They show scant evidence for adaptation to the plug and demonstrate a recovery from the impairment that occurs over a period of several months after restoration of normal peripheral function.
A Role for Voltage-Gated Potassium Channels in the Outgrowth of Retinal Axons in the Developing Visual System
Authors: McFarlane Sarah , Pollock Natashka S.
Published: April 2018

Neural activity is important for establishing proper connectivity in the developing visual system. Tetrodotoxin blockade of sodium (Na+)-dependent action potentials impairs the refining of synaptic connections made by developing retinal ganglion cells (RGCs), but does not affect their ability to get out to their target. Although this may suggest neural activity is not required for the directed extension of RGC axons, in many species developing RGCs express additional, Na+-independent ionic mechanisms. To test whether the ability of RGC axons to extend in a directed fashion is influenced by membrane excitability, we blocked the principal modulators of the neural activity of a neuron, voltage-dependent potassium (Kv) channels. First, we showed that RGCs and their growth cones express Kv channels when they are growing through the brain on the way to their main midbrain target, the optic tectum. Second, a Kv channel blocker, 4-aminopyridine (4-AP), was applied to the developingXenopusoptic projection. Blocking Kv channels inhibited RGC axon extension and caused aberrant routing of many RGC fibers. With the higher doses, <25% of embryos had a normal optic projection. These data suggest that Kv channel activity regulates the guidance of growing axons in the vertebrate brain.
Spatial Distributions of Guidance Molecules Regulate Chemorepulsion and Chemoattraction of Growth Cones
Authors: Bagnard Dominique , Thomasset Nicole , Lohrum Marion , Püschel Andreas W. , Bolz Jürgen
Published: April 2018

It is generally assumed that gradients of chemotropic molecules are instrumental to the wiring of the nervous system. Recently, two members of the secreted class III semaphorin protein family have been implicated as repulsive (Sema3A) and attractive (Sema3C) guidance molecules for cortical axons (Bagnard et al., 1998). Here, we show that stabilized gradients of increasing semaphorin concentrations elicit stereotyped responses from cortical growth cones, independent of the absolute concentration and the slope of these gradients. In contrast, neither repulsive effects of Sema3A nor attractive effects of Sema3C were observed when axons were growing toward decreasing semaphorin concentrations. Thus, growth cone guidance by gradients of chemotropic molecules is robust and reproducible, because it is primarily independent of the exact dimensions of the gradients.
Nitric Oxide Influences Injury-Induced Microglial Migration and Accumulation in the Leech CNS
Authors: Chen Aileen , Kumar Shanta M. , Sahley Christie L. , Muller Kenneth J.
Published: April 2018

Damage to the leech or mammalian CNS increases nitric oxide (NO) production and causes accumulation of phagocytic microglial cells at the injury site. The aim of this study was to determine whether NO plays a role in microglial migration and accumulation at lesions in which NO is generated by a rapidly appearing endothelial nitric oxide synthase (eNOS) in leeches. Immunohistochemistry and cytochemistry demonstrated active eNOS before and throughout the period of microglial accumulation at the lesion. Decreasing NO synthesis by application of the NOS inhibitorNw-nitro-l-arginine methyl ester (1 mm) significantly reduced microglial accumulation, whereas its inactive enantiomerNw-nitro-D-arginine methyl ester (1 mm) resulted in microglial accumulation similar to that in crushed controls. Increasing NO with the donor spermine NONOate (SPNO) (1 mm) also inhibited accumulation, but not in the presence of the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-teramethylimidazoline-oxyl-3-oxide (50 μm). The effect of SPNO was reversed by washout. SPNO application reduced average microglial migratory speeds and even reversibly arrested cell movement, as measured in living nerve cords. These results suggest that NO produced at a lesion may be a stop signal for microglia to accumulate there and that it can act on microglia early in their migration. Thus, NO may assume a larger role in nerve repair and recovery from injury by modulating accumulation of microglia, which appear to be important for axonal regeneration.
Human Arm Movements Described by a Low-Dimensional Superposition of Principal Components
Authors: Sanger Terence David
Published: April 2018

A new method for analyzing kinematic patterns during smooth movements is proposed. Subjects are asked to move the end of a two-joint manipulandum to copy a smooth initial target path. On subsequent trials the target path is the subject's actual movement from the preceding trial. Using Principal Components Analysis, it is shown that the trajectories have very low dimension and that they converge toward a linear superposition of the first few principal components. We show similar results for handwriting on an electronic pen tablet. We hypothesize that the low dimensionality and convergence are attributable to combined properties of the internal controller and the musculoskeletal system. The low dimensionality may allow for efficient descriptions of a large class of arm movements.