Epsilon toxin from Clostridium perfringens acts on oligodendrocytes without forming pores, and causes demyelination.

Epsilon toxin (ET) is produced by Clostridium perfringens types B and D and causes severe neurological disorders in animals. ET has been observed binding to white matter, suggesting that it may target oligodendrocytes. In primary cultures containing oligodendrocytes and astrocytes, we found that ET (10(-9) M and 10(-7) M) binds to oligodendrocytes, but not to astrocytes. ET induces an increase in extracellular glutamate, and produces oscillations of intracellular Ca(2+) concentration in oligodendrocytes. These effects occurred without any change in the transmembrane resistance of oligodendrocytes, underlining that ET acts through a pore-independent mechanism. Pharmacological investigations revealed that the Ca(2+) oscillations are caused by the ET-induced rise in extracellular glutamate concentration. Indeed, the blockade of metabotropic glutamate receptors type 1 (mGluR1) prevented ET-induced Ca(2+) signals. Activation of the N-methyl-D-aspartate receptor (NMDA-R) is also involved, but to a lesser extent. Oligodendrocytes are responsible for myelinating neuronal axons. Using organotypic cultures of cerebellar slices, we found that ET induced the demyelination of Purkinje cell axons within 24 h. As this effect was suppressed by antagonizing mGluR1 and NMDA-R, demyelination is therefore caused by the initial ET-induced rise in extracellular glutamate concentration. This study reveals the novel possibility that ET can act on oligodendrocytes, thereby causing demyelination. Moreover, it suggests that for certain cell types such as oligodendrocytes, ET can act without forming pores, namely through the activation of an undefined receptor-mediated pathway.journal articleresearch support, non-u.s. gov't2015 Mar2014 10 31importe

Evidence for insertional codemixing: mixed compounds and French nominal groups in Brussels Dutch

In this paper we analyse mixed compounds, such as legume+winkel ‘vegetable shop, greengrocery’ and winter+paletot ‘winter coat’ which contain a French and a Dutch element, and French nominal groups, such as carte d’identité ‘identity card’, and journal parlé ‘radio news’, which bilingual speakers from Brussels frequently insert into Brussels Dutch utterances. Using Muysken’s (2000) typology of bilingual speech, we claim that the mixed compounds and the nominal groups display the characteristics of insertional code-mixing. In addition, some evidence for the existence of a continuum between borrowing and code-switching can be obtained from these examples. As the multimorphemic units that are inserted into Dutch are neither single words, nor full constituents, their status in the lexicon raises interesting issues for researchers interested in the interface between syntax and the lexicon (see also Backus 2003). We try to argue that nominal groups such as carte d’identité and journal parlé are probably best seen as lexical templates or constructional idioms (Booij, 2002b). The insertion of French constructional idioms in Brussels Dutch represents an innovation in the lexical patterns that are available to speakers of this language, which is highly relevant for theories of language change

Functional Evidence of Multidrug Resistance Transporters (MDR) in Rodent Olfactory Epithelium

Background: P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP1) are membrane transporter proteins which function as efflux pumps at cell membranes and are considered to exert a protective function against the entry of xenobiotics. While evidence for Pgp and MRP transporter activity is reported for olfactory tissue, their possible interaction and participation in the olfactory response has not been investigated. Principal Findings: Functional activity of putative MDR transporters was assessed by means of the fluorometric calcein acetoxymethyl ester (calcein-AM) accumulation assay on acute rat and mouse olfactory tissue slices. Calcein-AM uptake was measured as fluorescence intensity changes in the presence of Pgp or MRP specific inhibitors. Epifluorescence microscopy measured time course analysis in the olfactory epithelium revealed significant inhibitor-dependent calcein uptake in the presence of each of the selected inhibitors. Furthermore, intracellular calcein accumulation in olfactory receptor neurons was also significantly increased in the presence of either one of the Pgp or MRP inhibitors. The presence of Pgp or MRP1 encoding genes in the olfactory mucosa of rat and mouse was confirmed by RT-PCR with appropriate pairs of speciesspecific primers. Both transporters were expressed in both newborn and adult olfactory mucosa of both species. To assess a possible involvement of MDR transporters in the olfactory response, we examined the electrophysiological response to odorants in the presence of the selected MDR inhibitors by recording electroolfactograms (EOG). In both animal species

Topological sound in active-liquid metamaterials

Liquids composed of self-propelled particles have been experimentally realized using molecular, colloidal, or macroscopic constituents. These active liquids can flow spontaneously even in the absence of an external drive. Unlike spontaneous active flow, the propagation of density waves in confined active liquids is not well explored. Here, we exploit a mapping between density waves on top of a chiral flow and electrons in a synthetic gauge field to lay out design principles for artificial structures termed topological active metamaterials. We design metamaterials that break time-reversal symmetry using lattices composed of annular channels filled with a spontaneously flowing active liquid. Such active metamaterials support topologically protected sound modes that propagate unidirectionally, without backscattering, along either sample edges or domain walls and despite overdamped particle dynamics. Our work illustrates how parity-symmetry breaking in metamaterial structure combined with microscopic irreversibility of active matter leads to novel functionalities that cannot be achieved using only passive materials

A comprehensive overview of radioguided surgery using gamma detection probe technology

The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology

InfoSyll: A Syllabary Providing Statistical Information on Phonological and Orthographic Syllables

here is now a growing body of evidence in various languages supporting the claim that syllables are functional units of visual word processing. In the perspective of modeling the processing of polysyllabic words and the activation of syllables, current studies investigate syllabic effects with subtle manipulations. We present here a syllabary of the French language aiming at answering new constraints when designing experiments on the syllable issue. The InfoSyll syllabary provides exhaustive characteristics and statistical information for each phonological syllable (e.g. /fi/) and for its corresponding orthographic syllables (e.g. fi, phi, phy, fee, fix, fis). Variables such as the type and token positional frequencies, the number and frequencies of the correspondences between orthographic and phonological syllables are provided. As discussed, such computations should allow precise controls, manipulations and quantitative descriptions of syllabic variables in the field of psycholinguistic research.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

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Do Consonant Sonority and Status Influence Syllable-Based Segmentation Strategies in a Visual Letter Detection Task? Developmental Evidence in French Children

International audienceThis article queries whether consonant sonority (sonorant vs. obstruent) and status (coda vs. onset) within intervocalic clusters influence syllable-based segmentation strategies. We used a modified version of the illusory conjunction paradigm to test whether French beginning, intermediate, and advanced readers were sensitive to an optimal “sonorant coda–obstruent onset” sonority profile within the syllable boundaries as a cue for a syllable-based segmentation. Data showed that children used a syllable-based segmentation that improved with reading skills and age. The results are discussed to support that the visual letter detection within pseudowords primarily and early relies on acoustic-phonetic cues within the syllable boundaries, whereas the syllable effect seems to be developmentally constrained by reading skills and age