Estudio de los efectos de un microambiente hipóxico en queratinocitos humanos in vitro y su correlato con alteraciones del microambiente en la patología de liquen plano oral

La hipoxia es un factor fundamental en el proceso de génesis tumoral, así como en patologías precursoras de cáncer, como es el Liquen Plano Oral (LPO). Objetivo: Determinar si es posible establecer una correlación entre las alteraciones que sufren queratinocitos normales en un microambiente hipóxico in vitro y alteraciones que aparecen en los queratinocitos en el epitelio de la mucosa oral en el contexto de la patología LPO. Métodos: Se estudiaron los cambios morfológicos mediante microscopía de contraste de fases, y la detección de marcadores asociados a hipoxia de queratinocitos humanos (HaCaT), como modelo celular oral, en un microambiente hipóxico generado por la variante del método “Hipoxia inducida por cubreobjetos”. Resultados: Mediante microscopía confocal se observó la presencia de los marcadores de hipoxia GLUT-1 y aductos de pimonidazol (Hipoxyprobe) en los cultivos celulares de HaCaT expuestos a un microambiente hipóxico. Además, se observó la presencia del marcador GLUT-1 mediante inmunohistoquímica en tejido epitelial humano derivado de biopsias de la patología LPO. Conclusiones: Se estableció una correlación entre las alteraciones detectadas en queratinocitos humanos inducidos a un microambiente hipóxico in vitro y las alteraciones detectadas in vivo en tejido epitelial de la mucosa oral

Induction of otic structures by canonical Wnt signalling in medaka

The Wnt family of signalling proteins is known to participate in multiple developmental decisions during embryogenesis. We misexpressed Wnt1 in medaka embryos and observed anterior truncations, similar to those described for ectopic activation of canonical Wnt signalling in other species. Interestingly, when we induced a heat-shock Wnt1 transgenic line exactly at 30% epiboly, we observed multiple ectopic otic vesicles in the truncated embryos. The vesicles then fused, forming a single large ear structure. These “cyclopic ears” filled the complete anterior region of the embryos. The ectopic induction of otic development can be explained by the juxtaposition of hindbrain tissue with anterior ectoderm. Fibroblast growth factor (Fgf) ligands are thought to mediate the otic-inducing properties of the hindbrain. However, signals different from Fgf3 and Fgf8 are necessary to explain the formation of the ectopic ear structures, suggesting that Wnt signalling is involved in the otic induction process in medaka

ADP-ribosylation of arginine

Arginine adenosine-5′-diphosphoribosylation (ADP-ribosylation) is an enzyme-catalyzed, potentially reversible posttranslational modification, in which the ADP-ribose moiety is transferred from NAD+ to the guanidino moiety of arginine. At 540 Da, ADP-ribose has the size of approximately five amino acid residues. In contrast to arginine, which, at neutral pH, is positively charged, ADP-ribose carries two negatively charged phosphate moieties. Arginine ADP-ribosylation, thus, causes a notable change in size and chemical property at the ADP-ribosylation site of the target protein. Often, this causes steric interference of the interaction of the target protein with binding partners, e.g. toxin-catalyzed ADP-ribosylation of actin at R177 sterically blocks actin polymerization. In case of the nucleotide-gated P2X7 ion channel, ADP-ribosylation at R125 in the vicinity of the ligand-binding site causes channel gating. Arginine-specific ADP-ribosyltransferases (ARTs) carry a characteristic R-S-EXE motif that distinguishes these enzymes from structurally related enzymes which catalyze ADP-ribosylation of other amino acid side chains, DNA, or small molecules. Arginine-specific ADP-ribosylation can be inhibited by small molecule arginine analogues such as agmatine or meta-iodobenzylguanidine (MIBG), which themselves can serve as targets for arginine-specific ARTs. ADP-ribosylarginine specific hydrolases (ARHs) can restore target protein function by hydrolytic removal of the entire ADP-ribose moiety. In some cases, ADP-ribosylarginine is processed into secondary posttranslational modifications, e.g. phosphoribosylarginine or ornithine. This review summarizes current knowledge on arginine-specific ADP-ribosylation, focussing on the methods available for its detection, its biological consequences, and the enzymes responsible for this modification and its reversal, and discusses future perspectives for research in this field

Analogical cognition: an insight into word meaning

Analogical cognition, extensively researched by Dedre Gentner and her colleagues over the past thirty five years, has been described as the core of human cognition, and it characterizes our use of many words. This research provides significant insight into the nature of word meaning, but it has been ignored by linguists and philosophers of language. I discuss some of the implications of the research for our account of word meaning. In particular, I argue that the research points to, and helps account for, a key explanatory role that linguistic meaning must play. The research also shows how words contribute to thought as opposed to merely being a means of conveying thought

Word frequency as a cue for identifying function words in infancy. Cognition

a b s t r a c t While content words (e.g., 'dog') tend to carry meaning, function words (e.g., 'the') mainly serve syntactic purposes. Here, we ask whether 17-month old infants can use one language-universal cue to identify function word candidates: their high frequency of occurrence. In Experiment 1, infants listened to a series of short, naturally recorded sentences in a foreign language (i.e., in French). In these sentences, two determiners appeared much more frequently than any content word. Following this, infants were presented with a visual object, and simultaneously with a word pair composed of a determiner and a noun. Results showed that infants associated the object more strongly with the infrequent noun than with the frequent determiner. That is, when presented with both the old object and a novel object, infants were more likely to orient towards the old object when hearing a label with a new determiner and the old noun compared to a label with a new noun and the old determiner. In Experiment 2, infants were tested using the same procedure as in Experiment 1, but without the initial exposure to French sentences. Under these conditions, infants did not preferentially associate the object with nouns, suggesting that the preferential association between nouns and objects does not result from specific acoustic or phonological properties. In line with various biases and heuristics involved in acquiring content words, we provide the first direct evidence that infants can use distributional cues, especially the high frequency of occurrence, to identify potential function words

Word frequency as a cue for identifying function words in infancy

International audienceWhile content words (e.g., 'dog') tend to carry meaning, function words (e.g., 'the') mainly serve syntactic purposes. Here, we ask whether 17-month old infants can use one language-universal cue to identify function word candidates: their high frequency of occurrence. In Experiment 1, infants listened to a series of short, naturally recorded sentences in a foreign language (i.e., in French). In these sentences, two determiners appeared much more frequently than any content word. Following this, infants were presented with a visual object, and simultaneously with a word pair composed of a determiner and a noun. Results showed that infants associated the object more strongly with the infrequent noun than with the frequent determiner. That is, when presented with both the old object and a novel object, infants were more likely to orient towards the old object when hearing a label with a new determiner and the old noun compared to a label with a new noun and the old determiner. In Experiment 2, infants were tested using the same procedure as in Experiment 1, but without the initial exposure to French sentences. Under these conditions, infants did not preferentially associate the object with nouns, suggesting that the preferential association between nouns and objects does not result from specific acoustic or phonological properties. In line with various biases and heuristics involved in acquiring content words, we provide the first direct evidence that infants can use distributional cues, especially the high frequency of occurrence, to identify potential function words. (C) 2010 Elsevier B.V. All rights reserved

Estudio de los efectos de un microambiente hipóxico en queratinocitos humanos in vitro y su correlato con alteraciones del microambiente en la patología de liquen plano oral

La hipoxia es un factor fundamental en el proceso de génesis tumoral, así como en patologías precursoras de cáncer, como es el Liquen Plano Oral (LPO).  Objetivo: Determinar si es posible establecer una correlación entre las alteraciones que sufren queratinocitos normales en un microambiente hipóxico in vitro y alteraciones que aparecen en los queratinocitos en el epitelio de la mucosa oral en el contexto de la patología LPO.  Métodos: Se estudiaron los cambios morfológicos mediante microscopía de contraste de fases, y la detección de marcadores asociados a hipoxia de queratinocitos humanos (HaCaT), como modelo celular oral, en un microambiente hipóxico generado por la variante del método “Hipoxia inducida por cubreobjetos”.  Resultados: Mediante microscopía confocal se observó la presencia de los marcadores de hipoxia GLUT-1 y aductos de pimonidazol (Hipoxyprobe) en los cultivos celulares de HaCaT expuestos a un microambiente hipóxico. Además, se observó la presencia del marcador GLUT-1 mediante inmunohistoquímica en tejido epitelial humano derivado de biopsias de la patología LPO.  Conclusiones: Se estableció una correlación entre las alteraciones detectadas en queratinocitos humanos inducidos a un microambiente hipóxico in vitro y las alteraciones detectadas in vivo en tejido epitelial de la mucosa oral