Predictive uncertainty in auditory sequence processing

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Activation of TRPV1 by Capsaicin Regulates ENaC

ENaC is a constitutively open heterotrimeric channel which regulates Na+ transport in tight epithelia of the kidney, lungs, colon and anterior tongue containing fungiform taste buds. The amiloride-sensitive ENaC is comprised of aβg subunits. Humans express an additional subunit, the d subunit. Therefore, humans contain both aβg-ENaC and dβg-ENaC functional channels. Relative to aβg-ENaC, the dβg-ENaC is 10-fold less sensitive to amiloride. In the mammalian anterior tongue, ENaC is expressed in fungiform salt sensing taste receptor cells and is the Na+-specific salt taste receptor. In mammals, salt elicits an inverted U shaped behavioral response. Lower concentrations of salt are appetitive while high salt concentrations are aversive. The appetitive salt concentrations are sensed via ENaC. Thus, modulating ENaC activity in fungiform taste receptor cells will, in turn, regulate salt intake. The aim of this project is to investigate the effect of a common food ingredient, capsaicin, on ENaC expression and function in two cell lines, HEK293 cells and cultured adult human fungiform taste bud cells (HBO cells). Capsaicin, a TRPV1 agonist was chosen because in previous studies, it modulated chorda tympani taste nerve responses to NaCl in a dose-dependent manner. Most importantly, capsaicin and other agonists of TRPV1 were effective in modulating human salt taste perception. It is likely that the effect of capsaicin is due to its interactions with TRPV1, because TRPV1 and ENaC subunits are co-expressed in cortical collecting duct cells (CCD) and in a subset of human taste bud cells. In support of this hypothesis, TRPV1 has been shown to regulate ENaC expression and function in CCD cells of rats and mice. Using immunohistochemical techniques, our results demonstrate that TRPV1 is co-localized with the d-ENaC subunit in HBO cells. Additionally, the results in HEK-293 cells suggest that the activation of TRPV1 via capsaicin has a modulatory effect on d-ENaC mRNA and protein expression as well ENaC channel function measured as Na+ flux

Distinctive growth requirements and gene expression patterns distinguish progenitor B cells from pre-B cells.

Long-term bone marrow cultures have been useful in determining gene expression patterns in pre-B cells and in the identification of cytokines such as interleukin 7 (IL-7). We have developed a culture system to selectively grow populations of B lineage restricted progenitors (pro-B cells) from murine bone marrow. Pro-B cells do not grow in response to IL-7, Steel locus factor (SLF), or a combination of the two. c-kit, the SLF receptor, and the IL-7 receptor are both expressed by pro-B cells, indicating that the lack of response is not simply due to the absence of receptors. Furthermore, SLF is not necessary for the growth of pro-B cells since they could be expanded on a stromal line derived from Steel mice that produces no SLF. IL-7 responsiveness in pre-B cells is associated with an increase in n-myc expression and is correlated with immunoglobulin (Ig) gene rearrangements. Although members of the ets family of transcription factors and the Pim-1 kinase are expressed by pro-B cells, n-myc is not expressed. Pro-B cells maintain Ig genes in the germline configuration, which is correlated with a low level of recombination activating genes 1 and 2 (Rag-1 and 2) mRNA expression, but high expression of sterile mu and terminal deoxynucleotidyl transferase. Pro-B cells are unable to grow separated from the stromal layer by a porous membrane, indicating that stromal contact is required for growth. These results suggest that pro-B cells are dependent on alternative growth signals derived from bone marrow stroma and can be distinguished from pre-B cells by specific patterns of gene expression

Immunoregulatory Cells And Mediators In Murine Bone Marrow

This thesis defines distinct immunoregulatory mechanisms which naturally exist in murine bone marrow (BM). Physical separation of BM cells revealed two immunoregulatory cell populations: a suppressor activity present in a fraction of large, low density BM cells predominantly of myeloid and blast cell morphology; and an enhancing activity contained in a fraction of small, high density BM cells enriched for lymphocytes. Both activities are associated with the production of soluble mediators which possess analogous function to the immunoregulatory cells.;The population of cells responsible for immune suppression have been referred to as Natural Suppressor (NS) cells. NS cells are unique in that they are not antigen- or MHC-restricted, and do not require specific priming to function. They suppress a variety of immune responses, including antibody (Ab), mitogen, and mixed lymphocyte reaction (MLR) responses. NS cells were routinely found in the BM of normal as well as severe combined immune-deficient (SCID) mice, and expressed no surface markers characteristic of B, T, M{dollar}\emptyset{dollar}, and NK/LAK cells. The culture of BM cells in IL-2 containing supernatants resulted in the generation of cells possessing potent NS as well as Natural Killer (NK) activity, suggesting that both NS and NK may be associated with a common family of cells.;Bone marrow cells secrete two soluble mediators which act in an analogous fashion to the suppressive and enhancing activities present in murine BM. These are bone marrow derived suppressor factor (BDSF) and bone marrow derived enhancing factor (BDEF). BDSF is contained in a low MW (1-10 kDa) fraction of BM culture supernatant which suppresses Ab and MLR, but not mitogen-driven responses. BDSF prevents production of IL-2 in the MLR, and BDSF-suppressed MLR responses can be reconstituted by the addition of exogenous IL-2. Therefore it is proposed that absence of IL-2 production due to BDSF results in clonal anergy or non-responsiveness.;BDEF ({dollar}\u3e{dollar} 10 kDa) augments Ab and MLR responses, but cannot synergize with mitogen to induce proliferation. BDEF is directly mitogenic for murine thymocytes, specifically those which do not express the receptor for the lectin peanut agglutinin (PNA{dollar}\sp-{dollar}) and most resemble mature T-cells. The ability of BDEF to induce T-cell proliferation may be intimately associated with augmentation of both humoral and cellular responses

Effects of local-market radio ownership concentration on radio localism, the public interest, and listener opinions and use of local radio

The Telecommunications Act of 1996 and ensuing radio ownership consolidation are blamed for harming radio localism and the public interest. Prior studies examined impacts attributed to consolidation on format diversity and other measures; however, none explored influences on listener perceptions. The present research sought to determine effects of local-market ownership concentration on listener opinions and use of radio—potentially indicative of stations’ localism and public service—by surveying listeners in markets categorized by ownership concentration levels. Findings suggest concentration does not strongly influence perceptions; however, overall results indicate potentially negative consequences from local and national consolidation on amounts of local music, news, and public-service programming; live-local programming; and station responsiveness. Findings suggest policy change that could enhance radio localism

Inducing a Grammar Without an Explicit Teacher: Incremental Distributed Prediction Feedback

A primary problem for a child learning her first language is that her ungrammatical utterances are rarely explicitly corrected. It has been argued that this dearth of negative evidence regarding the child's grammatical hypotheses makes it impossible for the child to induce the grammar of the language without substantial innate knowledge of some universal principles common to all natural grammars. However, recent connectionist models of language acquisition have employed a learning technique that circumvents the negative evidence problem. Moreover, this learning strategy is not limited to strictly connectionist architectures. What we call Incremental Distributed Prediction Feedback refers to when the learner simply listens to utterances in its environment and makes internal predictions on-line as to what elements of the grammar are more or less likely to immediately follow the current input. Once that subsequent input is received, those prediction contingencies (essentially, transitional probabilities) are slightly adjusted accordingly. Simulations with artificial grammars demonstrate that this learning strategy is faster and more realistic than depending on infrequent negative feedback to ungrammatical output Incremental Distributed Prediction Feedback allows the learner to produce its own negative evidence from positive examples of the language by comparing incrementally predicted input with actual input

The Ontogeny of Lexical Networks Toddlers Encode the Relationships Among Referents When Learning Novel Words

Although the semantic relationships among words have long been acknowledged as a crucial component of adult lexical knowledge, the ontogeny of lexical networks remains largely unstudied. To determine whether learners encode relationships among novel words, we trained 2-year-olds on four novel words that referred to four novel objects, which were grouped into two visually similar pairs. Participants then listened to repetitions of word pairs (in the absence of visual referents) that referred to objects that were either similar or dissimilar to each other. Toddlers listened significantly longer to word pairs referring to similar objects, which suggests that their representations of the novel words included knowledge about the similarity of the referents. A second experiment confirmed that toddlers can learn all four distinct words from the training regime, which suggests that the results from Experiment 1 reflected the successful encoding of referents. Together, these results show that toddlers encode the similarities among referents from their earliest exposures to new words

Toddlers Encode Similarities Among Novel Words from Meaningful Sentences

Toddlers can learn about the meanings of individual words from the structure and semantics of the sentences in which they are embedded. However, it remains unknown whether toddlers encode similarities among novel words based on their positions within sentences. In three experiments, two-year-olds listened to novel words embedded in familiar sentence frames. Some novel words consistently occurred in the subject position across sentences, and others in the object position across sentences. An auditory semantic task was used to test whether toddlers encoded similarities based on sentential position, for (a) pairs of novel words that occurred within the same sentence, and (b) pairs of novel words that occurred in the same position across sentences. The results suggest that while toddlers readily encoded similarity based on within-sentence occurrences, only toddlers with more advanced grammatical knowledge encoded the positional similarities of novel words across sentences. Moreover, the encoding of these cross-sentential relationships only occurred if the exposure sentences included a familiar verb. These studies suggest that the types of lexical relationships that toddlers learn depend on the child’s current level of language development, as well as the structure and meaning of the sentences surrounding the novel words

Balancing generalization and lexical conservatism : an artificial language study with child learners

Successful language acquisition involves generalization, but learners must balance this against the acquisition of lexical constraints. Such learning has been considered problematic for theories of acquisition: if learners generalize abstract patterns to new words, how do they learn lexically-based exceptions? One approach claims that learners use distributional statistics to make inferences about when generalization is appropriate, a hypothesis which has recently received support from Artificial Language Learning experiments with adult learners (Wonnacott, Newport, & Tanenhaus, 2008). Since adult and child language learning may be different (Hudson Kam & Newport, 2005), it is essential to extend these results to child learners. In the current work, four groups of children (6 years) were each exposed to one of four semi-artificial languages. The results demonstrate that children are sensitive to linguistic distributions at and above the level of particular lexical items, and that these statistics influence the balance between generalization and lexical conservatism. The data are in line with an approach which models generalization as rational inference and in particular with the predictions of the domain general hierarchical Bayesian model developed in Kemp, Perfors & Tenenbaum, 2006. This suggests that such models have relevance for theories of language acquisition

A corpus-based study of agrammatic aphasia: New evidence for the potential prominent part played by adaptive strategies in these patients' oral production

International audienceThis study investigates the plausibility of "adaptation theory" in oral agrammatic production by means of large and systematic corpora studies. The hypothesis of agrammatism being, at least partly, an adaptive behaviour is thus tested, following some assumptions put forward by Nespoulous (2000) and Hofstede and Kolk (1994). Variability in the use of strategies, combined with the improvement or decrease of fluency and / or grammatical accuracy, lead us to suggest that some "performance rules" are very likely to reflect linguistic output adjustments we observed, which may be due to the agrammatic speakers' adaptive abilities. The intervention of monitoring (focused attention on form) might be responsible for the inconsistent use of strategies