Citations

Molecular chaperones are essential proteins that participate in the regulation of steroid receptors in eukaryotes. The steroid aporeceptor complex contains the molecular chaperones Hsp90 and Hsp70, p48, the cyclophilin Cyp-40, and the associated proteins p23 and p60. In vitro folding assays showed that Cyp-40 and p23 functioned as molecular chaperones in a manner similar to that of Hsp90 or Hsp70. Although neither Cyp-40 nor p23 could completely refold an unfolded substrate, both proteins interacted with the substrate to maintain a nonnative folding-competent intermediate. Thus, the steroid aporeceptor complexes have multiple chaperone components that maintain substrates in an intermediate folded state.

This investigation evaluated a possible source of reduced intelligibility in hypokinetic dysarthric speech, namely the mismatch between listeners’ perceptual strategies and the acoustic information available in the dysarthric speech signal. A paradigm of error analysis was adopted in which listener transcriptions of phrases were coded for the presence and type of word boundary errors. Seventy listeners heard 60 phrases produced by speakers with hypokinetic dysarthria. The six-syllable phrases alternated strong and weak syllables and ranged in length from three to five words. Lexical boundary violations were defined as erroneous insertions or deletions of lexical boundaries that occurred either before strong or before weak syllables. A total of 1596 lexical boundary errors in the listeners’ transcriptions was identified unanimously by three independent judges. The pattern of errors generally conformed with the predictions of the Metrical Segmentation Strategy hypothesis [Cutler and Norris, J. Exp. Psychol. 14, 113–121 (1988)] which posits that listeners attend to strong syllables to identify word onsets. However, the strength of adherence to this pattern varied across speakers. Comparison of acoustic evidence of syllabic strength to lexical boundary error patterns revealed a source of intelligibility deficit associated with this particular type of dysarthric speech pattern.

CD1d-restricted invariant NKT (iNKT) cells are immunoregulatory cells whose loss exacerbates diabetes in nonobese diabetic (NOD) female mice. Here, we show that the relative numbers of iNKT cells from the pancreatic islets of NOD mice decrease at the time of conversion from peri-insulitis to invasive insulitis and diabetes. Conversely, NOD male mice who have a low incidence of diabetes showed an increased frequency of iNKT cells. Moreover, administration of α-galactosylceramide, a potent activating ligand presented by CD1d, ameliorated the development of diabetes in NOD female mice and resulted in the accumulation of iNKT cells and myeloid dendritic cells (DC) in pancreatic lymph nodes (PLN), but not in inguinal lymph nodes. Strikingly, injection of NOD female mice with myeloid DC isolated from the PLN, but not those from the inguinal lymph nodes, completely prevented diabetes. Thus, the immunoregulatory role of iNKT cells is manifested by the recruitment of tolerogenic myeloid DC to the PLN and the inhibition of ongoing autoimmune inflammation.

This investigation is the second in a series to examine a potential source of reduced intelligibility in dysarthric speech, namely the mismatch between listeners’ perceptual strategies and the acoustic information available in the dysarthric speech signal. Lexical boundary error (LBE) analysis was conducted on listener transcripts from phrases produced by speakers with hypokinetic dysarthria, ataxic dysarthria, and normal controls. By design, the hypokinetic and ataxic dysarthric tapes elicited similar intelligibility (words-correct) scores. However, they elicited different numbers and patterns of lexical boundary errors. The nature of the error pattern differences can be traced to the listeners’ use of available syllabic strength information to segment the acoustic stream. Specifically, although both dysarthric speech samples elicited numerous lexical boundary errors, those for the hypokinetic speech generally conformed to predictions offered from studies of degraded normal speech. Those for the ataxic speech did not conform strongly to such predictions. It appears that the prosodic deficits of the ataxic speech (tendency toward syllabic isochrony, excessive loudness variation, and reduced vowel working space consequent to reductions in vowel strength) posed more of a problem for listeners than did the prosodic deficits of the hypokinetic speech (rapid rate, monotony, reduced vowel working space).