Estimating phonation threshold pressure

Phonation threshold pressure (PTP) is the minimum subglottal pressure required to initiate vocal fold oscillation. Although potentially useful clinically, PTP is difficult to estimate noninvasively because of limitations to vocal motor control near the threshold of soft phonation. Previous investigators observed, for example, that trained subjects were unable to produce flat, consistent oral pressure peaks during/pae/syllable strings when they attempted to phonate as softly as possible (Verdolini-Marston, Titze, & Druker, 1990). The present study aimed to determine if nasal airflow or vowel context affected phonation threshold pressure as estimated from oral pressure (Smitheran & Hixon, 1981) in 5 untrained female speakers with normal velopharyngeal and voice function. Nasal airflow during /p/occlusion was observed for 3 of 5 participants when they attempted to phonate near threshold pressure. When the nose was occluded, nasal airflow was reduced or eliminated during /p/;however, individuals then evidenced compensatory changes in glottal adduction and/or respiratory effort that may be expected to alter PTP estimates. Results demonstrate the importance of monitoring nasal flow (or the flow zero point in undivided masks) when obtaining PTP measurements noninvasively. Results also highlight the need to pursue improved methods for noninvasive estimation of PTP.     

Glial development in the Drosophila CNS requires concomitant activation of glial and repression of neuronal differentiation genes

Two classes of glial cells are found in the embryonic Drosophila CNS, midline glial cells and lateral glial cells. Midline glial development is triggered by EGF-receptor signalling, whereas lateral glial development is controlled by the gcm gene. Subsequent glial cell differentiation depends partly on the pointed gene. Here we describe a novel component required for all CNS glia development. The tramtrack gene encodes two zinc-finger proteins, one of which, ttkp69, is expressed in all non-neuronal CNS cells. We show that ttkp69 is downstream of gcm and can repress neuronal differentiation. Double mutant analysis and coexpression experiments indicate that glial cell differentiation may depend on a dual process, requiring the activation of glial differentiation by pointed and the concomitant repression of neuronal development by tramtrack.     

Pegylated peptides. V. Carboxy-terminal PEGylated analogs of growth hormone-releasing factor (GRF) display enhanced duration of biological activity in vivo

In the present study, human growth hormone-releasing factor (hGRF) and analogs were successfully pegylated at the carboxy-terminus using a novel solid- and solution-phase strategy. Following synthesis, these pegylated hGRF analogs were evaluated for in vitro and in vivo biological activity. Specifically, hGRF (1-29)-NH2, [Ala15]-hGRF (1-29)-NH2, [desNH2Tyr1, D-Ala2, Ala15]-hGRF(1-29)-NH2 and [His1, Val2, Gln8, Ala15, Leu27]-hGRF(1-32)-OH were each C-terminally extended using a Gly-Gly-Cys-NH2 spacer (previously demonstrated not to alter intrinsic biological activity), and then monopegylated via coupling to an activated dithiopyridyl-PEG reagent. PEG moieties of 750, 2000, 5000 or 10,000 molecular weight (MW) were examined to determine the effect of polymer weight on activity. Initial biological evaluations in vitro revealed that all C-terminally pegylated hGRF analogs retained high growth hormone (GH)-releasing potencies, regardless of the MW of PEG polymer employed. Two of these pegylated hGRF analogs, [desNH2Tyr1, D-Ala2, Ala15]-hGRF (1-29)-Gly-Gly-Cys(NH2)-S-Nle-PEG5000 and [His1, Val2, Gln8, Ala15, Leu27]-hGRF(1-32)-Gly-Cys(NH2)-S-Nle-PEG5000, were subsequently evaluated in both pig and mouse models and found to be highly potent (in vivo potency range = 12-55-fold that of native hGRF). Relative to their non-pegylated counterparts, these two pegylated hGRF analogs exhibited enhanced duration of activity.     

Effects ofSolanum glycoalkaloids on chemosensilla in the Colorado potato beetle

Steroidal glycoalkaloids, found in species of the Solanaceae, elicit bursting activity in galeal and tarsal chemosensilla of adult Colorado potato beetles. The effect has an average latency of 6–12 sec, depending on the sensillum/alkaloid combination. A 20-sec alkaloid treatment is often suffficient to render galeal sensilla unresponsive to gamma-aminobutyric acid, normally an effective stimulant. The alkaloids have similar effects on galeal sensilla of larval Colorado potato beetles and on labellar chemosensilla of the blowfly. It is concluded that these compounds act independently of any specialized chemoreceptor in the Colorado potato beetle, and that association of the Colorado potato beetle with solanaceous plants has not led to evolution of a specific receptor forSolanum glycoalkaloids.