9 research outputs found
Learning to discriminate interaural time differences at low and high frequencies
This study investigated learning, in normal-hearing
adults, associated with training (i.e. repeated practice)
on the discrimination of ongoing interaural time difference
(ITD). Specifically, the study addressed an apparent
disparity in the conclusions of previous studies, which
reported training-induced learning at high frequencies
but not at low frequencies. Twenty normal-hearing adults
were trained with either low- or high-frequency stimuli,
associated with comparable asymptotic thresholds, or
served as untrained controls. Overall, trained listeners
learnt more than controls and over multiple sessions. The
magnitudes and time-courses of learning with the lowand
high-frequency stimuli were similar. While this is
inconsistent with the conclusion of a previous study with
low-frequency ITD, this previous conclusion may not be
justified by the results reported. Generalization of learning
across frequency was found, although more detailed
investigations of stimulus-specific learning are warranted.
Overall, the results are consistent with the notion that
ongoing ITD processing is functionally uniform across
frequency. These results may have implications for clinical
populations, such as users of bilateral cochlear implants
BMP-2 and TGFβ2 Shared Pathways Regulate Endocardial Cell Transformation
Valvular heart disease is a major cause of mortality and morbidity. Revealing the cellular processes and molecules that regulate valve formation and remodeling is required to develop effective therapies. A key step in valve formation during heart development is the epithelial-mesenchymal transformation (EMT) of a subpopulation of endocardial cells in the atrioventricular cushion (AVC). The type III transforming growth factor-β receptor (TGFβR3) regulates AVC endocardial cell EMT in vitro and mesenchymal cell differentiation in vivo. Little is known concerning the signaling mechanisms downstream of TGFβR3. Here we use endocardial cell EMT in vitro to determine the role of 2 well-characterized downstream TGFβ signaling pathways in TGFβR3-dependent endocardial cell EMT. Targeting of Smad4, the common mediator Smad, demonstrated that Smad signaling is required for EMT in the AVC and TGFβR3-dependent EMT stimulated by TGFβ2 or BMP-2. Although we show that Smads 1, 2, 3, and 5 are required for AVC EMT, overexpression of Smad1 or Smad3 is not sufficient to induce EMT. Consistent with the activation of the Par6/Smurf1 pathway downstream of TGFβR3, targeting ALK5, Par6, or Smurf1 significantly inhibited EMT in response to either TGFβ2 or BMP-2. The requirement for ALK5 activity, Par6, and Smurf1 for TGFβR3-dependent endocardial cell EMT is consistent with the documented role of this pathway in the dissolution of tight junctions. Taken together, our data demonstrate that TGFβR3-dependent endocardial cell EMT stimulated by either TGFβ2 or BMP-2 requires Smad4 and the activation of the Par6/Smurf1 pathway