The effects of osmotic stress on the structure and function of the cell nucleus.

Osmotic stress is a potent regulator of the normal function of cells that are exposed to osmotically active environments under physiologic or pathologic conditions. The ability of cells to alter gene expression and metabolic activity in response to changes in the osmotic environment provides an additional regulatory mechanism for a diverse array of tissues and organs in the human body. In addition to the activation of various osmotically- or volume-activated ion channels, osmotic stress may also act on the genome via a direct biophysical pathway. Changes in extracellular osmolality alter cell volume, and therefore, the concentration of intracellular macromolecules. In turn, intracellular macromolecule concentration is a key physical parameter affecting the spatial organization and pressurization of the nucleus. Hyper-osmotic stress shrinks the nucleus and causes it to assume a convoluted shape, whereas hypo-osmotic stress swells the nucleus to a size that is limited by stretch of the nuclear lamina and induces a smooth, round shape of the nucleus. These behaviors are consistent with a model of the nucleus as a charged core/shell structure pressurized by uneven partition of macromolecules between the nucleoplasm and the cytoplasm. These osmotically-induced alterations in the internal structure and arrangement of chromatin, as well as potential changes in the nuclear membrane and pores are hypothesized to influence gene transcription and/or nucleocytoplasmic transport. A further understanding of the biophysical and biochemical mechanisms involved in these processes would have important ramifications for a range of fields including differentiation, migration, mechanotransduction, DNA repair, and tumorigenesis.

Stream segregation on a single electrode as a function of pulse rate in cochlear implant listeners.

While cochlear implants (CIs) usually provide high levels of speech recognition in quiet, speech recognition in noise remains challenging. To overcome these difficulties, it is important to understand how implanted listeners separate a target signal from interferers. Stream segregation has been studied extensively in both normal and electric hearing, as a function of place of stimulation. However, the effects of pulse rate, independent of place, on the perceptual grouping of sequential sounds in electric hearing have not yet been investigated. A rhythm detection task was used to measure stream segregation. The results of this study suggest that while CI listeners can segregate streams based on differences in pulse rate alone, the amount of stream segregation observed decreases as the base pulse rate increases. Further investigation of the perceptual dimensions encoded by the pulse rate and the effect of sequential presentation of different stimulation rates on perception could be beneficial for the future development of speech processing strategies for CIs.