Bifurcations and limit cycles in cytosolic yeast calcium.

Calcium homeostasis is a fundamental cellular process in yeast. The regulation of the cytosolic calcium concentration is required for volume preservation and to regulate many vital calcium dependent processes such as mating and response to stress. The homeostatic mechanism is often studied by applying calcium pulses: sharply changing the calcium concentration in the yeast environment and observing the cellular response. To address these experimental investigations, several mathematical models have been proposed to describe this response. In this article we demonstrate that a previously studied model for this response predicts the presence of limit point instabilities and limit cycles in the dynamics of the calcium homeostasis system. We discuss the ways in which such dynamic characteristics can be observed with luminometric techniques. We contrast these predictions with experimentally observed responses and find that the experiments reveal a number of features that are consistent with modeling predictions. In particular, we find that equilibrium cytosolic concentrations have a sharp change in behavior as pulse size changes in the micromolar range. We show that such change is consistent with the presence of limit point instabilities. Additionally, we find that the response of synchronized yeast cells to millimolar range pulses is non-monotonic in its late stages. This response has characteristics similar to those associated with limit cycles.

Early and Mild Phases of Primary Progressive Aphasia: A Case Series.

BACKGROUND: The early and mild phases of various neurodegenerative diseases, sometimes described as Mild Cognitive Impairment (MCI), has been characterized as the transitional state between normal cognition and dementia. It is described as having cognitive decline not severe enough to cause functional impairment. MCI has been divided into amnestic and non-amnestic subtypes with the amnestic subtype most commonly progressing to AD. The MCI phase of other dementias such as DLB has also been described. There are very few reports summarizing this early phase of Primary Progressive Aphasia. AIMS: Our aim is to contribute to the clinical characterization of the early and mild phases of clinically suspect PPA in order to better describe the presenting features and neuropsychological profile. METHODS: This is a cross-sectional case series abstracted from our memory disorders clinic. We retrospectively queried and analyzed the cases of 9 patients with a primary diagnosis of MCI and secondary diagnosis of progressive aphasia. Acquired (non-degenerative) aphasias (e.g. stroke, mass) were excluded. RESULTS: Of the 9 cases, 5 were non-amnestic MCI and 4 were amnestic MCI, all with language as the primary domain. All eMCI cases were non-amnestic. Word finding difficulty was observed in 8 of the 9 cases and sentence repetition impairments in 8 of 8 tested. CONCLUSION: PPA is a syndrome with an underlying progressive neurodegenerative etiology that results in dementia. PPA, like other neurodegenerative conditions, can transition through an early (i.e. MCI) phase prior to the dementia phase. The clinical description of this early stage of PPA is predominantly characterized by word finding difficulty on observation, sentence repetition impairment on neuropsychological testing, and a diagnosis of MCI or early MCI (eMCI) with language as the primary impaired domain ± an amnestic component.