Spatial correlations constrain cellular lifespan and pattern formation in corneal epithelium homeostasis.

Homeostasis in adult tissues relies on the replication dynamics of stem cells, their progenitors and the spatial balance between them. This spatial and kinetic coordination is crucial to the successful maintenance of tissue size and its replenishment with new cells. However, our understanding of the role of cellular replicative lifespan and spatial correlation between cells in shaping tissue integrity is still lacking. We developed a mathematical model for the stochastic spatial dynamics that underlie the rejuvenation of corneal epithelium. Our model takes into account different spatial correlations between cell replication and cell removal. We derive the tradeoffs between replicative lifespan, spatial correlation length, and tissue rejuvenation dynamics. We determine the conditions that allow homeostasis and are consistent with biological timescales, pattern formation, and mutants phenotypes. Our results can be extended to any cellular system in which spatial homeostasis is maintained through cell replication.

A probabilistic model of startle response reveals opposite effects of acute versus chronic Methylphenidate treatment.

BACKGROUND: The startle response is considered as the major physio-behavioral indication of anxiety in health and disease conditions. However, due to different protocols of stimulation and measurement, the magnitude as well as the appearance of the startle response is inconsistent. NEW METHOD: We postulate that the startle probability and not merely the amplitude may bare information that will form a consistent physiological measure of anxiety. RESULTS: To examine the proof-of-concept of our suggested probability model, we evaluated the effects of acute (single) versus chronic (14 days) MPH administration on both startle amplitude and probability. We found that both acute and chronic MPH administration has yielded similar effects on startle amplitude. However, acute MPH increased the startle's probability while chronic MPH decreased it. Next, we evaluated the effects of acute versus chronic stress on the startle's parameters and found a complementary effect. Explicitly, acute stress increased the startle's probability while chronic stress increased the startle amplitude. In contrast, enriched environment had no significant effects. Finally, to further validate the probability measure, we show that Midazolam had significant anxiolytic effects. In the second part, we investigated the acoustic startle response parameters (e.g. background noise and pulse duration), to better understand the interplay between these parameters and the startle amplitude versus probability. CONCLUSIONS: We show that the probabilistic element of the startle response does not only point to deeper physiologic relationships but may also serve as "hidden variables" congruent but not entirely identical to the commonly researched amplitude of the startle response.