A distributed integral control mechanism for regulation of cholesterol concentration in the human retina.

Tight homeostatic control of cholesterol concentration within the complex tissue microenvironment of the retina is the hallmark of a healthy eye. By contrast, dysregulation of biochemical mechanisms governing retinal cholesterol homeostasis likely contributes to the aetiology and progression of age-related macular degeneration (AMD). While the signalling mechanisms maintaining cellular cholesterol homeostasis are well-studied, a systems-level description of molecular interactions regulating cholesterol balance within the human retina remains elusive.

p21 regulates expression of ECM components and promotes pulmonary fibrosis via CDK4 and Rb.

Fibrosis and accumulation of senescent cells are common tissue changes associated with aging. Here, we show that the CDK inhibitor p21 (CDKN1A), known to regulate the cell cycle and the viability of senescent cells, also controls the expression of extracellular matrix (ECM) components in senescent and proliferating cells of the fibrotic lung, in a manner dependent on CDK4 and Rb phosphorylation. p21 knockout protects mice from the induction of lung fibrosis.

Thermally activated particle motion in biased correlated Gaussian disorder potentials.

Thermally activated particle motion in disorder potentials is controlled by the large-ΔV tail of the distribution of height ΔV of the potential barriers created by the disorder. We employ the optimal fluctuation method to evaluate this tail for correlated quenched Gaussian potentials in one dimension in the presence of a small bias of the potential. We focus on the mean escape time (MET) of overdamped particles averaged over the disorder.