Biologically driven nonequilibrium fluctuations are often characterized by their non-Gaussianity or by an "effective temperature", which is frequency dependent and higher than the ambient temperature. We address these two measures theoretically by examining a randomly kicked particle, with a variable number of kicking motors, and show how these two indicators of nonequilibrium behavior can contradict. Our results are compared with new experiments on shape fluctuations of red-blood cell membranes, and demonstrate how the physical nature of the motors in this system can be revealed using these global measures of nonequilibrium.

The internal dynamics of active gels both in artificial (in vitro) model systems and inside the cytoskeleton of living cells has been extensively studied with experiments of recent years. These dynamics are probed using tracer particles embedded in the network of biopolymers together with molecular motors, and distinct nonthermal behavior is observed. We present a theoretical model of the dynamics of a trapped active particle, which allows us to quantify the deviations from equilibrium behavior, using both analytic and numerical calculations. We map the different regimes of dynamics in this system and highlight the different manifestations of activity: breakdown of the virial theorem and equipartition, different elasticity-dependent "effective temperatures," and distinct non-Gaussian distributions. Our results shed light on puzzling observations in active gel experiments and provide physical interpretation of existing observations, as well as predictions for future studies.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, which is refractory to all currently available treatments and bears dismal prognosis. About 70% of all PDAC cases harbor mutations in the TP53 tumor suppressor gene. Many of those are missense mutations, resulting in abundant production of mutant p53 (mutp53) protein in the cancer cells. Analysis of human PDAC patient data from The Cancer Genome Atlas (TCGA) revealed a negative association between the presence of missense mutp53 and infiltration of CD8+ T cells into the tumor. Moreover, CD8+ T cell infiltration was negatively correlated with the expression of fibrosis-associated genes. Importantly, silencing of endogenous mutp53 in KPC cells, derived from mouse PDAC tumors driven by mutant Kras and mutp53, down-regulated fibrosis and elevated CD8+ T cell infiltration in the tumors arising upon orthotopic injection of these cells into the pancreas of syngeneic mice. Moreover, the tumors generated by mutp53-silenced KPC cells were markedly smaller than those elicited by mutp53-proficient control KPC cells. Altogether, our findings suggest that missense p53 mutations may contribute to worse PDAC prognosis by promoting a more vigorous fibrotic tumor microenvironment and impeding the ability of the immune system to eliminate the cancer cells.

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