8 research outputs found
Efficient Network Reconstruction from Dynamical Cascades Identifies Small-World Topology of Neuronal Avalanches
Cascading activity is commonly found in complex systems with directed
interactions such as metabolic networks, neuronal networks, or disease spreading
in social networks. Substantial insight into a system's organization
can be obtained by reconstructing the underlying functional network architecture
from the observed activity cascades. Here we focus on Bayesian approaches and
reduce their computational demands by introducing the Iterative Bayesian (IB)
and Posterior Weighted Averaging (PWA) methods. We introduce a special case of
PWA, cast in nonparametric form, which we call the normalized count (NC)
algorithm. NC efficiently reconstructs random and small-world functional network
topologies and architectures from subcritical, critical, and supercritical
cascading dynamics and yields significant improvements over commonly used
correlation methods. With experimental data, NC identified a functional and
structural small-world topology and its corresponding traffic in cortical
networks with neuronal avalanche dynamics
Role of E2F3 expression in modulating cellular proliferation rate in human bladder and prostate cancer cells
Amplification and overexpression of the E2F3 gene at 6p22 in human bladder cancer is associated with increased tumour stage, grade and proliferation index, and in prostate cancer E2F3 overexpression is linked to tumour aggressiveness. We first used small interfering RNA technology to confirm the potential importance of E2F3 overexpression in bladder cancer development. Knockdown of E2F3 expression in bladder cells containing the 6p22 amplicon strongly reduced the extent of bromodeoxyuridine (BrdU) incorporation and the rate of cellular proliferation. In contrast, knockdown of CDKAL1/FLJ20342, another proposed oncogene, from this amplicon had no effect. Expression cDNA microarray analysis on bladder cancer cells following E2F3 knockdown was then used to identify genes regulated by E2F3, leading to the identification of known E2F3 targets such as Cyclin A and CDC2 and novel targets including pituitary tumour transforming gene 1, Polo-like kinase 1 (PLK1) and Caveolin-2. For both bladder and prostate cancer, we have proposed that E2F3 protein overexpression may cooperate with removal of the E2F inhibitor retinoblastoma tumor suppressor protein (pRB) to drive cellular proliferation. In support of this model, we found that ectopic expression of E2F3a enhanced the BrdU incorporation, a marker of cellular proliferation rate, of prostate cancer DU145 cells, which lack pRB, but had no effect on the proliferation rate of PC3 prostate cancer cells that express wild-type pRB. BrdU incorporation in PC3 cells could, however, be increased by overexpressing E2F3a in cells depleted of pRB. When taken together, these observations indicate that E2F3 levels have a critical role in modifying cellular proliferation rate in human bladder and prostate cancer