Activated TNF-α/NF-κB signaling via down-regulation of Fas-associated factor 1 in asbestos-induced mesotheliomas from Arf knockout mice

The human CDKN2A locus encodes 2 distinct proteins, p16(INK4A) and p14(ARF) [mouse p19(Arf)], designated INK4A (inhibitor of cyclin dependent kinase 4) and ARF (alternative reading frame) here, that are translated from alternatively spliced mRNAs. Human ARF is implicated as a tumor suppressor gene, mainly in association with the simultaneous deletion of INK4A. However, questions remain as to whether loss of ARF alone is sufficient to drive tumorigenesis. Here, we report that mice deficient for Arf are susceptible to accelerated asbestos-induced malignant mesothelioma (MM). MMs arising in Arf (+/−) mice consistently exhibit biallelic inactivation of Arf, but, unexpectedly, do not acquire additional recurrent genetic alterations that we previously identified in asbestos-induced MMs arising in Nf2 (+/−) mice. Array CGH analysis was used to detect a recurrent deletion at chromosome 4C6 in MMs from Arf (+/−) mice. A candidate gene in this region, Faf1 (FAS-associated factor 1), was further explored, because it encodes a protein implicated in tumor cell survival and in the pathogenesis of some human tumor types. We confirmed hemizygous loss of Faf1 and down-regulation of Faf1 protein in a series of MMs from Arf (+/−) mice, and we then showed that Faf1 regulates TNF-α-mediated NF-κB signaling, a pathway previously implicated in asbestos-induced oncogenesis of human mesothelial cells. Collectively, these data indicate that Arf inactivation has a significant role in driving MM pathogenesis, and implicate Faf1 as a key component in the TNF-α/NF-κB signaling node that has now been independently implicated in asbestos-induced oncogenesis

Capillary holdup between vertical spheres

The maximum volume of liquid bridge left between two vertically mounted spherical particles has been theoretically determined and experimentally measured. As the gravitational effect has not been neglected in the theoretical model, the liquid interface profile is nonsymmetrical around the X-axis. Symmetry in the interface profile only occurs when either the particle size ratio or the gravitational force becomes zero. In this paper, some equations are derived as a function of the spheres' sizes, gap width, liquid density, surface tension and body force (gravity/centrifugal) to estimate the maximum amount of liquid that can be held between the two solid spheres. Then a comparison is made between the result based on these equations and several experimental results