An agent-based model for mRNA export through the nuclear pore complex

mRNA export from the nucleus is an essential step in the expression of every protein- coding gene in eukaryotes, but many aspects of this process remain poorly understood. The density of export receptors that must bind an mRNA to ensure export, as well as how receptor distribution affects transport dynamics, is not known. It is also unclear whether the rate-limiting step for transport occurs at the nuclear basket, in the central channel, or on the cytoplasmic face of the nuclear pore complex. Using previously published biophysical and biochemical parameters of mRNA export, we implemented a three-dimensional, coarse-grained, agent-based model of mRNA export in the nanosecond regime to gain insight into these issues. On running the model, we observed that mRNA export is sensitive to the number and distribution of transport receptors coating the mRNA and that there is a rate-limiting step in the nuclear basket that is potentially associated with the mRNA reconfiguring itself to thread into the central channel. Of note, our results also suggest that using a single location-monitoring mRNA label may be insufficient to correctly capture the time regime of mRNA threading through the pore and subsequent transport. This has implications for future experimental design to study mRNA transport dynamics

Prior human polyomavirus and papillomavirus infection and incident lung cancer: a nested case–control study

PURPOSE: To test whether infection with select human polyomaviruses (HPyV) and human papillomaviruses (HPV) is associated with incident lung cancer. METHODS: We performed a nested case-control study, testing serum from the Carotene and Retinol Efficacy Trial (CARET), conducted 1985–2005, for antibodies to Merkel cell (MCV), KI (KIV), and WU (WUV) HPyVs as well as to six high-risk and two low-risk HPV types. Incident lung cancer cases (n=200) were frequency-matched with controls (n=200) on age, enrollment and blood draw dates, intervention arm assignment, and the number of serum freeze / thaw cycles. Sera were tested using multiplex liquid bead microarray antibody assays. We used logistic regression to assess the association between HPyV and HPV antibodies and lung cancer. RESULTS: There was no evidence of a positive association between levels of MCV, KIV, or WUV antibodies and incident lung cancer (P-corrected>0.10 for all trend tests; odds ratio (OR) range 0.72 to 1.09, P-corrected>0.10 for all). There was also no evidence for a positive association between HPV 16 or 18 infection and incident lung cancer (P-corrected≥0.10 for all trend tests; OR range 0.25 to 2.54, P>0.05 for all OR>1), but the number of persons with serologic evidence of these infections was small. CONCLUSIONS: Prior infection with any of several types of HPyV or HPV was not associated with subsequent diagnosis of lung cancer. Infection with these viruses likely does not influence a person’s risk of lung cancer in Western smoking populations