Spanning tree model and the assembly kinetics of RNA viruses.

Single-stranded RNA (ssRNA) viruses self-assemble spontaneously in solutions that contain the viral RNA genome molecules and viral capsid proteins. The self-assembly of empty capsids can be understood on the basis of free energy minimization. However, during the self-assembly of complete viral particles in the cytoplasm of an infected cell, the viral genome molecules must be selected from a large pool of very similar host messenger RNA molecules and it is not known whether this also can be understood by free energy minimization. We address this question using a simple mathematical model, the spanning tree model, that was recently proposed for the assembly of small ssRNA viruses. We present a statistical physics analysis of the properties of this model. RNA selection takes place via a kinetic mechanism that operates during the formation of the nucleation complex and that is related to Hopfield kinetic proofreading.

Packaging contests between viral RNA molecules and kinetic selectivity.

The paper presents a statistical-mechanics model for the kinetic selection of viral RNA molecules by packaging signals during the nucleation stage of the assembly of small RNA viruses. The effects of the RNA secondary structure and folding geometry of the packaging signals on the assembly activation energy barrier are encoded by a pair of characteristics: the wrapping number and the maximum ladder distance. Kinetic selection is found to be optimal when assembly takes place under conditions of supersaturation and also when the concentration ratio of capsid protein and viral RNA concentrations equals the stoichiometric ratio of assembled viral particles. As a function of the height of the activation energy barrier, there is a form of order-disorder transition such that for sufficiently low activation energy barriers, kinetic selectivity is erased by entropic effects associated with the number of assembly pathways.

Consumption of soy-based infant formula is not associated with early onset of puberty.

PURPOSE: The use of soy products is common in young children with cow milk allergy (CMA). The aim was to examine prospectively the association between infantile consumption of soy-based formula, growth parameters and early pubertal signs, in comparison to cow milk-based formula. METHODS: A nested case-control study was conducted, selected from a cohort of infants prospectively followed from birth until the age of 3 years for eating habits and the development of IgE-mediated CMA. Infants who consumed only soy-based formula were included in the soy group. The control group was randomly selected from those without IgE-CMA and not receiving soy formula. Study participants were reevaluated between ages 7.8 and 10.5 years by an interview, nutritional intake by 3 days diaries, and height, weight, and pubertal signs by physical examination. RESULTS: The soy-fed group included 29 participants (17 males), median age 8.92 years IQR (8.21, 9.42). The control group included 60 participants (27 males), median age 8.99 years IQR (8.35, 9.42). The groups had comparable height and BMI z scores (- 0.17 ± 1.08 versus - 0.16 ± 1.01, p = 0.96, and 0.67 ± 1.01 versus 0.53 ± 1.02, p = 0.56, for soy and control groups, respectively). Four (three males and one female) from the soy-group (13.8%) and eight females from the control-group (13.3%) had early pubertal signs (p = 0.95). No association was detected between puberty and infantile nutrition, after controlling for BMI and family data. No association with puberty or differences between groups were found in current daily consumption of soy, micronutrients, energy, carbohydrates, fat, and protein. CONCLUSIONS: This is the first prospective, physical examination-based study, demonstrating no association between infantile soy-based formula consumption and growth and puberty parameters.

Promyelocytic leukemia protein is required for gain of function by mutant p53.

Mutations in the p53 tumor suppressor are the most common genetic events in human cancer. These mutations not only result in a loss of wild-type p53 activity, but can also lead to a gain of new oncogenic properties. Understanding how these gained functions are regulated is in its infancy. In this study, we show that the promyelocytic leukemia (PML) protein is an important regulator of mutant p53. We show that PML interacts with mutant p53. Importantly, PML enhances the transcriptional activity of mutant p53. Unexpectedly, PML is required for the proliferation and colony formation of cancer cells bearing mutant p53. Down-regulation of PML expression inhibits the growth of mutant p53-expressing cancer cells, predominantly by promoting cell cycle arrest. Our results suggest that the tumor suppression function of PML depends on the status of p53. In the context of mutant p53, PML enhances its cancer-promoting activities.