MicroRNAs in the growth plate are responsive to nutritional cues: association between miR-140 and SIRT1

MicroRNAs (miRNAs) have been reported to be involved in a variety of functions, including skeletal development and longitudinal growth. The aim of this study was to investigate the role of miRNAs in food-restriction-induced growth attenuation and nutrition-induced catch-up growth in the epiphyseal growth plate (EGP). Prepubertal rats were fed ad libitum or were subjected to 40% food restriction for 10 days followed by a renewal of the regular food supply. At sacrifice, tibial EGPs were excised, and the total RNA was extracted and loaded on miRNA microarrays. The miRNA microarray yielded more than 400 miRNAs that are expressed in the EGP of mature animals. Results were confirmed by quantitative polymerase chain reaction. Chondrocyte-specific miR-140-3p showed the highest expression in the mature EGP, and it was one of the few miRNAs that were significantly reduced following nutrition restriction. Changes in predicted miRNA targets were then followed with Western immunoblotting. Direct binding was demonstrated using exogenous miRNA, the 3′UTR of the target mRNA and a luciferase reporter assay. Nutrition restriction induced an increase in the level of the miR-140-3p target, NAD+-dependent SIRT1. This study is the first to show that SIRT1 and miRNAs expressed in the mature EGP are responsive to nutritional cues. Nutrition-induced epigenetic regulation of growth activates two parts of the epigenetic world — miRNAs and histone deacetylases — that are interconnected. Deciphering the role of epigenetic regulation in growth may open a new era of research and pave the way for the development of new treatments for children with growth disorders.     

Window automata analysis of population dynamics in the immune system

A formalism based on window automata is proposed as a method to analyse complex population dynamics. The method is applied to a model of the immune network (Weisbuch, G.et al., 1990.J. theor. Biol. 146, 483–499), and used to predict which attractor the system reaches after antigenic stimulation, as a function of the parameters. The attractors of the dynamics are interpreted in terms of immune conditions such as vaccination or tolerance. Scaling laws that define the regimes in the parameter space corresponding to the specific attractor reached under antigenic stimulation are derived.     

Mathematical modeling of viral kinetics under immune control during primary HIV-1 infection

Primary human immunodeficiency virus (HIV) infection is characterized by an initial exponential increase of viral load in peripheral blood reaching a peak, followed by a rapid decline to the viral setpoint. Although the target-cell-limited model can account for part of the viral kinetics observed early in infection [Phillips, 1996. Reduction of HIV concentration during acute infection: independence from a specific immune response. Science 271 (5248), 497-499], it frequently predicts highly oscillatory kinetics after peak viremia, which is not typically observed in clinical data. Furthermore, the target-cell-limited model is unable to predict long-term viral kinetics, unless a delayed immune effect is assumed [Stafford et al., 2000. Modeling plasma virus concentration during primary HIV infection. J. Theor. Biol. 203 (3), 285-301]. We show here that extending the target-cell-limited model, by implementing a saturation term for HIV-infected cell loss dependent upon infected cell levels, is able to reproduce the diverse observed viral kinetic patterns without the assumption of a delayed immune response. Our results suggest that the immune response may have significant effect on the control of the virus during primary infection and may support experimental observations that an anti-HIV immune response is already functional during peak viremia.