Numerical Modelling Of The V-J Combinations Of The T Cell Receptor TRA/TRD Locus

T-Cell antigen Receptor (TR) repertoire is generated through rearrangements of V and J genes encoding α and β chains. The quantification and frequency for every V-J combination during ontogeny and development of the immune system remain to be precisely established. We have addressed this issue by building a model able to account for Vα-Jα gene rearrangements during thymus development of mice. So we developed a numerical model on the whole TRA/TRD locus, based on experimental data, to estimate how Vα and Jα genes become accessible to rearrangements. The progressive opening of the locus to V-J gene recombinations is modeled through windows of accessibility of different sizes and with different speeds of progression. Furthermore, the possibility of successive secondary V-J rearrangements was included in the modelling. The model points out some unbalanced V-J associations resulting from a preferential access to gene rearrangements and from a non-uniform partition of the accessibility of the J genes, depending on their location in the locus. The model shows that 3 to 4 successive rearrangements are sufficient to explain the use of all the V and J genes of the locus. Finally, the model provides information on both the kinetics of rearrangements and frequencies of each V-J associations. The model accounts for the essential features of the observed rearrangements on the TRA/TRD locus and may provide a reference for the repertoire of the V-J combinatorial diversity

NFATc1 controls the cytotoxicity of CD8+ T cells

NFAT nuclear translocation has been shown to be required for CD8+ T cell cytokine production in response to viral infection. Here the authors show NFATc1 controls the cytotoxicity and metabolic switching of activated CD8+ T cells required for optimal response to bacteria and tumor cells

The human IL-3 locus is regulated cooperatively by two NFAT-dependent enhancers that have distinct tissue-specific activities

Hawwari, Abbas ; Burrows, Joanna ; Vadas, Mathew A ; Cockerill, Peter

Reconstitution of T cell-specific transcription directed by composite NFAT/Oct elements

Andrew G. Bert, Joanna Burrows, Abbas Hawwari, Mathew A. Vadas and Peter N. Cockeril

Synchronous analysis of cyclo-non-stationary signals: A comprehensive study with aeronautic applications

International audienc

Deletion of retinoic acid-related orphan receptor gamma reduces body weight and hepatic lipids in mice by modulating the expression of lipid metabolism genes

Aim: Retinoic acid-related orphan receptor γ (RORγ) functions as a ligand-dependent transcription factor and its loss has been shown to affect the circadian expression of lipid metabolism genes. However, its effect on body weight gain and hepatic lipids is not well understood. In this study, we investigated the impact of Rorγ gene deletion on changes in body weight and hepatic lipids.Methods: Body weight and lipids were analyzed in the plasma and liver. Expression of lipid metabolism genes in the liver was evaluated in wild type and Rorγ knockout mice.Results: We show that deletion of RORγ results in reduced body weight and fewer lipids in the liver. Analysis of gene expression showed that deletion of Rorγ resulted in an overall lower expression of genes and transcription factors involved in lipid biosynthesis. We observed a decrease in the gene expression of cholesterol biosynthesis, efflux, and esterification but an increase in bile acid synthesis. There was a decrease in fatty acid and triglycerides biosynthesis genes and an increase in the fatty acid uptake genes. The decrease in the expression of lipid biosynthesis genes was accompanied by the decrease in the sterol response element binding protein (Srebp) genes. We observed an increase in the expression of peroxisome proliferator-activated receptor alpha (Ppara) and a decrease in the expression of acetyl-CoA carboxylase 2 (Acc2) genes.Conclusion: Our data suggest that RORγ regulates body weight and lipid metabolism genes and its modulation may be beneficial for the management of obesity and related lipid metabolic disorders

Using a smartphone camera to analyse rotating and vibrating systems: Feedback on the SURVISHNO 2019 contest

International audienceA smartphone is a low-cost pocket wireless multichannel multiphysical data acquisition system: the use of such a device for noise and vibration analysis is a challenging task. To what extent is it possible to carry out relevant analysis from it? The Survishno conference, held in Lyon in July 2019, proposed a contest to participants based on this subject. Two challenges were proposed, wherein each a mute video showing an object moving/excited at different frequencies was provided. Due to the frequencies set and the video sampling characteristics, special effects occurred and are visible on both videos. From the first video, participants were asked to estimate the Instantaneous Angular Speed (IAS) of a rotating fan. From the second video, they were asked to perform the modal analysis of a cantilever beam. This paper gathers the interesting ideas proposed by the contestants and proposes a global method to solve these two problems. One major point of the paper might be the advantageous use of the rolling shutter effect, a well-known artefact of smartphone videos, to perform advanced mechanical analyses: the consideration of the unavoidable slight phase shift between the acquisition of each pixel opens up the possibility to perform a dynamic analysis at frequencies that are much higher than the video frame rate