BackgroundDifferentiation of lymphocytes is frequently accompanied by cell cycle changes, interplay that is of central importance for immunity but is still incompletely understood. Here, we interrogate and quantitatively model how proliferation is linked to differentiation in CD4+ T cells.ResultsWe perform ex vivo single-cell RNA-sequencing of CD4+ T cells during a mouse model of infection that elicits a type 2 immune response and infer that the differentiated, cytokine-producing cells cycle faster than early activated precursor cells. To dissect this phenomenon quantitatively, we determine expression profiles across consecutive generations of differentiated and undifferentiated cells during Th2 polarization in vitro. We predict three discrete cell states, which we verify by single-cell quantitative PCR. Based on these three states, we extract rates of death, division and differentiation with a branching state Markov model to describe the cell population dynamics. From this multi-scale modelling, we infer a significant acceleration in proliferation from the intermediate activated cell state to the mature cytokine-secreting effector state. We confirm this acceleration both by live imaging of single Th2 cells and in an ex vivo Th1 malaria model by single-cell RNA-sequencing.ConclusionThe link between cytokine secretion and proliferation rate holds both in Th1 and Th2 cells in vivo and in vitro, indicating that this is likely a general phenomenon in adaptive immunity.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-0957-5) contains supplementary material, which is available to authorized users.

Several lines of evidence suggest that the Archean (4.0–2.5 Ga) mantle was hotter than today's potential temperature (TP) of 1350 °C. However, the magnitude of such difference is poorly constrained, with TP estimation spanning from 1500 to 1600 °C during the Meso‐Archean (3.2–2.8 Ga). Such differences have major implications for the interpreted mechanisms of continental crust generation on the early Earth, as their efficacy is highly sensitive to the TP. Here we integrate petrological modeling with thermomechanical simulations to understand the dynamics of crust formation during Archean. Our results predict that partial melting of primitive oceanic crust produces felsic melts with geochemical signatures matching those observed in Archean cratons from a mantle TP as low as 1450 °C thanks to lithospheric‐scale RayleighTaylor‐type instabilities. These simulations also infer the occurrence of intraplate deformation events that allow an efficient transport of crustal material into the mantle, hydrating it.

This is an invited commentary on the research field concerning the modelling of chromosome organization in the cell nucleus of eukaryotes

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This paper focuses on a thermodynamic model\ud built to predict the reduction of organic drug melting\ud temperature and enthalpy with nanocrystal size decrease.\ud Indeed, this valuable information enables us to evaluate the\ud increase of drug solubility, an aspect of paramount importance\ud for poorly water-soluble organic drugs since a solubility\ud increase is reflected in a bioavailability enhancement. In\ud particular, the model considers the effect of nanocrystals shape\ud (spherical, cylindrical, and parallelepiped-shaped) and morphology\ud (from platelet to needle nanocrystals) on the melting\ud temperature and enthalpy reduction with crystal size decrease.\ud Nimesulide, a typical nonsteroidal and poorly water-soluble\ud drug with anti-inflammatory action, has been chosen as a\ud model drug to test model reliability. Model outcomes suggest that the reduction of melting temperature and enthalpy mainly\ud depends on the ratio between crystals surface area and volume, i.e., on the ratio between the number of surface and bulk\ud molecules constituting the nanocrystal network. The obtained prediction of solubility enhancement and the successful\ud comparison with the outcomes obtained from a molecular dynamics approach, in terms of melting temperature and enthalpy\ud decrease, have confirmed the reliability of the proposed mode