Controlling periodic long-range signalling to drive a morphogenetic transition

Cells use signal relay to transmit information across tissue scales. However, the production of information carried by signal relay remains poorly characterised. To determine how the coding features of signal relay are generated, we used the classic system for long-range signalling: the periodic cAMP waves that drive Dictyostelium collective migration. Combining imaging and optogenetic perturbation of cell signalling states, we find that migration is triggered by an increase in wave frequency generated at the signalling centre. Wave frequency is regulated by cAMP wave circulation, which organises the long-range signal. To determine the mechanisms modulating wave circulation, we combined mathematical modelling, the general theory of excitable media and mechanical perturbations to test competing models. Models in which cell density and spatial patterning modulate the wave frequency cannot explain the temporal evolution of signalling waves. Instead, our evidence leads to a model where wave circulation increases the ability for cells to relay the signal, causing further increase in the circulation rate. This positive feedback between cell state and signalling pattern regulates the long-range signal coding that drives morphogenesis

Collective signalling drives rapid jumping between cell states

Development can proceed in "fits and starts", with rapid transitions between cell states involving concerted transcriptome-wide changes in gene expression. However, it is not clear how these transitions are regulated in complex cell populations, in which cells receive multiple inputs. We address this issue using Dictyostelium cells undergoing development in their physiological niche. A continuous single cell transcriptomics time series identifies a sharp "jump" in global gene expression marking functionally different cell states. By simultaneously imaging the physiological dynamics of transcription and signalling, we show the jump coincides with the onset of collective oscillations of cAMP. Optogenetic control of cAMP pulses shows that different jump genes respond to distinct dynamic features of signalling. Late jump gene expression changes are almost completely dependent on cAMP, while transcript changes at the onset of the jump require additional input. The coupling of collective signalling with gene expression is a potentially powerful strategy to drive robust cell state transitions in heterogeneous signalling environments. Based on the context of the jump, we also conclude that sharp gene expression transitions may not be sufficient for commitment

Clearing the slate: RNA turnover to enable cell state switching?

The distribution of mRNA in tissue is determined by the balance between transcription and decay. Understanding the control of RNA decay during development has been somewhat neglected compared with transcriptional control. Here, we explore the potential for mRNA decay to trigger rapid cell state transitions during development, comparing a bistable switch model of cell state conversion with experimental evidence from different developmental systems. We also consider another potential role for large-scale RNA decay that has emerged from studies of stress-induced cell state transitions, in which removal of mRNA unblocks the translation machinery to prioritise the synthesis of proteins that establish the new cell state

Cell and molecular transitions during efficient dedifferentiation

Dedifferentiation is a critical response to tissue damage, yet is not well understood, even at a basic phenomenological level. Developing Dictyostelium cells undergo highly efficient dedifferentiation, completed by most cells within 24 hr. We use this rapid response to investigate the control features of dedifferentiation, combining single cell imaging with high temporal resolution transcriptomics. Gene expression during dedifferentiation was predominantly a simple reversal of developmental changes, with expression changes not following this pattern primarily associated with ribosome biogenesis. Mutation of genes induced early in dedifferentiation did not strongly perturb the reversal of development. This apparent robustness may arise from adaptability of cells: the relative temporal ordering of cell and molecular events was not absolute, suggesting cell programmes reach the same end using different mechanisms. In addition, although cells start from different fates, they rapidly converged on a single expression trajectory. These regulatory features may contribute to dedifferentiation responses during regeneration

Chromatin motion is constrained by association with nuclear compartments in human cells

In comparison with many nuclear proteins, the movement of chromatin in nuclei appears to be generally constrained. These restrictions on motion are proposed to reflect the attachment of chromatin to immobile nuclear substructures

Marvel analysis of the measured high-resolution rovibrational spectra of H2S

44325 measured and assigned transitions of H$_2^{32}$S, the parent isotopologue of the hydrogen sulfide molecule, are collated from 33 publications into a single database and reviewed critically. Based on this information, rotation-vibration energy levels are determined for the ground electronic state using the Measured Active Rotational-Vibrational Energy Levels (MARVEL) technique. The ortho and para principal components of the measured spectroscopic network of H$_2^{32}$S are considered separately. The verified set of 25293 ortho- and 18778 para- H$_2^{32}$S transitions determine 3969 ortho and 3467 para energy levels. The Marvel results are compared with alternative data compilations, including a theoretical variational linelist.Comment: 39 pages, 3 figures, JQSRT, 201

The impact of spectral line wing cut-off : recommended standard method with application to MAESTRO opacity data base

KLC acknowledges funding from STFC under project number ST/V000861/1.When computing cross-sections from a line list, the result depends not only on the line strength, but also the line shape, pressure-broadening parameters, and line wing cut-off (i.e. the maximum distance calculated from each line centre). Pressure-broadening can be described using the Lorentz line shape, but it is known to not represent the true absorption in the far wings. Both theory and experiment have shown that far from the line centre, non-Lorentzian behaviour controls the shape of the wings and the Lorentz line shape fails to accurately characterize the absorption, leading to an underestimation or overestimation of the opacity continuum depending on the molecular species involved. The line wing cut-off is an often overlooked parameter when calculating absorption cross-sections, but can have a significant effect on the appearance of the spectrum since it dictates the extent of the line wing that contributes to the calculation either side of every line centre. Therefore, when used to analyse exoplanet and brown dwarf spectra, an inaccurate choice for the line wing cut-off can result in errors in the opacity continuum, which propagate into the modelled transit spectra, and ultimately impact/bias the interpretation of observational spectra, and the derived composition and thermal structure. Here, we examine the different methods commonly utilized to calculate the wing cut-off and propose a standard practice procedure (i.e. absolute value of 25 cm−1 for P ≤ 200 bar and 100 cm−1 for P > 200 bar) to generate molecular opacities which will be used by the open-access MAESTRO (Molecules and Atoms in Exoplanet Science: Tools and Resources for Opacities) data base. The pressing need for new measurements and theoretical studies of the far-wings is highlighted.Publisher PDFPeer reviewe

The impact of spectral line wing cut-off: recommended standard method with application to MAESTRO opacity data base

When computing cross-sections from a line list, the result depends not only on the line strength, but also the line shape, pressure-broadening parameters, and line wing cut-off (i.e. the maximum distance calculated from each line centre). Pressure-broadening can be described using the Lorentz line shape, but it is known to not represent the true absorption in the far wings. Both theory and experiment have shown that far from the line centre, non-Lorentzian behaviour controls the shape of the wings and the Lorentz line shape fails to accurately characterize the absorption, leading to an underestimation or overestimation of the opacity continuum depending on the molecular species involved. The line wing cut-off is an often overlooked parameter when calculating absorption cross-sections, but can have a significant effect on the appearance of the spectrum since it dictates the extent of the line wing that contributes to the calculation either side of every line centre. Therefore, when used to analyse exoplanet and brown dwarf spectra, an inaccurate choice for the line wing cut-off can result in errors in the opacity continuum, which propagate into the modelled transit spectra, and ultimately impact/bias the interpretation of observational spectra, and the derived composition and thermal structure. Here, we examine the different methods commonly utilized to calculate the wing cut-off and propose a standard practice procedure (i.e. absolute value of 25 cm−1 for P ≤ 200 bar and 100 cm−1 for P > 200 bar) to generate molecular opacities which will be used by the open-access MAESTRO (Molecules and Atoms in Exoplanet Science: Tools and Resources for Opacities) data base. The pressing need for new measurements and theoretical studies of the far-wings is highlighted

Early Release Science of the exoplanet WASP-39b with JWST NIRCam

Measuring the metallicity and carbon-to-oxygen (C/O) ratio in exoplanet atmospheres is a fundamental step towards constraining the dominant chemical processes at work and, if in equilibrium, revealing planet formation histories. Transmission spectroscopy provides the necessary means by constraining the abundances of oxygen- and carbon-bearing species; however, this requires broad wavelength coverage, moderate spectral resolution, and high precision that, together, are not achievable with previous observatories. Now that JWST has commenced science operations, we are able to observe exoplanets at previously uncharted wavelengths and spectral resolutions. Here we report time-series observations of the transiting exoplanet WASP-39b using JWST's Near InfraRed Camera (NIRCam). The long-wavelength spectroscopic and short-wavelength photometric light curves span 2.0 - 4.0 $\mu$m, exhibit minimal systematics, and reveal well-defined molecular absorption features in the planet's spectrum. Specifically, we detect gaseous H$_2$O in the atmosphere and place an upper limit on the abundance of CH$_4$. The otherwise prominent CO$_2$ feature at 2.8 $\mu$m is largely masked by H$_2$O. The best-fit chemical equilibrium models favour an atmospheric metallicity of 1-100$\times$ solar (i.e., an enrichment of elements heavier than helium relative to the Sun) and a sub-stellar carbon-to-oxygen (C/O) ratio. The inferred high metallicity and low C/O ratio may indicate significant accretion of solid materials during planet formation or disequilibrium processes in the upper atmosphere.Comment: 35 pages, 13 figures, 3 tables, Nature, accepte