A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

Extensive Transcriptional Regulation of Chromatin Modifiers during Human Neurodevelopment

Epigenetic changes, including histone modifications or chromatin remodeling are regulated by a large number of human genes. We developed a strategy to study the coordinate regulation of such genes, and to compare different cell populations or tissues. A set of 150 genes, comprising different classes of epigenetic modifiers was compiled. This new tool was used initially to characterize changes during the differentiation of human embryonic stem cells (hESC) to central nervous system neuroectoderm progenitors (NEP). qPCR analysis showed that more than 60% of the examined transcripts were regulated, and >10% of them had a >5-fold increased expression. For comparison, we differentiated hESC to neural crest progenitors (NCP), a distinct peripheral nervous system progenitor population. Some epigenetic modifiers were regulated into the same direction in NEP and NCP, but also distinct differences were observed. For instance, the remodeling ATPase SMARCA2 was up-regulated >30-fold in NCP, while it remained unchanged in NEP; up-regulation of the ATP-dependent chromatin remodeler CHD7 was increased in NEP, while it was down-regulated in NCP. To compare the neural precursor profiles with those of mature neurons, we analyzed the epigenetic modifiers in human cortical tissue. This resulted in the identification of 30 regulations shared between all cell types, such as the histone methyltransferase SETD7. We also identified new markers for post-mitotic neurons, like the arginine methyl transferase PRMT8 and the methyl transferase EZH1. Our findings suggest a hitherto unexpected extent of regulation, and a cell type-dependent specificity of epigenetic modifiers in neurodifferentiation

The looks of an odour : visualising neural odour response patterns in real time

Calcium imaging in insects reveals the neural response to odours, both at the receptor level on the antenna and in the antennal lobe, the first stage of olfactory information processing in the brain. Changes of intracellular calcium concentration in response to odour presentations can be observed by employing calcium-sensitive, fluorescent dyes. The response pattern across all recorded units is characteristic for the odour

RESEARCH Open Access The looks of an odour- Visualising neural odour response patterns in real time

Background: Calcium imaging in insects reveals the neural response to odours, both at the receptor level on the antenna and in the antennal lobe, the first stage of olfactory information processing in the brain. Changes of intracellular calcium concentration in response to odour presentations can be observed by employing calciumsensitive, fluorescent dyes. The response pattern across all recorded units is characteristic for the odour. Method: Previously, extraction of odour response patterns from calcium imaging movies was performed offline, after the experiment. We developed software to extract and to visualise odour response patterns in real time. An adaptive algorithm in combination with an implementation for the graphics processing unit enables fast processing of movie streams. Relying on correlations between pixels in the temporal domain, the calcium imaging movie can be segmented into regions that correspond to the neural units. Results: We applied our software to calcium imaging data recorded from the antennal lobe of the honeybee Apis mellifera and from the antenna of the fruit fly Drosophila melanogaster. Evaluation on reference data showed results comparable to those obtained by previous offline methods while computation time was significantly lower. Demonstrating practical applicability, we employed the software in a real-time experiment, performing segmentation of glomeruli- the functional units of the honeybee antennal lobe- and visualisation of glomerula

Alternative early neural differentiation to neural crest progenitors.

<p>(A) hESC were differentiated towards NCP and stained with antibodies specific for <i>OCT4</i> (no stain observed), <i>PAX6</i> (no stain observed), <i>NESTIN</i> and <i>HNK-1</i>. Cell nuclei were labeled with the DNA dye Hoechst H-33342 (blue). Scale bars: 100 µm. (B) Pairwise comparisons of hESC, NEP or NCP yielded 4277 differentially expressed transcripts. The heat map displays the genes after clustering according to the Pearson's correlation of their expression values across samples. The colors represent Z-scores of the row-wise normalized expression values for each gene. The dendrogram indicates the pattern similarities indicated by Spearman correlation distances (1- Spearman correlation coefficient) and shows a large separation of NCP from NEP and hESC. (C) The expression of early neuronal marker genes was measured in three preparations each of hESC, NEP and NCP by qPCR. The transcript levels of NEP and NCP were calculated relative to hESC. The relative gene expression levels were color coded (significant down-regulation vs. hESC in blue; significant up-regulation in red; non-significant changes marked by “N”. The genes showing different behavior in NEP vs NCP are displayed. All measures of variance and p-values are indicated in the supplemental material.</p

Regulation of epigenetic modifiers in NCP, and their comparison to NEP.

<p>The levels of epigenetic regulator gene transcripts were measured in hESC, NCP and NEP by qPCR, and the expression levels were calculated relative to the levels in hESC. All genes that showed significant up- or downregulation in NCP compared to hESC are displayed. The relative expression level (vs. hESC) was color coded, as illustrated in the chromatic scale in the bottom. Genes with >5-fold expression in NCP vs. hESC are shown in bold. For better comparison, the data for the same genes are shown for NEP in the right-hand column. Measures of variance and p-values are indicated in the supplemental material.</p

Synopsis of the regulation of different epigenetic modifier groups at different stages of neuronal differentiation.

<p>Four groups of epigenetic modifiers were selected for a comparison of relative expression levels of NEP, NCP and CTX. Data were obtained, and significances calculated as described earlier. All data are means ± SEM of three independent differentiations. (A) Genes that code for subunits of the BAF remodeling complex. (B) Genes that code for histone acetyl transferases (HAT). (C, D) Genes that are involved in PRC1 and PRC2 complex formation. *: p<0.05 vs hESC transcript level.</p

Transcriptional regulation of epigenetic modifiers during neuroepithelial differentiation.

<p>(A) The levels of epigenetic modifier transcripts of NEP and hESC were analyzed by qPCR in three independent cell preparations, and relative abundances were calculated. The data were color-coded, with up-regulated genes displayed in red and down-regulated genes in blue. Measures of variance and p-values are indicated in supplemental material, and only significantly regulated genes are displayed. Genes up-regulated >5-fold are displayed in bold. (B) The transcript levels of HDACs were determined for hESC, NEP, NCP and CTX. All expression levels of differentiated cells were normalized to those of hESC, and relative abundances are displayed. For instance, seven different HDACs were up-regulated in NEP compared to hESC. The dotted lines indicate 2-fold regulation levels. Data are means ± SEM of three independent differentiations. *: p<0.05</p

Effect of neuroectodermal differentiation on localization of histone marks.

<p>(A) hESC were differentiated towards NEP and stained with antibodies specific for Oct4, HNK-1 (neural crest marker), Pax6 (NEP marker) and nestin (neural stem cell marker). Nuclei were stained with the DNA dye H-33342 (blue). Scale bars: 100 µm. (B) GO analysis of the up-regulated genes in NEP compared to hESC (C) Whole cell extracts from hESC and NEP were analyzed by Western blot with antibodies specific for the indicated histone H3 modifications. Total histone H3 (Pan-H3) was used as loading control. (D) hESC and differentiated NEP were grown on glass cover slips and immunostained with antibodies specific for H3K9me3 or H4K20me3. The upper panels show grey-scale signal intensities of the stain, the lower panels show a superimposition of the same histone stain as above (red) with a DNA counter-stain (DAPI, blue). Arrows mark two cells with a diffuse H4K20me3 stain, which differs from the spot-like pattern always observed in hESC. Scale bars: 10 µm. (E) Chromatin immunoprecipitiation was perfomed from nuclei of hESC or NEP with antibodies specific for H3K4me3 and H3K27me3. The abundance of promoter regions of <i>OCT4, NANOG, PAX6</i> and <i>SOX2</i> was measured by qPCR with specific primers for the indicated genes. Data were compared to control samples prepared without specific antibody and are indicated as relative enrichment. Data are means ± SD from 2 experiments.</p