STUDY QUESTION: Can network modelling of single cell transcriptomic data identify cellular developmental trajectories of fallopian tube (FT) epithelium and reveal functional and pathological divergence from the endometrium? SUMMARY ANSWER: A bidirectional secretory and ciliated differentiation trajectory was apparent from a novel OVGP1+ progenitor population of FT epithelial cells. A causal network model of whole transcriptome action in the FT and endometrium revealed specific functional divergence between secretory cells of these tissues. The network model reflected the latest ectopic pregnancy genome wide association study (GWAS), invoking MUC1 and other candidate genes in mature secretory cells for ectopic and eutopic implantation. WHAT IS KNOWN ALREADY: The fallopian tube forms the in vivo peri-conceptual environment, which has a significant impact on programming offspring health. The fallopian tube epithelium establishes this environment, however the epithelial cell types are poorly characterised in health and disease. STUDY DESIGN, SIZE, DURATION Publicly available benign FT single cell RNA sequencing (scRNA-seq) samples from thirteen women across three studies were combined. Endometrial scRNA-seq samples from thirteen women from one study were used to demonstrate transcriptomic differences between the epithelia of the two tissues. Network models of transcriptomic action were constructed with hypergraphs. PARTICIPANTS/MATERIALS, SETTING, METHODS A meta-analysis of FT scRNA-seq samples was performed to identify epithelial populations. Differential gene expression assessed differences between fallopian tube and endometrial epithelial scRNA-seq data. Functional differences between secretory cells in the tissues were characterised using hypergraph models. To identify associations with ectopic pregnancy, expression quantitative trait loci (eQTLs) from a recent GWAS were mapped onto the network models. MAIN RESULTS AND THE ROLE OF CHANCE Epithelial cells (n=14,360) were clustered into 8 secretory and ciliated epithelial populations in the meta-analysis of 3 scRNA-seq datasets. A novel OVGP1+ epithelial progenitor cell was also identified, and its bi-directional differentiation to mature secretory or mature ciliated populations was mapped by RNA velocity analysis. This progenitor exhibited a high velocity magnitude (12.47) and low confidence (0.69), a combination strongly indicative of multipotent progenitor status. Comparing FT epithelial cells with endometrial epithelial cells revealed 5.3 fold fewer shared genes between FT and endometrial glandular secretory cells than between FT and endometrial ciliated cells, suggesting functional divergence of secretory cells along the reproductive tract. Hypergraphs were used to identify highly coordinated regions of the transcriptome robustly associated with functional gene networks. In the FT secretory cells, these networks were enriched for lipid (FDR<0.002) and immune (FDR<0.00007) related pathways. We mapped eQTLs from a GWAS meta-analysis of 7070 women with ectopic pregnancy over a range of significance (P = 1.68×10−21 − 5.8×10−4) to the hypergraphs of FT and endometrium. Of the 22 genes present in the hypergraphs, 13 of these clustered as highly coordinated genes. This demonstrated the functional importance of MUC1 in the FT and endometrium, (GWAS Study P = 5.32×10[minus]9) and identified additional genes ( SLC7A2, CLDN1, GLS, PEX6, PLXNA4, NR2F1, CLGN, PGGHG, ANKRD36 ) implicated in ectopic pregnancy and eutopic pregnancy. LIMITATIONS, REASONS FOR CAUTION The sample size of reproductive age women was limited in previous studies, and though causal network modelling was used and previous mechanistic data supports candidate gene involvement, no in vitro or in vivo validation of candidate was performed. WIDER IMPLICATIONS OF THE FINDINGS These findings consolidate the existing single cell transcriptomic datasets of the FT to provide a comprehensive understanding of epithelial populations and define functionally distinct secretory cells that contribute to the peri-conceptual environment of the FT. We further implicate the role of MUC1 and secretory cells in ectopic pregnancy and suggest future targets for investigating embryo implantation in the FT and endometrium. ### Competing Interest Statement The authors have declared no competing interest.

Semi-analytic models (SAMs) systematically predict higher stellar-mass scatter at a given halo mass than hydrodynamical simulations and most empirical models. Our goal is to investigate the physical origin of this scatter by exploring modifications to the physics in the SAM Dark Sage. We design two black hole formation models that approximate results from the IllustrisTNG 300-1 hydrodynamical simulation. In the first model, we assign a fixed black hole mass of $10^{6}\, \mathrm{M}_{\odot}$ to every halo that reaches $10^{10.5}\, \mathrm{M}_{\odot}$. In the second model, we disregard any black hole growth as implemented in the standard Dark Sage model. Instead, we force all black hole masses to follow the median black hole mass-halo mass relation in IllustrisTNG 300-1 with a fixed scatter. We find that each model on its own does not significantly reduce the scatter in stellar mass. To do this, we replace the native Dark Sage AGN feedback model with a simple model where we turn off cooling for galaxies with black hole masses above $10^{8}\, \mathrm{M}_{\odot}$. With this additional modification, the SMBH seeding and fixed conditional distribution models find a significant reduction in the scatter in stellar mass at halo masses between $10^{11-14}\, \mathrm{M}_{\odot}$. These results suggest that AGN feedback in SAMs acts in a qualitatively different way than feedback implemented in cosmological simulations. Either or both may require substantial modification to match the empirically inferred scatter in the Stellar Mass Halo Mass Relation (SMHMR).

After more than five years of development, we present a new version of DARK SAGE:, a semi-analytic model (SAM) of galaxy formation that breaks the mould for models of its kind. Included among the major changes is an overhauled treatment of stellar feedback that is derived from energy conservation, operates on local scales, affects gas gradually over time rather than instantaneously, and predicts a mass loading factor for every galaxy. Building on the model's resolved angular momentum structure of galaxies, we now consider the heating of stellar discs, delivering predictions for disc structure both radially and vertically. We add a further dimension to stellar discs by tracking the distribution of stellar ages in each annulus. Each annulus-age bin has its own velocity dispersion and metallicity evolved in the model. This allows DARK SAGE: to make structural predictions for galaxies that previously only hydrodynamic simulations could. We present the model as run on the merger trees of the highest-resolution gravity-only simulation of the MillenniumTNG suite. Despite its additional complexity relative to other SAMs, DARK SAGE: only has three free parameters, the least of any SAM, which we calibrate exclusively against the cosmic star formation history and the z = 0 stellar and H I mass functions using a particle-swarm optimisation method. The DARK SAGE: codebase, written in C and python, is publicly available at https://github.com/arhstevens/DarkSage.

Travel to academic conferences -- where international flights are the norm -- is responsible for a sizeable fraction of the greenhouse gas (GHG) emissions associated with academic work. In order to provide a benchmark for comparison with other fields, as well as for future reduction strategies and assessments, we estimate the CO2-equivalent emissions for conference travel in the field of astronomy for the prepandemic year 2019. The GHG emission of the international astronomical community's 362 conferences and schools in 2019 amounted to 42,500 tCO2e, assuming a radiative-forcing index factor of 1.95 for air travel. This equates to an average of 1.0 $\pm$ 0.6 tCO2e per participant per meeting. The total travel distance adds up to roughly 1.5 Astronomical Units, that is, 1.5 times the distance between the Earth and the Sun. We present scenarios for the reduction of this value, for instance with virtual conferencing or hub models, while still prioritizing the benefits conferences bring to the scientific community.

Aims. In this Virgo Environment Traced in CO (VERTICO) science paper, we aim to study how the star formation process depends on the galactic environment and gravitational interactions in the context of galaxy evolution. We explore the scaling relation between the star formation rate surface density (Σ SFR ) and the molecular gas surface density (Σ mol ), also known as the Kennicutt-Schmidt relation, in a subsample of Virgo cluster spiral galaxies. Methods. We used new Atacama Compact Array and Total Power (ACA+TP) observations from the VERTICO-Atacama Large Millimeter/submillimeter Array (ALMA) Large Program at 720 pc resolution to resolve the molecular gas content, as traced by the 12 CO (2 − 1) transition, across the disks of 37 spiral galaxies in the Virgo cluster. In combination with archival UV and IR observations used to determine the star formation rate (SFR), we estimated the parameters of the Kennicutt-Schmidt (KS) relation for the entire ensemble of galaxies, and within individual galaxies. Results. We find the KS slope for the entire population to be N = 0.97 ± 0.07, with a characteristic molecular gas depletion time of 1.86 Gyr for our full sample, which is in agreement with previous work in isolated, nearby star-forming galaxies. In individual galaxies, we find that the KS slope ranges between 0.69 and 1.40, and that typical star formation efficiencies of molecular gas can vary from galaxy to galaxy by a factor of ∼4. These galaxy-to-galaxy variations account for ∼0.20 dex in scatter in the ensemble KS relation, which is characterized by a 0.42 dex scatter. In addition, we find that the HI-deficient galaxies in the Virgo cluster show a steeper resolved KS relation and lower molecular gas efficiencies than HI-normal cluster galaxies. Conclusions. While the molecular gas content in galaxies residing in the Virgo cluster appears – to first order – to behave similarly to that in isolated galaxies, our VERTICO sample of galaxies shows that cluster environments play a key role in regulating star formation. The environmental mechanisms affecting the HI galaxy content also have a direct impact on the star formation efficiency of molecular gas in cluster galaxies, leading to longer depletion times in HI-deficient members.

Low water activity limits the habitability of aqueous environments, and salts present on Mars are known to reduce water activity. As environmental brines are not pure solutions of a single salt, predicting their water activity is difficult without direct measurement. Martian brines are likely complex and dominated by ions including sulfates and perchlorates, unlike typical terrestrial aqueous environments dominated by sodium chloride. We used the Pitzer model to predict the water activity of multicomponent brines and tested against laboratory-produced brines, including for the first time perchlorate salts that are known to exist on Mars. Our calculations match measurements of single-salt solutions and predict the water activity of multicomponent brines with an accuracy dependent on the quality of thermodynamic data available for a given ion combination. We tested the hypothesis that some salts will dominate the water activity, and therefore habitability, of multicomponent brines. Some salts, such as sodium and magnesium sulfates, did not strongly modulate the water activity of the solution, whereas others such as magnesium chloride and some perchlorates did. Applied to the history of Mars, the data suggest that sulfates and sodium chloride present in Noachian and early Hesperian environments would not have limited habitability. Perchlorates produced photochemically later in the Amazonian could impose a water activity limit at high concentrations that is not significantly changed by other salts. Overall we found that magnesium and calcium chlorides mixed with perchlorates can reach the lowest water activity values and therefore the lowest habitability of the brines tested.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Background Gene expression (GE) data have shown promise as a novel tool to aid in the diagnosis of childhood growth hormone deficiency (GHD) when comparing GHD children to normal children. The aim of this study was to assess the utility of GE data in the diagnosis of GHD in childhood and adolescence using non-GHD short stature children as a control group. Methods GE data was obtained from patients undergoing growth hormone stimulation testing. Data were taken for the 271 genes whose expression was utilized in our previous study. The synthetic minority oversampling technique was used to balance the dataset and a random forest algorithm applied to predict GHD status. Results 24 patients were recruited to the study and eight subsequently diagnosed with GHD. There were no significant differences in gender, age, auxology (height SDS, weight SDS, BMI SDS) or biochemistry (IGF-I SDS, IGFBP-3 SDS) between the GHD and non-GHD subjects. A random forest algorithm gave an AUC of 0.97 (95% CI 0.93 – 1.0) for the diagnosis of GHD. Conclusion This study demonstrates highly accurate diagnosis of childhood GHD using a combination of GE data and random forest analysis.

We analyze cold-gas distributions in Virgo cluster galaxies using resolved CO(2-1) (tracing molecular hydrogen, H2) and HI observations from the Virgo Environment Traced In CO (VERTICO) and the VLA Imaging of Virgo in Atomic Gas (VIVA) surveys. From a theoretical perspective, it is expected that environmental processes in clusters will have a stronger influence on diffuse atomic gas compared to the relatively dense molecular gas component, and that these environmental perturbations can compress the cold interstellar medium in cluster galaxies leading to elevated star formation. In this work we observationally test these predictions for star-forming satellite galaxies within the Virgo cluster. We divide our Virgo galaxy sample into HI-normal, HI-tailed, and HI-truncated classes and show, unsurprisingly, that the HI-tailed galaxies have the largest quantitative HI asymmetries. We also compare to a control sample of non-cluster galaxies and find that Virgo galaxies, on average, have HI asymmetries that are 40 +/- 10 per cent larger than the control. There is less separation between control, HI-normal, HI-tailed, and HI-truncated galaxies in terms of H2 asymmetries, and on average, Virgo galaxies have H2 asymmetries that are only marginally (20 +/- 10 per cent) larger than the control sample. We find a weak correlation between HI and H2 asymmetries over our entire sample, but a stronger correlation for those specific galaxies being strongly impacted by environmental perturbations. Finally, we divide the discs of the HI-tailed Virgo galaxies into a leading half and trailing half according to the observed tail direction. We find evidence for excess molecular gas mass on the leading halves of the disc. This excess molecular gas on the leading half is accompanied by an excess in star formation rate such that the depletion time is, on average, unchanged.

We study how environment regulates the star formation cycle of 33 Virgo Cluster satellite galaxies on 720 parsec scales. We present the first resolved star-forming main sequence for cluster galaxies, dividing the sample based on their global HI properties and comparing to a control sample of field galaxies. HI-poor cluster galaxies have reduced star formation rate (SFR) surface densities with respect to both HI-normal cluster and field galaxies (0.5 dex), suggesting that mechanisms regulating the global HI content are responsible for quenching local star formation. We demonstrate that the observed quenching in HI-poor galaxies is caused by environmental processes such as ram pressure stripping (RPS) simultaneously reducing molecular gas surface density and star formation efficiency (SFE), compared to regions in HI-normal systems (by 0.38 and 0.22 dex, respectively). We observe systematically elevated SFRs that are driven by increased molecular gas surface densities at fixed stellar mass surface density in the outskirts of early-stage RPS galaxies, while SFE remains unchanged with respect to the field sample. We quantify how RPS and starvation affect the star formation cycle of inner and outer galaxy discs as they are processed by the cluster. We show both are effective quenching mechanisms with the key difference being that RPS acts upon the galaxy outskirts while starvation regulates the star formation cycle throughout disc, including within the truncation radius. For both processes, the quenching is caused by a simultaneous reduction in molecular gas surface densities and SFE at fixed stellar mass surface density.

We use the Evolution and Assembly of GaLaxies and their Environments (eagle) and IllustrisTNG (The Next Generation) cosmological simulations to investigate the properties of the baryonic specific angular momentum (j), baryonic mass (M), and atomic gas fraction (f(atm)) plane for nearby galaxies. We find EAGLE and TNG to be in excellent agreement with each other. These simulations are also consistent with the results obtained with eXtended GALEX Arecibo SDSS Survey (xGASS) for gas fractions greater than 0.01. This implies that the disagreements previously identified between xGASS and predictions from simple analytical disc stability arguments also holds true for eagle and tng. For lower gas fraction (the regime currently unconstrained by observations), both simulations deviate from the plane but still maintain good agreement with each other. Despite the challenges posed by resolution limits at low gas fractions, our findings suggest a potential disconnect between angular momentum and gas fraction in the gas-poor regime, implying that not all gas-poor galaxies have low specific angular momentum.

Background: Single cell transcriptomics offers an avenue for predicting, with improved accuracy, the gene networks that are involved in the establishment of the first direct cell–cell interactions between the blastocyst and the maternal luminal epithelium. We hypothesised that in silico modelling of the maternal–embryonic interface may provide a causal model of these interactions, leading to the identification of genes associated with a successful initiation of implantation. Methods: Bulk and single cell RNA-sequencing of endometrial epithelium and scRNAseq of day 6 and 7 trophectoderm (TE) were used to model the initial encounter between the blastocyst and the maternal uterine lining epithelium in silico. In silico modelling of the maternal–embryonic interface was performed using hypernetwork (HN) analysis of genes mediating endometrial–TE interactions and the wider endometrial epithelial transcriptome. A hypernetwork analysis identifies genes that co-ordinate the expression of many other genes to derive a higher order interaction likely to be causally linked to the function. Potential interactions of TE with non-ciliated luminal cells, ciliated cells, and glandular cells were examined. Results: Prominent epithelial activities include secretion, endocytosis, ion transport, adhesion, and immune modulation. Three highly correlated clusters of 25, 22 and 26 TE-interacting epithelial surface genes were identified, each with distinct properties. Genes in both ciliated and non-ciliated luminal epithelial cells and glandular cells exhibit significant functional associations. Ciliated cells are predicted to bind to TE via galectin–glycan interaction. Day 6 and day 7 embryonic–epithelial interactomes are largely similar. The removal of aneuploid TE-derived mRNA invoked only subtle differences. No direct interaction with the maternal gland epithelial cell surface is predicted. These functional differences validate the in silico segregation of phenotypes. Single cell analysis of the epithelium revealed significant change with the cycle phase, but differences in the cell phenotype between individual donors were also present. Conclusions: A hypernetwork analysis can identify epithelial gene clusters that show correlated change during the menstrual cycle and can be interfaced with TE genes to predict pathways and processes occurring during the initiation of embryo–epithelial interaction in the mid-secretory phase. The data are on a scale that is realistic for functional dissection using current ex vivo human implantation models. A focus on luminal epithelial cells may allow a resolution to the current bottleneck of endometrial receptivity testing based on tissue lysates, which is confounded by noise from multiple diverse cell populations.