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The star formation and metal enrichment histories of galaxies - at any epoch - constitute one of the key properties of galaxies, and their measurement is a core aim of observational extragalactic astronomy. The lack of deep rest-frame optical coverage at high-redshift has made robust constraints elusive, but this is now changing thanks to the \emph{James Webb Space Telescope (JWST)}. In preparation for the constraints provided by \emph{JWST} we explore the star formation and metal enrichment histories of galaxies at $z=5-13$ using the First Light And Reionisation Epoch Simulations (FLARES) suite. Built on the EAGLE model, the unique strategy of FLARES allows us to simulate a wide range of stellar masses (and luminosities) and environments. While we predict significant redshift evolution of average ages and specific star formation rates our core result is a mostly flat relationship of age and specific star formation rate with stellar mass. We also find that galaxies in this epoch predominantly have strongly rising star formation histories, albeit with the magnitude dropping with redshift and stellar mass. In terms of chemical enrichment we predict a strong stellar mass - metallicity relation present at $z=10$ and beyond alongside significant $\alpha$-enhancement. Finally, we find no environmental dependence of the relationship between age, specific star formation rate, or metallicity with stellar mass., Comment: To be submitted to MNRAS. Comments welcome

Using the First Light And Reionisation Epoch Simulations (\textsc{Flares}) we explore the dust driven properties of massive high-redshift galaxies at $z\in[5,10]$. By post-processing the galaxy sample using the radiative transfer code \textsc{skirt} we obtain the full spectral energy distribution. We explore the resultant luminosity functions, IRX-$\beta$ relations as well as the luminosity-weighted dust temperatures in the Epoch of Reionisation (EoR). We find that most of our results are in agreement with the current set of observations, but under-predict the number densities of bright IR galaxies, which are extremely biased towards the most overdense regions. We see that the \textsc{Flares} IRX-$\beta$ relation (for $5\le z\le8$) predominantly follows the local starburst relation. The IRX shows an increase with stellar mass, plateauing at the high-mass end ($\sim10^{10}$M$_{\odot}$) and shows no evolution in the median normalisation with redshift. We also look at the dependence of the peak dust temperature ($T_{\mathrm{peak}}$) on various galaxy properties including the stellar mass, IR luminosity and sSFR, finding the correlation to be strongest with sSFR. The luminosity-weighted dust temperatures increase towards higher redshifts, with the slope of the $T_{\mathrm{peak}}$ - redshift relation showing a higher slope than the lower redshift relations obtained from previous observational and theoretical works. The results from \textsc{Flares}, which is able to provide a better statistical sample of high-redshift galaxies compared to other simulations, provides a distinct vantage point for the high-redshift Universe., Comment: 19 pages, 16 figures, Published in MNRAS. Data link: https://flaresimulations.github.io/data.html

Transmission between hosts is crucial to the growth, development and reproduction of many parasites. As a consequence, parasites are under selection to maximise transmission success and exhibit many behavioural and morphological adaptations that allow detection of, and movement between, hosts. However, transmission success is not determined by parasites alone, but is also shaped by host behaviours. Often, host behaviours function to minimise the risk of exposure to parasites; in some cases, however, host behaviours may be manipulated by parasites to increase transmission success. In this study, we investigated transmission of the parasitic mite Riccardoella oudemansi between slug (Limacus maculatus) hosts, considering the role of both host and parasite behaviour in determining transmission success. Host-host transmission occurred when slugs were in physical contact, but mites were also capable of moving across the substrate to locate new hosts, a process facilitated by mucus trails. We found no strong evidence that slugs avoid parasitised conspecifics, or that mites manipulate slug behaviour to increase transmission. Finally, mites showed a preference for the mucus of parasitised slugs, but did not discriminate between mucus from their own host and another parasitised slug. A general preference for mucus from parasitised slugs is likely to be important in encouraging mites to remain in close contact with their host and may also facilitate host-switching and outbreeding. We encourage further study of parasitism by Riccardoella in limacid slugs, where cross-species variation in host social behaviour may drive differences in the rate and success of parasite transmission across slug species.

The James Webb Space Telescope (JWST) is set to transform many areas of astronomy, one of the most exciting is the expansion of the redshift frontier to $z>10$. In its first year alone JWST should discover hundreds of galaxies, dwarfing the handful currently known. To prepare for these powerful observational constraints, we use the First Light And Reionisation Epoch (FLARES) simulations to predict the physical and observational properties of the $z>10$ population of galaxies accessible to JWST. This is the first time such predictions have been made using a hydrodynamical model validated at low redshift. Our predictions at $z=10$ are broadly in agreement with current observational constraints on the far-UV luminosity function and UV continuum slope $β$, though the observational uncertainties are large. We note tension with recent constraints $z\sim 13$ from Harikane et al. 2022 - compared to these constraints, FLARES predicts objects with the same space density should have an order of magnitude lower luminosity, though this is mitigated slightly if dust attenuation is negligible in these systems. Our predictions suggest that in JWST's first cycle alone, around $600$ galaxies should be identified at $z>10$, with the first small samples available at $z>13$., Submitted to MNRAS 20/04/2022

JWST has now made it possible to probe the rest-frame optical line emission of high-redshift galaxies extending to z~9, and potentially beyond. To aid in the interpretation of these emerging constraints, in this work we explore predictions for [OIII] emission in high-redshift galaxies using the First Light and Reionisation Epoch Simulations (FLARES). We produce predictions for the [OIII] luminosity function, its correlation with the UV luminosity, and the distribution of equivalent widths (EWs). We also explore how the [OIII] EW correlates with physical properties including specific star formation rate, metallicity, and dust attenuation. Our predictions are largely consistent with recent observational constraints on the luminosity function, average equivalent widths, and line ratios. However, they fail to reproduce the observed tail of high-EW sources and the number density of extreme line emitters. Possibilities to explain these discrepancies include an additional source of ionising photons and/or greater stochasticity in star formation in the model or photometric scatter and/or bias in the observations. With JWST now rapidly building larger samples and a wider range of emission lines the answer to this remaining discrepancy should be available imminently., Comment: 15 pages, accepted for publication in MNRAS, minor changes from original version

We present a mock image catalogue of ~100,000 MUV=-22.5 to -19.6 mag galaxies at z=7-12 from the BlueTides cosmological simulation. We create mock images of each galaxy with the James Webb (JWST), Hubble, Roman, and Euclid Space Telescopes, as well as Subaru, and VISTA, with a range of near- and mid-infrared filters. We perform photometry on the mock images to estimate the success of these instruments for detecting high-z galaxies. We predict that JWST will have unprecedented power in detecting high-z galaxies, with a 95% completeness limit at least 2.5 magnitudes fainter than VISTA and Subaru, 1.1 magnitudes fainter than Hubble, and 0.9 magnitudes fainter than Roman, for the same wavelength and exposure time. Focusing on JWST, we consider a range of exposure times and filters, and find that the NIRCam F356W and F277W filters will detect the faintest galaxies, with 95% completeness at m=27.4 mag in 10ks exposures. We also predict the number of high-z galaxies that will be discovered by upcoming JWST imaging surveys. We predict that the COSMOS-Web survey will detect ~1000 MUV, Comment: Published in MNRAS. The BlueTides Mock Image Catalogue is publicly available as a High Level Science Product (HLSP) via the Mikulski Archive for Space Telescopes (MAST), at https://doi.org/10.17909/er09-4527. Example codes for using the catalogue data are available at https://github.com/madelinemarshall/BlueTidesMockImageCatalogue

We present the intrinsic and observed sizes of galaxies at z ≥ 5 in the First Light And Reionisation Epoch Simulations (flares). We employ the large effective volume of flares to produce a sizeable sample of high-redshift galaxies with intrinsic and observed luminosities and half-light radii in a range of rest-frame ultraviolet (UV) and visual photometric bands. This sample contains a significant number of intrinsically ultracompact galaxies in the far-UV (1500 Å), leading to a negative intrinsic far-UV size–luminosity relation. However, after the inclusion of the effects of dust these same compact galaxies exhibit observed sizes that are as much as 50 times larger than those measured from the intrinsic emission, and broadly agree with a range of observational samples. This increase in size is driven by the concentration of dust in the core of galaxies, heavily attenuating the intrinsically brightest regions. At fixed luminosity we find a galaxy size redshift evolution with a slope of m = 1.21–1.87 depending on the luminosity sample in question, and we demonstrate the wavelength dependence of the size–luminosity relation that will soon be probed by the James Webb Space Telescope.

We measured bird diversity over an 800 m range in altitude to test the factors that influence changes in diversity, in the Atlantic Forest in the state of Sao Paulo, Brazil. We counted forest birds in nine 100 m transects comprising three-point counts, the center of each separated by 200 m. A total of 108 species were found, and diversity was distributed among sampling points and altitude formed a trough-shaped relationship of number of species by area, altitude, and, most strongly, slope. In Principal Coordinate Analysis we found that grouping points by similarity formed three distinct units that were united by altitude: the lowest at near sea level, 100–400 m, and 500–800 m. Thus, we demonstrate that, in the Atlantic Forest, turnover of species with altitude occurs, but unlike higher, often steeper, tropical gradients in Andean forests, where vegetation more clearly changes with elevation, species turnover is more likely to be associated with variables other than changes in vegetation, and which are often not included in studies of the elevation gradient in species richness. The mid-domain effect did not explain altitudinal gradient in diversity, while a quadratic relationship with altitude did, suggesting that reduced abundance and diversity are associated with steeper slopes.

PURPOSE: Down syndrome (DS) is caused by trisomy 21 (Ts21) and results in skeletal deficits including shortened stature, low bone mineral density and a predisposition to early onset osteoporosis. Ts21 causes significant alterations in skeletal development, morphology of the appendicular skeleton, bone homeostasis, age-related bone loss, and bone strength. However, the genetic or cellular origins of DS skeletal phenotypes remain unclear. RECENT FINDINGS: New studies reveal a sexual dimorphism in characteristics and onset of skeletal deficits that differ between DS and typically developing individuals. Age-related bone loss occurs earlier in the DS as compared to general population. SUMMARY: Perturbations of DS skeletal quality arise from alterations in cellular and molecular pathways affected by the overexpression of trisomic genes. Sex-specific alterations occur in critical developmental pathways that disrupt bone accrual, remodeling, and homeostasis and are compounded by aging, resulting in increased risks for osteopenia, osteoporosis and fracture in individuals with DS.

Studying medulloblastoma, the most common malignant paediatric brain tumour, requires simple yet realistic in vitro models. In this study, we optimised a robust, reliable, three-dimensional (3D) culture method for medulloblastoma able to recapitulate the spatial conformation, cell–cell and cell–matrix interactions that exist in vivo and in patient tumours. We show that, when grown under the same stem cell enriching conditions, SHH subgroup medulloblastoma cell lines established tight, highly reproducible 3D spheroids that could be maintained for weeks in culture and formed pathophysiological oxygen gradients. 3D spheroid culture also increased resistance to standard-of-care chemotherapeutic drugs compared to 2D monolayer culture. We exemplify how this model can enhance in vitro therapeutic screening approaches through dual-inhibitor studies and continual monitoring of drug response. Next, we investigated the initial stages of metastatic dissemination using brain-specific hyaluronan hydrogel matrices. RNA sequencing revealed downregulation of cell cycle genes and upregulation of cell movement genes and key fibronectin interactions in migrating cells. Analyses of these upregulated genes in patients showed that their expression correlated with early relapse and overall poor prognosis. Our 3D spheroid model is a significant improvement over current in vitro techniques, providing the medulloblastoma research community with a well-characterised and functionally relevant culture method.

The neurotypical spatiotemporal patterns of gene expression are disrupted in Down syndrome (DS) by trisomy of human chromosome 21 (Hsa21), resulting in altered behavioral development and brain circuitry. The Ts65Dn DS mouse model exhibits similar phenotypes to individuals with DS due to three copies of approximately one-half of the genes found on Hsa21. Dual-specificity Tyrosine Phosphorylation-regulated Kinase 1a (Dyrk1a), one of these triplicated genes, is an attractive target to normalize brain development due to its influence in cellular brain deficits seen in DS. We hypothesized that postnatal development of DYRK1A expression is dysregulated in trisomic animals, and found significant overexpression of DYRK1A in the hippocampus, cerebral cortex, and cerebellum at postnatal day (P) 15 in male-but not female-Ts65Dn mice. We then hypothesized the existence of sex-dependent effects of trisomy on neurobehavioral attributes during P16-17, and that administration of a DYRK1A inhibitor (CX-4945, ~75 mg/kg) beginning on P14 would normalize aberrant behavior in trisomic animals. Both male and female trisomic mice given control injections of phosphate buffered saline (PBS) displayed sustained levels of locomotor activity over a 10-minute test in contrast to the PBS-treated euploid animals that showed significant within-session habituation. Trisomic animals were more persistent in choosing to remain in home shavings in a preference test. Treatment with CX-4945 failed to confirm therapeutic effects. CX-4945 prevented growth, and both CX-4945 and its 10% dimethyl sulfoxide vehicle affected locomotor activity in trisomic and euploid groups, indicating a non-specific disruption of behavior. Despite the negative outcomes for CX-4945, the novel demonstration of sexually dimorphic DYRK1A expression in trisomic animals at P15 supports the broader hypothesis that overexpression of trisomic genes in DS can vary with age, sex, and brain region. Identifying the developmental timing of periods of dysregulated DYRK1A may be important for understanding individual differences in neurodevelopmental trajectories in DS and for developing effective therapeutic interventions targeting DYRK1A.

Animal models of Down syndrome (DS) provide an essential resource for understanding genetic, cellular, and molecular contributions to traits associated with trisomy 21 (Ts21). Recent genetic enhancements in the development of DS models, including the new TcHSA21rat model (Kazuki et al.), have potential to transform our understanding of and potential therapies for Ts21.

PURPOSE To evaluate the refractive impact of centripetal fragmentation using the miLOOP system for nucleus disassembly, which minimizes lens zonulocapsular instability associated with endocapsular lens manipulation. SETTING Private practice, Batesville, Indiana, USA. DESIGN Retrospective comparative consecutive series. METHODS Refractive outcomes were compared for consecutive patients who underwent cataract surgery and intraocular lens implantation before and after the introduction of a microinterventional endocapsular nucleus disassembly technique using the miLOOP system. Eyes with a history of previous surgery or ocular comorbidities were excluded. The primary outcome was the median absolute error (MedAE) from the preoperative predicted refraction. Secondary outcomes included corrected (CDVA) and uncorrected distance visual acuity (UDVA) and the proportion of eyes within predicted diopter (D) ranges. RESULTS A total of 118 eyes of 79 patients were analyzed, with 69 eyes undergoing conventional nuclear disassembly and 49 eyes receiving the microinterventional technique. The MedAE for eyes using conventional nucleus disassembly vs the microinterventional technique was 0.191 D vs 0.107 D, respectively (P = .002). For CDVA and UDVA, the microinterventional approach resulted in a trend toward a higher proportion of eyes achieving acuities better than 20/30, 20/25, and 20/20 compared with conventional techniques. The microinterventional approach showed a trend toward more eyes achieving less than ±0.25 D and ±0.50 D of prediction error from the predicted diopter range. CONCLUSIONS Microinterventional nuclear disassembly might improve refractive outcomes by reducing refractive prediction error.

Summary Nutritional equivalency feeding studies with diets containing genetically modified grain continue to be required by some regulatory agencies as part of the safety assessment of new events. These studies have long been conducted using broiler chickens, as they are very sensitive to nutritional deficiencies and antinutrients in the diet owing to their very rapid growth rate. A new transgenic maize product containing event DP-2O2216-6 (DP202216) with enhanced grain yield potential and an herbicide-tolerance trait has been developed. The nutritional equivalency of grain produced from maize containing this event with conventional grain was evaluated in a 42-D feeding trial with male and female Ross 708 broiler chickens. Broilers consuming diets produced with grain from DP202216 maize plants performed as well and produced similar organ, carcass, and parts yields as broilers consuming diets produced with nontransgenic near-isogenic control grain. In addition, the ranges of observed performance and carcass and organ yield trait values from DP202216 and control groups were similar to the respective ranges observed for broilers fed diets containing nontransgenic commercially available maize grains. Based on these results, it is concluded that grain from DP202216 maize is nutritionally equivalent to grain from nontransgenic near-isogenic maize, consistent with previously published reports on whole-food (where the edible crop tissue is incorporated in the feed) animal feeding studies for other genetically modified events.

When following the growth of structure in the Universe, we propose replacing merger trees with merger graphs, in which haloes can both merge and split into separate pieces. We show that this leads to smoother mass growth and eliminates catastrophic failures in which massive haloes have no progenitors or descendants. For those who prefer to stick with merger trees, we find that trees derived from our merger graphs have similar mass growth properties to previous methods, but again without catastrophic failures. For future galaxy formation modelling, two different density thresholds can be used to distinguish host haloes (extended galactic haloes, groups, and clusters) from higher density subhaloes: sites of galaxy formation.

Medulloblastoma is the most common malignant pediatric brain tumor. Current treatment involves surgery, chemotherapy, and craniospinal radiotherapy, and these are associated with a significant reduction in quality of life. Metastatic dissemination at diagnosis is found in up to 30% of medulloblastoma cases and, alongside therapy resistance, is a significant feature in determining poor outcome. Development of new therapeutic approaches requires models where drug resistance and migration can be readily quantified and that are representative of patient disease. 3D medulloblastoma (3D-MB) spheroids are a simple yet effective means of bridging the gap between 2D culture and in vivo methods, providing users with highly reproducible in vitro models that more accurately recapitulate tumor morphology, drug response, and migration from a tumor mass. Unlike other cancer types, medulloblastoma spheroids fail to grow in their different standard cell culture media; instead, each cell line requires the same stem cell-enriching conditions. This requirement, however, has the advantage that it allows direct comparison of growth and response between cell lines in the absence of any potential media bias. In addition, spheroids can be used to model the initial stages of metastatic dissemination, something that cannot be achieved in 2D culture, providing insight into key changes occurring in migratory cells. Here, we provide protocols that detail the initial generation and maintenance of 3D-MB spheroids from sonic-hedgehog, Group 3, and Group 4 medulloblastoma subgroups, as well as describing functional assays to study drug response and cell migration across hyaluronan matrices, which represent the extracellular matrix backbone of the brain parenchyma. Through application of these simple yet highly representative models, it will be possible to test novel therapeutics targeting metastasis and drug resistance, as well as to develop insights into the mechanistic processes driving relapse in this malignant pediatric brain tumor. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Generation and maintenance of 3D medulloblastoma (3D-MB) spheroids Support Protocol 1: Measuring spheroid size for coefficient-of-variation analysis Basic Protocol 2: Assessing drug response in 3D-MB spheroids Support Protocol 2: 384-well 3D-MB spheroid generation Basic Protocol 3: Immunohistochemical staining of 3D-MB spheroids Basic Protocol 4: Modeling metastatic dissemination using 3D-MB migration models Support Protocol 3: RNA extraction from 3D-MB spheroids.

We study the sizes of galaxies in the Epoch of Reionization using a sample of ~100,000 galaxies from the BlueTides cosmological hydrodynamical simulation from z=7 to 11. We measure the galaxy sizes from stellar mass and luminosity maps, defining the effective radius as the minimum radius which could enclose the pixels containing 50% of the total mass/light in the image. We find an inverse relationship between stellar mass and effective half-mass radius, suggesting that the most massive galaxies are more compact and dense than lower mass galaxies, which have flatter mass distributions. We find a mildly negative relation between intrinsic far-ultraviolet luminosity and size, while we find a positive size-luminosity relation when measured from dust-attenuated images. This suggests that dust is the predominant cause of the observed positive size-luminosity relation, with dust preferentially attenuating bright sight lines resulting in a flatter emission profile and thus larger measured effective radii. We study the size-luminosity relation across the rest-frame ultraviolet and optical, and find that the slope decreases at longer wavelengths; this is a consequence of the relation being caused by dust, which produces less attenuation at longer wavelengths. We find that the far-ultraviolet size-luminosity relation shows mild evolution from z=7 to 11, and galaxy size evolves with redshift as $R\propto(1+z)^{-m}$, where $m=0.662\pm0.009$. Finally, we investigate the sizes of z=7 quasar host galaxies, and find that while the intrinsic sizes of quasar hosts are small relative to the overall galaxy sample, they have comparable sizes when measured from dust-attenuated images., 12 pages, 10 figures. Accepted for publication in MNRAS

Trisomy 21 (Ts21) causes alterations in skeletal development resulting in decreased bone mass, shortened stature and weaker bones in individuals with Down syndrome (DS). There is a sexual dimorphism in bone mineral density (BMD) deficits associated with DS with males displaying earlier deficits than females. The relationships between causative trisomic genes, cellular mechanisms, and influence of sex in DS skeletal abnormalities remain unknown. One hypothesis is that the low bone turnover phenotype observed in DS results from attenuated osteoblast function, contributing to impaired trabecular architecture, altered cortical geometry, and decreased mineralization. DYRK1A, found in three copies in humans with DS, Ts65Dn, and Dp1Tyb DS model mice, has been implicated in the development of postnatal skeletal phenotypes associated with DS. Reduced copy number of Dyrk1a to euploid levels from conception in an otherwise trisomic Ts65Dn mice resulted in a rescue of appendicular bone deficits, suggesting DYRK1A contributes to skeletal development and homeostasis. We hypothesized that reduction of Dyrk1a copy number in trisomic osteoblasts would improve cellular function and resultant skeletal structural anomalies in trisomic mice. Female mice with a floxed Dyrk1a gene (Ts65Dn,Dyrk1afl/wt) were mated with male Osx-Cre+ (expressed in osteoblasts beginning around E13.5) mice, resulting in reduced Dyrk1a copy number in mature osteoblasts in Ts65Dn,Dyrk1a+/+/Osx-Cre P42 male and female trisomic and euploid mice, compared with littermate controls. Male and female Ts65Dn,Dyrk1a+/+/+ (3 copies of DYRK1A in osteoblasts) and Ts65Dn,Dyrk1a+/+/Osx-Cre (2 copies of Dyrk1a in osteoblasts) displayed similar defects in both trabecular architecture and cortical geometry, with no improvements with reduced Dyrk1a in osteoblasts. This suggests that trisomic DYRK1A does not affect osteoblast function in a cell-autonomous manner at or before P42. Although male Dp1Tyb and Ts65Dn mice exhibit similar skeletal deficits at P42 in both trabecular and cortical bone compartments between euploid and trisomic mice, female Ts65Dn mice exhibit significant cortical and trabecular deficits at P42, in contrast to an absence of genotype effect in female Dp1Tyb mice in trabecular bone. Taken together, these data suggest skeletal deficits in DS mouse models and are sex and age dependent, and influenced by strain effects, but are not solely caused by the overexpression of Dyrk1a in osteoblasts. Identifying molecular and cellular mechanisms, disrupted by gene dosage imbalance, that are involved in the development of skeletal phenotypes associated with DS could help to design therapies to rescue skeletal deficiencies seen in DS.