The Tiered Radio Extragalactic Continuum (T-RECS) simulation II: HI emission and continuum-HI cross-correlation

In this paper we extend the Tiered Radio Extragalactic Continuum Simulation (T-RECS) to include HI emission. The HI T-RECS model is based on the most recent HI mass function estimates, combined with prescriptions to convert HI mass to total integrated HI flux. It further models source size, morphology and kinematics, including rotational velocity and HI line width. The continuum T-RECS model is updated to improve the agreement with deeper number counts available at 150\,MHz. The model for star-forming galaxies (SFGs) is also modified according to the most recent indications of a star formation rate (SFR)--radio luminosity relation, which depends primarily on stellar mass rather than redshift. We further introduce prescriptions to associate an HI mass to the T-RECS radio continuum SFG and Active Galactic Nuclei (AGN) populations. This gives us a way to meaningfully associate counterparts between HI and continuum catalogues, thus building HI $\times$ continuum simulated observations. Clustering properties of the sources in both HI and continuum are reproduced by associating the galaxies to dark matter haloes of a cosmological simulation. We deliver a set of mock catalogues, as well as the code to produce them, which can be used for simulating observations and predicting results from radio surveys with existing and forthcoming radio facilities, such as the Square Kilometre Array (SKA)Comment: 18 pages, 10 figures, accepted by MNRA

Predicting preschool pain-related anticipatory distress: the relative contribution of longitudinal and concurrent factors

Anticipatory distress prior to a painful medical procedure can lead to negative sequelae including heightened pain experiences, avoidance of future medical procedures, and potential non-compliance with preventative healthcare such as vaccinations. Few studies have examined the longitudinal and concurrent predictors of pain-related anticipatory distress. This paper consists of two companion studies to examine both the longitudinal factors from infancy, as well as concurrent factors from preschool that predict pain-related anticipatory distress at the preschool age. Study 1 examined how well preschool pain-related anticipatory distress was predicted by infant pain responding at 2, 4, 6 and 12 months of age. In Study 2, using a developmental psychopathology framework, longitudinal analyses examined the predisposing, precipitating, perpetuating, and present factors that led to the development of anticipatory distress during routine preschool vaccinations. A sample of 202 caregiverchild dyads was observed during their infant and preschool vaccinations (OUCH Cohort) and was used for both studies. In Study 1, pain responding during infancy was not found to significantly predict pain-related anticipatory distress at preschool. In Study 2, a strong explanatory model was created whereby 40% of the variance in preschool anticipatory distress was explained. Parental behaviours from infancy and preschool were the strongest predictors of child anticipatory distress at preschool. Child age positively predicted child anticipatory distress. This strongly suggests that the involvement of parents in pain management interventions during immunization is one of the most critical factors in predicting anticipatory distress to the preschool vaccination

The ABCDs of Pain Management: A Double-Blind Randomized Controlled Trial Examining the Impact of a Brief Educational Video on Infants’ and Toddlers’ Pain Scores and Parent Soothing Behavior

Objectives To test the efficacy of a brief behavioral pain management strategy (The ABCDs of Needle Pain Management), delivered via video, on infants’ and toddlers’ pain scores and on parental soothing behavior. Methods This was a double-blind, parallel trial design. Parent–child dyads (N = 128) were recruited before their child’s 6-month (infant) or 18-month (toddler) vaccination in a pediatric clinic and randomly assigned to watch a 5-min treatment video or a placebo video. The primary outcome was the Modified Behavior Pain Scale (Taddio et al., Journal of Pain and Symptom Management, 10, pp. 456–463, 1995), coded during four epochs (Pain Reactivity, Pain Regulation 1 min, Pain Regulation 2 min, and Pain Regulation 3 min) after the last vaccination needle. Secondary analyses examined parental use of distraction, rocking, and physical comforting over this same time period. Results Results demonstrated a treatment effect for toddlers (18-month-olds) for the Pain Regulation 1 (d = 0.84) and Pain Regulation 2 (d = 0.76) postvaccination scores. Secondary analyses found differences in parental rocking and physical comforting between treatment conditions and between age-groups (d’s = 0.37–0.54). Conclusions The ABCD pain management strategy delivered via video was an effective way to reduce toddler pain after vaccination and increase parental use of rocking and physical comforting. The treatment effect was not demonstrated with infants

The F-box protein Cdc4/Fbxw7 is a novel regulator of neural crest development in Xenopus laevis.

BACKGROUND: The neural crest is a unique population of cells that arise in the vertebrate ectoderm at the neural plate border after which they migrate extensively throughout the embryo, giving rise to a wide range of derivatives. A number of proteins involved in neural crest development have dynamic expression patterns, and it is becoming clear that ubiquitin-mediated protein degradation is partly responsible for this. RESULTS: Here we demonstrate a novel role for the F-box protein Cdc4/Fbxw7 in neural crest development. Two isoforms of Xenopus laevis Cdc4 were identified, and designated xCdc4alpha and xCdc4beta. These are highly conserved with vertebrate Cdc4 orthologs, and the Xenopus proteins are functionally equivalent in terms of their ability to degrade Cyclin E, an established vertebrate Cdc4 target. Blocking xCdc4 function specifically inhibited neural crest development at an early stage, prior to expression of c-Myc, Snail2 and Snail. CONCLUSIONS: We demonstrate that Cdc4, an ubiquitin E3 ligase subunit previously identified as targeting primarily cell cycle regulators for proteolysis, has additional roles in control of formation of the neural crest. Hence, we identify Cdc4 as a protein with separable but complementary functions in control of cell proliferation and differentiation

An efficient platform for astrocyte differentiation from human induced pluripotent stem cells

Summary: Growing evidence implicates the importance of glia, particularly astrocytes, in neurological and psychiatric diseases. Here, we describe a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs), via a neural progenitor cell (NPC) intermediate. We evaluated this protocol across 42 NPC lines (derived from 30 individuals). Transcriptomic analysis demonstrated that hiPSC-astrocytes from four individuals are highly similar to primary human fetal astrocytes and characteristic of a non-reactive state. hiPSC-astrocytes respond to inflammatory stimulants, display phagocytic capacity, and enhance microglial phagocytosis. hiPSC-astrocytes also possess spontaneous calcium transient activity. Our protocol is a reproducible, straightforward (single medium), and rapid (<30 days) method to generate populations of hiPSC-astrocytes that can be used for neuron-astrocyte and microglia-astrocyte co-cultures for the study of neuropsychiatric disorders. : Brennand, Goate, and colleagues report a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs) via a neural progenitor cell (NPC) intermediate. hiPSC-astrocytes resemble primary human fetal astrocytes, have a transcriptional signature consistent with a non-reactive state, respond to inflammatory stimulants, and enhance microglial phagocytosis. Keywords: human induced pluripotent stem cell, iPSC, astrocyt

Camera traps and genetic identification of faecal samples for detection and monitoring of an Endangered ungulate.

Almost all Indochinese ungulates are classified as globally threatened but efforts to assess and monitor population status have been hampered by their rarity, cryptic nature and uncertainty in accurate identification from sightings. An improved approach is urgently needed to gather information about threatened ungulate species in order to effectively conserve them as, a lack of reliable monitoring methods means that basic information such as population sizes, distribution and habitat associations is currently unknown. Here, we used a combination of camera trapping and genetic detection of the Endangered Eld’s deer, Rucervus eldii, to investigate the utility of these methods to infer intensity of site use within a protected Cambodian dry forest. We asked: 1) Are Eld's deer present in our study area?; 2) How is site use influenced by local habitat?; and 3) Do camera traps or genetic detection perform better in terms of detection and monitoring? Camera traps were deployed and faecal samples collected from Chhaeb Wildlife Sanctuary in Northern Cambodia during the 2017 dry season. Faecal samples were identified as Eld’s deer using newly developed species-specific mitochondrial DNA primers. Camera traps recorded 20 Eld’s deer observations across 3905 trap-nights and 44 out of 71 collected faecal samples, identified by fieldworkers as likely to belong to Eld’s deer, were positively identified to be so. Camera trap surveys and genetic detection demonstrated that Eld’s deer were present in Chhaeb Wildlife Sanctuary, although the number of detections relative to sampling effort was low in both methods (detected at 29% and 1% of sample sites, respectively). Occupancy models showed that water level and tree diameter both had positive relationships, whilst human and domestic or feral pig activity had a negative relationship, with the relative intensity of Eld’s deer site use. Overall, our data suggest that both of our methods can prove effective for monitoring Eld’s deer but that repeated sampling is necessary to account for their low detectability in this area. We suggest that faecal samples are collected during future camera trap monitoring visits to maximise efficiency, increase detectability, and provide the most information to support conservation

Trypanosoma brucei BRCA2 acts in a life cycle-specific genome stability process and dictates BRC repeat number-dependent RAD51 subnuclear dynamics

Trypanosoma brucei survives in mammals through antigenic variation, which is driven by RAD51-directed homologous recombination of Variant Surface Glycoproteins (VSG) genes, most of which reside in a subtelomeric repository of &gt;1000 silent genes. A key regulator of RAD51 is BRCA2, which in T. brucei contains a dramatic expansion of a motif that mediates interaction with RAD51, termed the BRC repeats. BRCA2 mutants were made in both tsetse fly-derived and mammal-derived T. brucei, and we show that BRCA2 loss has less impact on the health of the former. In addition, we find that genome instability, a hallmark of BRCA2 loss in other organisms, is only seen in mammal-derived T. brucei. By generating cells expressing BRCA2 variants with altered BRC repeat numbers, we show that the BRC repeat expansion is crucial for RAD51 subnuclear dynamics after DNA damage. Finally, we document surprisingly limited co-localization of BRCA2 and RAD51 in the T. brucei nucleus, and we show that BRCA2 mutants display aberrant cell division, revealing a function distinct from BRC-mediated RAD51 interaction. We propose that BRCA2 acts to maintain the huge VSG repository of T. brucei, and this function has necessitated the evolution of extensive RAD51 interaction via the BRC repeats, allowing re-localization of the recombinase to general genome damage when needed

Using exomarkers to assess mitochondrial reactive species in vivo

Background: The ability to measure the concentrations of small damaging and signalling molecules such as reactive oxygen species (ROS) in vivo is essential to understanding their biological roles. While a range of methods can be applied to in vitro systems, measuring the levels and relative changes in reactive species in vivo is challenging. Scope of review: One approach towards achieving this goal is the use of exomarkers. In this, exogenous probe compounds are administered to the intact organism and are then transformed by the reactive molecules in vivo to produce a diagnostic exomarker. The exomarker and the precursor probe can be analysed ex vivo to infer the identity and amounts of the reactive species present in vivo. This is akin to the measurement of biomarkers produced by the interaction of reactive species with endogenous biomolecules. Major conclusions and general significance: Our laboratories have developed mitochondria-targeted probes that generate exomarkers that can be analysed ex vivo by mass spectrometry to assess levels of reactive species within mitochondria in vivo. We have used one of these compounds, MitoB, to infer the levels of mitochondrial hydrogen peroxide within flies and mice. Here we describe the development of MitoB and expand on this example to discuss how better probes and exomarkers can be developed. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn. Abbreviations: EPR, electron paramagnetic resonance; GFP, green fluorescent protein; 4-HNE, 4-hydroxynonenal; MitoB, 3-(dihydroxyboronyl)benzyltriphenylphosphonium bromide; MitoP, (3-hydroxybenzyl)triphenylphosphonium bromide; ROS, reactive oxygen species; SOD, superoxide dismutase; TPMP, methyltriphenylphosphonium; TPP, triphenylphosphonium catio

A Simple Nonviral Method to Generate Human Induced Pluripotent Stem Cells Using SMAR DNA Vectors

Induced pluripotent stem cells (iPSCs) are a powerful tool for biomedical research, but their production presents challenges and safety concerns. Yamanaka and Takahashi revolutionised the field by demonstrating that somatic cells could be reprogrammed into pluripotent cells by overexpressing four key factors for a sufficient time. iPSCs are typically generated using viruses or virus-based methods, which have drawbacks such as vector persistence, risk of insertional mutagenesis, and oncogenesis. The application of less harmful nonviral vectors is limited as conventional plasmids cannot deliver the levels or duration of the factors necessary from a single transfection. Hence, plasmids that are most often used for reprogramming employ the potentially oncogenic Epstein–Barr nuclear antigen 1 (EBNA-1) system to ensure adequate levels and persistence of expression. In this study, we explored the use of nonviral SMAR DNA vectors to reprogram human fibroblasts into iPSCs. We show for the first time that iPSCs can be generated using nonviral plasmids without the use of EBNA-1 and that these DNA vectors can provide sufficient expression to induce pluripotency. We describe an optimised reprogramming protocol using these vectors that can produce high-quality iPSCs with comparable pluripotency and cellular function to those generated with viruses or EBNA-1 vectors.</p

Neurodiversity, Networks, and Narratives: Exploring Intimacy and Expressive Freedom in the Time of Covid‐19

The Narratives of Neurodiversity Network (NNN) is a neurodivergent academic, creative, and educator collective that came together with allies during the Covid‐19 pandemic to create a network centred around emerging narratives about neurodiversity and exploring new ways of learning and socialising. The network focuses on exploring the roles of written, spoken, and visual narratives across cultural locations about neuro‐atypical experiences in generating improved agency and self‐advocacy for those who have been subject to pathologization through neuro‐normativity and intersecting oppression. During the last year, widening access to digital platforms has provided a space to explore these issues outside of traditional academic spaces. We run a monthly “Salon,” our mixed‐media “reading, listening, and watching” group, in an effort to find positive representation within contemporary culture. Discussions have moved beyond mimesis and into a consideration of how narrative and storyworlds can question the supposed naturalness of certain ways of being in and perceiving the world. This article interrogates the network’s core principles of nonhierarchical co‐production, including the roles of creativity, community, identity, and emancipatory research which were animated by the new techno‐social context. We consider the cultural lives of neurodiversity in the West and beyond, including ethical and aesthetic dimensions. We share a faith in the power of storytelling to inform new social identities for neurodivergent people and to inform scientific understandings of atypical cognition. In exploring this, we speak through a porous first‐person plural narrator, to unsettle the idea that there is a hegemonic “we” speaking on behalf of all neurodivergent people