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Head, J.

Publications and source records attributed to Head, J..

8 recordsLinked to original sources

Non-invasive genomic sampling uncovers novel connectivities and origins of confiscated gorillas

BackgroundGorillas are a group of African great apes with two species and four subspecies that are currently critically endangered or endangered. Previous studies that analysed the genetics of wild gorillas from non-invasive samples, such as faeces or hair, analysed short mitochondrial or nuclear markers, which may not reflect the wider nuclear genome. Recent technical advances in target capture hybridisation, enrich the endogenous DNA content of non-invasive samples, allowing contiguous genomic regions to be sequenced. ResultsHere, we generated georeferenced genetic data from faecal and hair samples of 280 wild gorillas, sampled from three of the four gorilla subspecies, across large parts of their present-day distributions. With this expanded representation of gorilla genetic diversity in the wild, we detected three population clusters in western lowland gorillas, with the Sangha River and its affluents acting as significant barriers to gene flow. We reconstructed patterns of past population connectivity between western lowland gorillas in the north-eastern distribution range and Cross River gorillas, which may have been facilitated by a migration corridor also used by the Central and Nigeria-Cameroon chimpanzee subspecies. Finally, we predicted the geographic origins of wild-born gorillas, achieving a mean prediction error of 65 km, with a population-level resolution for mountain gorillas and some populations of western lowland gorillas. ConclusionOur work characterises fine-scale population structure in western lowland gorillas, which will be informative for future conservation strategies. This proof of concept in predicting geographic locations of wild gorillas, will be useful for future applications to geolocalise trafficked or rescued gorillas.

evolutionary biology↗

Engineering a Bright Near-Infrared Fluorescent Protein by Screening a Comprehensive Phenotypic Landscape

Near-infrared fluorescent proteins (niRFPs) are valuable markers for tracking cellular phenomena as they offer greater imaging depth, lower background, and minimal invasiveness relative to other fluorescent probes. The small ultra red fluorescent protein (smURFP) is the brightest niRFP currently reported and has been the subject of several mutagenesis studies to improve its biophysical characteristics. Here, we demonstrate a systematic approach to exploring the mutational landscape of smURFP using a comprehensive deep mutational scanning (DMS) library to identify novel smURFP mutations which confer greater in vivo fluorescence. By observing changes in relative abundance between naive and fluorescence sorted populations, we provide analysis of the enrichment of all possible single-codon substitutions, insertions, and deletions for smURFP. Enriched populations yielded a series of seven single-codon substitutions which confer a three-fold increase in in vivo fluorescence in E. coli when combined. Finally, we assess the potential underlying mechanisms for increased fluorescence by characterizing the biophysical and photophysical properties of the mutant niRFP sequences. We confirm that two of the derived smURFP sequences have a higher molecular brightness than wild type and yield the brightest niRFP reported.

synthetic biology↗

Local genetic adaptation to habitat in wild chimpanzees

How populations adapt to their environment is a fundamental question in biology. Yet we know surprisingly little about this process, especially for endangered species such as non-human great apes. Chimpanzees, our closest living relatives, are particularly interesting because they inhabit diverse habitats, from rainforest to woodland-savannah. Whether genetic adaptation facilitates such habitat diversity remains unknown, despite having wide implications for evolutionary biology and conservation. Using 828 newly generated exomes from wild chimpanzees, we find evidence of fine-scale genetic adaptation to habitat. Notably, adaptation to malaria in forest chimpanzees is mediated by the same genes underlying adaptation to malaria in humans. This work demonstrates the power of non-invasive samples to reveal genetic adaptations in endangered populations and highlights the importance of adaptive genetic diversity for chimpanzees. One-Sentence SummaryChimpanzees show evidence of local genetic adaptation to habitat, particularly to pathogens, such as malaria, in forests.

evolutionary biology↗

Towards establishing a 24-hour, microplate-based, transcriptomics assay for rainbow trout embryos

There is interest in the development of early-life stage (ELS) tests with fish embryo models that are high-throughput and can generate transcriptomics point of departure (tPOD) values. The objective of this study was to establish a method in rainbow trout (Oncorhynchus mykiss) hatchlings that could satisfy both of these interests. We based our pilot method on recent efforts by U.S. EPA researchers to establish a larval fathead minnow high throughput transcriptomics assay. Here, 1-2 day post hatch trout were assayed in 24-well plates in which they were exposed for 24 hours to 12 different concentrations of test chemicals, including a negative control (DMSO, culture water). Test concentrations were anchored with a chemicals LC50 data from the US EPA ECOTOX database and EnviroTox database, and from this, concentrations were spaced on a half-log basis that spanned 6-7 orders of magnitude. In pilot study 1 we tested 3,4-dichloroaniline, CuSO4 (0.34 mg/L), and ethinylestradiol. In pilot study 2 we tested 3,4-dichloroaniline (58.5 mg/L), CuSO4 (0.34 and 0.41 mg/L), ethinylestradiol (>10 {micro}g/L), permethrin (>10 {micro}g/L), malathion (0.61 mg/L), 6PPD quinone (5.6 {micro}g/L), acetaldehyde (41.2 mg/L), 4-fluoroaniline (242.7 mg/L), glyphosate ([~]150 mg/L), ethanol (>1 g/L), thiamethoxam (>300 mg/L), and allyl alcohol (>30 mg/L). In both pilot studies derived LC50 values are provided in parentheses. Repeated studies of CuSO4 yielded consistent LC50 values (0.34, 0.34, 0.41 mg/L). The correlation between LC50s from the current study for rainbow trout embryos versus those from the literature on adult rainbow trout for 7 chemicals was r2 = 0.91. Work is underway to optimize transcriptomics assays from these samples using EcoToxChips and UPXome, with the ultimate goal to be able to derive transcriptomics points of departure. Taken together these results provide a foundation towards establishing a novel testing platform for chemical and environmental risk assessment that is much quicker (24 hrs), ethical (non-protected life stages), resource efficient (e.g., microplate-based, small volumes of chemicals), and more informative (molecular clues into MOA) than traditional bioassay approaches.

pharmacology and toxicology↗

Resource requirements for ecotoxicity testing: A comparison of traditional and new approach methods

Toxicity testing is under transformation as it aims to harness the potential of New Approach Methods (NAMs) as alternative test methods that may be less resource intensive (i.e., fewer animals, cheaper costs, quicker assays) than traditional approaches while also providing more data and information. While many stakeholders are of the opinion that this unfolding transformation holds significant promise as a more efficient and ethical way forward, few studies have compared the resources required for NAMs versus those needed for traditional animal-based toxicity tests, particularly in the field of ecotoxicology. The objective was to compare resources needed for traditional animal-based ecotoxicity tests versus alternative tests using emergent NAMs. From a bibliometric review, we estimate that traditional tests for a single chemical cost $118,000 USD, require 135 animals, and take 8 weeks. In comparison, alternative tests cost $2,600, require 20 animals (or none), and take up to 4 weeks to test 16 (to potentially hundreds of) chemicals. Based on our analysis we conclude that NAMs in ecotoxicology can be more advantageous than traditional methods in terms of resources required (i.e., monetary costs, number of animals needed, and testing times). We note, however, that the evidence underpinning these conclusions is relatively sparse. Moving forward, groups developing and applying NAMs should provide more detailed accounts of the resources required. In addition, there is also a need for carefully designed case studies that demonstrate the domain of applicability of NAMs (and make comparisons to traditional tests) to ultimately build confidence among the user community.

pharmacology and toxicology↗

Predicting range shifts of African apes under global change scenarios

AimModelling African great ape distribution has until now focused on current or past conditions, whilst future scenarios remain scarcely explored. Using an ensemble forecasting approach, we predicted changes in taxon-specific distribution under future scenarios of climate, land-use and human population changes. LocationSub-Saharan Africa MethodsWe compiled occurrence data on African ape populations from the IUCN A.P.E.S. database and extracted relevant human-, climate- and habitat-related predictors representing current and future (2050) conditions to predict taxon-specific distribution under a best- and a worst-case scenario, using ensemble forecasting. Given the large effect on model predictions, we further tested algorithm sensitivity by considering default and non-default modelling options. The latter included interactions between predictors and polynomial terms in correlative algorithms. ResultsThe future distributions of gorilla and bonobo populations are likely to be directly determined by climate-related variables. In contrast, future chimpanzee distribution is influenced mostly by anthropogenic variables. Both our modelling approaches produced similar model accuracy, although a slight difference in the magnitude of range change was found for Gorilla beringei beringei, G. gorilla diehli, and Pan troglodytes schweinfurthii. On average, a decline of 50% of the geographic range (non-default; or 55% default) is expected under the best scenario if no dispersal occurs (57% non-default or 58% default in worst scenario). However, new areas of suitable habitat are predicted to become available for most taxa if dispersal occurs (81% or 103% best, 93% or 91% worst, non-default and default, respectively), except for G. b. beringei. Main ConclusionsDespite the uncertainty in predicting the precise proportion of suitable habitat by 2050, both modelling approaches predict large range losses for all African apes. Thus, conservation planners urgently need to integrate land-use planning and simultaneously support conservation and climate change mitigation measures at all decision-making levels both in range countries and abroad.

ecology↗

Acute stressors experienced by layer breeders do not affect measures of stress and fear in their offspring

Stressors experienced by layer breeders during egg production can lead to changes in the egg hormone content, potentially impacting their offspring, the commercial layers. Genetic differences might also affect the offsprings susceptibility to maternal experiences. In this study, we tested if maternal stress affects measures of stress and fear in five strains of layer breeders: commercial brown 1 & 2, commercial white 1 & 2 and a pure line White Leghorn. Each strain was equally separated into two groups: "Maternal Stress" (MS), where hens were subjected to a series of 8 consecutive days of acute psychological stressors, and "Control," which received routine husbandry. Additional eggs from Control were injected either with corticosterone diluted in a vehicle solution ("CORT") or just "Vehicle." Stress- and fear-responses of the offspring were measured in a plasma corticosterone test and a combined human approach and novel object test. Both MS and CORT treatments failed to affect the measured endpoints in the offspring, but significant strain differences were found. The offspring of the white strains showed a higher physiological response compared to brown strains, but the White 2 offspring was consistently the least fearful strain in the behaviour tests. Our study found that the acute psychological stressors experienced by layer breeders did not affect the parameters tested in their offspring and that corticosterone does not seem to be the primary mediator of maternal stress in laying hens. This is highly important, as in poultry production, layer breeders are often subjected to short-term stressors. In addition, we successfully dissociated the physiological and behavioural parameters of stress response in laying hens, showing that increased concentrations of plasma corticosterone in response to stress is not directly associated with high levels of fear.

animal behavior and cognition↗

A cellular and spatial map of the choroid plexus across brain ventricles and ages

The choroid plexus (ChP), located in each brain ventricle, produces cerebrospinal fluid (CSF) and forms the blood-CSF barrier, but is under-characterized. Here, we combine single cell RNA-Seq and spatial mapping of RNA and proteins to construct an atlas of each ChP in the developing and adult mouse brain. Each ChP comprises of epithelial, endothelial, mesenchymal, immune, neuronal, and glial cells, with distinct subtypes, differentiation states and anatomical locations. Epithelial, fibroblast, and macrophage populations had ventricle-specific, regionalized gene expression programs across the developing brain. Key cell types are retained in adult, with loss of developmental signatures and maturation of ventricle-specific regionalization in the epithelial cells. Expression of cognate ligand-receptor pairs across cell subtypes suggests substantial cell-cell interactions within the ChP. Our atlas sheds new light on the development and function of the ChP brain barrier system, and will facilitate future studies on its role in brain development, homeostasis and disease.

neuroscience↗