NFAT5 genes are part of the osmotic regulatory system in Atlantic salmon (Salmo salar)

Acknowledgements This study was supported by a grant from the Biotechnology and Biological Sciences Research Council (BBSRC, BB/H008063/1), UK to DGH and SAM. Funding also came from Research Council Norway for project number 241016 for DGH and EJ. This work was carried out as part of a PhD thesis funded by the Marine Alliance of Science and Technology Scotland (MASTS).Peer reviewedPublisher PD

A Temporally Dynamic Gut Microbiome in Atlantic Salmon During Freshwater Recirculating Aquaculture System (RAS) Production and Post-seawater Transfer

This study was funded by the UKRI project ROBUSTSMOLT (BBSRC BB/S004270/1 and BB/S004432/1). There was also cofunding from the Scottish Aquaculture Innovation Centre. ACKNOWLEDGMENTS The authors would like to thank John Richmond and staff at MOWI and the Centre for Genome Enabled Biology and Medicine (CGEBM) at the University of Aberdeen, particularly Dr. Ewan Campbell, for help with amplification protocols, conducting 16S library preparation and sequencing. The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA729215.Peer reviewedPublisher PD

Cyclical DNA Methyltransferase 3a Expression Is a Seasonal and Estrus Timer in Reproductive Tissues

Acknowledgments We thank Gerald Lincoln for his critical feedback on a previous version of this manuscript. Author contributions included the following: T.J.S. conceived the project, designed the experiments, analyzed the data, and wrote the manuscript. E.W.J.L. conducted the experiments and analyzed the data. C.S.C. conducted the immunocytochemistry. M.L. conducted the HEK293 cell culture assays. E.M.C. and A.S.B. provided technical assistance. This work was supported by the University of Aberdeen College of Life Sciences and Medicine grant (to T.J.S.). E.W.J.L. was supported by a Society for Reproduction and Fertility undergraduate scholarship. Disclosure Summary: The authors have nothing to disclose.Peer reviewedPostprin

Microbiomes in the context of developing sustainable intensified aquaculture

With an ever-growing human population, the need for sustainable production of nutritional food sources has never been greater. Aquaculture is a key industry engaged in active development to increase production in line with this need while remaining sustainable in terms of environmental impact and promoting good welfare and health in farmed species. Microbiomes fundamentally underpin animal health, being a key part of their digestive, metabolic and defense systems, in the latter case protecting against opportunistic pathogens in the environment. The potential to manipulate the microbiome to the advantage of enhancing health, welfare and production is an intriguing prospect that has gained considerable traction in recent years. In this review we first set out what is known about the role of the microbiome in aquaculture production systems across the phylogenetic spectrum of cultured animals, from invertebrates to finfish. With a view to reducing environmental footprint and tightening biological and physical control, investment in “closed” aquaculture systems is on the rise, but little is known about how the microbial systems of these closed systems affect the health of cultured organisms. Through comparisons of the microbiomes and their dynamics across phylogenetically distinct animals and different aquaculture systems, we focus on microbial communities in terms of their functionality in order to identify what features within these microbiomes need to be harnessed for optimizing healthy intensified production in support of a sustainable future for aquaculture

Imprinting methylation in SNRPN and MEST1 in adult blood predicts cognitive ability

Genomic imprinting is important for normal brain development and aberrant imprinting has been associated with impaired cognition. We studied the imprinting status in selected imprints (H19, IGF2, SNRPN, PEG3, MEST1, NESPAS, KvDMR, IG-DMR and ZAC1) by pyrosequencing in blood samples from longitudinal cohorts born in 1936 (n = 485) and 1921 (n = 223), and anterior hippocampus, posterior hippocampus, periventricular white matter, and thalamus from brains donated to the Aberdeen Brain Bank (n = 4). MEST1 imprint methylation was related to childhood cognitive ability score (-0.416 95% CI -0.792,-0.041; p = 0.030), with the strongest effect evident in males (-0.929 95% CI -1.531,-0.326; p = 0.003). SNRPN imprint methylation was also related to childhood cognitive ability (+0.335 95%CI 0.008,0.663; p = 0.045). A significant association was also observed for SNRPN methylation and adult crystallised cognitive ability (+0.262 95%CI 0.007,0.517; p = 0.044). Further testing of significant findings in a second cohort from the same region, but born in 1921, resulted in similar effect sizes and greater significance when the cohorts were combined (MEST1; -0.371 95% CI -0.677,-0.065; p = 0.017; SNRPN; +0.361 95% CI 0.079,0.643; p = 0.012). For SNRPN and MEST1 and four other imprints the methylation levels in blood and in the five brain regions were similar. Methylation of the paternally expressed, maternally methylated genes SNRPN and MEST1 in adult blood was associated with cognitive ability in childhood. This is consistent with the known importance of the SNRPN containing 15q11-q13 and the MEST1 containing 7q31-34 regions in cognitive function. These findings, and their sex specific nature in MEST1, point to new mechanisms through which complex phenotypes such as cognitive ability may be inherited. These mechanisms are potentially relevant to both the heritable and non-heritable components of cognitive ability. The process of epigenetic imprinting-within SNRPN and MEST1 in particular-and the factors that influence it, are worthy of further study in relation to the determinants of cognitive ability

Modulation of gut microbiota composition and predicted metabolic capacity after nutritional programming with a plant-rich diet in Atlantic salmon (Salmo salar): insights across developmental stages

To promote sustainable aquaculture, the formulation of Atlantic salmon (Salmo salar) feeds has changed in recent decades, focusing on replacing standard marine-based ingredients with plant-based alternatives, increasingly demonstrating successful outcomes in terms of fish performance. However, little is known about how these plant-based diets may impact the gut microbiota at first feeding and onwards. Nutritional programming (NP) is one strategy applied for exposing fish to a plant-based (V) diet at an early stage in life to promote full utilisation of plant-based ingredients and prevent potential adverse impacts of exposure to a plant-rich diet later in life. We investigated the impact of NP on gut microbiota by introducing fish to plant ingredients (V fish) during first feeding for a brief period of two weeks (stimulus phase) and compared those to fish fed a marine-based diet (M fish). Results demonstrated that V fish not only maintained growth performance at 16 (intermediate phase) and 22 (challenge phase) weeks post first feeding (wpff ) when compared to M fish but also modulated gut microbiota. PERMANOVA general effects revealed gut microbiota dissimilarity by fish group (V vs. M fish) and phases (stimulus vs. intermediate vs. challenge). However, no interaction effect of both groups and phases was demonstrated, suggesting a sustained impact of V diet (nutritional history) on fish across time points/phases. Moreover, the V diet exerted a significant cumulative modulatory effect on the Atlantic salmon gut microbiota at 16 wpff that was not demonstrated at two wpff, although both fish groups were fed the M diet at 16 wpff. The nutritional history/dietary regime is the main NP influencing factor, whereas environmental and host factors significantly impacted microbiota composition in M fish. Microbial metabolic reactions of amino acid metabolism were higher in M fish when compared to V fish at two wpff suggesting microbiota played a role in digesting the essential amino acids of M feed. The excessive mucin O-degradation revealed in V fish at two wpff was mitigated in later life stages after NP, suggesting physiological adaptability and tolerance to V diet. Future studies are required to explore more fully how the microbiota functionally contributes to the NP

Contextualising Apartheid at the End of Empire: Repression, ‘Development’ and the Bantustans

This article examines the global dynamics of late colonialism and how these informed South African apartheid. More specifically, it locates the programmes of mass relocation and bantustan ‘self-government’ that characterised apartheid after 1959 in relation to three key dimensions. Firstly, the article explores the global circulation of idioms of ‘development’ and trusteeship in the first half of the twentieth century and its significance in shaping segregationist policy; secondly, it situates bantustan ‘selfgovernment’ in relation to the history of decolonisation and the partitions and federations that emerged as late colonial solutions; and, thirdly, it locates the tightening of rural village planning in the bantustans after 1960 in relation to the elaboration of anti-colonial liberation struggles, repressive southern African settler politics and the Cold War. It argues that, far from developing policies that were at odds with the global ‘wind of change’, South African apartheid during the 1960s and 1970s reflected much that was characteristic about late colonial strategy

Temporal changes in skin and gill microbiomes of Atlantic salmon in a recirculating aquaculture system – Why do they matter?

Mucosal surfaces are key components of teleost health, providing defence against opportunistic pathogens and other insults. Maintaining the integrity of mucosal surfaces and their associated microbial communities, especially the gill and skin that have large surface areas exposed to the environment is essential. Production of Atlantic salmon in land-based recirculating aquaculture systems (RAS) has increased significantly in recent years as it allows greater control over stability of the environment in which fish are reared, reduces water demand and minimises environmental impacts. However, little is known about the impact of the RAS environment upon the temporal dynamics of skin and gill mucosal microbiomes. In this study we examined microbial communities in gill mucus, skin mucus and rearing water throughout freshwater (FW) RAS production, and at 1-week and 4-weeks following transfer to seawater (SW) in open cage production using 16S rRNA sequencing. Microbial diversity and richness in skin and gill mucus of fish reared in a RAS system were temporally dynamic. Dynamics in richness and diversity were similar in the two mucosal tissues, and to some extent also mirrored that of the surrounding water. Dysbiosis indicated by an abrupt decline in diversity during FW production coincided with an increase in the relative abundance of two taxa belonging to the RAS-biofilter-associated nitrogen-cycling genus Hydrogenophaga in RAS tank water and this was also observed in gill and skin mucus. Extensive overlap in core taxa was observed between gill and skin mucus, but host-specific cores were non-existent during the dysbiotic event with all cores present in the rearing water. Diversity remained stable during the transition from FW to SW, but distinct community composition and core taxa were observed in the two environments. Although RAS are closely controlled, significant temporal variation could be observed in temperature as well as levels of CO2 and nitrogen compounds, reflecting the increasing biological load within the system over time. The results presented here suggest that, in terms of microbiomes, dysbiosis may occur in both the RAS environment and fish mucosal surfaces over time, but microbial communities have the capability to recover

Imprinting Methylation and Cognition, 2015-2020

Human cognition is an important determinant of educational and occupational success, social mobility, health, and longevity though it is not clear whether higher cognitive ability leads to better health and longevity through improved lifestyle choices and life opportunities or whether there is a common biological basis to a well-functioning brain and body. Cognitive ability is influenced both by genetics and the environment and epigenetic states are relevant to both. A particular class of epigenetics (imprinting) is known to be important for neurogenesis, brain function and behaviour. Epigenetic imprints are generally established in early life, they are often stable over time, and they can persist in a wide range of cell types many divisions and decades later. These characteristics make imprints particularly amenable to study in longitudinal cohort designs where only blood samples may be available. This study investigates the link between epigenetic imprinting and measures of cognitive function at age 11 and in adulthood using data from a well-characterised cohort born in 1936 and recruited at 64 years of age. We studied the average methylation in selected regions of imprints (H19, IGF2, SNRPN, PEG3, MEST1, NESPAS, KvDMR, IG-DMR and ZAC1) by pyrosequencing in DNA extracted from blood samples. The data consist of average percent methylation in selected regions of imprints (H19, IGF2, SNRPN, PEG3, MEST1, NESPAS, KvDMR, IG-DMR and ZAC1) measured by pyrosequencing in DNA extracted from blood samples. Measures of cognitive function are; MATSCO (Childhood Moray House Test Score); NART (National Adult Reading Test Score); RAVN (Raven’s Progressive Matrices).There is much evidence that early life experiences (from fetal life through childhood) can influence adult outcomes. However, the pathways and mechanisms by which earlier experiences become embedded in an individual's life-course and how they influence health and behavioral outcomes are still not clear. Epigenetics provides a key emerging platform for interdisciplinary research among the biological and social sciences to further understand the complex interactions between social phenomena and human biology and behavior. Epigenetics refers to information in the human genome other than that in the DNA sequence. Imprinting refers to a special kind of epigenetic marking of genes that occurs very early in development and is then often stable across the life course. There is increasing evidence for the importance of these epigenetic factors in brain function, cognition, mood and behavior. We aim to investigate the effect of the early social environment on epigenetic status and its relationship to cognition and mood in later life. The proposed study exploits existing data and samples collected from two important UK longitudinal studies (Aberdeen Birth Cohorts born in 1921 and 1936). The data held includes extensive information on early social environment, later life exposures, and changes in cognition, mood, and brain volumes into old age. We believe that our hypotheses, relating to germline imprints, is particularly appropriate to such longitudinal study designs. These epigenetic marks are influenced by the early environment, they are stable over decades, they typically occur in multiple tissue types, and they are known to influence behavior. This is a truly multidisciplinary project involving collaboration between researchers in three UK centers (University of Aberdeen, University College London, and University of Cambridge) with strong track records in the areas relevant to the call. It involves a number of social scientists and biological scientists and crucially involves the training of a post-doctoral scientist to work beyond traditional boundaries and contribute to the development of a new discipline that spans the biological and social sciences. This work is naturally complemented by our existing programme of research on the effects of the early environment on imprinting methylation in a contemporary birth cohort where we have extensive information on maternal diet, nutritional and socioeconomic status, maternal health, birth outcome, etc. In that study we are currently measuring in newborn blood the same imprinted regions that will be studied here. That work will be used to inform the interpretation of the early life findings from the proposed study and identify contemporary early exposures that influence imprints linked to later cognition and mood. We believe that this research provides a unique opportunity to; 1) directly measure the strength of association between early life factors, imprinting and cognition; 2) produce knowledge to underpin the development of evidence based strategies at different life stages to improve mental health and wellbeing; 3) generate specific hypotheses that can be tested in future studies in other human cohorts and brain tissue, such as that available within the MRC brain bank, 4) produce knowledge to inform the development of work in other species and model systems, and 5) contribute to the development of a new research discipline that encompasses the molecular and social sciences.</p

Functional divergence of type 2 deiodinase paralogs in the Atlantic salmon

Thyroid hormone (TH) is an ancestral signal linked to seasonal life history transitions throughout vertebrates. TH action depends upon tissue-localized regulation of levels of active TH (triiodothyronine, T3), through spatiotemporal expression of thyroid hormone deiodinase (dio) genes. We investigated the dio gene family in juvenile Atlantic salmon (Salmo salar) parr, which prepare for seaward migration in the spring (smoltification) through TH-dependent changes in physiology. We identified two type 2 deiodinase paralogs, dio2a and dio2b, responsible for conversion of thyroxine (T4) to T3. During smoltification, dio2b was induced in the brain and gills in zones of cell proliferation following increasing day length. Contrastingly, dio2a expression was induced in the gills by transfer to salt water (SW), with the magnitude of the response proportional to the plasma chloride level. This response reflected a selective enrichment for osmotic response elements (OREs) in the dio2a promoter region. Transcriptomic profiling of gill tissue from fish transferred to SW plus or minus the deiodinase inhibitor, iopanoic acid, revealed SW-induced increases in cellular respiration as the principal consequence of gill dio2 activity. Divergent evolution of dio2 paralogs supports organ-specific timing of the TH-dependent events governing the phenotypic plasticity required for migration to sea