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Background Despite sexual development being ubiquitous to vertebrates, the molecular mechanisms underpinning this fundamental transition remain largely undocumented in many organisms. We designed a time course experiment that successfully sampled the period when Atlantic salmon commence their trajectory towards sexual maturation. Results Through deep RNA sequencing, we discovered key genes and pathways associated with maturation in the pituitary-ovarian axis. Analyzing DNA methylomes revealed a bias towards hypermethylation in ovary that implicated maturation-related genes. Co-analysis of DNA methylome and gene expression changes revealed chromatin remodeling genes and key transcription factors were both significantly hypermethylated and upregulated in the ovary during the onset of maturation. We also observed changes in chromatin state landscapes that were strongly correlated with fundamental remodeling of gene expression in liver. Finally, a multiomic integrated analysis revealed regulatory networks and identified hub genes including TRIM25 gene (encoding the estrogen-responsive finger protein) as a putative key regulator in the pituitary that underwent a 60-fold change in connectivity during the transition to maturation. Conclusion The study successfully documented transcriptome and epigenome changes that involved key genes and pathways acting in the pituitary – ovarian axis. Using a Systems Biology approach, we identified hub genes and their associated networks deemed crucial for onset of maturation. The results provide a comprehensive view of the spatiotemporal changes involved in a complex trait and opens the door to future efforts aiming to manipulate puberty in an economically important aquaculture species.

Background A key developmental transformation in the life of all vertebrates is the transition to sexual maturity, whereby individuals are capable of reproducing for the first time. In the farming of Atlantic salmon, early maturation prior to harvest size has serious negative production impacts. Results We report genome wide association studies (GWAS) using fish measured for sexual maturation in freshwater or the marine environment. Genotypic data from a custom 50 K single nucleotide polymorphism (SNP) array was used to identify 13 significantly associated SNP for freshwater maturation with the most strongly associated on chromosomes 10 and 11. A higher number of associations (48) were detected for marine maturation, and the two peak loci were found to be the same for both traits. The number and broad distribution of GWAS hits confirmed a highly polygenetic nature, and GWAS performed separately within males and females revealed sex specific genetic behaviour for loci co-located with positional candidate genes phosphatidylinositol-binding clathrin assembly protein-like ( picalm) and membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 ( magi2) . Conclusions The results extend earlier work and have implications for future applied breeding strategies to delay maturation in this important aquaculture species.

Tasmanian Atlantic salmon ( S. salar ) broodstock can experience temperatures above 20 °C, which impairs reproductive development and inhibits ovulation. The present study investigated the prolonged use of gonadotropin releasing hormone analogue (GnRHa) during vitellogenesis as a means of maintaining endocrine function and promoting egg quality at elevated temperature in maiden and repeat spawning S. salar . GnRHa-treatment during vitellogenesis did not compensate for the negative effects of thermal challenge on the timing of ovulation, egg size, egg fertility or embryo survival in any fish maintained at 22 °C relative to 14 °C. The lack of effectiveness was reflected by the endocrine data, as plasma follicle stimulating hormone and luteinising hormone levels were not different between treated and untreated groups at 22 °C. Furthermore, plasma testosterone and E2 levels were unchanged in GnRHa-treated fish at 22 °C, and plasma levels were generally lower in both groups maintained at 22 °C relative to 14 °C. Transcription of vitellogenin, and zona pellucida B and C was not enhanced in GnRHa-treated fish relative to untreated fish at 22 °C, presumably due to observed suppression of plasma E2. These results indicate that thermal impairment of reproduction is likely to occur on multiple levels, and is difficult to overcome via hormonal manipulation.

In female Atlantic salmon ( Salmo salar ), exposure to warm summer temperatures causes a reduction in plasma 17β-estradiol (E2), which impairs downstream vitellogenesis and zonagenesis, and reduces egg fertility and embryo survival. The aim of the present study was to determine whether E2-treatment could offset thermal impairment of endocrine function and maintain egg quality in maiden (first-time-spawning) S. salar reared at 22 °C. Treatment with E2 at 22 °C stimulated vitellogenin ( vtg ) gene expression and subsequent protein synthesis which promoted oocyte growth and increased egg size relative to untreated fish at 14 and 22 °C. However, E2-treatment at 22 °C was not associated with an increase in egg fertility and embryo survival relative to untreated fish at 22 °C, despite the positive effects of E2-treatment on vitellogenesis and oocyte growth. As there was no evidence to suggest that the estrogen receptor alpha expression was suppressed by high temperature, this could be due to the lack of stimulation on zonagenesis by E2-treatment observed at high temperature during oocyte development. Our results demonstrate that treatment with E2 is not able to maintain zonagenesis or egg quality in maiden S. salar at high temperature, even when vtg gene expression, protein synthesis and subsequent oocyte growth is promoted. This implies that the mechanisms regulating zonagenesis, but not vitellogenesis are impaired at elevated temperature in female S. salar broodstock, and highlights the remarkable complexity of thermally induced endocrine disruption in fish.

Wild abalone (Family Haliotidae) populations have been severely affected by commercial fishing, poaching, anthropogenic pollution, environment and climate changes. These issues have stimulated an increase in aquaculture production; however production growth has been slow due to a lack of genetic knowledge and resources. We have sequenced a draft genome for the commercially important temperate Australian ‘greenlip’ abalone (Haliotis laevigata, Donovan 1808) and generated 11 tissue transcriptomes from a female adult abalone. Phylogenetic analysis of the greenlip abalone with reference to the Pacific abalone (Haliotis discus hannai) indicates that these abalone species diverged approximately 71 million years ago. This study presents an in-depth analysis into the features of reproductive dysfunction, where we provide the putative biochemical messenger components (neuropeptides) that may regulate reproduction including gonad maturation and spawning. Indeed, we isolate the egg-laying hormone neuropeptide and under trial conditions induce spawning at 80% efficiency. Altogether, we provide a solid platform for further studies aimed at stimulating advances in abalone aquaculture production. The H. laevigata genome and resources are made available to the public on the abalone ‘omics website, http://abalonedb.org.

The changing demands on the health sectors in low- and middle-income countries especially sub-Saharan African countries continue to challenge efforts to address critical shortages of the health workforce. Addressing these challenges have led to the evolution of \"non-physician clinicians\" (NPCs), that assume some physician roles and thus mitigate the continuing shortage of doctors in these countries. While it is agreed that changes are needed in physicians' roles and their training as part of the new continuum of care that includes NPCs, we disagree that such training should be geared solely at ensuring physicians dominated health systems. Discussions on the workforce models to suit low-income countries must avoid an endorsement of a culture of physician focused health systems as the only model for sub-Saharan Africa (SSA). It is also essential that training for NPCs be harmonized with that of physicians to clarify the technical roles of both.

Teleost fish exhibit a remarkable diversity in the control of sex determination, offering the opportunity to identify novel differentiation mechanisms and their ecological consequences. Here, we perform GWAS using 4715 fish and 46,501 SNP to map sex determination to three separate genomic locations in Atlantic salmon ( Salmo salar ). To characterize each, whole genome sequencing was performed to 30-fold depth of coverage using 20 fish representing each of three identified sex lineages. SNP polymorphism reveals male fish carry a single copy of the male specific region, consistent with an XX/XY or male heterogametric sex system. Haplotype analysis revealed deep divergence between the putatively ancestral locus on chromosome 2, compared with loci on chromosomes 3 and 6. Haplotypes in fish carrying either the chromosome 3 or 6 loci were nearly indistinguishable, indicating a founding event that occurred following the speciation event that defined Salmo salar from other salmonids. These findings highlight the evolutionarily fluid state of sex determination systems in salmonids, and resolve to the sequence level differences in animals with divergent sex lineages.

Background and objectives: The Scaling Up Nutrition (SUN) Movement was established in 2010 to encourage government led, collective action to end malnutrition in all forms. The SUN Business Network (SBN) is one of four networks supporting the SUN Movement and acts to engage and support the private sector to undertake business action on nutrition in support of national nutrition objectives. SBN operates at the global and national levels, with 13 national networks engaging the private sector on nutrition in Africa, Asia and Latin America. SBN wanted to establish a functioning private sector engagement and commitment platform on nutrition in Nigeria, aligned with the Government's nutrition strategy. Methods: Between August 2015 and April 2016 a strategy for private sector engagement was developed, following a review of national nutrition priorities, stakeholder interviews and analysis of existing business activities to address malnutrition in Nigeria. Priority areas for business action on nutrition were identified and a business engagement and commitment platform on nutrition developed. Results: 'Increasing consumer awareness and demand creation for nutritious foods' and 'nutrition in the agriculture value chain' were identified as priority areas for business action. These areas were validated by stakeholders including the Federal Ministries of Health, Agriculture and Budget and National Planning. SBN Nigeria launched its membership and commitment platform in April 2016, with 20 business members signing up with commitments to address malnutrition. As of end March 2017, the membership has grown to 44 businesses (59% small-medium enterprises, 23% multinationals). Commitments made include activities to include availability and/or affordability of nutritious products (47%), increasing consumer awareness of nutrition (26%) and increased food fortification and use of bio-fortified crops (13%). Businesses have also signed up to activities within the priority workstreams. Conclusions: SBN Nigeria was successfully launched as the only business platform dedicated to nutrition in the country. In order to deliver impact and ensure business action to improve nutrition, SBN Nigeria will convene workstreams for action in priority areas, facilitate partnerships and the provision of technical assistance as well as track progress of members' nutrition commitments. SBN Nigeria will monitor business progress towards their nutrition commitments and business impact on nutrition.

In this dissertation, I describe the philosophy of and techniques employed by evolutionary game theorists. I have considered various models used by evolutionary game theorists, and the dynamics of each model. I have compared the similarities and differences of each one, which are more viable in certain contexts, which fall apart under certain conditions and so on. Solution concepts for evolutionary games and their dynamical implications are discussed. The continuous replicator equation for two strategies is analysed rigorously using an argument based on bifurcations. The geometric point of view regarding ordinary differential equations is given a extensive coverage, including fixed points, periodic orbits, heteroclinic orbits, Lyapunov functions, manifolds, linearisation techniques and so on. Phase portraits and cobweb-staircase diagrams are produced using Matlab, the code for some of which are provided in an appendix at the end of this dissertation. There were some directions I wished to consider, but did not have the time nor scope: stochastic models, such as the Moran process [23] and Wright-Fisher model [15]; extensive form games, as covered in [6].

The ubiquitin-proteasome system is essential to all eukaryotes and has been shown to be critical to parasite survival as well, including Plasmodium falciparum, the causative agent of the deadliest form of malarial disease. Despite the central role of the ubiquitin-proteasome pathway to parasite viability across its entire life-cycle, specific inhibitors targeting the individual enzymes mediating ubiquitin attachment and removal do not currently exist. The ability to disrupt P. falciparum growth at multiple developmental stages is particularly attractive as this could potentially prevent both disease pathology, caused by asexually dividing parasites, as well as transmission which is mediated by sexually differentiated parasites. The deubiquitinating enzyme PfUCHL3 is an essential protein, transcribed across both human and mosquito developmental stages. PfUCHL3 is considered hard to drug by conventional methods given the high level of homology of its active site to human UCHL3 as well as to other UCH domain enzymes. Here, we apply the RaPID mRNA display technology and identify constrained peptides capable of binding to PfUCHL3 with nanomolar affinities. The two lead peptides were found to selectively inhibit the deubiquitinase activity of PfUCHL3 versus HsUCHL3. NMR spectroscopy revealed that the peptides do not act by binding to the active site but instead block binding of the ubiquitin substrate. We demonstrate that this approach can be used to target essential protein-protein interactions within the Plasmodium ubiquitin pathway, enabling the application of chemically constrained peptides as a novel class of anti-malarial therapeutics.Competing Interest StatementThe authors have declared no competing interest.