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Background Transcriptomic approaches (microarray and RNA-seq) have been a tremendous advance for molecular science in all disciplines, but they have made interpretation of hypothesis testing more difficult because of the large number of comparisons that are done within an experiment. The result has been a proliferation of techniques aimed at solving the multiple comparisons problem, techniques that have focused primarily on minimizing Type I error with little or no concern about concomitant increases in Type II errors. We have previously proposed a novel approach for setting statistical thresholds with applications for high throughput omics-data, optimal α, which minimizes the probability of making either error (i.e. Type I or II) and eliminates the need for post-hoc adjustments. Results A meta-analysis of 242 microarray studies extracted from the peer-reviewed literature found that current practices for setting statistical thresholds led to very high Type II error rates. Further, we demonstrate that applying the optimal α approach results in error rates as low or lower than error rates obtained when using (i) no post-hoc adjustment, (ii) a Bonferroni adjustment and (iii) a false discovery rate (FDR) adjustment which is widely used in transcriptome studies. Conclusions We conclude that optimal α can reduce error rates associated with transcripts in both microarray and RNA-seq experiments, but point out that improved statistical techniques alone cannot solve the problems associated with high throughput datasets – these approaches need to be coupled with improved experimental design that considers larger sample sizes and/or greater study replication.

Although 3,5,3′-triiodothyronine (T3) is considered to be the primary bioactive thyroid hormone (TH) due to its high affinity for TH nuclear receptors (TRs), new data suggest that 3,5-diiodothyronine (T2) can also regulate transcriptional networks. To determine the functional relevance of these bioactive THs, RNA-seq analysis was conducted in the cerebellum, thalamus-pituitary and liver of tilapia treated with equimolar doses of T2 or T3. We identified a total of 169, 154 and 2863 genes that were TH-responsive (FDR < 0.05) in the tilapia cerebellum, thalamus-pituitary and liver, respectively. Among these, 130, 96 and 349 genes were uniquely regulated by T3, whereas 22, 40 and 929 were exclusively regulated by T2 under our experimental paradigm. The expression profiles in response to TH treatment were tissue-specific, and the diversity of regulated genes also resulted in a variety of different pathways being affected by T2 and T3. T2 regulated gene networks associated with cell signalling and transcriptional pathways, while T3 regulated pathways related to cell signalling, the immune system, and lipid metabolism. Overall, the present work highlights the relevance of T2 as a key bioactive hormone, and reveals some of the different functional strategies that underpin TH pleiotropy.

In the environment, there are aquatic pollutants that disrupt androgen signaling in fish. Laboratory and field-based experiments have utilized omics technologies to characterize the molecular mechanisms underlying androgen-receptor agonism/antagonism. Transcriptomics and proteomics studies with 17β-trenbolone, a growth-promoting pharmaceutical found in water systems surrounding cattle feed lots, and androgens such as 17α-methyltestosterone and 17α-methyldihydrotestosterone, have been conducted in ovary and liver of fish that include the fathead minnow (FHM) (Pimephales promelas), common carp (Cyprinus carpio), Qurt medaka (Oryzias latipes), and zebrafish (Danio rerio). In this mini-review, we survey recent omics studies in fish and reveal that, despite the diversity of species and tissues examined, there are common cellular responses that are observed with waterborne androgenic treatments. Recurring themes in gene ontology include apoptosis, transport and oxidation of lipids, synthesis and transport of hormones, immune response, protein metabolism, and cell proliferation. However, we also discuss other mechanisms other than androgen receptor (AR) activation, such as responses to toxicant stress, estrogen receptor agonism, aromatization of androgens into estrogens, and inhibitory feedback mechanisms by high levels of androgens that may also explain molecular responses in fish. To further explore androgen-responsive protein networks, a sub-network enrichment analysis was performed on protein data collected from the livers of female FHMs exposed to 17β-trenbolone. We construct a putative AR-regulated protein/cell process network in the liver that includes B-lymphocyte differentiation, xenobiotic clearance, low-density lipoprotein oxidation, proliferation of smooth muscle cells, and permeability of blood vessels. We demonstrate that construction of protein networks can offer insight into cell processes that are potentially regulated by androgens.

Individual quality is often assessed using a static measure of body condition, such as size-corrected body mass. Plasma metabolites have the potential to provide information on the dynamics of physiological state and thus may be better measures of individual performance capacity (and fitness). We studied relationships between rate of mass change and circulating levels of triglycerides, glycerol, and β-hydroxybutyrate in captive Western Sandpipers (Calidris mauri). The rate of mass change over one and two days prior to blood sampling was positively related to residual triglyceride (controlling for body mass at sampling) and negatively related to residual glycerol and residual β-hydroxybutyrate. The relationship between metabolite level and mass change was still apparent over a seven-day interval for glycerol, but not for the other two metabolites. In a stepwise multiple regression of mass change over two days (controlling for body mass), only β-hydroxybutyrate and glycerol were entered in the model at P < 0.15. Analysis of group means for seven sampling events showed that body-mass change in a group of individuals was related to mean circulating levels of each metabolite, i.e. to a characteristic metabolite profile. Thus, it may be feasible to employ these metabolites to assess habitat quality based on animal performance (e.g. at migratory stopover sites), or to understand the effects of climatic or anthropogenic factors on the health and survival of animals.

American lobsters, Homarus americanus, prefer structurally complex cobble bottom for settlement and early development, but this habitat is sparse and some juveniles are likely forced to exploit other habitats, such as mud bottom. Size-at-age and body condition of juvenile lobsters may vary between cobble and mud habitats, due to differences in food and shelter the habitats provide. In this study, we used cobble-filled collectors deployed on mud and cobble bottom to capture juvenile lobsters occupying cobble and mud seafloor in a mixed-bottom embayment in the southwestern Bay of Fundy, Canada. We compared their size-at-age using a recently developed age-determination technique, and their body condition using mass–length relationship, RNA/DNA ratio and protein content. Individuals 3 and 4 years of age inhabiting mud bottom had greater carapace length than same-age conspecifics on cobble, which could be due to greater growth of juveniles in the less preferred mud habitat. We also found that for a similar carapace length lobsters on mud had slightly lower body mass than those on cobble. RNA/DNA ratio and protein content did not differ between juveniles sampled from the two habitats. Our results suggest that mud bottom represents a more important habitat for young lobsters than is currently appreciated. We hypothesize that mud bottom has become a more important juvenile habitat in recent years due to high lobster abundance, which may be forcing some juveniles to move from preferred but saturated cobble patches to other habitats, such as mud.

DNA methylation is an epigenetic regulator of gene expression, and this process has been shown to be disrupted by environmental contaminants. Di-2-(ethylhexyl) phthalate (DEHP) and related phthalate esters have been shown to affect development in early life stages of fish and can alter genomic methylation patterns in vertebrates. The objectives of this study were the following: (1) Describe the expression patterns of the DNA methyltransferase (dnmt) genes during early fathead minnow (FHM) development. These genes are critical for methylation and imprinting during development. (2) Determine the effects of DEHP on the development of FHM larvae [1 and 14 days post-hatch (dph)]. (3) Determine the effect of DEHP on dnmt expression and global methylation status in larval FHM. FHMs were first collected over a developmental time course [1, 3, 5, 6, and 14 days post-fertilization (dpf)] to investigate the expression patterns of five dnmt isoforms. The expression of dnmt1 and dnmt7 was relatively high in embryos at 1 dpf but was variable in expression, and these transcripts were later expressed at a lower level (>3 dpf); dnmt3 was significantly higher in embryos at 1 dpf compared to those at 3 dpf. Dnmt6 showed more of a constitutive pattern of expression during the first 2 weeks of development, and the mRNA levels of dnmt8 were higher in embryos at 5 and 6 dpf compared to those at 1 and 3 dpf, corresponding to the hatching period of the embryos. A waterborne exposure to three concentrations of DEHP (1, 10 and 100 µg/L) was conducted on 1-day FHM embryos for 24 h and on larval fish for 2 weeks, ending at 14 dpf. DEHP did not negatively affect survival, hatch rate, or the expression of dnmt isoforms in FHMs. There were no differences in global cytosine methylation following DEHP treatments in 14 dpf larvae, suggesting that environmentally relevant levels of DEHP may not affect global methylation at this stage of FHM development. However, additional targeted methylome studies are required to determine whether specific gene promoters are differently methylated following exposure to DEHP. This study offers new insight into the roles of the dnmt enzymes during FHM development.

Although 3,5,3′-triiodothyronine (T3) is considered to be the primary bioactive thyroid hormone (TH) due to its high affinity for TH nuclear receptors (TRs), new data suggest that 3,5-diiodothyronine (T2) can also regulate transcriptional networks. To determine the functional relevance of these bioactive THs, RNA-seq analysis was conducted in the cerebellum, thalamus-pituitary and liver of tilapia treated with equimolar doses of T2 or T3. We identified a total of 169, 154 and 2863 genes that were TH-responsive (FDR < 0.05) in the tilapia cerebellum, thalamus-pituitary and liver, respectively. Among these, 130, 96 and 349 genes were uniquely regulated by T3, whereas 22, 40 and 929 were exclusively regulated by T2 under our experimental paradigm. The expression profiles in response to TH treatment were tissue-specific, and the diversity of regulated genes also resulted in a variety of different pathways being affected by T2 and T3. T2 regulated gene networks associated with cell signalling and transcriptional pathways, while T3 regulated pathways related to cell signalling, the immune system, and lipid metabolism. Overall, the present work highlights the relevance of T2 as a key bioactive hormone, and reveals some of the different functional strategies that underpin TH pleiotropy.

Changes in tissue masses associated with egg production were investigated in female Zebra Finches Taeniopygia gutatta using dietary and hormonal manipulations. We tested three hypotheses: that changes in organ masses, (a) reflect utilisation of endogenous nutrient stores due to inadequate daily dietary intake, (b) involve changes in organ structure or ‘functional capacity', and (c) are initiated by onset of reproductive development (e.g. elevated plasma estrogen or yolk precursor levels, oviduct growth). Pectoral muscle lean dry mass was 18-22% lower in breeding females at the 1-egg stage compared to non-breeders, and this was independent of nutritional plane, i.e. similar changes occurred in birds provided with supplemental protein or egg food. Heart lean dry mass was also lower (16%) in breeding females, but only in birds on a low-quality seed diet, not in birds on supplemented diets. Decreases in total liver mass (14%) were due to changes in lipid content not lean dry mass, and were diet-dependent. These results demonstrate that changes in organ masses associated with egg production are complex, and do not simply reflect a general mobilisation of stored protein. We discuss why there is no hypertrophy of biosynthetic or metabolic ‘machinery' associated with egg production in birds (cf. reproducing mammals). Exogenous 17β-estradiol induced plasma levels of yolk precursors typical of breeding birds, and initiated oviduct growth (to 31% of mature size). However, estradiol treatment caused no change in mass of pectoral muscle, heart or liver, demonstrating that there is no simple relationship between onset of reproductive development and associated tissue mass changes.

The ability to rapidly adapt to novel situations is essential for survival, and this flexibility is impaired in many neuropsychiatric disorders 1 . Thus, understanding whether and how novelty prepares, or primes, brain circuitry to facilitate cognitive flexibility has important translational relevance. Exposure to novelty recruits the hippocampus and medial prefrontal cortex (mPFC) 2 and may prime hippocampal–prefrontal circuitry for subsequent learning-associated plasticity. Here we show that novelty resets the neural circuits that link the ventral hippocampus (vHPC) and the mPFC, facilitating the ability to overcome an established strategy. Exposing mice to novelty disrupted a previously encoded strategy by reorganizing vHPC activity to local theta (4–12 Hz) oscillations and weakening existing vHPC–mPFC connectivity. As mice subsequently adapted to a new task, vHPC neurons developed new task-associated activity, vHPC–mPFC connectivity was strengthened, and mPFC neurons updated to encode the new rules. Without novelty, however, mice adhered to their established strategy. Blocking dopamine D1 receptors (D1Rs) or inhibiting novelty-tagged cells that express D1Rs in the vHPC prevented these behavioural and physiological effects of novelty. Furthermore, activation of D1Rs mimicked the effects of novelty. These results suggest that novelty promotes adaptive learning by D1R-mediated resetting of vHPC–mPFC circuitry, thereby enabling subsequent learning-associated circuit plasticity. Exposure to a novel experience can ‘reset’ connections between the hippocampus and prefrontal cortex in mice, allowing them to overcome an existing learned behaviour and to replace it with a new one.

At the beginning, HEP experiments made use of photographical images both to record and store experimental data and to illustrate their findings. Then the experiments evolved and needed to find ways to visualize their data. With the availability of computer graphics, software packages to display event data and the detector geometry started to be developed. Here, an overview of the usage of event display tools in HEP is presented. Then the case of the ATLAS experiment is considered in more detail and two widely used event display packages are presented, Atlantis and VP1, focusing on the software technologies they employ, as well as their strengths, differences and their usage in the experiment: from physics analysis to detector development, and from online monitoring to outreach and communication. Towards the end, the other ATLAS visualization tools will be briefly presented as well. Future development plans and improvements in the ATLAS event display packages will also be discussed.