The culturable intestinal microbiota of triploid and diploid juvenile Atlantic salmon (Salmo salar) - a comparison of composition and drug resistance

<p>Abstract</p> <p>Background</p> <p>With the increased use of ploidy manipulation in aquaculture and fisheries management this investigation aimed to determine whether triploidy influences culturable intestinal microbiota composition and bacterial drug resistance in Atlantic salmon (<it>Salmo salar</it>). The results could provide answers to some of the physiological differences observed between triploid and diploid fish, especially in terms of fish health.</p> <p>Results</p> <p>No ploidy effect was observed in the bacterial species isolated, however, triploids were found to contain a significant increase in total gut microbiota levels, with increases in <it>Pseudomonas </it>spp., <it>Pectobacterium carotovorum</it>, <it>Psychrobacter </it>spp., <it>Bacillus </it>spp., and <it>Vibrio </it>spp., (12, 42, 9, 10, and 11% more bacteria in triploids than diploids, respectively), whereas a decrease in <it>Carnobacterium </it>spp., within triploids compared to diploids was close to significant (8% more bacteria in diploids). With the exception of gentamicin, where no bacterial resistance was observed, bacterial isolates originating from triploid hosts displayed increased resistance to antibacterials, three of which were significant (tetracycline, trimethoprim, and sulphonamide).</p> <p>Conclusion</p> <p>Results indicate that triploidy influences both the community and drug resistance of culturable intestinal microbiota in juvenile salmon. These results demonstrate differences that are likely to contribute to the health of triploid fish and have important ramifications on the use of antibacterial drugs within aquaculture.</p

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

Volatility in the Housing Market: Evidence on Risk and Return in the London Sub-market

The impact of volatility in housing market analysis is reconsidered via examination of the risk-return relationship in the London housing market is examined. In addition to providing the first empirical results for the relationship between risk (as measured by volatility) and returns for this submarket, the analysis offers a more general message to empiricists via a detailed and explicit evaluation of the impact of empirical design decisions upon inferences. In particular, the negative risk-return relationship discussed frequently in the housing market literature is examined and shown to depend upon typically overlooked decisions concerning components of the empirical framework from which statistical inferences are drawn

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Increased mitochondrial DNA diversity in ancient Columbia River basin Chinook salmon Oncorhynchus tshawytscha

The Columbia River and its tributaries provide essential spawning and rearing habitat for many salmonid species, including Chinook salmon (Oncorhynchus tshawytscha). Chinook salmon were historically abundant throughout the basin and Native Americans in the region relied heavily on these fish for thousands of years. Following the arrival of Europeans in the 1800s, salmon in the basin experienced broad declines linked to overfishing, water diversion projects, habitat destruction, connectivity reduction, introgression with hatchery-origin fish, and hydropower development. Despite historical abundance, many native salmonids are now at risk of extinction. Research and management related to Chinook salmon is usually explored under what are termed “the four H’s”: habitat, harvest, hatcheries, and hydropower; here we explore a fifth H, history. Patterns of prehistoric and contemporary mitochondrial DNA variation from Chinook salmon were analyzed to characterize and compare population genetic diversity prior to recent alterations and, thus, elucidate a deeper history for this species. A total of 346 ancient and 366 contemporary samples were processed during this study. Species was determined for 130 of the ancient samples and control region haplotypes of 84 of these were sequenced. Diversity estimates from these 84 ancient Chinook salmon were compared to 379 contemporary samples. Our analysis provides the first direct measure of reduced genetic diversity for Chinook salmon from the ancient to the contemporary period, as measured both in direct loss of mitochondrial haplotypes and reductions in haplotype and nucleotide diversity. However, these losses do not appear equal across the basin, with higher losses of diversity in the mid-Columbia than in the Snake subbasin. The results are unexpected, as the two groups were predicted to share a common history as parts of the larger Columbia River Basin, and instead indicate that Chinook salmon in these subbasins may have divergent demographic histories.Ye

Sub-lethal UV radiation during early life stages alters the behaviour, heart rate and oxidative stress parameters in zebrafish (Danio rerio)

Embargo until 01 October 2020Environmental UV radiation in sufficient doses, as a possible consequence of climate change, is potent enough to affect living organisms with different outcomes, depending on the exposure life stage. The aim of this project was to evaluate the potentially toxic effects of exposure to sub-lethal and environmentally relevant doses of UVA (9.4, 18. 7, 37.7 J/cm2) and UVB radiation (0.013, 0.025, 0.076 J/cm2) on the development and behaviour in early life stages (4.5–5.5 h post fertilization, hpf) of the zebrafish (Danio rerio). The used doses were all below the median lethal dose (LD50) and caused no significant difference in survival, deformities, or hatching between exposed and control groups. Compared to controls, there were transient UVA and UVB exposure effects on heart rate, with dose dependent reductions at 50 hpf, and at 60 hpf for UVA only. The UVB exposure caused an increasing trend in reactive oxygen species (ROS) formation at the two highest doses, even though only significant at 120 hpf for the second highest dose. Both UVA and UVB caused an increasing trend in lipid peroxidation (LPO) at the highest doses tested at 72 hpf. Furthermore, UVA exposure led to significant reductions in larval movement following exposure to the two highest doses of UVA, i.e., reduction in the time spent active and the total distance moved compared to control at 100 hpf, while no effect on the swimming speed was observed. The lowest dose of UVA had no effect on behaviour. In contrast, the highest dose of UVB led to a possible increase in the time spent active and a slower average swimming speed although these effects were not significant (p = 0.07). The obtained results show that UV doses below LD50 levels are able to cause changes in the behaviour and physiological parameters of zebrafish larvae, as well as oxidative stress in the form of ROS formation and LPO. Further testing is necessary to assess how this type of radiation and the effects observed could affect fish population dynamics.acceptedVersio

Sub-lethal UV radiation during early life stages alters the behaviour, heart rate and oxidative stress parameters in zebrafish (Danio rerio)

Environmental UV radiation in sufficient doses, as a possible consequence of climate change, is potent enough to affect living organisms with different outcomes, depending on the exposure life stage. The aim of this project was to evaluate the potentially toxic effects of exposure to sub-lethal and environmentally relevant doses of UVA (9.4, 18. 7, 37.7 J/cm2) and UVB radiation (0.013, 0.025, 0.076 J/cm2) on the development and behaviour in early life stages (4.5–5.5 h post fertilization, hpf) of the zebrafish (Danio rerio). The used doses were all below the median lethal dose (LD50) and caused no significant difference in survival, deformities, or hatching between exposed and control groups. Compared to controls, there were transient UVA and UVB exposure effects on heart rate, with dose dependent reductions at 50 hpf, and at 60 hpf for UVA only. The UVB exposure caused an increasing trend in reactive oxygen species (ROS) formation at the two highest doses, even though only significant at 120 hpf for the second highest dose. Both UVA and UVB caused an increasing trend in lipid peroxidation (LPO) at the highest doses tested at 72 hpf. Furthermore, UVA exposure led to significant reductions in larval movement following exposure to the two highest doses of UVA, i.e., reduction in the time spent active and the total distance moved compared to control at 100 hpf, while no effect on the swimming speed was observed. The lowest dose of UVA had no effect on behaviour. In contrast, the highest dose of UVB led to a possible increase in the time spent active and a slower average swimming speed although these effects were not significant (p = 0.07). The obtained results show that UV doses below LD50 levels are able to cause changes in the behaviour and physiological parameters of zebrafish larvae, as well as oxidative stress in the form of ROS formation and LPO. Further testing is necessary to assess how this type of radiation and the effects observed could affect fish population dynamics

Lamotrigine effects on immune gene expression in larval zebrafish

Purpose Despite growing evidence that neuroinflammation and pro-inflammatory cytokines are involved in the pathogenesis of seizures and epilepsy, this knowledge has not been incorporated in the proposed mechanism of action of any of the current antiseizure medications (ASMs). Here, we tested the hypothesis by assessing inflammation markers in larval zebrafish (Danio rerio) exposed to lamotrigine (LTG). Methods In order to establish the most appropriate LTG concentrations for the transcriptome analysis (RNAseq), we initially assessed for teratogenic (spinal cord deformation, heart oedema, failed inflation of the swim bladder) and behavioural effects (distance moved, time spent active, and average swimming speed during a light/dark test) in zebrafish larvae exposed to 0, 50, 100, 300, 500, 750, and 1000 μM LTG continuously between 5 and 120 h post fertilisation. Subsequently, we repeated the experiment with 0, 50, 100, or 300 μM LTG for transcriptomic analyses. Two databases (Kyoto Encyclopedia of Genes and Genomes; Gene Ontology) were used to interpret changes in gene expression between groups. Results Major teratogenic effects were observed at concentrations of ≥ 500 μM LTG, whereas behavioural changes were observed at ≥ 300 μM LTG. Transcriptome analysis revealed a non-linear response to LTG. From the suite of differentially expressed genes (DEG), 85% (n = 80 DEGs) were upregulated following exposure to 50 μM LTG, whereas 58% (n = 12 DEGs) and 91% (n = 210 DEGs) were downregulated in response to 100 and 300 μM LTG. The metabolic pathways affected following exposure to 50 and 300 μM LTG were associated with responses to inflammation and pathogens as well development and regulation of the immune system in both groups. Notable genes within the lists of DEGs included component complement 3 (C3.a), which was significantly upregulated in response to 50 μM LTG, whereas interleukin 1β (IL-1β) was significantly downregulated in the 300 μM LTG group. The lowest exposure of 50 μM LTG is regarded as clinically relevant to therapeutic exposure. Conclusion We demonstrated that LTG had an impact on the immune system, with a non-monotonic response curve. This dose-dependent relation could indicate that LTG can affect inflammatory responses and also at clinically relevant concentration. Further studies are needed to establish this method as a tool for screening the effects of ASMs on the immune system