| 1. |
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| 2. |
- Pinto, Dalila, et al.
(författare)
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Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders.
- 2014
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Ingår i: American journal of human genetics. - : Elsevier BV. - 1537-6605 .- 0002-9297. ; 94:5, s. 677-694
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Tidskriftsartikel (refereegranskat)abstract
- Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0× 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7× 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.
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| 3. |
- Abazajian, Kevork, et al.
(författare)
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CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
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Tidskriftsartikel (refereegranskat)abstract
- CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
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| 4. |
- Ade, Peter, et al.
(författare)
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The Simons Observatory : science goals and forecasts
- 2019
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
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Tidskriftsartikel (refereegranskat)abstract
- The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
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| 5. |
- Crossin, Glenn T., et al.
(författare)
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Early Life-History Consequences of Growth-Hormone Transgenesis in Rainbow Trout Reared in Stream Ecosystem Mesocosms
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- There is persistent commercial interest in the use of growth modified fishes for shortening production cycles and increasing overall food production, but there is concern over the potential impact that transgenic fishes might have if ever released into nature. To explore the ecological consequences of transgenic fish, we performed two experiments in which the early growth and survival of growth-hormone transgenic rainbow trout (Oncorhynchus mykiss) were assessed in naturalized stream mesocosms that either contained predators or were predator-free. We paid special attention to the survival bottleneck that occurs during the early life-history of salmonids, and conducted experiments at two age classes (first-feeding fry and 60 days post-first-feeding) that lie on either side of the bottleneck. In the late summer, the first-feeding transgenic trout could not match the growth potential of their wildtype siblings when reared in a hydrodynamically complex and oligotrophic environment, irrespective of predation pressure. Furthermore, overall survival of transgenic fry was lower than in wild-type (transgenic = 30% without predators, 8% with predators; wild-type = 81% without predators, 31% with predators). In the experiment with 60-day old fry, we explored the effects of the transgene in different genetic backgrounds (wild versus domesticated). We found no difference in overwinter survival but significantly higher growth by transgenic trout, irrespective of genetic background. We conclude that the high mortality of GH-transgenic trout during first-feeding reflects an inability to sustain the basic metabolic requirements necessary for life in complex, stream environments. However, when older, GH-transgenic fish display a competitive advantage over wild-type fry, and show greater growth and equal survival as wild-type. These results demonstrate how developmental age and time of year can influence the response of genotypes to environmental conditions. We therefore urge caution when extrapolating the results of GH-transgenesis risk assessment studies across multiple life-history or developmental stages.
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| 6. |
- Devlin, Robert H., et al.
(författare)
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Assessing Ecological and Evolutionary Consequences of Growth-Accelerated Genetically Engineered Fishes
- 2015
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Ingår i: BioScience. - : Oxford University Press (OUP). - 0006-3568 .- 1525-3244. ; 65:7, s. 685-700
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Tidskriftsartikel (refereegranskat)abstract
- Genetically engineered fish containing growth hormone (GH) transgenes have been synthesized for more than 25 years, now with modifications made in multiple aquacultured species. Despite significant improvements in production characteristics being realized, these fish have not yet entered commercial production. The very strong enhancement of growth rates that can arise from GH transgenesis in fish has generated public and scientific concern regarding ecological and food safety. Little ecological risk is anticipated from engineered strains kept in fully contained facilities, so the concern is largely directed toward the reliability of containment measures and determining whether robust ecological data, pertinent to nature, can be generated within research facilities to minimize uncertainty and allow reliable risk-assessment predictions. This article summarizes the growth, life history, and behavioral changes observed in GH-transgenic fish and discusses the environmental and evolutionary factors affecting the adaptation, plasticity, and fitness of transgenic fish and their potential consequences on natural ecosystems.
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| 7. |
- Leggatt, Rosalind A., et al.
(författare)
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Alternate Directed Anthropogenic Shifts in Genotype Result in Different Ecological Outcomes in Coho Salmon Oncorhynchus kisutch Fry
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Domesticated and growth hormone (GH) transgenic salmon provide an interesting model to compare effects of selected versus engineered phenotypic change on relative fitness in an ecological context. Phenotype in domestication is altered via polygenic selection of traits over multiple generations, whereas in transgenesis is altered by a single locus in one generation. These established and emerging technologies both result in elevated growth rates in culture, and are associated with similar secondary effects such as increased foraging, decreased predator avoidance, and similar endocrine and gene expression profiles. As such, there is concern regarding ecological consequences should fish that have been genetically altered escape to natural ecosystems. To determine if the type of genetic change influences fitness components associated with ecological success outside of the culture environments they were produced for, we examined growth and survival of domesticated, transgenic, and wild-type coho salmon fry under different environmental conditions. In simple conditions (i. e. culture) with unlimited food, transgenic fish had the greatest growth, while in naturalized stream tanks (limited natural food, with or without predators) domesticated fish had greatest growth and survival of the three fish groups. As such, the largest growth in culture conditions may not translate to the greatest ecological effects in natural conditions, and shifts in phenotype over multiple rather than one loci may result in greater success in a wider range of conditions. These differences may arise from very different historical opportunities of transgenic and domesticated strains to select for multiple growth pathways or counter-select against negative secondary changes arising from elevated capacity for growth, with domesticated fish potentially obtaining or retaining adaptive responses to multiple environmental conditions not yet acquired in recently generated transgenic strains.
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| 8. |
- Leggatt, Rosalind A., et al.
(författare)
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Growth-Enhanced Transgenic Coho Salmon (Oncorhynchus kisutch) Strains Have Varied Success in Simulated Streams : Implications for Risk Assessment
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Growth hormone (GH) transgenic fish have accelerated growth and could improve production efficiency in aquaculture. However, concern exists regarding potential environmental risks of GH transgenic fish should they escape rearing facilities. While environmental effects have been examined in some GH transgenic models, there is a lack of information on whether effects differ among different constructs or strains of transgenic fish. We compared growth and survival of wild-type coho salmon (Oncorhynchus kisutch) fry, a fast-growing GH transgenic strain containing a metallothionein promoter (T-MT), and three lines/strains containing a reportedly weaker histone-3 promoter (T-H3) in hatchery conditions and semi-natural stream tanks with varying levels of natural food and predators. Rank order of genotype size and survival differed with varying environmental conditions, both within and among experiments. Despite accelerated growth in hatchery conditions, T-MT fry gained little or no growth enhancement in stream conditions, had enhanced survival when food was limiting, and inconsistent survival under other conditions. Rank growth was inconsistent in T-H3 strains, with one strain having highest, and two strains having the lowest growth in stream conditions, although all T-H3 strains had consistently poor survival. These studies demonstrate the importance of determining risk estimates for each unique transgenic model independent of other models.
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| 9. |
- Lõhmus, Mare, et al.
(författare)
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Disruption of seasonality in growth hormone-transgenic coho salmon (Oncorhynchus kisutch) and the role of cholecystokinin in seasonal feeding behavior.
- 2008
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Ingår i: Hormones and behavior. - : Elsevier BV. - 1095-6867 .- 0018-506X. ; 54:4, s. 506-13
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Tidskriftsartikel (refereegranskat)abstract
- Seasonal variation in daily food intake is a well-documented phenomenon in many organisms including wild-type coho salmon where the appetite is noticeably reduced during periods of decreased day length and low water temperature. This reduction may in part be explained by altered production of cholecystokinin (CCK) and growth hormone (GH). CCK is a hormone produced in the brain and gut that mediates a feeling of satiety and thus has an inhibitory effect on food intake and foraging behaviour. Growth hormone (GH) enhances feeding behaviour and consequently growth, but its production is reduced during winter. The objectives of this study were: first, to compare the seasonal feeding behaviour of wild and GH-transgenic coho salmon; second, to determine the behavioural effect of blocking the action of CCK (by using devazepide) on the seasonal food intake; and third, to measure CCK expression in brain and gut tissues between the two genotypes across seasons. We found that, in contrast to wild salmon, food intake in transgenic salmon was not reduced during winter indicating that seasonal control of appetite regulation has been disrupted by constitutive production of GH in transgenic animals. Blocking of CCK increased food intake in both genotypes in all seasons. The increase was stronger in wild genotypes than transgenic fish; however blocking CCK in wild-type fish in winter did not elevate appetites to levels observed in the summer. The response to devazepide was generally faster in transgenic than in wild salmon with more rapid effects observed during summer than during winter, possibly due to a higher temperature in summer. Overall, a seasonal effect on CCK mRNA levels was observed in telencephalon with levels during winter being higher compared to the summer in wild fish, but with no seasonal effect in transgenic fish. No differences in seasonal CCK expression were found in hypothalamus. Higher levels of CCK were detected in the gut of both genotypes in winter compared to summer. Thus, CCK appears to mediate food intake among seasons in both wild-type and GH-transgenic salmon, and an altered CCK regulation may be responsible at least in part for the seasonal regulation of food intake.
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| 10. |
- Lohmus, Mare, et al.
(författare)
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Genotype-Temperature Interaction in the Regulation of Development, Growth, and Morphometrics in Wild-Type, and Growth-Hormone Transgenic Coho Salmon
- 2010
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 5:4, s. e9980-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The neuroendocrine system is an important modulator of phenotype, directing cellular genetic responses to external cues such as temperature. Behavioural and physiological processes in poikilothermic organisms (e. g. most fishes), are particularly influenced by surrounding temperatures. Methodology/Principal Findings: By comparing the development and growth of two genotypes of coho salmon (wild-type and transgenic with greatly enhanced growth hormone production) at six different temperatures, ranging between 8 degrees and 18 degrees C, we observed a genotype-temperature interaction and possible trend in directed neuroendocrine selection. Differences in growth patterns of the two genotypes were compared by using mathematical models, and morphometric analyses of juvenile salmon were performed to detect differences in body shape. The maximum hatching and alevin survival rates of both genotypes occurred at 12 degrees C. At lower temperatures, eggs containing embryos with enhanced GH production hatched after a shorter incubation period than wild-type eggs, but this difference was not apparent at and above 16 degrees C. GH transgenesis led to lower body weights at the time when the yolk sack was completely absorbed compared to the wild genotype. The growth of juvenile GH-enhanced salmon was to a greater extent stimulated by higher temperatures than the growth of the wild-type. Increased GH production significantly influenced the shape of the salmon growth curves. Conclusions: Growth hormone overexpression by transgenesis is able to stimulate the growth of coho salmon over a wide range of temperatures. Temperature was found to affect growth rate, survival, and body morphology between GH transgenic and wild genotype coho salmon, and differential responses to temperature observed between the genotypes suggests they would experience different selective forces should they ever enter natural ecosystems. Thus, GH transgenic fish would be expected to differentially respond and adapt to shifts in environmental conditions compared with wild type, influencing their ability to survive and interact in ecosystems. Understanding these relationships would assist environmental risk assessments evaluating potential ecological effects.
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