| 21. |
- Feng, Shaohong, et al.
(författare)
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Dense sampling of bird diversity increases power of comparative genomics
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833
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Tidskriftsartikel (refereegranskat)abstract
- Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
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| 22. |
- Frangou, Sophia, et al.
(författare)
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Cortical thickness across the lifespan : Data from 17,075 healthy individuals aged 3-90 years
- 2022
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Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 431-451
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Tidskriftsartikel (refereegranskat)abstract
- Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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| 23. |
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| 24. |
- Howells, Mark I., et al.
(författare)
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Calabashes for kilowatt-hours : Rural energy and market failure
- 2010
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Ingår i: Energy Policy. - : Elsevier. - 0301-4215 .- 1873-6777. ; 38:6, s. 2729-2738
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes how management and information failures can retard transitions from the traditional use of biomass fuel by low income rural consumers and micro-producers. In general, societies move away from traditional biomass use as economic development takes place. If one accepts the doctrine of revealed preference (built on the initial work of Samuelson, 1938), then these trends imply that such transitions provide net gains in utility. This paper shows how various "failures" entrench existing fuel use patterns-hindering the transition to new fuel use patterns. In order to qualitatively discuss how these transitions may take place, an indicative neo-classical description of consumer and producer behavior is used. Three types fuel-transition "driver" are identified. The effect of information and management failures on these drivers, and thus the energy transition, is discussed. Reference is made to a specific case study in which a partial transition from biomass occurred in response to an intervention to address an environmental management failure (the deforesting of a carbon sink.) It is concluded that interventions to encourage transitions to cleaner sustainable fuel use may need to recognize and address management and information failures in a systematic manner.
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| 25. |
- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 26. |
- Jonsson, Christina E., 1965-
(författare)
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Holocene climate and atmospheric circulation changes in northern Fennoscandia : Interpretations from lacustrine oxygen isotope records
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis investigates how variations in the oxygen isotopic composition of lake waters in northern Fennoscandia are recorded in lake sediment archives, especially diatoms, and how these variations can be used to infer past changes in climate and atmospheric circulation. Results from analyses of the oxygen isotopic composition of lake water samples (δ18Olakew) collected between 2001 and 2006 show that δ18O of northern Fennoscandian lakes is mainly controlled by the isotopic composition of the precipitation (δ18Op). Changes in local δ18Op depend on variations in ambient air temperature and changes in atmospheric circulation that lead to changes in moisture source, vapour transport efficiency, or winter to summer precipitation distribution. This study demonstrates that the amount of isotopic variation in lake water δ18O is determined by a combination of the original δ18Olakew, the amount and timing of the snowmelt, the amount of seasonally specific precipitation and groundwater, any evaporation effects, and lake water residence time. The fact that the same isotope shifts have been detected in various δ18Olakew proxies, derived from hydrologically different lakes, suggests that these records reflect regional atmospheric circulation changes. The results indicate that diatom biogenic silica isotope (δ18Odiatom) records can provide important information about changes in atmospheric circulation that can help explain temperature and precipitation changes during the Holocene. The reconstructed long-term Holocene decreasing δ18Op trend was likely forced by a shift from strong zonal westerly airflow (relatively high δ18Op) in the early Holocene to a more meridional flow pattern (relatively low δ18Op). The large δ18Olakew depletion recorded in the δ18O records around ca. 500 cal yr BP (AD 1450) may be due to a shift to more intense meridional airflow over northern Fennoscandia resulting in an increasing proportion of winter precipitation from the north or southeast. This climate shift probably marks the onset of the so-called Little Ice Age in this region.
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| 27. |
- Jonsson, Jakob, et al.
(författare)
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Offering an auto-play feature likely increases total gambling activity at online slot-machines : preliminary evidence from an interrupted time series experiment at a real-life online casino
- 2024
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Ingår i: Frontiers in Psychiatry. - 1664-0640. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Auto-play is a ubiquitous feature in online casino gambling and virtual slot machines especially, allowing gamblers to initiate spin sequences of pre-set length and value. While theoretical accounts diverge on the hypothesized causal effect on gambling behavior of using the auto-play feature, observational findings show that this feature is used to a higher degree by problem and/or high-intensity gamblers, suggesting that banning this feature may constitute a global responsible gambling measure. Direct, experimental research on causal effects of offering auto-play at online casinos is however lacking. Here, we report the findings of an interrupted time series experiment, conducted at a real-life online casino in Sweden, in which the auto-play feature was made available during a pre-set duration on 40 online slot machines, with 40 matched slots serving as control. Aggregated time series on daily betted amount, spins and net losses were analyzed using a structural Bayesian framework that compared observed developments during the peri-intervention period to modeled counterfactual estimates. Results suggest that offering an auto-play feature on online casinos likely increases total gambling activity in terms of betted amount (approx.+ 7-9%) and (perhaps) number of spins (approx. +3%) but has no effect on net losses. Limitations of studying auto-play effects on a population-level, as well as the complexities of banning this feature within a complex ecosystem of non-perfect channelization to licensed providers, are discussed, including suggestions for future research.
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| 28. |
- Jonsson, Philip, et al.
(författare)
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Single-Molecule Sequencing Reveals Estrogen-Regulated Clinically Relevant lncRNAs in Breast Cancer
- 2015
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Ingår i: Molecular Endocrinology. - : The Endocrine Society. - 0888-8809 .- 1944-9917. ; 29:11
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen receptor (ER)α-positive tumors are commonly treated with ERα antagonists or inhibitors of estrogen synthesis, but most tumors develop resistance, and we need to better understand the pathways that underlie the proliferative and tumorigenic role of this estrogen-activated transcription factor. We here present the first single-molecule sequencing of the estradiol-induced ERα transcriptome in the luminal A-type human breast cancer cell lines MCF7 and T47D. Sequencing libraries were prepared from the polyadenylated RNA fraction after 8 hours of estrogen or vehicle treatment. Single-molecule sequencing was carried out in biological and technical replicates and differentially expressed genes were defined and analyzed for enriched processes. Correlation analysis with clinical expression and survival were performed, and follow-up experiments carried out using time series, chromatin immunoprecipitation and quantitative real-time PCR. We uncovered that ERα in addition to regulating approximately 2000 protein-coding genes, also regulated up to 1000 long noncoding RNAs (lncRNAs). Most of these were up-regulated, and 178 lncRNAs were regulated in both cell lines. We demonstrate that Long Intergenic Non-protein Coding RNA 1016 (LINC01016) and LINC00160 are direct transcriptional targets of ERα, correlate with ERα expression in clinical samples, and show prognostic significance in relation to breast cancer survival. We show that silencing of LINC00160 results in reduced proliferation, demonstrating that lncRNA expression have functional consequences. Our findings suggest that ERα regulation of lncRNAs is clinically relevant and that their functions and potential use as biomarkers for endocrine response are important to explore.
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| 29. |
- Jonsson, Philip, et al.
(författare)
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Support of a bi-faceted role of estrogen receptor β (ERβ) in ERα-positive breast cancer cells.
- 2014
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Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 21:2, s. 143-160
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Tidskriftsartikel (refereegranskat)abstract
- The expression of estrogen receptor α (ERα) in breast cancer identifies patients most likely to respond to endocrine treatment. The second ER, ERβ, is also expressed in breast tumors, but its function and therapeutic potential need further study. Although in vitro studies have established that ERβ opposes transcriptional and proliferative functions of ERα, several clinical studies report its correlation with proliferative markers and poorer prognosis. The data demonstrate that ERβ opposes ERα are primarily based on transient expression of ERβ. Here, we explored the functions of constitutively expressed ERβ in ERα-positive breast cancer lines MCF7 and T47D. We found that ERβ, under these conditions heterodimerized with ERα in the presence and absence of 17β-estradiol, and induced genome-wide transcriptional changes. Widespread anti-ERα signaling was, however, not observed and ERβ was not antiproliferative. Tamoxifen antagonized proliferation and ER-mediated gene regulation both in the presence and absence of ERβ. In conclusion, ERβ's role in cells adapted to its expression appears to differ from its role in cells with transient expression. Our study is important because it provides a deeper understanding of ERβ's role in breast tumors that coexpress both receptors and supports an emerging bi-faceted role of ERβ.
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| 30. |
- Katchy, Anne, et al.
(författare)
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Coexposure to phytoestrogens and bisphenol a mimics estrogenic effects in an additive manner
- 2014
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 138:1, s. 21-35
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Tidskriftsartikel (refereegranskat)abstract
- Endocrine-disrupting chemicals (EDC) are abundant in our environment. A number of EDCs, including bisphenol A (BPA) can bind to the estrogen receptors (ER), ERα and ERβ, and may contribute to estrogen-linked diseases such as breast cancer. Early exposure is of particular concern; many EDCs cross the placenta and infants have measurable levels of, eg, BPA. In addition, infants are frequently fed soy-based formula (SF) that contains phytoestrogens. Effects of combined exposure to xeno- and phytoestrogens are poorly studied. Here, we extensively compared to what extent BPA, genistein, and an extract of infant SF mimic estrogen-induced gene transcription and cell proliferation. We investigated ligand-specific effects on ER activation in HeLa-ERα and ERβ reporter cells; on proliferation, genome-wide gene regulation and non-ER-mediated effects in MCF7 breast cancer cells; and how coexposure influenced these effects. The biological relevance was explored using enrichment analyses of differentially regulated genes and clustering with clinical breast cancer profiles. We demonstrate that coexposure to BPA and genistein, or SF, results in increased functional and transcriptional estrogenic effects. Using statistical modeling, we determine that BPA and phytoestrogens act in an additive manner. The proliferative and transcriptional effects of the tested compounds mimic those of 17β-estradiol, and are abolished by cotreatment with an ER antagonist. Gene expression profiles induced by each compound clustered with poor prognosis breast cancer, indicating that exposure may adversely affect breast cancer prognosis. This study accentuates that coexposure to BPA and soy-based phytoestrogens results in additive estrogenic effects, and may contribute to estrogen-linked diseases, including breast cancer.
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