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- Sliz, E., et al.
(författare)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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| 3. |
- Nehme, Ralda, et al.
(författare)
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The 22q11.2 region regulates presynaptic gene-products linked to schizophrenia
- 2022
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- It is unclear how the 22q11.2 deletion predisposes to psychiatric disease. To study this, we generated induced pluripotent stem cells from deletion carriers and controls and utilized CRISPR/Cas9 to introduce the heterozygous deletion into a control cell line. Here, we show that upon differentiation into neural progenitor cells, the deletion acted in trans to alter the abundance of transcripts associated with risk for neurodevelopmental disorders including autism. In excitatory neurons, altered transcripts encoded presynaptic factors and were associated with genetic risk for schizophrenia, including common and rare variants. To understand how the deletion contributed to these changes, we defined the minimal protein-protein interaction network that best explains gene expression alterations. We found that many genes in 22q11.2 interact in presynaptic, proteasome, and JUN/FOS transcriptional pathways. Our findings suggest that the 22q11.2 deletion impacts genes that may converge with psychiatric risk loci to influence disease manifestation in each deletion carrier.
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| 8. |
- Virkkala, Anna Maria, et al.
(författare)
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Statistical upscaling of ecosystem CO2 fluxes across the terrestrial tundra and boreal domain : Regional patterns and uncertainties
- 2021
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 27:17, s. 4040-4059
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Tidskriftsartikel (refereegranskat)abstract
- The regional variability in tundra and boreal carbon dioxide (CO2) fluxes can be high, complicating efforts to quantify sink-source patterns across the entire region. Statistical models are increasingly used to predict (i.e., upscale) CO2 fluxes across large spatial domains, but the reliability of different modeling techniques, each with different specifications and assumptions, has not been assessed in detail. Here, we compile eddy covariance and chamber measurements of annual and growing season CO2 fluxes of gross primary productivity (GPP), ecosystem respiration (ER), and net ecosystem exchange (NEE) during 1990–2015 from 148 terrestrial high-latitude (i.e., tundra and boreal) sites to analyze the spatial patterns and drivers of CO2 fluxes and test the accuracy and uncertainty of different statistical models. CO2 fluxes were upscaled at relatively high spatial resolution (1 km2) across the high-latitude region using five commonly used statistical models and their ensemble, that is, the median of all five models, using climatic, vegetation, and soil predictors. We found the performance of machine learning and ensemble predictions to outperform traditional regression methods. We also found the predictive performance of NEE-focused models to be low, relative to models predicting GPP and ER. Our data compilation and ensemble predictions showed that CO2 sink strength was larger in the boreal biome (observed and predicted average annual NEE −46 and −29 g C m−2 yr−1, respectively) compared to tundra (average annual NEE +10 and −2 g C m−2 yr−1). This pattern was associated with large spatial variability, reflecting local heterogeneity in soil organic carbon stocks, climate, and vegetation productivity. The terrestrial ecosystem CO2 budget, estimated using the annual NEE ensemble prediction, suggests the high-latitude region was on average an annual CO2 sink during 1990–2015, although uncertainty remains high.
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| 9. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 10. |
- Bianchi Piccinini, Giulio, 1982, et al.
(författare)
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How Do Drivers Respond to Silent Automation Failures? Driving Simulator Study and Comparison of Computational Driver Braking Models
- 2020
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Ingår i: Human Factors. - Chalmers University of Technology, Gothenburg, Sweden.; Volvo Group Trucks Technology, Gothenburg, Sweden.; Virginia Tech Transportation Institute, Blacksburg, USA.; University of Leeds, UK.; VTI, Gothenburg, Sweden. : SAGE Publications. - 1547-8181 .- 0018-7208. ; 62:7, s. 1212-1229
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This paper aims to describe and test novel computational driver models, predicting drivers’ brake reaction times (BRTs) to different levels of lead vehicle braking, during driving with cruise control (CC) and during silent failures of adaptive cruise control (ACC). Background: Validated computational models predicting BRTs to silent failures of automation are lacking but are important for assessing the safety benefits of automated driving. Method: Two alternative models of driver response to silent ACC failures are proposed: a looming prediction model, assuming that drivers embody a generative model of ACC, and a lower gain model, assuming that drivers’ arousal decreases due to monitoring of the automated system. Predictions of BRTs issued by the models were tested using a driving simulator study. Results: The driving simulator study confirmed the predictions of the models: (a) BRTs were significantly shorter with an increase in kinematic criticality, both during driving with CC and during driving with ACC; (b) BRTs were significantly delayed when driving with ACC compared with driving with CC. However, the predicted BRTs were longer than the ones observed, entailing a fitting of the models to the data from the study. Conclusion: Both the looming prediction model and the lower gain model predict well the BRTs for the ACC driving condition. However, the looming prediction model has the advantage of being able to predict average BRTs using the exact same parameters as the model fitted to the CC driving data. Application: Knowledge resulting from this research can be helpful for assessing the safety benefits of automated driving.
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