| 1. |
- Yeung, Edwina, et al.
(författare)
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Maternal age is related to offspring DNA methylation : a meta-analysis of results from the pace consortium
- 2024
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Ingår i: Aging Cell. - : John Wiley & Sons. - 1474-9718 .- 1474-9726.
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Tidskriftsartikel (refereegranskat)abstract
- Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta-analyzed epigenome-wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5–10 years old) from the Pregnancy and Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites in 13 loci with DNAm associated with maternal age (PFDR < 0.05). Eight of these CpGs were located near/in the MTNR1B gene, coding for a melatonin receptor. Regional analysis identified them together as a differentially methylated region consisting of 9 CpGs in/near MTNR1B, at which higher DNAm was associated with greater maternal age (PFDR = 6.92 × 10−8) in newborns. In childhood blood samples, these differences in blood DNAm of MTNR1B CpGs were nominally significant (p < 0.05) and retained the same positive direction, suggesting persistence of associations. Maternal age was also positively associated with higher DNA methylation at three CpGs in RTEL1-TNFRSF6B at birth (PFDR < 0.05) and nominally in childhood (p < 0.0001). Of the remaining 10 CpGs also persistent in childhood, methylation at cg26709300 in YPEL3/BOLA2B in external data was associated with expression of ITGAL, an immune regulator. While further study is needed to establish causality, particularly due to the small effect sizes observed, our results potentially support offspring DNAm as a mechanism underlying associations of maternal age with child health.
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| 2. |
- Block, Keith I., et al.
(författare)
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Designing a broad-spectrum integrative approach for cancer prevention and treatment
- 2015
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Ingår i: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 35, s. S276-S304
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Forskningsöversikt (refereegranskat)abstract
- Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.
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| 3. |
- Carneiro, Miguel, et al.
(författare)
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Dwarfism and Altered Craniofacial Development in Rabbits Is Caused by a 12.1 kb Deletion at the HMGA2 Locus
- 2017
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Ingår i: Genetics. - : GENETICS SOCIETY AMERICA. - 0016-6731 .- 1943-2631. ; 205:2, s. 955-965
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Tidskriftsartikel (refereegranskat)abstract
- The dwarf phenotype characterizes the smallest of rabbit breeds and is governed largely by the effects of a single dwarfing allele with an incompletely dominant effect on growth. Dwarf rabbits typically weigh under 1 kg and have altered craniofacial morphology. The dwarf allele is recessive lethal and dwarf homozygotes die within a few days of birth. The dwarf phenotype is expressed in heterozygous individuals and rabbits from dwarf breeds homozygous for the wild-type allele are normal, although smaller when compared to other breeds. Here, we show that the dwarf allele constitutes a similar to 12.1 kb deletion overlapping the promoter region and first three exons of the HMGA2 gene leading to inactivation of this gene. HMGA2 has been frequently associated with variation in body size across species. Homozygotes for null alleles are viable in mice but not in rabbits and probably not in humans. RNA-sequencing analysis of rabbit embryos showed that very few genes (4-29 genes) were differentially expressed among the three HMGA2/dwarf genotypes, suggesting that dwarfism and inviability in rabbits are caused by modest changes in gene expression. Our results show that HMGA2 is critical for normal expression of IGF2BP2, which encodes an RNA-binding protein. Finally, we report a catalog of regions of elevated genetic differentiation between dwarf and normal-size rabbits, including LCORL-NCAPG, STC2, HOXD cluster, and IGF2BP2. Levels and patterns of genetic diversity at the LCORL-NCAPG locus further suggest that small size in dwarf breeds was enhanced by crosses with wild rabbits. Overall, our results imply that small size in dwarf rabbits results from a large effect, loss-of-function (LOF) mutation in HMGA2 combined with polygenic selection.
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| 4. |
- Dou, S.X., et al.
(författare)
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Improvement of critical current density in the Bi-Pb-Sr-Ca-Cu-O system through hot isostatic pressing
- 1990
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Ingår i: Physica. C, Superconductivity. - 0921-4534 .- 1873-2143. ; 167:5-6, s. 525-528
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Tidskriftsartikel (refereegranskat)abstract
- The effects of hot isostatic pressing (HIPing) on densification and the superconducting properties of the Bi-Pb-Sr-Ca-O system were investigated. A relative density up to 95% and a critical current density greater than 1100 A/cm2 at 77 K were achieved through HIPing at 650°C for 2 h under 200 MPa argon. Under these conditions, the product gave a value of Jc four times that without HIPing. To was unaffected by HIPing for samples encapsulated with a combination of glass and silver tubes. However, To was suppressed from 103 K to 86 K for samples encapsulated with stainless steel and silver tubes while Jc increased from 260 A/ cm2 to 1086 A/cm2 during HIPing, indicating that the weak links were significantly improved. A new minor phase, having a composition of Bi/Pb/Sr/Ca/Cu=0.58/2.8/3.0/2.1/1.1, was observed in HIPed samples but its effect on Jc is not clear
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| 5. |
- Dou, Yujie, et al.
(författare)
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Reliability of using vegetation optical depth for estimating decadal and interannual carbon dynamics
- 2023
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Ingår i: Remote Sensing of Environment. - : Elsevier BV. - 0034-4257. ; 285
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Tidskriftsartikel (refereegranskat)abstract
- Vegetation optical depth (VOD) from satellite passive microwave sensors has enabled monitoring of aboveground biomass carbon dynamics by building a relationship with static carbon maps over space and then applying this relationship to VOD time series. However, uncertainty in this relationship arises from changes in water stress, as VOD is mainly determined by vegetation water content, which varies at diurnal to interannual scales, and depends on changes in both biomass and relative moisture content. Here, we studied the reliability of using VOD from various microwave frequencies and temporal aggregation methods for estimating decadal biomass carbon dynamics at the global scale. We used the VOD diurnal variations to represent the magnitude of vegetation water content buffering caused by climatic variations for a constant amount of dry biomass carbon. This magnitude of VOD diurnal variations was then used to evaluate the likelihood of VOD decadal variations in reflecting decadal dry biomass carbon changes. We found that SMOS-IC L-VOD and LPDR X-VOD can be reliably used to estimate decadal carbon dynamics for 76.7% and 69.9% of the global vegetated land surface, respectively, yet cautious use is warranted for some areas such as the eastern Amazon rainforest. Moreover, the annual VOD aggregated from the 95% percentile of the nighttime VOD retrievals was proved to be the most suitable parameter for estimating decadal biomass carbon dynamics among the temporal aggregation methods. Finally, we validated the use of annual VOD for estimating interannual carbon dynamics by comparing VOD changes between adjacent years against eddy covariance estimations of gross primary production from flux sites over several land cover classes across the globe. Despite the large difference in spatial scales between them, the positive correlation obtained supports the capability of satellite VOD in quantifying interannual carbon dynamics.
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| 6. |
- Lozano, Manuel, et al.
(författare)
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DNA methylation changes associated with prenatal mercury exposure : A meta-analysis of prospective cohort studies from PACE consortium
- 2022
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 204
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Tidskriftsartikel (refereegranskat)abstract
- Mercury (Hg) is a ubiquitous heavy metal that originates from both natural and anthropogenic sources and is transformed in the environment to its most toxicant form, methylmercury (MeHg). Recent studies suggest that MeHg exposure can alter epigenetic modifications during embryogenesis. In this study, we examined associations between prenatal MeHg exposure and levels of cord blood DNA methylation (DNAm) by meta-analysis in up to seven independent studies (n = 1462) as well as persistence of those relationships in blood from 7 to 8 year-old children (n = 794). In cord blood, we found limited evidence of differential DNAm at cg24184221 in MED31 (β = 2.28 × 10−4, p-value = 5.87 × 10−5) in relation to prenatal MeHg exposure. In child blood, we identified differential DNAm at cg15288800 (β = 0.004, p-value = 4.97 × 10−5), also located in MED31. This repeated link to MED31, a gene involved in lipid metabolism and RNA Polymerase II transcription function, may suggest a DNAm perturbation related to MeHg exposure that persists into early childhood. Further, we found evidence for association between prenatal MeHg exposure and child blood DNAm levels at two additional CpGs: cg12204245 (β = 0.002, p-value = 4.81 × 10−7) in GRK1 and cg02212000 (β = −0.001, p-value = 8.13 × 10−7) in GGH. Prenatal MeHg exposure was associated with DNAm modifications that may influence health outcomes, such as cognitive or anthropometric development, in different populations.
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| 7. |
- Mehta, Raghav, et al.
(författare)
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QU-BraTS : MICCAI BraTS 2020 Challenge on QuantifyingUncertainty in Brain Tumor Segmentation - Analysis of Ranking Scores and Benchmarking Results
- 2022
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Ingår i: Journal of Machine Learning for Biomedical Imaging. - 2766-905X. ; , s. 1-54
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Tidskriftsartikel (refereegranskat)abstract
- Deep learning (DL) models have provided the state-of-the-art performance in a wide variety of medical imaging benchmarking challenges, including the Brain Tumor Segmentation (BraTS) challenges. However, the task of focal pathology multi-compartment segmentation (e.g., tumor and lesion sub-regions) is particularly challenging, and potential errors hinder the translation of DL models into clinical workflows. Quantifying the reliability of DL model predictions in the form of uncertainties, could enable clinical review of the most uncertain regions, thereby building trust and paving the way towards clinical translation. Recently, a number of uncertainty estimation methods have been introduced for DL medical image segmentation tasks. Developing scores to evaluate and compare the performance of uncertainty measures will assist the end-user in making more informed decisions. In this study, we explore and evaluate a score developed during the BraTS 2019-2020 task on uncertainty quantification (QU-BraTS), and designed to assess and rank uncertainty estimates for brain tumor multi-compartment segmentation. This score (1) rewards uncertainty estimates that produce high confidence in correct assertions, and those that assign low confidence levels at incorrect assertions, and (2) penalizes uncertainty measures that lead to a higher percentages of under-confident correct assertions. We further benchmark the segmentation uncertainties generated by 14 independent participating teams of QU-BraTS 2020, all of which also participated in the main BraTS segmentation task. Overall, our findings confirm the importance and complementary value that uncertainty estimates provide to segmentation algorithms, and hence highlight the need for uncertainty quantification in medical image analyses. Our evaluation code is made publicly available at https://github.com/RagMeh11/QU-BraTS
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| 8. |
- Nhu, Viet-Ha, et al.
(författare)
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Shallow Landslide Susceptibility Mapping : A Comparison between Logistic Model Tree, Logistic Regression, Naïve Bayes Tree, Artificial Neural Network, and Support Vector Machine Algorithms
- 2020
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Ingår i: International Journal of Environmental Research and Public Health. - Switzerland : MDPI. - 1661-7827 .- 1660-4601. ; 17:8, s. 1-30
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Tidskriftsartikel (refereegranskat)abstract
- Shallow landslides damage buildings and other infrastructure, disrupt agriculture practices, and can cause social upheaval and loss of life. As a result, many scientists study the phenomenon, and some of them have focused on producing landslide susceptibility maps that can be used by land-use managers to reduce injury and damage. This paper contributes to this effort by comparing the power and effectiveness of five machine learning, benchmark algorithms—Logistic Model Tree, Logistic Regression, Naïve Bayes Tree, Artificial Neural Network, and Support Vector Machine—in creating a reliable shallow landslide susceptibility map for Bijar City in Kurdistan province, Iran. Twenty conditioning factors were applied to 111 shallow landslides and tested using the One-R attribute evaluation (ORAE) technique for modeling and validation processes. The performance of the models was assessed by statistical-based indexes including sensitivity, specificity, accuracy, mean absolute error (MAE), root mean square error (RMSE), and area under the receiver operatic characteristic curve (AUC). Results indicate that all the five machine learning models performed well for shallow landslide susceptibility assessment, but the Logistic Model Tree model (AUC = 0.932) had the highest goodness-of-fit and prediction accuracy, followed by the Logistic Regression (AUC = 0.932), Naïve Bayes Tree (AUC = 0.864), ANN (AUC = 0.860), and Support Vector Machine (AUC = 0.834) models. Therefore, we recommend the use of the Logistic Model Tree model in shallow landslide mapping programs in semi-arid regions to help decision makers, planners, land-use managers, and government agencies mitigate the hazard and risk.
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| 9. |
- Yu, Bingkun, et al.
(författare)
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Comparison of middle- and low-latitude sodium layer from a ground-based lidar network, the Odin satellite, and WACCM–Na model
- 2022
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 22:17, s. 11485-11504
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Tidskriftsartikel (refereegranskat)abstract
- The ground-based measurements obtained from a lidar network and the 6-year OSIRIS (optical spectrograph and infrared imager system) limb-scanning radiance measurements made by the Odin satellite are used to study the climatology of the middle- and low-latitude sodium (Na) layer. Up to January 2021, four Na resonance fluorescence lidars at Beijing (40.5∘ N, 116.0∘ E), Hefei (31.8∘ N, 117.3∘ E), Wuhan (30.5∘ N, 114.4∘ E), and Haikou (19.5∘ N, 109.1∘ E) collected vertical profiles of Na density for a total of 2136 nights (19 587 h). These large datasets provide multi-year routine measurements of the Na layer with exceptionally high temporal and vertical resolution. The lidar measurements are particularly useful for filling in OSIRIS data gaps since the OSIRIS measurements were not made during the dark winter months because they utilize the solar-pumped resonance fluorescence from Na atoms. The observations of Na layers from the ground-based lidars and the satellite are comprehensively compared with a global model of meteoric Na in the atmosphere (WACCM–Na). The lidars present a unique test of OSIRIS and WACCM (Whole Atmosphere Community Climate Model), because they cover the latitude range along 120∘ E longitude in an unusual geographic location with significant gravity wave generation. In general, good agreement is found between lidar observations, satellite measurements, and WACCM simulations. On the other hand, the Na number density from OSIRIS is larger than that from the Na lidars at the four stations within one standard deviation of the OSIRIS monthly average, particularly in autumn and early winter arising from significant uncertainties in Na density retrieved from much less satellite radiance measurements. WACCM underestimates the seasonal variability of the Na layer observed at the lower latitude lidar stations (Wuhan and Haikou). This discrepancy suggests the seasonal variability of vertical constituent transport modelled in WACCM is underestimated because much of the gravity wave spectrum is not captured in the model.
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