| 11. |
- DeCarolis, Joseph, et al.
(author)
-
Leveraging Open-Source Tools for Collaborative Macro-energy System Modeling Efforts
- 2020
-
In: Joule. - : Elsevier BV. - 2542-4351. ; 4:12, s. 2523-2526
-
Journal article (other academic/artistic)abstract
- The authors are founding team members of a new effort to develop an Open Energy Outlook for the United States. The effort aims to apply best practices of policy-focused energy system modeling, ensure transparency, build a networked community, and work toward a common purpose: examining possible US energy system futures to inform energy and climate policy efforts. Individual author biographies can be found on the project website: https://openenergyoutlook.org/. DeCarolis et al. articulate the benefits of forming collaborative teams with a wide array of disciplinary and domain expertise to conduct analysis with macro-energy system models. Open-source models, tools, and datasets underpin such efforts by enabling transparency, accessibility, and replicability among team members and with the broader modeling community.
|
|
| 12. |
- Lagou, Vasiliki, et al.
(author)
-
Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
- 2021
-
In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
-
Journal article (peer-reviewed)abstract
- Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
|
|
| 13. |
- Mueller, Ralf C., et al.
(author)
-
A high-quality genome and comparison of short-versus long-read transcriptome of the palaearctic duck Aythya fuligula (tufted duck)
- 2021
-
In: GigaScience. - : Oxford University Press. - 2047-217X. ; 10:12
-
Journal article (peer-reviewed)abstract
- Background: The tufted duck is a non-model organism that experiences high mortality in highly pathogenic avian influenza outbreaks. It belongs to the same bird family (Anatidae) as the mallard, one of the best-studied natural hosts of low-pathogenic avian influenza viruses. Studies in non-model bird species are crucial to disentangle the role of the host response in avian influenza virus infection in the natural reservoir. Such endeavour requires a high-quality genome assembly and transcriptome.Findings: This study presents the first high-quality, chromosome-level reference genome assembly of the tufted duck using the Vertebrate Genomes Project pipeline. We sequenced RNA (complementary DNA) from brain, ileum, lung, ovary, spleen, and testis using Illumina short-read and Pacific Biosciences long-read sequencing platforms, which were used for annotation. We found 34 autosomes plus Z and W sex chromosomes in the curated genome assembly, with 99.6% of the sequence assigned to chromosomes. Functional annotation revealed 14,099 protein-coding genes that generate 111,934 transcripts, which implies a mean of 7.9 isoforms per gene. We also identified 246 small RNA families.Conclusions: This annotated genome contributes to continuing research into the host response in avian influenza virus infections in a natural reservoir. Our findings from a comparison between short-read and long -read reference transcriptomics contribute to a deeper understanding of these competing options. In this study, both technologies complemented each other. We expect this annotation to be a foundation for further comparative and evolutionary genomic studies, including many waterfowl relatives with differing susceptibilities to avian influenza viruses.
|
|
| 14. |
- Cusack, Daniela Francis, et al.
(author)
-
Tradeoffs and Synergies in Tropical Forest Root Traits and Dynamics for Nutrient and Water Acquisition : Field and Modeling Advances
- 2021
-
In: Frontiers in Forests and Global Change. - : Frontiers Media S.A.. - 2624-893X. ; 4
-
Research review (peer-reviewed)abstract
- Vegetation processes are fundamentally limited by nutrient and water availability, the uptake of which is mediated by plant roots in terrestrial ecosystems. While tropical forests play a central role in global water, carbon, and nutrient cycling, we know very little about tradeoffs and synergies in root traits that respond to resource scarcity. Tropical trees face a unique set of resource limitations, with rock-derived nutrients and moisture seasonality governing many ecosystem functions, and nutrient versus water availability often separated spatially and temporally. Root traits that characterize biomass, depth distributions, production and phenology, morphology, physiology, chemistry, and symbiotic relationships can be predictive of plants’ capacities to access and acquire nutrients and water, with links to aboveground processes like transpiration, wood productivity, and leaf phenology. In this review, we identify an emerging trend in the literature that tropical fine root biomass and production in surface soils are greatest in infertile or sufficiently moist soils. We also identify interesting paradoxes in tropical forest root responses to changing resources that merit further exploration. For example, specific root length, which typically increases under resource scarcity to expand the volume of soil explored, instead can increase with greater base cation availability, both across natural tropical forest gradients and in fertilization experiments. Also, nutrient additions, rather than reducing mycorrhizal colonization of fine roots as might be expected, increased colonization rates under scenarios of water scarcity in some forests. Efforts to include fine root traits and functions in vegetation models have grown more sophisticated over time, yet there is a disconnect between the emphasis in models characterizing nutrient and water uptake rates and carbon costs versus the emphasis in field experiments on measuring root biomass, production, and morphology in response to changes in resource availability. Closer integration of field and modeling efforts could connect mechanistic investigation of fine-root dynamics to ecosystem-scale understanding of nutrient and water cycling, allowing us to better predict tropical forest-climate feedbacks.
|
|
| 15. |
- Dimou, Niki, et al.
(author)
-
Circulating levels of testosterone, sex hormone binding globulin and colorectal cancer risk: Observational and mendelian randomization analyses
- 2021
-
In: Cancer Epidemiology, Biomarkers and Prevention. - : AACR Publications. - 1055-9965 .- 1538-7755. ; 30:7, s. 1336-1348
-
Journal article (peer-reviewed)abstract
- Background: Epidemiologic studies evaluating associations between sex steroid hormones and colorectal cancer risk have yielded inconsistent results. To elucidate the role of circulating levels of testosterone, and sex hormone-binding globulin (SHBG) in colorectal cancer risk, we conducted observational and Mendelian randomization (MR) analyses.Methods: The observational analyses included 333,530 participants enrolled in the UK Biobank with testosterone and SHBG measured. HRs and 95% confidence intervals (CI) were estimated using multivariable Cox proportional hazards models. For MR analyses, genetic variants robustly associated with hormone levels were identified and their association with colorectal cancer (42,866 cases/42,752 controls) was examined using two-sample MR.Results: In the observational analysis, there was little evidence that circulating levels of total testosterone were associated with colorectal cancer risk; the MR analyses showed a greater risk for women (OR per 1-SD = 1.09; 95% CI, 1.01-1.17), although pleiotropy may have biased this result. Higher SHBG concentrations were associated with greater colorectal cancer risk for women (HR per 1-SD = 1.16; 95% CI, 1.05-1.29), but was unsupported by the MR analysis. There was little evidence of associations between free testosterone and colorectal cancer in observational andMRanalyses.Conclusions: Circulating concentrations of sex hormones are unlikely to be causally associated with colorectal cancer. Additional experimental studies are required to better understand the possible role of androgens in colorectal cancer development.
|
|
| 16. |
- James, Sarah-Naomi, et al.
(author)
-
A population-based study of head injury, cognitive function and pathological markers.
- 2021
-
In: Annals of clinical and translational neurology. - : Wiley. - 2328-9503. ; 8:4, s. 842-856
-
Journal article (peer-reviewed)abstract
- To assess associations between head injury (HI) with loss of consciousness (LOC), ageing and markers of later-life cerebral pathology; and to explore whether those effects may help explain subtle cognitive deficits in dementia-free individuals.Participants (n=502, age=69-71) from the 1946 British Birth Cohort underwent cognitive testing (subtests of Preclinical Alzheimer Cognitive Composite), 18 F-florbetapir Aβ-PET and MR imaging. Measures include Aβ-PET status, brain, hippocampal and white matter hyperintensity (WMH) volumes, normal appearing white matter (NAWM) microstructure, Alzheimer's disease (AD)-related cortical thickness, and serum neurofilament light chain (NFL). LOC HI metrics include HI occurring: (i) >15years prior to the scan (ii) anytime up to age 71.Compared to those with no evidence of an LOC HI, only those reporting an LOC HI>15years prior (16%, n=80) performed worse on cognitive tests at age 69-71, taking into account premorbid cognition, particularly on the digit-symbol substitution test (DSST). Smaller brain volume (BV) and adverse NAWM microstructural integrity explained 30% and 16% of the relationship between HI and DSST, respectively. We found no evidence that LOC HI was associated with Aβ load, hippocampal volume, WMH volume, AD-related cortical thickness or NFL (all p>0.01).Having a LOC HI aged 50's and younger was linked with lower later-life cognitive function at age ~70 than expected. This may reflect a damaging but small impact of HI; explained in part by smaller BV and different microstructure pathways but not via pathology related to AD (amyloid, hippocampal volume, AD cortical thickness) or ongoing neurodegeneration (serum NFL).
|
|
| 17. |
- Keshavan, Ashvini, et al.
(author)
-
Concordance of CSF measures of Alzheimer's pathology with amyloid PET status in a preclinical cohort: A comparison of Lumipulse and established immunoassays.
- 2020
-
In: Alzheimer's & dementia (Amsterdam, Netherlands). - : Wiley. - 2352-8729. ; 12:1
-
Journal article (peer-reviewed)abstract
- We assessed the concordance of cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau measured on the fully automated Lumipulse platform with pre-symptomatic Alzheimer's disease (AD) pathology on amyloid positron emission tomography (PET).In 72 individuals from the Insight 46 study, CSF Aβ40, Aβ42, total tau (t-tau), and phosphorylated tau at site 181 (p-tau181) were measured using Lumipulse, INNOTEST, and Meso Scale Discovery (MSD) assays, and inter-platform Pearson correlations were derived. Logistic regressions and receiver-operating characteristic analysis generated CSF cut-points optimizing concordance with 18F-florbetapir amyloid PET status (n=63).Measurements of CSF Aβ, p-tau181, and their ratios correlated well across platforms (r 0.84-.94, P<.0001); those of t-tau and t-tau/Aβ42 correlated moderately (r 0.57-0.79, P<.0001). The best concordance with amyloid PET (100% sensitivity and 94% specificity) was afforded by cut-points of 0.110 for Lumipulse Aβ42/Aβ40, 0.087 for MSD Aβ42/Aβ40, and 25.3 for Lumipulse Aβ42/p-tau181.The Lumipulse platform provides comparable sensitivity and specificity to established CSF immunoassays in identifying pre-symptomatic AD pathology.
|
|
| 18. |
- Keshavan, Ashvini, et al.
(author)
-
Population-based blood screening for preclinical Alzheimer's disease in a British birth cohort at age 70.
- 2021
-
In: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 144:2, s. 434-449
-
Journal article (peer-reviewed)abstract
- Alzheimer's disease has a preclinical stage when cerebral amyloid-β deposition occurs before symptoms emerge, and when amyloid-β-targeted therapies may have maximum benefits. Existing amyloid-β status measurement techniques, including amyloid PET and CSF testing, are difficult to deploy at scale, so blood biomarkers are increasingly considered for screening. We compared three different blood-based techniques-liquid chromatography-mass spectrometry measures of plasma amyloid-β, and single molecule array (Simoa) measures of plasma amyloid-β and phospho-tau181-to detect cortical 18F-florbetapir amyloid PET positivity (defined as a standardized uptake value ratio of >0.61 between a predefined cortical region of interest and eroded subcortical white matter) in dementia-free members of Insight 46, a substudy of the population-based British 1946 birth cohort. We used logistic regression models with blood biomarkers as predictors of amyloid PET status, with or without age, sex and APOE ε4 carrier status as covariates. We generated receiver operating characteristics curves and quantified areas under the curves to compare the concordance of the different blood tests with amyloid PET. We determined blood test cut-off points using Youden's index, then estimated numbers needed to screen to obtain 100 amyloid PET-positive individuals. Of the 502 individuals assessed, 441 dementia-free individuals with complete data were included; 82 (18.6%) were amyloid PET-positive. The area under the curve for amyloid PET status using a base model comprising age, sex and APOE ε4 carrier status was 0.695 (95% confidence interval: 0.628-0.762). The two best-performing Simoa plasma biomarkers were amyloid-β42/40 (0.620; 0.548-0.691) and phospho-tau181 (0.707; 0.646-0.768), but neither outperformed the base model. Mass spectrometry plasma measures performed significantly better than any other measure (amyloid-β1-42/1-40: 0.817; 0.770-0.864 and amyloid-β composite: 0.820; 0.775-0.866). At a cut-off point of 0.095, mass spectrometry measures of amyloid-β1-42/1-40 detected amyloid PET positivity with 86.6% sensitivity and 71.9% specificity. Without screening, to obtain 100 PET-positive individuals from a population with similar amyloid PET positivity prevalence to Insight 46, 543 PET scans would need to be performed. Screening using age, sex and APOE ε4 status would require 940 individuals, of whom 266 would proceed to scan. Using mass spectrometry amyloid-β1-42/1-40 alone would reduce these numbers to 623 individuals and 243 individuals, respectively. Across a theoretical range of amyloid PET positivity prevalence of 10-50%, mass spectrometry measures of amyloid-β1-42/1-40 would consistently reduce the numbers proceeding to scans, with greater cost savings demonstrated at lower prevalence.
|
|
| 19. |
- Lewis, Amanda M., et al.
(author)
-
Templates of expected measurement uncertainties for total neutron cross-section observables
- 2023
-
In: EPJ NUCLEAR SCIENCES & TECHNOLOGIES. - : EDP Sciences. - 2491-9292. ; 9
-
Journal article (peer-reviewed)abstract
- This paper provides a template of expected uncertainties and correlations for measurements of total neutron cross-section observables by transmission. Measurements with time-of-flight and mono-energetic neutron sources are covered. The information required for evaluations in the resonance region and high energy region is detailed, along with the template of uncertainties and correlations that can be used in the absence of other information.
|
|
| 20. |
- Morales Berstein, Fernanda, et al.
(author)
-
Assessing the causal role of epigenetic clocks in the development of multiple cancers : a Mendelian randomization study.
- 2022
-
In: eLIFE. - 2050-084X. ; 11
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Epigenetic clocks have been associated with cancer risk in several observational studies. Nevertheless, it is unclear whether they play a causal role in cancer risk or if they act as a non-causal biomarker.METHODS: We conducted a two-sample Mendelian randomization (MR) study to examine the genetically predicted effects of epigenetic age acceleration as measured by HannumAge (nine single-nucleotide polymorphisms (SNPs)), Horvath Intrinsic Age (24 SNPs), PhenoAge (11 SNPs), and GrimAge (4 SNPs) on multiple cancers (i.e. breast, prostate, colorectal, ovarian and lung cancer). We obtained genome-wide association data for biological ageing from a meta-analysis (N = 34,710), and for cancer from the UK Biobank (N cases = 2671-13,879; N controls = 173,493-372,016), FinnGen (N cases = 719-8401; N controls = 74,685-174,006) and several international cancer genetic consortia (N cases = 11,348-122,977; N controls = 15,861-105,974). Main analyses were performed using multiplicative random effects inverse variance weighted (IVW) MR. Individual study estimates were pooled using fixed effect meta-analysis. Sensitivity analyses included MR-Egger, weighted median, weighted mode and Causal Analysis using Summary Effect Estimates (CAUSE) methods, which are robust to some of the assumptions of the IVW approach.RESULTS: Meta-analysed IVW MR findings suggested that higher GrimAge acceleration increased the risk of colorectal cancer (OR = 1.12 per year increase in GrimAge acceleration, 95% CI 1.04-1.20, p = 0.002). The direction of the genetically predicted effects was consistent across main and sensitivity MR analyses. Among subtypes, the genetically predicted effect of GrimAge acceleration was greater for colon cancer (IVW OR = 1.15, 95% CI 1.09-1.21, p = 0.006), than rectal cancer (IVW OR = 1.05, 95% CI 0.97-1.13, p = 0.24). Results were less consistent for associations between other epigenetic clocks and cancers.CONCLUSIONS: GrimAge acceleration may increase the risk of colorectal cancer. Findings for other clocks and cancers were inconsistent. Further work is required to investigate the potential mechanisms underlying the results.FUNDING: FMB was supported by a Wellcome Trust PhD studentship in Molecular, Genetic and Lifecourse Epidemiology (224982/Z/22/Z which is part of grant 218495/Z/19/Z). KKT was supported by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme) and by the Hellenic Republic's Operational Programme 'Competitiveness, Entrepreneurship & Innovation' (OΠΣ 5047228). PH was supported by Cancer Research UK (C18281/A29019). RMM was supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol and by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). RMM is a National Institute for Health Research Senior Investigator (NIHR202411). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. GDS and CLR were supported by the Medical Research Council (MC_UU_00011/1 and MC_UU_00011/5, respectively) and by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). REM was supported by an Alzheimer's Society project grant (AS-PG-19b-010) and NIH grant (U01 AG-18-018, PI: Steve Horvath). RCR is a de Pass Vice Chancellor's Research Fellow at the University of Bristol.
|
|
