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1.
  • 2021
  • swepub:Mat__t
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2.
  • Zuntini, Alexandre R., et al. (author)
  • Phylogenomics and the rise of the angiosperms
  • 2024
  • In: NATURE. - 0028-0836 .- 1476-4687. ; 629, s. 843-850
  • Journal article (peer-reviewed)abstract
    • Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods(1,2). A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome(3,4). Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins(5-7). However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes(8). This 15-fold increase in genus-level sampling relative to comparable nuclear studies(9) provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.
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3.
  • Wang, Anqi, et al. (author)
  • Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
  • 2023
  • In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
  • Journal article (peer-reviewed)abstract
    • The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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4.
  • Santangelo, James S., et al. (author)
  • Global urban environmental change drives adaptation in white clover
  • 2022
  • In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
  • Journal article (peer-reviewed)abstract
    • Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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5.
  • Conti, David, V, et al. (author)
  • Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
  • 2021
  • In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
  • Journal article (peer-reviewed)abstract
    • Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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6.
  • Aharonian, F., et al. (author)
  • Discovery of a radiation component from the Vela pulsar reaching 20 teraelectronvolts
  • 2023
  • In: Nature Astronomy. - : Nature Publishing Group. - 2397-3366. ; 7:11, s. 1341-1350
  • Journal article (peer-reviewed)abstract
    • Gamma-ray observations have established energetic isolated pulsars as outstanding particle accelerators and antimatter factories. However, many questions are still open regarding the acceleration and radiation processes involved, as well as the locations where they occur. The radiation spectra of all gamma-ray pulsars observed to date show strong cutoffs or a break above energies of a few gigaelectronvolts. Using the High Energy Stereoscopic System's Cherenkov telescopes, we discovered a radiation component from the Vela pulsar which emerges beyond this generic cutoff and extends up to energies of at least 20 teraelectronvolts. This is an order of magnitude larger than in the case of the Crab pulsar, the only other pulsar detected in the teraelectronvolt energy range. Our results challenge the state-of-the-art models for the high-energy emission of pulsars. Furthermore, they pave the way for investigating other pulsars through their multiteraelectronvolt emission, thereby imposing additional constraints on the acceleration and emission processes in their extreme energy limit. The H.E.S.S. gamma-ray observatory has observed gamma rays with energies of at least 20 TeV from a pulsar, an energy regime that is hard to reconcile with the existing theories of gamma-ray production for such objects.
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7.
  • Mullins, Niamh, et al. (author)
  • Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
  • 2022
  • In: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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8.
  • Docherty, Anna R, et al. (author)
  • GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
  • 2023
  • In: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
  • Journal article (peer-reviewed)abstract
    • Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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9.
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10.
  • Feng, Shaohong, et al. (author)
  • Dense sampling of bird diversity increases power of comparative genomics
  • 2020
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833
  • Journal article (peer-reviewed)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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11.
  • Berne, Olivier, et al. (author)
  • PDRs4All : A JWST Early Release Science Program on Radiative Feedback from Massive Stars
  • 2022
  • In: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 134:1035
  • Journal article (peer-reviewed)abstract
    • Massive stars disrupt their natal molecular cloud material through radiative and mechanical feedback processes. These processes have profound effects on the evolution of interstellar matter in our Galaxy and throughout the universe, from the era of vigorous star formation at redshifts of 1-3 to the present day. The dominant feedback processes can be probed by observations of the Photo-Dissociation Regions (PDRs) where the far-ultraviolet photons of massive stars create warm regions of gas and dust in the neutral atomic and molecular gas. PDR emission provides a unique tool to study in detail the physical and chemical processes that are relevant for most of the mass in inter- and circumstellar media including diffuse clouds, proto-planetary disks, and molecular cloud surfaces, globules, planetary nebulae, and star-forming regions. PDR emission dominates the infrared (IR) spectra of star-forming galaxies. Most of the Galactic and extragalactic observations obtained with the James Webb Space Telescope (JWST) will therefore arise in PDR emission. In this paper we present an Early Release Science program using the MIRI, NIRSpec, and NIRCam instruments dedicated to the observations of an emblematic and nearby PDR: the Orion Bar. These early JWST observations will provide template data sets designed to identify key PDR characteristics in JWST observations. These data will serve to benchmark PDR models and extend them into the JWST era. We also present the Science-Enabling products that we will provide to the community. These template data sets and Science-Enabling products will guide the preparation of future proposals on star-forming regions in our Galaxy and beyond and will facilitate data analysis and interpretation of forthcoming JWST observations.
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12.
  • McCarrick, Heather, et al. (author)
  • The Simons Observatory Microwave SQUID Multiplexing Detector Module Design
  • 2021
  • In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 922:1
  • Journal article (peer-reviewed)abstract
    • Advances in cosmic microwave background (CMB) science depend on increasing the number of sensitive detectors observing the sky. New instruments deploy large arrays of superconducting transition-edge sensor (TES) bolometers tiled densely into ever larger focal planes. High multiplexing factors reduce the thermal loading on the cryogenic receivers and simplify their design. We present the design of focal-plane modules with an order of magnitude higher multiplexing factor than has previously been achieved with TES bolometers. We focus on the novel cold readout component, which employs microwave SQUID multiplexing (μmux). Simons Observatory will use 49 modules containing 70,000 bolometers to make exquisitely sensitive measurements of the CMB. We validate the focal-plane module design, presenting measurements of the readout component with and without a prototype detector array of 1728 polarization-sensitive bolometers coupled to feedhorns. The readout component achieves a 95% yield and a 910 multiplexing factor. The median white noise of each readout channel is 65 pA √Hz . This impacts the projected SO mapping speed by <8%, which is less than is assumed in the sensitivity projections. The results validate the full functionality of the module. We discuss the measured performance in the context of SO science requirements, which are exceeded.
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13.
  • Schijven, Dick, et al. (author)
  • Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium
  • 2023
  • In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:14
  • Journal article (peer-reviewed)abstract
    • Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
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14.
  • van Akkooi, Alexander C. J., et al. (author)
  • Neoadjuvant Systemic Therapy (NAST) in Patients with Melanoma: Surgical Considerations by the International Neoadjuvant Melanoma Consortium (INMC)
  • 2022
  • In: ANNALS OF SURGICAL ONCOLOGY. - : Springer Science and Business Media LLC. - 1068-9265 .- 1534-4681. ; 29:6, s. 3694-3708
  • Journal article (peer-reviewed)abstract
    • Exciting advances in melanoma systemic therapies have presented the opportunity for surgical oncologists and their multidisciplinary colleagues to test the neoadjuvant systemic treatment approach in high-risk, resectable metastatic melanomas. Here we describe the state of the science of neoadjuvant systemic therapy (NAST) for melanoma, focusing on the surgical aspects and the key role of the surgical oncologist in this treatment paradigm. This paper summarizes the past decade of developments in melanoma treatment and the current evidence for NAST in stage III melanoma specifically. Issues of surgical relevance are discussed, including the risk of progression on NAST prior to surgery. Technical aspects, such as the definition of resectability for melanoma and the extent and scope of routine surgery are presented. Other important issues, such as the utility of radiographic response evaluation and method of pathologic response evaluation, are addressed. Surgical complications and perioperative management of NAST related adverse events are considered. The International Neoadjuvant Melanoma Consortium has the goal of harmonizing NAST trials in melanoma to facilitate rapid advances with new approaches, and facilitating the comparison of results across trials evaluating different treatment regimens. Our ultimate goals are to provide definitive proof of the safety and efficacy of NAST in melanoma, sufficient for NAST to become an acceptable standard of care, and to leverage this platform to allow more personalized, biomarker-driven, tailored approaches to subsequent treatment and surveillance.
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15.
  • Abazajian, Kevork, et al. (author)
  • CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
  • 2022
  • In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
  • Journal article (peer-reviewed)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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16.
  • Jang, Seon-Kyeong, et al. (author)
  • Rare genetic variants explain missing heritability in smoking.
  • 2022
  • In: Nature human behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 6:11, s. 1577-1586
  • Journal article (peer-reviewed)abstract
    • Common genetic variants explain less variation in complex phenotypes than inferred from family-based studies, and there is a debate on the source of this 'missing heritability'. We investigated the contribution of rare genetic variants to tobacco use with whole-genome sequences from up to 26,257 unrelated individuals of European ancestries and 11,743 individuals of African ancestries. Across four smoking traits, single-nucleotide-polymorphism-based heritability ([Formula: see text]) was estimated from 0.13 to 0.28 (s.e., 0.10-0.13) in European ancestries, with 35-74% of it attributable to rare variants with minor allele frequencies between 0.01% and 1%. These heritability estimates are 1.5-4 times higher than past estimates based on common variants alone and accounted for 60% to 100% of our pedigree-based estimates of narrow-sense heritability ([Formula: see text], 0.18-0.34). In the African ancestry samples, [Formula: see text] was estimated from 0.03 to 0.33 (s.e., 0.09-0.14) across the four smoking traits. These results suggest that rare variants are important contributors to the heritability of smoking.
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17.
  • Maxwell, Tania L., et al. (author)
  • Global dataset of soil organic carbon in tidal marshes
  • 2023
  • In: Scientific Data. - : Springer Nature. - 2052-4463. ; 10:1
  • Journal article (peer-reviewed)abstract
    • Tidal marshes store large amounts of organic carbon in their soils. Field data quantifying soil organic carbon (SOC) stocks provide an important resource for researchers, natural resource managers, and policy-makers working towards the protection, restoration, and valuation of these ecosystems. We collated a global dataset of tidal marsh soil organic carbon (MarSOC) from 99 studies that includes location, soil depth, site name, dry bulk density, SOC, and/or soil organic matter (SOM). The MarSOC dataset includes 17,454 data points from 2,329 unique locations, and 29 countries. We generated a general transfer function for the conversion of SOM to SOC. Using this data we estimated a median (± median absolute deviation) value of 79.2 ± 38.1 Mg SOC ha−1 in the top 30 cm and 231 ± 134 Mg SOC ha−1 in the top 1 m of tidal marsh soils globally. This data can serve as a basis for future work, and may contribute to incorporation of tidal marsh ecosystems into climate change mitigation and adaptation strategies and policies.
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18.
  • Tran, Thao Thanh, et al. (author)
  • Inhibition of the master regulator of Listeria monocytogenes virulence enables bacterial clearance from spacious replication vacuoles in infected macrophages
  • 2022
  • In: PLoS Pathogens. - : Public Library Science. - 1553-7366 .- 1553-7374. ; 18:1
  • Journal article (peer-reviewed)abstract
    • A hallmark of Listeria (L.) monocytogenes pathogenesis is bacterial escape from maturing entry vacuoles, which is required for rapid bacterial replication in the host cell cytoplasm and cell-to-cell spread. The bacterial transcriptional activator PrfA controls expression of key virulence factors that enable exploitation of this intracellular niche. The transcriptional activity of PrfA within infected host cells is controlled by allosteric coactivation. Inhibitory occupation of the coactivator site has been shown to impair PrfA functions, but consequences of PrfA inhibition for L. monocytogenes infection and pathogenesis are unknown. Here we report the crystal structure of PrfA with a small molecule inhibitor occupying the coactivator site at 2.0 Å resolution. Using molecular imaging and infection studies in macrophages, we demonstrate that PrfA inhibition prevents the vacuolar escape of L. monocytogenes and enables extensive bacterial replication inside spacious vacuoles. In contrast to previously described spacious Listeria-containing vacuoles, which have been implicated in supporting chronic infection, PrfA inhibition facilitated progressive clearance of intracellular L. monocytogenes from spacious vacuoles through lysosomal degradation. Thus, inhibitory occupation of the PrfA coactivator site facilitates formation of a transient intravacuolar L. monocytogenes replication niche that licenses macrophages to effectively eliminate intracellular bacteria. Our findings encourage further exploration of PrfA as a potential target for antimicrobials and highlight that intra-vacuolar residence of L. monocytogenes in macrophages is not inevitably tied to bacterial persistence.
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19.
  • Antonelli, Alexandre, 1978, et al. (author)
  • Settling a family feud: a high-level phylogenomic framework for the Gentianales based on 353 nuclear genes and partial plastomes
  • 2021
  • In: American Journal of Botany. - : Wiley. - 0002-9122 .- 1537-2197. ; 108:7, s. 1143-1165
  • Journal article (peer-reviewed)abstract
    • Premise: Comprising five families that vastly differ in species richness—ranging from Gelsemiaceae with 13 species to the Rubiaceae with 13,775 species—members of the Gentianales are often among the most species-rich and abundant plants in tropical forests. Despite considerable phylogenetic work within particular families and genera, several alternative topologies for family-level relationships within Gentianales have been presented in previous studies. Methods: Here we present a phylogenomic analysis based on nuclear genes targeted by the Angiosperms353 probe set for approximately 150 species, representing all families and approximately 85% of the formally recognized tribes. We were able to retrieve partial plastomes from off-target reads for most taxa and infer phylogenetic trees for comparison with the nuclear-derived trees. Results: We recovered high support for over 80% of all nodes. The plastid and nuclear data are largely in agreement, except for some weakly to moderately supported relationships. We discuss the implications of our results for the order’s classification, highlighting points of increased support for previously uncertain relationships. Rubiaceae is sister to a clade comprising (Gentianaceae + Gelsemiaceae) + (Apocynaceae + Loganiaceae). Conclusions: The higher-level phylogenetic relationships within Gentianales are confidently resolved. In contrast to recent studies, our results support the division of Rubiaceae into two subfamilies: Cinchonoideae and Rubioideae. We do not formally recognize Coptosapelteae and Luculieae within any particular subfamily but treat them as incertae sedis. Our framework paves the way for further work on the phylogenetics, biogeography, morphological evolution, and macroecology of this important group of flowering plants.
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20.
  • Gemmell, Neil J., et al. (author)
  • The tuatara genome reveals ancient features of amniote evolution
  • 2020
  • In: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 584:7821, s. 403-409
  • Journal article (peer-reviewed)abstract
    • The tuatara (Sphenodon punctatus)—the only living member of the reptilian order Rhynchocephalia (Sphenodontia), once widespread across Gondwana1,2—is an iconic species that is endemic to New Zealand2,3. A key link to the now-extinct stem reptiles (from which dinosaurs, modern reptiles, birds and mammals evolved), the tuatara provides key insights into the ancestral amniotes2,4. Here we analyse the genome of the tuatara, which—at approximately 5 Gb—is among the largest of the vertebrate genomes yet assembled. Our analyses of this genome, along with comparisons with other vertebrate genomes, reinforce the uniqueness of the tuatara. Phylogenetic analyses indicate that the tuatara lineage diverged from that of snakes and lizards around 250 million years ago. This lineage also shows moderate rates of molecular evolution, with instances of punctuated evolution. Our genome sequence analysis identifies expansions of proteins, non-protein-coding RNA families and repeat elements, the latter of which show an amalgam of reptilian and mammalian features. The sequencing of the tuatara genome provides a valuable resource for deep comparative analyses of tetrapods, as well as for tuatara biology and conservation. Our study also provides important insights into both the technical challenges and the cultural obligations that are associated with genome sequencing.
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21.
  • Holder, Peter E., et al. (author)
  • Preparing for a changing future in recreational fisheries : 100 research questions for global consideration emerging from a horizon scan
  • 2020
  • In: Reviews in Fish Biology and Fisheries. - : Springer Science and Business Media LLC. - 0960-3166 .- 1573-5184. ; 30:1, s. 137-151
  • Research review (peer-reviewed)abstract
    • Recreational fisheries hold immense ecological, social, and economic value. The management of these fisheries is increasingly important as we move forward in the Anthropocene. Recreational fisheries managers face several challenges as fisheries often involve diverse social and ecological systems comprised of complex feedback and stakeholder motivations and needs. Here, we used a horizon scanning exercise to yield 100 research questions related to recreational fisheries science and management in the Anthropocene. Initial research questions (n = 205) were collected from recreational fisheries experts (i.e., stakeholders, managers, researchers) from various sectors (i.e., industry, government, NGOs) and geographic locations (14 countries: Australia, Brazil, Canada, Czech Republic, Germany, Italy, New Zealand, Norway, South Africa, Spain, Sweden, Switzerland, United Kingdom, USA). These questions were subsequently categorized, thematized, and refined by our authorship team, eventually yielding what we considered to be the top 100 research questions of relevance to management of recreational fisheries. The key themes include: human dimensions; bioeconomics; resource monitoring and data acquisition; governance; management-regulatory actions; management-stock and habitat enhancement; catch-and-release; impacts of recreational fisheries on populations, communities and ecosystems; threats and sustainability; and angler outreach, education and engagement. It is our intention that this comprehensive and forward-looking list will create a framework to guide future research within this field, and contribute to evidence-based recreational fisheries management and policy.
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22.
  • Moyroud, Edwige, et al. (author)
  • Cuticle chemistry drives the development of diffraction gratings on the surface of Hibiscus trionum petals
  • 2022
  • In: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 32:24, s. 5323-5334, 5323-5334.e1-e6
  • Journal article (peer-reviewed)abstract
    • Plants combine both chemical and structural means to appear colorful. We now have an extensive understanding of the metabolic pathways used by flowering plants to synthesize pigments, but the mechanisms remain obscure whereby cells produce microscopic structures sufficiently regular to interfere with light and create an optical effect. Here, we combine transgenic approaches in a novel model system, Hibiscus trionum, with chemical analyses of the cuticle, both in transgenic lines and in different species of Hibiscus, to investigate the formation of a semi-ordered diffraction grating on the petal surface. We show that regulating both cuticle production and epidermal cell growth is insufficient to determine the type of cuticular pattern produced. Instead, the chemical composition of the cuticle plays a crucial role in restricting the formation of diffraction gratings to the pigmented region of the petal. This suggests that buckling, driven by spatiotemporal regulation of cuticle chemistry, could pattern the petal surface at the nanoscale.
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23.
  • Sirressi, Mattia, 1995-, et al. (author)
  • CLusters in the Uv as EngineS (CLUES). II. Subkiloparsec-scale Outflows Driven by Stellar Feedback
  • 2024
  • In: Astronomical Journal. - 0004-6256 .- 1538-3881. ; 167:4
  • Journal article (peer-reviewed)abstract
    • We analyze the far-ultraviolet (1130−1770 Å rest frame) spectroscopy of 20 young (<50 Myr) and massive (>104M⊙) star clusters (YSCs) in 11 nearby star-forming galaxies. We probe the interstellar gas intervening along the line of sight, detecting several metal absorption lines of a wide range of ionization potentials, from 6.0 to 77.5 eV. Multiple-component Voigt fits to the absorption lines are used to study the kinematics of the gas. We find that nearly all targets in the sample feature gas outflowing from 30 up to 190 km s−1, often in both the neutral and ionized phases. The outflow velocities correlate with the underlying stellar population properties directly linked to the feedback: the mass of the YSCs, the photon production rate, and the instantaneous mechanical luminosity produced by stellar winds and supernovae. We detect a neutral inflow in four targets, which we interpret as likely not associated with the star cluster but tracing larger-scale gas kinematics. A comparison between the outflows' energy and that produced by the associated young stellar populations suggests an average coupling efficiency of 10% with a broad scatter. Our results extend the relation found in previous works between galactic outflows and the host galaxy star formation rate to smaller scales, pointing toward the key role that clustered star formation and feedback play in regulating galaxy growth.
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24.
  • Abbasi, Rasha, et al. (author)
  • IceCube search for neutrinos from GRB 221009A
  • 2023
  • In: Proceedings of 38th International Cosmic Ray Conference (ICRC 2023). - : Sissa Medialab Srl.
  • Conference paper (peer-reviewed)abstract
    •  GRB 221009A is the brightest Gamma Ray Burst (GRB) ever observed. The observed extremelyhigh flux of high and very-high-energy photons provide a unique opportunity to probe the predictedneutrino counterpart to the electromagnetic emission. We have used a variety of methods to searchfor neutrinos in coincidence with the GRB over several time windows during the precursor, promptand afterglow phases of the GRB. MeV scale neutrinos are studied using photo-multiplier ratescalers which are normally used to search for galactic core-collapse supernovae neutrinos. GeVneutrinos are searched starting with DeepCore triggers. These events don’t have directionallocalization, but instead can indicate an excess in the rate of events. 10 GeV - 1 TeV and >TeVneutrinos are searched using traditional neutrino point source methods which take into accountthe direction and time of events with DeepCore and the entire IceCube detector respectively. The>TeV results include both a fast-response analysis conducted by IceCube in real-time with timewindows of T0 − 1 to T0 + 2 hours and T0 ± 1 day around the time of GRB 221009A, as well asan offline analysis with 3 new time windows up to a time window of T0 − 1 to T0 + 14 days, thelongest time period we consider. The combination of observations by IceCube covers 9 ordersof magnitude in neutrino energy, from MeV to PeV, placing upper limits across the range forpredicted neutrino emission.
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25.
  • Alcorn, Sara R., et al. (author)
  • Low-Dose Image-Guided Pediatric CNS Radiation Therapy : Final Analysis From a Prospective Low-Dose Cone-Beam CT Protocol From a Multinational Pediatrics Consortium
  • 2020
  • In: Technology in Cancer Research & Treatment. - : SAGE PUBLICATIONS INC. - 1533-0346 .- 1533-0338. ; 19
  • Journal article (peer-reviewed)abstract
    • Background: Lower-dose cone-beam computed tomography protocols for image-guided radiotherapy may permit target localization while minimizing radiation exposure. We prospectively evaluated a lower-dose cone-beam protocol for central nervous system image-guided radiotherapy across a multinational pediatrics consortium.Methods: Seven institutions prospectively employed a lower-dose cone-beam computed tomography central nervous system protocol (weighted average dose 0.7 mGy) for patients <= 21 years. Treatment table shifts between setup with surface lasers versus cone-beam computed tomography were used to approximate setup accuracy, and vector magnitudes for these shifts were calculated. Setup group mean, interpatient, interinstitution, and random error were estimated, and clinical factors were compared by mixed linear modeling.Results: Among 96 patients, with 2179 pretreatment cone-beam computed tomography acquisitions, median age was 9 years (1-20). Setup parameters were 3.13, 3.02, 1.64, and 1.48 mm for vector magnitude group mean, interpatient, interinstitution, and random error, respectively. On multivariable analysis, there were no significant differences in mean vector magnitude by age, gender, performance status, target location, extent of resection, chemotherapy, or steroid or anesthesia use. Providers rated >99% of images as adequate or better for target localization.Conclusions: A lower-dose cone-beam computed tomography protocol demonstrated table shift vector magnitude that approximate clinical target volume/planning target volume expansions used in central nervous system radiotherapy. There were no significant clinical predictors of setup accuracy identified, supporting use of this lower-dose cone-beam computed tomography protocol across a diverse pediatric population with brain tumors.
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26.
  • Fecchio, Alan, et al. (author)
  • Global drivers of avian haemosporidian infections vary across zoogeographical regions
  • 2021
  • In: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 30:12, s. 2393-2406
  • Journal article (peer-reviewed)abstract
    • Aim: Macroecological analyses provide valuable insights into factors that influence how parasites are distributed across space and among hosts. Amid large uncertainties that arise when generalizing from local and regional findings, hierarchical approaches applied to global datasets are required to determine whether drivers of parasite infection patterns vary across scales. We assessed global patterns of haemosporidian infections across a broad diversity of avian host clades and zoogeographical realms to depict hotspots of prevalence and to identify possible underlying drivers. Location: Global. Time period: 1994–2019. Major taxa studied: Avian haemosporidian parasites (genera Plasmodium, Haemoproteus, Leucocytozoon and Parahaemoproteus). Methods: We amalgamated infection data from 53,669 individual birds representing 2,445 species world-wide. Spatio-phylogenetic hierarchical Bayesian models were built to disentangle potential landscape, climatic and biotic drivers of infection probability while accounting for spatial context and avian host phylogenetic relationships. Results: Idiosyncratic responses of the three most common haemosporidian genera to climate, habitat, host relatedness and host ecological traits indicated marked variation in host infection rates from local to global scales. Notably, host ecological drivers, such as migration distance for Plasmodium and Parahaemoproteus, exhibited predominantly varying or even opposite effects on infection rates across regions, whereas climatic effects on infection rates were more consistent across realms. Moreover, infections in some low-prevalence realms were disproportionately concentrated in a few local hotspots, suggesting that regional-scale variation in habitat and microclimate might influence transmission, in addition to global drivers. Main conclusions: Our hierarchical global analysis supports regional-scale findings showing the synergistic effects of landscape, climate and host ecological traits on parasite transmission for a cosmopolitan and diverse group of avian parasites. Our results underscore the need to account for such interactions, in addition to possible variation in drivers across regions, to produce the robust inference required to predict changes in infection risk under future scenarios.
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27.
  • Groot, Colin, et al. (author)
  • Differential patterns of gray matter volumes and associated gene expression profiles in cognitively-defined Alzheimer's disease subgroups
  • 2021
  • In: NeuroImage: Clinical. - : Elsevier BV. - 2213-1582. ; 30
  • Journal article (peer-reviewed)abstract
    • The clinical presentation of Alzheimer's disease (AD) varies widely across individuals but the neurobiological mechanisms underlying this heterogeneity are largely unknown. Here, we compared regional gray matter (GM) volumes and associated gene expression profiles between cognitively-defined subgroups of amyloid-β positive individuals clinically diagnosed with AD dementia (age: 66 ± 7, 47% male, MMSE: 21 ± 5). All participants underwent neuropsychological assessment with tests covering memory, executive-functioning, language and visuospatial-functioning domains. Subgroup classification was achieved using a psychometric framework that assesses which cognitive domain shows substantial relative impairment compared to the intra-individual average across domains, which yielded the following subgroups in our sample; AD-Memory (n = 41), AD-Executive (n = 117), AD-Language (n = 33), AD-Visuospatial (n = 171). We performed voxel-wise contrasts of GM volumes derived from 3Tesla structural MRI between subgroups and controls (n = 127, age 58 ± 9, 42% male, MMSE 29 ± 1), and observed that differences in regional GM volumes compared to controls closely matched the respective cognitive profiles. Specifically, we detected lower medial temporal lobe GM volumes in AD-Memory, lower fronto-parietal GM volumes in AD-Executive, asymmetric GM volumes in the temporal lobe (left < right) in AD-Language, and lower GM volumes in posterior areas in AD-Visuospatial. In order to examine possible biological drivers of these differences in regional GM volumes, we correlated subgroup-specific regional GM volumes to brain-wide gene expression profiles based on a stereotactic characterization of the transcriptional architecture of the human brain as provided by the Allen human brain atlas. Gene-set enrichment analyses revealed that variations in regional expression of genes involved in processes like mitochondrial respiration and metabolism of proteins were associated with patterns of regional GM volume across multiple subgroups. Other gene expression vs GM volume-associations were only detected in particular subgroups, e.g., genes involved in the cell cycle for AD-Memory, specific sets of genes related to protein metabolism in AD-Language, and genes associated with modification of gene expression in AD-Visuospatial. We conclude that cognitively-defined AD subgroups show neurobiological differences, and distinct biological pathways may be involved in the emergence of these differences.
  •  
28.
  • Groot, Colin, et al. (author)
  • Differential trajectories of hypometabolism across cognitively-defined Alzheimer's disease subgroups
  • 2021
  • In: NeuroImage: Clinical. - : Elsevier BV. - 2213-1582. ; 31
  • Journal article (peer-reviewed)abstract
    • Disentangling biologically distinct subgroups of Alzheimer's disease (AD) may facilitate a deeper understanding of the neurobiology underlying clinical heterogeneity. We employed longitudinal [18F]FDG-PET standardized uptake value ratios (SUVRs) to map hypometabolism across cognitively-defined AD subgroups. Participants were 384 amyloid-positive individuals with an AD dementia diagnosis from ADNI who had a total of 1028 FDG-scans (mean time between first and last scan: 1.6 ± 1.8 years). These participants were categorized into subgroups on the basis of substantial impairment at time of dementia diagnosis in a specific cognitive domain relative to the average across domains. This approach resulted in groups of AD-Memory (n = 135), AD-Executive (n = 8), AD-Language (n = 22), AD-Visuospatial (n = 44), AD-Multiple Domains (n = 15) and AD-No Domains (for whom no domain showed substantial relative impairment; n = 160). Voxelwise contrasts against controls revealed that all AD-subgroups showed progressive hypometabolism compared to controls across temporoparietal regions at time of AD diagnosis. Voxelwise and regions-of-interest (ROI)-based linear mixed model analyses revealed there were also subgroup-specific hypometabolism patterns and trajectories. The AD-Memory group had more pronounced hypometabolism compared to all other groups in the medial temporal lobe and posterior cingulate, and faster decline in metabolism in the medial temporal lobe compared to AD-Visuospatial. The AD-Language group had pronounced lateral temporal hypometabolism compared to all other groups, and the pattern of metabolism was also more asymmetrical (left < right) than all other groups. The AD-Visuospatial group had faster decline in metabolism in parietal regions compared to all other groups, as well as faster decline in the precuneus compared to AD-Memory and AD-No Domains. Taken together, in addition to a common pattern, cognitively-defined subgroups of people with AD dementia show subgroup-specific hypometabolism patterns, as well as differences in trajectories of metabolism over time. These findings provide support to the notion that cognitively-defined subgroups are biologically distinct.
  •  
29.
  • Ji, Yanzhu, et al. (author)
  • Orthologous microsatellites, transposable elements, and DNA deletions correlate with generation time and body mass in neoavian birds
  • 2022
  • In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:35
  • Journal article (peer-reviewed)abstract
    • The rate of mutation accumulation in germline cells can be affected by cell replication and/or DNA damage, which are further related to life history traits such as generation time and body mass. Leveraging the existing datasets of 233 neoavian bird species, here, we investigated whether generation time and body mass contribute to the interspecific variation of orthologous microsatellite length, transposable element (TE) length, and deletion length and how these genomic attributes affect genome sizes. In nonpasserines, we found that generation time is correlated to both orthologous microsatellite length and TE length, and body mass is negatively correlated to DNA deletions. These patterns are less pronounced in passerines. In all species, we found that DNA deletions relate to genome size similarly as TE length, suggesting a role of body mass dynamics in genome evolution. Our results indicate that generation time and body mass shape the evolution of genomic attributes in neoavian birds.
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30.
  • Lillis, Robert J., et al. (author)
  • MOSAIC: A satellite constellation to enable groundbreaking mars climate system science and prepare for human exploration
  • 2021
  • In: Planetary Science Journal. - : Institute of Physics (IOP). - 2632-3338. ; 2:5
  • Journal article (peer-reviewed)abstract
    • The Martian climate system has been revealed to rival the complexity of Earth's. Over the last 20 yr, a fragmented and incomplete picture has emerged of its structure and variability; we remain largely ignorant of many of the physical processes driving matter and energy flow between and within Mars' diverse climate domains. Mars Orbiters for Surface, Atmosphere, and Ionosphere Connections (MOSAIC) is a constellation of ten platforms focused on understanding these climate connections, with orbits and instruments tailored to observe the Martian climate system from three complementary perspectives. First, low-circular near-polar Sun-synchronous orbits (a large mothership and three smallsats spaced in local time) enable vertical profiling of wind, aerosols, water, and temperature, as well as mapping of surface and subsurface ice. Second, elliptical orbits sampling all of Mars' plasma regions enable multipoint measurements necessary to understand mass/energy transport and ion-driven escape, also enabling, with the polar orbiters, dense radio occultation coverage. Last, longitudinally spaced areostationary orbits enable synoptic views of the lower atmosphere necessary to understand global and mesoscale dynamics, global views of the hydrogen and oxygen exospheres, and upstream measurements of space weather conditions. MOSAIC will characterize climate system variability diurnally and seasonally, on meso-, regional, and global scales, targeting the shallow subsurface all the way out to the solar wind, making many first-of-their-kind measurements. Importantly, these measurements will also prepare for human exploration and habitation of Mars by providing water resource prospecting, operational forecasting of dust and radiation hazards, and ionospheric communication/positioning disruptions.
  •  
31.
  • Pereira, Laura, et al. (author)
  • The Living Infinite
  • 2022
  • In: Vector. - 0505-0448.
  • Journal article (other academic/artistic)
  •  
32.
  • Pereira, Laura, 1985-, et al. (author)
  • The living infinite : Envisioning futures for transformed human-nature relationships on the high seas
  • 2023
  • In: Marine Policy. - 0308-597X .- 1872-9460. ; 153
  • Journal article (peer-reviewed)abstract
    • We find ourselves at a critical crossroads for the future governance of the high seas, but the perceived remoteness of the global ocean creates a psychological barrier for people to engage with it. Given challenges of over-exploitation, inequitable access and other sustainability and equity concerns, current ocean governance mech-anisms are not fit-for-purpose. This decade offers opportunities for direct impact on ocean governance, however, triggering a global transformation on how we use and protect the half of our planet requires a concerted effort that is guided by shared values and principles across regions and sectors. The aim of the series of workshops outlined in this paper, was to undertake a futures thinking process that could use the Nature Futures Framework as a mechanism to bring more transformative energy into how humans conceptualise the high seas and therefore how we aim to govern the ocean. We found that engaging with the future through science fiction narratives allowed a more radical appreciation of what could be and infusing science with artistic elements can inspire audiences beyond academia. Thus, creative endeavours of co-production that promote and encourage imagi-nation to address current challenges should be considered as important tools in the science-policy interface, also as a way to elicit empathetic responses. This workshop series was a first, and hopefully promising, step towards generating a more creative praxis in how we imagine and then act for a better future for the high seas.
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33.
  • Segev, Gideon, et al. (author)
  • The 2022 solar fuels roadmap
  • 2022
  • In: Journal of Physics D. - : IOP Publishing. - 0022-3727 .- 1361-6463. ; 55:32
  • Journal article (peer-reviewed)abstract
    • Renewable fuel generation is essential for a low carbon footprint economy. Thus, over the last five decades, a significant effort has been dedicated towards increasing the performance of solar fuels generating devices. Specifically, the solar to hydrogen efficiency of photoelectrochemical cells has progressed steadily towards its fundamental limit, and the faradaic efficiency towards valuable products in CO2 reduction systems has increased dramatically. However, there are still numerous scientific and engineering challenges that must be overcame in order to turn solar fuels into a viable technology. At the electrode and device level, the conversion efficiency, stability and products selectivity must be increased significantly. Meanwhile, these performance metrics must be maintained when scaling up devices and systems while maintaining an acceptable cost and carbon footprint. This roadmap surveys different aspects of this endeavor: system benchmarking, device scaling, various approaches for photoelectrodes design, materials discovery, and catalysis. Each of the sections in the roadmap focuses on a single topic, discussing the state of the art, the key challenges and advancements required to meet them. The roadmap can be used as a guide for researchers and funding agencies highlighting the most pressing needs of the field.
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34.
  • Shannon, Casey P., et al. (author)
  • HEARTBiT : A Transcriptomic Signature for Excluding Acute Cellular Rejection in Adult Heart Allograft Patients
  • 2020
  • In: Canadian Journal of Cardiology. - : Elsevier BV. - 0828-282X. ; 36:8, s. 1217-1227
  • Journal article (peer-reviewed)abstract
    • Background: Nine mRNA transcripts associated with acute cellular rejection (ACR) in previous microarray studies were ported to the clinically amenable NanoString nCounter platform. Here we report the diagnostic performance of the resulting blood test to exclude ACR in heart allograft recipients: HEARTBiT. Methods: Blood samples for transcriptomic profiling were collected during routine post-transplantation monitoring in 8 Canadian transplant centres participating in the Biomarkers in Transplantation initiative, a large (n = 1622) prospective observational study conducted between 2009 and 2014. All adult cardiac transplant patients were invited to participate (median age = 56 [17 to 71]). The reference standard for rejection status was histopathology grading of tissue from endomyocardial biopsy (EMB). All locally graded ISHLT ≥ 2R rejection samples were selected for analysis (n = 36). ISHLT 1R (n = 38) and 0R (n = 86) samples were randomly selected to create a cohort approximately matched for site, age, sex, and days post-transplantation, with a focus on early time points (median days post-transplant = 42 [7 to 506]). Results: ISHLT ≥ 2R rejection was confirmed by EMB in 18 and excluded in 92 samples in the test set. HEARTBiT achieved 47% specificity (95% confidence interval [CI], 36%-57%) given ≥ 90% sensitivity, with a corresponding area under the receiver operating characteristic curve of 0.69 (95% CI, 0.56-0.81). Conclusions: HEARTBiT's diagnostic performance compares favourably to the only currently approved minimally invasive diagnostic test to rule out ACR, AlloMap (CareDx, Brisbane, CA) and may be used to inform care decisions in the first 2 months post-transplantation, when AlloMap is not approved, and most ACR episodes occur.
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35.
  • Sirressi, Mattia, et al. (author)
  • CLusters in the UV as EngineS (CLUES). I. Survey Presentation and FUV Spectral Analysis of the Stellar Light
  • 2022
  • In: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 164:5
  • Journal article (peer-reviewed)abstract
    • The CLusters in the Uv as EngineS (CLUES) survey is a Cosmic Origins Spectrograph (COS) campaign aimed at acquiring the 1130–1770 Å rest-frame spectroscopy of very young (<20 Myr) and massive (>104 M⊙) star clusters in galaxies that are part of the Hubble treasury program Legacy ExtraGalactic UV Survey. In this first paper of a series, we describe the CLUES sample consisting of 20 young star clusters and report their physical properties as derived by both multiwavelength photometry and far-UV (FUV) spectroscopy with Hubble Space Telescope. Thanks to the synergy of the two different data sets, we build a coherent picture of the diverse stellar populations found in each region (with sizes of 40–160 pc). We associate the FUV-brightest stellar population to the central targeted star cluster and the other modeled population to the diffuse stars that are included in the COS aperture. We observe better agreement between photometric and spectroscopic ages for star clusters younger than 5 Myr. For clusters older than 5 Myr, photometry and spectroscopy measurements deviate, with the latter producing older ages, due to the degeneracy of photometric models. FUV spectroscopy enables us to better constrain the stellar metallicities, a parameter that optical colors are insensitive to. Finally, the derived E(B − V) are quite similar, with a tendency for FUV spectroscopy to favor solutions with higher extinctions. The recovered masses are in agreement within a factor of 2 for all of the clusters.
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36.
  • Beal, Jacob, et al. (author)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • Journal article (peer-reviewed)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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37.
  • Choi, Seo Eun, et al. (author)
  • Development and validation of language and visuospatial composite scores in ADNI
  • 2020
  • In: Alzheimer's and Dementia: Translational Research and Clinical Interventions. - : Wiley. - 2352-8737. ; 6:1
  • Journal article (peer-reviewed)abstract
    • Introduction: Composite scores may be useful to summarize overall language or visuospatial functioning in studies of older adults. Methods:We used item response theory to derive composite measures for language (ADNI-Lan) and visuospatial functioning (ADNI-VS) from the cognitive battery administered in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We evaluated the scores among groups of people with normal cognition, mild cognitive impairment (MCI), and Alzheimer’s disease (AD) in terms of responsiveness to change, association with imaging findings, and ability to differentiate between MCI participants who progressed to AD dementia and those who did not progress. Results: ADNI-Lan andADNI-VSwere able to detect change over time and predict conversion fromMCI toAD. Theywere associated with most of the pre-specified magnetic resonance imaging measures. ADNI-Lan had strong associations with a cerebrospinal fluid biomarker pattern. Discussion: ADNI-Lan and ADNI-VS may be useful composites for language and visuospatial functioning in ADNI.
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38.
  • Cousins, Melanie, et al. (author)
  • Is scientific evidence enough? Using expert opinion to fill gaps in data in antimicrobial resistance research
  • 2023
  • In: PLOS ONE. - 1932-6203. ; 18:8
  • Journal article (peer-reviewed)abstract
    • BackgroundAntimicrobial Resistance (AMR) is a global problem with large health and economic consequences. Current gaps in quantitative data are a major limitation for creating models intended to simulate the drivers of AMR. As an intermediate step, expert knowledge and opinion could be utilized to fill gaps in knowledge for areas of the system where quantitative data does not yet exist or are hard to quantify. Therefore, the objective of this study was to identify quantifiable data about the current state of the factors that drive AMR and the strengths and directions of relationships between the factors from statements made by a group of experts from the One Health system that drives AMR development and transmission in a European context.MethodsThis study builds upon previous work that developed a causal loop diagram of AMR using input from two workshops conducted in 2019 in Sweden with experts within the European food system context. A secondary analysis of the workshop transcripts was conducted to identify semi-quantitative data to parameterize drivers in a model of AMR.Main findingsParticipants spoke about AMR by combining their personal experiences with professional expertise within their fields. The analysis of participants’ statements provided semi-quantitative data that can help inform a future of AMR emergence and transmission based on a causal loop diagram of AMR in a Swedish One Health system context.ConclusionUsing transcripts of a workshop including participants with diverse expertise across the system that drives AMR, we gained invaluable insight into the past, current, and potential future states of the major drivers of AMR, particularly where quantitative data are lacking.
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39.
  • Crane, Paul K., et al. (author)
  • Cognitively defined Alzheimer's dementia subgroups have distinct atrophy patterns
  • 2024
  • In: Alzheimer's and Dementia. - 1552-5260. ; 20:3, s. 1739-1752
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: We sought to determine structural magnetic resonance imaging (MRI) characteristics across subgroups defined based on relative cognitive domain impairments using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and to compare cognitively defined to imaging-defined subgroups. METHODS: We used data from 584 people with Alzheimer's disease (AD) (461 amyloid positive, 123 unknown amyloid status) and 118 amyloid-negative controls. We used voxel-based morphometry to compare gray matter volume (GMV) for each group compared to controls and to AD-Memory. RESULTS: There was pronounced bilateral lower medial temporal lobe atrophy with relative cortical sparing for AD-Memory, lower left hemisphere GMV for AD-Language, anterior lower GMV for AD-Executive, and posterior lower GMV for AD-Visuospatial. Formal asymmetry comparisons showed substantially more asymmetry in the AD-Language group than any other group (p = 1.15 × 10−10). For overlap between imaging-defined and cognitively defined subgroups, AD-Memory matched up with an imaging-defined limbic predominant group. DISCUSSION: MRI findings differ across cognitively defined AD subgroups.
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40.
  • Engler, Ian D, et al. (author)
  • Revision Rates After Primary Allograft ACL Reconstruction by Allograft Tissue Type in Older Patients.
  • 2023
  • In: Orthopaedic journal of sports medicine. - 2325-9671. ; 11:9
  • Journal article (peer-reviewed)abstract
    • While there is extensive literature on the use of allograft versus autograft in anterior cruciate ligament (ACL) reconstruction, there is limited clinical evidence to guide the surgeon in choice of allograft tissue type.To assess the revision rate after primary ACL reconstruction with allograft and to compare revision rates based on allograft tissue type and characteristics.Cohort study; Level of evidence, 3.Patients who underwent primary allograft ACL reconstructions at a single academic institution between 2015 and 2019 and who had minimum 2-year follow-up were included. Exclusion criteria were missing surgical or allograft tissue type data. Demographics, operative details, and subsequent surgical procedures were collected. Allograft details included graft tissue type (Achilles, bone-patellar tendon-bone [BTB], tibialis anterior or posterior, semitendinosus, unspecified soft tissue), allograft category (all-soft tissue vs bone block), donor age, irradiation duration and intensity, and chemical cleansing process. Revision rates were calculated and compared by allograft characteristics.Included were 418 patients (age, 39 ± 12years; body mass index, 30 ± 9kg/m2). The revision rate was 3% (11/418) at a mean follow-up of 4.9 ± 1.4years. There were no differences in revision rate according to allograft tissue type across Achilles tendon (3%; 3/95), BTB (5%; 3/58), tibialis anterior or posterior (3%; 5/162), semitendinosus (0%; 0/46), or unspecified soft tissue (0%; 0/57) (P = .35). There was no difference in revision rate between all-soft tissue versus bone block allograft (6/283 [2%] vs 5/135 [4%], respectively; P = .34). Of the 51% of grafts with irradiation data, all grafts were irradiated, with levels varying from 1.5 to 2.7 Mrad and 82% of grafts having levels of <2.0 Mrad. There was no difference in revision rate between the low-dose and medium-to high-dose irradiation cohorts (4% vs 6%, respectively; P = .64).Similarly low (0%-6%) revision rates after primary ACL reconstruction were seen regardless of allograft tissue type, bone block versus all-soft tissue allograft, and sterilization technique in 418 patients with mean age of 39 years. Surgeons may consider appropriately processed allograft tissue with or without bone block when indicating ACL reconstruction in older patients.
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41.
  • Gerkin, Richard C., et al. (author)
  • Recent Smell Loss Is the Best Predictor of COVID-19 Among Individuals With Recent Respiratory Symptoms
  • 2021
  • In: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 46
  • Journal article (peer-reviewed)abstract
    • In a preregistered, cross-sectional study, we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0–100 visual analog scales (VAS) for participants reporting a positive (C19+; n = 4148) or negative (C19−; n = 546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19− groups exhibited smell loss, but it was significantly larger in C19+ participants (mean ± SD, C19+: −82.5 ± 27.2 points; C19−: −59.8 ± 37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC = 0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0–10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4 < OR < 10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable.
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42.
  • Graells, Tiscar, et al. (author)
  • Exploring the factors that contribute to the successful implementation of antimicrobial resistance interventions : a comparison of high-income and low-middle-income countries
  • 2023
  • In: Frontiers in Public Health. - 2296-2565. ; 11
  • Journal article (peer-reviewed)abstract
    • IntroductionAntimicrobial resistance (AMR) is a challenge to modern medicine. Interventions have been applied worldwide to tackle AMR, but these actions are often not reported to peers or published, leading to important knowledge gaps about what actions are being taken. Understanding factors that influence the implementation of AMR interventions and what factors are relevant in low-middle-income countries (LMICs) and high-income countries (HICs) were the key objectives of this exploratory study, with the aim to identifying which priorities these contexts need.MethodsA questionnaire was used to explore context, characteristics, and success factors or obstacles to intervention success based on participant input. The context was analyzed using the AMR-Intervene framework, and success factors and obstacles to intervention success were identified using thematic analysis.ResultsOf the 77 interventions, 57 were implemented in HICs and 17 in LMICs. Interventions took place in the animal sector, followed by the human sector. Public organizations were mainly responsible for implementation and funding. Nine themes and 32 sub-themes emerged as important for intervention success. The themes most frequently reported were 'behavior', 'capacity and resources', 'planning', and 'information'. Five sub-themes were key in all contexts ('collaboration and coordination', 'implementation', 'assessment', 'governance', and 'awareness'), two were key in LMICs ('funding and finances' and 'surveillance, antimicrobial susceptibility testing and preventive screening'), and five were key in HICs ('mandatory', 'multiple profiles', 'personnel', 'management', and 'design').ConclusionLMIC sub-themes showed that funding and surveillance were still key issues for interventions, while important HIC sub-themes were more specific and detailed, including mandatory enforcement, multiple profiles, and personnel needed for good management and good design. While behavior is often underrated when implementing AMR interventions, capacity and resources are usually considered, and LMICs can benefit from sub-themes captured in HICs if tailored to their contexts. The factors identified can improve the design, planning, implementation, and evaluation of interventions.
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43.
  • Graells, Tiscar, et al. (author)
  • Studying Factors Affecting Success of Antimicrobial Resistance Interventions through the Lens of Experience : A Thematic Analysis
  • 2022
  • In: Antibiotics. - : MDPI AG. - 2079-6382. ; 11:5
  • Journal article (peer-reviewed)abstract
    • Antimicrobial resistance (AMR) affects the environment, and animal and human health. Institutions worldwide have applied various measures, some of which have reduced antimicrobial use and AMR. However, little is known about factors influencing the success of AMR interventions. To address this gap, we engaged health professionals, designers, and implementers of AMR interventions in an exploratory study to learn about their experience and factors that challenged or facilitated interventions and the context in which interventions were implemented. Based on participant input, our thematic analysis identified behaviour; institutional governance and management; and sharing and enhancing information as key factors influencing success. Important sub-themes included: correct behaviour reinforcement, financial resources, training, assessment, and awareness of AMR. Overall, interventions were located in high-income countries, the human sector, and were publicly funded and implemented. In these contexts, behaviour patterns strongly influenced success, yet are often underrated or overlooked when designing AMR interventions. Improving our understanding of what contributes to successful interventions would allow for better designs of policies that are tailored to specific contexts. Exploratory approaches can provide encouraging results in complex challenges, as made evident in our study. Remaining challenges include more engagement in this type of study by professionals and characterisation of themes that influence intervention outcomes by context.
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44.
  • Gregory, Sarah, et al. (author)
  • Mediterranean diet is associated with lower white matter lesion volume in Mediterranean cities and lower cerebrospinal fluid Aβ42 innon-Mediterranean cities in the EPAD LCS cohort.
  • 2023
  • In: Neurobiology of aging. - 1558-1497. ; 131, s. 29-38
  • Journal article (peer-reviewed)abstract
    • The Mediterranean diet (MedDiet) has been associated with better brain health and reduced incidence of dementia. Few studies have compared the effects of the MedDiet in early Alzheimer's disease or compared theeffects of the diet within and outside of the Mediterranean region. The Mediterranean diet adherence screener(MEDAS) and MEDAS continuous scores were calculated at the baseline visit of the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study (n=1625). The scores were included in linear regression models to test for associations with hippocampal volume, log-transformed white matter lesion volume, cerebrospinal fluid pTau18,and Aβ42. Higher MEDAS scores were associated with lower log-transformed white matter lesion volume (β: -0.07, standard error [SE]: 0.02, p<0.001). This association was only seen in the Mediterranean region (β: -0.12, SE: 0.03, p<0.001). In the non-Mediterranean region, higher MEDAS continuous scores were associated with lower cerebrospinal fluid Aβ42 (β: -68.30, SE: 14.32, p<0.001). More research is needed to understand the differences in the associations seen with the MedDiet and Alzheimer's disease biomarkers indifferent European regions.
  •  
45.
  • Holgerson, Meredith A., et al. (author)
  • Classifying Mixing Regimes in Ponds and Shallow Lakes
  • 2022
  • In: Water resources research. - : John Wiley & Sons. - 0043-1397 .- 1944-7973. ; 58:7
  • Journal article (peer-reviewed)abstract
    • Lakes are classified by thermal mixing regimes, with shallow waterbodies historically categorized as continuously mixing systems. Yet, recent studies demonstrate extended summertime stratification in ponds, underscoring the need to reassess thermal classifications for shallow waterbodies. In this study, we examined the summertime thermal dynamics of 34 ponds and shallow lakes across temperate North America and Europe to categorize and identify the drivers of different mixing regimes. We identified three mixing regimes: rarely (n = 18), intermittently (n = 10), and often (n = 6) mixed, where waterbodies mixed an average of 2%, 26%, and 75% of the study period, respectively. Waterbodies in the often mixed category were larger (≥4.17 ha) and stratification weakened with increased wind shear stress, characteristic of “shallow lakes.” In contrast, smaller waterbodies, or “ponds,” mixed less frequently, and stratification strengthened with increased shortwave radiation. Shallow ponds (<0.74 m) mixed intermittently, with daytime stratification often breaking down overnight due to convective cooling. Ponds ≥0.74 m deep were rarely or never mixed, likely due to limited wind energy relative to the larger density gradients associated with slightly deeper water columns. Precipitation events weakened stratification, even causing short-term mixing (hours to days) in some sites. By examining a broad set of shallow waterbodies, we show that mixing regimes are highly sensitive to very small differences in size and depth, with potential implications for ecological and biogeochemical processes. Ultimately, we propose a new framework to characterize the variable mixing regimes of ponds and shallow lakes.
  •  
46.
  • Kitko, Lisa, et al. (author)
  • Family Caregiving for Individuals With Heart Failure: A Scientific Statement From the American Heart Association
  • 2020
  • In: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 141:22, s. E864-E878
  • Journal article (peer-reviewed)abstract
    • Many individuals living with heart failure (HF) rely on unpaid support from their partners, family members, friends, or neighbors as caregivers to help manage their chronic disease. Given the advancements in treatments and devices for patients with HF, caregiving responsibilities have expanded in recent decades to include more intensive care for increasingly precarious patients with HF-tasks that would previously have been undertaken by healthcare professionals in clinical settings. The specific tasks of caregivers of patients with HF vary widely based on the patients symptoms and comorbidities, the relationship between patient and caregiver, and the complexity of the treatment regimen. Effects of caregiving on the caregiver and patient range from physical and psychological to financial. Therefore, it is critically important to understand the needs of caregivers to support the increasingly complex medical care they provide to patients living with HF. This scientific statement synthesizes the evidence pertaining to caregiving of adult individuals with HF in order to (1) characterize the HF caregiving role and how it changes with illness trajectory; (2) describe the financial, health, and well-being implications of caregiving in HF; (3) evaluate HF caregiving interventions to support caregiver and patient outcomes; (4) summarize existing policies and resources that support HF caregivers; and (5) identify knowledge gaps and future directions for providers, investigators, health systems, and policymakers.
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47.
  •  
48.
  • Léger, Anaïs, et al. (author)
  • AMR-Intervene : a social-ecological framework to capture the diversity of actions to tackle antimicrobial resistance from a One Health perspective
  • 2021
  • In: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 76:1, s. 1-21
  • Research review (peer-reviewed)abstract
    • The global threat of antimicrobial resistance (AMR) requires coordinated actions by and across different sectors. Increasing attention at the global and national Levels has Led to different strategies to tackle the challenge. The diversity of possible actions to address AMR is currently not well understood from a One Health perspective. AMR-Intervene, an interdisciplinary social-ecological framework, describes interventions to tackle AMR in terms of six components: (i) core information about the publication; (ii) social system; (iii) bio-ecological system; (iv) triggers and goals; (v) implementation and governance; and (vi) assessment. AMR-Intervene provides a broadly applicable framework, which can inform the design, implementation, assessment and reporting of interventions to tackle AMR and, in turn, enable faster uptake of successful interventions to build societal resilience to AMR.
  •  
49.
  • Léger, Anaïs, et al. (author)
  • Characterizing social-ecological context and success factors of antimicrobial resistance interventions across the One Health spectrum : analysis of 42 interventions targeting E. coli
  • 2021
  • In: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 21:1
  • Journal article (peer-reviewed)abstract
    • Background: Antimicrobial resistance (AMR) is among the most pressing One Health issues. While interventions and policies with various targets and goals have been implemented, evidence about factors underpinning success and failure of interventions in different sectors is lacking. The objective of this study is to identify characteristics of AMR interventions that increase their capacity to impact AMR. This study focuses on AMR interventions targeting E. coli.Methods: We used the AMR-Intervene framework to extract descriptions of the social and ecological systems of interventions to determine factors contributing to their success.Results: We identified 52 scientific publications referring to 42 unique E. coli AMR interventions. We mainly identified interventions implemented in high-income countries (36/42), at the national level (16/42), targeting primarily one sector of society (37/42) that was mainly the human sector (25/42). Interventions were primarily funded by governments (38/42). Most intervention targeted a low leverage point in the AMR system, (36/42), and aimed to change the epidemiology of AMR (14/42). Among all included publications, 55% (29/52) described at least one success factor or obstacle (29/52) and 19% (10/52) identified at least one success factor and one obstacle. Most reported success factors related to communication between the actors and stakeholders and the role of media, and stressed the importance of collaboration between disciplines and external partners. Described obstacles covered data quality, access to data and statistical analyses, and the validity of the results.Conclusions: Overall, we identified a lack of diversity regarding interventions. In addition, most published E. coli interventions were poorly described with limited evidence of the factors that contributed to the intervention success or failure. Design and reporting guidelines would help to improve reporting quality and provide a valuable tool for improving the science of AMR interventions.
  •  
50.
  • Li, Yafang, et al. (author)
  • Lung cancer in ever- and never-smokers : findings from multi-population GWAS studies
  • 2024
  • In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association For Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 33:3, s. 389-399
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer.METHODS: We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including expression quantitative trait loci (eQTL) colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants. We further evaluated the impact of smoking quantity on lung cancer risk for the variants associated with ever-smoking lung cancer.RESULTS: Five novel independent loci, GABRA4, intergenic region 12q24.33, LRRC4C, LINC01088, and LCNL1 were identified with the association at two or three populations (P < 5 × 10-8). Further functional analysis provided multiple lines of evidence suggesting the variants affect lung cancer risk through excessive DNA damage (GABRA4) or cis-regulation of gene expression (LCNL1). The risk of variants from 12 independent regions, including the well-known CHRNA5, associated with ever-smoking lung cancer was evaluated for never-smokers, light-smokers (packyear ≤ 20), and moderate-to-heavy-smokers (packyear > 20). Different risk patterns were observed for the variants among the different groups by smoking behavior.CONCLUSIONS: We identified novel variants associated with lung cancer in only ever- or never-smoking groups that were missed by prior main-effect association studies. IMPACT: Our study highlights the genetic heterogeneity between ever- and never-smoking lung cancer and provides etiologic insights into the complicated genetic architecture of this deadly cancer.
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