| 1. |
- Falster, Daniel, et al.
(author)
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AusTraits, a curated plant trait database for the Australian flora
- 2021
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In: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
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Journal article (peer-reviewed)abstract
- We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge.
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| 3. |
- Chirinos, Julio A., et al.
(author)
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Reduced Apolipoprotein M and Adverse Outcomes across the Spectrum of Human Heart Failure
- 2020
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In: Circulation. - 0009-7322. ; , s. 1463-1476
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Journal article (peer-reviewed)abstract
- Background: Apo (apolipoprotein) M mediates the physical interaction between high-density lipoprotein (HDL) particles and sphingosine-1-phosphate (S1P). Apo M exerts anti-inflammatory and cardioprotective effects in animal models. Methods: In a subset of PHFS (Penn Heart Failure Study) participants (n=297), we measured apo M by Enzyme-Linked ImmunoSorbent Assay (ELISA). We also measured total S1P by liquid chromatography-mass spectrometry and isolated HDL particles to test the association between apo M and HDL-associated S1P. We confirmed the relationship between apo M and outcomes using modified aptamer-based apo M measurements among 2170 adults in the PHFS and 2 independent cohorts: the Washington University Heart Failure Registry (n=173) and a subset of TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial; n=218). Last, we examined the relationship between apo M and ≈5000 other proteins (SomaScan assay) to identify biological pathways associated with apo M in heart failure. Results: In the PHFS, apo M was inversely associated with the risk of death (standardized hazard ratio, 0.56 [95% CI, 0.51-0.61]; P<0.0001) and the composite of death/ventricular assist device implantation/heart transplantation (standardized hazard ratio, 0.62 [95% CI, 0.58-0.67]; P<0.0001). This relationship was independent of HDL cholesterol or apo AI levels. Apo M remained associated with death (hazard ratio, 0.78 [95% CI, 0.69-0.88]; P<0.0001) and the composite of death/ventricular assist device/heart transplantation (hazard ratio, 0.85 [95% CI, 0.76-0.94]; P=0.001) in models that adjusted for multiple confounders. This association was present in both heart failure with reduced and preserved ejection fraction and was replicated in the Washington University cohort and a cohort with heart failure with preserved ejection fraction only (TOPCAT). The S1P and apo M content of isolated HDL particles strongly correlated (R=0.81, P<0.0001). The top canonical pathways associated with apo M were inflammation (negative association), the coagulation system (negative association), and liver X receptor/retinoid X receptor activation (positive association). The relationship with inflammation was validated with multiple inflammatory markers measured with independent assays. Conclusions: Reduced circulating apo M is independently associated with adverse outcomes across the spectrum of human heart failure. Further research is needed to assess whether the apo M/S1P axis is a suitable therapeutic target in heart failure.
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| 5. |
- Zaidi, Syed H., et al.
(author)
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Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival
- 2020
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In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR=0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR=1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features. Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds.
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| 6. |
- Harlid, Sophia, 1978-, et al.
(author)
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Diabetes mellitus in relation to colorectal tumor molecular subtypes : a pooled analysis of more than 9000 cases
- 2022
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In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 151:3, s. 348-360
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Journal article (peer-reviewed)abstract
- Diabetes is an established risk factor for colorectal cancer. However, colorectal cancer is a heterogeneous disease and it is not well understood whether diabetes is more strongly associated with some tumor molecular subtypes than others. A better understanding of the association between diabetes and colorectal cancer according to molecular subtypes could provide important insights into the biology of this association. We used data on lifestyle and clinical characteristics from the Colorectal Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), including 9756 colorectal cancer cases (with tumor marker data) and 9985 controls, to evaluate associations between reported diabetes and risk of colorectal cancer according to molecular subtypes. Tumor markers included BRAF and KRAS mutations, microsatellite instability and CpG island methylator phenotype. In the multinomial logistic regression model, comparing colorectal cancer cases to cancer-free controls, diabetes was positively associated with colorectal cancer regardless of subtype. The highest OR estimate was found for BRAF-mutated colorectal cancer, n = 1086 (ORfully adj: 1.67, 95% confidence intervals [CI]: 1.36-2.05), with an attenuated association observed between diabetes and colorectal cancer without BRAF-mutations, n = 7959 (ORfully adj: 1.33, 95% CI: 1.19-1.48). In the case only analysis, BRAF-mutation was differentially associated with diabetes (Pdifference = .03). For the other markers, associations with diabetes were similar across tumor subtypes. In conclusion, our study confirms the established association between diabetes and colorectal cancer risk, and suggests that it particularly increases the risk of BRAF-mutated tumors.
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| 7. |
- McVey, Mark J., et al.
(author)
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Platelet extracellular vesicles mediate transfusion-related acute lung injury by imbalancing the sphingolipid rheostat
- 2021
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 137:5, s. 690-701
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Journal article (peer-reviewed)abstract
- Transfusion-related acute lung injury (TRALI) is a hazardous transfusion complication with an associated mortality of 5% to 15%. We previously showed that stored (5 days) but not fresh platelets (1 day) cause TRALI via ceramide-mediated endothelial barrier dysfunction. As biological ceramides are hydrophobic, extracellular vesicles (EVs) may be required to shuttle these sphingolipids from platelets to endothelial cells. Adding to complexity, EV formation in turn requires ceramide. We hypothesized that ceramide-dependent EV formation from stored platelets and EV-dependent sphingolipid shuttling induces TRALI. EVs formed during storage of murine platelets were enumerated, characterized for sphingolipids, and applied in a murine TRALI model in vivo and for endothelial barrier assessment in vitro. Five-day EVs were more abundant, had higher long-chain ceramide (C16:0, C18:0, C20:0), and lower sphingosine-1-phosphate (S1P) content than 1-day EVs. Transfusion of 5-day, but not 1-day, EVs induced characteristic signs of lung injury in vivo and endothelial barrier disruption in vitro. Inhibition or supplementation of ceramide-forming sphingomyelinase reduced or enhanced the formation of EVs, respectively, but did not alter the injuriousness per individual EV. Barrier failure was attenuated when EVs were abundant in or supplemented with S1P. Stored human platelet 4-day EVs were more numerous compared with 2-day EVs, contained more long-chain ceramide and less S1P, and caused more endothelial cell barrier leak. Hence, platelet-derived EVs become more numerous and more injurious (more long-chain ceramide, less S1P) during storage. Blockade of sphingomyelinase, EV elimination, or supplementation of S1P during platelet storage may present promising strategies for TRALI prevention. Key Points: • EVs derived from stored platelets cause TRALI as a function of their elevated ceramide and decreased S1P content. • Inhibiting ceramide formation, supplementing S1P, or washing stored platelets could potentially reduce TRALI incidence and severity.
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| 8. |
- Mohammadi, Amir, et al.
(author)
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Application of Diffusive Gradients in Thin Films for Monitoring Groundwater Quality br
- 2022
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In: ACS - ES & T Water. - : American Chemical Society (ACS). - 2690-0637. ; 2:4, s. 518-526
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Journal article (peer-reviewed)abstract
- Diffusive gradients in thin films (DGTs) provide time-weighted solute concentrations in well-mixed fluvial environments. However, the DGT method has rarely been applied to relatively slowly moving groundwater systems, where the increased length of the diffusive boundary layer (DBL) must be accounted for, to give accurate concentration measurements. Because the DGT method pre-concentrates trace-level solutes (e.g., Cd2+) and averages out fluctuations in more dynamic contaminants (e.g., NO3-), it has potential advantages over conventional methods. This study evaluated the application of DGT methods for monitoring trace contaminants in groundwater, which are often present at levels below standard instrumental detection limits. We tested three different DGT deployment approaches using NO3- to estimate the DBL thickness: a static DGT suspension, a DGT shaker, and a pumped flow-cell unit coined the "universal DGT monitoring system" (UDMS). Unlike static and DGT shaker approaches, the UDMS reduced the DBL thickness (similar to 0.02 cm) to values within the range of well-mixed waters (DBL <= 0.03 cm). Comparable DBL thicknesses for NO3- and Cd2+ and correlations with grab sample measurements (R-2 = 0.99 and 0.98, respectively) demonstrate the suitability of DGTs combined with the UDMS for groundwater monitoring. This approach is particularly suitable for analysis of trace-level solutes including organic contaminants.
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| 9. |
- Pei, Zhangcheng, et al.
(author)
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Assessing the cloud radiative bias at Macquarie Island in the ACCESS-AM2 model
- 2023
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In: Atmospheric Chemistry And Physics. - 1680-7316 .- 1680-7324. ; 23:23, s. 14691-14714
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Journal article (peer-reviewed)abstract
- As a long-standing problem in climate models, large positive shortwave radiation biases exist at the surface over the Southern Ocean, impacting the accurate simulation of sea surface temperature, atmospheric circulation, and precipitation. Underestimations of low-level cloud fraction and liquid water content are suggested to predominantly contribute to these radiation biases. Most model evaluations for radiation focus on summer and rely on satellite products, which have their own limitations. In this work, we use surface-based observations at Macquarie Island to provide the first long-term, seasonal evaluation of both downwelling surface shortwave and longwave radiation in the Australian Community Climate and Earth System Simulator Atmosphere-only Model version 2 (ACCESS-AM2) over the Southern Ocean. The capacity of the Clouds and the Earth’s Radiant Energy System (CERES) product to simulate radiation is also investigated. We utilize the novel lidar simulator, the Automatic Lidar and Ceilometer Framework (ALCF), and all-sky cloud camera observations of cloud fraction to investigate how radiation biases are influenced by cloud properties.Overall, we find an overestimation of + 9.5 ± 33.5 W m−2 for downwelling surface shortwave radiation fluxes and an underestimation of −2.3 ± 13.5 W m−2 for downwelling surface longwave radiation in ACCESS-AM2 in all-sky conditions, with more pronounced shortwave biases of +25.0 ± 48.0 W m−2 occurring in summer. CERES presents an overestimation of +8.0 ± 18.0 W m−2 for the shortwave and an underestimation of −12.1 ± 12.2 W m−2 for the longwave in all-sky conditions. For the cloud radiative effect (CRE) biases, there is an overestimation of +4.8 ± 28.0 W m−2 in ACCESS-AM2 and an underestimation of −7.9 ± 20.9 W m−2in CERES. An overestimation of downwelling surface shortwave radiation is associated with an underestimated cloud fraction and low-level cloud occurrence. We suggest that modeled cloud phase is also having an impact on the radiation biases. Our results show that the ACCESS-AM2 model and CERES product require further development to reduce these radiation biases not just in shortwave and in all-sky conditions, but also in longwave and in clear-sky conditions.
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