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- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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- Oksvold, MP, et al.
(författare)
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Karonudib has potent anti-tumor effects in preclinical models of B-cell lymphoma
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 6317-
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Tidskriftsartikel (refereegranskat)abstract
- Chemo-immunotherapy has improved survival in B-cell lymphoma patients, but refractory/relapsed diseases still represent a major challenge, urging for development of new therapeutics. Karonudib (TH1579) was developed to inhibit MTH1, an enzyme preventing oxidized dNTP-incorporation in DNA. MTH1 is highly upregulated in tumor biopsies from patients with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma, hence confirming a rationale for targeting MTH1. Here, we tested the efficacy of karonudib in vitro and in preclinical B-cell lymphoma models. Using a range of B-cell lymphoma cell lines, karonudib strongly reduced viability at concentrations well tolerated by activated normal B cells. In B-cell lymphoma cells, karonudib increased incorporation of 8-oxo-dGTP into DNA, and prominently induced prometaphase arrest and apoptosis due to failure in spindle assembly. MTH1 knockout cell lines were less sensitive to karonudib-induced apoptosis, but were displaying cell cycle arrest phenotype similar to the wild type cells, indicating a dual inhibitory role of the drug. Karonudib was highly potent as single agent in two different lymphoma xenograft models, including an ABC DLBCL patient derived xenograft, leading to prolonged survival and fully controlled tumor growth. Together, our preclinical findings provide a rationale for further clinical testing of karonudib in B-cell lymphoma.
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| 11. |
- Jacquemyn, Hans, et al.
(författare)
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Habitat-driven variation in mycorrhizal communities in the terrestrial orchid genus Dactylorhiza
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Orchid species are critically dependent on mycorrhizal fungi for completion of their life cycle, particularly during the early stages of their development when nutritional resources are scarce. As such, orchid mycorrhizal fungi play an important role in the population dynamics, abundance, and spatial distribution of orchid species. However, less is known about the ecology and distribution of orchid mycorrhizal fungi. In this study, we used 454 amplicon pyrosequencing to investigate ecological and geographic variation in mycorrhizal associations in fourteen species of the orchid genus Dactylorhiza. More specifically, we tested the hypothesis that variation in orchid mycorrhizal communities resulted primarily from differences in habitat conditions where the species were growing. The results showed that all investigated Dactylorhiza species associated with a large number of fungal OTUs, the majority belonging to the Tulasnellaceae, Ceratobasidiaceae and Sebacinales. Mycorrhizal specificity was low, but significant variation in mycorrhizal community composition was observed between species inhabiting different ecological habitats. Although several fungi had a broad geographic distribution, Species Indicator Analysis revealed some fungi that were characteristic for specific habitats. Overall, these results indicate that orchid mycorrhizal fungi may have a broad geographic distribution, but that their occurrence is bounded by specific habitat conditions.
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| 12. |
- McCoy, Daniel T., et al.
(författare)
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Cloud feedbacks in extratropical cyclones : insight from long-term satellite data and high-resolution global simulations
- 2019
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 19:2, s. 1147-1172
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Tidskriftsartikel (refereegranskat)abstract
- A negative extratropical shortwave cloud feedback driven by changes in cloud optical depth is a feature of global climate models (GCMs). A robust positive trend in observed liquid water path (LWP) over the last two decades across the warming Southern Ocean supports the negative shortwave cloud feedback predicted by GCMs. This feature has been proposed to be due to transitions from ice to liquid with warming. To gain insight into the shortwave cloud feedback we examine extratropical cyclone variability and the response of extratropical cyclones to transient warming in GCM simulations. Multi-Sensor Advanced Climatology Liquid Water Path (MAC-LWP) microwave observations of cyclone properties from the period 1992-2015 are contrasted with GCM simulations, with horizontal resolutions ranging from 7 km to hundreds of kilometers. We find that inter-cyclone variability in LWP in both observations and models is strongly driven by the moisture flux along the cyclone's warm conveyor belt (WCB). Stronger WCB moisture flux enhances the LWP within cyclones. This relation-ship is replicated in GCMs, although its strength varies substantially across models. It is found that more than 80% of the enhancement in Southern Hemisphere (SH) extratropical cyclone LWP in GCMs in response to a transient 4K warming can be predicted based on the relationship between the WCB moisture flux and cyclone LWP in the historical climate and their change in moisture flux between the historical and warmed climates. Further, it is found that that the robust trend in cyclone LWP over the Southern Ocean in observations and GCMs is consistent with changes in the moisture flux. We propose two cloud feedbacks acting within extratropical cyclones: a negative feedback driven by Clausius-Clapeyron increasing water vapor path (WVP), which enhances the amount of water vapor available to be fluxed into the cyclone, and a feedback moderated by changes in the life cycle and vorticity of cyclones under warming, which changes the rate at which existing moisture is imported into the cyclone. Both terms contribute to increasing LWP within the cyclone. While changes in moisture flux predict cyclone LWP trends in the current climate and the majority of changes in LWP in transient warming simulations, a portion of the LWP increase in response to climate change that is unexplained by increasing moisture fluxes may be due to phase transitions. The variability in LWP within cyclone composites is examined to understand what cyclonic regimes the mixed-phase cloud feedback is relevant to. At a fixed WCB moisture flux cyclone LWP increases with increasing sea surface temperature (SST) in the half of the composite poleward of the low and decreases in the half equatorward of the low in both GCMs and observations. Cloud-top phase partitioning observed by the Atmospheric Infrared Sounder (AIRS) indicates that phase transitions may be driving increases in LWP in the poleward half of cyclones.
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| 13. |
- Mikryukov, Vladimir, et al.
(författare)
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Connecting the multiple dimensions of global soil fungal diversity
- 2023
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Ingår i: Science advances. - 2375-2548. ; 9:48
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Tidskriftsartikel (refereegranskat)abstract
- How the multiple facets of soil fungal diversity vary worldwide remains virtually unknown, hindering the management of this essential species-rich group. By sequencing high-resolution DNA markers in over 4000 topsoil samples from natural and human-altered ecosystems across all continents, we illustrate the distributions and drivers of different levels of taxonomic and phylogenetic diversity of fungi and their ecological groups. We show the impact of precipitation and temperature interactions on local fungal species richness (alpha diversity) across different climates. Our findings reveal how temperature drives fungal compositional turnover (beta diversity) and phylogenetic diversity, linking them with regional species richness (gamma diversity). We integrate fungi into the principles of global biodiversity distribution and present detailed maps for biodiversity conservation and modeling of global ecological processes.
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| 16. |
- Shefferson, Richard P., et al.
(författare)
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Drivers of vegetative dormancy across herbaceous perennial plant species
- 2018
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Ingår i: Ecology Letters. - : WILEY. - 1461-023X .- 1461-0248. ; 21:5, s. 724-733
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Tidskriftsartikel (refereegranskat)abstract
- Vegetative dormancy, that is the temporary absence of aboveground growth for 1year, is paradoxical, because plants cannot photosynthesise or flower during dormant periods. We test ecological and evolutionary hypotheses for its widespread persistence. We show that dormancy has evolved numerous times. Most species displaying dormancy exhibit life-history costs of sprouting, and of dormancy. Short-lived and mycoheterotrophic species have higher proportions of dormant plants than long-lived species and species with other nutritional modes. Foliage loss is associated with higher future dormancy levels, suggesting that carbon limitation promotes dormancy. Maximum dormancy duration is shorter under higher precipitation and at higher latitudes, the latter suggesting an important role for competition or herbivory. Study length affects estimates of some demographic parameters. Our results identify life historical and environmental drivers of dormancy. We also highlight the evolutionary importance of the little understood costs of sprouting and growth, latitudinal stress gradients and mixed nutritional modes.
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| 18. |
- Strand, D, et al.
(författare)
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Synthetic approaches to THP-containing annonaceous acetogenins.
- 2004
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Ingår i: Abstracts of Papers of the American Chemical Society. - Royal Inst Technol, Dept Chem, S-10044 Stockholm, Sweden. : AMER CHEMICAL SOC. - 0065-7727. ; 228, s. U27-U27
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 19. |
- Tedersoo, Leho, et al.
(författare)
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Global patterns in endemicity and vulnerability of soil fungi.
- 2022
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Ingår i: Global change biology. - : Wiley. - 1365-2486 .- 1354-1013. ; 28:22, s. 6696-6710
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Tidskriftsartikel (refereegranskat)abstract
- Fungi are highly diverse organisms, which provide multiple ecosystem services. However, compared with charismatic animals and plants, the distribution patterns and conservation needs of fungi have been little explored. Here, we examined endemicity patterns, global change vulnerability and conservation priority areas for functional groups of soil fungi based on six global surveys using a high-resolution, long-read metabarcoding approach. We found that the endemicity of all fungi and most functional groups peaks in tropical habitats, including Amazonia, Yucatan, West-Central Africa, Sri Lanka, and New Caledonia, with a negligible island effect compared with plants and animals. We also found that fungi are predominantly vulnerable to drought, heat and land-cover change, particularly in dry tropical regions with high human population density. Fungal conservation areas of highest priority include herbaceous wetlands, tropical forests, and woodlands. We stress that more attention should be focused on the conservation of fungi, especially root symbiotic arbuscular mycorrhizal and ectomycorrhizal fungi in tropical regions as well as unicellular early-diverging groups and macrofungi in general. Given the low overlap between the endemicity of fungi and macroorganisms, but high conservation needs in both groups, detailed analyses on distribution and conservation requirements are warranted for other microorganisms and soil organisms.
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