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- Ruilope, LM, et al.
(author)
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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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In: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Journal article (peer-reviewed)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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- Bowman, John L, et al.
(author)
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Insights into Land Plant Evolution Garnered from the Marchantia polymorpha Genome
- 2017
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In: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 171:2, s. 287-304.15
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Journal article (peer-reviewed)abstract
- The evolution of land flora transformed the terrestrial environment. Land plants evolved from an ancestral charophycean alga from which they inherited developmental, biochemical, and cell biological attributes. Additional biochemical and physiological adaptations to land, and a life cycle with an alternation between multicellular haploid and diploid generations that facilitated efficient dispersal of desiccation tolerant spores, evolved in the ancestral land plant. We analyzed the genome of the liverwort Marchantia polymorpha, a member of a basal land plant lineage. Relative to charophycean algae, land plant genomes are characterized by genes encoding novel biochemical pathways, new phytohormone signaling pathways (notably auxin), expanded repertoires of signaling pathways, and increased diversity in some transcription factor families. Compared with other sequenced land plants, M. polymorpha exhibits low genetic redundancy in most regulatory pathways, with this portion of its genome resembling that predicted for the ancestral land plant. PAPERCLIP.
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- Cardell, M., et al.
(author)
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Pyruvate dehydrogenase activity in the rat cerebral cortex following cerebral ischemia
- 1989
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In: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 9:3, s. 350-357
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Journal article (peer-reviewed)abstract
- The effect of cerebral ischemia on the activity of pyruvate dehydrogenase (PDH) enzyme complex (PDHC) was investigated in homogenates of frozen rat cerebral cortex following 15 min of bilateral common carotid occlusion ischemia and following 15 min, 60 min, and 6 h of recirculation after 15 min of ischemia. In frozen cortical tissue from the same animals, the levels of labile phosphate compounds, glucose, glycogen, lactate, and pyruvate were determined. In cortex from control animals, the rate of [1-14C]pyruvate decarboxylation was 9.6 ± 0.5 nmol CO2/(min-mg protein) or 40% of the total PDHC activity. This fraction increased to 89% at the end of 15 min of ischemia. At 15 min of recirculation following 15 min of ischemia, the PDHC activity decreased to 50% of control levels and was depressed for up to 6 h post ischemia. This decrease in activity was not due to a decrease in total PDHC activity. Apart from a reduction in ATP levels, the acute changes in the levels of energy metabolites were essentially normalized at 6 h of recovery. Dichloroacetate (DCA), an inhibitor of PDH kinase, given to rats at 250 mg/kg i.p four times over 2 h, significantly decreased blood glucose levels from 7.4 ± 0.6 to 5.1 ± 0.3 mmol/L and fully activated PDHC. In animals in which the plasma glucose level was maintained at control levels of 8.3 ± 0.5 μmol/g by intravenous infusion of glucose, the active portion of PDHC increased to 95 ± 4%. In contrast, the depressed PDHC activity at 15 min following ischemia was not affected by the DCA treatment. In both DCA + glucose-treated control and recovery groups, the pyruvate levels decreased by 50%. No significant difference in the lactate levels was seen. We conclude that the depressed postischemic PDHC activity is not due to loss of enzyme protein nor to an increased PDH kinase activity, but is probably due to a decreased activity of PDH phosphatase. This could in turn be secondary to a change in the cellular levels of PDH phosphatase regulators, most probably a decreased intramitochondrial concentration of calcium. The postischemic decrease in PDH activity may be related to the postischemic metabolic depression.
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- Kadoya, Taku, et al.
(author)
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Common processes drive metacommunity structure in freshwater fish
- 2024
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In: Global Ecology and Biogeography. - : John Wiley & Sons. - 1466-822X .- 1466-8238. ; 33:5, s. 1-14
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Journal article (peer-reviewed)abstract
- Aim: Environmental change affects metacommunity structure both directly—via abiotic factors and dispersal that affect species occurrence—and indirectly—via complex interactions among co-occurring species. We examined how the three main metacommunity factors—environmental conditions, spatial processes and species associations—affect metacommunity structure and whether responses are predictable in real-world systems by using novel methods to disentangle the drivers.Location: Eastern Asia, northern Europe and central North America.Time period: Contemporary.Major taxa studied: Freshwater fish. Methods: We used a dataset of freshwater fish species occurrences in temperate lakes in three countries in different biogeographic regions. We analysed co-occurrence patterns by using a joint species distribution model.Results: We demonstrated that environmental processes are the main drivers of species' distribution and diversity, suggesting that future climate change (anthropogenic alteration of abiotic factors) will heavily influence the structure of metacommunities. We also showed that spatial processes and species interactions mediated the influence of environmental processes, especially at the lake level.Main conclusions: Our results indicate that ongoing changes in metacommunity structure are modulated not only by the direct impacts of shifting abiotic factors but also by indirect effects of species interactions. Our global analysis indicates that even under the current high rate of environmental change, an identifiable set of underlying processes can be used to predict impacts of this change on metacommunity structure.
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- Warszawski, Lila, et al.
(author)
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All options, not silver bullets, needed to limit global warming to 1.5 °C : a scenario appraisal
- 2021
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In: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 16:6
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Journal article (peer-reviewed)abstract
- Climate science provides strong evidence of the necessity of limiting global warming to 1.5 °C, in line with the Paris Climate Agreement. The IPCC 1.5 °C special report (SR1.5) presents 414 emissions scenarios modelled for the report, of which around 50 are classified as '1.5 °C scenarios', with no or low temperature overshoot. These emission scenarios differ in their reliance on individual mitigation levers, including reduction of global energy demand, decarbonisation of energy production, development of land-management systems, and the pace and scale of deploying carbon dioxide removal (CDR) technologies. The reliance of 1.5 °C scenarios on these levers needs to be critically assessed in light of the potentials of the relevant technologies and roll-out plans. We use a set of five parameters to bundle and characterise the mitigation levers employed in the SR1.5 1.5 °C scenarios. For each of these levers, we draw on the literature to define 'medium' and 'high' upper bounds that delineate between their 'reasonable', 'challenging' and 'speculative' use by mid century. We do not find any 1.5 °C scenarios that stay within all medium upper bounds on the five mitigation levers. Scenarios most frequently 'over use' CDR with geological storage as a mitigation lever, whilst reductions of energy demand and carbon intensity of energy production are 'over used' less frequently. If we allow mitigation levers to be employed up to our high upper bounds, we are left with 22 of the SR1.5 1.5 °C scenarios with no or low overshoot. The scenarios that fulfil these criteria are characterised by greater coverage of the available mitigation levers than those scenarios that exceed at least one of the high upper bounds. When excluding the two scenarios that exceed the SR1.5 carbon budget for limiting global warming to 1.5 °C, this subset of 1.5 °C scenarios shows a range of 15–22 Gt CO2 (16–22 Gt CO2 interquartile range) for emissions in 2030. For the year of reaching net zero CO2 emissions the range is 2039–2061 (2049–2057 interquartile range).
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