| 1. |
- Imamura, Teruhiko, et al.
(författare)
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A case with recovery of response to tolvaptan associated with remission of acute kidney injury and increased urine osmolality
- 2013
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Ingår i: International Heart Journal. - : International Heart Journal Association. - 1349-2365 .- 1349-3299. ; 54:2, s. 115-118
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Tidskriftsartikel (refereegranskat)abstract
- Tolvaptan (TLV), a vasopressin type 2 receptor antagonist, has been demonstrated to be effective in patients with decompensated heart failure (HF) refractory to incremental doses of diuretics, but the responsiveness has not always been predictable. We have recently proposed that urine osmolality (U-OSM) is a valuable parameter for the prediction of responses to TLV, because U-OSM reflects the activity of the collecting ducts, where TLV plays its unique role. Acute kidney injury (AKI) is often associated with severe tubular dysfunction, including the collecting ducts, and in such cases a response to TLV may not be expected. We here experienced a patient with HF and AKI in whom TLV was not effective during AKI. We also observed recovery of responsiveness to TLV along with remission of AKI as well as increased U-OSM later on. We believe that this is the first report on the reversibility of the TLV response in relation to U-OSM.
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| 2. |
- Okada, Yukinori, et al.
(författare)
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Genetics of rheumatoid arthritis contributes to biology and drug discovery
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 506:7488, s. 376-381
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)(1). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating similar to 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2-4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation(5), cis-acting expression quantitative trait loci(6) and pathway analyses(7-9)-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
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| 3. |
- Takahashi, Daisuke, et al.
(författare)
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Abrupt community transitions and cyclic evolutionary dynamics in complex food webs
- 2013
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Ingår i: Journal of Theoretical Biology. - : Academia Press. - 0022-5193 .- 1095-8541. ; 337, s. 181-189
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the emergence and maintenance of biodiversity ranks among the most fundamental challenges in evolutionary ecology. While processes of community assembly have frequently been analyzed from an ecological perspective, their evolutionary dimensions have so far received less attention. To elucidate the eco-evolutionary processes underlying the long-term build-up and potential collapse of community diversity, here we develop and examine an individual-based model describing coevolutionary dynamics driven by trophic interactions and interference competition, of a pair of quantitative traits determining predator and prey niches. Our results demonstrate the (1) emergence of communities with multiple trophic levels, shown here for the first time for stochastic models with linear functional responses, and (2) intermittent and cyclic evolutionary transitions between two alternative community states. In particular, our results indicate that the interplay of ecological and evolutionary dynamics often results in extinction cascades that remove the entire trophic level of consumers from a community. Finally, we show the (3) robustness of our results under variations of model assumptions, underscoring that processes of consumer collapse and subsequent rebound could be important elements of understanding biodiversity dynamics in natural communities.
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| 4. |
- Takahashi, Daisuke, et al.
(författare)
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Cyclic transitions in simulated food-web evolution
- 2011
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Ingår i: Journal of Plant Interactions. - : Taylor & Francis. - 1742-9145 .- 1742-9153. ; 6:2-3, s. 181-182
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Tidskriftsartikel (refereegranskat)abstract
- Eco-evolutionary food-web models help elucidate the processes responsible for the emergence and maintenance of complex community structures. Using an individual-based model of evolving trophic and competitive interactions, we highlight a pattern of community macroevolution involving two meta-stable states, corresponding to a plant-herbivore community and a plant community, respectively. On the evolutionary timescale, our model exhibits cyclic transitions between these alternative community states. The model also helps understand the eco-evolutionary mechanisms underlying these recurrent rapid transitions, which end intermittent periods of near-stasis or punctuated equilibrium.
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| 5. |
- Yamauchi, Atsushi, et al.
(författare)
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Environmental variation does not always promote plasticity : evolutionarily realized reaction norm for costly plasticity
- 2014
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Ingår i: Evolutionary Ecology Research. - 1522-0613 .- 1937-3791. ; 16:8, s. 631-647
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Tidskriftsartikel (refereegranskat)abstract
- Question: How does environmental variability influence evolutionarily realized phenotypic plasticity? Mathematical method: Optimization in a spatially fluctuating environment. Key assumptions: Either the maintenance cost of plasticity results from the amount of phenotypic response, or it results from the slope of the reaction norm. And there are two alternative types of state-specific benefit functions: either the benefit is maximal at an intermediate phenotype, or it is a monotonically increasing function of phenotype. Conclusion: Organisms may not respond to rare environmental states. In this case, environmental variability suppresses two indices of phenotypic plasticity, i. e. the range of plasticity and the maximum slope of the reaction norm.
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