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The metabolic activity of the polymorphic CYP2D6 enzyme is dependent on the CYP2D6 genotype; however, the guidelines for translating the genotype into phenotype, which are of relevance for adequate drug dose personalization, are ambiguous. In the present study, retrospective therapeutic drug monitoring data from 4,700 CYP2D6 genotyped patients treated with risperidone, venlafaxine, and/or aripiprazole were analyzed to quantify the effect of CYP2D6 genotype on the CYP2D6 metabolic activities, as measured by metabolic ratios of these substrates. The patients were categorized into diplotypes based on the presence of normal function (CYP2D6Norm), nonfunctional (CYP2D6Nonf), and decreased function (CYP2D6Decr; i.e., CYP2D6*9, CYP2D6*10, and CYP2D6*41) CYP2D6 haplotypes. Significant correlations between the metabolic ratios were observed in patients (n = 77-103) cotreated with risperidone and venlafaxine, risperidone and aripiprazole, or venlafaxine and aripiprazole (ρ = 0.874, 0.785, and 0.644, respectively; P less then 0.001 for all). Relative metabolic CYP2D6 diplotype activity was calculated based on that the metabolic ratios, where median values for CYP2D6Nonf/Nonf and CYP2D6Norm/Norm subgroups were set to 0% and 100%, respectively. The relative CYP2D6 activities were 7.0% for CYP2D6Nonf/*41, 16.7% for CYP2D6Nonf/*9-10, 13.2% for CYP2D6*41/*41, 24.9% for CYP2D6*41/*9-10, 33.1% for CYP2D6*9-10/*9-10, 41.3% for CYP2D6Nonf/Norm, 55.0% for CYP2D6*41/Norm, 58.9% for CYP2D6*9-10/Norm, and 149.2% for CYP2D6Norm/Normx2. Compared with the CYP2D6Norm alleles, the activity scores of CYP2D6*41 and CYP2D6*9-10 alleles were estimated to be one sixth and one third, respectively. The results of this highly powered study provide a solid basis for the translation of the CYP2D6 genotype into a drug metabolic phenotype.
Leaf economic spectrum (LES) theory has historically been employed to inform vegetation models of ecosystem processes, but largely neglects intraspecific variation and biotic interactions. We attempt to integrate across environment-plant trait-herbivore interactions within a species at a range-wide scale.

We measured traits in 53 populations spanning the range of common milkweed (Asclepias syriaca) and used a common garden to determine the role of environment in driving patterns of intraspecific variation. We used a feeding trial to determine the role of plant traits in monarch (Danaus plexippus) larval development.

Trait-trait relationships largely followed interspecific patterns in LES theory and persisted in a common garden when individual traits change. Common milkweed showed intraspecific variation and biogeographic clines in traits. Clines did not persist in a common garden. Larvae ate more and grew larger when fed plants with more nitrogen. A longitudinal environmental gradient in precipitation cdistributions.
Climate change is having major impacts on alpine and arctic regions, and inter-annual variations in temperature are likely to increase. How increased climate variability will impact plant reproduction is unclear.

In a 4-year study on fruit production by an alpine plant community in northern Sweden, we applied three warming regimes (1) a static level of warming with open-top chambers (OTC), (2) press warming, a yearly stepwise increase in warming, and (3) pulse warming, a single-year pulse event of higher warming. We analyzed the relationship between fruit production and monthly temperatures during the budding period, fruiting period, and whole fruit production period and the effect of winter and summer precipitation on fruit production.

Year and treatment had a significant effect on total fruit production by evergreen shrubs, Cassiope tetragona, and Dryas octopetala, with large variations between treatments and years. Year, but not treatment, had a significant effect on deciduous shrubs and graminoids, both of which increased fruit production over the 4 years, while forbs were negatively affected by the press warming, but not by year. Fruit production was influenced by ambient temperature during the previous-year budding period, current-year fruiting period, and whole fruit production period. Minimum and average temperatures were more important than maximum temperature. In general, fruit production was negatively correlated with increased precipitation.

These results indicate that predicted increased climate variability and increased precipitation due to climate change may affect plant reproductive output and long-term community dynamics in alpine meadow communities.
These results indicate that predicted increased climate variability and increased precipitation due to climate change may affect plant reproductive output and long-term community dynamics in alpine meadow communities.
Photosynthetic light-response (PLR) curves for leaves are important components of models related to carbon fixation in forest ecosystems, linking the Mitscherlich equation and Michaelis-Menten equation to traits of the leaf economics spectrum (LES). However, models do not consider changes in leaf habits (i.e., evergreen and deciduous) and within-canopy shading variation in these PLR curves.

Here, we measured the PLR curves in sun and shade leaves of 44 evergreen and 31 deciduous species to examine the relationships between variables of the Mitscherlich equation and Michaelis-Menten equation, leaf nitrogen (N) and phosphorus (P) content, and leaf mass per area (LMA).

Small changes were caused by different leaf habits and shade variations in relationships linking variables of the two equations to leaf N and P content and LMA. Values of the scaling exponents for PLR curve parameters did not differ regardless of canopy position and leaf habit (P > 0.05). The PLR curves in species with different leaf habits (i.e., evergreen and deciduous) at different canopy positions could be predicted using the general allometric relations between leaf traits and PLR parameters in the two equations. For photosynthetic photon flux densities from 0 to 2000 μmol m
s
, approximately 71% (Mitscherlich equation) and 70% (Michaelis-Menten equation) of the net assimilation rates could be predicted.

These findings indicate that leaf net assimilation rates can be predicted through the large available data for LES traits. WST-8 Incorporation of values for these traits available in the LES databases into ecosystem models of forest productivity and carbon fixation warrants further investigation.
These findings indicate that leaf net assimilation rates can be predicted through the large available data for LES traits. Incorporation of values for these traits available in the LES databases into ecosystem models of forest productivity and carbon fixation warrants further investigation.
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