CONVERGENT AND CORRELATED EVOLUTION OF MAJOR LIFE‐HISTORY TRAITS IN THE ANGIOSPERM GENUS LEUCADENDRON (PROTEACEAE)

Natural selection is expected to cause convergence of life histories among taxa as well as correlated evolution of different life‐history traits. Here, we quantify the extent of convergence of five key life‐history traits (adult fire survival, seed storage, degree of sexual dimorphism, pollination mode, and seed‐dispersal mode) and test hypotheses about their correlated evolution in the genus Leucadendron (Proteaceae) from the fire‐prone South African fynbos. We reconstructed a new molecular phylogeny of this highly diverse genus that involves more taxa and molecular markers than previously. This reconstruction identifies new clades that were not detected by previous molecular study and morphological classifications. Using this new phylogeny and robust methods that account for phylogenetic uncertainty, we show that the five life‐history traits studied were labile during the evolutionary history of the genus. This diversity allowed us to tackle major questions about the correlated evolution of life‐history strategies. We found that species with longer seed‐dispersal distances tended to evolve lower pollen‐dispersal distance, that insect‐pollinated species evolved decreased sexual dimorphism, and that species with a persistent soil seed‐bank evolved toward reduced fire‐survival ability of adults.     

The new higher level classification of eukaryotes with emphasis on the taxonomy of protists

This revision of the classification of unicellular eukaryotes updates that of Levine et al. (1980) for the protozoa and expands it to include other protists. Whereas the previous revision was primarily to incorporate the results of ultrastructural studies, this revision incorporates results from both ultrastructural research since 1980 and molecular phylogenetic studies. We propose a scheme that is based on nameless ranked systematics. The vocabulary of the taxonomy is updated, particularly to clarify the naming of groups that have been repositioned. We recognize six clusters of eukaryotes that may represent the basic groupings similar to traditional "kingdoms." The multicellular lineages emerged from within monophyletic protist lineages: animals and fungi from Opisthokonta, plants from Archaeplastida, and brown algae from Stramenopiles.     

The origin of chloroplastic acetyl coenzyme A

Pyruvic dehydrogenase activity has been examined in a number of highly purified leaf organelles. In spinach leaf cell, the major activity is in the mitochrondrion with low activity in isolated chloroplasts. The major source of CO₂ derived from pyruvic acid metabolism in the isolated chloroplast is via the acetolactic synthase reaction localized in the chloroplast. Evidence is presented that the leaf mitochondrion contains both the pyruvic acid dehydrogenase and an acetyl coenzyme A hydrolase. It is suggested that free acetic acid is generated in the mitochrondrion and then moves to the chloroplast where acetyl coenzyme synthetase converts it from the metabolically inert acid to the very metabolically active acetyl coenzyme A.     

Phenome-Wide Association Studies on a Quantitative Trait: Application to TPMT Enzyme Activity and Thiopurine Therapy in Pharmacogenomics

Phenome-Wide Association Studies (PheWAS) investigate whether genetic polymorphisms associated with a phenotype are also associated with other diagnoses. In this study, we have developed new methods to perform a PheWAS based on ICD-10 codes and biological test results, and to use a quantitative trait as the selection criterion. We tested our approach on thiopurine S-methyltransferase (TPMT) activity in patients treated by thiopurine drugs. We developed 2 aggregation methods for the ICD-10 codes: an ICD-10 hierarchy and a mapping to existing ICD-9-CM based PheWAS codes. Eleven biological test results were also analyzed using discretization algorithms. We applied these methods in patients having a TPMT activity assessment from the clinical data warehouse of a French academic hospital between January 2000 and July 2013. Data after initiation of thiopurine treatment were analyzed and patient groups were compared according to their TPMT activity level. A total of 442 patient records were analyzed representing 10,252 ICD-10 codes and 72,711 biological test results. The results from the ICD-9-CM based PheWAS codes and ICD-10 hierarchy codes were concordant. Cross-validation with the biological test results allowed us to validate the ICD phenotypes. Iron-deficiency anemia and diabetes mellitus were associated with a very high TPMT activity (p = 0.0004 and p = 0.0015, respectively). We describe here an original method to perform PheWAS on a quantitative trait using both ICD-10 diagnosis codes and biological test results to identify associated phenotypes. In the field of pharmacogenomics, PheWAS allow for the identification of new subgroups of patients who require personalized clinical and therapeutic management.     

Noninvasive monitoring of fecal cortisol metabolites in the eastern chipmunk (Tamias striatus): validation and comparison of two enzyme immunoassays

Monitoring fecal glucocorticoid metabolites in wild animals, using enzyme immunoassays, enables the study of endocrinological patterns relevant to ecology and evolution. While some researchers use antibodies against the parent hormone (which is typically absent from fecal samples), others advocate the use of antibodies designed to detect glucocorticoid metabolites. We validated two assays to monitor fecal cortisol metabolites in the eastern chipmunk (Tamias striatus). We compared an antibody produced against cortisol and one produced against 5α-pregnane-3β, 11β, 21-triol-20-one using a radiometabolism study and an injection with adrenocorticotropic hormone (ACTH). Most cortisol metabolites were excreted in the urine (～83%). Peak excretion in the feces occurred 8 h after injection. Both assays detected an increase in fecal cortisol metabolite levels after injection of ACTH. Males, but not females, exhibited a circadian variation in metabolite levels. The sexes did not exhibit any difference over the time course and route of excretion or the relative increase in fecal cortisol metabolite levels after ACTH injection. The cortisol assay displayed higher reactivity to ACTH injection relative to baseline than did the metabolite assay. While both antibodies gave comparable results, the cortisol antibody was more sensitive to changes in plasma cortisol levels in eastern chipmunks.     

Structural basis for the light regulation of chloroplast NADP malate dehydrogenase

The activity of chloroplast NADP-malate dehydrogenase (NADP-MDH; EC 1.1.1.82) in both C3 and C4 plants is regulated by light intensity. In darkness, the activity of the enzyme can be less than 1% of the maximal activity found at high light intensities. The extent of activation in the light is dynamic, responding rapidly to changes in light intensity and adapting to changes in photosynthetic rate. Enzyme activation is caused by thioredoxin-catalyzed reduction of two regulatory disulfide bonds, while inactivation is accomplished by thioredoxin-catalyzed re-oxidation. In the case of NADP-MDH, the coenzyme substrates NADP+ and NADPH modify the rate of this interconversion and seem to be important to the extent of activation in vivo. The recent determination of the X-ray structure of the oxidized, dark form of NADP-MDH from the C4 plants Flaveria bidentis and Sorghum shows how oxidation of a disulfide bond can inactivate the enzyme. This review discusses the various structural features of NADP-MDH that seem to be responsible for the regulatory properties of the enzyme and emphasizes that large changes of activity can be accomplished by multiple, small, reinforcing changes rather than a single large change in a signal molecule concentration.     

Structure-activity relationship of biaryl acylsulfonamide analogues on the human EP(3) prostanoid receptor

Potent and selective ligands for the human EP3 prostanoid receptor are described. Biaryl compounds bearing a tethered ortho substituted acidic moiety were identified as potent EP3 antagonists based on the SAR described herein. The binding affinity of key compounds on all eight human prostanoid receptors is reported.