Analysis and visualization of H7 influenza using genomic,evolutionary and geographic information in a modular web service

We have reported previously on use of a web‐based application, Supramap ( http://supramap.org ) for the study of biogeographic, genotypic, and phenotypic evolution. Using Supramap we have developed maps of the spread of drug‐resistant influenza and host shifts in H1N1 and H5N1 influenza and coronaviruses such as SARS. Here we report on another zoonotic pathogen, H7 influenza, and provide an update on the implementation of Supramap as a web service. We find that the emergence of pathogenic strains of H7 is labile with many transitions from high to low pathogenicity, and from low to high pathogenicity. We use Supramap to put these events in a temporal and geospatial context. We identify several lineages of H7 influenza with biomarkers of high pathogenicity in regions that have not been reported in the scientific literature. The original implementation of Supramap was built with tightly coupled client and server software. Now we have decoupled the components to provide a modular web service for POY ( http://poyws.org ) that can be consumed by a data provider to create a novel application. To demonstrate the web service, we have produced an application, Geogenes ( http://geogenes.org ). Unlike in Supramap, in which the user is required to create and upload data files, in Geogenes the user works from a graphical interface to query an underlying dataset. Geogenes demonstrates how the web service can provide underlying processing for any sequence and metadata database. © The Willi Hennig Society 2012.     

Isotopically sensitive branching in the formation of cyclic monoterpenes: proof that (-)-alpha-pinene and (-)-beta-pinene are synthesized by the same monoterpene cyclase via deprotonation of a common intermediate

To determine whether the bicyclic monoterpene olefins (-)-alpha-pinene and (-)-beta-pinene arise biosynthetically from the same monoterpene cyclase by alternate deprotonations of a common carbocationic intermediate, the product distributions arising from the acyclic precursor [10-2H3,1-3H]geranyl pyrophosphate were compared with those resulting from incubation of [1-3H]geranyl pyrophosphate with (-)-pinene cyclase from Salvia officinalis. Alteration in proportions of the olefinic products generated by the partially purified pinene cyclase resulted from the suppression of the formation of (-)-beta-pinene (C10 deprotonation) by a primary deuterium isotope effect with a compensating stimulation of the formation of (-)-alpha-pinene (C4 deprotonation). (-)-Pinene cyclase as well as (+)-pinene cyclase also exhibited a decrease in the proportion of the acyclic olefin myrcene generated from the deuteriated substrate, accompanied by a corresponding increase in the commitment to cyclized products. The observation of isotopically sensitive branching, in conjunction with quantitation of the magnitude of the secondary deuterium isotope effect on the overall rate of product formation by the (+)- and (-)-pinene cyclases as well as two other monoterpene cyclases from the same tissue, supports the biosynthetic origin of (-)-alpha-pinene and (-)-beta-pinene by alternative deprotonations of a common enzymatic intermediate. A biogenetic scheme consistent with these results is presented, and alternate proposals for the origin of the pinenes are addressed.     

β-Amyloid (Aβ) Oligomers Impair Brain-derived Neurotrophic Factor Retrograde Trafficking by Down-regulating Ubiquitin C-terminal Hydrolase,UCH-L1

We previously found that BDNF-dependent retrograde trafficking is impaired in AD transgenic mouse neurons. Utilizing a novel microfluidic culture chamber, we demonstrate that Aβ oligomers compromise BDNF-mediated retrograde transport by impairing endosomal vesicle velocities, resulting in impaired downstream signaling driven by BDNF/TrkB, including ERK5 activation, and CREB-dependent gene regulation. Our data suggest that a key mechanism mediating the deficit involves ubiquitin C-terminal hydrolase L1 (UCH-L1), a deubiquitinating enzyme that functions to regulate cellular ubiquitin. Aβ-induced deficits in BDNF trafficking and signaling are mimicked by LDN (an inhibitor of UCH-L1) and can be reversed by increasing cellular UCH-L1 levels, demonstrated here using a transducible TAT-UCH-L1 strategy. Finally, our data reveal that UCH-L1 mRNA levels are decreased in the hippocampi of AD brains. Taken together, our data implicate that UCH-L1 is important for regulating neurotrophin receptor sorting to signaling endosomes and supporting retrograde transport. Further, our results support the idea that in AD, Aβ may down-regulate UCH-L1 in the AD brain, which in turn impairs BDNF/TrkB-mediated retrograde signaling, compromising synaptic plasticity and neuronal survival.     

A phylogenetic analysis and revised classification of the Monocotylidae Taschenberg, 1879 (Monogenea)

The Monocotylidae Taschenberg, 1879 is revised based on a cladistic analysis of relationships between the constituent species and genera. The monophyly of the family is supported by three apomorphic character states: division of the haptor into one central and eight peripheral loculi; the ovary looping the right intestinal caecum; and tetrahedral eggs. The family is divided into six subfamilies: Calicotylinae Monticelli, 1903 (comprising Calicotyle Diesing, 1850, Dictyocotyle Nybelin, 1941); Dasybatotreminae Bychowsky, 1957 (comprising Anoplocotyloides Young, 1967, Dasybatotrema Price, 1938, Timofeevia n. g., Troglocephalus Young, 1967); Decacotylinae n. subfam. (comprising Decacotyle Young, 1967, Papillicotyle Young, 1967); Heterocotylinae n. subfam. (comprising Heterocotyle Scott, 1904, Neoheterocotyle Hargis, 1955, Nonacotyle Ogawa, 1991, Potamotrygonocotyle Mayes, Brooks & Thorson, 1981, Spinuris Doran, 1953); Merizocotylinae Johnston & Tiegs, 1922 (comprising Cathariotrema Johnston & Tiegs, 1922, Empruthotrema Johnston & Tiegs, 1922, Merizocotyle Cerfontaine, 1894, Squalotrema Kearn & Green, 1983, Triloculotrema Kearn, 1993); and Monocotylinae Taschenberg, 1879 (comprising Clemacotyle Young, 1967, Dendromonocotyle Hargis, 1955, Monocotyle Taschenberg, 1878). The Dendromonocotylinae Hargis, 1955 is removed from subfamilial status and the two genera previously assigned to the subfamily are reassigned to the Monocotylinae. Timofeevia is proposed for Timofeevia rajae (Timofeeva, 1983) n. comb. (formerly Dasybatotrema rajae). Mycteronastes Kearn & Beverley-Burton, 1990 and Thaumatocotyle Scott, 1904 are synonymised with Merizocotyle. Gymnocalicotyle Nybelin, 1941 is not considered a distinct taxon. Revised diagnoses and keys for subfamilies and genera of the Monocotylidae are provided.     

Influence of adrenergic receptors on ovarian progesterone secretion in the pseudopregnant cat and oestradiol secretion in the oestrous cat

The infusion of isoprenaline or propranolol into the abdominal aorta of the pseudopregnant cat caused an increase or decrease respectively in the ovarian progesterone secretion rate. These observations suggest that the sympathetic innervation of the ovary has a physiological influence on normal progesterone secretion, and this mechanism may explain stress-related increases in progesterone concentrations. The infusion of isoprenaline or propranolol after the stimulation of follicular growth had no consistent or convincing effect on oestradiol secretion.