The malaria parasite Plasmodium vivax exhibits greater genetic diversity than Plasmodium falciparum

We sequenced and annotated the genomes of four P. vivax strains collected from disparate geographic locations, tripling the number of genome sequences available for this understudied parasite and providing the first genome-wide perspective of global variability in this species. We observe approximately twice as much SNP diversity among these isolates as we do among a comparable collection of isolates of P. falciparum, a malaria-causing parasite that results in higher mortality. This indicates a distinct history of global colonization and/or a more stable demographic history for P. vivax relative to P. falciparum, which is thought to have undergone a recent population bottleneck. The SNP diversity, as well as additional microsatellite and gene family variability, suggests a capacity for greater functional variation in the global population of P. vivax. These findings warrant a deeper survey of variation in P. vivax to equip disease interventions targeting the distinctive biology of this neglected but major pathogen.     

Winter preference, nutritive value, and other range use characteristics of Kochia prostrata (L.) Schrad

A cafeteria - style study was conducted during the winter for two years with tame mule deer to determine if there were preferential differences between accessions of forage kochia ( Kochia prostrata ). Deer consumed significantly more of P.I. numbers 314929, 330708, and 356826 than any of the other accessions. Other plant adaptive characteristics and nutritive qualities are also reported.         

Common sequence variants on 20q11.22 confer melanoma susceptibility

We conducted a genome-wide association pooling study for cutaneous melanoma and performed validation in samples totaling 2,019 cases and 2,105 controls. Using pooling, we identified a new melanoma risk locus on chromosome 20 (rs910873 and rs1885120), with replication in two further samples (combined P < 1 x 10(-15)). The per allele odds ratio was 1.75 (1.53, 2.01), with evidence for stronger association in early-onset cases.     

The conserved protein DCN-1/Dcn1p is required for cullin neddylation in C. elegans and S. cerevisiae

SCF-type E3 ubiquitin ligases are multi-protein complexes required for polyubiquitination and subsequent degradation of target proteins by the 26S proteasome. Cullins, together with the RING-finger protein Rbx1, form the catalytic core of the ligase, and recruit the substrate-recognition module. Cycles of covalent modification of cullins by the ubiquitin-like molecule Nedd8 (neddylation) and removal of Nedd8 by the COP9 signalosome (deneddylation) positively regulate E3 ligase activity. Here we report the identification and analysis of a widely conserved protein that is required for cullin neddylation in the nematode Caenorhabditis elegans and the yeast Saccharomyces cerevisiae. C. elegans DCN-1 and S. cerevisiae Dcn1p (defective in cullin neddylation) are characterized by a novel UBA-like ubiquitin-binding domain and a DUF298 domain of unknown function. Consistent with their requirements for neddylation, DCN-1 and Dcn1p directly bind Nedd8 and physically associate with cullins in both species. Moreover, overexpression of Dcn1p in yeast results in the accumulation of Nedd8-modified cullin Cdc53p. Both in vivo and in vitro experiments indicate that Dcn1p does not inhibit deneddylation of Cdc53p by the COP9 signalosome, but greatly increases the kinetics of the neddylation reaction.     

Newton's solution of the one-body problem

Communicated by C. A. Wilson     

Uridine-33 in yeast tRNA not essential for amber suppression

The nucleotide at position 33 on the 5' side of the anticodon of almost all tRNAs is a uridine. Crystallographic studies of different tRNAs reveal that although the precise orientation of uridine-33 is not always the same, it connects the anticodon stacked along the 3' side of the loop with the pyrimidine-32 stacked on the 5' side of the loop. The remarkably conserved nature of uridine-33 and its unique position in the anticodon loop structure has led to suggestions that this nucleotide has an essential role in the translational mechanism. We have developed a biochemical procedure to replace nucleotides 33-35 in yeast tRNATyr with any desired sequence and used it to construct amber suppressor tRNAs having different nucleotides at position 33. As all of these synthetic amber suppressor tRNAs functioned well in eukaryotic in vitro suppression assays, we conclude that uridine-33 does not have an obligatory role in the translation mechanism.     

Forecasting new product trial in a controlled test market environment

A number of researchers have developed models that use test market data to generate forecasts of a new product's performance. However, most of these models have ignored the effects of marketing covariates. In this paper we examine what impact these covariates have on a model's forecasting performance and explore whether their presence enables us to reduce the length of the model calibration period (i.e. shorten the duration of the test market). We develop from first principles a set of models that enable us to systematically explore the impact of various model ‘components’ on forecasting performance. Furthermore, we also explore the impact of the length of the test market on forecasting performance. We find that it is critically important to capture consumer heterogeneity, and that the inclusion of covariate effects can improve forecast accuracy, especially for models calibrated on fewer than 20 weeks of data. Copyright © 2003 John Wiley & Sons, Ltd.     

Inhibition of in vitro RNA synthesis by hycanthone, oxamniquine and praziquantel.

The schistosomicides, hycanthone, oxamniquine and praziquantel, were found to inhibit the in vitro RNA synthesis using isolated hamster liver nuclei. Preincubation of the nuclei with these drugs revealed that the inhibitory effect of oxamniquine was irreversible and progressed with time, whereas that of hycanthone and praziquantel was reversible. On the other hand, hycanthone and praziquantel have a high affinity for DNA but oxamniquine does not. The data indicate that the mechanism of inhibition by oxamniquine is different from that of hycanthone and praziquantel.     

2,6-Dichlorobenzylidene amino guanidine acetate (Wy-8678). A new hypotensive agent

Zusammenfassung Bei unanästhesierten Ratten und Hunden wurden die antihypertensiven Eigenschaften von 2,6-Dichlorobenzyliden-Aminoguanidin-Azetat (WY 8678), welches zu einer neuen Reihe von aktiven Substanzen gehört, sowie noch einige andere klinisch wirksame Substanzen an zwei experimentellen Modellen für Hypertension geprüft und dabei eine wesentliche Blutdrucksenkung festgestellt.