Effects of predation on real‐time host–parasite coevolutionary dynamics

The impact of community complexity on pairwise coevolutionary dynamics is theoretically dependent on the extent to which species evolve generalised or specialised adaptations to the multiple species they interact with. Here, we show that the bacteria Pseudomonas fluorescens diversifies into defence specialists, when coevolved simultaneously with a virus and a predatory protist, as a result of fitness trade‐offs between defences against the two enemies. Strong bacteria–virus pairwise coevolution persisted, despite strong protist‐imposed selection. However, the arms race dynamic (escalation of host resistance and parasite infectivity ranges) associated with bacteria–virus coevolution broke down to a greater extent in the presence of the protist, presumably through the elevated genetic and demographic costs of increased bacteria resistance ranges. These findings suggest that strong pairwise coevolution can persist even in complex communities, when conflicting selection leads to evolutionary diversification of different defence strategies.     

EMu: probabilistic inference of mutational processes and their localization in the cancer genome

The spectrum of mutations discovered in cancer genomes can be explained by the activity of a few elementary mutational processes. We present a novel probabilistic method, EMu, to infer the mutational signatures of these processes from a collection of sequenced tumors. EMu naturally incorporates the tumor-specific opportunity for different mutation types according to sequence composition. Applying EMu to breast cancer data, we derive detailed maps of the activity of each process, both genome-wide and within specific local regions of the genome. Our work provides new opportunities to study the mutational processes underlying cancer development. EMu is available at http://www.sanger.ac.uk/resources/software/emu/.     

Insulin/IGF-1 Signaling Regulates Proteasome Activity through the Deubiquitinating Enzyme UBH-4

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Tetra-n-propylammonium tetra-oxoruthenate(VII): a reagent of choice for the oxidation of diversely protected glycopyranoses and glycofuranoses to lactones

2,3,4,6-Tetra-O-benzyl- -glucopyranose, 2,3,5-tri-O-allyl- -ribofuranose, 2,3,5-tri-O-allyl- and -tri-O-benzyl- -arabinofuranose, and 2-deoxy-3,5-di-O-allyl- -erythro-pentofuranose were oxidized to their corresponding lactones 6–10 by dimethyl sulfoxide activated by oxalyl chloride, pyridinium dichromate in the presence of molecular sieves and acetic acid, and tetra-n-propylammonium tetra-oxoruthenate(VII) using 4-methylmorpholine N-oxide as cooxidant. With the latter reagent, analytically pure lactones were obtained in 83–98% yield. A multistep preparation of 3,4,6-tri-O-benzyl-2-deoxy- -arabino-hexono-1,5-lactone (14) from 3,4,6-tri-O-benzyl-1,5-anhydro-2-deoxy- -arabino-hex-1 enitol (65% overall yield) is described.     

Mannose-binding lectin variant associated with severe malaria in young African children

Mannose-binding lectin (MBL) is a serum protein which initiates innate immune responses to microbial pathogens by binding to non-self surface oligosaccharides. MBL deficiency is the most common congenital immunodeficiency of human and has been shown to predispose to infections, particularly in children and immune compromised. In a matched case-control study among 870 Ghanaian children, we examined the influence of six polymorphisms of the MBL2 gene on Plasmodium falciparum infection and severe malaria. A missense mutation resulting in low MBL activity (MBL2*C) was found in 35% of healthy controls, but in 42% of asymptomatically infected children (P=0.01), and in 46% of patients with severe malaria (P=0.007). Heterozygosity for MBL2*C was associated with increased odds of infection (odds ratio (OR), 1.6; 95% confidence interval (CI), 1.1-2.1), severe malaria (OR, 1.7; 95% CI, 1.2-2.4), and of severe anemia in particular (OR, 2.3; 95% CI, 1.4-3.8). The population attributable fraction of severe malaria cases attributable to MBL2*C heterozygosity was 17%. Our results suggest that the MBL pathway of the complement system is a critical determinant of both, susceptibility to P. falciparum infection and manifestation of severe malaria, particularly in young children in whom specific immune responses are weak or absent.     

Structural conservation between the actin monomer-binding sites of twinfilin and actin-depolymerizing factor (ADF)/cofilin

Twinfilin is an evolutionarily conserved actin monomer-binding protein that regulates cytoskeletal dynamics in organisms from yeast to mammals. It is composed of two actin-depolymerization factor homology (ADF-H) domains that show approximately 20% sequence identity to ADF/cofilin proteins. In contrast to ADF/cofilins, which bind both G-actin and F-actin and promote filament depolymerization, twinfilin interacts only with G-actin. To elucidate the molecular mechanisms of twinfilin-actin monomer interaction, we determined the crystal structure of the N-terminal ADF-H domain of twinfilin and mapped its actin-binding site by site-directed mutagenesis. This domain has similar overall structure to ADF/cofilins, and the regions important for actin monomer binding in ADF/cofilins are especially well conserved in twinfilin. Mutagenesis studies show that the N-terminal ADF-H domain of twinfilin and ADF/cofilins also interact with actin monomers through similar interfaces, although the binding surface is slightly extended in twinfilin. In contrast, the regions important for actin-filament interactions in ADF/cofilins are structurally different in twinfilin. This explains the differences in actin-interactions (monomer versus filament binding) between twinfilin and ADF/cofilins. Taken together, our data show that the ADF-H domain is a structurally conserved actin-binding motif and that relatively small structural differences at the actin interfaces of this domain are responsible for the functional variation between the different classes of ADF-H domain proteins.     

Cell Wall Lignin is Polymerised by Class Ⅲ Secretable Plant Peroxidases in Norway Spruce

Class Ⅲ secretable plant peroxidases occur as a large family of genes in plants with many functions and probable redundancy. In this review we are concentrating on the evidence we have on the catalysis of lignin polymerization by class Ⅲ plant peroxidases present in the apoplastic space in the xylem of trees. Some evidence exists on the specificity of peroxidase isozymes in lignin polymerization through substrate specificity studies, from antisense mutants in tobacco and poplar and from tissue and cell culture lines of Norway spruce (Picea abies) and Zinnia elegans. In addition, real time (RT-)PCR results have pointed out that many peroxidases have tissue specific expression patterns in Norway spruce. Through combining information on catalytic properties of the enzymes, on the expression patterns of the corresponding genes, and on the presence of monolignols and hydrogen peroxide in the apoplastic space, we can show that specific peroxidases catalyze lignin polymerization in the apoplastic space of Norway spruce xylem.