Genetic Diversity of the Cestode Echinococcus multilocularis in Red Foxes at a Continental Scale in Europe

Background

Alveolar echinococcosis (AE) is a severe helminth disease affecting humans, which is caused by the fox tapeworm Echinococcus multilocularis. AE represents a serious public health issue in larger regions of China, Siberia, and other regions in Asia. In Europe, a significant increase in prevalence since the 1990s is not only affecting the historically documented endemic area north of the Alps but more recently also neighbouring regions previously not known to be endemic. The genetic diversity of the parasite population and respective distribution in Europe have now been investigated in view of generating a fine-tuned map of parasite variants occurring in Europe. This approach may serve as a model to study the parasite at a worldwide level.

Methodology/Principal Findings

The genetic diversity of E. multilocularis was assessed based upon the tandemly repeated microsatellite marker EmsB in association with matching fox host geographical positions. Our study demonstrated a higher genetic diversity in the endemic areas north of the Alps when compared to other areas.

Conclusions/Significance

The study of the spatial distribution of E. multilocularis in Europe, based on 32 genetic clusters, suggests that Europe can be considered as a unique global focus of E. multilocularis, which can be schematically drawn as a central core located in Switzerland and Jura Swabe flanked by neighbouring regions where the parasite exhibits a lower genetic diversity. The transmission of the parasite into peripheral regions is governed by a “mainland–island” system. Moreover, the presence of similar genetic profiles in both zones indicated a founder event.     

The effect of heterotachy in multigene analysis using the neighbor joining method

Sequence alignments of multiple genes are routinely used to infer phylogenetic relationships among species. The analysis of their concatenation is more likely to give correct results under an assumption of homotachy (i.e., the evolutionary rates within lineages in each of the concatenated genes are constant during evolution). Here, we examine how the violation of homotachy (i.e., presence of within-site rate variation, called heterotachy) distorts species phylogenies. A theoretical examination has been conducted using a four taxon case and the neighbor joining (NJ) method, concluding that NJ recovers the incorrect tree when concatenated genes exhibit heterotachy. The application of average and weighted-average distance approaches, where gene boundaries are kept intact, overcomes the detrimental effect of heterotachy in multigene analysis using the NJ method.     

The Cryphonectria parasitica mitochondrial rns gene: Plasmid-like elements, introns and homing endonucleases

The mt-rns gene of Cryphonectria parasitica is 9872 bp long and includes two group I and two group II introns. An analysis of intronic protein-encoding sequences revealed that LAGLIDADG ORFs, which usually are associated with group I introns, were transferred at least twice into group II introns. A plasmid-like mitochondrial element (plME) that appears in high amounts in previously mutagen-induced mit1 and mit2 hypovirulent mutants of the Ep155 standard virulent strain of C. parasitica was found to be derived from a short region of the mt-rns gene, including the exon 1 and most of the first intron. The plME is a 4.2-kb circular, multimeric DNA and an autonomously-replicating mtDNA fragment. Although sexual transmission experiments indicate that the plME does not directly cause hypovirulence, its emergence is one manifestation of the many complex molecular and genetic events that appear to underlie this phenotype.     

Spiders are special: fear and disgust evoked by pictures of arthropods

Because all spiders are predators and most subdue their prey with poison, it has been suggested that fear of spiders is an evolutionary adaptation. However, it has not been sufficiently examined whether other arthropods similarly elicit fear or disgust. Our aim was to examine if all arthropods are rated similarly, if only potentially dangerous arthropods (spiders, bees/wasps) elicit comparable responses, or if spiders are rated in a unique way. We presented pictures of arthropods (15 spiders, 15 beetles, 15 bees/wasps, and 15 butterflies/moths) to 76 students who rated each picture for fear, disgust, and how dangerous they thought the animal is. They also categorized each animal into one of the four animal groups. In addition, we assessed the participants' fear of spiders and estimates for trait anxiety. The ratings showed that spiders elicit significantly greater fear and disgust than any other arthropod group, and spiders were rated as more dangerous. Fear and disgust ratings of spider pictures significantly predicted the questionnaire scores for fear of spiders, whereas dangerousness ratings of spiders and ratings of other arthropods do not provide any predictive power. Thus, spider fear is in fact spider specific. Our results demonstrate that potential harmfulness alone cannot explain why spiders are feared so frequently.     

Transaldolase: From biochemistry to human disease

The role of the enzyme transaldolase (TAL) in central metabolism, its biochemical properties, structure, and role in human disease is reviewed. The nearly ubiquitous enzyme transaldolase is a part of the pentose phosphate pathway and transfers a dihydroxyacetone group from donor compounds (fructose 6-phosphate or sedoheptulose 7-phosphate) to aldehyde acceptor compounds. The phylogeny of transaldolases shows that five subfamilies can be distinguished, three of them with proven TAL enzyme activity, one with unclear function, and the fifth subfamily comprises transaldolase-related enzymes, the recently discovered fructose 6-phosphate aldolases. The three-dimensional structure of a bacterial (Escherichia coli TAL B) and the human enzyme (TALDO1) has been solved. Based on the 3D-structure and mutagenesis studies, the reaction mechanism was deduced. The cofactor-less enzyme proceeds with a Schiff base intermediate (bound dihydroxyacetone). While a transaldolase deficiency is well tolerated in many microorganisms, it leads to severe symptoms in homozygous TAL-deficient human patients. The involvement of TAL in oxidative stress and apoptosis, in multiple sclerosis, and in cancer is discussed.     

Phylogenetic analysis of Fosterella L.B. Sm. (Pitcairnioideae, Bromeliaceae) based on four chloroplast DNA regions

The about 31 species of Fosterella L.B. Sm. (Bromeliaceae) are terrestrial herbs with a centre of diversity in the central South American Andes. To resolve infra- and intergeneric relationships among Fosterella and their putative allies, we conducted a phylogenetic analysis based on sequence data from four chloroplast DNA regions (matK gene, rps16 intron, atpB-rbcL and psbB-psbH intergenic spacers). Sequences were generated for 96 accessions corresponding to 60 species from 18 genera. Among these, 57 accessions represented 22 of the 31 recognized Fosterella species and one undescribed morphospecies. Maximum parsimony and Bayesian inference methods yielded well-resolved phylogenies. The monophyly of Fosterella was strongly supported, as was its sister relationship with a clade comprising Deuterocohnia, Dyckia and Encholirium. Six distinct evolutionary lineages were distinguished within Fosterella. Character mapping indicated that parallel evolution of identical character states is common in the genus. Relationships between species and lineages are discussed in the context of morphological, ecological and biogeographical data as well as the results of a previous amplified fragment length polymorphism (AFLP) study.     

Fate of the H-NS–Repressed bgl Operon in Evolution of Escherichia coli

In the enterobacterial species Escherichia coli and Salmonella enterica, expression of horizontally acquired genes with a higher than average AT content is repressed by the nucleoid-associated protein H-NS. A classical example of an H-NS–repressed locus is the bgl (aryl-β,D-glucoside) operon of E. coli. This locus is “cryptic,” as no laboratory growth conditions are known to relieve repression of bgl by H-NS in E. coli K12. However, repression can be relieved by spontaneous mutations. Here, we investigated the phylogeny of the bgl operon. Typing of bgl in a representative collection of E. coli demonstrated that it evolved clonally and that it is present in strains of the phylogenetic groups A, B1, and B2, while it is presumably replaced by a cluster of ORFans in the phylogenetic group D. Interestingly, the bgl operon is mutated in 20% of the strains of phylogenetic groups A and B1, suggesting erosion of bgl in these groups. However, bgl is functional in almost all B2 isolates and, in approximately 50% of them, it is weakly expressed at laboratory growth conditions. Homologs of bgl genes exist in Klebsiella, Enterobacter, and Erwinia species and also in low GC-content Gram-positive bacteria, while absent in E. albertii and Salmonella sp. This suggests horizontal transfer of bgl genes to an ancestral Enterobacterium. Conservation and weak expression of bgl in isolates of phylogenetic group B2 may indicate a functional role of bgl in extraintestinal pathogenic E. coli.     

Apoptosis Is Essential for Neutrophil Functional Shutdown and Determines Tissue Damage in Experimental Pneumococcal Meningitis

During acute bacterial infections such as meningitis, neutrophils enter the tissue where they combat the infection before they undergo apoptosis and are taken up by macrophages. Neutrophils show pro-inflammatory activity and may contribute to tissue damage. In pneumococcal meningitis, neuronal damage despite adequate chemotherapy is a frequent clinical finding. This damage may be due to excessive neutrophil activity. We here show that transgenic expression of Bcl-2 in haematopoietic cells blocks the resolution of inflammation following antibiotic therapy in a mouse model of pneumococcal meningitis. The persistence of neutrophil brain infiltrates was accompanied by high levels of IL-1β and G-CSF as well as reduced levels of anti-inflammatory TGF-β. Significantly, Bcl-2-transgenic mice developed more severe disease that was dependent on neutrophils, characterized by pronounced vasogenic edema, vasculitis, brain haemorrhages and higher clinical scores. In vitro analysis of neutrophils demonstrated that apoptosis inhibition completely preserves neutrophil effector function and prevents internalization by macrophages. The inhibitor of cyclin-dependent kinases, roscovitine induced apoptosis in neutrophils in vitro and in vivo. In wild type mice treated with antibiotics, roscovitine significantly improved the resolution of the inflammation after pneumococcal infection and accelerated recovery. These results indicate that apoptosis is essential to turn off activated neutrophils and show that inflammatory activity and disease severity in a pyogenic infection can be modulated by targeting the apoptotic pathway in neutrophils.     

Relevance of allosteric conformations and homocarnosine concentration on carnosinase activity

Activity of carnosinase (CN1), the only dipeptidase with substrate specificity for carnosine or homocarnosine, varies greatly between individuals but increases clearly and significantly with age. Surprisingly, the lower CN1 activity in children is not reflected by differences in CN1 protein concentrations. CN1 is present in different allosteric conformations in children and adults since all sera obtained from children but not from adults were positive in ELISA and addition of DTT to the latter sera increased OD450 values. There was no quantitative difference in the amount of monomeric CN1 between children and adults. Further, CN1 activity was dose dependently inhibited by homocarnosine. Addition of 80 μM homocarnosine lowered V _max for carnosine from 440 to 356 pmol/min/μg and increased K _m from 175 to 210 μM. The estimated K _i for homocarnosine was higher (240 μM). Homocarnosine inhibits carnosine degradation and high homocarnosine concentrations in cerebrospinal fluid (CSF) may explain the lower carnosine degradation in CSF compared to serum. Because CN1 is implicated in the susceptibility for diabetic nephropathy (DN), our findings may have clinical implications for the treatment of diabetic patients with a high risk to develop DN. Homocarnosine treatment can be expected to reduce CN1 activity toward carnosine, resulting in higher carnosine levels.