Schistosoma mansoni: the egg, biosynthesis of the shell and interaction with the host

The schistosome eggshell is a hardened and tanned structure made from cross-linked proteins. It is synthesized within the female worm from many different kinds of proteins and glycoproteins. Once the egg is released in the circulation, the outer surface of the eggshell is exposed and hence a direct site of interaction between the parasite and the host. The major eggshell protein is p14, but about one third of the eggshell is made from common cellular proteins, some of which are known to be immunogenic. This has many consequences for parasite-host interactions. However, so far, the eggshell has gained little attention from researchers. We will discuss the structure of the eggshell and its role in granuloma formation, host factor binding and egg excretion.     

Functions of the tegument of schistosomes: clues from the proteome and lipidome

The tegumental outer-surface of schistosomes is a unique double membrane structure that is of crucial importance for modulation of the host response and parasite survival. Although several tegumental proteins had been identified by classical biochemical approaches, knowledge on the entire molecular composition of the tegument was limited. The Schistosoma mansoni genome project, together with recently developed proteomic and lipidomic techniques, allowed studies on detailed characterisation of the proteins and lipids of the tegumental membranes. These studies identified tegumental proteins and lipids that confirm the function of the tegument in nutrient uptake and immune evasion. However, these studies also demonstrated that compared to the complete worm, the tegument is enriched in lipids that are absent in the host. The tegument is also enriched in proteins that share no sequence similarity to any sequence present in databases of species other than schistosomes. These results suggest that the unique tegumental structures comprise multiple unique components that are likely to fulfil yet unknown functions. The tegumental proteome and lipidome, therefore, imply that many unknown molecular mechanisms are employed by schistosomes to survive within their host.     

Habitat selection by chironomid larvae: fast growth requires fast food

1. Sediments have been considered as a habitat, a cover from predators and a source of food, but also as a source of potential toxic compounds. Therefore, the choice of a suitable substrate is essential for the development of chironomids. 2. For the midge Chironomus riparius (Meigen 1804) the growth rate of larvae has often been related to the food quality in sediments rather than to the amount of toxicants in the sediment. Both food quality and sediment-bound toxicants have been reported to determine the field distribution of chironomid larvae. 3. We therefore studied the habitat selection by C. riparius larvae of floodplain lake sediments, differing in both food quality and concentrations of sediment-bound toxicants. We offered the different sediments pairwise to the chironomid larvae in a choice experiment and their settlement in the paired sediments was determined after 10 days. 4. It was observed that larvae showed a clear preference for sediments with higher food quality, which also provided better growth conditions, and that the food quality overruled avoidance of the sediments with higher toxicant concentrations. 5. Our observations correspond with the persistence of this fast growing opportunistic chironomid species in organically enriched aquatic ecosystems independent of the contamination level.     

Euglena gracilis rhodoquinone:ubiquinone ratio and mitochondrial proteome differ under aerobic and anaerobic conditions

Euglena gracilis cells grown under aerobic and anaerobic conditions were compared for their whole cell rhodoquinone and ubiquinone content and for major protein spots contained in isolated mitochondria as assayed by two-dimensional gel electrophoresis and mass spectrometry sequencing. Anaerobically grown cells had higher rhodoquinone levels than aerobically grown cells in agreement with earlier findings indicating the need for fumarate reductase activity in anaerobic wax ester fermentation in Euglena. Microsequencing revealed components of complex III and complex IV of the respiratory chain and the E1beta subunit of pyruvate dehydrogenase to be present in mitochondria of aerobically grown cells but lacking in mitochondria from anaerobically grown cells. No proteins were identified as specific to mitochondria from anaerobically grown cells. cDNAs for the E1alpha, E2, and E3 subunits of mitochondrial pyruvate dehydrogenase were cloned and shown to be differentially expressed under aerobic and anaerobic conditions. Their expression patterns differed from that of mitochondrial pyruvate:NADP(+) oxidoreductase, the N-terminal domain of which is pyruvate:ferredoxin oxidoreductase, an enzyme otherwise typical of hydrogenosomes, hydrogen-producing forms of mitochondria found among anaerobic protists. The Euglena mitochondrion is thus a long sought intermediate that unites biochemical properties of aerobic and anaerobic mitochondria and hydrogenosomes because it contains both pyruvate:ferredoxin oxidoreductase and rhodoquinone typical of hydrogenosomes and anaerobic mitochondria as well as pyruvate dehydrogenase and ubiquinone typical of aerobic mitochondria. Our data show that under aerobic conditions Euglena mitochondria are prepared for anaerobic function and furthermore suggest that the ancestor of mitochondria was a facultative anaerobe, segments of whose physiology have been preserved in the Euglena lineage.     

A Gene Encoding the Plant-Like Alternative Oxidase is Present in Phytomonas but Absent in Leishmania spp.

The constituents of the respiratory chain are believed to differ among the trypanosomatids; bloodstream stages of African trypanosomes and Phytomonas promastigotes oxidize ubiquinol by a ubiquinol:oxygen oxidoreductase, also known as alternative oxidase, whereas Leishmania spp. oxidize ubiquinol via a classic cytochrome-containing respiratory chain. The molecular basis for this elementary difference in ubiquinol oxidation by the mitochondrial electron-transport chain in distinct trypanosomatids was investigated. The presence of a gene encoding the plant-like alternative oxidase could be demonstrated in Phytomonas and Trypanosoma brucei , trypanosomatids that are known to contain alternative oxidase activity. Our results further demonstrated that Leishmania spp. lack a gene encoding the plant-like alternative oxidase, and therefore, all stages of Leishmania spp. will lack the alternative oxidase protein. The observed fundamental differences between the respiratory chains of distinct members of the trypanosomatid family are thus caused by the presence or absence of a gene encoding the plant-like alternative oxidase.     

The organellar genome and metabolic potential of the hydrogen-producing mitochondrion of Nyctotherus ovalis

It is generally accepted that hydrogenosomes (hydrogen-producing organelles) evolved from a mitochondrial ancestor. However, until recently, only indirect evidence for this hypothesis was available. Here, we present the almost complete genome of the hydrogen-producing mitochondrion of the anaerobic ciliate Nyctotherus ovalis and show that, except for the notable absence of genes encoding electron transport chain components of Complexes III, IV, and V, it has a gene content similar to the mitochondrial genomes of aerobic ciliates. Analysis of the genome of the hydrogen-producing mitochondrion, in combination with that of more than 9,000 genomic DNA and cDNA sequences, allows a preliminary reconstruction of the organellar metabolism. The sequence data indicate that N. ovalis possesses hydrogen-producing mitochondria that have a truncated, two step (Complex I and II) electron transport chain that uses fumarate as electron acceptor. In addition, components of an extensive protein network for the metabolism of amino acids, defense against oxidative stress, mitochondrial protein synthesis, mitochondrial protein import and processing, and transport of metabolites across the mitochondrial membrane were identified. Genes for MPV17 and ACN9, two hypothetical proteins linked to mitochondrial disease in humans, were also found. The inferred metabolism is remarkably similar to the organellar metabolism of the phylogenetically distant anaerobic Stramenopile Blastocystis. Notably, the Blastocystis organelle and that of the related flagellate Proteromonas lacertae also lack genes encoding components of Complexes III, IV, and V. Thus, our data show that the hydrogenosomes of N. ovalis are highly specialized hydrogen-producing mitochondria.     

Glucose Transport and Metabolism in Mammalian-stage Schistosomes

Adult schistosomes transport nutrients from the host bloodstream across their outer body covering or tegument. The tegument is a cytologically unusual structure; it is a syncytium bounded externally by two lipid bilayer membranes. In this review, Patrick Skelly, Louis Tielens and Chuck Shoemaker reconsider our understanding of how glucose enters schistosomes across this unusual outer covering in the light of recent papers characterizing glucose transport proteins and glucose metabolism pathways in these parasites.     

Corvid re-caching without 'theory of mind': a model

Scrub jays are thought to use many tactics to protect their caches. For instance, they predominantly bury food far away from conspecifics, and if they must cache while being watched, they often re-cache their worms later, once they are in private. Two explanations have been offered for such observations, and they are intensely debated. First, the birds may reason about their competitors' mental states, with a 'theory of mind'; alternatively, they may apply behavioral rules learned in daily life. Although this second hypothesis is cognitively simpler, it does seem to require a different, ad-hoc behavioral rule for every caching and re-caching pattern exhibited by the birds. Our new theory avoids this drawback by explaining a large variety of patterns as side-effects of stress and the resulting memory errors. Inspired by experimental data, we assume that re-caching is not motivated by a deliberate effort to safeguard specific caches from theft, but by a general desire to cache more. This desire is brought on by stress, which is determined by the presence and dominance of onlookers, and by unsuccessful recovery attempts. We study this theory in two experiments similar to those done with real birds with a kind of 'virtual bird', whose behavior depends on a set of basic assumptions about corvid cognition, and a well-established model of human memory. Our results show that the 'virtual bird' acts as the real birds did; its re-caching reflects whether it has been watched, how dominant its onlooker was, and how close to that onlooker it has cached. This happens even though it cannot attribute mental states, and it has only a single behavioral rule assumed to be previously learned. Thus, our simulations indicate that corvid re-caching can be explained without sophisticated social cognition. Given our specific predictions, our theory can easily be tested empirically.     

Safety and Efficacy of ARA 290 in Sarcoidosis Patients with Symptoms of Small Fiber Neuropathy: A Randomized,Double-Blind Pilot Study

ARA 290 (a peptide designed to activate the innate repair receptor that arrests injury and initiates cytoprotection, antiinflammation and healing) reduces allodynia in preclinical neuropathy models. We studied the safety and efficacy of ARA 290 to reduce symptoms of small fiber neuropathy (SFN) in patients with sarcoidosis. A total of 22 patients diagnosed with sarcoidosis and symptoms of SFN were enrolled in a double-blind, placebo-controlled exploratory trial consisting of three times weekly intravenous dosing of ARA 290 (2 mg; n = 12) or placebo (n = 10) for 4 wks. Inclusion criteria were a diagnosis of neuropathy and a spontaneous pain score of ≥5 (Brief Pain Inventory [BPI]). Endpoints assessed were changes in pain intensity and the small fiber neuropathy screening list (SFNSL) score, quality of life (SF-36), depressive symptoms (Inventory of Depressive Symptomatology [IDS]) and fatigue (Fatigue Assessment Scale [FAS]). No safety concerns were raised by clinical or laboratory assessments. The ARA 290 group showed significant (p < 0.05) improvement at wk 4 in SFNSL score compared with placebo (Δ −11.5 ± 3.04 versus Δ −2.9 ± 3.34 [standard error of the mean]). Additionally, the ARA 290 group showed a significant change from baseline in the pain and physical functioning dimensions of the SF-36 (Δ −23.4 ± 5.5 and Δ −14.6 ± 3.9, respectively). The mean BPI and FAS scores improved significantly but equivalently in both patient groups. No change was observed in the IDS. ARA 290 appears to be safe in patients with sarcoidosis and can reduce neuropathic symptoms.     

Acetate:succinate CoA-transferase in the hydrogenosomes of Trichomonas vaginalis: identification and characterization

Acetate:succinate CoA-transferases (ASCT) are acetate-producing enzymes in hydrogenosomes, anaerobically functioning mitochondria and in the aerobically functioning mitochondria of trypanosomatids. Although acetate is produced in the hydrogenosomes of a number of anaerobic microbial eukaryotes such as Trichomonas vaginalis, no acetate producing enzyme has ever been identified in these organelles. Acetate production is the last unidentified enzymatic reaction of hydrogenosomal carbohydrate metabolism. We identified a gene encoding an enzyme for acetate production in the genome of the hydrogenosome-containing protozoan parasite T. vaginalis. This gene shows high similarity to Saccharomyces cerevisiae acetyl-CoA hydrolase and Clostridium kluyveri succinyl-CoA:CoA-transferase. Here we demonstrate that this protein is expressed and is present in the hydrogenosomes where it functions as the T. vaginalis acetate:succinate CoA-transferase (TvASCT). Heterologous expression of TvASCT in CHO cells resulted in the expression of an active ASCT. Furthermore, homologous overexpression of the TvASCT gene in T. vaginalis resulted in an equivalent increase in ASCT activity. It was shown that the CoA transferase activity is succinate-dependent. These results demonstrate that this acetyl-CoA hydrolase/transferase homolog functions as the hydrogenosomal ASCT of T. vaginalis. This is the first hydrogenosomal acetate-producing enzyme to be identified. Interestingly, TvASCT does not share any similarity with the mitochondrial ASCT from Trypanosoma brucei, the only other eukaryotic succinate-dependent acetyl-CoA-transferase identified so far. The trichomonad enzyme clearly belongs to a distinct class of acetate:succinate CoA-transferases. Apparently, two completely different enzymes for succinate-dependent acetate production have evolved independently in ATP-generating organelles.