Acoel flatworms are not platyhelminthes: evidence from phylogenomics

Acoel flatworms are small marine worms traditionally considered to belong to the phylum Platyhelminthes. However, molecular phylogenetic analyses suggest that acoels are not members of Platyhelminthes, but are rather extant members of the earliest diverging Bilateria. This result has been called into question, under suspicions of a long branch attraction (LBA) artefact. Here we re-examine this problem through a phylogenomic approach using 68 different protein-coding genes from the acoel Convoluta pulchra and 51 metazoan species belonging to 15 different phyla. We employ a mixture model, named CAT, previously found to overcome LBA artefacts where classical models fail. Our results unequivocally show that acoels are not part of the classically defined Platyhelminthes, making the latter polyphyletic. Moreover, they indicate a deuterostome affinity for acoels, potentially as a sister group to all deuterostomes, to Xenoturbellida, to Ambulacraria, or even to chordates. However, the weak support found for most deuterostome nodes, together with the very fast evolutionary rate of the acoel Convoluta pulchra, call for more data from slowly evolving acoels (or from its sister-group, the Nemertodermatida) to solve this challenging phylogenetic problem.     

Quantitative profiling of the pathological prion protein allotypes in bank voles by liquid chromatography-mass spectrometry

The conversion of the cellular prion protein (PrP(C)) into a misfolded isoform (PrP(TSE)) that accumulates in the brain of affected individuals is the key feature of transmissible spongiform encephalopaties (TSEs). Susceptibility to TSEs is influenced by polymorphisms of the prion gene suggesting that the presence of certain amino acid residues may facilitate the pathological conversion. In this work, we describe a quantitative, fast and reliable HPLC-MS method that allowed to demonstrate that in the brain of 109(Met/Ile) heterozygous bank voles infected with the mouse adapted scrapie strain 139A, there are comparable amounts of PrP(TSE) with methionine or isoleucine in position 109, suggesting that in this TSE model the two allotypes have similar rates of accumulation. This method can be easily adapted for the quantitative determination of PrP allotypes in the brain of other natural or experimental TSE models.     

Transthyretin and familial amyloidotic polyneuropathy. Recent progress in understanding the molecular mechanism of neurodegeneration

Familial amyloidotic polyneuropathy (FAP) is an inherited autosomal dominant disease that is commonly caused by accumulation of deposits of transthyretin (TTR) amyloid around peripheral nerves. The only effective treatment for FAP is liver transplantation. However, recent studies on TTR aggregation provide clues to the mechanism of the molecular pathogenesis of FAP and suggest new avenues for therapeutic intervention. It is increasingly recognized that there are common features of a number of protein-misfolding diseases that can lead to neurodegeneration. As for other amyloidogenic proteins, the most toxic forms of aggregated TTR are likely to be the low-molecular-mass diffusible species, and there is increasing evidence that this toxicity is mediated by disturbances in calcium homeostasis. This article reviews what is already known about the mechanism of TTR aggregation in FAP and describes how recent discoveries in other areas of amyloid research, particularly Alzheimer's disease, provide clues to the molecular pathogenesis of FAP.     

Novel alpha-conotoxins from Conus spurius and the alpha-conotoxin EI share high-affinity potentiation and low-affinity inhibition of nicotinic acetylcholine receptors

alpha-Conotoxins from marine snails are known to be selective and potent competitive antagonists of nicotinic acetylcholine receptors. Here we describe the purification, structural features and activity of two novel toxins, SrIA and SrIB, isolated from Conus spurius collected in the Yucatan Channel, Mexico. As determined by direct amino acid and cDNA nucleotide sequencing, the toxins are peptides containing 18 amino acid residues with the typical 4/7-type framework but with completely novel sequences. Therefore, their actions (and that of a synthetic analog, [gamma15E]SrIB) were compared to those exerted by the alpha4/7-conotoxin EI from Conus ermineus, used as a control. Their target specificity was evaluated by the patch-clamp technique in mammalian cells expressing alpha(1)beta(1)gammadelta, alpha(4)beta(2) and alpha(3)beta(4) nicotinic acetylcholine receptors. At high concentrations (10 microm), the peptides SrIA, SrIB and [gamma15E]SrIB showed weak blocking effects only on alpha(4)beta(2) and alpha(1)beta(1)gammadelta subtypes, but EI also strongly blocked alpha(3)beta(4) receptors. In contrast to this blocking effect, the new peptides and EI showed a remarkable potentiation of alpha(1)beta(1)gammadelta and alpha(4)beta(2) nicotinic acetylcholine receptors if briefly (2-15 s) applied at concentrations several orders of magnitude lower (EC(50), 1.78 and 0.37 nm, respectively). These results suggest not only that the novel alpha-conotoxins and EI can operate as nicotinic acetylcholine receptor inhibitors, but also that they bind both alpha(1)beta(1)gammadelta and alpha(4)beta(2) nicotinic acetylcholine receptors with very high affinity and increase their intrinsic cholinergic response. Their unique properties make them excellent tools for studying the toxin-receptor interaction, as well as models with which to design highly specific therapeutic drugs.     

DNA barcode and minibarcode identification of freshwater fishes from Cerrado headwater streams in Central Brazil

The extraordinary species diversity of the Neotropical freshwater fish fauna is world renown. Yet, despite rich species diversity, taxonomic and genetic resources for its Cerrado ichthyofauna remain poorly developed. We provide a reference library of 149 DNA barcodes for 39 species/lineages of Cerrado headwater stream fishes from the Brazilian Distrito Federal and nearby areas and test the utility of distance-based criteria, tree-based criteria and minibarcodes for specimen identification. Mean Kimura 2-parameter genetic distances within species to orders ranged 1·8–12·1%. However, mean intraspecific v. congeneric-interspecific distances (0·9–1·3%) overlapped extensively and distance-based barcoding failed to achieve correct identifications due to c. 4–12·1% error rates and 19·5% ambiguous identifications related to the presence of singletons. Overlap was reduced and best-match success rates improved drastically to 83·5% when Characidium barcodes representing potential misidentifications or undescribed species were removed. Tree-based monophyly criteria generally performed similarly to distance methods, correctly differentiating up to c. 85% of species/lineages despite neighbour-joining and Bayesian tree errors (random lineage-branching events, long-branch attraction). Five clusters (Ancistrus aguaboensis, Characidium spp., Eigenmannia trilineata, Hasemania hanseni and Hypostomus sp. 2) exhibited deep intraspecific divergences or para−/polyphyly and multiple Barcode Index Number assignments indicative of putative candidate species needing taxonomic re-examination. Sliding-window analyses also indicated that a 200 bp minibarcode region performed just as well at specimen identification as the entire barcode gene. Future DNA barcoding studies of Distrito Federal–Cerrado freshwater fishes will benefit from increased sampling coverage, as well as consideration of minibarcode targets for degraded samples and next-generation sequencing.     

Consistency of females’ stridulatory behaviour during inter‐sexual interactions in spiders

In a sexual context, it is expected that females base their choice of mate on the behaviours that males perform during courtship, as such behaviours are associated with the male's mate quality. Stridulation is one form of female communication in arthropods, for example, spiders. In spiders, stridulation during sexual interactions is relatively common in some groups but mainly restricted to males. In the pholcid spider Holocnemus pluchei (Pholcidae), both sexes have stridulatory organs. The aims of the present work were to: (a) determine possible differences in the frequency of occurrence of stridulation between females during inter‐sexual interactions, (b) establish female consistency in stridulation along repeated interactions and (c) analyse if female stridulation is associated with certain male behaviours during pre‐copulatory courtship and with male size. Female H. pluchei showed highly repeatable differences in their frequency of stridulation across consecutive encounters with males (ICC = 0.64). However, only a modest level of repeatability was detected in total time females spent stridulating across trials (ICC = 0.19). Females’ mean stridulatory behaviour did not change across ten consecutive trials spread across 20 days, and their behaviour was apparently unaffected by male persistence of copulatory attempted and/or size. These results imply that the frequency of female stridulatory behaviour is a trait that is highly characteristic of each individual. Finally, our work opens the door to determine whether behavioural consistency manifests in other ecological contexts and their functional implications.     

Purinergic Signalling in Parkinson’s Disease: A Multi-target System to Combat Neurodegeneration

Neurochemical Research - Parkinson’s disease (PD) is the second most common neurodegenerative disorder, characterized by progressive loss of dopaminergic neurons that results in...