The Mitochondrial Genome of Baylisascaris procyonis

BACKGROUND: Baylisascaris procyonis (Nematoda: Ascaridida), an intestinal nematode of raccoons, is emerging as an important helminthic zoonosis due to serious or fatal larval migrans in animals and humans. Despite its significant veterinary and public health impact, the epidemiology, molecular ecology and population genetics of this parasite remain largely unexplored. Mitochondrial (mt) genomes can provide a foundation for investigations in these areas and assist in the diagnosis and control of B. procyonis. In this study, the first complete mt genome sequence of B. procyonis was determined using a polymerase chain reaction (PCR)-based primer-walking strategy. METHODOLOGY/PRINCIPAL FINDINGS: The circular mt genome (14781 bp) of B. procyonis contained 12 protein-coding, 22 transfer RNA and 2 ribosomal RNA genes congruent with other chromadorean nematodes. Interestingly, the B. procyonis mtDNA featured an extremely long AT-rich region (1375 bp) and a high number of intergenic spacers (17), making it unique compared with other secernentean nematodes characterized to date. Additionally, the entire genome displayed notable levels of AT skew and GC skew. Based on pairwise comparisons and sliding window analysis of mt genes among the available 11 Ascaridida mtDNAs, new primer pairs were designed to amplify specific short fragments of the genes cytb (548 bp fragment) and rrnL (200 bp fragment) in the B. procyonis mtDNA, and tested as possible alternatives to existing mt molecular beacons for Ascaridida. Finally, phylogenetic analysis of mtDNAs provided novel estimates of the interrelationships of Baylisasaris and Ascaridida. CONCLUSIONS/SIGNIFICANCE: The complete mt genome sequence of B. procyonis sequenced here should contribute to molecular diagnostic methods, epidemiological investigations and ecological studies of B. procyonis and other related ascaridoids. The information will be important in refining the phylogenetic relationships within the order Ascaridida and enriching the resource of markers for systematic, population genetic and evolutionary biological studies of parasitic nematodes of socio-economic importance

Elucidating the clinical and molecular spectrum of SMARCC2-associated NDD in a cohort of 65 affected individuals

Purpose: Coffin-Siris and Nicolaides-Baraitser syndromes are recognizable neurodevelopmental disorders caused by germline variants in BAF complex subunits. The SMARCC2 BAFopathy was recently reported. Herein, we present clinical and molecular data on a large cohort. Methods: Clinical symptoms for 41 novel and 24 previously published affected individuals were analyzed using the Human Phenotype Ontology. For genotype-phenotype correlations, molecular data were standardized and grouped into non-truncating and likely gene-disrupting (LGD) variants. Missense variant protein expression and BAF-subunit interactions were examined using 3D protein modeling, co-immunoprecipitation, and proximity-ligation assays. Results: Neurodevelopmental delay with intellectual disability, muscular hypotonia, and behavioral disorders were the major manifestations. Clinical hallmarks of BAFopathies were rare. Clinical presentation differed significantly, with LGD variants being predominantly inherited and associated with mildly reduced or normal cognitive development, whereas non-truncating variants were mostly de novo and presented with severe developmental delay. These distinct manifestations and non-truncating variant clustering in functional domains suggest different pathomechanisms. In vitro testing showed decreased protein expression for N-terminal missense variants similar to LGD. Conclusion: This study improved SMARCC2 variant classification and identified discernible SMARCC2-associated phenotypes for LGD and non-truncating variants, which were distinct from other BAFopathies. The pathomechanism of most non-truncating variants has yet to be investigated

Demands of eicosapentaenoic acid (EPA) in Daphnia: are they dependent on body size?

Fatty acids contribute to the nutritional quality of the phytoplankton and, thus, play an important role in Daphnia nutrition. One of the polyunsaturated fatty acids (PUFAs)––eicosapentaenoic acid (EPA)––has been shown to predict carbon transfer between primary producers and consumers in lakes, suggesting that EPA limitation of Daphnia in nature is widespread. Although the demand for EPA must be covered by the diet, the demand of EPA in Daphnia that differ in body size has not been addressed yet. Here, we hypothesize that the demand for EPA in Daphnia is size-dependent and that bigger species have a higher EPA demand. To elucidate this, a growth experiment was conducted in which at 20 °C three Daphnia taxa (small-sized D. longispina complex, medium-sized D. pulicaria, and large-bodied D. magna) were fed Synechococcus elongatus supplemented with cholesterol and increasing concentrations of EPA. In addition, fatty acid analyses of Daphnia were performed. Our results show that the saturation threshold for EPA-dependent growth increased with increasing body size. This increase in thresholds with body size may provide another mechanism contributing to the prevalence of small-bodied cladocera in warm habitats and to the midsummer decline of large cladocera in eutrophic water bodies