Traditional Taxonomic Groupings Mask Evolutionary History: A Molecular Phylogeny and New Classification of the Chromodorid Nudibranchs

Chromodorid nudibranchs (16 genera, 300+ species) are beautiful, brightly colored sea slugs found primarily in tropical coral reef habitats and subtropical coastal waters. The chromodorids are the most speciose family of opisthobranchs and one of the most diverse heterobranch clades. Chromodorids have the potential to be a model group with which to study diversification, color pattern evolution, are important source organisms in natural products chemistry and represent a stunning and widely compelling example of marine biodiversity. Here, we present the most complete molecular phylogeny of the chromodorid nudibranchs to date, with a broad sample of 244 specimens (142 new), representing 157 (106 new) chromodorid species, four actinocylcid species and four additional dorid species utilizing two mitochondrial markers (16s and COI). We confirmed the monophyly of the Chromodorididae and its sister group relationship with the Actinocyclidae. We were also able to, for the first time, test generic monophyly by including more than one member of all 14 of the non-monotypic chromodorid genera. Every one of these 14 traditional chromodorid genera are either non-monophyletic, or render another genus paraphyletic. Additionally, both the monotypic genera Verconia and Diversidoris are nested within clades. Based on data shown here, there are three individual species and five clades limited to the eastern Pacific and Atlantic Oceans (or just one of these ocean regions), while the majority of chromodorid clades and species are strictly Indo-Pacific in distribution. We present a new classification of the chromodorid nudibranchs. We use molecular data to untangle evolutionary relationships and retain a historical connection to traditional systematics by using generic names attached to type species as clade names

The Staphylococcus aureus superantigen SElX is a bifunctional toxin that inhibits neutrophil function:SElX Inhibits Neutrophil Function

Bacterial superantigens (SAgs) cause Vβ-dependent T-cell proliferation leading to immune dysregulation associated with the pathogenesis of life-threatening infections such as toxic shock syndrome, and necrotizing pneumonia. Previously, we demonstrated that staphylococcal enterotoxin-like toxin X (SElX) from Staphylococcus aureus is a classical superantigen that exhibits T-cell activation in a Vβ-specific manner, and contributes to the pathogenesis of necrotizing pneumonia. Here, we discovered that SElX can also bind to neutrophils from human and other mammalian species and disrupt IgG-mediated phagocytosis. Site-directed mutagenesis of the conserved sialic acid-binding motif of SElX abolished neutrophil binding and phagocytic killing, and revealed multiple glycosylated neutrophil receptors for SElX binding. Furthermore, the neutrophil binding-deficient mutant of SElX retained its capacity for T-cell activation demonstrating that SElX exhibits mechanistically independent activities on distinct cell populations associated with acquired and innate immunity, respectively. Finally, we demonstrated that the neutrophil-binding activity rather than superantigenicity is responsible for the SElX-dependent virulence observed in a necrotizing pneumonia rabbit model of infection. Taken together, we report the first example of a SAg, that can manipulate both the innate and adaptive arms of the human immune system during S. aureus pathogenesis

A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains.

BACKGROUND: The mouse inbred line C57BL/6J is widely used in mouse genetics and its genome has been incorporated into many genetic reference populations. More recently large initiatives such as the International Knockout Mouse Consortium (IKMC) are using the C57BL/6N mouse strain to generate null alleles for all mouse genes. Hence both strains are now widely used in mouse genetics studies. Here we perform a comprehensive genomic and phenotypic analysis of the two strains to identify differences that may influence their underlying genetic mechanisms. RESULTS: We undertake genome sequence comparisons of C57BL/6J and C57BL/6N to identify SNPs, indels and structural variants, with a focus on identifying all coding variants. We annotate 34 SNPs and 2 indels that distinguish C57BL/6J and C57BL/6N coding sequences, as well as 15 structural variants that overlap a gene. In parallel we assess the comparative phenotypes of the two inbred lines utilizing the EMPReSSslim phenotyping pipeline, a broad based assessment encompassing diverse biological systems. We perform additional secondary phenotyping assessments to explore other phenotype domains and to elaborate phenotype differences identified in the primary assessment. We uncover significant phenotypic differences between the two lines, replicated across multiple centers, in a number of physiological, biochemical and behavioral systems. CONCLUSIONS: Comparison of C57BL/6J and C57BL/6N demonstrates a range of phenotypic differences that have the potential to impact upon penetrance and expressivity of mutational effects in these strains. Moreover, the sequence variants we identify provide a set of candidate genes for the phenotypic differences observed between the two strains

A new standard: Phenotyping in the German Mouse Clinic.

With the growing number of new interesting and valuable mouse mutants generated by various strategies (e.g. knock out, gene trapping or ENU-mutagenesis), the need for a comprehensive and standardized phenotypic characterization of these mouse models rises. A comprehensive analysis via a set of parameters relevant for many diseases will enable us to evaluate the potential power of these mouse models in order to further dissect biological pathways. The German Mouse Clinic (GMC), located at the GSF Research Centre in Munich, offers a comprehensive, standardized phenotype analysis of mouse mutants by specialists from various disciplines and from different institutions in Germany, working side by side at one place. The phenotypic screens focus on the areas of allergy, behavior, bone and cartilage, cardiovascular diseases, clinical chemistry, eye development and vision, energy metabolism, immunology, lung function, neurology, nociception, molecular phenotyping, steroid-metabolism, and pathology. Additional screens for host-pathogen interaction are performed at the GBF Research Centre in Braunschweig. The phenotypic analysis is performed on the basis of a scientific collaboration. In a primary screen, mice are analyzed for 240 key parameters of different pathways and organ systems. Parameters exhibiting conspicuous deviations in mutants compared to their controls will be followed up in more deep drilling secondary and tertiary tests. Within the European initiative EUMORPHIA, we have standardized and validated our screening procedure. In the near future, our centre will be part of the pan-European mouse phenotyping initiative EUMODIC. More than 50 mutant lines have been analyzed in the primary screen, and baseline data for 9 mouse inbred strains and hybrids are available. From the mutant lines, which comleted the primary screen, we found new or additional phenotypes in 47 mutant lines. At least subtle changes were detected in almost every mutant line. Secondary screens were recommended for 45 mutant lines. We will present data of the analysis of mouse models for human diseases e.g. data of a model for Down syndrome, osteogenesis imperfecta, and osteoarthritis. Our data contributed in these mutant lines either to the identification of the mouse lines as a model system for these diseases, or we added with our screening parameters further similarities of the mutant line to the human syndromes.   As a next step, we will include genotype-environment-interactions in the analysis of the mutant lines. We will switch from a constant to a variable environment by establishing “environmental platforms” with different standardized challenge experiments. This will help us to identify genetic predispositions as susceptibility factors for environmental influences