SNP data reveals the complex and diverse evolutionary history of the blue-ringed octopus genus (Octopodidae: Hapalochlaena) in the Asia-Pacific

The blue-ringed octopus species complex (Hapalochlaena spp.), known to occur from Southern Australia to Japan, currently contains four formally described species (Hapalochlaena maculosa, Hapalochlaena fasciata, Hapalochlaena lunulata and Hapalochlaena nierstraszi). These species are distinguished based on morphological characters (iridescent blue rings and/or lines) along with reproductive strategies. However, the observation of greater morphological diversity than previously captured by the current taxonomic framework indicates that a revision is required. To examine species boundaries within the genus we used mitochondrial (12S rRNA, 16S rRNA, cytochrome c oxidase subunit 1 [COI], cytochrome c oxidase subunit 3 [COIII] and cytochrome b [Cytb]) and genome-wide SNP data (DaRT seq) from specimens collected across its geographic range including variations in depth from 3 m to >100 m. This investigation indicates substantially greater species diversity present within the genus Hapalochlaena than is currently described. We identified 10,346 SNPs across all locations, which when analysed support a minimum of 11 distinct clades. Bayesian phylogenetic analysis of the mitochondrial COI gene on a more limited sample set dates the diversification of the genus to ∼30 mya and corroborates eight of the lineages indicated by the SNP analyses. Furthermore, we demonstrate that the diagnostic lined patterning of H. fasciata found in North Pacific waters and NSW, Australia is polyphyletic and therefore likely the result of convergent evolution. Several “deep water” (>100 m) lineages were also identified in this study with genetic convergence likely to be driven by external selective pressures. Examination of morphological traits, currently being undertaken in a parallel morphological study, is required to describe additional species within the complex

Adaptive venom evolution and toxicity in octopods is driven by extensive novel gene formation, expansion, and loss

Background: Cephalopods represent a rich system for investigating the genetic basis underlying organismal novelties. This diverse group of specialized predators has evolved many adaptations including proteinaceous venom. Of particular interest is the blue-ringed octopus genus (Hapalochlaena), which are the only octopods known to store large quantities of the potent neurotoxin, tetrodotoxin, within their tissues and venom gland. Findings: To reveal genomic correlates of organismal novelties, we conducted a comparative study of 3 octopod genomes, including the Southern blue-ringed octopus (Hapalochlaena maculosa). We present the genome of this species and reveal highly dynamic evolutionary patterns at both non-coding and coding organizational levels. Gene family expansions previously reported in Octopus bimaculoides (e.g., zinc finger and cadherins, both associated with neural functions), as well as formation of novel gene families, dominate the genomic landscape in all octopods. Examination of tissue-specific genes in the posterior salivary gland revealed that expression was dominated by serine proteases in non–tetrodotoxin-bearing octopods, while this family was a minor component in H. maculosa. Moreover, voltage-gated sodium channels in H. maculosa contain a resistance mutation found in pufferfish and garter snakes, which is exclusive to the genus. Analysis of the posterior salivary gland microbiome revealed a diverse array of bacterial species, including genera that can produce tetrodotoxin, suggestive of a possible production source. Conclusions: We present the first tetrodotoxin-bearing octopod genome H. maculosa, which displays lineage-specific adaptations to tetrodotoxin acquisition. This genome, along with other recently published cephalopod genomes, represents a valuable resource from which future work could advance our understanding of the evolution of genomic novelty in this family

Longitudinal strain is an independent predictor of survival and response to therapy in patients with systemic AL amyloidosis

AIMS: Cardiac involvement, a major determinant of prognosis in AL (light-chain immunoglobulin) amyloidosis, is characterized by an impairment of longitudinal strain (LS%). We sought to evaluate the utility of LS% in a prospectively observed series of patients. METHODS AND RESULTS: A total of 915 serial newly diagnosed AL patients with comprehensive baseline assessments, inclusive of echocardiography, were included. A total of 628/915 (68.6%) patients had cardiac involvement. The LS% worsened with advancing cardiac stage with mean −21.1%, −17.1%, −12.9%, and −12.1% for stages I, II, IIIa, and IIIb, respectively (P < 0.0001). There was a highly significant worsening of overall survival (OS) with worsening LS% quartile: LS% ≤−16.2%: 80 months, −16.1% to −12.2%: 36 [95% confidence interval (CI) 20.9–51.1] months, −12.1% to −9.1%: 22 (95% CI 9.1–34.9) months, and ≥−9.0%: 5 (95% CI 3.2–6.8) months (P < 0.0001). Improvement in LS% was seen at 12 months in patients achieving a haematological complete response (CR) (median improvement from −13.8% to −14.9% in those with CR and difference between involved and uninvolved light chain <10 mg/L). Strain improvement was associated with improved OS (median not reached at 53 months vs. 72 months in patients without strain improvement, P = 0.007). Patients achieving an LS% improvement and a standard N-terminal pro-brain natriuretic peptide-based cardiac response survived longer than those achieving a biomarker-based cardiac response alone (P < 0.0001). CONCLUSION: Baseline LS% is a functional marker that correlates with worsening cardiac involvement and is predictive of survival. Baseline LS% and an absolute improvement in LS% are useful additional measures of prognosis and response to therapy in cardiac AL amyloidosis, respectively

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

Multiword expressions at length and in depth: Extended papers from the MWE 2017 workshop

The annual workshop on multiword expressions takes place since 2001 in conjunction with major computational linguistics conferences and attracts the attention of an ever-growing community working on a variety of languages, linguistic phenomena and related computational processing issues. MWE 2017 took place in Valencia, Spain, and represented a vibrant panorama of the current research landscape on the computational treatment of multiword expressions, featuring many high-quality submissions. Furthermore, MWE 2017 included the first shared task on multilingual identification of verbal multiword expressions. The shared task, with extended communal work, has developed important multilingual resources and mobilised several research groups in computational linguistics worldwide. This book contains extended versions of selected papers from the workshop. Authors worked hard to include detailed explanations, broader and deeper analyses, and new exciting results, which were thoroughly reviewed by an internationally renowned committee. We hope that this distinctly joint effort will provide a meaningful and useful snapshot of the multilingual state of the art in multiword expressions modelling and processing, and will be a point point of reference for future work

Multiword expressions at length and in depth: Extended papers from the MWE 2017 workshop

The annual workshop on multiword expressions takes place since 2001 in conjunction with major computational linguistics conferences and attracts the attention of an ever-growing community working on a variety of languages, linguistic phenomena and related computational processing issues. MWE 2017 took place in Valencia, Spain, and represented a vibrant panorama of the current research landscape on the computational treatment of multiword expressions, featuring many high-quality submissions. Furthermore, MWE 2017 included the first shared task on multilingual identification of verbal multiword expressions. The shared task, with extended communal work, has developed important multilingual resources and mobilised several research groups in computational linguistics worldwide. This book contains extended versions of selected papers from the workshop. Authors worked hard to include detailed explanations, broader and deeper analyses, and new exciting results, which were thoroughly reviewed by an internationally renowned committee. We hope that this distinctly joint effort will provide a meaningful and useful snapshot of the multilingual state of the art in multiword expressions modelling and processing, and will be a point point of reference for future work

Multiword expressions at length and in depth: Extended papers from the MWE 2017 workshop

The annual workshop on multiword expressions takes place since 2001 in conjunction with major computational linguistics conferences and attracts the attention of an ever-growing community working on a variety of languages, linguistic phenomena and related computational processing issues. MWE 2017 took place in Valencia, Spain, and represented a vibrant panorama of the current research landscape on the computational treatment of multiword expressions, featuring many high-quality submissions. Furthermore, MWE 2017 included the first shared task on multilingual identification of verbal multiword expressions. The shared task, with extended communal work, has developed important multilingual resources and mobilised several research groups in computational linguistics worldwide. This book contains extended versions of selected papers from the workshop. Authors worked hard to include detailed explanations, broader and deeper analyses, and new exciting results, which were thoroughly reviewed by an internationally renowned committee. We hope that this distinctly joint effort will provide a meaningful and useful snapshot of the multilingual state of the art in multiword expressions modelling and processing, and will be a point point of reference for future work

Multiword expressions at length and in depth: Extended papers from the MWE 2017 workshop

The annual workshop on multiword expressions takes place since 2001 in conjunction with major computational linguistics conferences and attracts the attention of an ever-growing community working on a variety of languages, linguistic phenomena and related computational processing issues. MWE 2017 took place in Valencia, Spain, and represented a vibrant panorama of the current research landscape on the computational treatment of multiword expressions, featuring many high-quality submissions. Furthermore, MWE 2017 included the first shared task on multilingual identification of verbal multiword expressions. The shared task, with extended communal work, has developed important multilingual resources and mobilised several research groups in computational linguistics worldwide. This book contains extended versions of selected papers from the workshop. Authors worked hard to include detailed explanations, broader and deeper analyses, and new exciting results, which were thoroughly reviewed by an internationally renowned committee. We hope that this distinctly joint effort will provide a meaningful and useful snapshot of the multilingual state of the art in multiword expressions modelling and processing, and will be a point point of reference for future work