Shake it off: exploring drivers and outcomes of autotomy in marine invertebrates.

Autotomy refers to self-amputation where the loss of a limb or organ is generally said to be (1) in response to stressful external stimuli; (2) voluntary and nervously mediated; (3) supported by adaptive features that increase efficiency and simultaneously mediate the cost; and (4) morphologically delineated by a predictable breakage plane. It is estimated that this phenomenon has evolved independently nine different times across the animal kingdom, appearing in many different taxa, including vertebrate and invertebrate as well as aquatic and terrestrial animals. Marine invertebrates use this behaviour in a diversity of manners that have yet to be globally reviewed and critically examined. Here, published data from marine invertebrate taxa were used to explore instances of injury as an evolutionary driver of autotomy. Findings suggest that phyla (e.g. Echinodermata and Arthropoda) possibly experiencing high rates of injury (tissue damage or loss) are more likely to be able to perform autotomy. Additionally, this review looks at various morphological, physiological and environmental conditions that have either driven the evolution or maintained the behaviour of autotomy in marine invertebrates. Finally, the use of autotomic abilities in the development of more sustainable and less ecologically invasive fisheries is explored.

Marine-Derived Peptides with Anti-Hypertensive Properties: Prospects for Pharmaceuticals, Supplements, and Functional Food.

Hypertension, a major health concern linked to heart disease and premature mortality, has prompted a search for alternative treatments due to side effects of existing medications. Sustainable harvesting of low-trophic marine organisms not only enhances food security but also provides a variety of bioactive molecules, including peptides. Despite comprising only a fraction of active natural compounds, peptides are ideal for drug development due to their size, stability, and resistance to degradation. Our review evaluates the anti-hypertensive properties of peptides and proteins derived from selected marine invertebrate phyla, examining the various methodologies used and their application in pharmaceuticals, supplements, and functional food. A considerable body of research exists on the anti-hypertensive effects of certain marine invertebrates, yet many species remain unexamined. The array of assessments methods, particularly for ACE inhibition, complicates the comparison of results. The dominance of in vitro and animal in vivo studies indicates a need for more clinical research in order to transition peptides into pharmaceuticals. Our findings lay the groundwork for further exploration of these promising marine invertebrates, emphasizing the need to balance scientific discovery and marine conservation for sustainable resource use.

High-throughput segmentation, data visualization, and analysis of sea star skeletal networks.

The remarkably complex skeletal systems of the sea stars (Echinodermata, Asteroidea), consisting of hundreds to thousands of individual elements (ossicles), have intrigued investigators for more than 150 years. While the general features and structural diversity of isolated asteroid ossicles have been well documented in the literature, the task of mapping the spatial organization of these constituent skeletal elements in a whole-animal context represents an incredibly laborious process, and as such, has remained largely unexplored. To address this unmet need, particularly in the context of understanding structure-function relationships in these complex skeletal systems, we present an integrated approach that combines micro-computed tomography, automated ossicle segmentation, data visualization tools, and the production of additively manufactured tangible models to reveal biologically relevant structural data that can be rapidly analyzed in an intuitive manner. In the present study, we demonstrate this high-throughput workflow by segmenting and analyzing entire skeletal systems of the giant knobby star, Pisaster giganteus, at four different stages of growth. The in-depth analysis, presented herein, provides a fundamental understanding of the three-dimensional skeletal architecture of the sea star body wall, the process of skeletal maturation during growth, and the relationship between skeletal organization and morphological characteristics of individual ossicles. The widespread implementation of this approach for investigating other species, subspecies, and growth series has the potential to fundamentally improve our understanding of asteroid skeletal architecture and biodiversity in relation to mobility, feeding habits, and environmental specialization in this fascinating group of echinoderms.

Fusceulimoides kohtsukai gen. et sp. nov., a Minute Eulimid Gastropod Parasitic on the Little Brittle Star Ophiactis savignyi in Central Japan.

Gastropods of over a dozen genera in the family Eulimidae have been identified as parasites of brittle stars, and many more remain to be discovered and described for a comprehensive understanding of the evolutionary history of their host-parasite relationships. In this study, we describe Fusceulimoides kohtsukai gen. et sp. nov., parasitic on the little brittle star, Ophiactis savignyi (Ophiactidae), in Kanagawa, central Japan. The new genus is distinguished from other eulimid genera by the combination of following seven conchological characters: (1) a very small size of up to 1.7 mm high, (2) a colorless translucent appearance, (3) a conical pupiform shape with a paucispiral protoconch, (4) slightly convex teleoconch whorls, (5) a remarkably large body whorl occupying 65-70% of the total shell height, (6) a broad, somewhat squarish and laterally expanded aperture with a strongly curved outer lip, and (7) a developed parietal callus without an indentation or depression in the umbilical area. A multi-locus molecular phylogeny revealed its distant relationship to Hemiliostraca + Pyramidelloides, a previously known clade of ophiuroid parasites, thereby suggesting multiple origins of this host-parasite association in Eulimidae.

Morphological, Physiological and Mechanical Features of the Mutable Collagenous Tissues Associated with Autotomy and Evisceration in Dendrochirotid Holothuroids.

Evisceration in dendrochirotid sea cucumbers leads to expulsion of the digestive tract, pharyrngeal complex and coelomic fluid through rupture of the anterior body wall. This process involves failure of three mutable collagenous tissue (MCT) structures, the introvert, the pharyngeal retractor muscle tendon, and the intestine-cloacal junction. These are complex structures composed of several tissue strata. The MCT in the three autotomy structures contains collagen fibrils, unstriated microfibrils, and interfibrillar molecules. Neurosecretory-like processes (juxtaligamental-type) with large dense vesicles (LDVs) are prominent in the autotomy structures. Biomechanical tests show that these structures are not inherently weak. Failure of the autotomy structures can be elicited by manipulating the ionic environment and the changes are blocked by anaesthetics. Autotomy and evisceration are under neural control, but local neural elements and neurosecretory-like processes do not appear to be a source of factors that cause MCT destabilisation. The LDVs remain intact while the tissue destabilises. The coelomic fluid contains an evisceration inducing factor indicating a neurosecretory-like mediation of autotomy. This factor elicits muscle contraction and MCT destabilisation. As the autotomy structures are completely or partially surrounded by coelomic fluid, the agent(s) of change may be located in the coelom (systemic origin) as well as originate from cells within the MCT. The biochemistry and mechanism(s) of action of the evisceration factor are not known. This factor is a promising candidate for biodiscovery investigation.

Sex-specific expression of pheromones and other signals in gravid starfish.

BACKGROUND: Many echinoderms form seasonal aggregations prior to spawning. In some fecund species, a spawning event can lead to population outbreaks with detrimental ecosystem impacts. For instance, outbreaks of crown-of-thorns starfish (COTS), a corallivore, can destroy coral reefs. Here, we examine the gene expression in gravid male and female COTS prior to spawning in the wild, to identify genome-encoded factors that may regulate aggregation and spawning. This study is informed by a previously identified exoproteome that attracts conspecifics. To capture the natural gene expression profiles, we isolated RNAs from gravid female and male COTS immediately after they were removed from the Great Barrier Reef.  RESULTS: Sexually dimorphic gene expression is present in all seven somatic tissues and organs that we surveyed and in the gonads. Approximately 40% of the exoproteome transcripts are differentially expressed between sexes. Males uniquely upregulate an additional 68 secreted factors in their testes. A suite of neuropeptides in sensory organs, coelomocytes and gonads is differentially expressed between sexes, including the relaxin-like gonad-stimulating peptide and gonadotropin-releasing hormones. Female sensory tentacles-chemosensory organs at the distal tips of the starfish arms-uniquely upregulate diverse receptors and signalling molecules, including chemosensory G-protein-coupled receptors and several neuropeptides, including kisspeptin, SALMFamide and orexin. CONCLUSIONS: Analysis of 103 tissue/organ transcriptomes from 13 wild COTS has revealed genes that are consistently differentially expressed between gravid females and males and that all tissues surveyed are sexually dimorphic at the molecular level. This finding is consistent with female and male COTS using sex-specific pheromones to regulate reproductive aggregations and synchronised spawning events. These pheromones appear to be received primarily by the sensory tentacles, which express a range of receptors and signalling molecules in a sex-specific manner. Furthermore, coelomocytes and gonads differentially express signalling and regulatory factors that control gametogenesis and spawning in other echinoderms.

Evolutionary analyses of genes in Echinodermata offer insights towards the origin of metazoan phyla.

Despite recent studies discussing the evolutionary impacts of gene duplications and losses among metazoans, the genomic basis for the evolution of phyla remains enigmatic. Here, we employ phylogenomic approaches to search for orthologous genes without known functions among echinoderms, and subsequently use them to guide the identification of their homologs across other metazoans. Our final set of 14 genes was obtained via a suite of homology prediction tools, gene expression data, gene ontology, and generating the Strongylocentrotus purpuratus phylome. The gene set was subjected to selection pressure analyses, which indicated that they are highly conserved and under negative selection. Their presence across broad taxonomic depths suggests that genes required to form a phylum are ancestral to that phylum. Therefore, rather than de novo gene genesis, we posit that evolutionary forces such as selection on existing genomic elements over large timescales may drive divergence and contribute to the emergence of phyla.

Fatty Acid-Rich Extract from Holothuria atra for Hyperuricemia via Expressions Modulation of GLUT9a and GLUT9b in Rat Model.

An edible sea cucumber Holothuria atra has been hypothesized to have medicinal benefits against hyperuricemia owing to its bioactive compounds, including mono- and poly-unsaturated fatty acids. Herein, we aimed to investigate the fatty acids-rich extract produced from H. atra to treat hyperuricemic rats (Rattus novergicus). The extraction was carried out using n-hexane solvent and then administered to potassium oxonate-induced hyperuricemic rats, with allopurinol acting as a positive control. The extract (50, 100, 150 mg/kg body weight) and allopurinol (10 mg/kg) were administered QD through an oral route using a nasogastric tube. Serum uric acid, creatinine, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and blood urea nitrogen of the abdominal aortic blood were investigated. Our results suggested that the extract was rich in polyunsaturated (arachidonic acid) and monounsaturated fatty acids (oleic acid), in which its administration of 150 mg/kg could significantly reduce serum uric acid (p < 0.001), AST (p = 0.001), and ALT (p = 0.0302). The anti-hyperuricemic activity could be associated with the modulation of GLUT9 by the H. atra extract. In conclusion, the n-hexane extract from H. atra is a potential serum uric acid-lowering agent targeting GLUT9, where further investigations are crucially warranted.

Twinkle twinkle brittle star: the draft genome of Ophioderma brevispinum (Echinodermata: Ophiuroidea) as a resource for regeneration research.

BACKGROUND: Echinoderms are established models in experimental and developmental biology, however genomic resources are still lacking for many species. Here, we present the draft genome of Ophioderma brevispinum, an emerging model organism in the field of regenerative biology. This new genomic resource provides a reference for experimental studies of regenerative mechanisms. RESULTS: We report a de novo nuclear genome assembly for the brittle star O. brevispinum and annotation facilitated by the transcriptome assembly. The final assembly is 2.68 Gb in length and contains 146,703 predicted protein-coding gene models. We also report a mitochondrial genome for this species, which is 15,831 bp in length, and contains 13 protein-coding, 22 tRNAs, and 2 rRNAs genes, respectively. In addition, 29 genes of the Notch signaling pathway are identified to illustrate the practical utility of the assembly for studies of regeneration. CONCLUSIONS: The sequenced and annotated genome of O. brevispinum presented here provides the first such resource for an ophiuroid model species. Considering the remarkable regenerative capacity of this species, this genome will be an essential resource in future research efforts on molecular mechanisms regulating regeneration.

Mitogenomes Reveal Alternative Initiation Codons and Lineage-Specific Gene Order Conservation in Echinoderms.

The mitochondrial genetic code is much more varied than the standard genetic code. The invertebrate mitochondrial code, for instance, comprises six initiation codons, including five alternative start codons. However, only two initiation codons are known in the echinoderm and flatworm mitochondrial code, the canonical ATG and alternative GTG. Here, we analyzed 23 Asteroidea mitogenomes, including ten newly sequenced species and unambiguously identified at least two other start codons, ATT and ATC, both of which also initiate translation of mitochondrial genes in other invertebrates. These findings underscore the diversity of the genetic code and expand upon the suite of initiation codons among echinoderms to avoid erroneous annotations. Our analyses have also uncovered the remarkable conservation of gene order among asteroids, echinoids, and holothuroids, with only an interchange between two gene positions in asteroids over ∼500 Ma of echinoderm evolution.

The RNA virome of echinoderms.

Echinoderms are a phylum of marine invertebrates that include model organisms, keystone species, and animals commercially harvested for seafood. Despite their scientific, ecological, and economic importance, there is little known about the diversity of RNA viruses that infect echinoderms compared to other invertebrates. We screened over 900 transcriptomes and viral metagenomes to characterize the RNA virome of 38 echinoderm species from all five classes (Crinoidea, Holothuroidea, Asteroidea, Ophiuroidea and Echinoidea). We identified 347 viral genome fragments that were classified to genera and families within nine viral orders - Picornavirales, Durnavirales, Martellivirales, Nodamuvirales, Reovirales, Amarillovirales, Ghabrivirales, Mononegavirales, and Hepelivirales. We compared the relative viral representation across three life stages (embryo, larvae, adult) and characterized the gene content of contigs which encoded complete or near-complete genomes. The proportion of viral reads in a given transcriptome was not found to significantly differ between life stages though the majority of viral contigs were discovered from transcriptomes of adult tissue. This study illuminates the biodiversity of RNA viruses from echinoderms, revealing the occurrence of viral groups in natural populations.

Staying in place and moving in space: Contrasting larval thermal sensitivity explains distributional changes of sympatric sea urchin species to habitat warming.

For marine ectotherms, larval success, planktonic larval duration and dispersal trajectories are strongly influenced by temperature, and therefore, ocean warming and heatwaves have profound impacts on these sensitive stages. Warming, through increased poleward flow in regions with western boundary currents, such as the East Australia Current (EAC), provides opportunities for range extension as propagules track preferred conditions. Two sea urchin species, Centrostephanus rodgersii and Heliocidaris tuberculata, sympatric in the EAC warming hotspot, exhibit contrasting responses to warming. Over half a century, C. rodgersii has undergone marked poleward range extension, but the range of H. tuberculata has not changed. We constructed thermal performance curves (TPC) to determine if contrasting developmental thermal tolerance can explain this difference. The temperatures tested encompassed present-day distribution and forecast ocean warming/heatwave conditions. The broad and narrow thermal optimum (Topt) ranges for C. rodgersii and H. tuberculata larvae (7.2 and 4.7°C range, respectively) matched their realized (adult distribution) thermal niches. The cool and warm temperatures for 50% development to the feeding larva approximated temperatures at adult poleward range limits. Larval cool tolerances with respect to mean local temperature differed, 6.0 and 3.8°C respectively. Larval warm tolerances were similar for both species as are the adult warm range edges. The larvae of both species would be sensitive to heatwaves. Centrostephanus rodgersii has stayed in place and shifted in space, likely due to its broad cold-warm larval thermal tolerance and large thermal safety margins. Phenotypic plasticity of the planktonic stage of C. rodgersii facilitated its range extension. In contrast, larval cold intolerance of H. tuberculata explains its restricted range and will delay poleward extension as the region warms. In a warming ocean, we show that intrinsic thermal biology traits of the pelagic stage provide an integrative tool to explain species-specific variation in range shift patterns.

A subterminal growth zone at arm tip likely underlies life-long indeterminate growth in brittle stars.

BACKGROUND: Echinoderms are a phylum of marine invertebrates with close phylogenetic relationships to chordates. Many members of the phylum Echinodermata are capable of extensive post-traumatic regeneration and life-long indeterminate growth. Different from regeneration, the life-long elongation of the main body axis in adult echinoderms has received little attention. The anatomical location and the nature of the dividing progenitor cells contributing to adults' growth is unknown. RESULTS: We show that the proliferating cells that drive the life-long growth of adult brittle star arms are mostly localized to the subterminal (second from the tip) arm segment. Each of the major anatomical structures contains dividing progenitors. These structures include: the radial nerve, water-vascular canal, and arm coelomic wall. Some of those proliferating progenitor cells are capable of multiple rounds of cell division. Within the nervous system, the progenitor cells were identified as a subset of radial glial cells that do not express Brn1/2/4, a transcription factor with a conserved role in the neuronal fate specification. In addition to characterizing the growth zone and the nature of the precursor cells, we provide a description of the microanatomy of the four distal-most arm segments contrasting the distal with the proximal segments, which are more mature. CONCLUSIONS: The growth of the adult brittle star arms occurs via proliferation of progenitor cells in the distal segments, which are most abundant in the second segment from the tip. At least some of the progenitors are capable of multiple rounds of cell division. Within the nervous system the dividing cells were identified as Brn1/2/4-negative radial glial cells.

Rainbow bodies: Revisiting the diversity of coelomocyte aggregates and their synthesis in echinoderms.

The innate immunity of echinoderms has been a research focus since the early twentieth century, consistently providing ever deeper knowledge of its complexity and evolutionary aspects. At its core are coelomocytes, which are diverse cells collectively known to respond in a variety of ways, including via movement, phagocytosis, and aggregation. However, features of cellular immunity have never been compared in echinoderms from phylogenetic and distributional perspectives, to provide insight into ecological and evolutionary patterns. The present study catalyzed and characterized the formation of coelomocyte aggregates in members of all five extant classes of echinoderms. The morphological characteristics of these aggregates (including their colour, shape, texture, size) were assessed, as well as the major cells composing them. Coelomocyte diversity (both as free and aggregated forms) was determined to be maximum in class Holothuroidea, followed by Echinoidea, with the other classes showing similar levels of diversity. The colours of coelomocyte aggregates appeared to be more closely linked to phylogeny (classes, orders) rather than geographic range, or external colour of the species themselves. Asteroids and ophiuroids displayed primarily light-coloured aggregates, from transparent to green; while holothuroids, echinoids and crinoids demonstrated more vivid variants, from red to deep purple. The kinetics of aggregate formation and expulsion were monitored in selected species, showing immediate cellular response to foreign particulate matter in the form of encapsulation and various methods of expulsion, including through the dermal papillae of asteroids and the anus (cloaca) of holothuroids. The findings support that coelomocyte aggregate formation is a conserved immune response across all five extant classes of echinoderms with variations in their cell catalysts, complexity, shape, colour, and size.

A chromosome-level reference genome for the giant pink sea star, Pisaster brevispinus, a species severely impacted by wasting.

Efforts to protect the ecologically and economically significant California Current Ecosystem from global change will greatly benefit from data about patterns of local adaptation and population connectivity. To facilitate that work, we present a reference-quality genome for the giant pink sea star, Pisaster brevispinus, a species of ecological importance along the Pacific west coast of North America that has been heavily impacted by environmental change and disease. We used Pacific Biosciences HiFi long sequencing reads and Dovetail Omni-C proximity reads to generate a highly contiguous genome assembly of 550 Mb in length. The assembly contains 127 scaffolds with a contig N50 of 4.6 Mb and a scaffold N50 of 21.4 Mb; the BUSCO completeness score is 98.70%. The P. brevispinus genome assembly is comparable to the genome of the congener species P. ochraceus in size and completeness. Both Pisaster assemblies are consistent with previously published karyotyping results showing sea star genomes are organized into 22 autosomes. The reference genome for P. brevispinus is an important first step toward the goal of producing a comprehensive, population genomics view of ecological and evolutionary processes along the California coast. This resource will help scientists, managers, and policy makers in their task of understanding and protecting critical coastal regions from the impacts of global change.

Caspase-1 and Cathepsin B Inhibitors from Marine Invertebrates, Aiming at a Reduction in Neuroinflammation.

Neuroinflammation is a condition associated with several types of dementia, such as Alzheimer's disease (AD), mainly caused by an inflammatory response to amyloid peptides that induce microglial activation, with subsequent cytokine release. Neuronal caspase-1 from inflammasome and cathepsin B are key enzymes mediating neuroinflammation in AD, therefore, revealing new molecules to modulate these enzymes may be an interesting approach to treat neurodegenerative diseases. In this study, we searched for new caspase-1 and cathepsin B inhibitors from five species of Brazilian marine invertebrates (four cnidarians and one echinoderm). The results show that the extract of the box jellyfish Chiropsalmus quadrumanus inhibits caspase-1. This extract was fractionated, and the products monitored for their inhibitory activity, until the obtention of a pure molecule, which was identified as trigonelline by mass spectrometry. Moreover, four extracts inhibit cathepsin B, and Exaiptasia diaphana was selected for subsequent fractionation and characterization, resulting in the identification of betaine as being responsible for the inhibitory action. Both molecules are already found in marine organisms, however, this is the first study showing a potent inhibitory effect on caspase-1 and cathepsin B activities. Therefore, these new prototypes can be considered for the enzyme inhibition and subsequent control of the neuroinflammation.

Fatty Acids of Echinoderms: Diversity, Current Applications and Future Opportunities.

The phylum Echinodermata comprising the classes Asteroidea, Ophiuroidea, Echinoidea, Holothuroidea, and Crinodeia, is one of the important invertebrate groups. Members of this phylum live exclusively in marine habitats and are distributed in almost all depths and latitudes. Some of them, such as sea urchins and sea cucumbers, are commercially valuable and constitute a major fishery resource. Echinoderms are increasingly recognized as a unique source of various metabolites with a wide range of biological activities. The importance of dietary polyunsaturated fatty acids, such as eicosapentaenoic acid, in human health has drawn attention to echinoderms as a promising source of essential fatty acids (FAs). Extensive information on the FAs of the phylum has been accumulated to date. The biosynthetic capabilities and feeding habits of echinoderms explain the findings of the unusual FAs in them. Certain common and unusual FAs may serve as chemotaxonomic markers of the classes. The main goal of the review was to gather the relevant information on the distribution of FAs among the echinoderm classes, describe the structures, distribution, biosynthetic pathways, and bioactivity, with an emphasis on the FAs specific for echinoderms. A large part of the review is devoted to the FAs derived from echinoderms that exhibit various biological activities promising for potential therapeutic applications.

Ultrastructural and molecular analysis of the origin and differentiation of cells mediating brittle star skeletal regeneration.

BACKGROUND: Regeneration is the ability to re-grow body parts or tissues after trauma, and it is widespread across metazoans. Cells involved in regeneration can arise from a pool of undifferentiated proliferative cells or be recruited from pre-existing differentiated tissues. Both mechanisms have been described in different phyla; however, the cellular and molecular mechanisms employed by different animals to restore lost tissues as well as the source of cells involved in regeneration remain largely unknown. Echinoderms are a clade of deuterostome invertebrates that show striking larval and adult regenerative abilities in all extant classes. Here, we use the brittle star Amphiura filiformis to investigate the origin and differentiation of cells involved in skeletal regeneration using a combination of microscopy techniques and molecular markers. RESULTS: Our ultrastructural analyses at different regenerative stages identify a population of morphologically undifferentiated cells which appear in close contact with the proliferating epithelium of the regenerating aboral coelomic cavity. These cells express skeletogenic marker genes, such as the transcription factor alx1 and the differentiation genes c-lectin and msp130L, and display a gradient of morphological differentiation from the aboral coelomic cavity towards the epidermis. Cells closer to the epidermis, which are in contact with developing spicules, have the morphology of mature skeletal cells (sclerocytes), and express several skeletogenic transcription factors and differentiation genes. Moreover, as regeneration progresses, sclerocytes show a different combinatorial expression of genes in various skeletal elements. CONCLUSIONS: We hypothesize that sclerocyte precursors originate from the epithelium of the proliferating aboral coelomic cavity. As these cells migrate towards the epidermis, they differentiate and start secreting spicules. Moreover, our study shows that molecular and cellular processes involved in skeletal regeneration resemble those used during skeletal development, hinting at a possible conservation of developmental programmes during adult regeneration. Finally, we highlight that many genes involved in echinoderm skeletogenesis also play a role in vertebrate skeleton formation, suggesting a possible common origin of the deuterostome endoskeleton pathway.

Identification of New Purpuroine Analogues from the Arctic Echinodermata Pteraster militaris That Inhibit FLT3-ITD+ AML Cell Lines.

Isolation of bioactive products from the marine environment is considered a very promising approach to identify new compounds that can be used for further drug development. In this work we have isolated three new compounds from the purpuroine family by mass-guided preparative HPLC; purpuroine K-M. These compounds where screened for antibacterial- and antifungal activity, antibiofilm formation and anti-cell proliferation activity. Additionally, apoptosis-, cell cycle-, kinase binding- and docking studies were performed to evaluate the mechanism-of-action. None of the compounds showed activity in antibacterial-, antibiofilm- or antifungal assays. However, one of the isolated compounds, purpuroine K, showed activity against two cell lines, MV-4-11 and MOLM-13, two AML cell lines both carrying the FTL3-ITD mutation. In MV-4-11 cells, purpuroine K was found to increase apoptosis and arrest cells cycle in G1/G0, which is a common feature of FLT3 inhibitors. Interactions between purpuroine K and the FLT3 wild type or FLT3 ITD mutant proteins could however not be elucidated in our kinase binding and docking studies. In conclusion, we have isolated three novel molecules, purpuroine K-M, one of which (purpuroine K) shows a potent activity against FLT3-ITD mutated AML cell lines, however, the molecular target(s) of purpuroine K still need to be further investigated.

The first complete mitochondrial genome of the sand dollar Sinaechinocyamus mai (Echinoidea: Clypeasteroida).

Morphologic and molecular data often lead to different hypotheses of phylogenetic relationships. Such incongruence has been found in the echinoderm class Echinoidea. In particular, the phylogenetic status of the order Clypeasteroida is not well resolved. Complete mitochondrial genomes are currently available for 29 echinoid species, but no clypeasteroid had been sequenced to date. DNA extracted from a single live individual of Sinaechinocyamus mai was sequenced with 10× Genomics technology. This first complete mitochondrial genome (mitogenome) for the order Clypeasteroida is 15,756 base pairs in length. Phylogenomic analysis based on 34 ingroup taxa belonging to nine orders of the class Echinoidea show congruence between our new genetic inference and published trees based on morphologic characters, but also includes some intriguing differences that imply the need for additional investigation.