Genomic Signatures Supporting the Symbiosis and Formation of Chitinous Tube in the Deep-Sea Tubeworm Paraescarpia echinospica.

Vestimentiferan tubeworms are iconic animals that present as large habitat-forming chitinized tube bushes in deep-sea chemosynthetic ecosystems. They are gutless and depend entirely on their endosymbiotic sulfide-oxidizing chemoautotrophic bacteria for nutrition. Information on the genomes of several siboglinid endosymbionts has improved our understanding of their nutritional supplies. However, the interactions between tubeworms and their endosymbionts remain largely unclear due to a paucity of host genomes. Here, we report the chromosome-level genome of the vestimentiferan tubeworm Paraescarpia echinospica. We found that the genome has been remodeled to facilitate symbiosis through the expansion of gene families related to substrate transfer and innate immunity, suppression of apoptosis, regulation of lysosomal digestion, and protection against oxidative stress. Furthermore, the genome encodes a programmed cell death pathway that potentially controls the endosymbiont population. Our integrated genomic, transcriptomic, and proteomic analyses uncovered matrix proteins required for the formation of the chitinous tube and revealed gene family expansion and co-option as evolutionary mechanisms driving the acquisition of this unique supporting structure for deep-sea tubeworms. Overall, our study provides novel insights into the host's support system that has enabled tubeworms to establish symbiosis, thrive in deep-sea hot vents and cold seeps, and produce the unique chitinous tubes in the deep sea.

Host-Endosymbiont Genome Integration in a Deep-Sea Chemosymbiotic Clam.

Endosymbiosis with chemosynthetic bacteria has enabled many deep-sea invertebrates to thrive at hydrothermal vents and cold seeps, but most previous studies on this mutualism have focused on the bacteria only. Vesicomyid clams dominate global deep-sea chemosynthesis-based ecosystems. They differ from most deep-sea symbiotic animals in passing their symbionts from parent to offspring, enabling intricate coevolution between the host and the symbiont. Here, we sequenced the genomes of the clam Archivesica marissinica (Bivalvia: Vesicomyidae) and its bacterial symbiont to understand the genomic/metabolic integration behind this symbiosis. At 1.52 Gb, the clam genome encodes 28 genes horizontally transferred from bacteria, a large number of pseudogenes and transposable elements whose massive expansion corresponded to the timing of the rise and subsequent divergence of symbiont-bearing vesicomyids. The genome exhibits gene family expansion in cellular processes that likely facilitate chemoautotrophy, including gas delivery to support energy and carbon production, metabolite exchange with the symbiont, and regulation of the bacteriocyte population. Contraction in cellulase genes is likely adaptive to the shift from phytoplankton-derived to bacteria-based food. It also shows contraction in bacterial recognition gene families, indicative of suppressed immune response to the endosymbiont. The gammaproteobacterium endosymbiont has a reduced genome of 1.03 Mb but retains complete pathways for sulfur oxidation, carbon fixation, and biosynthesis of 20 common amino acids, indicating the host's high dependence on the symbiont for nutrition. Overall, the host-symbiont genomes show not only tight metabolic complementarity but also distinct signatures of coevolution allowing the vesicomyids to thrive in chemosynthesis-based ecosystems.

Signatures of Divergence, Invasiveness, and Terrestrialization Revealed by Four Apple Snail Genomes.

The family Ampullariidae includes both aquatic and amphibious apple snails. They are an emerging model for evolutionary studies due to the high diversity, ancient history, and wide geographical distribution. Insight into drivers of ampullariid evolution is hampered, however, by the lack of genomic resources. Here, we report the genomes of four ampullariids spanning the Old World (Lanistes nyassanus) and New World (Pomacea canaliculata, P. maculata, and Marisa cornuarietis) clades. The ampullariid genomes have conserved ancient bilaterial karyotype features and a novel Hox gene cluster rearrangement, making them valuable in comparative genomic studies. They have expanded gene families related to environmental sensing and cellulose digestion, which may have facilitated some ampullarids to become notorious invasive pests. In the amphibious Pomacea, novel acquisition of an egg neurotoxin and a protein for making the calcareous eggshell may have been key adaptations enabling their transition from underwater to terrestrial egg deposition.

Egg perivitelline fluid proteome of a freshwater snail: Insight into the transition from aquatic to terrestrial egg deposition.

RATIONALE: Proteins from the egg perivitelline fluid (PVF) are assumed to play critical roles in embryonic development, but for many groups of animals their identities remain unknown. Identifying egg PVF proteins is a critical step towards understanding their functions including their roles in evolutionary transition in habitats. METHODS: We applied proteomic and transcriptomic analysis to investigate the PVF proteome of the eggs of Pomacea diffusa, an aerial ovipositing freshwater snail in the family Ampullariidae. The PVF proteins were separated with the sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) method, and proteomic analysis was conducted using an LTQ Velos ion trap mass spectrometer coupled with liquid chromatography. Comparison of PVF proteomes and evolution analyses was performed between P. diffusa and other ampullariids. RESULTS: In total, 32 egg PVF proteins were identified from P. diffusa. They were categorized as PV1-like subunits, immune-responsive proteins, protein degradation, signaling and binding, transcription and translation, metabolism, oxidation-reduction and proteins with unknown function. Interestingly, the proteome includes a calcium-binding protein important in forming the hard eggshell that enabled the terrestrial transition. However, it does not include PV2, a neurotoxic protein that was assumed to be present in all Pomacea species. CONCLUSIONS: The PVF proteome data from P. diffusa can help us better understand the roles that reproductive proteins played during the transition from underwater to terrestrial egg deposition. Moreover, they could be useful in comparative studies of the terrestrialization in several groups of animals that occurred independently during their evolution.

AmpuBase: a transcriptome database for eight species of apple snails (Gastropoda: Ampullariidae).

BACKGROUND: Gastropoda, with approximately 80,000 living species, is the largest class of Mollusca. Among gastropods, apple snails (family Ampullariidae) are globally distributed in tropical and subtropical freshwater ecosystems and many species are ecologically and economically important. Ampullariids exhibit various morphological and physiological adaptations to their respective habitats, which make them ideal candidates for studying adaptation, population divergence, speciation, and larger-scale patterns of diversity, including the biogeography of native and invasive populations. The limited availability of genomic data, however, hinders in-depth ecological and evolutionary studies of these non-model organisms. RESULTS: Using Illumina Hiseq platforms, we sequenced 1220 million reads for seven species of apple snails. Together with the previously published RNA-Seq data of two apple snails, we conducted de novo transcriptome assembly of eight species that belong to five genera of Ampullariidae, two of which represent Old World lineages and the other three New World lineages. There were 20,730 to 35,828 unigenes with predicted open reading frames for the eight species, with N50 (shortest sequence length at 50% of the unigenes) ranging from 1320 to 1803 bp. 69.7% to 80.2% of these unigenes were functionally annotated by searching against NCBI's non-redundant, Gene Ontology database and the Kyoto Encyclopaedia of Genes and Genomes. With these data we developed AmpuBase, a relational database that features online BLAST functionality for DNA/protein sequences, keyword searching for unigenes/functional terms, and download functions for sequences and whole transcriptomes. CONCLUSIONS: In summary, we have generated comprehensive transcriptome data for multiple ampullariid genera and species, and created a publicly accessible database with a user-friendly interface to facilitate future basic and applied studies on ampullariids, and comparative molecular studies with other invertebrates.

De novo transcriptome analysis of Perna viridis highlights tissue-specific patterns for environmental studies.

BACKGROUND: The tropical green-lipped mussel Perna viridis is a common biomonitor throughout the Indo-Pacific region that is used for environmental monitoring and ecotoxicological investigations. However, there is limited molecular data available regarding this species. We sought to establish a global transcriptome database from the tissues of adductor muscle, gills and the hepatopancreas of P. viridis in an effort to advance our understanding of the molecular aspects involved during specific toxicity responses in this sentinel species. RESULTS: Illumina sequencing results yielded 544,272,542 high-quality filtered reads. After de novo assembly using Trinity, 233,257 contigs were generated with an average length of 1,264 bp and an N50 length of 2,868 bp; 192,879 assembled transcripts and 150,111 assembled unigenes were obtained after clustering. A total of 93,668 assembled transcripts (66,692 assembled genes) with putative functions for protein domains were predicted based on InterProScan analysis. Based on similarity searches, 44,713 assembled transcripts and 25,319 assembled unigenes were annotated with at least one BLAST hit. A total of 21,262 assembled transcripts (11,947 assembled genes) were annotated with at least one well-defined Gene Ontology (GO) and 5,131 assembled transcripts (3,181 assembled unigenes) were assigned to 329 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The quantity of assembled unigenes and transcripts obtained from male and female mussels were similar but varied among the three studied tissues, with the highest numbers recorded in the gills, followed by the hepatopancreas, and then the adductor muscle. Multivariate analyses revealed strong tissue-specific patterns among the three different tissues, but not between sexes in terms of expression profiles for annotated genes in various GO terms, and genes associated with stress responses and degradation of xenobiotics. The expression profiles of certain selected genes in each tissue type were further validated using real-time quantitative polymerase chain reaction assays and a similar tissue-specific trend was seen. CONCLUSIONS: The extensive sequence data generated from this study will provide a valuable molecular resource for facilitating environmental studies with P. viridis, and highlight the importance of tissue-specific approaches in the future.

Scallop-bacteria symbiosis from the deep sea reveals strong genomic coupling in the absence of cellular integration.

Previous studies have revealed tight metabolic complementarity between bivalves and their endosymbiotic chemosynthetic bacteria, but little is known about their interactions with ectosymbionts. Our analysis of the ectosymbiosis between a deep-sea scallop (Catillopecten margaritatus) and a gammaproteobacterium showed that bivalves could be highly interdependent with their ectosymbionts as well. Our microscopic observation revealed abundant sulfur-oxidizing bacteria (SOB) on the surfaces of the gill epithelial cells. Microbial 16S rRNA gene amplicon sequencing of the gill tissues showed the dominance of the SOB. An analysis of the SOB genome showed that it is substantially smaller than its free-living relatives and has lost cellular components required for free-living. Genomic and transcriptomic analyses showed that this ectosymbiont relies on rhodanese-like proteins and SOX multienzyme complex for energy generation, mainly on the Calvin-Benson-Bassham (CBB) cycle and peripherally on a phosphoenolpyruvate carboxylase for carbon assimilation. Besides, the symbiont encodes an incomplete tricarboxylic acid (TCA) cycle. Observation of the scallop's digestive gland and its nitrogen metabolism pathways indicates it does not fully rely on the ectosymbiont for nutrition. Analysis of the host's gene expression provided evidence that it could offer intermediates for the ectosymbiont to complete its TCA cycle and some amino acid synthesis pathways using exosomes, and its phagosomes, endosomes, and lysosomes might be involved in harvesting nutrients from the symbionts. Overall, our study prompts us to rethink the intimacy between the hosts and ectosymbionts in Bivalvia and the evolution of chemosymbiosis in general.

Transcriptomic analysis reveals the endocrine toxicity of tributyltin and triphenyltin on the whelk Reishia clavigera and mechanisms of imposex formation.

Organotin compounds (OTs) are endocrine disruptors that induce imposex in hundreds of gastropods, but little is known about their underlying molecular mechanisms. This study aimed to investigate the endocrine toxicity and molecular responses to tributyltin (TBT) and triphenyltin (TPT) exposure in the whelk Reishia clavigera, which often serves as a biomonitor for OT contamination. Over a 120-day exposure to environmentally relevant concentrations of TBT (1000 ng L-1) and TPT (500 ng L-1), we observed a significant increase in penis length in both male and female whelks. Notably, TPT exhibited a stronger potency in inducing pseudo-penis development and female sterility, even at a half dose of TBT. Bioaccumulation analysis also revealed higher persistence and accumulation of TPT in whelk tissues compared to TBT. Differential expression analysis identified a substantial number of differentially expressed genes (DEGs), with TPT exposure eliciting more DEGs than TBT. Our results demonstrated that OTs induced xenobiotic metabolism and metabolic dysregulation in the digestive gland, impaired multiple cellular functions and triggered neurotoxicity in the nervous system, and disrupted lipid homeostasis and oxidative stress in the gonads. Furthermore, imposex was possibly associated with disturbances in retinoic acid metabolism, nuclear receptor signaling, and neuropeptide activity. When compared to TBT, TPT exhibited a more pronounced endocrine-disrupting effect, attributable to its higher bioaccumulation and substantial interruption of transcriptional regulation, OT detoxification, and biosynthesis of retinoic acids in R. clavigera. Our results, therefore, highlight the importance of considering the differences in bioaccumulation and molecular toxicity between TBT and TPT in future risk assessments of these contaminants. Overall, our study provided molecular insights into the toxicity and transcriptome profiles in R. clavigera exposed to TBT and TPT, shedding light on the endocrine-disrupting effects and reproductive impairment in female gastropods.

Environmental occurrence, biological effects, and health implications of zinc pyrithione: A review.

Due to the detrimental effects on aquatic organisms and ecosystem, tributyltin as a antifouling agent have been banned worldwide since 1990s. As a replacement for tributyltin, zinc pyrithione (ZnPT) has emerged as a new environmentally friendly antifouling agent. However, the widespread use of ZnPT unavoidably leads to the occurrence and accumulation in aquatic environments, especially in waters with limited sunlight. Despite empirical evidence demonstrating the ecotoxicity and health risks of ZnPT to different organisms, there has been no attempt to compile and interpret this data. The present review revealed that over the past 50 years, numerous studies have documented the toxicity of ZnPT in various organisms, both in vitro and in vivo. However, long-term effects and underlying mechanisms of ZnPT on biota, particularly at environmentally realistic exposure levels, remain largely unexplored. In-depth studies are thus necessary to generate detailed ecotoxicological information of ZnPT for environmental risk assessment and management.

Dynamic changes in bacterial communities in three species of corals during the 2017 bleaching event in subtropical Hong Kong waters.

Bacteria play important roles in coral health, yet little is known about the dynamics of coral-associated bacterial communities during coral bleaching. Here, we reported the dynamic changes of bacterial communities in three scleractinian corals (Montipora peltiformis, Pavona decussata and Platygyra carnosa) during and after bleaching through amplicon sequencing. Our results revealed that the bacterial composition and dominant bacteria varied among the three coral species. The higher susceptibility of M. peltiformis to bleaching corresponded to a lower bacterial community diversity, and the dominant Synechococcus shifted in abundance during the bleaching and coral recovery phases. The resilient P. decussata and P. carnosa had higher bacterial diversity and a more similar bacterial composition between the healthy and bleached conditions. Overall, our study reveals the dynamic changes in coral-associated microbial diversity under different conditions, contributing to explaining the differential susceptibility of corals to extreme climate conditions.

A draft genome assembly of reef-building octocoral Heliopora coerulea.

Coral reefs are under existential threat from climate change and anthropogenic impacts. Genomic studies have enhanced our knowledge of resilience and responses of some coral species to environmental stress, but reference genomes are lacking for many coral species. The blue coral Heliopora is the only reef-building octocoral genus and exhibits optimal growth at a temperature close to the bleaching threshold of scleractinian corals. Local and high-latitude expansions of Heliopora coerulea were reported in the last decade, but little is known about the molecular mechanisms underlying its thermal resistance. We generated a draft genome of H. coerulea with an assembled size of 429.9 Mb, scaffold N50 of 1.42 Mb and BUSCO completeness of 94.9%. The genome contains 239.1 Mb repetitive sequences, 27,108 protein coding genes, 6,225 lncRNAs, and 79 miRNAs. This reference genome provides a valuable resource for in-depth studies on the adaptive mechanisms of corals under climate change and the evolution of skeleton in cnidarian.

Interactions among deep-sea mussels and their epibiotic and endosymbiotic chemoautotrophic bacteria: Insights from multi-omics analysis.

Endosymbiosis with Gammaproteobacteria is fundamental for the success of bathymodioline mussels in deep-sea chemosynthesis-based ecosystems. However, the recent discovery of Campylobacteria on the gill surfaces of these mussels suggests that these host-bacterial relationships may be more complex than previously thought. Using the cold-seep mussel ( Gigantidas haimaensis) as a model, we explored this host-bacterial system by assembling the host transcriptome and genomes of its epibiotic Campylobacteria and endosymbiotic Gammaproteobacteria and quantifying their gene and protein expression levels. We found that the epibiont applies a sulfur oxidizing (SOX) multienzyme complex with the acquisition of soxB from Gammaproteobacteria for energy production and switched from a reductive tricarboxylic acid (rTCA) cycle to a Calvin-Benson-Bassham (CBB) cycle for carbon assimilation. The host provides metabolic intermediates, inorganic carbon, and thiosulfate to satisfy the materials and energy requirements of the epibiont, but whether the epibiont benefits the host is unclear. The endosymbiont adopts methane oxidation and the ribulose monophosphate pathway (RuMP) for energy production, providing the major source of energy for itself and the host. The host obtains most of its nutrients, such as lysine, glutamine, valine, isoleucine, leucine, histidine, and folate, from the endosymbiont. In addition, host pattern recognition receptors, including toll-like receptors, peptidoglycan recognition proteins, and C-type lectins, may participate in bacterial infection, maintenance, and population regulation. Overall, this study provides insights into the complex host-bacterial relationships that have enabled mussels and bacteria to thrive in deep-sea chemosynthetic ecosystems.

Stable Symbiodiniaceae composition in three coral species during the 2017 natural bleaching event in subtropical Hong Kong.

Adaptive changes in endosymbiotic Symbiodiniaceae communities have been reported during and after bleaching events in tropical coral species, but little is known about such shifts in subtropical species. Here we examined the Symbiodiniaceae communities in three coral species (Montipora peltiformis, Pavona decussata, and Platygyra carnosa) based on samples collected during and after the 2017 bleaching event in subtropical Hong Kong waters. In all of the collected samples, ITS2 meta-sequencing revealed that P. decussata and P. carnosa were predominantly associated with Cladocopium C1 and C1c, whereas M. peltiformis was mainly associated with two Cladocopium C21 types and C1. For each species, the predominant endosymbionts exhibited high fidelity, and the relatively low abundance ITS2-types showed minor changes between the bleached and recovered corals. Our study provided the first details of coral-algal association in Hong Kong waters, suggesting the selection of certain genotypes as a potential adaptive mechanism to the marginal environmental conditions.

Comparative transcriptomics of two coral holobionts collected during the 2017 El Niño heat wave reveal differential stress response mechanisms.

Although coral species exhibit differential susceptibility to stressors, little is known about the underlying molecular mechanisms. Here we compared scleractinian corals Montipora peltiformis and Platygyra carnosa collected during the 2017 El Niño heat wave. Zooxanthellae density and chlorophyll a content declined and increased substantially during and after heat stress event, respective. However, the magnitude of change was larger in M. peltiformis. Transcriptome analysis showed that heat-stressed corals corresponded to metabolic depression and catabolism of amino acids in both hosts which might promote their survival. However, only M. peltiformis has developed the bleached coral phenotype with corresponding strong stress- and immune-related responses in the host and symbiont, and strong suppression of photosynthesis-related genes in the symbiont. Overall, our study reveals differences among species in the homeostatic capacity to prevent the development of the bleached phenotype under environmental stressors, eventually determining their likelihood of survival in the warming ocean.

Host-symbiont transcriptomic changes during natural bleaching and recovery in the leaf coral Pavona decussata.

Coral bleaching has become a major threat to coral reefs worldwide, but for most coral species little is known about their resilience to environmental changes. We aimed to understand the gene expressional regulation underlying natural bleaching and recovery in Pavona decussata, a dominant species of scleractinian coral in the northern South China Sea. Analyzing samples collected in 2017 from the field revealed distinct zooxanthellae density, chlorophyll a concentration and transcriptomic signatures corresponding to changes in health conditions of the coral holobiont. In the host, normal-looking tissues of partially bleached colonies were frontloaded with stress responsive genes, as indicated by upregulation of immune defense, response to endoplasmic reticulum, and oxidative stress genes. Bleaching was characterized by upregulation of apoptosis-related genes which could cause a reduction in algal symbionts, and downregulation of genes involved in stress responses and metabolic processes. The transcription factors stat5b and irf1 played key roles in bleaching by regulating immune and apoptosis pathways. Recovery from bleaching was characterized by enrichment of pathways involved in mitosis, DNA replication, and recombination for tissue repairing, as well as restoration of energy and metabolism. In the symbionts, bleaching corresponded to imbalance in photosystems I and II activities which enhanced oxidative stress and limited energy production and nutrient assimilation. Overall, our study revealed distinct gene expressional profiles and regulation in the different phases of the bleaching and recovery process, and provided new insight into the molecular mechanisms underlying the holobiont's resilience that may determine the species' fate in response to global and regional environmental changes.

Genomic insights into the sessile life and biofouling of barnacles (Crustacea: Cirripedia).

Members of the infraclass Cirripedia, commonly called barnacles, are unique among the subphylum Crustacea in that they exhibit a biphasic life cycle with a planktonic larval stage and a sessile adult stage. Understanding their unique sessile life and mechanisms of attachment are hampered by the lack of genomic resources. Here, we present a 746 Mb genome assembly of Lepas anserifera - the first sequenced stalked barnacle genome. We estimate that Cirripedia first arose ~495 million years ago (MYA) and further diversified since Mesozoic. A demographic analysis revealed remarkable population changes of the barnacle in relation to sea-level fluctuations in the last 2 MYA. Comparative genomic analyses revealed the expansion of a number of developmental related genes families in barnacle genomes, such as Br-C, PCP20 and Lola, which are potentially important for the evolution of metamorphosis, cuticle development and central nervous system. Phylogenetic analysis and tissue expression profiling showed the possible roles of gene duplication, functional diversification and co-option in shaping the genomic evolution of barnacles. Overall, our study provides not only a valuable draft genome for comparative genomic analysis of crustacean evolution, but also facilitates studies of biofouling control.

Transcriptomics reveal triphenyltin-induced molecular toxicity in the marine mussel Perna viridis.

Triphenyltin (TPT) is widely used as an active ingredient in antifouling paints and fungicides, and continuous release of this highly toxic endocrine disruptor has caused serious pollution to coastal marine ecosystems and organisms worldwide. Using bioassays and transcriptome sequencing, this study comprehensively investigated the molecular toxicity of TPT chloride (TPTCl) to the marine mussel Perna viridis which is a commercially important species and a common biomonitor for marine pollution in Southeast Asia. Our results indicated that TPTCl was highly toxic to adult P. viridis, with a 96-h LC10 and a 96-h EC10 at 18.7 µg/L and 2.7 µg/L, respectively. A 21-day chronic exposure to 2.7 µg/L TPTCl revealed a strong bioaccumulation of TPT in gills (up to 36.48 µg/g dry weight) and hepatopancreas (71.19 µg/g dry weight) of P. viridis. Transcriptome analysis indicated a time course dependent gene expression pattern in both gills and hepatopancreas. Higher numbers of differentially expressed genes were detected at Day 21 (gills: 1686 genes; hepatopancreas: 1450 genes) and at Day 28 (gills: 628 genes; hepatopancreas: 238 genes) when compared with that at Day 7 (gills: 104 genes, hepatopancreas: 112 genes). Exposure to TPT strongly impaired the endocrine system through targeting on nuclear receptors and putative steroid metabolic genes. Moreover, TPT widely disrupted cellular functions, including lipid metabolism, xenobiotic detoxification, immune response and endoplasmic-reticulum-associated degradation expression, which might have caused the bioaccumulation of TPT in the tissues and aggregation of peptides and proteins in cells that further activated the apoptosis process in P. viridis. Overall, this study has advanced our understanding on both ecotoxicity and molecular toxic mechanisms of TPT to marine mussels, and contributed empirical toxicity data for risk assessment and management of TPT contamination.

The Risk of QTc Prolongation in Non-Diabetic and Diabetic Patients Taking Tyrosine Kinase Inhibitors (TKIs)- A Patient Safety Project at a Private Oncology Practice.

Objective: To assess the prevalence of QTc prolongation in both non-diabetic and diabetic patients on TKIs. Some TKIs have been reported to cause QTc prolongation, which is prevalent in diabetes. However, there is no Risk Evaluation and Mitigation Strategy using series ECG to monitor those patients. Methods: Patients taking TKIs, with two ECGs recorded between 1 January 2010 and 31 December 2017 were selected from the electronic database. The QTc duration >450 ms was determined as prolonged. Percentage of QTc prolongation on participants were compared using Chi-Square test. Results: This study included 313 patients (age 66.1 ± 0.8 years and 57.5% are female) taking TKIs. In non-Diabetic patients, the prevalence of QTc prolongation is 19.1% (n = 253) before and 34.8% (n = 253) after treatment with TKIs (p < 0.001), respectively. In diabetic patients, the prevalence of QTc prolongation is 21.7% (n = 60) before and 40% (n = 60) after treatment with TKIs (p = 0.03), respectively. In addition, we examined the effect of modifying risk factors for cardiovascular disease (CVD) on the prevalence of QTc prolongation caused by TKIs. In non-diabetic patients, the prevalence of QTc prolongation is 33.3% (n = 57) before and 34.2% (n = 196) after risk factors modification (p = 0.91), respectively. In diabetic patients, the prevalence of QTc prolongation is 50% (n = 24) before and 33.3% (n = 36) after risk factors modification (p = 0.20), respectively. Conclusion: Use of TKIs is associated with a significantly increased risk of QTc prolongation for patients, particularly when patients are diabetic. Modification of risk factors for CVD does not significantly affect the prevalence of QTc prolongation caused by TKIs.

Multi-omic approach provides insights into osmoregulation and osmoconformation of the crab Scylla paramamosain.

Osmoregulation and osmoconformation are two mechanisms through which aquatic animals adapt to salinity fluctuations. The euryhaline crab Scylla paramamosain, being both an osmoconformer and osmoregulator, is an excellent model organism to investigate salinity adaptation mechanisms in brachyurans. In the present study, we used transcriptomic and proteomic approaches to investigate the response of S. paramamosain to salinity stress. Crabs were transferred from a salinity of 25 ppt to salinities of 5 ppt or 33 ppt for 6 h and 10 days. Data from both approaches revealed that exposure to 5 ppt resulted in upregulation of ion transport and energy metabolism associated genes. Notably, acclimation to low salinity was associated with early changes in gene expression for signal transduction and stress response. In contrast, exposure to 33 ppt resulted in upregulation of genes related to amino acid metabolism, and amino acid transport genes were upregulated only at the early stage of acclimation to this salinity. Our study reveals contrasting mechanisms underlying osmoregulation and osmoconformation within the salinity range of 5-33 ppt in the mud crab, and provides novel candidate genes for osmotic signal transduction, thereby providing insights on understanding the salinity adaptation mechanisms of brachyuran crabs.

The Scaly-foot Snail genome and implications for the origins of biomineralised armour.

The Scaly-foot Snail, Chrysomallon squamiferum, presents a combination of biomineralised features, reminiscent of enigmatic early fossil taxa with complex shells and sclerites such as sachtids, but in a recently-diverged living species which even has iron-infused hard parts. Thus the Scaly-foot Snail is an ideal model to study the genomic mechanisms underlying the evolutionary diversification of biomineralised armour. Here, we present a high-quality whole-genome assembly and tissue-specific transcriptomic data, and show that scale and shell formation in the Scaly-foot Snail employ independent subsets of 25 highly-expressed transcription factors. Comparisons with other lophotrochozoan genomes imply that this biomineralisation toolkit is ancient, though expression patterns differ across major lineages. We suggest that the ability of lophotrochozoan lineages to generate a wide range of hard parts, exemplified by the remarkable morphological disparity in Mollusca, draws on a capacity for dynamic modification of the expression and positioning of toolkit elements across the genome.