BackgroundThe venom of predatory marine cone snails mainly contains a diverse array of unique bioactive peptides commonly referred to as conopeptides or conotoxins. These peptides have proven to be valuable pharmacological probes and potential drugs because of their high specificity and affinity to important ion channels, receptors and transporters of the nervous system. Most previous studies have focused specifically on the conopeptides from piscivorous and molluscivorous cone snails, but little attention has been devoted to the dominant vermivorous species.ResultsThe vermivorous Chinese tubular cone snail, Conus betulinus, is the dominant Conus species inhabiting the South China Sea. The transcriptomes of venom ducts and venom bulbs from a variety of specimens of this species were sequenced using both next-generation sequencing and traditional Sanger sequencing technologies, resulting in the identification of a total of 215 distinct conopeptides. Among these, 183 were novel conopeptides, including nine new superfamilies. It appeared that most of the identified conopeptides were synthesized in the venom duct, while a handful of conopeptides were identified only in the venom bulb and at very low levels.ConclusionsWe identified 215 unique putative conopeptide transcripts from the combination of five transcriptomes and one EST sequencing dataset. Variation in conopeptides from different specimens of C. betulinus was observed, which suggested the presence of intraspecific variability in toxin production at the genetic level. These novel conopeptides provide a potentially fertile resource for the development of new pharmaceuticals, and a pathway for the discovery of new conotoxins.Electronic supplementary materialThe online version of this article (doi:10.1186/s13742-016-0122-9) contains supplementary material, which is available to authorized users.

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Recent studies reveal that organosulfates at the particle surface can be oxidized by gas-phase OH radicals with significant rates. Inorganic sulfur species, such as the bisulfate ion (HSO 4 − ) and sulfate ion (SO 4 2− ), can be formed upon these heterogeneous oxidation processes through the formation and subsequent reactions of sulfate radical anion (SO 4 •− ) in the particle phase. However, the amount of inorganic sulfur species produced in these heterogeneous oxidation reactions is not known. We investigate the heterogeneous OH oxidation of sodium methyl sulfate (CH 3 SO 4 Na), the smallest organosulfate detected in atmospheric particles, using an oxidation flow reactor at a relative humidity of 75 %. We quantify the kinetics by measuring the decay of CH 3 SO 4 Na and the amount of HSO 4 − and SO 4 2− formed upon oxidation using ion chromatography. Kinetic measurements determine the heterogeneous OH reaction rate to be (5.72 ± 0.14) × 10 −13 cm 3 molecule −1 s −1 , with an effective OH uptake coefficient, γ eff , of 0.31 ± 0.06. The molar yield of inorganic sulfur species, defined as the total number of moles of HSO 4 − and SO 4 2− formed per mole of CH 3 SO 4 Na consumed upon oxidation, is found to be significant and has an average value of 0.62 ± 0.18 upon oxidation. A kinetic model is developed to describe the kinetics and inorganic sulfur species formation upon oxidation. Model simulations suggest that CH 3 SO 4 Na tends to decompose rapidly into formaldehyde and SO 4•−, and the reaction of SO 4•− with CH 3 SO 4 Na plays a significant role in both governing the kinetics and the formation of inorganic sulfur species.

Abstract. Atmospheric pollution has many profound effects on human health, ecosystems, and the climate. Of concern are high concentrations and deposition of reactive nitrogen (Nr) species, especially of reduced N (gaseous NH3, particulate NH4+). Atmospheric chemistry and transport models (ACTMs) are crucial to understanding sources and impacts of Nr chemistry and its potential mitigation. Here we undertake the first evaluation of the global version of the EMEP MSC-W ACTM driven by WRF meteorology (1∘×1∘ resolution), with a focus on surface concentrations and wet deposition of N and S species relevant to investigation of atmospheric Nr and secondary inorganic aerosol (SIA). The model–measurement comparison is conducted both spatially and temporally, covering 10 monitoring networks worldwide. Model simulations for 2010 compared use of both HTAP and ECLIPSEE (ECLIPSE annual total with EDGAR monthly profile) emissions inventories; those for 2015 used ECLIPSEE only. Simulations of primary pollutants are somewhat sensitive to the choice of inventory in places where regional differences in primary emissions between the two inventories are apparent (e.g. China) but are much less sensitive for secondary components. For example, the difference in modelled global annual mean surface NH3 concentration using the two 2010 inventories is 18 % (HTAP: 0.26 µg m−3; ECLIPSEE: 0.31 µg m−3) but is only 3.5 % for NH4+ (HTAP: 0.316 µg m−3; ECLIPSEE: 0.305 µg m−3). Comparisons of 2010 and 2015 surface concentrations between the model and measurements demonstrate that the model captures the overall spatial and seasonal variations well for the major inorganic pollutants NH3, NO2, SO2, HNO3, NH4+, NO3-, and SO42- and their wet deposition in East Asia, Southeast Asia, Europe, and North America. The model shows better correlations with annual average measurements for networks in Southeast Asia (mean R for seven species: R7‾=0.73), Europe (R7‾=0.67), and North America (R7‾=0.63) than in East Asia (R5‾=0.35) (data for 2015), which suggests potential issues with the measurements in the latter network. Temporally, both model and measurements agree on higher NH3 concentrations in spring and summer and lower concentrations in winter. The model slightly underestimates annual total precipitation measurements (by 13 %–45 %) but agrees well with the spatial variations in precipitation in all four world regions (0.65–0.94 R range). High correlations between measured and modelled NH4+ precipitation concentrations are also observed in all regions except East Asia. For annual total wet deposition of reduced N, the greatest consistency is in North America (0.75–0.82 R range), followed by Southeast Asia (R=0.68) and Europe (R=0.61). Model–measurement bias varies between species in different networks; for example, bias for NH4+ and NO3- is largest in Europe and North America and smallest in East Asia and Southeast Asia. The greater uniformity in spatial correlations than in biases suggests that the major driver of model–measurement discrepancies (aside from differing spatial representativeness and uncertainties and biases in measurements) are shortcomings in absolute emissions rather than in modelling the atmospheric processes. The comprehensive evaluations presented in this study support the application of this model framework for global analysis of current and potential future budgets and deposition of Nr and SIA.

Although there are various Conus species with publicly available transcriptome and proteome data, no genome assembly has been reported yet. Here, using Chinese tubular cone snail (C. betulinus) as a representative, we sequenced and assembled the first Conus genome with original identification of 133 genome-widely distributed conopeptide genes. After integration of our genomics, transcriptomics, and peptidomics data in the same species, we established a primary genetic central dogma of diverse conopeptides, assuming a rough number ratio of ~1:1:1:10s for the total genes: transcripts: proteins: post-translationally modified peptides. This ratio may be special for this worm-hunting Conus species, due to the high diversity of various Conus genomes and the big number ranges of conopeptide genes, transcripts, and peptides in previous reports of diverse Conus species. Only a fraction (45.9%) of the identified conotopeptide genes from our achieved genome assembly are transcribed with transcriptomic evidence, and few genes individually correspond to multiple transcripts possibly due to intraspecies or mutation-based variances. Variable peptide processing at the proteomic level, generating a big diversity of venom conopeptides with alternative cleavage sites, post-translational modifications, and N-/C-terminal truncations, may explain how the 133 genes and ~123 transcripts can generate thousands of conopeptides in the venom of individual C. betulinus. We also predicted many conopeptides with high stereostructural similarities to the putative analgesic ω-MVIIA, addiction therapy AuIB and insecticide ImI, suggesting that our current genome assembly for C. betulinus is a valuable genetic resource for high-throughput prediction and development of potential pharmaceuticals.

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Background: For high morbidity rate but lack of early accurate screening, hepatocellular cancer (HCC) manifests as the fourth leading cause of cancer related death worldwide. Accumulating evidence demonstrated that a series of long noncoding RNA (lncRNA) have strong association with pathogenesis and clinical evaluation of HCC. LINC01554, one kind of lncRNA, has been found specifically enriched in liver tissue. However, the relationship between LINC01554 expression and HCC tumorigenesis remains unclear. Methods: The relative LINC01554 expression was measured in HCC tissues of 138 patients and several HCC cell lines using quantitative real-time PCR. Patients were grouped according to individual LINC01554 expression. Then, the potential association between LINC01554 expression in HCC tissues and clinical characteristics as well as prognostic information of patients was evaluated. Results: Compared to correspongding adjacent liver tissues, the LINC01554 expression in HCC was significantly down-regulated (P=0.001). And its expression levels in HCC cell lines were also remarkably lower than that in normal human hepatocyte cell line (P<0.001). Besides, the expression level of LINC01554 was significantly related to tumor size, multiple lesions, TNM stages, tumor recurrence rate as well as long-term survival in HCC patients (P<0.05). Conclusion: The research revealed that LINC01554 was down-regulated in HCC and it could be used for the accurate diagnosis and prognostic prediction of HCC patients.

The venom of each Conus species consists of a diverse array of neurophysiologically active peptides, which are mostly unique to the examined species. In this study, we performed high-throughput transcriptome sequencing to extract and analyze putative conotoxin transcripts from the venom ducts of 3 vermivorous cone snails (C. caracteristicus, C. generalis, and C. quercinus), which are resident in offshore waters of the South China Sea. In total, 118, 61, and 48 putative conotoxins (across 22 superfamilies) were identified from the 3 Conus species, respectively; most of them are novel, and some possess new cysteine patterns. Interestingly, a series of 45 unassigned conotoxins presented with a new framework of C-C-C-C-C-C, and their mature regions were sufficiently distinct from any other known conotoxins, most likely representing a new superfamily. O- and M-superfamily conotoxins were the most abundant in transcript number and transcription level, suggesting their critical roles in the venom functions of these vermivorous cone snails. In addition, we identified numerous functional proteins with potential involvement in the biosynthesis, modification, and delivery process of conotoxins, which may shed light on the fundamental mechanisms for the generation of these important conotoxins within the venom duct of cone snails.