scholarly journals Transcriptomic-Proteomic Correlation in the Predation-Evoked Venom of the Cone Snail, Conus imperialis

Marine Drugs ◽  
2019 ◽  
Vol 17 (3) ◽  
pp. 177 ◽  
Author(s):  
Ai-Hua Jin ◽  
Sébastien Dutertre ◽  
Mriga Dutt ◽  
Vincent Lavergne ◽  
Alun Jones ◽  
...  
Keyword(s):  
Geographical Location ◽  
Venom Gland ◽  
Feeding Habit ◽  
Poor Correlation ◽  
Stabilizing Selection ◽  
Cone Snail ◽  
Venom Composition ◽  
Cone Snails ◽  
And Gender ◽  
Labelling Method

Individual variation in animal venom has been linked to geographical location, feeding habit, season, size, and gender. Uniquely, cone snails possess the remarkable ability to change venom composition in response to predatory or defensive stimuli. To date, correlations between the venom gland transcriptome and proteome within and between individual cone snails have not been reported. In this study, we use 454 pyrosequencing and mass spectrometry to decipher the transcriptomes and proteomes of the venom gland and corresponding predation-evoked venom of two specimens of Conus imperialis. Transcriptomic analyses revealed 17 conotoxin gene superfamilies common to both animals, including 5 novel superfamilies and two novel cysteine frameworks. While highly expressed transcripts were common to both specimens, variation of moderately and weakly expressed precursor sequences was surprisingly diverse, with one specimen expressing two unique gene superfamilies and consistently producing more paralogs within each conotoxin gene superfamily. Using a quantitative labelling method, conotoxin variability was compared quantitatively, with highly expressed peptides showing a strong correlation between transcription and translation, whereas peptides expressed at lower levels showed a poor correlation. These results suggest that major transcripts are subject to stabilizing selection, while minor transcripts are subject to diversifying selection.

scholarly journals Ero1-Mediated Reoxidation of Protein Disulfide Isomerase Accelerates the Folding of Cone Snail Toxins

2018 ◽  
Vol 19 (11) ◽  
pp. 3418 ◽  
Author(s):  
Henrik O’Brien ◽  
Shingo Kanemura ◽  
Masaki Okumura ◽  
Robert Baskin ◽  
Pradip Bandyopadhyay ◽  
...  
Keyword(s):  
Protein Disulfide Isomerase ◽  
Venom Gland ◽  
Cone Snail ◽  
Disulfide Isomerase ◽  
Folding Rates ◽  
Cone Snails ◽  
And Function ◽  
Protein Disulfide ◽  
Insight Into

Disulfide-rich peptides are highly abundant in nature and their study has provided fascinating insight into protein folding, structure and function. Venomous cone snails belong to a group of organisms that express one of the largest sets of disulfide-rich peptides (conotoxins) found in nature. The diversity of structural scaffolds found for conotoxins suggests that specialized molecular adaptations have evolved to ensure their efficient folding and secretion. We recently showed that canonical protein disulfide isomerase (PDI) and a conotoxin-specific PDI (csPDI) are ubiquitously expressed in the venom gland of cone snails and play a major role in conotoxin folding. Here, we identify cone snail endoplasmic reticulum oxidoreductin-1 (Conus Ero1) and investigate its role in the oxidative folding of conotoxins through reoxidation of cone snail PDI and csPDI. We show that Conus Ero1 preferentially reoxidizes PDI over csPDI, suggesting that the reoxidation of csPDI may rely on an Ero1-independent molecular pathway. Despite the preferential reoxidation of PDI over csPDI, the combinatorial effect of Ero1 and csPDI provides higher folding yields than Ero1 and PDI. We further demonstrate that the highest in vitro folding rates of two model conotoxins are achieved when all three enzymes are present, indicating that these enzymes may act synergistically. Our findings provide new insight into the generation of one of the most diverse classes of disulfide-rich peptides and may improve current in vitro approaches for the production of venom peptides for pharmacological studies.

scholarly journals δ-Conotoxin SuVIA suggests an evolutionary link between ancestral predator defence and the origin of fish-hunting behaviour in carnivorous cone snails

2015 ◽  
Vol 282 (1811) ◽  
pp. 20150817 ◽  
Author(s):  
Ai-Hua Jin ◽  
Mathilde R. Israel ◽  
Marco C. Inserra ◽  
Jennifer J. Smith ◽  
Richard J. Lewis ◽  
...  
Keyword(s):  
Voltage Dependence ◽  
Venom Gland ◽  
Underlying Mechanism ◽  
Cone Snail ◽  
Evolutionary Transition ◽  
Hunting Behaviour ◽  
Defensive Role ◽  
Cone Snails ◽  
Nanomolar Range ◽  
Predator Defence

Some venomous cone snails feed on small fishes using an immobilizing combination of synergistic venom peptides that target K v and Na v channels. As part of this envenomation strategy, δ-conotoxins are potent ichtyotoxins that enhance Na v channel function. δ-Conotoxins belong to an ancient and widely distributed gene superfamily, but any evolutionary link from ancestral worm-eating cone snails to modern piscivorous species has not been elucidated. Here, we report the discovery of SuVIA, a potent vertebrate-active δ-conotoxin characterized from a vermivorous cone snail ( Conus suturatus ). SuVIA is equipotent at hNa V 1.3, hNa V 1.4 and hNa V 1.6 with EC 50 s in the low nanomolar range. SuVIA also increased peak hNa V 1.7 current by approximately 75% and shifted the voltage-dependence of activation to more hyperpolarized potentials from –15 mV to –25 mV, with little effect on the voltage-dependence of inactivation. Interestingly, the proximal venom gland expression and pain-inducing effect of SuVIA in mammals suggest that δ-conotoxins in vermivorous cone snails play a defensive role against higher order vertebrates. We propose that δ-conotoxins originally evolved in ancestral vermivorous cones to defend against larger predators including fishes have been repurposed to facilitate a shift to piscivorous behaviour, suggesting an unexpected underlying mechanism for this remarkable evolutionary transition.

scholarly journals A phylogeny-aware approach reveals unexpected venom components in divergent lineages of cone snails

2021 ◽  
Vol 288 (1954) ◽  
pp. 20211017
Author(s):  
Alexander Fedosov ◽  
Paul Zaharias ◽  
Nicolas Puillandre
Keyword(s):  
Biomedical Applications ◽  
De Novo ◽  
Toxin Gene ◽  
Cone Snail ◽  
Marine Gastropods ◽  
Venom Composition ◽  
Signal Region ◽  
Rare Gene ◽  
Cone Snails ◽  
First Time

Marine gastropods of the genus Conus are renowned for their remarkable diversity and deadly venoms. While Conus venoms are increasingly well studied for their biomedical applications, we know surprisingly little about venom composition in other lineages of Conidae. We performed comprehensive venom transcriptomic profiling for Conasprella coriolisi and Pygmaeconus traillii , first time for both respective genera. We complemented reference-based transcriptome annotation by a de novo toxin prediction guided by phylogeny, which involved transcriptomic data on two additional ‘divergent’ cone snail lineages, Profundiconus , and Californiconus . We identified toxin clusters (SSCs) shared among all or some of the four analysed genera based on the identity of the signal region—a molecular tag present in toxins. In total, 116 and 98 putative toxins represent 29 and 28 toxin gene superfamilies in Conasprella and Pygmaeconus , respectively; about quarter of these only found by semi-manual annotation of the SSCs. Two rare gene superfamilies, originally identified from fish-hunting cone snails, were detected outside Conus rather unexpectedly, so we further investigated their distribution across Conidae radiation. We demonstrate that both these, in fact, are ubiquitous in Conidae, sometimes with extremely high expression. Our findings demonstrate how a phylogeny-aware approach circumvents methodological caveats of similarity-based transcriptome annotation.

scholarly journals Combined Proteotranscriptomic-Based Strategy to Discover Novel Antimicrobial Peptides from Cone Snails

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 344
Author(s):  
Anicet Ebou ◽  
Dominique Koua ◽  
Audrey Addablah ◽  
Solange Kakou-Ngazoa ◽  
Sébastien Dutertre
Keyword(s):  
Antimicrobial Peptides ◽  
Marine Invertebrates ◽  
Current Knowledge ◽  
Venom Gland ◽  
Biologically Active ◽  
Cone Snail ◽  
Active Peptides ◽  
Speed Up ◽  
Cone Snails ◽  
Conventional Antibiotics

Despite their impressive diversity and already broad therapeutic applications, cone snail venoms have received less attention as a natural source in the investigation of antimicrobial peptides than other venomous animals such as scorpions, spiders, or snakes. Cone snails are among the largest genera (Conus sp.) of marine invertebrates, with more than seven hundred species described to date. These predatory mollusks use their sophisticated venom apparatus to capture prey or defend themselves. In-depth studies of these venoms have unraveled many biologically active peptides with pharmacological properties of interest in the field of pain management, the treatment of epilepsy, neurodegenerative diseases, and cardiac ischemia. Considering sequencing efficiency and affordability, cone snail venom gland transcriptome analyses could allow the discovery of new, promising antimicrobial peptides. We first present here the need for novel compounds like antimicrobial peptides as a viable alternative to conventional antibiotics. Secondly, we review the current knowledge on cone snails as a source of antimicrobial peptides. Then, we present the current state of the art in analytical methods applied to crude or milked venom followed by how antibacterial activity assay can be implemented for fostering cone snail antimicrobial peptides studies. We also propose a new innovative profile Hidden Markov model-based approach to annotate full venom gland transcriptomes and speed up the discovery of potentially active peptides from cone snails.

scholarly journals Diet Diversity in Carnivorous Terebrid Snails Is Tied to the Presence and Absence of a Venom Gland

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 108
Author(s):  
Juliette Gorson ◽  
Giulia Fassio ◽  
Emily S. Lau ◽  
Mandë Holford
Keyword(s):  
Venom Gland ◽  
Molecular Study ◽  
Strongly Correlated ◽  
Animal Evolution ◽  
Diet Diversity ◽  
Dietary Breadth ◽  
Venom Composition ◽  
Marine Snails ◽  
Predatory Strategy ◽  
Definition Of

Predator-prey interactions are thought to play a driving role in animal evolution, especially for groups that have developed venom as their predatory strategy. However, how the diet of venomous animals influences the composition of venom arsenals remains uncertain. Two prevailing hypotheses to explain the relationship between diet and venom composition focus on prey preference and the types of compounds in venom, and a positive correlation between dietary breadth and the number of compounds in venom. Here, we examined venom complexity, phylogenetic relationship, collection depth, and biogeography of the Terebridae (auger snails) to determine if repeated innovations in terebrid foregut anatomy and venom composition correspond to diet variation. We performed the first molecular study of the diet of terebrid marine snails by metabarcoding the gut content of 71 terebrid specimens from 17 species. Our results suggest that the presence or absence of a venom gland is strongly correlated with dietary breadth. Specifically, terebrid species without a venom gland displayed greater diversity in their diet. Additionally, we propose a revision of the definition of venom complexity in conoidean snails to more accurately capture the breadth of ecological influences. These findings suggest that prey diet is an important factor in terebrid venom evolution and diversification and further investigations of other understudied organisms, like terebrids, are needed to develop robust hypotheses in this area.

scholarly journals Prevalence of ABO blood groups in patients with haematological malignancies: a retrospective study

2020 ◽  
Vol 8 (1) ◽  
pp. 13-17
Author(s):  
Ashwin Mathew ◽  
Kirana Pailoor, ◽  
Konchady Deepthi ◽  
Suresh Shenoy
Keyword(s):  
Sex Ratio ◽  
Blood Group ◽  
Haematological Malignancy ◽  
Geographical Location ◽  
Blood Groups ◽  
Blood Type ◽  
Haematological Malignancies ◽  
Abo Blood Groups ◽  
College Hospital ◽  
And Gender

Background: The pattern and distribution of Haematological malignancies vary depending on age, sex and geographical location. Studies on the association between Haematological cancers and ABO blood types have been largely conflicting. The objective of our study was to determine the distribution of ABO blood groups among patients with Haematological malignancies and to correlate with age and gender. Materials and Methods: This was a chart based observational descriptive study involving the review of records of 85 patients with various Haematological malignancies in Father Muller Medical College Hospital for a period of two years from July 2017- June 2019. Age, gender, malignant condition, ABO and Rh blood group were collected for each case. Data was analyzed statistically by frequency and percentage. Results: The peak age incidence for various Haematological malignancies was in the fifth and sixth decades of life with a mean age of 47.The male to female sex ratio was almost 1:1. Majority of the patients were of the O blood group and an association of O blood group with various hematological malignancies with male preponderance was noted. Altogether, Leukemias were the most common Haematological malignancy observed in this study. Conclusion: The distribution, age and sex ratio of Haematological malignancies in our study was comparable to those reported by other authors with Acute Myeloid Leukemia (AML) being the most common Haematological malignancy in our environment. There was no significant association between Haematological cancers and ABO blood type of the patients, but probably individuals with O Rh positive blood group are more prone to

An Empirical Note on Health Information Digital Divide

2017 ◽  
Vol 8 (2) ◽  
pp. 15-34 ◽  
Author(s):  
Ajeya Jha ◽  
Jaya Rani Pandey
Keyword(s):  
Discriminant Analysis ◽  
Digital Divide ◽  
Health Information ◽  
Information Search ◽  
Geographical Location ◽  
Family Type ◽  
Online Health Information ◽  
Chi Square ◽  
And Gender ◽  
E Mail

Availability of healthcare information on internet has made it possible for patients or their relatives to search for such information. This study was undertaken to find answers to such questions. In all 754 respondents participated in the survey. The variables selected from literature survey and exploratory study are Health Information Digital Divide, Income, Having E-mail id, access to internet, geographical location, Education, family-type, age and gender. As the data is categorical the significance of difference has been calculated using Chi-square test. Later discriminant analysis was conducted to predict patients who make online health information search and the ones who do not. The result show that Income, Having E-mail id, access to internet, geographical location, Education and gender are significant factors that determine the propensity of people for online healthcare search. Age and family-type, however, were found to have no impact on such a behavior. Using discriminant analysis 94.5 percent patients who make online health information search could be correctly predicted.

scholarly journals International Journal of Epidemiology peer reviewers: global and gender distribution

2020 ◽  
Author(s):  
Gwinyai Masukume ◽  
Julio Gonzalez-Alvarez ◽  
Victor Grech
Keyword(s):  
Peer Review ◽  
Gender Inequality ◽  
Geographical Location ◽  
Gender Inequalities ◽  
Biomedical Journal ◽  
Gender Distribution ◽  
Health Related ◽  
Peer Reviewers ◽  
And Gender ◽  
Epidemiology Studies

The science of epidemiology studies and analyses the patterns, distributions and determinants of health-related entities. Peer review is crucial to the biomedical journal ecosystem. Furthermore, gender inequality persists in science and improving gender representation is a key international goal. For these reasons, we evaluated the geographical location and gender distribution of the International Journal of Epidemiology peer reviewers for 2018. There were 695 peer reviewers hailing from 41 countries. 77% (533) of the reviewers were from 20% (8) of these countries, a classical 80:20 Pareto distrubution. 41% (282) of peer reviewers were female. Although in line with the general underrepresentation of females reported in the literature, this proportion was much closer to parity than in other fields. Our investigation of peer reviewer 'epidemiology' demonstrates geographical and gender inequalities that can be further improved since diversity promotes innovation and a greater possibility for solving complex problems.

scholarly journals Vexitoxins: a novel class of conotoxin-like venom peptides from predatory gastropods of the genus Vexillum

2022 ◽  
Author(s):  
Ksenia G Kuznetsova ◽  
Sofia S Zvonareva ◽  
Rustam Ziganshin ◽  
Elena S Mekhova ◽  
Polina Yu Dgebuadze ◽  
...  
Keyword(s):  
Sequence Similarity ◽  
Venom Gland ◽  
Data Sets ◽  
Rna Seq ◽  
Proteomic Profiling ◽  
Post Translational Modifications ◽  
Origin And Evolution ◽  
The Family ◽  
Venom Evolution ◽  
Cone Snails

Venoms of predatory marine cone snails (the family Conidae, order Neogastropoda) are intensely studied because of the broad range of biomedical applications of the neuropeptides that they contain, conotoxins. Meanwhile anatomy in some other neogastropod lineages strongly suggests that they have evolved similar venoms independently of cone snails, nevertheless their venom composition remains unstudied. Here we focus on the most diversified of these lineages, the genus Vexillum (the family Costellariidae). We have generated comprehensive multi-specimen, multi-tissue RNA-Seq data sets for three Vexillum species, and supported our findings in two species by proteomic profiling. We show that venoms of Vexillum are dominated by highly diversified short cysteine-rich peptides that in many aspects are very similar to conotoxins. Vexitoxins possess the same precursor organization, display overlapping cysteine frameworks and share several common post-translational modifications with conotoxins. Some vexitoxins show detectable sequence similarity to conotoxins, and are predicted to adopt similar domain conformations, including a pharmacologically relevant inhibitory cysteine-know motif (ICK). The tubular gL of Vexillum is a notably more recent evolutionary novelty than the conoidean venom gland. Thus, we hypothesize lower divergence between the toxin genes, and their somatic counterparts compared to that in conotoxins, and we find support for this hypothesis in the molecular evolution of the vexitoxin cluster V027. We use this example to discuss how future studies on vexitoxins can inform origin and evolution of conotoxins, and how they may help addressing standing questions in venom evolution.

scholarly journals Prevalence of Burnout in Medical and Surgical Residents: A Meta-Analysis

2019 ◽  
Vol 16 (9) ◽  
pp. 1479 ◽  
Author(s):  
Zhi Xuan Low ◽  
Keith A. Yeo ◽  
Vijay K. Sharma ◽  
Gilberto K. Leung ◽  
Roger S. McIntyre ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Meta Analysis ◽  
Geographical Location ◽  
Burnout Syndrome ◽  
Contributing Factors ◽  
Surgical Residents ◽  
High Prevalence ◽  
Meta Regression ◽  
And Gender ◽  
Q Statistic

The burnout syndrome is characterized by emotional exhaustion, depersonalization, and reduced personal achievement. Uncertainty exists about the prevalence of burnout among medical and surgical residents. Associations between burnout and gender, age, specialty, and geographical location of training are unclear. In this meta-analysis, we aimed to quantitatively summarize the global prevalence rates of burnout among residents, by specialty and its contributing factors. We searched PubMed, PsycINFO, Embase, and Web of Science to identify studies that examined the prevalence of burnout among residents from various specialties and countries. The primary outcome assessed was the aggregate prevalence of burnout among all residents. The random effects model was used to calculate the aggregate prevalence, and heterogeneity was assessed by I2 statistic and Cochran’s Q statistic. We also performed meta-regression and subgroup analysis. The aggregate prevalence of burnout was 51.0% (95% CI: 45.0–57.0%, I2 = 97%) in 22,778 residents. Meta-regression found that the mean age (β = 0.34, 95% CI: 0.28–0.40, p < 0.001) and the proportion of males (β = 0.4, 95% CI = 0.10–0.69, p = 0.009) were significant moderators. Subgroup analysis by specialty showed that radiology (77.16%, 95% CI: 5.99–99.45), neurology (71.93%, 95% CI: 65.78–77.39), and general surgery (58.39%, 95% CI: 45.72–70.04) were the top three specialties with the highest prevalence of burnout. In contrast, psychiatry (42.05%, 95% CI: 33.09–51.58), oncology (38.36%, 95% CI: 32.69–44.37), and family medicine (35.97%, 95% CI: 13.89–66.18) had the lowest prevalence of burnout. Subgroup analysis also found that the prevalence of burnout in several Asian countries was 57.18% (95% CI: 45.8–67.85); in several European countries it was 27.72% (95% CI: 17.4–41.11) and in North America it was 51.64% (46.96–56.28). Our findings suggest a high prevalence of burnout among medical and surgical residents. Older and male residents suffered more than their respective counterparts.

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