The new COST Action European Venom Network (EUVEN)—synergy and future perspectives of modern venomics

Venom research is a highly multidisciplinary field that involves multiple subfields of biology, informatics, pharmacology, medicine, and other areas. These different research facets are often technologically challenging and pursued by different teams lacking connection with each other. This lack of coordination hampers the full development of venom investigation and applications. The COST Action CA19144–European Venom Network was recently launched to promote synergistic interactions among different stakeholders and foster venom research at the European level

Modern venomics – Current insights, novel methods and future perspectives in biological and applied animal venom research

Venoms have evolved >100 times in all major animal groups, and their components, known as toxins, have been fine-tuned over millions of years into highly effective biochemical weapons. There are many outstanding questions on the evolution of toxin arsenals, such as how venom genes originate, how venom contributes to the fitness of venomous species, and which modifications at the genomic, transcriptomic, and protein level drive their evolution. These questions have received particularly little attention outside of snakes, cone snails, spiders, and scorpions. Venom compounds have further become a source of inspiration for translational research using their diverse bioactivities for various applications. We highlight here recent advances and new strategies in modern venomics and discuss how recent technological innovations and multi-omic methods dramatically improve research on venomous animals. The study of genomes and their modifications through CRISPR and knockdown technologies will increase our understanding of how toxins evolve and which functions they have in the different ontogenetic stages during the development of venomous animals. Mass spectrometry imaging combined with spatial transcriptomics, in situ hybridization techniques, and modern computer tomography gives us further insights into the spatial distribution of toxins in the venom system and the function of the venom apparatus. All these evolutionary and biological insights contribute to more efficiently identify venom compounds, which can then be synthesized or produced in adapted expression systems to test their bioactivity. Finally, we critically discuss recent agrochemical, pharmaceutical, therapeutic, and diagnostic (so-called translational) aspects of venoms from which humans benefit

Solenodon genome reveals convergent evolution of venom in eulipotyphlan mammals

Venom systems are key adaptations that have evolved throughout the tree of life and typically facilitate predation or defense. Despite venoms being model systems for studying a variety of evolutionary and physiological processes, many taxonomic groups remain understudied, including venomous mammals. Within the order Eulipotyphla, multiple shrew species and solenodons have oral venom systems. Despite morphological variation of their delivery systems, it remains unclear whether venom represents the ancestral state in this group or is the result of multiple independent origins. We investigated the origin and evolution of venom in eulipotyphlans by characterizing the venom system of the endangered Hispaniolan solenodon (Solenodon paradoxus). We constructed a genome to underpin proteomic identifications of solenodon venom toxins, before undertaking evolutionary analyses of those constituents, and functional assessments of the secreted venom. Our findings show that solenodon venom consists of multiple paralogous kallikrein 1 (KLK1) serine proteases, which cause hypotensive effects in vivo, and seem likely to have evolved to facilitate vertebrate prey capture. Comparative analyses provide convincing evidence that the oral venom systems of solenodons and shrews have evolved convergently, with the 4 independent origins of venom in eulipotyphlans outnumbering all other venom origins in mammals. We find that KLK1s have been independently coopted into the venom of shrews and solenodons following their divergence during the late Cretaceous, suggesting that evolutionary constraints may be acting on these genes. Consequently, our findings represent a striking example of convergent molecular evolution and demonstrate that distinct structural backgrounds can yield equivalent functions

Do schools differ in suicide risk? the influence of school and neighbourhood on attempted suicide, suicidal ideation and self-harm among secondary school pupils

<br>Background: Rates of suicide and poor mental health are high in environments (neighbourhoods and institutions) where individuals have only weak social ties, feel socially disconnected and experience anomie - a mismatch between individual and community norms and values. Young people spend much of their time within the school environment, but the influence of school context (school connectedness, ethos and contextual factors such as school size or denomination) on suicide-risk is understudied. Our aim is to explore if school context is associated with rates of attempted suicide and suicide-risk at age 15 and self-harm at age 19, adjusting for confounders.</br> <br>Methods: A longitudinal school-based survey of 1698 young people surveyed when aged 11, (primary school), 15 (secondary school) and in early adulthood (age 19). Participants provided data about attempted suicide and suicide-risk at age 15 and deliberate self-harm at 19. In addition, data were collected about mental health at age 11, social background (gender, religion, etc.), and at age 15, perception of local area (e.g. neighbourhood cohesion, safety/civility and facilities), school connectedness (school engagement, involvement, etc.) and school context (size, denomination, etc.). A dummy variable was created indicating a religious 'mismatch', where pupils held a different faith from their school denomination. Data were analysed using multilevel logistic regression.</br> <br>Results: After adjustment for confounders, pupils attempted suicide, suicide-risk and self-harm were all more likely among pupils with low school engagement (15-18% increase in odds for each SD change in engagement). While holding Catholic religious beliefs was protective, attending a Catholic school was a risk factor for suicidal behaviours. This pattern was explained by religious 'mismatch': pupils of a different religion from their school were approximately 2-4 times more likely to attempt suicide, be a suicide-risk or self-harm.</br> <br>Conclusions: With several caveats, we found support for the importance of school context for suicidality and self-harm. School policies promoting school connectedness are uncontroversial. Devising a policy to reduce risks to pupils holding a different faith from that of their school may be more problematic.</br&gt

Show your beaks and we tell you what you eat: Different ecology in sympatric Antarctic benthic octopods under a climate change context

Sympatry can lead to higher competition under climate change and other environmental pressures, including in South Georgia, Antarctica, where the two most common octopod species, Adelieledone polymorpha and Pareledone turqueti, occur side by side. Since cephalopods are typically elusive animals, the ecology of both species is poorly known. As beaks of cephalopods are recurrently found in top predator's stomachs, we studied the feeding ecology of both octopods through the evaluation of niche overlapping and specific beak adaptations that both species present. A multidisciplinary approach combining carbon (δ13C) and nitrogen (δ15N) stable isotope signatures, mercury (Hg) analysis and biomaterials' engineering techniques was applied to investigate the beaks. An isotopic niche overlap of 95.6% was recorded for the juvenile stages of both octopod species, dropping to 19.2% for the adult stages. Both A. polymorpha and P. turqueti inhabit benthic ecosystems around South Georgia throughout their lifecycles (δ13C: −19.21 ± 1.87‰, mean ± SD for both species) but explore trophic niches partially different during adult life stages (δ15N: 7.01 ± 0.40‰, in A. polymorpha, and 7.84 ± 0.65‰, in P. turqueti). The beaks of A. polymorpha are less dense and significantly less stiff than in P. turqueti. Beaks showed lower mercury concentration relative to muscle (A. polymorpha - beaks: 0.052 ± 0.009  μg g−1, muscle: 0.322 ± 0.088  μg g−1; P. turqueti - beaks: 0.038 ± 0.009  μg g−1; muscle: 0.434 ± 0.128  μg g−1). Overall, both octopods exhibit similar habitats but different trophic niches, related to morphology/function of beaks. The high Hg concentrations in both octopods can have negative consequences on their top predators and may increase under the present climate change context.British Antarctic Survey for assisting in the collection of the specimens for this work. Many thanks to 3B's Research Group (University of Minho) and MAREFOZ who were responsible for analysing the physical properties of beaks and stable isotope signatures. A special thank you to our colleague José Queirós from MARE-UC (Coimbra, Portugal) for his suggestions and guidance. A debt of gratitude is also owed to Dr. A. Louise Allcock (NUI Galway) for her useful guidelines. This work is an international effort under the Scientific Committee on Antarctic Research (SCAR) associated programs, expert and action groups, namely SCAR AnT-ERA, SCAR EGBAMM and ICED. J.C. Xavier was supported by the Investigator Programme (IF/00616/2013) of the Foundation for Science and Technology (FCT-Portugal) and PROPOLAR, and F.R. Ceia was supported by a postdoctoral fellowship (SFRH/BPD/95372/2013) attributed by FCT-Portugal and the European Social Fund (POPH, EU). This study benefited from the strategic program of MARE, financed by FCT-Portugal (MARE- UID/MAR/04292/2019). We also acknowledge FCT-Portugal through a PhD grant to J. Seco (SRFH/PD/BD/113487

Convergent Evolution of Pain-Inducing Defensive Venom Components in Spitting Cobras

Preprint 20 páginas. The molecular data associated with species tree generation have been deposited to the nucleotide database of NCBI and the accession numbers are displayed in Table S7. The transcriptome data have been deposited in the SRA and TSA databases of NCBI and are associated with the BioProject accession number PRJA506018. Mass spectrometry data and database search results for top-down and bottom-up proteomic experiments are publicly available in the MassIVE repository under accession number MSV000081885 and in proteomXchange with accession number PXD008597.Convergent evolution provides unparalleled insights into the selective drivers underlying evolutionary change. While snakes use venom primarily for predation, and venom composition often reflects diet specificity, three lineages of spitting cobras have independently evolved the ability to use venom as a defensive projectile. Using gene, protein and functional analyses, we show that the three spitting lineages possess venom characterized by an upregulation of PLA2 toxins, which potentiate the action of venom cytotoxins to activate mammalian sensory neurons and cause enhanced pain. These repeated independent changes provide a fascinating example of convergent evolution across multiple phenotypic levels driven by exaptations. Notably, the timing of their origins suggests that defensive venom spitting may have evolved in response to the emergence of bipedal hominids in Africa and Asia.This work was funded from a studentship supported by Elizabeth Artin Kazandjian to T.D.K., grant PE 2600/1 from the German Research Foundation (DFG) to D.P., grant OPUS 1354156 from the US National Science Foundation to H.W.G., grants FAPESP 2017/18922-2 and 2019/05026-4 from the São Paulo Research Foundation to R.R.d.S, grants RPG-2012-627 and RFG-10193 from the Leverhulme Trust to R.A.H. and W.W., grant MR/L01839X/1 from the UK Medical Research Council to J.M.G., R.A.H., J.J.C. and N.R.C., fellowship DE160101142 from the Australian Research Council, and fellowship FRIPRO-YRT #287462 and grant DP160104025 from the Research Council of Norway to E.A.B.U., and a Sir Henry Dale Fellowship (200517/Z/16/Z) jointly funded by the Wellcome Trust and Royal Society to N.R.C.N