Toxins from scratch? Diverse, multimodal gene origins in the predatory robber fly Dasypogon diadema indicate a dynamic venom evolution in dipteran insects

Venoms and the toxins they contain represent molecular adaptations that have evolved on numerous occasions throughout the animal kingdom. However, the processes that shape venom protein evolution are poorly understood because of the scarcity of whole-genome data available for comparative analyses of venomous species.We performed a broad comparative toxicogenomic analysis to gain insight into the genomic mechanisms of venom evolution in robber flies (Asilidae). We first sequenced a high-quality draft genome of the hymenopteran hunting robber fly Dasypogon diadema, analysed its venom by a combined proteotranscriptomic approach, and compared our results with recently described robber fly venoms to assess the general composition and major components of asilid venom. We then applied a comparative genomics approach, based on 1 additional asilid genome, 10 high-quality dipteran genomes, and 2 lepidopteran outgroup genomes, to reveal the evolutionary mechanisms and origins of identified venom proteins in robber flies.While homologues were identified for 15 of 30 predominant venom protein in the non-asilid genomes, the remaining 15 highly expressed venom proteins appear to be unique to robber flies. Our results reveal that the venom of D. diadema likely evolves in a multimodal fashion comprising (i) neofunctionalization after gene duplication, (ii) expression-dependent co-option of proteins, and (iii) asilid lineage-specific orphan genes with enigmatic origin. The role of such orphan genes is currently being disputed in evolutionary genomics but has not been discussed in the context of toxin evolution. Our results display an unexpected dynamic venom evolution in asilid insects, which contrasts the findings of the only other insect toxicogenomic evolutionary analysis, in parasitoid wasps (Hymenoptera), where toxin evolution is dominated by single gene co-option. These findings underpin the significance of further genomic studies to cover more neglected lineages of venomous taxa and to understand the importance of orphan genes as possible drivers for venom evolution

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

Prevalence of bullying and aggressive behavior and their relationship to mental health problems among 12- to 15-year-old Norwegian adolescents

The aim of this study was to examine the relationships between being bullied and aggressive behavior and self-reported mental health problems among young adolescents. A representative population sample of 2,464 young Norwegian adolescents (50.8% girls) aged 12–15 years was assessed. Being bullied was measured using three items concerning teasing, exclusion, and physical assault. Self-esteem was assessed by Harter’s self-perception profile for adolescents. Emotional and behavioral problems were measured by the Moods and Feelings Questionnaire (MFQ) and the youth self-report (YSR). Aggressive behavior was measured by four items from the YSR. One-tenth of the adolescents reported being bullied, and 5% reported having been aggressive toward others during the past 6 months. More of the students being bullied and students being aggressive toward others reported parental divorce, and they showed higher scores on all YSR subscales and on the MFQ questions, and lower scores on the global self-worth subscale (Harter) than students not being bullied or aggressive. A few differences emerged between the two groups being bullied or being aggressive toward others: those who were aggressive showed higher total YSR scores, higher aggression and delinquency scores, and lower social problems scores, and reported higher scores on the social acceptance subscale (Harter) than bullied students. However, because social problems were demonstrated in both the involved groups, interventions designed to improve social competence and interaction skills should be integrated in antibullying programs

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

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

Observation of gravitational waves from the coalescence of a 2.5–4.5 M ⊙ compact object and a neutron star

We report the observation of a coalescing compact binary with component masses 2.5–4.5 M ⊙ and 1.2–2.0 M ⊙ (all measurements quoted at the 90% credible level). The gravitational-wave signal GW230529_181500 was observed during the fourth observing run of the LIGO–Virgo–KAGRA detector network on 2023 May 29 by the LIGO Livingston observatory. The primary component of the source has a mass less than 5 M ⊙ at 99% credibility. We cannot definitively determine from gravitational-wave data alone whether either component of the source is a neutron star or a black hole. However, given existing estimates of the maximum neutron star mass, we find the most probable interpretation of the source to be the coalescence of a neutron star with a black hole that has a mass between the most massive neutron stars and the least massive black holes observed in the Galaxy. We provisionally estimate a merger rate density of 55−47+127Gpc−3yr−1 for compact binary coalescences with properties similar to the source of GW230529_181500; assuming that the source is a neutron star–black hole merger, GW230529_181500-like sources may make up the majority of neutron star–black hole coalescences. The discovery of this system implies an increase in the expected rate of neutron star–black hole mergers with electromagnetic counterparts and provides further evidence for compact objects existing within the purported lower mass gap