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Venom represents a key adaptation of many venomous predators, allowing them to immobilise prey quickly through chemical rather than physical warfare. Evolutionary arms races between prey and a predator are believed to be the main factor influencing the potency and composition of predatory venoms. Predators with narrowly restricted diets are expected to evolve specifically potent venom towards their focal prey, with lower efficacy on alternative prey. Here, we evaluate hypotheses on the evolution of prey‐specific venom, focusing on the effect of restricted diet, prey defences, and prey resistance. Prey specificity as a potential evolutionary dead end is also discussed. We then provide an overview of the current knowledge on venom prey specificity, with emphasis on snakes, cone snails, and spiders. As the current evidence for venom prey specificity is still quite limited, we also overview the best approaches and methods for its investigation and provide a brief summary of potential model groups. Finally, possible applications of prey‐specific toxins are discussed. [ABSTRACT FROM AUTHOR]

Gut content metabarcoding has provided important insights into the food web ecology of spiders, the most dominant terrestrial arthropod predators. In small invertebrates, like spiders, gut content analysis is often performed on whole body DNA extracts of individual predators, from which prey sequences are selectively enriched and sequenced.Since many spider species are generalist predators, large numbers of samples comprising individual spider specimens must be analysed to recover an exhaustive image of a spider species' prey spectrum, which is costly and time‐consuming.Pooled processing of bulk samples of multiple specimens has been suggested to reduce the necessary workload and cost while still recovering a representative estimate of the prey diversity. However, it is still unclear if pooling approaches lead to bias in recovering the prey spectrum and if the results are comparable with data from individually processed spiders.Here, we test the effects of metabarcoding pooled spider gut content on the recovered taxonomic diversity and composition of prey. Using a newly adapted primer pair, which efficiently enriches COI barcode sequences of diverse arthropod prey groups while suppressing spider amplification, we test if pooling leads to reduced taxonomic diversity or skewed estimates of prey composition.Our results show that pooling and individual processing recover highly correlated taxonomic diversity and composition of prey. The only exception are very rare prey items which were less well recovered by pooling. Our results support pooling as a cost‐effective and time‐efficient approach to recover the diet of generalist predators for population‐level studies of spider trophic interactions. [ABSTRACT FROM AUTHOR]

Anthropogenic habitat modification is a major contributor to global change. While the modification of natural habitats to agroecosystems attracts most of the attention, little is known about the conversion of one natural ecosystem to another. Dry dipterocarp forest is the key dry forest type across Southeast Asia. Moderate fire disturbance is essential for its regeneration, but humans often prevent fire in these forests. Consequently, dry dipterocarps can change to dry evergreen forests through succession. The consequences of this conversion on food webs are unknown. Using the network approach, we compared the food webs of web-building spiders and their prey in the understory between dry dipterocarp (open canopy, uniform understory) and dry evergreen forests (closed canopy, heterogeneous understory) in north-eastern Thailand. Overall, we collected 560 individual web-building spiders belonging to 37 genera. Further, we collected 1139 prey items from spider webs belonging to 16 arthropod orders. The composition of captured prey and the network structure differed between the forest types. Specifically, the web-building spiders were more specialized and their niches overlapped less in dry dipterocarps than in dry evergreens. The differences in food-web structure were driven mostly by trophic groups turnover rather than interaction rewiring. Implications for insect conservation: The transformation of dry dipterocarp to dry evergreen forests from the prevention of fire disturbance may lead to an altered ecological function of web-building spiders in forest understories. As trophic links and their strength are rewired, habitat modification may also lead to changes in nutrient and energy flow in forest understories. [ABSTRACT FROM AUTHOR]

The male of the Bounty Island endemic Pacificana cockayni Hogg, 1904 is described for the first time and the female is redescribed. We attempted to place the monotypic genus Pacificana in an appropriate family based on cytochrome c oxidase subunit 1 DNA sequence data, however, our phylogenetic analysis was inconclusive. Morphologically, P. cockayni shares characters with the New Zealand genera Pakeha Forster & Wilton, 1973 (Cycloctenidae) and Otira Forster & Wilton, 1973 (Amaurobiidae) plus two Australian amaurobiid genera, Storenosoma Hogg, 1900 and Oztira Milledge, 2011. We note that while other spider species recorded from the Bounty Islands are found on other sub-Antarctic islands, Pacificana is not. We have not suggested a family placement until the placement of Otira, Oztira, Pakeha, and Storenosoma has been resolved by further, more extensive phylogenetic analysis. [ABSTRACT FROM AUTHOR]

The inhibition of Nav1.7 is a promising strategy for the development of analgesic treatments. Spider venom‐derived peptide toxins are recognized as significant sources of Nav1.7 inhibitors. However, their development has been impeded by limited selectivity. In this study, eight peptide toxins from three distinct spider venom Nav channel families demonstrated robust inhibition of hNav1.7, rKv4.2, and rKv4.3 (rKv4.2/4.3) currents, exhibiting a similar mode of action. The analysis of structure and function relationship revealed a significant overlap in the pharmacophore responsible for inhibiting hNav1.7 and rKv4.2 by HNTX‐III, although Lys25 seems to play a more pivotal role in the inhibition of rKv4.2/4.3. Pharmacophore‐guided rational design is employed for the development of an mGpTx1 analogue, mGpTx1‐SA, which retains its inhibition of hNav1.7 while significantly reducing its inhibition of rKv4.2/4.3 and eliminating cardiotoxicity. Moreover, mGpTx1‐SA demonstrates potent analgesic effects in both inflammatory and neuropathic pain models, accompanied by an improved in vivo safety profile. The results suggest that off‐target inhibition of rKv4.2/4.3 by specific spider peptide toxins targeting hNav1.7 may arise from a conserved binding motif. This insight promises to facilitate the design of hNav1.7‐specific analgesics, aimed at minimizing rKv4.2/4.3 inhibition and associated toxicity, thereby enhancing their suitability for therapeutic applications. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Compartment syndrome of the forearm has been associated with a variety of etiologies, including fractures, snake bites, complications of certain infections, and, very rarely, spider bites. Loxoscelism is the venom-related clinical manifestation of the bite of spiders of the genus Loxosceles, also called brown or fiddler (violinist) spiders. It manifests locally/regionally with pain, erythema, and edema, with subsequent necrotic plaque formation at the site of the bite. This condition can threaten the function and integrity of the limbs and, in severe cases, can be life-threatening. The basis of treatment is surgical decompression of the affected compartments to restore limb perfusion and avoid irreversible sequelae. Case Report: A 62-year-old male patient, without comorbidities, had edematous cutaneous loxoscelism and secondary development of acute compartment syndrome of the right forearm. He promptly visited the Emergency Department and underwent surgical treatment, in addition to the application of pharmacological treatment, under a multi-disciplinary team. The evolution was favorable. The biochemical levels of rhabdomyolysis decreased, the compartment syndrome resolved, the fasciotomies were closed, and the patient was discharged without further complications. Conclusions: Although arachnid bites are relatively uncommon in urban hospitals, it is crucial that general, vascular, and plastic surgeons maintain a high index of clinical suspicion for acute compartment syndrome. It is important to make an accurate differential diagnosis, and equally important is the interdisciplinary approach to treating this condition, ensuring prompt medical treatment and, if necessary, early surgical intervention. [ABSTRACT FROM AUTHOR]

Introduction Warfighters are exposed to life-threatening injuries daily and according to the Joint Trauma System Military Clinical Practice Guideline—Global Snake Envenomation Management snakebites are a concerning threat in all theaters of operation. Snake venom is a complex mixture of toxins including phospholipases A2 (PLA2) and snake venom metalloproteinases (SVMP) that produce myotoxic, hemotoxic, and cytotoxic injuries. Antibody-based antivenom is the standard of care but new approaches including small-molecule inhibitors have gained attention in recent years. Doxycycline is an effective inhibitor of human metalloproteinases and PLA2. The enzymatic activities of 3 phylogenetically distinct snakes: Agkistrodon piscivorus, Naja kaouthia , and Daboia russelii were tested under inhibitory conditions using doxycycline. Materials and Methods Enzymatic activity of PLA2 and SVMP was measured in N. kaouthia, D. russelii , and A. piscivorus venom alone and with doxycycline using EnzChek Phospholipase A2 and Gelatinase Assay Kits. A 1-way ANOVA with Tukey's post-hoc test was used to conduct comparative analysis. The median lethal dose of the venoms, the effective dose of doxycycline, and creatine kinase (CK) inhibition levels were measured in a murine model with adult Bagg Albino (BALB/c) mice using intramuscular injections. Median lethal and effective doses were determined using Spearman-Karber's method and a 1-way ANOVA with Tukey's post-hoc test was used to compare CK inhibition levels. Results Phospholipases A2 activity was reduced to 1.5% to 44.0% in all 3 venoms in a dose-dependent manner using 0.32, 0.16, and 0.08 mg/mL doxycycline when compared to venom-only controls (P  < .0001) (Fig. 1A). Snake venom metalloproteinases activity was reduced to 4% to 62% in all 3 venoms in a dose-dependent manner using 0.32, 0.16, and 0.08 mg/mL doxycycline (P  < .0001) (Fig. 1B). The lethal dose (LD50) values of the venoms in the murine model were calculated as follows: A. piscivorus  = 20.29 mg/kg (Fig. 2A), N. kaouthia  = 0.38 mg/kg (Fig. 2B), and D. russelii  = 7.92 mg/kg (Fig. 2C). The effective dose (ED50) of doxycycline in A. piscivorus was calculated to be 20.82 mg/kg and 72.07 mg/kg when treating D. russelii venom. No ED50 could be calculated when treating N. kaouthia venom (Fig. 3). Creatine kinase activity was significantly decreased in all 3 venoms treated with doxycycline (P  < .0001) (Fig. 4). FIGURE 1. In vitro doxycycline inhibition of PLA, and SVMP activity in whole venom. The AUC was calculated for PLA and SVMP activities for 20-min and 4-h time courses, respectively using EnzChek Phospholipase A2, assay kits, and EnzChek Gelatinase (SVMP) assay kits. (A) Inhibition of PLA2, with doxycycline (Dox) was tested at concentrations of 0.32 mg/mL, 0.16 mg/mL, and 0.08 mg/mL against A. piscivorus (4 μg/mL), N. kaouthia (4 μg/mL), and D. russelii (8 μg/mL) venom. A venom-only control was included. (B) Inhibition of SVMP with doxycycline was tested at concentrations of 0.32 mg/mL, 0.16 mg/mL, and 0.08 mg/mL against A. piscivorus (120 μg/ml.), N. kaouthia (125 μg/ml.), and D. russelii (250 μg/ml.). A venom-only control was included. An ordinary 1-way ANOVA with Tukey's post-hoc test was performed for inhibition assays to compare treatments to their respective venom controls. All error bars show mean ± SD, n  = 3, (****, P  < .0001). Open in new tab Download slide FIGURE 2. Percent survival of mice receiving various dosages for each venom studied and LDs, calculation. Adult BALB/c mice received intramuscular injections of various venom dosages for each venom, (A) A. piscivorus , (B) N. kaouthia , and (C) D. russelii. The resulting percent survival was measured across 48 h and the lethal dose 50 (LD50) was calculated using the Spearman-Karber method. In each graph, each treatment group (venom dosage) has n  = 5. Open in new tab Download slide FIGURE 3. Percent survival of mice receiving various doxycycline dosages for each venom studied and ED calculation. Adult BALB/c mice received intramuscular injections of various doxycycline dosages combined with 3 times the LD50 of cach venom [ A. piscivorus (AP) (60.87 mg/kg), N. kaouthia (NK) (1.14 mg/kg). D. russelii (DR) (23.76 mg/kg)] and the resulting percent survival was measured across 48 hours and the effective dose 50 (ED50) was calculated using the Spearman–Karber method. Each treatment group has n  = 5. Open in new tab Download slide FIGURE 4. Venom-induced CK activity with doxycycline-mediated inhibition. The amount of CK produced by mice exposed to one-fourth of the LD50, strength of A. piscivorus (AP) (5.07 mg/kg), N. kaouthia (NK) (0.095 mg/kg), or D. russelli (DR) (1.98 mg/kg) venom either with or without doxycycline (64 mg/kg). All error bars show mean, ± SD, n  = 5 (NaCl—Dox, AP NaCl), n-4 (NK Dox), and n-3 (AP Dox. NK NaCl, DR Dox, DR + NaCl). Statistical differences were determined using an ordinary 1-way ANOVA with Tukey's post-hoc test comparing each venom group within itself and to the doxycycline only control (**** P  < .0001). (*** P  < .001), (** P  < .01). (* P  < .05). Open in new tab Download slide Conclusion Doxycycline reduced PLA2- and SVMP-related lethality, particularly in A. piscivorus envenomings and in a limited capacity with D. russelii revealing its promise as a treatment for snakebites. In addition, CK activity, a common indicator of muscle damage was inhibited in mice that received doxycycline-treated venom. The doxycycline concentrations identified in the ED50 studies correspond to 1,456 to 5,061 mg dosages for a 70 kg human. Factors including venom yield and snake species would affect the actual dosage needed. Studies into high-dose doxycycline safety and its effectiveness against several snake species is needed to fully translate its use into humans. Based on this work, doxycycline could be used as a treatment en route to higher echelons of care, providing protection from muscle damage and reducing lethality in different snake species. [ABSTRACT FROM AUTHOR]

Snake venoms are intricate mixtures of enzymes and bioactive factors that induce a range of detrimental effects in afflicted hosts. Certain Viperids, including Bothrops jararacussu, harbor C-type lectins (CTLs) known for their modulation of a variety of host cellular responses. In this study, we isolated and purified BjcuL, a CTL from B. jararacussu venom and investigated its impact on endothelial cell behavior, contrasting it with human galectin-1 (Gal-1), a prototype member of the galectin family with shared β-galactoside-binding activity. We found that BjcuL binds to human dermal microvascular endothelial cells (HMECs) in a concentration- and carbohydrate-dependent fashion and reprograms the function of these cells, favoring a pro-inflammatory and pro-coagulant endothelial phenotype. In light of the quest for universal antagonists capable of mitigating the harmful consequences of snake venoms, BjcuL emerges as a promising target to be blocked in order to regulate pathological endothelial cell responses. [ABSTRACT FROM AUTHOR]

Fear of spiders is a widespread condition often disproportionate to the actual danger spiders pose to humans. Likely rooted in evolutionary history, fear of spiders might also have a cultural component. Recent studies have shown that a significant fraction of spider-related media reports are misleading and sensationalistic. Information-seeking behaviours serve as common coping mechanisms for our fears and anxieties, yet the link between spider-related news stories and such behaviors remains unexplored. We hypothesize that media reports foster concern about spiders, resulting in an increased awareness of spiders and health issues associated with them. We extracted 1486 reports in English from a public database providing a content-analysis of spider-related online traditional media reports published between 2010–2020. We examined whether the volume of spider-related queries in Google Trends, Wikipedia, and iNaturalist increased in the week following the publication of each news story. Sensationalistic news stories were associated with a small, significant increase in search volumes, compared to non-sensationalistic ones. The search volume for "brown recluse" (Loxosceles reclusa), which are potentially dangerous spiders, was higher after the publication date of news related to human-spider encounters. There was a significant positive relationship between the number of spider-related news stories published in a given month and the traffic on target spider-related Wikipedia pages, especially so for the page on brown recluse spiders. Our results suggest that traditional media have a detectable impact on the behaviour of the general public towards spiders, supporting the hypothesis that the fear of spiders is perpetuated by culture. Additionally, our findings indicate that information-seeking behaviour is a common response to learn about spiders and potentially fact-check spurious claims found in sensationalised news. By recognizing the role of media in shaping attitudes towards spiders and acknowledging the benefits of accurate representation, we can lay the foundation for a more informed and harmonious relationship between humans and spiders. [ABSTRACT FROM AUTHOR]

Consumers are thought to select food resources based on their nutritional content. While laboratory experiments have explored this, the nutritional dynamics of invertebrate predators have been scarcely studied in the field given various methodological constraints. The intersection of these nutritional dynamics with predator traits is also poorly characterised, leading to many gaps in our understanding of how different predators forage and feed in natural systems. Here, we integrate dietary metabarcoding with prey macronutrient (protein, lipid and carbohydrate) content and abundance to assess how nutrients and predator traits (sex, life stage and taxonomy) interactively drive prey preferences in the field, using spider–prey interactions as a model system. Different spider genera, sexes and life stages had nutritionally distinct diets. Our analyses demonstrated disproportionate foraging (selection and avoidance) for prey rich in different macronutrients, with the nature of these relationships differing between spider taxa, life stages and sexes. This may be explained by niche differentiation among spider groups, driven by biases toward prey rich in different nutrients, or nutrient‐specific foraging in which individual spiders vary their nutritional preferences to redress deficits, although further evidence is required to confirm this. This insight into the nutritional dynamics of generalist invertebrate predators extends our understanding beyond lab‐based behavioural assays and provides a novel framework for other complex real‐world systems. [ABSTRACT FROM AUTHOR]

Due to widespread atmospheric deposition of mercury (Hg), all aquatic food webs are contaminated with toxic methyl mercury (MeHg). At high concentrations, MeHg poses a health hazard to wildlife and humans. Spiders feeding in riparian habitats (hereafter referred to as riparian spiders) have been proposed as sentinels of MeHg contamination of aquatic systems. Riparian spiders are exposed to MeHg through their diets, and the concentration of MeHg in spiders is positively related to the proportion of MeHg‐contaminated emergent aquatic insects in their diets. The use of spiders as sentinels is complex because their MeHg concentrations can vary, not only among ecosystems but also between different spider taxa and as a function of spider body size. The objective of the present study was to examine how the level of ecosystem contamination, spider taxon, and spider body size interact to influence MeHg concentrations in four genera of riparian spiders from two rivers with different levels of Hg contamination. We collected four genera of riparian spiders (Tetragnatha sp., Larinioides sp., Pardosa sp., and Rabidosa sp.) from two sites along both the Clear Fork of the Trinity River and the West Fork of the Trinity River (Fort Worth, TX, USA). We analyzed concentrations of MeHg in different body sizes of spiders from each genus. We found that MeHg contamination of the river ecosystem, spider taxon, and spider body size were important determinants of MeHg concentration in riparian spiders. The results suggest that any of the four taxa of riparian spiders from the present study could be used as sentinels of aquatic MeHg contamination, but they should not be used interchangeably because of the interdependence between the effects of ecosystem contamination level, spider taxon, and body size. Future studies utilizing riparian spiders as sentinels of biomagnifying aquatic contaminants (e.g., MeHg, polychlorinated biphenyls) should consider the potentially complex interaction effects between ecosystem contamination level, spider taxon, and spider body size. Environ Toxicol Chem 2024;43:2169–2175. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

The potent neurotoxic venom of the black widow spider contains a cocktail of seven phylum-specific latrotoxins (LTXs), but only one, α-LTX, targets vertebrates. This 130 kDa toxin binds to receptors at presynaptic nerve terminals and triggers a massive release of neurotransmitters. It is widely accepted that LTXs tetramerize and insert into the presynaptic membrane, thereby forming Ca2+-conductive pores, but the underlying mechanism remains poorly understood. LTXs are homologous and consist of an N-terminal region with three distinct domains, along with a C-terminal domain containing up to 22 consecutive ankyrin repeats. Here we report cryoEM structures of the vertebrate-specific α-LTX tetramer in its prepore and pore state. Our structures, in combination with AlphaFold2-based structural modeling and molecular dynamics simulations, reveal dramatic conformational changes in the N-terminal region of the complex. Four distinct helical bundles rearrange and together form a highly stable, 15 nm long, cation-impermeable coiled-coil stalk. This stalk, in turn, positions an N-terminal pair of helices within the membrane, thereby enabling the assembly of a cation-permeable channel. Taken together, these data give insight into a unique mechanism for membrane insertion and channel formation, characteristic of the LTX family, and provide the necessary framework for advancing novel therapeutics and biotechnological applications. Black widow spider venom contains seven structurally related toxins acting at presynaptic nerve terminals. Here, the authors provide cryo-EM structures of vertebrate-specific αLTX in two states and decipher how the toxin forms cation-selective pores. [ABSTRACT FROM AUTHOR]

Featured Application: The application of this study is all computational studies considering venom peptides as potential sources of therapeutics. Animal venom has been gaining traction as a potential source of therapeutics for various diseases. Spiders encompass a wide variety of venom-producing species, of which tarantulas of the family Theraphosidae are widely known across the globe. Research towards tarantula venom therapeutics has led to its potential application as antinociceptives. Death receptors are cellular receptors that induce apoptosis—the body's natural suicide mechanism—to destroy malfunctioning cells. These are particularly of interest in cancer research, as this mechanism is tampered with, resulting in cancer cell proliferation. In this study, the viability of venom toxins from the Theraphosidae family of spiders to induce apoptosis by binding to human death receptors is investigated by carrying out anti-cancer screening, molecular docking, ADMET evaluation, then molecular dynamics and thermodynamic analysis twice, first to ascertain the best receptor–peptide systems per receptor, and secondly to more comprehensively describe binding stability and thermodynamics. Results point to favorable receptor–peptide interactions due to similarities in equilibrium behavior with the death ligand–death receptor systems, along with favorable end-state binding energies and ADMET analysis results. Further inquiry is recommended to assess the real-life efficacy and viability of theraphotoxins as apoptosis therapeutics and further improve on their ability to induce apoptosis. [ABSTRACT FROM AUTHOR]

This document is a list of contributors and acknowledgements for a study on the generation and characterization of monoclonal antibodies for a specific protein. It also includes a conflict of interest statement and information about the availability of the data. The document does not provide a summary of the study's findings or any additional information about the topic Low. [Extracted from the article]

Emerging evidence indicates that androgen receptor (AR) signaling plays a critical role in the pathogenesis of male-dominant urothelial cancer and its outgrowth. Meanwhile, latrophilins (LPHNs), a group of the G-protein-coupled receptors to which a spider venom latrotoxin (LTX) is known to bind, remain largely uncharacterized in neoplastic diseases. The present study aimed to determine the functional role of LPHN3 (encoded by the ADGRL3 gene), in association with AR signaling, in the progression of bladder cancer. In AR-positive bladder cancer lines, dihydrotestosterone considerably increased the expression levels of ADGRL3 and LPHN3, while chromatin immunoprecipitation assay revealed the binding of AR to the promoter region of ADGRL3. Treatment with LPHN3 ligands (e.g. α-LTX, FLRT3) resulted in the induction of ADGRL3 expression, as well as cell viability, in bladder cancer lines. By contrast, LPHN3 knockdown via shRNA virus infection significantly reduced the viability and migration of these cells. Immunohistochemistry in transurethral resection specimens further showed a strong correlation between LPHN3 and AR expression. Moreover, LPHN3 positivity in muscle-invasive bladder tumors, as an independent prognosticator, was associated with a significantly higher risk of disease progression and disease-specific mortality following radical cystectomy. These findings suggest that LPHN3 functions as a downstream effector of AR and promotes the growth of bladder cancer. [ABSTRACT FROM AUTHOR]

Latroeggtoxin‐VI (LETX‐VI), a peptide toxin discovered from the eggs of spider Latrodectus tredecimguttatus, was previously shown to promote the synthesis and release of dopamine in rat pheochromocytoma (PC12) cells, showing potential applications in the neurobiology and medicine. To further understand the structure and properties of LETX‐VI, the key residues were identified and their roles in the structure, function, and stability of LETX‐VI were analyzed in the present work. Based on the protein molecular docking, our previous work, and the relevant literature, the potential key residues of LETX‐VI were selected and identified by alanine‐scanning mutagenesis. The wild‐type LETX‐VI and its 13 mutants, including a double mutant, were prepared by gene cloning and heterologous expression in Escherichia coli, followed by activity, structure, and stability determination. The results demonstrated that the activity of the mutants K25A, R35A, K40A/R41A, and L45A, particularly R35A, to promote dopamine release from PC12 cells was significantly decreased compared with that of the wild‐type LETX‐VI, indicating that these mutated residues are the key residues. Circular dichroism (CD) analysis showed that the secondary structure of these mutants was not obviously different from that of wild‐type LETX‐VI, suggesting that mutation‐caused decrease in the activity of LETX‐VI is due to the changes in the binding site on the molecule surface, rather than the abnormal alternation of the molecular conformation of LETX‐VI. Acetonitrile (ACN) did not obviously influence the activity of LETX‐VI; however, 0.1% trifluoroacetic acid (TFA) treatment for 2 h significantly reduced its activity. Treatment with weakly acidic and basic buffers (pH ≥ 6.6) for 12 h was favorable for LETX‐VI and R35A to exert their activity. Higher temperatures (>37°C) decreased the activity of both wild‐type LETX‐VI and R35A. In conclusion, K25, R35, K40, R41, and L45 particularly R35 are the important functional site residues; during experiments, care should be taken to avoid the adverse influence of strong acid and high temperature on LETX‐VI. These observations have enhanced our understanding of the structure and properties of LETX‐VI and provided references for the subsequent modification of structure and function of LETX‐VI. [ABSTRACT FROM AUTHOR]

Hydrogels are useful drug release systems and tissue engineering scaffolds. However, synthetic hydrogels often require harsh gelation conditions and can contain toxic by‐products while naturally derived hydrogels can transmit pathogens and in general have poor mechanical properties. Thus, there is a need for a hydrogel that forms under ambient conditions, is non‐toxic, xeno‐free, and has good mechanical properties. A recombinant spider silk protein‐derived hydrogel that rapidly forms at 37 °C is recently developed. The temperature and gelation times are well‐suited for an injectable in situ polymerising hydrogel, as well as a 3D cell culture scaffold. Here, it is shown that the diffusion rate and the mechanical properties can be tuned by changing the protein concentration and that human fetal mesenchymal stem cells encapsulated in the hydrogels show high survival and viability. Furthermore, mixtures of recombinant spider silk proteins and green fluorescent protein (GFP) form gels from which functional GFP is gradually released, indicating that bioactive molecules are easily included in the gels, maintain activity and can diffuse through the gel. Interestingly, encapsulated ARPE‐19 cells are viable and continuously produce the growth factor progranulin, which is detected in the cell culture medium over the study period of 31 days. [ABSTRACT FROM AUTHOR]

Anti‐cancer peptides (ACPs) represent a promising potential for cancer treatment, although their mechanisms need to be further elucidated to improve their application in cancer therapy. Lycosin‐I, a linear amphipathic peptide isolated from the venom of Lycosa singorensis, shows significant anticancer potential. Herein, it is found that Lycosin‐I, which can self‐assemble into a nanosphere structure, has a multimodal mechanism of action involving lipid binding for the selective and effective treatment of leukemia. Mechanistically, Lycosin‐I selectively binds to the K562 cell membrane, likely due to its preferential interaction with negatively charged phosphatidylserine, and rapidly triggers membrane lysis, particularly at high concentrations. In addition, Lycosin‐I induces apoptosis, cell cycle arrest in the G1 phase and ferroptosis in K562 cells by suppressing the PI3K‐AKT‐mTOR signaling pathway and activating cell autophagy at low concentrations. Furthermore, intraperitoneal injection of Lycosin‐I inhibits tumor growth of K562 cells in a nude mouse xenograft model without causing side effects. Collectively, the multimodal effect of Lycosin‐I can provide new insights into the mechanism of ACPs, and Lycosin‐I, which is characterized by high potency and specificity, can be a promising lead for the development of anti‐leukemia drugs. [ABSTRACT FROM AUTHOR]

Simple Summary: Spiders are considered natural polyphagous bio-control agents of agro-ecosystems and the best indicators of environmental health. They have the ability to adapt to different environments and are, therefore, present in almost all types of terrestrial ecosystems. The behavior of spiders is influenced by different biotic and abiotic factors, such as roadside disturbance, which may affect normal web-building behavior. Spiders, Neoscona vigilans, were captured, body measurements were taken, and their web characteristics along the road premises were calculated. Web characteristics had a significant association with spider body characteristics and also with the distance from the road, which changed gradually as the webs were constructed closer to the road. Road disturbance had a negative impact on normal web construction as more defects were observed in the webs constructed closer to the road, while dramatically more perfect webs were observed as the distance from the road increased. We concluded that disturbances such as roadside traffic had diverse effects on spider behavior. The outcomes of this study provide insight into the role of traffic on the livelihood of spiders encountering human-influenced disturbance in the ecosystem. Orb web spiders are common and highly diversified animals found in almost all habitats. They have remarkable plasticity against biotic and abiotic factors, making them excellent indicators of environmental health. The web creation behavior of spiders is influenced by disturbances in the environment. The aim of this research was to observe the alteration in the web-building behavior of Neoscona vigilans caused by human activities, specifically traffic disturbances. Spider webs were located and photographed at nighttime along the roadside, and their web characteristics were calculated. Spiders were captured from webs for their body measurements. Spider fourth leg length, carapace width, and body length had a significant association with web size and diameter, CTL, capture area, and mesh size. The quantity of trapped prey, the height of the plant, and the foliage radius increased with the distance from the road. Conversely, anchor points and web elevation from the ground dropped. The highest and lowest proportions of anomalies (modifications/defects) were recorded as holes (52.7%) in 105 webs (100%) and supernumerary (0.7%) in 55 webs (52.4%), respectively. Road disturbance had a negative influence on the spider's behavior as the webs formed in close proximity to the road had a higher frequency of anomalies, with a gradual decrease distantly. We can gain further insight into how different environmental changes, disruptions, and pollutants lead to this imperfection in the otherwise flawless perfect structure of spider webs. [ABSTRACT FROM AUTHOR]

HxTx-Hv1h, a neurotoxic peptide derived from spider venom, has been developed for use in commercial biopesticide formulations. Cell Penetrating Peptides (CPPs) are short peptides that facilitate the translocation of various biomolecules across cellular membranes. Here, we evaluated the aphidicidal efficacy of a conjugated peptide, HxTx-Hv1h/CPP-1838, created by fusing HxTx-Hv1h with CPP-1838. Additionally, we aimed to establish a robust recombinant expression system for HxTx-Hv1h/CPP-1838. We successfully achieved the secretory production of HxTx-Hv1h, its fusion with Galanthus nivalis agglutinin (GNA) forming HxTx-Hv1h/GNA and HxTx-Hv1h/CPP-1838 in yeast. Purified HxTx-Hv1h exhibited contact toxicity against Megoura crassicauda, with a 48 h median lethal concentration (LC50) of 860.5 μg/mL. Fusion with GNA or CPP-1838 significantly enhanced its aphidicidal potency, reducing the LC50 to 683.5 μg/mL and 465.2 μg/mL, respectively. The aphidicidal efficacy was further improved with the addition of surfactant, decreasing the LC50 of HxTx-Hv1h/CPP-1838 to 66.7 μg/mL—over four times lower compared to HxTx-Hv1h alone. Furthermore, we engineered HxTx-Hv1h/CPP-1838 multi-copy expression vectors utilizing the BglBrick assembly method and achieved high-level recombinant production in laboratory-scale fermentation. This study is the first to document a CPP fusion strategy that enhances the transdermal aphidicidal activity of a natural toxin like HxTx-Hv1h and opens up the possibility of exploring the recombinant production of HxTx-Hv1h/CPP-1838 for potential applications. [ABSTRACT FROM AUTHOR]

Heptathela kimurai (Kishida, 1920) is a spider that belongs to the family Heptathelidae which is a basial lineage of spiders. The molecular information of ancestral species belonging to families like Heptathelidae is comparatively limited when compared to spider species from derived families. Here we present the complete mitochondrial genome sequence (mtDNA) of H. kimurai. The sequence was obtained using massively parallel sequencing technology. The circular genome was 14,224 bp in length, and the AT content was 69.53%. The H. kimurai mitochondrial genome contains 13 protein-coding genes (PCGs), 21 tRNA genes, and 2 rRNA genes. The majority of PCGs were found in the heavy strand. [ABSTRACT FROM AUTHOR]

Global change drives multiple facets of biodiversity including interaction diversity, which is fundamental for ecosystem functioning. However, studying trophic interactions is challenging in meta‐ecosystems, that is ecosystems connected by spatial flows of energy, materials and organisms across ecosystem boundaries. While analytical methods based on abundances of polyunsaturated fatty acids (PUFAs) and stable isotopes of amino acids (AAs) are being increasingly used, it has never been explored if both approaches could be: (i) combined in mixing models to enhance precision in dietary inference (ii) compared to disentangle transfers of various PUFAs and proteins in food webs in the wild.We explore the utility of analytical approaches based on PUFA abundances and AA isotopes to resolve resource transfers in a natural riparian food web. We focus on spiders and their potential prey from blue, green and brown sources to address three important and persisting methodological issues in food‐web ecology, namely whether (i) essential AA carbon isotopes can resolve protein origin from blue, green and brown resources, (ii) PUFA relative abundance and AA isotopes can be combined in a mixing model to provide higher precision estimates (i.e. narrower intervals) and (iii) combining the two approaches can unveil the coupling of protein and PUFA transfers in food webs.Our research demonstrates the power of AA isotopes and PUFAs to distinguish blue, green, and brown sources and their transfer up to consumers. We show that combining PUFA relative abundance and AA isotopes in a mixing model provides overall estimates similar to the individual estimates but significantly increases precision. In addition, we showcase how combining approaches unveil the coupling of protein and PUFA transfers. For instance, we show that most PUFAs are less concentrated from prey to predators, relative to proteins, highlighting uncoupling of PUFAs and protein transfer along food chains.We show for the first time the effectiveness of combining AA isotopes and PUFA abundances, particularly relevant for complex trophic interactions in a meta‐ecosystem context. Our study illustrates the trophic uncoupling of proteins and PUFAs, highlighting the necessity in combining both approaches. [ABSTRACT FROM AUTHOR]

Despite impressive progress in the field, there are still several major bottlenecks in producing fibers from recombinantly produced spider‐silk‐like proteins to replicate the extraordinary mechanical properties of spider major ampullate silk. The conventional artificial fiber spinning processes rely primarily on organic solvents to coagulate proteins into fibers and require complex post‐treatments to obtain fibers with valuable properties. This is due to challenges in obtaining soluble silk proteins, but also because the native silk spinning process leading to the hierarchical organization of the silk proteins is not fully understood and is hard to replicate in a manner applicable to industrial settings. Here, recombinant spider‐silk fusion proteins are efficiently produced and processed into as‐spun fibers with a toughness modulus of 120 MJ m−3 and extensibility of 255% using solely aqueous solutions. The spider‐silk fusion proteins assemble in a manner similar to that reported for native spider silk: they phase separate induced by salting out, followed by alignment and a secondary structure transition triggered by shear forces and dehydration. Finally, the design of the fusion silk proteins enables straightforward functionalization of the fibers under mild all‐aqueous conditions via a simple biomolecular click reaction both pre‐ and post‐spinning. [ABSTRACT FROM AUTHOR]

SUMMARY: Cotton is a globally cultivated crop, producing 87% of the natural fiber used in the global textile industry. The pigment glands, unique to cotton and its relatives, serve as a defense structure against pests and pathogens. However, the molecular mechanism underlying gland formation and the specific role of pigment glands in cotton's pest defense are still not well understood. In this study, we cloned a gland‐related transcription factor GhHAM and generated the GhHAM knockout mutant using CRISPR/Cas9. Phenotypic observations, transcriptome analysis, and promoter‐binding experiments revealed that GhHAM binds to the promoter of GoPGF, regulating pigment gland formation in cotton's multiple organs via the GoPGF‐GhJUB1 module. The knockout of GhHAM significantly reduced gossypol production and increased cotton's susceptibility to pests in the field. Feeding assays demonstrated that more than 80% of the cotton bollworm larvae preferred ghham over the wild type. Furthermore, the ghham mutants displayed shorter cell length and decreased gibberellins (GA) production in the stem. Exogenous application of GA3 restored stem cell elongation but not gland formation, thereby indicating that GhHAM controls gland morphogenesis independently of GA. Our study sheds light on the functional differentiation of HAM proteins among plant species, highlights the significant role of pigment glands in influencing pest feeding preference, and provides a theoretical basis for breeding pest‐resistant cotton varieties to address the challenges posed by frequent outbreaks of pests. Significance Statement: Pigment glands are essential for cotton's pest defense, but their formation mechanisms remained unclear. We demonstrated that the GhHAM transcription factor, through the GoPGF‐GhJUB1 pathway, is pivotal for gland development and pest resistance, offering new insights into breeding pest‐resistant cotton. [ABSTRACT FROM AUTHOR]

Snakebites affect about 1.8 million people annually. The current standard of care involves antibody-based antivenoms, which can be difficult to access and are generally not effective against local tissue injury, the primary cause of morbidity. Here, we used a pooled whole-genome CRISPR knockout screen to define human genes that, when targeted, modify cell responses to spitting cobra venoms. A large portion of modifying genes that conferred resistance to venom cytotoxicity was found to control proteoglycan biosynthesis, including EXT1, B4GALT7, EXT2, EXTL3, XYLT2, NDST1, and SLC35B2, which we validated independently. This finding suggested heparinoids as possible inhibitors. Heparinoids prevented venom cytotoxicity through binding to three-finger cytotoxins, and the US Food and Drug Administration–approved heparinoid tinzaparin was found to reduce tissue damage in mice when given via a medically relevant route and dose. Overall, our systematic molecular dissection of cobra venom cytotoxicity provides insight into how we can better treat cobra snakebite envenoming. Editor's summary: Snakebite is considered a neglected tropical disease by the World Health Organization, and although antibody-based antivenoms exist, they are species specific, are expensive, and require cold storage as well as intravenous administration in a health care setting. Here, Du and colleagues conducted a whole-genome CRISPR knockout screen to identify genes required for spitting cobra venom cytotoxicity. This screen highlighted genes involved in proteoglycan biosynthesis, suggesting that heparinoids could potentially block spitting cobra venom cytotoxicity. The heparinoid tinzaparin, given subcutaneously at the time of intradermal venom injection, effectively reduced the size of the resulting dermonecrotic lesions in mice, supporting the further evaluation of this drug for the treatment of local tissue damage from spitting cobra envenoming. —Melissa L. Norton [ABSTRACT FROM AUTHOR]

In organisms, liquid as a continuum intertwines architected components (organs), including nervous, vascular, and musculoskeletal systems. In this regard, spiders exhibit remarkable embodiments where hemolymph, which infuses the animal, simultaneously enables muscle activation and exoskeleton compliance. Previous works on spider‐inspired artificial systems have focused on disentangled aspects, such as pressurization and flexible structures, yet organism‐like liquid‐mediated physical intelligence integrating control, distribution of resources, actuation, and support is still to be demonstrated. Here a spider‐leg‐inspired soft exoskeleton integrating a muscular system is shown, enabled by the contained liquid through hydration for compliance conditioning and charge transport for muscle activation. A two‐photon polymerized 0.8 mm‐diameter exoskeleton is reported that contains an electrolyte solution and is actuated via contraction of an ionic electroactive polymer muscle operated at 0–1 V. The exoskeleton features reversible bending and compliant interaction with natural entities such as anthers, spider webs, and pollen grains. The reported technology demonstrator, which functionally intertwines muscularization, vascularization, and innervation via liquid, supports the development of liquid‐enabled systems based on embodied energy and multi‐material design, particularly for bioinspired soft robotics. [ABSTRACT FROM AUTHOR]

Coxsackievirus B3 (CVB3) is a member of the enterovirus genus and linked to several diseases, including myocarditis, which can progress to dilated cardiomyopathy. Despite ongoing preclinical efforts, no clinically approved vaccines against CVB3 are currently available, highlighting the urgent need for effective prophylactic solutions. In this study, a nanovaccine platform based on spider minor ampullate silk protein (MiSp) is introduced. This platform utilizes protein nanoparticles engineered from chimeric proteins that incorporate CVB3 antigenic peptides into customized MiSp, subsequently loaded with all‐trans retinoic acid (RA). These functional nanovaccines are capable of eliciting both mucosal and systemic immune responses following subcutaneous administration and demonstrate significant protective effects against CVB3 infection in mice. This study signifies an approach in peptide‐based parenteral vaccine strategies, utilizing engineered MiSp nanoparticles combined with RA. This methodology represents a promising pathway for preventing enterovirus infections by leveraging the unique immunomodulatory properties of spidroins and RA to combat these pathogens effectively. [ABSTRACT FROM AUTHOR]

Spider dragline silks exhibit remarkable mechanical properties, combining both high strength and toughness. These unique characteristics arise from the intricate structure of the silk, which requires atomic‐level information to understand its origins. 13C solid‐state NMR provides this detailed structural insight into spider dragline silk. In this review, 13C CP/MAS, 13C DD/MAS and 13C INEPT NMR spectroscopies are employed to reveal the structure of spider dragline silks together with 13C conformation‐dependent chemical shifts, 2D spin‐diffusion NMR, rotational echo double resonance, dipolar‐assisted rotational resonance, and angle‐dependent NMR. The primary structure of major ampullate of spider dragline silk consists of repeated polyalanine and a glycine‐rich regions. By analyzing the 13C conformation‐dependent chemical shifts and utilizing several solid‐state NMR techniques, it has been proposed that the glycine‐rich region primarily adopts a random coil conformation, including partially β‐sheet and β‐turn structures. This contradicts the previously suggested 31 helix conformation. On the other hand, the polyalanine region exhibits an antiparallel β‐sheet structure with staggered packing arrangements. Additionally, solid‐state NMR has also revealed the structure of fragelliform spider silk. These findings contribute to the understanding of the remarkable properties of spider dragline silks and provide insights into its atomic‐level architecture. [ABSTRACT FROM AUTHOR]

In the past decade, environmental DNA (eDNA) assays have become an essential tool to investigate species presence with samples from the environment instead of collected specimens. eDNA sampling techniques have proved their worth in freshwater and marine studies; now, some trends emerge for their use in terrestrial habitats and particularly to study arthropods. After a systematic review of the literature, we illustrate and analyse the diversity of such studies and discuss their benefits and drawbacks.We identified the most relevant research themes and focused on (i) the taxa and environmental sample types targeted and (ii) the details of the survey scheme. In parallel, we also assessed the available number of sequences from cytochrome c oxidase subunit I (COI), 16S and 18S barcode regions for four major taxa (spiders, centipedes, springtails and insects) in relation to their diversity.We found strong taxonomic and geographic biases regarding coverage per barcode. eDNA research on terrestrial arthropods mainly focuses on insect species that affect humanity in a positive or negative way, and the availability of sequences is much higher for species from temperate‐developed countries than from tropical ones. Moreover, although a high variety of environmental samples are being used, most studies do not assess the barcode completeness of the target taxa nor compare the efficacy of eDNA monitoring technique to other well established and known traditional techniques.Careful workflow designs and comparisons are needed before giving any management or conservation advice as eDNA monitoring does not come without error. Strengths and weaknesses of eDNA assays for conservation are discussed. [ABSTRACT FROM AUTHOR]

Latrophilins (LPHNs), a group of the G-protein–coupled receptor to which a spider venom latrotoxin (LTX) is known to bind, remain largely uncharacterized in neoplastic diseases. In the present study, we aimed to determine the role of LPHNs in the progression of prostate cancer. We assessed the actions of LPHNs, including LPHN1, LPHN2, and LPHN3, in human prostate cancer lines via their ligand (e.g., α-LTX, FLRT3) treatment or shRNA infection, as well as in surgical specimens. In androgen receptor (AR)-positive LNCaP/C4-2/22Rv1 cells, dihydrotestosterone considerably increased the expression levels of LPHNs, while chromatin immunoprecipitation assay revealed the binding of endogenous ARs, including AR-V7, to the promoter region of each LPHN. Treatment with α-LTX or FLRT3 resulted in induction in the cell viability and migration of both AR-positive and AR-negative lines. α-LTX and FLRT3 also enhanced the expression of Bcl-2 and phosphorylated forms of JAK2 and STAT3. Meanwhile, the knockdown of each LPHN showed opposite effects on all of those mediated by ligand treatment. Immunohistochemistry in radical prostatectomy specimens further showed the significantly elevated expression of each LPHN in prostate cancer, compared with adjacent normal-appearing prostate, which was associated with a significantly higher risk of postoperative biochemical recurrence in both univariate and multivariable settings. These findings indicate that LPHNs function as downstream effectors of ARs and promote the growth of androgen-sensitive, castration-resistant, or even AR-negative prostate cancer. [ABSTRACT FROM AUTHOR]

The escalating environmental impact of pollution and the imperative to reduce carbon emissions have heightened the significance of developing biobased materials from natural biomass for electronic devices. This study investigates the utilization of biofermentation‐produced recombinant spider silk and animal‐derived hemin to create a novel biobased electret for field‐effect transistor memory. A critical challenge arises from the incompatibility between natural photoresponsive molecules and insulating biomaterials, resulting in severe phase separation that compromises film quality and morphology uniformity. This study systematically examines the effects of various film deposition and manufacturing techniques on the biobased electret's morphology, phase separation, and performance. Different methods demonstrate distinct advantages in terms of molecular aggregation/segregation, morphological homogeneity, and device performance. Phototransistor memory devices fabricated using spin coating and spray coating techniques exhibit robust aggregations and high memory windows of ≈30 V. Conversely, devices produced through solution shearing and electrospinning methods display enhanced smooth morphologies and high photoresponsivity. The phototransistor memory comprising electrospun fibers holds the potential to achieve the highest memory ratio, reaching ≈105. These findings not only highlight the applications of biobased materials through scalable film deposition processes but also underscore the importance of refining their morphology, phase separation, and performance in optoelectronic devices. [ABSTRACT FROM AUTHOR]

The unique 3D structure of spider silk protein (spidroin) determines the excellent mechanical properties of spidroin fiber, but the difficulty of heterologous expression and poor spinning performance of recombinant spider silk protein limit its application. A high‐yield low‐molecular‐weight biomimetic spidroin (Amy‐6rep) is obtained by sequence modification, and its excellent spinning performance is verified by electrospinning it for use as a nanogenerator. Amy‐6rep increases the highly fibrogenic microcrystalline region in the core repeat region of natural spidroin with limited sequence length and replaces the polyalanine sequence with an amyloid polypeptide through structural similarity. Due to sequence modification, the expression of Amy‐6rep increased by ≈200%, and the self‐assembly performance of Amy‐6rep significantly increased. After electrospinning with Amy‐6rep, the nanofibers exhibit good tribopower generation capacity. In this paper, a biomimetic spidroin sequence design with high yield and good spinning performance is reported, and a strategy for electrospinning to produce an artificial nanogenerator is explored. [ABSTRACT FROM AUTHOR]

Multiple drug-resistant fungal species are associated with the development of diseases. Thus, more efficient drugs for the treatment of these aetiological agents are needed. Rondonin is a peptide isolated from the haemolymph of the spider Acanthoscurria rondoniae. Previous studies have shown that this peptide has antifungal activity against Candida sp. and Trichosporon sp. strains, acting on their genetic material. However, the molecular targets involved in its biological activity have not yet been described. Bioinformatics tools were used to determine the possible targets involved in the biological activity of Rondonin. The PharmMapper server was used to search for microorganismal targets of Rondonin. The PatchDock server was used to perform the molecular docking. UCSF Chimera software was used to evaluate these intermolecular interactions. In addition, the I-TASSER server was used to predict the target ligand sites. Then, these predictions were contrasted with the sites previously described in the literature. Molecular dynamics simulations were conducted for two promising complexes identified from the docking analysis. Rondonin demonstrated consistency with the ligand sites of the following targets: outer membrane proteins F (id: 1MPF) and A (id: 1QJP), which are responsible for facilitating the passage of small molecules through the plasma membrane; the subunit of the flavoprotein fumarate reductase (id: 1D4E), which is involved in the metabolism of nitrogenous bases; and the ATP-dependent Holliday DNA helicase junction (id: 1IN4), which is associated with histone proteins that package genetic material. Additionally, the molecular dynamics results indicated the stability of the interaction of Rondonin with 1MPF and 1IN4 during a 10 ns simulation. These interactions corroborate with previous in vitro studies on Rondonin, which acts on fungal genetic material without causing plasma membrane rupture. Therefore, the bioprospecting methods used in this research were considered satisfactory since they were consistent with previous results obtained via in vitro experimentation. [ABSTRACT FROM AUTHOR]

In many amphibians, males have sexually dimorphic breeding glands, which can produce proteinaceous or volatile pheromones, used for intraspecific communication. In this study we analyse two types of glands in the Mexican treefrog Ptychohyla macrotympanum (Hylidae)—large ventrolateral glands and small nuptial pads on their fingers—using histology, whole-transcriptome sequencing, and phylogenetic analyses. We found strong differences in glandular tissue composition and gene expression patterns between the two breeding gland types. In both glands we only found low expression of protein pheromone candidates. Instead, in the ventrolateral glands, gene expression was strikingly dominated by nicotinamide N -methyltransferase (NNMT)-like genes. The diversity of these genes was remarkably high, with at least 68 distinct NNMT-like genes. Our comparative phylogenetic analysis of the diversity of NNMT-like genes across vertebrates indicates that the extreme diversity of this gene is largely a frog-specific phenomenon and can be traced to large numbers of relatively recent gene duplications occurring independently in many lineages. The strong dominance and astonishing diversity of NNMT-like genes found in anurans in general, and in their sexually dimorphic breeding glands specifically, suggests an important function of NNMT-like proteins for anuran reproduction, possibly being related to volatile pheromone production. [ABSTRACT FROM AUTHOR]

Venom plays a crucial role in the defense and predation of venomous animals. Spiders (Araneae) are among the most successful predators and have a fascinating venom composition. Their venom mainly contains disulfide-rich peptides and large proteins. Here, we analyzed spider venom protein families, utilizing transcriptomic and genomic data, and highlighted their similarities and differences. We show that spiders have specific combinations of toxins for better predation and defense, typically comprising a core toxin expressed alongside several auxiliary toxins. Among them, the CAP superfamily is widely distributed and highly expressed in web-building Araneoidea spiders. Our analysis of evolutionary relationships revealed four subfamilies (subA-subD) of the CAP superfamily that differ in structure and potential functions. CAP proteins are composed of a conserved CAP domain and diverse C-terminal domains. CAP subC shares similar domains with the snake ion channel regulator svCRISP proteins, while CAP subD possesses a sequence similar to that of insect venom allergen 5 (Ag5). Furthermore, we show that gene duplication and selective expression lead to increased expression of CAP subD, making it a core member of the CAP superfamily. This study sheds light on the functional diversity of CAP subfamilies and their evolutionary history, which has important implications for fully understanding the composition of spider venom proteins and the core toxin components of web-building spiders. [ABSTRACT FROM AUTHOR]

Polyamines (PAs) are polycationic biogenic amines ubiquitously present in all life forms and are involved in molecular signaling and interaction, determining cell fate (e.g., cell proliferation, dif-ferentiation, and apoptosis). The intricate balance in the PAs' levels in the tissues will determine whether beneficial or detrimental effects will affect homeostasis. It's crucial to note that endoge-nous polyamines, like spermine and spermidine, play a pivotal role in our understanding of neu-rological disorders as they interact with membrane receptors and ion channels, modulating neuro-transmission. In spiders and wasps, monoamines (histamine, dopamine, serotonin, tryptamine) and polyamines (spermine, spermidine, acyl polyamines) comprise, with peptides and other sub-stances, the low molecular weight fraction of the venom. Acylpolyamines are venom components exclusively from spiders and a species of solitary wasp, which cause inhibition chiefly of iono-tropic glutamate receptors (AMPA, NMDA, and KA iGluRs) and nicotinic acetylcholine receptors (nAChRs). The first venom acylpolyamines ever discovered (argiopines, Joro and Nephila toxins, and philanthotoxins) have provided templates for the design and synthesis of numerous analogs. Thus far, analogs with high potency exert their effect at nanomolar concentrations, with high se-lectivity toward their ionotropic and ligand receptors. These potent and selective acylpolyamine analogs can serve biomedical purposes and pest control management. The structural modification of acylpolyamine with photolabile and fluorescent groups converted these venom toxins into use-ful molecular probes to discriminate iGluRs and nAchRs in cell populations. In various cases, the linear polyamines, like spermine and spermidine, constituting venom acyl polyamine backbones, have served as cargoes to deliver active molecules via a polyamine uptake system on diseased cells for targeted therapy. In this review, we examined examples of biogenic amines that play an essential role in neural homeostasis and cell signaling, contributing to human health and disease outcomes, which can be present in the venom of arachnids and hymenopterans. With an empha-sis on the spider and wasp venom acylpolyamines, we focused on the origin, structure, derivatiza-tion, and biomedical and biotechnological application of these pharmacologically attractive, chemically modular venom components. [ABSTRACT FROM AUTHOR]

PT1 peptide isolated from the venom of spider Geolycosa sp. is a modulator of P2X3 receptors that play a role in the development of inflammation and the transmission of pain impulses. The anti-inflammatory and analgesic efficacy of the PT1 peptide was studied in a model of complete Freund's adjuvant-induced paw inflammation in CD-1 mice. The analgesic activity of PT1 peptide was maximum after intramuscular injection at a dose of 0.01 mg/kg, which surpassed the analgesic effect of diclofenac at a dose of 1 mg/kg. The anti-inflammatory activity was maximum after intramuscular injection at a dose of 0.0001 mg/kg; a decrease in paw thickness was observed as soon as 2 h after the administration of the PT1 peptide against the background of inflammation development. All tested doses of PT1 peptide showed high anti-inflammatory activity 4 and 24 h after administration. PT1 peptide at a dose of 0.01 mg/kg when injected intramuscularly simultaneously produced high anti-inflammatory and analgesic effects compared to other doses of the peptide. Increasing the dose of PT1 peptide led to a gradual decrease in its analgesic and anti-inflammatory activity; increasing the dose of intramuscular injection to 0.1 and 1 mg/kg is inappropriate. [ABSTRACT FROM AUTHOR]

This document, published in the journal Biomedicines, discusses recent advances in the discovery of novel drugs from natural molecules. It highlights the potential of natural products as a source of new drugs, despite their structural complexity. The document explores various techniques and approaches, such as molecular biology, virtual screening, and metabolomics, that can be used to identify and develop drugs from natural compounds. It also presents specific examples of bioactive molecules derived from plants and their potential therapeutic applications. The document concludes by emphasizing the importance of natural products in drug discovery and discussing current limitations and future strategies in this field. [Extracted from the article]

Spiders are a diverse order of chelicerates that diverged from other arthropods over 500 million years ago. Research on spider embryogenesis, particularly studies using the common house spider Parasteatoda tepidariorum, has made important contributions to understanding the evolution of animal development, including axis formation, segmentation, and patterning. However, we lack knowledge about the cells that build spider embryos, their gene expression profiles and fate. Single-cell transcriptomic analyses have been revolutionary in describing these complex landscapes of cellular genetics in a range of animals. Therefore, we carried out single-cell RNA sequencing of P. tepidariorum embryos at stages 7, 8 and 9, which encompass the establishment and patterning of the body plan, and initial differentiation of many tissues and organs. We identified 20 cell clusters, from 18.5 k cells, which were marked by many developmental toolkit genes, as well as a plethora of genes not previously investigated. We found differences in the cell cycle transcriptional signatures, suggestive of different proliferation dynamics, which related to distinctions between endodermal and some mesodermal clusters, compared with ectodermal clusters. We identified many Hox genes as markers of cell clusters, and Hox gene ohnologs were often present in different clusters. This provided additional evidence of sub- and/or neo-functionalisation of these important developmental genes after the whole genome duplication in an arachnopulmonate ancestor (spiders, scorpions, and related orders). We also examined the spatial expression of marker genes for each cluster to generate a comprehensive cell atlas of these embryonic stages. This revealed new insights into the cellular basis and genetic regulation of head patterning, hematopoiesis, limb development, gut development, and posterior segmentation. This atlas will serve as a platform for future analysis of spider cell specification and fate, and studying the evolution of these processes among animals at cellular resolution. [ABSTRACT FROM AUTHOR]

Female sperm storage organs in arthropods are used as taxonomic characters since it is assumed that they do not change after maturation. However, in the Golden Silk spider, Trichonephila clavipes, the shape and sclerotization of the spermathecae change with a mating event. Moreover, mating in T. clavipes consists of several hundred copulations, but the male transfers all sperm during the first insertion of each pedipalp. Given this puzzling mating behaviour, we hypothesize that multiple copulations serve purposes other than sperm transfer and uptake, such as further altering the morphology of the storage site and/or transferring substances other than sperm. We compared virgin female T. clavipes with females after two copulations, one for each spermatheca, and after ad‐libitum mating. Each treatment consisted of two sub‐treatments in which the state of the sperm storage organs was inspected after a short (1–3 days) or a long (11 days) time interval after the female's final moult. The size of the spermathecae increased twofold in all mating treatments compared to virgin females. The thickness of the spermathecal wall increased significantly with time in all treatments similarly. The spermathecal epithelium, which releases secretion into the lumen of the spermathecae, seems most active in virgin females during the time when mating would normally occur and turns less active after mating and with age. The spermathecae contain secretion produced by the female before mating; and after mating, sperm and another secretion transferred by the male. The numerous sperm‐less matings in the ad‐libitum treatment resulted in male secretion in the copulatory ducts of the female genitalia, likely impeding sperm transfer by subsequent males. Out study shows that female genitalia can change considerably after having reached maturity and suggests that sperm‐less matings evolved in the context of sperm competition. [ABSTRACT FROM AUTHOR]

Envenomation by Loxosceles spiders can result in local and systemic pathologies. Systemic loxoscelism, which can lead to death, is characterized by intravascular hemolysis, platelet aggregation, and acute kidney injury. Sphingomyelinase D (SMase D) in Loxosceles spider venom is responsible for both local and systemic pathologies, and has been shown to induce metalloprotease activity. As the complement system is involved in many renal pathologies and is involved in hemolysis in systemic loxoscelism, the aim of this study was to investigate its role and the role of complement regulators and metalloproteases in an in vitro model of Loxosceles venom induced renal pathology. We investigated the effects of the venom/SMase D and the complement system on the HK-2 kidney cell line. Using cell viability assays, western blotting, and flow cytometry, we show that human serum, as a source of complement, enhanced the venom/SMase D induced cell death and the deposition of complement components and properdin. Inhibitors for ADAM-10 and ADAM-17 prevented the venom induced release of the of the complement regulator MCP/CD46 and reduced the venom/SMase D induced cell death. Our results show that the complement system can contribute to Loxosceles venom induced renal pathology. We therefore suggest that patients experiencing systemic loxoscelism may benefit from treatment with metalloproteinase inhibitors and complement inhibitors, but this proposition should be further analyzed in future pre-clinical and clinical assays. [ABSTRACT FROM AUTHOR]

Context: Due to their excellent biocompatibility and degradability, cellulose/spider silk protein composites hold a significant value in biomedical applications such as tissue engineering, drug delivery, and medical dressings. The interfacial interactions between cellulose and spider silk protein affect the properties of the composite. Therefore, it is important to understand the interfacial interactions between spider silk protein and cellulose to guide the design and optimization of composites. The study of the adsorption of protein on specific surfaces of cellulose crystal can be very complex using experimental methods. Molecular dynamics simulations allow the exploration of various physical and chemical changes at the atomic level of the material and enable an atomic description of the interactions between cellulose crystal planes and spider silk protein. In this study, molecular dynamics simulations were employed to investigate the interfacial interactions between spider silk protein (NTD) and cellulose surfaces. Findings of RMSD, RMSF, and secondary structure showed that the structure of NTD proteins remained unchanged during the adsorption process. Cellulose contact numbers and hydrogen bonding trends on different crystalline surfaces suggest that van der Waals forces and hydrogen bonding interactions drive the binding of proteins to cellulose. These findings reveal the interaction between cellulose and protein at the molecular level and provide theoretical guidance for the design and synthesis of cellulose/spider silk protein composites. Methods: MD simulations were all performed using the GROMACS-5.1 software package and run with CHARMM36 carbohydrate force field. Molecular dynamics simulations were performed for 500 ns for the simulated system. [ABSTRACT FROM AUTHOR]

Diet composition and its ecological drivers are rarely investigated in coexisting closely related species. We used a molecular approach to characterize the seasonal variation in diet composition in four spiny lizard species inhabiting a mountainous ecosystem. DNA metabarcoding revealed that the lizards Sceloporus aeneus, S. bicanthalis, S. grammicus, and S. spinosus mostly consumed arthropods of the orders Hemiptera, Araneae, Hymenoptera, and Coleoptera. The terrestrial lizards S. aeneus and S. bicanthalis mostly predated ants and spiders, whereas the arboreal–saxicolous S. grammicus and saxicolous S. spinosus largely consumed grasshoppers and leafhoppers. The taxonomic and phylogenetic diversity of the prey was higher during the dry season than the rainy season, likely because reduced prey availability in the dry season forced lizards to diversify their diets to meet their nutritional demands. Dietary and phylogenetic composition varied seasonally depending on the species, but only dietary composition varied with altitude. Seasonal dietary turnover was greater in S. spinosus than in S. bicanthalis, suggesting site‐specific seasonal variability in prey availability; no other differences among species were observed. S. bicanthalis, which lives at the highest altitude in our study site, displayed interseasonal variation in diet breadth. Dietary differences were correlated with the species' feeding strategies and elevational distribution, which likely contributed to the coexistence of these lizard species in the studied geographic area and beyond. [ABSTRACT FROM AUTHOR]

The article discusses the potential benefits of blocking acid-sensing ion channel 1a (ASIC1a) in reducing myocardial injury in rodent models of myocardial infarction (MI). The study found that administering the ASIC1a inhibitor, Hi1a, before or after the onset of ischemia reduced infarct size and prevented cardiac dysfunction associated with MI. Hi1a was also found to have minimal adverse effects on heart rhythm and blood pressure. The findings suggest that Hi1a could be a promising drug candidate for treating severe ischemic injury in patients with MI. Further research is needed to evaluate Hi1a in larger animal models and in co-morbid conditions to assess its potential for clinical translation. [Extracted from the article]

Scorpion venom peptides are generally classified into two main groups: the disulfide bridged peptides (DBPs), which usually target membrane-associated ion channels, and the non-disulfide bridged peptides (NDBPs), a smaller group with multifunctional properties. In the past decade, these peptides have gained interest because most of them display functions that include antimicrobial, anticancer, haemolytic, and anti-inflammatory activities. Our current study focuses on the short (9–19 amino acids) antimicrobial linear scorpion peptides. Most of these peptides display a net positive charge of 1 or 2, an isoelectric point at pH 9–10, a broad range of hydrophobicity, and a Grand Average of Hydropathy (GRAVY) Value ranging between −0.05 and 1.7. These features allow these peptides to be attracted toward the negatively charged phospholipid head groups of the lipid membranes of target cells, a force driven by electrostatic interactions. This review outlines the antimicrobial potential of short-chained linear scorpion venom peptides. Additionally, short linear scorpion peptides are in general more attractive for large-scale synthesis from a manufacturing point of view. The structural and functional diversity of these peptides represents a good starting point for the development of new peptide-based therapeutics. [ABSTRACT FROM AUTHOR]

Simple Summary: The description of a new species of camel spider, Gluvia brunnea sp. nov. Thorough morphological details, as well as molecular DNA and statistical analyses, serves to clearly differentiate this new species from Gluvia dorsalis (Latreille, 1817), the only species previously known from the Iberian Peninsula. We present the description of a new species of Solifugae from the Iberian Peninsula, Gluvia brunnea sp. nov., which has been found so far in southeast Spain. The morphological description is accompanied by molecular and multiple factor analyses, jointly giving full support to the specific status of the taxon. Finally, we discuss the intraspecific variability of both species, G. dorsalis and G. brunnea sp. nov., and the recent history of the genus. We also discuss the usefulness of multiple factor analysis for quantitatively separating species, and we stress that some specimens of this new species were found in Mesovoid Shallow Substratum stations, representing the very first time that Solifugae have been captured in this type of trap. [ABSTRACT FROM AUTHOR]

The pond wolf spider Pardosa pseudoannulata Bösenberg & Strand, 1906 (Araneae: Lycosidae) is an important predator of agricultural pests in southern, eastern and southeastern Asia. Here, we report the complete mitogenome of this spider reconstructed from Illumina sequencing data. The circular mitogenome length is 14,533 bp with the nucleotide composition A (33.3%), C (8.2%), G (15.2%), and T (43.3%). The P. pseudoannulata mitogenome comprises 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and a control region. Phylogenetic analyses of Lycosidae mitogenomes supported the monophyly of the subfamily Pardosinae and the two genera Pardosa and Alopecosa, and indicated the polyphyly of the subfamily Lycosinae and the paraphyly of its type genus Lycosa. In this study, P. pseudoannulata is the closest relative to P. pusiola. These results provide useful genetic information for future studies on the diversity, phylogeny, and evolution for wolf spiders. [ABSTRACT FROM AUTHOR]

In recent years, extensive research has delved into the pathophysiology of local reactions triggered by Bothrops snake venoms. Even though antivenom works well at reducing death and systemic effects, it is still not very effective in treating local reactions because it cannot counteract damage that has already been triggered. This limitation might be attributed to certain molecules that amplify the venom-induced innate response. While evidence suggests endogenous mediators at the venom site play a role in this envenomation, in Brazil, the concurrent use of anti-inflammatory agents or other drugs alongside antivenom remains uncommon. This study evaluated the pharmacological mediation of alterations in leukocyte–endothelium interactions following the experimental envenomation of mice with Bothrops jararaca venom, the main culprit of snake-related accidents in Southeast Brazil. We treated envenomed mice with inhibitors of different pharmacological pathways and observed the cremaster muscle microcirculation with intravital microscopy. We found that eicosanoids related to cyclooxygenase pathways and nitric oxide significantly contributed to B. jararaca venom-induced alterations in leukocyte–endothelium interactions. Conversely, lipoxygenase-mediated eicosanoids, histamine, and serotonin had minimal participation. Notably, dexamethasone and antivenom treatment diminished B. jararaca venom–induced alterations in leukocyte–endothelium interactions. The limited efficacy of the antivenom in managing Bothrops venom-induced local reactions emphasizes the critical need for supplementary treatments to enhance therapeutic outcomes. [ABSTRACT FROM AUTHOR]