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An unusually large amplitude spontaneous miniature endplate potentials (gMEPPs) occur naturally at low frequency at the vertebrate neuromuscular junction. Unlike the normal miniature endplate potentials (nMEPPs), these gMEPPs have long duration and long time to peak. More strikingly, gMEPPs seem to be independent of extracellular and intracellular Ca+2. and have a greater temperature sensitivity than nMEPPs. They are potentiated by tetrodotoxin but inhibited by acetylcholine (ACh) receptor blockers indicating ACh is the neurotransmitter responsible for gMEPPs. The frequency of gMEPPs is greatly increased in muscles weakened by various drugs, toxins or disease conditions suggesting that gMEPPs may be a part of possible neurotrophic mechanism to preserve effective neuromuscular transmission when the normal function is compromised. [ABSTRACT FROM AUTHOR]

Snakebites inflict significant injuries on humans and animals, posing a severe global public health challenge due to high mortality and morbidity rates. This study presents results against the venoms of Bothrops jararaca and Bothrops neuwiedi using sixteen synthetic hybrid molecules containing thiophene and triazoles, designated as 6a–h and 7a–h. The compounds were assessed for their ability to inhibit proteolytic and plasma coagulant activities induced by the snake venoms, and their toxicity was analyzed. Most derivatives demonstrated nontoxicity through in silico analysis with the Osiris Property Explorer tool and in vitro cytotoxic hemocompatibility on red blood cells. Notably, only derivative 6e exhibited toxicity to erythrocytes, while 6b, 6d, 7c, and 7f displayed mutagenic, tumorigenic, or adverse effects on the reproductive system. Derivatives 6a, 6c–h, 7c–e, 7g, or 7h effectively inhibited the coagulating activity of B. jararaca venom, while 6a–b, 6d–e, 6h, or 7a–f inhibited coagulation induced by B. neuwiedi venom. All derivatives demonstrated inhibition of the proteolytic activity caused by B. jararaca venom, and derivatives 6a–d and 7e–f inhibited the activity of B. neuwiedi venom. Consequently, these derivatives exhibited varying degrees of efficacy in countering two crucial toxic effects of B. jararaca or B. neuwiedi venoms, suggesting their potential as antivenoms against both species. [ABSTRACT FROM AUTHOR]

Snake venoms are complex mixtures of toxic proteins that hold significant medical, pharmacological and evolutionary interest. To better understand the genetic diversity underlying snake venoms, we developed VenomCap, a novel exon‐capture probe set targeting toxin‐coding genes from a wide range of elapid snakes, with a particular focus on the ecologically diverse and medically important subfamily Hydrophiinae. We tested the capture success of VenomCap across 24 species, representing all major elapid lineages. We included snake phylogenomic probes in the VenomCap capture set, allowing us to compare capture performance between venom and phylogenomic loci and to infer elapid phylogenetic relationships. We demonstrated VenomCap's ability to recover exons from ~1500 target markers, representing a total of 24 known venom gene families, which includes the dominant gene families found in elapid venoms. We find that VenomCap's capture results are robust across all elapids sampled, and especially among hydrophiines, with respect to measures of target capture success (target loci matched, sensitivity, specificity and missing data). As a cost‐effective and efficient alternative to full genome sequencing, VenomCap can dramatically accelerate the sequencing and analysis of venom gene families. Overall, our tool offers a model for genomic studies on snake venom gene diversity and evolution that can be expanded for comprehensive comparisons across the other families of venomous snakes. [ABSTRACT FROM AUTHOR]

In the Brazilian Amazon, snakebite envenomations (SBEs) disproportionately affect Indigenous populations, and have a significantly higher incidence and lethality than in non‐Indigenous populations. This qualitative study describes the Indigenous and biomedical healthcare domains for SBE care from the perspective of the Indigenous medical and nursing students in Manaus, Western Brazilian Amazon. In‐depth interviews were conducted with five Indigenous students from the Amazonas State University, between January and December 2021. The interviews were analyzed using inductive content analysis. We organized an explanatory model with five themes: (1) participants' identities; (2) causality levels in Indigenous and biomedical systems; (3) therapeutic itineraries in Indigenous and biomedical systems; (4) ideological implications of adding biomedical devices to Indigenous healing systems; and (5) therapeutic failure in and efficacy of Indigenous and biomedical systems. From a noncolonial perspective and seeking to increase the quality and acceptability of health care for the Indigenous populations of the Brazilian Amazon, the training of Indigenous health professionals presents itself as a promising strategy. For this goal, universities should serve as empowering settings for Indigenous health students that support them in their growth and development, raise their awareness of injustice, and catalyze change toward a culturally adapted and effective service for the users. [ABSTRACT FROM AUTHOR]

The eastern small eyed snake (Cryptophis nigrescens; CN) is an uncommon cause of snakebite in Australia despite the widespread distribution of the snake along the east coast of Australia. Diagnosis of envenomation relies on identification of the snake which is often not possible with animal snakebite cases. This study examined the immunoreactivity profile of CN venom towards specific rabbit IgG made against the medically relevant snake venom immunotypes found in Australia (tiger, brown, black, death adder and taipan). A simultaneous sandwich ELISA format was used to quantify CN venom binding to venom specific Protein A purified rabbit IgG. The binding profiles demonstrated weak binding of CN venom to rabbit IgG made against both tiger (N. scutatus) and black snake (P. australis) venoms with approximately 0.19% and 0.069% cross reactivity, respectively. However, the concentration of venom likely to be present in the urine of CN envenomed patients and the low cross reactivity suggest that envenomed veterinary patients are unlikely to be detected in the commercial snake venom detection kit. It is possible that CN envenomation is more common but may be underdiagnosed where snake venom antigen detection is relied upon solely. Serum biochemical abnormalities also overlap with other snake species found in the same geographical area. In respect of antivenom therapy, administration of tiger snake antivenom is supported by the binding data, but due to the low cross reactivity multiple vials may be required. Limited clinical evidence also supports the efficacy of tiger snake antivenom for envenomation by CN. [ABSTRACT FROM AUTHOR]

The advent of soft ionization mass spectrometry‐based proteomics in the 1990s led to the development of a new dimension in biology that conceptually allows for the integral analysis of whole proteomes. This transition from a reductionist to a global‐integrative approach is conditioned to the capability of proteomic platforms to generate and analyze complete qualitative and quantitative proteomics data. Paradoxically, the underlying analytical technique, molecular mass spectrometry, is inherently nonquantitative. The turn of the century witnessed the development of analytical strategies to endow proteomics with the ability to quantify proteomes of model organisms in the sense of "an organism for which comprehensive molecular (genomic and/or transcriptomic) resources are available." This essay presents an overview of the strategies and the lights and shadows of the most popular quantification methods highlighting the common misuse of label‐free approaches developed for model species' when applied to quantify the individual components of proteomes of nonmodel species (In this essay we use the term "non‐model" organisms for species lacking comprehensive molecular (genomic and/or transcriptomic) resources, a circumstance that, as we detail in this review‐essay, conditions the quantification of their proteomes.). We also point out the opportunity of combining elemental and molecular mass spectrometry systems into a hybrid instrumental configuration for the parallel identification and absolute quantification of venom proteomes. The successful application of this novel mass spectrometry configuration in snake venomics represents a proof‐of‐concept for a broader and more routine application of hybrid elemental/molecular mass spectrometry setups in other areas of the proteomics field, such as phosphoproteomics, metallomics, and in general in any biological process where a heteroatom (i.e., any atom other than C, H, O, N) forms integral part of its mechanism. [ABSTRACT FROM AUTHOR]

A reaction–diffusion system governing the predator–prey interaction with specialist predator and herd behavior for prey is investigated. Linear stability of the interior equilibrium is studied, and conditions guaranteeing the occurrence of Turing instability, induced by cross‐diffusion, are found, with a full characterization of the Turing instability region in the parameter space. Numerical simulations on the obtained results are provided. [ABSTRACT FROM AUTHOR]

Wasps have been neglected in toxinological studies, even with their diversity of species, when compared to other groups of venomous animals such as snakes, scorpions, and spiders. Solitary wasps, such as Pepsis decorata, are known for their mechanism of total or temporary paralysis of the host. In addition, their venoms are considered sources for studies of small peptides, bioactive peptides with neural and antimicrobial activities. In this work, some oligopeptides were analyzed by de novo sequencing identifying 39 oligopeptide sequences. Some sequences were similar to proctolin, a bradykinin‐potentiating peptide, and poneritoxin, one bradykinin‐related peptide. As proctolin‐like peptides were the major constituent in distinct experimental conditions, it was selected for further in silico studies in order to understand its possible importance as a constituent of wasp venom and whether these peptides could be of biotechnological importance. We investigate its binding mode comparing with proctolin and we further analyzed the importance of the tyrosine‐leucine‐glutamic acid (YLE) tripeptide‐motif conservation. This experimental, an in silico approach, increased the range of compounds identified in peptide analyses proving good characterization of little‐known peptidic compounds. [ABSTRACT FROM AUTHOR]

Introduction: Dilute Russell's viper venom time (dRVVT) and activated partial thromboplastin time (APTT) are the mainstay assays in lupus anticoagulant (LA) detection yet they have limitations, particularly in relation to interferences and specificity. The recently validated Taipan snake venom time (TSVT) screening with ecarin time (ET) confirmatory assays overcome many of those limitations due to the innate specificity engendered from direct prothrombin activation, and insensitivity to the effects of vitamin K antagonists (VKA). The present study aimed to further evidence diagnostic utility of TSVT/ET by performing them in samples from 116 nonanticoagulated patients with established triple‐positive antiphospholipid syndrome (APS). Methods: Samples were identified in three expert centres who performed dRVVT, APTT and solid phase antiphospholipid antibody assays with reagents from a variety of manufacturers. All samples additionally received TSVT/ET analysis using standardised reagents. Results: Ninety seven of 116 (83.6%) were dRVVT‐ and APTT‐positive, 85/97 (87.6%) of which were TSVT/ET‐positive, 9/116 (7.8%) were dRVVT‐positive only, 6 of which were TSVT/ET‐positive, and 10/116 (8.6%) were APTT‐positive only, 5 of which were TSVT/ET‐positive. 96/116 TSVT/ET‐positivity returned a high sensitivity for LA of 82.8%. Low coefficients of determination revealed weak relationships between LA potency and anticardiolipin and anti‐β2‐glycoprotein I antibody titres for all three LA assays. Conclusions: TSVT/ET has high sensitivity for the clinically significant LA found in triple positive APS patients. TSVT/ET can establish multiple LA assay positivity in nonanticoagulated patients negative for one of dRVVT or APTT, and is the only assay pairing insensitive to VKAs, the recommended anticoagulation for APS. [ABSTRACT FROM AUTHOR]

Atrial natriuretic peptide (ANP) plays a central role in the regulation of blood pressure and volume. ANP activities are mediated by natriuretic peptide receptor‐A (NPR‐A), a single‐pass transmembrane receptor harboring intrinsic guanylate cyclase activity. This study investigated the mechanism underlying NPR‐A‐dependent hormone recognition through the determination of the crystal structures of the NPR‐A extracellular hormone‐binding domain complexed with full‐length ANP, truncated mutants of ANP, and dendroaspis natriuretic peptide (DNP) isolated from the venom of the green Mamba snake, Dendroaspis angusticeps. The bound peptides possessed pseudo‐two‐fold symmetry, despite the lack of two‐fold symmetry in the primary sequences, which enabled the tight coupling of the peptide to the receptor, and evidently contributes to guanylyl cyclase activity. The binding of DNP to the NPR‐A was essentially identical to that of ANP; however, the affinity of DNP for NPR‐A was higher than that of ANP owing to the additional interactions between distinctive sequences in the DNP and NPR‐A. Consequently, our findings provide valuable insights that can be applied to the development of novel agonists for the treatment of various human diseases. [ABSTRACT FROM AUTHOR]

Snake venom contains a cocktail of compounds dominated by proteins and peptides, which make up the toxin. The toxin components of snake venom attack several targets in the human body including the neuromuscular system, kidney and blood coagulation system and cause pathologies. As such, the venom toxins can be managed and used for the treatment of these diseases. In this regard, Captopril used in the treatment of cardiovascular diseases was the first animal venom toxin‐based drug approved by the US Food and Drug Administration and the European Medicines Agency. Cancers cause morbidity and mortality worldwide. Due to side effects associated with the current cancer treatments including chemotherapy, radiotherapy, immunotherapy, hormonal therapy and surgery, there is a need to improve the efficacy of current treatments and/or develop novel drugs from natural sources including animal toxin‐based drugs. There is a long history of earlier and ongoing studies implicating snake venom toxins as potential anticancer therapies. Here, we review the role of crude snake venoms and toxins including phospholipase A2, L‐amino acid oxidase, C‐type lectin and disintegrin as potential anticancer agents tested in cancer cell lines and animal tumour models in comparison to normal cell lines. Some of the anti‐tumour activities of snake venom toxins include induction of cytotoxicity, apoptosis, cell cycle arrest and inhibition of metastasis, angiogenesis and tumour growth. We thus propose the advancement of multidisciplinary approaches to more pre‐clinical and clinical studies for enhanced bioavailability and targeted delivery of snake venom toxin‐based anticancer drugs. Snake venom contains toxins that attack different organs in the body. These toxins cause local and systemic pathologies. Ever since the approval of first snake venom‐based drug Captopril used in the treatment and management of cardiovascular diseases, there are ongoing researches towards the use of snake venom for the treatment of other diseases including cancer. Here, we have reviewed studies that reported the role of several snake venom and venom toxins including phospholipase A2, three‐finger toxins, L‐amino acid oxidase and disintegrin as potential anticancer agents. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy with charged particles at high dose and ultra‐high dose rate (uHDR) is a promising technique to further increase the therapeutic index of patient treatments. Dose rate is a key quantity to predict the so‐called FLASH effect at uHDR settings. However, recent works introduced varying calculation models to report dose rate, which is susceptible to the delivery method, scanning path (in active beam delivery) and beam intensity. Purpose: This work introduces an analytical dose rate calculation engine for raster scanned charged particle beams that is able to predict dose rate from the irradiation plan and recorded beam intensity. The importance of standardized dose rate calculation methods is explored here. Methods: Dose is obtained with an analytical pencil beam algorithm, using pre‐calculated databases for integrated depth dose distributions and lateral penumbra. Dose rate is then calculated by combining dose information with the respective particle fluence (i.e., time information) using three dose‐rate‐calculation models (mean, instantaneous, and threshold‐based). Dose rate predictions for all three models are compared to uHDR helium ion beam (145.7 MeV/u, range in water of approximatively 14.6 cm) measurements performed at the Heidelberg Ion Beam Therapy Center (HIT) with a diamond‐detector prototype. Three scanning patterns (scanned or snake‐like) and four field sizes are used to investigate the dose rate differences. Results: Dose rate measurements were in good agreement with in‐silico generated distributions using the here introduced engine. Relative differences in dose rate were below 10% for varying depths in water, from 2.3 to 14.8 cm, as well as laterally in a near Bragg peak area. In the entrance channel of the helium ion beam, dose rates were predicted within 7% on average for varying irradiated field sizes and scanning patterns. Large differences in absolute dose rate values were observed for varying calculation methods. For raster‐scanned irradiations, the deviation between mean and threshold‐based dose rate at the investigated point was found to increase with the field size up to 63% for a 10 mm × 10 mm field, while no significant differences were observed for snake‐like scanning paths. Conclusions: This work introduces the first dose rate calculation engine benchmarked to instantaneous dose rate, enabling dose rate predictions for physical and biophysical experiments. Dose rate is greatly affected by varying particle fluence, scanning path, and calculation method, highlighting the need for a consensus among the FLASH community on how to calculate and report dose rate in the future. The here introduced engine could help provide the necessary details for the analysis of the sparing effect and uHDR conditions. [ABSTRACT FROM AUTHOR]

The secreted phospholipase A2 (sPLA2) family of enzymes hydrolyzes glycerophospholipid substrates at the sn‐2 position of the acyl ester bond. Besides their roles in the degradation of phospholipids, these enzymes also play an important role in the immune response by promoting inflammation. The products of sPLA2‐catalysis (lysophospholipids and free fatty acids such as arachidonic acid) as well as secondary metabolites produced by the arachidonic acid cascade are mediators of inflammation and subsequent tissue injury. Based on their physiological functions, the sPLA2 enzymes are pharmacological targets for the treatment of diseases with an inflammatory component such as atherosclerosis and rheumatoid arthritis. Interestingly, sPLA2s may also have roles in various types of cancer such as malignant prostate cancer. While a number of sPLA2 inhibitors have been described, compounds which have been co‐crystallized with human sPLA2 enzymes are of much importance as such three‐dimensional structures provide valuable information regarding the structural requirements of good potency inhibitors as well as the molecular interactions between the enzyme and inhibitor. This review selected four structures of human sPLA2s complexed with inhibitors from the Protein Data Bank to illustrate the important molecular interactions of inhibitor compounds with the enzymes and to highlight the structural features important for interaction with the sPLA2 active site. In addition, the complex of the sPLA2 inhibitor, varespladib, with a Lys49‐PLA2‐like snake venom toxin is also discussed. Knowledge of the molecular interactions acquired from such structures would greatly aid the discovery of small molecule inhibitors of sPLA2s for the treatment of snakebite envenoming. The three‐dimensional structures presented in this review have been published by various research groups and have been deposited in the Protein Data Bank. [ABSTRACT FROM AUTHOR]

Recycling IgG antibodies bind to their target antigen at physiological pH in the blood stream and release them upon endocytosis when pH levels drop, allowing the IgG antibodies to be recycled into circulation via FcRn‐mediated cellular pathways, while the antigens undergo lysosomal degradation. This enables recycling antibodies to achieve comparable therapeutic effect at lower doses than their non‐recycling counterparts. The development of such antibodies is typically achieved by histidine doping of their variable regions or by performing in vitro antibody selection campaigns utilizing histidine doped libraries. Both are strategies that may introduce sequence liabilities. Here, we present a methodology that employs a naïve antibody phage display library, consisting of natural variable domains, to discover antibodies that bind α‐cobratoxin from the venom of Naja kaouthia in a pH‐dependent manner. As a result, an antibody was discovered that exhibits a 7‐fold higher off‐rate at pH 5.5 than pH 7.4 in bio‐layer interferometry experiments. Interestingly, no histidine residues were found in its variable domains, and in addition, the antibody showed pH‐dependent binding to a histidine‐devoid antigen mutant. As such, the results demonstrate that pH‐dependent antigen‐antibody binding may not always be driven by histidine residues. By employing molecular dynamics simulations, different protonation states of titratable residues were found, which potentially could be responsible for the observed pH‐dependent antigen binding properties of the antibody. Finally, given the typically high diversity of naïve antibody libraries, the methodology presented here can likely be applied to discover recycling antibodies against different targets ab initio without the need for histidine doping. [ABSTRACT FROM AUTHOR]

Nanotechnology can be used to produce nanoparticles (NPs) through the green route by using plant extract. NPs can be synthesized in many ways, but there is a growing need to build up high‐yield, low‐priced, harmless, and eco‐friendly procedures; thus, the green synthesis of NPs is one recent advancement in nanotechnology and nanoscience. The current study is designed for the development of an easy, feasible, and eco‐friendly, method for the biosynthesis of silver/gold (Ag/Au) monometallic NPs (MNPs) and their Ag/Au bimetallic NPs (BNPs) by using the metabolic extract of the novel Hippeastrum hybridum (HH) plant. The HH plant has not previously been used in the synthesis of BNPs. These NPs were then tested for their potential as a scavenger of different free radicals, that is, ferric chloride, 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH), hydrogen peroxide (H2O2), 2,2 azobis, 3‐ethyl benzothiazoline‐6‐sulphonic acid (ABTS), ammonium molybdate, anti‐enzyme activity against alpha‐amylase (α‐amylase), and snake venom enzyme acetylcholinesterase (AChE) to check their potential as antioxidants by using ultraviolet–visible (UV–vis) spectroscopy, energy dispersive x‐ray (EDX), scanning electron microscopy (SEM), x‐ray diffraction (XRD), and Fourier transform infrared (FT‐IR) spectroscopy investigations, MNPs and BNPs were both identified. According to UV–vis sharp peaks at 417, 576, and 542 nm were recorded, which corresponded to AgNPs, AuNPs, and BNPs, respectively. According to XRD examination, the crystal structure contains Ag, Au, and Ag/Au BNPs with average sizes of 13.3, 10.72, and 8.34 nm, respectively. Ag, Au, and Ag/Au BNPs possessed morphologies that were asymmetrical, according to SEM, and were calculated to be 40, 30, and 20 nm in size, respectively. The signal of Ag of the HH‐AgNPs was confirmed to be 22.75%, the Au signal of the HH‐AuNPs to be 48.08%, the Ag signal to be 12%, and the elemental Au signal to be 38.26% of the Ag/Au BNPs. The BNPs showed more significant activities as free radical scavengers with 86.58 ± 0.031 (ferric chloride), 50 ± 0.052 (molybdenum), 69.1 ± 0.31 (DPPH), 64.15 ± 0.31 (H2O2), and 70.55 ± 0.08 (ABTS) 50% inhibitory concentrations. BNPs competitively inhibit α‐amylase (Vmax remained unchanged, Km increased from 10.65% to 84.37% and 10.75% to 132.76%, respectively), while in the case of AChE, Km remained constant and Vmax decreased from 23.62% to 40.26% due to a non‐competitive type of inhibition. However, further research is suggested to reduce the drawbacks of NPs. [ABSTRACT FROM AUTHOR]

Time from birth or hatching to the first shed (postnatal ecdysis) in snakes ranges from about an hour to several weeks depending upon the species. We assessed patterns in time to postnatal ecdysis in 102 snake species for which we could source appropriate information, covering 2.6% of all extant snake species, and related measures to various biological traits. Reconstruction revealed ancestral time to postnatal ecdysis to be 11 days. Since time to postnatal ecdysis can be shorter or longer than the ancestral state, we argue that there are several competing drivers for time to postnatal ecdysis. A reduced time to postnatal ecdysis has evolved in several lineages, commonly in ambush‐foraging, viviparous vipers, while extended time to postnatal ecdysis is associated with oviparous species with maternal care. Of central importance is the impact of postnatal ecdysis on the scent levels of neonates, resulting in a reduction of time to postnatal ecdysis in chemically cryptic species, while the pivotal role of scent in mother–neonate recognition has resulted in the retention or extension of time to postnatal ecdysis. We showed that postnatal ecdysis improves chemical crypsis. The patterns revealed in this study suggest that measures of time to postnatal ecdysis can provide insights into the biology of snakes and be used as an indicator of certain life history traits. [ABSTRACT FROM AUTHOR]

Aims: Recent case reports have suggested that sodium‐glucose co‐transporter 2 (SGLT2) inhibitors may interact with statins to increase their risk of myotoxicity. We assessed the risk of myotoxicity reporting associated with concomitant use of SGLT2 inhibitors and statins. Methods: We queried the US Food and Drug Administration Adverse Event Reporting System (FAERS) from 2013 to 2021 for reports including SGLT2 inhibitors, statins or both. We estimated several measures of disproportionate reporting of myopathy and rhabdomyolysis associated with concomitant use of SGLT2 inhibitors and statins: reporting odds ratio (ROR) with 95% confidence interval (CI), Ω shrinkage measure (safety signal if >0) and an extension of the proportional reporting ratio (PRR) (two‐criteria set, safety signal if both criteria are met), using the full FAERS dataset as the reference set. In sensitivity analyses, we focussed on specific SGLT2 inhibitor‐statin pairs with higher interaction potential (canagliflozin‐rosuvastatin, empagliflozin‐rosuvastatin) and accounted for stimulated reporting. Results: There were 456 myopathy and 77 rhabdomyolysis reports involving both an SGLT2 inhibitor and a statin. Concomitant use of SGLT2 inhibitors and statins was not associated with an increased risk of myopathy (ROR 0.79, 95% CI 0.70 to 0.89) or rhabdomyolysis (ROR 0.58, 95% CI 0.41 to 0.83) reporting. For both outcomes, the Ω shrinkage measure was negative and only one criterion of the PRR extension was met. SGLT2 inhibitor‐statin pairs with higher interaction potential yielded potential signals for rhabdomyolysis; these signals disappeared after accounting for stimulated reporting. Conclusion: There was no increased risk of myotoxicity reporting associated with concomitant use of SGLT2 inhibitors and statins or for specific drug pairs. [ABSTRACT FROM AUTHOR]

Antagonistic coevolution between natural enemies can produce highly exaggerated traits, such as prey toxins and predator resistance. This reciprocal process of adaptation and counter‐adaptation may also open doors to other evolutionary novelties not directly involved in the phenotypic interface of coevolution. We tested the hypothesis that predator–prey coevolution coincided with the evolution of conspicuous coloration on resistant predators that retain prey toxins. In western North America, common garter snakes (Thamnophis sirtalis) have evolved extreme resistance to tetrodotoxin (TTX) in the coevolutionary arms race with their deadly prey, Pacific newts (Taricha spp.). TTX‐resistant snakes can retain large amounts of ingested TTX, which could serve as a deterrent against the snakes' own predators if TTX toxicity and resistance are coupled with a conspicuous warning signal. We evaluated whether arms race escalation covaries with bright red coloration in snake populations across the geographic mosaic of coevolution. Snake colour variation departs from the neutral expectations of population genetic structure and covaries with escalating clines of newt TTX and snake resistance at two coevolutionary hotspots. In the Pacific Northwest, bright red coloration fits an expected pattern of an aposematic warning to avian predators: TTX‐resistant snakes that consume highly toxic newts also have relatively large, reddish‐orange dorsal blotches. Snake coloration also seems to have evolved with the arms race in California, but overall patterns are less intuitively consistent with aposematism. These results suggest that interactions with additional trophic levels can generate novel traits as a cascading consequence of arms race coevolution across the geographic mosaic. see also the Perspective by John N. Thompson [ABSTRACT FROM AUTHOR]

The knowledge about interactions between predators and prey is essential for understanding the natural history of animals, especially snakes, which are cryptic organisms that are difficult to visualize in the wild. This article reports on the predation of lizards, frogs, bats and venomous snakes by the snake Philodryas nattereri, evidencing its generalist feeding habits. [ABSTRACT FROM AUTHOR]

DNA barcoding has greatly facilitated studies of taxonomy, biodiversity, biological conservation, and ecology. Here, we establish a reliable DNA barcoding library for Chinese snakes, unveiling hidden diversity with implications for taxonomy, and provide a standardized tool for conservation management. Our comprehensive study includes 1638 cytochrome c oxidase subunit I (COI) sequences from Chinese snakes that correspond to 17 families, 65 genera, 228 named species (80.6% of named species) and 36 candidate species. A barcode gap analysis reveals gaps, where all nearest neighbour distances exceed maximum intraspecific distances, in 217 named species and all candidate species. Three species‐delimitation methods (ABGD, sGMYC, and sPTP) recover 320 operational taxonomic units (OTUs), of which 192 OTUs correspond to named and candidate species. Twenty‐eight other named species share OTUs, such as Azemiops feae and A. kharini, Gloydius halys, G. shedaoensis, and G. intermedius, and Bungarus multicinctus and B. candidus, representing inconsistencies most probably caused by imperfect taxonomy, recent and rapid speciation, weak taxonomic signal, introgressive hybridization, and/or inadequate phylogenetic signal. In contrast, 43 species and candidate species assign to two or more OTUs due to having large intraspecific distances. If most OTUs detected in this study reflect valid species, including the 36 candidate species, then 30% more species would exist than are currently recognized. Several OTU divergences associate with known biogeographic barriers, such as the Taiwan Strait. In addition to facilitating future studies, this reliable and relatively comprehensive reference database will play an important role in the future monitoring, conservation, and management of Chinese snakes. [ABSTRACT FROM AUTHOR]

A biomimetic receptor for glucose has been developed with high affinity and selectivity. The receptor was efficiently synthesized in three steps through dynamic imine chemistry followed by imine‐to‐amide oxidation. The receptor features two parallel durene panels, forming a hydrophobic pocket for [CH⋅⋅⋅π] interactions, and two pyridinium residues directing four amide bonds towards the pocket. These pyridinium residues not only improve solubility but also provide polarized C−H bonds for hydrogen bonding. Experimental data and DFT calculations show that these polarized C−H bonds significantly enhance substrate binding. These findings demonstrate the power of dynamic covalent chemistry for creating molecular receptors and using polarized C−H bonds for boosted carbohydrate recognition in water, providing a foundation for developing glucose‐responsive materials and sensors. [ABSTRACT FROM AUTHOR]

The article focuses on the evaluation of newly developed dilute Russell's viper venom reagents for lupus anticoagulant (LA) detection. It reports on the comparison of the new reagents with established reagents and assesses their diagnostic performance, indicating that the new formulation shows promise for LA detection in clinical laboratories.

Understanding the molecular basis of adaptations in coevolving species requires identifying the genes that underlie reciprocally selected phenotypes, such as those involved in venom in snakes and resistance to the venom in their prey. In this regard, California ground squirrels (CGS; Otospermophilus beecheyi) are eaten by northern Pacific rattlesnakes (Crotalus oreganus oreganus), but individual squirrels may still show substantial resistance to venom and survive bites. A recent study using proteomics identified venom interactive proteins (VIPs) in the blood serum of CGS. These VIPs represent possible resistance proteins, but the sequences of genes encoding them are unknown despite the value of such data to molecular studies of coevolution. To address this issue, we analyzed a de novo assembled transcriptome from CGS liver tissue—where many plasma proteins are synthesized—and other tissues from this species. We then examined VIP sequences in terms of three characteristics that identify them as possible resistance proteins: evidence for positive selection, high liver expression, and nonsynonymous variation across CGS populations. Based on these characteristics, we identified five VIPs (i.e., α‐2‐macroglobulin, α‐1‐antitrypsin‐like protein GS55‐LT, apolipoprotein A‐II, hibernation‐associated plasma protein HP‐20, and hibernation‐associated plasma protein HP‐27) as the most likely candidates for resistance proteins among VIPs identified to date. Four of these proteins have been previously implicated in conferring resistance to the venom in mammals, validating our approach. When combined with the detailed information available for rattlesnake venom proteins, these results set the stage for future work focused on understanding coevolutionary interactions at the molecular level between these species. Research Highlights: Using RNA‐sequencing data from liver, we assembled a California ground squirrel transcriptome and used it to identify putative resistance proteins that interact with northern Pacific rattlesnake venom proteins setting the stage for molecular studies of coevolution. [ABSTRACT FROM AUTHOR]

Characterizing the diet of imperiled species using minimally invasive methods is crucial to understanding their ecology and conservation requirements. Here, we apply a DNA metabarcoding approach to study the diet of the eastern massasauga rattlesnake (Sistrurus catenatus), a Federally Threatened snake found throughout the Great Lakes region. Eighty‐three fecal samples collected across 10 different massasauga populations located in Michigan, USA, were sequenced, with 70 samples containing prey DNA. We used universal metazoan primers and developed a host‐specific oligonucleotide blocker to characterize their diet. We identified at least 12 different prey species, with eastern massasaugas exhibiting opportunistic feeding and a strong preference towards small mammals. Meadow voles (Microtus pennsylvanicus) were the most common prey item (70% of diet) followed by the northern short‐tailed shrew (Blarina brevicauda) and masked shrew (Sorex cinereus; 15.7% of diet each), along with occasional bird and snake prey. Adult individuals exhibited a more generalized diet, consuming a larger number of prey taxa on average. Younger snakes consumed a smaller variety of prey items and tended to consume smaller‐sized mammals such as masked shrews (Sorex cinereus) and northern short‐tailed shrews (Blarina brevicauda). We conclude that small mammals are a crucial part of eastern massasauga rattlesnake diet and recommend this be taken into consideration when conservation strategies are developed. The methods developed in this study can be applied to other reptile species, providing an accurate, minimally invasive, and thorough diet assessment for at‐risk reptile species. [ABSTRACT FROM AUTHOR]

The structure, composition, and shape of teeth have been related to dietary specialization in many vertebrate species, but comparative studies on snakes' teeth are lacking. Yet, snakes have diverse dietary habits that may impact the shape of their teeth. We hypothesize that prey properties, such as hardness and shape, as well as feeding behavior, such as aquatic or arboreal predation, or holding vigorous prey, impose constraints on the evolution of tooth shape in snakes. We compared the morphology of the dentary teeth of 63 species that cover the phylogenetic and dietary diversity of snakes, using 3D geometric morphometrics and linear measurements. Our results show that prey hardness, foraging substrate, and the main feeding mechanical challenge are important drivers of tooth shape, size, and curvature. Overall, long, slender, curved teeth with a thin layer of hard tissue are observed in species that need to maintain a grip on their prey. Short, stout, less curved teeth are associated with species that undergo high or repeated loads. Our study demonstrates the diversity of tooth morphology in snakes and the need to investigate its underlying functional implications to better understand the evolution of teeth in vertebrates. [ABSTRACT FROM AUTHOR]

Objective: The pathology of snake envenomation is closely tied to the severity of edema in the tissue surrounding the area of the bite. Elucidating the mechanisms that promote the development of such severe edema is critical to a better understanding of how to treat this life‐threatening injury. We focused on one of the most abundant venom components in North American viper venom, crotamine, and the effects it has on the cells and function of the lymphatic system. Methods: We used RT‐PCR to identify the location and relative abundance of crotamine's cellular targets (Kvα channels) within the tissues and cells of the lymphatic system. We used calcium flux, nitrate production, and cell morphometry to determine the effects of crotamine on lymphatic endothelial cells. We used tracer transport, node morphometry, and node deposition to determine the effects of crotamine on lymph transport in vivo. Results: We found that genes that encode targets of crotamine are highly present in lymphatic tissues and cells and that there is a differential distribution of those genes that correlates with phasic contractile activity. We found that crotamine potentiates calcium flux in human dermal lymphatic endothelial cells in response to stimulation with histamine and sheer stress (but not alone) and that it alters the production of nitric oxide in response to shear as well as changes the level of F‐actin polymerization of those same cells. Crotamine alters lymphatic transport of large molecular weight tracers to local lymph nodes and is deposited within the node mostly in the immediate subcapsular region. Conclusion: This evidence suggests that snake venom components may have an impact on the function of the lymphatic system. This needs to be studied in greater detail as there are numerous venom components that may have effects on aspects of the lymphatic system. This would not only provide basic information on the pathobiology of snakebite but also provide targets for improved therapeutics to treat snakebite. [ABSTRACT FROM AUTHOR]

The 2019–2020 Australian megafires were unprecedented in their intensity and extent. These wildfires may have caused high mortality of adult broad‐headed snakes Hoplocephalus bungaroides which shelter inside tree hollows during summer. We evaluated the impacts of two high‐intensity wildfires (2002 Touga Fire and 2020 Morton Fire) on a broad‐headed snake population in Morton National Park, south‐eastern Australia. We analysed a 29‐year mark–recapture data set to estimate survival rates of adults in years with and without wildfires, and with and without human disturbance to rock outcrops. To examine the short‐term effects of fire on occupancy, we analysed presence–absence data collected from 25 sites during 2019 and 2020. Estimates of occupancy were higher for 2020 (0.93 ± 0.09) than for 2019 (0.66 ± 0.14), while detection rates were constant (0.40 ± 0.06). Over the period 1992–2020, the best supported Cormack–Jolly–Seber model was one in which adult survival rates were high and stable (0.81 ± 0.04), but were 23% lower in years when humans disturbed rocks (0.63 ± 0.08). A model in which adult mortality was 20% higher in years with human disturbance and 14% higher in years with wildfires was also supported. Estimates of abundance revealed that the population declined by 34% after the Touga Fire, and 26% after the Morton Fire. Over the 29‐year study, the population has declined by 60%. Our results highlight how mortality events from wildfires need to be evaluated in the context of other threatening processes. For this population, the removal of snakes and associated habitat disturbance poses a more serious threat to population viability than infrequent wildfires. [ABSTRACT FROM AUTHOR]

Keywords: centipede; CT scan; diet; feeding; rear-fanged; rim rock crowned snake; Scolopendra; Tantilla oolitica; venom EN centipede CT scan diet feeding rear-fanged rim rock crowned snake Scolopendra Tantilla oolitica venom 1 5 5 01/04/23 20230101 NES 230101 The rim rock crowned snake ( I Tantilla oolitica i ) may be the rarest species of snake in North America (Ernst & Ernst, [5]). Anecdotal observations of snake-centipede encounters in rear-fanged I Tantilla i and African centipede eaters ( I Aparallactus i ) in the family Atractaspididae indicate that their venom can rapidly subdue their prey, whereas the snakes appear resistant to centipede venom (Rodríguez-Robles, [13]). We first conducted a standard CT scan of the specimen to visualize the densest structures, such as the snake's skeleton and the portion of the centipede outside the snake. Centipede, CT scan, diet, feeding, rear-fanged, rim rock crowned snake, Scolopendra, Tantilla oolitica, venom. [Extracted from the article]

The solid‐state thermal structure transformation of methylammonium vanadate, (CH3NH3)VO3, from −150 °C to 350 °C is reported. Variable‐temperature X‐ray single‐crystal structure analysis at 23, 0, −50, −100, and −150 °C reveal (CH3NH3)VO3 comprises of methylammonium cations and "snake‐like" ([VO3]−)n anion chains propagating along the c‐direction in the Pna21 space group. In between −150 and −100 °C, we observe a reversible structural transformation due to the re‐orientation of the methylammonium cations in the crystal packing, which is also confirmed by the reversible profiles observed in differential scanning calorimetry. The methylammonium vanadate is stable until at ca. 100 °C and further heating releases methylamine and water and V2O5 is formed at ca. 275 °C. Furthermore, we show that the methylammonium vanadate can be used as a negative staining reagent for visualizing SARS‐CoV‐2, allowing us to discern the spike proteins from the body of the virus using transmission electron microscopy. [ABSTRACT FROM AUTHOR]

Summary: After polyploidization originated from one interspecific hybridization event in Gossypium, Gossypium barbadense evolved to produce extra‐long staple fibres than Gossypium hirsutum (Upland cotton), which produces a higher fibre yield. The genomic diversity between G. barbadense and G. hirsutum thus provides a genetic basis for fibre trait variation. Recently, rapid accumulation of gene disruption or deleterious mutation was reported in allotetraploid cotton genomes, with unknown impacts on fibre traits. Here, we identified gene disruptions in allotetraploid G. hirsutum (18.14%) and G. barbadense (17.38%) through comparison with their presumed diploid progenitors. Relative to conserved genes, these disrupted genes exhibited faster evolution rate, lower expression level and altered gene co‐expression networks. Within a module regulating fibre elongation, a hub gene experienced gene disruption in G. hirsutum after polyploidization, with a 2‐bp deletion in the coding region of GhNPLA1D introducing early termination of translation. This deletion was observed in all of the 34 G. hirsutum landraces and 36 G. hirsutum cultivars, but not in 96% of 57 G. barbadense accessions. Retrieving the disrupted gene GhNPLA1D using its homoeolog GhNPLA1A achieved longer fibre length in G. hirsutum. Further enzyme activity and lipids analysis confirmed that GhNPLA1A encodes a typical phospholipase A and promotes cotton fibre elongation via elevating intracellular levels of linolenic acid and 34:3 phosphatidylinositol. Our work opens a strategy for identifying disrupted genes and retrieving their functions in ways that can provide valuable resources for accelerating fibre trait enhancement in cotton breeding. [ABSTRACT FROM AUTHOR]

Summary: The gel‐forming ability of myofibrillar protein (MP) is highly correlated with the characteristics of emulsified meat products. Incorporation of Agaricus bisporus (Ab) powder into MP gels may enhance its gel properties to facilitate the development of a novel and safe meat product. Therefore, this study investigated the effects of Ab powder on gel strength, water holding capacity (WHC), texture, rheological behaviour, LF‐NMR spin–spin relaxation (T2), microstructure and protein secondary structure of the MP gel system. The results indicated that the gel strength, WHC, G' value and G" value were significantly improved when the addition of Ab powder increased from 0% to 6% (P < 0.05). Meanwhile, the T2 relaxation time was shortened, and free water was transformed into immobilised water. The texture of the gel was improved when 1%–4% Ab powder was added compared to the control. Furthermore, Ab filled in the gel network and promoted the unfolding of MP α‐helix and the formation of MP β‐sheet during the thermal denaturation of MP, leading to a dense aggregated network structure. The study suggested that Ab could be a promising ingredient in improving chicken MP's gel properties and developing fat‐reduced meat products. [ABSTRACT FROM AUTHOR]

Summary: Lactobacillus plantarum was involved in producing low‐salt (2%, w/w) dry‐cured Spanish mackerel, and its effect on the degradation of myofibrillar protein and production of umami peptides was investigated. Results showed that the dominant microbiome of the sample was Lactobacillus plantarum, accounting for 95.7% of the microbial community. The umami peptides in this dry‐cured mackerel were extracted and separated by ultra‐filtration and gel filtration chromatography and further identified by Nano‐LC–MS/MS. Five umami‐enhancing peptides, including TFYNELRV (1040 Da), TFYNELR (941 Da), TLFQPSF (838 Da), LYANNVL (805 Da) and FAGDDAPRAVFPS (1348 Da), were identified to be derived from myofibrillar protein, and the percentage of their hydrophobic amino acid were 42.85%, 33.33%, 57.14%, 57.14% and 53.84%, respectively. The synthetic peptides of these five umami peptides showed an umami‐enhancing threshold value ranging from 0.34 to 0.45 mg mL−1 through sensory evaluation. The SDS‐PAGE analysis exhibited that actin band intensity was decreased during the processing of dry‐cured mackerel. Therefore, Lactobacillus plantarum has the potential to improve the hydrolysis of myofibrillar protein to produce umami peptides in dry‐cured mackerel. [ABSTRACT FROM AUTHOR]

Jatropha mollissima is endemic to Brazil and is used for traditional medicinal purposes, including the treatment of snakebite. In this study, latex obtained from this plant was fractioned using reversed‐phase chromatography, and the fractions were then screened for peptides. A 755 g/mol peptide was obtained, and MS/MS analyses indicated it had a cyclic sequence (Pro‐Leu‐Gly‐Val‐Leu‐Leu‐Tyr). This peptide sequence was present in the Jatropha genome database, and an identity value of 90.71%, an E‐value of 0.0, and a score of 883 with NO‐associated protein 1/chloroplastic/mitochondria of Jatropha curcas were obtained from the NCBI nonredundant protein sequence (nr) database. Molecular docking analyses performed with the peptide against a metalloendopeptidase belonging to Crotalus adamanteus snake venom suggested the cyclic peptide establishes favorable interactions with the catalytic site of the enzyme. Therefore, it could inhibit enzyme catalysis. This belief was corroborated by the formation of 6 hydrogen bonds with the linear form of the peptide. Tighter complexation of the cyclic form (41 kcal/mol more energetic) revealed better spatial blocking. The linear form outperformed the cyclic form in complexing the required energy, recruiting more catalytic residues (6/2), and in establishing more hydrogen bonds (6/3). However, cyclic folding provided a more significant spatial block within the catalytic site. The set of results suggests that the cycle peptide, here called Jatromollistatin, which was previously described as jatrophidin and pohlianin A in two other species of Jatropha, is a promising candidate to inhibit venom proteases. This belief is corroborated by the topical use of the latex for initial treatment of snakebites. [ABSTRACT FROM AUTHOR]

Background and Purpose: Venomous animals express numerous Kunitz‐type peptides. The mambaquaretin‐1 (MQ1) peptide identified from the Dendroaspis angusticeps venom is the most selective antagonist of the arginine‐vasopressin V2 receptor (V2R) and the only unique Kunitz‐type peptide active on a GPCR. We aimed to exploit other mamba venoms to enlarge the V2R‐Kunitz peptide family and gain insight into the MQ1 molecular mode of action. Experimental Approach We used a bio‐guided screening assay to identify novel MQs and placed them phylogenetically. MQs were produced by solid‐phase peptide synthesis and characterized in vitro by binding and functional tests and in vivo by diuresis measurement in rats. Key Results: Eight additional MQs were identified with nanomolar affinities for the V2R, all antagonists. MQs form a new subgroup in the Kunitz family, close to the V2R non‐active dendrotoxins and to two V2R‐active cobra toxins. Sequence comparison between active and non‐active V2R Kunitz peptides highlighted five positions, among which four are involved in V2R interaction and belong to the two large MQ1 loops. We finally determined that eight positions, part of these two loops, interact with the V2R. The variant MQ1‐K39A showed a higher affinity for the hV2R, but not for the rat V2R. Conclusions and Implications: A new function and mode of action is associated with the Kunitz peptides. The number of MQ1 residues involved in V2R binding is large and may explain its absolute selectivity. MQ1‐K39A represents the first step in the improvement of the MQ1 design from a medicinal perspective. [ABSTRACT FROM AUTHOR]

The substrate use by animals may influence both their morphology and diet. Species of the genus Chironius are among the most conspicuous frog‐eating, arboreal snakes in South America. The aim of the present study was to investigate whether diet and morphology relate to substrate use in five sympatric Chironius species from the Atlantic Forest. Our hypothesis is that habitat pressure is strong enough so that even closely related species will present differences. We collected morphological and diet data from specimens of C. bicarinatus, C. exoletus, C. foveatus, C. fuscus, and C. laevicollis housed in scientific collections. Information on habitat use were obtained by monitoring free‐ranging animals using thread‐bobbins and also from the literature. Our results demonstrate that C. foveatus is the most arboreal species, and C. laevicollis is the most terrestrial among the five studied species. Chironius foveatus is the slenderest, with one of the longest relative tail lengths, the narrowest ventral scales, the highest vertebral density, the largest eye diameter, green body color, and diet based on tree frogs (Hylidae). These traits indicate a higher arboreality for this species. On the other extreme, C. laevicollis is the stoutest species, and has the shortest tail, the largest head, the lowest vertebral density, and diet based on ground‐living frogs (Leptodactylidae). These traits indicate pronounced terrestriality for this species. The other three species have traits intermediate between the extremes showed by C. foveatus and C. laevicollis. We found evidence for a close relationship between arboreality or terrestriality, morphology, and diet. [ABSTRACT FROM AUTHOR]

Understanding the mechanisms that produce cellular cytotoxicity is fundamental in the field of toxicology. Cytotoxic stimuli can include organic toxins such as hemorrhagic snake venom, which can lead to secondary complications such as the development of necrotic tissue and profuse scarring. These clinical manifestations mimic cytotoxic responses induce by other organic compounds such as organic acids. We used hemorrhagic snake venom and human embryonic kidney cells (HEK 293T) as a model system to better understand the cellular responses involved in venom induced cytotoxicity. Cells stimulated with Crotalus atrox (CA) (western diamondback) venom for 4 or 10 h demonstrated significant cytotoxicity. Results from 2′,7′‐Dichlorodihydrofluorescein diacetate (H2DCF‐DA) assays determine CA venom stimulation induces a robust production of reactive oxygen species (ROS) over a 3‐h time course. In contrast, pretreatment with polyethylene glycol (PEG)‐catalase or N‐acetyl cysteine (NAC) prior to CA venom stimulation significantly blunted H2DCFDA fluorescence fold changes and showed greater cytoprotective effects than cells stimulated with CA venom alone. Pre‐ incubating HEK293T cells with the NADPH oxidase (NOX) pan‐inhibitor VAS2870 prior venom stimulation significantly minimized the venom‐induced oxidative burst at early timepoints (≤2 h). Collectively, our experiments show that pre‐application of antioxidants reduces CA venom induce cellular toxicity. This result highlights the importance of ROS in the early stages of cytotoxicity and suggests muting ROS production in noxious injuries may increase positive clinical outcomes. Understanding the mechanisms that produce cellular cytotoxicity is fundamental in the field of toxicology. We used hemorrhagic snake venom as a model system to better understand cytotoxicity from noxious stimuli. Cell stimulated with CA venom showed a robust production of reactive oxygen species (ROS). The pre‐application of antioxidants reduced CA venom‐induced ROS and cellular toxicity This result highlights the importance of ROS in the early stages of cytotoxicity and suggests muting ROS production in noxious injuries may increase positive clinical outcomes. [ABSTRACT FROM AUTHOR]

Each year, thousands of people fall victim to envenomings caused by cobras. These incidents often result in death due to paralysis caused by α‐neurotoxins from the three‐finger toxin (3FTx) family, which are abundant in elapid venoms. Due to their small size, 3FTxs are among the snake toxins that are most poorly neutralized by current antivenoms, which are based on polyclonal antibodies of equine or ovine origin. While antivenoms have saved countless lives since their development in the late 18th century, an opportunity now exists to improve snakebite envenoming therapy via the application of new biotechnological methods, particularly by developing monoclonal antibodies against poorly neutralized α‐neurotoxins. Here, we describe the use of phage‐displayed synthetic antibody libraries and the development and characterization of six synthetic antibodies built on a human IgG framework and developed against α‐cobratoxin – the most abundant long‐chain α‐neurotoxin from Naja kaouthia venom. The synthetic antibodies exhibited sub‐nanomolar affinities to α‐cobratoxin and neutralized the curare‐mimetic effect of the toxin in vitro. These results demonstrate that phage display technology based on synthetic repertoires can be used to rapidly develop human antibodies with drug‐grade potencies as inhibitors of venom toxins. [ABSTRACT FROM AUTHOR]

To achieve successful development, female parasitoids, while laying eggs, introduce various virulence factors, mainly venoms, into host insects to manipulate their physiology. Although numerous studies have been conducted to characterize the components of venoms that regulate host immune responses, few systematic investigations have been conducted on the roles of venom proteins in host metabolic regulation. In this investigation, we characterized a novel venom protein in Pachycrepoideus vindemiae called glucose‐6‐phosphate dehydrogenase (PvG6PDH) and showed it has a vital role in regulating host carbohydrate metabolism. PvG6PDH encodes 510 amino acids and features a signal peptide and two conserved "G6PDH" domains. Multiple sequence alignment showed it has high amino acid identity with G6PDH from other pteromalids, and quantitative polymerase chain reaction analysis and immunofluorescent staining demonstrated a significantly higher expression of PvG6PDH in the venom apparatus compared with the carcass. We report that PvG6PDH contributes to parasitism by inhibiting the glucose‐6‐phosphate (G6P) metabolism of host Drosophila melanogaster, as demonstrated by PvG6PDH injection and RNA interference analysis. Further tests revealed that the accumulation of host G6P was caused by the transcriptional inhibition of G6P‐metabolism‐related genes. These findings greatly contribute to our understanding of venom‐mediated host metabolic regulation, further laying the foundation for the development of venom proteins as biological agents for pest control. [ABSTRACT FROM AUTHOR]

The present review covers available results on the application of FT‐MS for the de novo sequencing of natural peptides of various animals: cones, bees, snakes, amphibians, scorpions, and so forth. As these peptides are usually bioactive, the animals efficiently use them as a weapon against microorganisms or higher animals including predators. These peptides represent definite interest as drugs of future generations since the mechanism of their activity is completely different in comparison with that of the modern antibiotics. Utilization of those peptides as antibiotics can eliminate the problem of the bacterial resistance development. Sequence elucidation of these bioactive peptides becomes even more challenging when the species genome is not available and little is known about the protein origin and other properties of those peptides in the study. De novo sequencing may be the only option to obtain sequence information. The benefits of FT‐MS for the top‐down peptide sequencing, the general approaches of the de novxxo sequencing, the difficult cases involving sequence coverage, isobaric and isomeric amino acids, cyclization of short peptides, the presence of posttranslational modifications will be discussed in the review. [ABSTRACT FROM AUTHOR]

A new strategy combined gold‐coated magnetic nanocomposites assisted enrichment with mass spectrometry was developed for the characterization of disulfide bond‐contained proteins from Chinese cobra (Naja atra) venom. In this work, core‐shell nanocomposites were synthesized by the seed‐mediated growth method and used for the enrichment of snake venom proteins containing disulfide bonds. A total of 3545 tryptic digested peptides derived from 96 venom proteins in Naja atra venom were identified. The venom proteins comprised 14 toxin families including three‐finger toxins, phospholipase A2, snake venom metalloproteinase, cobra venom factor, and so forth. Extra 16 venom proteins were detected exclusively in the nanocomposites set, among which 11 venom proteins were from the three‐finger toxins family. In the present study, the proposed simple and efficient protocol replaced the tedious and laborious technologies commonly used for pre‐separating crude snake venom, suggesting widely implementation in low‐abundance or trace disulfide bond‐contained proteins or peptides characterization. [ABSTRACT FROM AUTHOR]

Snake venom is produced, transported and delivered by the sophisticated venom delivery system (VDS). When snakes bite, the venom travels from the venom gland through the venom duct into needle‐like fangs that inject it into their prey. To counteract breakages, fangs are continuously replaced throughout life. Currently, the anatomy of the connection between the duct and the fang has not been described, and the mechanism by which the duct is reconnected to the replacement fang has not been identified. We examined the VDS in 3D in representative species from two families and one subfamily (Elapidae, Viperidae, Atractaspidinae) using contrast‐enhanced microCT (diceCT), followed by dissection and histology. We observed that the venom duct bifurcates immediately anterior to the fangs so that both the original and replacement fangs are separately connected and functional in delivering venom. When a fang is absent, the canal leading to the empty position is temporarily closed. We found that elapid snakes have a crescent‐shaped venom reservoir where venom likely pools before it enters the fang. These findings form the final piece of the puzzle of VDS anatomy in front‐fanged venomous snakes. Additionally, they provide further evidence for independent evolution of the VDS in these three snake taxa. [ABSTRACT FROM AUTHOR]

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B Method/Summary of work b : We developed an NBA pipeline that (1) generates patient-specific disease networks by integrating and mapping multifaceted datasets (that include differentially expressed genes from patient's transcriptomic data, the deregulated transcription factors, disease-specific genes from GWAS studies and drug targets of interest) on to the large-scale protein-protein interaction network, (2) identifies key molecules and pathways in the patient-specific disease network and (3) scores each identified potential drug target based on the network connectivity score (that reflects signal propagation) and expression level. J Neurosci; 30: 573 - 582. https://doi.org/10.1523/JNEUROSCI.3295-09.2010 Oral Communications, Tuesday 7th September Oral Communications - Cardiovascular & Respiratory B OC001 b B The effects of allopurinol treatment in early period of monocrotaline-induced rat pulmonary hypertension model b Gokcen Telli SP 1 sp , Inci Kazkayasi SP 1 sp , E. Inci Ergonul SP 2 sp and Serdar Uma SP 1 sp SP 1 sp I Department of Pharmacology, Hacettepe University Faculty of Pharmacy; i SP 2 sp I Republic of Turkey Ministry of Health i B Introduction/Background & aims b : Along with the greater understanding of the pathogenesis of pulmonary hypertension (PH), one of the new treatment approaches is to evaluate the effectiveness of drugs used in diseases with pathologies similar to that of PH [1]. This study investigates the effect of this drug on cell death and proliferative signalling pathways in AML cells in vitro. [Extracted from the article]

The proline‐rich oligopeptide from Bothrops jararaca snake venom, Bj‐PRO‐7a, promotes acute effects in blood pressure in hypertensive animals. However, the cardiac effects of this heptapeptide are completely unknown. Thus, we sought to evaluate whether the Bj‐PRO‐7a could protect against cardiac remodelling in spontaneously hypertensive rats (SHR). SHR were treated with Bj‐PRO‐7a (71 nmol/kg/day, s.c.) or saline for 28 days. Wistar rats were used as control. Systolic blood pressure (SBP) and heart rate (HR) were measured by tail‐cuff plethysmography. Cardiomyocyte diameter and interstitial and perivascular fibrosis of the left ventricle (LV) were evaluated using Picrosirius staining. Immunofluorescence was used to detect collagen I and III. Fibroblast proliferation was assessed by immunohistochemistry to detect proliferating cell nuclear antigen (PCNA). Protein expression was assessed by western blot. The superoxide dismutase and catalase activities and the concentration of lipid peroxidation products were evaluated in the LV. The SBP and HR were not different between treated and non‐treated SHR at the end of the treatment. However, Bj‐PRO‐7a attenuated the cardiomyocyte hypertrophy, deposition of interstitial and perivascular fibrosis and collagen I, and positive PCNA‐labelled fibroblasts. This peptide also reduced the increased levels of TBARS, expression and activity of catalase, and activity of SOD in LV from SHR. Also, the Bj‐PRO‐7a increased the expression of metalloproteinases‐2 in SHR hearts. These findings demonstrate that the Bj‐PRO‐7a reduced the pathological cardiac remodelling in a pressure‐independent manner in hypertensive rats through mechanisms mediated by oxidative stress regulation. [ABSTRACT FROM AUTHOR]

Background: Scorpion stings comprise a serious problem throughout the globe, especially in regions where they are more frequent. Despite a recent upsurge of interest in scorpion venoms by various research groups, there remain many challenges. Objective: Therefore, in this study, we aimed to study the toxicity and protein composition of venoms of Hottentotta saulcyi, Hottentotta schach and Androctonus crassicauda, three scorpion species collected in Iran. Materials and Methods: Scorpion species were collected from Esfahan farm scorpion company and maintained in the laboratory in containers that mimic their natural habitat. Venom was extracted from A. crassicauda, H. schach and H. saulcyi by electrical stimulation of 8 and 10 V. The toxicity of each venom was established by using four groups of male Swiss albino mice aged 2 months (weighting 18–20 g) for testing each dose of venom. One group was used as a control. Venom was injected into mice by subcutaneous route. Then, animals were monitored for 24 h and LD50 was estimated by the graphic method of Miller and Tainter. Thus, high‐performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method was used to determine amino acids in the venom, and protein concentrations were determined by the Biuret method. Results: LD50 of scorpion venoms by subcutaneous route was found to be 1.70 mg/kg b.w (A. crassicauda), 1.47 mg/kg b.w (H. saulcyi) and 0.85 mg/kg b.w (H. schach). A. crassicauda, H. saulcyi and H. schach contain 26, 30, and 31 amino acids, respectively. A. crassicauda contains low concentrations of alpha‐aminoadipic acid, beta‐aminoisobutyric acid, beta‐alanine and citrulline. H. saulcyi contains a concentration of hydroxylysine, whereas H. schach has no such concentration. A. crassicauda also had the highest levels of tyrosine and threonine. Only A. crassicauda venom contains a low proportion of proteins (14.80%) compared with those of H. schach (16.26%) and H. saulcyi (16.20%). Albumin content in the venoms was 11.7% (H. saulcyi), 5.4% (H. schach) and 4.4% (A. crassicauda). Conclusion: Scorpions venoms have a variable toxicity and an interesting composition in amino acids and proteins. Work on the development of anti‐venom is fundamental. [ABSTRACT FROM AUTHOR]

With the rapid development of commercial flexible/wearable devices, flexible batteries have attracted great attention as optimal power sources. However, a combination of high energy density and excellent arbitrary deformation ability is still a critical challenge to satisfy practical applications. Inspired by rigid and soft features of chemical molecular structures, novel bidirectional flexible snake‐origami lithium‐ion batteries (LIBs) with both high energy density and favorable flexibility are designed and fabricated. The flexible snake‐origami battery consists of rigid and soft segments, where the former is designed as the energy unit and the latter served as the deformation unit. With the unique features from such design, the as‐fabricated battery with calculating all the components exhibits a record‐setting energy density of 357 Wh L−1 (133 Wh kg−1), compared with the cell‐scale flexible LIBs achieved from both academic and industry. Additionally, a design principle is established to verify the validity of utilizing rigid‐soft‐coupled structure for enduring various deformations, and the intrinsic relationship between battery structure, energy density, and flexibility can be confirmed. The results suggest that the design principle and performance of bidirectional flexible snake‐origami batteries will provide a new reliable strategy for achieving high energy flexible batteries for wearable devices. [ABSTRACT FROM AUTHOR]

Introduction: The major systemic manifestation of hemotoxicity in human snakebite envenoming is venom‐induced consumption coagulopathy (VICC). A subset of patients with VICC develop thrombotic microangiopathy (TMA), in which acute kidney injury (AKI) occurs. We aimed to investigate the association between schistocytosis in snakebite patients with VICC and AKI, compared to non‐envenomed patients. Methods: Serial blood films collected from a prospective cohort of snakebite patients (Australian Snakebite Project) were examined. Cases were classified a priori as non‐envenomed snakebites (normal controls), envenomed without VICC, partial VICC without AKI, complete VICC without AKI, and VICC with AKI based on defined clinical and laboratory criteria. The percentage of schistocytes between groups was compared and correlated by Kendall's tau b test. Results: Seven hundred and eighty blood films from 234 snakebite cases were analyzed. There was a statistically significant correlation (τ =.69, SE.03, P <.001) for schistocytosis between the ordered groups of non‐envenomed snakebites, envenomed without VICC, partial VICC without AKI, complete VICC without AKI, and VICC with AKI groups. Patients with VICC and AKI had a platelet nadir median of 42 × 109/L (interquartile range [IQR] :25‐130 × 109/L), hemoglobin nadir of median 107 g/L (IQR 66‐122 g/L), and maximum LDH median of 1128 U/L (IQR 474‐3255 U/L). A 1.0% threshold for schistocytosis yielded 90% sensitivity (95% CI: 67%‐98%) and 71% specificity (95% CI: 62%‐79%) for predicting AKI in patients with VICC. Conclusion: Schistocyte quantitation has good diagnostic utility in snakebite patients with VICC. A definition of snakebite TMA as MAHA with ≥1.0% schistocytes and thrombocytopenia, would appear to be appropriate. [ABSTRACT FROM AUTHOR]

Aim: The emergence of venom is an evolutionary innovation that favoured the diversification and survival of snakes. The composition of snake venoms is known in detail from venom gland proteomic data. However, there is still a gap of knowledge about the forces that lead to the expression of different toxins in different proportions in the venom cocktail across space and time. Location: World. Time period: Modern. Major taxa studied: Elapidae and Viperidae. Methods: We integrated proteomic data with phylogenetic comparative methods to understand how ecological and biogeographic processes drive the evolution of snake venom. Results: We observed that more productive environments favour a more complex venom, with more toxins in similar proportions. We found that taxa that live on islands, where there is lower variability of resources, tended to present less complex venom dominated by few toxins. In such cases, the extent of an island's isolation seems to be a relevant factor for faster fixation of specific venom compositions. Main conclusion: We show that ecological and biogeographic processes, which can act differentially over time and space, affect the gene expression of toxins in snake venoms. [ABSTRACT FROM AUTHOR]

Motivation: The understanding of physiological adaptations, of evolutionary radiations and of ecological responses to global change urges for global, comprehensive databases of the functional traits of extant organisms. The ability to maintain an adequate water balance is a critical functional property influencing the resilience of animal species to climate variation. In terrestrial or semi‐terrestrial organisms, total water loss includes a significant contribution from evaporative water loss (EWL). The analysis of geographic and phylogenetic variation in EWL rates must however account for differences in methods and potential confounding factors, which influence standard measures of whole‐organism water loss. We compiled the global and standardized SquamEWL database of total, respiratory and cutaneous EWL for 325 species and subspecies of squamate reptiles (793 samples and 2,536 estimates) from across the globe. An extensive set of companion data and annotations associated with the EWL measurements of potential value for future investigation, including metabolic rate data, is provided. We present preliminary descriptive statistics for the compiled data, discuss gaps and biases, and identify promising avenues to update, expand and explore this database. Main types of variables contained: Standard water loss rates, geographic data, metabolic rates. Spatial location: Global. Time period: Data were obtained from extant species and were collected between 1945 and 2020. Major taxa: Reptilia, Squamata including lizards, snakes and amphisbaenians. Level of measurements: Individual samples of animals from the same species, locality, age class and sex category. Software format: csv. [ABSTRACT FROM AUTHOR]

The first toxin to give rise to the three‐finger protein (TFP) family was α‐bungarotoxin (α‐Bgt) from Bungarus multicinctus krait venom. α‐Bgt was crucial for research on nicotinic acetylcholine receptors (nAChRs), and in this Review article we focus on present data for snake venom TFPs and those of the Ly6/uPAR family from mammalians (membrane‐bound Lynx1 and secreted SLURP‐1) interacting with nAChRs. Recently isolated from Bungarus candidus venom, αδ‐bungarotoxins differ from α‐Bgt: they bind more reversibly and distinguish two binding sites in Torpedo californica nAChR. Naja kaouthia α‐cobratoxin, classical blocker of nAChRs, was shown to inhibit certain GABA‐A receptor subtypes, whereas α‐cobratoxin dimer with 2 intermolecular disulfides has a novel type of 3D structure. Non‐conventional toxin WTX has additional 5th disulfide not in the central loop, as α‐Bgt, but in the N‐terminal loop, like all Ly6/uPAR proteins, and inhibits α7 and Torpedo nAChRs. A water‐soluble form of Lynx1, ws‐Lynx1, was expressed in E. coli, its 1H‐NMR structure and binding to several nAChRs determined. For SLURP‐1, similar information was obtained with its recombinant analogue rSLURP‐1. A common feature of ws‐Lynx1, rSLURP‐1, and WTX is their activity against nAChRs and muscarinic acetylcholine receptors. Synthetic SLURP‐1, identical to the natural protein, demonstrated some differences from rSLURP‐1 in distinguishing nAChR subtypes. The loop II fragment of the Lynx1 was synthesized having the same µM affinity for the Torpedo nAChR as ws‐Lynx1. This review illustrates the productivity of parallel research of nAChR interactions with the two TFP groups. [ABSTRACT FROM AUTHOR]