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opencc-zeroDec 2022View details →

Data for: Epistatic effects between amino acid insertions and substitutions mediate toxin-resistance of vertebrate Na+, K+-ATPases

The recurrent evolution of resistance to cardiotonic steroids (CTS) across diverse animals most frequently involves convergent amino-acid substitutions in the H1-H2 extracellular loop of Na+, K+-ATPase (NKA). Previous work revealed that hystricognath rodents (e.g. chinchilla) and pterocliform birds (sandgrouse) have convergently evolved amino-acid insertions in the H1-H2 loop, but their functional significance was not known. Using protein engineering, we show that these insertions have distinct effects on CTS resistance in homologs of each of the two species that strongly depend on intramolecular interactions with other residues. Removing the insertion in the chinchilla NKA unexpectedly increases CTS resistance and decreases NKA activity. In the sandgrouse NKA, the amino acid insertion and substitution Q111R both contribute to an augmented CTS resistance without compromising ATPase activity levels. Molecular docking simulations provide additional insight into the biophysical mechanisms responsible for the context-specific mutational effects on CTS insensitivity of the enzyme. Our results highlight the diversity of genetic substrates that underlie CTS insensitivity in vertebrate NKA and reveal how amino-acid insertions can alter the phenotypic effects of point mutations at key sites in the same protein domain.

opencc-zeroMar 2023View details →

Conspicuous coloration of toxin-resistant predators implicates additional trophic interactions in a predator-prey arms race

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 co-varies with bright red coloration in snake populations across the geographic mosaic of coevolution. Snake color variation departs from the neutral expectations of population genetic structure and co-varies 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.

opencc-zeroApr 2023View details →

Data for: No physiological costs of dual sequestration of chemically different plant toxins in the milkweed bug Spilostethus saxatilis (Heteroptera: Lygaeidae)

Many herbivorous insects not only cope with plant toxins but also sequester them as a defense against predators and parasitoids. Sequestration is a product of the evolutionary arms race between plants and herbivorous insects and has been hypothesized to incur physiological costs due to specific adaptations required. Contradictory evidence about these costs exists for insects sequestering only one class of toxin, but very little is known about the physiological implications for species sequestering structurally different classes of compounds. Spilostethus saxatilis is a milkweed bug belonging to the cardenolide-sequestering heteropteran subfamily Lygaeinae (Heteroptera: Lygaeidae) that has shifted to the colchicine-containing plant Colchicum autumnale, a resource of chemically unrelated alkaloids. Using feeding-assays on artificial diet and chemical analysis, we assessed whether S. saxatilis is still able to sequester cardenolides apart from colchicine and related metabolites (colchicoids), and tested the effect of (1) either a natural cardenolide concentration (using ouabain as a model compound) or a natural colchicine concentration, (2) an increased concentration of both toxins, and (3) seeds of either Asclepias syriaca (cardenolides) or C. autumnale (colchicoids) on a set of life-history traits. For comparison, we assessed the same life-history traits in the milkweed bug Oncopeltus fasciatus exposed to cardenolides only. Although cardenolides and colchicoids have different physiological targets (Na+/K+-ATPase vs tubulin) and thus require different resistance traits, chronic exposure and sequestration of both isolated toxins caused no physiological costs such as reduced growth, increased mortality, lower fertility, or shorter adult life span in S. saxatilis. Indeed, an increased performance was observed in O. fasciatus and an according trend was found in S. saxatilis when feeding on isolated ouabain and isolated colchicine, respectively. Positive effects were even more pronounced when insects were provided with natural toxic seeds (i.e. C. autumnale for S. saxatilis and A. syriaca for O. fasciatus), especially in O. fasciatus. Our findings suggest, that S. saxatilis can sequester two chemically unrelated classes of plant compounds at a cost-free level, and that colchicoids may even play a beneficial role in terms of fertility.

opencc-zeroJul 2023View details →

Data from: Use of a toxin sequestered from exotic prey by a non-coevolved predator

Here, we chose a well-known system of invasive species to test whether non-coevolved predators can sequester and use toxins from exotic prey. Together with the invasive prickly pear plants, cochineal bugs (Dactylopius spp.) are spreading worldwide from their native range in the Americas. These insects produce carminic acid, a defensive anthraquinone that some specialized predators of cochineal bugs sequester for their own defense. We carried out a series of experiments to test whether non-coevolved predators in the exotic range of cochineal bugs can also sequester carminic acid and potentially benefit from this substance. We designed a series of experiments to test whether non-coevolved predators that feed on exotic cochineal bugs can sequester carminic acid and use it to release it on demand and repel their potential enemies. We first identified and quantified the resident predators that exploit cochineal bugs in the Mediterranean basin, an area invaded by cochineal bugs. Then, we determined whether the most abundant coccinellid predator tolerated, sequestered, and released carminic acid in the reflex-bleeding. Finally, we quantified the deterrent effect of carminic acid against antagonistic ants present in the invaded area. This data collection gathers different datasets collected by Ángel Plata between 2020 and 2022. It is organized in three different folders according to previously stated objectives. Each folder contains a file with the collected data. Besides the data, each folder contains README files that explain the methodology for collecting the data and README files that describe the structure of the data. When necessary, the calculation sheets and the codes related to statistical analysis and generation of figures are also included.

opencc-zeroJul 2023View details →

The plant toxin 4-methylsulfinylbutyl isothiocyanate decreases herbivore performance and modulate cellular and humoral immunity

Insect herbivores frequently encounter plant defense molecules, but the physiological and ecological consequences for their immune systems are not fully understood. The majority of studies attempting to relate levels of plant defensive chemistry to herbivore immune responses have used natural population or species-level variation in plant defensive chemistry. Yet, this potentially confounds the effects of plant defense chemistry with other potential traits that may affect the expression of herbivore immunity such as development time and nutritional quality. We have used an artificial diet containing known quantities of a plant toxin (4-methylsulfinylbutyl isothiocyanate; 4MSOB-ITC or ITC), an isothiocyanate present in many plants in the genus Brassica, to explicitly explore the effects of a plant toxin on the cellular and humoral immune responses of the generalist herbivore Trichoplusia ni (Lepidoptera: Noctuidae) that frequently feeds on glucosinolate-containing plants. Caterpillars feeding on diets with high concentrations of ITC experienced reduced survivorship and growth rates. High concentrations of ITC suppressed the appearance of several types of hemocytes and melanization activity, which are critical defenses against parasitic Hymenoptera and microbial pathogens. In terms of T. ni humoral immunity, only the antimicrobial peptide (AMP) genes lebocin and gallerimycin were significantly upregulated in caterpillars fed on diets containing high levels of 4MSOB-ITC relative to caterpillars that were provided with ITC-free diet. Surprisingly, challenging caterpillars with a non-pathogenic strain of Escherichia coli resulted in the upregulation of the AMP gene cecropin. Feeding on high concentrations of plant toxins hindered caterpillar development and decreased cellular immunity but conferred mixed effects on humoral immunity. Our findings provide novel insights into the effects of herbivore diet composition on insect performance demonstrating the role of specific plant defense toxins that shape herbivore immunity and trophic interactions.

opencc-zeroJul 2023View details →

Late instar monarch caterpillars sabotage milkweed to acquire toxins, not to disarm plant defense

Sabotaging milkweed by monarch caterpillars (Danaus plexippus) is a famous textbook example of disarming plant defense. By severing leaf veins or petioles, monarchs are thought to prevent the flow of toxic latex to their feeding site. Here we show that sabotaging by monarch caterpillars is not only an avoidance strategy. While young caterpillars appear to avoid latex, late-instar caterpillars actively ingest exuding latex, presumably to increase sequestration of toxic latex cardenolides used for defense against predators. Comparisons with caterpillars of the related but non-sequestering common crow butterfly (Euploea core) revealed three lines of evidence supporting our hypothesis. First, monarch caterpillars sabotage inconsistently and therefore the behavior is not obligatory to feed on milkweed, whereas sabotaging precedes each feeding event in Euploea caterpillars. Second, monarch caterpillars shift their behavior from latex avoidance in younger stages to eager drinking in later stages, whereas Euploea caterpillars consistently avoid latex and spit it out during sabotaging. Third, monarchs reared on detached leaves without latex, sequestered more cardenolides when caterpillars imbibed latex offered with a pipette. Thus, we conclude that monarch caterpillars have transformed the 'sabotage to avoid' strategy of their relatives into a 'sabotage to consume' strategy implying a novel behavioral adaptation to increase sequestration of cardenolides for defense.

zenodo36/100

Code and data for "Bordetella adenylate cyclase toxin elicits chromatin remodeling and transcriptional reprogramming that blocks differentiation of monocytes into macrophages"

# Code and data for "Bordetella adenylate cyclase toxin elicits chromatin remodeling and transcriptional reprogramming that blocks differentiation of monocytes into macrophages" - `pipeline` contains scripts for processing raw reads with `nf-core/rnaseq` Nextflow pipeline   - `setup_conda.sh` sets up a conda environment for Nextflow   - `samplesheet.csv` describes the samples   - `rna-seq-nextflow.sh` runs the analysis - `data` contains the quantifications by Salmon from the pipeline and data for the CRE motif (see `analysis.Rmd` for more details) - `analysis.Rmd` an R notebook containing a code to reproduce conclusions and figures in the paper and additional comments. The R environment (all packages) is reproducibly reconstructed via `renv` - run `renv::restore()` after loading the project. The generated figures and tables are stored in the `outputs` directory.

opencc-by-4.0Jul 2023View details →

zenodo36/100

Venom: Toxin Accessory Domain Search

This contains the different fasta files used and generated for the search of accessory domains fused with toxin proteins in a variety of venoms and tick saliva.  2023-06-15-updated-venom-tick-proteins.fasta :  fasta file of our custom "venom proteins from transcriptomes” data set, that was generated from the transcriptomes of venom glands of 124 species and from the salivary glands of 21 tick species uniprot-toxin-clustering_rep_seq.fasta: fasta file of all the representative sequences of the UniProt manually curated database of proteins and toxins from various venoms (from the animal toxin annotation project ) obtained after clustering. 2023-06-20-outliers-accessory-hits.fasta: fasta file of the accessory sequences identified on the toxin outliers observed in venoms and saliva. updated-accessory-toxin-clustering_rep_seq.fasta: fasta file of the representative sequences of the toxin outliers accessory sequences obtained after clustering.

opencc-by-4.0Aug 2023View details →

zenodo36/100

Data from "Tissue and toxin-specific divergent evolution in plant defense"

Files and code necessary to replicate the results from the manuscript are described as follows: Syrfampop.sas --> SAS code to conduct the analyses. HPLC_asyr.csv --> contains the cardenolide data of root, leaf and seed tissue from each individual plant belonging to multiple families of each of the two populations (main analysis in SAS code). chemmantelcorr.csv --> contains the correlation matrices between cardenolides within a given tissue (permutation test in SAS code) SS.csv --> contains the sums of squares matrices of cardenolide concentrations at the population and family levels for each tissue and whole plant after the MANOVA in the SAS code (used for the R code in Martin et al. (2008)). ehdbp.vcf --> Description of SNP data used for this study. ehdbp.arp --> SNP data in Arlequin format ready for FST analysis.

opencc-by-4.0Aug 2023View details →

Botulinum Toxin is a Potential Prophylactic Therapy for Minimizing Post-excisional Scarring (Allergan Botox Scar Study)

ClinicalTrials.gov study NCT02623829. IPD Sharing: Not stated. Countries: 1. Publications: 11.

closedIPD-NOFeb 2026View details →

"Follow the Sutures". A New Procedure for Injection of Botulinum Toxin for Chronic Migraine

ClinicalTrials.gov study NCT03543254. IPD Sharing: NO. Countries: 1. Publications: 1.

Randomized DB Controlled Trial of Botulinum Toxin A in Hemiplegic Shoulder Pain and Spasticity

ClinicalTrials.gov study NCT00661089. IPD Sharing: Not stated. Countries: 1. Publications: 1.

Safety and Efficacy Study of Botulinum Toxin Type A to Treat Lower Urinary Symptoms Due to Benign Prostatic Hyperplasia

ClinicalTrials.gov study NCT00284518. IPD Sharing: Not stated. Countries: 11. Publications: 1.

Condensed and Distributed Robotic Therapy in Spastic Stroke Post Botulinum Toxin Injection

ClinicalTrials.gov study NCT03321097. IPD Sharing: Not stated. Countries: 1. Publications: 1.

Safety and Efficacy Study of Botulinum Toxin Type A for the Treatment of Crow's Feet Lines and Frown Lines

ClinicalTrials.gov study NCT01189760. IPD Sharing: Not stated. Countries: 4. Publications: 1.

closedIPD-NOFeb 2026View details →

Botulinum Toxin Treatment of Glabellar Lines: Efficacy and Safety Study II

ClinicalTrials.gov study NCT02677805. IPD Sharing: NO. Countries: 1. Publications: 1.

controlledIPD-YESFeb 2026View details →

Botulinum Toxin Injection for the Management of BPH

ClinicalTrials.gov study NCT00451191. IPD Sharing: YES. Countries: 1. Publications: 1.

A Long-term Follow-up Study of Botulinum Toxin Type A in Patients With Overactive Bladder as a Result of Spinal Injury or Multiple Sclerosis

ClinicalTrials.gov study NCT00876447. IPD Sharing: Not stated. Countries: 22. Publications: 1.

Efficacy and Safety Study of Botulinum Toxin Type A Against Placebo to Treat Abnormal Contraction or Twitch of the Eyelid

ClinicalTrials.gov study NCT01896895. IPD Sharing: Not stated. Countries: 3. Publications: 3.