Publications by authors named "Danielle Ireland"

7 Publications

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Let it rip: The mechanics of self-bisection in asexual planarians determines their population reproductive strategies.

Phys Biol 2021 Oct 12. Epub 2021 Oct 12.

Biology Department, Swarthmore College, 500 College Ave, Swarthmore, Pennsylvania, 19081-1306, UNITED STATES.

Asexual freshwater planarians reproduce by transverse bisection (binary fission) into two pieces. This process produces a head and a tail, which fully regenerate within 1-2 weeks. How planarians split into two offspring - using only their musculature and substrate traction - is a challenging biomechanics problem. We found that three different species, Dugesia japonica, Girardia tigrina and Schmidtea mediterranea, have evolved three different mechanical solutions to self-bisect. Using time lapse imaging of the fission process, we quantitatively characterize the main steps of division in the three species and extract the distinct and shared key features. Across the three species, planarians actively alter their body shape, regulate substrate traction, and use their muscles to generate tensile stresses large enough to overcome the ultimate tensile strength of the tissue. Moreover, we show that how each planarian species divides dictates how resources are split among its offspring. This ultimately determines offspring survival and reproductive success. Thus, heterospecific differences in the mechanics of self-bisection of individual worms explain the observed differences in the population reproductive strategies of different planarian species.
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http://dx.doi.org/10.1088/1478-3975/ac2f29DOI Listing
October 2021

A Systematic Review to Compare Chemical Hazard Predictions of the Zebrafish Embryotoxicity Test With Mammalian Prenatal Developmental Toxicity.

Toxicol Sci 2021 08;183(1):14-35

Evidence-Based Toxicology Collaboration (EBTC), Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.

Originally developed to inform the acute toxicity of chemicals on fish, the zebrafish embryotoxicity test (ZET) has also been proposed for assessing the prenatal developmental toxicity of chemicals, potentially replacing mammalian studies. Although extensively evaluated in primary studies, a comprehensive review summarizing the available evidence for the ZET's capacity is lacking. Therefore, we conducted a systematic review of how well the presence or absence of exposure-related findings in the ZET predicts prenatal development toxicity in studies with rats and rabbits. A two-tiered systematic review of the developmental toxicity literature was performed, a review of the ZET literature was followed by one of the mammalian literature. Data were extracted using DistillerSR, and study validity was assessed with an amended SYRCLE's risk-of-bias tool. Extracted data were analyzed for each species and substance, which provided the basis for comparing the 2 test methods. Although limited by the number of 24 included chemicals, our results suggest that the ZET has potential to identify chemicals that are mammalian prenatal developmental toxicants, with a tendency for overprediction. Furthermore, our analysis confirmed the need for further standardization of the ZET. In addition, we identified contextual and methodological challenges in the application of systematic review approaches to toxicological questions. One key to overcoming these challenges is a transition to more comprehensive and transparent planning, conduct and reporting of toxicological studies. The first step toward bringing about this change is to create broad awareness in the toxicological community of the need for and benefits of more evidence-based approaches.
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http://dx.doi.org/10.1093/toxsci/kfab072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404989PMC
August 2021

Planarian Scrunching as a Quantitative Behavioral Readout for Noxious Stimuli Sensing.

J Vis Exp 2020 07 30(161). Epub 2020 Jul 30.

Biology Department, Swarthmore College; Physics Department, UC San Diego;

Freshwater planarians normally glide smoothly through ciliary propulsion on their ventral side. Certain environmental conditions, however, can induce musculature-driven forms of locomotion: peristalsis or scrunching. While peristalsis results from a ciliary defect, scrunching is independent of cilia function and is a specific response to certain stimuli, including amputation, noxious temperature, extreme pH, and ethanol. Thus, these two musculature-driven gaits are mechanistically distinct. However, they can be difficult to distinguish qualitatively. Here, we provide a protocol for inducing scrunching using various physical and chemical stimuli. We detail the quantitative characterization of scrunching, which can be used to distinguish it from peristalsis and gliding, using freely available software. Since scrunching is a universal planarian gait, albeit with characteristic species-specific differences, this protocol can be broadly applied to all species of planarians, when using appropriate considerations. To demonstrate this, we compare the response of the two most popular planarian species used in behavioral research, Dugesia japonica and Schmidtea mediterranea, to the same set of physical and chemical stimuli. Furthermore, the specificity of scrunching allows this protocol to be used in conjunction with RNA interference and/or pharmacological exposure to dissect the molecular targets and neuronal circuits involved, potentially providing mechanistic insight into important aspects of nociception and neuromuscular communication.
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http://dx.doi.org/10.3791/61549DOI Listing
July 2020

Cubital Tunnel Syndrome: Current Concepts.

Curr Rev Musculoskelet Med 2020 Aug;13(4):520-524

Philadelphia Hand to Shoulder Center, Philadelphia, PA, USA.

Purpose Of Review: Compressive neuropathy of the ulnar nerve across the elbow is a common diagnosis encountered frequently within a hand and upper extremity clinical practice. Appropriate and timely evaluation, diagnosis, objective testing, and evidence-based decisions regarding treatment options are paramount in the optimal care of the patient with this pathology. An understanding of current literature is critical in determining and understanding best practices.

Recent Findings: A thorough review of the recent literature regarding physical examination, diagnostic testing, and nonoperative versus operative results was performed. Regarding physical examination, the glenohumeral internal rotation test and scratch collapse test are more effective and sensitive than traditional maneuvers such as Tinel's testing and the elbow flexion test. Electrodiagnostic testing, magnetic resonance imaging, and ultrasound evaluation have all been shown to be effective in diagnosing cubital tunnel syndrome. However, no single test has proven itself to be superior. Nonoperative treatment can be successful for mild cases of cubital tunnel syndrome. Surgical release techniques comparing open with endoscopic release are equivocal, and in situ release versus transposition techniques show that transposition should not be performed routinely. The diagnosis and treatment of cubital tunnel syndrome do not have a well-defined algorithm based on current literature. The treating physician must therefore utilize the available information to determine a diagnostic and treatment plan individualized to the patient. More rigorous scientific studies are needed to determine the most effective surgical approaches for cubital tunnel syndrome.
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http://dx.doi.org/10.1007/s12178-020-09650-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340724PMC
August 2020

Dugesia japonica is the best suited of three planarian species for high-throughput toxicology screening.

Chemosphere 2020 Aug 8;253:126718. Epub 2020 Apr 8.

Department of Biology, Swarthmore College, Swarthmore, PA, USA; Department of Physics, University of California San Diego, La Jolla, CA, USA. Electronic address:

High-throughput screening (HTS) using new approach methods is revolutionizing toxicology. Asexual freshwater planarians are a promising invertebrate model for neurotoxicity HTS because their diverse behaviors can be used as quantitative readouts of neuronal function. Currently, three planarian species are commonly used in toxicology research: Dugesia japonica, Schmidtea mediterranea, and Girardia tigrina. However, only D. japonica has been demonstrated to be suitable for HTS. Here, we assess the two other species for HTS suitability by direct comparison with D. japonica. Through quantitative assessments of morphology and multiple behaviors, we assayed the effects of 4 common solvents (DMSO, ethanol, methanol, ethyl acetate) and a negative control (sorbitol) on neurodevelopment. Each chemical was screened blind at 5 concentrations at two time points over a twelve-day period. We obtained two main results: First, G. tigrina and S. mediterranea planarians showed significantly reduced movement compared to D. japonica under HTS conditions, due to decreased health over time and lack of movement under red lighting, respectively. This made it difficult to obtain meaningful readouts from these species. Second, we observed species differences in sensitivity to the solvents, suggesting that care must be taken when extrapolating chemical effects across planarian species. Overall, our data show that D. japonica is best suited for behavioral HTS given the limitations of the other species. Standardizing which planarian species is used in neurotoxicity screening will facilitate data comparisons across research groups and accelerate the application of this promising invertebrate system for first-tier chemical HTS, helping streamline toxicology testing.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350771PMC
August 2020

Pharmacological or genetic targeting of Transient Receptor Potential (TRP) channels can disrupt the planarian escape response.

PLoS One 2019 5;14(12):e0226104. Epub 2019 Dec 5.

Department of Biology, Swarthmore College, Swarthmore, Pennsylvania, United States of America.

In response to noxious stimuli, planarians cease their typical ciliary gliding and exhibit an oscillatory type of locomotion called scrunching. We have previously characterized the biomechanics of scrunching and shown that it is induced by specific stimuli, such as amputation, noxious heat, and extreme pH. Because these specific inducers are known to activate Transient Receptor Potential (TRP) channels in other systems, we hypothesized that TRP channels control scrunching. We found that chemicals known to activate TRPA1 (allyl isothiocyanate (AITC) and hydrogen peroxide) and TRPV (capsaicin and anandamide) in other systems induce scrunching in the planarian species Dugesia japonica and, except for anandamide, in Schmidtea mediterranea. To confirm that these responses were specific to either TRPA1 or TRPV, respectively, we tried to block scrunching using selective TRPA1 or TRPV antagonists and RNA interference (RNAi) mediated knockdown. Unexpectedly, co-treatment with a mammalian TRPA1 antagonist, HC-030031, enhanced AITC-induced scrunching by decreasing the latency time, suggesting an agonistic relationship in planarians. We further confirmed that TRPA1 in both planarian species is necessary for AITC-induced scrunching using RNAi. Conversely, while co-treatment of a mammalian TRPV antagonist, SB-366791, also enhanced capsaicin-induced reactions in D. japonica, combined knockdown of two previously identified D. japonica TRPV genes (DjTRPVa and DjTRPVb) did not inhibit capsaicin-induced scrunching. RNAi of DjTRPVa/DjTRPVb attenuated scrunching induced by the endocannabinoid and TRPV agonist, anandamide. Overall, our results show that although scrunching induction can involve different initial pathways for sensing stimuli, this behavior's signature dynamical features are independent of the inducer, implying that scrunching is a stereotypical planarian escape behavior in response to various noxious stimuli that converge on a single downstream pathway. Understanding which aspects of nociception are conserved or not across different organisms can provide insight into the underlying regulatory mechanisms to better understand pain sensation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226104PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894859PMC
March 2020

Screening for neurotoxic potential of 15 flame retardants using freshwater planarians.

Neurotoxicol Teratol 2019 May - Jun;73:54-66. Epub 2019 Mar 31.

Division of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USA; Department of Physics, University of California San Diego, La Jolla, CA 92093, USA; Department of Biology, Swarthmore College Swarthmore, PA 19081, USA. Electronic address:

Asexual freshwater planarians are an attractive invertebrate model for high-throughput neurotoxicity screening, because they possess multiple quantifiable behaviors to assess distinct neuronal functions. Planarians uniquely allow direct comparisons between developing and adult animals to distinguish developmentally selective effects from general neurotoxicity. In this study, we used our automated planarian screening platform to compare the neurotoxicity of 15 flame retardants (FRs), consisting of representative phased-out brominated (BFRs) and replacement organophosphorus FRs (OPFRs). OPFRs have emerged as a proposed safer alternative to BFRs; however, limited information is available on their health effects. We found 11 of the 15 FRs (3/6 BFRs, 7/8 OPFRs, and Firemaster 550) caused adverse effects in both adult and developing planarians with similar nominal lowest-effect-levels for BFRs and OPFRs. This suggests that replacement OPFRs are comparably neurotoxic to the phased-out compounds. BFRs were primarily systemically toxic, whereas OPFRs, except Tris(2-chloroethyl) phosphate, shared a behavioral phenotype in response to noxious heat at sublethal concentrations, indicating specific neurotoxic effects. We found this behavioral phenotype was correlated with cholinesterase inhibition, thus linking behavioral outcomes to molecular targets. By directly comparing effects on adult and developing planarians, we further found that one BFR (3,3',5,5'-Tetrabromobisphenol A) caused a developmental selective defect. Together, these results demonstrate that our planarian screening platform yields high content data from various behavioral and morphological endpoints, allowing us to distinguish selective neurotoxic effects and effects specific to the developing nervous system. Ten of these 11 bioactive FRs were previously found to be bioactive in other models, including cell culture and alternative animal models (nematodes and zebrafish). This level of concordance across different platforms emphasizes the urgent need for further evaluation of OPFRs in mammalian systems.
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http://dx.doi.org/10.1016/j.ntt.2019.03.003DOI Listing
May 2020
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