Biology subjects

Patel, R. N.

Publications and source records attributed to Patel, R. N..

7 recordsLinked to original sources

bioRxiv2023

Machine-learning guided Venom Induced Dermonecrosis Analysis tooL: VIDAL

Snakebite envenoming is a global public health issue that causes significant morbidity and mortality, particularly in low-income regions of the world. The clinical manifestations of envenomings vary depending on the snakes venom, with paralysis, haemorrhage, and necrosis being the most common and medically relevant effects. To assess the efficacy of antivenoms against dermonecrosis, a preclinical testing approach involves in vivo mouse models that mimic local tissue effects of cytotoxic snakebites in humans. However, current methods for assessing necrosis severity are time-consuming and susceptible to human error. To address this, we present the Venom Induced Dermonecrosis Analysis tool (VIDAL), a machine-learning-guided image-based solution that can automatically identify dermonecrotic lesions in mice, adjust for lighting biases, scale the image, extract lesion area and discolouration, and calculate the severity of dermonecrosis. We also introduce a new unit, the dermonecrotic unit (DnU), to better capture the complexity of dermonecrosis severity. Our tool is comparable to the performance of state-of-the-art histopathological analysis, making it an accessible, accurate, and reproducible method for assessing dermonecrosis. Given the urgent need to address the neglected tropical disease that is snakebite, high-throughput technologies such as VIDAL are crucial in developing and validating new and existing therapeutics for this debilitating disease.

pharmacology and toxicology↗

bioRxiv2023

An in vitro assay to investigate venom neurotoxin activity on muscle-type nicotinic acetylcholine receptor activation and for the discovery of toxin-inhibitory molecules

Snakebite envenoming is a neglected tropical disease that causes over 100,000 deaths annually. Envenomings result in variable pathologies, but systemic neurotoxicity is among the most serious and is currently only treated with difficult to access and variably efficacious commercial antivenoms. Venom-induced neurotoxicity is often caused by -neurotoxins antagonising the muscle-type nicotinic acetylcholine receptor (nAChR), a ligand-gated ion channel. Discovery of therapeutics targeting -neurotoxins is hampered by relying on binding assays that do not reveal restoration of receptor activity or more costly and/or lower throughput electrophysiology-based approaches. Here, we report the validation of a screening assay for nAChR activation using immortalised TE671 cells expressing the {gamma}-subunit containing muscle-type nAChR and a fluorescent dye that reports changes in cell membrane potential. Assay validation using traditional nAChR agonists and antagonists, which either activate or block ion fluxes, was consistent with previous studies. We then characterised antagonism of the nAChR by a variety of elapid snake venoms that cause muscle paralysis in snakebite victims, before defining the toxin-inhibiting activities of commercial antivenoms, and new types of snakebite therapeutic candidates, namely monoclonal antibodies, decoy receptors, and small molecules. Our findings show robust evidence of assay uniformity across 96-well plates and highlight the amenability of this approach for the future discovery of new snakebite therapeutics via screening campaigns. The described assay therefore represents a useful first-step approach for identifying -neurotoxins and their inhibitors in the context of snakebite envenoming, and it should provide wider value for studying modulators of nAChR activity from other sources.

pharmacology and toxicology↗

bioRxiv2022

Bumblebees navigate using path integration while walking

Path integration is a computational strategy that allows an animal to maintain an internal estimate of its position relative to a point of origin. Many species use path integration to navigate back to specific locations, typically their homes, after lengthy and convoluted excursions. Hymenopteran insects are impressive path integrators, directly returning to their hives after hundreds of meters of outward travel. Recent neurobiological insights have established hypotheses for how path integration may be mediated by the brains of bees, but clear ways to test these hypotheses in the laboratory are currently unavailable. Here we report that the bumblebee, Bombus terrestris, uses path integration while walking over short distances in an indoor arena. They estimate accurate vector distances after displacement and orient by artificial celestial cues. Walking bumblebees also exhibited systematic search patterns when home vectors failed to lead them accurately back to the nest, closely resembling searches performed by other species in natural conditions. We thus provide a robust experimental system to test navigation behavior in the laboratory that reflects most aspects of natural path integration. Importantly, we established this assay in an animal that is both readily available and resilient to invasive manipulations. In the future, our behavioral assay therefore can be combined with current electrophysiological techniques, opening a path towards directly probing the neural basis of the sophisticated vector navigation abilities of bees.

animal behavior and cognition↗

bioRxiv2020

Mantis shrimp rank the shape of an object over its color during recognition

Mantis shrimp are predatory crustaceans that commonly occupy burrows in shallow, tropical waters worldwide. Most of these animals inhabit structurally complex, benthic environments with an abundance of visual features that are regularly observed, including conspecifics, predators, prey, and landmarks for use in navigation. While these animals are capable of learning and discriminating color and polarization, it is unknown what specific attributes of a visual object are important for its recognition. Here we show that mantis shrimp of the species Neogonodactylus oerstedii can learn the shape of a trained target. Furthermore, when the shape and color of a target which they had been trained to identify were placed in conflict, N. oerstedii significantly chose the target of the trained shape over the target of the trained color. Thus, we conclude that the shape of a target is more important than its color for its recognition by N. oerstedii. Our findings suggest that the shapes of learned structures, such as landmarks or other animals, are important for N. oerstedii during object recognition.

animal behavior and cognition↗

bioRxiv2020

Landmark navigation in a mantis shrimp

Mantis shrimp are predatory crustaceans that commonly occupy burrows in shallow, tropical waters worldwide. Most of these animals inhabit structurally complex, benthic environments where many potential landmarks are available. Mantis shrimp of the species Neogonodactylus oerstedii return to their burrows between foraging excursions using path integration, a vector-based navigational strategy that is prone to accumulated error. Here we show that N. oerstedii can navigate using landmarks in parallel with their path integration system, offseting error generated when navigating using solely path integration. We also report that when the path integration and landmark navigation systems are placed in conflict, N. oerstedii will orient using either system or even switch systems enroute. How they make the decision to trust one navigational system over another is unclear. These findings add to our understanding of the refined navigational toolkit N. oerstedii relies upon to efficiently navigate back to its burrow, complementing its robust, yet error prone, path integration system with landmark guidance.

animal behavior and cognition↗

bioRxiv2020

Mantis shrimp navigate home using celestial and idiothetic path integration

Path integration is a robust mechanism that many animals employ to return to specific locations, typically their homes, during navigation. This efficient navigational strategy has never been demonstrated in a fully aquatic animal, where sensory cues used for orientation may differ dramatically from those available above the waters surface. Here we report that the mantis shrimp, Neogonodactylus oerstedii, uses path integration informed by a hierarchical reliance on the sun, overhead polarization patterns, and idiothetic (internal) orientation cues to return home when foraging, making them the first fully aquatic path-integrating animals yet discovered. We show that mantis shrimp rely on navigational strategies closely resembling those used by insect navigators, opening a new avenue for the investigation of the neural basis of navigation behaviors and the evolution of these strategies in arthropods and potentially other animals as well.

animal behavior and cognition↗

bioRxiv2020

Path integration error and adaptable search behaviors in a mantis shrimp

Mantis shrimp of the species Neogonodactylus oerstedii occupy small burrows in shallow waters throughout the Caribbean. These animals use path integration, a vector-based navigation strategy, to return to their homes while foraging. Here we report that path integration in N. oerstedii is prone to error accumulated during outward foraging paths and we describe the search behavior that N. oerstedii employs after it fails to locate its home following the route provided by its path integrator. This search behavior forms continuously expanding, non-oriented loops that are centered near the point of search initiation. The radius of this search is apparently scaled to the animals accumulated error during path integration, improving the effectiveness of the search. The search behaviors exhibited by N. oerstedii bear a striking resemblance to search behaviors in other animals, offering potential avenues for the comparative examination of search behaviors and how they are optimized in disparate taxa. Summary StatementMantis shrimp use path integration, an error-prone navigational strategy, when travelling home. When path integration fails, mantis shrimp employ a stereotyped yet flexible search pattern to locate their homes.

animal behavior and cognition↗