Biology subjects

Jones, M. D.

Publications and source records attributed to Jones, M. D..

5 recordsLinked to original sources

bioRxiv2024

Synthesis and in vitro evaluation shows disquaramide compounds are a promising class of anti-leishmanial drugs

An increasing number of treatment failures with current pharmaceutics, as well as a lack of a vaccine, demonstrates the need to develop new treatment options for leishmaniasis. Herein, we describe the synthesis and in vitro analysis of 24 disquaramide compounds targeting the Leishmania major parasite. Of the compounds that were evaluated, six of them (13, 19, 20, 22, 24, and 26) were capable of significantly decreasing the number of parasites by up to 42% compared to the control by day four. This demonstrates that disquaramides either impair parasite replication or have leishmancidal effects. Additionally, none of the disquaramide compounds tested displayed host cell cytotoxicity. These experiments provide evidence that disquaramides have the potential to be effective anti-leishmanial therapeutics.

microbiology↗

bioRxiv2021

How do King Cobras move across a major highway? Unintentional wildlife crossing structures may facilitate movement.

O_LIGlobal road networks continue to expand, and the wildlife responses to these landscape-level changes need to be understood to advise long-term management decisions. Roads have high mortality risk to snakes because snakes typically move slowly and can be intentionally targeted by drivers. C_LIO_LIWe investigated how radio-tracked King Cobras (Ophiophagus hannah) traverse a major highway in northeast Thailand, and if reproductive cycles were associated with road hazards. C_LIO_LIWe surveyed a 15.3km stretch of Highway 304 to determine if there were any locations where snakes, and other wildlife, could safely move across the road (e.g., culverts, bridges). We used recurse analysis to detect possible road-crossing events, and used subsets of King Cobra movement data to create dynamic Brownian Bridge Movement Models (dBBMM) in an attempt to show movement pathways association with possible unintentional crossing structures. We further used Integrated Step Selection Functions (ISSF) to assess seasonal differences in avoidance of major roads for adult King Cobras in relation to reproductive state. C_LIO_LIWe discovered 32 unintentional wildlife crossing locations capable of facilitating King Cobra movement across the highway. Our dBBMMs failed to show if underpasses were being used by telemetered individuals; however, the tracking locations pre- and post-crossing provided strong evidence of underpass use. Our ISSF suggested a lower avoidance of roads during the breeding season, though the results were inconclusive. With the high volume of traffic, large size of King Cobras and a 98.8% success rate of crossing the road in our study, we strongly suspect that individuals are using the unintentional crossing structures to safely traverse the road. C_LIO_LIFurther research is needed to determine the extent of wildlife underpass use at our study site and globally, alongside using previously proven fencing to facilitate their use. We propose that more consistent integration of drainage culverts and bridges could help mitigate the impacts of roads on some terrestrial wildlife, particularly in areas where roads fragment forests and wildlife corridors. C_LI

ecology↗

bioRxiv2020

Restricted constrictors: Space use and habitat selection of native Burmese pythons in Northeast Thailand

Animal movement and resource use are tightly linked. Investigating these links to understand how animals utilize space and select habitats is especially relevant in areas that have been affected by habitat fragmentation and agricultural conversion. We set out to explore the space use and habitat selection of Burmese pythons (Python bivittatus) in a patchy land use matrix dominated by agricultural crops and human settlements. We used radio telemetry to record daily locations of seven Burmese pythons over the course of our study period of approximately 22 months. We created dynamic Brownian Bridge Movement Models (dBBMMs) for all individuals, using occurrence distributions to estimate extent of movements and motion variance to reveal temporal patterns. Then we used integrated step selection functions to determine whether individual movements were associated with particular landscape features (aquatic agriculture, forest, roads, settlements, terrestrial agriculture, water), and whether there were consistent associations at the population level. Our dBBMM estimates suggested that Burmese pythons made use of small areas (98.97 {+/-} 35.42 ha), with low mean individual motion variance characterized by infrequent moves and long periods at a single location. At both the individual and population level, Burmese pythons in the agricultural matrix were associated with aquatic environments. Only one individual showed a strong avoidance for human settlements which is troublesome from a human-wildlife conflict angle, especially as Burmese pythons have been observed entering human settlements and consuming livestock in our study site. Our study is one of the first to contribute to the knowledge of Burmese python ecology in their native range as the majority of studies have focused on invasive populations.

ecology↗

bioRxiv2020

No room to roam: King Cobras reduce movement in agriculture

Studying animal movement provides insights into how animals react to land-use changes, specifically how animals can change their behaviour in agricultural areas. Recent reviews show a tendency for species to reduce movements in response to increased human landscape modification, but the study of movement has not been extensively explored in reptiles. We examined movements of a large reptilian predator, the King Cobra (Ophiophagus hannah), in Northeast Thailand. We used a consistent regime of radio-telemetry tracking to document movements across protected forest and adjacent agricultural areas. We then adapted GPS-targeting analytic methods to examine the movement using metrics of site reuse and dynamic Brownian Bridge Movement Model derived motion variance. Examination of motion variance demonstrated that King Cobra movements increased in forested areas and tended to decrease in agricultural areas. Our Integrated Step-Selection Functions indicated that when moving in agricultural areas King Cobras restricted their movements, thereby remaining within vegetated semi-natural areas, often located along the banks of irrigation canals. Site reuse metrics of residency time and number of revisits remained unaffected by distance to landscape features. Neither motion variance nor reuse metrics were consistently affected by the presence of threatening landscape features (e.g. roads, human settlements); suggesting that King Cobras will remain in close proximity to threats, provided habitat patches are available. Although King Cobras displayed heterogeneity in their response to agricultural landscapes, the overall trend suggested a reduction in movements when faced with fragmented habitat patches embedded in an otherwise inhospitable land-use matrix. Reductions in movements are consistent with findings for mammals and forest specialist species.

ecology↗

bioRxiv2017

Correction of copy number induced false positives in CRISPR screens

Cell autonomous cancer dependencies are now routinely identified using CRISPR loss-of-function screens. However, a bias exists that makes it difficult to assess the true essentiality of genes located in amplicons, since the entire amplified region can exhibit lethal scores. These false-positive hits can either be discarded from further analysis, which in cancer models can represent a significant number of hits, or methods can be developed to rescue the true-positives within amplified regions. We propose two methods to rescue true positive hits in amplified regions by correcting for this copy number artefact. The Local Drop Out (LDO) method uses the relative lethality scores within genomic regions to assess true essentiality and does not require additional orthogonal data (e.g. copy number value). LDO is meant to be used in screens covering a dense region of the genome (e.g. a whole chromosome or the whole genome). The General Additive Model (GAM) method models the screening data as a function of the known copy number values and removes the systematic effect from the measured lethality. GAM does not require the same density as LDO, but does require prior knowledge of the copy number values. Both methods have been developed with single sample experiments in mind so that the correction can be applied even in smaller screens. Here we demonstrate the efficacy of both methods at removing the copy number effect and rescuing hits from some of the amplified regions. We estimate a 70-80% decrease of false positive hits in regions of high copy number with either method.

bioinformatics↗