Biology subjects

Tyson, C.

Publications and source records attributed to Tyson, C..

6 recordsLinked to original sources

bioRxiv2024

Tumor localization strategies of multi-cancer early detection tests: a quantitative assessment

IntroductionBlood-based multi-cancer early detection (MCED) tests may expand the number of "screenable" cancers. Defining an optimal approach to diagnostic resolution for individuals with positive MCED test results is critical. Two prospective trials employed distinct diagnostic resolution approaches; one employed a molecular signal to predict tissue of origin (TOO) and the other used an imaging-based diagnostic strategy. Using mathematical modeling, we compared the diagnostic burden of each approach and characterized the risk of excess cancer incidence that may be attributable to radiation exposure associated with a false positive (FP) MCED test result and an imaging-based diagnostic strategy. MethodsA mathematical expression for diagnostic burden was derived using MCED test positive predictive value (PPV), molecular TOO localization accuracy, and the expected number of imaging procedures associated with each diagnostic outcome. Imaging and molecular TOO strategies were compared by estimating diagnostic burden across a wide range of MCED PPVs and TOO accuracies. Organ-specific radiation dose for diagnostic imaging was extracted from the literature and used as input to National Cancer Institute RADRat tool for estimating excess lifetime cancer risk due to radiation exposure. ResultsFor the molecular TOO diagnostic approach, an average of 2.1 procedures are required to reach diagnostic resolution for correctly-localized TPs, 4.4 procedures for incorrectly-localized TPs, and 4 procedures for FPs, vs. an average of 2.75 procedures for TPs and 2.4 for FPs with an imaging-based diagnostic strategy. Across the entire range of possible PPV and localization performance, a molecular TOO strategy resulted in a higher mean diagnostic burden: 3.6 procedures (SD 0.445) vs. 2.6 procedures (SD 0.1) for the imaging strategy. Predicted diagnostic burden was higher for molecular TOO in 95.5% of all possible PPV and TOO accuracy combinations; 79% or higher PPV would be required for a 90% accurate molecular TOO strategy to be less burdensome than imaging. The maximum rate of excess cancer incidence from radiation exposure for FP results from MCED screening between the ages of 50-84 was estimated at 64.6 per 100,000 (annual testing, 99% specificity), 48.5 per 100,000 (biennial testing, 98.5% specificity), and 64.6 per 100,000 (biennial testing, 98% specificity). ConclusionsThis analysis demonstrates that an imaging-based diagnostic strategy is more efficient than a molecular TOO-informed approach across 95.5% of all possible MCED PPV and TOO accuracy combinations. The use of an imaging-based approach for cancer localization can be efficient and low risk compared to a molecular-based approach.

cancer biology↗

bioRxiv2024

Ruvbl1 is required for the reproduction of the corn planthopper, Peregrinus maidis

Ruvbl1 (also known as TIP49, Pontin) encodes an ATPase of the AAA+ protein superfamily involved in several cellular functions, including chromatin remodeling, control of transcription, and cellular development (motility, growth, and proliferation). Here, we used an in-vivo RNA interference (RNAi) approach to evaluate the effect of Ruvbl1 silencing on the physiology of the corn planthopper, Peregrinus maidis. Silencing of P. maidis Ruvbl1 (PmRuvbl1) was correlated with visible morphology changes in female individuals with significant increases in body mass observed at 8 and 12 days after double strand RNA (dsRNA) injection. Ovary morphology was significantly affected in adult females with PmRuvbl1 silenced, with no mature oocytes observed at 8 and 12 days after gene silencing. Whereas no significant difference in egg laying was observed 4 days after dsRNA injection, significantly fewer eggs were laid in plants at 8 and 12 days after dsRNA treatment. Furthermore, dramatic reductions in egg hatching were observed at all time points after PmRuvbl1 silencing, compared to dsGFP-injected controls. These results extend PmRuvbl1 functions as a putative regulator of P. maidis reproduction and demonstrate the potential of Ruvbl1 to be further exploited as a target for RNAi-mediated insect control.

molecular biology↗

bioRxiv2024

Constant companions: Wild zebra finch pairs display extreme spatial cohesion

Many animals maintain long-term monogamous partnerships, but the extent to which partners associate varies substantially and has implications for the scope of cooperation between pair members. Zebra finches (Taeniopygia castanosis) are monogamously paired for life and maintain continuous partnerships, raising questions as to if and how they maintain pair cohesion despite being nonterritorial and having only short-range acoustic signals. While zebra finches are the best studied songbird in captivity, their social and spatial behaviour in the wild is poorly understood. Determining pair cohesion in songbirds to date has almost exclusively been studied at specific locations where pairs would be expected to meet, such as nesting or feeding sites, without quantifying broader movements. Here, we used solar-powered automated tracking to simultaneously monitor the movements of radio-tagged zebra finch pairs during periods with breeding activity. We reveal extremely high spatial cohesion with pairs using nearly identical home ranges and maintaining close spatial proximity across large areas. This characterisation of extremely high spatio-temporal coordination of zebra finch pairs provides important insights into the operation and benefits of monogamous relationships in highly mobile taxa, such as birds.

animal behavior and cognition↗

bioRxiv2024

Fingerprint localisation for fine-scale wildlife tracking using automated radio telemetry

1: Automated radio telemetry systems are among the most widely applicable method for tracking wildlife at fine spatiotemporal scales. These systems are increasingly applying large networks of simple receivers to detect radio signal strength (RSS) from radio tagged individuals. Analytical methods to derive position estimates using RSS localisation, however, are relatively underdeveloped in the field of wildlife tracking. Here, we apply approaches from indoor positioning systems to develop a new method, radio fingerprinting, for localizing radio tagged animals in structurally complex, outdoor environments. This method characterizes the RSS patterns at known locations to generate a radio map of the study area, which is then used to predict the location of new RSS patterns. 2: We conducted field tests to evaluate the localisation accuracy of radio fingerprinting relative to multilateration, a commonly used method for RSS localisation. To do so, we established an experimental receiver network covering multiple habitat types and compared the localisation accuracy of radio fingerprinting to multilateration. Additionally, we evaluated how a variety of features characteristic of typical tracking datasets affected the accuracy of both methods. 3: While both methods had a similar median error ([~]30 m), the fingerprint localisation method offered several advantages over multilateration. Multilateration localisation estimates were highly affected by missed detections from the nearest receiver to the test point, which occurred in 30% of cases. In these cases, the median error was 97 m, over a 3-fold increase. Distance to the nearest receiver also biased multilateration estimates with error increasing as the distance increased. Additionally, errors from multilateration estimates were higher in more densely vegetated areas. In contrast, fingerprinting position estimates were largely robust to each of these scenarios. 4: Automated radio telemetry enables the fine-scale, continuous tracking of range-resident animals. We present radio fingerprinting as a localisation method in outdoor environments where standard localisation methods may be inadequate. This approach can be applied to any automated radio telemetry hardware and to any study system where a radio map can be generated.

animal behavior and cognition↗

bioRxiv2023

Video-Microscopy-Based Automated Trajectory Determination for High-Velocity, Densely Clustered, Indistinguishable Objects Moving in A Directed Force Field

We present a method for tracking densely clustered, high-velocity, indistinguishable objects being spawned at a high rate and moving in a directed force field using only object centroids as inputs and no other image information. The algorithm places minimal restrictions on the velocities or accelerations of the objects being tracked and uses a methodology based on a scoring function and a back-tracking refinement process. This combination leads to successful tracking of hundreds of particles in challenging environments even when the displacement of the individual objects at successive times approaches the separation between neighboring objects in any one frame. We note that these cases can be particularly difficult to handle by existing methods. The performance of the algorithm is methodically examined by comparison to simulated trajectories which vary the temporal and spatial densities, velocities, and accelerations of the objects in motion, as well as the signal-to-noise ratio. Also, we demonstrate its capability by analyzing data from experiments with superparamagnetic microspheres moving in an inhomogeneous magnetic field in aqueous buffer at room temperature. Our method should be widely applicable since trajectory determination problems are ubiquitous in video microscopy applications in biology, materials science, physics, and engineering.

biophysics↗

bioRxiv2023

Exportin 1 is required for the reproduction and maize mosaic virus accumulation in its insect vector Peregrinus maidis

Exportin 1 (XPO1) is the major karyopherin-{beta} nuclear receptor mediating the nuclear export of hundreds of proteins and some classes of RNA and regulates several critical processes in the cell, including but not limited to, cell-cycle progression, transcription, translation, oncogenesis and longevity. Viruses have co-opted XPO1 to promote nucleocytoplasmic transport of viral proteins and RNA. Maize mosaic virus (MMV) is an Alphanucleorhabdovirus transmitted in a circulative propagative manner by the corn planthopper, Peregrinus maidis. MMV replicates in the nucleus of plant and insect hosts, and it remains unknown whether MMV co-opts P. maidis XPO1 (PmXPO1) to complete its life cycle. Because XPO1 plays multiple regulatory roles in cell functions and virus infection, we hypothesized that RNAi-mediated silencing of XPO1 would simultaneously and negatively affect MMV accumulation and insect physiology. Although PmXPO1 expression was not modulated during MMV infection, PmXPO1 knockdown negatively affected MMV accumulation in P. maidis at 12 and 15 days after microinjection. Likewise, PmXPO1 knockdown negatively affected P. maidis survival and reproduction. PmXPO1 exhibited tissue specific expression patterns with higher expression in the ovaries compared to the guts of adult females. Survival rate was significantly lower for PmXPO1 knockdown females, compared to controls, but no effect was observed for males. Adult females with PmXPO1 knockdown were heavier and had a larger abdomen compared to controls at 4, 8 and 12 days after dsRNA microinjection. Consistent with an increase in weight, glyceride content specifically and significantly increased in PmXPO1 knockdown female planthoppers. Ovary development was significantly inhibited, and mature eggs were not observed in adult females with PmXPO1 knockdown. Consistent with a major role of PmXPO1 in ovary function and egg production, oviposition and egg hatch in plants was dramatically reduced in dsRNA PmXPO1 treated insects compared with control. Altogether, these results suggest that PmXPO1 is a positive regulator of P. maidis reproduction and that it plays a proviral role in the insect vector supporting MMV infection.

molecular biology↗