Biology subjects

Davis, C. E.

Publications and source records attributed to Davis, C. E..

4 recordsLinked to original sources

bioRxiv2024

Ribosomal RNA transcription governs splicing through ribosomal protein RPL22

Ribosome biosynthesis is a cancer vulnerability executed by targeting RNA polymerase I (Pol I) transcription. We developed advanced, specific Pol I inhibitors to identify drivers of this sensitivity. By integrating multi-omics features and drug sensitivity data from a large cancer cell panel, we discovered that RPL22 frameshift mutation conferred Pol I inhibitor sensitivity in microsatellite instable cancers. Mechanistically, RPL22 directly interacts with 28S rRNA and mRNA splice junctions, functioning as a splicing regulator. RPL22 deficiency, intensified by 28S rRNA sequestration, promoted the splicing of its paralog RPL22L1 and p53 negative regulator MDM4. Chemical and genetic inhibition of rRNA synthesis broadly remodeled mRNA splicing controlling hundreds of targets. Strikingly, RPL22-dependent alternative splicing was reversed by Pol I inhibition revealing a ribotoxic stress-initiated tumor suppressive pathway. We identify a mechanism that robustly connects rRNA synthesis activity to splicing and reveals their coordination by ribosomal protein RPL22.

molecular biology↗

bioRxiv2020

Microsaccades during high speed continuous visual search

Here, we provide an analysis of the microsaccades that occurred during continuous visual search and targeting of small faces that we pasted either into cluttered background photos or into a simple gray background. Subjects continuously used their eyes to target singular 3-degree upright or inverted faces in changing scenes. As soon as the participants gaze reached the target face, a new face was displayed in a different and random location. Regardless of the experimental context (e.g. background scene, no background scene), or target eccentricity (from 4 to 20 degrees of visual angle), we found that the microsaccade rate dropped to near zero levels within only 12 milliseconds after trial onset. There were almost never any microsaccades before the saccade to the face. One subject completed 118 consecutive trials without a single microsaccade. However, in about 20% of the trials, there was a single corrective microsaccade that occurred almost immediately after the preceding saccades offset. These corrective microsaccades were task oriented because their facial landmark targeting distributions matched those of saccades within both the upright and inverted face conditions. Our findings show that a single feedforward pass through the visual hierarchy for each stimulus is likely all that is needed to effectuate prolonged continuous visual search. In addition, we provide evidence that microsaccades can serve perceptual functions like correcting saccades or effectuating task-oriented goals during continuous visual search.

neuroscience↗

bioRxiv2019

Stimulus Onset Hub: An open-source, low latency, and opto-isolated trigger box for neuroscientific research replicability and beyond.

There is currently a replication crisis in many fields of neuroscience and psychology, with some estimates claiming up to 64% of research in psychological science is not reproducible. Three common culprits which have been suspected to cause the failure to replicate such studies are small sample sizes, \"hypothesizing after the results are known,\" and \"p-hacking.\" Here, we introduce accurate stimulus timing as an additional possibility. Accurate stimulus onset timing is critical to almost all psychophysical research. Auditory, visual, or manual response time stimulus onsets are typically sent through wires to various machines that record data such as: eye gaze positions, electroencephalography, stereo electroencephalography, and electrocorticography. These stimulus onsets are collated and analyzed according to experimental condition. If there is variability in the temporal accuracy of the delivery of these onsets to external systems, the quality of the resulting data and scientific analyses will degrade. Here, we describe an approximately $200 Arduino based system and associated open-source codebase which achieved a 5.34 microsecond delay from the inputs to the outputs while electrically opto-isolating the connected external systems. Using an oscilloscope, the device is configurable for different environmental conditions particular to each laboratory (e.g. light sensor type, screen type, speaker type, stimulus type, temperature, etc). This low-cost open-source project delivered electrically isolated stimulus onset Transistor-Transistor Logic triggers with a median precision of 5.34 microseconds and was successfully tested with 7 different external systems that record eye and neurological data.

neuroscience↗

bioRxiv2019

Bacteria isolated from bengal cat (Felis catus x Prionailurus bengalensis) anal sac secretions produce volatile compounds associated with animal signaling

Anal sacs are an important odor producing organ found across the mammalian Order Carnivora. Secretions from the anal sac may be used as chemical signals by animals for behaviors ranging from defense to species recognition to signaling reproductive status. In addition, a recent study suggests that domestic cats utilize short-chain free fatty acids in anal sac secretions for individual recognition. The fermentation hypothesis is the idea that symbiotic microorganisms living in association with animals contribute to odor profiles used in chemical communication and that variation in these chemical signals reflects variation in the microbial community. Here we examine the fermentation hypothesis by characterizing volatile organic compounds (VOC) and bacteria isolated from anal sac secretions collected from a male bengal cat, a cross between a domestic cat and wild leopard cat (Felis catus x Prionailurus bengalensis).\n\nBoth left and right anal sacs of a male bengal cat were manually expressed (emptied) and collected. Half of the material was used to culture bacteria or to extract bacterial DNA and other half was used for VOC analysis. DNA was extracted from the anal sac secretions and used for a 16S rRNA gene sequence based characterization of the microbial community. Additionally, some of the material was plated out in order to isolate bacterial colonies. The same three taxa, Bacteroides fragilis, Tessaracoccus, and Finegoldia magna were abundant in the 16S rRNA gene sequence data and also isolated by culturing. Using Solid Phase Microextraction (SPME) gas chromatography-mass spectrometry (GC-MS), we tentatively identified 52 compounds from bengal cat anal sac secretions and 67 compounds from cultures of the three bacterial isolates chosen for further analysis.. Among 67 compounds tentatively identified from bacteria isolates, 52 were also found in the anal sac secretion.\n\nWe show that the bacterial community in the anal sac consists primarily of only a few abundant taxa and that isolates of these taxa produce numerous volatiles that are found in the combined anal sac volatile profile. Many of these volatiles are found in anal sac secretions from other carnivorans, and are also associated with known bacterial biosynthesis pathways. This supports the fermentation hypothesis and the idea that the anal sac is maintained at least in part to house bacteria that produce volatiles for the host.

animal behavior and cognition↗