Biology subjects

McCarthy, T.

Publications and source records attributed to McCarthy, T..

9 recordsLinked to original sources

bioRxiv2026

A screen for stress-induced sleep genes in C. elegans reveals a role for glutamate signaling

Sleep is an essential behavioral state that evolved early in animals, possibly with the advent of the nervous system. The complexity of sleep neural networks varies significantly across phylogeny, yet common signaling molecules exist. Stress-induced sleep (SIS) of Caenorhabditis elegans is controlled by two sleep interneurons (ALA and RIS), within a 302-celled nervous system. Even in this simple framework, a complex array of signaling molecules is expressed. Here, we surveyed some of these genes for roles in SIS. These included neuropeptides, g-protein coupled receptors, a two-pored potassium channel, and glutamate signaling components. We found that multiple genes are required for sleep maintenance (i.e., amounts), and/or the precise timing of sleep initiation. In particular, we identified an important role for glutamate signaling. The conserved ionotropic glutamate receptor glr-5, regulates sleep maintenance and timing, and is required in a 3-celled circuit of interneurons connected by gap junctions and chemical synapses with RIS. This work suggests that numerous redundant and/or parallel mechanisms have evolved to modulate a simple sleep-regulating circuit in C. elegans, and we speculate that conserved pathways may play similar roles in animals with more complex systems.

genetics↗

bioRxiv2022

Visual Perception of 3D Space and Shape in Time - Part I: 2D Space Perception by 2D Linear Translation

Visual perception plays a critical role in navigating space and extracting useful semantic information crucial to survival. To identify distant landmarks, we constantly shift gaze vectors through saccades, while still maintaining the visual perception of stable allocentric space. How can we sustain stable allocentric space so effortlessly? To solve this question, we have developed a new concept of NHT (Neural Holography Tomography). This model states that retinotopy is invisible (not available to consciousness) and must be converted to a time code by traveling alpha brainwaves to perceive objects consciously. According to this framework, if identical alpha phases are continually assigned to a landmark, we perceive its exact and consistent allocentric location. To test this hypothesis, we designed reaction time (RT) experiments to observe evidence of the predicted space-to-time conversion. Various visual stimuli were generated at a wide range of eccentricities either on a large TV (up to 40{degrees}) or by LED strips on a hemispherical dome (up to 60{degrees}). Participants were instructed to report the observed patterns promptly under either covert (no eye movement) or overt (with eye movement) conditions. As predicted, stimuli presented at the center of fixation always produced the fastest RTs. The additional RT delay was precisely proportional to the eccentricity of the peripheral stimulus presentation. Furthermore, both covert and overt attention protocols created the same RT delays, and trajectories of saccadic eye motions were in parallel to the overt RT vs. eccentricity. These findings strongly support our NHT model, in which the observed RT-eccentricity dependence is indicative of the spatiotemporal conversion required for maintaining a stable allocentric frame of reference. That is, we perceive space by time.

neuroscience↗

bioRxiv2022

Visual Perception of 3D Space and Shape in Time - Part III: 2D Shape Recognition by Log-Scaling

Human vision has a remarkable ability to recognize complex 3D objects such as faces that appear with any size and 3D orientations at any 3D location. If we initially memorize a face only with a normalized size and viewed from directly head on, the direct comparison between the one-sized memory and a new incoming image would demand tremendous mental frame translations in 7D. How can we perform such a demanding task so promptly and reliably as we experience the objects in the world around us? Intriguingly, our primary visual cortex exhibits a 2D retinotopy with a log-polar coordinate system, where scaling up/down of shape is converted to linear frame translation. As a result, mental scaling can be performed by linearly translating the memory or the perceptual image until they overlap with each other. According to our new model of NHT (Neural Holography Tomography), alpha brainwaves traveling at a constant speed can conduct this linear translation. With this scheme, every scaling up/down by a factor of two should take the same amount of extra mental time to recognize a smaller/larger face. To test this hypothesis, we designed a reaction time (RT) experiment, where participants were first asked to memorize sets of unfamiliar faces with a given specific size (4{degrees} or 8{degrees}). Following the memorization phase, similar stimuli with a wide range of sizes (from 1{degrees} to 32{degrees}) were presented, and RTs were recorded. As predicted, the increase in RT was proportional to the scaling factor in the log scale. Furthermore, we observed that RTs were fastest for 8{degrees} faces even if the memorized face was 4{degrees}. This supports our hypothesis that we always memorize faces at the exact size of ~8 {degrees}. To our surprise, the increases in RT were also consistent with the mentally-estimated depth sensation, which indicates that the apparent size of the recognized face can create a proper depth sensation.

neuroscience↗

bioRxiv2022

Visual Perception of 3D Space and Shape In Time - Part IV: 3D Shape Recognition by 3D Rotation

Human vision has a remarkable ability to recognize complex 3D objects such as faces that appear at any size and 3D orientations at any 3D location. If we initially memorize a face only with a normalized size upfront at the object center, the direct comparison between the one-sized memory and an incoming new image would demand tremendous mental frame translations in 7D. How can we perform such a demanding task so promptly as we experience it in our daily lives? This paper specifically addresses the recognition of human faces with arbitrary 3D orientation in the [Roll, Yaw, Pitch] axes. According to our new model of NHT (Neural Holography Tomography), space is represented by time utilizing the phase of the alpha brainwave. This principle should be applicable to any mental rotation in 3D; thus, it predicts that extra time is required to perceive a rotated face to revolve it back to upright by the constant-speed alpha wave. To assess this hypothesis, we designed a reaction time (RT) experiment, where participants were first asked to memorize sets of upright unfamiliar faces. Following the memorization phase, similar stimuli with a wide range of rotating faces in 3D were presented, and RTs were recorded. As expected, the memorized upfront face was the fastest RT. The excess of the RT was observed proportional to the rotating angle in all [Roll, Yaw, Pitch] axes. Roll had the flattest slope, whereas upper Pitch was the steepest. We suspect that Roll is the swiftest mental operation because it can be conducted by the linear frame translation on the log-polar retinotopy of the visual cortex.

neuroscience↗

bioRxiv2022

Visual Perception of 3D Space and Shape in Time - Part II: 3D Space Perception with Holographic Depth

Visual perception plays a critical role in navigating 3D space and extracting semantic information crucial to survival. Even though visual stimulation on the retina is fundamentally 2D, we seem to perceive the world around us in vivid 3D effortlessly. This reconstructed 3D space is allocentric and faithfully represents the external 3D world. How can we recreate stable 3D visual space so promptly and reliably? To solve this mystery, we have developed new concepts MePMoS (Memory-Prediction-Motion-Sensing) and NHT (Neural Holography Tomography). These models state that visual signal processing must be primarily top-down, starting from memory and prediction. Our brains predict and construct the expected 3D space holographically using traveling alpha brainwaves. Thus, 3D space is represented by the three time signals in three directions. To test this hypothesis, we designed reaction time (RT) experiments to observe predicted space-to-time conversion, especially as a function of distance. We placed LED strips on a horizontal plane to cover distances from close up to 2.5 m or 5 m, either using a 1D or a 2D lattice. Participants were instructed to promptly report observed LED patterns at various distances. As expected, stimulation at the fixation cue location always gave the fastest RT. Additional RT delays were proportional to the distance from the cue. Furthermore, both covert attention (without eye movements) and overt attention (with eye movements) created the same RT delays, and both binocular and monocular views resulted in the same RTs. These findings strongly support our predictions, in which the observed RT-depth dependence is indicative of the spatiotemporal conversion required for constructing allocentric 3D space. After all, we perceive and measure 3D space by time as Einstein postulated a century ago.

neuroscience↗

bioRxiv2021

DatumKB: A Database of Biological Experimental Results

1.DatumKB is a freely accessible database of experimental results involving the function and regulation of human proteins in cultured cells. The results are manually curated from biological research literature using a shorthand language and stored as datums. Datums were originally designed to be used as evidence for rules in a Pathway Logic model of intracellular signal transduction (STM8, http://pl.csl.sri.com/online.html) (1). They are independent units that can be understood by biologists, traced back to their source, and have enough structure to be interrogated computationally. The information is expressed using a controlled vocabulary with links to well known databases such as HUGO Gene Nomenclature Committee (HGNC), UniProt, PubChem, and Cellosaurus. DatumKB can be searched using a query interface and the results can be downloaded in the original datum format, a simplified text format, or a JSON file. Links to detailed documentation of datum structure and a tutorial for the search engine are provided. Database URLhttps://datum.csl.sri.com

cell biology↗

bioRxiv2020

The orchestrated cellular and molecular responses of the kidney to endotoxin define the sepsis timeline

Clinical sepsis is a highly dynamic state that progresses at variable rates and has life-threatening consequences. Staging patients along the sepsis timeline requires a thorough knowledge of the evolution of cellular and molecular events at the tissue level. Here, we investigated the kidney, an organ central to the pathophysiology of sepsis. Single cell RNA sequencing revealed the involvement of various cell populations in injury and repair to be temporally organized and highly orchestrated. We identified key changes in gene expression that altered cellular functions and can explain features of clinical sepsis. These changes converged towards a remarkable global cell-cell communication failure and organ shutdown at a well-defined point in the sepsis timeline. Importantly, this time point was also a transition towards the emergence of recovery pathways. This rigorous spatial and temporal definition of murine sepsis will uncover precise biomarkers and targets that can help stage and treat human sepsis.

bioinformatics↗

bioRxiv2019

Experience and relatedness influence mating interactions in a simultaneously hermaphroditic snail, Physa gyrina

The means by which animals assess potential mates is an important issue in studies of reproductive systems. I tested whether an individuals previous experiences and the relatedness of mates affected mating behavior in a simultaneous hermaphrodite snail, Physa gyrina. Previous work with this species showed reduced reproductive success resulting from both strong outbreeding and inbreeding. Thus, I predicted that individuals should prefer partners of intermediate relatedness. During activity trials, snails moved longer distances when exposed to chemical cues from conspecifics of lesser relatedness. Furthermore, during mating interactions, behavioral responses to relatedness varied with gender-role: male-role behaviors did not vary across relatedness treatments, while snails paired with either closely related or highly dissimilar partners increased their female-role resistance behaviors as interactions escalated. Experiences with their current partner also affected behavioral dynamics. Familiar pairs had fewer matings and longer latency times until a mating occurred than unfamiliar pairs. Snails acting in the female role also exhibited higher resistance rates in familiar pairs than in unfamiliar pairs. Previous, brief exposure to chemical cues in a non-mating context also influenced behavior during a subsequent mating interaction. Snails that were previously exposed to chemical cues from unfamiliar individuals tended to be more likely to occupy the male role following an encounter, and had significantly lower copulation frequencies and higher female-role resistance rates (i.e. were choosier) than those previously exposed to cues from familiar individuals. Overall, the results show that: 1) relatedness, past exposure to conspecific chemical cues, and experience with a current partner all influence mating behaviors in these snails; and 2) in these simultaneous hermaphrodites, an individuals responses depend on whether it is occupying the male or female role.

animal behavior and cognition↗

bioRxiv2018

A synthetic, three-dimensional bone marrow hydrogel

Three-dimensional (3D) synthetic hydrogels have recently emerged as desirable in vitro cell culture platforms capable of representing the extracellular geometry, elasticity, and water content of tissue in a tunable fashion. However, they are critically limited in their biological functionality. Hydrogels are typically decorated with a scant 1-3 peptide moieties to direct cell behavior, which vastly underrepresents the proteins found in the extracellular matrix (ECM) of real tissues. Further, peptides chosen are ubiquitous in ECM, and are not derived from specific proteins. We developed an approach to incorporate the protein complexity of specific tissues into the design of biomaterials, and created a hydrogel with the elasticity of marrow, and 20 marrow-specific cell-instructive peptides. Compared to generic PEG hydrogels, our marrow-inspired hydrogel improves stem cell differentiation and proliferation. We propose this tissue-centric approach as the next generation of 3D hydrogel design for applications in tissue engineering.

bioengineering↗