Biology subjects

Coleman, T.

Publications and source records attributed to Coleman, T..

8 recordsLinked to original sources

bioRxiv2026

Feasibility of an anterior abdominal electrode array for non-invasive measurement of uterine contractions across the menstrual cycle

While traditionally associated with pregnancy and labor, uterine contractions (UC) also occur throughout the menstrual cycle. Abnormalities in UC frequency and/or direction throughout the cycle are correlated with many uterine disorders, which can have downstream impacts on overall health, necessitating continuous monitoring throughout the cycle. Current UC monitoring technologies are invasive or bulky, and not suitable for routine monitoring. The most promising approach uses non-invasive surface abdominal electrodes in a method known as electrohysterography (EHG). However, current EHG methods remain unsuitable for longitudinal monitoring due to bulkiness and reliance on patient-specific anatomical scans. Furthermore, there are no simulations of non-pregnant UC to aid in resolving these limitations. In this work, we evaluate the feasibility of EHG using an electrode array placed only on the anterior abdomen of size 6.35 x 14 cm and without any knowledge of patient anatomy for non-invasive measurement of UC across the menstrual cycle though both simulation and experiment. We identify a signal-to-noise ratio necessary to resolve frequency, amplitude, and direction of UC in simulation. In experimental data, all recordings met the coherence criterion identified in simulation, and we find patterns across the menstrual cycle which are congruent with previous literature. These results demonstrate the feasibility of an anterior abdominal electrode array for monitoring UC across the menstrual cycle, a step towards wearable EHG.

bioengineering↗

bioRxiv2026

Vascular waveform analysis using Bayesian pulse deconvolution

Vascular waveforms, which measure bulk flow in blood vessels, are widely used to measure vital signs, diagnose conditions, and predict long-term health outcomes. Analyzing vascular waveforms depends on three fundamentally interdependent tasks: signal filtering, pulse timing detection, and pulse shape extraction. We hypothesized that Bayesian pulse deconvolution can achieve improved performance on all three tasks by solving them jointly. This method uses an analytical, generative model of vascular waveforms with priors informed by physical and biological domain knowledge. In simulations, Bayesian pulse deconvolution achieves better performance on all tasks compared with existing algorithms: 90% reduction of median filtering error, 60% reduction in pulse timing error, and 85% reduction in shape extraction error. The advantages in simulations extend to human recordings of photoplethysmography waveforms. Taking real time-synchronized electrocardiogram R-R intervals as a proxy ground truth, Bayesian pulse deconvolution achieves 40% lower pulse interval estimation error (RMSE = 5.1 ms) compared with typical algorithms (RMSE = 8.3 ms, p=1e-10). By extracting more accurate and informative insights from vascular waveforms, Bayesian pulse deconvolution could advance a wide array of health technologies that rely on interpreting signals from blood vessels.

bioengineering↗

bioRxiv2026

An integrated, scaled approach to resolve TSC2 variants of uncertain significance

Obtaining a precise genetic tuberous sclerosis diagnosis is a challenge as many missense TSC2 variants are variants of uncertain significance (VUS). VUS in TSC2 have been resolved by one-at-a-time functional assays, but these assays cannot scale to the 3,634 TSC2 missense VUS observed so far. To address this challenge, we used massively parallel sequencing to measure the steady-state abundance of almost 9,000 TSC2 missense variants and developed an mTOR pathway activity assay using genome editing and cell sorting to generate activity scores for 391 missense variants. 1,288 of 8,891 (14.49%) missense variants assayed had altered TSC2 abundance, and 69 of 391 (17.65%) missense variants assayed had altered mTOR pathway activity. Calibration and integration of these data into classification of variants identified in a clinical cohort putatively reclassified 212 of 276 (76.8%) TSC2 missense VUS. These datasets will lead to improved genetic diagnosis of tuberous sclerosis with potential positive impacts on the clinical management of patients and their families.

genetics↗

bioRxiv2025

Novel Olfactometer Reveals Brain-Breathing Interactions During Olfactory Perception

AO_SCPLOWBSTRACTC_SCPLOWOlfaction is fundamental to perception, memory, and emotion, yet the neural basis of human odor processing remains poorly understood. Here, we demonstrate that odor-evoked brain activity is organized by respiratory phase-not absolute time-revealing that natural breathing structures olfactory cortical dynamics. Using simultaneous nasal respiration and electroencephalography (EEG) recordings in 17 participants, we delivered naturalistic odors (peppermint, oregano, and grapefruit) synchronized to individual breathing cycles. Odor presentation elicited distinct, respiratory phase-locked event-related spectral perturbations (RPL-ERSPs) in frontal and temporal regions, emerging during the first breath after stimulus onset. The most discriminative neural signatures were theta-band activity during inhalation and alpha-band activity during exhalation, patterns that were obscured in traditional time-locked analyses due to natural variability in breath duration. Leave-one-subject-out cross-validation of RPL-ERSPs achieved reliable odor discrimination (peppermint: AUC = 0.78; oregano: AUC = 0.68; grapefruit: AUC = 0.61), establishing that phase-locked features generalize across individuals. To connect neural responses to perceptual experience without relying on precise odor naming--which is notoriously difficult and can be disproportionately impaired in some populations--we quantified odor recognition using free-response descriptions scored with a semantic-similarity approach. Behavioral recognition strength paralleled the neural decoding hierarchy across odors, establishing the perceptual validity of RPL-ERSPs. RPL-ERSPs also revealed rapid habituation, with decoding performance declining over repeated presentations, due to selective degradation of the most informative phase-locked features. Together, these findings establish respiratory rhythm as a temporal scaffold for human olfactory cortical processing, positioning RPL-ERSPs as a sensitive, task-free approach for assessing olfactory function. We provide an open-source, respiration-synchronized olfactometer design (<$500) to enable replication and broader adoption of this approach. 1 TeaserAligning brain activity to natural breathing unlocks objective neural markers of human smell perception.

neuroscience↗

bioRxiv2023

The biochemical impact of extracting an embedded adenylate kinase domain using circular permutation

Adenylate kinases (AKs) are phosphotransferases that are frequently employed as models to investigate protein structure-function relationships. Prior studies have shown that AK homologs of different stabilities retain cellular activity in cells following circular permutation that split the AMP binding domain into fragments coded at different ends of the primary structure, such that this domain was no longer embedded as a continuous polypeptide within the core domain. Herein, we show mesophilic and thermophilic AKs having this topological restructuring retain activity and substrate-binding characteristics of the parental AK. While permutation decreased the activity of both AK homologs at physiological temperatures, the catalytic activity of the thermophilic AK increased upon permutation when assayed >30{degrees}C below the melting temperature of the native AK. The thermostabilities of the permuted AKs were uniformly lower than native AKs, and they exhibited multi-phasic unfolding transitions, unlike the native AKs, which presented cooperative thermal unfolding. In addition, proteolytic digestion revealed that permutation destabilized each AK, and mass spectrometry suggested that the new termini within the AMP binding domain were responsible for the increased proteolysis sensitivity. These findings illustrate how changes in contact order can be used to tune enzyme activity and alter folding dynamics in multidomain enzymes. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/564053v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@1ee9ecdorg.highwire.dtl.DTLVardef@fbb415org.highwire.dtl.DTLVardef@ebdd90org.highwire.dtl.DTLVardef@11f4271_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2023

Light-Guided Rabies Virus Tracing for Neural Circuit Analysis

Neuronal tracing methods are essential tools to understand the fundamental architecture of neural circuits and their connection to the overall functional behavior of the brain. Viral vectors used to map these transsynaptic connections are capable of cell-type-specific and directional-specific labeling of the neuronal connections. Herein, we describe a novel approach to guide the transsynaptic spreading of the Rabies Virus (RV) retrograde tracer using light. We built a Baculovirus (BV) as a helper virus to deliver all the functional components necessary and sufficient for a nontoxic RV to spread from neuron to neuron, with a light-actuated gene switch to control the RV polymerase, the L gene. This design should allow for precisely controlled polysynaptic viral tracing with minimal viral toxicity. To use this system in a highly scalable and automated manner, we built optoelectronics for controlling this system in vitro with a large field of view using an off-the-shelf CMOS sensor, OLED display panel, and microcontrollers. We describe the assembly of these genetic circuits using the uLoop DNA assembly method and a library of genetic parts designed for the uLoop system. Combining these tools provides a framework for increasing the capabilities of nontoxic tracing through multiple synapses and increasing the throughput of neural tracing using viruses.

neuroscience↗

bioRxiv2022

Yeasts have evolved divergent enzyme strategies to deconstruct and metabolize xylan

Together with bacteria and fungi, yeasts actively take part in the global carbon cycle. Over a hundred yeast species have been shown to grow on the major plant polysaccharide xylan, which requires an arsenal of carbohydrate active enzymes. However, which enzymatic strategies yeasts use to deconstruct xylan and what specific biological roles they play in its conversion remain unclear. In fact, genome analyses reveal that many xylan-metabolizing yeasts lack expected xylanolytic enzymes. Guided by bioinformatics, we have here selected three xylan-metabolizing ascomycetous yeasts for in-depth characterization of growth behavior and xylanolytic enzymes. The savanna soil yeast Blastobotrys mokoenaii displays superior growth on xylan thanks to an efficient secreted glycoside hydrolase family 11 (GH11) xylanase; solving its crystal structure revealed a high similarity to xylanases from filamentous fungi. The termite gut-associated Scheffersomyces lignosus in contrast grows more slowly and its xylanase activity was found to be mainly cell surface-associated. The wood-isolated Wickerhamomyces canadensis surprisingly could not utilize xylan as the sole carbon source without adding xylooligosaccharides, exogenous xylanases or even by co-culturing with B. mokoenaii, suggesting that W. canadensis relies on initial xylan hydrolysis by neighboring cells. Furthermore, our characterization of a novel W. canadensis GH5 subfamily 49 (GH5_49) xylanase represents the first demonstrated activity in this subfamily. Our collective results provide new information on the variable xylanolytic systems evolved by yeasts and their potential roles in natural carbohydrate conversion. ImportanceMicrobes that take part in the degradation of the polysaccharide xylan, the major hemicellulose component in plant biomass, are equipped with specialized enzyme machineries to hydrolyze the polymer into monosaccharides for further metabolism. However, despite being found in virtually every habitat, little is known of how yeasts break down and metabolize xylan and what biological role they may play in its turnover in nature. Here, we have explored the enzymatic xylan deconstruction strategies of three underexplored yeasts from diverse environments: Blastobotrys mokoenaii from soil, Scheffersomyces lignosus from insect guts and Wickerhamomyces canadensis from trees, and show that each species has a distinct behavior regarding xylan conversion. These findings may be of high relevance for future design and development of microbial cell factories and biorefineries utilizing renewable plant biomass.

microbiology↗

bioRxiv2021

Focused Ultrasound Modulation of Hepatic Neural Plexus Restores Glucose Homeostasis in Diabetes

While peripheral glucose sensors are known to relay signals of substrate availability to integrative nuclei in the brain, the importance of these pathways in maintaining energy homeostasis and their contribution to disease remain unknown. Herein, we demonstrate that selective activation of the hepatoportal neural plexus via transient peripheral focused ultrasound (pFUS) induces glucose homeostasis in models of well-established insulin resistant diabetes. pFUS modulates sensory projections to the hindbrain and alters hypothalamic concentrations of neurotransmitters that regulate metabolism, resulting in potentiation of hypothalamic insulin signaling, leptin-independent inhibition of the orexigenic neuropeptide Y system, and therapeutic alteration in autonomic output to peripheral effector organs. Multiomic profiling confirms pFUS-induced modifications of key metabolic functions in liver, pancreas, muscle, adipose, kidney, and intestines. Activation of the hepatic nutrient sensing pathway not only restores nervous system coordination of peripheral metabolism in three different species but does so across these organ systems; several of which are current targets of antidiabetic drug classes. These results demonstrate the potential of hepatic pFUS as a novel/non-pharmacologic therapeutic modality to restore glucose homeostasis in metabolic diseases, including type II diabetes. One Sentence SummaryWe utilize a non-invasive ultrasound technique to activate a liver-brain sensory pathway and demonstrate its potential to induce durable normalization of glucose homeostasis in models of well-established insulin resistant diabetes.

biophysics↗