Biology subjects

Tang, C. Y.

Publications and source records attributed to Tang, C. Y..

6 recordsLinked to original sources

bioRxiv2026

A comparative framework for neocortical sulcal anatomy in pinnipeds

The transition of pinnipeds from terrestrial ancestors into marine environments provides a unique opportunity to examine how cortical organisation has changed with adaptation to life in water. Here, we examined neocortical sulcal anatomy in nine species representing all three extant pinniped families using cortical surfaces reconstructed from post-mortem MRI. Building on a standardised framework previously established for land-dwelling (fissiped) carnivorans, we developed identification criteria for major pinniped sulci and compared their configurations with those observed across fissipeds. Major sulci were broadly conserved, but pinnipeds exhibited characteristic modifications, including a complex, highly branched pseudosylvian configuration and distinct frontoparietal sulcal patterns, with further family-level variation in both territories. This observed variation in sulcal patterns may reflect pronounced differences in locomotor, tactile, and vocal specialisations, generating hypotheses about how cortical organisation may vary with adaptation to marine environments. Together, these findings establish a common anatomical framework across Carnivora for investigating how cortical organisation diversified in relation to behaviour and ecology.

neuroscience↗

bioRxiv2026

SOX9-mediated G1 elongation confers reserve stem cell-associated injury resistance in human intestinal stem cells

Background & Aims Dynamic cell cycle control is critical for intestinal crypt maintenance and injury responses, yet genetic regulators driving these changes remain poorly defined. As reserve intestinal stem cells (rISCs) are often considered to be slowly-cycling and can resist replication-dependent injury, factors that restrain proliferation may confer cytoprotection. Here, we define SOX9 as a regulator of intestinal stem cell (ISC) cycling and injury resistance. Methods Primary human ISCs were engineered to tune SOX9 levels, visualize cell cycle state, and manipulate cell cycle regulators. Using this system, we tested how SOX9 dosage impacts stemness, differentiation, proliferative recovery after SOX9 washout, and survival after 5-FU-mediated injury. Transcriptional analyses identified candidate links between SOX9 levels and cell cycle control, which were functionally tested using inducible INK4A (CDKN2A) and Cyclin D2 (CCND2) ISC lines. Results SOX9 induction lengthens the cell cycle in a dose-dependent manner largely by elongating G1 phase through the INK4A-Rb pathway. The effects of high SOX9 levels repressing proliferation and stem cell activity are reversible. SOX9 induction protects against 5-FU toxicity. This protection is mimicked by INK4A overexpression or pharmacological G1 phase arrest and repressed by CCND2 induction. Conclusions These findings identify SOX9-mediated G1 elongation as a reversible cytoprotective program that confers key functional properties associated with rISCs: proliferative restraint, retained stem cell potential, and resistance to replication-dependent injury. This positions G1 length as a potential determinant of which crypt cells survive injury to act as reserve stem cells.

cell biology↗

bioRxiv2023

An in vitro platform for quantifying cell cycle phase lengths in primary human intestinal stem cells

Background and AimsThe intestinal epithelium exhibits dynamic control of cell cycle phase lengths, yet no experimental platform exists for directly analyzing cell cycle phases in living human intestinal stem cells (ISCs). Here, we develop primary human ISC lines with two different reporter constructs to provide fluorescent readouts to analyze cell cycle phases in cycling ISCs. Methods3D printing was used to construct a collagen press for making chamber slides that support primary human ISC growth and maintenance within the working distance of a confocal microscope objective. The PIP-FUCCI fluorescent cell cycle reporter and a variant with H2A-mScarlet that allows for automated tracking of cell cycle phases (PIP-H2A) were used in human ISCs along with live imaging and EdU pulsing. An analysis pipeline combining free-to-use programs and publicly available code was compiled to analyze live imaging results. ResultsChamber slides with soft collagen pressed to a thickness of 0.3 mm concurrently support ISC cycling and confocal imaging. PIP-FUCCI ISCs were found to be optimal for snapshot analysis wherein all nuclei are assigned to a cell cycle phase from a single image. PIP-H2A ISCs were better suited for live imaging since constant nuclear signal allowed for more automated analysis. CellPose2 and TrackMate were used together to track cycling cells. ConclusionsWe present two complete platforms for analyzing cell cycle phases in living primary human ISCs. The PIP-FUCCI construct allows for cell cycle phase assignment from one image of living cells, the PIP-H2A construct allows for semi-automated direct quantification of cell cycle phase lengths in human ISCs using our computational pipeline. These platforms hold great promise for future studies on how pharmaceutical agents affect the intestinal epithelium, how cell cycle is regulated in human ISCs, and more.

cell biology↗

bioRxiv2023

Neuro-Environmental Interactions: a time sensitive matter

The assessment of resting state (rs) neurophysiological dynamics relies on the control of sensory, perceptual, and behavioral environments to minimize variability and rule-out confounding sources of activation during testing conditions. Here, we investigated how temporally-distal environmental inputs, specifically metal exposures experienced up to several months prior to scanning, affect functional dynamics measured using rs functional magnetic resonance imaging (rs-fMRI). We implemented an interpretable XGBoost-Shapley Additive Explanation (SHAP) model that integrated information from multiple exposure biomarkers to predict rs dynamics in typically developing adolescents. In 124 participants (53% females, ages: 13-25 years) enrolled in the Public Health Impact of Metals Exposure (PHIME) study, we measured concentrations of six metals (manganese, lead, chromium, cupper, nickel and zinc) in biological matrices (saliva, hair, fingernails, toenails, blood and urine) and acquired rs-fMRI scans. Using graph theory metrics, we computed global efficiency (GE) in 111 brain areas (Harvard Oxford Atlas). We used a predictive model based on ensemble gradient boosting to predict GE from metal biomarkers, adjusting for age and biological sex. Model performance was evaluated by comparing predicted versus measured GE. SHAP scores were used to evaluate feature importance. Measured versus predicted rs dynamics from our model utilizing chemical exposures as inputs were significantly correlated (p< 0.001, r = 0.36). Lead, chromium, and copper contributed most to the prediction of GE metrics. Our results indicate that a significant component of rs dynamics, comprising approximately 13% of observed variability in GE, is driven by recent metal exposures. These findings emphasize the need to estimate and control for the influence of past and current chemical exposures in the assessment and analysis of rs functional connectivity.

neuroscience↗

bioRxiv2022

Elephants have an adaptable prehensile grip

Elephants have long been observed to grip objects with their trunk, but little is known about how they adjust their strategy for different weights. In this study, we challenge a female African elephant at Zoo Atlanta to lift 20 to 60 kg barbell weights with only its trunk. We measure the trunks shape and wrinkle geometry from a frozen elephant trunk at the Smithsonian. We observe several strategies employed to accommodate heavier weights, including accelerating less, orienting the trunk more vertically, and wrapping the barbell with a greater trunk length. Mathematical models show that increasing barbell weights are associated with constant trunk tensile force and an increasing barbell-wrapping surface area due to the trunks wrinkles. Our findings may inspire the design of more adaptable soft robotic grippers that can improve grip using surface morphology such as wrinkles.

bioengineering↗

bioRxiv2019

Resting state functional connectivity in early post-anesthesia recovery is characterized by globally reduced anticorrelations

Though a growing body of literature is addressing the possible longer-term cognitive effects of anesthetics, to date no study has delineated the normal trajectory of neural recovery due to anesthesia alone in older adults. We obtained resting state functional magnetic resonance imaging scans on 62 healthy human volunteers between ages forty and eighty before, during, and after sevoflurane (general) anesthesia, in the absence of surgery, as part of a larger study on cognitive function post-anesthesia. Resting state networks expression decreased consistently one hour after emergence from anesthesia. This corresponded to a global reduction in anticorrelated functional connectivity post-anesthesia, seen across individual regions-of-interest. Positively correlated functional connectivity remained constant across peri-anesthetic states. All measures returned to baseline 1 day later, with individual regions-of-interest essentially returning to their pre-anesthesia connectivity levels. These results define normal peri-anesthetic changes in resting state connectivity in healthy older adults.

neuroscience↗