Biology subjects

Zhang, L.-Y.

Publications and source records attributed to Zhang, L.-Y..

7 recordsLinked to original sources

bioRxiv2026

Refractive index modulation by ultraviolet absorption of canonical amino acids for in vivo optical transparency

The inherent opacity of most mammalian tissues limits deep-tissue optical imaging and light delivery. In contrast, the natural transparency of certain species and ocular tissues has been hypothesized to involve proteins with unusually high refractive indices. Here, we systematically analyze the ultraviolet absorption and visible-range refractive index modulation of canonical amino acids to identify key contributors to high-refractive index proteins. We identify arginine as a leading candidate, combining strong ultraviolet absorption, efficient refractive index modulation, physiological pH, and biocompatibility. These properties are validated through successful achievement of optical transparency in both ex vivo and in vivo tissues. Our findings establish a foundation for using abundant endogenous biomolecules to achieve in vivo tissue transparency and suggest a strategy for engineering proteins enriched in high-performing amino acids to enable efficient, biocompatible tissue clearing.

biophysics↗

bioRxiv2026

Tartrazine clears live cells while preserving viability at high refractive indices and osmolality

Tissue-clearing techniques have transformed optical imaging of fixed specimens, yet their application to living systems remains limited by toxicity and removal of key tissue components. We recently demonstrated that absorbing molecules such as tartrazine can reversibly render live mouse skin transparent. Subsequently, it was reported that isotonic protein solutions can achieve ex vivo and in vivo cellular clearing. However, discrepancies remain regarding the optimal refractive index (RI) for live-cell clearing and the impact of elevated osmolality on cell viability. Here, using cultured mammalian cells, we systematically examine the dependence of optical contrast on medium RI and the effects of hyperosmolality. We find that, contrary to the recent report of an optimal RI of 1.36[~]1.37 for suspended cells, densely-packed adherent cells exhibit a monotonic decrease in phase contrast up to an RI of 1.41 with tartrazine. Moreover, even under highly hyperosmotic conditions ([~]1200 mOsm/kg), cultured cells exhibit minimal deformation and negligible loss of viability for up to 30 min in the clearing solution. These results demonstrate that tartrazine enables effective live-cell clearing at RI up to 1.41 while preserving viability under elevated osmolality, and motivate future studies to define optimal conditions for in vivo optical clearing. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=44 SRC="FIGDIR/small/717314v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@1ec9fbforg.highwire.dtl.DTLVardef@1ebe9e6org.highwire.dtl.DTLVardef@1492c3corg.highwire.dtl.DTLVardef@f75559_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2026

Diet quality shapes development and feeding circuits in poison frog tadpoles

From birth, offspring must balance internal energy state with the costs of signaling need to caregivers to secure nutrition for growth and healthy development. How diet during this period shapes the developing brain and behavior is a central question in biology, with growing relevance for understanding the developmental origins of metabolic disorders such as obesity. Yet the effects of early nutrition on growth, neural development, and behavior are rarely examined together within a single system. Here, we use poison frog tadpoles as a vertebrate model in which offspring develop outside a womb, can be reared independently under precisely controlled dietary conditions, and display diverse behaviors at a young age. By independently manipulating dietary quantity and quality, we link early nutrition to growth, brain development, and social behavior during ontogeny. Diet quantity increased body size, whereas diet quality accelerated development. Diet quality, but not quantity, shaped behavior: tadpoles fed a natural diet showed increased affiliation during food solicitation and reduced feeding, while aggression and risk avoidance remained unchanged. Diet also affected body and brain development differently, with artificial diets producing larger tadpoles but reduced volume in some brain regions, including areas associated with begging behavior. Anorexigenic urocortin-1 neurons were active during begging behavior and, together with another anorexigenic midbrain population, decreased in abundance under an artificial diet. Functionally, urocortin-1 reduced feeding without directly increasing begging, suggesting it gates socio-positive behavior by suppressing a competing drive rather than initiating it. Together, this work shows that dietary quantity and quality act on distinct developmental processes, with diet quality programming the brain circuits that permit begging behavior while growth is determined by food quantity.

neuroscience↗

bioRxiv2025

Color-neutral and reversible tissue transparency enables longitudinal deep-tissue imaging in live mice

Light scattering in biological tissue presents a significant challenge for deep in vivo imaging. Our previous work demonstrated the ability to achieve optical transparency in live mice using intensely absorbing dye molecules, which created transparency in the red spectrum while blocking shorter-wavelength photons. In this paper, we extend this capability to achieve optical transparency across the entire visible spectrum by employing molecules with strong absorption in the ultraviolet spectrum and sharp absorption edges that rapidly decline upon entering the visible spectrum. This new color-neutral and reversible tissue transparency method enables optical transparency for imaging commonly used fluorophores in the green and yellow spectra. Notably, this approach facilitates tissue transparency for structural and functional imaging of the live mouse brain labeled with yellow fluorescent protein and GCaMP through the scalp and skull. We show that this method enables longitudinal imaging of the same brain regions in awake mice over multiple days during development. Histological analyses of the skin and systemic toxicology studies indicate minimal acute or chronic damage to the skin or body using this approach. This color-neutral and reversible tissue transparency technique opens new opportunities for noninvasive deep-tissue optical imaging, enabling long-term visualization of cellular structures and dynamic activity with high spatiotemporal resolution and chronic tracking capabilities. Significance StatementTissue scattering represents a major barrier to deep tissue imaging in vivo. We recently showed that tissue can be rendered transparent in the red spectrum using intensely absorbing dye molecules. Here, we introduce a new, color-neutral and reversible tissue transparency approach. We demonstrate longitudinal structural and functional imaging in the deep tissue of awake mice.

bioengineering↗

bioRxiv2023

Conjunctive vector coding and place coding in hippocampus share a common directional signal

Vector coding is becoming increasingly understood as a major mechanism by which neural systems represent an animals location in both a global reference frame and a local, item-based reference frame. Landmark vector cells (LVCs) in the hippocampus complement classic place cells by encoding the vector relationship (angle and distance) between the individual and specific landmarks in the environment. How these properties of hippocampal principal cells interact is not known. We simultaneously recorded the activities of place cells and LVCs via in vivo calcium imaging of the CA1 region of freely moving rats during classic, cue-card rotation studies. The firing fields of place cells rotated relative to the center of the platform to follow the cue card rotation, whereas the firing fields of simultaneously recorded LVCs rotated by the same amount as the place cells, but the axis of rotation was the nearby local landmarks, not the environmental center. We identified a novel type of place cell that exhibited conjunctive coding of the classic place field properties and LVC properties. These results demonstrate the capacity of CA1 neurons to encode both world-centered spatial information and animals location relative to the local landmarks, with a common directional input presumably provided by the head direction cell system.

neuroscience↗

bioRxiv2022

A multivariate regressor of patterned dopamine release predicts relapse to cocaine

Drug addiction is characterized by a sustained vulnerability to relapse even after long periods of abstinence. A deeper understanding of the brain systems underlying this state could inform therapeutic strategies with novel prognostic biomarkers aimed at preventing renewed drug seeking. Most drugs of abuse, in particular psychostimulants such as cocaine, lead to long-lasting mesolimbic dopamine system adaptations, that ultimately facilitate drug seeking following exposure to drug-paired cues. This "dopaminergic hypothesis" of relapse has been previously addressed, but technical limitations in measuring in vivo dopamine release have precluded the assessment of its sufficiency without introducing pharmacological, electrical, or optogenetic confounds. Using a dopamine receptor-based fluorescent sensor in freely moving mice, we show that long-lasting dopamine recordings in the nucleus accumbens (NAc), throughout the animals entire history of cocaine self-administration, are strong predictors of relapse as well as the time it takes an animal to extinguish its drug seeking behavior. Moreover, we reveal previously unseen sex-specific trajectories of cocaine-related phasic dopamine responses from acquisition to relapse. We show that males exhibit higher-amplitude phasic dopamine responses, a trait accompanied by a greater resistance to extinguish their cocaine seeking, compared to females. Furthermore, we show that a semi-parametric model of the transition to extinction - using only multivariate patterns of dopamine release and sex as covariates - faithfully recapitulates male-specific vulnerability to persistent cocaine seeking. In conclusion, we present a predictive model of reinstatement behavior that uses information exclusively conveyed by NAc phasic dopamine responses, thus confirming, and actuating the sufficiency of the dopaminergic hypothesis of relapse.

neuroscience↗

bioRxiv2017

A Genetic Pathway Composed of EDT1/HDG11, ERECTA, and E2Fa Loci Regulates Water Use Efficiency by Modulating Stomatal Density

Improvement of crop drought resistance and water use efficiency (WUE) has been a major endeavor in agriculture. ERECTA is the first identified major effector of water use efficiency. However, the underlying molecular mechanism is not well understood. Here, we report a genetic pathway, composed of EDT1/HDG11, ERECTA, and E2Fa loci, which regulates water use efficiency by modulating stomatal density. The HD-START transcription factor EDT1/HDG11 transcriptionally activates ERECTA expression by binding to an HD cis-element in the ERECTA promoter. ERECTA in turn relies on E2Fa to control the expression of cell-cycle related genes and the transition from mitosis to endocycle, which leads to increased nuclear DNA content in leaf cells, and therefore increased cell size and decreased stomatal density. The decreased stomatal density improves plant WUE. Our study demonstrates the EDT1/HDG11-ERECTA-E2Fa genetic pathway that reduces stomatal density by increasing cell size, providing a new avenue to improve WUE of crops.

plant biology↗