Biology subjects

Kang, D.

Publications and source records attributed to Kang, D..

At least 19 recordsLinked to original sources

bioRxiv2026

Surfactant-Assisted Colorimetric Signal Enhancement in Paper-Based Glucose Sensing

Paper-based colorimetric sensors offer a low-cost and accessible platform for point-of-care (POC) analysis, but enzyme activity loss during coating and drying can weaken analytical signals and require high enzyme loadings or complex immobilization procedures. Although surfactants are widely used to improve wettability in paper-based assays, their potential contribution to colorimetric performance beyond these effects remains unclear. Here, we investigated surfactant-assisted colorimetric signal enhancement in a glucose assay implemented on a 96-puddle paper plate (96-PPP) and identified Tween 20 as the most effective surfactant. Its effect on detection performance became more pronounced as glucose oxidase (GOx) loading decreased; at 0.1 mg/mL GOx, Tween 20 lowered the limit of detection (LoD) from 0.113 to 0.034 mg/mL (approximately 3.3-fold) over a working range of 0-5 mg/mL, despite no statistically significant change in the measured contact angle at this loading. Tween 20 had no appreciable effect on the reaction in solution but preserved 95% of the apparent reaction rate constant after drying, compared with 11% without it, and atomic force microscopy (AFM) revealed a more dispersed dried enzyme morphology on mica. Tween 20-containing sensors also showed slower signal decay during repeated wetting-drying cycles and thermal stress, retained 77% (vs 26%) of the response at 400 mM NaCl, and exhibited within-PPP and between-batch coefficients of variation (CVs) below 10% (vs 12.3-19.5%), while maintaining glucose selectivity over potentially interfering molecules. These results indicate that Tween 20 enhances paper-based glucose sensing beyond wettability, in part by retaining enzyme cascade activity during drying, although the contributions of the individual enzymes and the underlying mechanism remain to be established.

bioengineering↗

bioRxiv2026

Network- and Measure-Specific Mid-Term Reliability of Multi-Echo Resting-State Functional Magnetic Resonance Imaging on a Compact 3 Tesla Scanner

1.IntroductionUnderstanding mid-term test-retest reliability and within-subject variability is important for interpreting changes observed in longitudinal and intervention studies. The reliability of resting-state functional magnetic resonance imaging (rs-fMRI) is known to vary across measures and brain regions. However, how reliability differs across functional networks and connectivity-and amplitude-based measures, and whether multi-echo acquisition and processing modify these patterns, remain incompletely characterized. MethodsTwenty-two healthy volunteers underwent two rs-fMRI sessions 15.7 {+/-} 4.0 days apart on a Compact 3T scanner. Multi-echo, middle-echo, and independently acquired single-echo datasets were compared, with multi-echo independent component analysis additionally evaluated as a denoising approach. Functional connectivity (FC) and three amplitude-based measures were evaluated using the Schaefer 400 parcellation. Reliability was systematically assessed using intraclass correlation coefficient (ICC), within-subject standard deviation (wSD), and systematic bias at edge or regional, and network levels. ResultsAcquisition-dependent differences in reliability were generally modest. Multi-echo acquisition and processing increased functional connectivity strength and the magnitude of amplitude-based measures and improved inferior cortical coverage, but these enhancements did not consistently translate into substantially higher ICC or lower wSD. In contrast, reliability showed clear network-dependent differences. FC reliability varied markedly across network pairs and was not explained by connectivity strength alone; pairs involving the default mode and control networks generally showed more favorable profiles than several somatomotor and visual network pairs. Fractional amplitude of low-frequency fluctuations (fALFF) also showed network-dependent reliability, with the most favorable regional reproducibility observed in the default mode and control networks and lower reproducibility in the somatomotor and visual networks. ConclusionThese findings provide practical mid-term reliability benchmarks for rs-fMRI on a Compact 3T scanner and show that measurement stability varies more clearly across measures and functional networks than across acquisition approaches. Key pointsO_LIMid-term test-retest reliability varied more clearly across resting-state measures and functional networks than across acquisition and processing approaches. C_LIO_LIMulti-echo acquisition and processing enhanced functional connectivity strength, amplitude-based signal magnitude, and inferior cortical coverage but did not consistently improve reliability. C_LIO_LIFunctional connectivity strength and fractional amplitude of low-frequency fluctuations showed distinct network-specific reliability profiles, with more favorable reproducibility in default mode and control networks than in several somatomotor and visual networks. C_LI

neuroscience↗

bioRxiv2026

Midgut damage triggers thromboxane A2-dependent hemocyte recruitment in Culex pipiens molestus

Mosquitoes transmit diverse pathogens through repeated blood feeding, a process that subjects the midgut to significant mechanical stress and cellular damage. While hemocyte association with the midgut is known to occur following injury, the mechanisms promoting their recruitment remain poorly defined. Given the conserved roles of eicosanoid signaling in injury responses, we hypothesized that thromboxane A2 (TXA2) mediates hemocyte recruitment to the damaged midgut. Here, we demonstrate that chemically induced midgut damage significantly increases both the number of hemocytes attached to the midgut and those in circulation. Pharmacological inhibition of cyclooxygenase suppresses hemocyte recruitment whereas supplementation with a stable TXA2 analog restores the response, indicating that TXA2 signaling is required for this process. To identify candidate enzymes involved in TXA2 biosynthesis, we performed in silico docking analyses and identified two cytochrome P450 (CYP) candidates. Among these, CYP6D3 was shown to be strongly upregulated in hemocyte populations following midgut damage. RNA interference-mediated knockdown of CYP6D3 significantly reduced both hemocyte recruitment to the midgut and systemic TXB2 levels, supporting its role in the eicosanoid-mediated immune response. Together, our findings demonstrate that TXA2 signaling drives hemocyte recruitment to the damaged mosquito midgut and suggest a conserved lipid-mediated mechanism underlying insect tissue-associated immune responses that may influence vector competence.

biochemistry↗

bioRxiv2026

Continuous Nuclear Export of p62/SQSTM1 Is Essential for Kidney Homeostasis

The selective autophagy receptor p62/SQSTM1 dynamically shuttles between the nucleus and cytoplasm through distinct nuclear localization and export signals, yet the physiological significance of this trafficking has remained unknown. Here, we generated mice carrying a deletion of the p62 nuclear export signal (dNES) to determine the in vivo role of p62 nuclear export. Homozygous dNES mice developed progressive podocyte injury, glomerulosclerosis, and fatal renal failure by 6-7 weeks of age, whereas heterozygous and dNES/- mice did not develop renal dysfunction. Loss of nuclear export caused constitutive nuclear accumulation of p62, accompanied by the formation of insoluble ubiquitin-positive aggregates and widespread alterations in the renal proteome, including activation of energy metabolism-related pathways and suppression of developmental programs. We previously demonstrated that the lipid peroxidation product 4-hydroxy-2-nonenal (4-HNE) inhibits the nuclear export receptor XPO1, resulting in nuclear retention of p62 in cultured cells. The present findings provide in vivo evidence that continuous nuclear export of p62 is indispensable for maintaining kidney homeostasis and reveal that excessive nuclear accumulation, rather than cytoplasmic depletion, underlies p62-mediated toxicity. Collectively, these findings establish continuous nuclear export of p62 as an essential mechanism for maintaining kidney homeostasis. Significance StatementThe adaptor protein p62/SQSTM1 continuously shuttles between the nucleus and cytoplasm, but the physiological significance of this trafficking has remained unknown. Here, we show that disrupting the nuclear export signal of p62 causes progressive podocyte injury, glomerulosclerosis, and fatal kidney failure through excessive nuclear accumulation and aggregate formation. In contrast, dNES/+ and dNES/- mice remain healthy, demonstrating that excessive nuclear accumulation, rather than cytoplasmic depletion, drives disease. These findings identify continuous nuclear export as a fundamental mechanism that prevents toxic nuclear accumulation of p62 and preserves kidney homeostasis.

cell biology↗

bioRxiv2026

Pore-Resolved High-Throughput Quantification of Amyloid Aggregation and Amplification

Amyloid fibrils are implicated in a wide spectrum of neurodegenerative and systemic disorders, yet their biological consequences are governed not only by total fibril content but also by how fibrillar species are organized, clustered, and amplified within heterogeneous populations. Conventional thioflavin T (ThT)-based assays provide sensitive sample-level readouts of {beta}-sheet-rich material but offer limited access to the local population structure underlying amyloid aggregation and amplification. Here, we introduce the Amyloid Pore Quantification (APQ) chip, a pore-resolved geometric partitioning platform that converts heterogeneous amyloid assembly states into fluorescence intensity distributions across thousands of defined pore-level units. Using hen egg-white lysozyme as a model amyloid-forming protein, we combine length-controlled truncated amyloid nanofibrils with vacuum-assisted ThT infiltration to establish a reproducible pore fluorescence intensity reference. APQ provided quantitative concentration-dependent calibration across a 50-fold concentration range, enabling bulk-comparable quantification while preserving pore-level distribution information. Deviations from this reference resolved pH-dependent fibril clustering near the isoelectric point as pore-signal suppression and accessibility loss, captured pepsin-associated fibrillar amplification as a population-wide increase in pore intensity, and distinguished monomer- and oligomer-driven fibril processing through coupled amplification-aggregation fingerprints. When benchmarked against ensemble fluorescence measurements and AFM morphological analysis, APQ revealed assembly-state changes that were not fully represented by sample-level ThT intensity alone. These results establish APQ as a high-throughput, distribution-aware analytical framework for translating amyloid aggregation and amplification into quantitative pore-resolved fingerprints.

bioengineering↗

bioRxiv2026

Deconstructing a behavioral state: parallel neural integrators control distinct features of an aversive behavioral state in C. elegans

Transient sensory stimuli can trigger long-lasting changes in behavior and cognition. For example, repeated aversive experiences can lead to persistent changes in arousal and mood. Specialized integrator circuits can store information about recent experiences, but how they are embedded within the architecture of the brain to control internal brain states remains poorly understood. We find that C. elegans accumulates evidence of past aversive experiences over minutes to generate a scalable behavioral state consisting of multiple behavioral changes. Using a brain-wide imaging screen, we identified a set of neurons that integrate aversive sensory stimuli over different timescales, from seconds to minutes. Neuronal perturbations show that these integrator neurons are critical for the aversive behavioral state. They control distinct behavioral features, such as changes in locomotion speed or increased responsiveness to subsequent aversive stimuli. Moreover, the integrator neurons function in parallel to one another, utilize different mechanisms to generate persistent neural activity, and signal through different transmitters. Our result show how a behavioral state can be decomposed into distinct behavioral features that map onto different neural integrators that act in parallel. Combined action of the integrators then generates the full set of behaviors that comprise the global state.

neuroscience↗

bioRxiv2026

Mechanochemically Programmed, Oligomer-Selective Amyloid Assembly via Axial Rotation

Amyloid oligomers have been widely implicated as primary cytotoxic intermediates; however, their selective and scalable production remains challenging due to rapid fibril amplification. Here, we demonstrated that sustained axial rotation enables programmable mechanochemical control over amyloid pathway selection without the use of chemical additives. Using a thermal axial rotator, native monomeric hen egg-white lysozyme was incubated at 60 {degrees}C under quantitatively tunable rotational speeds, imposing defined centrifugal forces and wall-associated shear that restructured the hydrodynamic boundary conditions. A discrete transition emerged near 600 RPM, separating the two distinct assembly regimes. Below this threshold, aggregation followed a fibril-amplifying pathway characterized by elevated {beta}-sheet content and elongated fibrillar morphologies. Above this threshold, fibrillar growth was strongly attenuated and oligomer-dominant assemblies predominated. Spectroscopic analyses and atomic force microscopy revealed that axial rotation redistributes the amyloid assembly states rather than simply suppressing aggregation. Functionally, the RPM-defined assemblies exhibited kinetically distinct seeding behaviors and induced divergent cytotoxic phenotypes in SH-SY5Y neuroblastoma cells. These findings establish axial rotation-mediated hydrodynamic boundary control as a scalable, chemical-free strategy for reprogramming amyloid assembly pathways and producing oligomer-rich assemblies with well-defined structural and functional properties.

bioengineering↗

bioRxiv2026

Cerebral Oxygen Budgeting: Network-Level BOLD Dynamics During Acute Hypoxia

Hypoxia constrains cerebral oxygen availability and challenges brain function. Previous work showed that functional connectivity reorganizes early during acute hypoxia, preceding cognitive deterioration, but the functional changes accompanying more severe hypoxic stress remain incompletely understood. We examined dynamic amplitude of low-frequency fluctuations (dALFF) in blood-oxygenation-level dependent (BOLD) fMRI during normoxia, sustained mild hypoxia, and transient severe hypoxia in healthy adults performing a continuous Go/No-go task with concurrent physiological monitoring. We characterized dALFF at whole-brain and network levels using a causal sliding-window approach, principal component analysis, and Schaefer's 17-network parcellation. Severe hypoxia elicited a non-monotonic, phase-dependent dALFF response that was not observed during normoxia or sustained mild hypoxia. Relative preservation during early hypoxia was followed by late-hypoxia suppression, which we operationally defined as a decompensation phase, and by a pronounced rebound after reoxygenation. Within this global response, dALFF became increasingly differentiated across intrinsic brain networks: DefaultA showed marked suppression, whereas SomMotB exhibited relative preservation or enhancement during decompensation. These changes were neither spatially uniform nor tightly synchronized with systemic oxygenation, while broadly overlapping temporally with cognitive deterioration. Together, these findings indicate that dALFF captures a complementary aspect of the brain's response to acute hypoxic stress, characterized by reversible, phase- and network-dependent reorganization of ongoing low-frequency BOLD dynamics under constrained oxygen availability.

neuroscience↗

bioRxiv2026

Multi-Omics Mapping of Human Kidney Reveals Complement-Mediated Cellular Dynamics During Progression of Focal Segmental Glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is a major cause of glucocorticoid-resistant nephrosis, yet its pathogenesis remains unclear. To define the molecular and cellular landscape of FSGS, we employed multi-omics approaches on independent human kidney biopsy cohorts. Proteomics revealed enhanced immune and complement activation. Spatial transcriptomics using a target gene panel constructed from the proteomics highlighted alternative pathway activation driven by complement factor D as a prominent feature. Complement activation emerged in glomeruli alongside altered signaling in podocytes and parietal epithelial cells (PECs): Podocytes displayed reduced PECAM1 and elevated macrophage migration inhibitory factor (MIF) signaling, and PECs display complement and collagen signaling as early events, and progressively acquired cellular activation, prompting glomerular fibrosis. These pathogenic signals propagated into adjacent interstitial regions, paralleling immune cell infiltration and fibrosis. These results uncover dynamics of dysregulated intercellular interactions originated from podocyte and PECs underlying the pathogenesis of FSGS, which provides insights into potential stage-specific interventions.

systems biology↗

bioRxiv2025

Loss of the Ferripyochelin Receptor FptA Drives Reduced Cefiderocol Susceptibility and Impairs Fitness in Pseudomonas aeruginosa PA14

Pseudomonas aeruginosa is an opportunistic human pathogen and a frequent cause of multidrug-resistant infections. This organism continues to evade antimicrobial therapy despite the clinical introduction of new anti-pseudomonal antibiotics over the past several years. One of these agents is cefiderocol (FDC), a novel siderophore-cephalosporin conjugate antibiotic that was designed to overcome both intrinsic and acquired {beta}-lactam resistance mechanisms in P. aeruginosa. However, studies have demonstrated that inactivation of TonB-dependent receptors, most notably the catechol siderophore receptor piuA can substantially curtail the drugs ability to permeate the bacterial outer membrane, leading to rapid development of resistance. In this study, we examined the FDC resistance mechanisms of the laboratory strain PA14. We demonstrated that inactivation of the ferripyochelin receptor FptA was a first-step mutation towards FDC resistance. Through transposon mutagenesis, we identified several resistance pathways following fptA inactivation, such as the loss of an additional FDC import porin and overexpression of the MuxABC-OpmB multidrug efflux system. Introduction of clinically-identified mutations analogous to these transposon insertions in the absence of fptA conferred full FDC non-susceptibility while preserving the activity of other antipseudomonal {beta}-lactam antibiotics. We also demonstrated that inactivation of fptA in a pyoverdine biosynthetic mutant disrupted bacterial iron homeostasis and conferred a fitness disadvantage. These FDC resistance mechanisms identified in PA14 highlight the long-term challenges of using FDC treatment for drug-resistant P. aeruginosa infections.

microbiology↗

bioRxiv2025

Brain functional connectivity initiates structured reorganization at a critical oxygen threshold during hypoxia

The human brain dynamically adapts to hypoxia, a reduction in oxygen essential for metabolism. The brains adaptive response to hypoxia, however, remains unclear. We investigated dynamic functional connectivity (FC) in healthy adults under acute hypoxia (FiO2 = 7.7%, 11.8%) using BOLD fMRI, physiological monitoring (PetO2, PetCO2, SpO2), and a Go/No-Go task. Principal component analysis identified a hypoxia-responsive FC component involving 400 cerebral parcels. This component emerged with a critical drop in PetO2 ([~]53 mmHg), preceding changes in SpO2, BOLD signals, and behavior. These FC changes were network-specific and centered on the default mode network (DMN), which selectively synchronized with other high-level cognitive networks. In contrast, visual networks remained stable and segregated from the DMN. These results suggest that the brain proactively reorganizes its functional architecture in anticipation of oxygen decline, rather than in response to it. FC-based markers may offer early indicators of vulnerability in neurological or neurodegenerative conditions.

neuroscience↗

bioRxiv2025

High-throughput microbiome profiling and co-occurrence with antibiotic resistance genes in Lucilia sericata

Blow flies such as Lucilia sericata (Diptera: Calliphoridae) serve important ecological functions as decomposers. However, due to their close association with decaying organic matter they also play potential roles as reservoirs for pathogenic bacteria and antimicrobial resistance genes (ARGs). In this study, we characterized the bacterial communities and resistome profiles of L. sericata specimens collected from six provinces across South Korea using 16S rRNA gene metabarcoding and targeted PCR screening. The microbiome was dominated by Dysgonomonas, Vagococcus, Pseudomonas, Ignatzschineria, and Providencia with geographic variation in community structure. Flies from Chungnam exhibited the lowest microbial diversity, while samples from Jeonnam and Gyeonggi showed greater richness and evenness. Beta diversity analyses confirmed geographic structuring of bacterial communities, with semi-urban, rural locations harboring more diverse taxa. Notably, opportunistic pathogens such as Proteus mirabilis and Providencia were detected, alongside a range of ARGs (blaTEM, ermB, sul1, aac(6')-Ib-cr, cat and mecA) and integron elements (intI and intII), suggesting that L. sericata may act as a reservoir of clinically important microbes and resistance genes. ImportanceThe environment plays a significant role in shaping the microbiome of flies. Due to their motile nature and close association with decomposing matter blow flies of the species Lucilia sericata can harbor diverse bacterial communities, including potential pathogens that threaten human and animal health. Furthermore, due to their synanthropic lifestyle, this species is also exposed to bacteria that host antibiotic resistance genes (ARGs). Here we investigate the role of blowflies as reservoirs of potential pathogens and ARGs using metabarcoding. Our study revealed a diverse microbiome and resistome shaped by location and possible biotic or abiotic factors. These findings provide baseline information for wildlife surveillance and emphasize the importance of including synanthropic flies in strategies aimed at controlling the dissemination of antibiotic resistance.

ecology↗

bioRxiv2025

ViFIT-assisted Histopathology: From H&E Style Standardization to Virtual Fiber Image Transformation

Deep learning-based virtual fiber staining provides a promising complement to routine H&E pathology. However, the reliance on predefined staining style inputs and manual intervention limits the clinical applicability of existing methods. To address these challenges, we introduce ViFIT-assisted histopathology, a two-stage diagnostic approach that integrates our proposed unsupervised deep learning-based virtual fiber transformation model (ViFIT). This approach enables the conversion of H&E-stained images with diverse styles into pathologist-preferred H&E images, while simultaneously generating content-consistent virtual fiber images containing label-free collagen fibers and stained reticular and elastic fibers. ViFIT-assisted histopathology reveals tumor-associated fibers and provides quantitative metrics across multiple intraoperative and postoperative cases. Experimental results demonstrate that ViFIT significantly outperforms state-of-the-art unsupervised methods in both style standardization and virtual staining, across various downstream tasks and cancer types. By eliminating the need for staining variation and manual annotation, ViFIT-assisted histopathology streamlines histopathology workflows, making it well-suited for multi-center consultations and differential diagnosis.

pathology↗

bioRxiv2024

Male-specific sNPF peptidergic circuits control energy balance for mating duration through neuron-glia interactions.

ABSTRACTThis study reveals a sexually dimorphic sNPF-sNPF-R circuit in the Drosophila brain that regulates energy balance behavior, specifically the shorter-mating-duration (SMD) response to sexual experience. sNPF is predominantly expressed in neurons, while sNPF-R is expressed in both neurons and glial cells, particularly astrocyte-like glia (ALG) in a subset of cells outside the mushroom body (MB) termed "Rishi cells" (RS cells). Sexual experience induces global alterations in calcium signaling and synaptic plasticity within this circuit, with sNPF-R expressing neurons and glia in RS cells playing a critical role in encoding sexual experience-related information into energy balance behavior related to mating duration. Neuronal glucose metabolism, specifically the Tret1l transporter, is essential for maintaining the high calcium levels and proper function of sNPF neurons near RS cells. This novel and intricate neuron-glia sNPF-sNPF-R network acts as critical circuits within the Drosophila brain for processing interval timing behaviors, highlighting the dynamic interplay between metabolism, neural circuits, and behavior in regulating energy balance.

neuroscience↗

bioRxiv2024

A functional screen for ubiquitin regulation identifies an E3 ligase secreted by Pseudomonas aeruginosa

Ubiquitin signaling controls many aspects of eukaryotic biology, including targeted protein degradation and immune defense. Remarkably, invading bacterial pathogens have adapted secreted effector proteins that hijack host ubiquitination to gain control over host responses. These ubiquitin-targeted effectors can exhibit, for example, E3 ligase or deubiquitinase activities, often without any sequence or structural homology to eukaryotic ubiquitin regulators. Such convergence in function poses a challenge to the discovery of additional bacterial virulence factors that target ubiquitin. To overcome this, we have developed a workflow to harvest natively secreted bacterial effectors and functionally screen them for ubiquitin regulatory activities. After benchmarking this approach on diverse ligase and deubiquitinase activities from Salmonella Typhimurium, Enteropathogenic Escherichia coli, and Shigella flexneri, we applied it to the identification of a cryptic E3 ligase activity secreted by Pseudomonas aeruginosa. We identified an unreported P. aeruginosa E3 ligase, which we have termed Pseudomonas Ub ligase 1 (PUL-1), that resembles none of the other E3 ligases previously established in or outside of the eukaryotic system. Importantly, in an animal model of P. aeruginosa infection, PUL-1 ligase activity plays an important role in regulating virulence. Thus, our workflow for the functional identification of ubiquitin-targeted effector proteins carries promise for expanding our appreciation of how host ubiquitin regulation contributes to bacterial pathogenesis.

microbiology↗

bioRxiv2024

Peptide inhibitors targeting FOXO4-p53 interactions and inducing senescent cancer cell-specific apoptosis

Cellular senescence, marked by irreversible cell cycle arrest and the secretion of proinflammatory factors, contributes to aging and cancer recurrence. Chemotherapy can also induce senescence; senescent cells often resist apoptosis and promote tumor recurrence. The interaction between FOXO4 and p53 sustains cell survival. Herein, we used biophysical techniques and conducted cellular experiments to develop a peptide inhibitor targeting this interaction to eliminate senescent cancer cells. We identified key regions in the p53 transactivation domain (TAD) involved in FOXO4 binding and designed an optimized peptide inhibitor (CPP-CAND) with improved cell permeability. CPP-CAND showed high selectivity and potency in inducing apoptosis in senescent cells by disrupting FOXO4-p53 foci and activating caspase pathways. It is effective against senescent cancer cells induced by doxorubicin and cisplatin, highlighting its potential as a senolytic drug. Thus, CPP-CAND is a promising therapeutic candidate with improved selectivity, efficacy, and cost-effectiveness.

biochemistry↗

bioRxiv2024

Experience instructs the refinement of feature-selectivity in the mouse primary visual thalamus

Neurons exhibit selectivity for specific features: a property essential for extracting and encoding relevant information in the environment. This feature-selectivity is thought to be modifiable by experience at the level of the cortex. Here, we demonstrate that selective exposure to a feature during development can instruct the population representation for that feature in the primary visual thalamus. This thalamic plasticity is not simply inherited from the cortex because it is still observed when recordings were performed in the absence of cortical feedback. Moreover, plasticity is blocked in mutant mice that exhibit deficits in retinogeniculate refinement, indicating that alterations in feature-selectivity are a direct result of changes in feedforward connectivity. These experience-dependent changes persist into older ages--highlighting the importance of this developmental period in shaping population coding in the thalamus. Our results show that salient environmental features are hard-wired into thalamic circuits during a discrete developmental window.

neuroscience↗

bioRxiv2024

Deep Neural Networks to Register and Annotate the Cells of the C. elegans Nervous System

Aligning and annotating the heterogeneous cell types that make up complex cellular tissues remains a major challenge in the analysis of biomedical imaging data. Here, we present a series of deep neural networks that allow for automatic non-rigid registration and cell identification, developed in the context of freely moving and deforming invertebrate nervous systems. A semi-supervised learning approach was used to train a C. elegans registration network (BrainAlignNet) that aligns pairs of images of the bending C. elegans head with single pixel-level accuracy. When incorporated into an image analysis pipeline, this network can link neurons over time with 99.6% accuracy. This network could also be readily purposed to align neurons from the jellyfish Clytia hemisphaerica, an organism with a vastly different body plan and set of movements. A separate network (AutoCellLabeler) was trained to annotate >100 neuronal cell types in the C. elegans head based on multi-spectral fluorescence of genetic markers. This network labels >100 different cell types per animal with 98% accuracy, exceeding individual human labeler performance by aggregating knowledge across manually labeled datasets. Finally, we trained a third network (CellDiscoveryNet) to perform unsupervised discovery of >100 cell types in the C. elegans nervous system: by comparing multi-spectral imaging data from many animals, it can automatically identify and annotate cell types without using any human labels. The performance of CellDiscoveryNet matched that of trained human labelers. These tools should be immediately useful for a wide range of biological applications and should be straightforward to generalize to many other contexts requiring alignment and annotation of dense heterogeneous cell types in complex tissues.

neuroscience↗