Biology subjects

Tu, K.

Publications and source records attributed to Tu, K..

9 recordsLinked to original sources

bioRxiv2026

Macronutrient Distribution and Protein Secondary Structure of Cool-Season Oats Revealed by Synchrotron-Based Mid-IR Spectroscopy and FTIR Chemical Imaging: Effects of Variety and Steam-Pressure Toasting Duration

This study aims to investigate changes in protein secondary structures (-helix, -sheet, random coils, and -turn) and macronutrient distribution in different cool-season oat varieties and steam-pressure toasting durations using synchrotron-based mid-infrared (Mid-IR) spectroscopy and Fourier Transform Infrared spectroscopy (FTIR) imaging. All oat samples, provided by the Crop Development Center at the University of Saskatchewan, were harvested over three consecutive years (2018, 2019, and 2020). The first experiment compared four oat varieties (CDC Arborg, CDC Nasser, CDC Haymaker, and Summit), while the second examined CDC Nasser oats subjected to steam-pressure toasting (SPT) at 121 for 0, 30, 60, 90, and 120 minutes. FTIR chemical imaging revealed that carbohydrates, proteins and lipids in the four oat varieties were mainly concentrated in the endosperm, aleurone layer and embryo, crease region, and remained unchanged after SPT. Peak-fitting deconvolution of the Amide I band (1700-1600 cm-1) and subsequent quantitative analysis revealed that the four oat varieties exhibited broadly similar protein secondary structure profiles, with statistically significant but subtle variety effects detected for -helix (P = 0.026), -turn (P = 0.047), and the -helix to -sheet ratio (P = 0.048), however, -sheet and random coil proportions did not differ significantly among varieties. In contrast, SPT induced pronounced structural rearrangements, with significant increase in -sheet proportion (P = 0.003) and significant decreases in random coil content (P = 0.026). Notably, 30 minutes of toasting was sufficient to significantly increase -sheet and decrease the random coil contents. These changes are consistent with heat-induced protein denaturation and intermolecular -sheet aggregation, where thermal energy breaks the hydrogen bonds that stabilize the disordered random coil conformation, causing the unfolded polypeptide chains to reassemble into highly ordered -sheet aggregates. After SPT, the peak centers of Amide I and II bands shifted to lower wavenumbers and both bands broadened while their intensities were maintained, reflecting the reorganization of the remaining protein into -sheet aggregates rather than any loss of amide-active protein. These findings suggest that, although genotype has a relatively minor effect on the protein secondary structure of oats, hydrothermal treatments fundamentally reorganize the protein matrix from a disordered to an ordered conformation, which may have implications for protein digestibility, solubility, and nutritional function.

biochemistry↗

bioRxiv2026

DyMoTree decodes early cell state transitions and drivers from single-cell transcriptomes using a tree-structured neural network

Inferring early cell fate from single-cell RNA-sequencing data is essential for identifying cellular origins and fate plasticity in development and disease. However, existing methods often fail to exploit tree-structured lineage trajectories, limiting the accuracy and interpretability of fate mapping. Here we present DyMoTree, a computational framework that models cell fate decisions as nonlinear mappings between progenitor and terminal cell states under explicit lineage constraints. By integrating lineage graphs with a tree-structured neural architecture, DyMoTree learns lineage-resolved cell-state transition maps from single-cell transcriptomes, enabling robust inference of early fate bias and identification of fate-specific progenitor substates and driver genes. Across simulations, lineage-tracing experiments, and in vivo systems, DyMoTree outperformed existing methods in resolving early fate biases. Applications to mouse embryogenesis, lung adenocarcinoma progression, and CAR-T immunotherapy revealed regulatory programs underlying developmental and disease-associated transitions. DyMoTree provides a general framework for modeling lineage-resolved cell-state dynamics underlying development and disease progression. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=156 SRC="FIGDIR/small/731114v2_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@11e715dorg.highwire.dtl.DTLVardef@1a4c695org.highwire.dtl.DTLVardef@e98805org.highwire.dtl.DTLVardef@1e14054_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2025

NQO1 phase condensation promotes stress granule assembly to facilitate pancreatic carcinogenesis

G3BP1 promotes pancreatic ductal adenocarcinoma (PDAC) tumorigenesis driven by oncogenic KRAS mutations through liquid-liquid phase separation (LLPS)-mediated assembly of stress granules (SGs). However, the regulatory mechanisms remain elusive. We identify the antioxidant enzyme NAD(P)H quinone dehydrogenase 1 (NQO1) as a novel SG regulator that enhances SG assembly in pancreatic cancer cells independently of reactive oxygen species (ROS). Mechanistic studies reveal that NQO1 does not regulate the expression of G3BP1 or other SG-associated genes. Instead, NQO1 undergoes LLPS dependent on its RNA-binding K homology (KH) like domain. Further analysis demonstrates that residues 121-131 of NQO1 directly interact with G3BP1s RNA-binding domain (RBD), enhancing the multivalency of G3BP1 complexes to potentiate LLPS-driven SG assembly. This interaction accelerates cell proliferation, KRAS mutation-induced acinar-to-ductal metaplasia (ADM), and pancreatic carcinogenesis. Notably, the interaction between NQO1 residues 121-131 and G3BP1s RBD is essential for NQO1 phase condensation under stress condition. Integrative analysis of human PDAC transcriptomic datasets reveals a weak association between NQO1 and G3BP1 levels. Importantly, both NQO1 and G3BP1 formed biological condensates and co-localized in the lesions of human PDAC tissue sections. Our study uncovers a novel KRAS mutation-driven mechanism of pancreatic carcinogenesis through the lens of phase separation, transcending conventional gene expression regulation and offering new insights into non-canonical KRAS-NQO1-G3BP1-SG regulatory networks in PDAC initiation.

cancer biology↗

bioRxiv2025

Somatic repetitive element insertions Define New Biomarkers in Pan-cancer genome

Repetitive elements insertions (REIs), including tandem repeat insertions (TRIs) and transposable element insertions (TEIs), constitute >90% of large-scale (>50bp) somatic insertions and are linked to diseases and cancer biomarkers. However, the genomic landscape of large-scale REIs in pan-cancer has not been well-characterized due to short-read sequencing limitations. Here, we detected somatic REIs in 325 cancer genomes across 12 cancer types using long-read whole-genome sequencing and customized algorithms. The diverse sequence patterns of somatic TRIs and the insertion mechanisms of somatic TEIs were characterized across different cancer types. We identified 152 high-frequency somatic TRIs, with 10 showing pan-cancer characteristics, including TRIs in SHROOM2, PALMD, and the enhancer of PTPRZ1. The MHC class II gene cluster exhibited the highest somatic TEI abundance, affecting [~]40% tumors. Adenocarcinomas and squamous cell carcinomas exhibited differing TEI distributions within this region. Our study highlights REIs as important but under-explored markers for personalized cancer diagnosis and immunotherapy.

genomics↗

bioRxiv2025

Accurate Somatic SV detection via sequence graph model-based local pan-genome optimization

Somatic structural variations (SVs) are critical genomic alterations in cancer genomes. Long-read sequencing (LRS) is theoretically optimal for detecting somatic SVs. However, influenced by reads-to-reference alignment errors, particularly in low-complexity or highly repetitive genomic intervals, current LRS-based somatic SV callers fail to accurately detect SVs. Moreover, the lack of comprehensive ground-truth datasets hinders accurate evaluation. Here, we introduce SVscope, a novel algorithm that fundamentally addresses these challenges by leveraging full-length sequence information from span-reads and integrating local graph-genome optimization with a random forest strategy. SVscope outperforms state-of-the-art methods on six paired long-read whole-genome sequencing (WGS) benchmark cell lines, achieving a maximum F1-score improvement of 16.7%. In simulated datasets, SVscope demonstrates superior performance in both somatic SV detection and read phasing tasks. Based on the findings from SVscope, we validated 47 somatic SVs, thereby significantly expanding the existing experimentally validated ground-truth somatic SV dataset by 69.1%.

bioinformatics↗

bioRxiv2024

Secreted cytokines from inflammatory macrophages modulate sex differences in valvular interstitial cells on hydrogel biomaterials

Patients with aortic valve stenosis (AVS) experience fibrosis and/or calcification in valve tissue, which leads to heart failure if left untreated. Inflammation is a hallmark of AVS and secreted cytokines from pro-inflammatory macrophages are thought to contribute to valve fibro-calcification by driving the activation of valvular interstitial cells (VICs) to myofibroblasts. However, the molecular mechanisms by which inflammatory cytokines differentially regulate myofibroblast activation as a function of biological sex are not fully defined. Here, we developed an in vitro hydrogel culture platform to culture male and female valvular interstitial cells (VICs) and characterize the sex-specific effects of inflammatory cytokines on VIC activation to myofibroblasts and osteoblast-like cells. Our data reveal that tumor necrosis factor alpha (TNF-) modulates female-specific myofibroblast activation via MAPK/ERK signaling, nuclear chromatin availability, and osteoblast-like differentiation via RUNX2 nuclear localization. Collectively, hydrogel biomaterials as cell culture platforms are critical for distinguishing sex differences in cellular phenotypes.

bioengineering↗

bioRxiv2022

A kinesin mediates VEGFR2 recycling and regulates VE-cadherin phosphorylation, essential for vascular permeability

Excessive vascular endothelial growth factor-A (VEGF-A) signaling induces vascular leakage and angiogenesis in diseases. VEGFR2 trafficking to the cell surface, mediated by kinesin-3 family protein KIF13B, is essential to respond to VEGF-A in inducing angiogenesis. However, the precise mechanism of how KIF13B regulates VEGF-induced signaling and endothelial permeability is unknown. Here we show that KIF13B-mediated recycling of internalized VEGFR2 through Rab11-positive recycling vesicle regulates VE-cadherin phosphorylation and endothelial permeability. Phosphorylated VEGFR2 at the cell-cell junction was internalized and associated with KIF13B in Rab5-positive early endosomes. KIF13B mediated VEGFR2 recycling through Rab11-positive recycling vesicle, and inhibition of this recycling attenuated phosphorylation of VEGFR2 at Y951, Src, and VE-cadherin at Y685, which are necessary for endothelial permeability. Failure of VEGFR2 trafficking to the cell surface induced accumulation and degradation of VEGFR2 in lysosomes. Furthermore, in the animal model of wet age-related macular degeneration (AMD), inhibition of KIF13B-mediated VEGFR2 trafficking also mitigated vascular leakage. Thus, the present results identify the fundamental role of VEGFR2 recycling to the cell surface in mediating vascular permeability, suggesting a promising strategy for mitigating vascular leakage associated with inflammatory diseases.

cell biology↗

bioRxiv2021

Amyloid-beta and tau pathologies are both necessary to induce novel stage-specific microglia subtypes during Alzheimer's disease progression.

It is unknown whether specific microglia are selectively induced by amyloid-{beta} (A{beta}), tau pathologies, or both in combination. To address this, we use single-cell RNA-sequencing to profile mice bearing both A{beta} and tau pathologies during Alzheimers disease (AD) progression. We identify novel microglia subtypes induced in a disease stage-specific manner. We show that during early-stage disease, interferon signaling induces a subtype of microglia termed EADAM. During late-stage disease, a second microglia subtype termed LADAM is detected. While EADAM and LADAM-like microglia are observed in other neurodegenerative models, the magnitude and composition of subtype markers are distinct from microglia observed with AD-like pathology. The pattern of EADAM- and LADAM-associated gene expression is observed in microglia from human AD, during the early and late stages of disease, respectively. Furthermore, we observe that several siglec genes are selectively expressed in either EADAM or LADAM. Siglecg is expressed in white-matter-associated LADAM, and expression of the human orthologue of Siglecg is progressively elevated in AD-stage-dependent manner but not shown in non-AD tauopathy. Our findings imply that both A{beta} and tau pathologies are required for disease stage-specific induction of EADAM and LADAM.

neuroscience↗

bioRxiv2019

Isometric exercise facilitates attention to salient events in women via the noradrenergic system

The locus coeruleus (LC) plays a critical role in regulating attention via the release of norepinephrine (NE), with levels of tonic LC activity constraining the intensity of phasic LC responses. However, the effects of manipulating tonic LC-NE activity on phasic activity have yet to be demonstrated in humans. In the current fMRI study, we used isometric handgrip to modulate tonic LC-NE activity in the time period immediately afterwards. During this post-handgrip time, an oddball detection task was used to probe how changes in tonic arousal influenced functional coordination between the LC and a right frontoparietal network that supports attentional selectivity. As expected, the frontoparietal network responded more to infrequent target and novel sounds than to frequent sounds. Across participants, greater LC-frontoparietal functional connectivity, pupil dilation, and faster oddball detection were all positively associated with LC MRI contrast from a neuromelanin-sensitive structural scan. Thus, LC structural integrity was related to LC functional dynamics and attentional performance during the oddball task. We also found that handgrip led to larger phasic pupil responses to oddball sounds, faster oddball detection speed, and greater frontoparietal network activation, suggesting that something that induces strong LC activity benefits attentional performance for at least the next few minutes. In addition, older women showed a similar benefit of handgrip on frontoparietal network activation as younger women, despite showing lower frontoparietal network activation overall. Together these findings suggest that a simple exercise may improve selective attention in healthy aging, at least for several minutes afterwards.\n\nHighlightsO_LIWe examined how handgrip affects arousal-attention dynamics during an oddball task\nC_LIO_LISalient stimuli enhanced pupil dilation and were detected faster post-handgrip\nC_LIO_LIA decrease in tonic pupil size after handgrip suggests norepinephrine depletion\nC_LIO_LIMRI-assessed LC integrity was related to oddball detection and pupil dilation\nC_LIO_LILC integrity also associated with LC-frontoparietal network functional connectivity\nC_LI

neuroscience↗