Biology subjects

Qu, M.

Publications and source records attributed to Qu, M..

12 recordsLinked to original sources

bioRxiv2025

An unrecognized and crucial role of chloroplast division in leaf variegation in Arabidopsis thaliana

Leaf variegation provides a valuable model for elucidating the molecular mechanisms that underlie chloroplast biogenesis, including both chloroplast development and division. While there has been notable advancement in comprehending the role of the Arabidopsis Yellow Variegated2 (VAR2), which encodes the AtFtsH2 subunit of the thylakoid FtsH metalloprotease complex, the exact mechanism governing leaf variegation formation remains elusive. In this study, time-course microscopy analyses of chloroplast number per cell from the first leaf pair revealed that most var2 cells lack chloroplasts. Interestingly, chloroplast biogenesis in the green sector of var2 leaves is significantly delayed but prolonged compared to the wild type (WT), leading to increased heterogeneity in chloroplast number and size among cells. These results suggest that chloroplast biogenesis in the green sector can partially compensate for the defect in the white sector. Additionally, approximately 15% of cells in var2 white sectors are devoid of plastids, and chloroplast number in guard cells is significantly lower in var2 than in WT, indicating that VAR2 mutations impair chloroplast division. Consistently, the var2 phenotype is exacerbated by knocking out key plastid division genes, including Paralog of Accumulation and Replication of Chloroplasts6 (PARC6) and Plastid Division1 (PDV1), but is fully rescued by overexpressing PDV1 or PDV2. Furthermore, VAR2 mutations inhibit etioplast development, while accelerating chloroplast biogenesis by knocking out Constitutively Photomorphogenic1 (COP1) rescues the var2 phenotype. Together, our findings reveal a novel role for VAR2 in plastid division and its essential function in chloroplast biogenesis, providing new insights into the mechanism underlying variegated leaf formation.

plant biology↗

bioRxiv2025

MiR-126 Improves the Therapeutic Effect of EPC in Hypertensive Ischemic Stroke

Background and PurposeHypertension promotes circulatory endothelial inflammation, reduces endothelial progenitor cell (EPC) function, and impairs their therapeutic potential following ischemic stroke. MiR-126 is known to regulate vascular development and angiogenesis. This study investigates the therapeutic potential of miR-126 by overexpressing it in EPCs to enhance their efficacy in hypertensive stroke conditions. MethodsAdult spontaneously hypertensive rats (SHRs, n=118) underwent permanent suture middle cerebral artery occlusion (MCAO) to induce ischemic stroke. One week post-stroke, animals were injected with EPCs overexpressing miR-126 or control EPCs. Treatment effects were evaluated over 35 days, using neurological scoring, infarct volume measurements, behavioral testing, and assessments of neuroinflammation, blood pressure, and angiogenesis. Exosomes from miR-126 overexpressing EPCs were isolated and analyzed for mechanistic studies. ResultsIn vitro, miR-126 enhanced EPC angiogenic function under stress. In vivo, miR-126 modified EPC treatment improved functional recovery, reduced infarct volume, and promoted angiogenesis compared to controls in SHRs. Furthermore, miR-126 treatment preserved the blood-brain barrier, reduced peripheral immune cell infiltration, and modulated neuroinflammation. Exosomes derived from miR-126 overexpression EPCs also promoted angiogenesis and reduced endothelial activation under stress conditions. ConclusionsEPC overexpressing miR-126 provides neuroprotection by enhancing angiogenesis, reducing ischemic injury, and preserving blood-brain barrier integrity in hypertensive stroke models. This approach modulates neuroinflammation and improves neurological outcomes, suggesting gene-modified EPCs as a promising strategy for ischemic stroke therapy, particularly under hypertensive conditions.

neuroscience↗

bioRxiv2024

Integrative analysis of transcriptome and metabolism reveals functional roles of redox homeostasis in low light and salt combined stress in Leymus chinensis

Soil salinity (Salt) is one of the major limiting factors of Leymus chinensis (named sheepgrass) performance and alters their primary metabolic process and gene expression. Salt stress could accelerate inhibitive effects concomitant with low light (LL-Salt). However, little is known about physiological and molecular mechanisms under such LL-Salt in sheepgrass. This study aims to uncover the key reprogrammed metabolic pathways induced by LL-Salt through an integrated analysis of transcriptome and metabolism. Plant seedlings were exposed to six combinations of light intensity (moderate light, ML, and LL) and NaCl concentrations (0, 50, and 200mM) for 20 days. Results suggest that the growth of sheepgrass seedlings was dramatically inhibited with severe lodging phenotype, especially when exposed to LL-Salt combined conditions. Activities of an antioxidant enzyme, catalase, were significantly increased in LL but significantly decreased in salt stress, leading to a reverse pattern for H2O2 in LL and salt stress. Transcriptome analysis reveals 4921 downregulated differentially expressed genes (DEGs) with carbon metabolism pathways were significantly enriched compared to light response without salt (ML_0 vs LL_0). There are 194 overlapped downregulated DEGs induced by two salt treatments (ML_50 vs ML_0 and ML_200 vs ML_0), where the carbon metabolism pathway was also significantly enriched. In terms of interactive effects of LL-Salt treatments, we found that there are 16 overlapped DEGs, including a phytochrome-interacting transcription factor 4 (PIF4) with upregulation in LL treatment while downregulation in salt treatment, which was validated by qPCR. Metabolism analysis confirmed that in carbon metabolism, the contents of seven differentially abundant metabolites (DAMs), including sucrose, were all downregulated in both LL and salt treatment. In contrast, serine and glycolate in the photorespiration pathway were downregulated in LL while upregulated in salt treatment. A photorespiration regulatory gene, glycolate oxidase expression, was confirmed by qPCR. Collectively, we found that serval antioxidant redox pathways, including photorespiration, GSG/GSSH redox, and ABA signaling, participated in response to LL and salt combined events and highlighted the roles of cellular redox homeostasis in LL-Salt response in sheepgrass.

plant biology↗

bioRxiv2024

Non-invasive brain-machine interface control with artificial intelligence copilots

Motor brain-machine interfaces (BMIs) decode neural signals to help people with paralysis move and communicate. Even with important advances in the last two decades, BMIs face key obstacles to clinical viability. Invasive BMIs achieve proficient cursor and robotic arm control but require neurosurgery, posing significant risk to patients. Non-invasive BMIs do not have neurosurgical risk, but achieve lower performance, sometimes being prohibitively frustrating to use and preventing widespread adoption. We take a step toward breaking this performance-risk tradeoff by building performant non-invasive BMIs. The critical limitation that bounds decoder performance in non-invasive BMIs is their poor neural signal-to-noise ratio. To overcome this, we contribute (1) a novel EEG decoding approach and (2) artificial intelligence (AI) copilots that infer task goals and aid action completion. We demonstrate that with this "AI-BMI," in tandem with a new adaptive decoding approach using a convolutional neural network (CNN) and ReFIT-like Kalman filter (KF), healthy users and a paralyzed participant can autonomously and proficiently control computer cursors and robotic arms. Using an AI copilot improves goal acquisition speed by up to 4.3x in the standard center-out 8 cursor control task and enables users to control a robotic arm to perform the sequential pick-and-place task, moving 4 randomly placed blocks to 4 randomly chosen locations. As AI copilots improve, this approach may result in clinically viable non-invasive AI-BMIs.

bioengineering↗

bioRxiv2024

Accurate estimation of SNP genotypes and genetic relatedness from DNA methylation data

Epigenome-wide association studies (EWAS) are susceptible to widespread confounding caused by population structure and genetic relatedness. Nevertheless, kinship estimation is challenging in EWAS without genotyping data. We propose MethylGenotyper, a method that for the first time enables accurate genotyping at thousands of SNPs directly from commercial DNA methylation microarrays. We model the intensities of methylation probes near SNPs with a mixture of three beta distributions corresponding to different genotypes and estimate parameters with an expectation-maximization algorithm. We conduct extensive simulations to demonstrate the performance of the method. When applying MethylGenotyper to Infinium EPIC array data of 4,662 Chinese, we obtain genotypes at 4,319 SNPs with a concordance rate of 98.26%, enabling the identification of 255 pairs of close relatedness. Furthermore, we show that MethylGenotyper allows for the estimation of both population structure and cryptic relatedness among 702 Australians of diverse ancestry. We have implemented MethylGenotyper in a publicly available R package to facilitate future large-scale EWAS.

bioinformatics↗

bioRxiv2023

UBAP2L drives scaffold assembly of nuclear pore complexes at the intact nuclear envelope

Assembly of macromolecular complexes at correct cellular sites is crucial for cell function. Nuclear pore complexes (NPCs) are large cylindrical assemblies with eightfold rotational symmetry, built through hierarchical binding of nucleoporins (Nups) forming distinct subcomplexes. Here, we uncover a direct role of ubiquitin-associated protein 2-like (UBAP2L) in the biogenesis of properly organized and functional NPCs at the intact nuclear envelope (NE) in human cells. UBAP2L localizes to the nuclear pores and drives the formation of the Y-complex, an essential scaffold component of the NPC, and its localization to the NE. UBAP2L facilitates the interaction of the Y-complex with POM121 and Nup153, the critical upstream factors in a well-defined sequential order of Nups assembly onto NE during interphase. Timely localization of the cytoplasmic Nup transport factor fragile X-related protein 1 (FXR1) to the NE and its interaction with the Y-complex are likewise dependent on UBAP2L. Thus, this NPC biogenesis mechanism integrates the cytoplasmic and the nuclear NPC assembly signals and ensures efficient nuclear transport, adaptation to nutrient stress and cellular proliferative capacity, highlighting the importance of NPC homeostasis at the intact nuclear envelope. TeaserLiao et al. show how UBAP2L drives the assembly of the scaffold elements into symmetrical and functional NPCs at the nuclear envelope in human cells.

cell biology↗

bioRxiv2023

PIF4 promotes water use efficiency during fluctuating light and drought resistance in rice

Molecular mechanism of intrinsic water use efficiency (iWUE) during fluctuating light (FL) was rarely understood. In this study, we investigated five parameters of iWUE under FL in 200 Minicore rice accessions. Among them, a novel trait, WUEFL (averaged iWUE during FL) has highest SNP heritability in these parameters. GWAS identifies six candidate genes, and PIF4 is highly expressed in high iWUEFL rice subgroup. Nine SNPs were significantly associated with iWUEFL, and v3 SNP located at -1,075 bp of PIF4 promoter shows highest sensitives to light. Deletion of v3 in a rice cultivar, WYG7 (PIF4v3m) leads to [~]20% reduction in iWUEFL, and overexpressing PIF4 causes 25% increase in iWUEFL under DS. There are 85% reduction in adenosine 3,5-diphosphate (PAP) amounts together with 73% increase in SAL1 gene abundance in PIF4v3m than WYG7. PIF4 transcriptionally repress and activate SAL1 and NHX1, respectively, through binding to G-box motifs of the two genes, which leads to 16% reduction and 5% increase in iWUEFL in co-overexpression rice lines of PIF4-SAL1 and PIF4-NHX1, respectively, relative to PIF4-OE under DS. We proposed that PIF4 promotes iWUEFL and stomatal adjustment via targeting the G-box motif of SAL1 and NHX1 genes during FL, eventually facilitating to drought resistance.

plant biology↗

bioRxiv2022

Actin cytoskeleton signaling via MRTF/SRF entrains circadian clock

The circadian clock is entrained to daily environmental cues. Integrin-linked intracellular signaling via actin cytoskeleton dynamics transduces extracellular matrix interactions to Myocardin-related Transcription Factor (MRTF)/Serum Response Factor (SRF)-mediated transcription. Actin cytoskeleton organization in liver displays diurnal oscillations and SRF-MRTF activity exert transcriptional control to entrain clock. By interrogating disparate upstream events involved in actin cytoskeleton-MRTF-A/SRF signaling cascade, here we show that this signaling cascade transduce cellular niche cues to modulate circadian clock function. Pharmacological inhibitions of MRTF-A/SRF, by disrupting actin polymerization or blocking ROCK kinase, induced period lengthening with augmented clock amplitude, and genetic loss-of-functions of Srf or Mrtf-a mimic that of actin-depolymerizing agents. In contrast, actin-polymerization induced by Jasplakinolide shortened period with attenuated amplitude. In addition, interfering with cell-matrix interaction through blockade of integrin, inhibition of focal adhesion kinase or attenuating matrix rigidity led to reduced period length while enhancing amplitude. Mechanistically, we identify that core clock repressors, Per2, Nr1d1, and Nfil3, are direct transcriptional targets of MRTF-A/SRF in mediating actin dynamic-induced clock response. Collectively, our findings defined an integrin-actin cytoskeleton-MRTF/SRF pathway in linking clock entrainment with extracellular microenvironment that may facilitate cellular adaptation to its physical niche. Summary statementOur study revealed the role of actin cytoskeleton-MRTF/SRF signaling in entraining circadian clock to its extracellular physical niche environment.

cell biology↗

bioRxiv2020

A non-enzymatic acetylation of lysine residues adversely affects the Rubisco activase protein stability

The post-translational modifications of non-histone (PTMs) proteins functions are crucial for the plant adaption to the changing environment. The Rubisco activase (RCA) plays a key role in the CO2 fixation through the Rubisco activation process. We reported that the RCA from tobacco leaf could be acetylated at several lysine residues including K126 and K164. The acetylation level changes under different light conditions (night and day) as well as under heat stress (45 {degrees}C). We further showed that the RCA can be non-enzymatically acetylated in vitro, especially by the acetyl-CoA (Ac-CoA) through direct interaction between them. Our results of the in vitro assay with deuterium labeled Ac-CoA (D2-Ac-CoA) show that the two conserved RCA lysine residues (K126 and K164) were acetylated by Ac-CoA, entraining a dramatic decline in its ATPase activity and a slight effect on the Rubisco activation process. Furthermore, we revealed that the higher RCA acetylation level induced its faster degradation in the chloroplast, which was not a direct consequence of ubiquitination. Eventually, our findings unraveled a new prominent role for the protein acetylation in modulating the RCA stability, which could certainly regulate the carbon assimilation efficiency towards a different energy status of the plants.

plant biology↗

bioRxiv2020

Surfaceome CRISPR Screen Identifies OLFML3 as a Rhinovirus-inducible IFN Antagonist

BackgroundRhinoviruses (RVs) cause more than half of common cold and, in some cases, more severe diseases. Functional genomics analyses of RVs using siRNA or genome-wide CRISPR screen uncovered a limited set of host factors, few of which has proven clinical relevance. ResultsHerein, we systematically compared genome-wide CRISPR screen and surface protein-focused CRISPR screen, referred to as surfaceome CRISPR screen, for their efficiencies in identifying RV host factors. It was found that surfaceome screen outperformed genome-wide screen in the success rate of hit identification. Importantly, using surfaceome screen we have identified olfactomedin like 3 (OLFML3) as a novel host factor of RV serotypes A and B including a clinical isolate. We found that OLFML3 was a RV-inducible suppressor of the innate immune response and that OLFML3 antagonized type I interferon (IFN) signaling in a SOCS3-dependent manner. ConclusionOur study has suggested that RV-induced OLFML3expression is an important mechanism for RV to hijack the immune system and underscored surfaceome CRISPR screen in identifying viral host factors.

molecular biology↗

bioRxiv2018

Nuclear receptor HNF4A trans-represses CLOCK:BMAL1 and acts as a core component of tissue-specific circadian networks

Either expression level or transcriptional activity of various nuclear receptors (NRs) have been demonstrated to be under circadian control. With a few exceptions, little is known about the roles of NRs as direct regulators of the circadian circuitry. Here we show that the nuclear receptor HNF4A strongly trans-represses the transcriptional activity of the CLOCK:BMAL1 heterodimer. We define a central role for HNF4A in maintaining cell-autonomous circadian oscillations in a tissue-specific manner in liver and colon cells. Not only transcript level but also genome-wide chromosome binding of HNF4A is rhythmically regulated in the mouse liver. ChIP-seq analyses revealed co-occupancy of HNF4A and CLOCK:BMAL1 at a wide array of metabolic genes involved in lipid, glucose and amino acid homeostasis. Taken together, we establish that HNF4A defines a novel feedback loop in tissue-specific mammalian oscillators and demonstrate its recruitment in the circadian regulation of metabolic pathways.\n\nSignificanceInterlocked feedback loops promote robustness and stability in a system and are a feature of circadian clocks in both animal and plants. The mammalian circadian clock is known to consist of two transcriptional feedback loops, relying on the transcriptional activity of the master complex CLOCK:BMAL1 and the feedback regulation by its target genes. Our research extends this knowledge by establishing a novel feedback loop in peripheral circadian oscillators and highlights the underlying mechanisms mediated by the unappreciated CLOCK:BMAL1 trans-repression activity of the circadian nuclear receptor HNF4A.

molecular biology↗

bioRxiv2017

Accurate Immune Repertoire Sequencing Reveals Malaria Infection Driven Antibody Lineage Diversification in Young Children

Accurately measuring antibody repertoire sequence composition in a small amount of blood is challenging yet important to the understanding of the repertoire response to infections and vaccinations. Here, we describe an accurate and high-coverage repertoire sequencing method, MIDCIRS, which uses as few as 1,000 naive B cells. Using it, we studied age-related antibody repertoire development and diversification before and during acute malaria in infants (< 12 months old) and toddlers (12 - 47 months old) with 4-8 ml of blood draws. Unexpectedly, we discovered high levels of somatic hypermutation (SHM) in infants as young as three months old. Antibody clonal lineage analysis revealed that both infants and toddlers increase SHM levels upon infection and memory B cells isolated from pre-malaria samples in malaria-experienced individuals continue to induce SHMs upon malaria rechallenge. These results highlight the vast potential of antibody repertoire diversification in infants and toddlers that has not been realized previously.

immunology↗