Biology subjects

WANG, M.

Publications and source records attributed to WANG, M..

7 recordsLinked to original sources

bioRxiv2025

Phosphate limitation triggers Fe3+-dependent polymyxin resistance in Enterobacteriaceae

Phosphate (Pi) scarcity, a pervasive stressor prevalent in bacterial infections and dysbiotic host environments, potently drives antimicrobial resistance (AMR) against cationic antibiotics like polymyxins across diverse bacterial taxa. While established Pi depletion-induced AMR mechanisms often involve membrane phospholipid remodelling, Enterobacteriaceae largely lack these pathways, leaving their Pi scarcity-driven AMR mechanism unresolved. Here, we reveal that Pi limitation robustly induces polymyxin resistance in Enterobacteriaceae through 4-amino-4-deoxy-L-arabinose (L-Ara4N) modification of the Gram-negative outer membrane component lipid A, reflecting a distinct adaptive strategy. This modification is driven by strong ugd-arn operon induction, mediated by the PmrAB two-component system. We discover that Pi depletion triggers cellular Mg{superscript 2} release, prompting compensatory Fe3 mobilization to the cell envelope that directly activates PmrAB. Crucially, this metal-dependent signaling axis offers a directly targetable mechanism for reversing polymyxin resistance, a significant deviation from the less accessible, PhoBR-regulated phospholipid remodelling strategies in other bacteria. We demonstrate that Mg{superscript 2} supplementation or Fe3 chelation effectively suppresses PmrAB activation and restores polymyxin susceptibility, thereby establishing a novel, metal-centric paradigm for understanding and pharmacological intervention in stress-induced AMR.

microbiology↗

bioRxiv2025

Microglial GSDMD-Mediated Pyroptosis Drives Neuroinflammation in Parkinson's Disease

RationaleParkinsons disease (PD), a globally prevalent neurodegenerative disorder, is characterized by substantia nigra dopaminergic neuron degeneration and striatal dopamine depletion. While microglial pyroptosis is implicated in neuroinflammation and neural injury via inflammatory cytokine release, the role of the CASPASE-1/GSDMD pathway in PD pathogenesis remains incompletely defined. Methods1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to construct PD model in vivo, GSDMD-knockout mice was employed to assess pyroptotic mechanisms. MPP-stimulated BV2 microglia were treated with a CASPASE-1 inhibitor in vitro. Microglia-specific GSDMD conditional knockout mice were generated to evaluate cell-type contributions to neuroinflammation and motor deficits. ResultsGSDMD deficiency attenuated MPTP-induced neuroinflammation, dopaminergic neuron loss, and motor dysfunction in vivo. MPP exposure triggered NLRP3 inflammasome activation and pyroptosis in BV2 microglia, which was suppressed by CASPASE-1 inhibition. Critically, microglia-specific GSDMD ablation mitigated nigrostriatal degeneration and dyskinesia in PD mice, confirming the centrality of microglial pyroptosis. ConclusionOur findings demonstrate that microglia drive neuroinflammation in PD via CASPASE-1/GSDMD-mediated pyroptosis, directly linking this pathway to dopaminergic neurodegeneration and motor impairment. Targeting GSDMD-dependent pyroptosis represents a promising therapeutic strategy.

neuroscience↗

bioRxiv2023

Difference in Kernel Shape and Endocarp Anatomy Promote Dehiscence in Pistachio Endocarp

A fully split shell in pistachio (Pistacia vera) is a trait that is preferred by consumers and is a criterion in evaluating the grade of the pistachio nut. However, while the expanding kernel has been hypothesized to provide the physical force needed for shell split, the mechanisms that control shell split remains unknown. Furthermore, it is intriguing how the shell, or endocarp, splits at the suture ridge when there is no clear dehiscence zone. The objectives of this study were to 1) identify traits associated with dehiscence in fruit in the high split rate cultivar Golden Hills when compared to the lower split rate cultivar Kerman and determine the anatomical features associated with endocarp dehiscence at the suture region, and 2) examine the effect of kernel shape on endocarp dehiscence. We determined that despite of the fact that the pistachio endocarp is primarily composed of a single type of polylobate schlerenchyma cell, specialization of cell shape and size at the suture site results in smaller, more flattened cells. We report that there is a furrowing of the shell at the dorsal and apical suture site, where dehiscence initiates. This furrowing is not observed at the ventral suture site or in the indehiscent fruit of Pistacia atlantica, a species that has been used as rootstock for P. vera. In addition, the size of the kernel in the sagittal axis (the width) is strongly associated with higher split rate. Based on our results, a tentative model emerges where, in the absence of specialized cell types, cell shape modification can create an anatomically distinct region that is mechanically weak in the endocarp for the initiation of dehiscence, while the force from the width of the kernel is necessary for the shell split rate difference as observed in cultivars.

plant biology↗

bioRxiv2023

Frequency-dependent Distribution of Different Subtypes of Spiral Ganglion Neurons in the Cochlea and the Changes During Aging

Sound information is transmitted from the cochlea to the brain mainly by type I spiral ganglion neurons (SGNs), which consist of different subtypes with distinct physiological properties and selective expression of molecular markers. It remains unclear how these SGN subtypes distribute along the tonotopic axis, and how the distribution pattern changes during aging that might underlie age-related hearing loss (ARHL). We investigated these questions using immunohistochemistry in three age groups of CBA/CaJ mice of either sex, including 2-5 months (young), 17-19 months (middle-age), and 28-32 months (old). Mouse cochleae were cryo-sectioned and triple-stained using antibodies against Tuj1, calretinin (CR) and calbindin (CB), which are reportedly expressed in all type I, subtype Ia, and subtype Ib SGNs, respectively. Labeled SGNs were classified into four groups based on the expression pattern of stained markers, including CR+ (subtype Ia), CB+ (subtype Ib), CR+CB+ (dual-labeled Ia/Ib), and CR-CB- (subtype Ic) neurons. The distribution of these SGN groups was analyzed in the apex, middle, and base regions of the cochleae. It showed that the prevalence of subtype Ia, Ib and dual-labeled Ia/Ib SGNs are high in the apex and low in the base. In contrast, the distribution pattern is reversed in Ic SGNs. Such frequency-dependent distribution is largely maintained during aging except for a preferential reduction of Ic SGNs, especially in the base. These findings suggest that sound processing of different frequencies involves distinct combinations of SGN subtypes, and the age-dependent loss of Ic SGNs in the base may especially impact high-frequency hearing during ARHL.

neuroscience↗

bioRxiv2023

Comprehensive Allergen Profile of Blomia tropicalis Provides Insights into the Component-Resolved Diagnosis of Mite Allergy

BackgroundBlomia (B.) tropicalis, as an important species of house dust mites (HDMs), plays a critical role in allergic diseases in tropical populations, but its allergen components are less investigated than those of other HDMs. Multiple omics methods have largely improved the identification of mite allergens. Here, we sought to identify a comprehensive allergen profile of B. tropicalis and advance the allergen component-resolved diagnosis (CRD) of mite allergy. MethodsReference mite allergen sequences were searched in a high-quality genome of B. tropicalis. Comparative analysis was performed for important allergen groups. ELISA was used to assess the allergenicities of recombinant proteins of specific allergens. ResultsA complete allergen profile of B. tropicalis was revealed, including thirty-seven allergen groups (up to Blo t 42). In-depth comparative analysis not only determined the homology of major allergen groups 5 and 21 but also shed light on the emergence and divergence of chitin-binding allergens. The specific Blo t 12 was identified to be a chitin-binding protein originating from the chitinase of allergen group 15. Immunoassays of recombinant proteins verified three novel allergens and the ELISA results suggested geographical differences in the B. tropicalis sensitization rate. ConclusionsThe comprehensive allergen profile revealed in B. tropicalis, the comparative analysis of allergen groups and the immunoassay assessment of recombinant proteins largely expanded our knowledge to B. tropicalis allergens and could ultimately benefit the CRD of HDM allergy.

immunology↗

bioRxiv2022

Resolving single-cell copy number profiling for large datasets

The advances of single-cell DNA sequencing (scDNA-seq) enable us to characterize the genetic heterogeneity of cancer cells. However, the high noise and low coverage of scDNA-seq impede the estimation of copy number variations (CNVs). In addition, existing tools suffer from intensive execution time and often fail on large datasets. Here, we propose SeCNV, a novel method that leverages structural entropy, to profile the copy numbers. SeCNV adopts a local Gaussian kernel to construct a matrix, depth congruent map, capturing the similarities between any two bins along the genome. Then SeCNV partitions the genome into segments by minimizing the structural entropy from the depth congruent map. With the partition, SeCNV estimates the copy numbers within each segment for cells. We simulate nine datasets with various breakpoint distributions and amplitudes of noise to benchmark SeCNV. SeCNV achieves a robust performance, i.e., the F1-scores are higher than 0.95 for breakpoint detections, significantly outperforming state-of-the-art methods. SeCNV successfully processes large datasets (>50,000 cells) within four minutes while other tools failed to finish within the time limit, i.e., 120 hours. We apply SeCNV to single-nucleus sequencing (SNS) datasets from two breast cancer patients and acoustic cell tagmentation (ACT) sequencing datasets from eight breast cancer patients. SeCNV successfully reproduces the distinct subclones and infers tumor heterogeneity. SeCNV is available at https://github.com/deepomicslab/SeCNV.

bioinformatics↗

bioRxiv2020

NMR spectroscopy analysis reveals an altered metabolic homeostasis in Arabidopsis seedlings treated with a cytokinesis inhibitor

In plant cytokinesis, de novo formation of a cell plate evolving into the new cell wall partitions the cytoplasm of the dividing cell. Cell plate formation involves highly orchestrated vesicle accumulation, fusion, and membrane network maturation supported by the temporary integration of elastic and pliable callose. The small molecule, Endosidin 7 (ES7) arrests late cytokinesis in Arabidopsis by inhibiting callose deposition at the cell plate. Its effect is specific, as it does not broadly affect endomembrane trafficking or cytoskeletal organization. It has emerged as a very valuable tool for dissecting this essential plant process. In order to gain deeper insights regarding its mode of action and the effects of cytokinesis inhibition on overall plant growth, we investigated the effect of ES7 through a nuclear magnetic resonance spectroscopy metabolomics approach. In this case study, profiles of Arabidopsis leaf and root tissues were analyzed at different growth stages and ES7 exposure levels. The results show tissue-specific changes in the plant metabolic profile across a developmental gradient, and the effect that ES7 treatment has on the corresponding metabolome. The ES7 induced profile suggests metabolic compensations in central metabolism pathways in response to cytokinesis inhibition. Further, this study shows that long-term treatment of ES7 disrupts the homeostasis of primary metabolism in Arabidopsis seedlings, likely via alteration of hormonal regulation.

biochemistry↗