Biology subjects

Bi, M.

Publications and source records attributed to Bi, M..

12 recordsLinked to original sources

bioRxiv2026

Soils from different landscape elements diverge in response to multiple global change factors

Global change factors (GCFs) are known to affect terrestrial ecosystems across a range of land-use types, including farmlands, grasslands, and forests. However, it remains unclear whether different landscape elements within the same region respond differently to the same global change pressures. Here, we investigated this question using four soils collected from co-located farmland, grassland, pine forest, and oak forest, representing distinct landscape elements under the same regional climatic conditions. Each soil was exposed to one of six individual GCFs, warming, drought, nitrogen deposition, salinity, microplastics, and antibiotics, as well as to all six factors combined. We found that landscape elements exhibited strongly divergent responses to the same GCFs. The effects on soil functions also varied among soils under combined stress, with responses diverging from different null-model predictions depending on soils and response variable. Moreover, landscape-element specific response patterns became more pronounced under multiple concurrent stressors. Overall, our findings show that landscape heterogeneity represents a mosaic of different capacities to resist and respond to global change, even under shared climatic and geographic conditions. Global change assessments and ecosystem models should therefore better account for landscape-level heterogeneity, and management strategies aimed at enhancing ecosystem resilience should be tailored to individual landscape elements.

ecology↗

bioRxiv2026

Gram-scale one-pot enzymatic synthesis of CDP-ribitol by a designed bifunctional fusion enzyme

D-Ribitol-5-phosphate (Rbo5P) plays vital roles in bacterial and mammalian development. In mammals, Rbo5P is an essential component of the O-mannosyl glycan on -dystroglycan, and its defective biosynthesis causes a group of dystroglycanopathies. Supplementation with cytidine diphosphate ribitol (CDP-ribitol, CDP-Rbo) and its analogues has shown therapeutic potential for certain dystroglycanopathies. However, facile and scalable strategies to prepare CDP-Rbo remain unavailable. Here, we report a practical one-pot enzymatic strategy for gram-scale CDP-Rbo production. Starting from inexpensive ribitol, Rbo5P is first generated by L-ribulokinase (AraB) and then converted to CDP-Rbo by CDP-ribitol pyrophosphorylase (TarI) in 90% yield. To streamline the process, AraB and TarI were fused into a single bifunctional biocatalyst, AraB-TarI, which converts ribitol directly into CDP-Rbo on a gram-scale in a one-step reaction. Furthermore, a nucleotide recycling strategy was developed to lower the cost and increase the atom economy from 47% to 75%. This work provides a green and scalable route to CDP-Rbo and a reliable material supply for developing therapeutics against dystroglycanopathies.

biochemistry↗

bioRxiv2026

A shear lag model of the podocyte foot process network predicts a mechanical feedback loop driving progressive effacement

The podocyte foot process network forms the final barrier of the kidneys glomerular filtration system. Under mechanical stress this network is prone to injury in which podocytes lose connectivity to their neighbors and begin the progression toward effacement, but what governs its mechanical resilience is unknown. We show that the network is built like a lap joint: two major processes coupled through interdigitating foot processes, a configuration that behaves as a classical shear lag system, with force concentrating at the joint ends and decaying over a characteristic transfer length set by geometry and stiffness. A discrete network model reproduces the continuum shear lag solution and identifies a hierarchy among governing parameters, with cytoskeletal stiffening of the major process amplifying foot process force more potently than basement membrane stiffness. Applying the model to morphometric data from puromycin aminonucleoside nephrosis, a model of human minimal change disease and early focal segmental glomerulosclerosis, reveals a mechanical positive feedback loop: force concentration drives foot process loss, which raises force on surviving segments and accelerates further loss. This nonlinear amplification implies a threshold beyond which failure becomes self-sustaining, analogous to the critical crack length in fracture mechanics.

biophysics↗

bioRxiv2025

Instant preparative droplet reaction assisted by shaking

Instant micro- and macro-preparative droplet reaction assisted by hand shaking (shake reaction) was found and observed, where reactions were carried out inside aqueous droplets dispersed in an organic solvent. This shake reaction was successfully benchmarked with both organic reactions of protein reduction by dithiothreitol and alkylation by iodoacetamide as well as biological reaction of protein digestion by enzyme trypsin. The reaction time of shake reaction was substantially shortened from the traditional bulk solution reactions, specifically 1 min for reduction (from 20 min), 1 min for alkylation (from 30 min), 5 min for digestion (from 960 min). The high efficiency of shake reaction comes from the micro-nano droplet formation assisted by shaking. Shake reaction can arguably be extended to any liquid-phase inorganic, organic and biological reactions from micro- to macro-preparative scale, and thus undoubtedly find wide applications in both academic research and industry production. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=161 SRC="FIGDIR/small/651440v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@ad1414org.highwire.dtl.DTLVardef@1014a1dorg.highwire.dtl.DTLVardef@1a8eccdorg.highwire.dtl.DTLVardef@15297fe_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2024

Structure and function of an intermediate GPCR-G protein complex

Unraveling the signaling roles of intermediate complexes is pivotal for G protein-coupled receptor (GPCR) drug development. Despite hundreds of GPCR-G{beta}{gamma} structures, these snapshots primarily capture the fully activated end-state complex. Consequently, a comprehensive understanding of the conformational transitions during GPCR activation and the roles of intermediate GPCR-G protein complexes in signaling remain elusive. Guided by a conformational landscape profiled by 19F quantitative NMR (19F-qNMR) and Molecular Dynamics (MD) simulations, we resolved the structure of an unliganded GPCR-G protein intermediate complex by blocking its transition to the fully activated end-state complex. More importantly, we presented direct evidence that the intermediate GPCR-Gs{beta}{gamma} complex initiates a rate-limited nucleotide exchange without progressing to the fully activated end-state complex, thereby bridging a significant gap in our understanding the complexity of GPCR signaling. Understanding the roles of individual conformational states and their complexes in signaling efficacy and bias will help us to design drugs that discriminately target a disease-related conformation.

biophysics↗

bioRxiv2023

Assembly of SARS-CoV-2 ribonucleosomes by truncated N* variant of the nucleocapsid protein

The Nucleocapsid (N) protein of SARS-CoV-2 compacts the RNA genome into viral ribonucleoprotein (vRNP) complexes within virions. Assembly of vRNPs is inhibited by phosphorylation of the N protein SR region. Several SARS-CoV-2 variants of concern carry N protein mutations that reduce phosphorylation and enhance the efficiency of viral packaging. Variants of the dominant B.1.1 viral lineage also encode a truncated N protein, termed N* or {Delta}(1-209), that mediates genome packaging despite lacking the N-terminal RNA-binding domain and SR region. Here, we show that {Delta}(1-209) and viral RNA assemble into vRNPs that are remarkably similar in size and shape to those formed with full-length N protein. We show that assembly of {Delta}(1-209) vRNPs requires the leucine-rich helix (LH) of the central disordered region, and that the LH promotes N protein oligomerization. We also find that fusion of a phosphomimetic SR region to {Delta}(1-209) inhibits RNA binding and vRNP assembly. Our results provide new insights into the mechanisms by which RNA binding promotes N protein self-association and vRNP assembly, and how this process is modulated by SR phosphorylation.

microbiology↗

bioRxiv2023

The landscape of m1A modification and its posttranscriptional regulatory functions in primary neurons

Cerebral ischaemia-reperfusion injury, during which neurons undergo oxygen-glucose deprivation/reoxygenation (OGD/R), is a notable pathological process in many neurological diseases. N1-methyladenosine (m1A) is an RNA modification that can affect gene expression and RNA stability. The m1A landscape and potential functions of m1A modification in neurons remain poorly understood. We explored RNA (mRNA, lncRNA, and circRNA) m1A modification in normal and OGD/R-treated neurons and the effect of m1A on diverse RNAs. We investigated the m1A landscape in primary neurons, identified m1A-modified RNAs, and found that OGD/R increased the number of m1A RNAs. m1A modification might also affect the regulatory mechanisms of noncoding RNAs, e.g., lncRNA-RBP interactions and circRNA translation. We showed that m1A modification mediates the circRNA/lncRNA-miRNA-mRNA ceRNA mechanism and that 3UTR methylation of mRNAs can hinder miRNA-mRNA binding. Three methylation patterns were identified, and genes with different patterns had intrinsic mechanisms with potential m1A-regulatory specificity. Systematic analysis of the m1A landscape in normal and OGD/R neurons lays a critical foundation for understanding RNA methylation and provides new perspectives and a theoretical basis for treating and developing drugs for OGD/R pathology-related diseases.

neuroscience↗

bioRxiv2023

Multifaceted roles of a light-responsive factor LhWRKY44 in promoting anthocyanin accumulation in Asiatic hybrid lilies (Lilium spp.)

The coloration of Asiatic hybrid lily results mostly from anthocyanin accumulation in flowers. Although anthocyanin accumulation-related genes and MBW complexes are well studied, the transcriptional regulation of WRKY transcription factors involved in anthocyanin accumulation remains poorly understood.Here, we identified a lily WRKY protein, LhWRKY44, whose expression is highly expressed downstream of LhHY5 by light and positively correlated with anthocyanin accumulation. LhWRKY44 overexpression enhanced anthocyanin accumulation and silencing decreased anthocyanin accumulation in flowers. As a trans-acting regulator, LhWRKY44 activited the anthocyanin biosynthesis pathway-related genes PAL and F3H by binding to the their promoters. And the encoded TF also participates in anthocyanin transport and targets the intracellular anthocyanin transport protein GST promoters. Additionally, a novel dual activity of LhWRKY44 and LhMYBSPLATTER regulatory module, with LhWRKY44 binds to the promoter of LhMYBSPLATTER and interacts with LhMYBSPLATTER, strongly enhanced the interaction of LhMYBSPLATTER and LhbHLH2, indirectly enhancing DFR, UFGT and GST expression targeted by LhMYBSPLATTER. These results show a regulatory mode for light-induced anthocyanin accumulation enhancement by LhWRKY44 in lily, expanding our understanding of the complex transcriptional regulatory hierarchy modulating anthocyanin accumulation.

molecular biology↗

bioRxiv2022

Reconstitution of the SARS-CoV-2 ribonucleosome provides insights into genomic RNA packaging and regulation by phosphorylation

The nucleocapsid (N) protein of coronaviruses is responsible for compaction of the [~]30-kb RNA genome in the [~]100-nm virion. Cryo-electron tomography suggests that each virion contains 35-40 viral ribonucleoprotein (vRNP) complexes, or ribonucleosomes, arrayed along the genome. There is, however, little mechanistic understanding of the vRNP complex. Here, we show that N protein, when combined with viral RNA fragments in vitro, forms cylindrical 15-nm particles similar to the vRNP structures observed within coronavirus virions. These vRNPs form in the presence of stem-loop-containing RNA and depend on regions of N protein that promote protein-RNA and protein-protein interactions. Phosphorylation of N protein in its disordered serine/arginine (SR) region weakens these interactions and disrupts vRNP assembly. We propose that unmodified N binds stem-loop-rich regions in genomic RNA to form compact vRNP complexes within the nucleocapsid, while phosphorylated N maintains uncompacted viral RNA to promote the proteins transcriptional function.

biochemistry↗

bioRxiv2021

WUSCHEL-Related Homeobox Genes Cooperate with Cytokinin Signalling to Promote Bulbil Formation in Lilium lancifolium

The bulbil is an important vegetative reproductive organ in triploid Lilium lancifolium. Based on our previously obtained transcriptome data, we screened two WUSCHCEL-related homeobox (WOX) genes closely related to bulbil formation, LlWOX9 and LlWOX11. However, the biological functions and regulatory mechanisms of LlWOX9 and LlWOX11 are unclear. In this study, we cloned the full-length coding sequences of LlWOX9 and LlWOX11. Transgenic Arabidopsis showed increased branch numbers, and the overexpression of LlWOX9 and LlWOX11 in stem segments promoted bulbil formation, while the silencing of LlWOX9 and LlWOX11 inhibited bulbil formation, indicating that LlWOX9 and LlWOX11 are positive regulators of bulbil formation. Cytokinins acting through type-B response regulators (type-B RRs) could bind to the promoters of LlWOX9 and LlWOX11 and promote their transcription. LlWOX11 could enhance cytokinin pathway signalling by inhibiting the transcription of type-A LlRR9. Our study enriches the understanding of the regulation of plant development by the WOX gene family and lays a foundation for further research on the molecular mechanism of bulbil formation in lily.

developmental biology↗

bioRxiv2021

Symmetry reduction in a hyperpolarization-activated homotetrameric ion channel

Plants obtain nutrients from the soil via transmembrane transporters and channels in their root hairs, from which ions radially transport in towards the xylem for distribution across the plant body. We determined structures of the hyperpolarization-activated channel AKT1 from Arabidopsis thaliana, which mediates K+ uptake from the soil into plant roots. These structures of AtAKT1 embedded in lipid nanodiscs show that the channel undergoes a reduction of C4 to C2 symmetry, possibly to regulate its electrical activation.

biophysics↗

bioRxiv2019

Coordinate Enhancer Reprogramming by GATA3 and AP1 Promotes Phenotypic Plasticity to Achieve Breast Cancer Endocrine Resistance

Acquired therapy resistance is a major problem for anticancer treatment, yet the underlying molecular mechanisms remain unclear. Using an established breast cancer cellular model for endocrine resistance, we show that hormone resistance is associated with enhanced phenotypic plasticity, indicated by a general downregulation of luminal/epithelial differentiation markers and upregulation of basal/mesenchymal invasive markers. Our extensive omics studies, including GRO-seq on enhancer landscapes, demonstrate that the global enhancer gain/loss reprogramming driven by the differential interactions between ER and other oncogenic transcription factors (TFs), predominantly GATA3 and AP1, profoundly alters breast cancer transcriptional programs. Our functional studies in multiple biological systems including culture and xenograft models of MCF7 and T47D lines support a coordinate role of GATA3 and AP1 in enhancer reprogramming that promotes phenotypic plasticity and endocrine resistance. Collectively, our study implicates that changes in TF-TF and TF-enhancer interactions can lead to genome-wide enhancer reprogramming, resulting in transcriptional dysregulations that promote plasticity and cancer therapy-resistance progression.

cancer biology↗