Biology subjects

Lv, P.

Publications and source records attributed to Lv, P..

15 recordsLinked to original sources

bioRxiv2026

Endosperm secretion remodels the maternal seed coat

In flowering plants and mammals, maternal tissues must accommodate the growth of the offspring they enclose. The maternal seed coat expands around the developing embryo and endosperm. Endosperm pressure and hormonal signals coordinate seed-coat development1,2, but whether the endosperm directly promotes maternal cell elongation remains unclear. Here we show that the coenocytic Arabidopsis endosperm directly supplies cell-wall-loosening proteins to maternal seed-coat walls. The seed-size-regulating HAIKU-WRKY10 pathway activates an endosperm secretory programme enriched in cell-wall-associated proteins. These proteins spread through a shared extracellular domain across multiple inner seed-coat layers, revealing an extensive functional maternal-filial interface through which the endosperm reaches maternal cells it does not directly contact. Among these proteins, three expansins are necessary and sufficient for maternal cell elongation and seed growth. The endosperm therefore promotes its own growth by enabling expansion of the maternal tissues that enclose it. Paternal DNA methylation and maternal Polycomb activity jointly regulate this programme, with Polycomb also required for timely shutdown of expansin expression. These findings link parental epigenetic states to maternal tissue expansion through proteins supplied by the offspring. This cross-generational control of growth parallels epigenetically regulated signaling from mammalian extraembryonic tissues3, suggesting a shared strategy for adapting the maternal environment to offspring development.

plant biology↗

bioRxiv2026

SemVac: A Semantic Vaccinology Paradigm Powered by LLMs for Antigen Discovery

Reverse vaccinology identifies vaccine antigens from pathogen genomes, yet existing methods rely mainly on sequence and structure and overlook the functional and immunological knowledge recorded in the published literature. We introduce semantic vaccinology, a paradigm in which large language models (LLMs) reason over literature-derived protein descriptions to predict protective antigens. Implemented as SemVac, the workflow retrieves publications linked to each protein through PaperBLAST, condenses the evidence into a structured semantic profile, and prompts an LLM to return an antigenicity probability. Benchmarked against a curated 246-protein bacterial benchmark and the specialized protein-language and geometric-deep-learning predictor PLGDL, the best of 14 general-purpose LLMs matched or exceeded the precision of PLGDL; the open-weight Kimi K2 0905 offered the strongest performance-cost balance. Predictions were robust to masking of vaccine keywords, reproducible across repeated inference, and generalized to a 1,200-protein cross-pathogen dataset. Surprisingly, explicit chain-of-thought reasoning increased recall but lowered precision in every model tested, revealing over-reasoning in biological scoring. Applied to the mpox virus proteome, SemVac recovered the established mpox antigen repertoire and prioritized uncharacterized candidates. Two of these, A30L and C19L, received independent experimental support in recent orthopoxvirus vaccine development, providing external validation. For one candidate, B20R, the model generated a coherent but false TNF-decoy narrative unsupported by curated annotations, demonstrating that LLM confabulation can be detected when reasoning traces are cross-checked against curated resources. Semantic vaccinology therefore establishes the literature as an explicit, auditable third modality alongside sequence and structure, while making its failure modes transparent and correctable.

immunology↗

bioRxiv2026

Conversion of a Viral Glycan Shield into a Binding Anchor via Causal-Driven Antibody Optimization

Therapeutic antibodies are challenged by rapidly evolving pathogens that exploit glycosylation to shield epitopes. SARS-CoV-2 JN.1 exemplifies this, escaping antibodies through the N354-linked glycan. However, targeting glycosylated epitopes remains vacant, as scarce and heterogeneous glycan structures render existing approaches ineffective. Here, we introduce the Antibody Evolution Nexus with Causal-Driven Simulation (AENCS), integrating molecular simulation with causal inference. Applying AENCS to restore S309 efficacy against JN.1, we identified ACC01, exhibiting [~]24-fold improved neutralization. With limited prior knowledge of the N354 glycosylation site, ACC01 stabilized this glycan conformation, facilitating the determination of its cryo-EM structure. Causal dissection revealed how this glycan shield is functionally inverted into a binding anchor through multi-layered interactions. This mechanistic conversion, combined with the conservation of N354 glycosylation, enabled ACC01 to maintain potent activity against the latest variant NB.1.8.1. Collectively, AENCS demonstrates causal-driven antibody engineering can illuminate cryptic glycosylated epitopes, providing viable paradigms for exploring this vacant frontier.

bioengineering↗

bioRxiv2025

Efficient Generation of Humanized Cloned Cattle via Embryonic Stem Cell-Mediated Dual-Round Site-Specific Editing

Transgenic cloning allows genetic modification in cattle, yet its translational potential is constrained by low cloning efficiency and limited gene-editing capacity, due largely to the restricted proliferative ability of somatic donor cells. Pluripotent stem cells (PSCs), with their unlimited self-renewal ability, represent a promising alternative to overcome these bottlenecks. Here, we first established stable bovine epiblast stem cell lines (bEpiSCs) and achieved site-specific integration of the HCSN2-HLF-GFP cassette into the {beta}-casein locus, with high transfection (72.07%) and correct integration efficiency (80.48%). Following Cre LoxP mediated excision of the selectable marker, we obtained marker free HCSN2-HLF bEpiSCs that retained pluripotency markers, tri lineage differentiation potential, and supported target protein expression in immortalized bovine mammary epithelial cells. When used as nuclear donors, these cells produced blastocysts with quality comparable to in vitro fertilization (IVF) embryos. Notably, cloning with HCSN2-HLF bEpiSCs resulted in the birth of twelve calves, with significantly higher birth and survival rates (30.71% and 16.74%, respectively) than those obtained using fibroblasts. Both PCR-based genotyping of the edited loci and microsatellite kinship analysis confirmed that all cloned calves were genetically derived from the HCSN2-HLF bEpiSCs. Collectively, this study establishes an efficient embryonic stem cell based platform for targeted gene editing and rapid production of multigene edited cloned cattle, offering a scalable strategy with strong potential for industrial translation.

bioengineering↗

bioRxiv2024

Activation of two noncanonical R proteins by an insect effector confers plant immunity to aphid infestation

Molecular characterization of resistance genes is crucial for efficiently understanding and fortifying plant immunity against insect herbivores. Here we report that RMES1A and RMES1B proteins confer resistance to the sorghum aphid Melanaphis sorghi when activated by an insect effector MsEF1. Map-based cloning plus genetic analysis of knockout mutants confirm that RMES1A and RMES1B are both required for aphid resistance. Upon aphid attack, RMES1A and RMES1B expression is elevated in the sclerenchyma cells and vascular bundles of leaves; the two proteins interact with MsEF1 in the exocysts, thus upregulating key defense processes such as reactive oxygen species burst. Structural modeling predicts that RMES1A and RMES1B each carry an ATP binding site and two leucine-rich-repeat domains but lack coiled-coil or Toll/Interleukin-1 receptor/resistance domain, thus likely representing a new type of resistance controlling proteins in plants. Our work reveals new genes and mechanisms for further deciphering and improving plant immunity to insect pests.

genetics↗

bioRxiv2023

Genetic Screen Identified Prmt5 as a Neuroprotection Target against Cerebral Ischemia

Epigenetic regulators present novel opportunities for both ischemic stroke research and therapeutic interventions. While previous work has implicated that they may provide neuroprotection by potentially influencing coordinated sets of genes and pathways, most of them remains largely uncharacterized in ischemic conditions. In this study, we used the oxygen-glucose deprivation (OGD) model in the immortalized mouse hippocampal neuronal cell line HT-22 and carried out an RNAi screen on epigenetic regulators. We identified Prmt5 as a novel negative regulator of neuronal cell survival after OGD, which presented a phenotype of translocation from the cytosol to the nucleus upon oxygen and energy depletion both in vitro and in vivo. Prmt5 bound to the chromatin and a large number of promoter regions to repress downstream gene expression. Silencing Prmt5 significantly dampened the OGD-induced changes for a large-scale of genes, and gene ontology analysis showed that Prmt5-target genes were highly enriched for Hedgehog signaling. Encouraged by the above observation, we treated mice with middle cerebral artery occlusion (MCAO) with the Prmt5 inhibitor EPZ015666 and found that Prmt5 inhibition sustain protection against neuronal death in vivo. Together, our findings revealed a novel epigenetic mechanism of Prmt5 in cerebral ischemia and uncovered a potential target for neuroprotection.

cell biology↗

bioRxiv2023

Predication of the Post Mining Land Use Based on Random Forest and DBSCAN

Mine reclamation is one of the most important stages of the mining activities in line with the basic principles of sustainable development. In this study, different post-mining land uses are evaluated in the Hongliulin mining area, which is located in Shen mu country of China. 145 soil samples were collected in the May,2021 by using the soil auger, and the sampling depths were 0-20 cm. The sampling points contains 45 to be reclaimed samples and 100 existing classification land use types. 14 environmental factors including soil organic matter (SOM), total nitrogen (TN) and other soil nutrients and terrain factors were extracted and calculated based on laboratory test and digital elevation map. Meanwhile, random forest classier was utilized to determine the post-mining land use based on GINI index and 14 environmental factors by using 100 existing classification land use types. 82 of 100 samples were utilized to build the model and the other 18 samples were utilized to validate the accuracy of the classification model. Density-Based Spatial Clustering of Applications with Noise (DBSCAN) techniques were utilized to determine the specific land use types in cropland, shrub and grassland. the random forest classier showed a great prediction capability, with only 1 miss-classified sample in the validation data-set, the accuracy of the classification model was 95%. Among the 45 samples to be reclaimed, 15 samples were classified into cropland, 23 samples were classified into shrub and grassland, 5 samples were classified into arbor land, 2 samples were classified into solar station. By using DBSCAN, the 58 samples classified into cropland in terms of the post-mining were separated into cluster 1 and 2, cluster 1 comprises 24 samples while cluster 2 comprises 34 samples. Among the 61 samples classified into shrubland and grassland, Cluster -1 comprises 24 samples and Cluster 0 comprise 22 samples. The results could provide technological support for land reclamation determination. The content of TN of C1 is 5 times more than C2 and 4 times more than C3. Also, the K valve of C1 column is maximum and over 0.4, which means the soil particle is relatively smaller and the soil texture of it is sandy loam. The TWI of C1 is minimum, in consideration of a positive valve of profile curvature and a negative valve of plan curvature. In terms of the 45 to be reclaimed samples, 15 samples were classified into C1, 23 samples were classified into C2, 5 samples were classified into C3, 2 samples were classified into C4. The valve of K and content of soil nutrients of the samples classified to be C1 column(C1-C) is maximum. Simultaneously, the slope steepness({degrees}) is below 5{degrees} and is perceived as gentle surface. Cluster 1 comprises 24 samples and the average content of TN, AP and SOM is 0.566g/kg, 11.93mg/kg and 19.975g/kg respectively, while Cluster 2 comprises 34 samples and the average content of TN, AP and SOM is 0.304g/kg, 3.12mg/kg and 8.36g/kg respectively. The result may contribute to the land use planning and idle land utilization strategy.

ecology↗

bioRxiv2022

Genome-scale mRNA transcriptomic insights into the mature growth dynamic of Cigar tobacco leaves

The harvest time is a key factor for cigar leaves with high quality, which varies greatly depending on the environment. Here, we performed a genome-scale mRNA transcriptomic analysis on the cigar cultivar CX-26 (Nicotiana tabacum L.) to evaluate the relationship between gene expression and growth state. The leaves were harvested with 67 (T1), 71(T2) and 75 (T3)-day growth. A total of 80,502 genes were detected in the CX-26 leaves, of which 64,611 genes were annotated on the reference genome. Principal component analysis showed that T1 and T2 leaves had a high overlapping pattern, while T3 leaves were distinct. Indeed, T1 and T2 leaves had fewer differential expressing genes (DEGs), while T3 leaves had 26,456 DGEs from T2 leaves, supporting the distinct growth of T3 leaves. GO annotations mainly enriched the photosynthesis-related metabolic process, catalytic activity and binding biological processes. KEEG analysis identified the key pathways including photosynthesisantenna proteins, plant hormone/MAPK signaling pathway and plant-pathogen interaction. The maturity regulation and defense response-associated hormones abscisic acid and jasmonate acid were higher in the T3 leaves than that in T1 and T2 leaves confirming the KEEG analysis. Furthermore, several photosynthesis-related enzymes and a transcription factor were highlighted in the gene regulatory network, which might regulate the dynamics of carbohydrate metabolism, lipid metabolism and energy metabolism. In summary, our study provides insight into the growth state of CX-26 cigar leaves.

plant biology↗

bioRxiv2022

The LEPIS-HuR-TMOD4 axis regulates hepatic cholesterol homeostasis and accelerates atherosclerosis

Long noncoding RNAs (lncRNAs) play an important role in the entire progression of atherosclerosis. In this study, we identified an uncharacterized lncRNA, Liver Expressions by PSRC1 Induce Specifically (LEPIS). The expression of LEPIS and its potential target tropomodulin 4 (TMOD4) in the liver of ApoE-/- mice fed a high-fat diet was increased. An ApoE-/- mouse model with the overexpression of LEPIS or TMOD4 in liver was established, and we found that both LEPIS and TMOD4 increased the burden of atherosclerosis and reduced hepatic cholesterol levels. Further study revealed that LEPIS and TMOD4 affect the expression of genes related to hepatic cholesterol homeostasis, including proprotein convertase subtilisin/kexin type9 (PCSK9) and low-density lipoprotein receptor (LDLR), which are closely related to hypercholesterolemia. Mechanistically, human antigen R (HuR), an RNA-binding protein, was shown to be critical for the regulation of TMOD4 by LEPIS. Further, we found that overexpression of LEPIS promoted the shuttling of HuR from the nucleus to the cytoplasm, enhanced the stability of TMOD4 mRNA, and in turn promoted the expression of TMOD4. In addition, TMOD4 was found to affect intracellular cholesterol levels through PCSK9. These results suggest that the LEPIS-HuR-TMOD4 axis is a potential intervention target for hepatic cholesterol homeostasis and atherosclerosis. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=183 SRC="FIGDIR/small/490400v1_ufig1.gif" ALT="Figure 1"> View larger version (59K): org.highwire.dtl.DTLVardef@c4af60org.highwire.dtl.DTLVardef@d5e7d1org.highwire.dtl.DTLVardef@1667d08org.highwire.dtl.DTLVardef@19abddd_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2022

Repressor element 1-silencing transcription factor deficiency yields profound hearing loss through Kv7.4 channel upsurge in auditory neurons and hair cells

Repressor element 1-silencing transcription factor (REST) is a transcriptional repressor that recognizes neuron-restrictive silencer elements in the mammalian genomes in a tissue- and cell-specific manner. The identity of REST target genes and molecular details of how REST regulates them are emerging. We performed conditional null deletion of Rest (cKO) in murine hair cells (HCs) and auditory neurons, spiral ganglion neurons (SGNs). Null-deletion of full-length REST resulted in normal HCs and SGNs development but manifested with progressive hearing loss in adulthood. We found that deletion of REST results in an increased abundance of Kv7.4 channels at the transcript, protein, and function levels. Specifically, we found that SGNs and HCs from Rest cKO mice displayed increased Kv7.4 expression and augmented Kv7 currents; SGNs excitability was also significantly reduced. Administration of Kv7.4 channel activator, fasudil, recapitulated progressive hearing loss in mice. In contrast, inhibition of the Kv7.4 channel by XE991 rescued the auditory phenotype of Rest cKO mice. Previous studies identified some loss-of-function mutations within the Kv7.4-coding gene, Kcnq4, as a causative factor for progressive hearing loss in mice and humans. Thus, the present findings revealed that a critical homeostatic Kv7.4 channel level is required for proper auditory functions.

neuroscience↗

bioRxiv2020

Auditory responses evoked by optical stimulation on the optogeneic-infected cochlear neurons in the guinea pigs

Cochlear implants (CIs) are by far the optimal option to partially restore hearing for the patients of sensorineural hearing impairment (HI) by electrically stimulating spiral ganglion neurons (SGNs). However, wide current spread from each electrode constitute an interface which restricts precision and quality of the electrical CIs. Recently, optogenetic stimulation of the cochlea has been proved as a more optimized approach via adeno-associated virus (AAV) carrying the gene encoding the light-sensitive channelrhodopsin-2. Here, we focus on summarizing recent work on stable and accurate ChR2 expression and compare the electrophysiological recording of optogenetic and acoustic stimulation in adult guinea pigs. Light stimulation generated auditory responses that was similar to that of acoustic stimulation. Moreover, normal hearing adult guinea pigs responded with a rise in amplitudes with increasing light intensity. In conclusion, optogenetic cochlear stimulation achieved good spectral selectivity of artificial sound encoding in a new adult rodent model, suggesting that the capabilities of optogenetics might be applied to improve cochlear implants in the future.

neuroscience↗

bioRxiv2020

Acute noise causes down-regulation of ECM protein expression in guinea pig cochlea

ObjectiveTo study the differences in cochlea protein expression before and after noise exposure using proteomics to reveal the pathological mechanism of noise-induced hearing loss (NIHL). MethodsA guinea pig NIHL model was established to test the ABR thresholds before and after noise exposure. The proteomics technology was used to study the mechanism of differential protein expression in the cochlea by noise stimulation. ResultsThe average hearing threshold of guinea pigs on the first day after noise exposure was 57.00{+/-}6.78dB SPL, high-frequency hearing loss was more severe than low frequency; the average hearing threshold on the seventh day after noise exposure was 45.83{+/-}6.07dB SPL, and the 4k Hz hearing threshold has the best recovery. The proteomics technology identified 3122 different inner ear proteins, of which six proteins related to the hearing were down-regulation: TenascinC, Collagen type XI alpha two chains, Collagen type II alpha one chain, Thrombospondin 2, Collagen type XI alpha one chain and Ribosomal protein L38, and are enriched in protein absorption, focal adhesion, and extracellular matrix receptor pathways. ConclusionImpulse noise can affect the expression of differential proteins through focal adhesion pathways. This data can provide an experimental basis for the research on the prevention and treatment of NIHL.

immunology↗

bioRxiv2019

Global analysis of epigenetic heterogeneity identifies divergent drivers of esophageal squamous cell carcinoma

Epigenetic landscapes can shape physiologic and disease phenotypes. We used integrative, high resolution multi-omics methods to characterize the oncogenic drivers of esophageal squamous cell carcinoma (ESCC). We found 98% of CpGs are hypomethylated across the ESCC genome and two-thirds occur in long non-coding (lnc)RNA regions. DNA methylation and epigenetic heterogeneity both coincide with chromosomal topological alterations. Gene body methylation, polycomb repressive complex occupancy, and CTCF binding sites associate with cancer-specific gene regulation. Epigenetically-mediated activation of non-canonical WNT signaling and the lncRNA ESCCAL-1 were validated as potential ESCC driver alterations. Gene-specific cancer driver roles of epigenetic alterations and heterogeneity are identified.

cell biology↗

bioRxiv2018

Rac1 Activated by DOCK1 in Combination with Rab31 Promotes the Development of Diabetic Retinopathy

BackgroundDiabetic retinopathy (DR) is one of the most common and severe microvascular complications of diabetes. Its a fundus lesion with specific changes, and its specific molecular mechanism is still unclear.\n\nMethodsAll target proteins and markers expression in the study was verified by qPCR and western bloting. The morphology and behavior of human retinal epithelial cells ARPE-19 were analyzed using immunofluorescent and apoptosis detection assays, respectively. And, Small GTPase activity was detected by the GST-pull assay.\n\nResultsWe found that DOCK1 showed high expression in high glucose-induced DR. Moreover, its high expression is positively correlated with Rab31 in tissues. DOCK1 promotes the activation of Rac1 and promotes apoptosis of retinal epithelial cells. Rab31 promotes the degradation of TJ proteins by promoting the transport of TJ proteins from the plasma membrane to the endosomes, thereby affecting the tight junctions of epithelial cells. Inhibition of Rac1 activity can effectively reduce cell apoptosis. Similarly, inhibition of Rab31 activity can significantly inhibit the degradation of TJ proteins.\n\nConclusionThis study based on the high glucose-induced DR cell model reveals the role of two mutually synergistic signaling pathways through the important cytological phenomena of apoptosis and damage of tight junctions. One is the degradation of TJ proteins caused by Rab31-mediated vesicle trafficking, and the other is the apoptosis of retinal epithelial cells mediated by DOCK1-Rac1.

cell biology↗

bioRxiv2017

The fruitENCODE project sheds light on the genetic and epigenetic basis of convergent evolution of climacteric fruit ripening

Fleshy fruit evolved independently multiple times during angiosperm history. Many climacteric fruits utilize the hormone ethylene to regulate ripening. The fruitENCODE project shows there are multiple evolutionary origins of the regulatory circuits that govern climacteric fruit ripening. Eudicot climacteric fruits with recent whole-genome duplications (WGDs) evolved their ripening regulatory systems using the duplicated floral identity genes, while others without WGD utilised carpel senescence genes. The monocot banana uses both leaf senescence and duplicated floral-identity genes, forming two interconnected regulatory circuits. H3K27me3 plays a conserved role in restricting the expression of key ripening regulators and their direct orthologs in both the ancestral dry fruit and non-climacteric fleshy fruit species. Our findings suggest that evolution of climacteric ripening was constrained by limited availability of signalling molecules and genetic and epigenetic materials, and WGD provided new resources for plants to circumvent this limit. Understanding these different ripening mechanisms makes it possible to design tailor-made ripening traits to improve quality, yield and minimize postharvest losses.\n\nOne Sentence SummaryThe fruitENCODE project discovered three evolutionary origins of the regulatory circuits that govern climacteric fruit ripening.

genomics↗