Biology subjects

Jiang, L.

Publications and source records attributed to Jiang, L..

At least 127 records · Page 7Linked to original sources

bioRxiv2024

Multi-View Integrative Approach For Imputing Short-Chain Fatty Acids and Identifying Key factors predicting Blood SCFA

Short-chain fatty acids (SCFAs) are the main metabolites produced by bacterial fermentation of dietary fiber within gastrointestinal tract. SCFAs produced by gut microbiotas (GMs) are absorbed by host, reach bloodstream, and are distributed to different organs, thus influencing host physiology. However, due to the limited budget or the poor sensitivity of instruments, most studies on GMs have incomplete blood SCFA data, limiting our understanding of the metabolic processes within the host. To address this gap, we developed an innovative multi-task multi-view integrative approach (M2AE, Multi-task Multi-View Attentive Encoders), to impute blood SCFA levels using gut metagenomic sequencing (MGS) data, while taking into account the intricate interplay among the gut microbiome, dietary features, and host characteristics, as well as the nuanced nature of SCFA dynamics within the body. Here, each view represents a distinct type of data input (i.e., gut microbiome compositions, dietary features, or host characteristics). Our method jointly explores both view-specific representations and cross-view correlations for effective predictions of SCFAs. We applied M2AE to two in-house datasets, which both include MGS and blood SCFAs profiles, host characteristics, and dietary features from 964 subjects and 171 subjects, respectively. Results from both of two datasets demonstrated that M2AE outperforms traditional regression-based and neural-network based approaches in imputing blood SCFAs. Furthermore, a series of gut bacterial species (e.g., Bacteroides thetaiotaomicron and Clostridium asparagiforme), host characteristics (e.g., race, gender), as well as dietary features (e.g., intake of fruits, pickles) were shown to contribute greatly to imputation of blood SCFAs. These findings demonstrated that GMs, dietary features and host characteristics might contribute to the complex biological processes involved in blood SCFA productions. These might pave the way for a deeper and more nuanced comprehension of how these factors impact human health.

bioinformatics↗

bioRxiv2024

The impact of high-fat and obesogenic diets on brain volume in a commercially available mouse model of fatty liver disease

The obesity pandemic poses significant health challenges, despite recent advancements in weight loss medications. Mouse models fed obesogenic diets serve as invaluable tools for dissecting the pleiotropic mechanisms underlying weight gain. Here, we utilize these models to analyze brain morphometrics using MRI techniques, inspired by similar findings in human studies linking obesity to brain volume changes. We hypothesize that the mouse model of obesity will exhibit brain volume alterations akin to those observed in obese humans, potentially shedding light on the neurological implications of obesity. To test our hypothesis, mice were provided free access to either regular chow or a diet consisting of high fat and high sugar and MRI scans for total brain volumes as well as volumes of specific brain regions were estimated and compared between obese and control mice. We found that obesogenic diets resulted in [~]13% greater weight gain compared to control chow diets. MRI brain scans revealed reduced total brain volume in obese mice that trended towards significance. In contrast, analysis of specific brain volumes showed an increase in neocortical regions of obese mice, that were significant when compared to controls. In conclusion, diet-induced obesity mouse models are a readily available avatar for studying the obesity epidemic, with significant increases in body weight within a reasonable timeframe. While weight gain among individual mice fed obesogenic diets showed some variability, MRI brain scans were able to reveal significant differences, especially within different anatomical regions of the brain.

neuroscience↗

bioRxiv2024

Pipeline for Assessing Tumor Immune Status Using Superplex Immunostaining and Spatial Immune Interaction Analysis

The characteristics of the tumor microenvironment (TME) are closely linked to tumor progression and treatment response. The TME comprises various cell types, their spatial distribution, cell-cell interactions, and their organization into cellular niches or neighborhoods. To capture this complexity, several spatial profiling technologies have been developed. However, challenges such as low throughput, high costs, and complicated data analysis have limited their widespread use in immune research. In this study, we introduce the Cyclic-multiplex TSA (CmTSA) staining platform, a high-throughput superplex staining technology based on tyramide signal amplification (TSA) immunostaining combined with an efficient fluorophore recycling method. The CmTSA platform allows for the labeling of 30-60 antigens across multiple parallel formalin-fixed paraffin-embedded (FFPE) slides. Furthermore, the automated CmTSA workflow requires only standard histological equipment and conventional immunohistochemistry (IHC) primary antibodies (Abs), significantly reducing costs. While the superplex images produced contain extensive multidimensional information, extracting the spatial features of the TME from raw pixel data can be challenging. To address this, we present a computer vision-based analysis pipeline, which begins with deep learning-based algorithms to segment individual cells and identify cell types based on defined annotation rules. It then evaluates the spatial distribution tendencies of each cell type, the interaction intensity between paired cells, and the multicellular functional niches. This comprehensive approach enables researchers to visualize and quantify the types, states, and levels of immune activities within the TME effectively, advancing tumor immunology research and precision immune medicine.

cancer biology↗

bioRxiv2024

The genetic architecture of cell-type-specific cis-regulation

AbstractGene expression and complex phenotypes are determined by the activity of cis-regulatory elements. However, an understanding of how extant genetic variants affect cis regulation remains limited. Here, we investigated the consequences of cis-regulatory diversity using single-cell genomics of >0.7 million nuclei across 172 Zea mays (maize) inbreds. Our analyses pinpointed cis-regulatory elements distinct to domesticated maize and revealed how historical transposon activity has shaped the cis-regulatory landscape. Leveraging population genetics principles, we fine-mapped [~]22,000 chromatin accessibility-associated genetic variants with widespread cell-type-specific effects. Variants in TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR binding sites were the most prevalent determinants of chromatin accessibility. Finally, integrating chromatin accessibility-associated variants, organismal trait variation, and population differentiation revealed how local adaptation has rewired regulatory networks in unique cellular context to alter maize flowering.

genetics↗

bioRxiv2024

Single-cell multidimensional profiling of tumor cell heterogeneity in supratentorial ependymomas

Supratentorial ependymomas are aggressive childhood brain cancers that retain features of neurodevelopmental cell types and segregate into molecularly and clinically distinct subgroups, suggesting different developmental roots. The developmental signatures as well as microenvironmental factors underlying aberrant cellular transformation and behavior across each supratentorial ependymoma subgroup are unknown. Here we integrated single cell- and spatial transcriptomics, as well as in vitro and in vivo live-cell imaging to define supratentorial ependymoma cell states, spatial organization, and dynamic behavior within the neural microenvironment. We find that individual tumor subgroups harbor two distinct progenitor-like cell states reminiscent of early human brain development and diverge in the extent of neuronal or ependymal differentiation. We further uncover several modes of spatial organization of these tumors, including a high order architecture influenced by mesenchymal and hypoxia signatures. Finally, we identify an unappreciated role for brain-resident cells in shifting supratentorial ependymoma cellular heterogeneity towards neuronal-like cells that co-opt immature neuronal morphology and invasion mechanisms. Collectively, these findings provide a multidimensional framework to integrate transcriptional and phenotypic characterization of tumor heterogeneity in supratentorial ependymoma and its potential clinical implications.

cancer biology↗

bioRxiv2024

SSRI antidepressant citalopram reverses the Warburg effect to inhibit hepatocellular carcinoma by directly targeting GLUT1

Although there is growing appreciation for effective repurposing of selective serotonin reuptake inhibitors (SSRIs) for cancer therapy, particularly hepatocellular carcinoma (HCC), efforts are hampered by limited knowledge of their molecular targets and mechanism of action. Global inverse gene-expression profiling method, drug affinity responsive target stability assay, and in silico molecular docking analysis was performed to identify the targets of SSRIs. Murine subcutaneous, orthotopic models, and patient-derived xenograft were employed to explore the therapeutic effects and underlying mechanisms of SSRIs in HCC. The clinical relevance of SSRI use was verified with real world data. SSRIs exhibit significant anti-HCC effects independent of their known target serotonin reuptake transporter. The glucose transporter 1 (GLUT1) is identified as a new target of SSRIs. Citalopram binds to and antagonizes GLUT1, resulting in reduced glycolytic flux and ATP generation. Mutant GLUT1 in the binding site E380 of citalopram compromises the inhibitory effects of citalopram on the Warburg effect and tumor growth. In preclinical models, citalopram dampens the growth kinetics of GLUT1high liver tumors and displays a synergistic effect with anti-PD-1 therapy. Retrospective analysis of health records found that SSRIs use is associated with a lower risk of metastasis among HCC patients. Our study reveals an unprecedented role of SSRIs in cancer metabolism, and establishes a rationale for repurposing SSRIs as potential anticancer drugs for HCC.

cancer biology↗

bioRxiv2024

The Microbiome and Metatranscriptome of a Panel from the Sarracenia Mapping Population Reveal Complex Assembly and Function Involving Host Influence.

Sarracenia provide an optimal system for deciphering the host-microbiome interactions at various levels. We analyzed the pitcher microbiomes and metatranscriptomes of the parental species, and F1 and F2 generations from the mapping population (Sarracenia purpurea X Sarracenia psittacina) utilizing high-throughput sequencing methods. This study aimed to examine the host influences on the microbiome structure and function and to identify the key microbiome traits. Our quality datasets included 8,892,553 full-length bacterial 16s rRNA gene sequences and 65,578 assembled metatranscripts with microbial protein annotations. The correlation network of the bacterial microbiome revealed the presence of 3-7 distinct community clusters, with 8 hub and 19 connector genera. The entire microbiome consisted of viruses, bacterial, archaea, and fungi. The richness and diversity of the microbiome varied among the parental species and offspring genotypes despite being under the same greenhouse environmental conditions. We have discovered certain microbial taxa that are genotype-enriched, including the community hub and connector genera. Nevertheless, there were no significant differences observed in the functional enrichment analysis of the metatranscriptomes across the different genotypes, suggesting a functional convergence of the microbiome. Our results revealed that the pitcher microcosm harbors both rhizosphere and phyllosphere microbiomes within its boundaries, resulting in a structurally diverse and functionally complex microbiome community. A total of 50,424 microbial metatranscripts were linked to plant growth-promoting microbial proteins. We show that this complex pitcher microbiome possesses various functions that contribute to plant growth promotion, such as biofertilization, bioremediation, phytohormone signaling, stress regulation, and immune response stimulation. Additionally, the pitcher microbiome exhibits traits related to microbe-microbe interactions, such as colonization of plant systems, biofilm formation, and microbial competitive exclusion. In summary, the demonstrated taxonomical divergence and functionally convergence of the pitcher microbiome are impacted by the host genetics, making it an excellent system for discovering novel beneficial microbiome traits.

plant biology↗

bioRxiv2024

Electrostatic interactions in nucleosome and higher-order structures are regulated by protonation state of histone ionizable residue

The nucleosome serves as the fundamental unit of chromatin organization, with electrostatic interactions acting as the driving forces in the folding of nucleosomes into chromatin. Perturbations in cellular pH conditions can lead to changes in the protonation states of titratable histone residues, impacting nucleosome surface electrostatic potentials and interactions. However, the effects of proton uptake or release of histone ionizable groups on nucleosome-partner protein interactions and higher-order chromatin structures remain largely unexplored. Here, we conducted comprehensive analyses of histone titratable residue pKa values in various nucleosome contexts, utilizing 96 experimentally determined structures. We revealed that pH-induced changes in histone residue protonation states modulated nucleosome surface electrostatic potentials and significantly influenced nucleosome-partner protein interactions. Furthermore, we observed that proton uptake or release often accompanied nucleosome-partner protein interactions, facilitating their binding processes. Additionally, using a dataset of 1266 recurrent histone cancer mutations, we systematically characterized their impact on nucleosome surface electrostatics, demonstrating their profound effects on electrostatic interactions between nucleosomes and partner proteins. Finally, our findings suggest that alterations in histone protonation or cancer mutations can also regulate nucleosome self-association, thereby modulating the organization and dynamics of higher-order chromatin structure.

biophysics↗

bioRxiv2024

Preeclampsia-specific immune cell network in placenta revealed by Cytometry by time of flight and single-cell RNA-seq

Preeclampsia (PE), a major cause of maternal and perinatal mortality with highly heterogeneous causes and symptoms, is usually complicated by gestational diabetes mellitus (GDM). However, a comprehensive understanding of the immune microenvironment in the placenta of PE and the differences between PE and GDM is still lacking. In this study, Cytometry by time of flight (CyTOF) indicated that the frequencies of memory-like Th17 cells (CD45RA-CCR7+IL-17A+CD4+), memory-like CD8+ T cells (CD38+CXCR3-CCR7+Helios-CD127-CD8+) and pro-inflam Macs (CD206-CD163-CD38midCD107alowCD86midHLA-DRmidCD14+) were increased, while the frequencies of anti-inflam Macs (CD206+CD163-CD86midCD33+HLA-DR+CD14+) and granulocyte myeloid-derived suppressor cells (gMDSCs, CD11b+CD15hiHLA-DRlow) were decreased in the placenta of PE compared with that of NP, but not in that of GDM or GDM&PE. The pro-inflam Macs were positively correlated with memory-like Th17 cells and memory-like CD8+ T cells but negatively correlated with gMDSCs. Single-cell RNA sequencing revealed that transferring the F4/80+CD206- pro-inflam Macs with a Folr2+Ccl7+Ccl8+C1qa+C1qb+C1qc+ phenotype from the uterus of PE mice to normal pregnant mice induced the production of memory-like IL-17a+Rora+Il1r1+TNF+Cxcr6+S100a4+CD44+ Th17 cells via IGF1-IGF1R, which contributed to the development and recurrence of PE. Pro-inflam Macs also induced the production of memory-like CD8+ T cells but inhibited the production of Ly6g+S100a8+S100a9+Retnlg+Wfdc21+ gMDSCs at the maternal-fetal interface, leading to PE-like symptoms in mice. In conclusion, this study revealed the PE-specific immune cell network, which was regulated by pro-inflam Macs, providing new ideas about the pathogenesis of PE.

immunology↗

bioRxiv2024

Ancestral SARS-CoV-2 immune imprinting persists on RBD but not NTD after sequential Omicron infections

Whether Omicron exposures could overcome ancestral SARS-CoV-2 immune imprinting remains controversial. Here we analyzed B cell responses evoked by sequential Omicron infections in vaccinated and unvaccinated individuals. Plasma neutralizing antibody titers against ancestral SARS-CoV-2 and variants indicate that immune imprinting is not consistently induced by inactivated or recombinant protein vaccines. However, once induced, immune imprinting is not countered by successive Omicron challenges. We compared binding specificities, neutralizing capacities, developing origins and targeting epitopes of monoclonal antibodies from individuals with or without immune imprinting. Although receptor-binding domain (RBD) and N-terminal domain (NTD) of spike are both primary targets for neutralizing antibodies, immune imprinting only shapes antibody responses to RBD by impeding the production of Omicron-specific neutralizing antibodies while facilitating the development of broadly neutralizing antibodies. We propose that immune imprinting can be either neglected by NTD-based vaccines to induce variant-specific antibodies or leveraged by RBD-based vaccines to induce broadly neutralizing antibodies.

immunology↗

bioRxiv2024

Geranylgeranylated-SCFFBXO10 Regulates Selective Outer Mitochondrial Membrane Proteostasis and Function

E3-ubiquitin ligases (E3s) are main components of the ubiquitin-proteasome system (UPS), as they determine substrate specificity in response to internal and external cues to regulate protein homeostasis. However, the regulation of membrane protein ubiquitination by E3s within distinct cell membrane compartments or organelles is not well understood. We show that FBXO10, the interchangeable component of the SKP1/CUL1/F-box ubiquitin ligase complex (SCF-E3), undergoes lipid-modification with geranylgeranyl isoprenoid at Cysteine953 (C953), facilitating its dynamic trafficking to the outer mitochondrial membrane (OMM). FBXO10 polypeptide does not contain a canonical mitochondrial targeting sequence (MTS); instead, its geranylgeranylation at C953 and the interaction with two cytosolic factors, PDE6{delta} (a prenyl group-binding protein), and HSP90 (a mitochondrial chaperone) orchestrate specific OMM targeting of prenyl-FBXO10 across diverse membrane compartments. The geranylgeranylation-deficient FBXO10(C953S) mutant redistributes away from the OMM, leading to impaired mitochondrial ATP production, decreased mitochondrial membrane potential, and increased mitochondrial fragmentation. Phosphoglycerate mutase 5 (PGAM5) was identified as a potential substrate of FBXO10 at the OMM using comparative quantitative mass spectrometry analyses of enriched mitochondria (LFQ-MS/MS), leveraging the redistribution of FBXO10(C953S). FBXO10, but not FBXO10(C953S), promoted polyubiquitylation and degradation of PGAM5. Examination of the role of this pathway in a physiological context revealed that the loss of FBXO10 or expression of prenylation-deficient-FBXO10(C953S) inhibited PGAM5 degradation, disrupted mitochondrial homeostasis, and impaired myogenic differentiation of human iPSCs and murine myoblasts. Our studies identify a mechanism for selective E3-ligase mediated regulation of mitochondrial membrane proteostasis and metabolic health, potentially amenable to therapeutic intervention.

cell biology↗

bioRxiv2024

Unlocking TAS2R14 activation through intricate multi-ligand binding networks

Bitter taste receptors, particularly TAS2R14, play central roles in discerning a wide array of bitter substances, ranging from dietary components to pharmaceutical agents1-3. In addition, TAS2R14 has broad expression in non-gustatory tissues, suggesting its important roles in selective physiological processes and therapeutic potential4. Here, we present cryo-electron microcopy structures of TAS2R14 in complex with flufenamic acid and aristolochic acid, coupling with G protein subtypes gustducin and Gi. Distinct from most known GPCRs, agonists of TAS2R14 bind to multiple intracellular pockets. We highlight the cholesterol molecules occupying an upper transmembrane site, typically the orthosteric pocket in other GPCRs, also binding in the entrance to an intracellular agonist binding pocket, suggesting an endogenous modulatory function5. The structural and mutagenesis analysis illuminate the receptors broad-spectrum ligand recognition and activation via intricate multiple ligand-binding sites. Furthermore, we unveil the structural configuration of gustducin and its interaction with TAS2R14, as well as the coupling mode of Gi1. This investigation should be instrumental in advancing our knowledge of the mechanisms underlying bitter taste recognition and response, with broader relevance to sensory biology and pharmacology.

biophysics↗

bioRxiv2024

Development of BODIPY-based fluorescent probes for highly selective amino acid identification

Amino acid sensing is a powerful tool for intra- and extra-cellular assays. We report herein the generation and optimization of bioconjugatable fluorescent reporter for pan-amino acid sensing, the OMNI probe, that through inductive electronics produces a unique photophysical response upon coupling to the -amino group of an amino acid depending on the identity of the adjacent side chain. Using an auto-photocatalyzed Meerwein arylation reaction, we created a library of bis-arylated 8-methylthio-BODIPY dye derivatives exhibiting improved spectral variation, brightness, dynamic range, robustness, water solubility, and reactivity. Aryl groups with optimal photophysical behaviors were combined to create asymmetric versions conferring high spectral range, brightness, and water solubility. Combining aryl group modifications yielded a set of engineered asymmetric probes that achieved complete spectral resolution in a multi-variable analysis (fluorescent emission, lifetime, brightness) for all twenty native amino acid-dye conjugates while increasing reactivity toward amino acids in aqueous buffer. With our robust OMNI probe design, pan-amino acid resolution and identification through high sensitivity fluorescence down to single molecules is now routinely possible for diverse potential applications including protein sequencing.

biochemistry↗

bioRxiv2024

Mechanical cues of extracellular matrix determines tumor innervation

Peripheral tumors can establish local autonomic and sensory nerve networks, termed as tumor innervation (TIN), to support tumorigenesis and metastasis. While nerve dependence in cancers is well-established, the mechanisms governing TIN remain unclear. Here, we report that extracellular matrix (ECM) stiffness, a major mechanical abnormality in the tumor microenvironment (TME), is an essential contributor of TIN. In preclinical models, reducing lysyl oxidase-mediated ECM crosslinking lowers tissue stiffness and TIN in pancreatic cancer, while inflammation-induced matrix stiffening boosts the hyperinnervation of the pancreatic precursor lesions. Mechanistically, {beta}1-containing integrins sense the mechanical cues exerted by ECM stiffness, and the translational co-activator YAP1 acts as an essential nuclear relay to induce the expression of neurotropic genes, particularly brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). 3D imaging of the whole cleared pancreas reveals that blockade of mechanosensor integrin {beta}1 or pharmacological inhibition of the mechanotransducer YAP1 effectively reduces TIN. In clinical settings, tumor samples with a dense, crosslinked, and stiffened ECM exhibit significant TIN. In summary, these findings identify ECM stiffness as an important driver of TIN and suggest that targeting integrin {beta}1/YAP1-dependent mechanotransduction may counteract TIN.

neuroscience↗

bioRxiv2024

scDTL: single-cell RNA-seq imputation based on deep transfer learning using bulk cell information

MotivationThe growing amount of single-cell RNA sequencing (scRNA-seq) data allows researchers to investigate cellular heterogeneity and gene expression profiles, providing a high-resolution view of transcriptome at the single-cell level. However, dropout events, which are often present in scRNA-seq data, remain challenges for downstream analysis. Although a number of studies have been developed to recover single-cell expression profiles, their performance is sometimes limited by not fully utilizing the inherent relations between genes. ResultsTo address the issue, we propose a deep transfer learning based approach called scDTL for scRNA-seq data imputation by exploring the bulk RNA-sequencing information. scDTL firstly trains an imputation model for bulk RNA-seq data using a denoising autoencoder (DAE). We then apply a domain adaptation architecture that builds a mapping between bulk gene and single-cell gene domains, which transfers the knowledge learned by the bulk imputation model to scRNA-seq learning task. In addition, scDTL employs a parallel operation with a 1D U-Net denoising model to provide gene representations of varying granularity, capturing both coarse and fine features of the scRNA-seq data. At the final step, we use the cross-channel attention mechanism to fuse the features learned from the transferred bulk imputer and U-Net model. In the evaluation, we conduct extensive experiments to demonstrate that scDTL based approach could outperform other state-of-the-art methods in the quantitative comparison and downstream analyses. Contactzhangd@szu.edu.cn or tianj@sustech.edu.cn

bioinformatics↗

bioRxiv2024

Bacteria adapt nutrient deprivation by reducing vacant 70S ribosomes via the silencing factor RsfS

Bacteria rapidly remodel protein synthesis to survive nutrient limitation, yet how inactive ribosomes are selectively regulated remains incompletely understood. Ribosome silencing factor S (RsfS) is the only known bacterial factor that selectively dissociates vacant 70S ribosomes, but its physiological function in bacterial adaptation has remained elusive. Here, we demonstrate that RsfS promotes bacterial survival during nutrient starvation by selectively dismantling non-translating vacant 70S ribosomes while sparing translating ribosomes. Biochemical analyses show that RsfS efficiently dissociates vacant 70S ribosomes but has little effect on programmed ribosomes in the pre-translocation or post-translocation states, thereby preserving ongoing protein synthesis. Ribosome profiling further reveals that loss of RsfS results in a global reduction in translational efficiency and widespread translational reprogramming during starvation. Mechanistically, dissociation of vacant ribosomes by RsfS suppresses futile EF-G-dependent GTP hydrolysis and prevents unnecessary energy expenditure associated with inactive ribosome cycling. Consistent with this mechanism, RsfS enhances bacterial adaptation to nutrient deprivation without compromising active translation. Together, our findings identify RsfS as a unique regulator of bacterial ribosome homeostasis that conserves cellular energy through selective dissociation of vacant 70S ribosomes, revealing a previously unrecognized strategy by which bacteria optimize translation under nutrient-limited conditions.

microbiology↗

bioRxiv2024

Information is asymmetry: spatial relations were encoded by asymmetric mnemonic manifolds

Substantial evidence suggests that working memory (WM) leverages relational representations to provide flexible support for cognitive functions, a capacity likely derived from the dynamic nature of neural codes in WM. However, how these dynamic codes represent and maintain relations remains unclear. Here, we examined the transformation of neural geometries in the dorsal prefrontal cortex of monkeys performing a visuospatial delayed-match/nonmatch task, where the monkeys were instructed to hold the spatial location of a white square in WM to match it with the spatial location of a subsequent square. We found that the sensory manifold during the squares presence and the mnemonic manifold after the squares offset both aligned with the stimulus manifold. However, significant differences emerged between the sensory and mnemonic manifolds, exhibiting little correlation in their neural geometries. Further analysis on the dynamic transformation from the sensory to mnemonic manifold revealed a process of expansion followed by flattening: the asymmetric sensory manifold first expanded into a symmetric neural geometry immediately after the squares onset offset, which then gradually flattened along dimensions different from those initially expanded, culminating in an asymmetric mnemonic manifold. This dynamic process of reconstruction not only remained its faithfulness to the stimulus geometry but also gained the flexibility to meet task demands. In sum, this transformation from asymmetry to symmetry and back to asymmetry in neural geometry precisely illustrates the dynamics of memory reconstruction, shedding lights on the subjective nature of WM that generates both accurate and illusory representation of the world we lived in.

neuroscience↗

bioRxiv2024

Large-scale multi-omics analyses identified root-microbiome associations underlying plant nitrogen nutrition

The microbiome determines the performance and fitness of the host plant. Nevertheless, the causal interaction between host genetic variation, gene regulation and the impact of the microbiome on the host phenotype remain unknown. Here we generated 1,341 paired root transcriptome, rhizosphere microbiome and root ionome samples and performed a multi-omics analyses of the host-microbe association at the root-soil interface using 175 rapeseeds (Brassica napus L.) resequenced ecotypes at two field environments. We observed the highest statistically explained variance for root nitrogen uptake among natural ionomic variation by overall transcriptome-wide gene expression and microbial abundance variation. Moreover, we identified significant genome-wide associations for 203 highly heritable amplicon sequence variants (ASVs) at multiple genetic loci regulated by eQTL hotspots associated with nitrogen metabolism components. These associations involved a central bacterial genus (Sphingopyxis), which plays a dominant role on gene regulatory effect on its variation regulated by eQTL hotspots. In addition, we performed high-throughput bacterial cultivation from rapeseed roots and subjected Sphingopyxis to whole genome sequencing. Finally, targeted metabolite profiling and confocal imaging assays demonstrated a host-microbiome regulatory effect on Sphingopyxis established by lateral root development and plant nitrogen nutrition. In summary, our integrative approach reveals the genetic basis of host-microbiome trait associations in the transcriptional, nutritional and environmental domains and suggests that the microbiome might have causal effects on root development with implications towards the breeding of nutrient-efficient crops.

plant biology↗