Biology subjects

Shao, Z.

Publications and source records attributed to Shao, Z..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Comparative study on the effects of different types of acute exercise on cortisol levels and cognitive functions

This study examines the different effects of dual-task and single-task exercises on cortisol levels and cognitive performance. Seventeen male college students participated, performing each exercise on separate days. Salivary samples were taken before and after exercise to assess cortisol levels. Cognitive functions were measured using the 2-Back Test, Bells Test, and Mental Rotation Test. Results showed that both exercises significantly improved reaction times across cognitive tests. However, dual-task exercise caused a more notable increase in cortisol levels (p=0.002) than the single-task. A negative correlation between post-exercise cortisol levels and reaction times suggests that higher cortisol levels might enhance cognitive processing speed. Cognitive performance ac-curacy remained unchanged across both exercises. These findings indicate that while both exercise types enhance cognitive speed, dual-task exercise triggers a greater cortisol response, potentially offering more benefits for cognitive processing speed without affecting accuracy. This research highlights the complex interaction between acute exercise, stress hormones, and cognitive function, providing insights into how different exercise types influence cognitive performance through hormonal pathways.

neuroscience↗

bioRxiv2024

Down regulation of Engase in Caenorhabditis elegans may improve its stresses adaptivity

Endo-beta-N-acetylglucosaminidase (ENGASE) is one of the key enzymes involved in the regulation of structure and function of glycoproteins. It is conserved from prokaryotic to eukaryotic cells. Although their activities in vitro and applications have been well studied, the biological function of ENGASE remains to be illustrated. In this study, we analyzed the molecular and physiological function of Engase from Caenorhabditis elegans homolog eng-1(CeEngase). We found that CeEngase knockout or knockdown increased the environmental stresses adaptability, such as heat stress and osmotic stress. Preliminary glycomics analysis showed that the basement membrane proteins of extracellular matrix may be the main targets of CeENGASE. In addition, CeENGASE may selectively prefer to N2H7 glycans on glycoproteins. In conclusion, our data illustrated that the defection and/or down regulation of CeEngase may provide a beneficially adaptation for stresses.

biochemistry↗

bioRxiv2024

Perfringolysin O pore-forming complexes are predominantly integral multiples of six subunits

Perfringolysin O is a well-studied bacterial cytolysin that forms large oligomeric pores with a wide range of sizes on membranes via a prepore intermediate. Here we examined the sizes of both PFO prepore and pore complexes electrophoretically using a multi-stack-gradient gel and found that, unexpectedly, there are only at most seven predominant sizes of either pores or prepores. Complexes extracted from each band exhibit contour lengths that are integral multiples of six subunits. High-resolution atomic force microscopy images of PFO pore complexes in supported bilayers also reveal a predominant hexameric-based stoichiometry. Thus, these results reveal a previously unknown structural hierarchy in PFO complexes, with larger complexes apparently built up from hexameric sub-complexes. We suggest that different inter-subunit interactions within and between the hexamers result in a likewise difference in the coordination of the prepore-to-pore transition within and between the hexamers, and is thus a critical feature of the allostery of this large multi-subunit complex.

biophysics↗

bioRxiv2024

Calneuron 1 reveals the pivotal roles in schizophrenia via perturbing human forebrain development and causing hallucination-like behavior in mice

Schizophrenia is a highly heritable neurodevelopmental disorder with unknown genetic pathogenic mechanisms. Here, we selected 11 schizophrenia risk genes and generated single-gene-knockout-precise-dorsal/ventral-forebrain-organoids (SKOPOS) via CRISPR-Cas9 system. 90 bulk and 249,430 single-cell RNA-sequencing of SKOPOS revealed that knockout of 11 risk genes lead to different levels of deficits in dorsal/ventral forebrain organoids. Among them, calneuron 1 (CALN1) acts as a pivotal pathogenic gene of schizophrenia via severe disruption of gene expression network, interaction with about 32% (34/106) known schizophrenia risk genes, delayed maturation and impaired spontaneous neural circuit in human developing forebrain. Furtherly, including the spontaneous abrupt burst spiking in cortical neurons and the defects of spatial memory, cognition and social ability, Caln1 KO mice surprisingly displayed spontaneous startle behavior and head-twitch response correlated with hallucination-like behavior, which could be inhibited by antipsychotic drug SEP-363856. In summary, CALN1 is identified as a pivotal pathogenic gene of schizophrenia in forebrain development.

neuroscience↗

bioRxiv2024

The transcripts of a gastrula-premarked enhancer prime posterior tissue development through cross-talk with morphogen effector

The regulatory mechanisms governing cell fate determination, particularly lineage diversification during mammalian embryonic development, remain poorly understood with in-depth regulatory paradigms yet to be fully elucidated. Here, leveraging the epigenetic landscape of mouse gastrula, we identified p-Enh, a pre-marked enhancer in primitive streak region, as pivotal regulator for posterior tissue development in mouse embryos. Morphological and single-cell transcriptomic analyses confirmed embryonic lethality phenotype with disrupted posterior tissue development trajectories in p-Enh-KO embryos. Molecularly, apart from regulating the neighboring coding-gene Cdx2 in cis, our findings suggest that p-Enh also modulate the global transcriptome and epigenomic landscape, which might through the transient production of eRNA in trans. Further investigation revealed p-Enh participate in the regulatory cascades of TGF-{beta} signaling. Chemical modulation of TGF-{beta} signaling can largely rescue the posterior development deficiency in in vitro gastruloids through a Cdx2-independent mechanism. Thus, we propose a potential model in which the broadly distributed p-Enh transcripts within the nucleus could serve as essential cross-modular coordinators, priming the posterior development of mouse embryo.

developmental biology↗

bioRxiv2024

EAP: a versatile cloud-based platform for comprehensive and interactive analysis of large-scale ChIP/ATAC-seq data sets

Epigenome profiling techniques such as ChIP-seq and ATAC-seq have revolutionized our understanding of gene expression regulation in tissue development and disease progression. However, increasing amount of ChIP/ATAC-seq data poses challenges in computational resources, and the absence of systematic tools for epigenomic analysis underscores the necessity for an efficient analysis platform. To address these issues, we developed the Epigenomic Analysis Platform (EAP, https://www.biosino.org/epigenetics), a scalable cloud-based tool that efficiently analyzes large-scale ChIP/ATAC-seq data sets. EAP employs advanced computational algorithms to derive biologically meaningful insights from heterogeneous datasets and automatically generates publication-ready figures and tabular results, enabling comprehensive epigenomic analysis and data mining in areas like cancer subtyping and therapeutic target discovery.

bioinformatics↗

bioRxiv2024

LHP1 and INO80 cooperate with ethylene signaling for warm ambient temperature response by activating specific bivalent genes

Ethylene signaling has been indicated as a potential positive regulator of plant warm ambient temperature response but its underlying molecular mechanisms are largely unknown. Here, we show that LHP1 and INO80 cooperate with ethylene signaling for warm ambient temperature response by activating specific bivalent genes. We found that the presence of warm ambient temperature activates ethylene signaling through EIN2 and EIN3, leading to an interaction between LHP1 and accumulated EIN2-C to co-regulate a subset of LHP1-bound genes marked by H3K27me3 and H3K4me3 bivalency. Furthermore, we demonstrate that INO80 is recruited to bivalent genes by interacting with EIN2-C and EIN3, promoting H3K4me3 enrichment and facilitating transcriptional activation in response to warm ambient temperature. Together, our findings illustrate a novel mechanism wherein ethylene signaling orchestrates LHP1 and INO80 to regulate warm ambient temperature response through activating specific bivalent genes in Arabidopsis.

plant biology↗

bioRxiv2024

A neutral process of genome reduction in marine bacterioplankton

Marine bacterioplankton communities are dominated by cells equipped with small genomes. Streamlining selection has been accepted as the main force driving their genome reduction. Here, we report that a neutral evolutionary mechanism governs genome reduction in the Roseobacter group that represents 5-20% of the bacterioplankton cells in coastal waters. Using representative strains that fall into three genome size groups (2-3, 3-4, and 4-5 Mbp), we measured their genomic mutation rates () through long-term mutation accumulation experiments followed by genome sequencing the resulting 437 mutant lines. We further calculated their effective population sizes (Ne) based on and the neutral genetic diversity of the studied species, the latter estimated based on multiple genome sequences of natural isolates collected from global oceans with their population structure considered. A surprising finding is that Ne scales positively with genome size, which is the opposite of the expectation from the streamlining selection theory. As the strength of random genetic drift is the inverse of Ne, this result instead suggests drift as the primary driver of genome reduction. Additionally, we report a negative scaling between and genome size, which is the first experimental evidence for the long-lasting hypothesis that mutation rate increases play a part in marine bacterial genome reduction. As scales inversely with Ne, genetic drift appears to be the ultimate cause of genome reduction in these Roseobacters. Our finding discounts, but is insufficient to reject, the streamlining theory because streamlining process is expected to be more effective in oligotrophic open ocean waters.

microbiology↗

bioRxiv2024

Histone acetyltransferase HAF2 associates with PDC to control H3K14ac and H3K23ac in ethylene response

Ethylene plays its essential roles in plant development, growth, and defense responses by controlling the transcriptional reprogramming, in which EIN2-C-directed regulation of histone acetylation is the first key-step for chromatin to perceive ethylene signaling. However, the histone acetyltransferase in this process remains unknown. Here, we identified histone acetyltransferase HAF2, and mutations in HAF2 confer plants with ethylene insensitivity. Furthermore, we found that HAF2 interacts with EIN2-C in response to ethylene. Biochemical assays demonstrated that the bromodomain of HAF2 binds to H3K14ac and H3K23ac peptides with a distinct affinity for H3K14ac; the HAT domain possesses acetyltransferase catalytic activity for H3K14 and H3K23 acetylation, with a preference for H3K14. ChIP-seq results provide additional evidence supporting the role of HAF2 in regulating H3K14ac and H3K23ac levels in response to ethylene. Finally, our findings revealed that HAF2 co-functions with pyruvate dehydrogenase complex (PDC) to regulate H3K14ac and H3K23ac in response to ethylene in an EIN2 dependent manner. Overall, this research reveals that HAF2 as a histone acetyltransferase that forms a complex with EIN2-C and PDC, collectively governing histone acetylation of H3H14ac and H3K23ac, preferentially for H3K14 in response to ethylene.

plant biology↗

bioRxiv2023

From sequence to ecology: siderophore-receptor coevolution algorithm predicts bacterial interactions in complex communities

Predicting bacterial social interactions from genome sequences is notoriously difficult. Here, we developed bioinformatic tools to predict whether secreted iron-scavenging siderophores stimulate or inhibit the growth of community members. Siderophores are chemically diverse and can be stimulatory or inhibitory depending on whether bacteria possess or lack corresponding uptake receptors. We focused on 1928 representative Pseudomonas genomes and developed a co-evolution algorithm to match all encoded siderophore synthetases to corresponding receptor gene groups with >90% accuracy based on experimental validation. We derived community-level iron interaction networks to show that selection for siderophore-mediated interactions differs across habitats and lifestyles. Specifically, dense networks of siderophore sharing and competition were observed among environmental (soil/water/plant) strains and non-pathogenic species, while only fragmented networks occurred among human-derived strains and pathogenic species. Altogether, our sequence-to-ecology approach empowers the analyses of social interactions among thousands of bacterial strains and uncovers ways for targeted intervention to microbial communities. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=87 SRC="FIGDIR/small/565711v3_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@60d907org.highwire.dtl.DTLVardef@48756eorg.highwire.dtl.DTLVardef@115aac1org.highwire.dtl.DTLVardef@17d76e5_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2023

Spatiotemporal Profiling Unveiling the Cellular Organization Patterns and Local Protumoral Immune Microenvironment Remodeling in Early Lung Adenocarcinoma Progression

Spatial cellular organization patterns (COPs) in tumor microenvironment influence the tumor progression and therapeutic response, however, little is known about the cellular composition and functional potential of these multicellular structures during lung adenocarcinoma progression. Here, we integrate spatial transcriptomics with single cell RNA sequencing to characterize the local tumor and immunological landscape of samples from 8 patients with early-stage lung adenocarcinoma at different pathological stages. We identified ten COPs that show distinct associations with local immune states and clinical outcomes, including survival and therapy response. The local infiltration levels of regulatory and dysfunctional immune cells are increased with pathological progression. Cell-to-cell interactions between malignant cells and tumor microenvironment (TME) cells were involved in protumor immune state remodeling. Finally, we detected a group of malignant cells that were specifically located at the tumor boundary, representing a more aggressive state, were involved in the invasion of invasive adenocarcinoma (IAC). Altogether, these results can improve our understanding of the local microenvironment characteristics that underlie LUAD progression and may facilitate the identification of drug targets to prevent invasive progression and biomarkers for diagnosis.

cell biology↗

bioRxiv2023

Nuclear Pyruvate Dehydrogenase Complex Regulates Histone Acetylation and Transcriptional Regulation in the Ethylene Response

Ethylene plays its essential roles in plant development, growth, and defense responses by controlling the transcriptional reprograming, in which EIN2-C-directed regulation of histone acetylation is the first key-step for chromatin to perceive ethylene signaling. But how the nuclear acetyl coenzyme A (acetyl CoA) is produced to ensure the ethylene-mediated histone acetylation is unknown. Here we report that ethylene triggers the accumulation of the pyruvate dehydrogenase complex (PDC) in the nucleus to synthesize nuclear acetyl CoA to regulate ethylene response. PDC is identified as an EIN2-C nuclear partner, and ethylene triggers its nuclear accumulation. Mutations in PDC lead to an ethylene-hyposensitivity that results from the reduction of histone acetylation and transcription activation. Enzymatically active nuclear PDC synthesize nuclear acetyl CoA for EIN2-C-directed histone acetylation and transcription regulation. These findings uncover a mechanism by which PDC-EIN2 converges the mitochondrial enzyme mediated nuclear acetyl CoA synthesis with epigenetic and transcriptional regulation for plant hormone response.

plant biology↗

bioRxiv2023

MiR-574-5p activates human TLR8 to promote autoimmune signaling and lupus

Endosomal single-stranded RNA-sensing Toll-like receptor-7/8 (TLR7/8) plays a pivotal role in inflammation and immune responses and autoimmune diseases. However, the mechanisms underlying the initiation of the TLR7/8-mediated autoimmune signaling remain to be fully elucidated. Here, we demonstrate that miR-574-5p is aberrantly upregulated in tissues of lupus prone mice and in the plasma of lupus patients, with its expression levels correlating with the disease activity. miR-574-5p binds to and activates human hTLR8 or its murine ortholog mTlr7 to elicit a series of MyD88-dependent immune and inflammatory responses. These responses include the overproduction of cytokines and interferons, the activation of STAT1 signaling and B lymphocytes, and the production of autoantigens. In a transgenic mouse model, the induction of miR-574-5p overexpression is associated with increased secretion of antinuclear and anti-dsDNA antibodies, increased IgG and C3 deposit in the kidney, elevated expression of inflammatory genes in the spleen. In lupus-prone mice, lentivirus-mediated silencing of miR-574-5p significantly ameliorates major symptoms associated with lupus and lupus nephritis. Collectively, these results suggest that the miR-574-5p-hTLR8/mTlr7 signaling is an important axis of immune and inflammatory responses, contributing significantly to the development of lupus and lupus nephritis.

immunology↗

bioRxiv2023

SIDERITE: Unveiling Hidden Siderophore Diversity in the Chemical Space Through Digital Exploration

Siderophores, a highly diverse family of secondary metabolites, play a crucial role in facilitating the acquisition of the essential iron. However, the current discovery of siderophore relies largely on manual approaches. In this work, we introduced SIDERTE, a digitized siderophore information database containing 872 siderophore records with 649 unique structures. Leveraging this digitalized dataset, we gained a systematic overview of siderophores by their clustering patterns in the chemical space. Building upon this, we developed a functional group-based method for predicting new iron-binding molecules. Applying this method to 4,314 natural product molecules from TargetMols Natural Product Library for high throughput screening, we experimentally confirmed that 40 out of the 48 molecules predicted as siderophore candidates possessed iron-binding abilities. Expanding our approach to the COCONUT natural product database, we predicted a staggering 3,199 siderophore candidates, showcasing remarkable structure diversity that are largely unexplored. Our study provides a valuable resource for accelerating the discovery of novel iron-binding molecules and advancing our understanding towards siderophores.

biochemistry↗

bioRxiv2023

A vast repertoire of secondary metabolites influences community dynamics and biogeochemical processes in cold seeps

In deep sea cold seeps, diverse microbial communities thrive on the geological seepage of hydrocarbons and inorganic compounds. These chemosynthetically-driven communities are unique in composition, ecology, and biogeochemical activities compared to photosynthetically-driven ecosystems. However, their biosynthetic capabilities remain largely unexplored. Here, we analyzed 81 metagenomes, 33 metatranscriptomes, and seven metabolomes derived from nine globally distributed areas of cold seeps to investigate the secondary metabolites produced by cold seep microbiomes. Cold seep microbiomes encode diverse, abundant, and novel biosynthetic gene clusters (BGCs). Most BGCs are affiliated with understudied bacteria and archaea, including key mediators of methane and sulfur cycling, and multiple candidate phyla. The BGCs encode diverse antimicrobial compounds (e.g. NRPS, PKSs, RiPPs) that potentially shape community dynamics, as well as compounds predicted to influence biogeochemical cycling, such as phosphonates, iron-acquiring siderophores, nitrogenase-protecting glycolipids, and methyl-CoM reductase-modifying proteins. BGCs from key players in cold seeps are widely distributed and highly expressed, with their abundance and expression levels varying with different sediment depths. Numerous unique natural products were detected through untargeted sediment metabolomics, demonstrating a vast, unexplored chemical space and validating in situ expression of the BGCs in cold seep sediments. Overall, these results demonstrate cold seep sediments potentially serve as a reservoir of hidden natural products and provide insights into microbial adaptation in chemosynthetically-driven ecosystems.

microbiology↗

bioRxiv2023

Preserved stimulus representations in frontal cortex as a potential neural mechanism for flexible control in working memory

When holding visual information temporarily in working memory (WM), the neural representation of the memorandum is distributed across various cortical regions, including visual and frontal cortices. However, the role of stimulus representation in visual and frontal cortices during WM has been controversial. Here we tested the hypothesis that stimulus representation persists in the frontal cortex to facilitate flexible control demands in WM. During functional MRI, participants flexibly switched between simple WM maintenance of visual stimulus or more complex rule-based categorization of maintained stimulus on a trial-by-trial basis. Our results demonstrated enhanced stimulus representation in the frontal cortex that tracked demands for active WM control and enhanced stimulus representation in the visual cortex that tracked demands for precise WM maintenance. This differential frontal stimulus representation traded off with the newly-generated category representation with varying control demands. Simulation using multi-module recurrent neural networks replicated human neural patterns when stimulus information was preserved for network readout. Altogether, these findings help reconcile the long-standing debate in WM research, and provide empirical and computational evidence that flexible stimulus representation in the frontal cortex during WM serves as a potential neural coding scheme to accommodate the ever-changing environment.

neuroscience↗

bioRxiv2023

Quasi-Equilibrium State Based Quantification of Biological Macromolecules in Single-Molecule Localization Microscopy

The stoichiometry of molecular components within supramolecular biological complexes is often an important property to understand their biological functioning, particularly within their native environment. While there are well established methods to determine stoichiometry in vitro, it is presently challenging to precisely quantify this property in vivo, especially with single molecule resolution that is needed for the characterization stoichiometry heterogeneity. Previous work has shown that optical microscopy can provide some information to this end, but it can be challenging to obtain highly precise measurements at higher densities of fluorophores. Here we provide a simple approach using already established procedures in single-molecule localization microscopy (SMLM) to enable precise quantification of stoichiometry within individual complexes regardless of the density of fluorophores. We show that by focusing on the number of fluorophore detections accumulated during the quasi equilibrium-state of this process, this method yields a 50-fold improvement in precision over values obtained from images with higher densities of active fluorophores. Further, we show that our method yields more correct estimates of stoichiometry with nuclear pore complexes and is easily adaptable to quantify the DNA content with nanodomains of chromatin within individual chromosomes inside cells. Thus, we envision that this straightforward method may become a common approach by which SMLM can be routinely employed for the accurate quantification of subunit stoichiometry within individual complexes within cells.

biophysics↗

bioRxiv2023

Long-read Transcriptome Landscapes of Primary and Metastatic Liver Cancers at Transcript Resolution

BackgroundThe liver is the sixth most common site of primary cancer in humans and is frequently colonized by metastases from cancers of other organs. Few studies have investigated the transcriptomic profiles of matched primary tumor and hepatic metastases of patients. Moreover, the read length of 100-200 bases in conventional short-read RNA sequencing is too short, which makes it difficult to directly infer the full-length transcript structure. To help develop effective treatments and improve survival, it is crucial to understand the complex and diverse molecular mechanisms of primary and metastatic liver cancers. MethodsNinety-five primary and secondary liver cancer patients who underwent hepatic resection were included with long-read sequencing isoform-sequencing and short-read RNA sequencing. We compared the transcriptome landscapes of primary and metastatic liver cancers and systematically investigated HCC, paired primary tumors and liver metastases, and matched non-tumor liver tissues. ResultsWe defined the full-length isoform-level transcriptome of human primary and metastatic liver cancers and identified isoform-level diversity in HCC and metastasis-associated transcriptome variations in metastatic liver cancers. Specific RNA transcripts and isoform switching events with clinical implications were profoundly discovered in liver cancer. Metastasis-specific transcripts that can predict the metastatic risk and identify the primary sites of cancers of unknown primary liver metastasis patients were defined. Additionally, we found that adjacent paracancerous liver tissues are abnormal and characterized the premetastatic immunological and metabolic alterations in the liver that favor the spread of cancer metastases. ConclusionsOur findings strongly highlight the powerfulness of full-length transcriptome profiling to yield novel biological insights into understanding the molecular basis of tumorigenesis and will further benefit the treatment of primary and metastatic liver cancers.

genomics↗