Biology subjects

Tao, S.

Publications and source records attributed to Tao, S..

At least 55 records · Page 3Linked to original sources

bioRxiv2023

Dual long-axis reorganization of hippocampus in youth

The reorganization of human hippocampus, especially its interaction with cortex, remains largely undefined in youth. The organization of a single hippocampal long-axis has been predominantly characterized as monotonic1-6, despite recent indications of nonmonotonic features in neuron density7 and geometric eigenmodes8. While the human cortical hierarchy has been well recognized for significant developmental and evolutionary advantages9-12, hippocampus has been typically considered an evolutionarily conserved brain structure1,13,14, and overlooked regarding its integrative role of cortical hierarchical processing during development. Here, we corroborated the presence and significance of a dual long-axis representation of the hippocampal connectome and geometry including both linear and quadratic gradients along its long-axis in youth. This finding was robust across two independent large-scale developmental cohorts. Charting development of the dual long-axis gradients underscored their specific contributions to the cortical hierarchy maturation from the frontoparietal and salience/ventral attention networks. The observed developmental variability in spontaneous brain activities in youth parallels the gradients of myelin content. During childhood through adolescence to early adulthood, the hippocampus reorganized the dual long-axis by gradually relaxing its geometric constraints on the intrinsic network organization of cortical spontaneous activity for refined executive functions. Molecular processes underlying such reorganization of the dual long-axis in hippocampus are linked to neural growth, stress hormone regulation, and neuroactive signaling. Our findings enrich the understanding of hippocampal-cortical reorganizational principles across structural, functional, and molecular dimensions as well as its maturation, and define the plasticity distribution within the human hippocampus at systems level, holding potentials to enhance and translate neurodevelopment and neuropsychiatric healthcare.

neuroscience↗

bioRxiv2023

SACNet: A Multiscale Diffeomorphic Convolutional Registration Network with Prior Neuroanatomical Constraints for Flexible Susceptibility Artifact Correction in Echo Planar Imaging

Susceptibility artifacts (SAs), inevitable in brain diffusion MR (dMRI) scans acquired using single-shot echo planar imaging (EPI), severely compromise the accurate detection of human brain structure. Existing SA correction (SAC) methods offer inadequate correction quality and limited applicability across diverse datasets with varied acquisition protocols. To address these challenges, we proposed SACNet, a SAC framework based on unsupervised registration convolutional networks, featuring: i) a novel diffeomorphism regularization function to avoid unnatural SAC warps, modified from a potential well function; ii) an integration with prior neuroanatomical constraints and coarse-to-fine processing strategy to enables multi-scale geometric and intensity recoveries in severe distorted areas; iii) a unified registration framework that incorporates multiple phase-encoding (PE) EPI images and structural images, ensuring compatibility with both single- and inverse-PE protocols, with or without field maps. Utilizing simulated dMRI images and over 2000 brain scans from neonatal, child, adult and traveling participants, our method consistently demonstrates state-of-the-art correction performance. Notably, SACNet effectively reduces SAs-related multicenter effects compared to existing methods. We have developed user-friendly tools using containerization techniques, hope to facilitate SAC correction quality across extensive neuroimaging studies.

neuroscience↗

bioRxiv2023

Functional connectome through the human life span

The lifespan growth of the functional connectome remains unknown. Here, we assemble task-free functional and structural magnetic resonance imaging data from 33,250 individuals aged 32 postmenstrual weeks to 80 years from 132 global sites. We report critical inflection points in the nonlinear growth curves of the global mean and variance of the connectome, peaking in the late fourth and late third decades of life, respectively. After constructing a fine-grained, lifespan-wide suite of system-level brain atlases, we show distinct maturation timelines for functional segregation within different systems. Lifespan growth of regional connectivity is organized along a primary-to-association cortical axis. These connectome-based normative models reveal substantial individual heterogeneities in functional brain networks in patients with autism spectrum disorder, major depressive disorder, and Alzheimers disease. These findings elucidate the lifespan evolution of the functional connectome and can serve as a normative reference for quantifying individual variation in development, aging, and neuropsychiatric disorders.

neuroscience↗

bioRxiv2023

Enriched zones of embedded ribonucleotides are associated with DNA replication and coding sequences in the human mitochondrial genome

Abundant ribonucleoside triphosphate (rNTP) incorporation in DNA by DNA polymerases in the form of ribonucleoside monophosphates (rNMPs) is a widespread phenomenon in nature, resulting in DNA structural change and genome instability. The rNMP distribution, characteristics, hotspots, and association with DNA metabolic processes in human mitochondrial DNA (hmtDNA) remain mostly unknown. Here, we utilize the ribose-seq technique to capture embedded rNMPs in mtDNA of six different human cell types with wild-type or mutant ribonuclease (RNase) H2 genotype. The rNMPs are preferentially embedded in the DNA of the light strand in most cell types studied, but not in the liver-tissue cells, in which the rNMPs are dominant on the heavy strand of hmtDNA. We uncover common rNMP hotspots and conserved rNMP-enriched zones across the entire hmtDNA, including in the replication-control region, which may result in the suppression of mtDNA replication. We also show that longer coding sequences have a significantly higher rNMP-embedment frequency per nucleotide. While the composition of the embedded rNMPs varies among the different cell types, by studying the genomic context of embedded rNMPs, we detected common rNMP-embedment patterns in hmtDNA. The genomic contexts of rNMPs found in hmtDNA are mainly distinct from those found in yeast mtDNA, highlighting a unique signature of rNTP incorporation by hmtDNA polymerase {gamma}.

genomics↗

bioRxiv2022

Structural connectome architecture shapes the maturation of cortical morphology from childhood to adolescence

Cortical thinning is an important hallmark of the maturation of brain morphology during childhood and adolescence. However, the connectome-based wiring mechanism that underlies cortical maturation remains unclear. Using neuroimaging, connectome, transcriptome, and computational modeling, we mapped cortical thinning patterns primarily located in lateral frontal and parietal heteromodal nodes during childhood and adolescence, which is structurally constrained by white matter network architecture and is particularly represented using a network-based diffusion model. Furthermore, connectome-based constraints are regionally heterogeneous, with the largest constraints residing in frontoparietal nodes, and are associated with gene expression signatures of microstructural neurodevelopmental events. These results are highly reproducible while using another independent dataset. Our findings advance our understanding of network-level mechanisms and the associated genetic basis that underlies the maturational process of cortical morphology during childhood and adolescence.

neuroscience↗

bioRxiv2022

Glucose modulates transcription factor dimerization to enable tissue differentiation

Glucose is a universal energy currency for living organisms, however, its non-energetic functions in processes such as differentiation are undefined. In epidermis, differentiating cells exhibit dynamic changes in gene expression1-4 driven by specific transcription factors (TFs)5-9. The interplay between such TFs and biomolecules that also change in this process is not understood. Metabolomic analyses revealed that increased intracellular glucose accompanies differentiation of epidermal keratinocytes. This elevation also occurred in differentiating cells from other tissues and was verified in epidermal tissue engineered with glucose sensors, which detected a glucose gradient that peaked in the outermost differentiated layers. Free glucose accumulation, unaccompanied by its increased metabolism, was essential for epidermal differentiation and required GLUT1, GLUT3, and SGLT1 transporters. Glucose affinity chromatography and azido-glucose click chemistry uncovered glucose binding to diverse regulatory proteins, including the IRF6 TF, whose epidermal knockout confirmed its requirement in glucose-dependent differentiation. Direct glucose binding enabled IRF6 dimerization, DNA binding, genomic localization, and induction of IRF6 target genes, including essential pro-differentiation TFs GRHL1, GRHL3, HOPX and PRDM1. The IRF6R84C mutant found in undifferentiated cancers was unable to bind glucose. These data identify a new role for glucose as a gradient morphogen that modulates protein multimerization in cellular differentiation.

molecular biology↗

bioRxiv2022

Tree and shrub richness modify subtropical tree productivity by modulating the diversity and community composition of soil bacteria and archaea

BackgroundDeclines in plant biodiversity often have negative consequences for plant community productivity, and it becomes increasingly acknowledged that this may be driven by shifts in soil microbial community composition. These relationships have been well-established in grasslands, and few studies also indicate that fungi play a role in driving tree diversity-productivity relationships in forests. However, the role of bacteria and archaea, which are also highly abundant in forest soils and perform pivotal ecosystem functions, has been largely overlooked. Here, we investigated how tree and shrub richness affects stand-level tree productivity via modulating bacterial and archaeal community diversity and composition. We used a landscape-scale, subtropical tree biodiversity experiment (BEF-China) where tree (1, 2 or 4 species) and shrub richness (0, 2, 4, 8 species) were modified. ResultsOur results showed that tree and shrub species richness affected bacterial diversity, community composition, and co-occurrence networks, but such effects were marginal for archaea. Both tree and shrub species richness increased stand-level tree productivity by modulating soil microbial community composition, with the effects being mediated via increases in soil C:N ratios. ConclusionsOur findings imply the importance of bacterial and archaeal communities in driving the relationship between plant diversity and productivity in subtropical forests and highlight that we may require better a understanding of prokaryotic communities in forest soils.

ecology↗

bioRxiv2022

Growth mindset promotes children's working memory performance through cortico-striatal interaction and fronto-parietal activation

Growth mindset--the belief that abilities are malleable through effort--drives motivation, action and achievement. Yet, the underlying mechanisms remain elusive, necessitating a unified framework that integrates cognitive, neural, and developmental processes. Leveraging longitudinal neuroimaging and computational modeling to reveal moment-to-moment decision responses and brain state dynamics during working memory (WM), we show that growth mindset enhances WM development from middle childhood to adolescence via nuanced cortico-striatal network dynamics that balance between brain state flexibility and stability. Behaviorally, children with higher growth mindset exhibited better WM performance both cross-sectionally and longitudinally, attributed to faster evidence accumulation during moment-to-moment information updating, especially under high task demands. Neurally, a higher growth mindset was associated with greater activation of the dorsal striatum, cingulo-opercular (action-mode), and fronto-parietal networks during WM, which further accounted for longitudinal WM improvement and latent evidence accumulation. Such cortico-striatal activation covaried with neurochemical mediators critical for motivation and executive functioning. Analyzing non-stationary network dynamics revealed that growth mindset optimized dynamical organization of cortico-striatal networks, with an activated state highly flexible to support moment-to-moment information updating and a deactivated state remaining stable across blocks to suppress irrelevant information. This suggests a balanced allocation of resources for accumulating evidence while suppressing noise during WM. Together, our findings support a neurocognitive framework in which growth mindset enhances WM development via nuanced orchestration of cortico-striatal networks to enable efficient dynamic computations and foster far-reaching cognitive development.

neuroscience↗

bioRxiv2022

Sequence Analysis of WRKY Transcription Factor Family in Dendrobium officinale

WRKY transcription factors are a key class of plant regulators that regulate Dendrobium growth, development, and stress tolerance. In this work, 74 Dendrobium WRKY genes were found in the Dendrobium whole genome file using tbtools software, hmmer3.0 software, pfam website, mega6.0 software, genedoc software, meme online analysis website, and other tools, and tbtools software was utilized after amino acid alignment. A phylogenetic tree of the Dendrobium and Arabidopsis WRKY transcription factors sequence alignment was built, as well as the chromosomal location, gene structure analysis, conserved domain analysis, and cis-acting element analysis of the Dendrobium WRKY gene. The phylogenetic tree comparison analysis revealed that Dendrobium WRKY transcription factors were classified into three groups: I, II, and III, with Group II subdivided into five subgroups: II-a, II-b, II-c, II-d, and II-e. According to amino acid alignment research, the Dendrobium WRKY transcription factor contains a highly conserved WRKYGQK sequence. According to gene chromosomal mapping, the Dendrobium WRKY gene was found to be irregularly distributed across many chromosomes of Dendrobium officinale. Introns vary greatly in terms of quantity and starting place. According to conserved domain analysis, the Dendrobium WRKY gene comprised diverse patterns in number and species, but all had the conserved domain WRKYGQK, and there were certain distinguishing motifs amongst subfamilies. Elements with a cis-action It was found that the Dendrobium WRKY gene has a lot of cis-acting elements, like light response, low temperature stress response, drought response, hormone response, growth differentiation responses.

bioinformatics↗

bioRxiv2021

Elevated ozone concentration and nitrogen addition increase poplar rust severity by shifting the phyllosphere microbial community

The tropospheric ozone and nitrogen deposition are two major environmental pollutants. Numerous studies have focused on the negative impacts of elevated O3 and the complementary effect of soil N addition to tree physiological characteristics. However, it was notoriously ignored of how elevated O3 with N addition affect tree immunity in face of pathogen infection, as well as of the important roles of phyllosphere microbiome community in host-pathogen-environment interplay. Here, we examined the effects of elevated O3 and soil N addition on poplar leaf rust (Melampsora larici-populina) severity of two susceptible hybrid poplars (clone 107: Populus euramericana cv. 74/76; clone 546: P. deltoides {subseteq} P. cathayana) in Free-Air-Controlled-Environment plots, besides, the link between Mlp-susceptibility and changes in microbial community was determined using Miseq amplicon sequencing. Rust severity of clone 107 significantly increased under elevated O3 or N addition only, however, the negative impact of elevated O3 could be significantly alleviated when simultaneously conducting N addition, likewise, this trade-off was also found in its phyllosphere microbial -diversity responding to elevated O3 and N addition. However, the rust severity of clone 546 did not significantly differ in the cases of elevated O3 and N addition. Mlp infection altered microbial community composition and increased its sensitivity to elevated O3 assessed by significantly different abundance of taxa. Elevated O3 and N addition reduced the complexity of microbial community, which may explain the increased severity of poplar rust. These findings demonstrated that poplars need shifting phyllosphere microbial associations to optimize plant immunity in response to environmental changes. ImportanceExploitation of the interaction mechanisms between host plants and pathogens is the essential basis in disease control. However, while much was known about the molecular determinants in pathogenesis process in the past decades, less is known about the role of nonpathogenic microbial community in plant-pathogen interaction, especially when some host plants are currently encountering severe environmental stresses, such as elevated ozone concentration and superfluous nitrogen addition. Thus, we targeted at the widespread and detriment rust disease (poplar-poplar rust) to dissect the influences of elevated ozone and nitrogen addition on rust disease severity and how phyllosphere microbial groups interacting with both poplars and rust pathogen under these biotic stresses. Our findings could be used to prescribe ecological information about poplar plantation in areas with high levels of ozone pollution and better understand the important roles of microbiome in plant heath.

microbiology↗

bioRxiv2021

Development of Functional Connectome Gradients during Childhood and Adolescence

Connectome mapping studies have documented a principal primary-to-transmodal gradient in the adult brain network, capturing a functional spectrum which ranges from perception and action to abstract cognition. However, how this gradient pattern develops and whether its development is linked to cognitive growth, topological reorganization, and gene expression profiles remain largely unknown. Using longitudinal resting-state functional magnetic resonance imaging data from 305 children (ages 6-14), we describe substantial changes in the primary-to-transmodal gradient between childhood and adolescence, including emergence as the principal gradient, expansion of global topography, and focal tuning in primary and default-mode regions. These gradient changes are mediated by developmental changes in network integration and segregation, and are associated with abstract processing functions such as working memory and expression levels of calcium ion regulated exocytosis, synaptic transmission, and axon and synapse part related genes. Our findings have implications for understanding connectome maturation principles in normal development and developmental disorders. TeaserOur study reported the maturation of the core connectome gradient and its association with cognitions and genes expression.

neuroscience↗

bioRxiv2021

Development of Large-Scale Brain Network Dynamics in Children

Functional brain networks require dynamic reconfiguration to support flexible cognitive function. However, the developmental principles shaping brain network dynamics remain poorly understood. Here, we report the longitudinal development of large-scale brain network dynamics during childhood and adolescence, and its connection with gene expression profiles. Using a multilayer network model, we show the temporally varying modular architecture of child brain networks, with higher network switching primarily in the association cortex and lower switching in the primary regions. This topographical profile exhibits progressive maturation, which manifests as reduced modular dynamics, particularly in the transmodal (e.g., default-mode and frontoparietal) and sensorimotor regions. These developmental refinements mediate age-related enhancements of global network segregation and are linked with the expression profiles of genes associated with the enrichment of ion transport and nucleobase-containing compound transport. These results highlight a progressive stabilization of brain dynamics, which expand our understanding of the neural mechanisms that underlie cognitive development.

neuroscience↗

bioRxiv2020

Baricitinib treatment resolves lower airway inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques

Effective therapeutics aimed at mitigating COVID-19 symptoms are urgently needed. SARS-CoV-2 induced hypercytokinemia and systemic inflammation are associated with disease severity. Baricitinib, a clinically approved JAK1/2 inhibitor with potent anti-inflammatory properties is currently being investigated in COVID-19 human clinical trials. Recent reports suggest that baricitinib may also have antiviral activity in limiting viral endocytosis. Here, we investigated the immunologic and virologic efficacy of baricitinib in a rhesus macaque model of SARS-CoV-2 infection. Viral shedding measured from nasal and throat swabs, bronchoalveolar lavages and tissues was not reduced with baricitinib. Type I IFN antiviral responses and SARS-CoV-2 specific T cell responses remained similar between the two groups. Importantly, however, animals treated with baricitinib showed reduced immune activation, decreased infiltration of neutrophils into the lung, reduced NETosis activity, and more limited lung pathology. Moreover, baricitinib treated animals had a rapid and remarkably potent suppression of alveolar macrophage derived production of cytokines and chemokines responsible for inflammation and neutrophil recruitment. These data support a beneficial role for, and elucidate the immunological mechanisms underlying, the use of baricitinib as a frontline treatment for severe inflammation induced by SARS-CoV-2 infection.

immunology↗

bioRxiv2020

Disproportionate presence of adenosine in mitochondrial and chloroplast DNA of Chlamydomonas reinhardtii

Ribonucleoside monophosphates (rNMPs) represent the most common non-standard nucleotides found in the genomic DNA of cells. The distribution of rNMPs in DNA has been studied only in limited genomes, such as yeast nuclear and mitochondrial DNA, as well as human mitochondrial DNA. In this study, we used the ribose-seq protocol and the Ribose-Map bioinformatics toolkit to reveal the distribution of rNMPs incorporated into the whole genome of a photosynthetic unicellular green alga, Chlamydomonas reinhardtii. The study presents the discovery of a disproportionate incorporation of adenosine in the mitochondrial and chloroplast DNA, in contrast to the nuclear DNA, relative to the nucleotide content of these C. reinhardtii genomes. Our results demonstrate that the rNMP content in the DNA of the algal organelles reflects an elevated ATP level present in the algal cells. In addition, we reveal specific rNMP biases and patterns in the mitochondrial, chloroplast and nuclear DNA of C. reinhardtii.

molecular biology↗

bioRxiv2020

Functional characterization of germline variants in the TMEM127 tumor suppressor reveals novel insights into its membrane topology and trafficking

PurposeTo better understand the function of the transmembrane protein TMEM127, a poorly known tumor suppressor gene associated with pheochromocytomas, paragangliomas and renal carcinomas, we evaluated patient-derived germline variants. MethodsSubcellular localization and steady-state levels of 21 tumor-associated, transiently expressed TMEM127 variants were compared to the wild-type protein using immunofluorescence and immunoblot analysis, respectively, in cells genetically modified to lack endogenous TMEM127. Membrane topology and endocytic mechanisms were also assessed. ResultsWe identified three subgroups of mutations and determined that 15 of the 21 variants (71%), including 9 of 15 missense variants (60%), are pathogenic or likely pathogenic, through loss of membrane binding ability, stability and/or internalization capability. Investigation into an N-terminal cluster of missense variants uncovered a previously unrecognized transmembrane domain, indicating that TMEM127 is a four-, not a three-, transmembrane domain-containing protein. Additionally, a C-terminal variant with predominant plasma membrane localization revealed an atypical, extended acidic, dileucine-based motif required for TMEM127 internalization through clathrin-mediated endocytosis. ConclusionWe characterized the functional deficits of several germline TMEM127 variants and identified novel structure-function features of TMEM127, namely, a fourth transmembrane domain and an endocytic motif. These findings will assist in TMEM127 variant interpretation and will help guide future studies investigating the cellular role of TMEM127.

genetics↗

bioRxiv2019

Transcriptome analysis of apple leaves infected by the rust fungus Gymnosporangium yamadae at two sporulation stages (spermogonia and aecia) reveals specific host responses, rust pathogenesis-related genes and a shift in the phyllosphere fungal community composition

Apple rust disease caused by Gymnosporangium yamadae is one of the major threats to apple orchards. In this study, dual RNA-seq analysis was conducted to simultaneously monitor gene expression profiles of G. yamadae and infected apple leaves during the formation of rust spermogonia and aecia. The molecular mechanisms underlying this compatible interaction at 10 and 30 days post inoculation (dpi) indicate a significant reaction from the host plant and comprise detoxication pathways at the earliest stage and the induction of secondary metabolism related pathways at 30dpi. Such host reactions have been previously reported in other rust pathosystems and may represent a general reaction to rust infection. G. yamadae transcript profiling indicates a conserved genetic program in spermogonia and aecia that is shared with other rust fungi, whereas secretome prediction reveals the presence of specific secreted candidate effector proteins expressed during apple infection. Unexpectedly, the survey of fungal unigenes in the transcriptome assemblies of inoculated and mock-inoculated apple leaves reveals that G. yamadae infection modifies the fungal community composition in the apple phyllosphere at 30 dpi. Collectively, our results provide novel insights into the compatible apple-apple rust interaction and advance the knowledge of this heteroecious demicyclic rust fungus.

genomics↗

bioRxiv2019

RSVdb: A comprehensive database of in vivo mRNA structure

RNA fulfills a crucial regulatory role in cells by folding into a complex RNA structure. To date, a chemical compound, dimethyl sulfate (DMS), has been developed to effectively probe the RNA structure at the transcriptome level. We proposed a database, RSVdb (https://taolab.nwafu.edu.cn/rsvdb/), for the browsing and visualization of transcriptome RNA structures. RSVdb, including 626,225 RNAs with validated DMS reactivity from 178 samples in 8 species, supports four main functions: information retrieval, research overview, structure prediction, and resource download. Users can search for species, studies, transcripts and genes of interest; browse the quality control of sequencing data and statistical charts of RNA structure information; preview and perform online prediction of RNA structures in silico and under DMS restraint of different experimental treatments; and download RNA structure data for species and studies. Together, RSVdb provides a reference for RNA structure and will support future research on the function of RNA structure at the transcriptome level.

bioinformatics↗

bioRxiv2019

Recombinase system-dependent copackaging strategy for highly efficient neurocircuit tracing

Mapping the detailed cell-type-specific input networks and neuronal projectomes are essential to understand brain function in normal and pathological states. However, several properties of current tracing systems, including labeling sensitivity, trans-synaptic efficiencies, reproducibility among different individuals and different Cre-driver animals, still remained unsatisfactory. Here, we developed MAP-ENVIVIDERS, a recombinase system-dependent vector mixing-based strategy for highly efficient neurocircuit tracing. MAP-ENVIVIDERS enhanced tracing efficiency of input networks across the whole brain, with over 10-fold improvement in diverse previously poor-labeled input brain regions and particularly, up to 70-fold enhancement in brainstem compared with the current standard rabies-virus-mediated systems. MAP-ENVIVIDERS was over 10-fold more sensitive for cell-type-specific labeling than previous strategies, enabling us to capture individual cell-type-specific neurons with extremely complex axonal branches and presynaptic axonal boutons, both about one order of magnitude than previously reported and considered. MAP-ENVIVIDERS provides powerful tools for deconstructing novel input/output circuitry towards functional studies and disorders-related mechanisms.

neuroscience↗