Biology subjects

Xiong, F.

Publications and source records attributed to Xiong, F..

At least 37 records · Page 2Linked to original sources

bioRxiv2023

Microglial cannabinoid receptor type1 mediates social memory deficits produced by adolescent THC exposure and 16p11.2 duplication

Adolescent cannabis use increases the risk for cognitive impairments and psychiatric disorders. Cannabinoid receptor type 1 (Cnr1) is expressed not only in neurons and astrocytes, but also in microglia, which shape synaptic connections during adolescence. Nonetheless, until now, the role of microglia in mediating the adverse cognitive effects of delta-9-tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, has been unexplored. Here, we report that adolescent THC exposure produces microglial apoptosis in the medial prefrontal cortex (mPFC), which was exacerbated in the mouse model of 16p11.2 duplication, a representative copy number variation (CNV) risk factor for psychiatric disorders. These effects are mediated by microglial Cnr1, leading to reduction in the excitability of mPFC pyramidal-tract neurons and deficits in social memory in adulthood. Our findings highlight the importance of microglial Cnr1 to produce the adverse effect of cannabis exposure in genetically vulnerable individuals.

neuroscience↗

bioRxiv2022

Whole Human-Brain Mapping of Single Cortical Neurons for Profiling Morphological Diversity and Stereotypy

Quantification of individual cells morphology and their distribution at the whole brain scale is essential to understand the structure and diversity of cell types. Despite recent technological advances, especially single cell labeling and whole brain imaging, for many prevailing animal models, it is exceedingly challenging to reuse similar technologies to study human brains. Here we propose Adaptive Cell Tomography (ACTomography), a low-cost, high-throughput, high-efficacy tomography approach, based on adaptive targeting of individual cells suitable for human-brain scale modeling of single neurons to characterize their 3-D structures, statistical distributions, and extensible for other cellular features. Specifically, we established a platform to inject dyes into cortical neurons in surgical tissues of 18 patients with brain tumors or other conditions and 1 donated fresh postmortem brain. We collected 3-D images of 1746 cortical neurons, of which 852 neurons were subsequentially reconstructed to quantify their local dendritic morphology, and mapped to standard atlases both computationally and semantically. In our data, human neurons are more diverse across brain regions than by subject age or gender. The strong stereotypy within cohorts of brain regions allows generating a statistical tensor-field of neuron morphology to characterize 3-D anatomical modularity of a human brain.

neuroscience↗

bioRxiv2022

Direct Force Measurement and Loading on Developing Tissues in Intact Avian Embryos

Developmental morphogenesis is driven by tissue stresses acting on tissue rheology. Direct measurements of forces in small tissues (100m-1mm) in situ such as in early embryos require high spatial precision and minimal invasiveness. Here we report tissue force microscopy (TiFM) integrating a vertical cantilever probe and live imaging to enable close-loop control of mechanical loading in early chicken embryos. By testing previously qualitatively characterized force-producing tissues in the elongating body axis, we show that TiFM quantitatively captures stress dynamics with high sensitivity. TiFM also provides the capacity of applying a stable, minimally-invasive and physiologically relevant load to drive tissue deformation, which alters morphogenetic progression and cell movements. Together, TiFM addresses a key technological gap in tissue force measurement and manipulation in small developing embryos, and promises to contribute to the quantitative understanding of complex multi-tissue mechanics during development.

developmental biology↗

bioRxiv2021

The Synechocystis ORF slr0201 product is involved in succinate dehydrogenase-mediated cyclic electron transfer around PSI

The Synechocystis sp. PCC 6803 open reading frame (ORF) slr0201 was originally annotated as heterodisulfide reductase B subunit (HdrB). The slr0201 encodes a 301-amino acid hypothetical protein with the predicted amino acid sequence significantly homologous to not only the HdrB from methanogenic bacteria, but also some novel succinate dehydrogenase C subunit (SdhC) found in Archaea and Campylobacter. Genetic manipulation via knocking-out approach created a{Delta} slr0201 mutant showing a{Delta} sdhB-like phenotype that was characterized by impaired succinate-dependent DCPIP reduction activities, reduced SDH-mediated respiratory electron transports, lower cellular contents of succinate and fumarate, slower KCN-induced increases in Chl fluorescence yield in the dark, and weak state 2/strong state 1 transitions, being indicative of a more oxidized PQ pool. In addition, slower re-reductions of the photosystem (PS) I reaction center P700 upon light-off were also monitored in the{Delta} slr0201, indicating functional involvements of Slr0201 in cyclic electron transfer around PSI. Both photoautptrophical and photomixotrophical growth rates of the{Delta} slr0201 strain resembled to those of the wild type, but substantial growth deteriorations occurred when arginine ([~]25 mM) or other two urea-cycle relevant amino acids (citrulline and ornithine) were added, which were attributed to generations and accumulations of certain hazardous metabolites. Based on the{Delta} sdhB-resembling phenotype, in conjunction with its high sequence similarities to some archaeal SdhC, we proposed that the slr0201 encodes a SDH function-relevant protein and is most likely the SdhC, a membrane anchoring subunit, which, while being genetically distinct from those in traditional bacterial SDH, belongs to the C subunit of novel archaeal SDH.

plant biology↗

bioRxiv2021

The Synechocystis sp. PCC 6803 open reading frame slr0201 that is homologous to sdhC from Archaea codes for a protein

A hypothetical protein encoded by Synechocystis sp. PCC 6803 open reading frame slr0201shows high sequence similarity to the C subunit of a group of unusual succinate dehydrogenases found in some archaeal species. Slr0201 was originally annotated as HdrB, the B subunit of heterodisulfide reductase, but appears to be SdhC instead. This protein was overexpressed in E. coli by cloning the PCR-derived slr0201 open reading frame into a pET16b-based expression vector. The overproduced Slr0201 accumulated predominantly in inclusion bodies with an apparent molecular mass of 33 kDa. The protein contained at least one [2Fe-2S] cluster based on UV-visible absorbance and CD spectra and EPR spectroscopy, in conjunction with stoichiometric analysis of protein-bound iron and sulfur content. Redox titration showed a midpoint potential (Em) of + 17 mV at pH 7.0, which is consistent with Slr0201 serving a role in transferring electrons between succinate and plastoquinone. Slr0201 was also overproduced in Synechocystis sp. PCC 6803 by introducing an additional, His-tagged slr0201 into the Synechocystis genome replacing psbA3, creating the slr0201+-His overexpression strain. Immunoblot analysis shows that Slr0201 is membrane-associated in the wild type. However, in the Slr0201+-His strain, immunoreaction occurred in both the membrane and soluble fractions, possibly as a consequence of processing near the N-terminus. The results obtained with Slr0201 are discussed in the light of one of the cyanobacterial SdhB subunits, which shares redox commonalities with archaeal SdhB.

molecular biology↗

bioRxiv2021

SARS-CoV-2 Restructures the Host Chromatin Architecture

SARS-CoV-2 has made >190-million infections worldwide, thus it is pivotal to understand the viral impacts on host cells. Many viruses can significantly alter host chromatin1, but such roles of SARS-CoV-2 are largely unknown. Here, we characterized the three-dimensional (3D) genome architecture and epigenome landscapes in human cells after SARS-CoV-2 infection, revealing remarkable restructuring of host chromatin architecture. High-resolution Hi-C 3.0 uncovered widespread A compartmental weakening and A-B mixing, together with a global reduction of intra-TAD chromatin contacts. The cohesin complex, a central organizer of the 3D genome, was significantly depleted from intra-TAD regions, supporting that SARS-CoV-2 disrupts cohesin loop extrusion. Calibrated ChIP-Seq verified chromatin restructuring by SARS-CoV-2 that is particularly manifested by a pervasive reduction of euchromatin modifications. Built on the rewired 3D genome/epigenome maps, a modified activity-by-contact model2 highlights the transcriptional weakening of antiviral interferon response genes or virus sensors (e.g., DDX58) incurred by SARS-CoV-2. In contrast, pro-inflammatory genes (e.g. IL-6) high in severe infections were uniquely regulated by augmented H3K4me3 at their promoters. These findings illustrate how SARS-CoV-2 rewires host chromatin architecture to confer immunological gene deregulation, laying a foundation to characterize the long-term epigenomic impacts of this virus.

molecular biology↗

bioRxiv2021

Mechanistic model: Analysis of diffusion dynamics of Lugol's chromoendoscopy in Basal layer-type squamous cell carcinoma in situ via Euler's method and Law of mass action

Basal layer-type squamous cell carcinoma in situ(BLSCC) is an aggressive malignancy tumor. In the past, it usually went ignored because its aggressive biological behavior is different from typical esophageal squamous cancer(SCC). For our mechanistic model, we analyzed diffusion dynamics of iodine stain in BLSCC with the help of Eulers method. We used the law of mass action description of the forming process of the iodine-glycogen Complex. Based on the above analysis, our mechanistic model reveals that the efficacy of Lugols chromoendoscopy is determined by the thickness of the squamous epithelial cell layer, which contains glycogen granules, and the convection of the interpupillary capillary loop(IPCL). A further inference can be made: the unique histological structure of BLSCC suggests Lugols chromoendoscopy does not detect some components of it because these components neither break enough squamous epithelial cells which contain glycogen granules nor contain enough number of IPCL in a specific time frame. Besides, if our mechanistic model starting point is BLSCC and typical SCC share the same evolution path, we found both their cytoplasm tends to solid phase from the iodine diffusion dynamics analysis in "pink color sign."

cancer biology↗

bioRxiv2021

Downregulation of Extraembryonic Tension Controls Body Axis Formation in Avian Embryos

Embryonic tissues undergoing shape change draw mechanical input from extraembryonic substrates. In avian eggs, the early blastoderm disk is under the tension of the vitelline membrane (VM). Here we report that the chicken VM characteristically downregulates tension and stiffness to facilitate stage-specific embryo morphogenesis. Experimental relaxation of the VM early in development impairs blastoderm expansion, while maintaining VM tension in later stages resists the convergence of the posterior body causing stalled elongation, failure of neural tube closure, and axis rupture. Biochemical and structural analysis shows that VM weakening is associated with the reduction of outer-layer glycoprotein fibers, which is caused by an increasing albumen pH due to CO2 release from the egg. Our results identify a previously unrecognized potential cause of body axis defects through mis-regulation of extraembryonic tissue tension.

developmental biology↗

bioRxiv2020

Automatic Recognition of Auditory Brainstem Response Characteristic Waveform based on BiLSTM

BackgroundAuditory brainstem response (ABR) test is widely used in newborn hearing screening and hearing disease diagnosis. Identifying and marking are challenging and repetitive tasks because of complex rules of ABR characteristic waveform and interference of background noise. MethodsThis study proposes an automatic method to recognize ABR characteristic waveform. First, binarization is created to mark 1024 sampling points accordingly. The selected characteristic area of ABR data is 0-8ms. The marking area is enlarged to expand feature information and reduce marking error. Second, a bi-directional long short-term memory (BiLSTM) network structure is established to improve relevance of sampling points, and an ABR sampling point classifier is obtained by training. Finally, mark points are obtained through thresholding. ResultsSpecific structure, related parameters, recognition effect, and noise resistance of network were explored in 614 sets of ABR clinical data, and recognition accuracy of waves I, III, and V can reach 92.91%. DiscussionThus, the proposed method can reduce the repetitive work of doctors and meet accuracy effectively. Therefore, this method has clinical potential.

bioinformatics↗

bioRxiv2020

A longitudinal study of white matter functional network in mild traumatic brain injury

The mild traumatic brain injury (mTBI) results in traumatic axonal injury, which damages the long-distance white matter (WM) connections and thus disrupts the functional connectome of large-scale brain networks that support cognitive function. Patterns of WM structural damage following mTBI were well documented using diffusion tensor imaging, however, the functional organization of WM and its association with grey matter functional networks (GM-FNs) and cognitive assessments remains unknown. The present study adopted resting-state functional magnetic resonance imaging to explore WM functional properties in mTBI patients (113 acute patients, 56 chronic patients, 47 healthy controls (HCs)). Eleven large-scale WM functional networks (WM-FNs) were constructed by the k-means clustering algorithm which carried out in voxel-wise WM functional connectivity (FC). Compared to HCs, acute mTBI patients showed enhanced FC between inferior fronto-occipital fasciculus (IFOF) WM-FN and primary sensorimotor WM-FNs, and cortical primary sensorimotor GM-FNs. And FC between IFOF WM-FN and anterior cerebellar GM-FN was positively correlated with information processing speed. Moreover, all of these WM-FNs abnormalities were returned to the normal level at the chronic stage. Our findings suggest the compensatory mechanism of cognitive deficits in the acute stage and its involvement in facilitating recovery from cognitive deficits in the chronic stage. The convergent damage of the IFOF network highlighted its key role in our understanding of the pathophysiology mechanism of mTBI patients and thus might be regarded as a biomarker in the acute stage and a potential indicator of treatment effect.

neuroscience↗

bioRxiv2020

Association of gut microbiota with cerebral cortex and cerebrovascular abnormality in human mild traumatic brain injury

Key roles of the gut-brain axis in brain injury development have been suggested in various mouse models; however, little is known about its functional significance in human mild traumatic brain injury (TBI). Here, we decipher this axis by profiling the gut microbiota in 98 acute mild TBI patients and 62 matched controls, and subgroup of them also measured circulating mediators and applied neuroimaging. Mild TBI patients had increased -diversity and different overall microbial compositions compared with controls. 25-microbial genus classifiers distinguish patients from controls with an area under the receiver operating characteristic curve (AUC) of 0.889, while adding serum mediators and neuroimaging features further improved performance even in a small sample size (AUC = 0.969). Numerous correlations existed between gut bacteria, aberrant cortical thickness and cerebrovascular injury. Co-occurrence network analysis revealed two unique gut-brain axes in patients: 1) altered intestinal Lachnospiraceae_NK4A136_group and Eubacterium_ruminantium_group-increased serum GDNF-subcallosal hypertrophy and cerebrovascular injury; 2) decreased intestinal Eubacterium_xylanophilum_group-upregulated IL-6-thinned anterior insula. Our findings provide a new integrated mechanistic understanding and diagnostic model of mild TBI.

microbiology↗

bioRxiv2019

Efficient generation of zebrafish maternal-zygotic mutants through transplantation of ectopically induced and Cas9/gRNA targeted PGCs

The CRISPR/Cas9 technology has been widely utilized for knocking out genes involved in various biological processes in zebrafish. Despite this technology is efficient for generating different mutations, one of the main drawbacks is low survival rates during embryogenesis when knocking out some embryonic lethal genes. To overcome this problem, we developed a novel strategy using a combination of CRISPR/Cas9 mediated gene knockout with primordial germ cells (PGCs) transplantation to facilitate and speed up the process of zebrafish mutant generation, particularly for embryonic lethal genes. First, we optimized the procedure for gRNA targeted PGCs transplantation (PGCT), by increasing the efficiencies of genome mutation in PGCs and induction of PGCs fates in donor embryos for PGCT. Second, the combined CRISPR/Cas9 with PGCT was utilized for generation of maternal zygotic (MZ) mutants of tcf7l1a (essential gene for head development), pou5f3 (essential gene for zygotic genome activation) and chd (essential gene for dorsal development) at F1 generation with high efficiency. Finally, we revealed some novel phenotypes in the maternal zygotic mutant of tcf7l1a and chd, while MZtcf7l1a showed elevated neural crest development, and MZchd have stronger ventralization than its zygotic counterparts. Therefore, this study presents an efficient and powerful method for generating MZ mutants of embryonic lethal genes in zebrafish.

developmental biology↗

bioRxiv2019

Renewal theory provides a universal quantitative framework to characterise the continuous regeneration of rotational events in cardiac fibrillation

BackgroundCardiac fibrillation is thought to be maintained by rotational activity, with pivoting regions called phase singularities (PSs). Despite a century of research, no clear quantitative framework exists to model the fundamental processes responsible for the continuous formation and destruction of rotors in fibrillation.\n\nObjectiveWe conducted a multi-modality, multi-species study of AF/VF under the hypothesis that PS formation/destruction in fibrillation can be modelled as self-regenerating renewal processes, producing exponential distributions of inter-event times governed by constant rate-parameters defined by the prevailing properties of the system.\n\nMethodsPS formation/destruction was studied and cross-validated in 5 models, using basket recordings and optical mapping from: i) human persistent AF (n = 20), ii) tachypaced sheep AF (n = 5), iii) rat AF (n = 4), iv) rat VF (n = 11) and v) computer simulated AF (SIM). Hilbert phase maps were constructed. PS lifetime data were fitted by exponential probability distribution functions (PDFs) computed using maximum entropy theory, and the rate parameter ({lambda}) determined. A systematic review was conducted to cross-validate with source data from literature.\n\nResultsPS destruction/formation distributions showed good fits to an exponential in all systems (R2 [≥] 0.90). In humans,{lambda} = 4.6%/ms (95%CI,4.3,4.9)), sheep 4.4%/ms (95%CI,4.1,4.7)), rat AF 38%/ms (95%CI,22,55), rat VF 46%/ms (95%CI,31.2,60.2) and SIM 5.4%/ms (95%CI,4.1,6.7). All PS distributions identified through systematic review were exponential with {lambda} comparable to experimental data.\n\nConclusionThese results provide a universal quantitative framework to explain rotor formation and destruction in AF/VF, and a platform for therapeutic advances in cardiac fibrillation.

physiology↗

bioRxiv2019

Changes in the Physicochemical Properties and Microbial Communities of Rhizospheric Soil after Cassava/Peanut Intercropping

Cassava/peanut intercropping is a popular cultivation method in southern China and has the advantages of apparently increased yield and economic efficiency compared with monoculture, however, the ecological benefits of this method are poorly understood. This study aimed to investigate the effects of intercropping on the physicochemical properties and microbial community structures of soil. Field trials were performed to determine the effects of cassava/peanut intercropping on rhizospheric soil nutrient content, enzyme activities, microbial quantity and microbial community structure. The microbial community was characterized by 16S rRNA tag-based high-throughput sequencing on the Illumina MiSeq platform. Results showed that cassava/peanut intercropping could improve the physicochemical properties of rhizospheric soil by increasing the available nutrient content, pH, bacterial quantity, and some enzyme activities and by altering the microbial community structure. 16S rRNA gene sequencing demonstrated that the microbial community structure varied between the intercropping and monoculture systems. Nitrospirae, Verrucomicrobia and Gemmatimonadetes were more abundant in the intercropping system than in the monocultures. Redundancy analysis (RDA) revealed that the abundances of DA101, Pilimelia and Ramlibacter were positively correlated with environmental parameters such as available nitrogen and pH, and these were dominant genera in the rhizospheric soil of the intercropped peanut plants.

ecology↗

bioRxiv2019

Pair-wise Comparison Analysis for Multiple Pool-sep: an efficient method identified anthocyanin biosynthesis genes in rice pericarp

The complex traits are derived from multiple genes and exhibit a large variety of phenotypes. High-throughput sequencing technologies have become the new strategies for mapping the important traits of crops. However, these methods have their own disadvantages and limitations. Here we introduced Pair-wise Comparison Analysis for Multiple Pool-seq (PCAMP) for mapping the candidate genomic regions involved in anthocyanin biosynthesis in rice pericarp. In this protocol, the second filial generation (F2) populations obtained by crossing two parents with different target traits were divided into n (n>=3) subpopulations according to their phenotypes. Thirty phenotypically identical individuals were selected from each subpopulation and DNA samples were extracted to form a pool for sequencing. Finally, we compared the SNP-index between every two Pool-seqs to map the candidate genomic regions. We applied PCAMP to analyse F2 populations and successfully identified five known genes and five new candidate genomic regions for anthocyanin biosynthesis in rice pericarp. These results demonstrate that PCAMP is an efficient new method for dissecting the complex traits of crops.

molecular biology↗

bioRxiv2018

Intracellular pH controls Wnt signaling downstream of glycolysis in the vertebrate embryo

Formation of the body of vertebrate embryos proceeds sequentially by posterior addition of tissues. While this process depends on aerobic glycolysis acting upstream of Wnt signaling in tail bud cells, the molecular details of this regulation are unknown. Here we used chicken embryos and human tail bud-like cells differentiated in vitro from iPS cells to show that glycolysis acts by increasing the intracellular pH (pHi) of tail bud cells. This promotes {beta}-catenin acetylation leading to Wnt signaling activation and the choice of a mesodermal fate at the expense of the neural fate in tail bud precursors. Our data suggest that by increasing the pHi of tail bud cells, aerobic glycolysis creates a favorable chemical environment for non-enzymatic acetylation of {beta}-catenin, ultimately triggering Wnt signaling.

developmental biology↗

bioRxiv2018

Heterogeneity of Sonic Hedgehog Response Dynamics and Fate Specification in Single Neural Progenitors

During neural tube patterning, a gradient of Sonic hedgehog (Shh) signaling specifies ventral progenitor fates. The cellular response to Shh is processed through a genetic regulatory network (GRN) to specify distinct fate decisions. This process integrates Shh response level, duration and other inputs and is affected by noise in signaling and cell position. How reliably Shh response profile predicts the fate choice of a single cell is unclear. Here we use live imaging to track neural progenitors in developing zebrafish and quantify both Shh and fate reporters in single cells over time. We found that there is significant heterogeneity between Shh response and fate choice in single cells. We quantitatively modeled reporter intensities to obtain single cell response levels over time and systematically evaluated their correlation with cell fate specification. Motor neuron progenitors (pMN) exhibit a high degree of variability in their Shh responses, which is particularly prominent in the posterior neural tube where the Shh response dynamics are similar to those of the more ventrally fated lateral floor plate cells (LFPs). Our results highlight the precision limit of morphogen-interpretation GRNs in small and dynamic target cell fields.

developmental biology↗

bioRxiv2018

Mechanical Coupling Coordinates the Co-elongation of Axial and Paraxial Tissues in Avian Embryos

Tissues undergoing morphogenesis impose mechanical effects on one another. How developmental programs adapt to or take advantage of these effects remains poorly explored. Here, using a combination of live imaging, modeling, and microsurgical perturbations, we show that the axial and paraxial tissues in the forming avian embryonic body coordinate their rates of elongation through mechanical interactions. First, a cell motility gradient drives paraxial presomitic mesoderm (PSM) expansion, resulting in compression of the axial neural tube and notochord; second, elongation of axial tissues driven by PSM compression and polarized cell intercalation pushes the caudal progenitor domain posteriorly; finally, the axial push drives progenitors to emigrate into the PSM to maintain tissue growth and cell motility. These interactions form an engine-like positive feedback loop, which ensures the tissue-coupling and self-sustaining characteristics of body elongation. Our results suggest a general role of inter-tissue forces in the coordination of complex morphogenesis involving distinct tissues.

developmental biology↗