Biology subjects

Ding, G.

Publications and source records attributed to Ding, G..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Tripartite organization of brain state dynamics underlying spoken narrative comprehension

Speech comprehension involves the dynamic interplay of multiple cognitive processes, from basic sound perception, to linguistic encoding, and finally to complex semantic-conceptual interpretations. How the brain handles the diverse streams of information processing remains poorly understood. Applying Hidden Markov Modeling to fMRI data obtained during spoken narrative comprehension, we reveal that the whole brain networks predominantly oscillate within a tripartite latent state space. These states are respectively characterized by high activities in the sensory-motor (State #1), bilateral temporal (State #2), and DMN (State #3) regions, with State #2 acting as a transitional hub. The three states are selectively modulated by the acoustic, word-level semantic and clause-level semantic properties of the narrative. Moreover, the alignment with the best performer in brain state expression can predict participants narrative comprehension scores. These results are reproducible with different brain network atlas and generalizable to two datasets consisting of young and older adults. Our study suggests that the brain underlies narrative comprehension by switching through a tripartite state space, with each state probably dedicated to a specific component of language faculty, and effective narrative comprehension relies on engaging those states in a timely manner.

neuroscience↗

bioRxiv2024

The stability of lower genital tract microbiota correlates with reproductive system function and in vitro fertilization and frozen embryo transfer outcomes in women with polycystic ovarian syndrome

We previously found that the lower genital tract (LGT) microbiota of polycystic ovarian syndrome (PCOS) women has altered when compared to healthy reproductive-aged women, however whether this alternation will have an impact on the reproductive system function and pregnancy outcomes of PCOS patients have not yet been identified. Between 2018 and 2021, we totally enrolled 191 reproductive-aged women in three independent case-control studies, 209 vaginal and 209 cervical swabs, and 9 cervical epithelial cells samples were collected from the study subjects. Firstly, we analyzed the correlation between LGT flora and clinical characteristics of 97 women (containing 47 PCOS patients and 50 control reproductive-aged women), canonical correspondence analysis (CCA) showed that LH/FSH ratio was the most relevant factor that was related to the dominant genera in women with PCOS (r2=0.233, p=0.001), and menstrual cycle frequency was also strongly related to the LGT organisms (r2=0.116, p=0.005). Next, through analysis of 72 PCOS patients who were underwent IVF-FET therapy, the FET outcome in PNB group (PCOS with relative abundance of Lactobacillus [≥]50%, n=57) was significant better than PDB group(PCOS patients with relative abundance of Lactobacillus<50%, n=15). Further, we randomly selected nine reproductive-aged PCOS patients (approximately half of them had altered LGT microbiota: Lactobacillus spp. [≤]50%, n=5) and simultaneously collected both LGT swabs and cervical epithelial cells from them. By synchronization analysis of RNA sequencing of the cervical epithelial cells and 16S rRNA sequencing of the microbes, we found that the gene expression profiles of the cells significantly differed between the PDB (PCOS patients with relative abundance of Lactobacillus<50%, n=4) and PNB (PCOS with relative abundance of Lactobacillus [≥]50%, n=5) groups. Above all, we systematically elucidate the potential relationship between LGT microbiota with the reproductive system function and IVF-FET outcomes in PCOS patients. Importancepolycystic ovarian syndrome (PCOS) women always suffered from poor pregnancy outcome: high incidence of abortion, preterm-birth, and premature rupture of membranes. Although some patients have improved their reproductive outcomes through assisted reproductive technology, the risk of early clinical pregnancy loss for PCOS patients after IVF treatment still ranges from 12% to 48%. As we previously found that the LGT flora of PCOS women had significant altered when compared with healthy parallel group, and more evidence showed that the genital tract microbiota may have a critical role in the process of embryo implantation and development, here we used multiple study groups to explore the potential relationship between LGT microbiota with reproductive system function and FET outcome in PCOS patients in this study. Our findings provide a new perspective for exploring novel therapy to improve the reproductive outcomes of PCOS patients.

physiology↗

bioRxiv2023

Quantifying cell viability through organelle ratiometric probing

Detecting cell viability is crucial in research involving the precancerous discovery of abnormal cells, the evaluation of treatments, and drug toxicity testing. Although conventional methods afford cumulative results regarding cell viability based on a great number of cells, they do not permit investigating cell viability at the single-cell level. In response, we rationally designed and synthesized a fluorescent probe, PCV-1, to visualize cell viability under the super-resolution technology of structured illumination microscopy. Given its sensitivity to mitochondrial membrane potential and affinity to DNA, PCV-1s ability to stain mitochondria and nucleoli was observed in live and dead cells, respectively. During cell injury induced by drug treatment, PCV-1s migration from mitochondria to the nucleolus was dynamically visualized at the single-cell level. By extension, harnessing PCV-1s excellent photostability and signal-to-noise ratio and by comparing the fluorescence intensity of the two organelles, mitochondria and nucleoli, we developed a powerful analytical assay named organelle ratiometric probing (ORP) that we applied to quantitatively analyze and efficiently assess the viability of individual cells, thereby enabling deeper insights into the potential mechanisms of cell death. In ORP analysis with PCV-1, we identified 0.3 as the cutoff point for assessing whether adding a given drug will cause apparent cytotoxicity, which greatly expands the probes applicability. To the best of our knowledge, PCV-1 is the first probe to allow visualizing cell death and cell injury under super-resolution imaging, and our proposed analytical assay using it paves the way for quantifying cell viability at the single-cell level.

cell biology↗

bioRxiv2023

Spatiotemporal transcriptome atlas of human embryos after gastrulation

The spatial and temporal atlas of gene expression in the human embryo at early gestation is critical in understanding embryo development, organogenesis, and disease origins. We obtained the spatiotemporal transcriptome from 90 sagittal sections of 16 whole human embryos from 3 to 8 post-conception weeks by Stereo-seq with high resolution and ultra-large field, establishing the development trajectory/regulatory profiling of 49 organs. We uncovered the organ-specific regulons as potential lineage-determining factors and identified the new regulatory networks during heart and brain development. The atlas refines the key organs/cell types vulnerable to virus infection and genetic disorders, and, reveals the dynamics of allelic gene expression in specific organs at different stages. These results present the first comprehensive delineation of the spatiotemporal transcriptomic dynamics of human organogenesis. One Sentence SummaryThe spatiotemporal transcriptome atlas presents a comprehensive delineation of human embryogenesis after gastrulation.

developmental biology↗

bioRxiv2022

A non-human primate model with Alzheimer's disease-like pathology induced by hippocampal overexpression of human tau

Alzheimers disease (AD) is one of the most burdening diseases of the century with no disease-modifying treatment yet. Non-human primates (NHPs) share genetic, anatomical and physiological similarities with humans, making them an ideal model for investigating the pathogenesis and therapeutics of AD. However, the applications of NHPs in AD research have been hindered by the paucity of spontaneous or induced monkey models for AD due to their long generation time, ethical considerations and technical challenges in making genetically modified monkeys. Here we developed an AD-like NHP model by overexpressing human tau in bilateral hippocampi of adult rhesus macaque monkeys. We evaluated the pathological features of these monkeys with immunostaining, cerebrospinal fluid (CSF) analysis, magnetic resonance imaging (MRI), positron emission tomography (PET) scan, and behavioral tests. We demonstrated that after hippocampal overexpression of human tau, the rhesus macaque monkeys displayed multiple pathological features of AD, including neurofibrillary tangle formation, neuronal loss, hippocampal atrophy, neuroinflammation, A{beta} clearance deficit, blood vessel damage and cognitive decline. This work establishes a human tau-induced AD-like NHP model that may facilitate mechanistic studies and therapeutic treatments for AD.

neuroscience↗

bioRxiv2022

JWA deficiency accelerates aging through disrupting intestinal epithelial homeostasis via Notch1/PPARγ/Stat5 axis

Aging usually suppresses the renewal and regeneration of intestinal epithelium. The imbalance of intestinal epithelial homeostasis may also be a promoter for aging. JWA responds to oxidative stress and repairs damaged DNA; it participates in multiple cellular processes like cell proliferation and differentiation. Here we identified JWA as a new aging-associated gene, whose deletion-accelerated aging in mice was related to intestinal epithelium atrophy. We further knocked out intestinal epithelial JWA and found it disrupted intestinal epithelial homeostasis, thus promoting aging in mice. Mechanistically, we discovered that JWA deficiency promoted Notch1 ubiquitination degradation via ERK/Fbxw7 cascade and interfered with the PPAR{gamma}/Stat5 signal axis. This reduced the intestinal stem cell function and altered the intestinal epithelial cell lineage distribution, finally suppressing the renewal and regeneration of intestinal epithelium. Our results demonstrated that JWA is a new aging-associated gene essential for the renewal and regeneration of intestinal epithelium. We also provide a new idea that maintaining intestinal epithelial homeostasis may be a potential anti-aging strategy in humans or mammals.

developmental biology↗

bioRxiv2021

Contrasting effects of accumulation and tolerance characteristics in Arabidopsis thaliana under Cr(III) and Cr(VI) stress

In this study, for the first time we investigated Cr(III) and Cr(VI) stress-induced physiological and biochemical responses in Arabidopsis thaliana. The capacity of A. thalian to accumulate Cr is closely related to the valence of chromium. Cr(VI) was more toxic than Cr(III) as indicated by chromium accumulation and growth inhibition. When the concentration of chromium is greater than 200M, the root length and biomass of A. thaliana are reduced. But interestingly, Cr(III) at 200M increased the root length and biomass of A. thaliana compared to the control. The transmission electron microscope shows that Cr(VI) can cause the chloroplasts damaged and the chlorophyll reduced more than Cr(III). The chloroplasts were filled the starch grains. An increase of lipid peroxidation in A. thaliana roots caused by Cr was measured, and this effect increases as the increasing Cr. It indicated that A. thaliana suffers from Cr-induced oxidative stress which resulted cell death in roots. To fight against oxidative stress, Ascorbate peroxidase and Glutathione reductase were activated by Cr in antioxidant defense. The inhibition of growth, the accumulation of chromium, the responses of antioxidant systems, and the ultra-morphological changes indicate that Cr(VI) was more toxic than Cr(III).

biochemistry↗

bioRxiv2021

Identification, analysis, and confirmation of seed storability-related loci in Dongxiang wild rice (Oryza rufipogon Griff.)

Dongxiang wild rice (Oryza rufipogon Griff.) (DXWR) has strong seed storability and identifying its elite gene resources may facilitate genetic improvements in rice seed storability. In this study, we developed two backcross inbred lines (BILs) populations, with DXWR as a common donor parent and two rice varieties (F6 and R974) as recipient parents. Bulked segregant analysis via whole genome sequencing (BSA-seq) was used to identify seed storability-related loci in the DXWR and F6 population. Two main genomic regions containing 18,550,000-20,870,000 bp on chromosome 4 and 7,860,000-9,780,000 bp on chromosome 9 were identified as candidate loci of DXWR seed storability; these overlapped partially with seed storability-related quantitative trait loci (QTLs) discovered in previous studies, suggesting that these loci may provide important regions for isolating the responsible genes. In total, 448 annotated genes were predicted within the identified regions, of which 274 and 82 had nonsynonymous and frameshift mutations, respectively. We detected extensive metabolic activities and cellular processes during seed storability and confirmed the effects of the seed storability-related candidate loci using four BILs from DXWR and R974. These results may facilitate the cloning of DXWR seed storability-related genes, thereby elucidating rice seed storability and its improvement potential.

genomics↗

bioRxiv2021

Development and verification of SSR markers from drought stress-responsive miRNAs in common wild rice

PREMISEDongxiang wild rice (Oryza rufipogon Griff., DXWR) is the northernmost common wild rice found in the world, which possesses abundant elite genetic resources. We developed a set of drought stress-responsive microRNA (miRNA)-based single sequence repeat (SSR) markers for DXWR, which will help breed drought stress-resistant rice varieties. METHODS AND RESULTSNinety-nine SSR markers were developed from the drought stress-responsive miRNAs of DXWR. The SSR loci were distributed in all 12 rice chromosomes and most were in chromosomes 2 and 6, with di- and trinucleotides being the most abundant repeat motifs. Nine out of ten synthesized SSR markers were displayed high levels of genetic diversity in the genomes of DXWR and 41 modern rice varieties worldwide. The number of alleles per locus ranged from 2 to 6, and the observed and expected heterozygosity ranged from 0.000 to 0.024 and 0.461 to 0.738, respectively. CONCLUSIONSThese SSR markers developed from drought stress-responsive miRNAs in DXWR could be additional tools for elite genes mapping and useful for drought stress-resistant rice breeding.

plant biology↗

bioRxiv2021

Genome-wide development of lncRNA-derived-SSR markers for Dongxiang wild rice (Oryza rufipogon Griff.)

Dongxiang wild rice (Oryza rufipogon Griff., DXWR) is the northernmost distributed common wild rice found in the world. It contains a large number of agronomically valuable genes, which makes it a natural gene pool for rice breeding. Molecular markers, especially simple repeat sequence (SSR) markers, play important roles in crop breeding. Although a large number of SSR markers have been developed, most of them are derived from the genome coding sequences, rarely from non-coding sequences. Meanwhile, long non-coding RNAs (lncRNAs), which are derived from the transcription of non-coding sequences, play vital roles in plant growth, development and stress responses. In this study, 1878 SSR loci were detected from the lncRNA sequences of DXWR, and 1258 lncRNA-derived-SSR markers were developed on the genome-wide scale. To verify the validity and applicability of these markers, 72 pairs of primers were randomly selected to test 44 rice materials. The results showed that 42 (58.33%) pairs of primers have abundant polymorphism among these rice materials; the polymorphism information content (PIC) values ranged from 0.04 to 0.87 with an average of 0.50; the genetic diversity index of SSR loci varied from 0.04 to 0.88 with an average of 0.56; and the number of alleles per marker ranged from 2 to 11 with an average of 4.36. Thus, we concluded that these lncRNA-derived-SSR markers are a very useful source for future basic and applied research, including genetic diversity analysis, QTL mapping, and molecular breeding programs, to make good use of the elite lncRNA genes from DXWR.

plant biology↗

bioRxiv2021

Large-scale field phenotyping using backpack LiDAR and GUI-based CropQuant-3D to measure structural responses to different nitrogen treatments in wheat

Plant phenomics is widely recognised as a key area to bridge the gap between traits of agricultural importance and genomic information. A wide range of field-based phenotyping solutions have been developed, from aerial-based to ground-based fixed gantry platforms and handheld devices. Nevertheless, several disadvantages of these current systems have been identified by the research community concerning mobility, affordability, throughput, accuracy, scalability, as well as the ability to analyse big data collected. Here, we present a novel phenotyping solution that combines a commercial backpack LiDAR device and our graphical user interface (GUI) based software called CropQuant-3D, which has been applied to phenotyping of wheat and associated 3D trait analysis. To our knowledge, this is the first use of backpack LiDAR for field-based plant research, which can acquire millions of 3D points to represent spatial features of crops. A key feature of the innovation is the GUI software that can extract plot-based traits from large, complex point clouds with limited computing time and power. We describe how we combined backpack LiDAR and CropQuant-3D to accurately quantify crop height and complex 3D traits such as variation in canopy structure, which was not possible to measure through other approaches. Also, we demonstrate the methodological advance and biological relevance of our work in a case study that examines the response of wheat varieties to three different levels of nitrogen fertilisation in field experiments. The results indicate that the combined solution can differentiate significant genotype and treatment effects on key morphological traits, with strong correlations with conventional manual measurements. Hence, we believe that the combined solution presented here could consistently quantify key traits at a larger scale and more quickly than heretofore possible, indicating the system could be used as a reliable research tool in large-scale and multi-location field phenotyping for crop research and breeding activities. We exhibit the systems capability in addressing challenges in mobility, throughput, and scalability, contributing to the resolution of the phenotyping bottleneck. Furthermore, with the fast maturity of LiDAR technologies, technical advances in image analysis, and open software solutions, it is likely that the solution presented here has the potential for further development in accuracy and affordability, helping us fully exploit available genomic resources.

bioinformatics↗

bioRxiv2021

A positive role of task-deactivated default mode network in narrative speech comprehension

During speech comprehension, as listeners need to keep tracking the external audio streams, the default mode network (DMN) is often de-activated and anticorrelated with task-positive networks. Such a pattern has been interpreted as the suppression of the DMN to support externally-oriented cognitive processes. Taking a "two-brain" approach, the current study demonstrated that, despite exhibiting deactivation and anticorrelated with the language network and executive control network, the DMN was not suppressed but played an active role in spoken narrative comprehension. This was evidenced by significant listener-speaker neural couplings in both the posterior and anterior DMN and the positive correlation between the coupling strength and listeners speech comprehension. Moreover, we demonstrated that the functionality of posterior DMN depended on its interaction with the executive control network, rather than its level of activation. Finally, Dynamic Causal Modeling together with the two-brain results indicates the language and executive control networks, the anterior DMN, and the posterior DMN occupied the bottom, intermediate and top layers of a hierarchical system, respectively. These results suggest that the DMN may primarily serve as an internally-oriented system that cooperates with the externally-oriented networks, which may allow the transformation of external acoustic signals into internal mental representations during language comprehension.

neuroscience↗

bioRxiv2020

Aberrant peripheral immune responses in acute Kawasaki disease with single-cell sequencing

Kawasaki disease (KD) is the most common cause of acquired heart disease in children in developed countries. Although diverse immune aberrance was reported, a global understanding of immune responses underlying acute KD was lacking. Based on single-cell sequencing, we profiled peripheral blood mononuclear cells from patients with acute KD before and after intravenous immunoglobulin therapy and from healthy controls. Most differentially expressed genes were derived from monocytes, with upregulation of immunoglobulin receptors, complement and receptors and downregulation of MHC class II receptors before therapy. The percentage of B cells was significantly increased before therapy and rapidly returned to normal after therapy. There was also an increased abundance of B-cell receptors with IGHA and IGHG after therapy, accompanied by massive oligoclonal expansion. The percentage of CD8 T cells was remarkably decreased during acute KD, especially the subset of effector memory CD8 T cells. All lymphocyte compartments were characterized by underexpressed interferon response pathways before therapy. The identification of unique innate and adaptive immune responses suggests potential mechanisms underlying pathogenesis and progression of KD.

immunology↗

bioRxiv2020

Genome assembly and transcriptome analysis provide insights into the anti-schistosome mechanism of Microtus fortis

Microtus fortis (M. fortis) so far is the only mammal host that exhibits intrinsic resistance against Schistosoma japonicum infection. However, the underlying molecular mechanisms of this intrinsic resistance are not yet known. Here we performed the first de novo genome assembly of M. fortis, comprehensive gene annotation and evolution analysis. Furthermore, we compared the recovery rate of schistosome, pathological change and liver transcriptome between non-permissive host M. fortis and susceptible host mouse at different time points after Schistosome infection. We reveal that Immune response of M. fortis and mouse is different in time and type. M. fortis activates immune and inflammatory responses on the 10th days post infection, involving in multiple pathways, such as leukocyte extravasation, antibody activation (especially IgG3), Fc-gamma receptor mediated phagocytosis, and interferon signaling cascade. The strong immune responses of M. fortis in early stages of infection play important roles in preventing the development of schistosome. On the contrary, intense immune response occurred in mouse in late stages of infection (28~42 days post infection), and cannot eliminate schistosome. Infected mouse suffers severe pathological injury and continuous decrease of important functions such as cell cycle and lipid metabolism. Our findings offer new insights to the intrinsic resistance mechanism of M. fortis against schistosome infection. The genome sequence also provides bases for future studies of other important traits in M. fortis.

bioinformatics↗

bioRxiv2020

Personalized anti-cancer drug combination prediction by an Integrated Multi-level Network

Anti-cancer drug combination is an effective solution to improve treatment efficacy and overcome resistance. Here we propose a network-based method (DComboNet) to prioritize the candidate drug combinations. The level one model is to predict generalized anti-cancer drug combination effectiveness and level two model is to predict personalized drug combinations. By integrating drugs, genes, pathways and their associations, DComboNet achieves better performance than previous methods, with high AUC value of around 0.8. The level two model performs better than level one model by introducing cancer sample specific transcriptome data into network construction. DComboNet is further applied on finding combinable drugs for sorafenib in hepatocellular cancer, and the results are verified with literatures and cell line experiments. More importantly, three potential mechanism modes of combinations were inferred based on network analysis. In summary, DComboNet is valuable for prioritizing drug combination and the network model may facilitate the understanding of the combination mechanisms.

bioinformatics↗

bioRxiv2020

Identifying a supramodal language network in human brain with individual fingerprint

Where is human language processed in the brain independent of its form? We addressed this issue by analyzing the cortical responses to spoken, written and signed sentences at the level of individual subjects. By applying a novel fingerprinting method based on the distributed pattern of brain activity, we identified a left-lateralized network composed by the superior temporal gyrus/sulcus (STG/STS), inferior frontal gyrus (IFG), precentral gyrus/sulcus (PCG/PCS), and supplementary motor area (SMA). In these regions, the local distributed activity pattern induced by any of the three language modalities can predict the activity pattern induced by the other two modalities, and such cross-modal prediction is individual-specific. The prediction is successful for speech-sign bilinguals across all possible modality pairs, but fails for monolinguals across sign-involved pairs. In comparison, conventional group-mean focused analysis detects shared cortical activations across modalities only in the STG, PCG/PCS and SMA, and the shared activations were found in two groups. This study reveals the core language system in the brain that is shared by spoken, written and signed language, and demonstrates that it is possible and desirable to utilize the information of individual differences for functional brain mapping.

neuroscience↗

bioRxiv2020

Diversity and Structural Variability of Bacterial Microbial Communities in Rhizocompartments of Desert Leguminous Plants

By assessing diversity variations of bacterial communities under different rhizocompartment types (i.e., roots, rhizosphere soil, root zone soil, and inter-shrub bulk soil), we explore the structural variability of bacterial communities in different root microenvironments under desert leguminous plant shrubs. Results will enable the influence of niche differentiation of plant roots and root soil on the structural stability of bacterial communities under three desert leguminous plant shrubs to be examined. High-throughput 16S rRNA genome sequencing was used to characterize diversity and structural differences of bacterial microbes in the rhizocompartments of three xeric leguminous plants. Results from this study confirm previous findings relating to niche differentiation in rhizocompartments under related shrubs, and they demonstrate that diversity and structural composition of bacterial communities have significant hierarchical differences across four rhizocompartment types under leguminous plant shrubs. Desert leguminous plants had significant effects on the enrichment and filtration of specific bacterial microbiomes across different rhizocompartments (P<0.05). The core bacterial microbiomes causing structure and composition variability of bacterial communities across different niches of desert leguminous plants are also identified. By investigating the influence of niches on the structural variability of soil bacterial communities with the differentiation of rhizocompartments under desert leguminous plant shrubs, we provide data support for the identification of dominant bacteria and future preparation of inocula, and provide a foundation for further study of the host plants-microbial interactions. IMPORTANCEColonization by plant communities make valued contribution to sand-fixing in poor ecological desert environments, thereby reducing the effects of wind erosion in these areas. Our study revealed that specific core bacterial microbiomes in under-shrub soil microbial communities had a significant hierarchical enrichment effect among rhizocompartments, and were filtered into roots. The root endophyte microbiomes thus formed had low abundance and diversity, but their structural variability was the highest. In addition, our data also verified that the rhizocompartments of under desert leguminous plant shrubs had a significant differentiation effect for the core bacterial microbiomes enriched and filtered by host plants, and that each rhizocompartment represented a unique niche of bacterial communities. Understanding the interactions between xeric shrubs and soil microbial communities is a fundamental step for describing desert soil ecosystems, which in turn can offer a microbe-associated reference for evaluating the restoration of desert vegetation.

ecology↗

bioRxiv2019

Effects of Endophytic Fungus MF23 on Dendrobium nobile Lindl. in an artificial primary environment

The quality of Dendrobium nobile Lindl. is related to the endophytic fungus. It had reported that the mycorrhizal fungus MF23 helps to increase the content of dendrobine, but few studies had explained the mechanism of the phenomenon. In previous study, we verified the symbiotic mechanism of the mycorrhizal fungus MF23 with D. nobile on the agar medium. In this study, the research carried on the bark medium, nearly like the natural environment, which had special meaning because of its benefits for the widely application. As a result, it showed a significant effect especially in the later period of the cultivation, suggesting that mycorrhizal fungus MF23 had a promotion for D. nobile in the natural environment, which enabled the application of the technique in the experimental field. It also implied that post-modification enzyme genes might play an important role in stimulating biosynthesis of dendrobine.

genetics↗