Biology subjects

Ming, D.

Publications and source records attributed to Ming, D..

10 recordsLinked to original sources

bioRxiv2025

TSdb: A Curated Database for Terpene Synthases and Their Application in Natural Product Mining

Terpenoids constitute natures most chemically diverse metabolite family with vital pharmaceutical and industrial applications, yet existing databases lack systematic integration of precursor metabolic enzymes (HMGR, DXS) and mechanistic insights into terpene diversification. To bridge this gap, we developed the Terpene Synthase Database (TSDB), distinguishing itself through three key innovations: (1) comprehensive integration of MVA/MEP pathway enzymes with downstream terpenoid synthases, (2) enhanced functional annotation via InterProScan domain mapping and phylogenetics to decode catalytic plasticity, and (3) unprecedented taxonomic breadth spanning 456,142 non-redundant sequences across 30,491 taxa. By consolidating data from BRENDA, UniProt, TeroKit, and ocean gene clusters through rigorous BLASTp deduplication (95% identity cutoff), TSDB reveals 3,499 Gene Ontology terms highlighting core functions like isoprenoid biosynthesis (GO:0019288) and metalloenzyme catalysis. Validation against MIBiG gene clusters (e.g., BGC0001324) demonstrates precise identification of terpene cyclases, P450 monooxygenases, and prenyltransferases with residue-level active site annotations. As the first resource connecting precursor metabolism to structural diversity, TSDB enables accurate gene-enzyme-product prediction for enzyme engineering and natural product discovery.

bioinformatics↗

bioRxiv2025

SenolyticSynergy: An Attention-Based Network for Discovering Novel Senolytic Combinations via Human Aging Genomics

Senolytics, a category of drugs targeting aging processes, have garnered significant attention since their emergence in 2015. Unlike traditional drug development approaches that rely on randomized screening, research on aging-related pharmaceuticals has employed mechanism-based strategies, resulting in the discovery of the pioneering combination therapy of dasatinib (D) and quercetin (Q). Although preliminary studies with senolytic drug combinations have shown promising outcomes, the predictive capabilities of the research in this field remain limited by the extensive experimental data requirements. In this study, we employed differential gene expression analysis and machine learning techniques to investigate the combinatorial effects of senolytic drugs. We identified 1624 core aging-related genes and used this dataset to retrain a multimodal attention mechanism model, creating a specialized framework: SenolyticSynergy for predicting effective senolytic drug combinations. We then utilized 63 established senolytic compounds as starting points for combination testing, developing a comprehensive dataset of 1953 potential drug combinations for aging interventions. Following rigorous filtration, we identified 190 high-confidence drug combinations and predicted their synergistic scores. Among these combinations, ten demonstrated exceptionally high synergistic scores, exceeding 8. The combination of temsirolimus and nitazoxanide ranked first and may be the most promising candidate. The analysis of literature data and computational studies of molecular structures using 3D modeling validated the accuracy of these predictions. This framework paves the way for large-scale research into anti-aging drug combinations, advancing research capabilities in this field. GRAPH ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=176 HEIGHT=200 SRC="FIGDIR/small/655258v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@26aae1org.highwire.dtl.DTLVardef@9ca730org.highwire.dtl.DTLVardef@a471ddorg.highwire.dtl.DTLVardef@2f8b7a_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2024

Mid1 deletion leads to cognitive dysfunction in Opitz syndrome by regulates neural rhythms through the inhibition of p-Creb by PP2Ac

MID1 is an E3 ubiquitin ligase of the tripartite motif (TRIM) subfamily of RING-containing protein1. MID1 is involved in many basic biological processes, especially during embryonic development. Mutation, truncation or complete deletion of MID1 gene is the cause of Opitz G/BBB syndrome (OS). OS is a rare genetic disease of nervous system, which is characterized by midline structural development defects during embryogenesis, including structural brain abnormalities, developmental retardation and mental retardation2. Although the function of MID1 has been studied for many years, the effect and mechanism of complete deletion of MID1 gene on OS nervous system still need to be further explored. Here we find that Mid1 gene is necessary for the normal development of hippocampus (HPC), and Mid1 gene knockout (Mid1-/y) mice showed a significant decrease in rhythm in HPC and abnormal synchronization of {gamma} rhythm in prefrontal cortex and hippocampus (PFC-HPC), showing decreased synaptic plasticity and learning and memory dysfunction.

neuroscience↗

bioRxiv2024

Dynamic Gamma Modulation of Hippocampal Place Cells Predominates Development of Theta Sequences

The experience-dependent spatial cognitive process requires sequential organization of hippocampal neural activities by theta rhythm, which develops to represent highly compressed information for rapid learning. However, how the theta sequences were developed in a finer time scale within theta cycles remains unclear. In this study, we found that sweep-ahead structure of theta sequences developing with exploration was predominantly dependent on a relatively large proportion of FG-cells, i.e. a subset of place cells dominantly phase-locked to fast gamma rhythms. These ensembles integrated compressed spatial information by cells consistently firing at precessing slow gamma phases within the theta cycle. Accordingly, the sweep-ahead structure of FG-cell sequences was positively correlated with the intensity of slow gamma phase precession, in particular during early development of theta sequences. These findings highlight the dynamic network-modulation by fast and slow gamma in the development of theta sequences which may further facilitate memory encoding and retrieval.

neuroscience↗

bioRxiv2023

Prestimulus neural variability affects behavioral performances mediated by poststimulus-evoked responses at the intraindividual and interindividual levels

There are significant intra-individual and inter-individual variabilities in audiovisual temporal perception. Previous studies have shown that prestimulus neural variability could reflect behavioral variabilities. We aimed to investigate whether prestimulus neural variability can predict behavioral variability in audiovisual temporal perception. Furthermore, We also explored whether prestimulus neural variability directly influences behavioral responses or indirectly impacts perceptual decisions through post-stimulus-evoked responses. We analyzed the electroencephalography (EEG) data from a paradigm where the twenty-eight human subjects performed a simultaneity judgment (SJ) task in the beep-flash stimulus. The prestimulus weighted permutation entropy (WPE) was the indicator of neural variability in this study. We found that prestimulus frontal WPE could predict the individuals TBW in auditory- and visual-leading conditions. In addition, increased prestimulus parietal WPE was associated with more asynchronous responses. Prestimulus frontal WPE may be associated with top-down cognitive control, while parietal WPE may be related to bottom-up cortical excitability. Furthermore, poststimulus evoked responses could mediate the relation between prestimulus WPE and the individuals TBW or perceptual responses. These results suggested that prestimulus WPE was a marker in reflecting intra-individual and inter-individual variabilities in audiovisual temporal perception. Significantly, prestimulus WPE might influence perceptual responses by affecting poststimulus sensory representations.

neuroscience↗

bioRxiv2023

Not alpha power: prestimulus beta power predicts the magnitude of individual temporal order bias for audiovisual stimuli

Individuals exhibit significant variations in audiovisual temporal order perception. Previous studies have investigated the neural mechanisms underlying these individual differences by analyzing ongoing neural oscillations using stimuli specific to each participant. This study explored whether these effects could extend to different paradigms with the same stimuli across subjects in each paradigm. The two human participants groups performed a temporal order judgment (TOJ) task in two experimental paradigms while recording EEG. One is the beep-flash paradigm, while the other is the stream-bounce paradigm. We focused on the correlation between individual temporal order bias (i.e., point of subjective simultaneity (PSS)) and spontaneous neural oscillations. In addition, we also explored whether the frontal cortex could modulate the correlation through a simple mediation model. We found that the beta band power in the auditory cortex could negatively predict the individuals PSS in the beep-flash paradigm. Similarly, the same effects were observed in the visual cortex during the stream-bounce paradigm. Furthermore, the frontal cortex could influence the power in the sensory cortex and further shape the individuals PSS. These results suggested that the individuals PSS was modulated by auditory or visual cortical excitability depending on the experimental stimuli. The frontal cortex could shape the relation between sensory cortical excitability and the individuals PSS in a top-down manner. In conclusion, our findings indicated that the prefrontal cortex could effectively regulate an individuals temporal order bias, providing insights into audiovisual temporal order perception mechanisms and potential interventions for modulating temporal perception.

neuroscience↗

bioRxiv2021

How alginate lyase produces quasi-monodisperse oligosaccharides: a normal mode analysis-based docking and molecular dynamics simulation study

Polysaccharide degradation products are widely used in medicine, health food, textile and other industries. The preparation of monosaccharides by enzymatic degradation is a key technology in bio industrial production. Unfortunately, most of the known digested products are complex oligosaccharide mixtures, which limit their industrial processing and application. In this study, we explored a docking technique based on normal mode analysis to examine the possible cleavage mechanism of an alginate lyase (AlyB) from Birio Splendidus, which contains the catalytic domain of polysaccharide lyase family 7 (PL7) and a CBM32 sugar binding module, and was observed to produce trisaccharide products with quasi-monosaccharide distribution. We compared the molecular interactions of the enzyme with the natural alginates, the polyMG whose products has the quasi-monodisperse distribution of tri-saccharide and two synthetic polysaccharides, the polyM and polyG whose products has a wider distribution of oligosaccharides. Our calculations quantitatively show that there are a series of deterministic conformational changes in the catalytic pocket, which control the specificity of the substrate; at the same time, it determines the uniformity of the final product together with the spatial position of the key catalytic sites. The dynamic simulations revealed that CBM domain plays a key role in assisting the release of tri-saccharides. Our data highlights the important role of enzyme flexibility in determining product uniformity, which may provide new insight into design of enzymes for the production of high-value mono-distributed oligosaccharides.

biochemistry↗

bioRxiv2021

Ameliorating Emotional Attention through Modulation of Neural Oscillations with Transcranial Alternating Current Stimulation

BackgroundNumerous clinical reports suggest that psychopathy like schizophrenia, anxiety and depressive disorder is accompanied by early attentional abnormalities in emotional information processing. In the past decade, the efficacy of transcranial alternating current stimulation (tACS) in changing emotional functioning has been repeatedly observed and has demonstrated a causal relationship between endogenous oscillations and emotional processing. However, tACS effects on emotional attention have not yet been tested. MethodsA total of 53 healthy participants were randomized to 2 groups, and they were subjected to active or sham tACS at individual alpha frequency (IAF) in the bilaterally dorsolateral prefrontal cortex (dlPFC). Participants and received this treatment for 20 min durations daily for 7 consecutive days. On days 1 and 7, electroencephalogram (EEG) recording of 8 minute resting with eyes open and closed. Responses to a facial emotion identification task were also recorded to measure alpha changes and event-related potential (ERP) alterations. ResultsOn day 7 after tACS, the active group showed a more clear elevation in alpha power at rest, especially in open state around stimulation area, compared to the sham group. ERPs revealed a significant larger P200 amplitude after active stimulation (p < 0.05), indicating attentional improvement in facial emotion processing. Additionally, a notable positive correlation (p < 0.05) between alpha power and P200 amplitude was found, providing an electrophysiological interpretation regarding the role of tACS in emotional attention modulation. In addition, the IAF-tACS showed an obvious advantage in alpha entrainment compared to an additional 10 Hz-tACS. ConclusionsThese results support a seminal outcome for the effect of IAF-tACS on emotional attention modulation, demonstrating a feasible and individual-specific therapy for neuropsychiatric disorders related to emotion processing, especially regarding oscillatory disturbances.

bioengineering↗

bioRxiv2020

Computational analysis of the adaptability of H9N2 avian influenza virus: A comparative docking simulation study

Influenza A virus, the H9N2 subtype, is an avian influenza virus that has long been circulating in the worldwide poultry industry and is occasionally found to be transmissible to humans. Evidence from genomic analysis suggests that H9N2 provides the genes for the H5N1 and H7N9 subtypes, which have been found to infect mammals and pose a threat to human health. However, due to the lack of a structural model of the interaction between H9N2 and host cells, the mechanism of the extensive adaptability and strong transformation capacity of H9N2 is not fully understood. In this paper, we collected 40 representative H9N2 virus samples reported recently, mainly in China and neighboring countries, and investigated the interactions between H9N2 hemagglutinin and the mammalian receptor, the polysaccharide -2,6-linked lactoseries tetrasaccharide c, at the atomic level using docking simulation tools. We categorized the mutations of studied H9N2 hemagglutinin according to their effects on ligand-binding interactions and the phylogenetic analysis. The calculations indicated that all the studied H9N2 viruses can establish a tight binding with LSTc although the mutations caused a variety of perturbations to the local conformation of the binding pocket. Our calculations suggested that a marginal equilibrium is established between the conservative ligand-receptor interaction and the conformational dynamics of the binding pocket, and it might be this equilibrium that allows the virus to accommodate mutations to adapt to a variety of environments. Our results provided a way to understand the adaptive mechanisms of H9N2 viruses, which may help predict its propensity to spread in mammals.

bioinformatics↗

bioRxiv2018

MinION sequencing enables rapid whole genome assembly of Rickettsia typhi in a resource-limited setting

The infrastructure challenges and costs of next-generation sequencing have been largely overcome, for many sequencing applications, by Oxford Nanopore Technologies portable MinION sequencer. However the question remains open whether MinION-based bacterial whole-genome sequencing (WGS) is by itself sufficient for the accurate assessment of phylogenetic and epidemiological relationships between isolates and whether such tasks can be undertaken in resource-limited settings. To investigate this question, we sequenced the genome of an isolate of Rickettsia typhi, an important and neglected cause of fever across much of the tropics and subtropics, for which only three genomic sequences previously existed. We prepared and sequenced libraries on a MinION in Vientiane, Lao PDR using v9.5 chemistry and in parallel we sequenced the same isolate on the Illumina platform in a genomics laboratory in the UK. The MinION sequence reads yielded a single contiguous assembly, in which the addition of Illumina data revealed 226 base-substitution and 5,856 in/del errors. The combined assembly represents the first complete genome sequence of a human R. typhi isolate collected in the last 50 years and differed from the genomes of existing strains collected over a 90-year time period at very few sites, and with no re-arrangements. Filtering based on the known error profile of MinION data improved the accuracy of the Nanopore-only assembly. However, the frequency of false-positive errors remained greater than true sequence divergence from recorded sequences. While Nanopore-only sequencing cannot yet recover phylogenetic signal in R. typhi, such an approach may be applicable for more diverse organisms.

genomics↗