Biology subjects

Jiang, X.

Publications and source records attributed to Jiang, X..

At least 163 records · Page 9Linked to original sources

bioRxiv2024

Social and spatial drivers of the multitiered structure of zebra finch social networks

Social network structure plays a key role in shaping processes in animal populations. These networks often show distinct patterns in humans and other large mammals, with relationship strengths organized into different tiers. Here, we used continuous, fine-scale tracking of four large captive colonies of zebra finches (Taeniopygia guttata), revealing that zebra finches consistently have 1-2 closest contacts, 6-7 close contacts, and 22-24 strong contacts. The identities of these contacts remain stable across days, with strong contacts maintained by spatial affinity while closest and close contacts are maintained by social choice. These results suggest that zebra finches egocentric networks and social structure are made up of consistent, differentiated relationships forming a multitiered social structure. The similarities in patterns to other species suggest that fundamental principles, such as limitations in time and the ability to move through social space, could drive common structural properties in animal social networks.

animal behavior and cognition↗

bioRxiv2024

Delineation of Single-cell Altas Provides New Insights for Development of Coronary Artery Lesions in Kawasaki Disease: Bad and Good Signaling Molecules

BackgroundKawasaki Disease (KD) is a vasculitis syndrome featured with a high and persistent fever and mainly affects children under 5 years of age. It is the leading cause of acquired heart disease in the form of coronary artery lesions (CALs) for children in developed countries. Most KD can be relieved with the high-dosage Intravenous immunoglobulin (IVIG) therapy, but a small proportion develop CALs after IVIG treatment. MethodsWe performed the single-cell RNA sequencing for the peripheral blood mononuclear cells (PBMCs) from three KD non-CAL patients whose samples were acquired before and after IVIG treatment and three KD CAL patients whose samples were acquired only after IVIG treatment. Cell-to-cell communication patterns were also analyzed in KD CAL and non-CAL patients ResultsOverall cell expression feature analyses show immunoglobulin and adaptive immunity related genes are upregulated in KD CAL patients while B cell activation related genes are downregulated in them. Pseudo-time analyses demonstrate that both KD non-CAL patients before treatment and KD CAL patients after treatment have a dysregulated B cell developmental trajectory while the former has a mixed T and B lineage and the latter has a mixed monocyte and B lineage. The early elevated expression of SPI1 could partly explain the dysregulated B cell development in KD CAL patients. Cell communication analyses propose a disorder cell communication pattern in KD non-CAL patients before treatment and some persistent bad cell-to-cell signals in KD CAL patients after treatment. There are four signaling molecules, APP, CCL, and MCH-II, whose expression is significantly increased in the CD14 and CD16 monocytes of KD CAL patients, where the expression of RESISTIN is significantly increased in those KD non-CAL patients. ConclusionsOur results suggest that APP, CCL, and MCH-II might be the bad signals for indicating the possible development of CAL while RESISTIN is a good one for protecting from CAL.

immunology↗

bioRxiv2024

Gut Microbial Utilization of the Alternative Sweetener, D-Allulose, via AlsE

D-allulose, a rare sugar with emerging potential as a low-calorie sweetener, has garnered attention as an alternative to other commercially available alternative sweeteners, such as sugar alcohols, which often cause severe gastrointestinal discomfort. D-allulose-6-phosphate 3-epimerase (AlsE) is a prokaryotic enzyme that converts D-allulose-6-phosphate into D-fructose-6-phopshate, enabling its use as a carbon source. However, the taxonomic breadth of AlsE across gut bacteria remains poorly understood, hindering insights into the utilization of D-allulose by microbial communities. In this study, we provide experimental evidence showing that Clostridium innocuum is capable of D-allulose metabolism via a homologous AlsE. A bioinformatics search of 85,202 bacterial genomes identified 116 bacterial species with AlsE homologs, suggesting a limited distribution of AlsE in bacteria. Additionally, Escherichia coli contains a copy of alsE, but it does not grow on D-allulose as a sole carbon source unless alsE is heterologously expressed. A metagenomic analysis revealed that 15.8% of 3,079 adult healthy human metagenomic samples that we analyzed contained alsE, suggesting a limited prevalence of the enzyme in the gut microbiome. These results suggest that the gut microbiome has limited capacity to metabolize D-allulose via alsE, supporting its use as an alternative sweetener with minimal impact on microbial composition and gastrointestinal symptoms. This finding also enables personalized nutrition, allowing diabetic individuals to assess their gut microbiota for alsE, and manage glycemic response while reducing gastrointestinal distress.

microbiology↗

bioRxiv2024

Plug-and-Play Myoelectric Control via a Self-Calibrating Random Forest Common Model

ObjectiveElectromyographic (EMG) signals show large variabilities over time due to factors such as electrode shifting, user behaviour variations, etc., substantially degrading the performance of myoelectric control models in long-term use. Previously one-time model calibration was usually required each time before usage. However, the EMG characteristics could change even within a short period of time. Our objective is to develop a self-calibrating model, with an automatic and unsupervised self-calibration mechanism. ApproachWe developed a computationally efficient random forest (RF) common model, which can (1) be pre-trained and easily adapt to a new user via one-shot calibration, and (2) keep calibrating itself once in a while by boosting the RF with new decision trees trained on pseudo-labels of testing samples in a data buffer. Main resultsOur model has been validated in both offline and real-time, both open and closed-loop, both intra-day and long-term (up to 5 weeks) experiments. We tested this approach with data from 66 able-bodied participants. We also explored the effects of bidirectional user-model co-adaption in closed-loop experiments. We found that the self-calibrating model could gradually improve its performance in long-term use. With visual feedback, users will also adapt to the dynamic model meanwhile learn to perform hand gestures with significantly lower EMG amplitudes (less muscle effort). SignificanceOur random forest-approach provides a new alternative built on simple decision tree for myoelectric control, which is explainable, computationally efficient, and requires minimal data for model calibration. Source codes are avaiable at: https://github.com/MoveR-Digital-Health-and-Care-Hub/self-calibrating-rf

neuroscience↗

bioRxiv2024

Revolutionizing large-scale DNA synthesis with microchip-based massive in parallel synthesis system

DNA synthesis serves as the fundamental enabling technology of engineering biology, aiming to provide DNA molecules of designed composition, length, and complexity at scale and low cost. Current high-throughput DNA synthesis technologies rely on intricate chip manufacturing and microfluidic systems to provide large-scale synthetic oligonucleotides, at the expense of low concentration and limited compatibility in the processing of longer DNA constructs assembly. Here, we report a microchip-based massive in parallel synthesis (mMPS), pioneering an "identification-sorting-synthesis-recycling" iteration mechanism to microchips for high throughput DNA synthesis. In comparison to microarray-based methods, we demonstrate that our method can increase the DNA product concentration by 4 magnitudes (to picomole-scale per sequence) and greatly simplifies the downstream processes for large-scale gene synthesis construction. By the construction of 1.97 million-diversity variant libraries that cover 1,254 human protein domains, we demonstrated the uniformity of the constructed variant libraries using mMPS-derived oligos is greatly improved, with amino acid distribution highly consistent as designed. In addition, by synthesizing 285 1kb-to-3kb genes with varying degrees of sequence complexity from previously reported strains A501 and 3DAC, potential ancestor of early archaea and bacteria, our result shows that the overall gene assembly success rate using mMPS-derived oligos is increased by 10-fold in comparison to other methods. Our mMPS technology holds the potential to close the gap between the quality and cost of writing DNA in increasing demand across many sectors of research and industrial activities.

synthetic biology↗

bioRxiv2024

Deep generative design of neutralizing nanobodies againstSARS-CoV-2 variants

In recent years, single-domain heavy chain antibodies (nanobodies), with only one-tenth the molecular weight of conventional antibodies, have emerged as important therapeutic proteins in the fight against SARS-CoV-2. However, the rapid mutation of the virus often renders existing nanobodies ineffective, underscoring the need to develop nanobodies that specifically target new variants. Traditional methods for discovering nanobodies are time-consuming and complex, making it difficult to efficiently identify nanobodies that bind to specific epitopes. To address this, we propose a de novo nanobody design method based on a Generative Adversarial Network (GAN). We developed a deep generative model, AiCDR, which consists of three discriminators and one generator. By determining the contribution of these three discriminators to the entire network, we can enhance the discrimination of generated sequences and reduce the similarity of the generated CDR3 sequences with natural peptides and random sequences, thereby ensuring their nature-like properties. These generated CDR3 sequences were then grafted onto humanized nanobody scaffolds, resulting in a structural library of approximately 104 nanobodies with natural-like properties. Using computational methods, we screened this library against the Spike (S) protein of the SARS-CoV-2 Omicron variant and identified 10 candidate nanobodies. Functional assays confirmed that two of these nanobodies exhibited neutralizing activity against the S protein. Our study demonstrates the potential of deep learning in nanobody design and offers a novel approach for developing nanobodies that target rapidly evolving viral variants.

bioinformatics↗

bioRxiv2024

Baicalein ameliorates experimental ulcerative colitis recurrency by downregulating neonatal Fc receptor via the NF-κB signaling pathway

Ulcerative colitis (UC) is a chronic autoimmune disease (AID) that causes mild to moderate, unpredictable symptoms, including diarrhea and abdominal pain. Against neonatal Fc receptors (FcRn) has been proven a unique AID treatment strategy by decreasing the effects of pathogenic autoantibody. Our previous study revealed that FcRn inhibition is beneficial in UC treatment through reducing colonic neutrophil extracellular traps (NET) formation via accelerating serum anti-neutrophil cytoplasm antibodies (ANCA) clearance. In this study, we initially confirmed the specific impact of downregulating FcRn in preventing UC relapse by injecting rAAV, that carrying Fcgrt-shRNA, in mice. Next, we investigated the inhibition effects and regulation mechanisms of baicalein (BCL) on FcRn and assessed its capacity to withstand UC recurrence using NCM460 cells and dextran sodium sulfate-induced mice models by determining the expression of FcRn and its related transcription factors. We also measured colonic NET-associated protein (NAP) expression and serum concentrations of IgG, ANCA, TNF-, IL-1{beta}, and c-reactive protein (CRP). UC inflammation severity was determined using the disease activity index (DAI) and histopathological score (HS). BCL treatment remarkably decreased the mRNA and protein contents of FcRn, p50, and p65 but did not impact STAT1 expression and the phosphorylation of I{kappa}B and STAT1. Long-term BCL administration inhibited colonic FcRn expression and reduced serum ANCA levels, colonic NAPs expression, serum inflammation-related indexes (including TNF-, IL-1{beta}, and CRP), DAI, and HS scores in UC mice during inflammation relapse better than salazosulfapyridine. Our study indicates that BCL ameliorates UC recurrency by inhibiting FcRn expression via p50/p65 heterodimer-mediated NF-{kappa}B signaling. Chemical compoundsChemical compounds studied in this article were listed below: Baicalein (PubChem CID: 5281605); Salazosulfapyridine (PubChem CID: 5339).

pharmacology and toxicology↗

bioRxiv2024

Stability vs flexibility: reshaping monolayer and bilayer archaeal membranes in silico

Cellular membranes differ across the tree of life. In most bacteria and eukaryotes, single-headed lipids self-assemble into flexible bilayer membranes. By contrast, thermophilic archaea tend to possess bilayer lipids together with double-headed, monolayer spanning bolalipids, which are thought to enable cells to survive in harsh environments. Here, using a minimal computational model for bolalipid membranes, we explore the trade-offs at play when forming membranes. We find that flexible bolalipids form membranes that resemble bilayer membranes because they are able to assume a U-shaped conformation. Conversely, rigid bolalipids, which resemble the bolalipids with cyclic groups found in thermophilic archaea, take on a straight conformation and form membranes that are stiff and prone to pore formation when they undergo changes in shape. Strikingly, however, the inclusion of small amounts of bilayer lipids in a bolalipid membrane is enough to achieve fluid bolalipid membranes that are both stable and flexible - resolving this trade-off. Our study suggests a mechanism by which archaea can tune the material properties of their membranes as and when required to enable them to survive in harsh environments and to undergo essential membrane remodelling events like cell division.

biophysics↗

bioRxiv2024

Diversity of ancestral brainstem noradrenergic neurons across species and multiple biological factors

The brainstem cell group, locus coeruleus (LC), is present across vertebrates and influences cardiorespiratory, metabolic, immune, and cognitive functions by activating in two putatively distinct firing patterns. Yet, the degree to which the LC firing rates and patterns are homogenous across species has never been assessed due to inherently limited sample sizes. To remedy this, we pooled cross-species data from 20 laboratories to show that firing rates differ across species and are modulated by sex, age, and type of in vitro or in vivo preparation. Contrary to the prevailing dual-mode firing pattern schema, we observed patterns spread across a low-dimensional manifold, with subregions enriched for specific biological factors and neurodegenerative disease models. Our findings show considerable diversity in an ancestral vertebrate neuromodulatory system.

neuroscience↗

bioRxiv2024

Gut Bacteria Metabolize Natural and Synthetic Steroid Hormones via the Reductive OsrABC Pathway

Steroid hormone metabolism by the gut microbiome affects host physiology, but the underlying microbial pathways remain incompletely understood. Here, we isolate a novel human gut bacterium, Clostridium steroidoreducensT strain HCS.1 that reduces cortisol and related steroid hormones to 3{beta},5{beta}-tetrahydrosteroid products. Through transcriptomics and enzymatic discovery, we establish the C. steroidoreducens OsrABC steroid hormone pathway. OsrA is a 3-oxo-{Delta}1-steroid hormone reductase that targets synthetic glucocorticoids, including prednisolone-- a frontline Crohns disease therapy. OsrB is a 3-oxo-{Delta}4-steroid reductase that converts steroid hormones to 5{beta}-dihydrosteroid intermediates, which OsrC subsequently reduces to 3{beta},5{beta}-tetrahydro products. Homologs of osrA and osrB predict steroid-reducing activity across gut bacteria and are enriched in Crohns disease patient metagenomes. Consistent with a role in modulating drug efficacy, C. steroidoreducens colonization decreases prednisolone bioavailability in gnotobiotic mice. These findings thus define a previously unrecognized pathway for microbial steroid hormone inactivation and establish a mechanistic basis for bacterial interference with anti-inflammatory therapies.

microbiology↗

bioRxiv2024

Gut Bacteria Encode Reductases that Biotransform Steroid Hormones

The metabolism of steroids by the gut microbiome affects hormone homeostasis, impacting host development, mental health, and reproductive functions. In this study, we identify the {Delta}4-3-ketosteroid 5{beta}-reductase, 3{beta}-hydroxysteroid dehydrogenase/{Delta}5-4 isomerase, and {Delta}6-3-ketosteroid reductase enzyme families encoded by common human gut bacteria. Through phylogenetic reconstruction and mutagenesis, We show that 5{beta}-reductase and {Delta}6-3-ketosteroid reductase have evolved to specialize in converting diverse 3-keto steroid hormones into their 5{beta}- and {Delta}6-reduced derivatives. We also find that the novel 3{beta}-hydroxysteroid dehydrogenase/{Delta}5-4 isomerase is fused with 5{beta}-reductase in multiple species, streamlining the multi-step conversion of pregnenolone, a steroid hormone precursor, into epipregnanolone. Through metagenomic analysis, we reveal that these enzymes are prevalent in healthy populations, being enriched in females over males. These findings provide the molecular basis for studying microbial steroid metabolism in the gut, offering insights into its potential impact on hormonal health in hosts, especially in the context of womens health.

microbiology↗

bioRxiv2024

High-risk neuropsychiatric copy number variants are associated with convergent transcriptomic changes in human brain cells

Large, recurrent copy number variants (CNVs) are among the strongest risk factors for neuropsychiatric conditions, contributing to multiple phenotypes with overlapping psychiatric and cognitive symptoms. However, the molecular basis of this convergent risk remains unknown. We evaluated the human brain transcriptome in carriers of nine high-risk neuropsychiatric CNVs and matched non-carriers using single nucleus RNA-sequencing. Brain tissue from carriers displayed widespread disruptions of gene expression, with thousands of differentially expressed genes, mostly located outside of the respective CNV regions. There were greater changes in deletions compared to reciprocal duplications. Functional enrichment analysis revealed changes in mitochondrial energy metabolism and synaptic function that converged across CNVs and cell types. For mirror CNVs, the direction of effects was often reversed between deletions and duplications and showed correlation with CNV gene dosage. These findings suggest that a shared pathophysiology underlies risk for convergent brain phenotypes across CNVs and point toward promising therapeutic targets.

genetics↗

bioRxiv2024

CCR2 limits inflammatory functions of CD8 TRM cells that impair recognition memory during recovery from WNV encephalitis

Central nervous system (CNS) resident memory CD8 T cells (TRM) that express IFN-{gamma} contribute to neurodegenerative processes, including synapse loss, leading to memory impairments. Here, we show that CCR2 signalling in CD8 TRM that persist within the hippocampus after recovery from CNS infection with West Nile virus (WNV) significantly prevents the development of memory impairments. Using CCR2-deficient mice, we determined that CCR2 expression is not essential for CNS T cell recruitment or virologic control during acute WNV infection. However, transcriptomic analyses of forebrain CCR2+ versus CCR2- CD8 TRM during WNV recovery reveal that CCR2 signalling significantly regulates hippocampal CD8 TRM phenotype and function via extrinsic and intrinsic effects, decreasing the expression of CD103 and granzyme A and IFN-{gamma}, respectively. Consistent with this, WNV-recovered Cd8acreCcr2fl/fl mice exhibit decreased recognition memory. Our findings highlight a neuroprotective role for CCR2 in limiting CD8 T cell-mediated neuroinflammation and cognitive deficits, providing insights into potential therapeutic targets for CNS infections.

immunology↗

bioRxiv2024

Listening to music modulates visual perception of paintings during binocular rivalry

Music, as a hierarchically organized art form, profoundly influences perception and mood through its rich information and intense emotion. While previous research has demonstrated that music can shape visual perception, its influences on visual awareness in aesthetic scenes remain largely unclear. In a series of five experiments involving 138 participants, we used the binocular rivalry paradigm to investigate how sad or lively Chinese folk music influences the perception of traditional Chinese paintings with varying aesthetic emotion (bleak vs. vivid). Paintings were presented in upright or inverted orientations or replaced by patches. Results revealed that sad music significantly increased both the average dominance duration and the predominance score of bleak paintings. Conversely, lively music with a faster tempo accelerated the switch rate of both paintings and patches. These effects were interdependent, exclusively for meaningful (upright) paintings, and correlated with individual sensitivity to musical reward. Our findings support the hierarchical predictive coding model of binocular rivalry, demonstrating that musical aesthetic emotion exerts top-down modulation, while musical tempo provides bottom-up entrainment, jointly shaping visual awareness of paintings.

systems biology↗

bioRxiv2024

Comprehensive Genomic and Evolutionary Analysis of Biofilm Matrix Clusters and Proteins in the Vibrio Genus

Vibrio cholerae pathogens cause cholera, an acute diarrheal disease resulting in significant morbidity and mortality worldwide. Biofilms in vibrios enhance their survival in natural ecosystems and facilitate transmission during cholera outbreaks. Critical components of the biofilm matrix include the Vibrio polysaccharides produced by the vps-1 and vps-2 gene clusters and the biofilm matrix proteins encoded in the rbm gene cluster, together comprising the biofilm matrix cluster. However, the biofilm matrix clusters and their evolutionary patterns in other Vibrio species remain underexplored. In this study, we systematically investigated the distribution, diversity, and evolution of biofilm matrix clusters and proteins across the Vibrio genus. Our findings reveal that these gene clusters are sporadically distributed throughout the genus, even appearing in species phylogenetically distant from V. cholerae. Evolutionary analysis of the major biofilm matrix proteins RbmC and Bap1 shows that they are structurally and sequentially related, having undergone structural domain and modular alterations. Additionally, a novel loop-less Bap1 variant was identified, predominantly represented in two phylogenetically distant Vibrio cholerae subspecies clades that share specific gene groups associated with the presence or absence of the protein. Furthermore, our analysis revealed that rbmB, a gene involved in biofilm dispersal, shares a recent common ancestor with Vibriophage tail proteins, suggesting that phages may mimic host functions to evade biofilm-associated defenses. Our study offers a foundational understanding of the diversity and evolution of biofilm matrix clusters in vibrios, laying the groundwork for future biofilm engineering through genetic modification.

evolutionary biology↗

bioRxiv2024

Molecular and physiological characterization of tillering and shade tolerance of dwarf mutants of perennial ryegrass

Tillering and shade tolerance are important traits in turfgrass, influenced by environmental factors, nutrients, and hormones. Shade stress negatively affects tillering. In this study, two dwarf mutants, shadow-1 and shadow-2, developed via Gamma-ray and fast-neutron mutagenesis, respectively, showed significantly higher tillering than the wild-type under greenhouse conditions. Both mutants demonstrated shade tolerance in plant height, grass quality, and color under 85% and 95% shade conditions, while shade-induced inhibition of tillering was observed in both the mutants and the wild-type. In comparison to wild-type plants under 95% shade conditions, we observed that the cytokinin biosynthetic gene IPT8 is upregulated, while the cytokinin inactivating gene CKX2 is downregulated in shadow-1. Similarly, the GA biosynthetic genes CPS1, GA2ox3, and GA20ox1 are upregulated, while the GA inactivating gene GA20ox8 is downregulated in the shadow-1 mutant. Furthermore, the ethylene biosynthetic genes ACS and ACO are also downregulated in the shadow-1 mutant. Consistently, we observed that wild-type plants exhibit increased GA and reduced CK levels, while shadow-1 mutant plants have reduced GA but increased CK levels. This explains the shadow-1 mutants shade tolerance in terms of plant height, grass quality, and color. Conversely, the tillering inhibitor genes CRY1, MAX2, and SnRK1 are upregulated in both wild-type and shadow-1 mutant plants. Our results provide novel insights into the mechanisms behind tillering and shade tolerance in turfgrasses under shade conditions.

plant biology↗

bioRxiv2024

A Refined Analysis of Neanderthal-Introgressed Sequences in Modern Humans with a Complete Reference Genome

BackgroundLeveraging long-read sequencing technologies, the first complete human reference genome, T2T-CHM13, corrects the assembly errors in prior references and addresses the remaining 8% of the genome. While the studies on archaic admixture in modern humans so far have been relying on the GRCh37 reference due to the archaic genome data, the impact of T2T-CHM13 in this field remains unknown. ResultsWe remapped the sequencing reads of the high-quality Altai Neanderthal and Denisovan genomes onto GRCh38 and T2T-CHM13 respectively. Compared with GRCh37, we found T2T-CHM13 has a significant improvement of read mapping quality in archaic samples. We then applied IBDmix to identify Neanderthal introgressed sequences in 2,504 individuals from 26 geographically diverse populations in different references. We observed different pre-phasing filtering strategies prevalently used in public data can largely impact determination of archaic ancestry, calling for consideration on the choice of filters. We discovered ~51Mb T2T-CHM13 unique Neanderthal sequences, which are predominantly located in regions where the variants distinct between the GRCh38 and T2T-CHM13 assemblies emerge. Besides, we unfolded new instances of population-specific archaic introgression in diverse populations, covering genes involved in metabolism, olfactory-related, and icon-channel. Finally, we integrated the introgressed sequences and adaptive signals with all references into a visualization database website, called ASH (www.arcseqhub.com), to facilitate the utilization of archaic alleles and adaptive signals in human genomics and evolutionary research. ConclusionsOur study refines the detection of archaic variations in modern humans, highlights the importance of T2T-CHM13 reference utility, and provides novel insights into functional consequences of archaic hominin admixture.

evolutionary biology↗

bioRxiv2024

Celastrol binds to pyruvate kinase and imitates the metabolic reprogramming of ATP

ATP is the final product of glycolysis and the TCA cycle. However, the counter-regulation of glycosis and TCA by ATP is poorly understood. Here we show that ATP analog celastrol (CLT) binds to the ATP binding pocket on pyruvate kinase PKM (PKM) while inducing allosteric regulation of PKM. Quantum calculation predicts hydrogen bond formation between CLT and asparagine. Liquid chromatography-mass spectrometry further identifies PKM as CLTs target. The inhibition of PKM is stronger and longer for CLT while weak and short for ATP. Notably, CLT-PKM interaction perfectly underlies the hypoglycemic effects by forming glucose carbon flux U turn before PKM. Besides, the PKM allostery induces a tricarboxylic acid (TCA) vortex which could promote amino acid and lipid degradation as the energy compensation, leading to a significant weight loss. Additionally, CLT exerts efficient antioxidant effects by altering the glucose flux to strengthen the pentose phosphate pathway. Consequently, the CLT-PKM interaction vividly reproduces the ATP-PKM interaction named "ATP resistance" in the diabetes pathogenesis.

pharmacology and toxicology↗