Biology subjects

Duan, T.

Publications and source records attributed to Duan, T..

11 recordsLinked to original sources

bioRxiv2026

Probiotic Lactiplantibacillus plantarum VB165 improves metabolic disorders in Insulin-Resistant Mice

This study investigated the effects of Lactiplantibacillus plantarum VB165, a probiotic strain with intrinsic -glucosidase inhibitor (AGI) activity, on metabolic disorders in high-fat diet (HFD)-induced insulin-resistant (IR) mice. Male C57BL/6 mice were divided into four groups: normal control diet (NCD), NCD supplemented with VB165, HFD, and HFD supplemented with VB165. After 16 weeks, VB165 supplementation significantly attenuated HFD-induced weight gain and reduced epididymal and inguinal white adipose tissue indices. VB165 also improved glucose intolerance and insulin resistance (IR), as demonstrated by oral glucose tolerance tests (OGTT) and insulin tolerance tests (ITT), and lowered fasting blood glucose, fasting insulin, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) levels. Additionally, it ameliorated dyslipidemia by reducing serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C), while alleviating hepatic steatosis and adipocyte hypertrophy. Mechanistically, VB165 enhanced intestinal barrier function by upregulating tight junction proteins (ZO-1 and Occludin), reduced systemic inflammation by lowering LPS, IL-6, and IL-1{beta}. Gut microbiota analysis revealed that VB165 modulated community composition, suppressing HFD-enriched genera (e.g., Ileibacterium and Coriobacteriaceae_UCG_002) and promoting beneficial taxa (e.g., Faecalibaculum and Oscillibacter). These findings demonstrate that L. plantarum VB165 improves HFD-induced metabolic disorders via multi-target mechanisms, highlighting its potential as a probiotic intervention for IR and related metabolic diseases.

microbiology↗

bioRxiv2026

The genetic architecture of local adaptation is historically contingent

Revealing the genetic basis of local adaptation is a common goal of evolutionary biology, but despite theoretical progress, general expectations for the genetic architecture of local adaptation are still unclear. Theoretical analyses usually model simplified ecologies or simplified genetic architectures of adaptive traits, so the interplay of these factors is missing from our understanding. In this study, we use simulations to explore how the interplay of ecological and genetic parameters influences the evolution and genetic architecture of local adaptation. With these simulations, we ask: i) What are the features of alleles that made the largest contribution to local adaptation, and how are they affected by polygenicity of adaptive traits, migration rates, demographic history, and the spatial pattern of the environment? And ii) does allele age moderate the confounding effect from population structure in genotype-environmental associations (GEA)? We find that the frequency, number, and phenotypic effect size of locally adaptive alleles are sensitive to trait polygenicity and demographic history, and that these factors shape the evolutionary dynamics of local adaptation. We find that population expansions can leave legacies in the genetic architecture of local adaptation, reducing the expected number of adaptive alleles relative to models with constant population size, and this effect is long-lasting. Compared to range expansion, other ecological variables known to affect the genetic basis of local adaptation had limited effects. Finally, allele age moderated the confounding effect of population structure and modified the causal effect of environmental variables on genotypes. Alleles that arose around the time of environmental changes often made large contributions to local adaptation, but young alleles often had the highest false positive rates and were the most common age category. We describe how incorporating allele age and its interactions with population structure and environmental variables may increase the sensitivity and specificity of GEA analysis. Overall, this work demonstrates the critical importance that a species demographic history can have on its genetic architecture of local adaptation.

genetics↗

bioRxiv2025

Effect of Chronic Stress on Whole Blood Transcriptome: A Meta-Analysis of Publicly Available Datasets from Rodent Models

BackgroundChronic stress increases risk for neuropsychiatric disorders in humans. By modeling stress-induced changes in animals, we may improve diagnosis or treatment of these disorders. Successful translation benefits from studies with sufficient statistical power and outcome measurements that can be directly compared across species. We performed a meta-analysis to examine the impact of chronic stress on the whole blood transcriptome. MethodsDatasets were systematically identified in Gemma, a database of reprocessed public transcriptional profiling studies; datasets GSE68076, GSE72262, and GSE84185 met inclusion/exclusion parameters. Each study exposed eight-week old mice to chronic stress (5-10 days social defeat stress or 6-8 weeks chronic mild stress). The final sample size was n=92 (n=45 Non-Stress/n=47 Stress). Stress-related differential expression in each dataset was quantified using the Limma pipeline followed by empirical Bayes moderation. For the 9,219 genes represented in all three datasets, we ran a meta-analysis of Log(2) Fold Changes using a random effects model and corrected for false discovery rate (FDR). Functional patterns were assessed with fast Gene Set Enrichment Analysis. Cell type specific enrichment for each of the differentially expressed genes was further explored using a public 10x genomics scRNA-Seq dataset from mouse peripheral blood mononuclear cells. ResultsFindings included 23 downregulated and 16 upregulated transcripts in stress-exposed mice (FDR<0.05). Results indicated a down-regulation in gene sets related to B cells, immune response, DNA and chromatin regulation, ribosomal activity, translation, and catabolic cellular processes. Upregulated gene sets related to erythrocytes and oxygen binding. ConclusionOur results provide molecular insight into stress-related immune dysregulation and add weight to the hypothesis that environmental stress escalates cellular aging, supporting the use of blood transcriptome as a bridge between human and rodent models. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=99 SRC="FIGDIR/small/657043v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@161fc2eorg.highwire.dtl.DTLVardef@1f358b9org.highwire.dtl.DTLVardef@145ef33org.highwire.dtl.DTLVardef@5b1169_HPS_FORMAT_FIGEXP M_FIG C_FIG Key pointsSuccessful translational research benefits from studies with outcome measurements that can be directly compared across species and sufficient statistical power. The present report is a meta-analysis of three mouse experiments examining the impact of chronic stress on the whole blood transcriptome. Our results provide insight into stress-related immune dysregulation and add weight to the hypothesis that environmental stress escalates cellular aging. These findings illustrate the utility of the blood transcriptome as a bridge between human and rodent models.

genomics↗

bioRxiv2025

Genetic architecture of the S-locus supergene revealed in a tetraploid distylous species

SummaryO_LIHeterostyly is a polymorphic floral adaptation controlled by supergenes and maintained in populations by disassortative mating. The molecular basis of distyly has been investigated in several unrelated families. Previous studies have been limited to diploid species and have not included Rubiaceae, which has the highest number of heterostylous species. C_LIO_LIHere, we investigate the genetic architecture of tetraploid Schizomussaenda henryi (Rubiaceae) to identify candidate style-length genes, evidence for hemizygosity and the potential role of gene duplication in the evolution of the S-locus. Chromosome-level genome assemblies and transcriptomic approaches identified the S-locus region comprised of four hemizygous genes. C_LIO_LIThe candidate gene SchzAUX22 may regulate style length and filament growth by acting in the auxin signaling pathway. Comparative studies of the two sub-genomes of S. henryi indicated strong similarities and no significant sub-genome dominance, as expected from autotetraploidy. Evidence from haplotype-resolved assemblies of a short-styled plant indicated that it possessed the ssSS genotype, consistent with autotetraploidy, which was estimated to have originated [~]3.6 Mya. Analysis of Ks values between S-locus genes and their paralogs indicated that the S-locus likely originated through stepwise duplication. C_LIO_LIOur study provides comprehensive genomic analysis of distyly in a polyploid and demonstrates that despite whole genome doubling the S-locus supergene remains intact and functional as an outbreeding mechanism. Our results contrast with many other heterostylous lineages where polyploidy is associated with breakdown of the polymorphism and transitions to self-fertilization. C_LI

plant biology↗

bioRxiv2023

Dominance between self-incompatibility alleles determines the mating system of Capsella allopolyploids

The shift from outcrossing to self-fertilization is one of the main evolutionary transitions in plants, and has broad effects on evolutionary trajectories. In Brassicaceae, the ability to impede self-fertilization is controlled by two genes, SCR and SRK, tightly linked within the S-locus. A series of small non-coding RNAs also encoded within the S-locus regulates the transcriptional activity of SCR alleles, resulting in a linear dominance hierarchy between them. Brassicaceae allopolyploid species are often self-compatible (SC) even when one of their parents is self-incompatible, but the causes of the loss of self-incompatibility (SI) in polyploid lineages have generally remained elusive. We used a series of synthetic hybrids obtained between self-fertilizing Capsella orientalis and outcrossing C. grandiflora to test whether the breakdown of SI in allopolyploid species, such as C. bursa-pastoris, could be explained by the dominance interactions between S-haplotypes inherited from the parental lineages. After establishing a database of reference S-allele sequences, we used RNA-sequencing data from young inflorescences to measure allele-specific expression of the SCR and SRK genes in diploid and tetraploid synthetic hybrids. We then compared the observed expression of SCR alleles with the predicted dominance relationship between S-haplotypes in pollen and with the seed set from autonomous self-fertilization in the synthetic hybrids. Our results formally establish that upon hybridization, the immediate effect on the mating system depends on the relative dominance between S-alleles inherited from the parental species. They illustrate that a detailed understanding of the genetic architecture of the control of SI is essential to predict the patterns of association between the mating system and changes in ploidy. Lay summaryPolyploidy is the inheritable condition of carrying more than two sets of chromosomes. It can result from within-species genome duplication (auto-polyploidy), or from the merging of sets of chromosomes from different species following hybridization (allo-polyploidy). Because sexual reproduction between individuals of different levels of ploidy is generally not successful, self-fertilization has been considered a key component of the establishment success of polyploid lineages. However, the reasons why the mating system of polyploids may differ from that of their parental species remains mysterious. In plants of the Brassicaceae family, several allopolyploid species arose from hybridization between an outcrossing and a self-fertilizing species, and in most cases the resulting lineages are self-fertilizing. It has been proposed that the mating system of these allopolyploids depends on the dominance relationships between the functional and non-functional self-incompatibility alleles inherited from the parental species. Here, we tested this prediction by characterizing at the transcriptional (RNA-seq) and phenotypic levels (estimation of autonomous seed production) a series of synthetic Capsella diploid and tetraploid hybrids. We found that the predicted dominance relationships matched the observed expression of self-incompatibility alleles, as well as the mating system phenotypes. Hence, the mating system of newly formed Capsella allotetraploids depends on the dominance relationship between self-incompatibility alleles inherited from the parents. Overall, our results improve our understanding of the mechanisms by which changes in ploidy can alter the system of mating over the course of evolution.

evolutionary biology↗

bioRxiv2023

Separating phases of allopolyploid evolution with resynthesized and natural Capsella bursa-pastoris

Allopolyploidization is a frequent evolutionary transition in plants that combines whole-genome duplication (WGD) and interspecific hybridization. The genome of an allopolyploid species results from initial interactions between parental genomes and long-term evolution. Telling apart the contributions of these two phases is essential to understanding the evolutionary trajectory of allopolyploid species. Here, we compared phenotypic and transcriptomic changes in natural and resynthesized Capsella allotetraploids with their diploid parental species. We focused on phenotypic traits associated with the selfing syndrome and on transcription-level phenomena such as expression level dominance, transgressive expression, and homoeolog expression bias. We found that selfing syndrome, high pollen and seed quality in natural allotetraploids likely resulted from long-term evolution. Similarly, transgressive expression and most down-regulated expression-level dominance were only found in natural allopolyploids. Natural allotetraploids also had more expression-level dominance toward the self-fertilizing parental species than resynthesized allotetraploids, mirroring the establishment of the selfing syndrome. However, short-term changes mattered, and 40% of the cases of expression-level dominance in natural allotetraploids were already observed in resynthesized allotetraploids. Resynthesized allotetraploids showed striking variation of homoeolog expression bias among chromosomes and individuals. Homoeologous synapsis was its primary source and may still be a source of genetic variation in natural allotetraploids. In conclusion, both short- and long-term mechanisms contributed to transcriptomic and phenotypic changes in natural allotetraploids. However, the initial gene expression changes were largely reshaped during long-term evolution leading to further morphological changes.

genetics↗

bioRxiv2020

The selfing syndrome overshadows other differences when comparing fitness across Capsella species

Self-fertilization has recurrently evolved from outcrossing. Self-fertilization provides an advantage in the short-term as individuals do not require a mate to reproduce, but self-fertilization is also associated with both decreased genetic diversity and accumulation of weakly deleterious mutations, which could, however, be alleviated in polyploid selfers. If pollinators are not limited, individual fitness is thus expected to be higher in outcrossers than in selfers. We measured several life history traits in four Capsella species under two different treatments (disturbed and undisturbed) to assess the effects of mating system and ploidy level on reproductive, vegetative and phenological traits. The experiment was carried out outdoor in Northwest Greece, within the range of the obligate outcrossing species, C. grandiflora, so it could be naturally pollinated and its fitness directly compared to that of its self-fertilizing relatives. Disturbance of the environment did not affect the phenotype in any of the four species. However, for most traits the obligate outcrossing species performed better than all selfing ones. In contrast, polyploidy did not seem to confer an advantage in terms of survival or reproduction compared to diploidy. Finally, plants from Asia and northern Europe had lower performances than accessions from southern Europe and the Middle-East.

evolutionary biology↗

bioRxiv2020

Comprehensive genome sequencing analysis as a promising option in the prenatal diagnosis of fetal structural anomalies: a prospective study.

PurposeGenome sequencing (GS) is a powerful tool for postnatal genetic diagnosis, but relevant clinical studies in the field of prenatal diagnosis are few. We aimed to evaluate the feasibility of GS as a first-line approach in prenatal diagnosis and compare its clinical value with the chromosomal microarray analysis (CMA) plus exome sequencing (ES) sequential testing. MethodsWe applied trio GS ([~]40-fold) in parallel with CMA plus ES to investigate the genetic basis for structural or growth anomalies in 111 fetuses and compared their results. ResultsGS covered all genetic variants in 22 diagnosed cases detected by CMA plus ES, yielding a diagnostic rate of 19.8% (22/110). Moreover, GS provided more comprehensive and precise genetic information than CMA plus ES, revealing twin fetuses with an imbalanced translocation arising from a balanced paternal translocation and one fetus with an extra pathogenic variant in the GJA8 gene, and incidentally identified intrauterine CMV infection in a growth-restricted fetus. ConclusionCompared with CMA plus ES, GS offers a more comprehensive view of the genetic etiology of fetal anomalies and provides clues for nongenetic factors such as intrauterine infection. Our study demonstrates the feasibility of GS as a promising first-line test in prenatal diagnosis.

genomics↗

bioRxiv2018

Towards the new normal: Transcriptomic and genomic changes in the two subgenomes of a 100,000 years old allopolyploid, Capsella bursa-pastoris

Allopolyploidy has played a major role in plant evolution but its impact on genome diversity and expression patterns remains to be understood. Some studies found important genomic and transcriptomic changes in allopolyploids, whereas others detected a strong parental legacy and more subtle changes. The allotetraploid C. bursa-pastoris originated around 100,000 years ago and one could expect the genetic polymorphism of the two subgenomes to become more similar and their transcriptomes to start functioning together. To test this hypothesis, we sequenced the genomes and the transcriptomes (three tissues) of allote-traploid C. bursa-pastoris and its parental species, the outcrossing C. grandiflora and the self-fertilizing C. orientalis. Comparison of the divergence in expression between subgenomes, on the one hand, and divergence in expression between the parental species, on the other hand, indicated a strong parental legacy with a majority of genes exhibiting a conserved pattern and cis-regulation. However, a large proportion of the genes that were differentially expressed between the two subgenomes, were also under trans-regulation reflecting the establishment of a new regulatory pattern. Parental dominance varied among tissues: expression in flowers was closer to that of C. orientalis and expression in root and leaf to that of C. grandiflora. Since deleterious mutations accumulated preferentially on the C. orientalis subgenome, the bias in expression towards C. orientalis observed in flowers suggests that expression changes could be adaptive and related to the selfing syndrome, while biases in the roots and leaves towards the C. grandiflora subgenome may be reflective of the differential genetic load.

evolutionary biology↗

bioRxiv2018

Parallelized Inference for Single Cell Transcriptomic Clustering with Split Merge Sampling on DPMM Model

Motivation: With the development of droplet based systems, massive single cell transcriptome data has become available, which enables analysis of cellular and molecular processes at single cell resolution and is instrumental to understanding many biological processes. While state-of-the-art clustering methods have been applied to the data, they face challenges in the following aspects: (1) the clustering quality still needs to be improved; (2) most models need prior knowledge on number of clusters, which is not always available; (3) there is a demand for faster computational speed.\n\nResults: We propose to tackle these challenges with Parallelized Split Merge Sampling on Dirichlet Process Mixture Model (the Para-DPMM model). Unlike classic DPMM methods that perform sampling on each single data point, the split merge mechanism samples on the cluster level, which significantly improves convergence and optimality of the result. The model is highly parallelized and can utilize the computing power of high performance computing (HPC) clusters, enabling massive inference on huge datasets. Experiment results show the model achieves about 7% improvement in clustering accuracy for small datasets and more than 20% improvement for large challenging datasets compared with current widely used models. In the mean time, the models computing speed is significantly faster.\n\nAvailability: Source code is publicly available on https://github.com/tiehangd/Para_DPMM/tree/master/Para_DPMM_package

bioinformatics↗

bioRxiv2017

Parental legacy, demography, and introgression influenced the evolution of the two subgenomes of the tetraploid Capsella bursa-pastoris (Brassicaceae)

Allopolyploidy is generally perceived as a major source of evolutionary novelties and as an instantaneous way to create isolation barriers. However, we do not have a clear understanding of how two subgenomes evolve and interact once they have fused in an allopolyploid species and how isolated they are from their relatives. Here, we address these questions by analyzing genomic and transcriptomic data of allotetraploid Capsella bursa-pastoris in three differentiated populations, Asia, Europe and the Middle East. We phased the two subgenomes, one descended from the outcrossing and highly diverse Capsella grandiflora (Cg) and the other one from the selfing and genetically depauperate Capsella orientalis (Co). For each subgenome, we assessed its relationship with the diploid relatives, temporal change of effective population size Ne, signatures of positive and negative selection, and gene expression patterns. Introgression between C. bursa-pastoris and its diploid relatives was widespread and the two subgenomes were impacted differentially depending on geographic region. In all three regions, Ne of the two subgenomes decreased gradually and the Co subgenome accumulated more deleterious changes than Cg. Selective sweeps were more common on the Cg subgenome in Europe and the Middle East, and on the Co subgenome in Asia. In contrast, differences in expression were limited with the Cg subgenome slightly more expressed than Co in Europe and the Middle-East. In summary, after more than 100,000 generations of co-existence, the two subgenomes of C. bursa-pastoris still retained a strong signature of parental legacy and were differentially affected by introgression and selection.

evolutionary biology↗