Biology subjects

Yan, T.

Publications and source records attributed to Yan, T..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Palmdelphin facilitates R-spondin2 secretion to activate Wnt signaling and promote colorectal cancer stemness and tumorigenesis

The Wnt signaling pathway is a key driver of stemness and progression which contributes to mortality in colorectal cancer (CRC). R-spondins bind to LGR receptors to inhibit ubiquitin E3 ligases, thus protecting Frizzled from degradation and activating downstream Wnt signaling. Herein, we identify Palmdelphin (PALMD) as a functional marker of CRC stem cells, interspersed between intestinal and colonic crypt base epithelial cells, and predictive of aggressive CMS4 CRC and poor survival. Gene knockdown and overexpression studies revealed that PALMD initiates paracrine activation of Wnt/{beta}-catenin signaling via interacting with and facilitating the secretion of R-spondin2 (RSPO2), resulting in enhanced stemness and tumor growth in vitro and in vivo. Physiologic or pharmacologic inhibition of the PALMD-RSPO2 axis using R-spondin2-specific antibody or 6-methyl-1,3,8-trihydroxyanthraquinone (emodin), respectively, attenuates PALMD- mediated Wnt reporter activation, self-renewal, and tumorigenesis in cell and patient-derived organoid models. Together, these findings identify PALMD as a previously unknown player in Wnt signaling in CRC, and underscore the pro-tumorigenic role of R-spondin2 in this context.

cancer biology↗

bioRxiv2025

Coro1a promotes the multivesicular body and plasma membrane fusion by facilitating PKM2-mediated SNAP-23 phosphorylation

During the formation of endosomal pathway-dependent extracellular vesicles (EVs), intraluminal vesicles in multivesicular bodies (MVBs) fuse with the plasma membrane (PM), releasing intraluminal vesicles to produce exosomes. Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, membrane fusion effector, is essential in this process. However, which SNARE complex is involved in MVB and PM fusion and how its assembly is regulated remain elusive. We have demonstrated that neddylation of Coro1a inhibits EV secretion by inducing Rab7-mediated degradation of MVBs. Here, we find that Coro1a increases EV biogenesis by promoting the assembly of SNARE complex STX-12-SNAP-23-VAMP-7 in a neddylation-independent manner. Coro1a activates PKM2 to enhance SNAP-23 phosphorylation in the presence of neddylation inhibitor MLN4924, which drives SNAP-23 to recruit more STX-12 and VAMP7, leading to increased formation of the STX-12-SNAP-23-VAMP-7 complex. Correspondingly, Coro1a-induced EV biogenesis is eliminated by PKM2 inhibitor or SNAP-23 silencing independent of neddylation. Reduced EVs from tumors due to Coro1a knockout cannot be observed in MLN4924-treated tumor mice with PKM2 inhibitor treatment either. Furthermore, Coro1a increases in tumor tissues from lung tumor patients with tumor progression, and high Coro1a indicates unfavorable survival of tumor patients, suggesting that increased Coro1a-mediated enhanced EV production from tumors accelerates tumor progression. Altogether, our data demonstrate that Coro1a facilitates EV biogenesis by promoting the assembly of STX-12-SNAP-23-VAMP-7 complex during MVB and PM fusion independent of neddylation, thereby being involved in the progression of EV-related diseases.

cell biology↗

bioRxiv2024

Positive impact of Type-A and -C response regulator genes on growth and panicle architecture in rice

Cytokinin signal transduction occurs through a "two-component system." Type-A and -C response regulators (RRs) are groups of proteins of similar structures constituting significant components of cytokinin signal transduction. In rice, 13 (Type-A) and two (Type-C) RRs have been identified to date; however, their functions remain partially known. In this study, we examined the expression patterns of Type-A and Type-C RRs in rice using RNA-Seq and confirmed their functions by constructing mutants of the 15 genes with CRISPR/Cas9. Almost all Type-A RRs played positive roles in the development of secondary branches and secondary spikelets, particularly RR2 and RR4. Notably, rr1 rr2 and rr8 rr12 rr13 higher-order mutants displayed small panicle sizes and decreased plant height. Additionally, both Type-C RRs played positive roles in regulating heading date. RNA-seq revealed several genes with significantly altered expression in the rr2 and rr4 mutants, with almost half of the differentially expressed genes (DEGs) overlapping between the two mutants. Many of the DEGs were associated with the cytokinin and abscisic acid pathways. Our findings provide new insights into the functions of Type-A and -C RRs in rice growth and may serve as a foundation for future studies focusing on cytokinin signaling.

plant biology↗

bioRxiv2024

Examination of Lipid Distributions in Hydrogel-Expanded Mouse Brain Tissue Using Imaging Mass Spectrometry

Imaging is an essential tool in biological research, and imaging mass spectrometry uniquely provides a label-free approach with high molecular specificity. However, imaging mass spectrometry is limited in spatial resolution, which in turn limits the biological structures and processes that can be studied at small dimensions. Custom lens setups and altered optical paths have been used to shrink the diameter of the incident laser beam probe in matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry to achieve high spatial resolutions (< 5 m). However, these research-grade instruments are complex and expensive, making high spatial resolution imaging experiments unrealistic for the broader community. An alternative method for improving spatial resolution is through physical magnification of the substrate, which has been well established in the subfield of expansion microscopy (ExM). ExM leverages superabsorbent hydrogels for isotropic expansion of tissues and retention of analytes containing fluorescent tags. While typical ExM involves covalently anchoring the analyte of interest to the hydrogel network, lipid retention without anchoring has been recently demonstrated for imaging mass spectrometry. Herein, we demonstrate expansion imaging mass spectrometry (ExIMS) of expanded, whole brain tissue and examine lipid distributions in both positive and negative ion mode across multiple brain structures. A linear expansion factor of 4.5-fold is achieved and used to obtain high spatial resolution images of mouse brain cerebellum. Approximately 95% of lipids in both positive and negative ion mode are retained in expanded tissue compared to unexpanded tissue. Additionally, the majority of lipid distributions across the brain are maintained post-expansion. Alterations to the hydrogel formulation (e.g., crosslinker density) can significantly affect the ability of ExIMS to maintain accurate lipid distributions in expanded tissue.

biochemistry↗

bioRxiv2024

Scalable Hypothalamic Arcuate Neuron Differentiation from Human Pluripotent Stem Cells Suitable for Modeling Metabolic and Reproductive Disorders

The hypothalamus, composed of several nuclei, is essential for maintaining our bodys homeostasis. The arcuate nucleus (ARC), located in the mediobasal hypothalamus, contains neuronal populations with eminent roles in energy and glucose homeostasis as well as reproduction. These neuronal populations are of great interest for translational research. To fulfill this promise, we used a robotic cell culture platform to provide a scalable and chemically defined approach for differentiating human pluripotent stem cells (hPSCs) into pro-opiomelanocortin (POMC), somatostatin (SST), tyrosine hydroxylase (TH) and gonadotropin-releasing hormone (GnRH) neuronal subpopulations with an ARC-like signature. This robust approach is reproducible across several distinct hPSC lines and exhibits a stepwise induction of key ventral diencephalon and ARC markers in transcriptomic profiling experiments. This is further corroborated by direct comparison to human fetal hypothalamus, and the enriched expression of genes implicated in obesity and type 2 diabetes (T2D). Genome-wide chromatin accessibility profiling by ATAC-seq identified accessible regulatory regions that can be utilized to predict candidate enhancers related to metabolic disorders and hypothalamic development. In depth molecular, cellular, and functional experiments unveiled the responsiveness of the hPSC-derived hypothalamic neurons to hormonal stimuli, such as insulin, neuropeptides including kisspeptin, and incretin mimetic drugs such as Exendin-4, highlighting their potential utility as physiologically relevant cellular models for disease studies. In addition, differential glucose and insulin treatments uncovered adaptability within the generated ARC neurons in the dynamic regulation of POMC and insulin receptors. In summary, the establishment of this model represents a novel, chemically defined, and scalable platform for manufacturing large numbers of hypothalamic arcuate neurons and serves as a valuable resource for modeling metabolic and reproductive disorders.

developmental biology↗

bioRxiv2024

The UFMylation pathway is impaired in Alzheimer's disease

BackgroundAlzheimers disease (AD) is characterized by the presence of neurofibrillary tangles made of hyperphosphorylated tau and senile plaques composed of beta-amyloid. These pathognomonic deposits have been implicated in the pathogenesis, although the molecular mechanisms and consequences remain undetermined. UFM1 is an important, but understudied ubiquitin-like protein that is covalently attached to substrates. This UFMylation has recently been identified as major modifier of tau aggregation upon seeding in experimental models. However, potential alterations of the UFM1 pathway in human AD brain have not been investigated yet. MethodsHere we used frontal and temporal cortex samples from individuals with or without AD to measure the protein levels of the UFMylation pathway in human brain. We used multivariable regression analyses followed by Bonferroni correction for multiple testing to analyze associations of the UFMylation pathway with neuropathological characteristics, primary biochemical measurements of tau and additional biochemical markers from the same cases. We further studied associations of the UFMylation cascade with cellular stress pathways using Spearman correlations with bulk RNAseq expression data and functionally validated these interactions using gene-edited neurons that were generated by CRISPR-Cas9. ResultsCompared to controls, human AD brain had increased protein levels of UFM1. Our data further indicates that this increase mainly reflects conjugated UFM1 indicating hyperUFMylation in AD. UFMylation was strongly correlated with pathological tau in both AD-affected brain regions. In addition, we found that the levels of conjugated UFM1 were negatively correlated with soluble levels of the deUFMylation enzyme UFSP2. Functional analysis of UFM1 and/or UFSP2 knockout neurons revealed that the DNA damage response as well as the unfolded protein response are perturbed by changes in neuronal UFM1 signaling. ConclusionsThere are marked changes in the UFMylation pathway in human AD brain. These changes are significantly associated with pathological tau, supporting the idea that the UFMylation cascade might indeed act as a modifier of tau pathology in human brain. Our study further nominates UFSP2 as an attractive target to reduce the hyperUFMylation observed in AD brain but also underscores the critical need to identify risks and benefits of manipulating the UFMylation pathway as potential therapeutic avenue for AD.

neuroscience↗

bioRxiv2024

Alterations of PINK1-PRKN signaling in mice during normal aging

The ubiquitin kinase-ligase pair PINK1-PRKN identifies and selectively marks damaged mitochondria for elimination via the autophagy-lysosome system (mitophagy). While this cytoprotective pathway has been extensively studied in vitro upon acute and complete depolarization of mitochondria, the significance of PINK1-PRKN mitophagy in vivo is less well established. Here we used a novel approach to study PINK1-PRKN signaling in different energetically demanding tissues of mice during normal aging. We demonstrate a generally increased expression of both genes and enhanced enzymatic activity with aging across tissue types. Collectively our data suggest a distinct regulation of PINK1-PRKN signaling under basal conditions with the most pronounced activation and flux of the pathway in mouse heart compared to brain or skeletal muscle. Our biochemical analyses complement existing mitophagy reporter readouts and provide an important baseline assessment in vivo, setting the stage for further investigations of the PINK1-PRKN pathway during stress and in relevant disease conditions.

neuroscience↗

bioRxiv2024

Mutation of GmDMP genes triggers haploid induction in soybean

The development of homozygous lines is a key step in plant breeding and production. Generally, homozygous lines can be obtained through traditional time-consuming way of several generations selfing or through a way of doubled haploid (DH) technology, which has obvious advantages to accelerate breeding. However, no effective haploid production system so far has been established in soybean. Here we show that mutations of the soybean GmDMP1 and GmDMP2 genes can be used to induce haploid with an average haploid induction rate of 0.61%. We also found that 22.9% of soybean haploids can produce seeds through spontaneous chromosome doubling. Those findings laid a solid foundation for establishing DH technology in soybean, which will accelerate soybean breeding.

genetics↗

bioRxiv2023

Adipose tissue eQTL meta-analysis reveals the contribution of allelic heterogeneity to gene expression regulation and cardiometabolic traits

Complete characterization of the genetic effects on gene expression is needed to elucidate tissue biology and the etiology of complex traits. Here, we analyzed 2,344 subcutaneous adipose tissue samples and identified 34K conditionally distinct expression quantitative trait locus (eQTL) signals in 18K genes. Over half of eQTL genes exhibited at least two eQTL signals. Compared to primary signals, non-primary signals had lower effect sizes, lower minor allele frequencies, and less promoter enrichment; they corresponded to genes with higher heritability and higher tolerance for loss of function. Colocalization of eQTL with conditionally distinct genome-wide association study signals for 28 cardiometabolic traits identified 3,605 eQTL signals for 1,861 genes. Inclusion of non-primary eQTL signals increased colocalized signals by 46%. Among 30 genes with [≥]2 pairs of colocalized signals, 21 showed a mediating gene dosage effect on the trait. Thus, expanded eQTL identification reveals more mechanisms underlying complex traits and improves understanding of the complexity of gene expression regulation.

genomics↗

bioRxiv2023

Chemoproteomics identifies proteoform-selective caspase-2 inhibitors

Caspases are a highly conserved family of cysteine-aspartyl proteases known for their essential roles in regulating apoptosis, inflammation, cell differentiation, and proliferation. Complementary to genetic approaches, small-molecule probes have emerged as useful tools for modulating caspase activity. However, due to the high sequence and structure homology of all twelve human caspases, achieving selectivity remains a central challenge for caspase-directed small-molecule inhibitor development efforts. Here, using mass spectrometry-based chemoproteomics, we first identify a highly reactive non-catalytic cysteine that is unique to caspase-2. By combining both gel-based activity-based protein profiling (ABPP) and a tobacco etch virus (TEV) protease activation assay, we then identify covalent lead compounds that react preferentially with this cysteine and afford a complete blockade of caspase-2 activity. Inhibitory activity is restricted to the zymogen or precursor form of monomeric caspase-2. Focused analogue synthesis combined with chemoproteomic target engagement analysis in cellular lysates and in cells yielded both pan-caspase reactive molecules and caspase-2 selective lead compounds together with a structurally matched inactive control. Application of this focused set of tool compounds to stratify caspase contributions to initiation of intrinsic apoptosis, supports compensatory caspase-9 activity in the context of caspase-2 inactivation. More broadly, our study highlights future opportunities for the development of proteoform-selective caspase inhibitors that target non-conserved and non-catalytic cysteine residues.

biochemistry↗

bioRxiv2023

Defining the Cell Surface Cysteinome using Two-step Enrichment Proteomics

The plasma membrane proteome is a rich resource of functional and therapeutically relevant protein targets. Distinguished by high hydrophobicity, heavy glycosylation, disulfide-rich sequences, and low overall abundance, the cell surface proteome remains undersampled in established proteomic pipelines, including our own cysteine chemoproteomics platforms. Here we paired cell surface glycoprotein capture with cysteine chemoproteomics to establish a two-stage enrichment method that enables chemoproteomic profiling of cell Surface Cysteinome. Our "Cys-Surf" platform captures >2,800 total membrane protein cysteines in 1,046 proteins, including 1,907 residues not previously captured by bulk proteomic analysis. By pairing Cys-Surf with an isotopic chemoproteomic readout, we uncovered 821 total ligandable cysteines, including known and novel sites. Cys-Surf also robustly delineates redox-sensitive cysteines, including cysteines prone to activation-dependent changes to cysteine oxidation state and residues sensitive to addition of exogenous reductants. Exemplifying the capacity of Cys-Surf to delineate functionally important cysteines, we identified a redox sensitive cysteine in the low-density lipoprotein receptor (LDLR) that impacts both the protein localization and uptake of LDL particles. Taken together, the Cys-Surf platform, distinguished by its two-stage enrichment paradigm, represents a tailored approach to delineate the functional and therapeutic potential of the plasma membrane cysteinome.

biochemistry↗

bioRxiv2023

Using a Deep Generation Network Reveals Neuroanatomical Specificity in Hemispheres

Asymmetry is an important property of brain organization, but its nature is still poorly understood. Capturing the neuroanatomical components specific to each hemisphere facilitates the understanding of the establishment of brain asymmetry. Since deep generative networks (DGNs) have powerful inference and recovery capabilities, we use one hemisphere to predict the opposite hemisphere by training the DGNs, which automatically fit the built-in dependencies between the left and right hemispheres. After training, the reconstructed images approximate the homologous components in the hemisphere. We use the difference between the actual and reconstructed hemispheres to measure hemisphere-specific components due to asymmetric expression of environmental and genetic factors. The results show that our model is biologically plausible and that our proposed metric of hemispheric specialization is reliable, representing a wide range of individual variation. Together, this work provides promising tools for exploring brain asymmetry and new insights into self-supervised DGNs for representing the brain.

neuroscience↗

bioRxiv2023

Single-cell transcriptomic profiling of human pancreatic islets reveals genes responsive to glucose exposure over 24 hours

Disruption of pancreatic islet function and glucose homeostasis can lead to the development of sustained hyperglycemia, beta cell glucotoxicity, and ultimately type 2 diabetes (T2D). In this study, we sought to explore the effects of hyperglycemia on human pancreatic islet (HPI) gene expression by exposing HPIs from two donors to low (2.8mM) and high (15.0mM) glucose concentrations over 24 hours, assaying the transcriptome at seven time points using single-cell RNA sequencing (scRNA-seq). We modeled time as both a discrete and continuous variable to determine momentary and longitudinal changes in transcription associated with islet time in culture or glucose exposure. Across all cell types, we identified 1,528 genes associated with time, 1,185 genes associated with glucose exposure, and 845 genes associated with interaction effects between time and glucose. We clustered differentially expressed genes across cell types and found 347 modules of genes with similar expression patterns across time and glucose conditions, including two beta cell modules enriched in genes associated with T2D. Finally, by integrating genomic features from this study and genetic summary statistics for T2D and related traits, we nominate 363 candidate effector genes that may underlie genetic associations for T2D and related traits.

genetics↗

bioRxiv2023

Functional interrogation of twenty type 2 diabetesassociated genes using isogenic hESC-derived β-like cells

Genetic studies have identified numerous loci associated with type 2 diabetes (T2D), but the functional role of many loci has remained unexplored. In this study, we engineered isogenic knockout human embryonic stem cell (hESC) lines for 20 genes associated with T2D risk. We systematically examined {beta}-cell differentiation, insulin production and secretion, and survival. We performed RNA-seq and ATAC-seq on hESC-{beta} cells from each knockout line. Analyses of T2D GWAS signals overlapping with HNF4A-dependent ATAC peaks identified a specific SNP as a likely causal variant. In addition, we performed integrative association analyses and identified four genes (CP, RNASE1, PCSK1N and GSTA2) associated with insulin production, and two genes (TAGLN3 and DHRS2) associated with sensitivity to lipotoxicity. Finally, we leveraged deep ATAC-seq read coverage to assess allele-specific imbalance at variants heterozygous in the parental hESC line, to identify a single likely functional variant at each of 23 T2D GWAS signals.

genetics↗

bioRxiv2023

Proximity-labeling chemoproteomics defines the subcellular cysteinome and inflammation-responsive mitochondrial redoxome

Proteinaceous cysteines function as essential sensors of cellular redox state. Consequently, defining the cysteine redoxome is a key challenge for functional proteomic studies. While proteome-wide inventories of cysteine oxidation state are readily achieved using established, widely adopted proteomic methods such as OxiCat, Biotin Switch, and SP3-Rox, they typically assay bulk proteomes and therefore fail to capture protein localization-dependent oxidative modifications. To obviate requirements for laborious biochemical fractionation, here, we develop and apply an unprecedented two step cysteine capture method to establish the Local Cysteine Capture (Cys-LoC), and Local Cysteine Oxidation (Cys-LOx) methods, which together yield compartment-specific cysteine capture and quantitation of cysteine oxidation state. Benchmarking of the Cys-LoC method across a panel of subcellular compartments revealed more than 3,500 cysteines not previously captured by whole cell proteomic analysis. Application of the Cys-LOx method to LPS stimulated murine immortalized bone marrow-derived macrophages (iBMDM), revealed previously unidentified mitochondria-specific inflammation-induced cysteine oxidative modifications including those associated with oxidative phosphorylation. These findings shed light on post-translational mechanisms regulating mitochondrial function during the cellular innate immune response.

biochemistry↗

bioRxiv2022

FCGRT, a cancer-derived immunoglobulin G binding protein, mediates the malignant phenotype of glioma

CIgG has received increasing attention, and was first discovered by our group to indicate poor prognosis in glioma. Furthermore, by protein mass spectrometry, we found that FCGRT can combine with CIgG. However, the study of FCGRT in glioma has not been reported. We used the CGGA325, TCGA dataset and immunohistochemistry to verify the importance of FCGRT on the prognosis of glioma patients. Single cell sequencing data analysis evaluated that the role of FCGRT in the microenvironment of glioma. Estimate, ssGSEA, EPIC and xCell were used for immune infiltration analysis. FCGRT was knocked down in U251 cells to detect the effect of FCGRT on the malignant development of glioma. These results showed that patients with higher FCGRT expression had a shorter overall survival. FCGRT was closely related to the tumor microenvironment, especially to macrophages in the tumor microenvironment (r=0.743, p<0.001). Interestingly we also found that FCGRT was positively correlated with IGHG1. Finally, we found that knock-down of FCGRT resulted in a decrease in proliferation, migration and invasion of U251 cells. Taken together, we believe that FCGRT is an independent prognostic factor for glioma patients, and its possible mechanism is to promote proliferation and invasion of tumor cells by interacting with CIgG.

bioinformatics↗

bioRxiv2022

Prewhitening and Normalization Help Detect a Strong Cross-Correlation Between Daily Wastewater SARS-CoV-2 RNA Abundance and COVID-19 Cases in a Community

Wastewater surveillance is a promising technology for real-time tracking and even early detection of COVID-19 infections in communities. Although correlation analysis between wastewater surveillance data and the daily clinical COVID-19 case numbers has been frequently conducted, the importance of stationarity of the time-series data has not been well addressed. In this study, we demonstrated that strong yet spurious correlation could arise from non-stationary time-series data in wastewater surveillance, and data prewhitening to remove trends helped to reveal distinct cross-correlation patterns between daily clinical case numbers and daily wastewater SARS-CoV-2 concentration during a lockdown period in 2020 in Honolulu, Hawaii. Normalization of wastewater SARS-CoV-2 concentration by the endogenous fecal viral markers in the same samples significantly improved the cross-correlation, and the best correlation was detected at a two-day lag of the daily clinical case numbers. The detection of a significant correlation between daily wastewater SARS-CoV-2 RNA abundance and clinical case numbers also suggests that disease burden fluctuation in the community should not be excluded as a contributor to the often observed weekly cyclic patterns of clinical cases. Water impactWastewater surveillance represents an emerging water technology with significant human health benefits. The study demonstrated that non-stationary time-series data could lead to spurious correlation, highlighting the need for prewhitening. Normalization strategies could alleviate variations in sample collection and analyses, which is useful for detecting actual underlying relationships between wastewater surveillance data and clinical data.

microbiology↗

bioRxiv2022

Generate a new crucian carp (Carassius auratus) strain without intermuscular bones by knocking out bmp6

Elimination of intermuscular bones (IMBs) is vital to the aquaculture industry of cyprinids. In our previous study, we characterized bmp6 as essential in the development of IMBs in zebrafish. Knockout of bmp6 results in the absence of IMBs in zebrafish without affecting growth and reproduction. Therefore, we hypothesized that bmp6 could be used to generate new cyprinid strains without IMBs by gene editing. In this study, we established a gene editing strategy for knocking out the two orthologs of bmp6 in diploid crucian carp (Carassius auratus). We obtained an F3 population with both orthologs knocked out, in which no IMBs were detected by bone staining and X-ray, indicating that the new strain without IMBs (named WUCI strain) was successfully generated. Furthermore, we extensively evaluated the performance of the new strain in growth, reproduction, nutrient components, muscle texture and structure, and metabolites in muscle. The results showed that the WUCI strain grew faster than the wild-type crucian carp at 4-month-age. The reproductive performance and flesh quality did not show significant differences between the WUCI strain and wild-type crucian carp. Moreover, the metabolomics analysis suggested that the muscle tissues of the WUCI strain significantly enriched some metabolites belonging to the Thiamine metabolism, Nicotinate and Nicotinamide Metabolism pathway, which plays beneficial effects in anti-aging, anti-oxidant, and anti-radiation damage. In conclusion, we established a strategy to eliminate IMBs in crucian carp and obtain a WUCI strain whose performance was expected compared to the wild-type crucian carp; meanwhile, the WUCI strain enriched some beneficial metabolites to human health in muscle tissue. This study is the first report that a farmed cyprinid strain without IMBs, which could be stably inherited, was obtained worldwide; it provided excellent germplasm for the cyprinids aquaculture industry and a useful molecular tool for eliminating IMBs in other cyprinids.

genetics↗