Biology subjects

Bi, Y.

Publications and source records attributed to Bi, Y..

At least 73 records · Page 4Linked to original sources

bioRxiv2022

Autologous humanized PDX modeling for immuno-oncology recapitulates the human tumor microenvironment

Interactions between immune and tumor cells are critical to determining cancer progression and response. In addition, preclinical prediction of immune-related drug efficacy is limited by inter-species differences between human and mouse, as well as inter-person germline and somatic variation. Here we develop an autologous system that models the TME in individual patients. With patient-derived bone marrow, we engrafted a patients hematopoietic system in MISTRG6 mice followed by patient-derived xenograft (PDX) tissue, providing a genetically matched autologous model. We used this system to prospectively study tumor-immune interactions in solid tumor patients. Autologous PDX mice generated innate and adaptive immune populations; these cells populated the TME; and tumors from autologously engrafted mice grew larger than tumors from non-engrafted littermate controls. Single-cell transcriptomics revealed a prominent VEGF-A signature in TME myeloid cells, and inhibition of human VEGF-A abrogated enhanced growth, demonstrating the utility of the autologous PDX system for pre-clinical testing.

cancer biology↗

bioRxiv2022

Dendritic cell Piezo1 integrating mechanical stiffness and inflammatory signals directs the differentiation of TH1 and Treg cells in cancer

Dendritic cells (DCs) play an important role in anti-tumor immunity by inducing T cell differentiation. Herein, we found that the mechanical sensor Piezo1 expressed by DCs integrates innate inflammatory stimuli and stiffness signals and directs the reciprocal differentiation of TH1 and regulatory T (Treg) cells in cancer. Genetic deletion of Piezo1 in DCs inhibited the generation of TH1 cells while driving the development of Treg cells in promoting cancer growth. Mechanistically, Piezo1-deficient DCs regulated the secretion of the polarizing cytokines TGF{beta}1 and IL-12, leading to increased TGF{beta}R2-p-Smad3 activity and decreased IL-12R{beta}2-p-STAT4 activity while inducing the reciprocal differentiation of Treg and TH1 cells. In addition, Piezo1 integrated the SIRT1-hypoxia-inducible factor-1 alpha (HIF1)-dependent metabolic pathway and calcium-calcineurin-NFAT signaling pathway to orchestrate reciprocal TH1 and Treg lineage commitment through DC-derived IL-12 and TGF{beta}1. Our studies provide critical insight for understanding the role of the DC-based mechanical regulation of immunopathology in directing T cell lineage commitment in tumor microenvironments.

immunology↗

bioRxiv2022

The way of the light: how visual information reaches the auditory cortex in congenitally deaf adults

Human and animal studies on cross-modal plasticity under congenital deafness suggest that early auditory cortex plays a significant role in the processing of visual information when congenitally deprived from its typical (auditory) input. However, the pathway by which early auditory cortex is fed with visual information is still understudied. Here we focused on addressing how visual information reaches the auditory cortex under congenital deafness. We put forth a mechanistic model that proposes that different corticocortical and subcortical connections play a central role in rerouting visual information to the early auditory cortex of congenitally deaf individuals. Specifically, we show, using Representational Connectivity Analysis (RCA) and Dynamic Causal Modeling (DCM), that connections from the right superior colliculus to the right inferior colliculus, as well as connections from right early visual cortical regions to the right early auditory cortex play a role in rerouting visual information to early auditory cortex in congenitally deaf individuals. These findings shed light on how visual information reaches the early auditory cortex of deaf individuals - specifically, they suggest that neuroplasticity reshapes subcortical connections in order to re-route visual information to the auditory stream.

neuroscience↗

bioRxiv2021

Brain intrinsic connection patterns underlying tool processing in human adults are present in neonates and not in macaques

Tool understanding and use are supported by a dedicated left-lateralized, intrinsically connected network in the human adult brain. To examine this networks phylogenic and ontogenetic origins, we compared resting-state functional connectivity (rsFC) among regions subserving tool processing in human adults to rsFC among homologous regions in human neonates and macaque monkeys (adolescent and mature). These homologous regions formed an intrinsic network in human neonates, but not in macaques. Network topological patterns were highly similar between human adults and neonates, and significantly less so between humans and macaques. The premotor-parietal rsFC had most significant contribution to the formation of the neonate tool network. These results suggest that an intrinsic brain network potentially supporting tool processing exists in the human brain prior to individual tool use experiences, and that the premotor-parietal functional connection in particular offers a brain basis for complex tool behaviors specific to humans.

neuroscience↗

bioRxiv2021

METTL3 facilitates hepatic fibrosis progression via m6A-YTHDF2 dependent silencing of GPR161

Hepatic fibrosis (HF) is a very common condition seen in millions of patients with various liver diseases. N6-methyladenosine (m6A) plays critical roles in various biological and pathological processes. However, the role of m6A and its main methyltransferase METTL3 in HF remains obscure. Here, we reported that METTL3 expression was elevated in HSCs from CCl4 induced fibrotic liver. METTL3 knockdown in HSCs mediated by recombinant adeno-associated-virus serotype 9 packed short hairpin RNA against METTL3 alleviated liver injury and fibrosis compared to empty carrier group. Mechanistically, the decreased liver fibrosis in CCl4-treated HSC-specific METTL3 knockdown mice was due to the increased GPR161 that is a suppressor of Hedgehog pathway, a well-known pathway to activate in liver injury and regeneration. As expect, GPR161 transferred into HSCs alleviated liver fibrosis and HSC activation. Forced GPR161 expression inhibited Gli3 activated form nuclear accumulation and subsequently suppressed fibrosis-associate gene expression. Conclusion, HSC-specific deletion of METTL3 inhibits liver fibrosis via elevated GPR161 expression, which subsequently suppressed Hedgehog pathway activation and fibrosis-associated genes expression, providing novel therapeutic targets for HF therapy. Synopsis O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=196 SRC="FIGDIR/small/472749v1_ufig1.gif" ALT="Figure 1"> View larger version (78K): org.highwire.dtl.DTLVardef@1245f3aorg.highwire.dtl.DTLVardef@e7effdorg.highwire.dtl.DTLVardef@13ce319org.highwire.dtl.DTLVardef@61be8b_HPS_FORMAT_FIGEXP M_FIG C_FIG The role of RNA m6A methyltransferase METTL3 in the progression of hepatic fibrosis is unclear. Here, we reveal that suppresses m6A modification by depletion of METTL3 in Hepatic Stellate Cells (HSCs), stabilizes the GPR161 transcripts, that involved in suppressing Hedgehog signaling pathway, through YTHDF2, thereby alleviating the fibrosis feature of CCl4-induced liver injury. O_LIDisruption of m6A methyltransferases METTL3 in HSCs alleviates liver fibrosis feature. C_LIO_LIMETTL3 depletion in liver HSCs suppresses its activation by suppressing Hedgehog signaling pathway through stabilizing GPR161 transcripts in an m6A-YTHDF2 dependent manner. C_LIO_LIGPR161 activates PKA that mediates phosphorylation and degradation of full-length Gli3 (Gli3-FL) protein, then the short Gli3 (Gli3-R) translocated into the nucleus and suppresses the fibrosis associated gene transcription. C_LIO_LIThe elevated METTL3 expression is attribute to its promoter H3K27ac modification. C_LI

molecular biology↗

bioRxiv2021

SC2MeNetDrug: A computational tool to uncover inter-cell signaling targets and identify relevant drugs based on single cell RNA-seq data

Single-cell RNA sequencing (scRNA-seq) is a powerful technology to investigate the transcriptional programs in stromal, immune, and disease cells, like tumor cells or neurons within the Alzheimers Disease (AD) brain or tumor microenvironment (ME) or niche. Cell-cell communications within ME play important roles in disease progression and immunotherapy response and are novel and critical therapeutic targets. Though many tools of scRNA-seq analysis have been developed to investigate the heterogeneity and sub-populations of cells, few were designed for uncovering cell-cell communications of ME and predicting the potentially effective drugs to inhibit the communications. Moreover, the data analysis processes of discovering signaling communication networks and effective drugs using scRNA-seq data are complex and involve a set of critical analysis processes and external supportive data resources, which are difficult for researchers who have no strong computational background and training in scRNA-seq data analysis. To address these challenges, in this study, we developed a novel open-source computational tool, sc2MeNetDrug (https://fuhaililab.github.io/sc2MeNetDrug/). It was specifically designed using scRNA-seq data to identify cell types within disease MEs, uncover the dysfunctional signaling pathways within individual cell types and interactions among different cell types, and predict effective drugs that can potentially disrupt cell-cell signaling communications. sc2MeNetDrug provided a user-friendly graphical user interface to encapsulate the data analysis modules, which can facilitate the scRNA-seq data-based discovery of novel inter-cell signaling communications and novel therapeutic regimens.

bioinformatics↗

bioRxiv2021

The role of visual experience in brain inter-individual variability

Visual cortex organization is highly consistent across individuals. But to what degree does this consistency depend on life experience, in particular sensory experience? In this study, we asked whether visual cortex reorganization in congenital blindness results in connectivity patterns that are particularly variable across individuals, focusing on resting-state functional connectivity (RSFC) patterns from primary visual cortex. We show that the absence of shared visual experience results in more-variable RSFC patterns across blind individuals than sighted controls. Increased variability is specifically found in areas that show a group difference between the blind and sighted in their RSFC. These findings reveal a relationship between brain plasticity and individual variability in which reorganization manifests variably across individuals. We further investigated the different patterns of reorganization in the blind, showing that the connectivity to frontal regions, proposed to have a role in reorganization of the visual cortex of the blind towards higher cognitive roles, is highly variable. In a supplementary analysis, we link some of the variability in visual-to-frontal connectivity to another environmental factor - duration of formal education. Together, these findings show a role of sensory and socioeconomic experience in imposing consistency on brain organization. By revealing the idiosyncratic nature of neural reorganization, these findings highlight the importance of considering individual differences in fitting sensory aids and restoration approaches for vision loss. Significance statementThe typical visual system is highly consistent across individuals. What are the origins of this consistency? Comparing the consistency of visual cortex connectivity between people born blind and sighted people, we showed that blindness results in higher variability, suggesting a key impact of individual experience on brain organization. Further, connectivity patterns that changed following blindness were particularly variable, resulting in diverse patterns of brain reorganization. Individual differences in reorganization were also directly affected by non-visual experiences in the blind (years of formal education). Together, these findings show a role of sensory and socioeconomic experiences in creating individual differences in brain organization and endorse the use of individual profiles for rehabilitation and restoration of vision loss.

neuroscience↗

bioRxiv2021

Humanoid robots are perceived as an evolutionary threat

Studying how we perceive humanoid robots will provide insights for a deeper understanding of human-robot interaction. Our ideas about humanoid robots are mainly informed by science fiction, and humanoid robots are generally described as an evolutionary threat in science fiction that has not been tested. The preparedness model has emphasized that the fear module is automatically activated by evolutionary threats, and its underlying neural circuit is centered on the amygdala. We hypothesized that if humanoid robots are perceived as an evolutionary threat even though humanoid robots are manmade, modern objects, we would expect to observe a monocular advantage for humanoid robots and an amygdala response to unconsciously presented humanoid robots that were previously only evident in evolutionary threats. Here, we observed a monocular advantage for the perception of humanoid robots the same as an evolutionary threat (i.e., snakes). Our neuroimaging analysis indicated that unconscious presentation of humanoid robot vs. human images led to significant amygdala activation. Despite a positive humanoid robot-related association had been established by associative learning (as evidenced by results of successfully weakening the negative implicit attitude to humanoid robots and enhancing functional connectivity between the amygdala and hippocampus), the amygdala could still automatically and quickly detect humanoid robots. Our results reveal that processing of information about humanoid robots displays automaticity with regard to recruitment of visual pathway and amygdala activation. Our findings that humans apparently perceive humanoid robots as an evolutionary threat may help inform redefinition of human-robot interaction and robot ethics.

neuroscience↗

bioRxiv2021

Investigating the active substance and mechanism of Jing-Fu-Kang granules via mass spectrometry technology and network pharmacology method

Jing-Fu-Kang granules (JFKG) is a famous Chinese patent medicine for the treatment of cervical spondylosis around the China, whereas the active substance and mechanism are not completely investigated clearly. In the current study, a rapid separation and identification method using UPLC-QE-Orbitrap-MS was established, 97 chemical constituents from JFKG were identified, and 16 prototype components from plasma samples after administration of JFKG were observed within 16 min. The structures of typical compounds were preliminarily speculated by comparing the retention time and fragmentation pattern. Furthermore, multiple databases were used to integrate the compound targets of JFKG, and the disease targets related to cervical spondylosis. After the intersection of the two sets of targets, a protein-protein interaction (PPI) network and a TCM-component-target-pathway-disease network were established, then using the DAVID database to perform gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis on the common targets to find related pathways. Finally, a total of 531 common targets and 136 pathways were found to participate in the mechanism. Our findings will help to further confirm the mechanism of JFKG for relieving cervical spondylosis, which will improve the scientific rationality of JFKG in clinical use, and can also assist in guiding doctors.

pharmacology and toxicology↗

bioRxiv2021

The first crested duck genome reveals clues to genetic compensation and crest cushion formation

The Chinese crested (CC) duck is a unique indigenous waterfowl breed with a phenotypic crest trait that affects its high survival rate. Therefore, the CC duck is an ideal model to investigate the genetic compensation response to maintain genetic stability. In the present study, we first generated a chromosome-level genome of CC ducks. Comparative genomics revealed genes related to tissue repair, immune function, and tumors were under strong positive selection, which suggested that these adaptive changes might enhance cancer resistance and immune response to maintain the genetic stability of CC ducks. We sub-assembled a Chinese spot-billed duck genome and detected genome-assembled structure variants among three ducks. Functional analysis revealed that a large number of structural variants were related to the immune system, which strongly suggests the occurrence of genetic compensation in the anti-tumor and immune systems to further support the survival of CC ducks. Moreover, we confirmed that the CC duck originated from the mallard ducks. Finally, we revealed the physiological and genetic basis of crest traits and identified a causative mutation in TAS2R40 that leads to crest formation. Overall, the findings of this study provide new insights into the role of genetic compensation in adaptive evolution.

genomics↗

bioRxiv2021

ERp44 is Required for Endocardial Cushion Development by Regulating VEGFA Secretion in Myocardium

Rationale: Endocardial cushions are precursors of the valvoseptal complex that separates the four heart chambers and control blood flow through the heart. Abnormalities in endocardial cushion development lead to atrioventricular septal defects (AVSDs), which affect 1 in 2,100 live births. Several genes have been implicated in the development of endocardial cushions. Specifically, endoplasmic reticulum-resident protein 44 (ERp44) has been found to play a role in the early secretory pathway, but its function in heart development has not been well studied. Objective: The goal of this study was to investigate the role of ERp44 in heart development in mice. Approach and Results: Using conventional and tissue-specific knockout mouse models, we demonstrated that ERp44 plays a specific role in heart development. ERp44 knockout (KO) mice were smaller in size, and most mice died during early postnatal life. KO hearts exhibited the typical phenotypes of congenital heart diseases, such as abnormal heart shapes as well as severe septal and valvular defects. Similar phenotypes were found in cTnt-cre+/-; Erp44fl/fl mice, which indicated that myocardial ERp44 principally controls endocardial cushion formation. Further studies demonstrated that the deletion of ERp44 significantly decreased the proliferation of cushion cells and impaired the endocardial-mesenchymal transition (EndMT), which was followed by endocardial cushion dysplasia. Finally, we found that ERp44 directly bound to VEGFA and controlled its release. Conclusions: ERp44 contributes to the development of the endocardial cushion by affecting the EndMT of cushion cells by regulating VEGFA release in myocardial cells.

developmental biology↗

bioRxiv2021

Computational mechanisms for neural representation of words

A critical way for humans to acquire, represent and communicate information is through language, yet the underlying computation mechanisms through which language contributes to our word meaning representations are poorly understood. We compared three major types of word computation mechanisms from large language corpus (simple co-occurrence, graph-space relations and neural-network-vector-embedding relations) in terms of the association of words brain activity patterns, measured by two functional magnetic resonance imaging (fMRI) experiments. Word relations derived from a graph-space representation, and not neural-network-vector-embedding, had unique explanatory power for the neural activity patterns in brain regions that have been shown to be particularly sensitive to language processes, including the anterior temporal lobe (capturing graph-common-neighbors), inferior frontal gyrus, and posterior middle/inferior temporal gyrus (capturing graph-shortest-path). These results were robust across different window sizes and graph sizes and were relatively specific to language inputs. These findings highlight the role of cumulative language inputs in organizing word meaning neural representations and provide a mathematical model to explain how different brain regions capture different types of language-derived information.

neuroscience↗

bioRxiv2021

A recombinant receptor-binding domain in trimeric form generates completely protective immunity against SARS-CoV-2 infection in nonhuman primates

Safe and effective vaccination is critical to combatting the COVID-19 pandemic. Here, we developed a trimeric SARS-CoV-2 receptor-binding domain (RBD) subunit vaccine candidate that simulates the natural structure of the spike (S) trimer glycoprotein. Immunization with RBD-trimer induced robust humoral and cellular immune responses and a high level of neutralizing antibodies that were maintained for at least 4 months. Moreover, the antibodies that were produced in response to the vaccine effectively neutralized the SARS-CoV-2 501Y.V2 variant. Of note, when the titers of the antibodies dropped to a sufficiently low level, only one boost quickly activated the anamnestic immune response, resulting in complete protection against the SARS-CoV-2 challenge in rhesus macaques without typical histopathological changes or viral replication in the lungs and other respiratory tissues. Our results indicated that immunization with SARS-CoV-2 RBD-trimer could raise long-term and broad immunity protection in nonhuman primates, thereby offering an optimal vaccination strategy against COVID-19.

immunology↗

bioRxiv2021

A tandem-repeat dimeric RBD protein-based COVID-19 vaccine ZF2001 protects mice and nonhuman primates

A safe, efficacious and deployable vaccine is urgently needed to control COVID-19 pandemic. We report here the preclinical development of a COVID-19 vaccine candidate, ZF2001, which contains tandem-repeat dimeric receptor-binding domain (RBD) protein with alum-based adjuvant. We assessed vaccine immunogenicity and efficacy in both mice and non-human primates (NHPs). ZF2001 induced high levels of RBD-binding and SARS-CoV-2 neutralizing antibody in both mice and NHPs, and also elicited balanced TH1/TH2 cellular responses in NHPs. Two doses of ZF2001 protected Ad-hACE2-transduced mice against SARS-CoV-2 infection, as detected by reduced viral RNA and relieved lung injuries. In NHPs, vaccination of either 25 g or 50 g ZF2001 prevented infection with SARS-CoV-2 in lung, trachea and bronchi, with milder lung lesions. No evidence of disease enhancement is observed in both models. ZF2001 is being evaluated in the ongoing international multi-center Phase 3 trials (NCT04646590) and has been approved for emergency use in Uzbekistan.

immunology↗

bioRxiv2021

Identification of novel bat coronaviruses sheds light on the evolutionary origins of SARS-CoV-2 and related viruses

Although a variety of SARS-CoV-2 related coronaviruses have been identified, the evolutionary origins of this virus remain elusive. We describe a meta-transcriptomic study of 411 samples collected from 23 bat species in a small (~1100 hectare) region in Yunnan province, China, from May 2019 to November 2020. We identified coronavirus contigs in 40 of 100 sequencing libraries, including seven representing SARS-CoV-2-like contigs. From these data we obtained 24 full-length coronavirus genomes, including four novel SARS-CoV-2 related and three SARS-CoV related genomes. Of these viruses, RpYN06 exhibited 94.5% sequence identity to SARS-CoV-2 across the whole genome and was the closest relative of SARS-CoV-2 in the ORF1ab, ORF7a, ORF8, N, and ORF10 genes. The other three SARS-CoV-2 related coronaviruses were nearly identical in sequence and clustered closely with a virus previously identified in pangolins from Guangxi, China, although with a genetically distinct spike gene sequence. We also identified 17 alphacoronavirus genomes, including those closely related to swine acute diarrhea syndrome virus and porcine epidemic diarrhea virus. Ecological modeling predicted the co-existence of up to 23 Rhinolophus bat species in Southeast Asia and southern China, with the largest contiguous hotspots extending from South Lao and Vietnam to southern China. Our study highlights both the remarkable diversity of bat viruses at the local scale and that relatives of SARS-CoV-2 and SARS-CoV circulate in wildlife species in a broad geographic region of Southeast Asia and southern China. These data will help guide surveillance efforts to determine the origins of SARS-CoV-2 and other pathogenic coronaviruses.

microbiology↗

bioRxiv2021

Recombinant chimpanzee adenovirus AdC7 expressing dimeric tandem-repeat RBD of SARS-CoV-2 spike protein protects mice against COVID-19

A safe and effective vaccine is urgently needed to control the unprecedented COVID-19 pandemic. Four adenovirus vectored vaccines expressing spike (S) protein have advanced into phase 3 trials, with three approved for use. Here, we generated several recombinant chimpanzee adenovirus (AdC7) vaccines expressing S, receptor-binding domain (RBD) or dimeric tandem-repeat RBD (RBD-tr2). We found vaccination via either intramuscular or intranasal route was highly immunogenic in mice to elicit both humoral and cellular (Th1-based) immune responses. AdC7-RBD-tr2 showed higher antibody responses compared with both AdC7-S and AdC7-RBD. Intranasal administration of AdC7-RBD-tr2 additionally induced mucosal immunity with neutralizing activity in bronchoalveolar lavage fluid. Either single-dose or two-dose mucosal administration of AdC7-RBD-tr2 protected mice against SARS-CoV-2 challenge, with undetectable subgenomic RNA in lung and relieved lung injury. These results support AdC7-RBD-tr2 as a promising COVID-19 vaccine candidate.

immunology↗

bioRxiv2020

Spoken language comprehension activates the primary visual cortex

Primary visual cortex (V1) is generally thought of as a low-level sensory area that primarily processes basic visual features. However, in congenitally blind individuals, V1 is involved in language processing, with no evidence of major changes in anatomical connectivity that could explain this seemingly drastic functional change. This is at odds with current accounts of neural plasticity, which emphasize the role of connectivity and conserved function in determining a neural tissues role even after atypical early experiences. To reconcile what appears to be unprecedented functional reorganization with known accounts of plasticity limitations, we tested whether V1 also responds to spoken language in sighted individuals. Using fMRI, we found that V1 in normally sighted individuals was indeed activated by comprehensible speech as compared to a reversed speech control condition, in a left-lateralized and focal manner. Activation in V1 for language was also significant and comparable for abstract and concrete words, suggesting it was not driven by visual imagery. Last, this activation did not stem from increased attention to the auditory onset of words, excluding general attention accounts. Together these findings suggest that V1 responds to verbal information even in sighted individuals, potentially to predict visual input. This capability might be the basis for the strong V1 language activation observed in people born blind, re-affirming the notion that plasticity is guided by pre-existing connectivity and abilities in the typically developed brain. Significance statementHow flexible is the human brain? Studies of congenitally blind individuals showed that language activates the primary visual cortex. This has been interpreted as evidence for unprecedented functional plasticity from a low-level visual to a language area. To reconcile these findings with known limitations of plasticity based on intrinsic physiology and connectivity, we tested if similar activation can be found in sighted participants. We show that left-lateralized primary visual cortex is activated by spoken language comprehension in sighted individuals, . This suggests that plasticity even in complete blindness from birth is not limitless and is guided by pre-existing connectivity and abilities in the typically-developed brain.

neuroscience↗

bioRxiv2020

Arabidopsis ACINUS is O-glycosylated and regulates transcription and alternative splicing of regulators of reproductive transitions

O-GlcNAc modification plays important roles in metabolic regulation of cellular status. Two homologs of O-GlcNAc transferase, SECRET AGENT (SEC) and SPINDLY (SPY), which have O-GlcNAc and O-fucosyl transferase activities, respectively, are essential in Arabidopsis but have largely unknown cellular targets. Here we show that AtACINUS is O-GlcNAcylated and O-fucosylated and mediates regulation of transcription, alternative splicing (AS), and developmental transitions. Knocking-out both AtACINUS and its distant paralog AtPININ causes severe growth defects including dwarfism, delayed seed germination and flowering, and abscisic acid (ABA) hypersensitivity. Transcriptomic and protein-DNA/RNA interaction analyses demonstrate that AtACINUS represses transcription of the flowering repressor FLC and mediates AS of ABH1 and HAB1, two negative regulators of ABA signaling. Proteomic analyses show AtACINUSs O-GlcNAcylation, O-fucosylation, and association with splicing factors, chromatin remodelers, and transcriptional regulators. Some AtACINUS/AtPININ-dependent AS events are altered in the sec and spy mutants, demonstrating a function of O-glycosylation in regulating alternative RNA splicing.

molecular biology↗