Biology subjects

Yu, J.

Publications and source records attributed to Yu, J..

At least 271 records · Page 15Linked to original sources

bioRxiv2023

Structural insights into the distinct protective mechanisms of human antibodies targeting ZIKV NS1

Zika virus (ZIKV) Non-structural protein 1 (NS1) plays an essential role in viral replication and immune evasion. Our understanding of the differential protective mechanism of NS1-targeting antibodies is limited. Here, we determined the cryoEM structures of ZIKV NS1 in complex with two group antibodies at 2.6-2.9[A]. Group I antibodies (3G2 and 4B8) potently recognize cell surface form of NS1 and multiple oligomeric forms of NS1 by occupy the epitopes on outer surface of dimeric NS1. IgG and Fab from group I antibodies completely abrogate sNS1-mediated endothelial dysfunction in vitro. Group II antibodies (4F10, 2E11, and 14G5) recognize the previously reported epitopes in distal end of the {beta}-ladder domain of monomeric NS1, and their blockade efficiency depends on the affinity with NS1 protein. These findings elucidate the correlation between the epitope recognition and the protective efficacy of anti-NS1 antibodies and highlight the distinct mechanisms of therapeutic potential of 3G2 and 4B8.

microbiology↗

bioRxiv2023

25-hydroxycholesterol mediates brain cytokine production and neutrophil infiltration in a mouse model of lipopolysaccharide-induced neuroinflammation

Neuroinflammation has been implicated in the pathogenesis of several neurologic and psychiatric disorders. Microglia are key drivers of neuroinflammation and in response to different inflammatory stimuli overexpress a proinflammatory signature of genes. Among these, Ch25h is a gene overexpressed in brain tissue from Alzheimers disease as well as various mouse models of neuroinflammation. Ch25h encodes cholesterol 25-hydroxylase, an enzyme that hydroxylates cholesterol to form 25-hydroxycholesterol (25HC). 25HC, an immune-oxysterol primarily produced by activated microglia, is further metabolized to 7,25-dihydroxycholesterol, which is a potent chemoattractant for leukocytes. We have also previously shown that 25HC increases production and secretion of the proinflammatory cytokine, IL-1{beta}, by mouse microglia treated with lipopolysaccharide (LPS). In the present study, wildtype (WT) and Ch25h-knockout (CKO) mice were peripherally administered LPS to induce an inflammatory state in the brain. In LPS-treated WT mice, Ch25h expression and 25HC levels increased in brain relative to vehicle-treated WT mice. Interestingly, 25HC levels were significantly higher in LPS-treated WT female compared to male mice. Activation of microglia and astrocytes in response to systemic LPS was suppressed in CKO mice relative to WT mice. Proinflammatory cytokine production and intra-parenchymal infiltration of neutrophils strongly correlated with brain 25HC levels and were significantly lower in CKO compared to WT mice. Overall, our results show that 25HC mediates a sex-specific proinflammatory response in the brain characterized by activation of both microglia and astrocytes but also by neutrophil migration into the brain parenchyma presumably due to 7,25-diHC produced from 25HC.

neuroscience↗

bioRxiv2023

Electrical Coupling between Parvalbumin Basket Cells is Reduced after Experimental Status Epilepticus

Acquired epilepsies, characterized by abnormal increase in hypersynchronous network activity, can be precipitated by various factors including brain injuries which cause neuronal loss and increases in network excitability. Electrical coupling between neurons, mediated by gap junctions, has been shown to enhance synchronous neuronal activity and promote excitotoxic neurodegeneration. Consequently, neuronal gap junctional coupling has been proposed to contribute to development of epilepsy. Parvalbumin expressing interneurons (PV-INs), noted for their roles in powerful perisomatic inhibition and network oscillations, have gap junctions formed exclusively by connexin 36 subunits which show changes in expression following seizures, and in human and experimental epilepsy. However, only a fraction of the connexin hemichannels form functional connections, leaving open the critical question of whether functional gap junctional coupling between neurons is altered during development of epilepsy. Using a pilocarpine induced status epilepticus (SE) model of acquired temporal lobe epilepsy in rat, this study examined changes in electrical coupling between PV-INs in the hippocampal dentate gyrus one week after SE. Contrary to expectations, SE selectively reduced the probability of electrical coupling between PV-INs without altering coupling coefficient. Both coupling frequency and coupling coefficient between non-parvalbumin interneurons remained unchanged after SE. The early and selective decrease in functional electrical coupling between dentate PV-INs after SE may represent a compensatory mechanism to limit excitotoxic damage of fast-spiking interneurons and network synchrony during epileptogenesis.

neuroscience↗

bioRxiv2023

PaGeSearch: A Tool for Identifying Genes within Pathways in Unannotated Genomes

In biological research, the identification and comparison of genes within specific pathways across the genomes of various species are invaluable. However, annotating the entire genome is resource-intensive and sequence similarity searches often yield results that are not actually genes. To address these limitations, we introduce PaGeSearch (Pathway Gene Search), a tool designed to identify genes from predefined lists, especially those in specific pathways, within genomes. The tool employs an initial sequence similarity search to identify relevant genomic regions, followed by targeted gene prediction and neural network-based result filtering. PaGeSearch suggests the regions that are most likely the orthologs of the genes in the query and is designed to be applicable for species within five classes: mammals, fish, birds, eudicotyledons, and liliopsida. When compared with GeMoMa, PaGeSearch consistently outperformed in terms of sensitivity and positive predictive value. Although its performance showed increased variability when applied to actual biological pathways, it nonetheless maintained an acceptable level of accuracy.

bioinformatics↗

bioRxiv2023

Conditional Chemoconnectomics: A Set of Libraries Targeting All Chemical Transmission Corresponding Genes Efficiently

Dissection of neural circuitry underlying behaviors is a central theme in neurobiology. We have previously proposed the concept of chemoconnectome (CCT) to cover the entire chemical transmission between neurons and target cells in an organize and created tools for studying it (CCTomics) by targeting all genes related to the CCT in Drosophila. Here we have created lines targeting the CCT in conditional manners after modifying GFP RNA interference, Flp-out and CRISPR/Cas9 technologies. All three strategies are validated to be highly effective with the best using chromatin-peptide fused Cas9 variants and scaffold optimized sgRNAs. As a proof of principle, we conduct a comprehensive intersection analysis of CCT genes expression profiles in the clock neurons, uncovering 43 CCT genes present in clock neurons. Specific elimination of each from clock neurons revealed that loss of the neuropeptide CNMa in two posterior dorsal clock neurons (DN1ps) or its receptor (CNMaR) caused advanced morning activity, indicating a suppressive role of CNMa-CNMaR on morning anticipation, opposite to the promoting role of PDF-PDFR on morning anticipation. These results demonstrate the effectiveness of conditional CCTomics and its tools created by us here and establish an antagonistic relationship between CNMa-CNMaR and PDF-PDFR signaling in regulating morning anticipation.

neuroscience↗

bioRxiv2023

OpenCell: A Low-cost, Open-Source, 3-in-1 device for DNA Extraction

High-cost DNA extraction procedures pose significant challenges for budget-constrained laboratories. To address this, we introduce OpenCell, an economical, open-source, 3-in-1 laboratory device that combines the functionalities of a bead homogenizer, a microcentrifuge, and a vortex mixer. OpenCell utilizes modular attachments that magnetically connect to a central rotating brushless motor. This motor couples to an epicyclic gearing mechanism, enabling efficient bead homogenization, vortex mixing, and centrifugation within one compact unit. OpenCells design incorporates multiple redundant safety features, ensuring both the devices and operators safety. Additional features such as RPM measurement, programmable timers, battery operation, and optional speed control make OpenCell a reliable and reproducible laboratory instrument. In our study, OpenCell successfully isolated DNA from Spinacia oleracea (spinach), with an average yield of 2.3 {micro}g and an A260/A280 ratio of 1.77, demonstrating its effectiveness for downstream applications such as Polymerase Chain Reaction (PCR) amplification. With its compact size (20 cm x 28 cm x 6.7 cm) and lightweight design (0.8 kg), comparable to the size and weight of a laptop, OpenCell is portable, making it an attractive component of a lab-in-a-backpack for resource-constrained environments in low-and-middle-income countries and synthetic biology in remote field stations. Leveraging the accessibility of 3D printing and off-the-shelf components, OpenCell can be manufactured and assembled at a low unit cost of less than $50, providing an affordable alternative to expensive laboratory equipment costing over $4000. OpenCell aims to overcome the barriers to entry in synthetic biology research and contribute to the growing collection of frugal and open hardware.

bioengineering↗

bioRxiv2023

Antigenicity and receptor affinity of SARS-CoV-2 BA.2.86 spike

Although the COVID-19 pandemic has officially ended1, SARS-CoV-2 continues to spread and evolve. Recent infections have been dominated by XBB.1.5 and EG.5.1 subvariants2. A new subvariant designated BA.2.86 has just emerged, spreading to 21 countries in 5 continents3. This virus contains 34 spike mutations compared to its BA.2 predecessor, thereby raising concerns about its propensity to evade existing antibodies. We examined its antigenicity using human sera and monoclonal antibodies (mAbs). Reassuringly, BA.2.86 was not more resistant to human sera than XBB.1.5 and EG.5.1, indicating that the new subvariant would not have a growth advantage in this regard. Importantly, sera from patients who had XBB breakthrough infection exhibited robust neutralizing activity against all viruses tested, suggesting that upcoming XBB.1.5 monovalent vaccines could confer added protection. The finding that the longer genetic distance of BA.2.86 did not yield a larger antigenic distance was partially explained by the mAb data. While BA.2.86 showed greater resistance to mAbs to subdomain 1 (SD1) and receptor-binding domain (RBD) class 2 and 3 epitopes, it was more sensitive to mAbs to class 1 and 4/1 epitopes in the "inner face" of RBD that is exposed only when this domain is in the "up" position. We also identified six new spike mutations that mediate antibody resistance, including E554K that threatens SD1 mAbs in clinical development. The BA.2.86 spike also had a remarkably high receptor affinity. The ultimate trajectory of this new SARS-CoV-2 variant will soon be revealed by continuing surveillance, but its worldwide spread is worrisome.

microbiology↗

bioRxiv2023

Microglial 25-hydroxycholesterol mediates neuroinflammation and neurodegeneration ina tauopathy mouse model

Alzheimers disease (AD) is characterized by amyloid plaques and neurofibrillary tangles in addition to neuroinflammation and changes in brain lipid metabolism. Recent findings have demonstrated that microglia are key drivers of neurodegeneration in tauopathy mouse models. A subset of microglia referred to as disease-associated microglia (DAM) display gene signatures signifying changes in proinflammatory signaling and lipid metabolism in mouse models of amyloid and tau pathology. Ch25h is a DAM gene encoding cholesterol 25-hydroxylase that produces 25-hydroxycholesterol (25HC), a known modulator of inflammation as well as lipid metabolism. However, whether Ch25h influences tau-mediated neuroinflammation and neurodegeneration is unknown. Here, we show that in the absence of Ch25h and the resultant reduction in 25HC there is strikingly reduced age-dependent neurodegeneration and neuroinflammation in the hippocampus and entorhinal/piriform cortex of PS19 mice, which express the P301S mutant human tau transgene. Transcriptomic analyses of bulk hippocampal tissue and single nuclei revealed that Ch25h deficiency in PS19 mice strongly suppressed proinflammatory cytokine and chemokine signaling in microglia and restored sterol synthesis. Our results suggest a key role for Ch25h/25HC in potentiating proinflammatory signaling to promote tau-mediated neurodegeneration. Ch25h may represent a novel therapeutic target for primary tauopathies, AD, and other neuroinflammatory diseases.

neuroscience↗

bioRxiv2023

Trapping non-cognate nucleotide upon initial binding for replication fidelity control in SARS-CoV-2 RNA dependent RNA polymerase

AbstractThe RNA dependent RNA polymerase (RdRp) in SARS-CoV-2 is a highly conserved enzyme responsible for viral genome replication/transcription. Here we investigate computationally natural non-cognate vs cognate nucleotide addition cycle (NAC) and intrinsic nucleotide selectivity during the viral RdRp elongation, focusing prechemically from initial nucleotide substrate binding (enzyme active site open) to insertion (active site closed) of RdRp in contrast with one-step only substrate binding process. Current studies have been first carried out using microsecond ensemble equilibrium all-atom molecular dynamics (MD) simulations. Due to slow conformational changes (from the open to closed) accompanying nucleotide insertion and selection, enhanced or umbrella sampling methods have been further employed to calculate free energy profiles of the non-cognate NTP insertion. Our studies show notable stability of noncognate dATP and GTP upon initial binding in the active-site open state. The results indicate that while natural cognate ATP and Remdesivir drug analogue (RDV-TP) are biased to be stabilized in the closed or insertion state, the natural non-cognate dATP and GTP can be well trapped in off-path initial binding configurations. Current work thus presents an intrinsic nucleotide selectivity mechanism of SARS-CoV-2 RdRp for natural substrate fidelity control in viral genome replication.

biophysics↗

bioRxiv2023

New structural features of the APC/C revealed by high resolution cryo-EM structures of apo-APC/C and the APC/C CDH1:EMI1 complex

The multi-subunit anaphase-promoting complex/cyclosome (APC/C) is a master regulator of cell division. It controls progression through the cell cycle by timely marking mitotic cyclins and other cell cycle regulatory proteins for degradation. The APC/C itself is regulated by the sequential action of its coactivator subunits CDC20 and CDH1, post-translational modifications, and its inhibitory binding partners EMI1 and the mitotic checkpoint complex (MCC). In this study, we took advantage of the latest developments in cryo-electron microscopy (cryo-EM) to determine the structures of human APC/CCDH1:EMI1 and apo-APC/C at 2.9 [A] and 3.2 [A] resolution, respectively, providing novel insights into the regulation of APC/C activity. The high-resolution maps allowed the unambiguous assignment of a previously unassigned -helix to the N-terminus of CDH1 (CDH11) in the APC/CCDH1:EMI1 ternary complex. We also identified a novel zinc-binding module in APC2 that confers structural stability to APC2, and we confirmed the presence of zinc ions experimentally. Finally, due to the higher resolution and well defined density of these maps, we were able to build, aided by AlphaFold predictions, several intrinsically disordered regions in different APC/C subunits that likely play a role in proper APC/C assembly and regulation of its activity.

cell biology↗

bioRxiv2023

Identification and functional analysis of extrachromosomal circular DNA in plasma extracellular vesicles of liver failure patients

Withdrawal statementThe authors have withdrawn their manuscript owing to having identified certain issues with the current representation of the data in the manuscript after performing further analyses of the bioinformatics data from their eccDNA sequencing results. Therefore, the authors do not wish this work to be cited as reference for the project. A revised and corrected version will be submitted in the future. If you have any questions, please contact the corresponding authors.

genomics↗

bioRxiv2023

High-throughput generic single-entity sequencing using droplet microfluidics

Single-cell sequencing has revolutionized our understanding of cellular heterogeneity by providing a micro-level perspective over the past decades. Although heterogeneity is essential for various biological communities, the currently demonstrated platform predominantly focuses on eukaryotic cells without cell walls and their transcriptomics 1,2, leaving significant gaps in the study of omics from other single biological entities such as bacteria and viruses. Due to the difficulty of isolating and acquiring their DNA3, contemporary methodologies for the characterization of generic biological entities remain conspicuously constrained, with low throughput4, compromised lysis efficiency5, and highly fragmented genomes6. Herein, we present the Generic Single Entity Sequencing platform (GSE-Seq), which boasts ample versatility, high throughput, and high coverage, and is enabled by an innovative workflow, addressing the critical challenges in single entities sequencing: (1) one-step manufacturing of massive barcodes, (2) degradable hydrogel-based in situ sample processing and whole genome amplification, (3) integrated in-drop library preparation, (4) compatible long-read sequencing. By GSE-Seq, we have achieved a significant milestone by enabling high-throughput, long-read single-entity profiling of dsDNA and ssDNA from single virus sequencing (SV-seq) and single bacteria sequencing (SB-seq) of the human gut and marine sediment for the first time. Notably, our analysis uncovered previously overlooked viral and bacterial dark matter and phage-host interactions. In summary, the presented conceptually new workflow offers a toolbox based on droplet microfluidics to tackle the persistent challenges in high-throughput profiling to generic applications, which hold immense promise for diverse biological entities, especially hard-to-lyse cells.

bioengineering↗

bioRxiv2023

weIMPUTE: A User-Friendly Web-Based Genotype Imputation Platform

Genotype imputation is a critical preprocessing step in genome-wide association studies (GWAS), enhancing statistical power for detecting associated single nucleotide polymorphisms (SNPs) by increasing marker size. In response to the needs of researchers seeking user-friendly graphical tools for imputation without requiring informatics or computer expertise, we have developed weIMPUTE, a web-based imputation graphical user interface (GUI). Unlike existing genotype imputation software, weIMPUTE supports multiple imputation software, including SHAPEIT, Eagle, Minimac4, Beagle, and IMPUTE2, while encompassing the entire workflow, from quality control to data format conversion. This comprehensive platform enables both novices and experienced users to readily perform imputation tasks. For reference genotype data owners, weIMPUTE can be installed on a server or workstation, facilitating web-based imputation services without data sharing. weIMPUTE represents a versatile imputation solution for researchers across various fields, offering the flexibility to create personalized imputation servers on different operating systems.

bioinformatics↗

bioRxiv2023

Large-scale population genomics of Malayan pangolins reveals deep diversification and a new species

BackgroundArchipelagos and oceanic islands often present high percentage of endemism due to rapid speciation. The Malayan pangolin is a species distributing at both mainland (southern Yunnan, China) and oceanic islands via Malayan peninsula, which may result in deep differentiation among populations. In-depth investigation of population structure and genetic consequences for such species is of vital importance for their protection and conservation, practically for the critically endangered Malayan pangolin that is suffering from poaching, illegal trade, and habitat loss. ResultsHere we carried out a large-scale population genomic analysis for Malayan pangolins, and revealed three highly distinct genetic populations in this species, two of which are now being reported for the first time. Based on multiple lines of genomic and morphological evidence, we postulate the existence of a new pangolin species (Manis_1). Genetic diversity and recent inbreeding were both at a moderate level for both Malayan pangolins and Manis_1, but mainland Malayan pangolins presented relatively lower genetic diversity, higher inbreeding and fitness cost than island populations. ConclusionsWe found extremely deep and graded differentiation in Malayan pangolins, with two newly discovered genetic populations and a new pangolin species that is closely related to the Philippine pangolin than the typical Malayan pangolin, but a distant relative of the Indian pangolin. Anthropogenic factors did not significantly weaken the basis of genetic sustainability for Malayan pangolins, but mainland Malayan pangolins should be paid more attention for conservation due to higher genetic risks than island populations.

genomics↗

bioRxiv2023

OsNAC2 maintains the homeostasis of immune responses to bacterial blight through the OsEREBP1 in rice

Rice bacterial blight, caused by Xanthomonas oryzae pv. Oryzae (Xoo), threatens plant growth and yield. However, the molecular mechanisms underlying rice immunity against Xoo remain elusive. Here, we demonstrated down-regulation of a NAC (NAM-ATAF-CUC) transcription factor OsNAC2 enhanced resistance to bacterial blight disease in rice. Consistently, salicylic acid (SA) biosynthesis was greatly attenuated when OsNAC2 overexpressed. Furthermore, study demonstrated that OsNAC2 can down-regulated the expression of SA synthesis genes, thus mediating SA signal transmission. Simultaneously, OsNAC2 interacted with OsEREBP1 (AP2/ERF family) in the nucleus, may be bloking the inhibition of OsNAC2 to OsICS1, OsPAL3 and so on. Furthermore, OsEREBP1 interacted with OsXb22a in the cytoplasm to exert its positive regulatory effects to bacterial blight. However, OsNAC2-overexpression kept OsEREBP1 in the nucleus and be rapidly degraded in pathogen infection, which adversely affects the interaction of OsEREBP1-OsXb22a. Our results determined that OsNAC2 inhibits the SA signaling and stably interacts with OsEREBP1 to maintain disease resistance. This OsNAC2-OsEREBP1-based homeostatic mechanism provides new insights into rice disease resistance, and it may be useful for improving the disease resistance of important crops through breeding.

molecular biology↗

bioRxiv2023

A versatile framework for drug-target interaction prediction by considering domain specific features

Predicting drug-target interaction (DTI) is a critical and rate-limiting step in drug discovery. Traditional wet-lab experiments are reliable but expensive and time-consuming. Recently, deep learning has revealed itself as a new and promising tool for accelerating the DTI prediction process because its powerful performance. Due to the vast chemical space, the DTI prediction models are typically expected to discover drugs or targets that are absent from the training set. However, generalizing prediction performance to novel drug-target pairs that belong to different distributions is a challenge for deep learning methods. In this work, we propose an Ensemble of models that capture both Domain-generIc and domain-Specific features (E-DIS) to learn diversity domain features and adapt to out-of-distribution (OOD) data. We employed Mixture-of-Experts (MOE) as a domain-specific feature extractor for the raw data to prevent the loss of any crucial features by the encoder during the learning process. Multiple experts are trained on different domains to capture and align domain-specific information from various distributions without accessing any data from unseen domains. We evaluate our approach using four benchmark datasets under both in-domain and cross-domain settings and compare it with advanced approaches for solving OOD generalization problems. The results demonstrate that E-DIS effectively improves the robustness and generalizability of DTI prediction models by incorporating diversity domain features.

bioinformatics↗

bioRxiv2023

Harnessing Gradients for Self-Assembly of Peptide-Based Nanocapsules: A Pathway to Advanced Drug Delivery Systems

Biological systems often create materials with intricate structures to achieve specialized functions. In comparison, precise control of structures in man-made materials has been challenging. Here, we report a serendipitous discovery of insect cuticle peptides (ICPs) spontaneously forming nanocapsules through a single-step solvent exchange process, where the concentration gradient resulting from mixing of water and aceton drives the localization and self-assembly of the peptides into hollow nanocapsules. The underlying driving force is the intrinsic affinity of the peptides for a particular solvent concentration, while the diffusion of water and acetone creates a gradient interface that triggers peptide localization and self-assembly. This gradient-mediated self-assembly offers a transformative pathway towards next-generation drug delivery systems based on peptide nanocapsules.

bioengineering↗

bioRxiv2023

Novel multifunctional glycan probes to elucidate specificities of diverse glycan recognition systems

Glycan microarrays of sequence-defined glycans are the most widely used approach for high-throughput studies of interactions of glycans with glycan binding proteins. Currently nitrocellulose (NC) coated or N-hydroxysuccinimide (NHS) functionalized glass slides are the two most commonly used surfaces for immobilizing glycan probes as noncovalent and covalent arrays, respectively. The mode of glycan presentation can have an influence on the microarray readouts and is an important consideration in the glycan recognition knowledgebase. Here we present the development of glycan probes, tagged with a novel type of tri-functional Fmoc-amino-azido (FAA) linker, which can be readily converted into lipid-tagged or amino-terminating glycan probes for generating neoglycolipid (NGL)-based noncovalent arrays as well as covalent arrays. The azido functionality in the FAA glycan probes provides a means to light up the glycans via biorthogonal Click chemistry so that they become scanner-readable on the covalent arrays, which represents an advance in array quality control. Here analyses were carried out with a diverse set of 36 glycan binding proteins (GBPs) to compare the performance of 44 glycans presented in a liposomal formulation as noncovalent arrays on NC coated slides and on two types of NHS slides as covalent arrays. With most of anti-glycan antibodies and plant lectins investigated, there were negligible or subtle differences in the binding detected in different arrays. However, there were some striking differences observed between the covalent and noncovalent arrays. These include binding of Lotus Tetragonolobus Lectin (LTL) on the covalent but not the noncovalent arrays, and a clear preference observed for glycans on the noncovalent array in the binding of adhesins (VP1 proteins) of two human polyomaviruses JCPyV and BKPyV, and the human immune lectins Siglecs 7 and 9. Subtle yet significant differences in the binding to low affinity glycan ligands were also observed with three bacterial toxins in different arrays. These results revealed interesting insights into the binding behaviour of different GBPs on the noncovalent and covalent arrays and highlight the importance to consider different array platforms in elucidating glycan mediated interactions. The FAA glycan probes can be readily rendered fluorescent via Click chemistry in solution, enabling the detection of GBPs at the surface of cells. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=149 SRC="FIGDIR/small/548266v1_ufig1.gif" ALT="Figure 1"> View larger version (66K): org.highwire.dtl.DTLVardef@8f2a49org.highwire.dtl.DTLVardef@1212409org.highwire.dtl.DTLVardef@c4ea39org.highwire.dtl.DTLVardef@1ed6a88_HPS_FORMAT_FIGEXP M_FIG C_FIG A new trifunctional linker can present glycans on different array surfaces for analyses of soluble glycan binding proteins or as fluorescent probes for binding by proteins at the surface of cells.

biochemistry↗