Biomedical subjects

Yuli Li

Publications and source records attributed to Yuli Li.

7 recordsLinked to original sources

PubMed2026

Spatially resolved single-cell atlas reveals the macroevolutionary trajectory of animal hearts.

Animal hearts display diverse anatomical structures during adaptive evolution. Here, we present a multiomics atlas of adult hearts from 27 species across chordates, arthropods, and mollusks. Joint analysis indicates that Bilateria hearts share a core gene repertoire, taking a stepwise "add-on" approach as a universal evolutionary strategy. The "proto-heart" is populated by key cell types, including cardiomyocytes, fibroblasts, endothelial cells, and neural cells, which maintained core signatures while evolving with shifts in living environments and corresponding adaptations in the cardiovascular system. Additionally, we reveal an evolutionarily conserved cardiomyocyte state dynamic potentially linked to cardiac development and stress responses. Finally, we identify a common molecular program underpinning chamber evolution from a ventricular foundation. This work establishes a resource for understanding the intrinsic mechanisms of heart evolution.

Animals↗

PubMed2025

A method for the detection and enrichment of endogenous cereblon substrates.

C-terminal cyclic imides are posttranslational modifications (PTMs) on proteins that are recognized and removed by the E3 ligase substrate adapter cereblon (CRBN). Despite the observation of these modifications across the proteome by mass spectrometry-based proteomics, an orthogonal and generalizable method to visualize the C-terminal cyclic imide would enhance detection, sensitivity, and throughput of endogenous CRBN substrate characterization. Here, we develop an antibody-like reagent, termed "cerebody," for visualizing and enriching C-terminal cyclic imide-modified proteins. We describe the engineering of CRBN derivatives to produce cerebody and use it to identify CRBN substrates by western blot and enrichment from whole-cell and tissue lysates. CRBN substrates identified by cerebody enrichment are mapped, validated, and further characterized for dependence on the C-terminal cyclic imide modification. These methods will accelerate the characterization of endogenous CRBN substrates and their regulation.

Humans↗

PubMed2004

KARMA: a web server application for comparing and annotating heterogeneous microarray platforms.

We have developed a universal web server application (KARMA) that allows comparison and annotation of user-defined pairs of microarray platforms based on diverse types of genome annotation data (across different species) collected from multiple sources. The application is an effective tool for diverse microarray platforms, including arrays that are provided by (i) the Keck Microarray Resource at Yale, (ii) commercially available Affymetrix GeneChips and spotted arrays and (iii) custom arrays made by individual academics. The tool provides a web interface that allows users to input pairs of test files that represent diverse array platforms for either single or multiple species. The program dynamically identifies analogous DNA fragments spotted or synthesized on multiple microarray platforms based on the following types of information: (i) NCBI-Unigene identifiers, if the platforms being compared are within the same species or (ii) NCBI-Homologene data, if they are cross-species. The single-species comparison is implemented based on set operations: intersection, union and difference. Other forms of retrievable annotation data, including LocusLink, SwissProt and Gene Ontology (GO), are collected from multiple remote sites and stored in an integrated fashion using an Oracle database. The KARMA database, which is updated periodically, is available on line at the following URL: http://ymd.med.yale.edu/karma/cgi-bin/karma.pl.

Gene Expression Profiling↗

PubMed2004

LFIRE-1/HFREP-1, a liver-specific gene, is frequently downregulated and has growth suppressor activity in hepatocellular carcinoma.

We have previously identified several novel genes, which are differentially expressed among human normal liver and hepatocellular carcinomas (HCCs). The full-length liver fibrinogen-related gene-1 (LFIRE-1) cDNA was cloned from the human normal liver cDNA library. LFIRE-1 is highly homologous to HFREP-1 with discrepancy at 5' untranslated region (UTR) and encodes the same fibrinogen-related protein, which suggest that these two sequences might be alternative splicing forms of the same gene, LFIRE-1/HFREP-1, located at human chromosome 8p22. The LFIRE-1 and HFREP-1 are specifically expressed in normal human liver tissue, but reduced or undetectable in most of HCC specimens at both RNA and protein level. Furthermore, the reduction or nonexpression of LFIRE-1/HFREP-1 is significantly associated with the degree of tumor differentiation. Loss of heterozygosity (LOH) analysis revealed allelic loss of LFIRE-1/HFREP-1 on chromosome 8p22 in 57.1% (24/42) of HCC specimens. We detected three inactivation mutations among 45 cases of HCC specimens examined, two of which lost the remaining allele and the third had a replacement of conserved cysteine residue with glycine residue. Notably, the downregulation of LFIRE-1/HFREP-1 expression is frequently associated with allelic loss. The reduction of LFIRE-1/HFREP-1 expression by antisense approach enhances cancer cell proliferation and colony formation in soft agar. Moreover, restoration of exogenous wild-type LFIRE-1/HFREP-1 expression but not LFIRE-1/HFREP-1 missense mutations in human HCC cells inhibited their anchorage-dependent or -independent growth in vitro, and suppressed their tumorigenicity in nude mice. In conclusion, our data demonstrated that liver-specific gene LFIRE-1/HFREP-1 was frequently downregulated and might possess growth suppressor activity in HCC.

5' Untranslated Regions↗

PubMed2002

Effect of oxymatrine on murine fulminant hepatitis and hepatocyte apoptosis.

OBJECTIVE: To evaluate the protective effects and mechanism of action of oxymatrine (OM) on the experimental fulminant hepatitis (FH) and early hepatocyte apoptosis in murine liver tissue. METHODS: Fulminant hepatitis mice were induced by injecting lipopolysaccharide (LPS) intraperitoneally (ip) in galactosamine (GalN) sensitized mice. Two separate experiments were designed, including saline control group, fulminant hepatitis group and oxymatrine pretreated group (50 mg/kg, intraperitoneally, bid x 3 days). The levels of serum tumor necrosis factor alpha (TNFa) in mice from two experiments were determined at 5-hour and 7.5-hour after injecting galactosamine/lipopolysaccharide. Mouse liver samples at 5-hour time point were obtained for in situ end labeling (ISEL) staining and ultrastructural observation of apoptotic cells under transmission electron microscope (TEM). Liver samples at 7.5-hour time point were taken for hematoxylin-eosin (HE) staining and immunohistochemical staining of Fas and its ligand (FasL). RESULTS: As compared with the fulminant hepatitis group, the levels of serum tumor necrosis factor alpha in mice from the OM pretreated group at 5-hour and 7.5-hour time point were all significantly decreased (P < 0.05 and P < 0.01 respectively). Hepatocyte apoptosis in mice at 5-hour time point was significantly inhibited (P < 0.01). Both the degree of liver injury and the degree of Fas and Fas ligand expression in the OM pretreated group were reduced remarkably (P < 0.01 and 0.05 respectively) when compared with the saline control group. CONCLUSIONS: Oxymatrine protects mice from fulminant hepatitis induced by GalN/LPS and may block hepatocyte apoptosis and subsequent necrosis through downregulating the production of serum tumor necrosis factor alpha and the expression of Fas and Fas ligand in liver tissue.

Alkaloids↗

PubMed2002

YMD: a microarray database for large-scale gene expression analysis.

The use of microarray technology to perform parallel analysis of the expression pattern of a large number of genes in a single experiment has created a new frontier of medical research. The vast amount of gene expression data generated from multiple microarray experiments requires a robust database system that allows efficient data storage, retrieval, secure access, data dissemination, and integrated data analyses. To address the growing needs of microarray researchers at Yale and their collaborators, we have built the Yale Microarray Database (YMD). YMD is Web-accessible with the following features: (i) a Web program that tracks DNA samples between source plates and arrays, (ii) the capability of finding common genes/clones across different array platforms, (iii) an image file server, (iv) laboratory-based user management and access privileges, (v) project management, (vi) template data entry, (vii) linking gene expression data to annotation databases for functional analysis. YMD is currently being used on a pilot basis by several laboratories for different organisms and array platforms.

Databases, Nucleic Acid↗

PubMedDate not supplied

A dynamic approach to mapping coordinates between microplates and microarrays.

The retrieval of useful data from spotted microarray slides requires keeping track of which microplate wells and DNA sample corresponds to each spot on each array slide. Existing approaches are closely coupled with the type of arrayer in use and are computer operating-system-specific. To support the microarray researcher community at large who use different arrayers and computer platforms, increased flexibility, generality, and portability of these approaches are required. In this paper, we describe a general algorithm that correlates the well positions of DNA samples in each microplate to the positions of the spots on each array slide. Based on this algorithm, we have implemented a flexible and platform-independent program named MicroArray Convolutor (MAC) that provides a Web solution allowing the user to: (a) import a text file that identifies the DNA samples and their well locations, (b) select a transformation method that converts data in 96-well plate format into 384-well plate format, and (c) specify the output format of the array lists dependant on the configuration of the array platform as well as the downstream analysis software chosen for the array. MAC and its source code can be accessed via the following Web address: http://ymd.med.yale.edu/kei-cgi/kc_mac_dev8.pl.

Algorithms↗