Biomedical subjects

Ling Yuan

Publications and source records attributed to Ling Yuan.

6 recordsLinked to original sources

PubMed2026

Evidence supporting the role of GIGYF2 in synapse development and autism.

Autism spectrum disorder (ASD) is a heterogeneous condition in which genetically defined subtypes offered insights into underlying biological mechanisms and potential targeted treatments. Here, we investigate the clinical and pathogenic significance of GIGYF2 variants in ASD through an integrated approach combining clinical genetics, conditional knockout (cKO) mouse models, neurobiology, and molecular studies. Through targeted sequencing, large-scale genomic data analysis of neurodevelopmental disorder cohorts, and international collaborations, we identified ten affected individuals from eight families harboring de novo or dominantly inherited likely gene-disruptive (LGD) variants and 13 affected individuals from 13 families with de novo missense variants in GIGYF2. Clinical characterization of 16 probands with GIGYF2 variants revealed common features, including ASD, language problems, intellectual disability, and anxiety. In a Gigyf2 cKO mouse model, we observed pronounced autistic-like behaviors, cognitive deficits, and anxiety-like behaviors, mirroring phenotypes observed in affected individuals. Mechanistically, Gigyf2 deficiency disrupted synaptic homeostasis, as evidenced by altered spine density and miniature excitatory postsynaptic currents, and impaired IGF-1R/mTOR signaling, along with dysregulation of synapse-related genes such as Nrp2. Pharmacological inhibition of mTOR with rapamycin or Torin1, as well as Nrp2 knockdown rescued synaptic defects in Gigyf2 KO neurons. These findings define a novel ASD subtype associated with GIGYF2 variants and establish GIGYF2 as a key regulator of synaptic development and function, implicating GIGYF2 dysfunction in ASD pathogenesis and highlighting the IGF-1R/mTOR pathway as a potential therapeutic target for GIGYF2-related ASD subtype.

Journal Article↗

PubMed2005

Directed evolution of metabolic pathways.

The modification of cellular metabolism is of biotechnological and commercial significance because naturally occurring metabolic pathways are the source of diverse compounds used in fields ranging from medicine to bioremediation. Directed evolution is the experimental improvement of biocatalysts or cellular properties through iterative genetic diversification and selection procedures. The creation of novel metabolic functions without disrupting the balanced intracellular pool of metabolites is the primary challenge of pathway manipulation. The introduction of coordinated changes across multiple genetic elements, in conjunction with functional selection, presents an integrated approach for the modification of metabolism with benign physiological consequences. Directed evolution formats take advantage of the dynamic structures of genomes and genomic sub-structures and their ability to evolve in multiple directions in response to external stimuli. The elucidation, design and application of genome-restructuring mechanisms are key elements in the directed evolution of cellular metabolic pathways.

Biotechnology↗

PubMed2005

Laboratory-directed protein evolution.

Systematic approaches to directed evolution of proteins have been documented since the 1970s. The ability to recruit new protein functions arises from the considerable substrate ambiguity of many proteins. The substrate ambiguity of a protein can be interpreted as the evolutionary potential that allows a protein to acquire new specificities through mutation or to regain function via mutations that differ from the original protein sequence. All organisms have evolutionarily exploited this substrate ambiguity. When exploited in a laboratory under controlled mutagenesis and selection, it enables a protein to "evolve" in desired directions. One of the most effective strategies in directed protein evolution is to gradually accumulate mutations, either sequentially or by recombination, while applying selective pressure. This is typically achieved by the generation of libraries of mutants followed by efficient screening of these libraries for targeted functions and subsequent repetition of the process using improved mutants from the previous screening. Here we review some of the successful strategies in creating protein diversity and the more recent progress in directed protein evolution in a wide range of scientific disciplines and its impacts in chemical, pharmaceutical, and agricultural sciences.

DNA Shuffling↗

PubMed2005

[Phototactic behavior of Daphnia carinata as an indicator of chromium biotoxicity].

The study on the phototactic behavior of Daphnia carinata clone Dc42 as an indicator of chromium biotoxicity showed that the phototaxis inhibition ratio (Rpi) of D. carinata could better indicate the chromium status in water. There was a negative linear correlation between phototactic index (Ip) and Cr6+ concentration in standardized K2Cr2O7 solutions (R2=0.8089, P<0.001). The detection limit of Cr6+ by Ip was 0.056 mg x L(-1), much lower than that of LC50 or EC50, and the mean precision index for detection reached up to 5.46%, which suggested the sensitivity, precision and reliability of this method in monitoring chemicals biotoxicity.

Animals↗

PubMed2003

Changes in phototactic behavior of Daphnia magna clone C1 242 in response to copper, cadmium and pentachlorophenol.

In order to develop a sound biotechnique for monitoring water quality that builds on the previous experiments carried out in our laboratory, a specific D. magna clone C1 242 was used to study the effects of pollutants on phototactic behavior. In all experiments, the animals showed a stable and repeatable phototactic index approximated 0.2 in the presence and 0.4 in the absence of fish kairomones, which decreased significantly in response to pollutants. There existed no pollutant x fish kairomone interaction, indicating the changes in phototactic behavior of animals imposed by pollutants were independent of the presence of fish kairomones. The detection limits for changes in phototactic behavior of D. magna clone C1 242 are 0.04 mg/L for copper, 0.02 mg/L for cadmium, and 0.80 mg/L for PCP, respectively, quite lower than LC50 (48 h). The changes in phototactic behavior in presence to pollutants occurred quickly (3 h) compared to the period over whole acute toxicity tests. Therefore, D. magna clone C1 242 could be potentially used to monitor water quality. Moreover, the phototactic behavior did not decrease further in the pollutant mixtures employed in our experiments compared to individual pollutants, except in the Cd-PCP treatment. This fact suggests that the formation of water quality criteria must be based upon pollutant mixture tests.

Analysis of Variance↗

PubMed2002

Polyenoic fatty acid isomerase from the marine alga Ptilota filicina: protein characterization and functional expression of the cloned cDNA.

The recently described enzyme, polyenoic fatty acid isomerase (PFI), from the marine alga Ptilota filicina J. Argardh has been analyzed with respect to its protein structure and an associated cofactor. The enzyme was purified to homogeneity (as judged by SDS-PAGE and silver staining). By sedimentation equilibrium ultracentrifugation the mass of the native enzyme was estimated to be 125 kDa. The N-terminal peptide sequence derived from this protein was used to isolate two very similar cDNA clones encoding novel 500-amino acid proteins, both with calculated molecular masses of 55.9 kDa and pIs of 4.87. The data predict translation of a preprotein containing a signal peptide of 21 amino acids that is removed during maturation. Deglycosylation assays demonstrate that native PFI from P. filicina is a glycoprotein. The purified protein is chromophoric with a flavin-like UV spectrum and sequence analysis reveals the presence of a flavin-binding motif near the mature N-terminus. Heterologous expression of active PFI in Arabidopsis, using one of the cDNA clones, was successful as evidenced by conversion of arachidonic acid to a conjugated triene in an in vitro assay of the transgenic plant tissues.

Amino Acid Sequence↗