Biomedical subjects

Yun Deng

Publications and source records attributed to Yun Deng.

At least 19 recordsLinked to original sources

PubMed2025

A General Framework for Branch Length Estimation in Ancestral Recombination Graphs.

Inference of Ancestral Recombination Graphs (ARGs) is of central interest in the analysis of genomic variation. ARGs can be specified in terms of topologies and coalescence times. The coalescence times are usually estimated using an informative prior derived from coalescent theory, but this may generate biased estimates and can also complicate downstream inferences based on ARGs. Here we introduce, POLEGON, a novel approach for estimating branch lengths for ARGs which uses an uninformative prior. Using extensive simulations, we show that this method provides improved estimates of coalescence times and lead to more accurate inferences of effective population sizes under a wide range of demographic assumptions (population expansion, bottleneck, split, etc). It also improves other downstream inferences including estimates of mutation rates. We apply the method to data from the 1000 Genomes Project to investigate population size histories and differential mutation signatures across populations. We also estimate coalescence times in the HLA region, and show that they exceed 30 million years in multiple segments.

Ancestral Recombination Graph↗

PubMed2025

Robust and accurate Bayesian inference of genome-wide genealogies for hundreds of genomes.

The Ancestral Recombination Graph (ARG), which describes the genealogical history of a sample of genomes, is a vital tool in population genomics and biomedical research. Recent advancements have substantially increased ARG reconstruction scalability, but they rely on approximations that can reduce accuracy, especially under model misspecification. Moreover, they reconstruct only a single ARG topology and cannot quantify the considerable uncertainty associated with ARG inferences. Here, to address these challenges, we introduce SINGER (sampling and inferring of genealogies with recombination), a method that accelerates ARG sampling from the posterior distribution by two orders of magnitude, enabling accurate inference and uncertainty quantification for hundreds of whole-genome sequences. Through extensive simulations, we demonstrate SINGER's enhanced accuracy and robustness to model misspecification compared to existing methods. We demonstrate the utility of SINGER by applying it to individuals of British and African descent within the 1000 Genomes Project, identifying signals of population differentiation, archaic introgression and strong support for ancient polymorphism in the human leukocyte antigen region shared across primates.

Humans↗

PubMed2024

Development of methodology to support molecular endotype discovery from synovial fluid of individuals with knee osteoarthritis: The STEpUP OA consortium.

OBJECTIVES: To develop a protocol for largescale analysis of synovial fluid proteins, for the identification of biological networks associated with subtypes of osteoarthritis. METHODS: Synovial Fluid To detect molecular Endotypes by Unbiased Proteomics in Osteoarthritis (STEpUP OA) is an international consortium utilising clinical data (capturing pain, radiographic severity and demographic features) and knee synovial fluid from 17 participating cohorts. 1746 samples from 1650 individuals comprising OA, joint injury, healthy and inflammatory arthritis controls, divided into discovery (n = 1045) and replication (n = 701) datasets, were analysed by SomaScan Discovery Plex V4.1 (>7000 SOMAmers/proteins). An optimised approach to standardisation was developed. Technical confounders and batch-effects were identified and adjusted for. Poorly performing SOMAmers and samples were excluded. Variance in the data was determined by principal component (PC) analysis. RESULTS: A synovial fluid standardised protocol was optimised that had good reliability (<20% co-efficient of variation for >80% of SOMAmers in pooled samples) and overall good correlation with immunoassay. 1720 samples and >6290 SOMAmers met inclusion criteria. 48% of data variance (PC1) was strongly correlated with individual SOMAmer signal intensities, particularly with low abundance proteins (median correlation coefficient 0.70), and was enriched for nuclear and non-secreted proteins. We concluded that this component was predominantly intracellular proteins, and could be adjusted for using an 'intracellular protein score' (IPS). PC2 (7% variance) was attributable to processing batch and was batch-corrected by ComBat. Lesser effects were attributed to other technical confounders. Data visualisation revealed clustering of injury and OA cases in overlapping but distinguishable areas of high-dimensional proteomic space. CONCLUSIONS: We have developed a robust method for analysing synovial fluid protein, creating a molecular and clinical dataset of unprecedented scale to explore potential patient subtypes and the molecular pathogenesis of OA. Such methodology underpins the development of new approaches to tackle this disease which remains a huge societal challenge.

Humans↗

PubMed2023

Ypel5 regulates liver development and function in zebrafish.

YPEL5 is a member of the Yippee-like (YPEL) gene family that is evolutionarily conserved in eukaryotic species. To date, the physiological function of YPEL5 has not been assessed due to a paucity of genetic animal models. Here, using CRISPR/Cas9-mediated genome editing, we generated a stable ypel5-/- mutant zebrafish line. Disruption of ypel5 expression leads to liver enlargement associated with hepatic cell proliferation. Meanwhile, hepatic metabolism and function are dysregulated in ypel5-/- mutant zebrafish, as revealed by metabolomic and transcriptomic analyses. Mechanistically, Hnf4a is identified as a crucial downstream mediator that is positively regulated by Ypel5. Zebrafish hnf4a overexpression could largely rescue ypel5 deficiency-induced hepatic defects. Furthermore, PPARα signaling mediates the regulation of Hnf4a by Ypel5 through directly binding to the transcriptional enhancer of the Hnf4a gene. Herein, this work demonstrates an essential role of Ypel5 in hepatocyte proliferation and function and provides the first in vivo evidence for a physiological role of the ypel5 gene in vertebrates.

Animals↗

PubMed2006

Genome-wide reverse genetics framework to identify novel functions of the vertebrate secretome.

BACKGROUND: Understanding the functional role(s) of the more than 20,000 proteins of the vertebrate genome is a major next step in the post-genome era. The approximately 4,000 co-translationally translocated (CTT) proteins - representing the vertebrate secretome - are important for such vertebrate-critical processes as organogenesis. However, the role(s) for most of these genes is currently unknown. RESULTS: We identified 585 putative full-length zebrafish CTT proteins using cross-species genomic and EST-based comparative sequence analyses. We further investigated 150 of these genes (Figure 1) for unique function using morpholino-based analysis in zebrafish embryos. 12% of the CTT protein-deficient embryos resulted in specific developmental defects, a notably higher rate of gene function annotation than the 2%-3% estimate from random gene mutagenesis studies. CONCLUSION: This initial collection includes novel genes required for the development of vascular, hematopoietic, pigmentation, and craniofacial tissues, as well as lipid metabolism, and organogenesis. This study provides a framework utilizing zebrafish for the systematic assignment of biological function in a vertebrate genome.

Amino Acid Sequence↗

PubMed2006

Cloning and expression of a novel human gene, Isl-2, encoded a LIM-homeodomain protein.

The LIM-homeodomain (LIM-HD) proteins have a homeodomain and two N-terminal LIM domains, which consist of a conserved cysteine- and histidine-rich structure of two tandem repeated zinc fingers. LIM domain is involved in protein-protein interactions during transcriptional regulation. LIM-HD proteins are classically suggested as major transcriptional regulators which, in cooperation with other transcription factors, play critical roles in several developing systems and organs, such as nervous system, pancreas, and heart. Here we have cloned the full-length cDNA of human Isl-2 from a human embryo heart cDNA library. The gene contains six exons and spans 5.7 kb in chromosome 15q23 region, and transcribes a 1.9 kb mRNA that encodes a protein with 359 amino acid residues. The predicted protein, containing two tandem LIM motifs in N-terminal and a homeodomain domain, is well conserved, especially in the LIM and DNA-binding domains. Northern blot analysis shows that human Isl-2 is expressed in every human tissue examined at adult stage and during embryonic developmental stages from 34 days to 24 weeks at different levels in tissues. The broad expression of Isl-2 gene in tissues during embryogenesis and adult development suggests that it may be involved in both differentiation and maintenance of these tissues and might play an important role.

Amino Acid Sequence↗

PubMed2006

A novel zinc-finger protein ZNF436 suppresses transcriptional activities of AP-1 and SRE.

Mitogen-activated protein kinases (MAPKs) are evolutionary conserved enzymes in cell signal transduction connecting cell-surface receptors to critical regulatory targets within cells and control cell survival, adaptation, and proliferation. Previous studies revealed that zinc finger proteins are involved in the regulation of the MAPK signaling pathways. Here we report the identification and characterization of a novel human zinc finger protein, ZNF436. The cDNA of ZNF436 is 3.8 kb, encoding 470 amino acids in the nucleus. The protein is highly conserved in evolution across different vertebrate species from rat to human. RT-PCR indicates that ZNF436 is expressed in all the human fetal tissues examined, with a high level in brain and heart. Overexpression of pCMV-tag2A-ZNF436 in the COS-7 cells represses the transcriptional activities of SRE and AP-1. These results suggest that ZNF436 is a member of the zinc finger transcription factor family and may act as a negative regulator in gene transcription mediated by the MAPK signaling pathways.

Amino Acid Sequence↗

PubMed2006

A novel human gene ZNF415 with five isoforms inhibits AP-1- and p53-mediated transcriptional activity.

The zinc finger proteins are the single largest class of transcription factors in human genome. Previous studies revealed that zinc finger proteins are involved in transcriptional activation and regulation of apoptosis, etc. Alternative splicing emerges as a major mechanism of generating protein diversity and many zinc finger proteins reported have isoforms. In this article, we identify and characterize five isoforms of a novel zinc finger gene named ZNF415; these five isoforms were named ZNF415-1 to ZNF415-5. The five isoforms display different subcellular localization and are expressed at different levels in both embryonic and adult tissues. Furthermore, the splicing variants of ZNF415 display different transcriptional activity. Except for ZNF415-1, overexpression of the other ZNF415 isoforms in COS-7 cells inhibits the transcriptional activities of AP-1 and p53, suggesting that the ZNF415 protein may be involved in AP-1- and p53-mediated transcriptional activity.

Animals↗

PubMed2006

A novel human zinc finger protein ZNF540 interacts with MVP and inhibits transcriptional activities of the ERK signal pathway.

Mitogen-activated protein kinases (MAPKs) are evolutionarily conserved enzymes in cell signal transduction. Previous studies revealed that zinc finger proteins are involved in the regulation of the MAPK signaling pathways. Here we report the identification and characterization of a novel human zinc finger protein, ZNF540. The cDNA of ZNF540 is 3.3kb, encoding 660 amino acids in the nucleus and the cytoplasm. Northern blot analysis indicates that ZNF540 is expressed in most of the fetal tissues. Overexpression of FLAG-ZNF540 in COS-7 cells represses the transcriptional activities of SRE and ELK-1, which can be relieved by siRNA. MVP, one of MAPK scaffold proteins, is identified as a potential ZNF540-binding protein. This interaction is detected by a yeast two-hybrid assay, reporter gene assays, and co-immunoprecipitation. Taken together, these results suggest that ZNF540 may act as a transcriptional repressor in MAPK signaling pathway to mediate cellular functions.

Amino Acid Sequence↗

PubMed2006

ZNF325, a novel human zinc finger protein with a RBaK-like RB-binding domain, inhibits AP-1- and SRE-mediated transcriptional activity.

Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of eukaryotic cell regulation. The zinc-finger-containing transcription factors have been previously revealed to be involved in the regulation of the MAPK signaling pathways. Here, we have identified a novel human zinc-finger transcriptional repressor, ZNF325, that contains a RBaK-like RB-binding domain and 15 tandem repeated C2H2 type zinc fingers. Northern blot analysis indicates that a 2.7 kb transcript specific for ZNF325 is widely expressed in all tissues examined at adult stage and in most of the embryonic tissues. Overexpression of ZNF325 in COS-7 cells inhibits the transcriptional activities of AP-1 and SRE. The deletion and RNAi analysis indicate that the C2H2 zinc finger motifs represent the basal transcriptional repressive activity. These results indicate that the ZNF325 protein may act as a novel transcription repressor in MAPK signaling pathway to mediate cellular functions.

Amino Acid Sequence↗

PubMed2006

Adsorption behaviors of L-arginine from aqueous solutions on a spherical cellulose adsorbent containing the sulfonic group.

An investigation was conducted regarding the adsorption and desorption of L-arginine from aqueous solutions with a new spherical cellulose adsorbent containing the sulfonic group. The adsorption of L-arginine on the adsorbent was time, pH, initial concentration of L-arginine and temperature dependent. The adsorption process followed the Langmuir adsorption isotherm, and was endothermic (DeltaH =24.66 KJ/mol). Almost 100% L-arginine adsorbed on the adsorbent could be recovered with a 2.0 mol/L NH4OH or 2.0 mol/L NH4Cl aqueous solution. After 25 and 40 cycles of adsorption and desorption, the decrease in adsorption capacity reached to 4.9% and 20.3%, respectively.

Adsorption↗

PubMed2006

ZNF569, a novel KRAB-containing zinc finger protein, suppresses MAPK signaling pathway.

Transcription factors play an essential role in altering gene expression. A great progress about transcription factors has been made towards the understanding of normal physiological processes, embryonic development, and human diseases. Here we report the identification and characterization of a novel KRAB-containing zinc-finger protein, ZNF569, which is isolated from a human embryonic heart cDNA library. ZNF569 encodes a putative protein of 686 amino acids. The protein is conserved across different species during evolution. Expression of ZNF569 was found in most of the examined human adult and embryonic tissues with a higher level in heart and skeletal muscles. The KRAB and ZNF motifs of ZNF569 represent potent repression domains. When ZNF569 is fused to Gal-4 DNA-binding domain and co-transfected with VP-16, ZNF569 protein suppresses transcriptional activity. Overexpression of ZNF569 in COS-7 cells inhibited the transcriptional activities of SRE and AP-1, which may be silenced by siRNA. The results suggest that ZNF569 protein may act as a transcriptional repressor that suppresses MAPK signaling pathway to mediate cellular functions.

Amino Acid Motifs↗

PubMed2006

pi-Conjugated chelating polymers with charged iridium complexes in the backbones: synthesis, characterization, energy transfer, and electrochemical properties.

A series of pi-conjugated chelating polymers with charged iridium (Ir) complexes in the backbones were synthesized by a Suzuki polycondensation reaction, leading to homogeneous polymeric materials that phosphoresce red light. The fluorene and bipyridine (bpy) segments were used as polymer backbones. 5,5'-Dibromobipyridine served as a ligand to form a charged iridium complex monomer with 1-(9'9-dioctylfluorene-2-yl)isoquinoline (Fiq) as the cyclometalated ligand. Chemical and photophysical characterization confirmed that Ir complexes were incorporated into the backbones as one of the repeat units by means of the 5,5'-dibromobipyridine ligand. Chelating polymers showed almost complete energy transfer from the host fluorene segments to the guest Ir complexes in the solid state when the feed ratio was 2 mol %. In the films of the corresponding blend system, however, energy transfer was not complete even when the content of Ir complexes was as high as 16 mol %. Both intra- and intermolecular energy-transfer processes existed in this host-guest system, and the intramolecular energy transfer was a more efficient process. All chelating polymers displayed good thermal stability, redox reversibility, and film formation. These chelating polymers also showed more efficient energy transfer than the corresponding blended system and the mechanism of incorporation of the charged Ir complexes into the pi-conjugated polymer backbones efficiently avoided the intrinsic problems associated with the blend system, thus offering promise in optoelectronic applications.

Journal Article↗

PubMed2006

hnulp1, a basic helix-loop-helix protein with a novel transcriptional repressive domain, inhibits transcriptional activity of serum response factor.

Many bHLH proteins are involved in cardiac development and cardiovascular diseases. Herein, we identified and characterized the human homologue (hnulp1) of mouse gene nulp1. The predicted protein contains a bHLH domain and a DUF654 domain in N-terminal and C-terminal, respectively. Northern blot analysis shows that a 2.3-kb transcript expressed broadly in early human embryonic and adult tissues, especially with a higher level in adult heart. hnulp1 is a transcription repressor when fused to GAL4 DNA-binding domain and co-transfected with VP-16, in which DUF654 motif represents the basal transcriptional repressive activity. Treatment of cells with trichostatin A can relieve this repression, suggesting that the DUF654 motif acts through increasing deacetylase activity at the GAL4-driven promoter. Overexpression of hnulp1 protein in COS-7 cells inhibits the transcriptional activity of serum response factor (SRF), suggesting that hnulp1 may act as a novel bHLH transcriptional repressor in SRF signaling pathway to mediate cellular functions.

Amino Acid Sequence↗

PubMed2006

A new amide from Thyrocarpus glochidiatus.

A new amide, 4-hydroxy-N-[4-[3-(4-hydroxy-phenyl)-E-acryloylamino]-butyl]-benzamide, trivially named as glochidiatusamide (1), along with 5 known compounds, beta-sitosterol, daucosterol, coffee acid, ethyl caffeate, and kaempferol-3-O-beta-D-glucoside, were isolated from the ethanol extract of Thyrocarpus glochidiatus Maxim. Their structures were elucidated by the spectral and chemical evidence.

Benzamides↗

PubMed2006

Expression and identification of a novel apoptosis gene Spata17 (MSRG-11) in mouse spermatogenic cells.

In this study, anti-spermatogenesis-associated 17 (Spata17) polyclonal antibody was prepared by immunizing New Zealand white rabbits with a synthesized peptide corresponding to the amino acid sequence 7-23 of the mouse Spata17 protein. Immunohistochemical analysis revealed that Spata17 protein was most abundant in the cytoplasm of round spermatids and elongating spermatids within seminiferous tubules of the adult testis. The expression of Spata17 mRNA in cultured mouse spermatogonia (GC-1) cells was almost undetectable. In an experimental unilateral cryptorchidism model of an adult mouse, the expression of Spata17 mRNA had no obvious difference with the normal testis until postoperation day 1, but gradually decreased from day 3 and was almost undetectable on day 17. Immunohistochemical analysis revealed that the protein was almost undetectable within seminiferous tubules of an experimental unilateral cryptorchidism model of the adult testis on postoperation day 8. Flow cytometry analysis showed that the expression of Spata17 protein in the GC-1 cell line could accelerate GC-1 cell apoptosis. The effect increases with the increasing of the transfected dose of pcDNA3.1(-)/Spata17. By Hoechst 33258 staining, a classical way of identifying apoptotic cells, we further confirmed that the apoptosis was induced by expression of Spata17 in transfected GC-1 cells.

Animals↗

PubMed2006

[A new sesqui-norlignan from Herpetospermum pedunculosum].

AIM: To study the chemical components from the bioactive extract of Herpetospermum pedunculosum, a Tibetan medicinal herb for liver diseases. METHODS: The isolation and purification of this extract were conducted by means of silica gels column chromatography and preparative HPLC. The structures of the compounds were elucidated based on their physical and chemical features, and spectral data. RESULTS: Two lignans were isolated from this extract. They were elucidated as herpetone (I), dehydrodiconiferyl alcohol (II). CONCLUSION: Compound I is a new compound with the rare structure of sesqui-norlignan. Compound II is isolated from the genus of Herpetospermum for the first time.

Chromatography, Gel↗

PubMed2005

Identification of a novel testis-specific gene mtLR1, which is expressed at specific stages of mouse spermatogenesis.

A novel testis-specific gene termed mtLR1 was identified by digital differential display. Sequence analyses revealed that mtLR1 protein contains an amino terminus leucine-rich repeat domain and shows 33% similarities to PIDD which functions in p53-mediated apoptosis. Northern blot analysis showed that mtLR1 mRNA was specifically expressed in adult mouse testis, and RT-PCR results also showed that mtLR1 was exclusively expressed in adult testis and not in spermatogonial cells. The expression of mtLR1 mRNA was developmentally upregulated in the testes during sexual maturation and was, conversely, downregulated by experimental cryptorchidism in vivo. We also showed that the expression of mtLR1 mRNA was relatively highly sensitive to heat stress in vitro. The green fluorescent protein produced by pEGFP-C3/mtLR1 was only detected in the cytoplasm of spermatogonia cell line GC-1 after 24 h posttransfection. Immunohistochemical analysis revealed that the protein is most abundant in the cytoplasm of spermatocytes and round spermatids within seminiferous tubules of the adult testis. The time-dependent expression pattern of mtLR1 in postnatal mouse testes suggested that mtLR1 gene might be involved in the regulation of spermatogenesis and sperm maturation.

Aging↗