Biomedical subjects

Lili Yang

Publications and source records attributed to Lili Yang.

15 recordsLinked to original sources

PubMed2026

Hepatotoxicity of OBS: A review of the emerging PFOS substitute.

As an alternative to perfluorooctanesulfonic acid (PFOS), sodium perfluorononenyl oxobenzene sulfonate (OBS) is widely used due to its cost-effectiveness. Multiple studies have shown that the liver is a classic target organ for OBS. However, there is currently no systematic review on the hepatotoxic effects of OBS. This review systematically summarizes the exposure characteristics of OBS in the environment and human populations, as well as its mechanisms of liver toxicity. In vivo studies consistently demonstrate that OBS induces hepatotoxic effects, such as hepatomegaly, vacuolization, elevated serum transaminases, and lipid dysregulation, though the manifestation of these phenotypes varies across species and exposure routes. In vitro evidence further shows that OBS reduces cell viability and survival, and triggers necrosis accompanied by inflammation. Mechanistically, oxidative stress, inflammatory signaling, and metabolism disorder are implicated. Critically, most existing work addresses subacute or subchronic exposure, leaving a gap in chronic risk assessment for long-term, low-dose OBS exposure. Moreover, mechanistic studies have focused predominantly on downstream transcriptional and signaling changes, with limited exploration of upstream epigenetic controls. Overall, this study aims to provide a comprehensive reference for future toxicological investigations and liver injury risk assessments related to OBS exposure.

Humans↗

PubMed2026

Plasmids as persistent genetic reservoirs of bacterial defense systems in wastewater treatment.

BACKGROUND: Bacterial antiphage defense systems play essential roles in microbial ecology, yet their dynamics within urban wastewater systems (UWS) remain poorly characterized. RESULTS: In this study, we performed comprehensive metagenomic and plasmidome analyses on 78 wastewater samples collected during two seasons and four sampling points across UWS from three European countries. We observed a significant reduction in the abundance, diversity, and mobility potential of defense systems during biological treatment. However, these reductions were not directly correlated with changes in microbial abundance. Defense systems were significantly enriched on plasmids, particularly conjugative plasmids, where their gene density was approximately twice as high as on chromosomes and remained relatively stable across compartments. In contrast to chromosomal defense systems, plasmid-borne systems exhibited more frequent co-localization with a wide range of mobile genetic elements (MGEs)-associated genes, thereby facilitating multilayered dissemination networks. Furthermore, we detected a strong correlation between phage abundance and host defense system profiles, indicating ongoing phage-host co-evolutionary dynamics in these environments. CONCLUSIONS: In summary, our results demonstrate that UWS reduce the abundance and diversity of bacterial defense system genes. However, plasmid-associated defense systems can persist through shared mobile genetic reservoirs. These findings underscore the critical role of plasmids in bacterial immunity and provide new insights into defense system dynamics within urban wastewater environments.

Plasmids↗

PubMed2006

Genetic mapping of two powdery mildew resistance genes in einkorn (Triticum monococcum L.) accessions.

Powdery mildew is a severe foliar disease for wheat and could cause great yield loss in epidemic years. To explore new powdery mildew resistance genes, two einkorn accessions including TA2033 and M80, both resistant to this disease, were studied for the inheritance of resistance. Each accession possessed a single but different dominant resistance gene that was designated as Mlm2033 and Mlm80, respectively. Marker mapping indicated that they are both linked to Xgwm344 on the long arm of chromosome 7A. To establish their genetic relationship with Pm1 on 7AL, five RFLP markers previously reported to co-segregate with Pm1a were converted to STS markers. Three of them detected polymorphism between the mapping parents and were mapped close to Mlm2033 or Mlm80 or both. Xmag2185, the locus determined by the STS marker derived from PSR680, one of the RFLP markers, was placed less than 2 cM away from them. The allelism test indicated that Mlm2033 and Mlm80 are likely allelic to each other. In addition, through comparative and EST mapping, more markers linked to these two genes were identified. The high density mapping of Mlm2033 and Mlm80 will contribute to map-based cloning of the Pm1 locus. The markers for both genes will also facilitate their transfer to wheat.

Ascomycota↗

PubMed2006

Targeting lentiviral vectors to specific cell types in vivo.

We have developed an efficient method to target lentivirus-mediated gene transduction to a desired cell type. It involves incorporation of antibody and fusogenic protein as two distinct molecules into the lentiviral surface. The fusogen is constructed by modifying viral envelope proteins, so that they lack the ability to bind to their cognate receptor but still retain the ability to trigger pH-dependent membrane fusion. Thus, the specificity of such a lentiviral vector is solely determined by the antibody, which is chosen to recognize a specific surface antigen of the desired cell type. This specific binding then induces endocytosis of the surface antigen, bringing the lentivirus into an endosome. There, the fusogen responds to the low pH environment and mediates membrane fusion, allowing the virus core to enter the cytosol. Using CD20 as a target antigen for human B cells, we have demonstrated that this targeting strategy is effective both in vitro and in intact animals. This methodology is flexible and can be extended to other forms of cell type-specific recognition to mediate targeting. The only requirement is that the antibody (or other binding protein) must be endocytosed after interaction with its cell surface-binding determinant.

Animals↗

PubMed2005

Long-term in vivo provision of antigen-specific T cell immunity by programming hematopoietic stem cells.

A method to genetically program mouse hematopoietic stem cells to develop into functional CD8 or CD4 T cells of defined specificity in vivo is described. For this purpose, a bicistronic retroviral vector was engineered that efficiently delivers genes for both alpha and beta chains of T cell receptor (TCR) to hematopoietic stem cells. When modified cell populations were used to reconstruct the hematopoietic lineages of recipient mice, significant percentages of antigen-specific CD8 or CD4 T cells were observed. These cells expressed normal surface markers and responded to peptide antigen stimulation by proliferation and cytokine production. Moreover, they could mature into memory cells after peptide stimulation. Using TCRs specific for a model tumor antigen, we found that the recipient mice were able to partially resist a challenge with tumor cells carrying the antigen. By combining cells modified with CD8- and CD4-specific TCRs, and boosting with dendritic cells pulsed with cognate peptides, complete suppression of tumor could be achieved and even tumors that had become established would regress and be eliminated after dendritic cell/peptide immunization. This methodology of "instructive immunotherapy" could be developed for controlling the growth of human tumors and attacking established pathogens.

Animals↗

PubMed2005

A novel GCAP1 missense mutation (L151F) in a large family with autosomal dominant cone-rod dystrophy (adCORD).

PURPOSE: To elucidate the phenotypic and biochemical characteristics of a novel mutation associated with autosomal dominant cone-rod dystrophy (adCORD). METHODS: Twenty-three family members of a CORD pedigree underwent clinical examinations, including visual acuity tests, standardized full-field ERG, and fundus photography. Genomic DNA was screened for mutations in GCAP1 exons using DNA sequencing and single-strand conformational polymorphism (SSCP) analysis. Function and stability of recombinant GCAP1-L151F were tested as a function of [Ca(2+)], and its structure was probed by molecular dynamics. RESULTS: Affected family members experienced dyschromatopsia, hemeralopia, and reduced visual acuity by the second to third decade of life. Electrophysiology revealed a nonrecordable photopic response with later attenuation of the scotopic response. Affected family members harbored a C-->T transition in exon 4 of the GCAP1 gene, resulting in an L151F missense mutation affecting the EF hand motif 4 (EF4). This change was absent in 11 unaffected family members and in 100 unrelated normal subjects. GCAP1-L151F stimulation of photoreceptor guanylate cyclase was not completely inhibited at high physiological [Ca(2+)], consistent with a lowered affinity for Ca(2+)-binding to EF4. CONCLUSIONS: A novel L151F mutation in the EF4 hand domain of GCAP1 is associated with adCORD. The clinical phenotype is characterized by early cone dysfunction and a progressive loss of rod function. The biochemical phenotype is best described as persistent stimulation of photoreceptor guanylate cyclase, representing a gain of function of mutant GCAP1. Although a conservative substitution, molecular dynamics suggests a significant change in Ca(2+)-binding to EF4 and EF2 and changes in the shape of L151F-GCAP1.

Adolescent↗

PubMed2004

Transgenic tall fescue containing the Agrobacterium tumefaciens ipt gene shows enhanced cold tolerance.

Embryogenic calli of Festuca arundinacea were transformed with the Agrobacterium tumefaciens isopentenyl transferase (ipt) gene driven by a maize ubiquitin promoter. Tillering ability, levels of chlorophyll a and b, and cold tolerance were greatly increased in the transgenic turfgrass, which resulted in the plants remaining more vigorous and staying green longer under lower temperatures.

Acclimatization↗

PubMed2004

Diversity of guanylate cyclase-activating proteins (GCAPs) in teleost fish: characterization of three novel GCAPs (GCAP4, GCAP5, GCAP7) from zebrafish (Danio rerio) and prediction of eight GCAPs (GCAP1-8) in pufferfish (Fugu rubripes).

The guanylate cyclase-activating proteins (GCAPs) are Ca(2+)-binding proteins of the calmodulin (CaM) gene superfamily that function in the regulation of photoreceptor guanylate cyclases (GCs). In the mammalian retina, two GCAPs (GCAP 1-2) and two transmembrane GCs have been identified as part of a complex regulatory system responsive to fluctuating levels of free Ca(2+). A third GCAP, GCAP3, is expressed in human and zebrafish (Danio rerio) retinas, and a guanylate cyclase-inhibitory protein (GCIP) has been shown to be present in frog cones. To explore the diversity of GCAPs in more detail, we searched the pufferfish (Fugu rubripes) and zebrafish (Danio rerio) genomes for GCAP-related gene sequences (fuGCAPs and zGCAPs, respectively) and found that at least five additional GCAPs (GCAP4-8) are predicted to be present in these species. We identified genomic contigs encoding fuGCAPl-8, fuGCIP, zGCAPl-5, zGCAP7 and zGCIP. We describe cloning, expression and localization of three novel GCAPs present in the zebrafish retina (zGCAP4, zGCAP5, and zGCAP7). The results show that recombinant zGCAP4 stimulated bovine rod outer segment GC in a Ca(2+)-dependent manner. RT-PCR with zGCAP specific primers showed specific expression of zGCAPs and zGCIP in the retina, while zGCAPl mRNA is also present in the brain. In situ hybridization with anti-sense zGCAP4, zGCAP5 and zGCAP7 RNA showed exclusive expression in zebrafish cone photoreceptors. The presence of at least eight GCAP genes suggests an unexpected diversity within this subfamily of Ca(2+)-binding proteins in the teleost retina, and suggests additional functions for GCAPs apart from stimulation of GC. Based on genome searches and EST analyses, the mouse and human genomes do not harbor GCAP4-8 or GCIP genes.

Amino Acid Sequence↗

PubMed2004

A novel mutation (I143NT) in guanylate cyclase-activating protein 1 (GCAP1) associated with autosomal dominant cone degeneration.

PURPOSE: To identify pathogenic mutations in the guanylate cyclase-activating protein 1 (GCAP1) and GCAP2 genes and to characterize the biochemical effect of mutation on guanylate cyclase (GC) stimulation. METHODS: The GCAP1 and GCAP2 genes were screened by direct sequencing for mutations in 216 patients and 421 patients, respectively, with various hereditary retinal diseases. A mutation in GCAP1 segregating with autosomal dominant cone degeneration was further evaluated biochemically by employing recombinant proteins, immunoblotting, Ca2+-dependent stimulation of GC, fluorescence emission spectra, and limited proteolysis in the absence and presence of Ca2+. RESULTS: A novel GCAP1 mutation, I143NT (substitution of Ile at codon 143 by Asn and Thr), affecting the EF4 Ca2+-binding loop, was identified in a heterozygote father and son with autosomal dominant cone degeneration. Both patients had much greater loss of cone function versus rod function; previous histopathologic evaluation of the father's eyes at autopsy (age 75 years) showed no foveal cones but a few, scattered cones remaining in the peripheral retina. Biochemical analysis showed that the GCAP1-I143NT mutant adopted a conformation susceptible to proteolysis, and the mutant inhibited GC only partially at high Ca2+ concentrations. Individual patients with atypical or recessive retinitis pigmentosa (RP) had additional heterozygous GCAP1-T114I and GCAP2 gene changes (V85M and F150C) of unknown pathogenicity. CONCLUSIONS: A novel GCAP1 mutation, I143NT, caused a form of autosomal dominant cone degeneration that destroys foveal cones by mid-life but spares some cones in the peripheral retina up to 75 years. Properties of the GCAP1-I143NT mutant protein suggested that it is incompletely inactivated by high Ca2+ concentrations as should occur with dark adaptation. The continued activity of the mutant GCAP1 likely results in higher-than-normal scotopic cGMP levels which may, in turn, account for the progressive loss of cones.

Adult↗

PubMed2003

Essential role for STAT5 signaling in CD25+CD4+ regulatory T cell homeostasis and the maintenance of self-tolerance.

A population of CD25(+)CD4(+) regulatory T cells (T regs) functions to maintain immunological self tolerance by inhibiting autoreactive T cell responses. CD25(+)CD4(+) T regs are present in low, but steady, numbers in the peripheral lymphoid tissues of healthy mice. Recent studies have shown that IL-2 is an essential growth factor for these cells. How this cytokine functions to regulate CD25(+)CD4(+) T reg homeostasis and prevent autoimmune disease remains unknown. In conventional CD4(+) T cells, IL-2 triggers signaling pathways that promote proliferation and survival by activating the STAT5 transcription factor and by increasing the expression of the antiapoptotic protein, Bcl-2. We show here that bcl-2 deficiency does not affect CD25(+)CD4(+) T reg homeostasis, and that ectopic expression of this molecule fails to rescue CD25(+)CD4(+) T reg numbers or to prevent the development of autoimmunity in IL-2-deficient mice. Furthermore, transient activation of STAT5 is sufficient to increase CD25(+)CD4(+) T reg numbers in IL-2-deficient mice. Our study uncovers an essential role for STAT5 in maintaining CD25(+)CD4(+) T reg homeostasis and self-tolerance.

Animals↗

PubMed2003

A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference.

RNA interference (RNAi) has recently emerged as a specific and efficient method to silence gene expression in mammalian cells either by transfection of short interfering RNAs (siRNAs; ref. 1) or, more recently, by transcription of short hairpin RNAs (shRNAs) from expression vectors and retroviruses. But the resistance of important cell types to transduction by these approaches, both in vitro and in vivo, has limited the use of RNAi. Here we describe a lentiviral system for delivery of shRNAs into cycling and non-cycling mammalian cells, stem cells, zygotes and their differentiated progeny. We show that lentivirus-delivered shRNAs are capable of specific, highly stable and functional silencing of gene expression in a variety of cell types and also in transgenic mice. Our lentiviral vectors should permit rapid and efficient analysis of gene function in primary human and animal cells and tissues and generation of animals that show reduced expression of specific genes. They may also provide new approaches for gene therapy.

Animals↗

PubMed2002

Pseudophosphorylated prolactin (S179D PRL) inhibits growth and promotes beta-casein gene expression in the rat mammary gland.

We have investigated the individual roles of unmodified prolactin (U-PRL) and a mimic of phosphorylated PRL (S179D PRL) in mammary development. Recombinant versions of the PRLs were delivered to rats throughout pregnancy at a rate of 6 microg/24 h per rat and to non-pregnant females at a rate of 24 microg/24 h per rat. Measurement of progesterone, corticosterone, and estradiol showed no effect of the administered PRLs on the levels of these other mammotropic hormones. Histological and morphometric analysis showed U-PRL to cause mammary growth, whereas S179D PRL inhibited growth. Molecular analysis demonstrated decreased beta-casein expression in the mammary glands of the U-PRL-treated animals at term and increased beta-casein expression in the mammary glands of the S179D PRL-treated animals. Superior beta-casein gene expression in response to S179D PRL versus U-PRL was confirmed in HC11 cells. We conclude that U-PRL is important for growth, whereas S179D PRL promotes at least one measure of differentiated function in the mammary gland.

Amino Acid Substitution↗

PubMed2002

Generation of functional antigen-specific T cells in defined genetic backgrounds by retrovirus-mediated expression of TCR cDNAs in hematopoietic precursor cells.

We have developed an alternative to transgenesis for producing antigen-specific T cells in vivo. In this system, clonal naive T cells with defined antigen specificity are generated by retrovirus-mediated expression of T cell antigen receptor cDNAs in RAG1-deficient murine hematopoietic precursor cells. These T cells can be stimulated to proliferate and produce cytokines by exposure to antigen in vitro, and they become activated and expand in vivo after immunization. IL-2-deficient T cells generated by this technique show decreased proliferation and cytokine production, both of which can be rescued by exogenous addition of this growth factor. Thus, retrovirus-mediated expression of T cell antigen receptor cDNAs in hematopoietic precursor cells permits the rapid and efficient analysis of the life history of antigen-specific T cells in different genetic backgrounds and may allow for the long-term production of antigen-specific T cells with different functional properties for prophylactic and therapeutic purposes.

Animals↗

PubMed2002

Maternal prolactin composition can permanently affect epidermal gammadeltaT cell function in the offspring.

There have been few studies aimed at determining the effects of maternal peptide hormones on the developing fetus and even fewer aimed at determining the long-term consequences of abnormalities in maternal hormone exposure. In this study, we have examined the effect of maternal prolactin (PRL) on the production, seeding and long-term function of a T lymphocyte subset for which the precursors are only present during fetal life. Using this system, we can determine long-term consequences of maternal hormone exposure without concern for the subsequent influence of the offspring's endocrine milieu. Recombinant versions of the two major forms of the pituitary hormone, PRL, were administered to rats throughout pregnancy. Administration of a molecular mimic of phosphorylated PRL (PP-PRL) resulted in a marked increase in the level of apoptosis in the thymus of newborn pups, an effect that was not duplicated by administration of unmodified PRL. The increased thymic apoptosis in the animals exposed to PP-PRL resulted in decreased epidermal seeding of gammadeltaT cells and a markedly decreased gammadeltaT cell-modulated epidermal response in the offspring. This decreased gammadeltaT cell modulated response persisted to adulthood. We conclude that maternal PRL composition during pregnancy can have a permanent effect on at least one component of the developing immune system.

Animals↗

PubMed2002

[Effects of refined konjac meal on lipid metabolism and blood viscosity of rats fed by high fat forage].

Male SD rats are fed by high fat diet supplemented with refined konjac meal for 6 weeks and the effect of refined konjac meal on the serum lipid peroxides (LPO) and blood viscosity are observed. The results showed that the refined konjac meal can obviously decrease serum cholesterol, triglyceride and serum LPO of rats in comparison with those of rats fed only by high fat forage, and can elevate, at the same time, the high density lipoprotein-cholesterol and high density lipoprotein-cholesterol/triglyceride value. It is also shown that the refined konjac meal can decrease the blood viscosity, but has no effect on forage intake and weight gain of rats.

Animals↗