2K Papers found (0.016 seconds)

Liu D et al. (2011) Antioxid Redox Signal "p53, oxidative stress, and aging."

[

Antioxid Redox Signal,

2011]

Mammalian aging is associated with elevated levels of oxidative damage of DNA, proteins, and lipids as a result of unbalanced prooxidant and antioxidant activities. Accumulating evidence indicates that oxidative stress is a major physiological inducer of aging. p53, the guardian of the genome that is important for cellular responses to oxidative stresses, might be a key coordinator of oxidative stress and aging. In response to low levels of oxidative stresses, p53 exhibits antioxidant activities to eliminate oxidative stress and ensure cell survival; in response to high levels of oxidative stresses, p53 exhibits pro-oxidative activities that further increase the levels of stresses, leading to cell death. p53 accomplishes these context-dependent roles by regulating the expression of a panel of genes involved in cellular responses to oxidative stresses and by modulating other pathways important for oxidative stress responses. The mechanism that switches p53 function from antioxidant to prooxidant remains unclear, but could account for the findings that increased p53 activities have been linked to both accelerated aging and increased life span in mice. Therefore, a balance of p53 antioxidant and prooxidant activities in response to oxidative stresses could be important for longevity by suppressing the accumulation of oxidative stresses and DNA damage.

Liu D et al. (2018) BMC Bioinformatics "Inferring synteny between genome assemblies: a systematic evaluation."

Liu D, Hunt M, Tsai IJ

[

BMC Bioinformatics,

2018]

BACKGROUND: Genome assemblies across all domains of life are being produced routinely. Initial analysis of a new genome usually includes annotation and comparative genomics. Synteny provides a framework in which conservation of homologous genes and gene order is identified between genomes of different species. The availability of human and mouse genomes paved the way for algorithm development in large-scale synteny mapping, which eventually became an integral part of comparative genomics. Synteny analysis is regularly performed on assembled sequences that are fragmented, neglecting the fact that most methods were developed using complete genomes. It is unknown to what extent draft assemblies lead to errors in such analysis. RESULTS: We fragmented genome assemblies of model nematodes to various extents and conducted synteny identification and downstream analysis. We first show that synteny between species can be underestimated up to 40% and find disagreements between popular tools that infer synteny blocks. This inconsistency and further demonstration of erroneous gene ontology enrichment tests raise questions about the robustness of previous synteny analysis when gold standard genome sequences remain limited. In addition, assembly scaffolding using a reference guided approach with a closely related species may result in chimeric scaffolds with inflated assembly metrics if a true evolutionary relationship was overlooked. Annotation quality, however, has minimal effect on synteny if the assembled genome is highly contiguous. CONCLUSIONS: Our results show that a minimum N50 of 1Mb is required for robust downstream synteny analysis, which emphasizes the importance of gold standard genomes to the science community, and should be achieved given the current progress in sequencing technology.

Liu D et al. (2016) Biomicrofluidics "An automated microfluidic system for screening Caenorhabditis elegans behaviors using electrotaxis."

Selvaganapathy PR, Liu D, Gupta B

[

Biomicrofluidics,

2016]

Caenorhabditis elegans (C. elegans) is a widely used animal model to study mechanisms of biological processes and human diseases. To facilitate manipulations of C. elegans in the laboratory, researchers have developed various tools that permit careful monitoring of behavior and changes in cellular processes. Earlier, we had reported a novel microfluidic assay device to study the neuronal basis of movement and to investigate the effects of cellular and environmental factors that can induce degeneration in certain neurons leading to movement disorder. The system involved the use of an electric field to perform electrotaxis assays, which allows detailed examination of movement responses of animals. One of the potential uses of this system is to perform genetic and chemical screenings for neuroprotective factors; however, it could not be done due to manual operations and low throughput. In this paper, we present an integrated microfluidic system that automates screening of C. elegans behavioral response using electrotaxis. The core component of system is a multilayer poly dimethyl siloxane (PDMS) device, which enables C. elegans loading, capture, flush, release, electrotaxis, and clean sequentially with the help of other components. The system is capable of screening C. elegans, at a throughput of more than 20 worms per hour, automatically and continually without human intervention. To demonstrate the effectiveness of the system, C. elegans neuronal mutants were screened, and the phenotype data were extracted and analyzed. We envision that the automatic screening potential of the system will accelerate the study of neuroscience, drug discovery, and genetic screens in C. elegans.

LIU, D. et al. (2017) International Worm Meeting "A correlation of germ cells and male somatic sex development in C. elegans."

YU, B., Liu, P., Li, X., LIU, D.

[

International Worm Meeting,

2017]

Sex development/differentiation is a combinatorial effect of both genetic and environmental determinants. In a developing gonad, sex determinant gene and sex hormone coordinate to determine the sex of both germ and somatic cells, while maintenance of germ cell sex is regulated by signals from somatic gonad cells. Increasingly accumulated evidence reveals a role of germ cells in somatic sex development that is not restricted to the gonad, yet the underlying mechanism remains to be explored. To investigate the relationship between germ cells and somatic sex development in a well-defined system, we use germ line deficient mutant worm (C. elegans) and find that male-specific organs/tissues such as mating rays, trunk/tail diagonal muscles and somatic gonad are malformed in the absence of germ cells, whereas mutant hermaphrodites do not show any morphological defects. In addition, vitellogenin encoding genes are abnormally expressed in male intestine cells, indicating a feminized intestine. Thus, the presence of germ cells is essential for male somatic sex differentiation and/or maintenance. By profiling gene expression of germ-free worms and confirmation, germ cells appear genetically upstream of a key somatic sex determination pathway component, HER-1. RNAi screening of 58 nuclear hormone receptor (NHR) genes, which are also identified via analyzing profiled gene expression of male germ-free mutant, indicates that nhr-23 is downstream of her-1, regulating development of mating ray. While nhr-14 is negatively regulated by germ cells and upstream of mab-3, responsible for the ectopic expression of vitellogenin genes in male intestine. Therefore, germ cells likely coordinate male somatic sex development/differentiation, in which the steroid hormones are largely involved, although C. elegans worm lacks an endocrine system.

Liu D et al. (2007) Mol Cell Biol "The human SETMAR protein preserves most of the activities of the ancestral Hsmar1 transposase."

Buisine N, Chalmers R, Bischerour J, Bigot Y, Liu D, Siddique A

[

Mol Cell Biol,

2007]

Transposons have contributed protein coding sequences to a unexpectedly large number of human genes. Except for the V(D)J recombinase and telomerase, all remain of unknown function. Here we investigate the activity of the human SETMAR protein, a highly expressed fusion between a histone H3 methylase and a mariner family transposase. Although SETMAR has demonstrated methylase activity and a DNA repair phenotype, its mode of action and the role of the transposase domain remain obscure. As a starting point to address this problem, we have dissected the activity of the transposase domain in the context of the full-length protein and the isolated transposase domain. Complete transposition of an engineered Hsmar1 transposon by the transposase domain was detected, although the extent of the reaction was limited by a severe defect for cleavage at the 3'' ends of the element. Despite this problem, SETMAR retains robust activity for the other stages of the Hsmar1 transposition reaction, namely, site-specific DNA binding to the transposon ends, assembly of a paired-ends complex, cleavage of the 5'' end of the element in Mn(2+), and integration at a TA dinucleotide target site. SETMAR is unlikely to catalyze transposition in the human genome, although the nicking activity may have a role in the DNA repair phenotype. The key activity for the mariner domain is therefore the robust DNA-binding and looping activity which has a high potential for targeting the histone methylase domain to the many thousands of specific binding sites in the human genome provided by copies of the Hsmar1 transposon.

Liu D et al. (2020) Aging (Albany NY) "Carnitine promotes recovery from oxidative stress and extends lifespan in C. elegans."

Li L, Ou ZL, Zeng X, Liu D

[

Aging (Albany NY),

2020]

Carnitine is required for transporting fatty acids into the mitochondria for -oxidation. Carnitine has been used as an energy supplement but the roles in improving health and delaying aging remain unclear. Here we show in C. elegans that L-carnitine improves recovery from oxidative stress and extends lifespan. L-carnitine promotes recovery from oxidative stress induced by paraquat or juglone and improves mobility and survival in response to H2O2 and human amyloid (A) toxicity. L-carnitine also alleviates the oxidative stress during aging, resulting in moderate but significant lifespan extension, which was dependent on SKN-1 and DAF-16. Long-lived worms with germline loss (glp-1) or reduced insulin receptor activity (daf-2) recover from aging-associated oxidative stress faster than wild-type controls and their long lifespans were not further increased by L-carnitine. A new gene, T08B1.1, aligned to a known carnitine transporter OCTN1 in humans, is required for L-carnitine uptake in C. elegans. T08B1.1 expression is elevated in daf-2 and glp-1 mutants and its knockdown prevents L-carnitine from improving oxidative stress recovery and prolonging lifespan. Together, our study suggests an important role of L-carnitine in oxidative stress recovery that might be important for healthy aging in humans.

Liu D et al. (2013) Environ Toxicol Pharmacol "Realgar bioleaching solution is a less toxic arsenic agent in suppressing the Ras/MAPK pathway in Caenorhabditis elegans."

Bai Y, Zhi D, Yu Q, Liu D, Zhou T, Wan F, Li H

[

Environ Toxicol Pharmacol,

2013]

To explore other arsenic derivatives with anticancer effects and fewer adverse effects, realgar bioleaching solution (RBS) has been found to be a viable approach. Here we used C. elegans as a model organism to its possible efficacy for anti-cancer effect of RBS. Our results indicated that RBS significantly suppressed the multivulva (Muv) phenotype of let-60 ras(gf) mutant that was positive correlated to arsenic concentrations in worms and also inhibited Muv phenotype of lin-15(lf) upstream of Ras/MAPK pathway, but did not affect the Muv phenotype resulting from loss-of-function mutations of lin-l(lf) downstream of Ras/MAPK pathway, which may be mechanism-based. In toxicity tests, RBS did not lead to reduction resulting from arsenic trioxide (ATO) in the number of pharyngeal pumping which was orthologous to vertebrate heart beating in wild type C. elegans. Overall, RBS was likely to be a potential anti-cancer drug candidate with high efficiency and low toxicity.

Liu D et al. (2019) Theranostics "Using near-infrared enhanced thermozyme and scFv dual-conjugated Au nanorods for detection and targeted photothermal treatment of Alzheimer's disease."

Li W, Shan Y, Liu X, Jiang X, Kuai Z, Shi Y, Gao R, Bai S, Liu D, Liu J, Kong W

[

Theranostics,

2019]

Investigation of targeting inhibitors of A aggregation, heme-A peroxidase-like activity and efficient detectors of A aggregation, are of therapeutic value and diagnostics significance for the treatment of Alzheimer's disease (AD). Due to the complex pathogenesis of AD, theranostics treatment with multiple functions are necessary. Herein we constructed the NIR absorption property of gold nanorods (GNRs) loaded with single chain variable fragment (scFv) 12B4 and thermophilic acylpeptide hydrolase (APH) ST0779 as a smart theranostic complex (GNRs-APH-scFv, GAS), which possesses both rapid detection of A aggregates and NIR photothermal treatment that effectively disassembles A aggregates and inhibits A-mediated toxicity. Methods: We screened targeting anti-A scFv 12B4 and thermophilic acylpeptide hydrolase as amyloid-degrading enzyme, synthesized GAS gold nanorods complex. The GAS was evalued by A inhibition and disaggregation assays, A detection assays, A mediated toxicity assays in vitro. In vivo, delaying A-induced paralysis in AD model of Caenorhabditis elegans was also tested by GAS. Results: In vitro, GAS has a synergistic effect to inhibit and disassociate A aggregates, in addition to decrease heme-A peroxidase-like activity. In cultured cells, treatment with GAS reduces A-induced cytotoxicity, while also delaying A-mediated paralysis in CL4176 C.elegans model of AD. Furthermore, the photothermal effect of the GAS upon NIR laser irradiation not only helps disassociate the A aggregates but also boosts APH activity to clear A. The GAS, as a targeting detector and inhibitor, allows real-time detection of A aggregates. Conclusion: These results firstly highlight the combination of scFv, APH and nanoparticles to be theranostic AD drugs. Taken together, our strategy provides a new thought into the design of smart compounds for use as efficiently therapeutic and preventive agents against AD. Moreover, our design provides broad prospects of biomedical strategy for further theranostics application in those diseases caused by abnormal protein.

Liu D et al. (2024) J Agric Food Chem "EGCG Alleviates the Aging Toxicity Induced by 3-MCPD via IIS Pathway in Caenorhabditis elegans with Abnormal Reproduction and Heat Shock Protein."

Song Y, Yu Q, Xie J, Chen Y, Zheng B, Liu D, Chen X

[

J Agric Food Chem,

2024]

This study aimed to investigate the mitigation effect of epigallocatechin gallate (EGCG) on aging induced by 3-monochloropropane-1,2-diol (3-MCPD) in Caenorhabditis elegans, evaluate health indicators during the process, and reveal the underlying mechanism through transcriptomics and identification of mutants. The results showed that EGCG alleviated the declined fertility, shortened lifespan, reduced body size, weakened movement, increased reactive oxygen species and lipofuscin, and damaged antioxidative stress response and excessive heat shock proteins caused by 3-MCPD. Transcriptomics study indicated that treatment with 3-MCPD and EGCG altered gene expression, and gene mutants confirmed the involvement of insulin/IGF-1 signaling pathway in mediating the process that EGCG alleviated the aging toxicity induced by 3-MCPD. The study showed that EGCG alleviated the aging toxicity induced by 3-MCPD.

Liu D et al. (2025) Mol Immunol "Ovalbumin alters DAF-16 Class-II/I gene expressions via insulin/insulin-like growth factor-1 signaling to initiate the innate immune response of Caenorhabditis elegans."

Tong P, Yao K, Pei H, Chen H, Gao J, Liu D

[

Mol Immunol,

2025]

Innate immunity, as a significant defense system of the body, plays a key role in allergic reactions, but the mechanism of how food allergens trigger innate immune signaling is still unclear. Ovalbumin (OVA) is a model allergen in food allergy studies. Previous studies by our group have demonstrated that the innate immunity of Caenorhabditis elegans (C. elegans) elicited by OVA treatment was related to the insulin/insulin-like growth factor-1 signaling (IIS) pathway, but the details remain unknown. Therefore, in this study, the molecular mechanism of innate immune signaling transduction of C. elegans stimulated by OVA was determined using genetic mutations as well as RT-PCR, GFP fluorescence visualization monitoring, and slow-killing experiments. Results showed that the expression levels of DAF-16-class-I/II genes in the IIS pathway were significantly changed in C. elegans after OVA treatment, and the upstream gene daf-2 played an important role, which up-regulated the levels of DAF-16-class-II genes dod-22 and F55G11.8 by the daf-2-pqm-1 pathway, and down-regulated the level of DAF-16-class-I gene thn-2 by the daf-2-daf-16 pathway. Moreover, the upstream genes daf-2 and nhr-14, and the transcription factors DAF-16, PQM-1, and SKN-1 in the IIS pathway all participated in the up-regulations of DAF-16-class-II genes dod-17, dod-24, and F55G11.2. In conclusion, details of OVA activating innate immunity in C. elegans through the IIS pathway are reported here, and the results can be further extrapolated to mammals, which will contribute to a better understanding of the mechanism of the occurrence of food allergic reactions from the perspective of innate immunity.

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