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  • Oxford University Press (OUP)  (11)
  • 1
    Online Resource
    Online Resource
    Role of Focal Adhesion Kinase in Regulating YB–1–Mediated Paclitaxel Resistance in Ovarian Cancer
    Oxford University Press (OUP) ; 2013
    In:  JNCI: Journal of the National Cancer Institute Vol. 105, No. 19 ( 2013-10-2), p. 1485-1495
    Details
    In: JNCI: Journal of the National Cancer Institute, Oxford University Press (OUP), Vol. 105, No. 19 ( 2013-10-2), p. 1485-1495
    Type of Medium: Online Resource
    ISSN: 1460-2105 , 0027-8874
    URL: Article
    DOI: 10.1093/jnci/djt210
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2013
    detail.hit.zdb_id: 2992-0
    detail.hit.zdb_id: 1465951-7
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  • 2
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    Online Resource
    Folate deficiency enhances the in vitro genotoxicity of bile acids in human colon and liver cells
    Oxford University Press (OUP) ; 2022
    In:  Mutagenesis Vol. 37, No. 1 ( 2022-04-02), p. 34-43
    Details
    In: Mutagenesis, Oxford University Press (OUP), Vol. 37, No. 1 ( 2022-04-02), p. 34-43
    Abstract: Obese subjects have a high baseline of genotoxic stress, but the underlying mechanism is poorly understood. Given that obesity is associated with high bile acids (BA) and low folate, we aimed to determine the interactive effect of folate deficient or supplementation to the genotoxicity and cytotoxicity of BA in human colon and liver cells. NCM460 and L-02 cells were cultured in folate-deficient (22.6 nM) and replete (2260 nM) Roswell Park Memorial Institute (RPMI)-1640 medium with or without 50 μM deoxycholic acid (DCA) or lithocholic acid (LCA) for 7 days. Moreover, these cells were cultured in folate supplemented (5.65, 11.3 and 22.6 μM) and standard (2.26 μM) medium with 200 μM DCA or LCA for 7 days. Genotoxicity and cytotoxicity were measured using the cytokinesis-block micronucleus cytome assay. Our results showed that under folate-replete condition, 50 μM DCA or LCA significantly increased the rate of micronuclei (MN) in NCM460 and L-02 cells. Significantly, the MN-inducing effect of 50 μM DCA or LCA was further enhanced by folate deficiency. Interestingly, folate supplementation exerted a dose-dependent manner to significantly decrease the rates of MN, nucleoplasmic bridges, nuclear buds, apoptosis, and necrosis induced by 200 μM DCA or LCA in NCM460 and L-02 cells. In conclusion, the genotoxicity of moderate BA (50 μM) was exacerbated by folate deficiency and folate supplementation could efficiently protect cells against the genotoxicity and cytotoxicity of high BA (200 μM).
    Type of Medium: Online Resource
    ISSN: 0267-8357 , 1464-3804
    URL: Article
    DOI: 10.1093/mutage/geab041
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1497468-X
    SSG: 12
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  • 3
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    Hyperandrogenism in POMCa-deficient zebrafish enhances somatic growth without increasing adiposity
    Oxford University Press (OUP) ; 2020
    In:  Journal of Molecular Cell Biology Vol. 12, No. 4 ( 2020-05-18), p. 291-304
    Details
    In: Journal of Molecular Cell Biology, Oxford University Press (OUP), Vol. 12, No. 4 ( 2020-05-18), p. 291-304
    Abstract: The endocrine regulatory roles of the hypothalamic–pituitary–adrenocortical axis on anxiety-like behavior and metabolic status have been found throughout animal taxa. However, the precise effects of the balancing adrenal corticosteroid biosynthesis under the influence of adrenocorticotrophic hormone (ACTH), a pro-opiomelanocortin (POMC)-derived peptide, on animal energy expenditure and somatic growth remain unknown. POMC has also been identified as one of the candidate loci for polycystic ovary syndrome, which features hyperandrogenism and some prevalence of obesity in patients. Here we show that zebrafish lacking functional POMCa exhibit similar phenotypes of stress response and body weight gain but not obesity as observed in mammalian models. In contrast with the impaired anorexigenic signaling cascade of melanocyte-stimulating hormones and leptin, which are responsible for their obesity-prone weight gain observed in various pomc mutant mammals, analyses with our pomca mutant series indicate that ACTH is the key regulator for the phenotype with enhanced somatic growth without obesity in pomca-deficient zebrafish. Hypocortisolism associated with hyperandrogenism has been observed in the pomca-deficient zebrafish, with enhanced activation of mammalian target of rapamycin complex 1; reutilization of amino acids and fatty acid β-oxidation are observed in the muscle tissue of the pomca-deficient fish. After reducing hyperandrogenism by crossing our pomca mutant fish with a cyp17a1-deficient background, the phenotype of enhanced somatic growth in pomca-deficient fish was no longer observed. Thus, our work also demonstrated that the role of POMCa in stress response seems to be conserved in vertebrates, whereas its effect on adipostasis is unique to teleosts.
    Type of Medium: Online Resource
    ISSN: 1759-4685
    URL: Article
    DOI: 10.1093/jmcb/mjz053
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2500949-7
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  • 4
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    Rbm46, a novel germ cell-specific factor, modulates meiotic progression and spermatogenesis
    Oxford University Press (OUP) ; 2021
    In:  Biology of Reproduction Vol. 104, No. 5 ( 2021-05-07), p. 1139-1153
    Details
    In: Biology of Reproduction, Oxford University Press (OUP), Vol. 104, No. 5 ( 2021-05-07), p. 1139-1153
    Abstract: It has been suggested that many novel RNA-binding proteins (RBPs) are required for gametogenesis, but the necessity of few of these proteins has been functionally verified. Here, we identified one RBP, Rbm46, and investigated its expression pattern and role in zebrafish reproduction. We found that rbm46 is maternally provided and specifically expressed in the germ cells of gonadal tissues using in situ hybridization, reverse transcription-PCR, and quantitative real-time polymerase chain reaction (qRT-PCR). Two independent rbm46 mutant zebrafish lines were generated via the transcription activator-like effector nuclease technique. Specific disruption of rbm46 resulted in masculinization and infertility in the mutants. Although the spermatogonia appeared grossly normal in the mutants, spermatogenesis was impaired, and meiosis events were not observed. The introduction of a tp53M214K mutation could not rescue the female-to-male sex-reversal phenotype, indicating that rbm46 acts independently of the p53-dependent apoptotic pathway. RNA sequencing and qRT-PCR subsequently indicated that Rbm46 might be involved in the posttranscriptional regulation of functional genes essential for germ cell development, such as nanos3, dazl, and sycp3, during gametogenesis. Together, our results reveal for the first time the crucial role of rbm46 in regulating germ cell development in vivo through promotion of germ cell progression through meiosis prophase I.
    Type of Medium: Online Resource
    ISSN: 0006-3363 , 1529-7268
    URL: Article
    DOI: 10.1093/biolre/ioab016
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1469812-2
    SSG: 12
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  • 5
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    Community-based Intervention for Obstructive Sleep Apnea in the General Population: A Randomized Controlled Trial
    Oxford University Press (OUP) ; 2024
    In:  SLEEP ( 2024-06-21)
    Details
    In: SLEEP, Oxford University Press (OUP), ( 2024-06-21)
    Abstract: To investigate the engagement and health outcomes of community-based intervention for obstructive sleep apnea (OSA) in the general population. Methods We conducted a 3-month randomized controlled trial in two communities in southern China. We initially screened the general population for high-risk OSA and further diagnosis using home sleep testing. Eligible participants were randomly (1:1) assigned to either a control or continuous positive airway pressure-based integrated intervention group. The primary outcomes were multimodal indicators reflecting health outcomes, including health-related quality of life (Short Form-36 [SF-36]), sleep-related symptoms, and cardiometabolic risk. Results Of the 2,484 participants screened, 1,423 identified as having high-risk OSA were considered for telephone invitations to participate in the trial. Of these, 401 participants responded positively (28.2%), 279 were diagnosed with OSA, and 212 were randomized. The intervention significantly improved several domains of SF-36, including physical functioning (intergroup difference, 2.8; P=0.003), vitality (2.3; P=0.031), and reported health transition (6.8; P=0.005). Sleep-related symptoms, including Epworth Sleepiness Scale (-0.7; P=0.017), Fatigue Severity Scale (-3.0; P=0.022), Insomnia Severity Index (-1.8; P & lt;0.001), and Pittsburgh Sleep Quality Index (-0.7; P=0.032), also showed significant improvements. Although the intervention did not significantly alter glycolipid metabolism, ventricular function, or cardiac structural remodeling, it achieved a significant reduction in systolic (-4.5 mmHg; P=0.004) and diastolic blood pressure (-3.7 mmHg; P & lt;0.001). Conclusions Community-based intervention for previously undiagnosed OSA in the general population yielded improvements in health-related quality of life, sleep-related symptoms, and blood pressure. However, engagement in the intervention program was low.
    Type of Medium: Online Resource
    ISSN: 0161-8105 , 1550-9109
    URL: Article
    DOI: 10.1093/sleep/zsae132
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 2056761-3
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  • 6
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    Online Resource
    Independent Evolution of Sex Chromosomes and Male Pregnancy–Related Genes in Two Seahorse Species
    Oxford University Press (OUP) ; 2023
    In:  Molecular Biology and Evolution Vol. 40, No. 1 ( 2023-01-04)
    Details
    In: Molecular Biology and Evolution, Oxford University Press (OUP), Vol. 40, No. 1 ( 2023-01-04)
    Abstract: Unlike birds and mammals, many teleosts have homomorphic sex chromosomes, and changes in the chromosome carrying the sex-determining locus, termed “turnovers”, are common. Recent turnovers allow studies of several interesting questions. One question is whether the new sex-determining regions evolve to become completely non-recombining, and if so, how and why. Another is whether (as predicted) evolutionary changes that benefit one sex accumulate in the newly sex-linked region. To study these questions, we analyzed the genome sequences of two seahorse species of the Syngnathidae, a fish group in which many species evolved a unique structure, the male brood pouch. We find that both seahorse species have XY sex chromosome systems, but their sex chromosome pairs are not homologs, implying that at least one turnover event has occurred. The Y-linked regions occupy 63.9% and 95.1% of the entire sex chromosome of the two species and do not exhibit extensive sequence divergence with their X-linked homologs. We find evidence for occasional recombination between the extant sex chromosomes that may account for their homomorphism. We argue that these Y-linked regions did not evolve by recombination suppression after the turnover, but by the ancestral nature of the low crossover rates in these chromosome regions. With such an ancestral crossover landscape, a turnover can instantly create an extensive Y-linked region. Finally, we test for adaptive evolution of male pouch–related genes after they became Y-linked in the seahorse.
    Type of Medium: Online Resource
    ISSN: 0737-4038 , 1537-1719
    URL: Article
    DOI: 10.1093/molbev/msac279
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2024221-9
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  • 7
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    SMAD3 promotes expression and activity of the androgen receptor in prostate cancer
    Oxford University Press (OUP) ; 2023
    In:  Nucleic Acids Research Vol. 51, No. 6 ( 2023-04-11), p. 2655-2670
    Details
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 51, No. 6 ( 2023-04-11), p. 2655-2670
    Abstract: Overexpression of androgen receptor (AR) is the primary cause of castration-resistant prostate cancer, although mechanisms upregulating AR transcription in this context are not well understood. Our RNA-seq studies revealed that SMAD3 knockdown decreased levels of AR and AR target genes, whereas SMAD4 or SMAD2 knockdown had little or no effect. ChIP-seq analysis showed that SMAD3 knockdown decreased global binding of AR to chromatin. Mechanistically, we show that SMAD3 binds to intron 3 of the AR gene to promote AR expression. Targeting these binding sites by CRISPRi reduced transcript levels of AR and AR targets. In addition, ∼50% of AR and SMAD3 ChIP-seq peaks overlapped, and SMAD3 may also cooperate with or co-activate AR for AR target expression. Functionally, AR re-expression in SMAD3-knockdown cells partially rescued AR target expression and cell growth defects. The SMAD3 peak in AR intron 3 overlapped with H3K27ac ChIP-seq and ATAC-seq peaks in datasets of prostate cancer. AR and SMAD3 mRNAs were upregulated in datasets of metastatic prostate cancer and CRPC compared with primary prostate cancer. A SMAD3 PROTAC inhibitor reduced levels of AR, AR-V7 and AR targets in prostate cancer cells. This study suggests that SMAD3 could be targeted to inhibit AR in prostate cancer.
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    URL: Article
    DOI: 10.1093/nar/gkad043
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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  • 8
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    High Expression of FoxP1 Is Associated With Improved Survival in Patients With Non–Small Cell Lung Cancer
    Oxford University Press (OUP) ; 2012
    In:  American Journal of Clinical Pathology Vol. 138, No. 2 ( 2012-08-01), p. 230-235
    Details
    In: American Journal of Clinical Pathology, Oxford University Press (OUP), Vol. 138, No. 2 ( 2012-08-01), p. 230-235
    Type of Medium: Online Resource
    ISSN: 1943-7722 , 0002-9173
    URL: Article
    DOI: 10.1309/AJCPDHQFNYJZ01YG
    RVK:
    YV 2000
    RVK:
    XA 18700
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2012
    detail.hit.zdb_id: 2039921-2
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  • 9
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    FLAGS: A Flexible and Adaptive Association Test for Gene Sets Using Summary Statistics
    Oxford University Press (OUP) ; 2016
    In:  Genetics Vol. 202, No. 3 ( 2016-03-01), p. 919-929
    Details
    In: Genetics, Oxford University Press (OUP), Vol. 202, No. 3 ( 2016-03-01), p. 919-929
    Abstract: Genome-wide association studies (GWAS) have been widely used for identifying common variants associated with complex diseases. Despite remarkable success in uncovering many risk variants and providing novel insights into disease biology, genetic variants identified to date fail to explain the vast majority of the heritability for most complex diseases. One explanation is that there are still a large number of common variants that remain to be discovered, but their effect sizes are generally too small to be detected individually. Accordingly, gene set analysis of GWAS, which examines a group of functionally related genes, has been proposed as a complementary approach to single-marker analysis. Here, we propose a flexible and adaptive test for gene sets (FLAGS), using summary statistics. Extensive simulations showed that this method has an appropriate type I error rate and outperforms existing methods with increased power. As a proof of principle, through real data analyses of Crohn’s disease GWAS data and bipolar disorder GWAS meta-analysis results, we demonstrated the superior performance of FLAGS over several state-of-the-art association tests for gene sets. Our method allows for the more powerful application of gene set analysis to complex diseases, which will have broad use given that GWAS summary results are increasingly publicly available.
    Type of Medium: Online Resource
    ISSN: 1943-2631
    URL: Article
    DOI: 10.1534/genetics.115.185009
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
    detail.hit.zdb_id: 1477228-0
    SSG: 12
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  • 10
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    COMBAT: A Combined Association Test for Genes Using Summary Statistics
    Oxford University Press (OUP) ; 2017
    In:  Genetics Vol. 207, No. 3 ( 2017-11-01), p. 883-891
    Details
    In: Genetics, Oxford University Press (OUP), Vol. 207, No. 3 ( 2017-11-01), p. 883-891
    Abstract: Many gene-based association tests have been proposed for genomewide association studies (GWAS). However, the power of existing gene-based tests is... Genome-wide association studies (GWAS) have been widely used for identifying common variants associated with complex diseases. Traditional analysis of GWAS typically examines one marker at a time, usually single nucleotide polymorphisms (SNPs), to identify individual variants associated with a disease. However, due to the small effect sizes of common variants, the power to detect individual risk variants is generally low. As a complementary approach to SNP-level analysis, a variety of gene-based association tests have been proposed. However, the power of existing gene-based tests is often dependent on the underlying genetic models, and it is not known a priori which test is optimal. Here we propose a combined association test (COMBAT) for genes, which incorporates strengths from existing gene-based tests and shows higher overall performance than any individual test. Our method does not require raw genotype or phenotype data, but needs only SNP-level P-values and correlations between SNPs from ancestry-matched samples. Extensive simulations showed that COMBAT has an appropriate type I error rate, maintains higher power across a wide range of genetic models, and is more robust than any individual gene-based test. We further demonstrated the superior performance of COMBAT over several other gene-based tests through reanalysis of the meta-analytic results of GWAS for bipolar disorder. Our method allows for the more powerful application of gene-based analysis to complex diseases, which will have broad use given that GWAS summary results are increasingly publicly available.
    Type of Medium: Online Resource
    ISSN: 1943-2631
    URL: Article
    DOI: 10.1534/genetics.117.300257
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2017
    detail.hit.zdb_id: 1477228-0
    SSG: 12
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