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  • 1
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2016
    In:  Journal of Surgical Case Reports Vol. 2016, No. 6 ( 2016-06), p. rjw112-
    In: Journal of Surgical Case Reports, Oxford University Press (OUP), Vol. 2016, No. 6 ( 2016-06), p. rjw112-
    Type of Medium: Online Resource
    ISSN: 2042-8812
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
    detail.hit.zdb_id: 2580919-2
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  • 2
    In: Translational Oncology, Elsevier BV, Vol. 37 ( 2023-11), p. 101758-
    Type of Medium: Online Resource
    ISSN: 1936-5233
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2443840-6
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  • 3
    Online Resource
    Online Resource
    Agricultural Research Communication Center ; 2018
    In:  Indian Journal Of Agricultural Research , No. 00 ( 2018-05-25)
    In: Indian Journal Of Agricultural Research, Agricultural Research Communication Center, , No. 00 ( 2018-05-25)
    Abstract: The present study was undertaken to investigate design values of pressurized pumping system. To begin with the estimated range of moisture requirement required to attain sowing moisture for different soil type was determined. For loamy sand soil an application range of aqueous fertilizer was 0.15-092 liter per meter for raising moisture from 3 to 7% to germination moisture of 14 per cent. Whereas, for sandy loam soil the same was 0.17-1.34 liter per meter for raising moisture from 4 to 12 % to germination moisture of 20 per cent and for loam soil it was 0.23-1.59 liter per meter for raising moisture from 8 to 16 % to germination moisture of 27 per cent. Based on estimation, an aqueous fertilizer requirement of 5500 to 8000 l/ha was required in experimental field with clay loam soil. To optimize different pump variables for required discharge rate five levels of pump rotational speeds i.e. 1998, 1665, 1332, 999 and 666 rpm, four levels of line pressure staring from fully opened valve i.e. gauge pressure of 0 kg/cm2, by reducing valve opening area up to 2, 4 and 6 kg/cm2 and three levels of nozzle sizes i.e. 8, 10 and 12 mm were taken. Pump rotational speed influenced discharge directly in a linear manner at fully opened valve for all pump speeds for each nozzle. As line pressure increased the discharge rate decreased. A reduction to the flow of 2 to 6 times was obtained by creating the line pressure through control valve at rotational speed of 1998 to 666 rpm. The selected design values for pressurized pumping system were pump rotational speed from 666, 999, 1332 and 1665 rpm, line pressure of 0, 2 or 4 kg/cm2 and nozzle size of 10 mm.
    Type of Medium: Online Resource
    ISSN: 0976-058X , 0367-8245
    Language: Unknown
    Publisher: Agricultural Research Communication Center
    Publication Date: 2018
    detail.hit.zdb_id: 2569845-X
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  • 4
    In: NAR Cancer, Oxford University Press (OUP), Vol. 5, No. 3 ( 2023-06-09)
    Abstract: The hypoxic milieu is a critical modulator of aerobic glycolysis, yet the regulatory mechanisms between the key glycolytic enzymes in hypoxic cancer cells are largely unchartered. In particular, the M2 isoform of pyruvate kinase (PKM2), the rate-limiting enzyme of glycolysis, is known to confer adaptive advantages under hypoxia. Herein, we report that non-canonical PKM2 mediates HIF-1α and p300 enrichment at PFKFB3 hypoxia-responsive elements (HREs), causing its upregulation. Consequently, the absence of PKM2 activates an opportunistic occupancy of HIF-2α, along with acquisition of a poised state by PFKFB3 HREs-associated chromatin. This poised nature restricts HIF-2α from inducing PFKFB3 while permitting the maintenance of its basal-level expression by harboring multiple histone modifications. In addition, the clinical relevance of the study has been investigated by demonstrating that Shikonin blocks the nuclear translocation of PKM2 to suppress PFKFB3 expression. Furthermore, TNBC patient-derived organoids and MCF7 cells-derived xenograft tumors in mice exhibited substantial growth inhibition upon shikonin treatment, highlighting the vitality of targeting PKM2. Conclusively, this work provides novel insights into the contributions of PKM2 in modulating hypoxic transcriptome and a previously unreported poised epigenetic strategy exhibited by the hypoxic breast cancer cells for ensuring the maintenance of PFKFB3 expression.
    Type of Medium: Online Resource
    ISSN: 2632-8674
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 3025038-9
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  • 5
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2018
    In:  Cell Death & Disease Vol. 9, No. 8 ( 2018-08-01)
    In: Cell Death & Disease, Springer Science and Business Media LLC, Vol. 9, No. 8 ( 2018-08-01)
    Abstract: The histone modifiers (HMs) are crucial for chromatin dynamics and gene expression; however, their dysregulated expression has been observed in various abnormalities including cancer. In this study, we have analyzed the expression of HMs in microarray profiles of head and neck cancer (HNC), wherein a highly significant overexpression of p21-activated kinase 2 (PAK2) was identified which was further validated in HNC patients. The elevated expression of PAK2 positively correlated with enhanced cell proliferation, aerobic glycolysis and chemoresistance and was associated with the poor clinical outcome of HNC patients. Further, dissection of molecular mechanism revealed an association of PAK2 with c-Myc and c-Myc-dependent PKM2 overexpression, wherein we showed that PAK2 upregulates c-Myc expression and c-Myc thereby binds to PKM promoter and induces PKM2 expression. We observed that PAK2–c-Myc–PKM2 axis is critical for oncogenic cellular proliferation. Depletion of PAK2 disturbs the axis and leads to downregulation of c-Myc and thereby PKM2 expression, which resulted in reduced aerobic glycolysis, proliferation and chemotherapeutic resistance of HNC cells. Moreover, the c-Myc complementation rescued PAK2 depletion effects and restored aerobic glycolysis, proliferation, migration and invasion in PAK2-depleted cells. The global transcriptome analysis of PAK2-depleted HNC cells revealed the downregulation of various genes involved in active cell proliferation, which indicates that PAK2 overexpression is critical for HNC progression. Together, these results suggest that the axis of PAK2–c-Myc–PKM2 is critical for HNC progression and could be a therapeutic target to reduce the cell proliferation and acquired chemoresistance and might enhance the efficacy of standard chemotherapy which will help in better management of HNC patients.
    Type of Medium: Online Resource
    ISSN: 2041-4889
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
    detail.hit.zdb_id: 2541626-1
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  • 6
    In: Oncogenesis, Springer Science and Business Media LLC, Vol. 10, No. 8 ( 2021-08-06)
    Abstract: Epithelial splicing regulatory protein 1 (ESRP1) is an RNA binding protein that governs the alternative splicing events related to epithelial phenotypes. ESRP1 contributes significantly at different stages of cancer progression. ESRP1 expression is substantially elevated in carcinoma in situ compared to the normal epithelium, whereas it is drastically ablated in cancer cells within hypoxic niches, which promotes epithelial to mesenchymal transition (EMT). Although a considerable body of research sought to understand the EMT-associated ESRP1 downregulation, the regulatory mechanisms underlying ESRP1 upregulation in primary tumors remained largely uncharted. This study seeks to unveil the regulatory mechanisms that spatiotemporally fine-tune the ESRP1 expression during breast carcinogenesis. Our results reveal that an elevated expression of transcription factor E2F1 and increased CpG hydroxymethylation of the E2F1 binding motif conjointly induce ESRP1 expression in breast carcinoma. However, E2F1 fails to upregulate ESRP1 despite its abundance in oxygen-deprived breast cancer cells. Mechanistically, impelled by the hypoxia-driven reduction of tet methylcytosine dioxygenase 3 (TET3) activity, CpG sites across the E2F1 binding motif lose the hydroxymethylation marks while gaining the de novo methyltransferase-elicited methylation marks. These two oxygen-sensitive epigenetic events work in concert to repel E2F1 from the ESRP1 promoter, thereby diminishing ESRP1 expression under hypoxia. Furthermore, E2F1 skews the cancer spliceome by upregulating splicing factor SRSF7 in hypoxic breast cancer cells. Our findings provide previously unreported mechanistic insights into the plastic nature of ESRP1 expression and insinuate important implications in therapeutics targeting breast cancer progression.
    Type of Medium: Online Resource
    ISSN: 2157-9024
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2674437-5
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  • 7
    In: iScience, Elsevier BV, Vol. 26, No. 6 ( 2023-06), p. 106804-
    Type of Medium: Online Resource
    ISSN: 2589-0042
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2927064-9
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  • 8
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2009
    In:  Indian Journal of Surgery Vol. 71, No. 1 ( 2009-2), p. 35-37
    In: Indian Journal of Surgery, Springer Science and Business Media LLC, Vol. 71, No. 1 ( 2009-2), p. 35-37
    Type of Medium: Online Resource
    ISSN: 0972-2068 , 0973-9793
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2009
    detail.hit.zdb_id: 2109793-8
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  • 9
    In: Asian Journal of Surgery, Elsevier BV, Vol. 27, No. 4 ( 2004-10), p. 294-298
    Type of Medium: Online Resource
    ISSN: 1015-9584
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2004
    detail.hit.zdb_id: 2031317-2
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  • 10
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2019-12)
    Abstract: The deregulated alternative splicing of key glycolytic enzyme, Pyruvate Kinase muscle isoenzyme (PKM) is implicated in metabolic adaptation of cancer cells. The splicing switch from normal PKM1 to cancer-specific PKM2 isoform allows the cancer cells to meet their energy and biosynthetic demands, thereby facilitating the cancer cells growth. We have investigated the largely unexplored epigenetic mechanism of PKM splicing switch in head and neck cancer (HNC) cells. Considering the reversible nature of epigenetic marks, we have also examined the utility of dietary-phytochemical in reverting the splicing switch from PKM2 to PKM1 isoform and thereby inhibition of HNC tumorigenesis. Methods We present HNC-patients samples, showing the splicing-switch from PKM1-isoform to PKM2-isoform analyzed via immunoblotting and qRT-PCR. We performed methylated-DNA-immunoprecipitation to examine the DNA methylation level and chromatin-immunoprecipitation to assess the BORIS (Brother of Regulator of Imprinted Sites) recruitment and polII enrichment. The effect of dietary-phytochemical on the activity of denovo-DNA-methyltransferase-3b (DNMT3B) was detected by DNA-methyltransferase-activity assay. We also analyzed the Warburg effect and growth inhibition using lactate, glucose uptake assay, invasion assay, cell proliferation, and apoptosis assay. The global change in transcriptome upon dietary-phytochemical treatment was assayed using Human Transcriptome Array 2.0 (HTA2.0). Results Here, we report the role of DNA-methylation mediated recruitment of the BORIS at exon-10 of PKM -gene regulating the alternative-splicing to generate the PKM2-splice-isoform in HNC. Notably, the reversal of Warburg effect was achieved by employing a dietary-phytochemical, which inhibits the DNMT3B, resulting in the reduced DNA-methylation at exon-10 and hence, PKM -splicing switch from cancer-specific PKM2 to normal PKM1. Global-transcriptome-analysis of dietary-phytochemical-treated cells revealed its effect on alternative splicing of various genes involved in HNC. Conclusion This study identifies the epigenetic mechanism of PKM -splicing switch in HNC and reports the role of dietary-phytochemical in reverting the splicing switch from cancer-specific PKM2 to normal PKM1-isoform and hence the reduced Warburg effect and growth inhibition of HNC. We envisage that this approach can provide an effective way to modulate cancer-specific-splicing and thereby aid in the treatment of HNC.
    Type of Medium: Online Resource
    ISSN: 1471-2407
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2041352-X
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