GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    A longitudinal resource for population neuroscience of school-age children and adolescents in China
    Springer Science and Business Media LLC ; 2023
    In:  Scientific Data Vol. 10, No. 1 ( 2023-08-21)
    Details
    In: Scientific Data, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2023-08-21)
    Abstract: During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013–2022), the first ten-year stage of the lifespan CCNP (2013–2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0–17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the “Chinese Data-sharing Warehouse for In-vivo Imaging Brain” in the Chinese Color Nest Project (CCNP) – Lifespan Brain-Mind Development Data Community ( https://ccnp.scidb.cn ) at the Science Data Bank.
    Type of Medium: Online Resource
    ISSN: 2052-4463
    URL: Article
    DOI: 10.1038/s41597-023-02377-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2775191-0
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Evaluation of biased agonism mediated by dual agonists of the GLP-1 and glucagon receptors
    Elsevier BV ; 2020
    In:  Biochemical Pharmacology Vol. 180 ( 2020-10), p. 114150-
    Details
    In: Biochemical Pharmacology, Elsevier BV, Vol. 180 ( 2020-10), p. 114150-
    Type of Medium: Online Resource
    ISSN: 0006-2952
    URL: Article
    DOI: 10.1016/j.bcp.2020.114150
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 1496199-4
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Combination of RUNX1 inhibitor and gemcitabine mitigates chemo‐resistance in pancreatic ductal adenocarcinoma by modulating BiP/PERK/eIF2α-axis-mediated endoplasmic reticulum stress
    Springer Science and Business Media LLC ; 2023
    In:  Journal of Experimental & Clinical Cancer Research Vol. 42, No. 1 ( 2023-09-11)
    Details
    In: Journal of Experimental & Clinical Cancer Research, Springer Science and Business Media LLC, Vol. 42, No. 1 ( 2023-09-11)
    Abstract: Gemcitabine (GEM)-based chemotherapy is the first-line option for pancreatic ductal adenocarcinoma (PDAC). However, the development of drug resistance limits its efficacy, and the specific mechanisms remain largely unknown. RUNX1, a key transcription factor in hematopoiesis, also involved in the malignant progression of PDAC, but was unclear in the chemoresistance of PDAC. Methods Comparative analysis was performed to screen GEM-resistance related genes using our single-cell RNA sequencing(scRNA-seq) data and two public RNA-sequencing datasets (GSE223463, GSE183795) for PDAC. The expression of RUNX1 in PDAC tissues was detected by qRT-PCR, immunohistochemistry (IHC) and western blot. The clinical significance of RUNX1 in PDAC was determined by single-or multivariate analysis and survival analysis. We constructed the stably expressing cell lines with shRUNX1 and RUNX1, and successfully established GEM-resistant cell line. The role of RUNX1 in GEM resistance was determined by CCK8 assay, plate colony formation assay and apoptosis analysis in vitro and in vivo. To explore the mechanism, we performed bioinformatic analysis using the scRNA-seq data to screen for the endoplasm reticulum (ER) stress signaling that was indispensable for RUNX1 in GEM resistance. We observed the cell morphology in ER stress by transmission electron microscopy and validated RUNX1 in gemcitabine resistance depended on the BiP/PERK/eIF2α pathway by in vitro and in vivo oncogenic experiments, using ER stress inhibitor(4-PBA) and PERK inhibitor (GSK2606414). The correlation between RUNX1 and BiP expression was assessed using the scRNA-seq data and TCGA dataset, and validated by RT-PCR, immunostaining and western blot. The mechanism of RUNX1 regulation of BiP was confirmed by ChIP-PCR and dual luciferase assay. Finally, the effect of RUNX1 inhibitor on PDAC was conducted in vivo mouse models, including subcutaneous xenograft and patient-derived xenograft (PDX) mouse models. Results RUNX1 was aberrant high expressed in PDAC and closely associated with GEM resistance. Silencing of RUNX1 could attenuate resistance in GEM-resistant cell line, and its inhibitor Ro5-3335 displayed an enhanced effect in inhibiting tumor growth, combined with GEM treatment, in PDX mouse models and GEM-resistant xenografts. In detail, forced expression of RUNX1 in PDAC cells suppressed apoptosis induced by GEM exposure, which was reversed by the ER stress inhibitor 4-PBA and PERK phosphorylation inhibitor GSK2606414. RUNX1 modulation of ER stress signaling mediated GEM resistance was supported by the analysis of scRNA-seq data. Consistently, silencing of RUNX1 strongly inhibited the GEM-induced activation of BiP and PERK/eIF2α signaling, one of the major pathways involved in ER stress. It was identified that RUNX1 directly bound to the promoter region of BiP, a primary ER stress sensor, and stimulated BiP expression to enhance the reserve capacity for cell adaptation, which in turn facilitated GEM resistance in PDAC cells. Conclusions This study identifies RUNX1 as a predictive biomarker for response to GEM-based chemotherapy. RUNX1 inhibition may represent an effective strategy for overcoming GEM resistance in PDAC cells.
    Type of Medium: Online Resource
    ISSN: 1756-9966
    URL: Article
    DOI: 10.1186/s13046-023-02814-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2430698-8
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Structural insights into multiplexed pharmacological actions of tirzepatide and peptide 20 at the GIP, GLP-1 or glucagon receptors
    Springer Science and Business Media LLC ; 2022
    In:  Nature Communications Vol. 13, No. 1 ( 2022-02-25)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2022-02-25)
    Abstract: Glucose homeostasis, regulated by glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon (GCG) is critical to human health. Several multi-targeting agonists at GIPR, GLP-1R or GCGR, developed to maximize metabolic benefits with reduced side-effects, are in clinical trials to treat type 2 diabetes and obesity. To elucidate the molecular mechanisms by which tirzepatide, a GIPR/GLP-1R dual agonist, and peptide 20, a GIPR/GLP-1R/GCGR triagonist, manifest their multiplexed pharmacological actions over monoagonists such as semaglutide, we determine cryo-electron microscopy structures of tirzepatide-bound GIPR and GLP-1R as well as peptide 20-bound GIPR, GLP-1R and GCGR. The structures reveal both common and unique features for the dual and triple agonism by illustrating key interactions of clinical relevance at the near-atomic level. Retention of glucagon function is required to achieve such an advantage over GLP-1 monotherapy. Our findings provide valuable insights into the structural basis of functional versatility of tirzepatide and peptide 20.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-022-28683-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2553671-0
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    A novel isoform of ATOH8 promotes the metastasis of breast cancer by regulating RhoC
    Oxford University Press (OUP) ; 2021
    In:  Journal of Molecular Cell Biology Vol. 13, No. 1 ( 2021-04-10), p. 59-71
    Details
    In: Journal of Molecular Cell Biology, Oxford University Press (OUP), Vol. 13, No. 1 ( 2021-04-10), p. 59-71
    Abstract: Metastases are the main cause of cancer-related mortality in breast cancer. Although significant progress has been made in the field of tumor metastasis, the exact molecular mechanisms involved in tumor metastasis are still unclear. Here, we report that ATOH8-V1, a novel isoform of ATOH8, is highly expressed in breast cancer and is a negative prognostic indicator of survival for patients. Forced expression of ATOH8-V1 dramatically enhances, while silencing of ATOH8-V1 decreases the metastasis of breast cancer cell lines. Moreover, ATOH8-V1 directly binds to the RhoC promoter and stimulates the expression of RhoC, which in turn enhances the metastasis of breast cancer. Altogether, our data demonstrate that ATOH8-V1 is a novel pro-metastatic factor that enhances cancer metastasis, suggesting that ATOH8-V1 is a potential therapeutic target for treatment of metastatic cancers.
    Type of Medium: Online Resource
    ISSN: 1759-4685
    URL: Article
    DOI: 10.1093/jmcb/mjaa050
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2500949-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Liposomal Nanoparticles Carrying anti-IL6R Antibody to the Tumour Microenvironment Inhibit Metastasis in Two Molecular Subtypes of Breast Cancer Mouse Models
    Ivyspring International Publisher ; 2017
    In:  Theranostics Vol. 7, No. 3 ( 2017), p. 775-788
    Details
    In: Theranostics, Ivyspring International Publisher, Vol. 7, No. 3 ( 2017), p. 775-788
    Type of Medium: Online Resource
    ISSN: 1838-7640
    URL: Article
    DOI: 10.7150/thno.17237
    Language: English
    Publisher: Ivyspring International Publisher
    Publication Date: 2017
    detail.hit.zdb_id: 2592097-2
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Cryo-electron microscopy structure of the glucagon receptor with a dual-agonist peptide
    Elsevier BV ; 2020
    In:  Journal of Biological Chemistry Vol. 295, No. 28 ( 2020-07), p. 9313-9325
    Details
    In: Journal of Biological Chemistry, Elsevier BV, Vol. 295, No. 28 ( 2020-07), p. 9313-9325
    Type of Medium: Online Resource
    ISSN: 0021-9258
    URL: Article
    DOI: 10.1074/jbc.RA120.013793
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2141744-1
    detail.hit.zdb_id: 1474604-9
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Structural analysis of the dual agonism at GLP-1R and GCGR
    Proceedings of the National Academy of Sciences ; 2023
    In:  Proceedings of the National Academy of Sciences Vol. 120, No. 33 ( 2023-08-15)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 33 ( 2023-08-15)
    Abstract: Glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR), two members of class B1 G protein–coupled receptors, play important roles in glucose homeostasis and energy metabolism. They share a high degree of sequence homology but have different functionalities. Unimolecular dual agonists of both receptors developed recently displayed better clinical efficacies than that of monotherapy. To study the underlying molecular mechanisms, we determined high-resolution cryo-electron microscopy structures of GLP-1R or GCGR in complex with heterotrimeric G s protein and three GLP-1R/GCGR dual agonists including peptide 15, MEDI0382 (cotadutide) and SAR425899 with variable activating profiles at GLP-1R versus GCGR. Compared with related structures reported previously and supported by our published pharmacological data, key residues responsible for ligand recognition and dual agonism were identified. Analyses of peptide conformational features revealed a difference in side chain orientations within the first three residues, indicating that distinct engagements in the deep binding pocket are required to achieve receptor selectivity. The middle region recognizes extracellular loop 1 (ECL1), ECL2, and the top of transmembrane helix 1 (TM1) resulting in specific conformational changes of both ligand and receptor, especially the dual agonists reshaped ECL1 conformation of GLP-1R relative to that of GCGR, suggesting an important role of ECL1 interaction in executing dual agonism. Structural investigation of lipid modification showed a better interaction between lipid moiety of MEDI0382 and TM1-TM2 cleft, in line with its increased potency at GCGR than SAR425899. Together, the results provide insightful information for the design and development of improved therapeutics targeting these two receptors simultaneously.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2303696120
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2023
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    LIMS1 Promotes Pancreatic Cancer Cell Survival under Oxygen–Glucose Deprivation Conditions by Enhancing HIF1A Protein Translation
    American Association for Cancer Research (AACR) ; 2019
    In:  Clinical Cancer Research Vol. 25, No. 13 ( 2019-07-01), p. 4091-4103
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 25, No. 13 ( 2019-07-01), p. 4091-4103
    Abstract: Oxygen and glucose deprivation is a common feature of the solid tumor. Regulatory network underlying the adaptation of cancer cells to the harsh microenvironment remains unclear. We determined the mechanistic role of LIM and senescent cell antigen-like–containing domain protein 1 (LIMS1) in cancer cell survival under oxygen–glucose deprivation conditions. Experimental Design: The expression level of LIMS1 was determined by IHC staining and analyzing the mRNA expression profiles from The Cancer Genome Atlas of three human solid tumors. Roles of LIMS1 in cancer cell metabolism and growth were determined by molecular and cell biology methods. A jetPEI nanocarrier was used as the vehicle for anti-LIMS1 siRNAs in mouse models of cancer therapeutics. Results: LIMS1 expression was drastically elevated in pancreatic ductal adenocarcinoma (PDAC). High LIMS1 level was associated with advanced TNM stage and poor prognosis of patients with tumor. Increased LIMS1 expression was pivotal for tumor cells to survive in the oxygen–glucose deprivation conditions. Mechanistically, LIMS1 enhanced GLUT1 expression and membrane translocation, which facilitated tumor cell adaptation to the glucose deprivation stress. Furthermore, LIMS1 promoted HIF1A protein translation by activating AKT/mTOR signaling, while hypoxia-inducible factor 1 (HIF1) transactivated LIMS1 transcription, thus forming a positive feedback loop in PDAC cell adaptation to oxygen deprivation stress. Inhibition of LIMS1 with jetPEI nanocarrier–delivered anti-LIMS1 siRNAs significantly increased cell death and suppressed tumor growth. Conclusions: LIMS1 promotes pancreatic cancer cell survival under oxygen–glucose deprivation conditions by activating AKT/mTOR signaling and enhancing HIF1A protein translation. LIMS1 is crucial for tumor adaptation to oxygen–glucose deprivation conditions and is a promising therapeutic target for cancer treatment.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-18-3533
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Abstract 1956: The basic helix-loop-helix (bHLH) transcriptional factor ATOH8 promotes the stemness of breast cancer cells via Oct4 and Nanog
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Research Vol. 74, No. 19_Supplement ( 2014-10-01), p. 1956-1956
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 1956-1956
    Abstract: Breast cancer is the leading cause of cancer mortality in women with a high incidence of recurrence and eventual treatment failure. The last decade has yielded substantial evidence that cancer stem cells (CSCs) contribute to tumor relapse, metastasis and chemoresistance. CSCs are regulated by complex interactions with the components of the tumor microenvironment through networks of cytokines and growth factors, including the IL6-STAT3 signaling pathway. Although the IL6 signaling pathway has been extensively characterized, the network of effector genes and proteins that regulates the CSC population remains poorly understood. Here, we show that ATOH8 is a downstream effector of IL6-STAT3 signaling which promotes the stemness of breast cancer cells. ATOH8 is significantly increased after IL6 stimulation and can be directly regulated by STAT3. Ectopic expression of ATOH8 in 4T1 or T-47D cells is sufficient to increases the CSC sub-population and enhances tumorogenesis in mice. Mechanistically, ATOH8 promotes the expression of Oct3/4 and Nanog, key regulators of CSC renewed. Accordingly, Knock-down of ATOH8 in EMT6 or MDA-MB-231 cells is associated with decreased expression of Oct3/4 and Nanog and reduces the CSC sub-population. In patients, ATOH8 expression is a negative prognostic indicator for overall survival. Together, the results identify ATOH8 as a downstream effector of IL6-STAT3 signaling that compromises long-term surviving in breast cancer. Citation Format: Antao Chang, Yanan Chen, Wenzhi Shen, Ruifang Gao, Wei Zhou, Yunping Luo, Na Luo, Dwayne Stupack, Rong Xiang. The basic helix-loop-helix (bHLH) transcriptional factor ATOH8 promotes the stemness of breast cancer cells via Oct4 and Nanog. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1956. doi:10.1158/1538-7445.AM2014-1956
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2014-1956
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...