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  • Frontiers Media SA  (13)
  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Cell and Developmental Biology Vol. 9 ( 2021-10-28)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 9 ( 2021-10-28)
    Abstract: Tet (Ten eleven translocation) family proteins-mediated 5-hydroxymethylcytosine (5hmC) is highly enriched in the neuronal system, and is involved in diverse biological processes and diseases. However, the function of 5hmC in astrocyte remains completely unknown. In the present study, we show that Tet1 deficiency alters astrocyte morphology and impairs neuronal function. Specific deletion of Tet1 in astrocyte impairs learning and memory ability of mice. Using 5hmC high-throughput DNA sequencing and RNA sequencing, we present the distribution of 5hmC among genomic features in astrocyte and show that Tet1 deficiency induces differentially hydroxymethylated regions (DhMRs) and alters gene expression. Mechanistically, we found that Tet1 deficiency leads to the abnormal Ca 2+ signaling by regulating the expression of GluA1, which can be rescued by ectopic GluA1. Collectively, our findings suggest that Tet1 plays important function in astrocyte physiology by regulating Ca 2+ signaling.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2737824-X
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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2020
    In:  Frontiers in Molecular Biosciences Vol. 7 ( 2020-12-4)
    In: Frontiers in Molecular Biosciences, Frontiers Media SA, Vol. 7 ( 2020-12-4)
    Abstract: Breast cancer cell lines are frequently used to elucidate the molecular mechanisms of the disease. However, a large proportion of cell lines are affected by problems such as mislabeling and cross-contamination. Therefore, it is of great clinical significance to select optimal breast cancer cell lines models. Using tamoxifen survival-related genes from breast cancer tissues as the gold standard, we selected the optimal cell line model to represent the characteristics of clinical tissue samples. Moreover, using relative expression orderings of gene pairs, we developed a gene pair signature that could predict tamoxifen therapy outcomes. Based on 235 consistently identified survival-related genes from datasets GSE17705 and GSE6532, we found that only the differentially expressed genes (DEGs) from the cell line dataset GSE26459 were significantly reproducible in tissue samples (binomial test, p = 2.13E-07). Finally, using the consistent DEGs from cell line dataset GSE26459 and tissue samples, we used the transcriptional qualitative feature to develop a two-gene pair ( TOP2A , SLC7A5 ; NMU , PDSS1 ) for predicting clinical tamoxifen resistance in the training data (logrank p = 1.98E-07); this signature was verified using an independent dataset (logrank p = 0.009909). Our results indicate that the cell line model from dataset GSE26459 provides a good representation of the characteristics of clinical tissue samples; thus, it will be a good choice for the selection of drug-resistant and drug-sensitive breast cancer cell lines in the future. Moreover, our signature could predict tamoxifen treatment outcomes in breast cancer patients.
    Type of Medium: Online Resource
    ISSN: 2296-889X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2814330-9
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2024
    In:  Frontiers in Bioengineering and Biotechnology Vol. 12 ( 2024-3-22)
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 12 ( 2024-3-22)
    Abstract: The Chinese hamster ovarian (CHO) cells serve as a common choice in biopharmaceutical production, traditionally cultivated in stirred tank bioreactors (STRs). Nevertheless, the pursuit of improved protein quality and production output for commercial purposes demand exploration into new bioreactor types. In this context, inverted frustoconical shaking bioreactors (IFSB) present unique physical properties distinct from STRs. This study aims to compare the production processes of an antibody-based biotherapeutic in both bioreactor types, to enhance production flexibility. The findings indicate that, when compared to STRs, IFSB demonstrates the capability to produce an antibody-based biotherapeutic with either comparable or enhanced bioprocess performance and product quality. IFSB reduces shear damage to cells, enhances viable cell density (VCD), and improves cell state at a 5-L scale. Consequently, this leads to increased protein expression (3.70 g/L vs 2.56 g/L) and improved protein quality, as evidenced by a reduction in acidic variants from 27.0% to 21.5%. Scaling up the culture utilizing the Froude constant and superficial gas velocity ensures stable operation, effective mixing, and gas transfer. The IFSB maintains a high VCD and cell viability at both 50-L and 500-L scales. Product expression levels range from 3.0 to 3.6 g/L, accompanied by an improved acidic variants attribute of 20.6%–22.7%. The IFSB exhibits superior productivity and product quality, underscoring its potential for incorporation into the manufacturing process for antibody-based biotherapeutics. These results establish the foundation for IFSB to become a viable option in producing antibody-based biotherapeutics for clinical and manufacturing applications.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2719493-0
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  • 4
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 7 ( 2016-09-21)
    Type of Medium: Online Resource
    ISSN: 1664-462X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2016
    detail.hit.zdb_id: 2687947-5
    detail.hit.zdb_id: 2613694-6
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Microbiology Vol. 14 ( 2023-8-11)
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 14 ( 2023-8-11)
    Abstract: Verticillium wilt is a disastrous disease caused by Verticillium dahliae that severely damages the production of cotton in China. Even under homogeneous conditions, the same cotton cultivar facing V. dahliae tends to either stay healthy or become seriously ill and die. This binary outcome may be related to the interactions between microbiome assembly and plant health. Understanding how the rhizosphere microbiome responds to V. dahliae infection is vital to controlling Verticillium wilt through the manipulation of the microbiome. In this study, we evaluated the healthy and diseased rhizosphere microbiome of two upland cotton cultivars that are resistant to V. dahliae , Zhong 2 (resistant) and Xin 36 (susceptible), using 16S rRNA and ITS high-throughput sequencing. The results showed that the healthy rhizosphere of both resistant cultivar and susceptible cultivar had more unique bacterial ASVs than the diseased rhizosphere, whereas fewer unique fungal ASVs were found in the healthy rhizosphere of resistant cultivar. There were no significant differences in alpha diversity and beta diversity between the resistant cultivar and susceptible cultivar. In both resistant cultivar and susceptible cultivar, bacterial genera such as Pseudomonas and Acidobacteria bacterium LP6 , and fungal genera such as Cephalotrichum and Mortierella were both highly enriched in the diseased rhizosphere, and Pseudomonas abundance in diseased rhizospheres was significantly higher than that in the healthy rhizosphere regardless of the cultivar type. However, cultivar and V. dahliae infection can cause composition changes in the rhizosphere bacterial and fungal communities, especially in the relative abundances of core microbiome members, which varied significantly, with different responses in the two cotton cultivars. Analysis of co-occurrence networks showed that resistant cultivar has a more complex network relationship than susceptible cultivar in the bacterial communities, and V. dahliae has a significant impact on the bacterial community structure. These findings will further broaden the understanding of plant-rhizosphere microbiome interactions and provide an integrative perspective on the cotton rhizosphere microbiome, which is beneficial to cotton health and production.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587354-4
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Plant Science Vol. 12 ( 2021-10-8)
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 12 ( 2021-10-8)
    Abstract: Rapeseed ( Brassica napus L.) is an important oilseed crop in the world. Its productivity is significantly influenced by numerous abiotic stresses, including cold stress (CS). Consequently, enhancement in CS tolerance is becoming an important area for agricultural investigation and crop improvement. Therefore, the current study aimed to identify the stress-responsive genes, metabolites, and metabolic pathways based on a combined transcriptome and metabolome analysis to understand the CS responses and tolerance mechanisms in the cold-tolerant (C18) and cold-sensitive (C6) rapeseed varieties. Based on the metabolome analysis, 31 differentially accumulated metabolites (DAMs) were identified between different comparisons of both varieties at the same time points. From the transcriptome analysis, 2,845, 3,358, and 2,819 differentially expressed genes (DEGs) were detected from the comparison of C6-0 vs. C18-0, C6-1 vs. C18-1, and C6-7 vs. C18-7. By combining the transcriptome and metabolome data sets, we found that numerous DAMs were strongly correlated with several differentially expressed genes (DEGs). A functional enrichment analysis of the DAMs and the correlated DEGs specified that most DEGs and DAMs were mainly enriched in diverse carbohydrates and amino acid metabolisms. Among them, starch and sucrose metabolism and phenylalanine metabolism were significantly enriched and played a vital role in the CS adaption of rapeseed. Six candidate genes were selected from the two pathways for controlling the adaption to low temperature. In a further validation, the T-DNA insertion mutants of their Arabidopsis homologous, including 4cl3, cel5, fruct4, ugp1, axs1 , and bam2/9 , were characterized and six lines differed significantly in levels of freezing tolerance. The outcome of the current study provided new prospects for the understanding of the molecular basis of CS responses and tolerance mechanisms in rapeseed and present a set of candidate genes for use in improving CS adaptability in the same plant.
    Type of Medium: Online Resource
    ISSN: 1664-462X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2687947-5
    detail.hit.zdb_id: 2613694-6
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  • 7
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 7 ( 2017-01-06)
    Type of Medium: Online Resource
    ISSN: 1664-462X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2017
    detail.hit.zdb_id: 2687947-5
    detail.hit.zdb_id: 2613694-6
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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Plant Science Vol. 13 ( 2022-9-6)
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 13 ( 2022-9-6)
    Abstract: Thidiazuron (TDZ) is a novel and efficient cytokinin commonly used in tissue culture, and numerous studies have demonstrated that TDZ can increase berry size. However, no study to date has explored the effect of TDZ on seed size of Brassica napus and the mechanism. To shed light on the effect of TDZ on the seed size of B. napus , four different concentrations of TDZ were applied to B. napus . Results indicated that TDZ treatment could increase the seed diameter and silique length of B. napus to varying degrees and 100 and 200 μmol/L TDZ treatments were the most effective with a 3.6 and 4.6% increase in seed diameter, respectively. In addition, the yield of B. napus was also substantially increased under TDZ treatment. On the other hand, confocal micrographs of embryos and cotyledon cells suggested that embryos and their cotyledon epidermal cells treated with 200 μmol/L TDZ were obviously larger in size than the control. Furthermore, TDZ promoted the upregulation of some key maternal tissue growth-related genes, including two G-protein signaling genes ( AGG3 and RGA1 ) and two transcriptional regulators ( ANT and GS2 ). The expression analysis of genes related to the auxin metabolic pathways, G-protein signaling, endosperm growth and transcriptional regulators confirmed that treatment with TDZ negatively regulated the key genes ABI5 , AGB1 , AP2 , ARF2 , and ARF18 during bud development stage and florescence. The results strongly suggested that TDZ might regulate the transcriptional levels of key genes involved in auxin metabolic pathways, G-protein signaling, endosperm growth and transcriptional regulators, which resulted in bigger cotyledon epidermal cells and seed size in B. napus . This study explored the mechanism of TDZ treatment on the seed size of B. napus and provided an important reference for improving rapeseed yield.
    Type of Medium: Online Resource
    ISSN: 1664-462X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2687947-5
    detail.hit.zdb_id: 2613694-6
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  • 9
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Neuroscience Vol. 16 ( 2022-5-20)
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 16 ( 2022-5-20)
    Abstract: Dynamic functional connectivity (FC) analysis can capture time-varying properties of connectivity; however, studies focusing on dynamic FC in patients with end-stage renal disease (ESRD) are very limited. This is the first study to explore the dynamic aspects of whole-brain FC and topological properties in ESRD patients. Resting-state functional magnetic resonance imaging data were acquired from 100 ESRD patients [50 hemodialysis (HD) patients and 50 non-dialysis patients] and 64 healthy controls (HCs). Independent component analysis, a sliding-window approach and graph-theory methods were used to study the dynamic FC properties. The intrinsic brain FC were clustered into four configuration states. Compared with HCs, both patient groups spent longer time in State 3, in which decreased FC between subnetworks of the default mode network (DMN) and between the dorsal DMN and language network was observed in these patients, and a further reduction in FC between the DMN subnetworks was found in HD patients compared to non-dialysis patients. The number of transitions and the variability of global and local efficiency progressively decreased from that in HCs to that of non-dialysis patients to that of HD patients. The completion time of Trail Making Test A and Trail Making Test B positively correlated with the mean dwell time of State 3 and negatively correlated with the number of transitions in ESRD patients. Our findings suggest impaired functional flexibility of network connections and state-specific FC disruptions in patients with ESRD, which may underlie their cognitive deficits. HD may have an adverse effect on time-varying FC.
    Type of Medium: Online Resource
    ISSN: 1662-453X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2411902-7
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  • 10
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Pharmacology Vol. 14 ( 2023-11-23)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 14 ( 2023-11-23)
    Abstract: Introduction: Target therapy for cancer cell mutation has brought attention to several challenges in clinical applications, including limited therapeutic targets, less patient benefits, and susceptibility to acquired due to their clear biological mechanisms and high specificity in targeting cancers with specific mutations. However, the identification of truly lethal synthetic lethal therapeutic targets for cancer cells remains uncommon, primarily due to compensatory mechanisms. Methods: In our pursuit of core therapeutic targets (CTTs) that exhibit extensive synthetic lethality in cancer and the corresponding potential drugs, we have developed a machine-learning model that utilizes multiple levels and dimensions of cancer characterization. This is achieved through the consideration of the transcriptional and post-transcriptional regulation of cancer-specific genes and the construction of a model that integrates statistics and machine learning. The model incorporates statistics such as Wilcoxon and Pearson, as well as random forest. Through WGCNA and network analysis, we identify hub genes in the SL network that serve as CTTs. Additionally, we establish regulatory networks for non-coding RNA (ncRNA) and drug-target interactions. Results: Our model has uncovered 7277 potential SL interactions, while WGCNA has identified 13 gene modules. Through network analysis, we have identified 30 CTTs with the highest degree in these modules. Based on these CTTs, we have constructed networks for ncRNA regulation and drug targets. Furthermore, by applying the same process to lung cancer and renal cell carcinoma, we have identified corresponding CTTs and potential therapeutic drugs. We have also analyzed common therapeutic targets among all three cancers. Discussion: The results of our study have broad applicability across various dimensions and histological data, as our model identifies potential therapeutic targets by learning multidimensional complex features from known synthetic lethal gene pairs. The incorporation of statistical screening and network analysis further enhances the confidence in these potential targets. Our approach provides novel theoretical insights and methodological support for the identification of CTTs and drugs in diverse types of cancer.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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