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  • Frontiers Media SA  (18)
  • 1
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 17 ( 2023-3-14)
    Abstract: Fear and sleep impairments common co-exist, but the underlying mechanisms remain unclear. Hypothalamic orexinergic neurons are involved in the regulation of sleep-wake and fear expression. The ventrolateral preoptic area (VLPO) is an essential brain region to promote sleep, and orexinergic axonal fibers projecting to the VLPO are involved in the maintenance of sleep-wake. Neural pathways from hypothalamic orexin neurons to the VLPO might mediate sleep impairments induced by conditioned fear. Methods To verify above hypothesis, electroencephalogram (EEG) and electromyogram (EMG) were recorded for analysis of sleep-wake states before and 24 h after conditioned fear training. The retrograde tracing technique and immunofluorescence staining was used to identify the projections from the hypothalamic orexin neurons to the VLPO and to observe their activation in mice with conditioned fear. Moreover, optogenetic activation or inhibition of hypothalamic orexin-VLPO pathways was performed to observe whether the sleep-wake can be regulated in mice with conditioned fear. Finally, orexin-A and orexin receptor antagonist was administered into the VLPO to certify the function of hypothalamic orexin-VLPO pathways on mediating sleep impairments induced by conditioned fear. Results It was found that there was a significant decrease in the non-rapid eye movement (NREM) and rapid eye movement (REM) sleep time and a significant increase in the wakefulness time in mice with conditioned fear. The results of retrograde tracing technique and immunofluorescence staining showed that hypothalamic orexin neurons projected to the VLPO and observed the CTB labeled orexin neurons were significantly activated (c-Fos+) in the hypothalamus in mice with conditioned fear. Optogenetic activation of hypothalamic orexin to the VLPO neural pathways significantly decreased NREM and REM sleep time and increased wakefulness time in mice with conditioned fear. A significant decrease in NREM and REM sleep time and an increase in wakefulness time were observed after the injection of orexin-A into the VLPO, and the effects of orexin-A in the VLPO were blocked by a pre-administrated dual orexin antagonist (DORA). Conclusion These findings suggest that the neural pathways from hypothalamic orexinergic neurons to the VLPO mediate sleep impairments induced by conditioned fear.
    Type of Medium: Online Resource
    ISSN: 1662-453X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2411902-7
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  • 2
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    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-6-13)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-6-13)
    Abstract: Background: The farnesoid X receptor (FXR) is a key factor regulating hepatic bile acid synthesis and enterohepatic circulation. Repression of bile acid synthesis by the FXR is a potential strategy for treating cholestatic liver disease. However, the role of intestinal FXR on the intestinal barrier and intestinal microbiota needs further investigation. Materials: Intestinal tissues were collected from patients with biliary atresia or without hepatobiliary disease. Then, intestinal mRNA levels of FXR-related molecules were determined. To investigate the effect of FXR activation, bile-duct-ligation rats were treated with obeticholic acid [OCA (5 mg/kg/day)] or vehicle (0.5% methyl cellulose) per oral gavage for 14 days. The mRNA levels of intestinal FXR, SHP, TNF-α, FGF15 and bile acid transporter levels were determined. In addition, the intestinal permeability, morphologic changes, and composition of the intestinal microbiota were evaluated. Gut Microbiome was determined by 16S rDNA MiSeq sequencing, and functional profiling of microbial communities was predicted with BugBase and PICRUSt2. Finally, the role of OCA in injured intestinal epithelial cell apoptosis and proliferation was examined by pretreatment with lipopolysaccharide (LPS) in Caco-2 cells. Results: The downstream of the FXR in ileum tissues was inhibited in biliary obstruction. Activation of the FXR signaling pathway by OCA significantly reduced liver fibrosis and intestinal inflammation, improved intestinal microbiota, and protected intestinal mucosa in BDL rats. OCA also altered the functional capacities of ileum microbiota in BDL rats. Significant differences existed between the controls and BDL rats, which were attenuated by OCA in the alpha diversity analysis. Principal coordinates analysis showed that microbial communities in BDL rats clustered separately from controls, and OCA treatment attenuated the distinction. Bugbase and PICRUSt2 analysis showed that OCA changed the composition and structure of the intestinal microbiota and improved the metabolic function of the intestinal microbiota by increasing the relative abundance of beneficial bacteria and reducing the relative abundance of harmful bacteria. Moreover, OCA reduced the apoptosis induced by LPS in Caco-2 cells. Conclusion: The FXR agonist, OCA, activates the intestinal FXR signaling pathway and improves the composition and structure of the intestinal microbiota and intestinal barrier in BDL rats.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 3
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    Frontiers Media SA ; 2020
    In:  Frontiers in Neuroscience Vol. 14 ( 2020-9-23)
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 14 ( 2020-9-23)
    Type of Medium: Online Resource
    ISSN: 1662-453X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2411902-7
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  • 4
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    Frontiers Media SA ; 2023
    In:  Frontiers in Plant Science Vol. 14 ( 2023-5-30)
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 14 ( 2023-5-30)
    Abstract: Kernel-using apricot ( Prunus armeniaca L.) is an economically important fruit tree species in arid areas owing to its hardiness and cold and drought tolerance. However, little is known about its genetic background and trait inheritances. In the present study, we first evaluated the population structure of 339 apricot accessions and the genetic diversity of kernel-using apricots using whole genome re-sequencing. Second, the phenotypic data of 222 accessions were investigated for two consecutive seasons (2019 and 2020) for 19 traits, including kernel and stone shell traits and the pistil abortion rate of flowers. Heritability and correlation coefficient of traits were also estimated. The stone shell length (94.46%) showed the highest heritability, followed by the length/width ratio (92.01%) and length/thickness ratio (92.00%) of the stone shell, whereas breaking force of the nut (17.08%) exhibited a very low heritability. A genome-wide association study (GWAS) using general linear model and generalized linear mixed model revealed 122 quantitative trait loci (QTLs). The QTLs of the kernel and stone shell traits were unevenly assigned on the eight chromosomes. Out of the 1,614 candidate genes identified in the 13 consistently reliable QTLs found using the two GWAS methods and/or in the two seasons, 1,021 were annotated. The sweet kernel trait was assigned to chromosome 5 of the genome, similar to the almond, and a new locus was also mapped at 17.34–17.51 Mb on chromosome 3, including 20 candidate genes. The loci and genes identified here will be of significant use in molecular breeding efforts, and the candidate genes could play essential roles in exploring the mechanisms of genetic regulation.
    Type of Medium: Online Resource
    ISSN: 1664-462X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2687947-5
    detail.hit.zdb_id: 2613694-6
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  • 5
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    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Genetics Vol. 12 ( 2021-10-18)
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 12 ( 2021-10-18)
    Abstract: Purpose: Glioblastoma multiforme (GBM) is the most widely occurring brain malignancy. It is modulated by a variety of genes, and patients with GBM have a low survival ratio and an unsatisfactory treatment effect. The irregular regulation of RNA binding proteins (RBPs) is implicated in several malignant neoplasms and reported to exhibit an association with the occurrence and development of carcinoma. Thus, it is necessary to build a stable, multi-RBPs signature-originated model for GBM prognosis and treatment response prediction. Methods: Differentially expressed RBPs (DERBPs) were screened out based on the RBPs data of GBM and normal brain tissues from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Program (GTEx) datasets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses on DERBPs were performed, followed by an analysis of the Protein-Protein Interaction network. Survival analysis of the DERBPs was conducted by univariate and multivariate Cox regression. Then, a risk score model was created on the basis of the gene signatures in various survival-associated RBPs, and its prognostic and predictive values were evaluated through Kaplan-Meier analysis and log-rank test. A nomogram on the basis of the hub RBPs signature was applied to estimate GBM patients’ survival rates. Moreover, western blot was for the detection of the proteins. Results: BICC1, GNL3L, and KHDRBS2 were considered as prognosis-associated hub RBPs and then were applied in the construction of a prognostic model. Poor survival results appeared in GBM patients with a high-risk score. The area under the time-dependent ROC curve of the prognostic model was 0.723 in TCGA and 0.707 in Chinese Glioma Genome Atlas (CGGA) cohorts, indicating a good prognostic model. What was more, the survival duration of the high-risk group receiving radiotherapy or temozolomide chemotherapy was shorter than that of the low-risk group. The nomogram showed a great discriminating capacity for GBM, and western blot experiments demonstrated that the proteins of these 3 RBPs had different expressions in GBM cells. Conclusion: The identified 3 hub RBPs-derived risk score is effective in the prediction of GBM prognosis and treatment response, and benefits to the treatment of GBM patients.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606823-0
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  • 6
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    Frontiers Media SA ; 2022
    In:  Frontiers in Plant Science Vol. 13 ( 2022-2-14)
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 13 ( 2022-2-14)
    Abstract: Improving fruit quality is one of the main tasks in modern commercial apricot breeding. Because of the lack of high-density linkage maps and fine mapping, it is difficult to obtain molecular markers that can assist in breeding for quantitative inheritance of fruit quality traits. In this study, specific-locus amplified fragment sequencing was used to genotype 169 seedlings of F1 apricot ( Prunus armeniaca L.) progenies derived from crossing “Chuanzhihong” (H) with “Saimaiti” (S). After aligning to the Prunus armeniaca reference genome and filtering out low-quality variants, 6,012 high-quality single nucleotide polymorphisms were obtained and employed to construct a genetic map for each parent. The genetic linkage maps showed eight linkage groups of apricot, covering a distance of 809.6 cM in “H” and 1076.4 cM in “S”. The average distance between markers in “H” and “S” was 0.62 and 0.95 cM, respectively. To map quantitative trait loci (QTLs) for fruit quality, we investigated fruit quality traits, including fruit weight (FW), fruit height (FH), fruit lateral width (FL), fruit ventral width (FV), soluble solids content (SSC), and fruit firmness (FF) for all seedlings genotyped in 2018 and 2019. Eleven and nine QTLs linked to fruit quality traits were anchored on the “H” and “S” maps, respectively, and 1,138 putative candidate genes for 16 most significant regions on the corresponding chromosome were identified based on gene annotation. Among them, fruit size contained 648 genes in 11 intervals on the reference genome, SSC contained 372 genes in 3 intervals, and FF contained 117 genes in 2 intervals. Our findings uncovered the genetic basis of apricot fruit quality, and provided candidate genes for further molecular genetic studies on fruit quality and QTL targets for future marker-assisted selection of apricot quality improvement breeding.
    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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  • 7
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    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Microbiology Vol. 13 ( 2022-9-8)
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 13 ( 2022-9-8)
    Abstract: Roseburia intestinalis is an anaerobic bacterium that produces butyric acid and belongs to the phylum Firmicutes. There is increasing evidence that this bacterium has positive effects on several diseases, including inflammatory bowel disease, atherosclerosis, alcoholic fatty liver, colorectal cancer, and metabolic syndrome, making it a potential “Next Generation Probiotic.” We investigated the genomic characteristics, probiotic properties, cytotoxicity, oral toxicity, colonization characteristics of the bacterium, and its effect on the gut microbiota. The genome contains few genes encoding virulence factors, three clustered regularly interspaced short palindromic repeat (CRISPR) sequences, two Cas genes, no toxic biogenic amine synthesis genes, and several essential amino acid and vitamin synthesis genes. Seven prophages and 41 genomic islands were predicted. In addition to a bacteriocin (Zoocin A), the bacterium encodes four metabolic gene clusters that synthesize short-chain fatty acids and 222 carbohydrate-active enzyme modules. This bacterium is sensitive to antibiotics specified by the European Food Safety Authority, does not exhibit hemolytic or gelatinase activity, and exhibits some acid resistance. R. intestinalis adheres to intestinal epithelial cells and inhibits the invasion of certain pathogens. In vitro experiments showed that the bacterium was not cytotoxic. R. intestinalis did not affect the diversity or abundance of the gut flora. Using the fluorescent labelling method, we discovered that R. intestinalis colonizes the cecum and mucus of the colon. An oral toxicity study did not reveal any obvious adverse effects. The lethal dose (LD)50 of R. intestinalis exceeded 1.9 × 10 9 colony forming units (CFU)/kg, whereas the no observed adverse effect level (NOAEL) derived from this study was 1.32 × 10 9  CFU/kg/day for 28 days. The current research shows that, R. intestinalis is a suitable next-generation probiotic considering its probiotic properties and safety.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587354-4
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  • 8
    In: Frontiers in Psychiatry, Frontiers Media SA, Vol. 14 ( 2023-2-2)
    Abstract: One of the most frequent side effects of atypical antipsychotics is hyperprolactinemia (HPRL), and metformin or aripiprazole co-prescription is regarded as an effective therapy option for reducing prolactin (PRL) levels. However, whether either of the two drugs can reduce PRL levels in patients with long-term hospitalized chronic schizophrenia with co-morbid type 2 diabetes (T2DM) has not been adequately reported. Methods In our study, long-term hospitalized chronic schizophrenia patients with co-T2DM who were prescribed olanzapine or risperidone as the primary antipsychotic medication were enrolled. A total of 197 of these cases with co-prescribed aripiprazole were set up as the study group (co-Ari group), and the other 204 cases without co-prescribed aripiprazole were set up as the control group (non-Ari group). The two groups’ variations in each target parameter were compared, and the variables affecting PRL levels were examined. Results Compared to the non-Ari group, fasting blood glucose (FBG), blood uric acid (UA), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in the co-Ari group, but there was no difference in PRL levels. Co-prescribing aripiprazole had no impact on PRL levels in all patients with co-T2DM, and aripiprazole dose had no impact on PRL levels in the clinical subgroup of the co-Ari group. Conclusion Aripiprazole not only worsened the severity of index disturbances associated to metabolism in long-term hospitalized chronic schizophrenia patients with co-T2DM on metformin-based hypoglycemic medications but also failed to lower PRL levels.
    Type of Medium: Online Resource
    ISSN: 1664-0640
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2564218-2
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  • 9
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    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-7-28)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-7-28)
    Abstract: Multiple myeloma (MM) is a malignant plasma cell disorder affecting mainly the elderly population. Revolutionary progress in immunotherapy has been made recently, including monoclonal antibodies and chimeric antigen receptor T cell (CAR-T) therapies; however, the high relapse rate remains problematic. Therefore, combination therapies against different targets would be a reasonable strategy. In this study, we present a new X-chromosome encoded testis-cancer antigen (CTA) AKAP4 as a potential target for MM. AKAP4 is expressed in MM cell lines and MM primary malignant plasma cells. HLA-A*0201-restricted cytotoxic T lymphocytes (CTLs) induced by dendritic cells (DCs) transduced with an adenovirus vector encoding the full-length AKAP4 gene were demonstrated to lyse AKAP4 + myeloma cells. Seven of the 12 candidate epitopes predicated by the BIMAS and SYFPEITH algorithms were able to bind HLA-A*0201 in the T2 binding assay, of which only two peptides were able to induce CTL cytotoxicity in the co-culture of peptide-loaded human mature dendritic cells and the autologous peripheral blood mononuclear cells (PBMCs) from the same HLA-A*0201 donor. The AKAP4 630–638 VLMLIQKLL was identified as the strongest CTL epitope by the human IFN-γ ELISPOT assay. Finally, the VLMLIQKLL-specific CTLs can lyse the HLA-A*0201 + AKAP4 + myeloma cell line U266 in vitro , and inhibit tumor growth in the mice bearing U266 tumors in vivo . These results suggest that the VLMLIQKLL epitope could be used to develop cancer vaccine or T-cell receptor transgenic T cells (TCR-T) to kill myeloma cells.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 10
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 8 ( 2017-10-13)
    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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