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  • Oxford University Press (OUP)  (62)
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  • Oxford University Press (OUP)  (62)
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  • 1
    Online Resource
    Online Resource
    Antifungal resistance-modifying multiplexing action of Momordica charantia protein and phosphorylated derivatives on the basis of growth-dependent gene coregulation in Candida albicans
    Oxford University Press (OUP) ; 2021
    In:  Medical Mycology Vol. 59, No. 6 ( 2021-06-04), p. 515-527
    Details
    In: Medical Mycology, Oxford University Press (OUP), Vol. 59, No. 6 ( 2021-06-04), p. 515-527
    Abstract: Fungal growth-dependent gene coregulation is strongly implicated in alteration of gene-encoding target proteases ruling with an antifungal resistance niche and biology of resistant mutants. On the basis of multi-alterative processes in this platform, the resistance-modifying strategy is designed in ketoconazole resistant Candida albicans and evaluated with less selective Momordica charantia protein and allosterically phosphorylated derivatives at the Thr102, Thr24 and Thr255 sites, respectively. We demonstrate absolutely chemo-sensitizing efficacy regarding stepwise-modifying resistance in sensitivity, by a load of only 26.23–40.00 μg/l agents in Sabouraud's dextrose broth. Five successive modifying-steps realize the decreasing of ketoconazole E-test MIC50 from 11.10 to a lower level than 0.10 mg/l. With the ketoconazole resistance-modifying, colony undergoes a high-frequency morphological switch between high ploidy (opaque) and small budding haploid (white). A cellular event in the first modifying-step associates with relatively slow exponential growth (ie, a 4-h delay)-dependent action, mediated by agents adsorption. Moreover, multiple molecular roles are coupled with intracellularly and extracellularly binding to ATP-dependent RNA helicase dbp6; the 0.08–2.45 fold upregulation of TATA-box-binding protein, rRNA-processing protein and translation initiation factor 5A; and the 7.52–55.33% decrease of cytochrome P450 lanosterol 14α-demethylase, glucan 1, 3-β glucosidase, candidapepsin-1 and 1-acylglycerol-3-phosphate O-acyltransferase. Spatial and temporal gene coregulation, in the transcription and translation initiation stages with rRNA-processing, is a new coprocessing platform enabling target protease attenuations for resistance-impairing. An updated resistance-modifying measure of these agents in the low-dose antifungal strategic design may provide opportunities to a virtually safe therapy that is in high dose-dependency.
    Type of Medium: Online Resource
    ISSN: 1369-3786 , 1460-2709
    URL: Article
    DOI: 10.1093/mmy/myaa070
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2020733-5
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    The DIRECT consortium and the REST-meta-MDD project: towards neuroimaging biomarkers of major depressive disorder
    Oxford University Press (OUP) ; 2022
    In:  Psychoradiology Vol. 2, No. 1 ( 2022-06-09), p. 32-42
    Details
    In: Psychoradiology, Oxford University Press (OUP), Vol. 2, No. 1 ( 2022-06-09), p. 32-42
    Abstract: Despite a growing neuroimaging literature on the pathophysiology of major depressive disorder (MDD), reproducible findings are lacking, probably reflecting mostly small sample sizes and heterogeneity in analytic approaches. To address these issues, the Depression Imaging REsearch ConsorTium (DIRECT) was launched. The REST-meta-MDD project, pooling 2428 functional brain images processed with a standardized pipeline across all participating sites, has been the first effort from DIRECT. In this review, we present an overview of the motivations, rationale, and principal findings of the studies so far from the REST-meta-MDD project. Findings from the first round of analyses of the pooled repository have included alterations in functional connectivity within the default mode network, in whole-brain topological properties, in dynamic features, and in functional lateralization. These well-powered exploratory observations have also provided the basis for future longitudinal hypothesis-driven research. Following these fruitful explorations, DIRECT has proceeded to its second stage of data sharing that seeks to examine ethnicity in brain alterations in MDD by extending the exclusive Chinese original sample to other ethnic groups through international collaborations. A state-of-the-art, surface-based preprocessing pipeline has also been introduced to improve sensitivity. Functional images from patients with bipolar disorder and schizophrenia will be included to identify shared and unique abnormalities across diagnosis boundaries. In addition, large-scale longitudinal studies targeting brain network alterations following antidepressant treatment, aggregation of diffusion tensor images, and the development of functional magnetic resonance imaging-guided neuromodulation approaches are underway. Through these endeavours, we hope to accelerate the translation of functional neuroimaging findings to clinical use, such as evaluating longitudinal effects of antidepressant medications and developing individualized neuromodulation targets, while building an open repository for the scientific community.
    Type of Medium: Online Resource
    ISSN: 2634-4416
    URL: Article
    DOI: 10.1093/psyrad/kkac005
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 3076092-6
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  • 3
    Online Resource
    Online Resource
    UNC13B variants associated with partial epilepsy with favourable outcome
    Oxford University Press (OUP) ; 2021
    In:  Brain Vol. 144, No. 10 ( 2021-11-29), p. 3050-3060
    Details
    In: Brain, Oxford University Press (OUP), Vol. 144, No. 10 ( 2021-11-29), p. 3050-3060
    Abstract: The unc-13 homolog B (UNC13B) gene encodes a presynaptic protein, mammalian uncoordinated 13-2 (Munc13-2), which is highly expressed in the brain—predominantly in the cerebral cortex—and plays an essential role in synaptic vesicle priming and fusion, potentially affecting neuronal excitability. However, the functional significance of the UNC13B mutation in human disease is not known. In this study, we screened for novel genetic variants in a cohort of 446 unrelated cases (families) with partial epilepsy without acquired causes by trio-based whole-exome sequencing. UNC13B variants were identified in 12 individuals affected by partial epilepsy and/or febrile seizures from eight unrelated families. The eight probands all had focal seizures and focal discharges in EEG recordings, including two patients who experienced frequent daily seizures and one who showed abnormalities in the hippocampus by brain MRI; however, all of the patients showed a favourable outcome without intellectual or developmental abnormalities. The identified UNC13B variants included one nonsense variant, two variants at or around a splice site, one compound heterozygous missense variant and four missense variants that cosegregated in the families. The frequency of UNC13B variants identified in the present study was significantly higher than that in a control cohort of Han Chinese and controls of the East Asian and all populations in the Genome Aggregation Database (gnomAD). Computational modelling, including hydrogen bond and docking analyses, suggested that the variants lead to functional impairment. In Drosophila, seizure rate and duration were increased by Unc13b knockdown compared to wild-type flies, but these effects were less pronounced than in sodium voltage-gated channel alpha subunit 1 (Scn1a) knockdown Drosophila. Electrophysiological recordings showed that excitatory neurons in Unc13b-deficient flies exhibited increased excitability. These results indicate that UNC13B is potentially associated with epilepsy. The frequent daily seizures and hippocampal abnormalities but ultimately favourable outcome under anti-epileptic therapy in our patients indicate that partial epilepsy caused by UNC13B variant is a clinically manageable condition.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awab164
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Energetic transients joint analysis system for multi-INstrument (ETJASMIN) for GECAM – I. Positional, temporal, and spectral analyses
    Oxford University Press (OUP) ; 2022
    In:  Monthly Notices of the Royal Astronomical Society Vol. 514, No. 2 ( 2022-06-17), p. 2397-2406
    Details
    In: Monthly Notices of the Royal Astronomical Society, Oxford University Press (OUP), Vol. 514, No. 2 ( 2022-06-17), p. 2397-2406
    Abstract: Gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor (GECAM) is a dedicated mission, launched in December 2020, for gamma-ray transients, including gamma-ray bursts (GRBs) and soft gamma repeater (SGR) bursts in the multimessenger and multiwavelength astronomy era. Since GECAM consists of two independent spacecrafts (or say instruments), and the framework of data analysis for multiple spacecrafts is distinctive from that for only one spacecraft, which is the case for most GRB missions, we developed a dedicated pipeline called Energetic Transients Joint Analysis System for Multi-INstrument (ETJASMIN) for GECAM mission. This pipeline has been naturally extended to incorporate data from other gamma-ray instruments, including the operating missions, such as Insight-HXMT/HE, Fermi/GBM, Swift/BAT, INTEGRAL/SPI-ACS, Konus-Wind, and GRID, as well as the forthcoming missions, such as SVOM/GRM and HEBS. In this paper, we present this pipeline with a focus on the data analysis procedures, methodology, and results in terms of the localization, verification (classification), spectral, and temporal analyses of gamma-ray transients. We show that this pipeline could provide more accurate, reliable, and comprehensive results than that of individual spacecraft, which is beneficial for gamma-ray transients observation.
    Type of Medium: Online Resource
    ISSN: 0035-8711 , 1365-2966
    URL: Article
    DOI: 10.1093/mnras/stac999
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2016084-7
    SSG: 16,12
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  • 5
    Online Resource
    Online Resource
    A Study of Human Leukocyte Antigen Mismatched Cellular Therapy (Stem Cell Microtransplantation) in High-Risk Myelodysplastic Syndrome or Transformed Acute Myelogenous Leukemia
    Oxford University Press (OUP) ; 2016
    In:  Stem Cells Translational Medicine Vol. 5, No. 4 ( 2016-04-01), p. 524-529
    Details
    In: Stem Cells Translational Medicine, Oxford University Press (OUP), Vol. 5, No. 4 ( 2016-04-01), p. 524-529
    Abstract: The treatment outcomes of myelodysplastic syndrome (MDS) and transformed acute myelogenous leukemia (tAML) remain very unsatisfactory. We designed a combination of human leukocyte antigen (HLA)-mismatched hematopoietic stem cell microtransplantation (MST) with chemotherapy for patients with MDS and tAML and evaluated its effects and toxicity. Patients were between 13 and 79 years old. Patients with MDS (n = 21) were given HLA-mismatched MST combined with decitabine and cytarabine; patients with tAML (n = 22) were given HLA-mismatched MST combined with decitabine and cytarabine, and also mitoxantrone. Patients in complete remission (CR) also received MST plus decitabine and medium-dose cytarabine chemotherapy without graft-versus-host disease (GVHD) prophylaxis. The overall response rate of the patients with MDS was significantly higher than that of those with tAML (81% vs. 50%; p = .03). The CR rates were 52.4% and 36.4% in the two groups, respectively. There was no difference in the cytogenetic CR rate between the MDS and tAML groups (85.7% vs. 70%, respectively; p = .7). The 24-month overall survival of the patients with MDS was significantly higher than that of the patients with tAML (84.7% and 34.1%, respectively; p = .003). The median recovery times of neutrophils and platelets were, respectively, 14 and 17 days in the patients with MDS, and 16 and 19 days in those with tAML. The treatment-related mortality rates were 4.8% and 18.2%, respectively, in the MDS and tAML groups (p = .34). No GVHD was observed in any patient. Microtransplantation combined with decitabine and chemotherapy may provide a novel, effective, and safe treatment for high-risk MDS and tAML. Significance Microtransplantation (MST) refers to regular chemotherapy combined with granulocyte colony-stimulating factor-mobilized peripheral blood stem cell infusion of human leukocyte antigen-mismatched donor cells without using immunosuppressive agents. It aims to support hematopoietic recovery and perform graft-versus-leukemia (GVL) effects but differs from traditional allogeneic stem cell transplantation because the rate of donor cell chimerism is low and there is and no graft-versus-host disease (GVHD) risk. Thus, a trial was designed to evaluate the safety and efficacy of MST in patients with myelodysplastic syndrome and those with transformed acute myelogenous leukemia. Higher complete remission and cytogenetic complete response rates were observed, and the treatment improved disease progress-free survival, sped hematopoietic recovery, and avoided GVHD.
    Type of Medium: Online Resource
    ISSN: 2157-6564 , 2157-6580
    URL: Article
    DOI: 10.5966/sctm.2015-0196
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
    detail.hit.zdb_id: 2642270-0
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  • 6
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    Online Resource
    Color-related chlorophyll and carotenoid concentrations of Chinese kale can be altered through CRISPR/Cas9 targeted editing of the carotenoid isomerase gene BoaCRTISO
    Oxford University Press (OUP) ; 2020
    In:  Horticulture Research Vol. 7, No. 1 ( 2020-12)
    Details
    In: Horticulture Research, Oxford University Press (OUP), Vol. 7, No. 1 ( 2020-12)
    Abstract: The carotenoid isomerase gene ( BoaCRTISO ) of Chinese kale was targeted and edited using the CRISPR/Cas9 system in the present study. The results showed a high mutation rate (81.25%), and 13 crtiso mutants were obtained. Only two types of mutations, insertions and replacements, were found. Both the total and individual carotenoid and chlorophyll concentrations of the biallelic and homozygous mutants were reduced, and the total levels declined by 11.89–36.33%. The color of the biallelic and homozygous mutants changed from green to yellow, likely reflecting a reduction in the color-masking effect of chlorophyll on carotenoids. The expression levels of most carotenoid and chlorophyll biosynthesis-related genes, including CRTISO , were notably lower in the mutants than in the WT plants. In addition, the functional differences between members of this gene family were discussed. In summary, these findings indicate that CRISPR/Cas9 is a promising technique for the quality improvement of Chinese kale and other Brassica vegetables.
    Type of Medium: Online Resource
    ISSN: 2662-6810 , 2052-7276
    URL: Article
    DOI: 10.1038/s41438-020-00379-w
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2781828-7
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  • 7
    Online Resource
    Online Resource
    Clinical Significance of Potassium Channel and NLRP3 Expression in Platelets of Active Ulcerative Colitis
    Oxford University Press (OUP) ; 2019
    In:  Inflammatory Bowel Diseases Vol. 25, No. 10 ( 2019-09-18), p. e115-e116
    Details
    In: Inflammatory Bowel Diseases, Oxford University Press (OUP), Vol. 25, No. 10 ( 2019-09-18), p. e115-e116
    Type of Medium: Online Resource
    ISSN: 1078-0998 , 1536-4844
    URL: Article
    DOI: 10.1093/ibd/izz109
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 8
    Online Resource
    Online Resource
    Transmission of Mycobacterium tuberculosis in China: A Population-Based Molecular Epidemiologic Study
    Oxford University Press (OUP) ; 2015
    In:  Clinical Infectious Diseases Vol. 61, No. 2 ( 2015-07-15), p. 219-227
    Details
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 61, No. 2 ( 2015-07-15), p. 219-227
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    URL: Article
    DOI: 10.1093/cid/civ255
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2015
    detail.hit.zdb_id: 2002229-3
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  • 9
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    Efficacy, Safety, and Immunogenicity of an Escherichia coli-Produced Bivalent Human Papillomavirus Vaccine: An Interim Analysis of a Randomized Clinical Trial
    Oxford University Press (OUP) ; 2020
    In:  JNCI: Journal of the National Cancer Institute Vol. 112, No. 2 ( 2020-02-01), p. 145-153
    Details
    In: JNCI: Journal of the National Cancer Institute, Oxford University Press (OUP), Vol. 112, No. 2 ( 2020-02-01), p. 145-153
    Abstract: The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. Methods A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18–45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission. Results In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. Conclusions The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18–associated high-grade genital lesions and persistent infection in women.
    Type of Medium: Online Resource
    ISSN: 0027-8874 , 1460-2105
    URL: Article
    DOI: 10.1093/jnci/djz074
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2992-0
    detail.hit.zdb_id: 1465951-7
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  • 10
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    CBMT-02. miR-124, -128, AND -137 COMBINATION THERAPY AGAINST GLIOBLASTOMA
    Oxford University Press (OUP) ; 2018
    In:  Neuro-Oncology Vol. 20, No. suppl_6 ( 2018-11-05), p. vi32-vi32
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 20, No. suppl_6 ( 2018-11-05), p. vi32-vi32
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noy148.121
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2094060-9
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