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  • 1
    In: Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC, Vol. 146, No. 7 ( 2020-07), p. 1659-1670
    Abstract: Desmoplastic small round cell tumors (DSRCTs) are highly malignant and very rare soft tissue sarcomas with a high unmet need for new therapeutic options. Therefore, we examined poly(ADP-ribose) polymerase 1 (PARP1) and Schlafen-11 (SLFN11) expression in DSRCT tumor tissue and the combination of PARP inhibitor olaparib with the alkylating agent temozolomide (TMZ) in a preclinical DSRCT model. Methods PARP1 and SLFN11 have been described as predictive biomarkers for response to PARP inhibition. Expression of PARP1 and SLFN11 was assessed in 16 and 12 DSRCT tumor tissue samples, respectively. Effects of single-agent olaparib, and olaparib and TMZ combination treatment were examined using the preclinical JN-DSRCT-1 model. In vitro, single-agent and combination treatment effects on cell viability, the cell cycle, DNA damage and apoptosis were examined. Olaparib and TMZ combination treatment was also assessed in vivo. Results PARP1 and SLFN11 expression was observed in 100% and 92% of DSRCT tumor tissues, respectively. Olaparib treatment reduced cell viability and cell migration in a dose-dependent manner in vitro. Drug synergy between olaparib and TMZ was observed in vitro and in vivo. Combination treatment led to a cell-cycle arrest and induction of DNA damage and apoptosis, even when combined at low dosages. Conclusion We show high PARP1 and SLFN11 expression in DSRCT tumor material and antitumor effects following olaparib and TMZ combination treatment in a preclinical DSRCT model. This suggests that olaparib and TMZ combination treatment could be a potential treatment option for DSRCTs.
    Type of Medium: Online Resource
    ISSN: 0171-5216 , 1432-1335
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 1459285-X
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  • 2
    In: Microorganisms, MDPI AG, Vol. 9, No. 6 ( 2021-05-21), p. 1116-
    Abstract: Bacteria encounter elevated copper (Cu) concentrations in multiple environments, varying from mining wastes to antimicrobial applications of copper. As the role of the environment in the bacterial response to Cu ion exposure remains elusive, we used a tagRNA-seq approach to elucidate the disparate responses of two morphotypes of Caulobacter crescentus NA1000 to moderate Cu stress in a complex rich (PYE) medium and a defined poor (M2G) medium. The transcriptome was more responsive in M2G, where we observed an extensive oxidative stress response and reconfiguration of the proteome, as well as the induction of metal resistance clusters. In PYE, little evidence was found for an oxidative stress response, but several transport systems were differentially expressed, and an increased need for histidine was apparent. These results show that the Cu stress response is strongly dependent on the cellular environment. In addition, induction of the extracytoplasmic function sigma factor SigF and its regulon was shared by the Cu stress responses in both media, and its central role was confirmed by the phenotypic screening of a sigF::Tn5 mutant. In both media, stalked cells were more responsive to Cu stress than swarmer cells, and a stronger basal expression of several cell protection systems was noted, indicating that the swarmer cell is inherently more Cu resistant. Our approach also allowed for detecting several new transcription start sites, putatively indicating small regulatory RNAs, and additional levels of Cu-responsive regulation.
    Type of Medium: Online Resource
    ISSN: 2076-2607
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2720891-6
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  • 3
    In: Journal of Biological Chemistry, Elsevier BV, Vol. 299, No. 10 ( 2023-10), p. 105207-
    Type of Medium: Online Resource
    ISSN: 0021-9258
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2141744-1
    detail.hit.zdb_id: 1474604-9
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2020
    In:  Frontiers in Microbiology Vol. 11 ( 2020-6-3)
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 11 ( 2020-6-3)
    Type of Medium: Online Resource
    ISSN: 1664-302X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2587354-4
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  • 5
    Online Resource
    Online Resource
    MDPI AG ; 2020
    In:  Genes Vol. 11, No. 9 ( 2020-09-04), p. 1049-
    In: Genes, MDPI AG, Vol. 11, No. 9 ( 2020-09-04), p. 1049-
    Abstract: Bacteria are increasingly used for biotechnological applications such as bioremediation, biorecovery, bioproduction, and biosensing. The development of strains suited for such applications requires a thorough understanding of their behavior, with a key role for their transcriptomic landscape. We present a thorough analysis of the transcriptome of Cupriavidus metallidurans CH34 cells acutely exposed to copper by tagRNA-sequencing. C. metallidurans CH34 is a model organism for metal resistance, and its potential as a biosensor and candidate for metal bioremediation has been demonstrated in multiple studies. Several metabolic pathways were impacted by Cu exposure, and a broad spectrum of metal resistance mechanisms, not limited to copper-specific clusters, was overexpressed. In addition, several gene clusters involved in the oxidative stress response and the cysteine-sulfur metabolism were induced. In total, 7500 transcription start sites (TSSs) were annotated and classified with respect to their location relative to coding sequences (CDSs). Predicted TSSs were used to re-annotate 182 CDSs. The TSSs of 2422 CDSs were detected, and consensus promotor logos were derived. Interestingly, many leaderless messenger RNAs (mRNAs) were found. In addition, many mRNAs were transcribed from multiple alternative TSSs. We observed pervasive intragenic TSSs both in sense and antisense to CDSs. Antisense transcripts were enriched near the 5′ end of mRNAs, indicating a functional role in post-transcriptional regulation. In total, 578 TSSs were detected in intergenic regions, of which 35 were identified as putative small regulatory RNAs. Finally, we provide a detailed analysis of the main copper resistance clusters in CH34, which include many intragenic and antisense transcripts. These results clearly highlight the ubiquity of noncoding transcripts in the CH34 transcriptome, many of which are putatively involved in the regulation of metal resistance.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527218-4
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  • 6
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2021
    In:  World Journal of Microbiology and Biotechnology Vol. 37, No. 3 ( 2021-03)
    In: World Journal of Microbiology and Biotechnology, Springer Science and Business Media LLC, Vol. 37, No. 3 ( 2021-03)
    Abstract: The antimicrobial applications of copper (Cu) are exploited in several industries, such as agriculture and healthcare settings. While Cu is capable of efficiently killing microorganisms, sub-lethal doses can induce a viable-but-non-culturable (VBNC) state in bacteria of many distinct clades. VBNC cells cannot be detected by standard culture-based detection methods, and can become a threat to plants and animals as they often retain virulent traits upon resuscitation. Here we discuss the putative mechanisms of the Cu-induced VBNC state. Common observations in Cu-induced VBNC cells include a cellular response to reactive oxygen species, the exhaustion of energy reserves, and a reconfiguration of the proteome. While showing partial overlap with other VBNC state-inducing stressors, these changes seem to be part of an adaptive response to Cu toxicity. Furthermore, we argue that Cu resistance mechanisms such as P-type ATPases and multicopper oxidases may ward off entry into the VBNC state to some extent. The spread of these mechanisms across multi-species populations could increase population-level resistance to Cu antimicrobials. As Cu resistance mechanisms are often co-selected with antibiotic resistance mechanisms, this threat is exacerbated.
    Type of Medium: Online Resource
    ISSN: 0959-3993 , 1573-0972
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1499109-3
    SSG: 12
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  • 7
    In: Frontiers in Space Technologies, Frontiers Media SA, Vol. 2 ( 2022-1-3)
    Abstract: Maintaining crew health and safety are essential goals for long-term human missions to space. Attaining these goals requires the development of methods and materials for sustaining the crew’s health and safety. Paramount is microbiological monitoring and contamination reduction. Microbial biofilms are of special concern, because they can cause damage to spaceflight equipment and are difficult to eliminate due to their increased resistance to antibiotics and disinfectants. The introduction of antimicrobial surfaces for medical, pharmaceutical and industrial purposes has shown a unique potential for reducing and preventing biofilm formation. This article describes the development process of ESA’s BIOFILMS experiment, that will evaluate biofilm formation on various antimicrobial surfaces under spaceflight conditions. These surfaces will be composed of different metals with and without specified surface texture modifications. Staphylococcus capitis subsp. capitis, Cupriavidus metallidurans and Acinetobacter radioresistens are biofilm forming organisms that have been chosen as model organisms. The BIOFILMS experiment will study the biofilm formation potential of these organisms in microgravity on the International Space Station on inert surfaces (stainless steel AISI 304) as well as antimicrobial active copper (Cu) based metals that have undergone specific surface modification by Ultrashort Pulsed Direct Laser Interference Patterning (USP-DLIP). Data collected in 1 x g has shown that these surface modifications enhance the antimicrobial activity of Cu based metals. In the scope of this, the interaction between the surfaces and bacteria, which is highly determined by topography and surface chemistry, will be investigated. The data generated will be indispensable for the future selection of antimicrobial materials in support of human- and robotic-associated activities in space exploration.
    Type of Medium: Online Resource
    ISSN: 2673-5075
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 3035407-9
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