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  • 1
    In: Molecules, MDPI AG, Vol. 27, No. 21 ( 2022-11-01), p. 7429-
    Abstract: The Menshutkin reaction represents the alkylation of tertiary amines by alkyl halide where the reactants are neutral and the products, quaternary ammonium salts, are two ions with opposite signs. The most commonly used organic solvents in quaternization reactions are volatile organic solvents (VOSs), namely acetone, anhydrous benzene, dry dichloromethane (DCM), dimethylformamide (DMF) and acetonitrile (ACN). The purpose of this work was to examine eutectic solvents as a “greener” alternative to conventional solvents so that quaternization reactions take place in accordance with the principles of green chemistry. Herein, sixteen eutectic solvents were used as replacements for volatile organic ones in quaternization reactions of isonicotinamide with substituted phenacyl bromides. The reactions were carried out at 80 °C by three synthetic approaches: conventional (4–6 h), microwave (20 min) and ultrasound (3 h). Microwave-assisted organic reactions produced the highest yields, where in several reactions, the yield was almost quantitative. The most suitable eutectic solvents were based on choline chloride (ChCl) as the hydrogen bond acceptor (HBA) and glycerol, oxalic or levulinic acid as hydrogen bond donors (HBDs). The benefits of these three deep eutectic solvents (DESs) as a medium for quaternization reactions are the simplicity of their preparation for large-scale production, with inexpensive, available and nontoxic starting materials, as well as their biodegradability.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2008644-1
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  • 2
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2022
    In:  Scientific Reports Vol. 12, No. 1 ( 2022-01-12)
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-01-12)
    Abstract: We report rare simultaneous observations of columniform sprites and associated gravity waves (GWs) using the Transient Luminous Events (TLEs) camera and All-sky imager at Prayagraj (25.5° N, 81.9° E, geomag. lat. ~ 16.5° N), India. On 30 May 2014, a Mesoscale Convective System generated a group of sprites over the north horizon that reached the upper mesosphere. Just before this event, GWs (period ~ 14 min) were seen in OH broadband airglow (emission peak ~ 87 km) imaging that propagated in the direction of the sprite occurrence and dissipated in the background atmosphere thereby generating turbulence. About 9–14 min after the sprite event, another set of GWs (period ~ 11 min) was observed in OH imaging that arrived from the direction of the TLEs. At this site, we also record Very Low Frequency navigational transmitter signal JJI (22.2 kHz) from Japan. The amplitude of the JJI signal showed the presence of GWs with ~ 12.2 min periodicities and ~ 18 min period. The GWs of similar features were observed in the ionospheric Total Electron Content variations recorded at a nearby GPS site. The results presented here are important to understand the physical coupling of the troposphere with the lower and upper ionosphere through GWs.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
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  • 3
    In: Cellular and Molecular Life Sciences, Springer Science and Business Media LLC, Vol. 78, No. 14 ( 2021-07), p. 5587-5604
    Abstract: To clarify whether differential compartmentalization of Survivin impacts temozolomide (TMZ)-triggered end points, we established a well-defined glioblastoma cell model in vitro (LN229 and A172) and in vivo, distinguishing between its nuclear and cytoplasmic localization. Expression of nuclear export sequence (NES)-mutated Survivin (SurvNESmut-GFP) led to impaired colony formation upon TMZ. This was not due to enhanced cell death but rather due to increased senescence. Nuclear-trapped Survivin reduced homologous recombination (HR)-mediated double-strand break (DSB) repair, as evaluated by γH2AX foci formation and qPCR-based HR assay leading to pronounced induction of chromosome aberrations. Opposite, clones, expressing free-shuttling cytoplasmic but not nuclear-trapped Survivin, could repair TMZ-induced DSBs and evaded senescence. Mass spectrometry-based interactomics revealed, however, no direct interaction of Survivin with any of the repair factors. The improved TMZ-triggered HR activity in Surv-GFP was associated with enhanced mRNA and stabilized RAD51 protein expression, opposite to diminished RAD51 expression in SurvNESmut cells. Notably, cytoplasmic Survivin could significantly compensate for the viability under RAD51 knockdown. Differential Survivin localization also resulted in distinctive TMZ-triggered transcriptional pathways, associated with senescence and chromosome instability as shown by global transcriptome analysis. Orthotopic LN229 xenografts, expressing SurvNESmut exhibited diminished growth and increased DNA damage upon TMZ, as manifested by PCNA and γH2AX foci expression, respectively, in brain tissue sections. Consequently, those mice lived longer. Although tumors of high-grade glioma patients expressed majorly nuclear Survivin, they exhibited rarely NES mutations which did not correlate with survival. Based on our in vitro and xenograft data, Survivin nuclear trapping would facilitate glioma response to TMZ.
    Type of Medium: Online Resource
    ISSN: 1420-682X , 1420-9071
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1458497-9
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    American Geophysical Union (AGU) ; 2021
    In:  Journal of Geophysical Research: Atmospheres Vol. 126, No. 20 ( 2021-10-27)
    In: Journal of Geophysical Research: Atmospheres, American Geophysical Union (AGU), Vol. 126, No. 20 ( 2021-10-27)
    Abstract: A high percentage (90 ) of dancing sprites were produced by a large asymmetric MCS which developed in strong convective conditions over the Mediterranean Sea The sprite parent flashes mainly initiated at the edge of the convective region and propagated 100–200 km across the stratiform region An especially bright and wide sprite sequence was produced by three distinct positive CG strokes that occurred within 3 ms and were separated by 54 km
    Type of Medium: Online Resource
    ISSN: 2169-897X , 2169-8996
    Language: English
    Publisher: American Geophysical Union (AGU)
    Publication Date: 2021
    detail.hit.zdb_id: 710256-2
    detail.hit.zdb_id: 2016800-7
    detail.hit.zdb_id: 2969341-X
    SSG: 16,13
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  • 5
    Online Resource
    Online Resource
    American Geophysical Union (AGU) ; 2023
    In:  Journal of Geophysical Research: Atmospheres Vol. 128, No. 10 ( 2023-05-27)
    In: Journal of Geophysical Research: Atmospheres, American Geophysical Union (AGU), Vol. 128, No. 10 ( 2023-05-27)
    Abstract: Transient luminous events, lightning, and MF and VLF signal perturbations from a thunderstorm system in the Adriatic Sea are analyzed 63 elves are observed, with 14 associated LOREs. No sprites or halos Several early VLF perturbations caused by either +/−CG or IC lighting discharges are found to not be accompanied by any TLE type
    Type of Medium: Online Resource
    ISSN: 2169-897X , 2169-8996
    Language: English
    Publisher: American Geophysical Union (AGU)
    Publication Date: 2023
    detail.hit.zdb_id: 710256-2
    detail.hit.zdb_id: 2016800-7
    detail.hit.zdb_id: 2969341-X
    SSG: 16,13
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  • 6
    In: Cellular and Molecular Life Sciences, Springer Science and Business Media LLC, Vol. 80, No. 10 ( 2023-10)
    Type of Medium: Online Resource
    ISSN: 1420-682X , 1420-9071
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1458497-9
    SSG: 12
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  • 7
    In: Cancers, MDPI AG, Vol. 13, No. 9 ( 2021-04-22), p. 2019-
    Abstract: Senescence is an important consequence of cytostatic drug-based tumor therapy. Here we analyzed to which degree the anticancer drug oxaliplatin induces cell death, cell cycle arrest, and senescence in colorectal cancer (CRC) cells and elucidated the role of p53. Oxaliplatin treatment resulted in the G2-phase arrest in all CRC lines tested (HCT116p53+/+, HCT116p53−/−, LoVo, SW48 and SW480). Immunoblot analysis showed that within the p53-competent lines p53 and p21CIP1 are activated at early times upon oxaliplatin treatment. However, at later times, only LoVo cells showed sustained activation of the p53/p21CIP1 pathway, accompanied by a strong induction of senescence as measured by senescence-associated β-Gal staining and induction of senescence-associated secretory phenotype (SASP) factors. Opposite to LoVo, the p53/p21CIP1 response and senescence induction was much weaker in the p53-proficient SW48 and SW480 cells, which was due to deficiency for p14ARF. Thus, among lines studied only LoVo express p14ARF protein and siRNA-mediated knockdown of p14ARF significantly reduced sustained p53/p21CIP1 activation and senescence. Vice versa, ectopic p14ARF expression enhanced oxaliplatin-induced senescence in SW48 and SW480 cells. Our data show that oxaliplatin-induced senescence in CRC cells is dependent on p53 proficiency; however, a significant induction can only be observed upon p14ARF-mediated p53 stabilization.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 8
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 19, No. 24 ( 2022-12-14), p. 16819-
    Abstract: The aim of the present study was to evaluate the safety parameters, nutritional value and sensory profile of the meat from spiny-cheek crayfish (Faxonius limosus), captured from the Danube River in Serbia. To achieve this, we determined their microbiological safety, chemical composition, minerals and heavy metals, fatty acid and amino acid profile, as well as a sensory profile of the meat. The obtained results showed that the meat from crayfish was microbiologically safe. Crayfish meat has a high nutritional quality, high protein content (18.12%) and a total of 17 detected amino acids, of which essential amino acids constituted 6.96 g/100 g sample. Additionally, the crayfish meat was characterized by high levels of essential polyunsaturated fatty acids (PUFA), particularly n-3 PUFA, at an optimal ratio of n-3/n-6 and with low values of atherogenic and thrombogenic indices. Predominant macrominerals in the meat are K, followed by Na, Ca, P and Mg, whereas the content of microminerals was in the following order: Zn 〉 Cu 〉 Fe 〉 Mn. The concentrations of accumulated toxic metals (Cd, Pb, As and Hg) did not exceed the maximum allowed levels. Sensory analysis confirmed that the meat from spiny-cheek crayfish has the potential to become a new food source of essential nutrients.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2175195-X
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  • 9
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 48, No. 21 ( 2020-12-02), p. 12085-12101
    Abstract: Transcriptional regulation of DNA repair is of outmost importance for the restoration of DNA integrity upon genotoxic stress. Here we report that the potent environmental carcinogen benzo[a]pyrene (B[a] P) activates a cellular DNA damage response resulting in transcriptional repression of mismatch repair (MMR) genes (MSH2, MSH6, EXO1) and of RAD51, the central homologous recombination repair (HR) component, ultimately leading to downregulation of MMR and HR. B[a] P-induced gene repression is caused by abrogated E2F1 signalling. This occurs through proteasomal degradation of E2F1 in G2-arrested cells and downregulation of E2F1 mRNA expression in G1-arrested cells. Repression of E2F1-mediated transcription and silencing of repair genes is further mediated by the p21-dependent E2F4/DREAM complex. Notably, repression of DNA repair is also observed following exposure to the active B[a]P metabolite BPDE and upon ionizing radiation and occurs in response to a p53/p21-triggered, irreversible cell cycle arrest marking the onset of cellular senescence. Overall, our results suggest that repression of MMR and HR is an early event during genotoxic-stress induced senescence. We propose that persistent downregulation of DNA repair might play a role in the maintenance of the senescence phenotype, which is associated with an accumulation of unrepairable DNA lesions.
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 16 ( 2021-08-13), p. 4072-
    In: Cancers, MDPI AG, Vol. 13, No. 16 ( 2021-08-13), p. 4072-
    Abstract: Colorectal cancer (CRC) belongs to the most common tumor types, and half of all CRC harbor missense mutations in the TP53 tumor suppressor gene. In addition to genetically caused loss of function of p53, epigenetic alterations (DNA methylation, histone modifications, micro-RNAs) contribute to CRC development. In this review, we focused on epigenetic alterations related to the entire p53 signaling pathway upstream and downstream of p53. Methylation of genes which activate p53 function has been reported, and methylation of APC and MGMT was associated with increased mutation rates of TP53. The micro-RNA 34a activates TP53 and was methylated in CRC. Proteins that regulate TP53 DNA methylation, mutations, and acetylation of TP53-related histones were methylated in CRC. P53 regulates the activity of numerous downstream proteins. Even if TP53 is not mutated, the function of wildtype p53 may be compromised if corresponding downstream genes are epigenetically inactivated. Thus, the role of p53 for CRC development, therapy response, and survival prognosis of patients may be much more eminent than previously estimated. Therefore, we propose that novel diagnostic devices measuring the entirety of genetic and epigenetic changes in the “p53 signalome” have the potential to improve the predictive and prognostic power in CRC diagnostics and management.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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