https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52876 Wed 28 Feb 2024 11:01:07 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19948 Wed 27 Jul 2022 13:58:56 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45284 Wed 26 Oct 2022 17:20:38 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36481 Wed 20 May 2020 16:22:43 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46956 Wed 19 Jul 2023 14:21:24 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48379 Saccostrea glomerata. Oysters were exposed to a “low” and a “high” mixture of (xeno) estrogens (representative of Australian and global receiving waters respectively) for 7 days and digestive gland, gill, and gonad tissue were sampled for quantification of polar metabolites by ¹H NMR spectroscopy. Exposure to both mixtures lowered body mass and altered the metabolite profile in the digestive glands. Comparatively, gills, and ovaries demonstrated lesser sensitivity to the mixtures, with significant metabolomic alterations observed only for the high mixture. The male gonad did not respond to either estrogenic exposure. In the responsive tissues, major metabolites including amino acids, carbohydrates, intermediates of the tricarboxylic acid cycle and ATP were all down-regulated and exhibited tissue-specific patterns of down-regulation with the greatest proportion of metabolites down-regulated due to estrogenic exposure in the digestive gland. Exposure to (xeno) estrogen mixtures representative of concentrations reported in receiving waters in Australia and globally can impact the metabolome and associated energy metabolism, especially in the digestive gland, translating to lower pools of available ATP energy for potential cellular homeostasis, somatic maintenance and growth, reproduction and fitness.]]> Wed 15 Mar 2023 14:50:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38681 Wed 13 Mar 2024 13:59:01 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14499 Wed 11 Apr 2018 10:21:55 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50962 Tue 22 Aug 2023 11:38:37 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54375 Tue 20 Feb 2024 20:24:25 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38714 Tue 18 Jan 2022 15:19:16 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55147 256 mg/L) revealed modified expression of several genes related to membrane transport (porin ompK36 and efflux pump regulator oqxR) and nitroreductase activity (ribC and nfsB, involved in nitrofurantoin reduction). Untargeted metabolomics analysis of total metabolites extracted at 1 and 4 h post-nitrofurantoin treatment revealed that exposure to the drug caused a delayed effect on the metabolome which was most pronounced after 4 h. Pathway enrichment analysis illustrated that several complex interrelated metabolic pathways related to nitrofurantoin bacterial killing (aminoacyl-tRNA biosynthesis, purine metabolism, central carbohydrate metabolism, and pantothenate and CoA biosynthesis) and the development of nitrofurantoin resistance (riboflavin metabolism) were significantly perturbed. This study highlights for the first time the key role of efflux pump regulator oqxR in nitrofurantoin resistance and reveals global metabolome perturbations in response to nitrofurantoin, in K. pneumoniae.]]> Tue 16 Apr 2024 15:16:15 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45550 Tue 01 Nov 2022 10:56:22 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50515 Thu 27 Jul 2023 14:34:40 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43316 Thu 15 Sep 2022 14:15:31 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46928 Thu 08 Dec 2022 12:25:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49092 Thu 04 May 2023 15:02:47 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27299 Sat 24 Mar 2018 07:38:31 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27778 Staphylococcus aureus is thought to be due to its extraordinary capacity to rapidly adapt to changes in environmental conditions. This study was carried out to investigate whether the cytoplasmic profiles of metabolites and proteins of S. aureus were altered in response to prolonged exposure to cold stress. Metabolic profiling and proteomics were used to characterise alterations in cytoplasmic proteins and metabolites in cells from the mid-exponential phase of growth under ideal conditions at 37 °C and compared with equivalent cells exposed to prolonged cold stress for 2 weeks at 4 °C. Principle component analysis (PCA) of the metabolomic and proteomic data indicated that, at the mid-exponential phase of growth, prolonged cold stress conditions generated cells with different metabolite and protein profiles compared with those grown at 37 °C. Nine ribosomal proteins and citric acid were substantially elevated in the cytoplasmic fractions from the cells adapted to cold-stress but most amino acids showed a reduction in their concentration in cold-stressed samples. The data provided strong evidence supporting the hypothesis that specific changes in metabolic homeostasis and protein composition were critical to the adaptive processes required for survival under cold stress. Biological significance: Work in our laboratory has shown that prolonged exposure of S. aureus to cold stress can result in the formation of small colony variants (SCVs) associated with significant alterations in the cell wall composition [8]. Further studies revealed that S. aureus altered cell size and cell wall thickness in response to exposure to cold temperatures, alterations in pH and exposure to antibiotics [10]. The current study has utilised the prolonged exposure to cold stress as a model system to explore changes in the proteome and associated metabolic homeostasis following environmental challenges. The study provides an improved understanding of how S. aureus adapts to the changing environment whilst in transition between human hosts. The results indicated an unexpected production of 9 ribosomal proteins and citric acid in response to cold stress suggesting specific survival roles for these proteins and citric acid as an adaptation mechanism for empowering survival under these conditions.]]> Sat 24 Mar 2018 07:37:06 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25518 Sat 24 Mar 2018 07:26:01 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45522 Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The combination of polymyxin B and sertraline showed synergistic antibacterial activity in checkerboard and static time-kill assays at clinically relevant concentrations against both polymyxin-susceptible and polymyxin-resistant isolates. The potential antimicrobial mode of action of the combination was investigated against P.aeruginosa FADDI-PA024 using untargeted metabolomics alongside scanning and transmission electron microscopy (EM). Scanning and transmission EM revealed that the polymyxin B and sertraline combination resulted in greater damage to the bacterial cell compared to each drug alone. Metabolomics results showed that the combination significantly affected the bacterial ability to remodel its outer membrane. This was reflected by the major perturbation of glycerophospholipids and fatty acids and the pantothenate and coenzyme A (CoA) pathways, which feed fatty acid elongation (e.g., trans-hexadec-2-enoyl-CoA) as well as inhibit the biosynthesis of lipopolysaccharide and peptidoglycan. The combination also inhibited the polymyxin resistance phosphoethanolamine (pEtN) lipid A modification pathway, indicated by the declined levels of phosphoethanolamine. In summary, the present study highlights the potential possibilities of a polymyxin-sertraline combination for the treatment of infections caused by multidrug resistant Gram-negative bacteria such as central nervous system (CNS) infections via direct intraventricular/intrathecal delivery.]]> Mon 31 Oct 2022 14:09:59 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38317 via esterification. Among them, compounds 2e (IC₅₀ =105 nM) and 3b (IC₅₀ =114 nM) displayed excellent ACE inhibitory activity in vitro, and exhibited non-toxic to H9c2 cells. The interactions between ACE and compounds were predicted by molecular docking respectively. In verapamil-induced zebrafish HF model, the activity assay showed that these two derivatives could improve cardiovascular physiological indexes including heart beats, venous congestion, heart dilation, cardiac output, ejection fraction and fractional shortening in a dose-dependent manner. A UPLC-QTOF-MS-based serum metabolomics approach was applied to explore the latent mechanism. A total of 25 differentiated metabolites and 8 perturbed metabolic pathways were identified. These results indicated that pyxinol fatty acid ester derivatives 2e and 3b might be considered as potent drug candidates against heart failure and deserved further research and development.]]> Mon 29 Jan 2024 18:52:01 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52959 Mon 29 Jan 2024 18:42:22 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54174 Mon 12 Feb 2024 09:35:16 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54741 Mon 11 Mar 2024 14:25:54 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:39571 Mon 08 Aug 2022 11:34:21 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37588 Mon 03 Apr 2023 13:16:07 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51933 Fri 22 Sep 2023 11:06:44 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47306 Fri 13 Jan 2023 10:52:32 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41757 Fri 12 Aug 2022 11:42:23 AEST ]]>