https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50960 Wed 28 Feb 2024 15:22:37 AEDT ]]> 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:46956 Wed 19 Jul 2023 14:21:24 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:2982 Wed 11 Apr 2018 11:06:16 AEST ]]> 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:38138 Wed 04 Aug 2021 15:42:40 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55011 Wed 03 Apr 2024 10:12:43 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:28957 Thu 28 Oct 2021 12:37:23 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26066 Thu 20 Aug 2020 09:19:59 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44086 Thu 06 Oct 2022 15:34:32 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:12352 Sat 24 Mar 2018 08:18:31 AEDT ]]> 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:23305 Sat 24 Mar 2018 07:16:19 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32163 Mon 23 Sep 2019 13:47:08 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47564 Mon 23 Jan 2023 13:18:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53926 Mon 22 Jan 2024 16:49:22 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53051 Fri 17 Nov 2023 11:59:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53066 Fri 17 Nov 2023 11:52:33 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46225 Fri 09 Dec 2022 14:48:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:39078 de novo CNOT1 variants, including missense, splice site, and nonsense variants, who present with a clinical spectrum of intellectual disability, motor delay, speech delay, seizures, hypotonia, and behavioral problems. To link CNOT1 dysfunction to the neurodevelopmental phenotype observed, we generated variant-specific Drosophila models, which showed learning and memory defects upon CNOT1 knockdown. Introduction of human wild-type CNOT1 was able to rescue this phenotype, whereas mutants could not or only partially, supporting our hypothesis that CNOT1 impairment results in neurodevelopmental delay. Furthermore, the genetic interaction with autism-spectrum genes, such as ASH1L, DYRK1A, MED13, and SHANK3, was impaired in our Drosophila models. Molecular characterization of CNOT1 variants revealed normal CNOT1 expression levels, with both mutant and wild-type alleles expressed at similar levels. Analysis of protein-protein interactions with other members indicated that the CCR4-NOT complex remained intact. An integrated omics approach of patient-derived genomics and transcriptomics data suggested only minimal effects on endonucleolytic nonsense-mediated mRNA decay components, suggesting that de novo CNOT1 variants are likely haploinsufficient hypomorph or neomorph, rather than dominant negative. In summary, we provide strong evidence that de novo CNOT1 variants cause neurodevelopmental delay with a wide range of additional co-morbidities. Whereas the underlying pathophysiological mechanism warrants further analysis, our data demonstrate an essential and central role of the CCR4-NOT complex in human brain development.]]> Fri 06 May 2022 12:37:33 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52991 Fri 03 Nov 2023 16:05:35 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42774 Fri 02 Sep 2022 11:00:23 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51355 Fri 01 Sep 2023 13:43:26 AEST ]]>