https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50215 Wed 28 Feb 2024 15:09:52 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49099 Wed 13 Mar 2024 13:56:45 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54163 Tue 06 Feb 2024 13:06:40 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:43823 Tue 04 Oct 2022 11:04:24 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51476 Thu 07 Sep 2023 10:45:46 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31327 Thu 03 Feb 2022 12:22:23 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:5196 Thu 01 Aug 2019 17:32:00 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19294 Sat 24 Mar 2018 07:56:07 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21833 HFE gene. There is evidence from both human and animal studies that HFE gene variants may affect brain function and modify risks of brain disease. To investigate how disruption of HFE influences brain transcript levels, we used microarray and real-time reverse transcription polymerase chain reaction to assess the brain transcriptome in Hfe^−/− mice relative to wildtype AKR controls (age 10 weeks, n ≥ 4/group). The Hfe^−/− mouse brain showed numerous significant changes in transcript levels (p < 0.05) although few of these related to proteins directly involved in iron homeostasis. There were robust changes of at least 2-fold in levels of transcripts for prominent genes relating to transcriptional regulation (FBJ osteosarcoma oncogene Fos, early growth response genes), neurotransmission (glutamate NMDA receptor Grin1, GABA receptor Gabbr1) and synaptic plasticity and memory (calcium/calmodulin-dependent protein kinase IIα Camk2a). As previously reported for dietary iron-supplemented mice, there were altered levels of transcripts for genes linked to neuronal ceroid lipofuscinosis, a disease characterized by excessive lipofuscin deposition. Labile iron is known to enhance lipofuscin generation which may accelerate brain aging. The findings provide evidence that iron loading disorders can considerably perturb levels of transcripts for genes essential for normal brain function and may help explain some of the neurologic signs and symptoms reported in hemochromatosis patients.]]> Sat 24 Mar 2018 07:52:17 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22117 + T-helper 2 lymphocyte-like (Th type-2) inflammatory responses in the lung. Although IL-25 up-regulates IL-13 in the lung, the contribution of this and other type 2 cytokine signalling pathways to the induction and persistence of airways hyper-reactivity (AHR) and allergic inflammation are unclear. Objective: To determine the downstream factors employed by IL-25 to induce Th type-2 pulmonary inflammation and AHR. Methods: IL-25 was delivered to the airways of BALB/c mice by intra-tracheal (i.t.) instillation and AHR and Th type-2 inflammatory responses were characterized in wild type (WT) and Th type-2-cytokine and -signalling pathway-deficient (−/−) mice. Results: IL-25 treatment resulted in AHR, eosinophilic inflammation, mucus hypersecretion and a progressive increase in the production of Th type-2 cytokines in the lungs. Levels of arginase-I (arg-I) and eotaxin were also elevated by IL-25 treatment. A significant reduction in AHR, and attenuation of mucus production was observed in IL-25-treated IL-13^−/−, IL-4 receptor alpha (IL-4Rα^−/−)- and signal-transducer-and-activator-of-transcription-factor-6 (STAT6^−/−)-deficient mice. AHR was also inhibited in IL-4^−/−- and IL-5/eotaxin(1)^−/−- deficient mice treated with IL-25, however, mucus hypersecretion was not completely ablated. IL-25 promoted Th type-2 responses by directly acting on naïve T cells. Conclusion: IL-25 potently (single dose) induces sustained AHR and acute pulmonary inflammation with eosinophilia. IL-25-induced AHR is dependent on the production of Th type-2 cytokines, and removal of IL-13 and its signal transduction pathway prevents IL-25-induced airways inflammation and AHR. IL-25 potently induces inflammatory cascades that may exacerbate allergic airways inflammation by promoting Th type-2 cytokine responses in conjunction with the up-regulation of factors (eotaxin and arg-I) that can amplify inflammation associated with allergic disorders. Dysregulation in IL-25 production may predispose to features of allergic airways disease.]]> Sat 24 Mar 2018 07:13:18 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23144 mut), a model of a rare type of hereditary hemochromatosis, relative to wildtype control mice. The results were compared with our previous findings in dietary iron-supplemented wildtype mice and Hfe^−/− mice, a model of a common type of hereditary hemochromatosis. For transcripts showing significant changes relative to controls across all three models, there was perfect (100%) directional concordance (i.e. transcripts were increased in all models or decreased in all models). Comparison of the two models of hereditary hemochromatosis, which showed more pronounced changes than the dietary iron-supplemented mice, revealed numerous common molecular effects. Pathway analyses highlighted changes for genes relating to long-term depression (6.8-fold enrichment, p = 5.4 × 10⁻⁷) and, to a lesser extent, long-term potentiation (3.7-fold enrichment, p = 0.01), with generalized reductions in transcription of key genes from these pathways, which are involved in modulating synaptic strength and efficacy and are essential for memory and learning. The agreement across the models suggests the findings are robust and strengthens previous evidence that iron loading disorders affect the brain. Perturbations of brain phenomena such as long-term depression and long-term potentiation might partly explain neurologic symptoms reported for some hemochromatosis patients.]]> Sat 24 Mar 2018 07:10:33 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36313 Mon 23 Aug 2021 12:41:47 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40023 Mon 04 Jul 2022 09:22:32 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34624 CKO mice by conditional deletion of the liver kinase B1 (LKB1) tumor suppressor gene, Stk11 (serine threonine kinase 11), in the fetal Müllerian duct mesenchyme (MDM), the caudal remnant of which is thought to be assimilated by the urogenital sinus primordial mesenchyme in males during fetal development. We show that MDM cells contribute to the postnatal stromal cells at the dorsal aspect of the prostatic urethra by lineage tracing. The Stk11^CKO mice develop prostatic hyperplasia with bladder outlet obstruction, most likely because of stromal expansion. The stromal areas from prostates of Stk11^CKO mice, with or without significant expansion, were estrogen receptor positive, which is consistent with both MD mesenchyme-derived cells and the purported importance of estrogen receptors in BPH development and/or progression. In some cases, stromal hyperplasia was admixed with epithelial metaplasia, sometimes with keratin pearls, consistent with squamous cell carcinomas. Mice with conditional deletion of both Stk11 and Pten developed similar features as the Stk11^CKO mice, but at a highly accelerated rate, often within the first few months after birth. Western blot analyses showed that the loss of LKB1 and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) induces activation of the phospho-5' adenosine monophosphateactivated protein kinase and phospho-AKT serine/threonine kinase 1 signaling pathways, as well as increased total and active ß-catenin. These results suggest that activation of these signaling pathways can induce hyperplasia of the MD stroma, which could play a significant role in the etiology of human BPH.]]> Fri 05 Apr 2019 11:33:46 AEDT ]]>