https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7417 Sat 24 Mar 2018 11:13:40 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7584 Sat 24 Mar 2018 10:45:51 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15983 50% of asthma-related healthcare costs. New investigations into the pathogenesis of glucocorticoid resistance in severe asthma indicate that pulmonary macrophages may play central roles in promoting airway inflammation, particularly in asthma that is resistant to steroid therapy. Importantly, factors that are linked to the activation of pulmonary macrophages may contribute to glucocorticoid resistance and severe asthma. Here, we review recent advances in understanding the roles of pulmonary macrophages in the mechanisms of glucocorticoid resistance and the pathogenesis of severe asthma. We discuss the role of macrophage phenotype, infection, IFN-γ, LPS, associated signaling pathways, TNF-α, MIF, and other macrophage-associated factors. Understanding the pathogenesis of steroid-resistant severe asthma will contribute to the identification of optimal therapeutic strategies for the effective management of the disease.]]> Sat 24 Mar 2018 08:23:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20751 Sat 24 Mar 2018 08:00:25 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20774 6 by cNLS Mapper), while 8 nuclear proteins lacked any cNLS. In addition, we developed a new strategy to predict which cargoes bind to importin a through the conserved C-terminal acidic domain (ARM repeats 9-10), and provided functional validation of a predicted importin α C-terminal binding segment in Senataxin and Smarca4. Evaluation of this set of candidate binding partners from spermatogenic cells using several bioinformatics approaches provides new evidence that individual importin αs may serve unique and nonredundant roles in mediating cellular differentiation.]]> Sat 24 Mar 2018 08:00:22 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19725 P<0.05), miR-103 (P<0.01), and miR-107 (P<0.05) expression, a decrease in IR (P<0.05), phopsho- Akt (P<0.01), and phospho-FoxO1 (P<0.01) abundance, and a paradoxical decrease in 11ßHSD1 (P<0.05), PEPCK-C (P<0.01), and PEPCK-M (P<0.05) expression in lambs. These changes were ablated by a period of moderate dietary restriction imposed during the periconceptional period. Maternal dietary restriction alone also resulted in decreased abundance of a separate subset of hepatic insulin-signaling molecules, namely, IRS1 (P<0.05), PDK1 (P<0.01), phospho-PDK1 (P<0.05), and aPKCζ (P<0.05) and in decreased PEPCK-C (P<0.01) and G6Pase (P<0.01) expression in the lamb. Our findings highlight the sensitivity of the epigenome to maternal nutrition around conception and the need for dietary interventions that maximize metabolic benefits and minimize metabolic costs for the next generation.-Nicholas, L. M., Rattanatray, L., MacLaughlin, S. M., Ozanne, S. E., Kleemann, D. O.,Walker, S. K., Morrison, J. L., Zhang, S., Muhlhausler, B. S., Martin-Gronert, M. S., McMillen, I. C. Differential effects of maternal obesity and weight loss in the periconceptional period on the epigenetic regulation of hepatic insulin-signaling pathways in the offspring.]]> Sat 24 Mar 2018 07:53:44 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27976 50 = 6.7 nM) led to a significant reduction in dynamin phosphorylation (10.3% vs. 27.3%; P < 0.001), acrosomal exocytosis (9.7% vs. 25.7%; P < 0.01), and in vitro fertilization (53% vs. 100%; P < 0.01). GSK3 was shown to be present in developing germ cells where it colocalized with dynamin in the peri-acrosomal domain. However, additional GSK3 was acquired by maturing mouse spermatozoa within the male reproductive tract, via a novel mechanism involving direct interaction of sperm heads with extracellular structures known as epididymal dense bodies. These data reveal a novel mode for the cellular acquisition of a protein kinase and identify a key role for GSK3 in the regulation of sperm maturation and acrosomal exocytosis.—Reid, A. T., Anderson, A. L., Roman, S. D., McLaughlin, E. A., McCluskey, A., Robinson, P. J., Aitken, R. J., Nixon, B. Glycogen synthase kinase 3 regulates acrosomal exocytosis in mouse spermatozoa via dynamin phosphorylation.]]> Sat 24 Mar 2018 07:38:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28444 -/-Vim^-/- mice, b-wave amplitudes were increased. Moreover, we found that Kir (inward rectifier K⁺) channel protein expression was reduced in the retinas of GFAP^-/-Vim^-/- mice and that Kir-mediated current amplitudes were lower in Müller glial cells isolated from these mice. Studies have shown that the IF system, in addition, is involved in the retinal response to injury and that attenuated Müller cell reactivity and reduced photoreceptor cell loss are observed in IF-deficient mice after experimental retinal detachment. We investigated whether the lack of IF proteins would affect cell survival in a retinal ischemia-reperfusion model. We found that although cell loss was induced in both genotypes, the number of surviving cells in the inner retina was lower in IF-deficient mice. Our findings thus show that the inability to produce GFAP and Vim affects normal retinal physiology and that the effect of IF deficiency on retinal cell survival differs, depending on the underlying pathologic condition.]]> Sat 24 Mar 2018 07:29:01 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27749 Drosophila and also shown to be vital to sperm development and reproductive potential in the mouse. We focus in depth on the role and function of the vertebrate Musashi ortholog Musashi-1 (MSI1). Through detailed expression studies and utilizing our novel transgenic Msi1 testis-specific overexpression model, we have identified 2 unique RNA-binding targets of MSI1 in spermatogonia, Msi2 and Erh, and have demonstrated a role for MSI1 in translational regulation. We have also provided evidence to suggest that nuclear import protein, IPO5, facilitates the nuclear translocation of MSI1 to the transcriptionally silenced XY chromatin domain in meiotic pachytene spermatocytes, resulting in the release of MSI1 RNA-binding targets. This firmly establishes MSI1 as a master regulator of posttranscriptional control during early spermatogenesis and highlights the significance of the subcellular localization of RNA binding proteins in relation to their function.]]> Sat 24 Mar 2018 07:27:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26537 95% of sperm. Anapparent molecular rearrangement in the complex occurs, bringing PRKACA and TCP11 into proximity. Taken together, these results suggest a role for the novel complex of SPIF, PRKACA, and TCP11 during spermcapacitation, fertilization, and embryogenesis.]]> Sat 24 Mar 2018 07:23:27 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22126 Sat 24 Mar 2018 07:09:58 AEDT ]]>