https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46784 Wed 30 Nov 2022 13:21:59 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53095 Wed 27 Mar 2024 12:12:14 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19948 Wed 27 Jul 2022 13:58:56 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40462 Wed 27 Jul 2022 11:59:24 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19079 Wed 20 May 2020 07:11:37 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37132 Wed 19 Aug 2020 14:02:44 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27267 Wed 17 Nov 2021 16:32:46 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24338 Wed 17 Nov 2021 16:29:37 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30252 N-linked sialylated glycoproteins in rat epididymal sperm and investigate whether they are regulated during epididymal transit. Sialylated glycopeptides from caput, corpus, and cauda spermatozoa were enriched using titanium dioxide beads. Bound N-linked glycopeptides were released by enzymatic deglycosylation using PNGase F and then analyzed by liquid chromatography tandem-mass spectrometry. A total of 92 unique N-linked sialylated glycopeptides were identified from 65 different proteins. These included members of the disintegrin and metalloproteinase domain-containing protein family (ADAM), Basigin, and Testis-expressed protein 101 (TEX101). Remarkably, label-free quantification showed that more than half of these peptides (48/92) were regulated during epididymal transit. Of interest, the protein TEX101 exhibited PNGase F-resistant deglycosylation under the conditions used in this study. The results from this study showed that changes in the N-linked sialoglycoprotein profile is a major hallmark of sperm maturation in rats.]]> Wed 11 Apr 2018 17:21:10 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:15122 Wed 11 Apr 2018 15:13:29 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:2527 Wed 11 Apr 2018 14:30:38 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28369 Wed 11 Apr 2018 14:08:08 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:26157 Wed 11 Apr 2018 13:31:01 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25775 Wed 11 Apr 2018 13:20:33 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:4511 Wed 11 Apr 2018 13:20:14 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21426 Wed 11 Apr 2018 11:46:49 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:1286 Wed 11 Apr 2018 11:40:47 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17083 a, R_d and R_e rough LPS mutants. The SAR analysis enabled by the binding data suggested that, in addition to the important role played by the lipid A and core components of LPS, it is predominately the unique species- and strain-specific carbohydrate structure of the O-antigen polysaccharide that largely determines the binding affinity for AGP. Together, these data are consistent with the role of AGP in the binding and transport of LPS in plasma during acute-phase inflammatory responses to invading Gram-negative bacteria.]]> Wed 11 Apr 2018 11:39:50 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25253 Wed 11 Apr 2018 11:30:48 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27621 Wed 11 Apr 2018 10:16:30 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41662 Wed 10 Aug 2022 11:10:24 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36947 Pseudomonas aeruginosa (P. aeruginosa) in the lungs of cystic fibrosis patients makes eradication of infections with antibiotic therapy very difficult. The lipopeptide antibiotics polymyxin B and colistin are currently the last-resort therapies for infections caused by multidrug-resistant P. aeruginosa. In the present study, we investigated the antibacterial activity of a series of polymyxin lipopeptides (polymyxin B, colistin, FADDI-003, octapeptin A₃, and polymyxin A₂) against a panel of polymyxin-susceptible and polymyxin-resistant P. aeruginosa cystic fibrosis isolates grown under planktonic or biofilm conditions in artificial sputum and their interactions with sputum component biomolecules. In sputum media under planktonic conditions, the lipopeptides FADDI-003 and octapeptin A₃ displayed very promising activity against the polymyxin-resistant isolate FADDI-PA066 (polymyxin B minimum inhibitory concentration (MIC) = 32 mg/L), while retaining their activity against the polymyxin-sensitive strains FADDI-PA021 (polymyxin B MIC = 1 mg/L) and FADDI-PA020 (polymyxin B MIC = 2 mg/L). Polymyxin A₂ was only effective against the polymyxin-sensitive isolates. However, under biofilm growth conditions, the hydrophobic lipopeptide FADDI-003 was inactive compared to the more hydrophilic lipopeptides, octapeptin A₃, polymyxin A₂, polymyxin B, and colistin. Transmission electron micrographs revealed octapeptin A₃ caused reduction in the cell numbers in biofilm as well as biofilm disruption/“antibiofilm” activity. We therefore assessed the interactions of the lipopeptides with the component sputum biomolecules, mucin, deoxyribonucleic acid (DNA), surfactant, F-actin, lipopolysaccharide, and phospholipids. We observed the general trend that sputum biomolecules reduce lipopeptide antibacterial activity. Collectively, our data suggests that, in the airways, lipopeptide binding to component sputum biomolecules may reduce antibacterial efficacy and is dependent on the physicochemical properties of the lipopeptide.]]> Wed 09 Mar 2022 15:59:20 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50850 Wed 09 Aug 2023 09:39:07 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51988 Tue 26 Sep 2023 10:47:02 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18188 Tue 23 Jun 2015 18:36:40 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34845 Thu 28 Oct 2021 12:35:34 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51207 Thu 24 Aug 2023 15:00:51 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48399 Thu 11 May 2023 13:36:21 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25164 Pseudomonas aeruginosa. The in vitro synergistic activity of polymyxin B combined with ivacaftor or lumacaftor was assessed using checkerboard and static time-kill assays against a panel of polymyxin-susceptible and polymyxin-resistant P. aeruginosa isolates from the lungs of CF patients. Polymyxin B, ivacaftor, and lumacaftor were ineffective when used individually against polymyxin-resistant (MIC ≥ 4 mg/L) isolates. However, when used together, the combination of clinically relevant concentrations of polymyxin B (2 mg/L) combined with ivacaftor (8 mg/L) or ivacaftor (8 mg/L) + lumacaftor (8 mg/L) displayed synergistic killing activity against polymyxin-resistant P. aeruginosa isolates as demonstrated by a 100-fold decrease in the bacterial count (CFU/mL) even after 24 h. The combinations also displayed excellent antibacterial activity against P. aeruginosa under CF relevant conditions in a sputum medium assay. The combination of lumacaftor (alone) with polymyxin B showed additivity against P. aeruginosa. The potential antimicrobial mode of action of the combinations against P. aeruginosa was investigated using different methods. Treatment with the combinations induced cytosolic GFP release from P. aeruginosa cells and showed permeabilizing activity in the nitrocefin assay, indicating damage to both the outer and inner Gram-negative cell membranes. Moreover, scanning and transmission electron micrographs revealed that the combinations produce outer membrane damage to P. aeruginosa cells that is distinct from the effect of each compound per se. Ivacaftor was also shown to be a weak inhibitor of the bacterial DNA gyrase and topoisomerase IV with no effect on either human type I or type IIα topoisomerases. Lumacaftor displayed the ability to increase the cellular production of damaging reactive oxygen species. In summary, the combination of polymyxin B with KALYDECO or ORKAMBI exhibited synergistic activity against highly polymyxin-resistant P. aeruginosa CF isolates and can be potentially useful for otherwise untreatable CF lung infections.]]> Thu 04 Nov 2021 10:40:12 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36366 Thu 02 Apr 2020 13:13:30 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41254 Sat 30 Jul 2022 12:54:22 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:8340 Sat 24 Mar 2018 10:47:11 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:11888 Sat 24 Mar 2018 10:31:26 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:7891 Sat 24 Mar 2018 08:35:08 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:3007 Sat 24 Mar 2018 08:33:06 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:9963 Sat 24 Mar 2018 08:14:26 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:10935 Sat 24 Mar 2018 08:13:21 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:11318 Sat 24 Mar 2018 08:12:33 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19261 Sat 24 Mar 2018 08:06:38 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19083 Sat 24 Mar 2018 08:05:24 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19082 Sat 24 Mar 2018 08:05:20 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17528 Sat 24 Mar 2018 08:03:55 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17419 Sat 24 Mar 2018 08:01:38 AEDT ]]> https://ogma.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://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19949 Sat 24 Mar 2018 07:58:32 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20031 Sat 24 Mar 2018 07:50:54 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20019 Sat 24 Mar 2018 07:50:53 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19306 Sat 24 Mar 2018 07:50:00 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:5181 Sat 24 Mar 2018 07:47:49 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:5193 Sat 24 Mar 2018 07:47:44 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:5289 Sat 24 Mar 2018 07:46:30 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:5003 Sat 24 Mar 2018 07:44:13 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41 Sat 24 Mar 2018 07:42:12 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29442 Sat 24 Mar 2018 07:39:22 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29533 2+-binding tyrosine-phosphorylation-regulated protein (CABYR) has been implicated in sperm physiological function in several in vitro studies. It has also been implicated as a potential cause of and diagnostic tool in asthenozoospermic human males. CABYR is known to be localized to the fibrous sheath, an accessory structure in the flagellar principal piece. Utilizing the CRISPR–Cas9 technology, we have knocked out this gene in mice to understand its role in male fertility. Cabyr-knockout male mice showed severe subfertility with a defect in sperm motility as well as a significant disorganization in the fibrous sheath. Further, abnormal configuration of doublet microtubules was observed in the Cabyr-knockout spermatozoa, suggesting that the fibrous sheath is important for the correct organization of the axoneme. Our results show that it is the role of CABYR in the formation of the fibrous sheath that is essential for male fertility.]]> Sat 24 Mar 2018 07:32:26 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25432 Sat 24 Mar 2018 07:31:54 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27256 Sat 24 Mar 2018 07:29:12 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27252 in vitro microbiological assays. We show that fibrinogen, complement C4, haptoglobulin, α-1-antitrypsin, fibronectin, transferrin, immunoglobulin G, hemopexin, and humans serum albumin are responsible for the majority of the sequestering activity in plasma. No binding was observed to α-1-acid-glycoprotein. The findings of this study have broad reaching implications for antibiotic drug design and for dose tailoring to suit the plasma protein levels of individual patients in order to maximize the clinical efficacy of important first-line antibiotics such as ertapenem.]]> Sat 24 Mar 2018 07:29:09 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27253 Sat 24 Mar 2018 07:29:09 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27751 Sat 24 Mar 2018 07:27:46 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27056 Sat 24 Mar 2018 07:25:20 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:4868 Sat 24 Mar 2018 07:18:43 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22257 Sat 24 Mar 2018 07:17:39 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22095 Sat 24 Mar 2018 07:15:17 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22207 R²= 0.89) in untreated populations of human spermatozoa emphasized the pathophysiological significance of these findings. The latter also provide a biochemical explanation for the self-perpetuating nature of oxidative stress in the male germ line, with the products of lipid peroxidation stimulating free radical generation by the sperm mitochondria in a positive feedback loop.]]> Sat 24 Mar 2018 07:11:16 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23971 Sat 24 Mar 2018 07:10:04 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42360 Mon 22 Aug 2022 14:01:23 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48057 Mon 20 Feb 2023 12:15:16 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37687 90% purity. Properties of these cultured adult Sertoli cells were then compared with those of cultured Sertoli cells derived from 20-day-old mice (also > 90% purity). By cell counting, bromo-2-deoxyuridine incorporation, and metaphase plate detection, we demonstrated that only adult Sertoli cells did not proliferate throughout 12 culture days. In contrast, Sertoli cells derived from 20-day-old mice still proliferated until Day 10 in culture. The morphology and profiles of intracellular lipidomics and spent medium proteomics of the 2 cultures were also different. Cultured adult Sertoli cells were larger in size and contained higher levels of triacylglycerols, cholesteryl esters, and seminolipid, and the proteins in their spent medium were mainly engaged in cellular metabolism. In contrast, proteins involved in cell division, including anti-Mullerian hormone, cell division cycle protein 42 (CDC42), and collagen isoforms, were at higher levels in Sertoli cell cultures derived from 20-day-old mice. Therefore, cultured Sertoli cells derived from 10-week-old mice, rather than those from 20-day-old animals, should be used for studies on properties of adult Sertoli cells.]]> Mon 15 Mar 2021 15:08:53 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17366 Mon 15 Jan 2024 14:36:47 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40400 Mon 11 Jul 2022 13:55:46 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40845 Mon 08 Aug 2022 15:39:55 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42820 Mon 05 Sep 2022 11:35:27 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54093 Mon 05 Feb 2024 09:20:48 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50539 Fri 28 Jul 2023 09:14:39 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42239 Fri 26 Aug 2022 09:43:19 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40160 Fri 22 Jul 2022 13:28:02 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31380 Pseudomonas aeruginosa using neutron reflectometry, together with fluorimetric and calorimetry methods. For the first time, our neutron reflectometry results reveal that the interaction of octapeptin A3 with the Gram-negative outer membrane involves an initial transient polar interaction with the phospholipid and lipid A headgroups, followed by the penetration of the entire octapeptin molecule into the fatty acyl core of the outer membrane. This mechanism contrasts with that of polymyxin B, which specifically targets lipid A, whereas octapeptins appear to target both lipid A and phospholipids. Furthermore, the mechanism of octapeptins does not appear to be highly dependent on an initial complementary electrostatic interaction with lipid A, which accounts for their ability to bind to lipid A of polymyxin-resistant Gram-negative bacteria that is modified with cationic moieties that act to electrostatically repel the cationic polymyxin molecule. The presented findings shed new light on the mechanism whereby octapeptins penetrate the outer membrane of polymyxin-resistant Gram-negative pathogens and highlight their potential as candidates for development as new antibiotics against problematic multi-drug-resistant pathogens.]]> Fri 18 Sep 2020 14:00:17 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35929 MED12 alterations in 39 of 65 fibroids (60%) from 14 patients. Using isobaric tagged-based quantitative mass spectrometry on three selected patients (n = 9 fibroids), we observed a common set of upregulated ( > 1.5-fold) and downregulated ( < 0.66-fold) proteins in small, medium, and large fibroid samples of annotated MED12 status. These two sets of upregulated and downregulated proteins were the same in all patients, regardless of variations in fibroid size and MED12 status. We then focused on one of the significant upregulated ECM proteins and confirmed the differential expression of periostin using western blotting and immunohistochemical analysis. Our study defined the proteome of uterine fibroids and identified that increased ECM protein expression, in particular periostin, is a hallmark of uterine fibroids regardless of MED12 mutation status. This study sets the foundation for further investigations to analyze the mechanisms regulating ECM overexpression and the functional role of upregulated ECM proteins in leiomyogenesis.]]> Fri 17 Jan 2020 11:35:08 AEDT ]]>