https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54520 5% O2. Through the generation of a germline-specific Epas1 knockout mouse line, and through modulation of EPAS1 levels in primary cultures of spermatogonia with the small drug molecule Daprodustat, we have demonstrated that EPAS1 is required for robust SSC function in regenerative conditions (post-transplantation and post-chemotherapy), via the regulation of key cellular processes such as metabolism. These findings shed light on the relationship between hypoxia and male fertility and will potentially facilitate optimization of in vitro culture conditions for infertility treatment pipelines using SSCs, such as those directed at pediatric cancer survivors.]]> Wed 28 Feb 2024 16:12:13 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45249 Wed 26 Oct 2022 19:43:42 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15648 Wed 11 Apr 2018 17:00:24 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27033 Xenopus and is expressed during ovarian development in Drosophila. In mammals Musashi is important for spermatogenesis and male fertility, but its role in the ovary has yet to be characterized. In this study we determined the expression of mammalian Musashi proteins MSI1 and MSI2 during mouse folliculogenesis, and through the use of a MSI2-specific knockout mouse model we identified that MSI2 is essential for normal follicle development. Time-course characterization of MSI1 and MSI2 revealed distinct differences in steady-state mRNA levels and protein expression/localization at important developmental time-points during folliculogenesis. Using a gene-trap mouse model that inactivates Msi2, we observed a significant decrease in ovarian mass, and change in follicle-stage composition due to developmental blocking of antral stage follicles and pre-antral follicle loss through atresia. We also confirmed that hormonally stimulated Msi2-deficient mice produce significantly fewer MII oocytes (60.9% less than controls, p < 0.05). Furthermore, the majority of these oocytes are of poor viability (62.2% non-viable/apoptotic, p < 0.05), which causes a reduction in female fertility evidenced by decreased litter size in Msi2-deficient animals (33.1% reduction to controls, p < 0.05). Our findings indicate that MSI1 and MSI2 display distinct expression profiles during mammalian folliculogenesis and that MSI2 is required for pre-antral follicle development.]]> Wed 11 Apr 2018 16:39:10 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27739 Wed 11 Apr 2018 11:56:44 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28064 Wed 11 Apr 2018 09:24:57 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45607 Wed 02 Nov 2022 14:14:14 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51128 6,000 proteins, encompassing the selective loss and gain of several hundred proteins. Further, we demonstrate epididymal-driven activation of RHOA-mediated signaling pathways is an important component of sperm maturation. These data contribute molecular insights into the complexity of proteomic changes associated with epididymal sperm maturation.]]> Tue 22 Aug 2023 15:52:22 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:35957 Tue 21 Jan 2020 11:08:08 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:39108 Tue 10 May 2022 10:14:50 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:39106 Tue 10 May 2022 09:39:30 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36571 Tue 09 Jun 2020 11:40:42 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34061 Tue 05 Feb 2019 14:14:54 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30867 H)-one based Hedgehog signalling pathway (HSP) inhibitors we have developed two new classes of HSP inhibitors based on: L-tryptophan and benzo[1,3]dioxol-5-ylmethyl-[2-(1H-indol-3-yl)-ethyl]-amine. Synthesis of focused compound libraries identified six _L-tryptophan based inhibitors, and two stimulators, of Gli at 10 μM compound concentration. 2,4-Dichloro-13 and indole 16 suppressed mRNA expression of Ptch₁ in Shh LIGHT2 cells, with 13 suppressing and 16 stimulating Gli₂ mRNA expression. Focused library development of the benzo[1,3]dioxol-5-ylmethyl-[2-(1H-indol-3-yl)-ethyl]-amine scaffold afforded two sub-micro molar potent inhibitors of Gli expression with 5-methoxy-1H-indole-2-carboxylic acid benzo[1,3]dioxol-5-ylmethyl-[2-(1H-indol-3-yl)-ethyl]-amide 29 and 5-chloro-1H-indole-2-carboxylic acid benzo[1,3]dioxol-5-ylmethyl-[2-(1H-indol-3-yl)-ethyl]-amide 30 returning IC₅₀ values of 0.5 and 0.24 μM, respectively. Neither 29 nor 30 acted directly on Smo with our data supporting inhibition of the HSP downstream of Smo.]]> Sat 24 Mar 2018 07:26:40 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49719 Mon 29 May 2023 15:14:02 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54975 Mon 25 Mar 2024 15:21:41 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36974 Fri 24 Jul 2020 14:55:41 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55287 Fri 10 May 2024 16:22:11 AEST ]]>