https://novaprd-lb.newcastle.edu.au/vital/access/manager/Index ${session.getAttribute("locale")} 5 https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:46767 HIST1H3B/C and H3F3A), altering the epigenetic landscape of primitive oligodendrocyte or astrocyte precursor cells of the pontine region of the brainstem. Lysine‐to‐methionine point mutations at amino acid 27 (H3K27M) co‐occur with alterations in signaling genes, including the receptor tyrosine kinases (PDGFR/KIT/VEGFR/MET/EGFR), activin A receptor (ACVR1), intracellular kinases (PI3K/AKT/mTOR), cyclin‐dependent kinases (CDKs1/4/6), transcriptional regulators (MYCN), and tumor suppressors (PTEN/TP53). This cooperation drives gene expression signatures that inhibit cellular differentiation (ID1/2, Hedgehog) and promotes malignant transformation. Unique to DIPG, is the frequency of co‐occurring sets of genomic insults. However, mapping of the oncogenic signaling pathways activated in response to recurring mutations is unresolved. Herein, known oncogenic signal pathways activated in response to recurring somatic mutations and gene amplifications in DIPG are reviewed. Additionally, an important role for high‐resolution quantitative proteomics/phosphoproteomics in the characterization of signaling cascades are highlighted. These regulate the cell cycle, epigenetics and anti‐apoptotic processes, information critical for the development of improved treatment strategies for DIPG.]]> Wed 30 Nov 2022 11:45:04 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:37385 Wed 28 Oct 2020 18:12:02 AEDT ]]> https://novaprd-lb.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://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:52590 Wed 28 Feb 2024 15:32:45 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:52876 Wed 28 Feb 2024 11:01:07 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:45249 Wed 26 Oct 2022 19:43:42 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:45260 Wed 26 Oct 2022 18:02:18 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:45204 Wed 26 Oct 2022 15:29:09 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:43523 Wed 21 Sep 2022 11:25:36 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:40952 Wed 20 Jul 2022 15:22:13 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:49349 Wed 17 Apr 2024 10:02:24 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:47168 Wed 14 Dec 2022 15:48:43 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:40283 Wed 13 Mar 2024 08:47:04 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:30804 Wed 11 Apr 2018 12:10:05 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:27712 Wed 11 Apr 2018 12:01:24 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:27739 Wed 11 Apr 2018 11:56:44 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:30207 350 microRNAs (miRNAs), a developmentally important sRNA class, the majority (~60%) of which are also represented by the miRNA signature of spermatozoa. This includes >50 miRNAs that were found exclusively in epididymal sperm and epididymosomes, but not in the surrounding soma. We also documented substantial changes in the epididymosome miRNA cargo, including significant fold changes in almost half of the miRNAs along the length of the epididymis. Finally, we provide the first direct evidence for the transfer of several prominent miRNA species between mouse epididymosomes and spermatozoa to afford novel insight into a mechanism of intercellular communication by which the sRNA payload of sperm can be selectively modified during their post-testicular maturation.]]> Wed 11 Apr 2018 11:13:04 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:34663 Wed 10 Apr 2019 13:35:43 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:37820 Wed 09 Feb 2022 15:58:38 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:38419 Wed 08 Sep 2021 16:10:39 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:46915 Wed 07 Dec 2022 09:37:40 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:44031 5-years following diagnosis, however, for those that fail upfront therapies, survival is poor. Reactive oxygen species (ROS) are elevated in a range of cancers and are emerging as significant contributors to the leukaemogenesis of ALL. ROS modulate the function of signalling proteins through oxidation of cysteine residues, as well as promote genomic instability by damaging DNA, to promote chemotherapy resistance. Current therapeutic approaches exploit the pro-oxidant intracellular environment of malignant B and T lympho-blasts to cause irreversible DNA damage and cell death, however these strategies impact normal haematopoiesis and lead to long lasting side-effects. Therapies suppressing ROS production, espe-cially those targeting ROS producing enzymes such as the NADPH oxidases (NOXs), are emerging alternatives to treat cancers and may be exploited to improve the ALL treatment. Here, we discuss the roles that ROS play in normal haematopoiesis and in ALL. We explore the molecular mechanisms underpinning overproduction of ROS in ALL, and their roles in disease progression and drug resistance. Finally, we examine strategies to target ROS production, with a specific focus on the NOX enzymes, to improve the treatment of ALL.]]> Wed 05 Oct 2022 15:18:52 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:43968 Wed 05 Oct 2022 14:15:31 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:50158 Wed 05 Jul 2023 15:35:31 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:38138 Wed 04 Aug 2021 15:42:40 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:45607 Wed 02 Nov 2022 14:14:14 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:55214 Wed 01 May 2024 10:39:22 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:47818 Wed 01 Feb 2023 09:51:54 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:49743 Tue 30 May 2023 15:29:49 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:47613 Tue 24 Jan 2023 11:43:18 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:51137 Tue 22 Aug 2023 15:58:50 AEST ]]> https://novaprd-lb.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://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:40723 Tue 21 Mar 2023 18:42:13 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:35957 Tue 21 Jan 2020 11:08:08 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:43152 Tue 13 Sep 2022 15:28:32 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:33177 Tue 11 Sep 2018 12:15:39 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:44354 Tue 11 Oct 2022 19:42:45 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:35042 Tue 11 Jun 2019 14:20:01 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:39108 Tue 10 May 2022 10:14:50 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:39106 Tue 10 May 2022 09:39:30 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:35834 Kifc1 and Kifc5b, in aged oocytes; family members selectively targeted for expression regulation by endo-siRNAs of elevated abundance. The implications of reduced Kifc1 and Kifc5b expression were explored using complementary siRNA-mediated knockdown and pharmacological inhibition strategies, both of which led to increased rates of aneuploidy in otherwise healthy young oocytes. Collectively, our data raise the prospect that altered sRNA abundance, specifically endo-siRNA abundance, could influence the quality of the aged oocyte.]]> Tue 10 Dec 2019 16:34:23 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:36571 Tue 09 Jun 2020 11:40:42 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:39495 Crocodylus porosus as a tractable model for understanding crocodilian sperm physiology. In extending our systematic characterisation of saltwater crocodile spermatozoa, in this study we examined the development of motility during sperm transport through the excurrent duct system of the male crocodile. The results show that approximately 20% of crocodile testicular spermatozoa are immediately motile but experience a gradient of increasing motility (percentage motile and rate of movement) as they transit the male reproductive tract (epididymis). Moreover, we confirmed that, as in ejaculated crocodile spermatozoa, increased intracellular cAMP levels promoted a significant and sustained enhancement of sperm motility regardless of whether the cells were isolated from the testis or epididymis. Along with the development of artificial reproductive technologies, this research paves the way for the opportunistic recovery, storage and potential utilisation of post-mortem spermatozoa from genetically valuable animals.]]> Tue 09 Aug 2022 14:34:34 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:40953 Tue 07 Nov 2023 09:51:49 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:33498 Tue 06 Nov 2018 11:19:37 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:34061 Tue 05 Feb 2019 14:14:54 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:43870 Tue 04 Oct 2022 12:28:50 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:43823 Tue 04 Oct 2022 11:04:24 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:34727 Tue 03 Sep 2019 17:57:47 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:34948 Tue 03 Sep 2019 17:57:02 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:34015 Tue 03 Sep 2019 17:54:59 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:34016 Thu 30 May 2019 15:47:52 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:34014 Thu 30 May 2019 15:41:20 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:34868 Thu 30 May 2019 15:31:33 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:44824 Thu 27 Oct 2022 12:44:28 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:45372 Chd4 expression significantly impairs SSC regenerative capacity, causing a ∼50% reduction in colonization of recipient testes. An scRNA-seq comparison revealed reduced expression of “self-renewal” genes following Chd4 knockdown, along with increased expression of signature progenitor genes. Co-immunoprecipitation analyses demonstrated that CHD4 regulates gene expression in spermatogonia not only through its traditional association with the remodeling complex NuRD, but also via interaction with the GDNF-responsive transcription factor SALL4. Cumulatively, the results of this study depict a previously unappreciated role for CHD4 in controlling fate decisions in the spermatogonial pool.]]> Thu 27 Oct 2022 12:14:10 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:44994 Thu 27 Oct 2022 09:09:41 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:38313 Thu 26 Aug 2021 13:31:44 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:49642 Thu 25 May 2023 08:40:46 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:37398 Thu 16 Nov 2023 12:24:42 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:43344 Thu 15 Sep 2022 15:19:01 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:43294 Thu 15 Sep 2022 12:51:41 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:35956 Thu 14 May 2020 15:11:42 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:47101 Thu 06 Jul 2023 14:06:28 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:32118 Thu 03 May 2018 12:11:55 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:32117 Thu 03 May 2018 12:04:54 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:30490 Thu 03 Feb 2022 12:19:24 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:42690 Thu 01 Sep 2022 09:06:31 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:29633 2+2+ release and the suite of molecular modifications that sweep through the oocyte to ensure the successful union of the parental germlines and ensure embryogenic fidelity.]]> Sat 24 Mar 2018 07:41:53 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:27718 via the enzyme, cytochrome P450, family 2, subfamily E, polypeptide 1 (CYP2E1). Acrylamide was administered to male CD1 mice for three or sixmonths at a dose of 0.18 mg/kg bodyweight/day. DNA damage was detected in germ cells and maturespermatozoa of exposed mice without compromising their overall fertility. The use of resveratrol, anantioxidant and known CYP2E1 inhibitor, was found to ameliorate the DNA damage in both germ cells andspermatozoa. However, extended resveratrol treatment (six months, 10.0 mg/kg bw/week) resulted inpremature activation of these cells. Thus the DNA damage found in spermatozoa after chronic acrylamideadministration can be alleviated but an alternative CYP2E1 inhibitor may be required.]]> Sat 24 Mar 2018 07:24:39 AEDT ]]> https://novaprd-lb.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://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:49719 Mon 29 May 2023 15:14:02 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:51259 Mon 28 Aug 2023 13:50:03 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:37797 Mon 26 Apr 2021 12:23:37 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:54975 Mon 25 Mar 2024 15:21:41 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:32871 in vitro fertilisation, though displayed reduced developmental competence beyond the 2-cell stage (P=0.02). To account for these findings, we analysed the efficacy of DSB resolution, revealing a significant reduction in DSB lesions 4 h post-ETP treatment. Notably, this response was completely abrogated by pharmacological inhibition of key elements (DNA-PKcs and DNA ligase IV) of the canonical non-homologous end joining DNA repair pathway, thus providing the first evidence implicating this reparative cascade in the protection of the maternal genome.]]> Mon 23 Sep 2019 10:15:15 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:47477 0.05). Collectively, our acute heat stress model supports the existence of heat susceptible stages of germ cell development, with the round spermatids being most perturbed and spermatogonial stem cells exhibiting resistance to this insult. Such findings were complemented by our chronic heat stress model, which further supported the vulnerability of the round spermatid population.]]> Mon 23 Jan 2023 11:33:24 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:42359 Mon 22 Aug 2022 14:08:27 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:54399 Mon 18 Mar 2024 13:06:51 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:40758 Mon 18 Jul 2022 13:54:17 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:40738 Mon 18 Jul 2022 13:12:16 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:40400 Mon 11 Jul 2022 13:55:46 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:34117 Mon 11 Feb 2019 16:05:21 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:33479 Mon 05 Nov 2018 11:10:42 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:51402 Mon 04 Sep 2023 14:52:16 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:36447 Mon 04 May 2020 16:14:04 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:48239 Mon 01 May 2023 14:49:55 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:41288 Mon 01 Aug 2022 11:41:21 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:40281 Fri 29 Jul 2022 13:23:12 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:45427 Fri 28 Oct 2022 11:48:22 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:51228 Fri 25 Aug 2023 11:51:38 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:36974 Fri 24 Jul 2020 14:55:41 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:41982 Fri 19 Apr 2024 11:58:15 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:53140 Fri 17 Nov 2023 11:42:18 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:49362 Fri 12 May 2023 12:35:13 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:37679 Fri 12 Mar 2021 10:57:58 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:55287 Fri 10 May 2024 16:22:11 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:51529 Fri 08 Sep 2023 12:10:33 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:48188 Fri 07 Jul 2023 11:41:15 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/manager/Repository/uon:38175 Fri 06 Aug 2021 14:14:50 AEST ]]>