https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51223 Wed 28 Feb 2024 15:37:01 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54555 Wed 28 Feb 2024 09:08:42 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45256 1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.]]> Wed 26 Oct 2022 20:06:39 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45113 Wed 26 Oct 2022 13:33:42 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45073 TP53, with 0.5 cm wider heads in increaser-allele carriers versus non-carriers during mid-childhood, suggesting a previously unrecognized role of TP53 transcripts in human cranial development.]]> Wed 26 Oct 2022 11:49:10 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45015 Wed 26 Oct 2022 10:10:38 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37757 ARF in human and p19^ARF in mouse) that binds to and inhibits mouse double minute 2 homolog (MDM2) leading to p53 activation, whereas p53 suppresses c-Myc through a combination of mechanisms involving transcriptional inactivation and microRNA-mediated repression. Nonetheless, the regulatory interactions between c-Myc and p53 are not retained by cancer cells as is evident from the often-imbalanced expression of c-Myc over wildtype p53. Although p53 repression in cancer cells is frequently associated with the loss of ARF, we disclose here an alternate mechanism whereby c-Myc inactivates p53 through the actions of the c-Myc-Inducible Long noncoding RNA Inactivating P53 (MILIP). MILIP functions to promote p53 polyubiquitination and turnover by reducing p53 SUMOylation through suppressing tripartite-motif family-like 2 (TRIML2). MILIP upregulation is observed amongst diverse cancer types and is shown to support cell survival, division and tumourigenicity. Thus our results uncover an inhibitory axis targeting p53 through a pan-cancer expressed RNA accomplice that links c-Myc to suppression of p53.]]> Wed 17 Nov 2021 16:28:34 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50369 Wed 17 Apr 2024 15:45:50 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30180 2 drawdown during the last glacial period were linked to iron (Fe) fertilization of subantarctic surface waters. The principal source of this Fe is thought to be dust transported from southern mid-latitude deserts. However, uncertainty exists over contributions to CO₂ sequestration from complementary Fe sources, such as the Antarctic ice sheet, due to the difficulty of locating and interrogating suitable archives that have the potential to preserve such information. Here we present petrographic, geochemical and microbial DNA evidence preserved in precisely dated subglacial calcites from close to the East Antarctic Ice-Sheet margin, which together suggest that volcanically-induced drainage of Fe-rich waters during the Last Glacial Maximum could have reached the Southern Ocean. Our results support a significant contribution of Antarctic volcanism to subglacial transport and delivery of nutrients with implications on ocean productivity at peak glacial conditions.]]> Wed 11 Apr 2018 17:19:42 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29116 Wed 11 Apr 2018 15:54:07 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27945 Puma-dependent neuronal apoptosis. Of particular importance to the developing brain is the direct NMDAR-dependent transcriptional control of glutathione biosynthesis, disruption of which can lead to degeneration. Notably, these activity-dependent cell-autonomous mechanisms were found to cooperate with non-cell-autonomous Nrf2-driven support from astrocytes to maintain neuronal GSH levels in the face of oxidative insults. Thus, developmental NMDAR hypofunction and glutathione system deficits, separately implicated in several neurodevelopmental disorders, are mechanistically linked.]]> Wed 11 Apr 2018 14:57:38 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31399 Wed 11 Apr 2018 14:16:38 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17140 Wed 11 Apr 2018 13:06:31 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22665 Wed 11 Apr 2018 12:37:33 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28242 Wed 11 Apr 2018 12:02:15 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14353 Wed 11 Apr 2018 11:50:58 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30645 148,000 samples to reveal huge differences in range changes associated with climate change across 35 plankton taxa. While the range of dinoflagellates and copepods tended to closely track the velocity of climate change (the rate of isotherm movement), the range of the diatoms moved much more slowly. Differences in range shifts were up to 900 km in a recent warming period, with average velocities of range movement between 7 km per decade northwards for taxa exhibiting niche plasticity and 99 km per decade for taxa exhibiting niche conservatism. The differing responses of taxa to global warming will cause spatial restructuring of the plankton ecosystem with likely consequences for grazing pressures on phytoplankton and hence for biogeochemical cycling, higher trophic levels and biodiversity.]]> Wed 11 Apr 2018 11:01:43 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22750 Wed 11 Apr 2018 10:56:04 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20566 Wed 11 Apr 2018 10:41:17 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24536 Wed 11 Apr 2018 09:53:13 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41790 Wed 07 Feb 2024 18:05:12 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34208 −8) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.]]> Wed 04 Sep 2019 09:48:47 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34119 -4) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10^-7). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.]]> Wed 04 Sep 2019 09:40:14 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:55011 Wed 03 Apr 2024 10:12:43 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54476 Tue 27 Feb 2024 14:57:03 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52014 Tue 26 Sep 2023 11:42:59 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44958 MYCN oncogene amplification and consequent N-Myc oncoprotein over-expression die of the disease. Here our analyses of RNA sequencing data identify the long noncoding RNA lncNB1 as one of the transcripts most over-expressed in MYCN -amplified, compared with MYCN -non-amplified, human neuroblastoma cells and also the most over-expressed in neuroblastoma compared with all other cancers. lncNB1 binds to the ribosomal protein RPL35 to enhance E2F1 protein synthesis, leading to DEPDC1B gene transcription. The GTPase-activating protein DEPDC1B induces ERK protein phosphorylation and N-Myc protein stabilization. Importantly, lncNB1 knockdown abolishes neuroblastoma cell clonogenic capacity in vitro and leads to neuroblastoma tumor regression in mice, while high levels of lncNB1 and RPL35 in human neuroblastoma tissues predict poor patient prognosis. This study therefore identifies lncNB1 and its binding protein RPL35 as key factors for promoting E2F1 protein synthesis, N-Myc protein stability and N-Myc-driven oncogenesis, and as therapeutic targets.]]> Tue 25 Oct 2022 13:40:49 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53962 Tue 23 Jan 2024 12:39:27 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:43840 Tue 21 Mar 2023 17:30:07 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54329 Tue 20 Feb 2024 15:59:35 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54322 Tue 20 Feb 2024 15:58:30 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41168 Tue 15 Aug 2023 14:44:00 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:43133 Tue 13 Sep 2022 15:14:32 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47028 Tue 13 Dec 2022 15:55:21 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44342 Tue 11 Oct 2022 19:28:24 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41379 Tue 04 Apr 2023 19:08:51 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33145 Tue 03 Sep 2019 18:18:48 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34876 Tue 03 Sep 2019 18:18:22 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51319 Thu 31 Aug 2023 14:31:50 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51301 Thu 31 Aug 2023 14:21:09 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53500 Thu 30 Nov 2023 15:58:22 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38058 + ions maintain a complete hydration shell while passing between the transmembrane cavity and cytosol, which must be accommodated. To put the canonical model to the test, we locked the conformation of a Kir K⁺ channel to prevent widening of the narrow collar. Unexpectedly, conduction was unimpaired in the locked channels. In parallel, we employed all-atom molecular dynamics to simulate K⁺ ions moving along the conduction pathway between the lower cavity and cytosol. During simulations, the constriction did not significantly widen. Instead, transient loss of some water molecules facilitated K⁺ permeation through the collar. The low free energy barrier to partial dehydration in the absence of conformational change indicates Kir channels are not gated by the canonical mechanism.]]> Thu 29 Jul 2021 12:11:45 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45201 P = 3.96 x 10^-14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.]]> Thu 27 Oct 2022 15:06:39 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45069 JMJD6 gene at 17q21-ter activates gene transcription. Here we show that JMJD6 forms protein complexes with N-Myc and BRD4, and is important for E2F2, N-Myc and c-Myc transcription. Knocking down JMJD6 reduces neuroblastoma cell proliferation and survival in vitro and tumor progression in mice, and high levels of JMJD6 expression in human neuroblastoma tissues independently predict poor patient prognosis. In addition, JMJD6 gene is associated with transcriptional super-enhancers. Combination therapy with the CDK7/super-enhancer inhibitor THZ1 and the histone deacetylase inhibitor panobinostat synergistically reduces JMJD6, E2F2, N-Myc, c-Myc expression, induces apoptosis in vitro and leads to neuroblastoma tumor regression in mice, which are significantly reversed by forced JMJD6 over-expression. Our findings therefore identify JMJD6 as a neuroblastoma tumorigenesis factor, and the combination therapy as a treatment strategy.]]> Thu 27 Oct 2022 14:03:24 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45314 Thu 27 Oct 2022 13:56:29 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37758 regenerating islet-derived (REG) gene family are important regulators of many cellular processes. Here we functionally characterise a non-protein coding product of the family, the long noncoding RNA (lncRNA) REG1CP that is transcribed from a DNA fragment at the family locus previously thought to be a pseudogene. REG1CP forms an RNA–DNA triplex with a homopurine stretch at the distal promoter of the REG3A gene, through which the DNA helicase FANCJ is tethered to the core promoter of REG3A where it unwinds double stranded DNA and facilitates a permissive state for glucocorticoid receptor α (GRα)-mediated REG3A transcription. As such, REG1CP promotes cancer cell proliferation and tumorigenicity and its upregulation is associated with poor outcome of patients. REG1CP is also transcriptionally inducible by GRα, indicative of feedforward regulation. These results reveal the function and regulation of REG1CP and suggest that REG1CP may constitute a target for cancer treatment.]]> Thu 27 Jan 2022 15:55:02 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40967 Thu 21 Jul 2022 08:38:13 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35094 Thu 20 Jun 2019 15:56:20 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52651 Thu 19 Oct 2023 15:18:29 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35949 Thu 13 Jan 2022 10:29:39 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35958 Thu 09 Dec 2021 11:04:31 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34211 Thu 09 Dec 2021 11:02:18 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21277 Sat 24 Mar 2018 07:54:41 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23064 combined=3.32 x 10(^-15), OR=1.72) and independent from rs3731217, the previously reported ALL-associated variant in this region. Of correlated SNPs tagged by this locus, only rs662463 is significant in African Americans, suggesting it is a plausible causative variant. Functional analysis shows that rs662463 is a cis-eQTL for CDKN2B, with the risk allele associated with lower expression, and suggests that rs662463 influences BCP-ALL risk by regulating CDKN2B expression through CEBPB signalling. Functional analysis of rs3731217 suggests it is associated with BCP-ALL by acting within a splicing regulatory element determining CDKN2A exon 3 usage (P=0.01). These findings provide new insights into the critical role of the CDKN2 locus in BCP-ALL aetiology.]]> Sat 24 Mar 2018 07:12:28 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50778 Sat 05 Aug 2023 10:20:13 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21234 Mon 23 Sep 2019 13:08:04 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32383 20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r =-0.62, P = 5.30 × 10 -5 ) but not between CCT and primary open-angle glaucoma (r =-0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.]]> Mon 23 Sep 2019 12:09:41 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42354 Mon 22 Aug 2022 14:01:38 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35062 6+ doped Ni(OH)₂ nanosheet sample (w-Ni(OH)₂) with an outstanding oxygen evolution reaction (OER) performance that is, in a 1 M KOH medium, an overpotential of 237 mV is obtained reaching a current density of 10 mA/cm². Moreover, at high current density of 80 mA/cm², the overpotential value is 267 mV. The corresponding Tafel slope is measured to be 33 mV/dec. The d⁰ W⁶⁺ atom with a low spin-state has more outermost vacant orbitals, resulting in more water and OH- groups being adsorbed on the exposed W sites of the Ni(OH)₂ nanosheet. Density functional theory (DFT) calculations confirm that the O radical and O-O coupling are both generated at the same site of W⁶⁺. This work demonstrates that W⁶⁺ doping can promote the electrocatalytic water oxidation activity of Ni(OH)2 with the highest performance.]]> Mon 19 Aug 2019 16:37:22 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44579 Mon 17 Oct 2022 14:17:20 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30005 Mon 17 Oct 2022 12:06:14 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50969 Mon 14 Aug 2023 15:18:37 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24831 -8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ~11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.]]> Mon 11 Mar 2019 12:13:11 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44169 Mon 10 Oct 2022 10:06:31 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40592 Mon 08 Aug 2022 15:18:18 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53002 Mon 06 Nov 2023 08:44:55 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31419 Mon 02 Mar 2020 14:10:50 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54960 Fri 22 Mar 2024 15:34:43 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42303 Fri 17 May 2024 16:00:48 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:43403 Fri 16 Sep 2022 10:05:31 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51704 Fri 15 Sep 2023 13:56:01 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48014 Fri 07 Jul 2023 13:26:33 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51343 Fri 01 Sep 2023 13:34:03 AEST ]]>