https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 Shapeshifting bullvalene-linked vancomycin dimers as effective antibiotics against multidrug-resistant gram-positive bacteria https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51679 Wed 28 Feb 2024 16:22:30 AEDT ]]> LncRNA IDH1-AS1 links the functions of c-Myc and HIF1a via IDH1 to regulate the Warburg effect https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47540 Wed 24 Jan 2024 15:22:27 AEDT ]]> Common coding variant in SERPINA1 increases the risk for large artery stroke https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34568 Wed 17 Nov 2021 16:28:59 AEDT ]]> A large-scale analysis of task switching practice effects across the lifespan https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49449 Wed 17 May 2023 15:05:23 AEST ]]> Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51038 P = 1.098 × 10-8) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.]]> Wed 16 Aug 2023 10:23:55 AEST ]]> Striatum and pre-SMA facilitate decision-making under time pressure https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:4650 Wed 11 Apr 2018 16:49:30 AEST ]]> MicroRNA-149*, a p53-responsive microRNA, functions as an oncogenic regulator in human melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13811 Wed 11 Apr 2018 15:41:21 AEST ]]> Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25874 Mycobacterium vaccae, an immunoregulatory environmental microorganism, reduced subordinate, flight, and avoiding behavioral responses to a dominant aggressor in a murine model of chronic psychosocial stress when tested 1-2wk following the final immunization. Furthermore, immunization with M. vaccae prevented stress-induced spontaneous colitis and, in stressed mice, induced anxiolytic or fear-reducing effects as measured on the elevated plus-maze, despite stress-induced gut microbiota changes characteristic of gut infection and colitis. Immunization with M. vaccae also prevented stress-induced aggravation of colitis in a model of inflammatory bowel disease. Depletion of regulatory T cells negated protective effects of immunization with M. vaccae on stress-induced colitis and anxiety-like or fear behaviors. These data provide a framework for developing microbiome- and immunoregulation-based strategies for prevention of stress-related pathologies.]]> Wed 11 Apr 2018 10:26:13 AEST ]]> PP2A methylation controls sensitivity and resistance to ß-amyloid-induced cognitive and electrophysiological impairments https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30261 Wed 11 Apr 2018 10:01:07 AEST ]]> MdERDL6-mediated glucose efflux to the cytosol promotes sugar accumulation in the vacuole through up-regulating TSTs in apple and tomato https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:39306 +/sugar antiporters MdTST1 and MdTST2. Overexpression of MdERDL6-1 unexpectedly increased not only glucose (Glc) concentration but also that of fructose (Fru) and sucrose (Suc) in transgenic apple and tomato leaves and fruits. RNA sequencing (RNA-seq) and expression analyses showed an up-regulation of TST1 and TST2 in the transgenic apple and tomato lines overexpressing MdERDL6-1. Further studies established that the increased sugar concentration in the transgenic lines correlated with up-regulation of TST1 and TST2 expression. Suppression or knockout of SlTST1 and SlTST2 in the MdERDL6-1–overexpressed tomato background reduced or abolished the positive effect of MdERDL6-1 on sugar accumulation, respectively. The findings demonstrate a regulation of TST1 and TST2 by MdERDL6-1, in which Glc exported by MdERDL6-1 from vacuole up-regulates TST1 and TST2 to import sugars from cytosol to vacuole for accumulation to high concentrations. The results provide insight into the regulatory mechanism of sugar accumulation in vacuoles mediated by the coordinated action of two classes of tonoplast sugar transporters.]]> Wed 10 Aug 2022 11:02:07 AEST ]]> Humans adapt to social diversity over time https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45575 Wed 02 Nov 2022 08:16:58 AEDT ]]> The N-Myc-responsive lncRNA MILIP promotes DNA double-strand break repair through non-homologous end joining https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51136 Tue 22 Aug 2023 15:58:29 AEST ]]> Short-chain diamines are the physiological substrates of PACE family efflux pumps https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37182 Acinetobacter baumannii has rapidly emerged as a major cause of gram-negative hospital infections worldwide. A. baumannii encodes for the transport protein AceI, which confers resistance to chlorhexidine, a widely used antiseptic. AceI is also the prototype for the recently discovered proteobacterial antimicrobial compound efflux (PACE) family of transport proteins that confer resistance to a range of antibiotics and antiseptics in many gram-negative bacteria, including pathogens. The gene encoding AceI is conserved in the core genome of A. baumannii, suggesting that it has an important primordial function. This is incongruous with the sole characterized substrate of AceI, chlorhexidine, an entirely synthetic biocide produced only during the last century. Here we investigated a potential primordial function of AceI and other members of the PACE family in the transport of naturally occurring polyamines. Polyamines are abundant in living cells, where they have physiologically important functions and play multifaceted roles in bacterial infection. Gene expression studies revealed that the aceI gene is induced in A. baumannii by the short-chain diamines cadaverine and putrescine. Membrane transport experiments conducted in whole cells of A. baumannii and Escherichia coli and also in proteoliposomes showed that AceI mediates the efflux of these short-chain diamines when energized by an electrochemical gradient. Assays conducted using 8 additional diverse PACE family proteins identified 3 that also catalyze cadaverine transport. Taken together, these results demonstrate that short-chain diamines are common substrates for the PACE family of transport proteins, adding to their broad significance as a novel family of efflux pumps.]]> Thu 27 Aug 2020 12:47:49 AEST ]]> Single-cell transcriptomic analysis reveals the immune landscape of lung in steroid-resistant asthma exacerbation https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48011 + memory T cells were the predominant sources of interleukin (IL)-4 and IL-13 transcripts whose expressions were dexamethasone resistant. Production of IL-13 by these cells was validated by IL-13-reporter mice. Neutralization of IL-13 abolished HDM/LPS-induced airway hyperresponsiveness, airway inflammation, and decreased mucus hypersecretion. Furthermore, using Ingenuity Pathway Analysis systems, we identified canonical pathways and upstream regulators that regulate the activation of basophils, ILC2, and CD8+ memory T cells. Our study provides mechanistic insights and an important reference resource for further understanding of the immune landscape during asthma exacerbation.]]> Thu 23 Mar 2023 10:07:13 AEDT ]]> Oceanographic boundaries constrain microbial diversity gradients in the South Pacific Ocean https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43319 Thu 15 Sep 2022 14:29:31 AEST ]]> Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7560 Sat 24 Mar 2018 08:42:06 AEDT ]]> A central role for venom in predation by Varanus komodoensis (Komodo Dragon) and the extinct giant Varanus (Megalania) priscus https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:8224 Sat 24 Mar 2018 08:40:37 AEDT ]]> Pituitary autoantibodies in autoimmune polyendocrine syndrome type 1 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:3113 Sat 24 Mar 2018 08:29:09 AEDT ]]> Negative regulation of eosinophil recruitment to the lung by the chemokine monokine induced by INF-γ (Mig, CXCL9) https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1493 Sat 24 Mar 2018 08:28:05 AEDT ]]> Cortico-striatal connections predict control over speed and accuracy in perceptual decision making https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11281 Sat 24 Mar 2018 08:12:43 AEDT ]]> Late-surviving megafauna in Tasmania, Australia, implicate human involvement in their extinction https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5209 Sat 24 Mar 2018 07:47:45 AEDT ]]> Phagocytosis executes delayed neuronal death after focal brain ischemia https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28633 Sat 24 Mar 2018 07:38:53 AEDT ]]> Human hippocampus represents space and time during retrieval of real-world memories https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26476 Sat 24 Mar 2018 07:27:14 AEDT ]]> Mutations in ionotropic AMPA receptor 3 alter channel properties and are associated with moderate cognitive impairment in humans https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:3341 Sat 24 Mar 2018 07:22:35 AEDT ]]> Supermodeled sabercat, predatory behavior in Smilodon fatalis revealed by high-resolution 3D computer simulation https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:3448 150 years of study, many questions remain concerning its predatory behavior. Were the “sabers” used to take down large prey? Were prey killed with an eviscerating bite to the abdomen? Was its bite powerful or weak compared with that of modern big cats? Here we quantitatively assess the sabercat's biomechanical performance using the most detailed computer reconstructions yet developed for the vertebrate skull. Our results demonstrate that bite force driven by jaw muscles was relatively weak in S. fatalis, one-third that of a lion (Panthera leo) of comparable size, and its skull was poorly optimized to resist the extrinsic loadings generated by struggling prey. Its skull is better optimized for bites on restrained prey where the bite is augmented by force from the cervical musculature. We conclude that prey were brought to ground and restrained before a killing bite, driven in large part by powerful cervical musculature. Because large prey is easier to restrain if its head is secured, the killing bite was most likely directed to the neck. We suggest that the more powerful jaw muscles of P. leo may be required for extended, asphyxiating bites and that the relatively low bite forces in S. fatalis might reflect its ability to kill large prey more quickly, avoiding the need for prolonged bites.]]> Sat 24 Mar 2018 07:20:26 AEDT ]]> Serum amyloid A opposes lipoxin A<sub>4</sub> to mediate glucocorticoid refractory lung inflammation in chronic obstructive pulmonary disease https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23760 4 (LXA,sub>4) can also interact with ALX/FPR2 receptors and lead to allosteric inhibition of SAA-initiated epithelial responses (pA2 13 nM). During acute exacerbation, peripheral blood SAA levels increased dramatically and were disproportionately increased relative to LXA4. Human lung macrophages (CD68⁺) colocalized with SAA and GCs markedly increased SAA in vitro (THP-1, pEC50 43 nM). To determine its direct actions, SAA was administered into murine lung, leading to induction of CXC chemokine ligand 1/2 and a neutrophilic response that was inhibited by 15-epi-LXA4 but not dexamethasone. Taken together, these findings identify SAA as a therapeutic target for inhibition and implicate SAA as a mediator of GC-resistant lung inflammation that can overwhelm organ protective signaling by lipoxins at ALX/FPR2 receptors.]]> Sat 24 Mar 2018 07:11:08 AEDT ]]> Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50977 Mon 14 Aug 2023 15:24:38 AEST ]]> Maternal tract factors contribute to paternal seminal fluid impact on metabolic phenotype in offspring https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37563 Fri 21 Jan 2022 09:37:20 AEDT ]]> In-cell structures of conserved supramolecular protein arrays at the mitochondria-cytoskeleton interface in mammalian sperm https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48463 Fri 17 Mar 2023 12:14:38 AEDT ]]> Loss of expression of both miR-15/16 loci in CML transition to blast crisis https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49365 Fri 12 May 2023 12:42:20 AEST ]]> Specific deletion of LKB1/Stk11 in the Müllerian duct mesenchyme drives hyperplasia of the periurethral stroma and tumorigenesis in male mice https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34624 CKO mice by conditional deletion of the liver kinase B1 (LKB1) tumor suppressor gene, Stk11 (serine threonine kinase 11), in the fetal Müllerian duct mesenchyme (MDM), the caudal remnant of which is thought to be assimilated by the urogenital sinus primordial mesenchyme in males during fetal development. We show that MDM cells contribute to the postnatal stromal cells at the dorsal aspect of the prostatic urethra by lineage tracing. The Stk11CKO mice develop prostatic hyperplasia with bladder outlet obstruction, most likely because of stromal expansion. The stromal areas from prostates of Stk11CKO mice, with or without significant expansion, were estrogen receptor positive, which is consistent with both MD mesenchyme-derived cells and the purported importance of estrogen receptors in BPH development and/or progression. In some cases, stromal hyperplasia was admixed with epithelial metaplasia, sometimes with keratin pearls, consistent with squamous cell carcinomas. Mice with conditional deletion of both Stk11 and Pten developed similar features as the Stk11CKO mice, but at a highly accelerated rate, often within the first few months after birth. Western blot analyses showed that the loss of LKB1 and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) induces activation of the phospho-5' adenosine monophosphateactivated protein kinase and phospho-AKT serine/threonine kinase 1 signaling pathways, as well as increased total and active ß-catenin. These results suggest that activation of these signaling pathways can induce hyperplasia of the MD stroma, which could play a significant role in the etiology of human BPH.]]> Fri 05 Apr 2019 11:33:46 AEDT ]]> Mitochondrial small heat shock protein mediates seed germination via thermal sensing https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47862 Fri 03 Feb 2023 13:53:58 AEDT ]]> Dual functions for OVAAL in initiation of RAF/MEK/ERK prosurvival signals and evasion of p27-mediated cellular senescence https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:35545 Fri 03 Dec 2021 10:33:29 AEDT ]]> Bovine and human endometrium-derived hydrogels support organoid culture from healthy and cancerous tissues https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51354 Fri 01 Sep 2023 13:44:28 AEST ]]>