Twin studies: research in genes, teeth and faces

This book is about an ongoing long-term research initiative led by researchers from the School of Dentistry at the University of Adelaide. It provides an overview of the studies carried out over more than thirty years of the teeth and faces of Australian twins and their families. It provides some historical perspectives of such studies and gives an insight into the technological and scientific changes that have occurred, including various twin models that enable exploration of genetic, epigenetic and environmental contributions to variation in teeth and faces. The volume should be of interest to students planning to undertake research involving twins as well as to researchers and academics in the fields of dentistry and craniofacial biology. Its interdisciplinary approach also demonstrates how studies mainly focused on dental features can have broader implications in clarifying general biological mechanisms.by Grant C Townsend, Sandra K Pinkerton, James R Rogers, Michelle R Bockmann and Toby E Hughe

Effects of food-borne nanomaterials on gastrointestinal tissues and microbiota

Ingestion of engineered nanomaterials is inevitable due to their addition to food and prevalence in food packaging and domestic products such as toothpaste and sun cream. In the absence of robust dosimetry and particokinetic data, it is currently challenging to accurately assess the potential toxicity of food-borne nanomaterials. Herein, we review current understanding of gastrointestinal uptake mechanisms, consider some data on the potential for toxicity of the most commonly encountered classes of food-borne nanomaterials (including TiO2 , SiO2 , ZnO, and Ag nanoparticles), and discuss the potential impact of the luminal environment on nanoparticle properties and toxicity. Much of our current understanding of gastrointestinal nanotoxicology is derived from increasingly sophisticated epithelial models that augment in vivo studies. In addition to considering the direct effects of food-borne nanomaterials on gastrointestinal tissues, including the potential role of chronic nanoparticle exposure in development of inflammatory diseases, we also discuss the potential for food-borne nanomaterials to disturb the normal balance of microbiota within the gastrointestinal tract. The latter possibility warrants close attention given the increasing awareness of the critical role of microbiota in human health and the known impact of some food-borne nanomaterials on bacterial viability. For further resources related to this article, please visit the WIREs website.</p

Identification of Melatonin-Regulated Genes in the Ovine Pituitary Pars Tuberalis, a Target Site for Seasonal Hormone Control

The pars tuberalis (PT) of the pituitary gland expresses a high density of melatonin (MEL) receptors and is believed to regulate seasonal physiology by decoding changes in nocturnal melatonin secretion. Circadian clock genes are known to be expressed in the PT in response to the decline (Per1) and onset (Cry1) of MEL secretion, but to date little is known of other molecular changes in this key MEL target site. To identify transcriptional pathways that may be involved in the diurnal and photoperiod-transduction mechanism, we performed a whole genome transcriptome analysis using PT RNA isolated from sheep culled at three time points over the 24-h cycle under either long or short photoperiods. Our results reveal 153 transcripts where expression differs between photoperiods at the light-dark transition and 54 transcripts where expression level was more globally altered by photoperiod (all time points combined). Cry1 induction at night was associated with up-regulation of genes coding for NeuroD1 (neurogenic differentiation factor 1), Pbef / Nampt (nicotinamide phosphoribosyltransferase) , Hif1α (hypoxia-inducible factor-1α), and Kcnq5 (K channel) and down-regulation of Rorβ, a key clock gene regulator. Using in situ hybridization, we confirmed day-night differences in expression for Pbef / Nampt, NeuroD1, and Rorβ in the PT. Treatment of sheep with MEL increased PT expression for Cry1, Pbef / Nampt, NeuroD1, and Hif1α, but not Kcnq5. Our data thus reveal a cluster of Cry1-associated genes that are acutely responsive to MEL and novel transcriptional pathways involved in MEL action in the PT

Preliminary study of the oral mycobiome of children with and without dental caries

Children’s oral health is in a dire state, with dental decay (caries) being one of the most common chronic diseases. While the role of bacteria in the oral microbiome and dental caries is established, the contribution of fungi is relatively unknown. We assessed the oral mycobiome in childhood (n = 17), to determine if the composition of fungi varies between children with and without caries. Oral mycobiome composition was assessed by using Illumina MiSeq to sequence the ITS2 region, which was amplified from dental plaque. This revealed that the oral mycobiome in the investigated children contained 46 fungal species. Candida albicans was the most abundant species and was ubiquitous in all samples, indicating this species may not be involved in caries development as previously suggested. While the overall diversity of fungi was similar, independent of caries status (p > 0.05), we found caries influenced the abundance of specific fungi. Children without caries had a significantly higher abundance of 17 species compared to children with caries, which had three enriched species (p < 0.001). While the differentially abundant species between health and caries may be specific to an Australian population, our findings indicate the mycobiome plays a role in oral health.Jacquelyn M. Fechney, Gina V. Browne, Neeta Prabhu, Laszlo Irinyi, Wieland Meyer, Toby Hughes, Michelle Bockmann, Grant Townsend, Hanieh Salehi and Christina J. Adle

Differential network analysis of oral microbiome metatranscriptomes identifies community scale metabolic restructuring in dental caries

Advance access publication date: 18 October 2022Dental caries is a microbial disease and the most common chronic health condition, affecting nearly 3.5 billion people worldwide. In this study, we used a multiomics approach to characterize the supragingival plaque microbiome of 91 Australian children, generating 658 bacterial and 189 viral metagenome-assembled genomes with transcriptional profiling and gene-expression network analysis. We developed a reproducible pipeline for clustering sample-specific genomes to integrate metagenomics and metatranscriptomics analyses regardless of biosample overlap. We introduce novel feature engineering and compositionally-aware ensemble network frameworks while demonstrating their utility for investigating regime shifts associated with caries dysbiosis. These methods can be applied when differential abundance modeling does not capture statistical enrichments or the results from such analysis are not adequate for providing deeper insight into disease. We identified which organisms and metabolic pathways were central in a coexpression network as well as how these networks were rewired between caries and caries-free phenotypes. Our findings provide evidence of a core bacterial microbiome that was transcriptionally active in the supragingival plaque of all participants regardless of phenotype, but also show highly diagnostic changes in the ways that organisms interact. Specifically, many organisms exhibit high connectedness with central carbon metabolism to Cardiobacterium and this shift serves a bridge between phenotypes. Our evidence supports the hypothesis that caries is a multifactorial ecological disease.Josh L. Espinoza, Manolito Torralba, Pamela Leong, Richard Saffery, Michelle Bockmann, Claire Kuelbs, Suren Singh, Toby Hughes, Jeffrey M. Craig, Karen E. Nelson and Chris L. Dupon

Baryon masses from lattice QCD: Beyond the perturbative chiral regime

Consideration of the analytic properties of pion-induced baryon self-energies leads to new functional forms for the extrapolation of light baryon masses. These functional forms reproduce the leading non-analytic behavior of chiral perturbation theory, the correct non-analytic behavior at the $N \pi$ threshold and the appropriate heavy-quark limit. They involve only three unknown parameters, which may be obtained by fitting to lattice data. Recent dynamical fermion results from CP-PACS and UKQCD are extrapolated using these new functional forms. We also use these functions to probe the limit of applicability of chiral perturbation theory to the extrapolation of lattice QCD results.Derek B. Leinweber, Anthony W. Thomas, Kazuo Tsushima, and Stewart V. Wrigh

Automated protein resonance assignments of magic angle spinning solid-state NMR spectra of β1 immunoglobulin binding domain of protein G (GB1)

Magic-angle spinning solid-state NMR (MAS SSNMR) represents a fast developing experimental technique with great potential to provide structural and dynamics information for proteins not amenable to other methods. However, few automated analysis tools are currently available for MAS SSNMR. We present a methodology for automating protein resonance assignments of MAS SSNMR spectral data and its application to experimental peak lists of the β1 immunoglobulin binding domain of protein G (GB1) derived from a uniformly 13C- and 15N-labeled sample. This application to the 56 amino acid GB1 produced an overall 84.1% assignment of the N, CO, CA, and CB resonances with no errors using peak lists from NCACX 3D, CANcoCA 3D, and CANCOCX 4D experiments. This proof of concept demonstrates the tractability of this problem

Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders.

International audienceSHANK3 (also known as ProSAP2) regulates the structural organization of dendritic spines and is a binding partner of neuroligins; genes encoding neuroligins are mutated in autism and Asperger syndrome. Here, we report that a mutation of a single copy of SHANK3 on chromosome 22q13 can result in language and/or social communication disorders. These mutations concern only a small number of individuals, but they shed light on one gene dosage-sensitive synaptic pathway that is involved in autism spectrum disorders

Heterogeneous Nuclear Ribonucleoprotein K Interacts with Abi-1 at Postsynaptic Sites and Modulates Dendritic Spine Morphology

BACKGROUND: Abelson-interacting protein 1 (Abi-1) plays an important role for dendritic branching and synapse formation in the central nervous system. It is localized at the postsynaptic density (PSD) and rapidly translocates to the nucleus upon synaptic stimulation. At PSDs Abi-1 is in a complex with several other proteins including WASP/WAVE or cortactin thereby regulating the actin cytoskeleton via the Arp 2/3 complex. PRINCIPAL FINDINGS: We identified heterogeneous nuclear ribonucleoprotein K (hnRNPK), a 65 kDa ssDNA/RNA-binding-protein that is involved in multiple intracellular signaling cascades, as a binding partner of Abi-1 at postsynaptic sites. The interaction with the Abi-1 SH3 domain is mediated by the hnRNPK-interaction (KI) domain. We further show that during brain development, hnRNPK expression becomes more and more restricted to granule cells of the cerebellum and hippocampal neurons where it localizes in the cell nucleus as well as in the spine/dendritic compartment. The downregulation of hnRNPK in cultured hippocampal neurons by RNAi results in an enlarged dendritic tree and a significant increase in filopodia formation. This is accompanied by a decrease in the number of mature synapses. Both effects therefore mimic the neuronal morphology after downregulation of Abi-1 mRNA in neurons. CONCLUSIONS: Our findings demonstrate a novel interplay between hnRNPK and Abi-1 in the nucleus and at synaptic sites and show obvious similarities regarding both protein knockdown phenotypes. This indicates that hnRNPK and Abi-1 act synergistic in a multiprotein complex that regulates the crucial balance between filopodia formation and synaptic maturation in neurons

Development of the oral resistome during the first decade of life

Published online: 09 March 2023Antibiotic overuse has promoted the spread of antimicrobial resistance (AMR) with significant health and economic consequences. Genome sequencing reveals the widespread presence of antimicrobial resistance genes (ARGs) in diverse microbial environments. Hence, surveillance of resistance reservoirs, like the rarely explored oral microbiome, is necessary to combat AMR. Here, we characterise the development of the paediatric oral resistome and investigate its role in dental caries in 221 twin children (124 females and 97 males) sampled at three time points over the first decade of life. From 530 oral metagenomes, we identify 309 ARGs, which significantly cluster by age, with host genetic effects detected from infancy onwards. Our results suggest potential mobilisation of ARGs increases with age as the AMR associated mobile genetic element, Tn916 transposase was co-located with more species and ARGs in older children. We find a depletion of ARGs and species in dental caries compared to health. This trend reverses in restored teeth. Here we show the paediatric oral resistome is an inherent and dynamic component of the oral microbiome, with a potential role in transmission of AMR and dysbiosis.Smitha Sukumar, FangWang, Carra A. Simpson, Cali E. Willet, Tracy Chew, Toby E. Hughes, Michelle R. Bockmann, Rosemarie Sadsad, F. ElizabethMartin, Henry W. Lydecker, Gina V. Browne, KylieM. Davis, Minh Bui, ElenaMartinez, Christina J. Adle