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We identifi ed and isolated a novel Hendra virus (HeV) variant not detected by routine testing from a horse in Queensland, Australia, that died from acute illness with signs consistent with HeV infection. Using whole-genome sequencing and phylogenetic analysis, we determined the variant had ≈83% nt identity with prototypic HeV. In silico and in vitro comparisons of the receptor-binding protein with prototypic HeV support that the human monoclonal antibody m102.4 used for postexposure prophylaxis and current equine vaccine will be eff ective against this variant. An updated quantitative PCR developed for routine surveillance resulted in subsequent case detection. Genetic sequence consistency with virus detected in grey-headed fl ying foxes suggests the variant circulates at least among this species. Studies are needed to determine infection kinetics, pathogenicity, reservoir-species associations, viral- host coevolution, and spillover dynamics for this virus. Surveillance and biosecurity practices should be updated to acknowledge HeV spillover risk across all regions frequented by fl ying foxes.

Background Borrelia are important disease-causing tick- and louse-borne spirochaetes than can infect a wide variety of vertebrates, including humans and reptiles. Reptile-associated (REP) Borrelia , once considered a peculiarity, are now recognised as a distinct and important evolutionary lineage, and are increasingly being discovered worldwide in association with novel hosts. Numerous novel Borrelia spp. associated with monitor lizards ( Varanus spp.) have been recently identified throughout the Indo-Pacific region; however, there is a lack of genomic data on these Borrelia . Methods We used metagenomic techniques to sequence almost complete genomes of novel Borrelia spp. from Varanus varius and Varanus giganteus from Australia, and used long- and short-read technologies to sequence the complete genomes of two strains of a novel Borrelia sp. previously isolated from ticks infesting Varanus salvator from Indonesia. We investigated intra- and interspecies genomic diversity, including plasmid diversity and relatedness, among Varanus -associated Borrelia and other available REP Borrelia and, based on 712 whole genome orthologues, produced the most complete phylogenetic analysis, to the best of our knowledge, of REP Borrelia to date. Results The genomic architecture of Varanus -associated Borrelia spp. is similar to that of Borrelia spp. that cause relapsing fever (RF), and includes a highly conserved megaplasmid and numerous smaller linear and circular plasmids that lack structural consistency between species. Analysis of PF32 and PF57/62 plasmid partitioning genes indicated that REP Borrelia plasmids fall into at least six distinct plasmid families, some of which are related to previously defined Borrelia plasmid families, whereas the others appear to be unique. REP Borrelia contain immunogenic variable major proteins that are homologous to those found in Borrelia spp. that cause RF, although they are limited in copy number and variability and have low sequence identities to RF variable major proteins. Phylogenetic analyses based on single marker genes and 712 single copy orthologs also definitively demonstrated the monophyly of REP Borrelia as a unique lineage. Conclusions In this work we present four new genomes from three novel Borrelia , and thus double the number of REP Borrelia genomes publicly available. The genomic characterisation of these Borrelia clearly demonstrates their distinctiveness as species, and we propose the names Borrelia salvatorii , ‘ Candidatus Borrelia undatumii’, and ‘ Candidatus Borrelia rubricentralis’ for them. Graphical Abstract

Automated standoff detection and classification of explosives based on their characteristic vapours would be highly desirable. Biologically derived odorant receptors have potential as the explosive recognition element in novel biosensors. Caenorhabditis elegans' genome contains over 1,000 uncharacterised candidate chemosensory receptors. It was not known whether any of these respond to volatile chemicals derived from or associated with explosives. We assayed C. elegans for chemotactic responses to chemical vapours of explosives and compounds associated with explosives. C. elegans failed to respond to many of the explosive materials themselves but showed strong chemotaxis with a number of compounds associated with commercial or homemade explosives. Genetic mutant strains were used to identify the likely neuronal location of a putative receptor responding to cyclohexanone, which is a contaminant of some compounded explosives, and to identify the specific transduction pathway involved. Upper limits on the sensitivity of the nematode were calculated. A sensory adaptation protocol was used to estimate the receptive range of the receptor. The results suggest that C. elegans may be a convenient source of highly sensitive, narrowly tuned receptors to detect a range of explosive-associated volatiles.

Often the Old English riddles of the Exeter Book are discussed in isolation or in pairs or groups. Seldom are the enigmata read in conjunction with other Old English poems or placed within the prevalent literary movements of the period. Through such contextualization, however, one can develop a better understanding of the entire corpus of Anglo-Saxon poetry as well as the literary world within these texts. This dissertation undertakes such a study. Each chapter discusses the riddles within a different context. Chapter 1 explores the foundation of these poems through an investigation of the intersections between the Old English riddles and their Latin sources and analogues. Chapter 2 places the enigmata in their cultural contexts, as both Volksrätsel and Kunstätsel. Chapter 3 looks at the riddles in fight of poems that express the heroic ideal. And chapter 4 reads the riddles in comparison to elegies, a genre that expresses the plight of those who fall victim to the cruel realities of the Anglo-Saxon world.

A novel Hendra virus (HeV) variant was identified from a horse that suffered acute fatal disease consistent with HeV infection through multidisciplinary and interagency syndromic sentinel surveillance research. Novel molecular assays for HeV detection are described in the light of routine testing failure. In silico analysis of the variant receptor-binding protein in comparison with prototypic HeV supported that the monoclonal antibody m102.4 used for post-exposure prophylaxis, as well as the equine vaccine, should be effective also against this novel variant. Similarity of this virus (99%) to a partial sequence detected from a South Australian grey-headed flying fox, along with case exposure to this species in Queensland, suggests the variant circulates at least across the range of this flying fox species. Investigation into HeV diversity, comparative kinetics and pathogenicity, reservoir-species associations, viral-host co-evolution and spillover dynamics should be prioritized. Biosecurity practices should be updated to appreciate HeV spillover risk across all regions frequented by flying foxes regardless of species. Competing Interest Statement The authors have declared no competing interest.

Background CONSORT guidelines call for precise reporting of behavior change interventions: we need rigorous methods of characterizing active content of interventions with precision and specificity. Objectives The objective of this study is to develop an extensive, consensually agreed hierarchically structured taxonomy of techniques [behavior change techniques (BCTs)] used in behavior change interventions. Methods In a Delphi-type exercise, 14 experts rated labels and definitions of 124 BCTs from six published classification systems. Another 18 experts grouped BCTs according to similarity of active ingredients in an open-sort task. Inter-rater agreement amongst six researchers coding 85 intervention descriptions by BCTs was assessed. Results This resulted in 93 BCTs clustered into 16 groups. Of the 26 BCTs occurring at least five times, 23 had adjusted kappas of 0.60 or above. Conclusions “BCT taxonomy v1,” an extensive taxonomy of 93 consensually agreed, distinct BCTs, offers a step change as a method for specifying interventions, but we anticipate further development and evaluation based on international, interdisciplinary consensus.

Human respiratory syncytial virus (RSV) is an important cause of acute respiratory infection with the most severe disease in the young and elderly. Non-pharmaceutical interventions and travel restrictions for controlling COVID-19 have impacted the circulation of most respiratory viruses including RSV globally, particularly in Australia, where during 2020 the normal winter epidemics were notably absent. However, in late 2020, unprecedented widespread RSV outbreaks occurred, beginning in spring, and extending into summer across two widely separated regions of the Australian continent, New South Wales (NSW) and Australian Capital Territory (ACT) in the east, and Western Australia. Through genomic sequencing we reveal a major reduction in RSV genetic diversity following COVID-19 emergence with two genetically distinct RSV-A clades circulating cryptically, likely localised for several months prior to an epidemic surge in cases upon relaxation of COVID-19 control measures. The NSW/ACT clade subsequently spread to the neighbouring state of Victoria and to cause extensive outbreaks and hospitalisations in early 2021. These findings highlight the need for continued surveillance and sequencing of RSV and other respiratory viruses during and after the COVID-19 pandemic, as mitigation measures may disrupt seasonal patterns, causing larger or more severe outbreaks. Non-pharmaceutical interventions for COVID-19 also reduced incidence of respiratory pathogens such as respiratory syncytial virus (RSV). Here, the authors report the resurgence of RSV in Australia following lifting of some of the restrictions and describe reduction in genetic diversity in circulating clades.

Vascular Ehlers Danlos Syndrome (vEDS) is a connective tissue disorder caused by COL3A1 mutations for which there are no treatments due to a limited understanding of underlying mechanisms. We aimed to identify the molecular insults of mutations, focusing on collagen folding, to establish if targeting protein folding represents a potential therapeutic approach. Analysis of two novel COL3A1 glycine mutations, G189S and G906R, in primary patient fibroblast cultures revealed secretion of misfolded collagen III and intracellular collagen retention leading to lower extracellular collagen levels. This was associated with matrix defects, endoplasmic reticulum (ER) stress, reduced cell proliferation and apoptosis. The ER stress was mediated by activation of IRE1 and PERK signalling arms with evidence of allelic heterogeneity. To establish if promoting ER protein folding capacity or protein degradation represents novel therapeutic avenues, we investigated the efficacy of FDA-approved small molecules. The chemical chaperone 4-phenylbutyric acid (PBA) rescued the ER stress and thermostability of secreted collagen leading to reduced apoptosis and matrix defects, and its efficacy was influenced by duration, dosage and allelic heterogeneity. Targeting protein degradation with carbamazepine (CBZ), or PBA-CBZ in combination did not increase treatment efficacy. These data establish that ER stress is a molecular mechanism in vEDS that can be influenced by the position of COL3A1 mutation. It combines with matrix defects due to reduced collagen III levels and/or mutant protein secretion to vEDS pathogenesis. Targeting protein folding using FDA-approved chemical chaperones represents a putative mechanism-based therapeutic approach for vEDS that can rescue intra- and extracellular defects.

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 237 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson’s disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

A groundswell to include Indigenous Knowledge in the school science curriculum has led to the inclusion of Aboriginal and Torres Strait Islander Histories and Cultures (generally known as Indigenous perspectives) in the overall Australian Curriculum (AC) and the Australian Curriculum: Science (ACS). However, the experiences in other countries, their states and provinces are quite different and diverse, particularly when it comes to incorporating Indigenous Knowledge in resistant disciplines such as science. The AC and ACS are examined and compared with similar curriculum from elsewhere. The causes of resistance to the inclusion of Indigenous perspectives are identified, as well as other structural impediments. Strategies such as the Two-Ways or Two-Eyed Seeing approaches with epistemic insight are seen as a functional way of bridging Indigenous and Western cultures for policy makers, curriculum developers, educators and teachers, and ultimately students.