The EBV-encoded oncoprotein, LMP1, induces an epithelial-to-mesenchymal transition (EMT) via Its CTAR1 domain through integrin-mediated ERK-MAPK signalling

The Epstein⁻Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) oncogene can induce profound effects on epithelial growth and differentiation including many of the features of the epithelial-to-mesenchymal transition (EMT). To better characterise these effects, we used the well-defined Madin Darby Canine Kidney (MDCK) epithelial cell model and found that LMP1 expression in these cells induces EMT as defined by characteristic morphological changes accompanied by loss of E-cadherin, desmosomal cadherin and tight junction protein expression. The induction of the EMT phenotype required a functional CTAR1 domain of LMP1 and studies using pharmacological inhibitors revealed contributions from signalling pathways commonly induced by integrin⁻ligand interactions: extracellular signal-regulated kinases/mitogen-activated protein kinases (ERK-MAPK), PI3-Kinase and tyrosine kinases, but not transforming growth factor beta (TGFβ). More detailed analysis implicated the CTAR1-mediated induction of Slug and Twist in LMP1-induced EMT. A key role for β1 integrin signalling in LMP1-mediated ERK-MAPK and focal adhesion kianse (FAK) phosphorylation was observed, and β1 integrin activation was found to enhance LMP1-induced cell viability and survival. These findings support an important role for LMP1 in disease pathogenesis through transcriptional reprogramming that enhances tumour cell survival and leads to a more invasive, metastatic phenotype

The role of the oral microbiota in chronic non-communicable disease and its relevance to the Indigenous health gap in Australia

Background: Aboriginal Australians and Torres Strait Islanders (hereafter respectfully referred to as Indigenous Australians) experience disproportionately poor health and low life expectancy compared to non-Indigenous Australians. Poor oral health is a critical, but understudied, contributor to this health gap. A considerable body of evidence links poor oral health to increased risks of other chronic non-communicable conditions, such as diabetes, cardiovascular disease, chronic kidney disease, and poor emotional wellbeing. Main: The oral microbiota is indisputably associated with several oral diseases that disproportionately affect Indigenous Australians. Furthermore, a growing literature suggests direct and indirect links between the oral microbiota and systemic chronic non-communicable diseases that underpin much of the Indigenous health gap in Australia. Recent research indicates that oral microbial communities are shaped by a combination of cultural and lifestyle factors and are inherited from caregivers to children. Systematic differences in oral microbiota diversity and composition have been identified between Indigenous and non-Indigenous individuals in Australia and elsewhere, suggesting that microbiota-related diseases may be distinct in Indigenous Australians. Conclusion: Oral microbiota research involving Indigenous Australians is a promising new area that could benefit Indigenous communities in numerous ways. These potential benefits include: (1) ensuring equity and access for Indigenous Australians in microbiota-related therapies; (2) opportunities for knowledge-sharing and collaborative research between scientists and Indigenous communities; and (3) using knowledge about the oral microbiota and chronic disease to help close the gaps in Indigenous oral and systemic health.Matilda Handsley‑Davis, Lisa Jamieson, Kostas Kapellas, Joanne Hedges and Laura S. Weyric

Momentum transfer using chirped standing wave fields: Bragg scattering

We consider momentum transfer using frequency-chirped standing wave fields. Novel atom-beam splitter and mirror schemes based on Bragg scattering are presented. It is shown that a predetermined number of photon momenta can be transferred to the atoms in a single interaction zone.Comment: 4 pages, 3 figure

Motion-Induced Radiation from a Dynamically Deforming Mirror

A path integral formulation is developed to study the spectrum of radiation from a perfectly reflecting (conducting) surface. It allows us to study arbitrary deformations in space and time. The spectrum is calculated to second order in the height function. For a harmonic traveling wave on the surface, we find many different regimes in which the radiation is restricted to certain directions. It is shown that high frequency photons are emitted in a beam with relatively low angular dispersion whose direction can be controlled by the mechanical deformations of the plate.Comment: 4 pages, 2 eps figues included, final version as appeared in PR

Biocultural Drivers of Salivary Microbiota in Australian Aboriginal and Torres Strait Islander Children

Published: 18 March 2021.Australian Aboriginal and Torres Strait Islander children experience unacceptably high rates of dental caries compared to their non-Indigenous Australian counterparts. Dental caries significantly impacts the quality of life of children and their families, particularly in remote communities. While many socioeconomic and lifestyle factors impact caries risk, the central role of the oral microbiota in mediating dental caries has not been extensively investigated in these communities. Here, we examine factors that shape diversity and composition of the salivary microbiota in Aboriginal and Torres Strait Islander children and adolescents living in the remote Northern Peninsula Area (NPA) of Far North Queensland. We employed 16S ribosomal RNA amplicon sequencing to profile bacteria present in saliva collected from 205 individuals aged 4–17 years from the NPA. Higher average microbial diversity was generally linked to increased age and salivary pH, less frequent toothbrushing, and proxies for lower socioeconomic status (SES). Differences inmicrobial composition were significantly related to age, salivary pH, SES proxies, and active dental caries. Notably, a feature classified as Streptococcus sobrinus increased in abundance in children who reported less frequent tooth brushing. A specific Veillonella feature was associated with caries presence, while features classified as Actinobacillus/Haemophilus and Leptotrichia were associated with absence of caries; a Lactobacillus gasseri feature increased in abundance in severe caries. Finally, we statistically assessed the interplay between dental caries and caries risk factors in shaping the oral microbiota. These data provide a detailed understanding of biological, behavioral, and socioeconomic factors that shape the oral microbiota and may underpin caries development in this group. This information can be used in the future to improve tailored caries prevention and management optionsMatilda Handsley-Davis, Emily Skelly, Newell W. Johnson, Kostas Kapellas, Ratilal Lalloo, Jeroen Kroon, and Laura S. Weyric

Improvements in Modeling 90 degree Bleed Holes for Supersonic Inlets

The modeling of porous bleed regions as boundary conditions in computational fluid dynamics (CFD) simulations of supersonic inlet flows has been improved through a scaling of sonic flow coefficient data for 90deg bleed holes. The scaling removed the Mach number as a factor in computing the sonic flow coefficient and allowed the data to be fitted with a quadratic equation, with the only factor being the ratio of the plenum static pressure to the surface static pressure. The implementation of the bleed model into the Wind-US CFD flow solver was simplified by no longer requiring the evaluation of the flow properties at the boundary-layer edge. The quadratic equation can be extrapolated to allow the modeling of small amounts of blowing, which can exist when recirculation of the bleed flow occurs within the bleed region. The improved accuracy of the bleed model was demonstrated through CFD simulations of bleed regions on a flat plate in supersonic flow with and without an impinging oblique shock. The bleed model demonstrated good agreement with experimental data and three-dimensional CFD simulations of bleed holes

Laboratory contamination over time during low-biomass sample analysis

Bacteria are not only ubiquitous on earth but can also be incredibly diverse within clean laboratories and reagents. The presence of both living and dead bacteria in laboratory environments and reagents is especially problematic when examining samples with low endogenous content (e.g., skin swabs, tissue biopsies, ice, water, degraded forensic samples or ancient material), where contaminants can outnumber endogenous microorganisms within samples. The contribution of contaminants within high-throughput studies remains poorly understood because of the relatively low number of contaminant surveys. Here, we examined 144 negative control samples (extraction blank and no-template amplification controls) collected in both typical molecular laboratories and an ultraclean ancient DNA laboratory over 5 years to characterize long-term contaminant diversity. We additionally compared the contaminant content within a home-made silica-based extraction method, commonly used to analyse low endogenous content samples, with a widely used commercial DNA extraction kit. The contaminant taxonomic profile of the ultraclean ancient DNA laboratory was unique compared to modern molecular biology laboratories, and changed over time according to researcher, month and season. The commercial kit also contained higher microbial diversity and several human-associated taxa in comparison to the home-made silica extraction protocol. We recommend a minimum of two strategies to reduce the impacts of laboratory contaminants within low-biomass metagenomic studies: (a) extraction blank controls should be included and sequenced with every batch of extractions and (b) the contributions of laboratory contamination should be assessed and reported in each high-throughput metagenomic study.Laura S. Weyrich, Andrew G. Farrer, Raphael Eisenhofer, Luis A. Arriola Jennifer Young, Caitlin A. Selway, Matilda Handsley‐Davis, Christina J. Adler James Breen, Alan Coope