Transcriptional profiling of suberoylanilide hydroxamic acid (SAHA) regulated genes in mineralizing dental pulp cells at early and late time points

Dental pulp tissue can be damaged by a range of irritants, however, if the irritation is removed and/or the tooth is adequately restored, pulp regeneration is possible (Mjör and Tronstad, 1974 [1]). At present, dental restorative materials limit healing by impairing mineralization and repair processes and as a result new biologically-based materials are being developed (Ferracane et al., 2010 [2]). Previous studies have highlighted the benefit of epigenetic modification by histone deacetylase inhibitor (HDACi) application to dental pulp cells (DPCs), which induces changes to chromatin architecture, promoting gene expression and cellular-reparative events (Duncan et al., 2013 [3]; Paino et al., 2014 [4]). In this study a genome-wide transcription profiling in epigenetically-modified mineralizing primary DPC cultures was performed, at relatively early and late time-points, to identify differentially regulated transcripts that may provide novel therapeutic targets for use in restorative dentistry. Here we provide detailed methods and analysis on these microarray data which has been deposited in Gene Expression Omnibus (GEO): GSE67175

The material role of digital media in connecting with, within, and beyond museums

The connective potentials of digital media have been positioned as a key part of a contemporary museum visitor experience. Using a sociology of translation, we construct a network of visitor experiences using data from a digital media engagement project at a large and multi-sited museum in the United Kingdom. These experiences relate to (dis)connections with the museum, museum objects, and other visitors. Through this analysis we disclose the often contradictory roles of the non-human, including and going beyond the digital, as contributors to the success and failure of attempts to change museum visitor experiences through engagement activities rooted in narratives of participation and connectivity

A Simplified Method to Distinguish Farmed (Salmo salar) from Wild Salmon: Fatty Acid Ratios Versus Astaxanthin Chiral Isomers

Mislabeling of farmed and wild salmon sold in markets has been reported. Since the fatty acid content of fish may influence human health and thus consumer behavior, a simplified method to identify wild and farmed salmon is necessary. Several studies have demonstrated differences in lipid profiles between farmed and wild salmon but no data exists validating these differences with government-approved methods to accurately identify the origin of these fish. Current methods are both expensive and complicated, using highly specialized equipment not commonly available. Therefore, we developed a testing protocol using gas chromatography (GC), to determine the origin of salmon using fatty acid profiles. We also compared the GC method with the currently approved FDA (United States Food and Drug Administration) technique that uses analysis of carotenoid optical isomers and found 100% agreement. Statistical validation (n = 30) was obtained showing elevated 18:2n-6 (z = 4.56; P = 0.0001) and decreased 20:1n-9 (z = 1.79; P = 0.07) in farmed samples. The method is suitable for wide adaptation because fatty acid methyl ester analysis is a well-established procedure in labs that conduct analysis of lipid composition and food constituents. GC analysis for determining the origin of North American salmon compared favorably with the astaxanthin isomer technique used by the FDA and showed that the fatty acid 18:2n-6 was the key indicator associated with the origin of these salmon

Origin of line broadening in the electronic absorption spectra of conjugated polymers: Three-pulse-echo studies of MEH-PPV in toluene

Integrated three-pulse stimulated echo peak shift data are compared for N,N-bis-dimethylphenyl-1-2,4,6,8-perylenetetracarbonyl diamide and poly[2-(2'-ethylhexyloxy)-5-methoxy-1,4-phenylenevinylene] (MEH-PPV) in toluene solvent. These two molecules represent a model probe of solvation dynamics and a prototypical soluble, electroluminescent conjugated polymer, respectively. The results indicate that it is inappropriate to describe the linear absorption spectrum of MEH-PPV as being primarily inhomogeneously broadened. Conformational disorder along the polymer backbone gives rise to an ensemble of polyene electronic oscillators that are strongly coupled to each other. As a consequence, fluctuations in the electronic energy gap on a time-scale of 50-fs derive primarily from bath-mediated exciton scattering. The data reported here provide an explanation for the broad, structureless electronic absorption of MEH-PPV. This interpretation provides a valuable insight into the nature of the initial photoexcited state, and the efficient population of the emissive state

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16–20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement

Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

Background The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p