Ethnicity and the Writing of Medieval Scottish history

Historians have long tended to define medieval Scottish society in terms of interactions between ethnic groups. This approach was developed over the course of the long nineteenth century, a formative period for the study of medieval Scotland. At that time, many scholars based their analysis upon scientific principles, long since debunked, which held that medieval 'peoples' could only be understood in terms of 'full ethnic packages'. This approach was combined with a positivist historical narrative that defined Germanic Anglo-Saxons and Normans as the harbingers of advances of Civilisation. While the prejudices of that era have largely faded away, the modern discipline still relies all too often on a dualistic ethnic framework. This is particularly evident in a structure of periodisation that draws a clear line between the 'Celtic' eleventh century and the 'Norman' twelfth. Furthermore, dualistic oppositions based on ethnicity continue, particularly in discussions of the law, kingship, lordship and religion

Microbial Successions Are Associated with Changes in Chemical Profiles of a Model Refrigerated Fresh Pork Sausage during an 80-Day Shelf Life Study

Fresh pork sausage is produced without a microbial kill step and therefore chilled or frozen to control microbial growth. In this report, the microbiota in a chilled fresh pork sausage model produced with or without an antimicrobial combination of sodium lactate and sodium diacetate was studied using a combination of traditional microbiological methods and deep pyrosequencing of 16S rRNA gene amplicons. In the untreated system, microbial populations rose from 102 to 106 CFU/g within 15 days of storage at 4°C, peaking at nearly 108 CFU/g by day 30. Pyrosequencing revealed a complex community at day 0, with taxa belonging to the Bacilli, Gammaproteobacteria, Betaproteobacteria, Actinobacteria, Bacteroidetes, and Clostridia. During storage at 4°C, the untreated system displayed a complex succession, with species of Weissella and Leuconostoc that dominate the product at day 0 being displaced by species of Pseudomonas (P. lini and P. psychrophila) within 15 days. By day 30, a second wave of taxa (Lactobacillus graminis, Carnobacterium divergens, Buttiauxella brennerae, Yersinia mollaretti, and a taxon of Serratia) dominated the population, and this succession coincided with significant chemical changes in the matrix. Treatment with lactate-diacetate altered the dynamics dramatically, yielding a monophasic growth curve of a single species of Lactobacillus (L. graminis), followed by a uniform selective die-off of the majority of species in the population. Of the six species of Lactobacillus that were routinely detected, L. graminis became the dominant member in all samples, and its origins were traced to the spice blend used in the formulation

Determinants of Dwell Time in Visual Search: Similarity or Perceptual Difficulty?

The present study examined the factors that determine the dwell times in a visual search task, that is, the duration the gaze remains fixated on an object. It has been suggested that an item’s similarity to the search target should be an important determiner of dwell times, because dwell times are taken to reflect the time needed to reject the item as a distractor, and such discriminations are supposed to be harder the more similar an item is to the search target. In line with this similarity view, a previous study shows that, in search for a target ring of thin line-width, dwell times on thin linewidth Landolt C’s distractors were longer than dwell times on Landolt C’s with thick or medium linewidth. However, dwell times may have been longer on thin Landolt C’s because the thin line-width made it harder to detect whether the stimuli had a gap or not. Thus, it is an open question whether dwell times on thin line-width distractors were longer because they were similar to the target or because the perceptual decision was more difficult. The present study de-coupled similarity from perceptual difficulty, by measuring dwell times on thin, medium and thick line-width distractors when the target had thin, medium or thick line-width. The results showed that dwell times were longer on target-similar than target-dissimilar stimuli across all target conditions and regardless of the line-width. It is concluded that prior findings of longer dwell times on thin linewidth-distractors can clearly be attributed to target similarity. As will be discussed towards the end, the finding of similarity effects on dwell times has important implications for current theories of visual search and eye movement control

The UniProt-GO Annotation database in 2011

The GO annotation dataset provided by the UniProt Consortium (GOA: http://www.ebi.ac.uk/GOA) is a comprehensive set of evidenced-based associations between terms from the Gene Ontology resource and UniProtKB proteins. Currently supplying over 100 million annotations to 11 million proteins in more than 360 000 taxa, this resource has increased 2-fold over the last 2 years and has benefited from a wealth of checks to improve annotation correctness and consistency as well as now supplying a greater information content enabled by GO Consortium annotation format developments. Detailed, manual GO annotations obtained from the curation of peer-reviewed papers are directly contributed by all UniProt curators and supplemented with manual and electronic annotations from 36 model organism and domain-focused scientific resources. The inclusion of high-quality, automatic annotation predictions ensures the UniProt GO annotation dataset supplies functional information to a wide range of proteins, including those from poorly characterized, non-model organism species. UniProt GO annotations are freely available in a range of formats accessible by both file downloads and web-based views. In addition, the introduction of a new, normalized file format in 2010 has made for easier handling of the complete UniProt-GOA data se

Genome-wide common and rare variant analysis provides novel insights into clozapine-associated neutropenia

The antipsychotic clozapine is uniquely effective in the management of schizophrenia; however, its use is limited by its potential to induce agranulocytosis. The causes of this, and of its precursor neutropenia, are largely unknown, although genetic factors have an important role. We sought risk alleles for clozapine-associated neutropenia in a sample of 66 cases and 5583 clozapine-treated controls, through a genome-wide association study (GWAS), imputed human leukocyte antigen (HLA) alleles, exome array and copy-number variation (CNV) analyses. We then combined associated variants in a meta-analysis with data from the Clozapine-Induced Agranulocytosis Consortium (up to 163 cases and 7970 controls). In the largest combined sample to date, we identified a novel association with rs149104283 (odds ratio (OR)=4.32, P=1.79 × 10−8), intronic to transcripts of SLCO1B3 and SLCO1B7, members of a family of hepatic transporter genes previously implicated in adverse drug reactions including simvastatin-induced myopathy and docetaxel-induced neutropenia. Exome array analysis identified gene-wide associations of uncommon non-synonymous variants within UBAP2 and STARD9. We additionally provide independent replication of a previously identified variant in HLA-DQB1 (OR=15.6, P=0.015, positive predictive value=35.1%). These results implicate biological pathways through which clozapine may act to cause this serious adverse effec

An Expanded Evaluation of Protein Function Prediction Methods Shows an Improvement In Accuracy

Background: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging. Results: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2. Conclusions: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent

An expanded evaluation of protein function prediction methods shows an improvement in accuracy

Background: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging. Results: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2. Conclusions: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent. Keywords: Protein function prediction, Disease gene prioritizationpublishedVersio

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

The role and regulation of sugar transporters in Arabidopsis

This thesis describes a number of different approaches to understand the role of sugar transporters in Arabidopsis thaliana.  Insertion mutants from the Sainsbury Laboratory Arabidopsis dSpm Transposant (SLAT) collection were used to investigate the function of the sucrose transporters AtSUC1 and AtSUC2.  Phenotypic analyses of these mutants demonstrate that AtSUC1 and AtSUC2 have substantially different roles in growth and development of Arabidopsis.  The suc1-1 mutant was similar to wild-type (WT) plants in terms of general growth and development.  In contrast, knocking out AtSUC2 had severe effects at all developmental stages.  The suc2 mutants were severely retarded in their growth and, at maturity, were significantly smaller in height with fewer and smaller leaves and a reduced number of flowers.  Siliques developed in some cases, but these were generally shorter in length and produced significantly smaller seed than in WT plants.  Importantly, although previously isolated suc2 mutants were reported as sterile, those isolated in this study could produce viable seed although viability varied between individual plants.  Exogenously supplied sucrose did not fully rescue the suc2 mutant phenotype. An alternative approach to understanding gene function is to investigate the regulation of gene expression.  This was undertaken for representation genes from two important sugar transporter families, the disaccharide transporter, AtSUC2 and the monosaccharide transporter, AtSTP4.  Gene expression was investigated in Arabidopsis seedlings using RT-PCR and reporter gene technology concentrating on two potential regulators of sugar transporter gene expression, sugar availability and light.  Both activate signalling pathways in plants and sugar transporters may be targets for regulation by these stimuli.  Experiments using transgenic Arabidopsis plants containing promoter:  GUS fusions demonstrated that AtSUC2 and AtSTP4 were both expressed in all organs with AtSUC2 expression concentrated in the vascular tissue.  Neither AtSUC2 nor AtSTP4 expression was dramatically different in light- and dark-grown seedlings.</p