High-resolution transcription atlas of the mitotic cell cycle in budding yeast.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Extensive transcription of non-coding RNAs has been detected in eukaryotic genomes and is thought to constitute an additional layer in the regulation of gene expression. Despite this role, their transcription through the cell cycle has not been studied; genome-wide approaches have only focused on protein-coding genes. To explore the complex transcriptome architecture underlying the budding yeast cell cycle, we used 8 bp tiling arrays to generate a 5 minute-resolution, strand-specific expression atlas of the whole genome. RESULTS: We discovered 523 antisense transcripts, of which 80 cycle or are located opposite periodically expressed mRNAs, 135 unannotated intergenic non-coding RNAs, of which 11 cycle, and 109 cell-cycle-regulated protein-coding genes that had not previously been shown to cycle. We detected periodic expression coupling of sense and antisense transcript pairs, including antisense transcripts opposite of key cell-cycle regulators, like FAR1 and TAF2. CONCLUSIONS: Our dataset presents the most comprehensive resource to date on gene expression during the budding yeast cell cycle. It reveals periodic expression of both protein-coding and non-coding RNA and profiles the expression of non-annotated RNAs throughout the cell cycle for the first time. This data enables hypothesis-driven mechanistic studies concerning the functions of non-coding RNAs

Rapid Review of National Qualifications Experience 2020

Summary of findings - This report draws upon a range of evidence, including stakeholder testimony (generated in panel and individual interviews) and analysis of relevant documentation (including government and SQA emails). - SQA, the government, local authorities and schools faced an extremely difficult set of circumstances, within which there were no easy solutions. In this context, a workable system for qualifications, the Alternative Certification Model (ACM), was developed. This was based on three core principles and four stages. - All parties involved in the process were found to have acted with integrity, with the best interests of students in mind. - Respondents (teachers, lecturers, head teachers and local authority officials) generally found that SQA guidance was clear and useful. - The generation of estimated grades, while clearly undertaken with integrity in the majority of centres, has been subject to variation (in the types of evidence available, the processes followed for internal moderation and the support given by local authorities), which has impacted on reliability and consistency of assessment at this stage. - The statistical approach to moderation could have been more transparent earlier in the process, and moreover it has led to anomalies in grade adjustment, especially at the level of subject cohorts within centres and individuals. - There is widespread criticism by respondents of SQA for a perceived lack of transparency and a failure to engage in participative development of solutions with stakeholders. - While the application of the appeals process offered an in-principle technical solution to address these anomalies, it paid insufficient attention to the severe impact on those students obliged to undergo it (in terms of mental health and wellbeing, missed opportunities to transition into Higher Education, etc.). - Principles relating to what data is appropriate to be held by certain organisations at certain points in time.(i.e. SQA, the Scottish Government), which make perfect sense in normal times (e.g. arrangements around data sharing), appear to have impeded the development of actions that might have led to an earlier anticipation and mitigation of subsequent problems. - The equalities implications of an over-reliance on a statistical approach, premised on comparison with historical cohort data, had been raised repeatedly from April onwards, but seem to have been under-emphasised by both the government and SQA until late in the process. - Many stakeholders believe that, subsequently, opportunities were missed (or dismissed) to engage in qualitative moderation of the statistical process (e.g. sense-checking of anomalous cohort patterns by local authorities). - There has been an erosion of trust/confidence in SQA amongst teachers and young people, and damaged relations in some cases between young people and their teachers. - Communications (with professionals and with young people and their families) has been a constant source of criticism. - Our overall assessment is that, despite the extremely difficult environment for decision making, there are points in the process where different decisions may have led to better outcomes and at least partially avoided the controversy that ensued in August 2020. Of course, we are making this observation with the benefit of hindsight, thus our primary intention is to illustrate how the system can benefit from lessons learned in 2020 to avoid a similar predicament in 2021

Rapid Review of National Qualifications Experience 2020

Summary of findings - This report draws upon a range of evidence, including stakeholder testimony (generated in panel and individual interviews) and analysis of relevant documentation (including government and SQA emails). - SQA, the government, local authorities and schools faced an extremely difficult set of circumstances, within which there were no easy solutions. In this context, a workable system for qualifications, the Alternative Certification Model (ACM), was developed. This was based on three core principles and four stages. - All parties involved in the process were found to have acted with integrity, with the best interests of students in mind. - Respondents (teachers, lecturers, head teachers and local authority officials) generally found that SQA guidance was clear and useful. - The generation of estimated grades, while clearly undertaken with integrity in the majority of centres, has been subject to variation (in the types of evidence available, the processes followed for internal moderation and the support given by local authorities), which has impacted on reliability and consistency of assessment at this stage. - The statistical approach to moderation could have been more transparent earlier in the process, and moreover it has led to anomalies in grade adjustment, especially at the level of subject cohorts within centres and individuals. - There is widespread criticism by respondents of SQA for a perceived lack of transparency and a failure to engage in participative development of solutions with stakeholders. - While the application of the appeals process offered an in-principle technical solution to address these anomalies, it paid insufficient attention to the severe impact on those students obliged to undergo it (in terms of mental health and wellbeing, missed opportunities to transition into Higher Education, etc.). - Principles relating to what data is appropriate to be held by certain organisations at certain points in time.(i.e. SQA, the Scottish Government), which make perfect sense in normal times (e.g. arrangements around data sharing), appear to have impeded the development of actions that might have led to an earlier anticipation and mitigation of subsequent problems. - The equalities implications of an over-reliance on a statistical approach, premised on comparison with historical cohort data, had been raised repeatedly from April onwards, but seem to have been under-emphasised by both the government and SQA until late in the process. - Many stakeholders believe that, subsequently, opportunities were missed (or dismissed) to engage in qualitative moderation of the statistical process (e.g. sense-checking of anomalous cohort patterns by local authorities). - There has been an erosion of trust/confidence in SQA amongst teachers and young people, and damaged relations in some cases between young people and their teachers. - Communications (with professionals and with young people and their families) has been a constant source of criticism. - Our overall assessment is that, despite the extremely difficult environment for decision making, there are points in the process where different decisions may have led to better outcomes and at least partially avoided the controversy that ensued in August 2020. Of course, we are making this observation with the benefit of hindsight, thus our primary intention is to illustrate how the system can benefit from lessons learned in 2020 to avoid a similar predicament in 2021

Exploring Curriculum Making in Scottish Secondary Schools: Trends and Effects

This article presents the findings from a recent study funded by the Nuffield Foundation, which aimed to provide insights into the experiences of young people and teachers in secondary schools across Scotland under the Curriculum for Excellence (CfE). Our research has uncovered a decrease in the number of National Qualifications entries in S4 under CfE, a phenomenon commonly referred to in Scotland as 'curriculum narrowing.' Furthermore, we have identified evidence of social stratification in overall and subject entry patterns in S4, with students from disadvantaged areas experiencing a more significant decline in entries and being limited to a narrower range of subjects. Marina Shapira is an Associate Professor in Sociology in the Faculty of Social Sciences at the University of Stirling and the Principal Investigator on the Nuffield Foundation funded project: Choice, attainment and positive destinations: exploring the impact of curriculum policy change on young people. Additionally, our study has revealed signs of curriculum fragmentation during the Broad General Education phase (years S1-S3). The findings from our study also suggest that the curriculum decisions made in schools are primarily driven by the demand for better attainment data, particularly in National Qualifications during the Senior Phase (school years S4-S6), with less emphasis on what it means for an individual to become an educated person in a modern and complex society. Based on our findings, we have concluded that curriculum fragmentation and narrowing under CfE have a detrimental impact on the progression and attainment of young people. Schools that offer a broader curriculum in S4 demonstrate higher enrolment rates for Higher qualifications in S5 and Advanced Higher qualifications in S6. In contrast, schools that offer a narrower curriculum in S4, particularly those in deprived areas, are more likely to experience delays in higher-level qualification entry. A broader curriculum in S4 has been associated with improved performance in National 5 qualifications, higher scores in international tests such as PISA English and Maths, and higher scores on OECD measures of global competences. On the other hand, a narrower curriculum is correlated with less favourable outcomes after leaving school, especially in terms of Higher Education enrolment

A Poly-N-Acetylglucosamine−Shiga Toxin Broad-Spectrum Conjugate Vaccine for Shiga Toxin-Producing Escherichia coli

ABSTRACT Many pathogens produce the β-(1−6)-linked poly-N-acetylglucosamine (PNAG) surface polysaccharide that is being developed as a broadly protective antimicrobial vaccine. However, it is unknown whether systemically injected PNAG vaccines or antibodies would provide protective immunity against pathogens confined to the gastrointestinal tract such as Shiga toxin (Stx)-producing Escherichia coli (STEC), an important group of gastrointestinal (GI) pathogens for which effective immunotherapeutics are lacking. To ascertain whether systemic IgG antibody to PNAG impacts this infectious situation, a vaccine consisting of a synthetic nonamer of nonacetylated PNAG, 9GlcNH2, conjugated to the Shiga toxin 1b subunit (9GlcNH2-Stx1b) was produced. Rabbit antibodies raised to the conjugate vaccine were tested for bacterial killing and toxin neutralization in vitro and protection against infection in infant mice. Cell surface PNAG was detected on all 9 STEC isolates tested, representing 6 STEC serogroups, including E. coli O157:H7. Antibody to the 9GlcNH2-Stx1b conjugate neutralized Stx1 potently and Stx2 modestly. For O157:H7 and O104:H4 STEC strains, antibodies elicited by the 9GlcNH2-Stx1b conjugate possessed opsonic killing and bactericidal activity. Following intraperitoneal injection, antibodies to both PNAG and Stx were needed for infant mouse protection against O157 STEC. These antibodies also mediated protection against the Stx2-producing O104:H4 strain that was the cause of a recent outbreak in Germany, although sufficient doses of antibody to PNAG alone were protective against this strain in infant mice. Our observations suggest that vaccination against both PNAG and Stx, using a construct such as the 9GlcNH2-Stx1b conjugate vaccine, would be protective against a broad range of STEC serogroups

Behavioural syndrome in a solitary predator is independent of body size and growth rate.

Models explaining behavioural syndromes often focus on state-dependency, linking behavioural variation to individual differences in other phenotypic features. Empirical studies are, however, rare. Here, we tested for a size and growth-dependent stable behavioural syndrome in the juvenile-stages of a solitary apex predator (pike, Esox lucius), shown as repeatable foraging behaviour across risk. Pike swimming activity, latency to prey attack, number of successful and unsuccessful prey attacks was measured during the presence/absence of visual contact with a competitor or predator. Foraging behaviour across risks was considered an appropriate indicator of boldness in this solitary predator where a trade-off between foraging behaviour and threat avoidance has been reported. Support was found for a behavioural syndrome, where the rank order differences in the foraging behaviour between individuals were maintained across time and risk situation. However, individual behaviour was independent of body size and growth in conditions of high food availability, showing no evidence to support the state-dependent personality hypothesis. The importance of a combination of spatial and temporal environmental variation for generating growth differences is highlighted

Reports of Perceived Adverse Events of Stimulant Medication on Cognition, Motivation, and Mood:Qualitative Investigation and the Generation of Items for the Medication and Cognition Rating Scale

Items were identified that capture potential/perceived cognitive, motivational, and mood-related adverse events of MPH. The items generated will allow us to further develop and psychometrically examine their prevalence, and the extent to which they are associated with medication adherence, treatment outcome, impairment, and other reported adverse events (e.g., loss of appetite/cardiovascular effects)

Cholinesterase Inhibitors in Mild Cognitive Impairment: A Systematic Review of Randomised Trials

A systematic review of trials of cholinesterase inhibitors for preventing transition of mild cognitive impairment (MCI) to dementia, conducted by Roberto Raschetti and colleagues, found no difference between treatment and control groups and concluded that uncertainty regarding the definition of MCI casts doubts on the validity of such trials

The discovery, distribution and diversity of DNA viruses associated with Drosophila melanogaster in Europe

International audienceDrosophila melanogaster is an important model for antiviral immunity in arthropods, but very few DNA viruses have been described from the family Drosophilidae. This deficiency limits our opportunity to use natural host-pathogen combinations in experimental studies, and may bias our understanding of the Drosophila virome. Here we report fourteen DNA viruses detected in a metagenomic analysis of approximately 6500 pool-sequenced Drosophila, sampled from 47 European locations between 2014 and 2016. These include three new nudiviruses, a new and divergent entomopoxvirus, a virus related to Leptopilina boulardi filamentous virus, and a virus related to Musca domestica salivary gland hypertrophy virus. We also find an endogenous genomic copy of galbut virus, a dsRNA partitivirus, segregating at very low frequency. Remarkably, we find that Drosophila Vesanto virus, a small DNA virus previously described as a bidnavirus, may be composed of up to 12 segments and thus represent a new lineage of segmented DNA viruses. Two of the DNA viruses, Drosophila Kallithea nudivirus and Drosophila Vesanto virus are relatively common, found in 2% or more of wild flies. The others are rare, with many likely to be represented by a single infected fly. We find that virus prevalence in Europe reflects the prevalence seen in publicly-available datasets, with Drosophila Kallithea nudivirus and Drosophila Vesanto virus the only ones commonly detectable in public data from wild-caught flies and large population cages, and the other viruses being rare or absent. These analyses suggest that DNA viruses are at lower prevalence than RNA viruses in D. melanogaster, and may be less likely to persist in laboratory cultures. Our findings go some way to redressing an earlier bias toward RNA virus studies in Drosophila, and lay the foundation needed to harness the power of Drosophila as a model system for the study of DNA viruses