The Impact of Doctoral Study on University Lecturers’ Construction of Self within a changing Higher Education policy context

This paper explores the impact of lectures’ individual current doctoral study on their own and collective constructions of self in a changing Higher Education (HE) policy context. It focuses on how lecturers, drawn from a professional knowledge background, make sense of new institutional requirements for new lectures to have doctorates. The lecturers themselves, through ‘facilitated collaborative auto-ethnography’, generate the substantial data and analysis for this research. This study exposes the enormous pressure of the doctorate on their lives and reveals different ways in which they resist particular forms of language, affiliations and positioning within their institution. However, of particular significance in this study is their own agency and collective voice, through using their developing cultural tools of research to ‘be’ researchers, in and beyond their own doctoral studies, in order to understand their own changing identities within HE. The study therefore reveals complex, contradictory and unexpected responses to HE policy

Protocol for a multicentre study to assess feasibility, acceptability, effectiveness and direct costs of TRIumPH (Treatment and Recovery In PsycHosis): integrated care pathway for psychosis

INTRODUCTION: Duration of untreated psychosis (time between the onset of symptoms and start of treatment) is considered the strongest predictor of symptom severity and outcome. Integrated care pathways that prescribe timeframes around access and interventions can potentially improve quality of care. METHODS AND ANALYSIS: A multicentre mixed methods study to assess feasibility, acceptability, effectiveness and analysis of direct costs of an integrated care pathway for psychosis. A pragmatic, non-randomised, controlled trial design is used to compare the impact of Treatment and Recovery In PsycHosis (TRIumPH; Intervention) by comparison between NHS organisations that adopt TRIumPH and those that continue with care as usual (Control). Quantitative and qualitative methods will be used. We will use routinely collected quantitative data and study-specific questionnaires and focus groups to compare service user outcomes, satisfaction and adherence to intervention between sites that adopt TRIumPH versus sites that continue with usual care pathways. SETTING: 4 UK Mental health organisations. Two will implement TRIumPH whereas two will continue care as usual. PARTICIPANTS: Staff, carers, individuals accepted to early intervention in psychosis teams in participating organisations for the study period. INTERVENTION: TRIumPH—Integrated Care Pathway for psychosis that has a holistic approach and prescribes time frames against interventions; developed using intelligence from data; co-produced with patients, carers, clinicians and other stakeholders. OUTCOMES: Feasibility will be assessed through adherence to the process measures. Satisfaction and acceptability will be assessed using questionnaires and focus groups. Effectiveness will be assessed through data collection and evaluation of patient outcomes, including clinical, functional and recovery outcomes, physical health, acute care use. Outcome measures will be assessed at baseline, 12 and 24 months to measure whether there is an effect and if so, whether this is sustained over time. Outcomes measures at the adopter sites will be compared to their own baseline and against comparator sites. ETHICS AND DISSEMINATION: Ethics approval was obtained from East of Scotland Research Ethics Service (REC Ref no: LR/15/ES/0091). The results will be disseminated through publications, conference presentations, reports to the organisation. STUDY REGISTRATION: UK Clinical Research Network Portfolio: 19187

An Easy-To-Use Simulation Program Demonstrates Variations in Bacterial Cell Cycle Parameters Depending on Medium and Temperature

Many studies are performed on chromosome replication and segregation in Escherichia coli and other bacteria capable of complex replication with C phases spanning several generations. For such investigations an understanding of the replication patterns, including copy numbers of origins and replication forks, is crucial for correct interpretation of the results

DNA methylation dynamics of the human preimplantation embryo

In mammals, cytosine methylation is predominantly restricted to CpG dinucleotides and stably distributed across the genome, with local, cell type-specific regulation directed by DNA binding factors1-3. This comparatively static landscape dramatically contrasts the events of fertilization, where the paternal genome is globally reprogrammed. Paternal genome demethylation includes the majority of CpGs, though methylation is maintained at several notable features4-7. While these dynamics have been extensively characterized in the mouse, only limited observations are available in other mammals, and direct measurements are required to understand the extent to which early embryonic landscapes are conserved8-10. We present genome-scale DNA methylation maps of human preimplantation development and embryonic stem cell (ESC) derivation, confirming a transient state of global hypomethylation that includes most CpGs, while sites of persistent maintenance are primarily restricted to gene bodies. While most features share similar dynamics to mouse, maternally contributed methylation is divergently targeted to species-specific sets of CpG island (CGI) promoters that extend beyond known Imprint Control Regions (ICRs). Retrotransposon regulation is also highly diverse and transitions from maternally to embryonically expressed, species-specific elements. Together, our data confirm that paternal genome demethylation is a general attribute of early mammalian development that is characterized by distinct modes of epigenetic regulation

Maternal cadmium, iron and zinc levels, DNA methylation and birth weight

Background Cadmium (Cd) is a ubiquitous and environmentally persistent toxic metal that has been implicated in neurotoxicity, carcinogenesis and obesity and essential metals including zinc (Zn) and iron (Fe) may alter these outcomes. However mechanisms underlying these relationships remain limited. Methods We examined whether maternal Cd levels during early pregnancy were associated with offspring DNA methylation at regulatory sequences of genomically imprinted genes and weight at birth, and whether Fe and Zn altered these associations. Cd, Fe and Zn were measured in maternal blood of 319 women ≤12 weeks gestation. Offspring umbilical cord blood leukocyte DNA methylation at regulatory differentially methylated regions (DMRs) of 8 imprinted genes was measured using bisulfite pyrosequencing. Regression models were used to examine the relationships among Cd, Fe, Zn, and DMR methylation and birth weight. Results Elevated maternal blood Cd levels were associated with lower birth weight (p = 0.03). Higher maternal blood Cd levels were also associated with lower offspring methylation at the PEG3 DMR in females (β = 0.55, se = 0.17, p = 0.05), and at the MEG3 DMR in males (β = 0.72, se = 0.3, p = 0.08), however the latter association was not statistically significant. Associations between Cd and PEG3 and PLAGL1 DNA methylation were stronger in infants born to women with low concentrations of Fe (p < 0.05). Conclusions Our data suggest the association between pre-natal Cd and offspring DNA methylation at regulatory sequences of imprinted genes may be sex- and gene-specific. Essential metals such as Zn may mitigate DNA methylation response to Cd exposure. Larger studies are required

Decreased replication origin activity in temporal transition regions

Experimental attempts to activate replication origins within the temporal transition region in the IgH locus in mouse embryonic stem cells were not successful, and thus, why and how they become activated in B cells remains unclear

"Dreaming in colour’: disabled higher education students’ perspectives on improving design practices that would enable them to benefit from their use of technologies"

The focus of this paper is the design of technology products and services for disabled students in higher education. It analyses the perspectives of disabled students studying in the US, the UK, Germany, Israel and Canada, regarding their experiences of using technologies to support their learning. The students shared how the functionality of the technologies supported them to study and enabled them to achieve their academic potential. Despite these positive outcomes, the students also reported difficulties associated with: i) the design of the technologies, ii) a lack of technology know-how and iii) a lack of social capital. When identifying potential solutions to these difficulties the disabled students imagined both preferable and possible futures where faculty, higher education institutions, researchers and technology companies are challenged to push the boundaries of their current design practices

Distinct Methylation Changes at the IGF2-H19 Locus in Congenital Growth Disorders and Cancer

Background: Differentially methylated regions (DMRs) are associated with many imprinted genes. In mice methylation at a DMR upstream of the H19 gene known as the Imprint Control region (IC1) is acquired in the male germline and influences the methylation status of DMRs 100 kb away in the adjacent Insulin-like growth factor 2 (Igf2) gene through long-range interactions. In humans, germline-derived or post-zygotically acquired imprinting defects at IC1 are associated with aberrant activation or repression of IGF2, resulting in the congenital growth disorders Beckwith-Wiedemann (BWS) and Silver-Russell (SRS) syndromes, respectively. In Wilms tumour and colorectal cancer, biallelic expression of IGF2 has been observed in association with loss of methylation at a DMR in IGF2. This DMR, known as DMR0, has been shown to be methylated on the silent maternal IGF2 allele presumably with a role in repression. The effect of IGF2 DMR0 methylation changes in the aetiology of BWS or SRS is unknown. Methodology/Principal Findings: We analysed the methylation status of the DMR0 in BWS, SRS and Wilms tumour patients by conventional bisulphite sequencing and pyrosequencing. We show here that, contrary to previous reports, the IGF2 DMR0 is actually methylated on the active paternal allele in peripheral blood and kidney. This is similar to the IC

Late Replicating Domains Are Highly Recombining in Females but Have Low Male Recombination Rates: Implications for Isochore Evolution

In mammals sequences that are either late replicating or highly recombining have high rates of evolution at putatively neutral sites. As early replicating domains and highly recombining domains both tend to be GC rich we a priori expect these two variables to covary. If so, the relative contribution of either of these variables to the local neutral substitution rate might have been wrongly estimated owing to covariance with the other. Against our expectations, we find that sex-averaged recombination rates show little or no correlation with replication timing, suggesting that they are independent determinants of substitution rates. However, this result masks significant sex-specific complexity: late replicating domains tend to have high recombination rates in females but low recombination rates in males. That these trends are antagonistic explains why sex-averaged recombination is not correlated with replication timing. This unexpected result has several important implications. First, although both male and female recombination rates covary significantly with intronic substitution rates, the magnitude of this correlation is moderately underestimated for male recombination and slightly overestimated for female recombination, owing to covariance with replicating timing. Second, the result could explain why male recombination is strongly correlated with GC content but female recombination is not. If to explain the correlation between GC content and replication timing we suppose that late replication forces reduced GC content, then GC promotion by biased gene conversion during female recombination is partly countered by the antagonistic effect of later replicating sequence tending increase AT content. Indeed, the strength of the correlation between female recombination rate and local GC content is more than doubled by control for replication timing. Our results underpin the need to consider sex-specific recombination rates and potential covariates in analysis of GC content and rates of evolution

Association of cord blood methylation fractions at imprinted insulin-like growth factor 2 (IGF2), plasma IGF2, and birth weight

status: publishe