Polyadenylation Mediated by LINE-1

Transposable elements (TEs) are sequences that change position within the genome and play an important role in genome expansion. TEs are grouped into two categories based on their transposition mechanism. Class 1 retrotransposons spread via target-primed reverse transcription (RNA to DNA) into different genomic locations. Long interspersed element 1 (L1) is a class 1 retrotransposon that is able to move autonomously, as they encode the protein machinery with an endonuclease and reverse transcriptase activity, to insert themselves back into the genome. L1s were the focus of this study, because they are implicated in creating alternate poly(A) sites in genes. We analyzed 778,128 isoforms produced from 12 samples of long-read RNA (PacBio HiFi) sequencing data to investigate if L1s introduce polyadenylation sites. Isoforms were filtered based on L1 location within the isoforms’ 3’UTR, resulting in roughly 3,000 isoforms, spread across 757 genes. L1 subfamilies have arisen throughout evolutionary history due to species-specific substitutions. The L1 subfamilies in the dataset are mostly mammalian specific, while only 43 contain primate specific L1s. The majority of the L1s studied were classified as L1M5 (329), L1ME4b (165), L1MB7 (105), and L1ME4c (105). These L1s contain canonical and noncanonical polyadenylation signals within their 3’UTRs. Alternatively polyadenylated mRNA variants, generated from the same gene, are likely bound by different combinations of trans-acting factors that can affect mRNA localization, translation, stability, and decay. Understanding the roles of L1s in alternative polyadenylation will shed light on the impact of TEs on processing efficiency of gene expression

Systems, interactions and macrotheory

A significant proportion of early HCI research was guided by one very clear vision: that the existing theory base in psychology and cognitive science could be developed to yield engineering tools for use in the interdisciplinary context of HCI design. While interface technologies and heuristic methods for behavioral evaluation have rapidly advanced in both capability and breadth of application, progress toward deeper theory has been modest, and some now believe it to be unnecessary. A case is presented for developing new forms of theory, based around generic “systems of interactors.” An overlapping, layered structure of macro- and microtheories could then serve an explanatory role, and could also bind together contributions from the different disciplines. Novel routes to formalizing and applying such theories provide a host of interesting and tractable problems for future basic research in HCI

Sky cover from MFRSR observations

The diffuse all-sky surface irradiances measured at two nearby wavelengths in the visible spectral range and their modeled clear-sky counterparts are the main components of a new method for estimating the fractional sky cover of different cloud types, including cumuli. The performance of this method is illustrated using 1-min resolution data from a ground-based Multi-Filter Rotating Shadowband Radiometer (MFRSR). The MFRSR data are collected at the US Department of Energy Atmospheric Radiation Measurement (ARM) Climate Research Facility (ACRF) Southern Great Plains (SGP) site during the summer of 2007 and represent 13 days with cumuli. Good agreement is obtained between estimated values of the fractional sky cover and those provided by a well-established independent method based on broadband observations

Submerged in the mainstream? A case study of an immigrant learner in a New Zealand primary classroom

Immigrant children from diverse language backgrounds face not only linguistic challenges when enrolled in mainstream English-medium classrooms, but also difficulties adjusting to an unfamiliar learning community. The culture of primary school classrooms in New Zealand typically reflects conventions across three dimensions: interactional, instructional task performance and cognitive-academic development. All three dimensions are underpinned by the culturally specific discourse conventions involved in language socialisation. New learners may be helped by classmates or their teacher to understand and successfully use these conventions, but left on their own they may sink rather than swim. This is a case study of one Taiwanese 11-year old boy, 'John', who entered a New Zealand primary classroom midway through the school year. John's basic conversational ability was sound, but he did not possess the interactive classroom skills needed to operate in the new culture of learning. Selected from a wider study of the classroom, transcript data from audio-recorded excerpts of John's interactions over several months with his teacher and classmates are interpreted from perspectives derived from sociocultural and language socialisation theories. The article concludes with a brief consideration of the extent to which John constructed, or was constrained from constructing meaningful learning experiences, and suggestions for further research and reflection

Could psoralen plus ultraviolet A1 (“PUVA1”) work? Depth penetration achieved by phototherapy lamps

Funding: PhD Studentship UK EPRSC EP/N509759/1.Psoralen and ultraviolet A (PUVA) is useful in treating various hand and foot skin diseases.1 Most cases of psoriasis respond well to phototherapy or PUVA. However, for some diseases, such as palmoplantar pustular psoriasis, PUVA is not always sufficient to produce therapeutic effect. If PUVA fails, it is sometimes necessary to progress to other treatments such as Grenz ray therapy (where available),2 systemic retinoid or systemic immunosuppression. Could “PUVA1” (psoralen combined with ultraviolet A1 long wavelength ultraviolet A [UVA]) work in cases where conventional PUVA (psoralen plus broadband UVA) has been inadequate?PostprintPeer reviewe

Variation in the helminth community structure in bank voles (Clethrionomys glareolus) from three comparable localities in the Mazury Lake District region of Poland

We tested the null hypothesis that populations of hosts trapped in isolated neighbouring locations showing comparable habitat quality, should support similar helminth parasite communities. The study was undertaken in a 2-week period in late summer in NE Poland in a single year, thereby eliminating seasonal and between-year variation in parasite burdens. A total of 139 Clethrionomys glareolus (bank vole) were sampled from 3 forest sites of similar habitat quality. Total species richness was 11 (6 nematodes and 5 cestodes) with 85±6% of the voles carrying at least 1 species and an overall mean species richness of 1±4. At the component community level, the fewest species of helminths were recorded from site 2 (n=6, compared with 9 at each of the other sites), but site 3 had the lowest Berger-Parker Dominance Index and the highest Simpson's Index of Diversity. At the infracommunity level, site 3 had the highest mean no. of helminthspecies}vole, the highest mean Brillouin's Index of Diversity but the lowest mean no. of helminths/vole. Voles from sites 1 and 3 differed in the nematodes that were most common (site 1, Heligmosomum mixtum ± 95%; site 3, Heligmosomoides glareoli ± 79±3%). At site 2 no species exceeded 50% but prevalence of Syphacia petrusewiczi was higher than at the other sites. The prevalence of cestodes was too low to test reliably (12±9%), but the highest prevalence of adult cestodes was recorded at site 1 (22±5%compared with 4±9 and 1±7%for sites 2 and 3 respectively). Host sex did not ifluence infection, but mean species richness increased with age. The different sites were responsible for most of the variation in our data, and the intrinsic factors (sex and age) were less important in shaping the component community structure of helminths. We conclude that even locations in relative close proximity to one another (13±25 km), selected on the basis of similar habitat quality, have rodent populations that differ in their helminth parasite communities, although for reasons other than the factors quantified in the present study

Local variation in endoparasite intensities of bank voles (Clethrionomys glareolus )from ecologically similar sites: morphometric and endocrine correlates

Much interest has centred recently on the role of adaptive trade-offs between the immune system and other components of life history in determining resistance and parasite intensities among hosts. Steroid hormones, particularly glucocorticoids and sex steroids, provide a plausible mechanism for mediating such trade-offs. A basic assumption behind the hypothesis, however, is that steroid activity will generally correlate with reduced resistance and thus greater parasite intensities. Here, we present some findings from a field study of bank voles (Clethrionomys glareolus ) in which we have looked at associations between parasite intensities, anatomical and morphometric measures relating to endocrine function and life history variation in three local populations inhabiting similar but mutually isolated woodland habitats. In general, sites with greater parasite intensities were those in which male C. glareolus had significantly larger adrenal glands, testes and seminal vesicles for their age and body size. Females also showed a site difference in adrenal gland weight. Some aspects of site-related parasite intensity were associated with asymmetry in adrenal gland weight and hind foot length, which may have reflected developmental effects on glucocorticoid activity

Computer-based diabetes self-management interventions for adults with type 2 diabetes mellitus

BACKGROUND: Diabetes is one of the commonest chronic medical conditions, affecting around 347 million adults worldwide. Structured patient education programmes reduce the risk of diabetes-related complications four-fold. Internet-based self-management programmes have been shown to be effective for a number of long-term conditions, but it is unclear what are the essential or effective components of such programmes. If computer-based self-management interventions improve outcomes in type 2 diabetes, they could potentially provide a cost-effective option for reducing the burdens placed on patients and healthcare systems by this long-term condition. OBJECTIVES: To assess the effects on health status and health-related quality of life of computer-based diabetes self-management interventions for adults with type 2 diabetes mellitus. SEARCH METHODS: We searched six electronic bibliographic databases for published articles and conference proceedings and three online databases for theses (all up to November 2011). Reference lists of relevant reports and reviews were also screened. SELECTION CRITERIA: Randomised controlled trials of computer-based self-management interventions for adults with type 2 diabetes, i.e. computer-based software applications that respond to user input and aim to generate tailored content to improve one or more self-management domains through feedback, tailored advice, reinforcement and rewards, patient decision support, goal setting or reminders. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the abstracts and extracted data. A taxonomy for behaviour change techniques was used to describe the active ingredients of the intervention. MAIN RESULTS: We identified 16 randomised controlled trials with 3578 participants that fitted our inclusion criteria. These studies included a wide spectrum of interventions covering clinic-based brief interventions, Internet-based interventions that could be used from home and mobile phone-based interventions. The mean age of participants was between 46 to 67 years old and mean time since diagnosis was 6 to 13 years. The duration of the interventions varied between 1 to 12 months. There were three reported deaths out of 3578 participants.Computer-based diabetes self-management interventions currently have limited effectiveness. They appear to have small benefits on glycaemic control (pooled effect on glycosylated haemoglobin A1c (HbA1c): -2.3 mmol/mol or -0.2% (95% confidence interval (CI) -0.4 to -0.1; P = 0.009; 2637 participants; 11 trials). The effect size on HbA1c was larger in the mobile phone subgroup (subgroup analysis: mean difference in HbA1c -5.5 mmol/mol or -0.5% (95% CI -0.7 to -0.3); P < 0.00001; 280 participants; three trials). Current interventions do not show adequate evidence for improving depression, health-related quality of life or weight. Four (out of 10) interventions showed beneficial effects on lipid profile.One participant withdrew because of anxiety but there were no other documented adverse effects. Two studies provided limited cost-effectiveness data - with one study suggesting costs per patient of less than $140 (in 1997) or 105 EURO and another study showed no change in health behaviour and resource utilisation. AUTHORS' CONCLUSIONS: Computer-based diabetes self-management interventions to manage type 2 diabetes appear to have a small beneficial effect on blood glucose control and the effect was larger in the mobile phone subgroup. There is no evidence to show benefits in other biological outcomes or any cognitive, behavioural or emotional outcomes

Schizophrenia and the progression of emotional expression in relation to others

Gaining an improved understanding of people diagnosed with schizophrenia has the potential to influence priorities for therapy. Psychosis is commonly understood through the perspective of the medical model. However, the experience of social context surrounding psychosis is not well understood. In this research project we used a phenomenological methodology with a longitudinal design to interview 7 participants across a 12-month period to understand the social experiences surrounding psychosis. Eleven themes were explicated and divided into two phases of the illness experience: (a) transition into emotional shutdown included the experiences of not being acknowledged, relational confusion, not being expressive, detachment, reliving the past, and having no sense of direction; and (b) recovery from emotional shutdown included the experiences of being acknowledged, expression, resolution, independence, and a sense of direction. The experiential themes provide clinicians with new insights to better assess vulnerability, and have the potential to inform goals for therapy