Molecular Marker Linkage Map for Apple

Linkage maps for two apple clones, White Angel and Rome Beauty, were constructed using isozyme and DNA polymorphisms segregating in a population produced from a Rome Beauty × White Angel cross. The linkage map for White Angel consists of 253 markers arranged in 24 linkage groups and extends over 950 cM. The Rome Beauty map contains 156 markers on 21 linkage groups. The White Angel map was taken as the standard, and we were able to identify linkage groups in Rome Beauty homologous to 13 White Angel linkage groups. The location of several genes not segregating in the Rome Beauty × White Angel population could be determined on the basis of known linkages with segregating markers. Hence, the standard map for apple now contains about 360 markers, with most linkage groups saturated at 10-15 cM. The double pseudotestcross format of the mapping population permitted the comparison of recombination frequencies in male and female parents in certain regions of the genome where appropriate markers were available. The recombination frequencies observed for the approximately 170 cM that were comparable gave no indication that a sex-related difference in recombination rate was characteristic of appl

A dose-ranging, parallel group, split-face, single-blind phase II study of light emitting diode-red light (LED-RL) for skin scarring prevention: study protocol for a randomized controlled trial.

BackgroundSkin fibrosis is a significant global health problem that affects over 100 million people annually and has a profoundly negative impact on quality of life. Characterized by excessive fibroblast proliferation and collagen deposition, skin fibrosis underlies a wide spectrum of dermatologic conditions ranging from pathologic scars secondary to injury (e.g., burns, surgery, trauma) to immune-mediated diseases. Effective anti-scarring therapeutics remain an unmet need, underscoring the importance of developing novel approaches to treat and prevent skin fibrosis. Our in vitro data show that light emitting diode-red light (LED-RL) can modulate key cellular and molecular processes involved in skin fibrosis. In two phase I clinical trials (STARS 1 and STARS 2), we demonstrated the safety and tolerability of LED-RL at fluences of 160 J/cm2 up to 480 J/cm2 on normal human skin.Methods/designCURES (Cutaneous Understanding of Red-light Efficacy on Scarring) is a dose-ranging, randomized, parallel group, split-face, single-blind, mock-controlled phase II study to evaluate the efficacy of LED-RL to limit post-surgical skin fibrosis in subjects undergoing elective mini-facelift surgery. Thirty subjects will be randomly allocated to three treatment groups to receive LED-RL phototherapy or temperature-matched mock irradiation (control) to either periauricular incision site at fluences of 160 J/cm2, 320 J/cm2, or 480 J/cm2. Starting one week post-surgery (postoperative days 4-8), treatments will be administered three times weekly for three consecutive weeks, followed by efficacy assessments at 30 days, 3 months, and 6 months. The primary endpoint is the difference in scar pliability between LED-RL-treated and control sites as determined by skin elasticity and induration measurements. Secondary outcomes include clinical and photographic evaluations of scars, 3D skin imaging analysis, histological and molecular analyses, and adverse events.DiscussionLED-RL is a therapeutic modality of increasing importance in dermatology, and has the potential to limit skin fibrosis clinically by decreasing dermal fibroblast activity and collagen production. The administration of LED-RL phototherapy in the early postoperative period may optimize wound healing and prevent excessive scarring. The results from this study may change the current treatment paradigm for fibrotic skin diseases and help to pioneer LED-RL as a safe, non-invasive, cost-effective, portable, at-home therapy for scars.Trial registrationClinicalTrials.gov, NCT03795116 . Registered on 20 December 2018

Cytokine receptor expression in human lymphoid tissue: analysis by fluorescence microscopy

A highly-sensitive flourescence method, capable of detecting cytokine receptors present at low concentrations (around I DO molecules per cell) by flow cytometry, was adapted for use on tissue sections. This method was used to examine the expression of several cytokine receptors in lymphoid ti ss ues. lL-2 receptors were distributed broadly, with higher concentrations in T cell areas. lL-1 receptor Type I was detected in T cell areas and in the follicular mantle, and was strongly expressed on vasc ular endothelium. IL-6 receptor was found at very low concentration, both within and outside germinal centres. The gp 130 molecule, which is involved in the functional receptor complex for IL-6 and several other cytokines, was present at higher concentrations, particularly in the germinal centre. Analysis of receptor expression in secondary lymphoid tissue provides evidence bearing on the physiological roles of cytokines, as these tissues contain cells at various stages of physiological activation located in well-defined functional zones.Heddy Zola, Jodie Ridings, Helen Weedon, Michael Fusco, Roger W. Byard, Peter J. Macardl

Structure and play: rethinking regulation in the higher education sector

This paper explores possible tactics for academics working within a context of increasing regulation and constraint. One suggested tactic is to move outside of a creativity-conformity binary. Rather than understanding creativity and conformity as separable, where one is seen as excluding the other, the authors consider the potential of examining the relationships between them. The theme of 'structure and play' illustrates the argument. In the first part of the paper, using various examples from art and design - fields generally associated with creativity - the authors explore the interrelatedness of creativity and conformity. For example, how might design styles, which are generally understood as creative outcomes, constrain creativity and lead to conformity within the design field? Is fashion producing creativity or conformity? Conversely, the ways in which conformity provides the conditions for creativity are also examined. For example, the conformity imposed by the state on artists in the former communist bloc contributed to a thriving underground arts movement which challenged conformity and state regulation. Continuing the theme of 'structure and play', the authors recount a story from an Australian university which foregrounds the ongoing renegotiation of power relations in the academy. This account illustrates how programmatic government in a university, with its aim of regulating conduct, can contribute to unanticipated outcomes. The authors propose that a Foucauldian view of distributed power is useful for academics operating in a context of increasing regulation, as it brings into view sites where power might begin to be renegotiated

Multilingual gendered identities: female undergraduate students in London talk about heritage languages

In this paper I explore how a group of female university students, mostly British Asian and in their late teens and early twenties, perform femininities in talk about heritage languages. I argue that analysis of this talk reveals ways in which the participants enact ‘culturally intelligible’ gendered subject positions. This frequently involves negotiating the norms of ‘heteronormativity’, constituting femininity in terms of marriage, motherhood and maintenance of heritage culture and language, and ‘girl power’, constituting femininity in terms of youth, sassiness, glamour and individualism. For these young women, I ask whether higher education can become a site in which they have the opportunities to explore these identifications and examine other ways of imagining the self and what their stories suggest about ‘doing being’ a young British Asian woman in London

Development of oedema is associated with an improved glycaemic response in patients initiating thiazolidinediones: a MASTERMIND study

Abstracts of the 51st EASD Annual Meeting, Stockholm, Sweden, 14–18 September 2015This is the author accepted manuscript. The final version is available from Springer VerlagBackground and aims: Oedema is a common and serious side effect of thiazolidinedione therapy. A stratified medicines approach would aim to give thiazolidinediones to patients likely to have a good glycaemic response but to not develop oedema. We investigated whether oedema was associated with glycaemic response to thiazolidinedione therapy. Materials and methods: We retrospectively studied 11,459 patients initiating a thiazolidinedione from UK primary care data (Clinical Practice Research Datalink), and identified medical records of new oedema in the subsequent twelve months. Response was defined as change in HbA1c at twelve months and was adjusted for baseline HbA1c, baseline BMI, gender and compliance (medication possession ratio). In secondary analyses we restricted oedema classification to patients with concomitant weight gain. As a comparison the same analysis was performed in 13,089 patients initiating a sulfonylurea. Results: The 5% of patients with recorded oedema on thiazolidinediones had a mean (CI) 2.2 (1.1-3.2)mmol/mol greater fall in HbA1c (p3 kg (p< 0.001) and a 3.6 (1.8-5.4)mmol/mol greater fall when weight gain >5 kg (p3 kg (p=0.19). Conclusion: Patients with Type 2 diabetes who develop oedema on initiating thiazolidinediones have an improved glycaemic response, and more severe oedema may be associated with greater reductions in HbA1c. An association between oedema and glycaemic response was not observed in patients initiating sulfonylureas. This supports glycaemic lowering and fluid retention being mediated by a common pathway of thiazolidinedione drug action.Supported by: MRC grant MR-K005707-

Adherence to oral glucose-lowering therapies and associations with 1-year HbA_1c:A retrospective cohort analysis in a large primary care database

JOURNAL ARTICLEOBJECTIVE: The impact of taking oral glucose-lowering medicines intermittently, rather than as recommended, is unclear. We conducted a retrospective cohort study using community-acquired U.K. clinical data (Clinical Practice Research Database [CPRD] and GoDARTS database) to examine the prevalence of nonadherence to treatment for type 2 diabetes and investigate its potential impact on HbA1c reduction stratified by type of glucose-lowering medication. RESEARCH DESIGN AND METHODS: Data were extracted for patients treated between 2004 and 2014 who were newly-prescribed metformin, sulfonylurea, thiazolidinedione, or dipeptidyl peptidase-4 inhibitors and who continued to obtain prescriptions over 1 year. Cohorts were defined by prescribed medication type, and good adherence was defined as a medication possession ratio ≥0.8. Linear regression was used to determine potential associations between adherence and 1-year baseline-adjusted HbA1c reduction. RESULTS: In CPRD and GoDARTS, 13% and 15% of patients, respectively, were nonadherent. Proportions of nonadherent patients varied by the oral glucose-lowering treatment prescribed (range 8.6% [thiazolidinedione] to 18.8% [metformin]). Nonadherent, compared with adherent, patients had a smaller HbA1c reduction (0.4% [4.4mmmol/mol] and 0.46% [5.0 mmol/mol] for CPRD and GoDARTs, respectively). Difference in HbA1c response for adherent compared with nonadherent patients varied by drug (range 0.38% [4.1 mmol/mol] to 0.75% [8.2 mmol/mol] lower in adherent group). Decreasing levels of adherence were consistently associated with a smaller reduction in HbA1c. CONCLUSIONS: Reduced medication adherence for commonly used glucose-lowering therapies among patients persisting with treatment is associated with smaller HbA1c reductions compared with those taking treatment as recommended. Differences observed in HbA1c responses to glucose-lowering treatments may be explained in part by their intermittent use.A.J.F. and R.R.H. are National Institute for Health Research (NIHR) Senior Investigators and receive additional support from the Oxford NIHR Biomedical Research Centre. M.N.W. was supported by a Wellcome Trust Institutional Strategic Support Award (WT097835MF). E.R.P. holds a Wellcome Trust New Investigator award. The MASTERMIND consortium is funded by the U.K. Medical Research Council MR-K005707-1. The funder of the trial had no role in study design, data collection, data analysis, data interpretation, or writing of the report

Sequencing PDX1 (insulin promoter factor 1) in 1788 UK individuals found 5% had a low frequency coding variant, but these variants are not associated with Type 2 diabetes

OnlineOpen Article. This is a copy of an article published in Diabetic Medicine. This journal is available online at: http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1464-5491Genome-wide association studies have identified >30 common variants associated with Type 2 diabetes (>5% minor allele frequency). These variants have small effects on individual risk and do not account for a large proportion of the heritable component of the disease. Monogenic forms of diabetes are caused by mutations that occur in <1:2000 individuals and follow strict patterns of inheritance. In contrast, the role of low frequency genetic variants (minor allele frequency 0.1-5%) in Type 2 diabetes is not known. The aim of this study was to assess the role of low frequency PDX1 (also called IPF1) variants in Type 2 diabetes

‘I see my section scar like a battle scar’: The ongoing embodied subjectivity of maternity

YesThough many women may be dissatisfied with their bodies, maternity represents a period when the body deviates significantly from Western beauty ideals. However, the developing corpus of literature is contradictory and there is limited knowledge about the longer-term implications of maternity. Further, much of the early postpartum literature focuses on body image, precluding consideration of broader embodiment and other potential issues. Taking account of recent feminist critiques about acknowledging women’s reproductive capacities, the study reported here explores the embodied subjectivity of longer-term bodily changes resulting from pregnancy, childbirth and early mothering. The data explored are from three focus groups. Mothers were recruited from two universities in the North of England, UK. Data were transcribed and analysed thematically and discursively using a feminist and poststructuralist approach, while also taking account of where language was elusive. A number of contradictory, yet interrelated embodied constructions were identified including the aesthetic, the maternal, the suffering/sentient, the strong and the embarrassing body. New insights are offered, in that, not only are the postpartum body and the ‘work of mothering’ inextricably linked, but also that maternal embodied identities are in continuous process across the life course and may have implications for health and well-being

From the cell membrane to the nucleus: unearthing transport mechanisms for Dynein

Mutations in the motor protein cytoplasmic dynein have been found to cause Charcot-Marie-Tooth disease, spinal muscular atrophy, and severe intellectual disabilities in humans. In mouse models, neurodegeneration is observed. We sought to develop a novel model which could incorporate the effects of mutations on distance travelled and velocity. A mechanical model for the dynein mediated transport of endosomes is derived from first principles and solved numerically. The effects of variations in model parameter values are analysed to find those that have a significant impact on velocity and distance travelled. The model successfully describes the processivity of dynein and matches qualitatively the velocity profiles observed in experiments