Chronic glucokinase activation reduces glycaemia and improves glucose tolerance in high-fat diet fed mice.

Glucokinase (GK) plays a key role in maintaining glucose homeostasis by promoting insulin secretion from pancreatic beta cells and increasing hepatic glucose uptake. Here we investigate the effects of acute and chronic GK activation on glucose tolerance and insulin secretion in mice with diet-induced insulin resistance. In the acute study, a small molecule GK activator (GKA71) was administered to mice fed a high-fat diet for 8weeks. In the long-term study, GKA71 was provided in the diet for 4weeks to high-fat diet-fed mice. Glucose tolerance was measured after intravenous glucose administration, and insulin secretion was measured both in vivo and in vitro. Acute GK activation efficiently improved glucose tolerance in association with increased insulin secretion after intravenous glucose both in control and high-fat fed mice. Chronic GK activation significantly reduced basal plasma glucose and insulin, and improved glucose tolerance despite reduced insulin secretion after intravenous glucose, suggesting improved insulin sensitivity. Isolated islets from chronically GKA71-treated mice displayed augmented insulin secretion at 8.3mmol/l glucose, without affecting glucose oxidation. High-fat diet fed mice had reduced glycogen and increased triglyceride in liver compared to control mice, and these parameters were not altered by long-term GK activation. We conclude that GK activation in high-fat diet-fed mice potently reduces glycaemia and improves glucose tolerance, with combined effect both to stimulate insulin secretion from islets and improve insulin sensitivity

Forensic analysis of the microbiome of phones and shoes

© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Microbiome 3 (2015): 21, doi:10.1186/s40168-015-0082-9.Microbial interaction between human-associated objects and the environments we inhabit may have forensic implications, and the extent to which microbes are shared between individuals inhabiting the same space may be relevant to human health and disease transmission. In this study, two participants sampled the front and back of their cell phones, four different locations on the soles of their shoes, and the floor beneath them every waking hour over a 2-day period. A further 89 participants took individual samples of their shoes and phones at three different scientific conferences. Samples taken from different surface types maintained significantly different microbial community structures. The impact of the floor microbial community on that of the shoe environments was strong and immediate, as evidenced by Procrustes analysis of shoe replicates and significant correlation between shoe and floor samples taken at the same time point. Supervised learning was highly effective at determining which participant had taken a given shoe or phone sample, and a Bayesian method was able to determine which participant had taken each shoe sample based entirely on its similarity to the floor samples. Both shoe and phone samples taken by conference participants clustered into distinct groups based on location, though much more so when an unweighted distance metric was used, suggesting sharing of low-abundance microbial taxa between individuals inhabiting the same space. Correlations between microbial community sources and sinks allow for inference of the interactions between humans and their environment.This work was enabled by the generous support of the Alfred P Sloan foundation. This work was supported in part by the U.S. Dept. of Energy under Contract DE-AC02-06CH11357. S.M.G. was supported by an EPA STAR Graduate Fellowship and by a National Institutes of Health Training Grant 5 T-32 EB-009412

“We’re on a Merry-Go-Round”: Reflections of Patients and Carers after Completing Treatment for Sarcoma

Sarcoma is a rare cancer that has a significant impact on patients’ and carers’ quality of life. Despite this, there has been a paucity of research exploring the diverse experiences of patients and carers following sarcoma treatment. The aim of this study was to explore patients’ and carers’ reflections on life after treatment for sarcoma. A qualitative research design with a social constructionist epistemology was used. Participants included patients previously treated for sarcoma (n = 21) and family carers of patients treated for sarcoma (n = 16). Participants completed semi-structured interviews which were analysed using thematic analysis. Three primary themes were identified: “This journey is never going to be over”, “But what happens when I am better?”, and finding a silver lining. Participants represented sarcoma as having a long-term, and sometimes indefinite, threat on their life that they had limited control over. Conclusions: This study highlight the heterogeneous and ongoing needs of sarcoma survivors and their families. Patients and carers strove to translate their experiences in a meaningful way, such as by improving outcomes for other people affected by sarcoma. Parental carers in particular attempted to protect the patient from the ongoing stress of managing the disease

Analysis of plant and fungal transcripts from resistant and susceptible phenotypes of Leptospermum scoparium challenged by Austropuccinia psidii

Austropuccinia psidii is the causal pathogen of myrtle rust disease of Myrtaceae. To gain understanding of the initial infection process, gene expression in germinating Austropuccinia psidii urediniospores and in Leptospermum scoparium inoculated leaves were investigated via analyses of RNAseq samples taken 24 and 48 hours post inoculation (hpi). Principal component analyses of transformed transcript count data revealed differential gene expression between the uninoculated L. scoparium control plants that correlated with the three plant leaf resistance phenotypes (immunity, hypersensitive response and susceptibility). Gene expression in the immune resistant plants did not significantly change in response to fungal inoculation, while susceptible plants showed differential expression of genes in response to fungal challenge. A putative disease resistance gene, jg24539.t1, was identified in the L. scoparium hypersensitive response phenotype family. Expression of this gene may be associated with the phenotype and could be important for further understanding the plant hypersensitive response to A. psidii challenge. Differential expression of pathogen genes was found between samples taken 24 and 48 hpi, but there were no significant differences in pathogen gene expression that were associated with the three different plant leaf resistance phenotypes. There was a significant decrease in the abundance of fungal transcripts encoding three putative effectors and a putative carbohydrate-active enzyme between 24 and 48 hpi, suggesting that the encoded proteins are important during the initial phase of infection. These transcripts, or their translated proteins, may be potential targets to impede the early phases of fungal infection by this wide-host range obligate biotrophic basidiomycete

Embodied Discourses of Literacy in the Lives of Two Preservice Teachers

This study examines the emerging teacher literacy identities of Ian and A.J., two preservice teachers in a graduate teacher education program in the United States. Using a poststructural feminisms theoretical framework, the study illustrates the embodiment of literacy pedagogy discourses in relation to the literacy courses’ discourse of comprehensive literacy and the literacy biographical discourses of Ian and A.J. The results of this study indicate the need to deconstruct how the discourse of comprehensive literacy limits how we, as literacy teacher educators, position, hear and respond to our preservice teachers and suggests the need for differentiation in our teacher education literacy courses

Homelessness in autistic women: defining the research agenda

Background: Current evidence suggests that autistic individuals are at high risk for becoming and remaining in a cycle of homelessness. Key risk factors for homelessness disproportionately affect autistic people; however, we have limited understanding of how to best support autistic individuals accessing services. This gap in the evidence base is particularly acute for autistic women. Objective: As a first step to address this gap, we aimed to (1) map gaps in knowledge and practice; (2) identify priority areas for research and (3) develop recommendations for how to implement novel research and practice in this area. Methods: We conducted a collaborative workshop with an interdisciplinary group of 26 stakeholders to address our aims. Stakeholders included autistic women with experience of homelessness, researchers, health professionals, NGO representatives, and service providers. Results and recommendations: Two research priority areas were identified to map the prevalence and demographics of autistic women experiencing homelessness, and to delineate risk and protective factors for homelessness. Priority areas for improving provision of support included staff training to improve communication, awareness of autism and building trust with service providers, and recommendations for practical provision of support by services. Conclusions: Future research is critical to increase our knowledge of the pathways leading to homelessness for autistic women, and barriers to engaging with homelessness and social services. We need to use this knowledge to develop new ways of delivering targeted and inclusive support for autistic women, which could prevent or shorten periods of homelessness

“It’s Always Been a Second Class Cancer”: An Exploration of the Experiences and Journeys of Bereaved Family Carers of People with Sarcoma

Sarcomas are a group of rare and aggressive cancers, which develop in bones and connec-tive tissue throughout the body. Sarcomas account for only 1–2% of all cancers worldwide; however, mortality rates for sarcoma are high with approximately two in four sarcoma patients dying following a diagnosis. Delays in diagnosis, poor management of symptoms, patients’ high symptom loads and high carer burden are all associated with carer distress, which may lead to complications after bereavement. The experience of having a family member referred for palliative care is also distress-ing for carers, with the realisation that their family member is dying. This study aimed to explore the experiences of bereaved family carers of people diagnosed with sarcoma. A qualitative descriptive design using a social constructionist framework was adopted. Interviews were conducted with sixteen participants, and thematic analysis was used to identify patterns in the data. Four overarch-ing themes emerged: beginning the journey; moving through treatment; transitioning to palliative care; and experiencing bereavement. The narratives were coherent and potent, and people reflected on their journeys. Interventions and supports for bereaved carers could include opportunities for counselling to support reflections, supports for developing a narrative such as writing therapy, and preparation for the death of the family member

Variable-Pitch Rectangular Cross-section Radiofrequency Coils for the Nitrogen-14 Nuclear Quadrupole Resonance Investigation of Sealed Medicines Packets

This work was partly funded by a technology transfer award from the Wellcome Trust (U.K.). Additional funding was provided by the European Commission as part of 7th Framework Programme under Grant No. 261670

HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype.

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 × 10-8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification

Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study.

Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist