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Peter Goodliffe served as a radiographer for the British Army in France and India during World War II. Since 1960 he has taught photography and related visual studies, most recently at Oxford University. His work has been exhibited in England and Sicily, hislatest show at the Library in Warminster (1992). Presently involved in writing a book on the nature of landscape, he divides his time between Oxford and Palermo

Spatiotemporal development of the forebrain in the Dp(16)1Yey/+ mouse model of Down syndrome

Down syndrome (DS), or trisomy 21 (Ts21), is the most common genetic developmental disorder with a prevalence of about one in 700 live births. The triplication of human chromosome 21 (Hsa21) that characterizes this disorder results in a constellation of cognitive and physical alterations. The cognitive deficits range from mild to severe, and persist throughout life. Post-mortem studies of individuals with DS have revealed various neuropathologic abnormalities that are thought to underlie cognitive dysfunction, including: disruption of neurogenesis, corticogenesis, synapse formation, and myelination. However, the etiology of these alterations remains largely unknown. In order to elucidate the genetic basis of DS-phenotypes, several mouse models have been developed. The Ts65Dn, Ts1Cje, and Ts16 models, recapitulate DS-related phenotypes and have extended our knowledge of the associated pathological changes. Despite this progress, genetic dissimilarities in mouse models may confound phenotypic comparisons between mouse models and human DS. Specifically, the aforementioned models have a limited subset of triplicated Hsa-21 homologs or contain non-syntenic genes. Recently, a novel mouse model, the Dp(16)1Yey/+ (or Dp16), that has the entire Hsa-21 syntenic region of Mmu16 triplicated and no non-syntenic genes has been developed, suggesting that Dp16 may present phenotypes more closely matching the human disorder. In this study, we present the first comprehensive analysis of Dp16 embryonic, young and adult brains that includes a focus on the proliferative, inhibitory/excitatory neuronal and oligodendrocyte-lineage phenotypes using histological, immunohistochemical, and behavioral assessments. We hypothesize that due to the larger triplicated segment, the Dp16 mouse model better recapitulates DS-related neuropathologies relative to other mouse models. Despite the extended triplication, Dp16 animals lack DS-related embryonic phenotypes, however, behavioral and cellular phenotypes arise during the 2nd week following birth. The Dp16 is the first model of DS to develop postnatal phenotypes in the absence of changes to embryonic brain development, as such, Dp16 may not be a reliable model to further understand brain development in the DS fetus. However, when used in conjuncture with other models, the Dp16 will be a useful tool in understanding the contribution of aneuploidy and gene dosage to DS-phenotypes in mouse models of DS

Editors\u27 introduction: the importance of reflective practice

In this issue of LTHE we highlight the importance of reflection in understanding and developing learning and teaching in universities and colleges. Reflection has been described as an active process of exploration and discovery which often leads to very unexpected outcomes (Boud et al, 1985, p. 7). While everyone may agree that experience is an important part of an educator\u27s developmental journey, the ability to reflect on that experience is a vital element of being able to learn from it

Exploration of the Psychosocial Impact of Coeliac Disease on Adults and Their Family Members

Coeliac disease (CD) is an autoimmune condition triggered by the consumption of gluten; a protein found in grains. In addition to the biological impact, CD impacts the psychosocial wellbeing of people with the condition. The sole treatment available for CD is a life-long gluten-free diet. Food and eating form a key behaviour in daily family life. The management of CD takes place in the family home and external social environment. Family can influence the behaviour and health of individual members. Evidence of how CD impacts family members, and how families support the management of CD is sparse. This thesis explored the lived experiences of nine families with an adult with coeliac disease, examining the psychosocial impact through an integrated biopsychosocial theoretical framework. The research adopted a participatory approach consulting with adult, child, and young person groups, on the research design. Individual (n=18) and dyadic (n=3) participant-generated photo-elicited interviews were conducted via online synchronous video. Transcribed interview data were analysed using reflexive thematic analysis. Data generated three distinct themes of family life; adjusting to life with CD; family life at home with food; and navigating the external social world. An overarching theme, ‘the perpetual presence of coeliac disease’, threaded these themes together. The adult with CD had the initial burden of orchestrating family adjustment to CD. All family members changed food related behaviours at home, constructing a conducive environment to support the management of CD. In the wider social world, stigma and negative affect were experienced by children and adults with CD. This thesis contributes to participatory research methods literature, demonstrating feasibility of public consultation, and application of participatory-photograph methods online. The research contributes to the wider literature on the psychosocial impact on families living with CD, having implications for the inclusion of family members in the management of CD

Coordinated regulation of Myc trans-activation targets by Polycomb and the Trithorax group protein Ash1

<p>Abstract</p> <p>Background</p> <p>The Myc oncoprotein is a transcriptional regulator whose function is essential for normal development. Myc is capable of binding to 10% of the mammalian genome, and it is unclear how a developing embryo controls the DNA binding of its abundant Myc proteins in order to avoid Myc's potential for inducing tumorigenesis.</p> <p>Results</p> <p>To identify chromatin binding proteins with a potential role in controlling Myc activity, we established a genetic assay for dMyc activity in <it>Drosophila</it>. We conducted a genome-wide screen using this assay, and identified the Trithorax Group protein Ash1 as a modifier of dMyc activity. Ash1 is a histone methyltransferase known for its role in opposing repression by Polycomb. Using RNAi in the embryo and Affymetrix microarrays, we show that <it>ash1 </it>RNAi causes the increased expression of many genes, suggesting that it is directly or indirectly required for repression in the embryo, in contrast to its known role in maintenance of activation. Many of these genes also respond similarly upon depletion of <it>Pc </it>and <it>pho </it>transcripts, as determined by concurrent microarray analysis of <it>Pc </it>and <it>pho </it>RNAi embryos, suggesting that the three are required for low levels of expression of a common set of targets. Further, many of these overlapping targets are also activated by Myc overexpression. We identify a second group of genes whose expression in the embryo requires Ash1, consistent with its previously established role in maintenance of activation. We find that this second group of Ash1 targets overlaps those activated by Myc and that ectopic Myc overcomes their requirement for Ash1.</p> <p>Conclusion</p> <p>Genetic, genomic and chromatin immunoprecipitation data suggest a model in which Pc, Ash1 and Pho are required to maintain a low level of expression of embryonic targets of activation by Myc, and that this occurs, directly or indirectly, by a combination of disparate chromatin modifications.</p

The European Debt Crisis in France and Germany through the Lens of the 1930s: A Polanyian Reading

Introduction: In The Great Transformation, Karl Polanyi develops a critique of the nineteenth and twentieth liberal project to create a self-regulating market economy in terms of both its economic and political ramifications. This critique focuses first and foremost on his analysis of the dysfunction of the interwar gold standard, broken down in terms of its international and national articulations. Internationally, Polanyi conceived the gold standard as an institutional mechanism that created and extended the free market economic system across the globe. Politically, it constituted the anchor underpinning the Pax Britannica of the second half of the nineteenth century and, during a fleeting moment in the second half of the 1920s, the liberal Europe of Locarno. At the domestic level, the gold standard served as the policing agent of economic liberalism that went hand in hand with constitutional liberalism as the twin institutional foundations of the 19th century social order. Accordingly, the breakdown of the gold standard during the 1930s augured for Polanyi the destruction of this liberal European economic and political order. The emergence of explicitly anti-liberal political and economic regimes on the continent disrupted the international balance of power and set the stage for the conflagration of World War II. Thus, the breakdown of the interwar gold standard provided “the invisible link between the disintegration of [the] world economy since the turn of the century and the transformation of a whole civilization in the 1930s,” thereby underscoring the historic failure of “the utopian endeavor of economic liberalism to set up a self-regulating market system.”

mTOR: A Mechanistic Target of Muscle and Cancer Crosstalk

In the United States, the number of colon and breast cancer cases that are attributed to physical inactivity lead the exercise-associated cases of heart disease and type II diabetes. For the millions of people in the United States burdened with breast cancer, there is a noted substantial risk reduction with increased physical activity. Previous research has investigated skeletal muscle’s endocrine-like potential on inflammation and cancer metabolism; however there is limited investigation into exercise-facilitated suppression of cancer’s major anabolic pathway, the mechanistic target of rapamycin (mTOR) pathway. While previous cancer research has established that mTOR’s activity is dysregulated in cancer, little is known about the impact of exercise on the regulation of anabolic/proliferative features of breast cancer cells, nor has exercise been evaluated as a mediator of muscle and cancer crosstalk. This project’s objective is to determine how exercise is affecting the biological regulation of tumorgenesis (a critical component of treatment innovation) via the mTOR pathway, and how that regulation is mediated by skeletal muscle contraction. While research efforts and analyses about the mTOR pathway have led to key insights into its regulation of apoptotic and autophagic signaling in cancer, these efforts do not capture the complete profile of mTOR control on cell growth and survival, nor address preliminary data indicating that cellular proliferation rates are significantly reduced in breast cancer cells treated with excretion factors arising from contracting skeletal muscle (“exercise”). The work presented here-in utilizes a research approach consisting of cell culture and animal models to investigate key mechanistic foundations that underlie the biological regulation of breast cancer in individuals who partake in exercise. Specifically, the MCF7 epithelial breast cancer cell line, a hemicorpus hind limb perfusion (HHLP) surgery, and pharmacological interventions allow for evaluation of skeletal muscle’s endocrine ability, global protein synthesis, signal transduction and gene expression. The investigators’ consideration of musclecancer crosstalk via exercise lays the foundation for future evaluation of muscle-derived biomolecules (ie. microRNA) as a potential crosstalk mediators. This project’s successful completion proposes key mechanistic foundations that underlie the biological regulation of breast cancer, contributing greatly to science’s efforts towards novel translational investigation of the beneficial relationship between muscle and cancer crosstalk. Establishing a casual role for exercise as primary cancer prevention would have major translational impact in cancer prevention and patient survivorship, with even a small reduction in incidence of cancer resulting in multi- billion dollar health care savings

“I’ll look after the kids while you go and have a shower”: An Evaluation of a service to address mild to moderate maternal perinatal mental health problems

Background: Perinatal mental health (PMH) problems are a major public health concern because they may impair parenting ability which potentially has an immediate and long-term impact on the physical, cognitive and emotional health of the child. Aims: We evaluated a Perinatal Support Service (PSS) which supports positive attachment between mothers with PMH problems and their child, to evidence its impact on maternal mental health and maternal-infant interaction. Method: Using a mixed-methods approach, anonymised pre and post service outcomes data from 123 clients, fourteen interviews and a focus group discussion were analysed. Results: We found significant improvement in anxiety (t (55) = 6.96, p<.01, 95% CI [3.15, 5.70]), and depression (t (55) = 6.58, p <.01, 95% CI [3.03, 5.68]) on the HADS, and on the GAD -7 (t (12) = 4.541, p = .001, 95% CI [3.48,9.90]) after the PSS. Anxiety post service (M=9.08, SD = 4.96) was lower than baseline anxiety (M=15.77, SD = 4.68). Receiving emotional and practical support contributed to improvements in mental health and mother-child interaction. Conclusion: Given the paucity of PMH services in the UK, it is imperative that services such as the PSS continue to receive funding to address unmet PMH needs

Synchronous reorientation of the Woodlark Basin spreading center

Abstract A sidescan and multibeam bathymetry survey of the Woodlark Basin reveals that its 500-km-long spreading center reoriented synchronously, without propagation, about 80 ka. There is no evidence of the V-shaped pseudofault geometry typical of spreading center propagation, nor of the progressive fanning of seafloor fabric characteristic of spreading center rotation. The reorientation is recognized by a sharp contact between two seafloor fabric trends, and ruptured off-axis lithosphere formed up to 0.7 m.y. previously. The length of the reoriented spreading segments and the tendency to fault pre-reorientation seafloor fabric are controlled by the strength of the lithosphere, the angle of the reorientation, and the length of preexisting spreading and transform segments. We document the process of synchronous reorientation in the Woodlark Basin and propose that it may occur in other ocean basins