Healthy Ageing in Smart Villages? Observations from the Field

In the context of demographically ageing communities across rural Europe Smart Villages have considerable potential to promote ageing healthy. Whilst in principle supporting healthy ageing in the context of the Smart Village might appear a relatively straightforward endeavour, in operational terms, successful development of smart, 21st century villages relies upon, and sometimes assumes, an appropriate interplay of socio-technological factors. Articulated through a lens provided by the digital ecosystem model advocated by the European Network for Rural Development (2018), this paper offers some observations from the field. We acknowledge the challenges faced by remote rural places in their journey to become ‘smart places’ and identify formal and informal interventions that could better position rural communities to become part of a wider, smart society

Expression stability of commonly used reference genes in canine articular connective tissues

<p>Abstract</p> <p>Background</p> <p>The quantification of gene expression in tissue samples requires the use of reference genes to normalise transcript numbers between different samples. Reference gene stability may vary between different tissues, and between the same tissue in different disease states. We evaluated the stability of 9 reference genes commonly used in human gene expression studies. Real-time reverse transcription PCR and a mathematical algorithm were used to establish which reference genes were most stably expressed in normal and diseased canine articular tissues and two canine cell lines stimulated with lipolysaccaride (LPS).</p> <p>Results</p> <p>The optimal reference genes for comparing gene expression data between normal and diseased infrapatella fat pad were <it>RPL13A </it>and <it>YWHAZ </it>(M = 0.56). The ideal reference genes for comparing normal and osteoarthritic (OA) cartilage were <it>RPL13A </it>and <it>SDHA </it>(M = 0.57). The best reference genes for comparing normal and ruptured canine cranial cruciate ligament were <it>B2M </it>and <it>TBP </it>(M = 0.59). The best reference genes for normalising gene expression data from normal and LPS stimulated cell lines were <it>SDHA </it>and <it>YWHAZ </it>(K6) or <it>SDHA </it>and <it>HMBS </it>(DH82), which had expression stability (M) values of 0.05 (K6) and 0.07 (DH82) respectively. The number of reference genes required to reduce pairwise variation (V) to <0.20 was 4 for cell lines, 5 for cartilage, 7 for cranial cruciate ligament and 8 for fat tissue. Reference gene stability was not related to the level of gene expression.</p> <p>Conclusion</p> <p>The reference genes demonstrating the most stable expression within each different canine articular tissue were identified, but no single reference gene was identified as having stable expression in all different tissue types. This study underlines the necessity to select reference genes on the basis of tissue and disease specific expression profile evaluation and highlights the requirement for the identification of new reference genes with greater expression stability for use in canine articular tissue gene expression studies.</p

Identification of new reference genes for the normalisation of canine osteoarthritic joint tissue transcripts from microarray data

<p>Abstract</p> <p>Background</p> <p>Real-time reverse transcriptase quantitative polymerase chain reaction (real-time RT-qPCR) is the most accurate measure of gene expression in biological systems. The comparison of different samples requires the transformation of data through a process called normalisation. Reference or housekeeping genes are candidate genes which are selected on the basis of constitutive expression across samples, and allow the quantification of changes in gene expression. At present, no reference gene has been identified for any organism which is universally optimal for use across different tissue types or disease situations. We used microarray data to identify new reference genes generated from total RNA isolated from normal and osteoarthritic canine articular tissues (bone, ligament, cartilage, synovium and fat). RT-qPCR assays were designed and applied to each different articular tissue. Reference gene expression stability and ranking was compared using three different mathematical algorithms.</p> <p>Results</p> <p>Twelve new potential reference genes were identified from microarray data. One gene (mitochondrial ribosomal protein S7 [<it>MRPS7</it>]) was stably expressed in all five of the articular tissues evaluated. One gene HIRA interacting protein 5 isoform 2 [<it>HIRP5</it>]) was stably expressed in four of the tissues evaluated. A commonly used reference gene glyceraldehyde-3-phosphate dehydrogenase (<it>GAPDH</it>) was not stably expressed in any of the tissues evaluated. Most consistent agreement between rank ordering of reference genes was observed between <it>Bestkeeper©</it> and geNorm, although each method tended to agree on the identity of the most stably expressed genes and the least stably expressed genes for each tissue. New reference genes identified using microarray data normalised in a conventional manner were more stable than those identified by microarray data normalised by using a real-time RT-qPCR methodology.</p> <p>Conclusion</p> <p>Microarray data normalised by a conventional manner can be filtered using a simple stepwise procedure to identify new reference genes, some of which will demonstrate good measures of stability. Mitochondrial ribosomal protein S7 is a new reference gene worthy of investigation in other canine tissues and diseases. Different methods of reference gene stability assessment will generally agree on the most and least stably expressed genes, when co-regulation is not present.</p

‘It’s revolutionised how we do things’: then and now - a case study of Internet behaviours in a remote rural community

This document is the final version of a published work that appeared in final form in Proceedings of the XXVI European Society for Rural Sociology Congress: Places of Possibility? Rural Societies in a Neoliberal World, 18-21 August, Aberdeen, Scotland. To access the final edited and published work see http://esrs2015.hutton.ac.uk/sites/www.esrs2015.eu/files/Final%20ESRS%202015%20congress%20proceedings.pdfThe Digital Economy has opened up new opportunities for societal wellbeing across many domains of life. However, the market dependency of the landscape of connection has resulted in communities which have inadequate broadband infrastructure and are off the digital map. This form of digital exclusion is most notable in remote, rural areas. In this paper we draw upon the Rural Public Access WiFi Service research study that is focused upon enabling Internet connectivity for commercially ‘hard to reach’ rural areas in the UK. Enabling broadband connectivity to those who were previously unable to access the Internet demonstrates benefits, which translate into the positive role that improved digital connectivity can have on the wellbeing of individuals and remote rural communities at large

Sex, stress and sleep apnoea: decreased susceptibility to upper airway muscle dysfunction following intermittent hypoxia in females

Obstructive sleep apnoea syndrome (OSAS) is a devastating respiratory control disorder more common in men than women. The reasons for the sex difference in prevalence are multifactorial, but are partly attributable to protective effects of oestrogen. Indeed, OSAS prevalence increases in post-menopausal women. OSAS is characterized by repeated occlusions of the pharyngeal airway during sleep. Dysfunction of the upper airway muscles controlling airway calibre and collapsibility is implicated in the pathophysiology of OSAS, and sex differences in the neuro-mechanical control of upper airway patency are described. It is widely recognized that chronic intermittent hypoxia (CIH), a cardinal feature of OSAS due to recurrent apnoea, drives many of the morbid consequences characteristic of the disorder. In rodents, exposure to CIH-related redox stress causes upper airway muscle weakness and fatigue, associated with mitochondrial dysfunction. Of interest, in adults, there is female resilience to CIH-induced muscle dysfunction. Conversely, exposure to CIH in early life, results in upper airway muscle weakness equivalent between the two sexes at 3 and 6 weeks of age. Ovariectomy exacerbates the deleterious effects of exposure to CIH in adult female upper airway muscle, an effect partially restored by oestrogen replacement therapy. Intriguingly, female advantage intrinsic to upper airway muscle exists with evidence of substantially greater loss of performance in male muscle during acute exposure to severe hypoxic stress. Sex differences in upper airway muscle physiology may have relevance to human OSAS. The oestrogen–oestrogen receptor α axis represents a potential therapeutic target in OSAS, particularly in post-menopausal women

The emergence of resistance to the benzimidazole anthlemintics in parasitic nematodes of livestock is characterised by multiple independent hard and soft selective sweeps

Anthelmintic resistance is a major problem for the control of parasitic nematodes of livestock and of growing concern for human parasite control. However, there is little understanding of how resistance arises and spreads or of the “genetic signature” of selection for this group of important pathogens. We have investigated these questions in the system for which anthelmintic resistance is most advanced; benzimidazole resistance in the sheep parasites Haemonchus contortus and Teladorsagia circumcincta. Population genetic analysis with neutral microsatellite markers reveals that T. circumcincta has higher genetic diversity but lower genetic differentiation between farms than H. contortus in the UK. We propose that this is due to epidemiological differences between the two parasites resulting in greater seasonal bottlenecking of H. contortus. There is a remarkably high level of resistance haplotype diversity in both parasites compared with drug resistance studies in other eukaryotic systems. Our analysis suggests a minimum of four independent origins of resistance mutations on just seven farms for H. contortus, and even more for T. circumincta. Both hard and soft selective sweeps have occurred with striking differences between individual farms. The sweeps are generally softer for T. circumcincta than H. contortus, consistent with its higher level of genetic diversity and consequent greater availability of new mutations. We propose a model in which multiple independent resistance mutations recurrently arise and spread by migration to explain the widespread occurrence of resistance in these parasites. Finally, in spite of the complex haplotypic diversity, we show that selection can be detected at the target locus using simple measures of genetic diversity and departures from neutrality. This work has important implications for the application of genome-wide approaches to identify new anthelmintic resistance loci and the likelihood of anthelmintic resistance emerging as selection pressure is increased in human soil-transmitted nematodes by community wide treatment programs

Stem cell patterning and fate in human epidermis

AbstractWithin human epidermis there are two types of proliferating keratinocyte: stem cells, which have high proliferative potential, and transit-amplifying cells, which are destined to undergo terminal differentiation after a few rounds of division. We show that, in vivo, stem cells express higher levels of the α2β1, and α3β1 integrins than transit-amplifying cells and that this can be used both to determine the location of stem cells within the epidermis and to isolate them directly from the tissue. The distribution of stem cells and transit-amplifying cells is not random: patches of integrin-bright and integrin-dull cells have a specific location with respect to the epidermal-dermal junction that varies between body sites and that correlates with the distribution of S phase cells. Stem cell patterning can be recreated in culture, in the absence of dermis, and appears to be subject to autoregulation

Editorial

This nasen Virtual Issue comprises articles from all three nasen journals, providing a set of 9 papers on the theme 'Working with Parents'. This e-compilation of papers from our three Journals represents a collaborative attempt to celebrate the long-standing engagement between parents and education professionals and services in support of children and young people who experience special educational needs or disabilities (SEND)

Veiled disclosures and queer articliations readings of literacy and cinematic works by Bryher and Pool

This thesis uses three case studies to consider the creative negotiations that Bryher (Annie Winifred Ellerman (1894-1983)) and POOL (1927-1933), the experimental film group of which she was a member, deployed in order to represent, and to speak as, dissident sexual subjectivities in the interwar period. 1 explore their various 'queer articulations’ - the attempts to both ‘speak out’ and ‘speak back’ - in four literary and cinematic works. 1 introduce the term ‘veiled disclosure' to consider how Bryher and POOL circumvented both social censure and artistic censorship by seeking to address a particular readership - those viewers or readers attuned to difference - while simultaneously concealing their subversive contents from the audience at large. Queer articulation, however, also refers to Bryher and POOL’S repeated attempts to forge links, both creative and political, across difference, especially in response to fascist nationalisms. The first chapter frames my interdisciplinary project in relation to queer feminist theory, and argues for the necessity of using a queer theoretical lens for interpreting Bryher and POOL’S work. In my second chapter, 1 read Bryher’s two early ‘autobiographical fictions,’ Development (1920) and Two Selves (1923) as an attempt to ‘speak out,’ rather than come out. In so doing, 1 argue that Bryher’s texts were also an effort to forge a queer reading community not just to remedy her own isolation but that of other ‘queer’ subjects too. My third chapter explores the impact which cultural censorship had on POOL’S 1930 silent film Borderline, and, more specifically, how the almost contemporaneous banning of Radclyffe Hall’s The Well o f Loneliness (1928) informed its production. I read the film as an attempt to ‘speak back’ to English censors, with Bryher’s performance as the nameless manageress being the fulcrum of POOL’S retort. In Chapter 4, I focus on Bryher’s little-known novella Manchester (1935-6), reading it alongside two pieces of film criticism, the writer’s ‘Dope or Stimulus’ (1928) plus ‘The Hollywood Code’ (1931), which reveal her as a prescient critic of mass culture, especially in relation to the category of kitsch. Alongside functioning as a critique of the homogeneity of Hollywood productions, I argue that Manchester was also a call to arms, which encouraged the English population to heed the devastation unfolding in mainland Europe