Hypoxia-induced epigenetic modifications are associated with cardiac tissue fibrosis and the development of a myofibroblast-like phenotype

Ischemia caused by coronary artery disease and myocardial infarction leads to aberrant ventricular remodeling and cardiac fibrosis. This occurs partly through accumulation of gene expression changes in resident fibroblasts, resulting in an overactive fibrotic phenotype. Long-term adaptation to a hypoxic insult is likely to require significant modification of chromatin structure in order to maintain the fibrotic phenotype. Epigenetic changes may play an important role in modulating hypoxia-induced fibrosis within the heart. Therefore, the aim of the study was to investigate the potential pro-fibrotic impact of hypoxia on cardiac fibroblasts and determine whether alterations in DNA methylation could play a role in this process. This study found that within human cardiac tissue, the degree of hypoxia was associated with increased expression of collagen 1 and alpha-smooth muscle actin (ASMA). In addition, human cardiac fibroblast cells exposed to prolonged 1% hypoxia resulted in a pro-fibrotic state. These hypoxia-induced pro-fibrotic changes were associated with global DNA hypermethylation and increased expression of the DNA methyltransferase (DNMT) enzymes DNMT1 and DNMT3B. Expression of these methylating enzymes was shown to be regulated by hypoxia-inducible factor (HIF)-1α. Using siRNA to block DNMT3B expression significantly reduced collagen 1 and ASMA expression. In addition, application of the DNMT inhibitor 5-aza-2'-deoxycytidine suppressed the pro-fibrotic effects of TGFβ. Epigenetic modifications and changes in the epigenetic machinery identified in cardiac fibroblasts during prolonged hypoxia may contribute to the pro-fibrotic nature of the ischemic milieu. Targeting up-regulated expression of DNMTs in ischemic heart disease may prove to be a valuable therapeutic approach.

Hypoxia-induced DNA hypermethylation in human pulmonary fibroblasts is associated with Thy-1 promoter methylation and the development of a pro-fibrotic phenotype

BACKGROUND: Pulmonary fibrosis is a debilitating and lethal disease with no effective treatment options. Understanding the pathological processes at play will direct the application of novel therapeutic avenues. Hypoxia has been implicated in the pathogenesis of pulmonary fibrosis yet the precise mechanism by which it contributes to disease progression remains to be fully elucidated. It has been shown that chronic hypoxia can alter DNA methylation patterns in tumour-derived cell lines. This epigenetic alteration can induce changes in cellular phenotype with promoter methylation being associated with gene silencing. Of particular relevance to idiopathic pulmonary fibrosis (IPF) is the observation that Thy-1 promoter methylation is associated with a myofibroblast phenotype where loss of Thy-1 occurs alongside increased alpha smooth muscle actin (α-SMA) expression. The initial aim of this study was to determine whether hypoxia regulates DNA methylation in normal human lung fibroblasts (CCD19Lu). As it has been reported that hypoxia suppresses Thy-1 expression during lung development we also studied the effect of hypoxia on Thy-1 promoter methylation and gene expression.

METHODS: CCD19Lu were grown for up to 8 days in hypoxia and assessed for global changes in DNA methylation using flow cytometry. Real-time PCR was used to quantify expression of Thy-1, α-SMA, collagen I and III. Genomic DNA was bisulphite treated and methylation specific PCR (MSPCR) was used to examine the methylation status of the Thy-1 promoter.

RESULTS: Significant global hypermethylation was detected in hypoxic fibroblasts relative to normoxic controls and was accompanied by increased expression of myofibroblast markers. Thy-1 mRNA expression was suppressed in hypoxic cells, which was restored with the demethylating agent 5-aza-2'-deoxycytidine. MSPCR revealed that Thy-1 became methylated following fibroblast exposure to 1% O2.

CONCLUSION: These data suggest that global and gene-specific changes in DNA methylation may play an important role in fibroblast function in hypoxia.

Childhood Attention Problems and the Development of Comorbid Symptoms at the Transition to High School: The Mediating Role of Parent and Peer Relationships

Children with Attention-Deficit/Hyperactivity Disorder (ADHD) are at increased risk for the development of depression and delinquent behavior. Children and adolescents with ADHD also experience difficulty creating/maintaining high quality friendships and parent-child relationships, and these difficulties may contribute to the development of co-morbid internalizing and externalizing symptoms in adolescence. However, there is limited research examining whether high quality friendships and parent-child relationships mediate the relation between ADHD and the emergence of these co-morbid symptoms at the transition to high school. This study examines the mediating role of relationship quality in the association between ADHD and depressive symptoms/delinquent behaviors at this developmentally significant transition point. Results revealed significant indirect effects of grade 6 attention problems on grade 9 depressive symptoms through friendship quality and quality of the mother-child relationship in grade 8. Interventions targeting parent and peer relationships may be valuable for youth with ADHD to promote successful transitions to high school.

Vegetative and reproductive development of shoots of different order of three maize hybrids at two contrasting population densities

p.21-32

Fundamental improvements needed for timely promulgation of health program regulations, Department of Health, Education and Welfare : report of the Comptroller General of the United States.

Date stamped on cover.

Human motivation and professional practice: of knights, knaves and social workers

Efforts to improve the efficiency and responsiveness of public services by harnessing the self-interest of professionals in state agencies have been widely debated in the recent literature on welfare state reform. In the context of social services, one way in which British policy-makers have sought to effect such changes has been through the "new community care" of the 1990 NHS and Community Care Act. Key to this is the concept of care management, in which the identification of needs and the provision of services are separated, purportedly with a view to improving advocacy, choice and quality for service users. This paper uses data from a wide-ranging qualitative study of access to social care for older people to examine the success of the policy in these terms, with specific reference to its attempts to harness the rational self-interest of professionals. While care management removes one potential conflict of interests by separating commissioning and provision, the responsibility of social care professionals to comply with organizational priorities conflicts with their role of advocacy for their clients, a tension rendered all the more problematic by the perceived inadequacy of funding. Moreover, the bureaucracy of the care management process itself further negates the approach's supposedly client-centred ethos. The definitive version is available at www.blackwell-synergy.com

Effect of temperature on genomic and some biological indices during embryonic and larval development of Caspian trout Salmo trutta caspius Kessler, 1877

Since 1966 especially recent decade, Caspian trout (Salmo trutta caspius Kessler, 1877) considered as a strategic endemic species for Caspian Sea fisheries resources also coldwater aquaculture in Iran. Nowadays habitat condition effects on this subspecies during life stages, artificial breeding and incubation period noticed by research and execution sessions of fisheries in Iran. Incubation duration of Caspian trout from artificial fertilization followed by green egg and eyed egg, hatching and yolk sac absorption identified as most sensitive stages for fish and any pollution, stress and deviation by natural life conditions of embryo up to larvae could provide possible mortalities and observable or hidden alterations. Among all vital factors for Caspian trout welfare even in conservation plans and stocks rehabilitation programs or recent attempts for domestication of this fish for introduction to cold water aquaculture industry, water temperature as the most important physical factor which might conserve or induce stress to rearing environment condition is not considered yet. In hatcheries activities, the temperature for incubation and rearing Caspian trout eggs is determining by available water temperature and wide range of temperatures in governmental or private farms is using depend on the water resources availability. Also global climate change consideration and increase temperature trend accompany with group of physical and chemical factors provided by fish farm discharges and other source points entered to the migration pathway of Caspian trout in spawning season were not investigated before. Natural spawning migration pathway is upstream of Caspian tout south and south west rivers especially in Cheshmehkileh upstream in Tonekabon, Iran directed this research focus on the mentioned location. For simulation of natural spawning bed for Caspian trout, water supplied from the upstream of Daryasar branch as headwater of Cheshmehkileh River which provided REDD water condition for in vitro incubation. Green eggs treatments of wild and F1 cultured brooders both 3+ were incubated. Incubation implemented in dark, constant temperature (4, 8, 12 degree centigrade) and DO–pH–temperature digital monitoring in 3 recycling incubators ended to yolk sac absorption and entering larval stage. Hatching success, possible genome alterations by HSP70 gene expression and comet assay implemented as diagnostic tools in 3 life stages of eyed egg– Alevin and Larvae. Numbers and diameters of larvae white fiber muscles measured by histology experiment and Hematoxylin–eosine staining. Results stated significant effect of incubation temperature on hatching success, genome and white fiber muscles of wild and F1 samples. Hatching success measured as 31% and 38% for cultured and wild cold treatments, 79% and 91% for normal and 64% and 73% for warm cultured and wild treatments respectively. Considerable mortality occurred for cold treatment and 8 degree centigrade stated the best thermal condition in normal incubator according to hatching success in wild Caspian trout samples.

Positron Emission Tomography (PET) Tumor Segmentation and Quantification: Development of New Algorithms

Tumor functional volume (FV) and its mean activity concentration (mAC) are the quantities derived from positron emission tomography (PET). These quantities are used for estimating radiation dose for a therapy, evaluating the progression of a disease and also use it as a prognostic indicator for predicting outcome. PET images have low resolution, high noise and affected by partial volume effect (PVE). Manually segmenting each tumor is very cumbersome and very hard to reproduce. To solve the above problem I developed an algorithm, called iterative deconvolution thresholding segmentation (IDTS) algorithm; the algorithm segment the tumor, measures the FV, correct for the PVE and calculates mAC. The algorithm corrects for the PVE without the need to estimate camera’s point spread function (PSF); also does not require optimizing for a specific camera. My algorithm was tested in physical phantom studies, where hollow spheres (0.5-16 ml) were used to represent tumors with a homogeneous activity distribution. It was also tested on irregular shaped tumors with a heterogeneous activity profile which were acquired using physical and simulated phantom. The physical phantom studies were performed with different signal to background ratios (SBR) and with different acquisition times (1-5 min). The algorithm was applied on ten clinical data where the results were compared with manual segmentation and fixed percentage thresholding method called T50 and T60 in which 50% and 60% of the maximum intensity respectively is used as threshold. The average error in FV and mAC calculation was 30% and -35% for 0.5 ml tumor. The average error FV and mAC calculation were ~5% for 16 ml tumor. The overall FV error was ~10% for heterogeneous tumors in physical and simulated phantom data. The FV and mAC error for clinical image compared to manual segmentation was around -17% and 15% respectively. In summary my algorithm has potential to be applied on data acquired from different cameras as its not dependent on knowing the camera’s PSF. The algorithm can also improve dose estimation and treatment planning.

The Dynamic and Changing Development of EERA Networks

In this article the authors use two EERA networks as a case for a discussion on the development of research networks within the European Educational Research Association (EERA). They contend that EERA networks through their way of working create a European research space. As their case shows, the development of networks is diverse. The emergence of networks and the current group of thirty-one networks do not display a coherent and unified system. Thus they argue that EERA networks have to be studied as an open complex system in order to comprehend the multiplicity and creative and innovative space that these networks represent. They create a space for knowledge production in a European context, enabling educational researchers to see and experience their research in a more diverse setting.

Vale dos Vinhedos and the development of geographical indications in Brazil.

2012

Introduction

"TRAINING FOR THE UNIVERSAL MUSEUM" addresses a theme of our time. A Canadian, Marshall McLuhan, coined the phrase "global village" for this age which has witnessed mass travel, mass communications, even mass credit. Are we now about to see the "mass museum", a museum presumably homogenized and popularized for whatever constitutes the greatest cohort of global visitor which might arrive on the doorsteps of every-museum, every-where? The contributors to this volume think not. But there is in these papers some evidence of worry that we as individuals and institutions responsible for the education and professional development of museum workers are failing to consider seriously the impacts of the "global" forces at work in modern societies. Angelica Ruge discusses how the Germans are re-organizing museum training into a cohesive scheme, searching out the best elements from the former two states that now comprise the new German state. Margaret Greeves and Chris Newbery document the British search for a value free (and universally applicable?) set of museological skills which will underpin performance standards in the workplace. Both of these papers offer a response to the redefinition of the post-modern national state which as we watch, is redrawing political boundaries on every continent, and emphasizing the portability of skills and learning for the itinerant knowledge-industry worker.

Reading at Risk

Reading may be in jeopardy as we advance along the information superhighway. Is literacy to be technology's first roadkill?

A formação do professor de matemática e o trabalho com projetos na escola

O objetivo do presente texto é apresentar os resultados de uma pesquisa que procurou discutir a formação dos professores de Matemática que trabalham com projetos e documentar a maneira da implementação dessa proposta na escola. Os dados são provenientes de entrevistas com dez professores de Matemática, os quais atuam no Ensino Fundamental ou Médio. Seus relatos possibilitam identificar três formas diferentes de trabalhos com projetos: i) individualmente e por iniciativa própria; ii) por sugestão da escola, de forma fragmentada; iii) coletivamente. Não há indícios de que a formação inicial desses professores os tenha influenciado a trabalhar com projetos. Esse preparo foi construído ao longo de suas carreiras, através da participação em cursos de formação continuada, da experiência com a prática e das interferências de suas características pessoais.

Conceptions of mathematics teacher education : thoughts among teacher educators in Tanzania

This study addresses the question of teacher educators’ conceptions of mathematics teacher education (MTE) in teacher colleges in Tanzania, and their thoughts on how to further develop it. The tension between exponents of content as opposed to pedagogy has continued to cause challenging conceptual differences, which also influences what teacher educators conceive as desirable in the development of this domain. This tension is connected to the dissatisfaction of parents and teachers with the failure of school mathematics. From this point of view, the overall aim was to identify and describe teacher educators’ various conceptions of MTE. Inspired by the debate among teacher educators about what the balance should be between subject matter and pedagogical knowledge, it was important to look at the theoretical faces of MTE. The theoretical background involved the review of what is visible in MTE, what is yet to be known and the challenges within the practice. This task revealed meanings, perspectives in MTE, professional development and assessment. To do this, two questions were asked, to which no clear solutions satisfactorily existed. The questions to guide the investigation were, firstly, what are teacher educators’ conceptions of MTE, and secondly, what are teacher educators’ thoughts on the development of MTE? The two questions led to the choice of phenomenography as the methodological approach. Against the guiding questions, 27 mathematics teacher educators were interviewed in relation to the first question, while 32 responded to an open-ended questionnaire regarding question two. The interview statements as well as the questionnaire responses were coded and analysed (classified). The process of classification generated patterns of qualitatively different ways of seeing MTE. The results indicate that MTE is conceived as a process of learning through investigation, fostering inspiration, an approach to learning with an emphasis on problem solving, and a focus on pedagogical knowledge and skills in the process of teaching and learning. In addition, the teaching and learning of mathematics is seen as subject didactics with a focus on subject matter and as an organized integration of subject matter, pedagogical knowledge and some school practice; and also as academic content knowledge in which assessment is inherent. The respondents also saw the need to build learner-educator relationships. Finally, they emphasized taking advantage of teacher educators’ neighbourhood learning groups, networking and collaboration as sustainable knowledge and skills sharing strategies in professional development. Regarding desirable development, teacher educators’ thoughts emphasised enhancing pedagogical knowledge and subject matter, and to be determined by them as opposed to conventional top-down seminars and workshops. This study has revealed various conceptions and thoughts about MTE based on teacher educators´ diverse history of professional development in mathematics. It has been reasonably substantiated that some teacher educators teach school mathematics in the name of MTE, hardly distinguishing between the role and purpose of the two in developing a mathematics teacher. What teacher educators conceive as MTE and what they do regarding the education of teachers of mathematics revealed variations in terms of seeing the phenomenon of interest. Within limits, desirable thoughts shed light on solutions to phobias, and in the same way low self-esteem and stigmatization call for the building of teacher educator-student teacher relationships.