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1.
Elife ; 92020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31958057

RESUMO

The RAS proteins are GTP-dependent switches that regulate signaling pathways and are frequently mutated in cancer. RAS proteins concentrate in the plasma membrane via lipid-tethers and hypervariable side-chain interactions in distinct nano-domains. However, little is known about RAS membrane dynamics and the details of RAS activation of downstream signaling. Here we characterize RAS in live human and mouse cells using single molecule tracking methods and estimate RAS mobility parameters. KRAS4b exhibits confined mobility with three diffusive states distinct from the other RAS isoforms (KRAS4a, NRAS, and HRAS); and although most of the amino acid differences between RAS isoforms lie within the hypervariable region, the additional confinement of KRAS4b is largely determined by the protein's globular domain. To understand the altered mobility of an oncogenic KRAS4b we used complementary experimental and molecular dynamic simulation approaches to reveal a detailed mechanism.

2.
J Nutr Educ Behav ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31601528

RESUMO

OBJECTIVE: This study examined the role of migration and acculturation in the diet of Ghanaian migrants in Europe by (1) comparing food intake of Ghanaian migrants in Europe with that of Ghanaians living in Ghana and (2) assessing the association between acculturation and food intake. DESIGN: Data from the cross-sectional multicenter study Research on Obesity and Diabetes among African Migrants were used. Food intake was assessed using a Ghana-specific food propensity questionnaire (134 items and 14 food groups); foods were grouped based on a model of dietary change proposed by Koctürk-Runefors. SETTING: Ghana, London, Amsterdam, and Berlin. PARTICIPANTS: A total of 4,534 Ghanaian adults living in Ghana and Europe, with complete dietary data. Of these, 1,773 Ghanaian migrants had complete acculturation data. MAIN OUTCOME MEASURE: Food intake (the weighted intake frequency per week of food categories). ANALYSIS: Linear regression. RESULTS: Food intake differed between Ghanaians living in Ghana and Europe. Among Ghanaian migrants in Europe, there were inconsistent and small associations between acculturation and food intake, except for ethnic identity, which was consistently associated with intake only of traditional staples. CONCLUSIONS AND IMPLICATIONS: Findings indicate that migration is associated with dietary changes that cannot be fully explained by ethnic, cultural, and social acculturation. The study provides limited support to the differential changes in diet suggested by the Koctürk-Runefors' model of dietary change.

3.
Glob Health Promot ; : 1757975919848925, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31319777

RESUMO

Asset-based approaches to health promotion have become increasingly popular as a way to tackle health inequalities by empowering people in more disadvantaged communities to use local resources and increase control over health and its determinants. However, questions remain about how they work in practice. This article presents the findings from a systematic scoping review of the empirical literature on asset-based approaches in communities. The aim was to identify the key elements of asset-based approaches, and how they are operationalised in interventions aimed at promoting health and reducing inequalities in local communities. Four databases were searched (Medline, PsycINFO, CINAHL, ASSIA) and papers were included if they described interventions explicitly adopting an asset-based approach but excluded if limited to asset identification. Thirty articles were included in the review. Data were extracted on the type of assets that the intervention built upon, how assets were mobilised, the expected outcomes and evaluation methods. A framework is presented that synthesises the key characteristics of asset-based interventions to promote health in communities. Three main approaches to mobilising assets were identified in the literature: (A) connecting assets, (B) raising awareness of assets and (C) enabling assets to thrive. It is argued that asset-based approaches to health promotion take a wide variety of forms, making it difficult to anticipate outcomes and to evaluate interventions. The framework presented here can be used to better understand the processes through which asset-based approaches work in practice to promote health and reduce inequalities.

4.
Appetite ; 140: 190-196, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31103443

RESUMO

In the UK, ethnic minority groups tend to have higher levels of poverty than the white British population and therefore may be at high risk of food insecurity. Ghanaians, living in Ghana or as migrants are thought to have a high level of social support in their communities, but the role of this resource in relation to food security is unknown. We explored participants' perceptions of social and economic factors influencing food security among Ghanaian migrants in Greater Manchester. Participants aged ≥25 years (n = 31) of Ghanaian ancestry living in Greater Manchester were interviewed using a semi-structured interview guide developed by the researchers. Participants varied in socioeconomic status (SES), gender and migration status. Interviews were transcribed verbatim and analysed thematically using a framework approach. Participants offered similar accounts of the social and economic factors influencing food security. Accounts were based on participants' perceptions and/or personal experiences of food insecurity within the community. Participants indicated that they and their fellow Ghanaians can 'manage' even when they described quite challenging food access environments. This has negative implications on their food choices in the UK. Participants reported food insecure households may be reluctant to make use of food banks for fear of 'gossip' and 'pride'. Paradoxically, this reluctance does not extend to close network. Many participants described the church and other social groups as a trusted base in which people operate; support given through these channels is more acceptable than through the 'official context'. Government assisted food banks could partner with the social groups within this community given that these are more trusted. Keywords: food insecurity; food choice; social networks; Ghanaians; healthy eating; migrants.

5.
Cancer Res ; 79(9): 2379-2391, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30862714

RESUMO

Hepatocellular carcinoma (HCC) is a genetically heterogeneous disease for which a dominant actionable molecular driver has not been identified. Patients with the stem cell-like EpCAM+AFP+ HCC subtype have poor prognosis. Here, we performed a genome-wide RNAi screen to identify genes with a synthetic lethal interaction with EpCAM as a potential therapeutic target for the EpCAM+AFP+ HCC subtype. We identified 26 candidate genes linked to EpCAM/Wnt/ß-catenin signaling and HCC cell growth. We further characterized the top candidate PMPCB, which plays a role in mitochondrial protein processing, as a bona fide target for EpCAM+ HCC. PMPCB blockage suppressed EpCAM expression and Wnt/ß-catenin signaling via mitochondria-related reactive oxygen species production and FOXO activities, resulting in apoptosis and tumor suppression. These results indicate that a synthetic lethality screen is a viable strategy to identify actionable drivers of HCC and identify PMPCB as a therapeutically vulnerable gene in EpCAM+ HCC subpopulations. SIGNIFICANCE: This study identifies PMPCB as critical to mitochondrial homeostasis and a synthetic lethal candidate that selectively kills highly resistant EpCAM+ HCC tumors by inactivating the Wnt/ß-catenin signaling pathway.

6.
Health Soc Care Community ; 27(1): 199-206, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30198072

RESUMO

There is a need for greater conceptual clarity in place-based initiatives that seek to give residents of disadvantaged neighbourhoods more control over action to address the social determinants of health inequalities at a local level. In this article, we address this issue as it relates to the concepts of participation and inclusion. We draw on qualitative data generated during the first phase of the Communities in Control Study, a longitudinal multisite independent evaluation of the impact of Big Local on the social determinants of health and health inequalities. Big Local is a resident-led area improvement initiative in England, funded by the UK Big Lottery Fund. Initiatives focused on community empowerment are increasingly prominent in public health policy and practice globally. Approaches emphasise the promotion of greater control over decisions and action among individuals, groups, and communities, particularly those living in disadvantaged circumstances. However, when it comes to participation and inclusion in taking action and making decisions, the field is characterised by conceptual confusion. This risks undermining the impact of these initiatives. While participation and inclusion are necessary conditions for empowerment and collective control, they are not necessarily sufficient. Sufficiency requires attention to the breadth of participation (i.e., to inclusion) and to the depth of participation (i.e., the extent to which it is experienced as empowering and ultimately enables the exercise of collective control over decisions and actions). In observing how different Big Local resident-led partnerships across England are tackling the day-to-day challenges of engaging with their communities, we reveal the potential for policy and practice of reframing, and therefore clarifying (to highlight the different roles they have) the concepts of participation and inclusion in terms of depth and breadth.

7.
Sociol Health Illn ; 40(7): 1142-1155, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29916556

RESUMO

This study explores the ways in which social networks might shape accounts about food practices. Drawing on insights from the work of Christakis and Fowler () whose claims about the linkages between obesity and social networks have been the subject of vigorous debate in the sociological literature, we present qualitative data from a study of women's' accounts of social networks and food practices, conducted in Nottingham, England. We tentatively suggest that whilst social networks in their broadest sense, might shape what was perceived to be normal and acceptable in relation to food practices (and provide everyday discursive resources which normalise practice), the relationship between the two is more complex than the linear relationship proposed by Christakis and Fowler. Here, we introduce the idea of assumed shared food narratives (ASFNs), which, we propose, sheds light on motive talk about food practices, and which also provide practical and discursive resources to actors seeking to protect and defend against 'untoward' behaviour, in the context of public health messages around food and eating. We suggest that understanding ASFNs and the ways in which they are embedded in social networks represents a novel way of understanding food and eating practices from a sociological perspective.


Assuntos
Alimentos , Rede Social , Adulto , Inglaterra , Comportamento Alimentar/psicologia , Feminino , Preferências Alimentares/psicologia , Humanos , Entrevistas como Assunto , Pessoa de Meia-Idade , Narração , Pesquisa Qualitativa , Adulto Jovem
8.
Placenta ; 66: 65-73, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29884304

RESUMO

INTRODUCTION: Currently there are no clinical screening tests available to identify pregnancies at risk of developing preeclampsia (PET) and/or intrauterine growth restriction (IUGR), both of which are associated with abnormal placentation. Metabolic profiling is now a stable analytical platform used in many laboratories and has successfully been used to identify biomarkers associated with various pathological states. METHODS: We used nuclear magnetic resonance spectroscopy (NMR) to metabolically profile serum samples collected from 143 pregnant women at 26-41 weeks gestation with pregnancy outcomes of PET, IUGR, PET IUGR or small for gestational age (SGA) that were age-matched to normal pre/term pregnancies. RESULTS: Spectral analysis found no difference in the measured metabolites from normal term, pre-term and SGA samples, and of 25 identified metabolites, only glutamate was marginally different between groups. Of the identified metabolites, 3-methylhistidine, creatinine, acetyl groups and acetate, were determined to be independent predictors of PET and produced area under the curves (AUC) = 0.938 and 0.936 for the discovery and validation sets. Only 3-hydroxybutyrate was determined to be an independent predictor of IUGR, however the model had low predictive power (AUC = 0.623 and 0.581 for the discovery and validation sets). CONCLUSIONS: A sub-panel of metabolites had strong predictive power for identifying PET samples in a validation dataset, however prediction of IUGR was more difficult using the identified metabolites. NMR based metabolomics can identify metabolites strongly associated with disease and has the potential to be useful in developing early clinical screening tests for at risk pregnancies.


Assuntos
Metaboloma , Metabolômica/métodos , Complicações na Gravidez/sangue , Complicações na Gravidez/diagnóstico , Adulto , Biomarcadores/sangue , Análise Química do Sangue/métodos , Estudos de Casos e Controles , Feminino , Retardo do Crescimento Fetal/sangue , Retardo do Crescimento Fetal/diagnóstico , Ácido Glutâmico/sangue , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Espectroscopia de Ressonância Magnética/métodos , Insuficiência Placentária/sangue , Insuficiência Placentária/diagnóstico , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/diagnóstico , Gravidez
9.
Cell Rep ; 22(7): 1889-1902, 2018 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-29444439

RESUMO

KRAS can bind numerous effector proteins, which activate different downstream signaling events. The best known are RAF, phosphatidylinositide (PI)-3' kinase, and RalGDS families, but many additional direct and indirect effectors have been reported. We have assessed how these effectors contribute to several major phenotypes in a quantitative way, using an arrayed combinatorial siRNA screen in which we knocked down 41 KRAS effectors nodes in 92 cell lines. We show that every cell line has a unique combination of effector dependencies, but in spite of this heterogeneity, we were able to identify two major subtypes of KRAS mutant cancers of the lung, pancreas, and large intestine, which reflect different KRAS effector engagement and opportunities for therapeutic intervention.


Assuntos
Oncogenes , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Adenilato Quinase/metabolismo , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Redes e Vias Metabólicas/efeitos dos fármacos , Modelos Biológicos , Mutação/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Bibliotecas de Moléculas Pequenas/farmacologia
10.
Methods Mol Biol ; 1710: 233-246, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29197007

RESUMO

Functional cell-based assays are useful for comparing the effect of a treatment, drug, or condition on cells in culture. Cell lines are a commonly used model to replicate a normal biological process or a pathological condition. Trophoblasts within the placenta are required to perform a variety of functions, which include proliferation, differentiation, migration, and invasion for efficient placentation to occur. These functions are impaired in trophoblasts from preeclamptic pregnancies, and therefore functional cell-based assays can be utilized to measure differences and dissect molecular regulatory pathways.


Assuntos
Trofoblastos/citologia , Apoptose , Adesão Celular , Linhagem Celular , Movimento Celular , Proliferação de Células , Técnicas Citológicas/métodos , Feminino , Citometria de Fluxo/métodos , Humanos , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/patologia , Gravidez , Transdução de Sinais , Trofoblastos/metabolismo , Trofoblastos/patologia
11.
Mol Hum Reprod ; 24(2): 94-109, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29272530

RESUMO

STUDY QUESTION: What is the association between placental formyl peptide receptor 2 (FPR2) and trophoblast and endothelial functions in pregnancies affected by foetal growth restriction (FGR)? SUMMARY ANSWER: Reduced FPR2 placental expression in idiopathic FGR results in significantly altered trophoblast differentiation and endothelial function in vitro. WHAT IS KNOWN ALREADY: FGR is associated with placental insufficiency, where defective trophoblast and endothelial functions contribute to reduced feto-placental growth. STUDY DESIGN, SIZE, DURATION: The expression of FPR2 in placental tissues from human pregnancies complicated with FGR was compared to that in gestation-matched uncomplicated control pregnancies (n = 25 from each group). Fpr2 expression was also determined in placental tissues obtained from a murine model of FGR (n = 4). The functional role of FPR2 in primary trophoblasts and endothelial cells in vitro was assessed in diverse assays in a time-dependent manner. PARTICIPANTS/MATERIALS, SETTING, METHODS: Placentae from third-trimester pregnancies complicated by idiopathic FGR (n = 25) and those from gestation-matched pregnancies with appropriately grown infants as controls (n = 25) were collected at gestation 27-40 weeks. Placental tissues were also collected from a spontaneous CBA/CaH × DBA/2 J murine model of FGR. Placental FPR2/Fpr2 mRNA expression was determined by real-time PCR, while protein expression was examined by immunoblotting and immunohistochemistry. siRNA transfection was used to silence FPR2 expression in primary trophoblasts and in human umbilical vein endothelial cells (HUVEC), and the quantitation of cytokines, chemokines and apoptosis was performed following a cDNA array analyses. Functional effects of trophoblast differentiation were measured using HCGB/ß-hCG and syncytin-2 expression as well as markers of apoptosis, tumour protein 53 (TP53), caspase 8, B cell lymphoma 2 (BCL2) and BCL associated X (BAX). Endothelial function was assessed by proliferation, network formation and permeability assays. MAIN RESULTS AND THE ROLE OF CHANCE: Placental FPR2/Fpr2 expression was significantly decreased in FGR placentae (n = 25, P < 0.05) as well as in murine FGR placentae compared to controls (n = 4, P < 0.05). FPR2 siRNA (siFPR2) in term trophoblasts significantly increased differentiation markers, HCGB and syncytin-2; cytokines, interleukin (IL)-6, CXCL8; and apoptotic markers, TP53, caspase 8 and BAX, but significantly reduced the expression of the chemokines CXCL12 and its receptors CXCR4 and CXCR7; CXCL16 and its receptor, CXCR6; and cytokine, IL-10, compared with control siRNA (siCONT). Treatment of HUVECs with siFPR2 significantly reduced proliferation and endothelial tube formation, but significantly increased permeability of HUVECs. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Reduced expression of placental FPR2/Fpr2 was observed in the third trimester at delivery after development of FGR, suggesting that FPR2 is associated with FGR pregnancies. However, there is a possibility that the decreased placental FPR2 observed in FGR may be a consequence rather than a cause of FGR, although our in vitro functional analyses using primary trophoblasts and endothelial cells suggest that FPR2 may have a direct or indirect regulatory role on trophoblast differentiation and endothelial function in FGR. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study linking placental FPR2 expression with changes in the trophoblast and endothelial functions that may explain the placental insufficiency observed in FGR. STUDY FUNDING/COMPETING INTERESTS: P.M. and P.R.E. received funding from the Australian Institute of Musculoskeletal Science, Western Health, St. Albans, Victoria 3021, Australia. M.L. is supported by a Career Development Fellowship from the National Health and Medical Research Council (NHMRC; Grant no. 1047025). Monash Health is supported by the Victorian Government's Operational Infrastructure Support Programme. The authors declare that there is no conflict of interest in publishing this work.


Assuntos
Retardo do Crescimento Fetal/metabolismo , Placenta/metabolismo , Receptores de Formil Peptídeo/metabolismo , Receptores de Lipoxinas/metabolismo , Apoptose/genética , Apoptose/fisiologia , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Feminino , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Receptores de Formil Peptídeo/genética , Receptores de Lipoxinas/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Trofoblastos/citologia , Trofoblastos/metabolismo
12.
Int J Behav Nutr Phys Act ; 14(1): 154, 2017 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-29115995

RESUMO

BACKGROUND: Some ethnic minority populations have a higher risk of non-communicable diseases than the majority European population. Diet and physical activity behaviours contribute to this risk, shaped by a system of inter-related factors. This study mapped a systems-based framework of the factors influencing dietary and physical activity behaviours in ethnic minority populations living in Europe, to inform research prioritisation and intervention development. METHODS: A concept mapping approach guided by systems thinking was used: i. Preparation (protocol and terminology); ii. Generating a list of factors influencing dietary and physical activity behaviours in ethnic minority populations living in Europe from evidence (systematic mapping reviews) and 'eminence' (89 participants from 24 academic disciplines via brainstorming, an international symposium and expert review) and; iii. Seeking consensus on structuring, rating and clustering factors, based on how they relate to each other; and iv. Interpreting/utilising the framework for research and interventions. Similar steps were undertaken for frameworks developed for the majority European population. RESULTS: Seven distinct clusters emerged for dietary behaviour (containing 85 factors) and 8 for physical activity behaviours (containing 183 factors). Four clusters were similar across behaviours: Social and cultural environment; Social and material resources; Psychosocial; and Migration context. Similar clusters of factors emerged in the frameworks for diet and physical activity behaviours of the majority European population, except for 'migration context'. The importance of factors across all clusters was acknowledged, but their relative importance differed for ethnic minority populations compared with the majority population. CONCLUSIONS: This systems-based framework integrates evidence from both expert opinion and published literature, to map the factors influencing dietary and physical activity behaviours in ethnic minority groups. Our findings illustrate that innovative research and complex interventions need to be developed that are sensitive to the needs of ethnic minority populations. A systems approach that encompasses the complexity of the inter-related factors that drive behaviours may inform a more holistic public health paradigm to more effectively reach ethnic minorities living in Europe, as well as the majority host population.


Assuntos
Dieta/etnologia , Grupos Étnicos , Exercício , Comportamentos Relacionados com a Saúde/etnologia , Grupos Minoritários , Cultura , Europa (Continente) , Humanos , Saúde Pública , Pesquisa , Fatores de Risco , Meio Social , Migrantes
13.
Soc Sci Med ; 187: 20-28, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28647642

RESUMO

A growing body of research attests to the impact of welfare regimes on health and health equity. However, the mechanisms that link different kinds of welfare entitlement to health outcomes are less well understood. This study analysed the accounts of 29 older adults in England to delineate how the form of entitlement to welfare and other resources (specifically, whether this was understood as a universal entitlement or as targeted to those in need) impacts on the determinants of health. Mechanisms directly affecting access to material resources (through deterring uptake of benefits) have been well documented, but those that operate through psychosocial and more structural pathways less so, in part because they are more challenging to identify. Entitlement that was understood collectively, or as arising from financial or other contributions to a social body, had positive impacts on wellbeing beyond material gains, including facilitating access to important health determinants: social contact, recognition and integration. Entitlement understood as targeted in terms of individualised concepts of need or vulnerability deterred access to material resources, but also fostered debate about legitimacy, thus contributing to negative impacts on individual wellbeing and the public health through the erosion of social integration. This has important implications for both policy and evaluation. Calls to target welfare benefits at those in most need emphasise direct material pathways to health impact. We suggest a model for considering policy change and evaluation which also takes into account how psychosocial and structural pathways are affected by the nature of entitlement.


Assuntos
Apoio Financeiro , Equidade em Saúde/normas , Seguridade Social/economia , Seguridade Social/psicologia , Cobertura Universal do Seguro de Saúde/normas , Idoso , Idoso de 80 Anos ou mais , Feminino , Equidade em Saúde/economia , Humanos , Londres , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Medicina Estatal/organização & administração
14.
Ann Hum Biol ; 44(5): 454-463, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28535737

RESUMO

BACKGROUND: Previous studies have identified a process of dietary acculturation when migrant groups adopt the food patterns of the host country. AIM: The aim of this study was to explore the influence of migration on dietary practices and the process of dietary acculturation amongst Ghanaians living in the UK. SUBJECT AND METHODS: A qualitative study of adults aged ≥25 years (n = 31) of Ghanaian ancestry living in Greater Manchester using face-to-face interviews. Participants varied in socioeconomic status, gender and migration status. Interviews were transcribed verbatim and analysed thematically. RESULTS: Three distinct dietary practice typologies were discernible that differed in terms of typical meal formats, meal contexts, structure and patterning of meals, food preparation and purchasing behaviours: (i) continuity practices; (ii) flexible practices; and (iii) changed practices. The identified practices were shaped by interrelating factors that fell into four main clusters: social and cultural environment; accessibility of foods; migration context; and food beliefs/perceptions. CONCLUSION: Participants retained, to a varying degree, some aspects of Ghanaian dietary practices, whilst adopting key features of UK food culture. This study demonstrates the complexity of dietary change, indicating that it is not a linear process and it is dependent on several factors.


Assuntos
Aculturação , Dieta , Preferências Alimentares , Migração Humana , Adulto , Idoso , Feminino , Gana/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Migrantes , Reino Unido
15.
Placenta ; 60 Suppl 1: S5-S9, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28108031

RESUMO

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2016 there were twelve themed workshops, four of which are summarized in this report. These workshops covered innovative technologies applied to new and traditional areas of placental research: 1) genomic communication; 2) bioinformatics; 3) trophoblast biology and pathology; 4) placental transport systems.


Assuntos
Pesquisa Biomédica/métodos , Biologia Computacional/métodos , Congressos como Assunto , Genômica/métodos , Troca Materno-Fetal , Placenta/fisiologia , Animais , Transporte Biológico , Pesquisa Biomédica/tendências , Biologia Computacional/tendências , Metilação de DNA , Exoma , Feminino , Genômica/tendências , Humanos , Agências Internacionais , Placenta/citologia , Placenta/patologia , Placenta/fisiopatologia , Gravidez , Complicações na Gravidez/patologia , Complicações na Gravidez/fisiopatologia , Sociedades Científicas , Trofoblastos/citologia , Trofoblastos/patologia , Trofoblastos/fisiologia
16.
Sci Rep ; 6: 28811, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27363493

RESUMO

Intrauterine growth restriction (IUGR) is a pathology of pregnancy that results in failure of the fetus to reach its genetically determined growth potential. In developed nations the most common cause of IUGR is impaired placentation resulting from poor trophoblast function, which reduces blood flow to the fetoplacental unit, promotes hypoxia and enhances production of bioactive lipids (TXA2 and isoprostanes) which act through the thromboxane receptor (TP). TP activation has been implicated as a pathogenic factor in pregnancy complications, including IUGR; however, the role of TP isoforms during pregnancy is poorly defined. We have determined that expression of the human-specific isoform of TP (TPß) is increased in placentae from IUGR pregnancies, compared to healthy pregnancies. Overexpression of TPα enhanced trophoblast proliferation and syncytialisation. Conversely, TPß attenuated these functions and inhibited migration. Expression of the TPß transgene in mice resulted in growth restricted pups and placentae with poor syncytialisation and diminished growth characteristics. Together our data indicate that expression of TPα mediates normal placentation; however, TPß impairs placentation, and promotes the development of IUGR, and represents an underappreciated pathogenic factor in humans.


Assuntos
Retardo do Crescimento Fetal/metabolismo , Placenta/metabolismo , Trofoblastos/metabolismo , Adulto , Animais , Animais Recém-Nascidos , Linhagem Celular Tumoral , Feminino , Retardo do Crescimento Fetal/genética , Humanos , Hipóxia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Gravidez , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Receptores de Tromboxano A2 e Prostaglandina H2/genética , Receptores de Tromboxano A2 e Prostaglandina H2/metabolismo , Tromboxano A2/metabolismo
17.
Int J Behav Nutr Phys Act ; 13: 85, 2016 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-27465354

RESUMO

BACKGROUND: Europe has a growing population of ethnic minority groups whose dietary behaviours are potentially of public health concern. To promote healthier diets, the factors driving dietary behaviours need to be understood. This review mapped the broad range of factors influencing dietary behaviour among ethnic minority groups living in Europe, in order to identify research gaps in the literature to guide future research. METHODS: A systematic mapping review was conducted (protocol registered with PROSPERO 2014: CRD42014013549). Nine databases were searched for quantitative and qualitative primary research published between 1999 and 2014. Ethnic minority groups were defined as immigrants/populations of immigrant background from low and middle income countries, population groups from former Eastern Bloc countries and minority indigenous populations. In synthesizing the findings, all factors were sorted and structured into emerging clusters according to how they were seen to relate to each other. RESULTS: Thirty-seven of 2965 studies met the inclusion criteria (n = 18 quantitative; n = 19 qualitative). Most studies were conducted in Northern Europe and were limited to specific European countries, and focused on a selected number of ethnic minority groups, predominantly among populations of South Asian origin. The 63 factors influencing dietary behaviour that emerged were sorted into seven clusters: social and cultural environment (16 factors), food beliefs and perceptions (11 factors), psychosocial (9 factors), social and material resources (5 factors), accessibility of food (10 factors), migration context (7 factors), and the body (5 factors). CONCLUSION: This review identified a broad range of factors and clusters influencing dietary behaviour among ethnic minority groups. Gaps in the literature identified a need for researchers to explore the underlying mechanisms that shape dietary behaviours, which can be gleaned from more holistic, systems-based studies exploring relationships between factors and clusters. The dominance of studies exploring 'differences' between ethnic minority groups and the majority population in terms of the socio-cultural environment and food beliefs suggests a need for research exploring 'similarities'. The evidence from this review will feed into developing a framework for the study of factors influencing dietary behaviours in ethnic minority groups in Europe.


Assuntos
Dieta , Emigrantes e Imigrantes , Grupos Étnicos , Comportamento Alimentar , Grupos Minoritários , Grupo com Ancestrais do Continente Asiático , Europa (Continente) , Humanos
18.
Mol Pharmacol ; 89(2): 263-72, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26668215

RESUMO

Despite improvements in the management of liver cancer, the survival rate for patients with hepatocellular carcinoma (HCC) remains dismal. The survival benefit of systemic chemotherapy for the treatment of liver cancer is only marginal. Although the reasons for treatment failure are multifactorial, intrinsic resistance to chemotherapy plays a primary role. Here, we analyzed the expression of 377 multidrug resistance (MDR)-associated genes in two independent cohorts of patients with advanced HCC, with the aim of finding ways to improve survival in this poor-prognosis cancer. Taqman-based quantitative polymerase chain reaction revealed a 45-gene signature that predicts overall survival (OS) in patients with HCC. Using the Connectivity Map Tool, we were able to identify drugs that converted the gene expression profiles of HCC cell lines from ones matching patients with poor OS to profiles associated with good OS. We found three compounds that convert the gene expression profiles of three HCC cell lines to gene expression profiles associated with good OS. These compounds increase histone acetylation, which correlates with the synergistic sensitization of those MDR tumor cells to conventional chemotherapeutic agents, including cisplatin, sorafenib, and 5-fluorouracil. Our results indicate that it is possible to modulate gene expression profiles in HCC cell lines to those associated with better outcome. This approach also increases sensitization of HCC cells toward conventional chemotherapeutic agents. This work suggests new treatment strategies for a disease for which few therapeutic options exist.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Linhagem Celular Tumoral , Estudos de Coortes , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Taxa de Sobrevida/tendências , Resultado do Tratamento
19.
BMC Public Health ; 15: 996, 2015 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-26423051

RESUMO

BACKGROUND: Although it is increasingly acknowledged that social networks are important to our understanding ofoverweight and obesity, there is limited understanding about the processes by which such networks shapetheir progression. This paper reports the findings of a scoping review of the literature that sought to identify the key processes through which social networks are understood to influence the development of overweight and obesity. METHODS: A scoping review was conducted. Forty five papers were included in the final review, the findings of which were synthesised to provide an overview of the main processes through which networks have been understood to influence the development of overweight and obesity. RESULTS: Included papers addressed a wide range of research questions framed around six types of networks: a paired network (one's spouse or intimate partner); friends and family (including work colleagues and people within social clubs); ephemeral networks in shared public spaces (such as fellow shoppers in a supermarket or diners in a restaurant); people living within the same geographical region; peers (including co-workers, fellow students, fellow participants in a weight loss programme); and cultural groups (often related toethnicity). As individuals are embedded in many of these different types of social networks at any one time, the pathways of influence from social networks to the development of patterns of overweight and obesity are likely to be complex and interrelated. Included papers addressed a diverse set of issues: body weight trends over time; body size norms or preferences; weight loss and management; physical activity patterns; and dietary patterns. DISCUSSION: Three inter-related processes were identified: social contagion (whereby the network in which people are embedded influences their weight or weight influencing behaviours), social capital (whereby sense of belonging and social support influence weight or weight influencing behaviours), and social selection (whereby a person's network might develop according to his or her weight). CONCLUSIONS: The findings have important implications for understanding about methods to target the spread of obesity, indicating that much greater attention needs to be paid to the social context in which people make decisions about their weight and weight influencing behaviours.


Assuntos
Relações Interpessoais , Obesidade/etiologia , Capital Social , Meio Social , Adulto , Feminino , Humanos , Masculino , Obesidade/prevenção & controle , Sobrepeso , Apoio Social
20.
J Aging Stud ; 34: 113-22, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26162731

RESUMO

In many welfare states, 'austerity' policies have ignited debates about the fairness and cost-effectiveness of universal welfare benefits, with benefits received by older citizens a particular topic of concern. Empirical studies suggest that conditionality generates problems of access and uptake but, to date, there has been little research on how different conditions of entitlement are understood by older citizens. This study drew on interviews with 29 older citizens from three areas of England to explore how eligibility for and uptake of different kinds of welfare benefits were understood. In interviews, current entitlement was understood in relation to a generational habitus, in which 'our generation' was framed as sharing cohort experiences, and moral orientations to self-reliance, hard work and struggle. Entitlement to some welfare benefits was taken for granted as a reward owed by the state to its citizens for hard-earned lives. State transfers such as pensions, free travel and fuel subsidies were congruent with a nationalised generational habitus, and fostered recognition, self-worth and the sense of a generation as a collective. In contrast, transfers contingent on economic or need-based conditionality were more explicitly framed as 'benefits', and negatively associated with vulnerability and moral contestation. Uptake was therefore often incompatible with their generational habitus. Calls for introducing further conditionality to benefits for older adults are often based on claims that this will increase fairness and equality. Our analysis suggests, however, that introducing conditionality has the potential to promote inequality and foster differentiation and division, within the older population and between generations.


Assuntos
Relação entre Gerações , Seguridade Social , Idoso , Idoso de 80 Anos ou mais , Recessão Econômica , Definição da Elegibilidade , Inglaterra , Feminino , Reforma dos Serviços de Saúde , Política de Saúde , Humanos , Benefícios do Seguro , Masculino , Pessoa de Meia-Idade , Pensões , Aposentadoria/psicologia , Previdência Social
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