629 research outputs found

    Solar powered biohydrogen production requires specific localization of the hydrogenase

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    This work was supported by BBSRC Grant (BB/G021856/1) to SJB, PJN and CWM. We acknowledge support from the U.S. DoE, Biological and Environmental Research Program to MB, the U.S. DoE Fuel Cell Technologies Office (contract number DE-AC36-08-GO28308) to CAE and EPSRC (EP/F00270X/1) to MB and PJN

    Telomerase activity in melanoma and non-melanoma skin cancer

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    Telomeres are specialized structures consisting of repeat arrays of TTAGGGn located at the ends of chromosomes. They are essential for chromosome stability and, in the majority of normal somatic cells, telomeres shorten with each cell division. Most immortalized cell lines and tumours reactivate telomerase to stabilize the shortening chromosomes. Telomerase activation is regarded as a central step in carcinogenesis and, here, we demonstrate telomerase activation in premalignant skin lesions and also in all forms of skin cancer. Telomerase activation in normal skin was a rare event, and among 16 samples of normal skin (one with a history of chronic sun exposure) 12.5% (2 out of 16) exhibited telomerase activity. One out of 16 (6.25%) benign proliferative lesions, including viral and seborrhoeic wart samples, had telomerase activity. In premalignant actinic keratoses and Bowen's disease, 42% (11 out of 26) of samples exhibited telomerase activity. In the basal cell carcinoma and cutaneous malignant melanoma (CMM) lesions, telomerase was activated in 77% (10 out of 13) and 69% (22 out of 32) respectively. However, only 25% (3 out of 12) of squamous cell carcinomas (SCC) had telomerase activity. With the exception of one SCC sample, telomerase activity in a positive control cell line derived from a fibrosarcoma (HT1080) was not inhibited when mixed with the telomerase-negative SCC or CMM extracts, indicating that, overall, Taq polymerase and telomerase inhibitors were not responsible for the negative results. Mean telomere hybridizing restriction fragment (TRF) analysis was performed in a number of telomerase-positive and -negative samples and, although a broad range of TRF sizes ranging from 3.6 to 17 kb was observed, a relationship between telomerase status and TRF size was not found

    Smoking and health-related quality of life in English general population: Implications for economic evaluations

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    Copyright @ 2012 Vogl et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.Background: Little is known as to how health-related quality of life (HRQoL) when measured by generic instruments such as EQ-5D differ across smokers, ex-smokers and never-smokers in the general population; whether the overall pattern of this difference remain consistent in each domain of HRQoL; and what implications this variation, if any, would have for economic evaluations of tobacco control interventions. Methods: Using the 2006 round of Health Survey for England data (n = 13,241), this paper aims to examine the impact of smoking status on health-related quality of life in English population. Depending upon the nature of the EQ-5D data (i.e. tariff or domains), linear or logistic regression models were fitted to control for biology, clinical conditions, socio-economic background and lifestyle factors that an individual may have regardless of their smoking status. Age- and gender-specific predicted values according to smoking status are offered as the potential 'utility' values to be used in future economic evaluation models. Results: The observed difference of 0.1100 in EQ-5D scores between never-smokers (0.8839) and heavy-smokers (0.7739) reduced to 0.0516 after adjusting for biological, clinical, lifestyle and socioeconomic conditions. Heavy-smokers, when compared with never-smokers, were significantly more likely to report some/severe problems in all five domains - mobility (67%), self-care (70%), usual activity (42%), pain/discomfort (46%) and anxiety/depression (86%) -. 'Utility' values by age and gender for each category of smoking are provided to be used in the future economic evaluations. Conclusion: Smoking is significantly and negatively associated with health-related quality of life in English general population and the magnitude of this association is determined by the number of cigarettes smoked. The varying degree of this association, captured through instruments such as EQ-5D, may need to be fed into the design of future economic evaluations where the intervention being evaluated affects (e.g. tobacco control) or is affected (e.g. treatment for lung cancer) by individual's (or patients') smoking status

    Comparing the immune response to a novel intranasal nanoparticle PLGA vaccine and a commercial BPI3V vaccine in dairy calves

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    peer-reviewedBackground There is a need to improve vaccination against respiratory pathogens in calves by stimulation of local immunity at the site of pathogen entry at an early stage in life. Ideally such a vaccine preparation would not be inhibited by the maternally derived antibodies. Additionally, localized immune response at the site of infection is also crucial to control infection at the site of entry of virus. The present study investigated the response to an intranasal bovine parainfluenza 3 virus (BPI3V) antigen preparation encapsulated in PLGA (poly dl-lactic-co-glycolide) nanoparticles in the presence of pre-existing anti-BPI3V antibodies in young calves and comparing it to a commercially available BPI3V respiratory vaccine. Results There was a significant (P < 0.05) increase in BPI3V-specific IgA in the nasal mucus of the BPI3V nanoparticle vaccine group alone. Following administration of the nanoparticle vaccine an early immune response was induced that continued to grow until the end of study and was not observed in the other treatment groups. Virus specific serum IgG response to both the nanoparticle vaccine and commercial live attenuated vaccine showed a significant (P < 0.05) rise over the period of study. However, the cell mediated immune response observed didn’t show any significant rise in any of the treatment groups. Conclusion Calves administered the intranasal nanoparticle vaccine induced significantly greater mucosal IgA responses, compared to the other treatment groups. This suggests an enhanced, sustained mucosal-based immunological response to the BPI3V nanoparticle vaccine in the face of pre-existing antibodies to BPI3V, which are encouraging and potentially useful characteristics of a candidate vaccine. However, ability of nanoparticle vaccine in eliciting cell mediated immune response needs further investigation. More sustained local mucosal immunity induced by nanoparticle vaccine has obvious potential if it translates into enhanced protective immunity in the face of virus outbreak

    Identification of human papillomavirus DNA gene sequences in human breast cancer

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    Human papilloma viruses (HPVs) are accepted as being carcinogenic in human cervical and anogenital cancers. The suspicion that HPVs may also have a role in human breast cancer is based on the identification of HPVs in human breast tumours and the immortalisation of normal human breast cells by HPV types 16 and 18. For this investigation, DNA that had been previously extracted and fresh frozen at −70°C from 50 unselected invasive ductal breast cancer specimens were screened by polymerase chain reaction (PCR) for HPV type 16, 18 and 33 gene sequences. We show that HPV 18 gene sequences are present in DNA extracted from breast tumours in Australian women. Overall, 24 (48%) of the 50 samples were HPV positive. Overall no correlations with tumour grade, patient survival, steroid receptor status, ERB-2, p53 expression and mutation were observed. Human papilloma viruses may have a role in human breast cancer. We speculate that HPVs may be transmitted by hand from the female perineum to the breast

    Early and Middle Holocene Hunter-Gatherer Occupations in Western Amazonia: The Hidden Shell Middens

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    We report on previously unknown early archaeological sites in the Bolivian lowlands, demonstrating for the first time early and middle Holocene human presence in western Amazonia. Multidisciplinary research in forest islands situated in seasonally-inundated savannahs has revealed stratified shell middens produced by human foragers as early as 10,000 years ago, making them the oldest archaeological sites in the region. The absence of stone resources and partial burial by recent alluvial sediments has meant that these kinds of deposits have, until now, remained unidentified. We conducted core sampling, archaeological excavations and an interdisciplinary study of the stratigraphy and recovered materials from three shell midden mounds. Based on multiple lines of evidence, including radiocarbon dating, sedimentary proxies (elements, steroids and black carbon), micromorphology and faunal analysis, we demonstrate the anthropogenic origin and antiquity of these sites. In a tropical and geomorphologically active landscape often considered challenging both for early human occupation and for the preservation of hunter-gatherer sites, the newly discovered shell middens provide evidence for early to middle Holocene occupation and illustrate the potential for identifying and interpreting early open-air archaeological sites in western Amazonia. The existence of early hunter-gatherer sites in the Bolivian lowlands sheds new light on the region's past and offers a new context within which the late Holocene "Earthmovers" of the Llanos de Moxos could have emerged. © 2013 Lombardo et al

    The Pioneer Anomaly

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    Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

    Karl Popper e Amartya Sen

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    Orientador : Ramón García FernándezCo-orientador : John Bryan DavisTese (doutorado) - Universidade Federal do Paraná, Setor de Ciências Sociais Aplicadas, Programa de Pós-Graduação em Desenvolvimento Econômico. Defesa: Curitiba, [2005]Inclui bibliografiaResumo: As avaliações de políticas públicas ou outras iniciativas voltadas ao desenvolvimento seguem diferentes métodos de análise, desde o mais orientado ao mercado ao que busca incluir considerações sociais e éticas. Quando o interesse é avaliar como diferentes tipos de intervenções sociais poderiam ocasionar mudanças na vida das pessoas, existe a necessidade de um método através do qual o pessoal de uma agência de desenvolvimento (economistas ou outras pessoas interessadas no assunto) seja capaz de identificar e avaliar esses impactos e não tão somente de calcular a relação entre o investimento na referida intervenção e a sua taxa interna de retorno. Nesse sentido, esta tese aceita como ponto de partida que Karl Popper desenvolveu uma metodologia que permite arquitetar a intervenção social de forma que seja possível acompanhar tal intervenção e discutir seus efeitos de forma participativa e crítica ao mesmo tempo. Para suprir a falta de aprofundamento ético na abordagem de Popper, destaco a tentativa de resgatar a moral no discurso da economia empreendida por Amartya Sen, com sua ênfase nas liberdades individuais, na capacidade de deliberação e na discussão pública e crítica como elementos essenciais para a avaliação do bem-estar individual e dos arranjos sociais. O propósito é mostrar que a perspectiva metodológica-social de Popper, complementada com a ênfase na moral de Sen para as avaliações de bem-estar individual e social, permite a constituição de temas que podem ser usados na apresentação e apreciação de ferramentas avaliativas de políticas públicas ou outras iniciativas de desenvolvimento. A importância dos fatores sociais nas tentativas de intervenções na ordem econômica e social, a possibilidade da discussão pública dessas intervenções e de seus resultados, bem como a influência das instituições e tradições em todo esse processo, constituíram os temas ressaltados na tese. Comparamos finalmente algumas metodologias de avaliação dos impactos econômicos e sociais propostas para medir os resultados de tentativas de intervenção, e concluímos afirmando que as perspectivas de Popper e Sem podem servir como base para um aprofundamento e melhora dessas diversas metodologias.Abstract: The appreciation of public policies or of other development initiatives are based on different evaluative methods, from the market oriented ones to those which take into account social and ethical considerations. When the interest is to investigate how different kinds of social interventions could change people's life, there is a need for a method by which the staff of a development agency (economists and others interested in this issue) could identify and evaluate these impacts, and not just calculate the relation between the ammount invested in the project and its internal rate of return. Therefore, this thesis assumes that Karl Popper presents a methodology by means of which it is possible to plan a social intervention in a way that allows to follow it, as well as to discuss its effects on people's life. In order to improve Popper's lack of a more profound ethical discussion, it is argued that Amartya Sen's attempts to bring moral judgments to economics discourse, stressing his emphasis on individual freedoms, self- scrutiny and public reasoning as essential elements for evaluating individual well-being and social arrangements. The purpose of our thesis is to show that Popper's methodological-social perspective, improved with Sen's emphasis on moral judgments to evaluate individual well-being and social welfare, allows the development of themes which can be used to present and appreciate evaluative tools of public policy or other development initiatives. The subjects developed in this thesis include the importance of social factors in the practice of social intervention, the possibility to discuss these interventions and their consequences, and the influence of traditions and institutions during the whole development project. My conclusion, after presenting and appreciating some evaluative methods, is that the evolution of these methods could follow the need for an improvement in the knowledge about the relationship between social intervention and human development

    Insight on genes affecting tuber development in potato upon <i>Potato spindle tuber viroid</i> (PSTVd) infection

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    Potato (Solanum tuberosum L) is a natural host of Potato spindle tuber viroid (PSTVd) which can cause characteristic symptoms on developing plants including stunting phenotype and distortion of leaves and tubers. PSTVd is the type species of the family Pospiviroidae, and can replicate in the nucleus and move systemically throughout the plant. It is not well understood how the viroid can affect host genes for successful invasion and which genes show altered expression levels upon infection. Our primary focus in this study is the identification of genes which can affect tuber formation since viroid infection can strongly influence tuber development and especially tuber shape. In this study, we used a large-scale method to identify differentially expressed genes in potato. We have identified defence, stress and sugar metabolism related genes having altered expression levels upon infection. Additionally, hormone pathway related genes showed significant up- or down-regulation. DWARF1/DIMINUTO, Gibberellin 7-oxidase and BEL5 transcripts were identified and validated showing differential expression in viroid infected tissues. Our study suggests that gibberellin and brassinosteroid pathways have a possible role in tuber development upon PSTVd infection
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