209 research outputs found

    Studio International Magazine: Tales from Peter Townsend’s editorial papers 1965 -75

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    When Peter Townsend was appointed editor of Studio International in November 1965 it was the longest running British art magazine, founded 1893 as The Studio by Charles Holme with editor Gleeson White. Townsend’s predecessor, GS Whittet adopted the additional International in 1964, devised to stimulate advertising. The change facilitated Townsend’s reinvention of the radical policies of its founder as a magazine for artists with an international outlook. His decision to appoint an International Advisory Committee as well as a London based Advisory Board show this commitment. Townsend’s editorial in January 1966 declares the magazine’s aim, ‘not to ape’ its ancestor, but ‘rediscover its liveliness.’ He emphasised magazine’s geographical position, poised between Europe and the US, susceptible to the influences of both and wholly committed to neither, it would be alert to what the artists themselves wanted. Townsend’s policy pioneered the magazine’s presentation of new experimental practices and art-for-the-page as well as the magazine as an alternative exhibition site and specially designed artist’s covers. The thesis gives centre stage to a British perspective on international and transatlantic dialogues from 1965- 1975, presenting case studies to show the importance of the magazine’s influence achieved through Townsend’s policy of devolving responsibility to artists and key assistant editors, Charles Harrison, John McEwen, and contributing editor Barbara Reise. Reise’s work with the Minimalists cemented their reputations in the UK. Seth Siegelaub, the innovative New York art dealer guest edited the exhibition in the July/August 1970 issue. Harrison’s support of Conceptual art led to SI May 1971, an exhibition venture with the New York Culture Center. McEwen was responsible for the Fish issue, May 1974. Peter Townsend’s papers are the only known surviving papers in the magazine’s history. They are independent of the publication and provide off- scene accounts into the commissions. Leads found in Townsend’s archive trace connections to other archives which led to interviews. In interviews and archives often it is the anecdotal story that raises circumstantial evidence giving fuel to reconsider familiar accounts

    Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.

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    Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention

    Risk Factors for Obesity and High Blood Pressure in Chinese American Children: Maternal Acculturation and Children’s Food Choices

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    The objective of this study is to explore risk factors associated with overweight and high blood pressure in Chinese American children. Students and their parents were recruited from Chinese language schools in the San Francisco Bay Area. Data were collected on 67 children and their mothers, and included children’s weight, height, waist and hip circumferences, blood pressure, level of physical activity, dietary intake, usual food choice, knowledge about nutrition and physical activity, and self-efficacy regarding diet and physical activity. Mothers completed questionnaires on demographic data and acculturation. About 46% of children had a body mass index exceeding the 85th percentile. Lower level of maternal acculturation is a risk factor for overweight and higher waist to hip ratio. Children’s unhealthy food choices were predictive of high body mass index and high systolic blood pressure, whereas older age and less physical activity in children were predictors of high diastolic blood pressure. Developing culturally sensitive and developmentally appropriate interventions to reduce overweight and high blood pressure is critical to reduce health disparities among minority children

    Improvement in the Reproducibility and Accuracy of DNA Microarray Quantification by Optimizing Hybridization Conditions

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    BACKGROUND: DNA microarrays, which have been increasingly used to monitor mRNA transcripts at a global level, can provide detailed insight into cellular processes involved in response to drugs and toxins. This is leading to new understandings of signaling networks that operate in the cell, and the molecular basis of diseases. Custom printed oligonucleotide arrays have proven to be an effective way to facilitate the applications of DNA microarray technology. A successful microarray experiment, however, involves many steps: well-designed oligonucleotide probes, printing, RNA extraction and labeling, hybridization, and imaging. Optimization is essential to generate reliable microarray data. RESULTS: Hybridization and washing steps are crucial for a successful microarray experiment. By following the hybridization and washing conditions recommended by an oligonucleotide provider, it was found that the expression ratios were compressed greater than expected and data analysis revealed a high degree of non-specific binding. A series of experiments was conducted using rat mixed tissue RNA reference material (MTRRM) and other RNA samples to optimize the hybridization and washing conditions. The optimized hybridization and washing conditions greatly reduced the non-specific binding and improved the accuracy of spot intensity measurements. CONCLUSION: The results from the optimized hybridization and washing conditions greatly improved the reproducibility and accuracy of expression ratios. These experiments also suggested the importance of probe designs using better bioinformatics approaches and the need for common reference RNA samples for platform performance evaluation in order to fulfill the potential of DNA microarray technology

    Population genetic structure of the malaria vector Anopheles nili in sub-Saharan Africa

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    <p>Abstract</p> <p>Background</p> <p><it>Anopheles nili </it>is a widespread efficient vector of human malaria parasites in the humid savannas and forested areas of sub-Saharan Africa. Understanding <it>An. nili </it>population structure and gene flow patterns could be useful for the development of locally-adapted vector control measures.</p> <p>Methods</p> <p>Polymorphism at eleven recently developed microsatelitte markers, and sequence variation in four genes within the 28s rDNA subunit (ITS2 and D3) and mtDNA (COII and ND4) were assessed to explore the level of genetic variability and differentiation among nine populations of <it>An. nili </it>from Senegal, Ivory Coast, Burkina Faso, Nigeria, Cameroon and the Democratic Republic of Congo (DRC).</p> <p>Results</p> <p>All microsatellite loci successfully amplified in all populations, showing high and very similar levels of genetic diversity in populations from West Africa and Cameroon (mean Rs = 8.10-8.88, mean He = 0.805-0.849) and much lower diversity in the Kenge population from DRC (mean Rs = 5.43, mean He = 0.594). Bayesian clustering analysis of microsatellite allelic frequencies revealed two main genetic clusters in the dataset. The first one included only the Kenge population and the second grouped together all other populations. High Fst estimates based on microsatellites (Fst > 0.118, P < 0.001) were observed in all comparisons between Kenge and all other populations. By contrast, low Fst estimates (Fst < 0.022, P < 0.05) were observed between populations within the second cluster. The correlation between genetic and geographic distances was weak and possibly obscured by demographic instability. Sequence variation in mtDNA genes matched these results, whereas low polymorphism in rDNA genes prevented detection of any population substructure at this geographical scale.</p> <p>Conclusion</p> <p>Overall, high genetic homogeneity of the <it>An. nili </it>gene pool was found across its distribution range in West and Central Africa, although demographic events probably resulted in a higher level of genetic isolation in the marginal population of Kenge (DRC). The role of the equatorial forest block as a barrier to gene flow and the implication of such findings for vector control are discussed.</p

    Targeting Several CAG Expansion Diseases by a Single Antisense Oligonucleotide

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    To date there are 9 known diseases caused by an expanded polyglutamine repeat, with the most prevalent being Huntington's disease. Huntington's disease is a progressive autosomal dominant neurodegenerative disorder for which currently no therapy is available. It is caused by a CAG repeat expansion in the HTT gene, which results in an expansion of a glutamine stretch at the N-terminal end of the huntingtin protein. This polyglutamine expansion plays a central role in the disease and results in the accumulation of cytoplasmic and nuclear aggregates. Here, we make use of modified 2′-O-methyl phosphorothioate (CUG)n triplet-repeat antisense oligonucleotides to effectively reduce mutant huntingtin transcript and protein levels in patient-derived Huntington's disease fibroblasts and lymphoblasts. The most effective antisense oligonucleotide, (CUG)7, also reduced mutant ataxin-1 and ataxin-3 mRNA levels in spinocerebellar ataxia 1 and 3, respectively, and atrophin-1 in dentatorubral-pallidoluysian atrophy patient derived fibroblasts. This antisense oligonucleotide is not only a promising therapeutic tool to reduce mutant huntingtin levels in Huntington's disease but our results in spinocerebellar ataxia and dentatorubral-pallidoluysian atrophy cells suggest that this could also be applicable to other polyglutamine expansion disorders as well

    Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles

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    Saliva is a readily accessible and informative biofluid, making it ideal for the early detection of a wide range of diseases including cardiovascular, renal, and autoimmune diseases, viral and bacterial infections and, importantly, cancers. Saliva-based diagnostics, particularly those based on metabolomics technology, are emerging and offer a promising clinical strategy, characterizing the association between salivary analytes and a particular disease. Here, we conducted a comprehensive metabolite analysis of saliva samples obtained from 215 individuals (69 oral, 18 pancreatic and 30 breast cancer patients, 11 periodontal disease patients and 87 healthy controls) using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). We identified 57 principal metabolites that can be used to accurately predict the probability of being affected by each individual disease. Although small but significant correlations were found between the known patient characteristics and the quantified metabolites, the profiles manifested relatively higher concentrations of most of the metabolites detected in all three cancers in comparison with those in people with periodontal disease and control subjects. This suggests that cancer-specific signatures are embedded in saliva metabolites. Multiple logistic regression models yielded high area under the receiver-operating characteristic curves (AUCs) to discriminate healthy controls from each disease. The AUCs were 0.865 for oral cancer, 0.973 for breast cancer, 0.993 for pancreatic cancer, and 0.969 for periodontal diseases. The accuracy of the models was also high, with cross-validation AUCs of 0.810, 0.881, 0.994, and 0.954, respectively. Quantitative information for these 57 metabolites and their combinations enable us to predict disease susceptibility. These metabolites are promising biomarkers for medical screening

    Mechanics rules cell biology

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    Cells in the musculoskeletal system are subjected to various mechanical forces in vivo. Years of research have shown that these mechanical forces, including tension and compression, greatly influence various cellular functions such as gene expression, cell proliferation and differentiation, and secretion of matrix proteins. Cells also use mechanotransduction mechanisms to convert mechanical signals into a cascade of cellular and molecular events. This mini-review provides an overview of cell mechanobiology to highlight the notion that mechanics, mainly in the form of mechanical forces, dictates cell behaviors in terms of both cellular mechanobiological responses and mechanotransduction

    Bowel management for the treatment of pediatric fecal incontinence

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    Fecal incontinence is a devastating underestimated problem, affecting a large number of individuals all over the world. Most of the available literature relates to the management of adults. The treatments proposed are not uniformly successful and have little application in the pediatric population. This paper presents the experience of 30 years, implementing a bowel management program, for the treatment of fecal incontinence in over 700 pediatric patients, with a success rate of 95%. The main characteristics of the program include the identification of the characteristics of the colon of each patient; finding the specific type of enema that will clean that colon and the radiological monitoring of the process
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