721 research outputs found

    Maternal Fructose Intake Causes Developmental Reprogramming of Hepatic Mitochondrial Catalytic Activity and Lipid Metabolism in Weanling and Young Adult Offspring

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    Excess dietary fructose is a major public health concern, yet little is known about its influence on offspring development and later-life disease when consumed in excess during pregnancy. To determine whether increased maternal fructose intake could have long-term consequences on offspring health, we investigated the effects of 10% w/v fructose water intake during preconception and pregnancy in guinea pigs. Female Dunkin Hartley guinea pigs were fed a control diet (CD) or fructose diet (FD; providing 16% of total daily caloric intake) ad libitum 60 days prior to mating and throughout gestation. Dietary interventions ceased at day of delivery. Offspring were culled at day 21 (D21) (weaning) and at 4 months (4 M) (young adult). Fetal exposure to excess maternal fructose intake significantly increased male and female triglycerides at D21 and 4 M and circulating palmitoleic acid and total omega-7 through day 0 (D0) to 4 M. Proteomic and functional analysis of significantly differentially expressed proteins revealed that FD offspring (D21 and 4 M) had significantly increased mitochondrial metabolic activities of β-oxidation, electron transport chain (ETC) and oxidative phosphorylation and reactive oxygen species production compared to the CD offspring. Western blotting analysis of both FD offspring validated the increased protein abundances of mitochondrial ETC complex II and IV, SREBP-1c and FAS, whereas VDAC1 expression was higher at D21 but lower at 4 M. We provide evidence demonstrating offspring programmed hepatic mitochondrial metabolism and de novo lipogenesis following excess maternal fructose exposure. These underlying asymptomatic programmed pathways may lead to a predisposition to metabolic dysfunction later in life

    Multiple range query optimization in spatial databases

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    Improving questions on sexual partnerships: Lessons learned from cognitive interviews for Britain's third national survey of sexual attitudes and lifestyles ("Natsal-3")

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    Patterns of sexual partnership formation and dissolution are key drivers of sexually transmitted infection transmission. Sexual behavior survey participants may be unable or unwilling to report accurate details about their sexual partners, limiting the potential to capture information on sexual mixing and timing of partnerships. We examined how questions were interpreted, including recall strategies and judgments made in selecting responses, to inform development of a module on recent sexual partnerships in Britain’s third National Survey of Sexual Attitudes and Lifestyles (“Natsal-3”). Face-to-face cognitive interviews were conducted with 14 men and 18 women aged 18–74 years, during development work for Natsal-3. People with multiple recent partners were purposively sampled and questions were presented as a computer-assisted self-interview. Participants were generally agreeable to answering questions about their sexual partners and practices. Interpretation of questions designed to measure concurrent (overlapping) partnerships was broadly consistent with the epidemiological concept of concurrency. Partners’ ages, genders, ethnicity, and participants’ perceptions of whether partner(s) had had concurrent partnerships were reported without offense. Recall problems and lack of knowledge were reported by some participants (of all ages), especially about former, casual, and/or new partnerships, and some reported guessing partners’ ages and dates of sex. Generally, participants were able to answer questions about their sexual partners accurately, even when repeated for multiple partners. Cognitive interviews provided insight into the participants’ understanding of, ability to answer, and willingness to answer questions. This enabled us to improve questions used in previous surveys, refine new questions, and ensure the questionnaire order was logical for participants

    A tale of two capitalisms: preliminary spatial and historical comparisons of homicide rates in Western Europe and the USA

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    This article examines comparative homicide rates in the United States and Western Europe in an era of increasingly globalized neoliberal economics. The main finding of this preliminary analysis is that historical and spatial correlations between distinct forms of political economy and homicide rates are consistent enough to suggest that social democratic regimes are more successful at fostering the socio-cultural conditions necessary for reduced homicide rates. Thus Western Europe and all continents and nations should approach the importation of American neo-liberal economic policies with extreme caution. The article concludes by suggesting that the indirect but crucial causal connection between political economy and homicide rates, prematurely pushed into the background of criminological thought during the ‘cultural turn’, should be returned to the foreground

    Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

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    Over 30 years ago Professor David Barker first proposed the theory that events in early life could explain an individual\u27s risk of non-communicable disease in later life: the developmental origins of health and disease (DOHaD) hypothesis. During the 1990s the validity of the DOHaD hypothesis was extensively tested in a number of human populations and the mechanisms underpinning it characterised in a range of experimental animal models. Over the past decade, researchers have sought to use this mechanistic understanding of DOHaD to develop therapeutic interventions during pregnancy and early life to improve adult health. A variety of animal models have been used to develop and evaluate interventions, each with strengths and limitations. It is becoming apparent that effective translational research requires that the animal paradigm selected mirrors the tempo of human fetal growth and development as closely as possible so that the effect of a perinatal insult and/or therapeutic intervention can be fully assessed. The guinea pig is one such animal model that over the past two decades has demonstrated itself to be a very useful platform for these important reproductive studies. This review highlights similarities in the in utero development between humans and guinea pigs, the strengths and limitations of the guinea pig as an experimental model of DOHaD and the guinea pig\u27s potential to enhance clinical therapeutic innovation to improve human health. (Figure presented.)

    Improving pregnancy outcomes in humans through studies in sheep

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    Experimental studies that are relevant to human pregnancy rely on the selection of appropriate animal models as an important element in experimental design. Consideration of the strengths and weaknesses of any animal model of human disease is fundamental to effective and meaningful translation of preclinical research. Studies in sheep have made significant contributions to our understanding of the normal and abnormal development of the fetus. As a model of human pregnancy, studies in sheep have enabled scientists and clinicians to answer questions about the etiology and treatment of poor maternal, placental, and fetal health and to provide an evidence base for translation of interventions to the clinic. The aim of this review is to highlight the advances in perinatal human medicine that have been achieved following translation of research using the pregnant sheep and fetus

    Linking microscale morphologies to localised performance in singlet fission quantum dot photon multiplier thin films

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    Hybrid small-molecule/quantum dot films have the potential to reduce thermalization losses in single-junction photovoltaics as photon multiplication devices. Here grazing incidence X-ray scattering, optical microscopy and IR fluorescence microscopy (probing materials at two distinct wavelengths), provide new insight into highly complex morphologies across nm and μm lengthscales to provide direct links between morphologies and photon multiplication performance. Results show that within the small molecule crystallites three different QD morphologies may be identified; (i) large quantum dot aggregates at the crystallite nucleus, (ii) relatively well-dispersed quantum dots and (iii) as aggregated quantum dots “swept” from the growing crystallite and that regions containing aggregate quantum dot features lead to relatively poor photon multiplication performance. These results establish how combinations of scattering and microscopy may be employed to reveal new insights into the structure and function of small molecule:quantum dot blends
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