1,721,007 research outputs found
Maternal undernutrition leads to endothelial dysfunction in adult male rat offspring independent of postnatal diet
No full textIncreasing evidence suggests a role for prenatal environment in the onset of cardiovascular and metabolic disease in later life. In the rat, undernutrition in utero and a postnatal high-fat diet gives rise to a phenotype similar to the metabolic syndrome. As endothelial dysfunction is a feature of both CVD and the metabolic syndrome we investigated the impact of maternal undernutrition and/or postnatal high-fat on endothelial function. Virgin Wistar rats were mated and randomly assigned to groups to receive food either ad libitum (control) or at 30 % of ad libitum intake throughout gestation. At postnatal day 250, a cohort from each group was challenged with a high-fat diet (D12451, 45 % energy from fat; Research Diets, Inc., New Brunswick, NJ, USA) for the remainder of the study. At 1 year of age, small mesenteric arteries were dissected and mounted on a wire myograph and responses to phenylephrine, endothelin, acetylcholine, leptin and sodium nitroprusside assessed. Vasoconstriction to endothelin was significantly enhanced in all groups compared with controls (-log effective concentration equal to 50 % of the maximal response (pEC50); P < 0.001). Endothelium-dependent vasodilatation to acetylcholine was significantly blunted in all groups compared with controls (% maximum response; P < 0.01), while dilatation to leptin and sodium nitroprusside was similar in all groups. These data demonstrate that both maternal undernutrition and postnatal high fat lead to vascular alterations and suggest that maternal undernutrition alone is at least as detrimental to offspring endothelial function as a long-term exposure to a high-fat diet in the offspring<br/
Leptin reversal of the metabolic phenotype: evidence for the role of developmental plasticity in the development of the metabolic syndrome
No full textEvents in early life are associated with changes in the risk of disease in later life. There is increasing evidence that these associations are mediated by permanent transcriptional changes in metabolic pathways, in some cases linked to epigenetic alterations. We have proposed that this phenomenon of 'developmental induction' is not a manifestation of pathophysiological processes but rather represents the consequence of developmental decisions made during fetal and early postnatal life to maximize subsequent fitness. However, this fitness advantage is lost if the early and later environments are mismatched. Rats undernourished in utero by maternal underfeeding develop features of the metabolic syndrome, especially if fed on a high-fat diet, but transient neonatal treatment with leptin reverses induction of this adverse metabolic phenotype. This observation demonstrates that developmental programming is reversible and provides strong support for the match-mismatch or predictive model for the origins of developmental programming
Pre- and postnatal nutritional histories influence reproductive maturation and ovarian function in the rat
No full textBackgroundWhile prepubertal nutritional influences appear to play a role in sexual maturation, there is a need to clarify the potential contributions of maternal and childhood influences in setting the tempo of reproductive maturation. In the present study we employed an established model of nutritional programming to evaluate the relative influences of prenatal and postnatal nutrition on growth and ovarian function in female offspring.MethodsPregnant Wistar rats were fed either a calorie-restricted diet, a high fat diet, or a control diet during pregnancy and/or lactation. Offspring then were fed either a control or a high fat diet from the time of weaning to adulthood. Pubertal age was monitored and blood samples collected in adulthood for endocrine analyses.ResultsWe report that in the female rat, pubertal timing and subsequent ovarian function is influenced by the animal's nutritional status in utero, with both maternal caloric restriction and maternal high fat nutrition resulting in early pubertal onset. Depending on the offspring's nutritional history during the prenatal and lactational periods, subsequent nutrition and body weight gain did not further influence offspring reproductive tempo, which was dominated by the effect of prenatal nutrition. Whereas maternal calorie restriction leads to early pubertal onset, it also leads to a reduction in adult progesterone levels later in life. In contrast, we found that maternal high fat feeding which also induces early maturation in offspring was associated with elevated progesterone concentrations.ConclusionsThese observations are suggestive of two distinct developmental pathways leading to the acceleration of pubertal timing but with different consequences for ovarian function. We suggest different adaptive explanations for these pathways and for their relationship to altered metabolic homeostasis
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
No full text“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Decoding the regulatory landscape of psychiatric and alcohol use disorders
No full textEpidemiological research has shown that psychiatric and substance use disorders are
multimorbid conditions that are characterized by significant and complex genetic etiology. While
genome-wide association studies (GWAS) have identified thousands of single-nucleotide
polymorphisms (SNPs) associated with psychiatric and substance use disorders, the mechanisms
by which these SNPs contribute to the observed multimorbidities remain largely unknown. This
is because more than 90% of these SNPs reside in the non-coding regions of the genome, which
makes interpretation of their functional impacts challenging. To address this challenge, I integrated
different distinct levels of biological information (i.e. SNPs, gene expression, spatial genome
organization and protein-protein interactions) to identify tissue-specific regulatory impacts of
psychiatric and alcohol dependence-associated SNPs on biological pathways. This enabled me to
determine potential regulatory mechanisms that can explain the underlying multimorbidity among
these phenotypes. First, I have analysed 2,893 GWAS SNPs associated with attention-deficit
hyperactivity disorder (ADHD), anxiety, bipolar disorder (BD), unipolar depression (UD),
schizophrenia and cognitive functioning to identify the genes and biological pathways they control.
The analysis revealed 33 genes and 62 pathways that were commonly affected by tissue-specific
regulatory interactions associated with all six phenotypes. Next, I have identified the tissue-specific
regulatory landscape of alcohol dependence (AD). Of the AD regulatory interactions I identified,
42% were associated with genes encoding alcohol dehydrogenase (ADH) and aldehyde
dehydrogenase (ALDH) enzymes, and they were mostly linked to adipose and gastrointestinal
tissues. Further analyses of the global patterns of ADH and ALDH regulatory interactions
revealed ADH associations with AD-related traits and ALDH associations with psychiatric
disorders and cognition. Finally, I have identified the cortex-specific regulatory impacts of 344
SNPs associated with autism spectrum disorder, and showed that these SNPs were also linked to
other psychiatric disorders (e.g. schizophrenia, ADHD, BD). Subsequent protein-protein
interaction analysis revealed that these SNPs impact on immune pathways, fatty acid metabolism,
ribosome biogenesis, aminoacyl-tRNA biosynthesis and spliceosomes in the fetal cortex. By
contrast in the adult cortex, they largely affect immune pathways. Collectively, these results
highlight potential regulatory mechanisms and key pathways underlying the development of
psychiatric and substance use disorders, and their observed multi/co-morbidities. This integrative
approach, in combination with clinical studies, will contribute to personalized mechanistic
understandings of these complex disorders
Oraanga Meitaki: Early-life health for lifelong and transgenerational wellbeing in the Cook Islands
No full textNon-communicable diseases (NCDs) are the number one cause of death worldwide, disproportionately affecting developing countries. In the Cook Islands, 89.5% of adults are overweight, and 33% are diagnosed with an NCD. The Developmental Origins of Health and Disease (DOHaD) paradigm indicates that early-life environmental exposures can influence lifelong and transgenerational health and has informed global risk-reduction and health promotion strategies. However, there is a lack of this research in developing countries, particularly in Pacific Island nations. Given the very high NCD burden carried by these nations, this gap in evidence requires urgent attention.
This research was based in Rarotonga, Cook Islands, and aimed to explore the relevance of DOHaD for this setting. The five key objectives included: conducting a systematic review to identify geographical gaps in global DOHaD research, creating a health profile of Year 9 students (13-14-year-olds) living in Rarotonga, investigating associations between birth factors and health in Rarotongan-born adolescents, engaging Cook Islands community members to explore options for communicating DOHaD messages and co-constructing a local early-life nutrition resource. A partnership between the University of Auckland and the Cook Islands Ministries of Health and Education underpinned this project. The main frameworks utilised in this collaborative project were critical realism, the Tivaevae model, community-based participatory research and integrated knowledge translation.
Key findings indicated that of the 538 adolescents measured in Rarotonga, 62.4% were affected by overweight/obesity, 39.8% had raised blood pressure, and 37.3% had raised total cholesterol. When matched with early-life factors, inverse associations were found between newborn head circumference and adolescent blood pressure (p=0.038), birth order and adolescent blood glucose levels (p=0.017), and between birth weight and central obesity in adolescence (p=0.044). In order to translate this evidence into meaningful outcomes, a local early-life nutrition resource was co-constructed with input and critique from 60 participants across ten professional and lay groups in Rarotonga.
Overall, this research highlighted the relevance of DOHaD for the Cook Islands and the opportunity for strategies to be co-constructed and implemented in order to reduce the growing NCD burden and to optimise the health of future generations
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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