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    Shared mechanisms underlying the impact of maternal psychophysical stress and obesity on offspring neurodevelopment

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    Vulnerability to mental illness might find its roots very early during development, already during fetal life. In fact, prenatal adversities can affect brain development by shaping neuronal circuits involved in stress responses, resulting in embedded biological traces that persist throughout life. In this perspective, maternal environment plays a pivotal role in driving fetal neurodevelopment, even more important than purely heritable genetic background. Chapter 1 of this thesis introduces the concept that maternal obesity - a growing public health issue - can be considered as a stressor that, by contributing to establish a sub-optimal intrauterine environment, may derange fetal neurodevelopment. We reviewed in detail clinical and preclinical evidence showing an association between the prenatal exposure to an “obesogenic environment” and a higher risk for the occurrence of neurodevelopmental and psychiatric disorders. An ever increasing body of evidence shows that similar mental health outcomes in the offspring have been observed as a result of either maternal obesity or maternal distress during pregnancy. Thus, in Chapter 2 we propose a “funnel effect” model hypothesizing that prenatal stressors of different nature might trigger shared stress-responsive pathways affecting neuroendocrine system, immune-inflammatory processes and energy metabolism regulation, ultimately resulting in increased vulnerability to psychopathology. Chapter 3 and Chapter 4 (original studies) investigate the shared biological mechanisms underlying the above-mentioned stressors and their effects during specific time windows across neurodevelopment in two C57Bl6/N mouse models of maternal psychophysical stress (PNS) and maternal obesity (mHFD). We focused on oxidative stress as a central player driving fetal brain programming by adverse prenatal conditions. Also for this reason in our mouse models, we administered as preventive strategy the antioxidant N-acetyl-cysteine (NAC) to protect fetal neurodevelopment from stress-derived derangements. In particular, when we focused on the short-term effects, we found a widespread pro-inflammatory profile in fetal brains exposed either to PNS or mHFD - with females being more susceptible - to be associated to placental dysfunctions (Chapter 3). Moreover, investigation of the long-term effects of PNS and mHFD specifically during adolescence showed similar effects in the offspring, characterized by reduced brain anti-oxidant defenses and impairments in hippocampal Bdnf levels, overall leading to alterations in the emotional behavior and hypothalamic-pituitary-adrenal axis functionality, in a sex-dependent fashion. Maternal NAC administration, by restoring the redox balance, showed long-term protective effects on brain development (Chapter 4). Together, our findings contribute to support our original “funnel effect” model to explain the converging effects of different stressors on offspring brain development. Above all, a pivotal role of redox signaling was highlighted as the orchestrator of a synchronized response to early adversities by the neuroendocrine and the immune system, among others. In addition, we unveil clear sex-specific differences that drive the programming effects of prenatal stressors on neurodevelopment

    Inflammatory Signatures of Maternal Obesity as Risk Factors for Neurodevelopmental Disorders: Role of Maternal Microbiota and Nutritional Intervention Strategies

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    Obesity is a main risk factor for the onset and the precipitation of many non-communicable diseases. This condition, which is associated with low-grade chronic systemic inflammation, is of main concern during pregnancy leading to very serious consequences for the new generations. In addition to the prominent role played by the adipose tissue, dysbiosis of the maternal gut may also sustain the obesity-related inflammatory milieu contributing to create an overall suboptimal intrauterine environment. Such a condition here generically defined as “inflamed womb” may hold long-term detrimental effects on fetal brain development, increasing the vulnerability to mental disorders. In this review, we will examine the hypothesis that maternal obesity-related gut dysbiosis and the associated inflammation might specifically target fetal brain microglia, the resident brain immune macrophages, altering neurodevelopmental trajectories in a sex-dependent fashion. We will also review some of the most promising nutritional strategies capable to prevent or counteract the effects of maternal obesity through the modulation of inflammation and oxidative stress or by targeting the maternal microbiota

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

    Dispelling the Myths Behind First-author Citation Counts

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    We 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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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