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From animal to human epigenetics
No full textA rat story: Behavioral epigenetics beginnings
Human neurodevelopment is a dynamic and protracted process. It starts in the pre-natal life,
driven by genetic information, and continues unfolding following region-specific pathways up
to early adulthood (Gogtay et al., 2004; Koenderink & Uylings, 1995; Petanjek et al., 2011). Es
pecially during the pre-natal and early post-natal life, the developing brain depends on and is
sensitive to external inputs that shape its architecture and fine-tune neural connectivity patterns
according to environmental requirements (Branchi & Cirulli, 2014; Fox, Levitt, & Nelson, 2010;
Hensch, 2005; Takesian & Hensch, 2013; Teicher, Samson, Anderson, & Ohashi, 2016). Environ
mental inputs are therefore critical for a normative development. On the other hand, adverse
conditions occurring during sensitive periods for the nervous system maturation can interact
with genetic make-up and bias developmental trajectories toward maladaptive outcomes, as dem
onstrated by increased occurrence of psychopathology and psychiatric conditions following
childhood neglect, maltreatment and abuse (Benjet, Borges, & Medina-Mora, 2010; Bick &
Nelson, 2016; Cohen, Brown, & Smaile, 2001; Green et al., 2010; Kessler et al., 2010;
Widom, 1999).
It has been suggested that modifications of adult brain function and behavior changes induced
by early experiences can be determined by changes in the epigenetic status of specific genes (Bale
et al., 2010; Fraga et al., 2005; Maccari, Krugers, Morley-Fletcher, Szyf, & Brunton, 2014;
Tsankova, Renthal, Kumar, & Nestler, 2007). In fact, epigenetic mechanisms, including DNA
methylation, histone modifications, and non-coding RNAs regulation can be affected by various
extrinsic factors, providing a molecular link between external cues and gene expression (Kang
et al., 2011; Maze et al., 2014; Nord, Pattabiraman, Visel, & Rubenstein, 2015; Shibata,
Gulden, & Sestan, 2015).
Human studies evidence that individuals exposed to adversity in early post-natal life (Romens,
McDonald, Svaren, & Pollak, 2015; Tyrka, Price, Marsit, Walters, & Carpenter, 2012; van der
Knaap et al., 2014), or during pre-natal life (Mulligan, D’Errico, Stees, & Hughes, 2012; Perroud
et al., 2014) exhibit altered methylation of genes involved in hypothalamic-pituitary-adrenal (HPA)
axis functionality, as the NR3C1 gene coding glucocorticoid receptors (GR), a key element for the ho
meostasis of stress response system (Herman et al., 2016; Sapolsky, Meaney, & McEwen, 1985).
In turn, altered NR3C1 methylation levels have been associated to emotional and behavioral problems, externalizing and internalizing symptoms (Cicchetti & Handley, 2017; Dadds, Moul, Hawes, Mendoza
Diaz, & Brennan, 2015; Parade et al., 2016; Perroud et al., 2014; van der Knaap, van Oort, Verhulst,
Oldehinkel, & Riese, 2015). Further, reduced levels of NR3C1 messenger RNA (mRNA) and mRNA
transcripts, as well as increased cytosine methylation of the NR3C1 promoter were found in suicide
victims with a history of childhood abuse compared to suicide victims without childhood trauma
and controls (McGowan et al., 2009).
Finally, longitudinal studies on very preterm infant admitted to neonatal intensive care unit, and
thus subjected to pain-related stress and maternal separation, evidence an altered serotonin transporter
gene (SLC6A4) methylation status, predictive of enhanced socio-emotional stress reactivity and asso
ciated with less-than-optimal score at Personal-Social scale of Griffith Mental Development Scales at
12 months of age (Fumagalli et al., 2018; Montirosso et al., 2016; Provenzi, Guida, &
Montirosso, 2018).
Taken together, these findings corroborate an association between environmental experiences,
epigenetic modifications and behavioral outcomes.
Nevertheless, the cascade of biochemical events through which the environment is embedded in the
individual biology, affecting physiology and behavior remains unclear. In addition, not all individuals
exposed to early life adversity develop health issues, psychopathology or psychiatric disorders
(Collishaw et al., 2007; Yehuda & LeDoux, 2007). Though, the genetic make-up, epigenetic charac
teristics, and risk and protective factors that render individuals differently sensitive to environmental
influences are not yet understood (Belsky et al., 2009; Belsky & Pluess, 2009; Branchi, 2011).
Several aspects hamper the possibility to draw firm conclusions from human studies. Retrospective
designs rely on indirect information about the conditions of the participant, and even when information
is available or directly collected within prospective studies, it is virtually impossible to disentangle the
contribution of multiple factors occurring in pre-natal and post-natal life on specific physiological and
behavioral outcomes.
Moreover, both retrospective and prospective human studies depend on availability and access to
appropriate tissues for epigenetic analysis and are based primarily on saliva, blood and buccal cells
samples. Nonetheless, epigenetic patterns appear to be tissue and gene specific (Forest et al., 2018;
Smith et al., 2015) and there is little consensus on how much changes observed in peripheral tissues
may correlates each other and resemble changes in nervous tissue (Di Sante et al., 2018; Thompson
et al., 2013; Walton et al., 2016).
Animal models have strongly stimulated and complemented human studies (Phillips & Roth,
2019)(Box 1). Indeed, the animal models allow to prospectively manipulate the onset, quality, du
ration and predictability of environmental exposures under controlled conditions and to evaluate im
mediate, long-term and trans-generational consequences on candidate gene expression and behavior.
Laboratory animals can be exposed to aversive or permissive environments at different develop
mental time points and both genomic and non-genomic inheritance can be systematically investigated
(Bohacek & Mansuy, 2015, 2017; Francis, Diorio, Liu, & Meaney, 1999; Jirtle & Skinner, 2007;
Mitchell et al., 2016; Richards, 2006). In addition, since epigenetic reactions are bidirectional and po
tentially reversible (Cervoni & Szyf, 2001; Roth, Denu, & Allis, 2001) the causal relationship between
different epigenetic identities and behavioral outcomes can be addressed in animal models by admin
istering specific molecular compounds able to promote or inhibit epigenetic mechanisms as DNA
methylation (Keller, Doherty, & Roth, 2018, 2019; Weaver et al., 2004, 2005; Weaver, Meaney, &
Szyf, 2006).
Here, we report the contribution of animal studies, in particular, laboratory rats (Rattus norvegicus)
and mice (Mus musculus), to the field of human behavioral epigenetics. The chapter focuses on the role
of maternal environment as one of the most studied vectors in inducing epigenetic modifications and
enduring phenotype in the offspring. In addition, studies on the interplay among genetic polymor
phisms, epigenome and aversive environments in contributing to psychiatric disorders and, as a bright
note, on the effect of the exposure to permissive environment (with attention to environmental enrich
ment) will be reported
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Pre-reproductive parental enriching experiences influence progeny’s developmental trajectories
Full text linkWhile the positive effects of environmental enrichment (EE) applied after weaning, in adulthood, during aging, or even in the presence of brain damage have been widely described, the transgenerational effects of pre-reproductive EE have been less examined. And yet, this issue is remarkable given that parental environmental experience may imprint offspring's phenotype over generations through many epigenetic processes. Interactions between individual and environment take place lifelong even before conception. In fact, the environment pre-reproductively experienced by the mother and/or the father exerts a substantial impact on neural development and motor and cognitive performances of the offspring, even if not directly exposed to social, cognitive, physical and/or motor enrichment. Furthermore, pre-reproductive parental enrichment exerts a transgenerational impact on coping response to stress as well as on the social behavior of the offspring. Among the effects of pre-reproductive parental EE, a potentiation of the maternal care and a decrease in global methylation levels in the frontal cortex and hippocampus of the progeny have been described. Finally, pre-reproductive EE modifies different pathways of neuromodulation in the brain of the offspring (involving brain-derived neurotrophic factor, oxytocin and glucocorticoid receptors). The present review highlights the importance of pre-reproductive parental enrichment in altering the performances not only of animals directly experiencing it, but also of their progeny, thus opening the way to new hypotheses on the inheritance mechanisms of behavioral trait
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe 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
Full text linkWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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