1,721,116 research outputs found
Neural mechanisms of female aggression: Implications on the oxytocin and vasopressin systems
Full text linkAggression is defined as a social behavior that has the intention of physically harming a conspecific. In nature, aggressive behavior emerges whenever an individuum, engages in conflict over essential resources for its survival, such as food, water, territory, and mating partners. Thus, aggression may act as an evolutive force controlling populational levels and keeping hierarchy. However, in humans, when expressed out-of-context and in exacerbated manner aggressive behavior becomes disruptive constituting a severe burden on society. This is especially evident in the excessive as well as pathological levels of aggression expressed by individuals suffering from conduct disorder (CD) in childhood and anti-social personality disorder (ASPD) in adulthood. As violent aggressive behavior causes serious damage not only to the victims but also to the perpetrators, scientists have worked throughout the last decades to understand the neurobiological underpinnings of escalated aggression. In order to do so, several rodent models have been established to study aggressive behavior, using mostly males as model organisms whereas females have been rarely studied. Nevertheless, recent evidence shows that women and girls may develop ASPD and CD just like men and boys, respectively. Additionally, there are some new indications that the neurobiology of aggression might be sex-specific in humans and rodents. Thus, new animal models are necessary to understand the neural mechanisms of female aggression.
In my thesis, I first established and utilized two rat models of female aggression based on different etiologic strategies, namely post-weaning social isolation (PWSI) was used as a model of early life stress-induced aggression whereas a combination of social isolation and aggressive training was used to enhance aggression in an ethological setting in adults rats. These models allowed me to investigate the role of the brain oxytocin (OXT) and vasopressin (AVP) systems on aggressive behavior. Both neuropeptides are known to regulate social including aggressive behaviors in males and lactating females.
Although aggression is a naturally occurring behavior in animals and humans, exacerbated aggressive behavior may also emerge as a maladaptive response to stress. Especially, early life adverse experiences are known to evoke violent aggressive behavior. Thus, in chapter 2 post-weaning social isolation (PWSI) was used as a reliable model of early life stress-induced (ELS) aggression in order to compare its effects on male and female aggression as well as on the endogenous OXT and AVP systems. My results show that males and females displayed similar levels of aggression independent of the housing conditions and that PWSI increased aggression in both male and female Wistar rats. However, abnormal aggression was displayed in a sex-dependent manner, i.e. females exhibited elevated aggression towards juveniles, whereas males tended to show more attack bites and attacks towards vulnerable body parts. In addition, PWSI also impaired social discrimination in both sexes. From a neurobiological point of view, PWSI decreased OXTmRNA in the paraventricular nucleus of the hypothalamus (PVN) and OXT receptor (OXTR) binding in the nucleus accumbens (NAcc), independent of the sex. Regarding the AVP system, I have found that PWSI rats showed decreased AVP 1a receptor (V1aR) binding in the dentate gyrus (DG) and lateral hypothalamus (LH) independent of sex. However, the anterior part of the BNST was affected by PWSI in a sex-dependent manner, i.e. in control conditions, females exhibited higher V1aR binding than males in this region, but after PWSI females had lower V1aR binding than males. Thus, my data supports PWSI as a reliable rat model to instigate exaggerated as well as abnormal aggression not only in males but also in females. In addition, OXTRs in the NAcc and V1aR in the BNSTa, DG, and LH may play a role in the link between PWSI and aggression in rats.
In chapter 3, in order to specifically investigate the role of OXT and AVP on female aggression, social isolation, as well as successive encounters with a same-sex and unknown conspecific (aggression training) (IST), were used to enhance the mild levels os aggression displayed by group-housed (GH) and non-trained females. In comparison to low aggressive GH controls, highly aggressive IST females exhibited elevated levels of OXT and reduced levels of AVP in both CSF and LS in response to a female intruder test (FIT). Furthermore, both OXTR and V1aR binding were decreased in the ventral (vLS) and dorsal (dLS) portion of the LS of IST rats, respectively. Manipulation of both neuropeptide systems using a combination of neuropharmacological, chemo- and optogenetic approaches resulted in dramatic changes in aggression. Elevating OXT availability either centrally or in the vLS of GH rats enhanced aggression. Accordingly, blockade of OXTR, via OXTR antagonist, either centrally or in the vLS decreased aggressive display in IST rats. Regarding the AVP system, synthetic AVP administrated either locally in the dLS or centrally (intracerebroventricular) decreased aggression in IST rats.
Due to the fact of OXT and AVP effects appear to be region- and receptor-specific, i.e. OXT acted via OXTR in the vLS and AVP acted via V1aR in the dLS, I decided to verify whether those two neural populations within the LS interact with each other in a single-cell level after OXTR activation using whole-cell voltage-clamp. OXTR activation increased GABAergic inhibition of dLS neurons whereas decreased GABAergic inhibition of vLS neurons. Next, I decided to evaluate whether those differences in activity were also reflected in vivo after an aggressive encounter, using pERK as a neural activity marker. Aggression differentially regulated pERK expression in the LS, i.e. GABAergic neurons in the dLS showed decreased whereas in the vLS showed increased activation after the FIT. In line with that, pharmacological inhibition of the dLS and vLS enhanced and reduced female aggression, respectively. Taken together this part of my thesis shows that the balance between OXT and AVP release within the LS regulates female aggression in a receptor and region-specific manner via modulating GABAergic neurotransmission.
Overall, this thesis shows that females are able to develop escalated as well as abnormal aggression just like males. In addition, the OXT and the AVP system seem to be main players in regulating aggressive behavior in female Wistar rats, especially, regarding their role in controlling aggression by acting on the LS
Structure-function relationships of the disease-linked A218T oxytocin receptor variant
Full text linkVarious single nucleotide polymorphisms (SNPs) in the oxytocin receptor (OXTR) gene have been associated with behavioral traits, autism spectrum disorder (ASD) and other diseases. The non-synonymous SNP rs4686302 results in the OXTR variant A218T and has been linked to core characteristics of ASD, trait empathy and preterm birth. However, the molecular and intracellular mechanisms underlying those associations are still elusive. Here, we uncovered the molecular and intracellular consequences of this mutation that may affect the psychological or behavioral outcome of oxytocin (OXT)-treatment regimens in clinical studies, and provide a mechanistic explanation for an altered receptor function. We created two monoclonal HEK293 cell lines, stably expressing either the wild-type or A218T OXTR. We detected an increased OXTR protein stability, accompanied by a shift in Ca2+ dynamics and reduced MAPK pathway activation in the A218T cells. Combined whole-genome and RNA sequencing analyses in OXT-treated cells revealed 7823 differentially regulated genes in A218T compared to wild-type cells, including 429 genes being associated with ASD. Furthermore, computational modeling provided a molecular basis for the observed change in OXTR stability suggesting that the OXTR mutation affects downstream events by altering receptor activation and signaling, in agreement with our in vitro results. In summary, our study provides the cellular mechanism that links the OXTR rs4686302 SNP with genetic dysregulations associated with aspects of ASD
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
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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