1,720,983 research outputs found
Metaplastic Effects of Ketamine and MK-801 on Glutamate Receptors Expression in Rat Medial Prefrontal Cortex and Hippocampus
Get PDFKetamine and MK-801 by blocking NMDA receptors may induce reinforcing effects as well as schizophrenia-like symptoms. Recent results showed that ketamine can also effectively reverse depressive signs in patients' refractory to standard therapies. This evidence clearly points to the need of characterization of effects of these NMDARs antagonists on relevant brain areas for mood disorders. The aim of the present study was to investigate the molecular changes occurring at glutamatergic synapses 24 h after ketamine or MK-801 treatment in the rat medial prefrontal cortex (mPFC) and hippocampus (Hipp). In particular, we analyzed the levels of the glutamate transporter-1 (GLT-1), NMDA receptors, AMPA receptors subunits, and related scaffolding proteins. In the homogenate, we found a general decrease of protein levels, whereas their changes in the post-synaptic density were more complex. In fact, ketamine in the mPFC decreased the level of GLT-1 and increased the level of GluN2B, GluA1, GluA2, and scaffolding proteins, likely indicating a pattern of enhanced excitability. On the other hand, MK-801 only induced sparse changes with apparently no correlation to functional modification. Differently from mPFC, in Hipp, both substances reduced or caused no changes of glutamate receptors and scaffolding proteins expression. Ketamine decreased NMDA receptors while increased AMPA receptors subunit ratios, an effect indicative of permissive metaplastic modulation; conversely, MK-801 only decreased the latter, possibly representing a blockade of further synaptic plasticity. Taken together, these findings indicate a fine tuning of glutamatergic synapses by ketamine compared to MK-801 both in the mPFC and Hipp
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
MALADAPTIVE PLASTICITY IN ANOREXIA NERVOSA: EVIDENCE OF A PERIPHERY-TO-BRAIN CROSSTALK IN A PRECLINICAL MODEL
Get PDFAnorexia Nervosa (AN) is a devastating psychiatric disorder affecting pubescent females ninefold more than males, in a period of life extremely vulnerable to external stimuli: the adolescence. AN begins with a self-induced restrictive diet to lose weight, below 85% of expected body mass index, that in combination with intense physical activity and aberrant body image concern, it progresses to an out-of-control spiral. In this condition, the positive experience of control on food intake and intense exercise is indeed extremely rewarding for the patient, reinforcing the dieting behavior. AN is associated with the highest mortality rate among the wide family of psychiatric disorders, and despite the knowledge about the clinical symptomatology, AN etiopathogenesis remains unclear, treatment is challenging and often hampered by high relapse. At the neurobiological level, patients suffering from AN display altered neural activity, morphological and functional connectivity in the fronto-striatal and thalamo-cortical circuits. In particular, hypoglutamatergic transmission and aberrant excitability of cortical and striatal regions observed in AN patients might underpin cognitive deficits that fuel the vicious cycle of dieting behavior. It has been suggested that the driving force of such abnormal behavior might be represented by an altered balance between reward and inhibition mechanisms in the brain, the first mainly mediated by the Nucleus Accumbens (NAc), and the latter being normally triggered by the medial prefrontal cortex (mPFC) that is immature and still growing during adolescence. Such dysfunctional mechanisms combined with alterations in the levels of appetite modulators, such as ghrelin and leptin, and dysregulations in peripheral organs and metabolic active tissues functionality may lead to a distorted response to salient stimuli, such as food, fueling the maintenance of the anorexic phenotype. AN is not only a brain disorder but it is rather a systemic disease that affects the whole body, particularly skeletal muscles and circulating hormones, suggesting the presence of a crosstalk between peripheral signals and brain functions.
Therefore, the main goal of this project is to investigate from a preclinical point of view the neurobiological mechanisms involved in the pathophysiology of AN. We pointed our attention to the possibility that the combination of food restriction with intense exercise, the hallmarks of AN, activates dysfunctional periphery-to-brain crosstalk that may drive for weight loss seeking inducing aberrant dieting behaviors, affecting reward processes and cognition, via altered neurometabolic pathways in specific areas of the brain, and in turn, promoting the long-lasting maintenance of AN disorder.
Therefore, with the aim to investigate the central and peripheral alterations in biological mechanisms that may support the anorexic condition and induce cognitive impairments, we employed the well-known animal model of AN, the activity-based anorexia (ABA) rat model, which recapitulates human AN by combining caloric restriction and physical exercise to induce self-induced body-weight loss. We have demonstrated that, under a paradigm of food restriction and free access to a mechanical activity wheel, adolescent female rats showed reduced food intake, reduced body weight and increased running activity on the wheel, thus developing the anorexic phenotype.
To dissect the neurobiological underpinnings of this condition and the cognitive-related dysfunctions during a critical developmental period, we performed structural, morphological and molecular studies on critical brain areas of the reward system, crucially involved in processing feeding information and in mediating high-level cognitive functions such as the NAc and the mPFC. In both AN patients and animal models of AN, evidence exists of glutamate homeostasis dysfunctions, which has been proposed as a signal of altered processing of food reward. Thus, we firstly focused our attention on critical determinants of the glutamatergic synapse evaluating AMPA, NMDA receptors, their scaffolding proteins and their localization at the post-synaptic density, dendritic spines density and morphology, and lastly cognitive-related outcomes. Furthermore, based on the hypothesis that the energy imbalance, via altered regulation of molecules released by peripheral organs, can lead to the alteration of neurocircuits responsible for motivational and cognitive processes, we performed a neurometabolic analysis of the PGC1/FNDC5/Irisin/BDNF pathway, linking molecular alterations in skeletal muscle with alterations in the hippocampus (Hip), respectively involved in physical activity and in memory and learning processes. All the molecular analysis has been performed at two time points: early after the induction of the anorexic phenotype at post-natal day (PND) 42, which mimics the acute phase of the pathology, and after a period of body weight recovery at PND49, in order to investigate both the alterations induced by the AN acute phase and the potential long-lasting alterations that persist even after the body weight recovery period.
Overall, our analysis revealed that the combination of a restricted regimen of food intake and free wheel access induced a general dysregulation of the glutamatergic homeostasis in both NAc and mPFC regions. We observed AMPA and NMDA receptor subunit reorganization and retention in different subcellular fractions, paralleled with structural changes in dendritic spines density and morphology and altered temporal memory performance. Of note, all these alterations persist even after the body weight recovery. Interestingly, the analysis of the neurometabolic axis on the PGC1/FNDC5/Irisin/BDNF pathway revealed an initial hyperactivation of the axis induced by the induction of the acute phase of AN, as shown by increased PGC1 and FNDC5 protein levels in muscle tissues and increased irisin plasma levels observed at PND42. In the Hip, BDNF transcription was increased, while protein translation was reduced specifically in ABA rats. After body weight recovery, despite PGC1 and FNDC5 protein levels were normalized, BDNF expression in the Hip was persistently reduced, suggesting its putative involvement, not only in altering the hippocampal neuroplasticity, but also in the induction of associative reward learning alterations that may underpins the observed long-lasting memory deficits.
In conclusion, the obtained results point toward the reorganization of the glutamatergic synapse structure and composition in crucial brain areas of the reward system, as critical factor in driving the motivational mechanisms that fuel the maladaptive behaviors underlying AN. Moreover, our data provides novel insights in the involvement of a periphery-to-brain neurometabolic crosstalk even when body weight is restored. These molecular determinants of maladaptive plasticity could represent a signal of altered processing of food reward, and a vulnerability trait for relapse. Moreover, the herein shown AN-induced dysregulation of the glutamatergic system and hippocampal BDNF system coupled with an altered metabolic profile might be the trigger that could lead, in turn, to cognitive dysfunction, which is consistently observed in AN patients
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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
- …
