1,721,022 research outputs found
Selective ligands for the angiotensin ii receptors
No full textIn the past decade a great deal of structural information for class A-GPCRs (G protein-coupled receptors) has emerged. However, the structural and electronic basis of ligand selectivity for closely related receptor subtypes such as the angiotensin receptors AT1aR and AT2R, which present completely diverse biological functions in response to the same ligand, is poorly understood. In order to monitor complex responses in bio systems it is useful to have ligands that present a gradient in terms of selectivity. In this study we present an efficient method to tune ligand selectivity for the two angiotensin II receptor subtypes, AT1aR and AT2R, by controlling aromatic - prolyl interactions in angiotensin II, through alternation of aromatic electronics. On the basis of this strategy, an AT2R selective and high affinity agonist analogue (Ki=3 nM) was obtained
Brain Asymmetries: the lateralization of three different cognitive processes
Full text linkThe hemispheric lateralization has received attention across years because its implication in determine behavioural and individual differences. Specifically, the left hemisphere’s expansion and specialization in the course of the evolution received a lot of attention for its involvement in language functioning. Nevertheless, also the right hemisphere expanded and, in particular, the right parietal lobe increased its dimension and its connections, becoming a specialized area for the multisensory integration mechanisms. Even if the parietal lobe has been extensively studied, there are still unanswered questions about the lateralization of different cognitive processes related to this area.
Given the broad implication of the parietal areas in several cognitive processes, in this thesis three stand-alone studies on healthy population are presented. The studies are independent even if all of them aim at exploring the lateralization of cognitive processes typically related to the parietal areas. A hierarchical structure was followed from the most basic to the most complex cognitive process: (i) visuo-spatial attention, (ii) motor behaviour and (iii) body representation.
In the first study, thirty-six right- and left-handers participants were tested during perceptual (Line Bisection) and representational (Mental Number Line) tasks. Taking into consideration the attentional bias (pseudoneglect), results showed a greater difference between the perceptual and representational domains in the left-handers group. This difference is led by a bias farther to the left in the representational domain, but not in the perceptual one, compared to right-handers. These results suggest that right- and left-handers are differently affected by attentional asymmetries depending on the domain being representational or perceptual.
The second study aimed at exploring the lateralization of the bimanual temporal coupling effect. Thirty-two participants were tested during a bimanual task while the transcranial Direct Current Stimulation was applied over right and left parietal area. Results highlight different effects of the stimulation depending on the level of complexity of the movement.
In the third study, eighteen participants were tested during implicit (not requiring awareness) and explicit (requiring awareness) body-schema related tasks while a cathodic or sham transcranial Direct Current Stimulation was delivered on the right parietal area. Results highlight an effect of stimulation specific for the implicit task, and selective for identification processes rather than widespread to motor related aspects. These results challenge the general idea of a right hemispheric dominance, and rather suggest that body schema processes rely on a bilateral network dependent on awareness encompassing both the left and the right hemisphere.
The three studies together highlight that a black or white hemispheric lateralization of cognitive processes related to parietal areas is not feasible at this point. Indeed, specific features (domain, complexity and awareness) play an important role in concluding for a right or left dominance. For this reason, future studies are needed in order to clarify their weight using different techniques together
MUTATED FORM OF NADPH OXIDASES
No full textThe present invention relates to a mutation of the catalytic domain of a NADPH oxidase (NOX) and the use thereof to facilitate crystal structure determination, and to the corresponding mutated form of NOX and the use thereof to design and produce chemical scaffolds for the generation of NOX ligands effective in different diseases
Regulation of the serotonin transporter by interacting proteins
No full textThe serotonin transporter (SERT) plays a critical role in the maintenance of normal neurotransmission by serotonin [5-hydroxytryptamine (5-HT)]. Recent evidence suggests that SERT and other neurotransmitter transporters are tightly regulated. Activation of protein kinase C results in a decrease in SERT-mediated 5-HT uptake, which is due to an internalization of the transporter. However, to date little is known about the mechanism and proteins involved in the down-regulation of the transporter. One candidate SERT-regulatory protein is the SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) protein, syntaxin 1A (Syn1A), which has recently been implicated in the regulation of ion channels as well as the SERT-related gamma-aminobutyric acid- and glycine-transporters. Using 5-HT uptake assays, confocal microscopy and glutathione S-transferase (GST) pull-down assays we showed that Syn1A also interacts with SERT and alters the subcellular localization of the transporter, resulting in a reduction of 5-HT transport. In addition, we have used the yeast two-hybrid system to search for novel regulatory proteins that interact with the cytoplasmic N-terminal domain of SERT. By screening rat brain cDNA library we have identified six potential SERT-binding proteins. Here we also present progress towards the elucidation of the biological relevance of these proteins and their potential role for the regulation of the serotonin transporter
Multiple dissociations in patients with disorders of body awareness: Implications for the study of consciousness
No full text
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
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