1,720,973 research outputs found
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
Structure network-based landscape of rhodopsin misfolding by mutations and algorithmic prediction of small chaperone action
Full text linkFailure of a protein to achieve its functional structural state and normal cellular location contributes to the etiology and pathology of heritable human conformational diseases. The autosomal dominant form of retinitis pigmentosa (adRP) is an incurable blindness largely linked to mutations of the membrane protein rod opsin. While the mechanisms underlying the noxious effects of the mutated protein are not completely understood, a common feature is the functional protein conformational loss. Here, the wild type and 39 adRP rod opsin mutants were subjected to mechanical unfolding simulations coupled to the graph theory-based protein structure network analysis. A robust computational model was inferred and in vitro validated in its ability to predict endoplasmic reticulum retention of adRP mutants, a feature linked to the mutation-caused misfolding. The structure-based approach could also infer the structural determinants of small chaperone action on misfolded protein mutants with therapeutic implications. The approach is exportable to conformational diseases linked to missense mutations in any membrane protein
Calpain Activation Is the Major Cause of Cell Death in Photoreceptors Expressing a Rhodopsin Misfolding Mutation
Full text linkThe majority of mutations in rhodopsin (RHO) cause misfolding of the protein and has been linked to degeneration of photoreceptor cells in the retina. A lot of attention has been set on targeting ER stress for the development of new therapies for inherited retinal degeneration caused by mutations in the RHO gene. Nevertheless, the cell death pathway activated by RHO misfolded protein is still debated. In this study, we analyzed the retina of the knock-in mouse expressing the P23H misfolded mutant RHO. We found persistent unfolded protein response (UPR) during degeneration. Interestingly, long-term stimulation of the PERK branch of ER stress had a protective effect by phosphorylating nuclear factor erythroid 2–related factor 2 (NRF2) transcription factor, associated with antioxidant responses. Otherwise, we provide evidence that increased intracellular calcium and activation of calpains strongly correlated with rod photoreceptor cell death. By blocking calpain activity, we significantly decreased the activation of caspase-7 and apoptosis-inducing factor (AIF), two cell death effectors, and cell demise, and effectively protected the retina from degeneration caused by the P23H dominant mutation in RHO
Serotonergic modulation by 5-HT7 receptors in mouse spinal cord dorsal horn
No full textBackground
Serotonergic receptors of the 5-HT7 type (5-HT7Rs) are widely expressed in the central nervous system, where they modulate seve ral functions, such as sleep induction, learning, mood, and vegetative behaviours. Along the pain axis, 5-HT7Rs are expressed on
nociceptive primary afferent fibers and in the dorsal horn, both on neurons and astrocytes. [1]. Behavioural experiments have produ ced controversial results about anti- and pro-nociceptive actions of 5-HT7Rs. The low agonist selectivity and the different pain animal
models used have likely contributed to the heterogeneity of the results [2].
To investigate the effects of 5-HT7Rs on spinal pain, we have performed an electrophysiological study on mouse spinal cord slices,
using the selective agonist LP-211 [3]. The recorded neurons have been functionally characterized, in order to identify the neural
circuits involved in the serotonergic modulation.
Methods
Patch-clamp recording was performed on lamina II neurons in spinal cord slices obtained from postnatal CD1 mice (P15-P25) [4]. Excitatory
postsynaptic currents (EPSCs) were recorded in voltage clamp; evoked EPSCs were elicited by stimulating the dorsal root with a suction
electrode in the Aδ and C fibers range.
Results
Application of 1 μM LP-211 to the spinal cord slice induced a facilitation of glutamatergic transmission: the frequency of spontaneous
EPSCs was significantly increased in a subpopulation of neurons (control: 0.9±0.2 Hz; LP-211: 1.8±0.6 Hz; 5 responsive neurons out of
8). The recorded neurons were characterized from their firing pattern: significant effects of LP-211 were observed in both tonic and de layed firing neurons, corresponding to inhibitory and excitatory interneurons, respectively.
Application of 1 μM LP-211 in the presence of 10 μM SB269970 (a 5-HT7R antagonist) did not alter spontaneous EPSC frequency in 11
lamina II neurons, confirming the involvement of 5-HT7Rs in glutamate release facilitation.
EPSCs evoked by dorsal root stimulation were also tested with LP-211. The currents, evoked by paired pulse protocol, were significantly
potentiated by the compound (mean potentiation: 19±4.2%; 4 responsive neurons out 7). The second EPSC was less potentiated than
the first and the paired pulse ratio decreased in 3 neurons.
Conclusion
The compound LP-211 is able to selectively activate 5-HT7Rs in the dorsal horn, causing a facilitatory effect of both spontaneous and
evoked EPSCs. The decrease of paired-pulse ratio suggests that LP-211 activates presynaptic 5-HT7Rs, increasing glutamate release.
The study of specific effects of these receptors on the different neuron populations will be critical to determine whether 5-HT7Rs exert
anti- or pro-nociceptive effects at the spinal level.
References
1. Cortes-Altamirano JL et al., Curr. Neuropharm, 2018, 16:210-221
2. Bardoni R, Curr. Neuropharm, 2019, 17:1133-1145
3. Hedlund PB et al, Neurosci Lett. 2010 481:12-6.
4. Betelli C et al., Mol. Pain, 2015, 11:
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
Differential Contribution of Calcium-Activated Proteases and ER-Stress in Three Mouse Models of Retinitis Pigmentosa Expressing P23H Mutant RHO
No full textAutosomal dominant retinitis pigmentosa (adRP) is mainly caused by mutations responsible for rhodopsin (RHO) misfolding. Although it was previously proved that unfolded RHO is retained into the endoplasmatic reticulum (ER) eliciting ER-stress, consequent mechanisms underlying photoreceptor degeneration need to be further clarified. Several animal models of RHO mutants have been developed for this purpose and for development of neuroprotective treatments. Here, we compared two of the most used models of adRP, the P23H mutant RHO transgenic and knock-in mouse models, in order to define which are their limits and potentials. Although they were largely used, the differences on the activation of the cell death pathways occurring in these two models still remain to be fully characterized. We present data proving that activation of calpains is a mechanism of cell death shared by both models and that molecules targeting calpains are neuroprotective. Conversely, the role of ER-stress contribution to cell death appears to be divergent and remains controversial
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
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