1,721,078 research outputs found
SCREENING DEI GENI ¿PACEMAKER¿ IN PAZIENTI CON EPILESSIA IDIOPATICA GENERALIZZATA: IDENTIFICAZIONE DI UNA MUTAZIONE RECESSIVA NEL CANALE HHCN2
Full text linkIt is well established that several forms of inheritable idiopathic epilepsy sindrome are ion channelopathies, that is pathologies associated with dysfunctional ion channels, even if the functional link between channel dysfunction and clinical phenotype is often unresolved.
Hyperpolarization-activated, Cyclic-Nucleotide gated (HCN) channels are a class of voltage- and cAMP-dependent channels. They mediate the hyperpolarization-activated Ih current, which control synaptic integration and intrinsic excitability in various brain areas. Ih is pathologically altered after experimentally-induced seizures and has been proposed to have a role in different forms of epileptogenesis. Hcn1 and Hcn2 genes variants have been identified in patients with febrile seizure or GEFS+. While existing data therefore clearly show a link between HCN channel dysfunction and epileptogenesis, no specific mutation-induced HCN channel modification has so far been correlated functionally with increased neuronal excitability. To investigate this we used a candidate gene approach and screened a panel of idiopathic generalized epilepsy patients and related families for mutations in the Hcn1 and Hcn2 genes.
We found a form of sporadic IGE associated with a recessive point mutation in the gene coding for the HCN2 channel. The protein mutation E515K is located in the C-linker region (exon 5 of the Hcn2 gene). Functional analysis revealed that homomeric mutant, but not heteromeric wild-type/E515K channels, have a negative shift in the activation kinetics. Furthermore, the time-constant curve for homomeric E515K channels was also shifted to the negative direction. Moreover, omomeric mutant, but not heteromeric wild type/mutant channels, showed a lowering of the threshold of action potential firing and a strongly increased cell excitability and firing frequency when compared to wild-type channels.
In conclusion, our results show that the homozygous E515K mutation in human HCN2 channels is a loss-of-function mutation causing a large negative shift of the activation curve and slowing of activation, and a consequent strong reduction of Ih availability near resting voltages. These changes cause a substantial increase of neuronal excitability, a condition predisposing to epileptogenesis, and are associated with a recessive type of inheritance compatible with the idiopathic generalized epilepsy of the proband in the family pedigree
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
Artificial Neural Networks for the Representation of Axisymmetric Magnetic Fields in TWT Collectors
No full textVariations 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
Spatial changes in calcium signaling during the establishment of neuronal polarity and synaptogenesis
Full text linkCalcium imaging techniques were used to obtain a clear although indirect evidence about the distribution of functional glutamate receptors of NMDA and non-NMDA type in cultured hippocampal neurons during establishment of polarity and synaptogenesis. Glutamate receptors were expressed and were already functional as early as one day after plating. At this stage NMDA and non-NMDA receptors were distributed in all plasmalemmal areas. During the establishment of neuronal polarity, responses to either types of glutamate receptors became restricted to the soma and dendrites. Compartmentalization of glutamate receptors occurred at stages of development when synaptic vesicles were already fully segregated to the axon. Formation of synapses was accompanied by a further redistribution of receptors, which segregated to synapse-enriched portions of dendrites. Receptor compartmentalization and dendritic redistribution as well as accumulation of synaptic vesicles at synaptic sites occurred also in neurons cultured in the presence of either the sodium channel blocker tetrodotoxin or glutamate receptor antagonists. These results indicate that signals generated by neuronal electrical activity or receptor activation are not involved in the establishment of neuronal polarity and synaptogenesis
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
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