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    Steroid hormones and receptors of the GABAA supramolecular complex. 1. Benzodiazepine receptor level changes in some extrahypothalamic brain areas of the female rat following sex steroid treatment

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    The effects of sex steroid hormones on the different receptor binding sites of the GABA(A) molecule remain unclear. In this report we have demonstrated, using autoradiography techniques, that the distribution pattern of the benzodiazepine receptors (a component of the GABA(A) molecule) in some extrahypothalamic brain regions is altered by both in vivo and in vitro sex steroid hormone treatment. In vivo administration of the sex steroids estradiol and progesterone induced a significant change in [H-3]flunitrazepam (benzodiazepine agonist) binding levels in the amygdala, and cortico and posterior brain nuclei of the female rat. In fact, elevated and diminished receptor-binding levels were obtained in the corticomedial amygdala nucleus and in the pontine central gray matter respectively, following the administration of estradiol. Significant hormonal effects were also shown for animals that received only a progesterone dose, as demonstrated by the increased and decreased receptor levels in the basolateral amygdala nucleus and cortex lamina VI and in the substantia nigra pars reticulata, respectively. It was interesting, at this point, to investigate whether the hormone effects on [H-3]flunitrazepam binding changes might be mediated through a GABA-dependent activity, because the benzodiazepine and GABA(A) receptors are coupled to a chloride ion channel in an allosteric manner. When 50 muM GABA was added to the incubation medium, substantially altered binding levels were recorded in animals that received progesterone replacement therapy only. The GABA-induced progesterone effects both increased substantially the binding levels in the oriens-pyramidalis CA1 layer of the hippocampus and in the intermediate gray layer of the superior colliculus as well as reducing receptor levels in the substantia nigra pars reticulata. Due to the significant progesterone effects on [H-3]flunitrazepam binding, we also examined whether progesterone per se or whether the potent progesterone metabolite 3alpha-hydroxy-5alpha-dihydroprogesterone was responsible for the receptor-binding changes. Addition of this progesterone metabolite not only produced greater binding changes in brain areas that responded to the in vivo progesterone treatment but also increased, in a GABA-dependent manner, [H-3]flunitrazepam binding levels in the lateral amygdala nucleus. These results suggest that the anxiolytic, sedative and anti-aggressive behavioral effects, which are progesterone-dependent, are very likely mediated via a steroid-GABAergic interaction

    Steroid hormones and receptors of the GABAA supramolecular complex. 2. Progesterone and estrogen inhibitory effects on the chloride ion channel receptor in different forebrain areas of the female rat

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    The inhibitory effect of female sex steroid hormones on the binding of [S-35]t-butylbicyclophosphorothionate [S-35]TBPS to the chloride ion channel receptor in different forebrain areas of the female rat proved to be of a differential nature. The in vivo administration of estradiol and estradiol + progesterone were responsible for substantially lower chloride ion channel receptor levels in brain areas that contain elevated steroid receptors, such as the medial preoptic area, the cortico-medial amygdala nucleus, the vertical limb diagonal band-medial septal nucleus and the cortex lamina V. The administration of progesterone alone reduced receptor levels in the oriens-pyramidalis CA1 layer of the hippocampus, caudate putamen, cortex lamina VI (brain areas that contain little if any steroid receptors) and in the lateral and basolateral amygdala nucleus (brain sites that contain noninducible progesterone receptors). On the basis of the progesterone-inhibitory activity on the chloride ion channel receptors, it was important to investigate whether progesterone per se or whether the potent progesterone metabolites 3alpha-hydroxy-5alpha-dihydroprogesterone (3alpha,5alpha-THP) and 3beta-hydroxy-5beta-dihydroprogesterone (3beta,5beta-THP) were involved in the binding level changes, and to establish the specific brain sites where these steroid effects occur. In fact, in vitro addition of the 5alpha-reduced progesterone metabolite produced even greater depressive effects on [S-35]TBPS binding not only in the same brain areas as the in vivo progesterone replacement therapy but also in some sites that provided significant receptor level changes following the sequential administration of estradiol + progesterone. However, when the 5beta-reduced metabolite was tested on the binding of [S-35]TBPS to the chloride ion channel receptor, only the basolateral amygdala nucleus, the cortex lamina VI and the dorsolateral septal nucleus exhibited changes. Because the steroid-mediated chloride ion flux is regulated in a GABA-dependent manner, we next checked for the type of GABA effects on the chloride ion channel receptor levels and found that GABA not only intensified the 3alpha,5alpha-THP inhibitory effects but, together with this progesterone metabolite, was also involved in binding changes in the vertical limb diagonal band-medial septal nucleus. It is interesting to note that the GABA effects on 5beta-metabolite-induced receptor changes were not of the enhancing type, but tended, rather, to be inhibitory. Moreover, the addition of the GABA antagonist bicuculline to the in vitro hormone treatment in the presence of GABA, caused a notable and specific inhibitory effect only to 3alpha,5alpha-THP-induced chloride ionophore receptor levels, indicating that this metabolite is probably the main modulator involved in the progesterone-dependent GABAergic functions via a specific interaction with the neurosteroid site of the GABA molecule in the various brain areas

    Effects of progesterone on [35S] t-butylbicyclophosphorothionate binding in some forebrain areas of the female rat and its correlation to aggressive behavior

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    The antiaggressive effects of progesterone (P) were evaluated in association with alterations in [35S] t-butylbicyclophosphorothionate (TBPS; chloride ion channel antagonist) binding in some forebrain sites of the female rat using in vitro quantitative autoradiography. The administration of 4 mg P was followed by a reduction in the frequency of different aggressive behaviors such as circling, nose-to-nose and fighting (mostly of the defensive nature) in ovariectomized (OVX) sexually mature rats, housed in pairs, during male-female encounters. Quantitative autoradiography data revealed that the same P dose, at the forebrain level, was responsible for low [35S] t-butylbicyclophosphorothionate binding levels in the medial preoptic area, lateral and basolateral amygdala nucleus and oriens-pyramidalis hippocampus CA1 layer, with even lower values being obtained following the in vitro addition of the potent P metabolite 5 alpha-pregnan-3 alpha-ol-20-one. These results suggests that the probable antiaggressive role of P during heterosexual encounters may be regulated by a local potent metabolite acting at the membrane site of the GABA complex

    Muscle system organization in the Echinoderms. I. Intervertebral muscles of Ophioderma longicaudum (Ophiuroidea)

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    The intervertebral muscles of the arm of the serpent star Ophioderma longicaudum have been observed under the electron microscope. These fibers, enabling the arm to move in all directions, show an ultrastructural morphology not easily ascribed to any muscle fiber category. They are internally organized into scaled bundles of filaments, determining, in cross section, alternating A- and I- zones. Inside these bundles the homologous filaments are staggered lengthwise and distributed according to a regular pattern. The arrangement into step-like bundles is emphasized by the distribution of the Z-elements, regularly inserted in the middle of the I-zone. These muscles, therefore, have an organization neither recalling that of a cross striated muscle nor that of a smooth muscle. More possibilities of comparison can be made with the helical muscle systems. The most evident analogies may be found in the myofilament arrangement of some molusc muscles (abductor muscle of the oyster), both in the distribution of the contractile elements and in the probable paramyosinic axis inside the thick filaments. The muscles of the Ophioderma arm, however, if compared with the 'classic helical muscle', lack a precise preferential obliquity, defined by the stagger of the filaments and of the Z-bodies toward a unique direction. These muscles, therefore, probably represent a model of fiber verging on the helical organization

    Differential modulation of [3H]flunitrazepam binding in female rat brain by sex steroid hormones

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    Quantitative autoradiographic analysis revealed changes in [3H]flunitrazepam (a benzodiazepine agonist) binding in the anterior hypothalamus nucleus, the medial preoptic area and the cortico-medial amygdala nucleus following in vivo estradiol. The administration of 4 mg of progesterone, but not 1 mg, increased the binding of [3H]flunitrazepam in the basolateral amygdaloid nucleus and in the oriens-pyramidalis CA1 layer of the hippocampus. Exposure of brain sections in vitro to the potent, naturally occurring progesterone metabolite, 3 alpha-hydroxy-5 alpha-dihydroprogesterone, induced GABA-dependent changes in flunitrazepam binding, similar to the changes induced by progesterone, thus suggesting that different steroid mechanisms are implicated in the control of flunitrazepam binding

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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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