Prominence of the training data preparation in geomagnetic storm prediction using deep neural networks.

The direct interaction between large-scale interplanetary disturbances emitted from the Sun and the Earth's magnetosphere can lead to geomagnetic storms representing the most severe space weather events. In general, the geomagnetic activity is measured by the Dst index. Consequently, its accurate prediction represents one of the main subjects in space weather studies. In this scenario, we try to predict the Dst index during quiet and disturbed geomagnetic conditions using the interplanetary magnetic field and the solar wind parameters. To accomplish this task, we analyzed the response of a newly developed neural network using interplanetary parameters as inputs. We strongly demonstrated that the training procedure strictly changes the capability of giving correct forecasting of stormy and disturbed geomagnetic periods. Indeed, the strategy proposed for creating datasets for training and validation plays a fundamental role in guaranteeing good performances of the proposed neural network architecture.

Is there a role for agomelatine in the treatment of anxiety disorders?A review of published data.

Anxiety disorders (Ads) are the most common type of psychiatric disorders, Pharmacologic options studied for treating ADs may include benzodiazepines, tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRIs), noradrenergic and specific serotonergic antidepressants (NaSSA) and serotonin and noradrenaline reuptake inhibitors (SNRIs). Agomelatine, a new melatonergic antidepressant, has been shown effective in various types of mood disorders. Moreover, some evidence points towards a possible efficacy of such a drug in the treatment of ADs. Therefore, the aim of this review was to elucidate current (facts and views) data on the role of agomelatine in the treatment of ADs. The trials evaluating agomelatine in the treatment of generalized anxiety disorder are few but, overall, encouraging in regards to its efficacy. However, further randomized, placebo-controlled studies on larger samples use are needed. Apart from some interesting case reports, no large studies are, to date, present in literature regarding agomelatine in the treatment of other ADs, such as panic disorder, social anxiety disorder, obsessive-compulsive disorder and post-traumatic stress disorder. Therefore, the clinical efficacy and the relative good tolerability of agomelatine in generalized anxiety (GAD) warrants further investigation in ADs.

Increase in messenger ribonucleic acid encoding the myometrial gap junction protein, connexin-43, requires protein synthesis and is associated with increased expression of the activator protein-1, c-fos.

Expression of the myometrial gap junction protein connexin-43 (Cx-43) increases dramatically with the onset of labor in association with an increase in the plasma estrogen to progesterone ratio. Moreover, we reported that the levels of messenger RNA (mRNA) and protein encoded by the Cx-43 gene are regulated positively by estrogen and negatively by progesterone in both pregnant and nonpregnant rats. However, although the Cx-43 gene has been reported to be responsive to estrogen, it does not contain a palindromic estrogen response element. It does, however, contain a consensus activator protein-1 (AP-1)-binding site that may be of significance, as estrogen has been reported to increase expression of the AP-1 proteins, Fos and Jun, in the uterus. Therefore, we tested the hypothesis that the increase in Cx-43 mRNA levels in the myometrium during labor and after estrogen administration is mediated indirectly through induction of trans-activating factors, of which Fos and Jun are putative candidates. Treatment of nonpregnant ovariectomized rats with cyclohexamide blocked the estrogen-induced increase in Cx-43 mRNA in the myometrium, suggesting that this action of estrogen requires newly synthesized protein. Estrogen treatment alone induced an increase in mRNA encoding c-fos and c-jun in nonpregnant rats, which preceded by 2-3 h an increase in Cx-43 mRNA. Labor was also associated with a coincident expression of c-fos and Cx-43 in the myometrium, although there was no change in c-jun mRNA levels during this period. These associative data were strengthened by our observation that in paradigms in which labor was induced prematurely by ovariectomy or blocked by treatment with progesterone, changes in c-fos expression were closely matched by changes in Cx-43 mRNA. These data support our hypothesis that estrogen (and, by extension, labor-)-induced increases in Cx-43 mRNA are mediated indirectly through newly synthesized trans-activating factors. Moreover, the temporal correlation between the expression of c-fos and Cx-43 and the presence of AP-1 cis-acting elements within the Cx-43 promoter suggest that c-fos may be one of these trans-activating proteins.

Myometrial transcriptional regulation of the gap junction gene, connexin-43.

The mechanisms that enable the myometrium to switch from a state of relative quiescence during pregnancy to a muscle that is spontaneously active, very responsive to endogenous uterotonins and exhibits a high degree of cell-cell coordination are poorly understood. It is hypothesized that this switch or 'activation' of the myometrium results from the coordinated expression of a cassette of 'contraction-associated proteins'. The molecular mechanisms that regulate the expression of one of these, namely the myometrial gap junction protein connexin-43 (Cx-43), have been analysed. Myometrial Cx-43 expression is significantly increased during labour, associated with an increase in plasma oestrogen:progesterone, and positively regulated by oestrogen in non-pregnant rats. The genomic structure of the murine Cx-43 gene and the sequence of its 5' flanking sequence are reported here. This region functions as a promoter and contains several putative cis-acting elements which may be important in the regulation of Cx-43 transcription. Among these elements are several half-palindromic sequences that may function as oestrogen response elements and several AP-1 sites that may bind the transcription factors Fos and Jun. Oestrogen treatment of cells transiently transfected with a plasmid containing the Cx-43 promoter linked to the chloramphenicol acetyl transferase (CAT) gene, increased CAT activity indicating that the murine Cx-43 gene is oestrogen responsive. In addition, treatment of rats with oestrogen significantly increased mRNA encoding c-fos and c-jun in the myometrium and this occurred before any increase in Cx-43 mRNA. These data suggest that oestrogen may increase transcription of the Cx-43 gene through direct mechanisms (via the putative oestrogen response elements) or indirect mechanisms (by increased expression of c-fos and c-jun acting via the putative AP-1 sites). Since oestrogen may be an important modulator of myometrial activation, these mechanisms may be critical to the processes leading to increased synthesis of gap junctions at term and, hence, to the onset of labour.