An enhanced expression of the immediate early gene, Egr-1, is associated with neuronal apoptosis in culture

Cultured cerebellar granule cells grown in medium containing 10 mM K+ (K10) underwent apoptosis after four to five days in vitro, unless they were rescued by the addition of insulin-like growth factor-I. The few GABAergic neurons present in the cultures were more resistant to apoptotic degeneration, as indicated by double fluorescent staining with the chromatin dye Hoechst 33258 and with glutamate decarboxylase-67 antibodies. As compared with sister cultures grown in 25 mM K+, K10 cultures showed an increased expression of the Egr-1 protein and a reduced expression of the Fos protein, The increase in Egr-1 was more substantial in granule cells than in GABAergic neurons, and was not oberved in K10 cultures chronically exposed to insulin-like growth factor-I. To examine the temporal relationship between the increase in Egr-1 and the development of programmed cell death, we induced apoptosis in K25 cultures at six days in vitro by replacing their medium with serum-free K10 medium. A substantial, but transient, increase in Egr-1 expression was observed in granule cells 6 h after switching the medium, a time that preceded the appearance of the phoenotypical markers of apoptotic death. An early reduction in the Fos protein was observed after switching the medium from K25 into serum-free K10, but also after switching the medium into serum-free K25, a condition which was not associated with the development of apoptosis nor with the increase in Egr-1. We suggest that a transient induction of Egr-1 contributes to the chain of events leading to the execution phase of neuronal apoptosis in culture. (C) 1999 IBRO. Published by Elsevier Science Ltd

Four cases of progressive multifocal leukoencephalopathy in iatrogenic immunocompromised patients

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by John Cunningham Virus (JCV). We report four PML cases in immunocompromised patients, respectively treated with (1) Natalizumab, (2) Rituximab, (3) autologous stem-cell transplantation, and (4) Tacrolimus. All patients underwent neurological examination, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), JCV-DNA research on biological samples, and lymphocytes subpopulation study. All cases presented with motor, behavioural, and cognitive disorders. Visual, sensitive, and cerebellar deficits developed in three cases. MRI revealed widespread progressive demyelinating areas with active borders; three patients presented contrast enhancement. One patient developed inflammatory reconstitution syndrome (IRIS). At MRS, all cases presented decreased N-acetyl-aspartate (NAA) and three cases showed increased choline (Cho). In one patient, plasma and urine tested positive for JCV-DNA, while cerebrospinal fluid (CSF) analysis confirmed JCV in two patients. The fourth patient had a low JCV-DNA blood titer and brain biopsy showed subacute necrosis. Two patients had abnormal lymphocyte subpopulations. Three patients underwent therapy with Mirtazapine, one of whom received Mefloquine in add-on. No clinical response was registered. Clinical onset, MRI and MRS were highly suggestive of PML in all patients, despite three cases presented contrast enhancement. In three cases JCV-DNA detection in biological samples confirmed the diagnosis. The fourth patient fulfilled diagnosis of “presumptive PML”. Our data confirm the importance to complete the diagnostic workup despite the presence of findings not completely consistent with classical PML. We hypothesize that atypical characteristics could due to the clinical conditions leading to PML

Correction: Shekarkar Azgomi et al. A Rapid and Simple Multiparameter Assay to Quantify Spike-Specific CD4 and CD8 T Cells after SARS-CoV-2 Vaccination: A Preliminary Report

In the original publication, there was a mistake in Figure 1A, as published [1]. A FACS plot for IL-2 production was duplicated during the editing of the Figure through mere error, between non-stimulated and stimulated conditions. In detail, we duplicated the sixth plot of the upper row from the third plot of the middle row. The corrected Figure 1 appears below. The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated

Batoid abundances, spatial distribution, and life history traits in the strait of sicily (Central mediterranean sea): Bridging a knowledge gap through three decades of survey

Batoid species play a key role in marine ecosystems but unfortunately they have globally declined over the last decades. Given the paucity of information, abundance data and the main life history traits for batoids, obtained through about three decades of bottom trawl surveys, are presented and discussed. The surveys were carried out in two areas of the Central Mediterranean (South of Sicily and Malta Island), in a timeframe ranging from 1990 to 2018. Excluding some batoids, the abundance trends were stable or increasing. Only R. clavata, R. miraletus, and D. oxyrinchus showed occurrence and abundance indexes notable enough to carry out more detailed analysis. In particular, spatial distribution analysis of these species highlighted the presence of two main hotspots in Sicilian waters whereas they seem more widespread in Malta. The lengths at first maturity (L50) were 695 and 860, 635 and 574, and 364 and 349 mm total length (TL), respectively, for females and males of D. oxyrinchus, R. clavata, and R. miraletus. The asymptotic lengths (L∞) and the curvature coefficients (K) were 1365 and 1240 (K = 0.11 and 0.26), 1260 and 1100 (K = 0.16 and 0.26), and 840 and 800 mm TL (K = 0.36 and 0.41), respectively, for females and males of D. oxyrinchus, R. clavata, and R. miraletus. The lack of detailed quantitative historical information on batoids of Sicily and Malta does not allow to analytically judge the current status of the stocks, although the higher abundance of some species within Malta raises some concern for the Sicilian counterpart. In conclusion, suitable actions to protect batoids in the investigated area are recommended

Foxp3 and gata3 polymorphisms, vitamin d3 and multiple sclerosis

Background: Regulatory T cells (Tregs) alterations have been implicated in the pathogenesis of Multiple Sclerosis (MS). Recently, a crucial role of the X-Linked Forkhead Box P3 (FoxP3) for the development and the stability of Tregs has emerged, and FOXP3 gene polymorphisms have been associated with the susceptibility to autoimmune diseases. The expression of Foxp3 in Tregs is regulated by the transcription factor GATA binding-protein 3 (GATA3) and vitamin D3 . The aim of this retrospective case-control study was to investigate the potential association between FOXP3 and GATA3 genetic variants, Vitamin D3, and MS risk. Methods: We analyzed two polymorphisms in the FOXP3 gene (rs3761547 and rs3761548) and a polymorphism in the GATA3 gene (rs3824662) in 106 MS patients and 113 healthy controls. Serum 25(OH)D3 was also measured in all participants. Results: No statistically significant genotypic and allelic differences were found in the distribution of FOXP3 rs3761547 and rs3761548, or GATA3 rs3824662 in the MS patients, compared with controls. Patients that were homozygous for rs3761547 had lower 25(OH)D3 levels. Conclusions: Our findings did not show any association among FOXP3 and GATA3 SNPs, vitamin D3, and MS susceptibility

Effect of 1\u3b1,25(OH)2 vitamin D3 in mutant P53 glioblastoma cells: Involvement of neutral sphingomyelinase1

Glioblastoma is one the most aggressive primary brain tumors in adults, and, despite the fact that radiation and chemotherapy after surgical approaches have been the treatments increasing the survival rates, the prognosis of patients remains poor. Today, the attention is focused on highlighting complementary treatments that can be helpful in improving the classic therapeutic approaches. It is known that 1\u3b1,25(OH)2 vitamin D3, a molecule involved in bone metabolism, has many serendipidy effects in cells. It targets normal and cancer cells via genomic pathway by vitamin D3 receptor or via non-genomic pathways. To interrogate possible functions of 1\u3b1,25(OH)2 vitamin D3 in multiforme glioblastoma, we used three cell lines, wild-type p53 GL15 and mutant p53 U251 and LN18 cells. We demonstrated that 1\u3b1,25(OH)2 vitamin D3 acts via vitamin D receptor in GL15 cells and via neutral sphingomyelinase1, with an enrichment of ceramide pool, in U251 and LN18 cells. Changes in sphingomyelin/ceramide content were considered to be possibly responsible for the differentiating and antiproliferative effect of 1\u3b1,25(OH)2 vitamin D in U251 and LN18 cells, as shown, respectively, in vitro by immunofluorescence and in vivo by experiments of xenotransplantation in eggs. This is the first time 1\u3b1,25(OH)2 vitamin D3 is interrogated for the response of multiforme glioblastoma cells in dependence on the p53 mutation, and the results define neutral sphingomyelinase1 as a signaling effector

Variation-based design of an AM demodulator in a printed complementary organic technology

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Somatic deletion in exon 10 of aryl hydrocarbon receptor gene in human GH-secreting pituitary tumors

Objective/Purpose: The aryl hydrocarbon receptor (AHR) pathway plays a critical role in the biology of Growth Hormone (GH)-secreting pituitary tumor (somatotropinoma). Germline rs2066853 AHR variant was found to be more frequent among acromegaly patients and associated with a more severe disease with larger invasive somatropinoma, and with resistance to somatostatin analogs treatment in patients living in polluted areas. However, no somatic changes in AHR gene have been reported so far in acromegaly patients. On that basis, the aim of the study was to assess at the somatic level the AHR gene status encompassing exon 10 region, also because of the high rate of variants found in this genomic region. Methods: A cohort of 13 patients aged 20\u201376 years with biochemical, clinical and histological diagnosis of somatotropinoma was studied. DNA and RNA from pituitary tumor histological samples have been extracted and analyzed by PCR and direct sequencing for AHR gene variants, and compared with corresponding patients\u2019 germline DNA as well as normal pituitary tissue as reference control. Results: A degenerated letter codes in the region corresponding to AHR exon 10 (c.1239-c.2056) was detected in somatotropinomas-derived DNA but not in that of matched germline and pituitary normal tissue. By multiple PCR and sequencing analysis, we observed amplification only before codon 1246 and after codon 1254, confirming the presence of a tumor-restricted somatic deletion in the 5\u2019 upstream region of AHR exon 10. Analysis of PCR-amplified cDNA revealed a wildtype sequence of exon 9 and 10 in normal pituitary tissue, and a wildtype sequence of exon 9 and 10 up to codon 1246 and no sequence after the deletion region (c.1246-c.1254) in 6 out of 9 tumor samples. Patients carrying the germline rs2066853 AHR variant showed no somatic LOH at the corresponding genetic locus. Conclusion: This is the first demonstration of a recurrent somatic deletion in the exon 10 of the AHR gene in somatotropinomas. The functional impact of this genetic finding needs to be clarifie

Giacomo Serpotta e il "pareggiamento delle arti": la decorazione degli oratori fra manipolazione vitalistica e vocazione classicista

ABSTRACT GIACOMO SERPOTTA AND THE “EQUALIZATION OF THE ARTS”: DECORATION OF THE ORATORIES BETWEEN VITALISTIC MANIPULATION AND CLASSICIST VOCATION Ettore Sessa The value of the whole of Giacomo Serpotta's artistic vision in the orchestration of the figu¬rative apparatuses of his oratories was certainly one of the principal primers of his historical-critical raising in the modernist period. In 1901 Mauceri and in 1911 Ricci and Basile heighten a profile of it, however synthetic, of angling and above all of different breath from the rediscovery realized in positivist age. Classifiable, in fact, among the eighteenth century precedents of Gesamtkunstwerk aesthetical plant (according to a rather diffused custom within the artistic historiography of modernist culturaI area or of decadentist origin, as in different formalistic demonstrations of the wealthiest society Belle Époque) the progress of Serpottas artistic way towards tangible expressions of the idea of «the whole work of art» has a unmistakable im¬print of his and, at the same time, a feasibility thanks to the plasticism of gestures and to the uni¬tary multiplicity of his modeled. In his oratories arrangements the "realist" component, not exempted from hedonistic sensual witty remarks, acts on a foundation of Hellenic taste (also in the use of profiles and architectural elements). With wise modulation and with dosing diversified for intensity, according the nature of the subjects, combines history (see the «teatrini» with perspective sceneries, among which the Lepanto battle), micro history (from feminine allegorical subjects, to attractive dames modernly adorned with ends and brocades, to "picciotti" proudly ragged and to the anecdotal of the daily life), mysticism (from the devotional subjects to the allegories of the virtues), obscurity (from numerological components to philosophical attributes) and, finally, mythology (from the allegorical correspondences between Christianity and paganism to classical simbology). Despite the actual halving of this group of oratories (was destroyed by traumatic events as earthquakes and war actions, or by villainous demolitions big part of Serpottas works, among which the SS. Sacrament oratories to Kalsa and those of Saint Maria del Ponticello), the comparison among the palermitan examples reached us entire allows the individualization of the characters of originality typical of the generaI composition, over that of those figurative unanimously accredited among the most valid of the late- Baroque European sculpture. The typical scheme of these oratories, places with a strong secular imprint (predisposed as for cultural reunions how as for the preclusive congregational assemblies, to which the only ones not admitted affiliate were the artists), has as constants: the hall with a rectangular plant; the skiff or pavilion vault with plaster decorations dissimulating the constructive geometry; the sculptural wall register above of a high plinth; windows on the greatest sides (in number of three); two doors in the counterfacade, originally with desk for the assemblies in central position, below the principal devotional allegorical composition. The first oratory to which Giacomo Serpotta imposes an unitary imprint, except the cappellone only defined between 1717 and the following year) is that of SS. Rosary in S. Cita; he has worked since 1685 to 1688 on behalf of SS. Rosary Company. Serpotta is twenty nine, but already since almost ten years, after the apprenticeship with subordinate roles, he showed himself almost beginning in mute with the decorations of Madonna of the Pity church in Monreale, where he operated like Procopio De' Ferrari's collaborator, and perhaps with his interventions in 1678 in the lateral walls of S. Mercurio oratory, to which follow the 1679 decoration works in the Charity oratory in St. Bartholomeo of the Incurable people (no more existing), perhaps S. Pietro and S. Paolo statues dating back to 1680 for the greatest altar in Gancia church, the marble model for Charles H's equestrian monument for Messina (then realized in 1684) and during the two years 1683-1684 the scenic decorations for the transept altars of Carmine Maggiore church (where he collaborates with his brother Giuseppe and realizes the couples of twisted columns gilded and commented by a theory of plaster miniature scenes disposed according to a spiral development). Immediately after S. Cita oratory he realized, between 1688 and 1691, the decorative apparatuses of the Sacrament oratory in S. Nicolò to Kalsa (destroyed because of 1823 earthquake). Only eight years after the completion of this work (about which it was hypothesized that it were an advancement in comparison to the intervention in S. Cita) Giacomo Serpotta is entrusted by S. Francesco from Assisi and S. Lorenzo Companies to realize the complex allegorical and explanatory cycle of the plasters of S. Lorenzo orato¬ry. He worked partly on Giacomo Amato's sketches (to which are probably owed the reform interventions that confer to this oratory a great architectural "squaring" in comparison to others), completing the presbytery within 1706, while already from 1701 he is busy in the definition of the walls. In 1703 he began the counter facade with the monumental wall framework and high-relief representation of St. Lorenzo Martyrdom