MOD derived pyrochlore films as buffer layer for all-chemical YBCO coated conductors

We report a detailed study performed on La2Zr2O7 (LZO) pyrochlore material grown by Metal-Organic Decomposition (MOD) method as buffer layers for YBa2Cu3O7-x (YBCO) coated conductors. High quality epitaxial LZO thin films have been obtained on single crystal (SC) and Ni-5%at.W substrates. In order to evaluate structural and morphological properties, films have been characterized by means of X-ray diffraction analyses (XRD), atomic force microscope (AFM) and scanning electron microscope (SEM). Precursors solutions and heat treatments have been studied by thermogravimetric analyses (TG-DTA-DTG) and infrared spectra (FT-IR) with the aim of optimizing the annealing process. Thin films of YBCO have been deposited by pulsed laser ablation (PLD) on this buffer layers. The best results obtained on SC showed YBCO films with critical temperature values above 90 K, high self field critical current density values (Jc > 1 MA/cm2) and high irreversibility field values (8.3 T) at 77 K together with a rather high depinning frequency vp (0.5 T, 77 K)>44 GHz as determined at microwaves. The best results on Ni-5%at.W has been obtained introducing in the heat treatment a pyrolysis process at low temperature in air in order to remove the residual organic part of the precursor solution

Activation of NRF2 and ATF4 Signaling by the Pro-Glutathione Molecule I-152, a Co-Drug of N-Acetyl-Cysteine and Cysteamine

I-152 combines two pro-glutathione (GSH) molecules, namely N-acetyl-cysteine (NAC) and cysteamine (MEA), to improve their potency. The co-drug efficiently increases/replenishes GSH levels in vitro and in vivo; little is known about its mechanism of action. Here we demonstrate that I-152 not only supplies GSH precursors, but also activates the antioxidant kelch-like ECH-associated protein 1/nuclear factor E2-related factor 2 (KEAP1/NRF2) pathway. The mechanism involves disulfide bond formation between KEAP1 cysteine residues, NRF2 stabilization and enhanced expression of the γ-glutamil cysteine ligase regulatory subunit. Accordingly, a significant increase in GSH levels, not reproduced by treatment with NAC or MEA alone, was found. Compared to its parent compounds, I-152 delivered NAC more efficiently within cells and displayed increased reactivity to KEAP1 compared to MEA. While at all the concentrations tested, I-152 activated the NRF2 pathway; high doses caused co-activation of activating transcription factor 4 (ATF4) and ATF4-dependent gene expression through a mechanism involving Atf4 transcriptional activation rather than preferential mRNA translation. In this case, GSH levels tended to decrease over time, and a reduction in cell proliferation/survival was observed, highlighting that there is a concentration threshold which determines the transition from advantageous to adverse effects. This body of evidence provides a molecular framework for the pro-GSH activity and dose-dependent effects of I-152 and shows how synergism and cross reactivity between different thiol species could be exploited to develop more potent drugs

Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation

none14sìThe insulin-like growth factor-1 (IGF-1) signaling pathway is crucial for the regulation of growth and development. The correct processing of the IGF-1Ea prohormone (proIGF-1Ea) and the IGF-1 receptor (IGF-1R) peptide precursor requires proper N-glycosylation. Deficiencies of N-linked glycosylation lead to a clinically heterogeneous group of inherited diseases called Congenital Disorders of Glycosylation (CDG). The impact of N-glycosylation defects on IGF-1/IGF-1R signaling components is largely unknown. In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts showed hypoglycosylation of the proIGF-1Ea and lower IGF-1 secretion when compared with control (CTR). Lower IGF-1 serum concentration was observed in ALG3-CDG, ALG8-CDG and in some patients with PMM2-CDG, supporting our in vitro data. Furthermore, reduced IGF-1R expression level was observed in ALG3-CDG, ALG8-CDG and in some PMM2-CDG fibroblasts. IGF-1-induced IGF-1R activation was lower in most PMM2-CDG fibroblasts and was associated with decreased ERK1/2 phosphorylation as compared to CTR. In general, CDG fibroblasts showed a slight upregulation of Endoplasmic Reticulum (ER) stress genes compared with CTR, uncovering mild ER stress in CDG cells. ER-stress-related gene expression negatively correlated with fibroblasts IGF-1 secretion. This study provides new evidence of a direct link between N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components. Further studies are warranted to determine the clinical consequences of reduced systemic IGF-1 availability and local activity in patients with CDG.openDi Patria, Laura; Annibalini, Giosuè; Morrone, Amelia; Ferri, Lorenzo; Saltarelli, Roberta; Galluzzi, Luca; Diotallevi, Aurora; Bocconcelli, Matteo; Donati, Maria Alice; Barone, Rita; Guerrini, Renzo; Jaeken, Jaak; Stocchi, Vilberto; Barbieri, ElenaDi Patria, Laura; Annibalini, Giosuè; Morrone, Amelia; Ferri, Lorenzo; Saltarelli, Roberta; Galluzzi, Luca; Diotallevi, Aurora; Bocconcelli, Matteo; Donati, Maria Alice; Barone, Rita; Guerrini, Renzo; Jaeken, Jaak; Stocchi, Vilberto; Barbieri, Elen

Rationale for BepiColombo Studies of Mercury's Surface and Composition

BepiColombo has a larger and in many ways more capable suite of instruments relevant for determination of the topographic, physical, chemical and mineralogical properties of Mercury's surface than the suite carried by NASA's MESSENGER spacecraft. Moreover, BepiColombo's data rate is substantially higher. This equips it to confirm, elaborate upon, and go beyond many of MESSENGER's remarkable achievements. Furthermore, the geometry of BepiColombo's orbital science campaign, beginning in 2026, will enable it to make uniformly resolved observations of both northern and southern hemispheres. This will offer more detailed and complete imaging and topographic mapping, element mapping with better sensitivity and improved spatial resolution, and totally new mineralogical mapping. We discuss MESSENGER data in the context of preparing for BepiColombo, and describe the contributions that we expect BepiColombo to make towards increased knowledge and understanding of Mercury's surface and its composition. Much current work, including analysis of analogue materials, is directed towards better preparing ourselves to understand what BepiColombo might reveal. Some of MESSENGER's more remarkable observations were obtained under unique or extreme conditions. BepiColombo should be able to confirm the validity of these observations and reveal the extent to which they are representative of the planet as a whole. It will also make new observations to clarify geological processes governing and reflecting crustal origin and evolution. We anticipate that the insights gained into Mercury's geological history and its current space weathering environment will enable us to better understand the relationships of surface chemistry, morphologies and structures with the composition of crustal types, including the nature and mobility of volatile species. This will enable estimation of the composition of the mantle from which the crust was derived, and lead to tighter constraints on models for Mercury's origin including the nature and original heliocentric distance of the material from which it formed.Peer reviewe

Ubiquitin is conjugated to the cytoskeletal protein α-spectrin in mature erythrocytes

none4noneD. CORSI; L. GALLUZZI; R. CRINELLI; M. MAGNANID., Corsi; Galluzzi, Luca; Crinelli, Rita; Magnani, Maur

Confronto delle caratteristiche del MMPI-A tra minorenni autori di reato e adolescenti che hanno subito maltrattamenti

The Minnesota Multiphasic Personality Inventory–Adolescent (MMPI–A) is the self-report test most commonly applied to assess personality charatceristics, behavior difficulties, and psychopathology among adolescents. However, the literature on the use of the MMPI-A in different forensic populations remains limited. The current investigation was designed to identify differences in the MMPI–A scales between adolescents with a history of child maltreatment (CM), juvenile convicted of different type of offenses (JOs) or adolescents who never had contact with the Juvenile Justice and with no history childhood maltreatment. We found that adolescents in CM group had higher ANX, BIZ, LSE, and SOD scores compared with adolescents in JOs group; while they had higher BIZ, TRT and MAC scores compared with adolescents in control group. Adolescents in JOs group had higher LSE and MAC scores compared with adolescents in control group. Finding differences in personality profiles between differentforensic populations could lead to the creation of more appropriate treatments as well as a better understanding of the possible responses to outcomes of treatments.Il Minnesota Multiphasic Personality Inventory-Adolescent (MMPI-A) è il test di autovalutazione più comunemente applicato per valutare i tratti della personalità, le difficoltà comportamentali e la psicopatologia tra gli adolescenti. Tuttavia, la letteratura sull'uso dell'MMPI-A in diverse popolazioni forensi rimane limitata. L'attuale indagine è stata progettata per identificare le differenze nelle scale MMPI-A tra adolescenti con una storia di maltrattamenti subiti (CM), minori condannati per diversitipi di reati (JO) o adolescenti che non hanno mai avuto contatti con la Giustizia Minorile e senza storia maltrattamenti infantili. Abbiamo scoperto che gli adolescenti nel gruppo CM avevano punteggi ANX, BIZ, LSE e SOD più alti rispetto agli adolescenti nel gruppo JOs; mentre avevano punteggi BIZ, TRT e MAC più alti rispetto agli adolescenti nel gruppo di controllo. Gli adolescenti nel gruppo JOs avevano punteggi MAC più alti rispetto agli adolescenti nel gruppo di controllo. Trovare differenze nei profili di personalità tra diverse popolazioni forensi potrebbe portare alla creazione di trattamenti più appropriati, nonché a una migliore comprensione delle possibili risposte agli esiti dei trattamenti.&nbsp

Induction of Endoplasmic Reticulum Stress Response by the Indole-3-Carbinol Cyclic Tetrameric Derivative CTet in Human Breast Cancer Cell Lines

BACKGROUND: Indole-3-carbinol and its metabolic products are considered promising chemopreventive and anticancer agents. Previously we have shown that the indole-3-carbinol cyclic tetrameric derivative CTet induces autophagy and inhibits cell proliferation via inhibition of Akt activity and overexpression of p21/CDKN1A and GADD45A, in both estrogen receptor-positive (MCF-7) and triple negative (MDA-MB-231) breast cancer cell lines. In the present study, we further characterize the autophagic response and investigate the mechanism through which CTet regulates these events. METHODOLOGY/PRINCIPAL FINDINGS: Analysis of gene expression microarray data and subsequent confirmation by quantitative real-time PCR, showed that CTet is able to induce up-regulation of key signaling molecules involved in endoplasmic reticulum (ER) stress response (e.g. DDIT3/CHOP, CHAC1, ATF3, HSPA5/BiP/GRP78, CEBPB, ASNS) and autophagy (e.g. MAP1LC3B), in both MCF-7 and MDA-MB-231 cell lines. Moreover, the monitoring of Xbp-1 splicing confirmed the activation of IRE1/Xbp-1 ER stress response branch after CTet treatment. The role of autophagic processes (known to be induced by ER stress) was investigated further through ATG5 gene silencing and pharmacological inhibition of AVOs formation. CTet was shown to induce an autophagy-related cell death. Moreover, CTet-treated cells stained with Hoechst/PI revealed the presence of necrotic processes without evidence of apoptosis. CONCLUSIONS/SIGNIFICANCE: The ER stress response was identified as the main upstream molecular mechanism through which CTet acts in both hormone-responsive and triple-negative breast cancer cells. Because of its important role in cancer development, ER stress is a potential target in cancer therapy. The abiltiy of CTet to induce ER stress response and subsequently activate a death program in tumor cells confirms this molecule as a promising anticancer agent

A synthetic thiol molecule releasing N-acetyl-l-cysteine and cysteamine drives early up-regulation of immunoproteasome subunits in the lymph nodes of mice infected with LP-BM5 leukemia retrovirus

: Thiol molecules have been recently re-considered as drug candidates in viral infections because of their ability to induce redox changes which interfere with virus life cycle and modulate the host immune response. Little is known about the molecular mechanisms of their immunomodulatory properties. Here we show that I-152, a thiol molecule metabolized to release N-acetyl-l-cysteine and cysteamine and acting as a pro-glutathione agent, causes early up-regulation of immunoproteasome subunits in the lymph nodes of murine leukemia virus infected mice. This evidence suggests that the immunoproteasome may be modulated by thiol-based compounds with important implications in understanding redox-controlled immunoregulation