A study on the stability of superconducting YBa2Cu3O7−x phase

The thermal stability of the superconducting phase of nominal composition YBa₂Cu₃O_7–x -sintered pellets has been studied with respect to different temperatures (ranging from 300 to 950° C), time (ranging from 1 to 72 h), oxygen partial pressure (from 4 Pa to 1 atm) and carbon dioxide partial pressure (from 10^–4 Pa to 1 atm). Annealed samples were characterized by X-ray diffraction analysis, optical microscopy, and resistive measurements of the superconductive transition temperature. A stability field of the orthorhombic and tetragonal phases was obtained, showing a region of coexistance. The decomposition of the 1 2 3 phase is found to be strongly influenced by the presence of a small amount of CO₂ (1 p.p.m.) in the sintering atmosphere. A sintering process is proposed to avoid the formation of by-products.     

Temperature dependence of resistivity for thermally diffused V3Si multilayer films

Results concerning V₃Si films produced by a simple annealed multilayer technique are reported together with X-ray diffraction patterns, Auger spectroscopy, and Rutherford backscattering analysis. Low-temperature electrical resistivity measurements are discussed. It is found that the V₃Si films exhibit aT ² dependence in the temperature rangeT _c T23 K and aT ^2.6 dependence in the rangeT _c T40 K. The normal-state resistivity in the whole temperature range (T _c T600 K) is analyzed in the framework of Cote-Meisel theory. Consistent values of the saturation resistivity _m and of the Debye temperature are obtained by fitting the experimental data with the Cote-Meisel expression for (T).     

Genetic Architecture and Molecular,Imaging and Prodromic Markers in Dementia with Lewy Bodies: State of the Art,Opportunities and Challenges

Dementia with Lewy bodies (DLB) is one of the most common causes of dementia and belongs to the group of α-synucleinopathies. Due to its clinical overlap with other neurodegenerative disorders and its high clinical heterogeneity, the clinical differential diagnosis of DLB from other similar disorders is often difficult and it is frequently underdiagnosed. Moreover, its genetic etiology has been studied only recently due to the unavailability of large cohorts with a certain diagnosis and shows genetic heterogeneity with a rare contribution of pathogenic mutations and relatively common risk factors. The rapid increase in the reported cases of DLB highlights the need for an easy, efficient and accurate diagnosis of the disease in its initial stages in order to halt or delay the progression. The currently used diagnostic methods proposed by the International DLB consortium rely on a list of criteria that comprises both clinical observations and the use of biomarkers. Herein, we summarize the up-to-now reported knowledge on the genetic architecture of DLB and discuss the use of prodromal biomarkers as well as recent promising candidates from alternative body fluids and new imaging techniques.     

Evidence for a Negative Correlation between Human Reactive Enamine-Imine Intermediate Deaminase A (RIDA) Activity and Cell Proliferation Rate: Role of Lysine Succinylation of RIDA

Reactive intermediate deaminase (Rid) proteins are enzymes conserved in all domains of life. UK114, a mammalian member of RidA subfamily, has been firstly identified as a component of liver perchloric acid-soluble proteins (L-PSP). Although still poorly defined, several functions have been attributed to the mammalian protein UK114/RIDA, including the reactive intermediate deamination activity. The expression of UK114/RIDA has been observed in some tumors, arousing interest in this protein as an evaluable tumor marker. However, other studies reported a negative correlation between UK114/RIDA expression, tumor differentiation degree and cell proliferation. This work addressed the question of UK114/RIDA expression in human non-tumor HEK293 cell lines and in some human tumor cell lines. Here we reported that human RIDA (hRIDA) was expressed in all the analyzed cell line and subjected to lysine (K-)succinylation. In HEK293, hRIDA K-succinylation was negatively correlated to the cell proliferation rate and was under the control of SIRT5. Moreover, K-succinylation clearly altered hRIDA quantification by immunoblotting, explaining, at least in part, some discrepancies about RIDA expression reported in previous studies. We found that hRIDA was able to deaminate reactive enamine-imine intermediates and that K-succinylation drastically reduced deaminase activity. As predicted by in silico analysis, the observed reduction of deaminase activity has been related to the drastic alterations of hRIDA structure inferred by K-succinylation. The role of hRIDA and the importance of its K-succinylation in cell metabolism, especially in cancer biology, have been discussed.     

High-Fat Diet Leads to Reduced Protein O-GlcNAcylation and Mitochondrial Defects Promoting the Development of Alzheimer’s Disease Signatures

The disturbance of protein O-GlcNAcylation is emerging as a possible link between altered brain metabolism and the progression of neurodegeneration. As observed in brains with Alzheimer’s disease (AD), flaws of the cerebral glucose uptake translate into reduced protein O-GlcNAcylation, which promote the formation of pathological hallmarks. A high-fat diet (HFD) is known to foster metabolic dysregulation and insulin resistance in the brain and such effects have been associated with the reduction of cognitive performances. Remarkably, a significant role in HFD-related cognitive decline might be played by aberrant protein O-GlcNAcylation by triggering the development of AD signature and mitochondrial impairment. Our data support the impairment of total protein O-GlcNAcylation profile both in the brain of mice subjected to a 6-week high-fat-diet (HFD) and in our in vitro transposition on SH-SY5Y cells. The reduction of protein O-GlcNAcylation was associated with the development of insulin resistance, induced by overfeeding (i.e., defective insulin signaling and reduced mitochondrial activity), which promoted the dysregulation of the hexosamine biosynthetic pathway (HBP) flux, through the AMPK-driven reduction of GFAT1 activation. Further, we observed that a HFD induced the selective impairment of O-GlcNAcylated-tau and of O-GlcNAcylated-Complex I subunit NDUFB8, thus resulting in tau toxicity and reduced respiratory chain functionality respectively, highlighting the involvement of this posttranslational modification in the neurodegenerative process.     

Bone Marrow-Mesenchymal Stromal Cell Secretome as Conditioned Medium Relieves Experimental Skeletal Muscle Damage Induced by Ex Vivo Eccentric Contraction

Bone marrow-mesenchymal stem/stromal cells (MSCs) may offer promise for skeletal muscle repair/regeneration. Growing evidence suggests that the mechanisms underpinning the beneficial effects of such cells in muscle tissue reside in their ability to secrete bioactive molecules (secretome) with multiple actions. Hence, we examined the effects of MSC secretome as conditioned medium (MSC-CM) on ex vivo murine extensor digitorum longus muscle injured by forced eccentric contraction (EC). By combining morphological (light and confocal laser scanning microscopies) and electrophysiological analyses we demonstrated the capability of MSC-CM to attenuate EC-induced tissue structural damages and sarcolemnic functional properties’ modifications. MSC-CM was effective in protecting myofibers from apoptosis, as suggested by a reduced expression of pro-apoptotic markers, cytochrome c and activated caspase-3, along with an increase in the expression of pro-survival AKT factor. Notably, MSC-CM also reduced the EC-induced tissue redistribution and extension of telocytes/CD34⁺ stromal cells, distinctive cells proposed to play a “nursing” role for the muscle resident myogenic satellite cells (SCs), regarded as the main players of regeneration. Moreover, it affected SC functionality likely contributing to replenishment of the SC reservoir. This study provides the necessary groundwork for further investigation of the effects of MSC secretome in the setting of skeletal muscle injury and regenerative medicine.     

Confocal Blood Flow Videomicroscopy of Thrombus Formation over Human Arteries and Local Targeting of P2X7

Atherothrombosis exposes vascular components to blood. Currently, new antithrombotic therapies are emerging. Herein we investigated thrombogenesis of human arteries with/without atherosclerosis, and the interaction of coagulation and vascular components, we and explored the anti-thrombogenic efficacy of blockade of the P2X purinoceptor 7 (P2X7). A confocal blood flow videomicroscopy system was performed on cryosections of internal mammary artery (IMA) or carotid plaque (CPL) determining/localizing platelets and fibrin. Blood from healthy donors elicited thrombi over arterial layers. Confocal microscopy associated thrombus with tissue presence of collagen type I, laminin, fibrin(ogen) and tissue factor (TF). The addition of antibodies blocking TF (aTF) or factor XI (aFXI) to blood significantly reduced fibrin deposition, variable platelet aggregation and aTF + aFXI almost abolished thrombus formation, showing synergy between coagulation pathways. A scarce effect of aTF over sub-endothelial regions, more abundant in tissue TF and bundles of laminin and collagen type I than deep intima, may suggest tissue thrombogenicity as molecular structure-related. Consistently with TF-related vascular function and expression of P2X7, the sections from CPL but not IMA tissue cultures pre-treated with the P2X7 antagonist A740003 demonstrated poor thrombogenesis in flow experiments. These data hint to local targeting studies on P2X7 modulation for atherothrombosis prevention/therapy.     

Film Blowing of Biodegradable Polymer Nanocomposites for Agricultural Applications

Films for agricultural applications, such as greenhouses films or mulching films are generally made of polyolefins such as linear low-density polyethylene (LLDPE) or low-density polyethylene. However, the use of biodegradable and/or compostable polymers is increasing, which enjoy the additional advantage that they can be left on the site since a fine life would be gradually assimilated to the underlying soil. Nevertheless, biodegradable polymeric films often do not have suitable mechanical performances. In this work, biodegradable polymer-based nanocomposite films are prepared by film blowing and compared with traditional LLDPE based nanocomposites. In particular, a biodegradable polymer blend and two different inorganic nanofillers (an organo-modified clay and a calcium carbonate with a hydrophobic coating) are used for the preparation of the nanocomposites. A detailed investigation of obtained materials is performed through rheological, mechanical, and optical characterizations. Adding nanofillers led to an increase of rigidity and tear strength of blown films without negatively affecting their ductility.