SERPINB3 delays glomerulonephritis and attenuates the lupus-like disease in lupus murine models by inducing a more tolerogenic immune phenotype

Objective: To explore the effects of SERPINB3 administration in murine lupus models with a focus on lupus-like nephritis. Methods: 40 NZB/W F1 mice were subdivided into 4 groups and intraperitoneally injected with recombinant SERPINB3 (7.5 \u3bcg/0.1 mL or 15 \u3bcg/0.1 mL) or PBS (0.1 mL) before (group 1 and 2) or after (group 3 and 4) the development of proteinuria ( 65100 mg/dl). Two additional mice groups were provided by including 20 MRL/lpr mice which were prophylactically injected with SERPINB3 (10 mice, group 5) or PBS (10 mice, group 6). Time of occurrence and levels of anti-dsDNA and anti-C1q antibodies, proteinuria and serum creatinine, overall- and proteinuria-free survival were assessed in mice followed up to natural death. Histological analysis was performed in kidneys of both lupus models. The Th17:Treg cell ratio was assessed by flow-cytometry in splenocytes of treated and untreated MRL/lpr mice. Statistical analysis was performed using non parametric tests and Kaplan-Meier curves, when indicated. Results: Autoantibody levels and proteinuria were significantly decreased and time of occurrence significantly delayed in SERPINB3-treated mice vs. controls. In agreement with these findings, proteinuria-free and overall survival were significantly improved in SERPINB3-treated groups vs. controls. Histological analysis demonstrated a lower prevalence of severe tubular lesions in kidneys of group 5 vs. group 6. SERPINB3-treated mice showed an overall trend toward a reduced prevalence of severe lesions in both strains. Th17:Treg ratio was significantly decreased in splenocytes of MRL/lpr mice treated with SERPINB3, compared to untreated control mice. Conclusions: SERPINB3 significantly improves disease course and delays the onset of severe glomerulonephritis in lupus-prone mice, possibly inducing a more tolerogenic immune phenotype

Spectrum of turbulent Kelvin-waves cascade in superfluid helium

To explain the observed decay of superfluid turbulence at very low temperature, it has been proposed that a cascade of Kelvin waves (analogous to the classical Kolmogorov cascade) transfers kinetic energy to length scales which are small enough that sound can be radiated away. We report results of numerical simulations of the interaction of quantized vortex filaments. We observe the development of the Kelvin-waves cascade, and compute the statistics of the curvature, the amplitude spectrum (which we compare with competing theories) and the fractal dimension.Comment: 32 pages, 22 figure

Tuning Polyamidoamine Design to Increase Uptake and Efficacy of Ruthenium Complexes for Photodynamic Therapy

Nanomedicine holds great promises to change the way drugs are delivered to their target, owing to the use of nano-sized drug carriers capable to enter cells and be trafficked intracellularly via energy dependent pathways [1, 2]. This is very different from the way most drugs arrive to their target, often based simply on their solubility and partition coefficients in lipids and water. Despite some valuable successes, drug delivery remains rather challenging and several factors are still limiting its potential. Among such factors, it has emerged, for instance, that most nano-sized carriers entering cells via endocytosis are later trafficked along the endolysosomal pathway to the lysosomes, where the low pH and abundant proteases can degrade and destroy the internalised cargo. Strategies to escape the endosomes and lysosomes are being investigated. Among the many polymer species employed as drug delivery vectors, linear polyamidoamines (PAAs) are very interesting and promising materials. In this communication it will be presented a new polycationic PAA endowed with a luminescent Ru complex (Ru-PhenAN) and its ability to target the cell nucleus. It shows unique trafficking to the cell nucleus of all the treated cells, also at polymer doses as low as cytotoxicity is very low. Also, it will be shown the efficacy of Ru-PhenAN as photosensitizers for photodynamic therapy (PDT), a treatment of pathological conditions based on the photo-activation of a bioactive compound, which is not harmful in the absence of light irradiation [3]

Osteopontin as Candidate Biomarker of Coronary Disease despite Low Cardiovascular Risk: Insights from CAPIRE Study

Stratification according high cardiovascular (CV) risk categories, still represents a clinical challenge. In this analysis of the CAPIRE study (NCT02157662), we investigate whether inflammation could fit between CV risk factors (RFs) and the presence of coronary artery disease (CAD). In total, 544 patients were included and categorized according with the presence of CAD and CV risk factor burden (low/multiple). The primary endpoint was to verify any independent association of neutrophil-related biomarkers with CAD across CV risk categories. The highest values of osteo-pontin (OPN) were detected in the low RF group and associated with CAD (23.2 vs. 19.4 ng/mL; p = 0.001), although no correlation with plaque extent and/or composition were observed. Con-versely, myeloperoxidase (MPO) and resistin did not differ by CAD presence. Again, OPN was identified as independent variable associated with CAD but only in the low RF group (adjOR 8.42 [95% CI 8.42\u201346.83]; p-value = 0.015). As an ancillary finding, a correlation linked OPN with the neutrophil degranulation biomarker MPO (r = 0.085; p = 0.048) and resistin (r = 0.177; p = 3.4 7 10 125 ). In the present study, OPN further strengthens its role as biomarker of CAD, potentially bridging subclinical CV risk with development of atherosclerosis

Vortex length, vortex energy and fractal dimension of superfluid turbulence at very low temperature

By assuming a self-similar structure for Kelvin waves along vortex loops with successive smaller scale features, we model the fractal dimension of a superfluid vortex tangle in the zero temperature limit. Our model assumes that at each step the total energy of the vortices is conserved, but the total length can change. We obtain a relation between the fractal dimension and the exponent describing how the vortex energy per unit length changes with the length scale. This relation does not depend on the specific model, and shows that if smaller length scales make a decreasing relative contribution to the energy per unit length of vortex lines, the fractal dimension will be higher than unity. Finally, for the sake of more concrete illustration, we relate the fractal dimension of the tangle to the scaling exponents of amplitude and wavelength of a cascade of Kelvin waves.Comment: 12 pages, 1 figur

Changes in the pyruvic acid content correlates with phenotype traits in onion clones

Consumer demand is oriented toward onion cultivars with lower pungency, and the pyruvic acid content of onions is highly correlated with their pungency. Therefore, breeding programmes might be based on the pyruvic acid content of the parental bulbs. The present study was performed using 97 onion clones with the aim of correlating the pyruvic acid levels with phenotype traits in the different genotypes used in breeding programmes. The onion bulbs were provided from the breeding company with blind labels, and four bulbs were individually analysed for each clone. A comparison between the spectrophotometric and HPLC determination of pyruvic acid was also carried out and showed an excellent linear regression with an R 2 = 0.951. The pyruvic acid was studied in correlation with tunic colours, pungency and precocity, and the highest correlation coefficient was found for red skinned onions. The lowest pyruvate content was found in white onions, with 6.5 \u3bcmol g -1 FW, whereas higher values (8.4-8.5 \u3bcmol g -1 FW) were observed in yellow and red onions. The chemical analyses were compared with panel taste assessments. The results confirmed that the pungency and pyruvic acid content were positively and significantly correlated (P<0.0001),even when the coefficient resulted in a relatively low value (r = 0.515). The precocity trait was associated with pyruvate content: precocious onions, in particular, showed lower pungency

Solution conformation and dynamics of the ion pairs originating from the reaction of B(C6F5)(3) with bisindenyl dimethyl zirconium complexes

The two ion pairs [(4,7-Me(2)indenyl)(2)ZrMe](+)[MeB(C6F5)(3)](-) (1b) and [(indenyl)(2)ZrMe](+) [MeB(C6F5)(3)](-) (2b) have been generated in situ by reaction of stoichiometric B(C6F5)(3) with the corresponding dimethyl zirconocenes. It has been shown that molecular mechanics computations, guided by experimental H-1/H-1 NOE correlations, can provide information on the conformers present in solution. The dynamics of the ion pairs has also been investigated, showing the occurrence of both the processes previously characterized for this class of compounds, namely the B(C6F5)(3) migration between the two methyl groups and dissociation-recombination of the whole [MeB(C6F5)(3)](-) anion, the latter process being much faster than the first one (about three order of magnitude). Moreover, it has been shown that in certain conditions intermolecular processes can occur, which mimic the above-mentioned dissociative exchanges. In particular, the presence of species containing loosely bound [MeB(C6F5)(3)](-) anion fastens the exchange of this anion, while the presence of free B(C6F5)(3) accelerates its exchange between the two methyl sites

The Association of Fatigue With Decreasing Regularity of Locomotion During an Incremental Test in Trained and Untrained Healthy Adults

Fatigue is a key factor that affects human motion and modulates physiology, biochemistry, and performance. Prolonged cyclic human movements (locomotion primarily) are characterized by a regular pattern, and this extended activity can induce fatigue. However, the relationship between fatigue and regularity has not yet been extensively studied. Wearable sensor methodologies can be used to monitor regularity during standardized treadmill tests (e.g., the widely used Bruce test) and to verify the effects of fatigue on locomotion regularity. Our study on 50 healthy adults [27 males and 23 females; &lt;40&nbsp;years; five dropouts; and 22 trained (T) and 23 untrained (U) subjects] showed how locomotion regularity follows a parabolic profile during the incremental test, without exception. At the beginning of the trial, increased walking speed in the absence of fatigue is associated with increased regularity (regularity index, RI, a. u., null/unity value for aperiodic/periodic patterns) up until a peak value (RI&nbsp;=&nbsp;0.909 after 13.8&nbsp;min for T and RI&nbsp;=&nbsp;0.915 after 13.4&nbsp;min for U subjects; median values, n. s.) and which is then generally followed (after 2.8 and 2.5&nbsp;min, respectively, for T/U, n. s.) by the walk-to-run transition (at 12.1&nbsp;min for both T and U, n. s.). Regularity then decreases with increased speed/slope/fatigue. The effect of being trained was associated with significantly higher initial regularity [0.845 (T) vs 0.810 (U), p&nbsp;&lt;&nbsp;0.05 corrected], longer test endurance [23.0&nbsp;min (T) vs 18.6&nbsp;min (U)], and prolonged decay of locomotor regularity [8.6&nbsp;min (T) vs 6.5&nbsp;min (U)]. In conclusion, the monitoring of locomotion regularity can be applied to the Bruce test, resulting in a consistent time profile. There is evidence of a progressive decrease in regularity following the walk-to-run transition, and these features unveil significant differences among healthy trained and untrained adult subjects

Aggregation and ionization equilibria of bis(pentafluorophenyl)borinic acid driven by hydrogen-bonding with tetrahydrofuran

Bis(pentafluophenyl)borinic acid, Ar2BOH (1, Ar = C6F5), in dichloromethane solution is present as an equilibrium mixture of monomeric (1m) and trimeric (1t) forms. Previous studies showed that water affects both the position and the rate of this equilibrium. Here, the behavior of 1 in the presence of tetrahydrofuran (THF), a nucleophile able to behave as a Lewis base and H-bond acceptor only, has been studied, by monitoring with H-1 and F-19 NMR the course of titrations performed directly into NMR tubes. The addition, at 183 K, of 0.33 equiv of THF caused the instantaneous and quantitative formation of the hydrogen-bonded adduct between the trimer 1t and one molecule of THF. Homo- and heteronuclear 2D NMR correlation experiments led to a solution structure consistent with the C2-optimized geometry obtained by PM3 computations. The H-bonding of the THF molecule causes major deformations of the molecular geometry of the trimer, so that only one molecule of THF can interact with the trimer, in spite of its three OH groups. Intra- and intermolecular exchange processes involving this adduct have been investigated by 2D EXSY experiments, showing flopping of the cycle conformation, rotation of the aromatic rings around their B-C bonds, and exchange of THF among the three OH groups, in addition to the exchange between free 1t and the adduct. When the amount of added THF was higher than 0.33 equiv, an unexpected ionization process occurred, leading to the cation [Ar2B(OH2)2]+ and to deprotonated 1t, i.e., to the anion [Ar6B3O3H2]- of Cs symmetry. On increasing the temperature, progressive partial fragmentation of the trimeric species was observed. Both B-11 NMR evidence and PM3 computations indicated that, at variance with what is observed in the interaction with H2O, the interaction between THF and 1m occurs preferentially via an H-bonded adduct, Ar2BO-H...THF, rather than a Lewis acid-base complex, Ar2B(OH)(THF). This confirms the poor Lewis acidity of the boron atom of 1m