Glutathione increase by the n-butanoyl glutathione derivative (GSH-C4) inhibits viral replication and induces a predominant Th1 immune profile in old mice infected with influenza virus

During aging, glutathione (GSH) content declines and the immune system undergoes a deficiency in the induction of Th1 response. Reduced secretion of Th1 cytokines, which is associated with GSH depletion, could weaken the host defenses against viral infections. We first evaluated the concentration of GSH and cysteine in organs of old mice; then, the effect of the administration of the N-butanoyl GSH derivative (GSH-C4) on the response of aged mice infected with influenza A PR8/H1N1 virus was studied through the determination of GSH concentration in organs, lung viral titer, IgA and IgG1/IgG2a production and Th1/Th2 cytokine profile. Old mice had lower GSH than young mice in organs. Also the gene expression of endoplasmic reticulum (ER) stress markers involved in GSH metabolism and folding of proteins, i.e. Nrf2 and PDI, was reduced. Following infection, GSH content remained low and neither infection nor GSH-C4 treatment affected Nrf2 expression. In contrast, PDI expression was upregulated during infection and appeared counterbalanced by GSH-C4. Moreover, the treatment with GSH-C4 increased GSH content in organs, reduced viral replication and induced a predominant Th1 response. In conclusion, GSH-C4 treatment could be used in the elderly to contrast influenza virus infection by inducing immune response, in particular the Th1 profile

Cost of coexisting with a relict large carnivore population: Impact of apennine brown bears, 2005–2015

Human-carnivore conflicts are a major conservation issue. As bears are expanding their range in Europe’s human-modified landscapes, it is increasingly important to understand, prevent, and address human-bear conflicts and evaluate mitigation strategies in areas of historical coexis-tence. Based on verified claims, we assessed costs, patterns, and drivers of bear damages in the relict Apennine brown bear population in the Abruzzo Lazio and Molise National Park (PNALM), central Italy. During 2005–2015, 203 ± 71 (SD) damage events were verified annually, equivalent to 75,987 ± 30,038 €/year paid for compensation. Most damages occurred in summer and fall, with livestock depredation, especially sheep and cattle calves, prevailing over other types of damages, with apiaries ranking second in costs of compensation. Transhumant livestock owners were less impacted than residential ones, and farms that adopted prevention measures loaned from the PNALM were less susceptible to bear damages. Livestock farms chronically damaged by bears represented 8 ± 3% of those annually impacted, corresponding to 24 ± 6% of compensation costs. Further improvements in the conflict mitigation policy adopted by the PNALM include integrated prevention, conditional compensation, and participatory processes. We discuss the implications of our study for Human-bear coexistence in broader contexts

MRI-based assessment of the pineal gland in a large population of children aged 0-5 years and comparison with pineoblastoma: part I, the solid gland.

Differentiation between normal solid (non-cystic) pineal glands and pineal pathologies on brain MRI is difficult. The aim of this study was to assess the size of the solid pineal gland in children (0-5 years) and compare the findings with published pineoblastoma cases. We retrospectively analyzed the size (width, height, planimetric area) of solid pineal glands in 184 non-retinoblastoma patients (73 female, 111 male) aged 0-5 years on MRI. The effect of age and gender on gland size was evaluated. Linear regression analysis was performed to analyze the relation between size and age. Ninety-nine percent prediction intervals around the mean were added to construct a normal size range per age, with the upper bound of the predictive interval as the parameter of interest as a cutoff for normalcy. There was no significant interaction of gender and age for all the three pineal gland parameters (width, height, and area). Linear regression analysis gave 99 % upper prediction bounds of 7.9, 4.8, and 25.4 mm(2), respectively, for width, height, and area. The slopes (size increase per month) of each parameter were 0.046, 0.023, and 0.202, respectively. Ninety-three percent (95 % CI 66-100 %) of asymptomatic solid pineoblastomas were larger in size than the 99 % upper bound. This study establishes norms for solid pineal gland size in non-retinoblastoma children aged 0-5 years. Knowledge of the size of the normal pineal gland is helpful for detection of pineal gland abnormalities, particularly pineoblastoma

Magneto-Optical and Multiferroic Properties of Transition-Metal (Fe, Co, or Ni)-Doped ZnO Layers Deposited by ALD

ZnO doped with transition metals (Co, Fe, or Ni) that have non-compensated electron spins attracts particular interest as it can induce various magnetic phenomena and behaviors. The advanced atomic layer deposition (ALD) technique makes it possible to obtain very thin layers of doped ZnO with controllable thicknesses and compositions that are compatible with the main microelectronic technologies, which further boosts the interest. The present study provides an extended analysis of the magneto optical MO Kerr effect and the dielectric properties of (Co, Fe, or Ni)-doped ZnO films prepared by ALD. The structural, magneto optical, and dielectric properties were considered in relation to the technological details of the ALD process and the corresponding dopant effects. All doped samples show a strong MO Kerr behavior with a substantial magnetization response and very high values of the Kerr polarization angle, especially in the case of ZnO/Fe. In addition, the results give evidence that Fe-doped ZnO also demonstrates a ferroelectric behavior. In this context, the observed rich and versatile physical nature and functionality open up new prospects for the application of these nanostructured materials in advanced electronic, spintronic, and optical devices

Retinoblastoma Is Characterized by a Cold, CD8+ Cell Poor, PD-L1- Microenvironment, Which Turns Into Hot, CD8+ Cell Rich, PD-L1+ After Chemotherapy

PURPOSE. To investigate the impact of chemotherapy (CHT) on human retinoblastoma (RB) tumor microenvironment (TME).CASES AND METHODS. Ninety-four RBs were studied, including 44 primary RBs treated by upfront surgery (Group 1) and 50 primary RBs enucleated after CHT (CHT), either intraarterial (IAC; Group 2, 33 cases) or systemic (S-CHT; Group 3, 17 cases). Conventional and multiplexed immunohistochemistry were performed to make quantitative comparisons among the three groups, for the following parameters: tumor-infiltrating inflammatory cells (TI-ICs); programmed cell death protein 1 (PD-1) positive TI-ICs; Ki67 proliferation index; gliosis; PD-1 ligand (PD-L1) protein expression; vessel number. We also correlated these TME factors with the presence of histological high-risk factors (HHRF+) and RB anaplasia grade (AG).RESULTS. After CHT, a decrease in both RB burden and Ki67 positivity was observed. In parallel, most subsets of TI-ICs, PD-1+ TI-ICs, gliosis, and PD-L1 protein expression significantly increased (P < 0.001, P = 0.02, P < 0.001, respectively). Vessel number did not significantly vary. Age, HHRFs+ and AG were significantly different between primary and chemoreduced RBs (P < 0.001, P = 0.006, P = 0.001, respectively) and were correlated with most TME factors.CONCLUSIONS. CHT modulates host antitumor immunity by reorienting the RB TME from anergic into an active, CD8+, PD-L1+ hot state. Furthermore, some clinicopathological characteristics of RB correlate with several factors of TME. Our study adds data in favor of the possibility of a new therapeutic scenario in human RB

Analogue neural networks on correlated random graphs

We consider a generalization of the Hopfield model, where the entries of patterns are Gaussian and diluted. We focus on the high-storage regime and we investigate analytically the topological properties of the emergent network, as well as the thermodynamic properties of the model. We find that, by properly tuning the dilution in the pattern entries, the network can recover different topological regimes characterized by peculiar scalings of the average coordination number with respect to the system size. The structure is also shown to exhibit a large degree of cliquishness, even when very sparse. Moreover, we obtain explicitly the replica symmetric free energy and the self-consistency equations for the overlaps (order parameters of the theory), which turn out to be classical weighted sums of 'sub-overlaps' defined on all possible sub-graphs. Finally, a study of criticality is performed through a small-overlap expansion of the self-consistencies and through a whole fluctuation theory developed for their rescaled correlations: Both approaches show that the net effect of dilution in pattern entries is to rescale the critical noise level at which ergodicity breaks down.Comment: 34 pages, 3 figure