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

Dating long thrust systems on Mercury: new clues on the thermal evolution of the planet

The global tectonics of Mercury is dominated by contractional features mainly represented by lobate scarps, high relief ridges, and wrinkle ridges. These structures are the expression of thrust faults and are linear or arcuate features widely distributed on Mercury. Locally, these structures are arranged in long systems characterized by a preferential orientation and non-random spatial distribution. In this work we identified five thrust systems, generally longer than 1000 km. They were named after the main structure or crater encompassed by the system as: Thakur, Victoria, Villa Lobos, Al-Hamadhani, and Enterprise. In order to gain clues about their formation, we dated them using the buffered crater counting technique, which can be applied to derive the ages of linear landforms such as faults, ridges and channels. To estimate the absolute age for the end of the thrust system's activity, we applied both Le Feuvre and Wieczorek Production Function and Neukum Production Functions. Moreover, to further confirm the results obtained with the buffered crater counting method, the classic stratigraphic approach has been adopted, in which a faulted and an unfaulted craters were dated for each system. The results gave consistent ages and suggested that the most movements along major structures all over Mercury most likely ended at about 3.6–3.8 Ga. This gives new clues to better understand the tectonics of the planet and, therefore, its thermal evolution. Indeed, the early occurrence of tectonic activity in the planet's history, well before than predicted by the thermophysical models, coupled with the orientation and spatial distribution of the thrust systems, suggests that other processes beside global contraction, like mantle downwelling or tidal despinning, could have contributed to the first stage of the planet's history. Keywords: Mercury, Thrust systems, Crater counting, Thermal evolution, Planetary geology, Structural geolog

a sonographic quantitative cutoff value of cerebral venous outflow in neurologic diseases a blinded study of 115 subjects

BACKGROUND AND PURPOSE: The autonomic nervous system maintains constant cerebral venous blood outflow in changing positions. Alterations in cerebral autoregulation can be revealed by postural changes at quantitative color Doppler sonography. The aim of this study was to reach an optimal cutoff value of the difference between the cerebral venous blood outflow in the supine and seated positions that can discriminate healthy controls from patients with multiple sclerosis and those with other neurologic diseases and to evaluate its specificity, sensitivity, and diagnostic accuracy. MATERIALS AND METHODS: One hundred fifteen subjects (54 with MS, 31 healthy controls, 30 with other neurologic diseases) underwent a blinded quantitative color Doppler sonography evaluation of cerebral venous blood outflow in the supine and sitting positions. An optimal difference value between the supine and sitting positions of the cerebral venous blood outflow cutoff value was sought. RESULTS: The difference value between supine and sitting positions of the cerebral venous blood outflow was ≤ 503.24 in 38/54 (70.37%) patients with MS, 9/31 (29.03%) healthy controls, and 13/30 (43.33%) subjects with other neurological diseases. A difference value between supine and sitting positions of the cerebral venous blood outflow at a 503.24 cutoff reached a sensitivity at 70.37%, a 70.96% specificity, a 80.85% positive predictive value, and a 57.89% negative predictive value; the quantitative color Doppler sonography parameters yielded significant differences. The difference value between supine and sitting positions of cerebral venous blood outflow ≤ 503.24 assessed the significant difference between MS versus other neurological diseases. CONCLUSIONS: Alteration of cerebral venous blood outflow discriminated MS versus other neurologic diseases and MS versus healthy controls. The difference value between supine and sitting positions of cerebral venous blood outflow ≤ 503.24 was statistically associated with MS

An automated fluorescence videomicroscopy assay for the detection of mitotic catastrophe

Mitotic catastrophe can be defined as a cell death mode that occurs during or shortly after a prolonged/aberrant mitosis, and can show apoptotic or necrotic features. However, conventional procedures for the detection of apoptosis or necrosis, including biochemical bulk assays and cytofluorometric techniques, cannot discriminate among pre-mitotic, mitotic and post-mitotic death, and hence are inappropriate to monitor mitotic catastrophe. To address this issue, we generated isogenic human colon carcinoma cell lines that differ in ploidy and p53 status, yet express similar amounts of fluorescent biosensors that allow for the visualization of chromatin (histone H2B coupled to green fluorescent protein (GFP)) and centrosomes (centrin coupled to the Discosoma striata red fluorescent protein (DsRed)). By combining high-resolution fluorescence videomicroscopy and automated image analysis, we established protocols and settings for the simultaneous assessment of ploidy, mitosis, centrosome number and cell death (which in our model system occurs mainly by apoptosis). Time-lapse videomicroscopy showed that this approach can be used for the high-throughput detection of mitotic catastrophe induced by three mechanistically distinct anti-mitotic agents (dimethylenastron (DIMEN), nocodazole (NDZ) and paclitaxel (PTX)), and – in this context – revealed an important role of p53 in the control of centrosome number

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