Antiadipogenic properties of retinol in primary cultured differentiating human adipocyte precursor cells

The aim of this study was to investigate the effect of retinol on the human adipose conversion process using primary cultured human adipocyte precursor cells. When these cells were seeded in a medium containing retinol (concentrations ranging from 3.5 nM to 3.5 muM), cell proliferation was slightly inhibited by high concentrations of retinol, as demonstrated by cell counting and [(3)H]-thymidine incorporation. Moreover, the differentiation capacities of these cells were markedly and dose-dependently inhibited by retinol, as shown by the reduced expression of the lipogenic enzyme glycerol-3-phosphate dehydrogenase and by microscopic morphological analysis. These results strongly suggest that retinol, by inhibiting the ability of human preadipocytes to convert into mature adipocytes, could be of potential interest in the prevention of human adipose tissue development in general and of cellulitis in particular.     

The Environmental Pollutant Cadmium Promotes Influenza Virus Replication in MDCK Cells by Altering Their Redox State

Cadmium (Cd) is a toxic heavy metal that is considered an environmental contaminant. Several sources of human exposure to Cd, including employment in primary metal industries, production of certain batteries, foods, soil and cigarette smoke, are known. Its inhalation has been related to different respiratory diseases and toxic effects, among which alterations of the physiological redox state in individuals exposed to the metal have been described. Host-cell redox changes characteristic of oxidative stress facilitate the progression of viral infection through different mechanisms. In this paper, we have demonstrated that pre-treatment with CdCl₂ of MDCK cells increased influenza virus replication in a dose-dependent manner. This phenomenon was related to increased viral protein expression (about 40% compared with untreated cells). The concentration of CdCl₂, able to raise the virus titer, also induced oxidative stress. The addition of two antioxidants, a glutathione (GSH) derivative or the GSH precursor, N-acetyl-l-cysteine, to Cd pre-treated and infected cells restored the intracellular redox state and significantly inhibited viral replication. In conclusion, our data demonstrate that Cd-induced oxidative stress directly increases the ability of influenza virus to replicate in the host-cell, thus suggesting that exposure to heavy metals, such as this, could be a risk factor for individuals exposed to a greater extent to the contaminant, resulting in increased severity of virus-induced respiratory diseases.     

Molecular Determinants of Soft Tissue Sarcoma Immunity: Targets for Immune Intervention

Soft tissue sarcomas (STSs) are a family of rare malignant tumors encompassing more than 80 histologies. Current therapies for metastatic STS, a condition that affects roughly half of patients, have limited efficacy, making innovative therapeutic strategies urgently needed. From a molecular point of view, STSs can be classified as translocation-related and those with a heavily rearranged genotype. Although only the latter display an increased mutational burden, molecular profiles suggestive of an “immune hot” tumor microenvironment are observed across STS histologies, and response to immunotherapy has been reported in both translocation-related and genetic complex STSs. These data reinforce the notion that immunity in STSs is multifaceted and influenced by both genetic and epigenetic determinants. Cumulative evidence indicates that a fine characterization of STSs at different levels is required to identify biomarkers predictive of immunotherapy response and to discover targetable pathways to switch on the immune sensitivity of “immune cold” tumors. In this review, we will summarize recent findings on the interplay between genetic landscape, molecular profiling and immunity in STSs. Immunological and molecular features will be discussed for their prognostic value in selected STS histologies. Finally, the local and systemic immunomodulatory effects of the targeted drugs imatinib and sunitinib will be discussed.     

1,2-Mannobioside mimic: synthesis, DC-SIGN interaction by NMR and docking, and antiviral activity

The design and preparation of carbohydrate ligands for DC-SIGN is a topic of high interest because of the role played by this C-type lectin in immunity and infection processes. The low chemical stability of carbohydrates against enzymatic hydrolysis by glycosylases has stimulated the search for new alternatives more stable in vivo. Herein, we present a good alternative for a DC-SIGN ligand based on a mannobioside mimic with a higher enzymatic stability than the corresponding disaccharide. NMR and docking studies have been performed to study the interaction of this mimic with DC-SIGN in solution demonstrating that this pseudomannobioside is a good ligand for this lectin. In vitro studies using an infection model with Ebola pseudotyped virus demonstrates that this compound presents an antiviral activity even better than the corresponding disaccharide and could be an interesting ligand to prepare multivalent systems with higher affinities for DC-SIGN with potential biomedical applications.     

Efficient two-step Positronium laser excitation to Rydberg levels

Antihydrogen production by charge exchange reaction between Positronium atoms and antiprotons requires efficient excitation of Positronium atoms up to high-n levels (Rydberg levels). A two-step optical excitation, the first from ground to n=3 and the second from this level to a Rydberg level, is proposed and a suitable laser system is discussed. The requirements on the energy and bandwidth of the excitation laser suggest the use of optical parametric generation technology for both wavelengths. The laser system is composed by two subsystems: one for the generation of 205 nm radiation and the other for the generation of 1670 nm radiation. We have separately developed and tested the laser sources and results are here presented.     

Convolutional neural network framework for wind turbine electromechanical fault detection

Effective and timely health monitoring of wind turbine gearboxes and generators is essential to reduce the costs of operations and maintenance activities, especially offshore. This paper presents a scalable and lightweight convolutional neural network (CNN) framework using high-dimensional raw condition monitoring data for the automatic detection of multiple wind turbine electromechanical faults. The proposed approach leverages the potential of combining information from a variety of signals to learn features and to discriminate the types of fault and their severity. As a result of the CNN layers used to extract features from the signals, this architecture works in the time domain and can digest high-resolution multi-sensor data streams in real-time. To overcome the inherent black-box nature of AI models, this research proposes two interpretability techniques, multidimensional scaling and layer-wise relevance propagation, to analyse the proposed model's inner-working and identify the signal features relevant for fault classification. Experimental results show high performance and classification accuracies above 99.9% for all fault cases tested, demonstrating the efficacy of the proposed fault-detection system.     

Assessment of fumonisins B1 and B2 levels in commercial maize-based food products by liquid chromatography with fluorimetric detection and postcolumn chemical derivatization

The occurrence of the fumonisins B(1) and B(2) in maize-based food products marketed in Italy was examined. A simply and reliable chromatographic method with fluorimetric detection and postcolumn o-phtalaldehyde derivatization was used for a monitoring of 100 samples (8 flours, 21 corn-meal, 16 snacks, 7 maize samples, 13 gluten-free products, and 35 corn-flakes) bought in local supermarkets during the years 2008 and 2009. The presence of both fumonisins B(1) and B(2), at a concentration higher than 15 μg/kg, was observed in all samples of corn-meal and maize-flour, in 75% of snacks, in 57% of maize samples, in 54% of gluten-free products, and in 29% of corn-flakes. A total of 7 samples including 4 corn-meals, 2 maize-flours, and 1 maize showed a value exceeding the maximum level fixed in the Regulation 1126/2007/EC; no positive sample was observed in corn-flakes, snacks, and gluten-free foods. Fumonisins contamination, on the whole range of maize-based food products analyzed, emphasizes the need of improve agricultural practices, and increase official control and monitoring studies.     

Investigation of rpoS and dps genes in sodium hypochlorite resistance of Salmonella Enteritidis SE86 isolated from foodborne illness outbreaks in southern Brazil

In Rio Grande do Sul, southern Brazil, Salmonella Enteritidis is one of the principal microorganisms responsible for foodborne disease. The present study was conducted to compare the sodium hypochlorite resistance of Salmonella Enteritidis SE86 with that of other strains of Salmonella Enteritidis isolated from different regions of the world and to investigate the involvement of the rpoS and dps genes in resistance to this disinfectant. We tested five Salmonella Enteritidis wild-type (WT) strains isolated from different countries, two mutant strains of Salmonella Enteritidis SE86, and two tagged (3XFLAG) strains of Salmonella Enteritidis SE86 for their resistance to sodium hypochlorite (200 ppm). The survival of the WT and attenuated strains was determined based on bacterial counts, and tagged proteins (Dps and RpoS) were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting with anti-FLAG antibodies. None of the WT strains of Salmonella Enteritidis were totally inactivated after 20 min. The SE86 strain lacking dps was more sensitive to sodium hypochlorite than was the WT SE86 strain, with a 2-log reduction in counts after 1 min. The RpoS and Dps proteins were actively expressed under the conditions tested, indicating that in Salmonella Enteritidis SE86 these genes, which are expressed when in contact with sodium hypochlorite, are related to oxidative stress.     

Activation of Peripheral Blood Mononuclear Cells and Leptin Secretion: New Potential Role of Interleukin-2 and High Mobility Group Box (HMGB)1

Activation of innate immunity and low-grade inflammation contributes to hyperglycemia and an onset of Type 2 Diabetes Mellitus (T2DM). Interleukin-2 (IL-2), leptin, High Mobility Group Box-1 (HMGB-1), and increased glucose concentrations are mediators of these processes also by modulating peripheral blood mononuclear cells (PBMCs) response. The aim of this study was to investigate if HMGB-1 and IL-2 turn on PBMCs and their leptin secretion. In isolated human PBMCs and their subpopulations from healthy individuals and naïve T2DM patients, leptin release, pro-inflammatory response and Toll-like Receptors (TLRs) activation was measured. After treatment with IL-2 and HMGB1, NK (Natural Killer) have the highest amount of leptin secretion, whilst NK-T have the maximal release in basal conditions. TLR4 (TAK242) and/or TLR2 (TLR2-IgA) inhibitors decreased leptin secretion after IL-2 and HMGB1 treatment. A further non-significant increase in leptin secretion was reported in PBMCs of naive T2DM patients in response to IL-2 and HMGB-1 stimulation. Finally, hyperglycemia or hyperinsulinemia might stimulate leptin secretion from PBMCs. The amount of leptin released from PBMCs after the different treatments was enough to stimulate the secretion of IL-1β from monocytes. Targeting leptin sera levels and secretion from PBMCs could represent a new therapeutic strategy to counteract metabolic diseases such as T2DM.