Milk from cows fed a diet with a high forage:concentrate ratio improves inflammatory state,oxidative stress,and mitochondrial function in rats

Excessive energy intake may evoke complex biochemical processes characterized by inflammation, oxidative stress, and impairment of mitochondrial function that represent the main factors underlying noncommunicable diseases. Because cow milk is widely used for human nutrition and in food industry processing, the nutritional quality of milk is of special interest with respect to human health. In our study, we analyzed milk produced by dairy cows fed a diet characterized by a high forage:concentrate ratio (high forage milk, HFM). In view of the low n-6:n-3 ratio and high content of conjugated linoleic acid of HFM, we studied the effects of this milk on lipid metabolism, inflammation, mitochondrial function, and oxidative stress in a rat model. To this end, we supplemented for 4 wk the diet of male Wistar rats with HFM and with an isocaloric amount (82 kJ, 22 mL/d) of milk obtained from cows fed a diet with low forage:concentrate ratio, and analyzed the metabolic parameters of the animals. Our results indicate that HFM may positively affect lipid metabolism, leptin:adiponectin ratio, inflammation, mitochondrial function, and oxidative stress, providing the first evidence of the beneficial effects of HFM on rat metabolism.     

Analysis of a homologous series of non-reducing oligosaccharides from Arnica montana L. Roots

The oligosaccharide component compositions of a series of non-reducing oligosaccharides extracted from the roots of Arnica montana L. has been determined by gel permeation chromatography (g.p.c.). The range of oligosaccharides present was found to extend beyond the octasaccharide previously reported. with 16% to 19% of the oligosaccharides having a degree of polymerisation of between 11 and 19 and almost 3% having a degree of polymerisation greater than 20. The chromatographic behaviour of this series of oligosaccharides is compared with that observed for series of D-gluco-oligosaccharides.     

Complementary Effects of Carbamylated and Citrullinated LL37 in Autoimmunity and Inflammation in Systemic Lupus Erythematosus

LL37 acts as T-cell/B-cell autoantigen in Systemic lupus erythematosus (SLE) and psoriatic disease. Moreover, when bound to “self” nucleic acids, LL37 acts as “danger signal,” leading to type I interferon (IFN-I)/pro-inflammatory factors production. T-cell epitopes derived from citrullinated-LL37 act as better antigens than unmodified LL37 epitopes in SLE, at least in selected HLA-backgrounds, included the SLE-associated HLA-DRB1*1501/HLA-DRB5*0101 backgrounds. Remarkably, while “fully-citrullinated” LL37 acts as better T-cell-stimulator, it loses DNA-binding ability and the associated “adjuvant-like” properties. Since LL37 undergoes a further irreversible post-translational modification, carbamylation and antibodies to carbamylated self-proteins other than LL37 are present in SLE, here we addressed the involvement of carbamylated-LL37 in autoimmunity and inflammation in SLE. We detected carbamylated-LL37 in SLE-affected tissues. Most importantly, carbamylated-LL37-specific antibodies and CD4 T-cells circulate in SLE and both correlate with disease activity. In contrast to “fully citrullinated-LL37,” “fully carbamylated-LL37” maintains both innate and adaptive immune-cells’ stimulatory abilities: in complex with DNA, carbamylated-LL37 stimulates plasmacytoid dendritic cell IFN-α production and B-cell maturation into plasma cells. Thus, we report a further example of how different post-translational modifications of a self-antigen exert complementary effects that sustain autoimmunity and inflammation, respectively. These data also show that T/B-cell responses to carbamylated-LL37 represent novel SLE disease biomarkers.     

Mutual Prodrugs of 5-Fluorouracil: From a Classic Chemotherapeutic Agent to Novel Potential Anticancer Drugs

The development of potent antitumor agents with a low toxicological profile against healthy cells is still one of the greatest challenges facing medicinal chemistry. In this context, the “mutual prodrug” approach has emerged as a potential tool to overcome undesirable physicochemical features and mitigate the side effects of approved drugs. Among broad-spectrum chemotherapeutics available for clinical use today, 5-fluorouracil (5-FU) is one of the most representative, also included in the World Health Organization model list of essential medicines. Unfortunately, severe side effects and drug resistance phenomena are still the primary limits and drawbacks in its clinical use. This review describes the progress made over the last ten years in developing 5-FU-based mutual prodrugs to improve the therapeutic profile and achieve targeted delivery to cancer tissues.     

A New Tool to Study Parkinsonism in the Context of Aging: MPTP Intoxication in a Natural Model of Multimorbidity

The diurnal rodent Octodon degus (O. degus) is considered an attractive natural model for Alzheimer’s disease and other human age-related features. However, it has not been explored so far if the O. degus could be used as a model to study Parkinson’s disease. To test this idea, 10 adult male O. degus were divided into control group and MPTP-intoxicated animals. Motor condition and cognition were examined. Dopaminergic degeneration was studied in the ventral mesencephalon and in the striatum. Neuroinflammation was also evaluated in the ventral mesencephalon, in the striatum and in the dorsal hippocampus. MPTP animals showed significant alterations in motor activity and in visuospatial memory. Postmortem analysis revealed a significant decrease in the number of dopaminergic neurons in the ventral mesencephalon of MPTP animals, although no differences were found in their striatal terminals. We observed a significant increase in neuroinflammatory responses in the mesencephalon, in the striatum and in the hippocampus of MPTP-intoxicated animals. Additionally, changes in the subcellular expression of the calcium-binding protein S100β were found in the astrocytes in the nigrostriatal pathway. These findings prove for the first time that O. degus are sensitive to MPTP intoxication and, therefore, is a suitable model for experimental Parkinsonism in the context of aging.     

Compatibilization of an immiscible blend of EPDM and POM with an Ionomer

Immiscible blends of ethylene-propylene-diene-monomer (EPDM) and polyoxymethylene (POM), when EPDM is the major phase were compatibilized on the addition of an ionomer, poly(ethylene-co-methacrylic acid). The inclusion of the ionomer reduced the interfacial tension between the two phases, such that the diameter of the POM domains were significantly reduced to between 0.5 and 2 μm, typical of that required to toughen ductile polymers. The mechanical properties of the resultant compatibilized blends were significantly enhanced with increases in Young's modulus (↑54%), tensile strength (σ, ↑139%), elongation at break (ε, ↑97%), and tensile toughness (↑500%) with increasing ionomer content, relative to EPDM rubber alone. The ShoreA hardness of the compatibilized blend was 70.1 compared with 56.8 for the immiscible binary blend and, 50.2 for neat EPDM rubber.     

A Survey of Airworthiness and Certification for UAS

The Italian SMAT project is a civilian program supported by Piemonte Region developed for the territorial monitoring and surveillance and for the prevention of natural hazards. In a different way from the previous surveillance programs, the SMAT project is based on the use of several unmanned platforms that are able to cooperate through ground coordination and control station. The flight in non-segregated airspace, needed in order to accomplish the territorial monitoring mission, is a main issue to be investigated and defined, because of the current lack of a common consensus and agreement on the regulations of UAS. The present work outlines the international initiatives that deal with the development of the regulatory framework on airworthiness and certification of UAS and their potential impact on the SMAT project.     

Formal methods integration for the specification of dependable distributed systems

This paper describes a real-world case study in the specification and analysis of dependable distributed systems. The case study is an automated transport system with safety requirements. In order to manage the complexity of the problem of specifying the dynamic behavior of the whole system, a compositional approach is used, based on the integration of the trace logic of the Communicating Sequential Processes (CSP) theory, and stochastic Petri nets (SPNs). It is argued that the integration of different formal methods is a useful approach in the definition of practical engineering methodologies for the specification, design and analysis of complex dependable distributed systems.     

Inverse Analysis of Impact Test Data: Experimental Study on Polymeric Materials Displaying Brittle Behaviour

This paper deals with the influence of the testing equipment on impact load measurements. A previously developed method of analysis and processing of the experimental data based on a refined analogical model of the impact event and inverse problem techniques is used. This method makes it possible to obtain the mechanical response of the material, notwithstanding the disturbance of the dynamic effects associated to the test. Results from tests carried out both on falling weight and swing pendulum instrumented testing machines are compared. It is shown that this method can give an accurate estimation of the actual bending force in impact testing independent of the testing equipment.