The Landscape of microRNAs in βCell: Between Phenotype Maintenance and Protection

Diabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia mainly due to pancreatic β cell death and/or dysfunction, caused by several types of stress such as glucotoxicity, lipotoxicity and inflammation. Different patho-physiological mechanisms driving β cell response to these stresses are tightly regulated by microRNAs (miRNAs), a class of negative regulators of gene expression, involved in pathogenic mechanisms occurring in diabetes and in its complications. In this review, we aim to shed light on the most important miRNAs regulating the maintenance and the robustness of β cell identity, as well as on those miRNAs involved in the pathogenesis of the two main forms of diabetes mellitus, i.e., type 1 and type 2 diabetes. Additionally, we acknowledge that the understanding of miRNAs-regulated molecular mechanisms is fundamental in order to develop specific and effective strategies based on miRNAs as therapeutic targets, employing innovative molecules.     

Precision Oncology via NMR-Based Metabolomics: A Review on Breast Cancer

Precision oncology is an emerging approach in cancer care. It aims at selecting the optimal therapy for the right patient by considering each patient’s unique disease and individual health status. In the last years, it has become evident that breast cancer is an extremely heterogeneous disease, and therefore, patients need to be appropriately stratified to maximize survival and quality of life. Gene-expression tools have already positively assisted clinical decision making by estimating the risk of recurrence and the potential benefit from adjuvant chemotherapy. However, these approaches need refinement to further reduce the proportion of patients potentially exposed to unnecessary chemotherapy. Nuclear magnetic resonance (NMR) metabolomics has demonstrated to be an optimal approach for cancer research and has provided significant results in BC, in particular for prognostic and stratification purposes. In this review, we give an update on the status of NMR-based metabolomic studies for the biochemical characterization and stratification of breast cancer patients using different biospecimens (breast tissue, blood serum/plasma, and urine).     

A declarative two-level framework to specify and verify workflow and authorization policies in service-oriented architectures

The specification of distributed service-oriented applications spans several levels of abstraction, e.g., the protocol for exchanging messages, the set of interface functionalities, the types of the manipulated data, the workflow, the access policy, etc. Many (even executable) specification languages are available to describe each level in separation. However, these levels may interact in subtle ways (for example, the control flow may depend on the values of some data variables) so that a precise abstraction of the application amounts to more than the sum of its per level components. This problem is even more acute in the design phase when automated analysis techniques may greatly help the difficult task of building “correct” applications faced by designers. To alleviate this kind of problems, this paper introduces a framework for the formal specification and automated analysis of distributed service-oriented applications in two levels: one for the workflow and one for the authorization policies. The former allows one to precisely describe the control and data parts of an application with their mutual dependencies. The latter focuses on the specification of the criteria for granting or denying third-party applications the possibility to access shared resources or to execute certain interface functionalities. These levels can be seen as abstractions of one or of several levels of specification mentioned above. The novelty of our proposal is the possibility to unambiguously specify the—often subtle—interplay between the workflow and policy levels uniformly in the same framework. Additionally, our framework allows us to define and investigate verification problems for service-oriented applications (such as executability and invariant checking) and give sufficient conditions for their decidability. These results are non-trivial because their scope of applicability goes well beyond the case of finite state spaces allowing for applications manipulating variables ranging over infinite domains. As proof of concept, we show the suitability and flexibility of our approach on two quite different examples inspired by industrial case studies.     

The effect of ionising radiation on photosynthetic oxygenic microorganisms for survival in space flight revealed by automatic photosystem II-based biosensors

Photosynthetic microorganisms are expected to be useful to maintain an oxygenic atmosphere and to provide biomass for astronauts in the International Space Station as well as in future long-term space flights. However, fluxes of complex ionizing radiation of various intensities and energies make space an extreme environment for the microorganisms, affecting their photosynthetic efficiency. To automatically monitor the photosynthetic Photosystem II (PSII) activity of microorganisms under space conditions an optical biosensor, which utilizes chlorophyll fluorescence as biological transduction system, was built; the PSII activity was monitored by the biosensor during balloon flights at stratospheric altitudes of about 40 km. The effect of space stress on quantum yield of PSII varied among the tested species depending on the growth light conditions at which they were exposed during the flights.     

A State of the Art of Antioxidant Properties of Curcuminoids in Neurodegenerative Diseases

Neurodegenerative diseases represent a set of pathologies characterized by an irreversible and progressive, and a loss of neuronal cells in specific areas of the brain. Oxidative phosphorylation is a source of energy production by which many cells, such as the neuronal cells, meet their energy needs. Dysregulations of oxidative phosphorylation induce oxidative stress, which plays a key role in the onset of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). To date, for most neurodegenerative diseases, there are no resolute treatments, but only interventions capable of alleviating the symptoms or slowing the course of the disease. Therefore, effective neuroprotection strategies are needed. In recent years, natural products, such as curcuminoids, have been intensively explored and studied for their therapeutic potentials in several neurodegenerative diseases. Curcuminoids are, nutraceutical compouns, that owen several therapeutic properties such as anti-oxidant, anti-inflammatory and neuroprotective effects. In this context, the aim of this review was to provide an overview of preclinical and clinical evidence aimed to illustrate the antioxidant effects of curcuminoids in neurodegenerative diseases. Promising results from preclinical studies encourage the use of curcuminoids for neurodegeneration prevention and treatment.     

Glass and Jamming Rheology in Soft Particles Made of PNIPAM and Polyacrylic Acid

The phase behaviour of soft colloids has attracted great attention due to the large variety of new phenomenologies emerging from their ability to pack at very high volume fractions. Here we report rheological measurements on interpenetrated polymer network microgels composed of poly(N-isopropylacrylamide) (PNIPAM) and polyacrylic acid (PAAc) at fixed PAAc content as a function of weight concentration. We found three different rheological regimes characteristic of three different states: a Newtonian shear-thinning fluid, an attractive glass characterized by a yield stress, and a jamming state. We discuss the possible molecular mechanisms driving the formation of these states.     

Experimental evaluation of plowing and scratch hardness of aqueous two-component polyurethane (2K-PUR) coatings on glass and polycarbonate

Scratch resistance of aqueous two-component (2K-PUR) polyurethane coatings deposited on glass and polycarbonate was investigated by constant mode scratch tests. Penetration and residual depths as well as scratch widths were experimentally evaluated. A first analytical model was applied to estimate plowing and scratch hardness of the polyurethane coatings according to contact pressure and load rate and the corresponding 3D maps were drawn out. The experimental findings allowed mapping the scratch response the polyurethane coatings came through varying the applied load, load rate and substrate compliance, thus establishing the basis for the development of useful tools for failure prediction of the investigated coating systems in a broad range of operational conditions.     

Diet supplementation with donkey milk upregulates liver mitochondrial uncoupling,reduces energy efficiency and improves antioxidant and antiinflammatory defences in rats

Dietary PUFA, mainly those of the n‐3 family, are known to play essential roles in the maintenance of energy balance and in the reduction of body fat deposition through the upregulation of mitochondrial uncoupling that is the main source of reactive oxygen species. We hypothesized that rat supplementation with raw donkey's milk (DM), characterized by low‐fat content and higher n3:n6 ratio, may affect energy balance, lipid metabolism, and prooxidant status as compared to animals treated with cow's milk. In the present study, the effects of drinking raw DM (for 4 weeks) on energy balance, lipid metabolism, antiinflammatory, and antioxidant/detoxifying defences was compared to that produced by rat intake of an iso‐energetic amount of raw cow's milk. The hypolipidemic effect produced by DM paralleled with the enhanced mitochondrial activity/proton leakage and with the increased activity or expression of mitochondrial markers namely, carnitine palmitoyl transferase and uncoupling protein 2. The association of decreased energy efficiency with reduced proinflammatory signs (TNF‐α and LPS levels) with the significant increase antioxidant (total thiols) and detoxifying enzyme activities (glutathione‐S‐transferase NADH quinone oxidoreductase) in DM‐treated animals, indicated that beneficial effects were attributable, at least in part, to the activation of nuclear factor 2 erythroid‐related factor 2 pathway.