ENERGY EXPENDITURE, GLUCOSE METABOLISM AND BODY COMPOSITION IN BABOONS AT BASELINE AND AFTER A PARTIAL PANCREATECTOMY AND A 13 WEEKS OF CONTINUOUS INFUSION OF EXENATIDE

Type 2 diabetes mellitus (T2DM) is an extremely complex endocrine and metabolic disease, and the two major causes are impaired insulin secretion and increased insulin resistance in several organs and tissues. A non-human primate is an invaluable model for the study of human diseases due to their close genetic, anatomical and physiological similarities to humans. They are widely used in biomedical research aiming to elucidate the physiological and molecular mechanisms of different diseases, such as cardiovascular diseases, metabolic syndrome, age-related changes in metabolic parameters, obesity, T2DM, atherosclerosis etc. This entire project has different aims; the first is to confirm that baboons are a very suitable model for studying metabolic diseases such as cardiovascular diseases, metabolic syndrome, age-related changes in metabolic parameters, obesity etc, and confirm baboons as a model in a physical activity studies related to improving health and well-being. In fact, the first study was conducted to evaluate the SenseWear\uae Armband (SWA), a metabolic holter used in humans to estimate the resting and the total energy expenditure in baboon and verify his reliability to estimate energy expenditure during resting and different activities also in non-human primates. The second and more complex study was related to elucidate, at least in part, the effects of a continuous infusion of a medication for the treatment of T2DM (Exenatide) in a non-human primate, in a model with impaired \u3b2-cell function, reporting a insulin sensitizing effect in the Exenatide-treated group, an increase insulin sensitivity and \u3b2-cells function and decrease in total body weight. This type of research could be extremely valuable for helping to develop potential new treatments for T2DM. In conclusion, in the first study we demonstrated that the SWA is a reliable and simple method to estimate total energy expenditure (TEE) and resting energy expenditure (REE) in non-human primate, baboons, by placing it in the \u201cmetabolic jacket\u201d. In the second study we found a powerful, direct, insulin sensitizing effect of EXE on normal glucose tolerant baboons. These studies provide novel solid basis for further clinical trials aimed at preserving and supporting subjects with diabetes or at high risk of developing it

Salix shrub encroachment along a 1000 m elevation gradient triggers a major ecosystem change in the European Alps

Shrub encroachment, a globally recognized response to climate warming, usually involves late successional species in mountain environments, without alteration to climax communities. We show that a major ecosystem change is occurring in the European Alps across a 1000 m elevation gradient, with pioneer hygrophilous Salix shrubs, previously typical of riparian forests, wetlands and avalanche ravines, encroaching into the climax communities of subalpine and alpine belts shrublands and grasslands, as well as snowbeds, pioneer vegetation and barren grounds in the nival belt. We analyzed Salix recruitment through dendrochronological methods, and assessed its relationships with climate and atmospheric CO2 concentration. The dendrochronological data indicated that Salix encroachment commenced in the 1950s (based on the age of the oldest Salix individuals, recruited in 1957), and that it was correlated with increasing atmospheric CO2 concentration, spring warming and snow cover decrease. Hygrophilous Salix shrubs are expanding their distribution both through range filling and upwards migration, likely achieving competitive replacement of species of subalpine and alpine climax communities. They benefit from climate warming and CO2 fertilization and are not sensitive to spring frost damage and soil limitations, being observed across a gradient of soil conditions from loose glacial sediments in recently deglaciated areas (where soils had not had sufficient time to develop) to mature soils such as podzols (when colonizing late successional subalpine shrublands). Salix encroachment may trigger ecosystem and landscape transformations, promoting the development of forests that replace pre-existing subalpine shrublands, and of open woodlands invading alpine grasslands and snowbeds, making the alpine environment similar to sub-Arctic and Arctic areas. This results in a new threat to the conservation of the plant species, communities and landscapes typical of the alpine biota, as mountain ranges such as the Alps provide limited opportunities for upward migration and range-shift

Determination of the geographical origin of green coffee beans using NIR spectroscopy and multivariate data analysis

In this work, near infrared (NIR) spectroscopy and multivariate data analysis were investigated as a fast and non disruptive method to classify green coffee beans on continents and countries bases. FT-NIR spectra of 191 coffee samples, origin from 2 continents and 9 countries, were acquired by two different laboratories. Laboratory-independent Partial Least Square-Discriminant Analysis and interval PIS-DA models were developed by following a hierarchical approach, i.e. considering at first the continent and then the country of origin as discrimination rule. The best continent-based classification model was able to identify correctly more than 98% in prediction, whereas 100% of them were correctly predicted by the best country-based classification model. The inter-laboratory reliability of the proposed method was confirmed by McNemar test, since no significant differences (P > 0.05) were found. Furthermore, a validation was performed predicting the spectral test set of a laboratory using the model developed by the other one

The Raman Fingerprint of Graphene

Graphene is the two-dimensional (2d) building block for carbon allotropes of every other dimensionality. It can be stacked into 3d graphite, rolled into 1d nanotubes, or wrapped into 0d fullerenes. Its recent discovery in free state has finally provided the possibility to study experimentally its electronic and phonon properties. Here we show that graphene's electronic structure is uniquely captured in its Raman spectrum that clearly evolves with increasing number of layers. Raman fingerprints for single-, bi- and few-layer graphene reflect changes in the electronic structure and electron-phonon interactions and allow unambiguous, high-throughput, non-destructive identification of graphene layers, which is critically lacking in this emerging research area

Preserving the Integrity of Liposomes Prepared by Ethanol Injection upon Freeze-Drying: Insights from Combined Molecular Dynamics Simulations and Experimental Data

The freeze-drying of complex formulations, such as liposomes, is challenging, particularly if dispersions contain residual organic solvents. This work aimed to investigate the effects of possible protectants, namely sucrose, trehalose and/or poly(vinyl pyrrolidone) (PVP), on the main features of the dried product using a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)-based liposomal dispersion prepared by ethanol injection and containing ethanol up to 6%, as a model. The interactions among vesicles and protectants were preliminary screened by Molecular Dynamics (MD) simulations, which have been proved useful in rationalizing the selection of protectant(s). The freeze-drying protocol was based on calorimetric results. Overall data suggested a stronger cryo-protectant effect of trehalose, compared with sucrose, due to stronger interactions with the DPPC bilayer and the formation of highly ordered clusters around the lipids. The effect further improved in the presence of PVP. Differently from the other tested protectants, the selected trehalose/PVP combination allows to preserve liposome size, even in the presence of 6% ethanol, as demonstrated by Nanoparticle Tracking Analysis (NTA). Nevertheless, it should be also underlined that cakes blew out at an ethanol concentration higher than 1% v/v, probably due to the poor cohesion within the cake and solvent vapour pressure upon sublimation

Characterisation of a track structure imaging detector

The spatial distribution of radiation-induced ionisations in sub-cellular structures plays an important role in the initial formation of radiation damage to biological tissues. Using the nanodosimetry approach, physical characteristics of the track structure can be measured and correlated to DNA damage. In this work, a novel nanodosimeter is presented, which detects positive ions produced by radiation interacting with a gas-sensitive volume in order to obtain a high resolution image of the radiation track structure. The characterisation of the detector prototype was performed and different configurations of the device were tested by varying the detector cathode material and the working gas. Preliminary results show that the ionisation cluster size distribution can be obtained with this approach. Further work is planned to improve the detector efficiency in order to register the complete three-dimensional track structure of ionising radiatio

Design of pressure-sensitive adhesive suitable for the preparation of transdermal patches by hot-melt printing

This work aimed to design low-melting pressure sensitive adhesives and to demonstrate the feasibility of the preparation of (trans)dermal patches by hot-melt ram extrusion printing. This approach allows defining both the geometry of (trans)dermal patch and the drug strength easily according to patient needs. The preparation steps are the mixing of a poly-ammonium methacrylate polymer (i.e. Eudragit RL and RS) with a suitable amount of plasticizer (triacetin or tributyl citrate) and drug (ketoprofen or nicotine), the melting in the ram extruder, and the printing on the backing layer foil. The formulations were characterized in terms of rheological and adhesive properties, in vitro drug release and skin permeation profiles. The (trans)dermal patches made of Eudragit RL or Eudragit RS plasticized with the 40% triacetin could be printed at 90 \ub0C giving formulations with suitable adhesive properties and without cold flow after 1 month of storage at 40 \ub0C. Furthermore, the overall results showed that the performances of printed (trans)dermal patches overlapped those made by solvent casting, suggesting that the proposed solvent-free technology can be useful to treat cutaneous pathologies when the availability of (trans)dermal patches with size and shape that perfectly fit with the skin area affected by the disease improves the safety of the pharmacological treatment

A glimpse in critical attributes to design cutaneous film forming systems based on ammonium methacrylate

A film forming system based on Eudragit\uae RL (EuRL) was designed aiming to evidence the relevance of formulative variables on the following critical attributes: film forming rate, outward stickiness, Young modulus (Y) and in vitro drug skin permeation. Different solvent mixtures (acetone and isopropanol in the range from 10:90 to 40:60 v/v), polymer concentrations (10-30 % w/w), and plasticizer types and concentrations (triacetin or tributyl citrate, up to 50% of EuRL) were evaluated. EuRL dissolved in 80/20 or 70/30 v/v isopropanol/acetone mixtures at the concentration of 20% and plasticized with tributyl citrate (20 or 30% with respect to polymer) gave films with negligible stickiness and Y lower than 3 MPa. This value should assure an intimate and prolonged contact with the skin since it was significantly lower than Y of human stratum corneum (55 MPa). The optimized formulations were able to sustain the skin permeation of ibubrofen, ketoprofen and flurbiprofen and evidenced the importance of each formulative variable. In particular, relatively slow solvent evaporation rate can determine an initial \u201cburst\u201d effect and can influence the drug permeation in the initial hours. Conversely, when the solvent evaporation rate is not discriminant, the thermodynamic activity remains the main parameter driving the skin permeation

Lactic acid bacteria with cholesterol-lowering properties for dairy applications: In vitro and in situ activity.

Cholesterol-lowering activity is one of the most promising properties of lactic acid bacteria with probiotic characteristics. In the present study, 58 potentially probiotic lactic acid bacteria were tested for their ability to survive in vitro digestion and reduce cholesterol in a medium containing cholesterol and bile acids. The best-performing strains (Lactobacillus casei VC199, Lactobacillus paracasei ssp. paracasei SE160 and VC213, Lactobacillus plantarum VS166 and VS513, Enterococcus faecium VC223, and Enterococcus lactis BT161) resulted in a 42 to 55% reduction of the cholesterol level in broth and were further tested in cheese manufacture. The cholesterol content in all the cheeses decreased with ripening. All the strains were present in the cheese at levels higher than 107 cfu/g until 60 d of ripening, the highest reductions (up to 23%) being obtained when Lb. paracasei ssp. paracasei VC213 and E. lactis BT161 were added during the cheese-making. The adjunct cultures had no negative effect on the sensory characteristics of the cheese. Thus, these strains with proven in vitro properties are good candidates for novel probiotic-containing formulations and could be used to functionalize foods such as dairy fermented products