Cachexia,a Systemic Disease beyond Muscle Atrophy

Cachexia is a complication of dismal prognosis, which often represents the last step of several chronic diseases. For this reason, the comprehension of the molecular drivers of such a condition is crucial for the development of management approaches. Importantly, cachexia is a syndrome affecting various organs, which often results in systemic complications. To date, the majority of the research on cachexia has been focused on skeletal muscle, muscle atrophy being a pivotal cause of weight loss and the major feature associated with the steep reduction in quality of life. Nevertheless, defining the impact of cachexia on other organs is essential to properly comprehend the complexity of such a condition and potentially develop novel therapeutic approaches.     

Strategies to Modulate Specialized Metabolism in Mediterranean Crops: From Molecular Aspects to Field

Plant specialized metabolites (SMs) play an important role in the interaction with the environment and are part of the plant defense response. These natural products are volatile, semi-volatile and non-volatile compounds produced from common building blocks deriving from primary metabolic pathways and rapidly evolved to allow a better adaptation of plants to environmental cues. Specialized metabolites include terpenes, flavonoids, alkaloids, glucosinolates, tannins, resins, etc. that can be used as phytochemicals, food additives, flavoring agents and pharmaceutical compounds. This review will be focused on Mediterranean crop plants as a source of SMs, with a special attention on the strategies that can be used to modulate their production, including abiotic stresses, interaction with beneficial soil microorganisms and novel genetic approaches.     

Taxonomy of digital community currency platforms*

ABSTRACT

Community currencies are used to pay for products or services within specific groups defined by geographical boundaries or specific common interests. Financial crises, social emergence in developing countries, and increased access to digital devices have stimulated a growing number of communities worldwide to develop digital currency projects. These projects use technologies ranging from traditional plastic cards to mobile phones and blockchain technologies. Following the design science research approach, this paper analyzes digital community currencies (DCCs) by developing a taxonomy based on platform architecture, governance, transactionality and virtuality. By investigating 22 DCC platforms around the world, 4 groups were distinguished: local, proprietary, commons and cyber. The identification of these four different groups of digital community currencies allows us to better discuss the potentials and limitations of each one of them. The presented taxonomy can be useful to researchers and practitioners both to explain and to design DCC platforms. Discussing each of the emerging categories from the proposed taxonomy helps us to provide insights into DCCs, offering a new theoretical frame for investigating the particular case of digital payment platforms.     

Cyanobacterial blooms in the central basin of Lake Erie: Potentials for cyanotoxins and environmental drivers

Lake Erie western basin (WB) cyanobacterial blooms are a yearly summer occurrence; however, blooms have also been reported in the offshore waters of the central basin (CB), and very little is known about what drives these blooms or their potential for cyanobacterial toxins. Cyanobacteria Index was quantified using MODIS and MERIS data for the CB between 2003 and 2017, and water samples were collected between 2013 and 2017. The goals were to 1) quantify cyanobacteria, 2) determine environmental drivers of CB blooms, and 3) determine the potential for cyanobacterial toxins in the CB. Dolichospermum (Anabaena) occurred in the CB during July before the onset of the WB bloom, and then in August and September, the cyanobacteria community shifted towards Microcystis. The largest Dolichospermum blooms (2003, 2012, 2013, and 2015) were associated with reduced water clarity (Secchi disk depth?<?4?m), whereas large CB Microcystis blooms (2011 and 2015) were associated with large WB blooms. Dolichospermum blooms occurred in high nitrate concentrations (>20?μmol/L) and high nitrogen-to?phosphorus ratios (>100), which indicate nutrient concentrations or ratios did not select for Dolichospermum. Additionally, the sxtA gene, but not mcyE or microcystins, were detected in the CB during July 2016 and 2017. The mcyE gene and microcystins were detected in the CB during August 2016 and 2017. The results indicate the CB's potential for cyanotoxins shifts from saxitoxins to microcystins throughout the summer. Continued monitoring of cyanobacteria and multiple cyanobacterial toxins is recommended to ensure safe drinking water for CB coastal communities.     

Quinone‐Fused Pyrazoles through 1,3‐Dipolar Cycloadditions: Synthesis of Tricyclic Scaffolds and in vitro Cytotoxic Activity Evaluation on Glioblastoma Cancer Cells

A novel and straightforward synthesis of highly substituted isoquinoline‐5,8‐dione fused tricyclic pyrazoles is reported. The key step of the synthetic sequence is a regioselective, Ag₂CO₃ promoted, 1,3‐dipolar cycloaddition of C‐heteroaryl‐N‐aryl nitrilimines and substituted isoquinoline‐5,8‐diones. The broad functional group tolerability and mild reaction conditions were found to be suitable for the preparation of a small library of compounds. These scaffolds were designed to interact with multiple biological residues, and two of them, after brief synthetic elaborations, were analyzed by molecular docking studies as potential anticancer drugs. In vitro studies confirmed the potent anticancer effects, showing promising IC₅₀ values as low as 2.5 μm against three different glioblastoma cell lines. Their cytotoxic activity was finally positively correlated to their ability to inhibit PI3K/mTOR kinases, which are responsible for the regulation of diverse cellular processes in human cancer cells.     

Hybrid amperometric and conductometric chemical sensor based on conducting polymer nanojunctions

We report on a hybrid chemical sensor that can perform either amperometric or conductometric detection alone or simultaneously. It consists of an array of electrode pairs in which the two electrodes in each pair are separated with micrometer to nanometer-scale gaps. The gaps are bridged with conducting polymer (polyaniline) so that one can measure the conductance of the polymer bridge like a conventional Chem-FET. The electrode geometries are designed to allow simultaneously detection of electrochemical current like a conventional microelectrode amperometric sensor. The hybrid device provides increased selectivity for detection of analytes in complex matrixes and may provide new insights into the electrochemical reaction mechanisms of analytes. As an example, we have demonstrated the detection of dilute neurotransmitter (dopamine) in the presence of its concentrated major physiological interferent, ascorbic acid, which is not possible using either the amperometric or the conductometric techniques alone.     

Dynamic fatigue and strength characterization of three ceramic materials

Fracture strength and fatigue parameters of three ceramic materials submitted to dynamic fatigue were evaluated. A machinable leucite-reinforced dental ceramic, aluminum oxide, and yttria-stabilized zirconia (YSZ) were tested. The inert strength of the materials was determined in air (25 °C) at stressing rates of 70, 250, 400 MPa/s for Porcelain, Alumina and YSZ respectively. The data was analyzed using a two-parameter Weibull distribution. The Weibull modulus (m) and the characteristic of fracture (σ ₀) parameters were determined for each material. Specimens were also tested in 3-point bending at different stressing rates in distilled/deionized water at 37 °C (dynamic fatigue) in order to calculate the fatigue parameters n and ln B. The strength for each material was characterized using Strength–Probability–Time (SPT) diagrams for 1 day, 1 year and 10 years. YSZ showed a high-fracture strength σ ₀ (1,459 MPa) at a failure probability of 63.2% and high resistance to subcritical crack growth. YSZ and alumina showed better resistance to slow crack growth than porcelain, indicating less susceptibility to strength degradation by stress corrosion. Lifetime predictions after 10 years indicate a reduction of 50%, 36% and 29% in strength for porcelain, alumina and YSZ respectively. YSZ seems to be a very promising material for long-term dental and biomedical applications.