A Comparison of Network-Based Methods for Drug Repurposing along with an Application to Human Complex Diseases

Drug repurposing strategy, proposing a therapeutic switching of already approved drugs with known medical indications to new therapeutic purposes, has been considered as an efficient approach to unveil novel drug candidates with new pharmacological activities, significantly reducing the cost and shortening the time of de novo drug discovery. Meaningful computational approaches for drug repurposing exploit the principles of the emerging field of Network Medicine, according to which human diseases can be interpreted as local perturbations of the human interactome network, where the molecular determinants of each disease (disease genes) are not randomly scattered, but co-localized in highly interconnected subnetworks (disease modules), whose perturbation is linked to the pathophenotype manifestation. By interpreting drug effects as local perturbations of the interactome, for a drug to be on-target effective against a specific disease or to cause off-target adverse effects, its targets should be in the nearby of disease-associated genes. Here, we used the network-based proximity measure to compute the distance between the drug module and the disease module in the human interactome by exploiting five different metrics (minimum, maximum, mean, median, mode), with the aim to compare different frameworks for highlighting putative repurposable drugs to treat complex human diseases, including malignant breast and prostate neoplasms, schizophrenia, and liver cirrhosis. Whilst the standard metric (that is the minimum) for the network-based proximity remained a valid tool for efficiently screening off-label drugs, we observed that the other implemented metrics specifically predicted further interesting drug candidates worthy of investigation for yielding a potentially significant clinical benefit.     

Optimization of spray drying process of Sargassum muticum color extract

ABSTRACT

Sargassum muticum is categorized as a brown seaweed species which has been used as a dye fabric colorant in certain regions of Asia. The brown extracts of S. muticum also have antioxidant properties, which could enhance the color and nutrients in food products. However, the color extract is unstable, and also limits the application. This study was performed to encapsulate the color extract with maltodextrin and stabilize the color extract by spray drying technique using combinations of various levels of inlet temperature and feed flow rate. Initially, S. muticum powder was analyzed for moisture content, water activity, solubility, and color properties for optimization purposes. This study showed that the optimum inlet temperature and feed flow rate of the spray drying process to produce good-quality, stable, and acceptable powder properties were at 140°C and 3?rpm, respectively, with 4% of maltodextrin. Then, the powder was analyzed for density, compressibility index, hygroscopicity, particle size, and antioxidant properties. This study represents an interesting food additive to be incorporated in functional food due to the attractive brown colorant and the presence of antioxidants.     

Corrosion of zinc in simulated carbonated concrete pore solutions

The electrochemical behaviour of pure Zn and galvanized steel in solutions simulating the pore solution of carbonated concrete has been studied by means of potentiodynamic polarization tests and polarization resistance measurements. Pure Zn was chosen because it simulates well the behaviour of galvanized steel, yielding more reproducible results. The effect of different degrees of carbonation and the presence of different chloride contents in the simulated pore solutions was investigated. Results show that at a given pH (about 9.5) the corrosion susceptibility of Zn depends on anions concentration (carbonate and bicarbonate). The results obtained in simulated carbonated concrete pore solutions show that with low anion concentration Zn does not passivate while in presence of high levels of carbonate and bicarbonate the corrosion resistance is improved. Besides, the presence of chloride increases the corrosion susceptibility.     

Far-off and close-up dry matter intake modulate indicators of immunometabolic adaptations to lactation in subcutaneous adipose tissue of pasture-based transition dairy cows

The common practice of increasing dietary energy density during the close-up dry period (last ～3 wk prepartum) has been recently associated with a higher incidence of metabolic disorders after calving. Despite these reports, over-feeding of metabolizable energy (ME) during the far-off, nonlactating period is a common management policy aimed at achieving optimum calving body condition score (BCS) in pasture-based systems, as cows are generally thinner than total mixed ration cows at the end of lactation. Our hypothesis was that both far-off and close-up overfeeding influence the peripartum adipose tissue changes associated with energy balance and inflammatory state. Sixty mid-lactation, grazing dairy cows of mixed age and breed were randomly allocated to 1 of 2 groups that were managed through late lactation to achieve a low and high BCS (approximately 4.25 and 5.0 on a 10-point scale) at dry-off. The low BCS cows were then overfed ME to ensure that they achieved the same BCS as the higher BCS group by calving. Within each rate of BCS gain treatment, cows were offered 65, 90, or 120% of their pre-calving ME requirements for 3 wk pre-calving in a 2 × 3 factorial arrangement of treatments (i.e., 10 cows/treatment). Subcutaneous adipose tissue was collected via biopsy at ?1, 1, and 4 wk relative to parturition. Quantitative PCR was used to measure mRNA and microRNA expression of targets related to adipogenesis and inflammation. Cows overfed in the far-off period had increased expression of miR-143 and miR-378 prepartum (?1 wk) indicating greater adipogenesis, consistent with their rapid gain in BCS following dry-off. Furthermore, the lower postpartum expression of IL6, TNF, TLR4, TLR9, and miR-145, and a higher abundance of miR-99a indicated lower body fat mobilization in early lactation in the same group. In the close-up period, feeding either 65 or 120% of ME requirements caused changes in FASN, IL1B, IL6R, TLR9, and the microRNA miR-143, miR-155, and miR-378. Their respective expression patterns indicate a tentative negative-feedback mechanism in metabolically compromised, feed-restricted cows, and a possible immune-related stimulation of lipolysis in apparently static adipocytes in overfed cows. Data from cows fed 90% of ME requirements indicate the existence of a balance between lipolytic (inflammatory-related) and anti-lipolytic signals, to prime the mobilization machinery in light of imminent lactation. Overall, results indicate that far-off dry cow nutrition influences peripartum adipose tissue metabolism, with neither strategy negatively affecting the physiological adaptation to lactation. Furthermore, to ensure a favorable transition, cows should be subjected to a small feed restriction in the close-up period, irrespective of far-off nutritional management.     

Role of physical abnormalities in interpersonal perception and behavior.

Explores the impact of physical abnormalities on interpersonal relationships and investigates 1 technique available to the stigmatized to influence that impact. This technique is to indicate that the abnormality may be freely discussed or that it is a forbidden topic. The 60 male undergraduate Ss were introduced to an ostensibly naive student who was in reality a confederate and appeared either as an amputee in a wheelchair or as only slightly crippled. The shocks Ss were induced to administer the confederate were less painful when he was severely than when he was slightly crippled. It was concluded that all stigmata do not have the same interpersonal consequences and that the most marked effects occur for behaviors of which Ss have little awareness. (15 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Synchrotron radiolysis and mass spectrometry: a new approach to research on the actin cytoskeleton

Hydroxyl radicals generated from millisecond exposure of aqueous solutions to synchrotron X-rays react with proteins to yield stable oxidative modifications of solvent-accessible amino acid side chains. Following proteolysis, HPLC/MS analysis is performed to quantitate the side chain reactivities, and MS/MS analysis is used to identify the modification site(s). Side chain reactivity is shown to be correlated with solvent accessibility; thus the method provides detailed site-specific information about protein structure. The application of these techniques to the study of the actin cytoskeleton is described in detail, including defining the binding sites of monomeric actin with gelsolin segment-1, the actin monomer binding surface on cofilin, the divalent cation-dependent structure changes of monomeric actin, and the conformational changes associated with actin filamentous assembly.     

Industrial corrosion monitoring

The paper describes the experience accumulated on electrochemical methods for corrosion monitoring. Electrical resistance, linear polarization, electrochemical potential and amperometric measurements are described and their reliability is evaluated together with that of the related commercial equipments. The main drawbacks of each method (e.g. sensibility, linear or non linear response, causes of error and correction…) are discussed.