Food‐derived immunomodulatory peptides

Food proteins contain specific amino acid sequences within their structures that may positively impact bodily functions and have multiple immunomodulatory effects. The functional properties of these specific sequences, also referred to as bioactive peptides, are revealed only after the degradation of native proteins during digestion processes. Currently, milk proteins have been the most explored source of bioactive peptides, which presents an interesting opportunity for the dairy industry. However, plant‐ and animal‐derived proteins have also been shown to be important sources of bioactive peptides. This review summarizes the in vitro and in vivo evidence of the role of various food proteins as sources of immunomodulatory peptides and discusses the possible pathways involving these properties. © 2016 Society of Chemical Industry     

CMOS Design of a Current-Mode Multiplier/Divider Circuit with Applications to Fuzzy Controllers

Multiplier and divider circuits are usually required in the fields of analog signal processing and parallel-computing neural or fuzzy systems. In particular, this paper focuses on the hardware implementation of fuzzy controllers, where the divider circuit is usually the bottleneck. Multiplier/divider circuits can be implemented with a combination of A/D-D/A converters. An efficient design based on current-mode data converters is presented herein. Continuous-time algorithmic converters are chosen to reduce the control circuitry and to obtain a modular design based on a cascade of bit cells. Several circuit structures to implement these cells are presented and discussed. The one that is selected enables a better trade-off speed/power than others previously reported in the literature while maintaining a low area occupation. The resulting multiplier/divider circuit offers a low voltage operation, provides the division result in both analog and digital formats, and it is suitable for applications of low or middle resolution (up to 9 bits) like applications to fuzzy controllers. The analysis is illustrated with Hspice simulations and experimental results from a CMOS multiplier/divider prototype with 5-bit resolution. Experimental results from a CMOS current-mode fuzzy controller chip that contains the proposed design are also included.     

Short‐circuit current of solar cells under artificial light

A model to estimate the short‐circuit current of a solar cell under artificial light from the short‐circuit current of the same solar cell under AM1.5 1 kW/m² is described. The results may help designers of solar‐powered portable equipment and consumer products working indoors or under a mixture of artificial and sunlight. It is concluded that the ratio of the short‐circuit currents of the same solar cell generated under fluorescent light of 1 lux illuminance divided by the short‐circuit current generated under standard 1 Sun AM1.5 conditions is around 3 × 10⁻⁶ for typical crystalline silicon and CIS solar cells. This value is one order of magnitude greater if the light source considered is an incandescent lamp. In the case of amorphous silicon solar cells the value of the ratio is close to 8 × 10⁻⁶ either for fluorescent or incandescent lamps. CdTe solar cells are also considered, and this factor is about 4 × 10⁻⁶ under fluorescent light, and four times bigger when an incandescent lamp is used. Some measurements performed validate the figures obtained. Copyright © 2002 John Wiley & Sons, Ltd.     

The Veterinary Anti-Parasitic Selamectin Is a Novel Inhibitor of the Mycobacterium tuberculosis DprE1 Enzyme

Avermectins are macrocyclic lactones with anthelmintic activity. Recently, they were found to be effective against Mycobacterium tuberculosis, which accounts for one third of the worldwide deaths from antimicrobial resistance. However, their anti-mycobacterial mode of action remains to be elucidated. The activity of selamectin was determined against a panel of M. tuberculosis mutants. Two strains carrying mutations in DprE1, the decaprenylphosphoryl-β-D-ribose oxidase involved in the synthesis of mycobacterial arabinogalactan, were more susceptible to selamectin. Biochemical assays against the Mycobacterium smegmatis DprE1 protein confirmed this finding, and docking studies predicted a binding site in a loop that included Leu275. Sequence alignment revealed variants in this position among mycobacterial species, with the size and hydrophobicity of the residue correlating with their MIC values; M. smegmatis DprE1 variants carrying these point mutations validated the docking predictions. However, the correlation was not confirmed when M. smegmatis mutant strains were constructed and MIC phenotypic assays performed. Likewise, metabolic labeling of selamectin-treated M. smegmatis and M. tuberculosis cells with ¹⁴C-labeled acetate did not reveal the expected lipid profile associated with DprE1 inhibition. Together, our results confirm the in vitro interactions of selamectin and DprE1 but suggest that selamectin could be a multi-target anti-mycobacterial compound.     

Mesenchymal Stem Cells Delivery in Individuals with Different Pathologies: Multimodal Tracking,Safety and Future Applications

Due to their ease of isolation and their properties, mesenchymal stem cells (MSCs) have been widely investigated. MSCs have been proved capable of migration towards areas of inflammation, including tumors. Therefore, they have been suggested as vectors to carry therapies, specifically to neoplasias. As most of the individuals joining clinical trials that use MSCs for cancer and other pathologies are carefully recruited and do not suffer from other diseases, here we decided to study the safety and application of iv-injected MSCs in animals simultaneously induced with different inflammatory pathologies (diabetes, wound healing and tumors). We studied this by in vitro and in vivo approaches using different gene reporters (GFP, hNIS, and f-Luc) and non-invasive techniques (PET, BLI, or fluorescence). Our results found that MSCs reached different organs depending on the previously induced pathology. Moreover, we evaluated the property of MSCs to target tumors as vectors to deliver adenoviruses, including the interaction between tumor microenvironment and MSCs on their arrival. Mechanisms such as transdifferentiation, MSC fusion with cells, or paracrine processes after MSCs homing were studied, increasing the knowledge and safety of this new therapy for cancer.     

Floating Ricobendazole Delivery Systems: A 3D Printing Method by Co-Extrusion of Sodium Alginate and Calcium Chloride

At present, the use of benzimidazole drugs in veterinary medicine is strongly limited by both pharmacokinetics and formulative issues. In this research, the possibility of applying an innovative semi-solid extrusion 3D printing process in a co-axial configuration was speculated, with the aim of producing a new gastro-retentive dosage form loaded with ricobendazole. To obtain the drug delivery system (DDS), the ionotropic gelation of alginate in combination with a divalent cation during the extrusion was exploited. Two feeds were optimized in accordance with the printing requirements and the drug chemical properties: the crosslinking ink, i.e., a water ethanol mixture containing CaCl₂ at two different ratios 0.05 M and 0.1 M, hydroxyethyl cellulose 2% w/v, Tween 85 0.1% v/v and Ricobendazole 5% w/v; and alginate ink, i.e., a sodium alginate solution at 6% w/v. The characterization of the dried DDS obtained from the extrusion of gels containing different amounts of calcium chloride showed a limited effect on the ink extrudability of the crosslinking agent, which on the contrary strongly influenced the final properties of the DDS, with a difference in the polymeric matrix toughness and resulting effects on floating time and drug release.     

Extraction and partial characterization of a coagulant preparation from Silybum marianum flowers. Its action on bovine caseinate

An outstanding parameter in cheese making is the type of coagulant, which greatly influences the characteristics of the final products. Proteolysis is the most important set of biochemical changes during ripening of most cheeses, and is carried out, in different magnitude, by proteolytic agents originated in milk, rennet (or rennet substitute), and starter and non-starter micro-organisms (Silva & Malcata, 2000). The demand for alternative sources of milk coagulants, to replace the expensive and limited natural rennet supplies, has increased (Esteves et al. 2001). All commercial enzymes employed as milk coagulant are aspartic proteinases, which are most active at acidic pH and preferentially cleave peptide bonds between residues with hydrophobic side-chains (Silva & Malcata, 1999). Because of the presence of aspartic proteinases, aqueous crude extracts from flowers of Cynara cardunculus (Veríssimo et al. 1995, 1996), Cynara humilis, and/or Cynara scolymus are traditionally employed in the Iberian Peninsula as vegetable rennet for cheesemaking (Reis et al. 2000). Milk clotting activity was also proved in flowers of Centaurea calcitrapa and Onopordum turcicum (Tamer, 1993; Domingos et al. 1998). All these species are included within the Asteraceae family and furthermore in the same tribe: Cardueae Cass.= Cynareae Less. (Ariza Espinar & Delucchi, 1998). When a potential rennet substitute is studied, it is particularly important to evaluate adequately the degradation patterns of the caseins because of their effects on yield, consistency, and flavour of the final cheese (Fox, 1989). It is important to guarantee a well-balanced breakdown of curd proteins (caseins) in order to avoid formation of undesired attributes in cheese such as low viscosity and high bitterness (Visser, 1993). One of the most frequently used methods to monitor proteolytic processes on caseins is urea-polyacrylamide gel electrophoresis. On the other hand, tricine-SDS polyacrylamide gel electrophoresis improves the separation, identification and quantification of casein hydrolysates because it allows the visualization of large and small peptides (Pardo & Natalucci, 2001), with the additional advantage of allowing the estimation of molecular masses. Both methods are then suitable to characterize the performance of vegetable rennet in different ways. This preliminary study had the following objectives: the partial characterization of (i) the aspartic proteolytic activity present in flowers of Silybum marianum (L.) Gaertn. (Asteraceae); and (ii) the hydrolytic profile of bovine caseins.     

Lipid deterioration during chilled storage of Atlantic pomfret (Brama brama)

Lipid damage produced during Atlantic pomfret (Brama brama) chilled storage (up to 19 d) was studied. The formation of various lipid parameters, such as free fatty acid and conjugated dienes (CD), peroxide value, thiobarbituric acid reactive substances and fluorescent compounds was measured in 2 different white muscle zones (dorsal and ventral). The results were compared with the formation of volatile amines (total volatile base‐nitrogen, TVB‐N, trimethylamine‐nitrogen, TMA‐N). A gradual lipid hydrolysis was observed in both zones during the entire experiment. CD and peroxides formation was prominent during the experiment, whereas peroxides showed the highest value at day 15 in both zones followed by a peroxide breakdown at day 19. Interaction of oxidized lipids with nucleophilic compounds present in the fish muscle led to a gradual development of fluorescent material during storage in both zones. The mean value of the lipid content tended to be higher in the ventral zone than in the dorsal one, although significant differences could not be detected (p >0.05). Concerning the lipid damage, very small differences (p <0.05) could be assessed between both zones. TVB‐N content showed no variation till day 15. At day 19, a sharp increase was observed for both muscle zones. In the case of TMA, a gradual increase was observed in both muscles during the 19‐day storage. Higher mean values of TVB‐N and TMA‐N indices were obtained for the ventral than for the dorsal zone. This might be due to the fact that the ventral zone is close to the viscera, where microorganisms are known to concentrate. Of all the different indices tested for quality assessment, TMA‐N and the formation of fluorescent compounds were strongest related to the duration of storage (r²≥0.87). These might therefore be the most accurate parameters to follow quality loss of chilled Atlantic pomfret.     

Ranking of TOA Measurements Based on the Estimate of the NLOS Propagation Contribution in a Wireless Location System

The presence of non-line-of-sight (NLOS) propagation is a key issue that limits the accuracy of wireless location systems. The lack of direct sight causes the measurements obtained by location systems to be so unpredictable that they can produce high inaccuracies in the estimation of the mobile station location. In this paper we propose a novel technique to improve location reliability and accuracy in cases where NLOS propagation is present. For that, in registers of time of arrival (TOA) measurements taken from each base station (BS) in view, we detect the presence of NLOS propagation and estimate the ratio of the measurements coming from NLOS propagation. With this estimate we can assess how much is NLOS propagation affecting the measurements taken from each BS and then we can identify the best measurements and BSs to achieve the highest accuracies in location.     

Effect of a flax seed (Linum usitatissimum) soaking treatment on the frozen storage stability of mackerel (Scomber scombrus) fillets

The effect of a flax seed (Linum usitatissimum) soaking on the development of rancidity in frozen mackerel (Scomber scombrus) was studied. Fresh mackerel fillets were soaked in an aqueous flax seed extract for 20 min and then kept frozen (?20 °C) for up to 7 months. A parallel experiment with non‐soaked fillets was carried out under the same conditions. The development of rancidity was measured by biochemical (free fatty acids, peroxides, conjugated dienes and trienes, secondary oxidation products, fluorescent and browning compounds and lipoxygenase activity) and sensory (general aspect, odour and colour) analyses. An inhibitory effect of the soaking treatment on rancidity development was observed according to the peroxide content and the formation of fluorescence and browning. A lower lipoxygenase activity was detected at 1 month in the soaked fillets; after this, no differences were obtained between either type of sample, whose activities at month 7 were negligible. According to the sensory analyses, non‐soaked fillets had fair quality at 1 month and were rejectable at 3 months, while the soaked ones were still of good quality at 1 month and rejectable at 5 months. According to the present results, soaking in an aqueous flax seed extract could be useful for inhibiting the development of rancidity in fatty fish fillets. Copyright © 2006 Society of Chemical Industry