Modeling the flux of metabolites in the juvenile hormone biosynthesis pathway using generalized additive models and ordinary differential equations

Juvenile hormone (JH) regulates development and reproductive maturation in insects. The corpora allata (CA) from female adult mosquitoes synthesize fluctuating levels of JH, which have been linked to the ovarian development and are influenced by nutritional signals. The rate of JH biosynthesis is controlled by the rate of flux of isoprenoids in the pathway, which is the outcome of a complex interplay of changes in precursor pools and enzyme levels. A comprehensive study of the changes in enzymatic activities and precursor pool sizes have been previously reported for the mosquito Aedes aegypti JH biosynthesis pathway. In the present studies, we used two different quantitative approaches to describe and predict how changes in the individual metabolic reactions in the pathway affect JH synthesis. First, we constructed generalized additive models (GAMs) that described the association between changes in specific metabolite concentrations with changes in enzymatic activities and substrate concentrations. Changes in substrate concentrations explained 50% or more of the model deviances in 7 of the 13 metabolic steps analyzed. Addition of information on enzymatic activities almost always improved the fitness of GAMs built solely based on substrate concentrations. GAMs were validated using experimental data that were not included when the model was built. In addition, a system of ordinary differential equations (ODE) was developed to describe the instantaneous changes in metabolites as a function of the levels of enzymatic catalytic activities. The results demonstrated the ability of the models to predict changes in the flux of metabolites in the JH pathway, and can be used in the future to design and validate experimental manipulations of JH synthesis.Facultad de Ciencias ExactasCentro Regional de Estudios Genómico

How micronutrients influence the physiology of mosquitoes

Micronutrients or non-energetic nutrients (NEN) are needed in reduced amounts, but are essential for many mosquito physiological processes that influence biological traits from vector competence to reproductive capacity. The NEN include amino acids (AA), vitamins, salts, metals and sterols. Free AA play critical roles controlling most physiological processes, from digestion to reproduction. Particularly proline connects metabolic pathways in energy production, flight physiology and ammonia detoxification. Metal, in particular iron and calcium, salts, sterol and vitamin homeostasis are critical for cell signaling, respiration, metabolism and reproduction. Micronutrient homeostasis influence the symbiotic relationships with microorganisms, having important implications in mosquitoes’ nutrition, physiology and behavior, as well as in mosquito immunity and vector competence

The insulin/TOR signal transduction pathway is involved in the nutritional regulation of juvenile hormone synthesis in Aedes aegypti

Juvenile hormone (JH) levels must be modulated to permit the normal progress of development and reproductive maturation in mosquitoes. JH is part of a transduction system that assesses nutritional information and controls reproduction in mosquitoes. Adult female Aedes aegypti show nutritionally-dependent dynamic changes in corpora allata (CA) JH biosynthetic activities. A coordinated expression of most JH biosynthetic enzymes has been described in female pupae and adult mosquitoes; increases or decreases in transcript levels for all the enzymes were concurrent with increases or decreases in JH synthesis; suggesting that transcriptional changes are at least partially responsible for the dynamic changes of JH biosynthesis. The goal of the present study is to identify signaling network components responsible for the nutritionaldependent changes of JH synthesis in the CA of mosquitoes. The insulin/TOR signaling network plays a central role in the transduction of nutritional signals that regulate cell growth and metabolism in insects. These pathways have also been suggested as a link between nutritional signals and JH synthesis regulation in the CA of cockroaches and flies. We used a combination of in vitro studies and in vivo genetic knockdown experiments to explore nutritional signaling pathways in the CA. Our results suggest that the insulin/TOR pathway plays a role in the transduction of the nutritional information that regulates JH synthesis in mosquitoes. Transcriptional regulation of the genes encoding JH biosynthetic enzymes is at least partially responsible for these nutritionally modulated changes of JH biosynthesis

Antimicrobial and anticarcinogenic activity of bioactive peptides derived from abalone viscera (Haliotis fulgens and Haliotis corrugata)

Abstract Bioactive peptides have been studied in several sources due to their valuable potential in the pharmaceutical and food industries. Abalone viscera, which are normally discarded as byproducts, are a rich source of protein. Thus, the aim of this study was to explore the potential bioactivity of peptides derived from abalone viscera (Haliotis fulgens and Haliotis corrugata) after hydrolysis with a commercial mixture of enzymes. The hydrolysates obtained were fractionated using gel filtration chromatography. The resulting hydrolysate fractions were investigated for their antimicrobial and cytotoxic activities, including the expression of gelatinases mmp-2 and mmp-9 in human prostate cancer cell lines (PC3). Results showed antimicrobial activity for protein fractions of H. corrugata against Proteus mirabilis and Pseudomona aeuroginosa (66.2–116.25 kDa), Bacillus subtilis (6.5–21.5 kDa), and Aspergillus niger (97.4–116.25 kDa), while H. fulgens peptide fractions (200–31 kDa) displayed activity against six bacterial strains, and fractions from 116.25 to 21.5 kDa had effects on the fungus A. niger, Alternaria alternata, and Aspergillus flavus. Additionally, protein fractions displayed cytotoxic activity, inhibiting 30.4–53.8% of PC3 cellular growth. Selected fractions decreased the PMA-induced and not-induced expressions of mmp-2 and mmp-9 in PC3 cells. Abalone viscera, as byproducts, can be used as a potential source of antimicrobial and anticancer peptides