Bromopyrrole Alkaloids as Lead Compounds against Protozoan Parasites

In the present study, 13 bromopyrrole alkaloids, including the oroidin analogs hymenidin (2), dispacamide B (3) and dispacamide D (4), stevensine (5) and spongiacidin B (6), their derivatives lacking the imidazole ring bromoaldisin (7), longamide B (8) and longamide A (9), the dimeric oroidin derivatives sceptrin (10) and dibromopalau’amine (11), and the non-oroidin bromopyrrolohomoarginin (12), manzacidin A (13), and agelongine (14), obtained from marine sponges belonging to Axinella and Agelas genera have been screened in vitro against four parasitic protozoa, i.e., two Trypanosoma species (T. brucei rhodesiense and T. cruzi), Leishmania donovani and Plasmodium falciparum (K1 strain, a chloroquine resistant strain), responsible of human diseases with high morbidity and, in the case of malaria, high mortality. Our results indicate longamide B (8) and dibromopalau’amine (11) to be promising trypanocidal and antileishmanial agents, while dispacamide B (3) and spongiacidin B (6) emerge as antimalarial lead compounds. In addition, evaluation of the activity of the test alkaloids (2–14) against three different enzymes (PfFabI, PfFabG, PfFabZ) involved in the de novo fatty acid biosynthesis pathway of P. falciparum (PfFAS-II) identified bromopyrrolohomoarginin (12) as a potent inhibitor of PfFabZ. The structural similarity within the series of tested molecules allowed us to draw some preliminary structure-activity relationships. Tests against the mammalian L6 cells revealed important clues on therapeutic index of the metabolites. This is the first detailed study on the antiprotozoal potential of marine bromopyrrole alkaloids.     

The Brazil Eucalyptus Potential Productivity Project: Influence of water,nutrients and stand uniformity on wood production

We examined the potential growth of clonal Eucalyptus plantations at eight locations across a 1000+ km gradient in Brazil by manipulating the supplies of nutrients and water, and altering the uniformity of tree sizes within plots. With no fertilization or irrigation, mean annual increments of stem wood were about 28% lower (16.2 Mg ha⁻¹ yr⁻¹, about 33 m³ ha⁻¹ yr⁻¹) than yields achieved with current operational rates of fertilization (22.6 Mg ha⁻¹ yr⁻¹, about 46 m³ ha⁻¹ yr⁻¹). Fertilization beyond current operational rates did not increase growth, whereas irrigation raised growth by about 30% (to 30.6 Mg ha⁻¹ yr⁻¹, about 62 m³ ha⁻¹ yr⁻¹). The potential biological productivity (current annual increment) of the plantations was about one-third greater than these values, if based only on the period after achieving full canopies. The biological potential productivity was even greater if based only on the full-canopy period during the wet season, indicating that the maximum biological productivity across the sites (with irrigation, during the wet season) would be about 42 Mg ha⁻¹ yr⁻¹ (83 m³ ha⁻¹ yr⁻¹). Stands with uniform structure (trees in plots planted in a single day) showed 13% greater growth than stands with higher heterogeneity of tree sizes (owing to a staggered planting time of up to 80 days). Higher water supply increased growth and also delayed by about 1 year the point where current annual increment and mean annual increment intersected, indicating opportunities for lengthening rotations for more productive treatments as well as the influence of year-to-year climate variations on optimal rotations periods. The growth response to treatments after canopy closure (mid-rotation) related well with full-rotation responses, offering an early opportunity for estimating whole-rotation yields. These results underscore the importance of resource supply, the efficiency of resource use, and stand uniformity in setting the bounds for productivity, and provide a baseline for evaluating the productivity achieved in operational plantations. The BEPP Project showed that water supply is the key resource determining levels of plantation productivity in Brazil. Future collaboration between scientists working on silviculture and genetics should lead to new insights on the mechanisms connecting water and growth, leading to improved matching of sites, clones, and silviculture.     

Effect of supramolecular structures on thermoplastic zein-lignin bionanocomposites

The effect of alkaline lignin (AL) and sodium lignosulfonate (LSS) on the structure of thermoplastic zein (TPZ) was studied. Protein structural changes and the nature of the physical interaction between lignin and zein were investigated by means of X-ray diffraction and Fourier transform infrared (FT-IR) spectroscopy and correlated with physical properties. Most relevant protein structural changes were observed at low AL concentration, where strong H-bondings between the functional groups of AL and the amino acids in zein induced a destructuring of inter- and intramolecular interactions in α-helix, β-sheet, and β-turn secondary structures. This destructuring allowed for an extensive protein conformational modification which, in turn, resulted in a strong improvement of the physical properties of the bionanocomposite.     

Aerophobin-1 from the Marine Sponge Aplysina aerophoba Modulates Osteogenesis in Zebrafish Larvae

Longer life expectancy has led to an increase in efforts directed to the discovery of new healing agents for disorders related to aging, such as bone diseases. Harboring an incredible variety of bioactive metabolites, marine organisms are standing out as fruitful sources also in this therapeutic field. On the other hand, the in vivo zebrafish model has proven to be an excellent low-cost screening platform for the fast identification of molecules able to regulate bone development. By using zebrafish larvae as a mineralization model, we have thus evaluated the effects of the crude acetonic extract from the marine sponge Aplysina aerophoba and its bromotyrosine components on bone development. Obtained results led to the selection of aerophobin-1 (1) as a promising candidate for applications in regenerative medicine, paving the way for the development of a novel therapeutic option in osteoporosis treatment.     

Antispasmodic saponins from bulbs of red onion, Allium cepa L. var. Tropea

A phytochemical analysis of the polar extract from the red bulbs of Allium cepa L. var. Tropea, typical of Calabria, a southern region of Italy, was performed extensively for the first time, leading to the isolation of four new furostanol saponins, named tropeoside A1/A2 (1a/1b) and tropeoside B1/B2 (3a/3b), along with the respective 22-O-methyl derivatives (2a/2b and 4a/4b), almost certainly extraction artifacts. High concentrations of ascalonicoside A1/A2 (5a/5b) and ascalonicoside B (6), previously isolated from Allium ascalonicum Hort., were also found. This is the first report of furostanol saponins in this A. cepa variety. The chemical structures of the new compounds were established through a combination of extensive nuclear magnetic resonance, mass spectrometry and chemical analyses. High concentrations of quercetin, quercetin 4(I)-glucoside, taxifolin, taxifolin 7-glucoside, and phenylalanine were also isolated. The new saponins were found to possess antispasmodic activity in the guinea pig isolated ileum; such an effect might contribute to explaining the traditional use of onion in the treatment of disturbances of the gastrointestinal tract.     

Characterization and Optimization of Extrusion Cooking for the Manufacture of Third‐Generation Snacks with Winter Squash (Cucurbita moschata D.) Flour

The aim of this work was to study the effects of barrel temperature (BT, 93.5–140.5°C), feed moisture (FM, 21.3–34.7%), and winter squash flour content (SFC, 0.43–15.6%) on physicochemical properties of microwave‐expanded third‐generation snack foods obtained by extrusion. Physicochemical properties used for optimization were expansion index (EI), penetration force (PF), specific mechanical energy (SME), and total color difference (ΔE). Response surface methodology was used for the analysis of data. The highest values of EI and lowest values of PF were found at high BT and low FM. The lowest values of SME were obtained at high levels of FM throughout the range of BT and SFC, whereas the highest values of ΔE were obtained at high SFC and low FM. Increasing levels of SFC increased ΔE values, whereas EI and SME values decreased. The best processing conditions (EI > 6.0, PF < 9.5 N, SME < 172 kJ/kg, and ΔE < 18) were found in the range of BT, 122–141°C; FM, 24.7–29.5%; and SFC, 0–10.9%. Under optimal process conditions, the retention of total carotenoids was higher than 60%. It is possible to manufacture third‐generation snack foods with good physicochemical properties, which could bring a health benefit because of the presence of carotenoids and dietary fiber in winter squash flour.     

Nitrogen mineralization from an organically managed soil and nitrogen accumulation in lettuce

The potential of an organically managed Cambic Arenosol to supply nitrogen (N) from either an applied commercial organic fertilizer (granulated hen manure), a compost produced on‐farm, or four different mixtures of both fertilizers was studied in a laboratory incubation and a pot experiment with lettuce. In the incubation experiment, a significant higher apparent N mineralization occurred after hen‐manure application (53.4% of the organic N applied) compared to compost (4.5%) or mixed‐fertilizer application (8.7% to 16.7%). The apparent N mineralization in a mixed treatment consisting of compost and half rate of hen manure (15.4% of the organic N applied) was significantly higher than that estimated based on the N mineralization for compost and hen‐manure treatments (7.6%), proving that a combined application of both fertilizers enhanced organic‐N mineralization when compared to separate fertilizer supply. In the pot experiment, a higher lettuce fresh‐matter yield was obtained with hen manure (1.9 kg m^–2) than with compost (1.7 kg m^–2) or unfertilized control treatment (1.3 kg m^–2). Combined application of compost with only a half rate of hen manure led to yields (2.0 kg m^–2) equal to those obtained with only hen manure. A good correlation was observed between the N‐mineralization incubation data and the N accumulated by lettuce plants in the pot experiment (r = 0.983). Hence, in the organic production of baby‐leaf lettuce, a mixture of compost and hen manure appears to be a good fertilization alternative, since it allows a reduction by half of the typical amount of commercial fertilizer usually applied (granulated hen manure), cutting fertilization costs, and providing an amount of available N that allows maintaining lettuce yields.     

Pituitary adenoma predisposition caused by germline mutations in the AIP gene

Pituitary adenomas are common in the general population, and understanding their molecular basis is of great interest. Combining chip-based technologies with genealogy data, we identified germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene in individuals with pituitary adenoma predisposition (PAP). AIP acts in cytoplasmic retention of the latent form of the aryl hydrocarbon receptor and also has other functions. In a population-based series from Northern Finland, two AIP mutations account for 16% of all patients diagnosed with pituitary adenomas secreting growth hormone and for 40% of the subset of patients who were diagnosed when they were younger than 35 years of age. Typically, PAP patients do not display a strong family history of pituitary adenoma; thus, AIP is an example of a low-penetrance tumor susceptibility gene.     

Post-catastrophe Analysis of the Fundão Tailings Dam Failure in the Doce River System,Southeast Brazil: Potentially Toxic Elements in Affected Soils

On November 5, 2015, after the collapse of the Fundão tailings dam, a massive amount of iron mine waste was released into the Doce River system in southeast Brazil. The aim of our study was to determine the mass fractions of potentially toxic elements in soil affected by the deposition of material by the waste wave. A preliminary screening was performed with portable X-ray fluorescence spectrometry (PXRF) and principal component analysis (PCA). The EPA 3050B method was further applied to digest the samples for quantitative determination of As, Ba, Cr, Cu, Mn, Ni, Pb, V, and Zn by inductively coupled plasma mass spectrometry. PCA was useful to classify the mine waste samples based on the Fe signal from the PXRF spectra, in spite of the heterogeneous nature of the material discharged into the Doce River system. The anomalous levels of As (up to 164 mg kg^?1) and Mn (as high as 2410 mg kg^?1) found in some mine waste and affected soil samples are within the background ranges typically observed in the soils of the Iron Quadrangle region. The toxicity characteristic leaching procedure shows no evidence of hazards regarding As, but a high natural background level of Mn was found in the mobile fraction. This preliminary environmental assessment highlights the importance of evaluation of long-term effects on soil directly impacted, as well as on the aquatic biota of the Doce River system and adjacent coastal environment given the large affected area, which includes regions with varying background levels of toxic elements.     

Aurantoside J: a new tetramic acid glycoside from Theonella swinhoei. Insights into the antifungal potential of aurantosides

The chemical investigation of an Indonesian specimen of Theonella swinhoei afforded four aurantosides, one of which, aurantoside J (5), is a new compound. The structure of this metabolite, exhibiting the unprecedented N-α-glycosidic linkage between the pentose and the tetramate units, has been determined through detailed spectroscopic analysis. The four obtained aurantosides have been tested against five fungal strains (four Candida and one Fusarium) responsible of invasive infections in immuno-compromised patients. The non-cytotoxic aurantoside I (4) was the single compound to show an excellent potency against all the tested strains, thus providing valuable insights about the antifungal potential of this class of compounds and the structure-activity relationships.