Novel series of substituted biphenylmethyl urea derivatives as MCH-R1 antagonists for the treatment of obesity

We have designed and synthesized two novel series of MCH-R1 antagonists based on a substituted biphenylmethyl urea core. SAR was explored, suggesting that optimal binding with the receptor was achieved when the biphenylmethyl group and the linker were substituted on the same nitrogen of the urea moiety. Compound 1-(3'-cyano-4-biphenylmethyl)-3-(2-hydroxy-1,1-dimethylethyl)-1-{2-[1-(4-methylbenzyl)-4-piperidinyl]ethyl}urea 2t showed the best antagonist binding activity to the MCH-R1 with a 43 nM K(i).     

In silico and in vivo analysis of ABI3 and VAL2 genes during somatic embryogenesis of Coffea arabica: competence acquisition and developmental marker genes

Plant Cell, Tissue and Organ Culture (PCTOC) - The employment of biotechnology-based approaches such as somatic embryogenesis has been applied to several plants including Coffea sp. Despite the...     

Climate change and voltinism of Mythimna sequax: the location and choice of phenological models matter

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Plants Probiotics as a Tool to Produce Highly Functional Fruits: The Case of Phyllobacterium and Vitamin C in Strawberries

The increasing interest in the preservation of the environment and the health of consumers is changing production methods and food consumption habits. Functional foods are increasingly demanded by consumers because they contain bioactive compounds involved in health protection. In this sense biofertilization using plant probiotics is a reliable alternative to the use of chemical fertilizers, but there are few studies about the effects of plant probiotics on the yield of functional fruits and, especially, on the content of bioactive compounds. In the present work we reported that a strain of genus Phyllobacterium able to produce biofilms and to colonize strawberry roots is able to increase the yield and quality of strawberry plants. In addition, the fruits from plants inoculated with this strain have significantly higher content in vitamin C, one of the most interesting bioactive compounds in strawberries. Therefore the use of selected plant probiotics benefits the environment and human health without agronomical losses, allowing the production of highly functional foods.     

Hydroxyl radical formation as a result of the interaction between primaquine and reduced pyridine nucleotides. Catalysis by hemoglobin and microsomes

Kinetic, circular dichroism, and NADH and NADPH fluorescence quenching studies indicate that these compounds interact with the antimalarial drug primaquine (PQ). The affinity of both pyridine nucleotides for PQ is similar. The data are in contrast with a previous report (Thornalley et al. (1983) Biochem. Pharmacol. 32, 3571-3575) suggesting specificity for the interaction with NADPH. The complex was seen to facilitate electron transfer from NAD(P)H to oxygen, generating oxygen-free radicals which were detected by the spin-trapping technique and to flavin nucleotides, giving rise to flavin semiquinone radicals which were demonstrated by direct ESR spectroscopy under anaerobic conditions. A twofold increase in oxygen uptake and hydroxyl radical generation by the NAD(P)H-PQ complex was observed in the presence of hemoglobin. This effect was independent of heme concentration (in the range 1 X 10(-5)-1 X 10(-4) M) and oxidation state of the iron. Under anaerobic conditions, the NAD(P)H-PQ complex reduces Fe-III to Fe-II hemoglobin, and under aerobic conditions about 65% of the heme chromophore is irreversibly destroyed. Superoxide dismutase inhibits hydroxyl radical generation by the NAD(P)H-PQ pair; this effect is not observed in the presence of hemoglobin. In the presence of microsomes there is a 10-fold increase in both oxygen consumption and hydroxyl radical generation by the NAD(P)H-PQ pair. The fact that both pyridine nucleotides are active, and the inability of SKF 525A in decreasing hydroxyl radical generation, suggests that microsomal reductases are involved in the catalysis.     

Profile of micronucleus frequencies and nuclear abnormalities in different species of electric fishes (Gymnotiformes) from the Eastern Amazon

The frequency of spontaneous micronucleus (MN) formation in fish species needs to be determined to evaluate their usefulness for genotoxic biomonitoring. The definition of a good bioindicator takes into account the current knowledge of its metabolic traits as well as other factors including its feeding behavior and relationship to the environment. In this study, we compared the basal frequencies of micronucleated erythrocytes and nuclear abnormalities (NA) among different species of the fish Order Gymnotiformes (Rhamphichthys marmoratus, Steatogenys elegans, Sternopygus macrurus, Parapteronotus hasemani, Gymnotus mamiraua, Gymnotus arapaima, Brachyhypopomus beebei, Brachyhypopomus n. sp. BENN) sampled in several localities of the Eastern Amazon. A baseline of MN and NA frequency in these fish was determined, enabling the identification of potentially useful species as models for genotoxicity studies. Only one impacted sample collected at a site in the River Caripetuba showed a significant number of NAs, which may be due to the release of wastewater by neighbouring mining industries and by the burnt fuel released by the small boats used by a local community. Our results may provide support for further studies in areas of the Eastern Amazon affected by mining, deforestation and other anthropogenic activities.     

Environmental distribution and genetic diversity of vegetative compatibility groups determine biocontrol strategies to mitigate aflatoxin contamination of maize by Aspergillus flavus

Maize infected by aflatoxin‐producing Aspergillus flavus may become contaminated with aflatoxins, and as a result, threaten human health, food security and farmers' income in developing countries where maize is a staple. Environmental distribution and genetic diversity of A. flavus can influence the effectiveness of atoxigenic isolates in mitigating aflatoxin contamination. However, such information has not been used to facilitate selection and deployment of atoxigenic isolates. A total of 35 isolates of A. flavus isolated from maize samples collected from three agro‐ecological zones of Nigeria were used in this study. Ecophysiological characteristics, distribution and genetic diversity of the isolates were determined to identify vegetative compatibility groups (VCGs). The generated data were used to inform selection and deployment of native atoxigenic isolates to mitigate aflatoxin contamination in maize. In co‐inoculation with toxigenic isolates, atoxigenic isolates reduced aflatoxin contamination in grain by > 96%. A total of 25 VCGs were inferred from the collected isolates based on complementation tests involving nitrate non‐utilizing (nit^?) mutants. To determine genetic diversity and distribution of VCGs across agro‐ecological zones, 832 nit^? mutants from 52 locations in 11 administrative districts were paired with one self‐complementary nitrate auxotroph tester‐pair for each VCG. Atoxigenic VCGs accounted for 81.1% of the 153 positive complementations recorded. Genetic diversity of VCGs was highest in the derived savannah agro‐ecological zone (H = 2.61) compared with the southern Guinea savannah (H = 1.90) and northern Guinea savannah (H = 0.94) zones. Genetic richness (H = 2.60) and evenness (E₅ = 0.96) of VCGs were high across all agro‐ecological zones. Ten VCGs (40%) had members restricted to the original location of isolation, whereas 15 VCGs (60%) had members located between the original source of isolation and a distance > 400 km away. The present study identified widely distributed VCGs in Nigeria such as AV0222, AV3279, AV3304 and AV16127, whose atoxigenic members can be deployed for a region‐wide biocontrol of toxigenic isolates to reduce aflatoxin contamination in maize.     

Anti-atherogenic and anti-angiogenic activities of polyphenols from propolis

Propolis is a polyphenol-rich resinous substance extensively used to improve health and prevent diseases. The effects of polyphenols from different sources of propolis on atherosclerotic lesions and inflammatory and angiogenic factors were investigated in LDL receptor gene (LDLr?/?) knockout mice. The animals received a cholesterol-enriched diet to induce the initial atherosclerotic lesions (IALs) or advanced atherosclerotic lesions (AALs). The IAL or AAL animals were divided into three groups, each receiving polyphenols from either the green, red or brown propolis (250 mg/kg per day) by gavage. After 4 weeks of polyphenol treatment, the animals were sacrificed and their blood was collected for lipid profile analysis. The atheromatous lesions at the aortic root were also analyzed for gene expression of inflammatory and angiogenic factors by quantitative real-time polymerase chain reaction and immunohistochemistry. All three polyphenol extracts improved the lipid profile and decreased the atherosclerotic lesion area in IAL animals. However, only polyphenols from the red propolis induced favorable changes in the lipid profiles and reduced the lesion areas in AAL mice. In IAL groups, VCAM, MCP-1, FGF, PDGF, VEGF, PECAM and MMP-9 gene expression was down-regulated, while the metalloproteinase inhibitor TIMP-1 gene was up-regulated by all polyphenol extracts. In contrast, for advanced lesions, only the polyphenols from red propolis induced the down-regulation of CD36 and the up-regulation of HO-1 and TIMP-1 when compared to polyphenols from the other two types of propolis. In conclusion, polyphenols from propolis, particularly red propolis, are able to reduce atherosclerotic lesions through mechanisms including the modulation of inflammatory and angiogenic factors.     

Influence of Soil Physical Properties on Plants of the Mussununga Ecosystem, Brazil

Distribution ranges of plant species are related to physical variables of ecosystems that limit plant growth. Therefore, each plant species response to physical factors builds up the functional diversity of an ecosystem. The higher the species richness of an ecosystem, the larger the probability of maintaining functions and the higher the potential number of plant functional groups (FGs). Thus, the richness potentially increases the number of functions of the highly diverse Atlantic Rainforest domain in Brazil. Severe plant growth limitations caused by stress, however, decrease species richness. In the Spodosols of the Mussununga, an associated ecosystem of Atlantic Rainforest, the percentage of fine sand is directly related to water retention. Moreover, the depth of the cementation layer in the Mussununga??s sandy soil is a physical factor that can affect the plants?? stress gradients. When a shallow cementation layer depth is combined with low water retention in soils and with low fine sand percentage, the double stresses of flooding in the rainy season and water scarcity in the dry season result. This study aimed to identify FGs among Mussununga plant species responding to water stress gradients of soil and to verify the effects of the gradients on plant species richness of the Mussununga. A canonical correspondence analysis (CCA) of species abundance and soil texture variables was performed on 18 plots in six physiognomies of the Mussununga. Species richness rarefactions were calculated for each vegetation form to compare diversity. The two main axes of the CCA showed two FGs responding to soil texture and cementation layer depth: stress tolerator species and mesic species. Physical variables affect plant diversity, with species richness rising as the fine sand proportion also rises in the Mussununga. The effect of the cementation layer is not significantly related to species richness variation.