Proteomic,metabolic and immunological changes in Biomphalaria glabrata infected with Schistosoma mansoni

Mansonic schistosomiasis is a neglected disease transmitted by Biomphalaria spp. snails. Understanding what happens inside the intermediate host is important to develop more efficient ways of reducing schistosomiasis prevalence. Our purpose was to characterize metabolic and immunological changes in Biomphalaria glabrata 24 h after exposure to Schistosoma mansoni. For this purpose, proteins were extracted from snails’ whole tissue with Tris-Urea buffer and digested with tripsin. Mass spectrometry was performed and analyzed with MaxQuant and Perseus software. Also, the hemolymph of five snails 24 h post exposure was collected, and the numbers of hemocytes, levels of urea, uric acid, nitric oxide, calcium, glycogen and alanine and aspartate aminotransferases activities were assessed. Snails were also dissected for measurement of glycogen content in the cephalopodal region and gonoda-digestive gland complex. Globin domain proteins were found to be up-regulated; also the number of circulating hemocytes was significantly higher after 24 h of exposure to the parasite. NO levels were higher 24 h post exposure. Several proteins associated with energy metabolism were found to be up-regulated. Glycogen analysis showed a significant decrease in the gonad-digestive gland complex glycogen content. We found several proteins which seem to be associated with the host immune response, most of which were up-regulated, however some were down-regulated, which may represent an important clue in understanding B. glabrata – S. mansoni compatibility.     

Design,synthesis and biological activity of a novel ethylenediamine derivatives as H1 receptor antagonists

In this study, a series of novel ethylenediamine compounds were obtained by structural modification of the lead compounds with thonzylamine, and using the principle of modifying by bioisostere formation and modification with alkyl groups. In vitro assay, the biological activities showed that the target compounds have good properties in inhibiting mast cell degranulation and releasing histamine and β-aminohexidase, such as the compounds 5c, 5g, 5k, 5l and 5o, especially of compound 5k to mast cell degranulation is IC₅₀ = 0.0106 ± 0.001 μmol?L^?1, histamine release was IC₅₀ = 0.0192 ± 0.005 μmol?L^?1 and β-hexosaminidase release was IC₅₀ = 0.0455 ± 0.002 μmol?L^?1 in vitro. At the same time, in vivo biological activities assay results showed that have a good Histamie induce bronchospasm effect with relatively long duration and good protective effect in vivo, among which the protective effect of compound 5k was 79.74 ± 0.30%, compounds 5c, 5g, 5k, 5l and 5o could inhibit the capillary permeability of increasing which were caused by histamine.     

A redescription of Antispastis clarkei Pastrana (Lepidoptera,Glyphipterigidae) immature stages,with notes on the life history and phylogenetic placement of the genus

Antispastis Meyrick, 1926 is a poorly known genus of leaf-mining micromoths endemic to the Neotropics, with still uncertain taxonomic position within the Yponomeutoidea. In the present study, the egg, larva and pupa of A. clarkei Pastrana, previously known only from Argentina, are described and illustrated with the aid of optical and scanning electron microscopy. Data on life history, including histology of the mine, are also provided. Family placement of the genus is reassessed based on comparison of morphology and DNA sequences with closely related lineages. The larvae form blotch mines on the upper surface of Solanum L. (Solanaceae) leaves, feeding on palisade parenchyma in all instars. Pupation occurs outside the mine, in an inverted basket-like, large-meshed cocoon constructed on the plant surface. DNA analysis of Cytochrome oxidase I gene of A. clarkei revealed interspecific differences averaging 10% with A. xylophragma, which provided species separation matching morphological differences. Antispastis was closely related phylogenetically to Digitivalva, clustering in the Acrolepiinae together with the genera Acrolepia and Acrolepiopsis, and ultimately placed within Glyphipterigidae. The geographical distribution of A. clarkei is expanded to the Southern Atlantic forest (Rio Grande do Sul and Paraná states, Brazil).     

Schistosoma mansoni does not and cannot oxidise fatty acids,but these are used for biosynthetic purposes instead

Adult schistosomes, parasitic flatworms that cause the tropical disease schistosomiasis, have always been considered to be homolactic fermenters and, in their energy metabolism, strictly dependent on carbohydrates. However, more recent studies suggested that fatty acid β-oxidation is essential for egg production by adult female Schistosoma mansoni. To address this conundrum, we performed a comprehensive study on the lipid metabolism of S. mansoni. Incubations with [¹⁴C]-labelled fatty acids demonstrated that adults, eggs and miracidia of S. mansoni did not oxidise fatty acids, as no ¹⁴CO₂ production could be detected. We then re-examined the S. mansoni genome using the genes known to be involved in fatty acid oxidation in six eukaryotic model reference species. This showed that the earlier automatically annotated genes for fatty acid oxidation were in fact incorrectly annotated. In a further analysis we could not detect any genes encoding β-oxidation enzymes, which demonstrates that S. mansoni cannot use this pathway in any of its lifecycle stages. The same was true for Schistosoma japonicum and all other schistosome species that have been sequenced. Absence of β-oxidation, however, does not imply that fatty acids from the host are not metabolised by schistosomes. Adult schistosomes can use and modify fatty acids from their host for biosynthetic purposes and incorporate those in phospholipids and neutral lipids. Female worms deposit large amounts of these lipids in the eggs they produce, which explains why interference with the lipid metabolism in females will disturb egg formation, even though fatty acid β-oxidation does not occur in schistosomes. Our analyses of S. mansoni further revealed that during the development and maturation of the miracidium inside the egg, changes in lipid composition occur which indicate that fatty acids deposited in the egg by the female worm are used for phospholipid biosynthesis required for membrane formation in the developing miracidium.     

Discovery of novel PTHR1 antagonists: Design,synthesis, and structure activity relationships

The discovery and optimization of a novel series of PTHR1 antagonists are described. Starting from known PTHR1 antagonists, we identified more potent 1,4-benzodiazepin-2-one derivatives by means of a scaffold-hopping approach. The representative compound 23 (DS08210767) exhibited nanomolar-level PTHR1 antagonist activity and potential oral bioavailability in a pharmacokinetic study.     

Information from the mitochondrial genomes of two egg parasitoids,Gonatocerus sp. and Telenomus sp., reveals a controversial phylogenetic relationship between Mymaridae and Scelionidae

The taxonomic status and phylogenetic affinities of Mymaridae and Scelionidae are controversial, based on similarities between these families in the characteristics of adults, larvae, and eggs. In this study, we sequenced the mitochondrial (mt) genomes of representatives from these two families and found that the derived secondary structure of tRNA-Arg was the same in each family due to the absence of the D-stem. The segment of “cox1 trnL₂ cox2 trnK trnD atp8 atp6 cox3” in Gonatocerus sp. (Mymaridae) is conserved and distinct from those of four other species of Chalcidoidea but similar to that in Proctotrupoidea and Platygastroidea. However, phylogenetic analysis indicated that Gonatocerus sp. was sister group to other species of Chalcidoidea. Comparisons based on complete gene orders may be more useful in a phylogenetic and systematic context, as different branches may exhibit partially homoplastic gene orders.     

Design,synthesis and molecular modelling of new bulky Fananserin derivatives with altered pharmacological profile as potential antidepressants

It is now known that many neurotransmitter systems are responsible for diseases of the central nervous system (CNS). One of the most common CNS disease is depression. Considering that in the treatment and the genesis of depression, the most important are the serotonin receptors from 5-HT_1A, 5-HT_2A, 5-HT₆ and 5-HT₇ groups, and dopamine D₂R this article describes searching for group of new ligands for mentioned receptors. In the searching for potentially useful compound, we decided to start from the structure of well-known Fananserin. We tried to developed new derivatives, with changed profile of activity compared to Fananserin. Literature analysis and virtual screening emerged group of halogenated long-chain arylpiperazines derivatives of 1,8 naphthosultam/lactam with hexyl carbon chain to synthesis. The compounds obtaining method was developed with a microwave assisted synthesis. Reactions were carried out in acetonitrile, water or in solvent-free conditions. The obtained compounds were tested for their affinity for the serotonin receptors mentioned above. The work managed to obtain compounds acting on selected serotonin receptors, including multifunctional 5-HT_1A/5-HT₇/D₂ ligand 5k, dual 5-HT_1A/D₂ ligand 5j and selective 5-HT_1A ligands 5r and 5c. The SAR analysis showed a visible dependence of affinity for the 5-HT₆ receptors from structure of ligands. This relationship was discussed using molecular docking methods. A conformal analysis was also performed for selected ligands and the Fukui indexes were calculated using the DFT (B3LYP/6-311+G (d,p) level of theory) methods. The conducted research and analysis using molecular docking methods allows for selecting further pathways of structural modifications in the design of new ligands for serotonin receptors belonging to the group mentioned. What is more, conducted research show the potential using of Fukui indices to predict the biological activity of new molecules.     

Ultrasound-assisted extraction of some branded tea: Optimization based on polyphenol content,antioxidant potential and thermodynamic study

Tea is one of the top beverages used around the world every day, which contains a high amount of polyphenols and antioxidants. The main aim of this research is to quantify some marketed black tea (Rabea, Lipton, Alkbous, Green gold and Haritham) for phenolic contents and antioxidant potential evaluation by ultrasound solvent extraction and was compared with conventional extraction. Ultrasonic extraction was optimized by considering frequencies (26 kHz, 40 kHz), temperature (30, 40 and 50 °C), and power (30, 40 and 50%) at a fixed time of 30 min. In both the ultrasonic frequencies, 40 °C temperature and 40% power combination exhibited highest cumulative yield (mg/100 g DW), total phenolic content (mg gallic acid/g DW), flavonoids (mg/g DW) and DPPH radical scavenging activity (%) in all branded tea. Within each brand of tea, at any temperature-power combination at particular frequency results were not significantly different. But, at a similar condition of temperature power results were found significantly different between two frequencies. Furthermore, ultrasonic extraction process was analyzed thermodynamically by selecting some basic parameters. Thermodynamics results showed the extraction process was feasible, spontaneous and irreversible. Also, 26 kHz ultrasonic probe is more appropriate for the extraction purpose and thermodynamically more acceptable as compared to 40 kHz ultrasonic bath. Moreover, Haritham was selected as the best tea brand due to its high polyphenol contents and antioxidant potential.     

Notes on the species of Naarda Walker, 1866 (Lepidoptera: Erebidae,Hypeninae) from mainland China,with the description of a new species and establishment of a new synonymy

The species Naarda postpallida de Joannis, 1929 is reported for the first time from mainland China. Naarda pectinata Sugi, 1982 is synonymised with N. postpallida on the basis of material from Vietnam. This species can immediately be recognised by its dark grey forewing, white hindwing and several genital characters. The female genitalia of N. postpallida, together with those of N. lingualis Tóth and Ronkay, 2015 are presented for the first time. Naarda macrostigma sp. n. is described. The hitherto known nine Chinese Naarda species are listed. With nineteen figures.www.zoobank.org/urn:lsid:zoobank.org:pub:092AE905-08AA-4818-BDA8-2B9EF150793A     

Rational modification of Mannich base-type derivatives as novel antichagasic compounds: Synthesis,in vitro and in vivo evaluation

The current chemotherapy against Chagas disease is inadequate and insufficient. A series of ten Mannich base-type derivatives have been synthesized to evaluate their in vitro antichagasic activity. After a preliminary screening, compounds 7 and 9 were subjected to in vivo assays in a murine model. Both compounds caused a substantial decrease in parasitemia in the chronic phase, which was an even better result than that of the reference drug benznidazole. In addition, compound 9 also showed better antichagasic activity during the acute phase. Moreover, metabolite excretion, effect on mitochondrial membrane potential and the inhibition of superoxide dismutase (SOD) studies were also performed to identify their possible mechanism of action. Finally, docking studies proposed a binding mode of the Fe-SOD enzyme similar to our previous series, which validated our design strategy. Therefore, the results suggest that these compounds should be considered for further preclinical evaluation as antichagasic agents.     

Engineering of filamentous fungi for efficient conversion of lignocellulose: Tools,recent advances and prospects

Filamentous fungi, as the main producers of lignocellulolytic enzymes in industry, need to be engineered to improve the economy of large-scale lignocellulose conversion. Investigation of the cellular processes involved in lignocellulolytic enzyme production, as well as optimization of enzyme mixtures for higher hydrolysis efficiency, have provided effective targets for the engineering of lignocellulolytic fungi. Recently, the development of efficient genetic manipulation systems in several lignocellulolytic fungi opens up the possibility of systems engineering of these strains. Here, we review the recent progresses made in the engineering of lignocellulolytic fungi and highlight the research gaps in this area.