Synergistic efficacy of botanical blends with and without synthetic insecticides against Aedes aegypti and Culex annulirostris mosquitoes.

Increasing insecticide resistance requires strategies to prolong the use of highly effective vector control compounds. The use of combinations of insecticides with other insecticides and phytochemicals is one such strategy that is suitable for mosquito control. In bioassays with Aedes aegypti and Culex annulirostris mosquitoes, binary mixtures of phytochemicals with or without synthetic insecticides produced promising results when each was applied at a LC25 dose. All mixtures resulted in 100% mortality against Cx. annulirostris larvae within 24 h rather than the expected mortality of 50%. All mixtures acted synergistically against Ae. aegypti larvae within the first 24 h except for one mixture that showed an additive effect. We conclude that mixtures are more effective than insecticides or phytochemicals alone and that they enable a reduced dose to be applied for vector control potentially leading to improved resistance management and reduced costs.     

The effect of inorganic and organic pollutants on sperm motility of some freshwater teleosts

Using four different sperm types from brown trout Salmo trutta fario (Salmonidae), chub Leuciscus cephalus (Cyprinidae), burbot Lota lota (Gadidae) and African catfish Clarias gariepinus (Clariidae) the effect of inorganic (cadmium, copper, mercury, lead, zinc and nitrite) and organic (cyclohexane and 2,4‐dichlorophenol) environmental pollutants on sperm motility was investigated. Spermatozoa were activated in double distilled water containing the different test substances and the motility was compared to controls of similar pH. From the investigated motility variables the sperm motility rate and swimming velocity reacted most to the environmental pollutants whereby the changes depended on the species and on the test substance. African catfish spermatozoa were the most resistant, chub and burbot spermatozoa showed medium resistance and brown trout spermatozoa were the most sensitive to the pollutants. With exception of 2,4‐dichlorophenol and zinc the effective concentrations of the tested pollutants exceeded the recommendation for surface waters 100–10·000‐fold and were in a range lethal for the fish themselves. Therefore, it was concluded that fish sperm motility is not a suitable marker for risk assessment of environmental pollutants.     

A molecular analysis of the phylogenetic position of the suborder Cavernicola within the Tricladida (Platyhelminthes), with the description of a new species of stygobiont flatworm from Benin

This paper presents a new species of cavernicolan planarian from the African continent, which enabled us to determine the position of the suborder Cavernicola within the order Tricladida on a molecular basis. A recent paper suggested a sister‐group relationship between Cavernicola and marine triclads. However, our work is the first molecular study to demonstrate unequivocally that the Cavernicola does not group with either the freshwater planarians or the land planarians, i.e. is not closely related to the suborder Continenticola, and corroborates the suggested sister‐group relationship with the marine triclads or Maricola. Two possible scenarios are proposed for the evolution of the Cavernicola from marine ancestors. The new species is assigned to the genus Novomitchellia and is characterized by the absence of eyes. Testicular follicles are numerous and only dorsal, extending from behind the ovaries to the posterior end of the body. The vasa deferentia separately penetrate the penis bulb and the seminal vesicle. The penis papilla is very short and blunt, and the penis bulb musculature is weak. A long and narrow copulatory bursa is situated behind the gonopore. The common oviduct is orientated perpendicularly to the short bursal canal.     

A novel series of C<Subscript>18</Subscript>–C<Subscript>22</Subscript><Emphasis Type="Italic">trans</Emphasis> ω3 PUFA from Northern and Southern Hemisphere strains of the marine haptophyte <Emphasis Type="Italic">Imantonia rotunda</Emphasis>

A series of novel C₁₈–C₂₂ trans ω3 polyunsaturated fatty acids (PUFA) with a single trans double bond in the ω3 position was found in Northern and Southern Hemisphere strains of the marine haptophyte Imantonia rotunda. The novel ω3 PUFA were identified as 18:3(9c,12c,15t) (0.2–1.8 % of total fatty acids), 18:4(6c,9c,12c,15t) (1.9–4.1 %), 18:5 (3c,6c,9c,12c,15t) (0.7–8.8 %), 20:5(5c,8c,11c,14c,17t) (1.2–4.1 %) and 22:6(4c,7c,10c,13c,16c,19t) (0.3–4.3 %), and were accompanied by larger proportions of the all cis isomers: 18:3ω3(9,12,15) (2.7–3.5 %), 18:4ω3(6,9,12,15) (9.3–14.3 %), 18:5ω3(3,6,9,12,15) (7.8–18.5 %), 20:5ω3(5,8,11,14,17) (3.2–3.9 %), 22:5ω3(7,10,13,16,19) (0.1–0.3 %) and 22:6ω3(4,7,10,13,16,19) (2.3–5.2 %). GC analysis of FAME using a non-polar column did not reveal the trans isomers as they coeluted with the all cis PUFA. However, GC using a polar column resolved the trans PUFA from the all cis PUFA, with the trans isomers eluting before the all cis isomers. GC-MS of FAME fractionated by argentation solid-phase chromatography confirmed the molecular ions of all components. FAME were derivatized to form 4,4-dimethyloxazoline (DMOX) derivatives, and GC-MS revealed the same double bond positions for each trans and cis FAME. The results suggest that the ω3 trans double bond originated from the Δ15/ω3 desaturation of 18:2(9c,12c), suggesting that this desaturase has dual cis/trans activity in these species. These results indicate that 18:3(9c,12c,15?t) was the precursor trans isomer produced for the trans series and further desaturation by the common Δ6 desaturase to produce the trans tetraene and successive elongations and desaturations led to the subsequent series of trans ω3 PUFA isomers. To our knowledge, this is the first report of these trans ω3 isomers occurring in strains of I. rotunda. These trans ω3 PUFA may be used as biomarkers in marine food webs for this species and with their unique structure may be biologically active.     

Allosteric HIV‐1 integrase inhibitors promote aberrant protein multimerization by directly mediating inter‐subunit interactions: Structural and thermodynamic modeling studies

Allosteric HIV‐1 integrase (IN) inhibitors (ALLINIs) bind at the dimer interface of the IN catalytic core domain (CCD), and potently inhibit HIV‐1 by promoting aberrant, higher‐order IN multimerization. Little is known about the structural organization of the inhibitor‐induced IN multimers and important questions regarding how ALLINIs promote aberrant IN multimerization remain to be answered. On the basis of physical chemistry principles and from our analysis of experimental information, we propose that inhibitor‐induced multimerization is mediated by ALLINIs directly promoting inter‐subunit interactions between the CCD dimer and a C‐terminal domain (CTD) of another IN dimer. Guided by this hypothesis, we have built atomic models of inter‐subunit interfaces in IN multimers by incorporating information from hydrogen‐deuterium exchange (HDX) measurements to drive protein‐protein docking. We have also developed a novel free energy simulation method to estimate the effects of ALLINI binding on the association of the CCD and CTD. Using this structural and thermodynamic modeling approach, we show that multimer inter‐subunit interface models can account for several experimental observations about ALLINI‐induced multimerization, including large differences in the potencies of various ALLINIs, the mechanisms of resistance mutations, and the crucial role of solvent exposed R‐groups in the high potency of certain ALLINIs. Our study predicts that CTD residues Tyr226, Trp235 and Lys266 are involved in the aberrant multimer interfaces. The key finding of the study is that it suggests the possibility of ALLINIs facilitating inter‐subunit interactions between an external CTD and the CCD‐CCD dimer interface.     

NAD(P)H: quinone oxidoreductase 1 inducer activity of novel 4-aminoquinazoline derivatives

Fourteen novel 4-aminoquinazoline derivatives 2–15 were designed and synthesized. The structure of the newly synthesized compounds was established on the basis of elemental analyses, IR, ¹H-NMR, ¹³C-NMR, and mass spectral data. The compounds were evaluated for their potential cytoprotective activity in murine Hepa1c1c7 cells. All of the synthesized compounds showed concentration-dependent ability to induce the cytoprotective enzyme NAD(P)H: quinone oxidoreductase (NQO1) with potencies in the low- to sub-micromolar range. This approach offers an encouraging framework which may lead to the discovery of potent cytoprotective agents.     

Efficacy of certain chemical compounds on common bean rust disease

The aim of the present study was to evaluate the efficacy of some chemical compounds to management rust disease on common bean under greenhouse and field conditions. In vitro, the effect of four chemical compounds, i.e. phosphoric acid at concentrations 0.3 and 0.6%, benzoic acid, Bion® (BTH), and pyrocatechol at concentrations 4 and 8 mM from each, as well as fungicide, Tilt 25%, 0.25 and 0.5 cm³/l water on urediniospores germination of Uromyces appendiculatus was tested on water agar medium. All these compounds decreased the germination of urediniospores percentage. Under greenhouse and field experiments, application of these compounds led to decrease in disease incidence compared to the control treatments. Benzoic acid at 2015 growing seasons was the most effective in reduction of disease incidence more than the other compounds, whereas the disease incidence decreased from 59.92 to 21.43% and from 68.43 to 18.41% under greenhouse and field conditions, respectively.     

Computational Design of TrkB Peptide Inhibitors and Their Biological Effects on Ovarian Cancer Cell Lines

There are large numbers of different intracellular signaling pathways regulated by Tyrosine kinases (Trk) receptors. Trk receptors, especially TrkB, are also frequently overexpressed in a variety of human malignant tumors. In this study, we have computationally designed small peptide-based inhibitors of TrkB and investigated their effects on the proliferation and apoptosis of two ovarian cancer cell lines. Molecular docking of TrkB with its ligand and antagonist, BDNF and Cyclotraxin B respectively, was carried out using HADDOCK program. A peptide library was constructed based on the critical residues involved in the TrkB binding site. After docking and optimization, two selected peptides were purchased and their effects on the viability and apoptosis of the cells were evaluated by performing MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) test and flow cytometry assay. Subsequently, the levels of expression and phosphorylation statues of TrkB and its two downstream genes including MAPK3 and eIF4E were assessed with western blot. We found that designed peptides effectively reduced TrkB, MAPK3 and eIF4E phosphorylation, reduced cell viability and induced apoptosis in the treated cells when compared to untreated cells. In conclusion, the BDNF/TrkB signaling is shown to be attenuated substantially in the presence of peptide inhibitors suggesting a strong inhibitory potential of the designed peptides for Trk family.     

Leishmania donovani: Therapeutic and prophylactic action of antimony dextran glycoside (RL-712) in the golden hamster

Antimony dextran glycoside (RL-712, manufactured by Rosco A/S Pharmaceutical Taastrup, Denmark) produced a remarkable decrease in Leishmania donovani densities in hamster spleen and liver when administered in a single intraperitoneal (ip) dose of 500 mg Sb/kg body weight or in 600 mg Sb/kg body weight divided into two or three equal parts injected at weekly intervals beginning 15 days after intracardial inoculation of 10 million amastigotes, and also in a single ip dose of 300 mg Sb/kg body weight 14, 7, and 0 days before intracardial inoculation of 10 million amastigotes. No parasites were detected on using a single dose of 500 mg Sb/kg body weight followed by 100 mg Sb/kg body weight one week later.When the drug was administered in a dose of 500 mg Sb/kg body weight either 10 days before subcutaneous inoculation of 60 million promastigotes or eight days before intracardial inoculation of five million promastigotes, no parasites were recovered by smear or culture from the spleen and liver.Results show the prophylactic and therapeutic actions of this drug against L. donovani in the hamster.