Differential immediate and sustained memory enhancing effects of alpha7 nicotinic receptor agonists and allosteric modulators in rats

The α7 nicotinic acetylcholine receptor (nAChR) is a potential target for the treatment of cognitive deficits in patients with schizophrenia, ADHD and Alzheimer's disease. Here we test the hypothesis that upregulation of α7 nAChR levels underlies the enhanced and sustained procognitive effect of repeated administration of α7 nAChR agonists. We further compare the effect of agonists to that of α7 nAChR positive allosteric modulators (PAMs), which do not induce upregulation of the α7 nAChR. Using the social discrimination test as a measure of short-term memory, we show that the α7 nAChR agonist A-582941 improves short-term memory immediately after repeated (7× daily), but not a single administration. The α7 nAChR PAMs PNU-120596 and AVL-3288 do not affect short-term memory immediately after a single or repeated administration. This demonstrates a fundamental difference in the behavioral effects of agonists and PAMs that may be relevant for clinical development. Importantly, A-582941 and AVL-3288 increase short-term memory 24 hrs after repeated, but not a single, administration, suggesting that repeated administration of both agonists and PAMs may produce sustained effects on cognitive performance. Subsequent [(125)I]-bungarotoxin autoradiography revealed no direct correlation between α7 nAChR levels in frontal cortical or hippocampal brain regions and short-term memory with either compound. Additionally, repeated treatment with A-582941 did not affect mRNA expression of RIC-3 or the lynx-like gene products lynx1, lynx2, PSCA, or Ly6H, which are known to affect nAChR function. In conclusion, both α7 nAChR agonists and PAMs exhibit sustained pro-cognitive effects after repeated administration, and altered levels of the α7 nAChR per se, or that of endogenous regulators of nAChR function, are likely not the major cause of this effect.     

Synthesis and in vitro antiproliferative activity of new 11-aminoalkylamino-substituted 5H- and 6H-indolo[2,3-b]quinolines; structure-activity relationships of neocryptolepines and 6-methyl congeners

The present report describes the synthesis and antiproliferative evaluation of certain 11-aminoalkylamino-substituted 5H- and 6H-indolo[2,3-b]quinolines and their methylated derivatives. These 5-Me- and 6-Me-indolo[2,3-b]quinoline derivatives 10-14, 20 were prepared by amination at the C-11 position of the 11-chloro-5-methyl-5H- and 11-chloro-6-methyl-6H-indolo[2,3-b]quinolines with different substituents on the quinoline ring. The 11-aminoalkylaminomethylated 23, the homologue of 11, was prepared from the same intermediate for a further SAR study. These intermediates are accessible from 4-substituted anilines or their N-methylated analogues and methyl indole-3-carboxylate as a counterpart. The in vitro antiproliferative assay indicated that the 5-methylated derivatives 10-14 are more cytotoxic than their respective 6-methylated 6H-indolo[2,3-b]quinoline derivatives 20. Among them, N-(3-aminopropyl)-2-bromo-5-methyl-5H-indolo[2,3-b]quinolin-11-amine 12f was the most cytotoxic with a mean IC(50) value of 0.12 μM against human leukemia MV4-11 cell line, and also exhibited selective cytotoxicities against A549 (lung cancer), HCT116 (colon cancer) cell lines and normal fibroblast BALB/3T3 with IC(50) values of 0.543, 0.274 and 0.869 μM, respectively. The binding constant of products 12f and 20f to salmon fish sperm DNA were also evaluated using UV-vis absorption spectroscopy, indicating intercalation binding with a constant of 2.93×10(5) and 3.28×10(5)Lmol(-1), respectively.     

Improvement of antioxidant activity of chitosan by chemical treatment and ionizing radiation

Modification of chitosan (CS) to N-maleoylchitosan (NMCS), N-phthaloylchitosan (NPhCS) and sulfonated-chitosan (SCS) was done using maleic anhydride, phthalic anhydride and chlorosulfonic acid, respectively followed by exposing them to γ-rays at different doses. The molecular weights and structural changes of irradiated chitosan derivatives were determined by GPC, FT-IR and UV-vis spectrophotometer. The molecular weights decreased with increasing irradiation dose. Results revealed that the main polysaccharide structure remained after irradiation. To investigate the enhancement of antioxidant activity of chitosan and its derivatives of different molecular weights, radical mediated lipid peroxidation inhibition, scavenging effect of DPPH radicals, reducing power and ferrous ion chelating activity assays were used. Chitosan derivatives with different molecular weights exhibit antioxidant activity. The lower the molecular weights of chitosan and its derivatives, the higher the antioxidant activity. NMCS possessed high scavenging effect on DPPH radicals compared with NPhCS, SCS and ascorbic acid. The irradiated chitosan and its derivatives could be used as natural antioxidants.     

Ex Vivo Application of Secreted Metabolites Produced by Soil-Inhabiting Bacillus spp. Efficiently Controls Foliar Diseases Caused by Alternaria spp.

Bacterial biological control agents (BCAs) are largely used as live products to control plant pathogens. However, due to variable environmental and ecological factors, live BCAs usually fail to produce desirable results against foliar pathogens. In this study, we investigated the potential of cell-free culture filtrates of 12 different bacterial BCAs isolated from flower beds for controlling foliar diseases caused by Alternaria spp. In vitro studies showed that culture filtrates from two isolates belonging to Bacillus subtilis and Bacillus amyloliquefaciens displayed strong efficacy and potencies against Alternaria spp. The antimicrobial activity of the culture filtrate of these two biological control agents was effective over a wider range of pH (3.0 to 9.0) and was not affected by autoclaving or proteolysis. Comparative liquid chromatography-mass spectrometry (LC-MS) analyses showed that a complex mixture of cyclic lipopeptides, primarily of the fengycin A and fengycin B families, was significantly higher in these two BCAs than inactive Bacillus spp. Interaction studies with mixtures of culture filtrates of these two species revealed additive activity, suggesting that they produce similar products, which was confirmed by LC-tandem MS analyses. In in planta pre- and postinoculation trials, foliar application of culture filtrates of B. subtilis reduced lesion sizes and lesion frequencies caused by Alternaria alternata by 68 to 81%. Taken together, our studies suggest that instead of live bacteria, culture filtrates of B. subtilis and B. amyloliquefaciens can be applied either individually or in combination for controlling foliar diseases caused by Alternaria species.     

Potential use of green macroalgae Ulva lactuca as a feed supplement in diets on growth performance,feed utilization and body composition of the African catfish,Clarias gariepinus

This study aimed to evaluate the effects of diet containing the green macroalgae, Ulva lactuca, on the growth performance, feed utilization and body composition of African catfish Clarias gariepinus. Four experimental diets were formulated: D1 as a control group and D2, D3 and D4 which included 10%, 20% and 30% U. lactuca meal, respectively. 180 African catfish, weighing 9.59 ± 0.43 g, and with an average length of 11.26 ± 0.21, (mean ± SE) were divided into four groups corresponding to the different feeding regimes. The final body weight of the fish showed insignificant differences (P > 0.05) between the control and fish fed D2, whereas, there was a significant difference (P < 0.05) between these two diets compared with D3 and D4, with weights of 70.52, 60.92, 40.57 and 35.66 g recorded for D1, D2, D3 and D4, respectively. In the same trend significant differences were also evident in weight gain, specific growth rate and feed utilization. Fish fed with a diet containing 20% or 30% U. lactuca meal had poorer growth performance and feed utilization. Protein productive value, protein efficiency ratio, daily dry feed intake and total feed intake were also significantly lower in fish fed with D3 and D4 than in the control D1 and D2.Overall, the results of the experiment revealed that African catfish fed a diet with U. lactuca included at 20% and 30% levels showed poorer growth and feed utilization than the control group and fish fed diets containing 10% of U. lactuca.     

Genetic relationships among populations of Aedes aegypti from Uruguay and northeastern Argentina inferred from ISSR‐PCR data

Aedes aegypti (L.) (Diptera: Culicidae), the main vector of yellow fever and dengue viruses, was eradicated from Argentina between 1955 and 1963, but reinvaded the country in 1986. In Uruguay, the species was reintroduced in 1997. In this study we used highly polymorphic inter‐simple sequence repeats (ISSR) markers to analyse the genetic structure of Ae. aegypti populations from Uruguay and northeastern Argentina to identify possible colonization patterns of the vector. Overall genetic differentiation among populations was high (F_ST = 0.106) and showed no correlation with geographic distance, which is consistent with the short time since the reintroduction of the species in the area. Differentiation between pairs of Argentine populations (F_ST 0.072 to 0.221) was on average higher than between Uruguayan populations (F_ST?0.044 to 0.116). Bayesian estimation of population structure defined four genetic clusters and most populations were admixtures of two of them: Mercedes and Treinta y Tres (Uruguay) were mixtures of clusters 1 and 3; Salto (Uruguay) and Paraná (Argentina) of clusters 1 and 4; Fray Bentos (Uruguay) of clusters 2 and 3, and Gualeguaychú (Argentina) of clusters 2 and 3. Posadas and Buenos Aires in Argentina were fairly genetically homogeneous. Our results suggest that Ae. aegypti recolonized Uruguay from bordering cities in Argentina via bridges over the Uruguay River and also from Brazil.     

Identification of potentially safe promising fungal cell factories for the production of polyketide natural food colorants using chemotaxonomic rationale

Background  

Colorants derived from natural sources look set to overtake synthetic colorants in market value as manufacturers continue to meet the rising demand for clean label ingredients – particularly in food applications. Many ascomycetous fungi naturally synthesize and secrete pigments and thus provide readily available additional and/or alternative sources of natural colorants that are independent of agro-climatic conditions. With an appropriately selected fungus; using in particular chemotaxonomy as a guide, the fungal natural colorants could be produced in high yields by using the optimized cultivation technology. This approach could secure efficient production of pigments avoiding use of genetic manipulation.     

Effects of nestboxes on the breeding biology of Southern House Wrens Troglodytes aedon bonariae in the southern temperate zone

Nestboxes are known to increase clutch size, enhance breeding success and affect the social mating system of several cavity nesters. Although in recent years various cavity nesters have been studied in nestboxes in South America, the effects of boxes on the biology of the study species are unknown. We evaluated the effects of nestboxes on the breeding biology and social mating system of Southern House Wrens Troglodytes aedon bonariae by comparing birds breeding in nestboxes and tree cavities in two cattle ranches in Buenos Aires Province, Argentina. Southern House Wrens nesting in boxes had higher breeding success but, contrary to studies on the temperate zone, we did not find differences in clutch size between Wrens breeding in nestboxes and tree cavities. The main causes of nest failure in tree cavities were nest predation and flooding of the cavity (70 and 23% of the failures, respectively) while in nestboxes predation and desertion were the most important causes of failure (38 and 34% of the failures, respectively). The social mating system of Southern House Wrens is monogamy with biparental care, and neither was affected by the boxes. Males did not attract secondary females to additional nestboxes; however, nestboxes are safer breeding sites than tree cavities, and females seemed to prefer males with nestboxes on their territory. These results suggest that nest quality alone might be not enough for secondary females to accept polygyny.     

Do carnivorous plants use volatiles for attracting prey insects?

1.  Scientists have been fascinated by carnivorous plants for centuries and they have thoroughly investigated how these plants can benefit from insect capture for example through increased growth, earlier flowering, and increased seed production. How prey is actually lured into the traps, however, is less well understood. Trapping prey may be achieved in a random way, for example by camouflaging the traps (hiding them in the surrounding vegetation), so that prey is trapped by accidental landing on the trap leaves or wind drift, or in the other extreme, trapping may involve mimicry of other attractive resources such as fruits or flowers by using specific visual or olfactory signals to attract a specific prey assemblage.
2.  We investigated for the first time volatiles of the trapping leaves of carnivorous plant species by dynamic headspace methods. We present data on the venus flytrap Dionaea muscipula , the sundew Drosera binata , and the North American pitcher plants Sarracenia flava , Sarracenia leucophylla , Sarracenia minor , and Sarracenia purpurea . A large number of compounds and relatively high emission rates were found in three of the North American pitcher plants ( S. flava , S. leucophylla , and S. minor ) with compounds typically found in flowers or fruits. This suggests together with other features (e.g. colour, nectar production) that these traps are possibly flower or fruit mimics. The leaves of S. purpurea , Dionaea muscipula , and Drosera binata emitted much weaker scents with lower numbers of components, consisting mainly of volatiles typically emitted from green leaves.
3.  We discuss whether or not the use of volatiles for attracting prey animals is linked with specific trapping mechanisms and whether carnivorous plants can be grouped into specialized 'olfactory syndromes'.