C-Terminal Domain Deletion Enhances the Protective Activity of cpa/cpb Loaded Solid Lipid Nanoparticles against Leishmania major in BALB/c Mice

Background

We have demonstrated that vaccination with pDNA encoding cysteine proteinase Type II (CPA) and Type I (CPB) with its unusual C-terminal extension (CTE) can partially protect BALB/c mice against cutaneous leishmanial infection. Unfortunately, this protection is insufficient to completely control infection without booster injection. Furthermore, in developing vaccines for leishmaniasis, it is necessary to consider a proper adjuvant and/or delivery system to promote an antigen specific immune response. Solid lipid nanoparticles have found their way in drug delivery system development against intracellular infections and cancer, but not Leishmania DNA vaccination. Therefore, undefined effect of cationic solid lipid nanoparticles (cSLN) as an adjuvant in enhancing the immune response toward leishmanial antigens led us to refocus our vaccine development projects.

Methodology/Principal Findings

Three pDNAs encoding L. major cysteine proteinase type I and II (with or without CTE) were formulated by cSLN. BALB/c mice were immunized twice by 3-week interval, with cSLN-pcDNA-cpa/b, pcDNA-cpa/b, cSLN-pcDNA-cpa/b^-CTE, pcDNA-cpa/b^-CTE, cSLN, cSLN-pcDNA and PBS. Mice vaccinated with cSLN-pcDNA-cpa/b^-CTE showed significantly higher levels of parasite inhibition related to protection with specific Th1 immune response development, compared to other groups. Parasite inhibition was determined by different techniques currently available in exploration vacciation efficacy, i.e., flowcytometry on footpad and lymph node, footpad caliper based measurements and imaging as well as lymph node microtitration assay. Among these techniques, lymph node flowcytometry was found to be the most rapid, sensitive and easily reproducible method for discrimination between the efficacy of vaccination strategies.

Conclusions/Significance

This report demonstrates cSLN''s ability to boost immune response magnitude of cpa/cpb^-CTE cocktail vaccination against leishmaniasis so that the average parasite inhibition percent could be increased significantly. Hence, cSLNs can be considered as suitable adjuvant and/or delivery systems for designing third generation cocktail vaccines.     

A guaianolide from Centaurea behen

The aerial parts of Centaurea behen afforded in addition to known lactones a new derivative of solstitialin A.     

Stomatal response characteristics of Tradescantia virginiana grown at high relative air humidity

Plants produced at high relative air humidity (RH) show poor control of water loss after transferring to low RH, a phenomenon which is thought to be due to their stomatal behaviour. The stomatal anatomy and responses of moderate (55%) and high (90%) RH grown Tradescantia virginiana plants to treatments that normally induce stomatal closure, i.e. desiccation, abscisic acid (ABA) application and exposure to darkness were studied using attached or detached young, fully expanded leaves. Compared with plants grown at moderate RH the transpiration rate, stomatal conductance and aperture of high RH grown plants measured at the same condition (40% RH) were, respectively, 112, 139 and 132% in light and 141, 188 and 370% in darkness. Besides the differences in stomatal size (guard cell length was 56.7 and 73.3 µm for moderate and high RH grown plants, respectively), there was a clear difference in stomatal behaviour. The stomata responded to desiccation, ABA and darkness in both moderate and high RH grown plants, but the high variability of stomatal closure in high RH grown plants was striking. Some stomata developed at high RH closed in response to darkness or to a decrease in relative water content to the same extent as did stomata from moderate RH grown plants, whereas others closed only partly or did not close at all. Evidently, some as yet unidentified physiological or anatomical changes during development disrupt the normal functioning of some stomata in leaves grown at high RH. The failure of some stomata to close fully in response to ABA suggests that ABA deficiency was not responsible for the lack of stomatal closure in response to desiccation.     

Guaianolides from Acroptilon repens

Two new guaianolides have been isolated from the aerial parts of Acroptilon repens.     

Sesterterpenes from Salvia hypoleuca

The aerial parts of Salvia hypoleuca afforded two sesterterpenes with a previously unknown carbon skeleton.     

Effect of Lactobacillus casei on Innate Immunity Responses and Aeromonas hydrophila Resistance in Shabot,Tor grypus

Probiotics and Antimicrobial Proteins - For investigating the possible effect of Lactobacillus casei on the immune status of Shabot, Tor grypus, 480 fish weighing...     

The role of abscisic acid in disturbed stomatal response characteristics of Tradescantia virginiana during growth at high relative air humidity

In this study, the role of abscisic acid (ABA) in altered stomatal responses of Tradescantia virginiana leaves grown at high relative air humidity (RH) was investigated. A lower ABA concentration was found in leaves grown at high RH compared with leaves grown at moderate RH. As a result of a daily application of 20 microM ABA to leaves for 3 weeks during growth at high RH, the stomata of ABA-treated leaves grown at high RH showed the same behaviour as did the stomata of leaves grown at moderate RH. For example, they closed rapidly when exposed to desiccation. Providing a high RH around a single leaf of a plant during growth at moderate RH changed the stomatal responses of this leaf. The stomata in this leaf grown at high RH did not close completely in response to desiccation in contrast to the stomata of the other leaves from the same plant. The ABA concentration on a fresh weight basis, though not on a dry weight basis, of this leaf was significantly lower than that of the others. Moreover, less closure of stomata was found in the older leaves of plants grown at high RH in response to desiccation compared with younger leaves. This was correlated with a lower ABA concentration in these leaves on a fresh weight basis, though not on a dry weight basis. Stomata of leaves grown at moderate RH closed in response to short-term application of ABA or sodium nitroprusside (SNP), while for leaves grown at high RH there was a clear difference in stomatal responses between the leaf margins and main-vein areas. The stomatal aperture in response to short-term application of ABA or SNP at the leaf margins of leaves grown at high RH remained significantly wider than in the main-vein areas. It was concluded that: (i) a long-term low ABA concentration in well-watered plants during growth at high RH could be a reason for less or no stomatal closure under conditions of drought stress; and (ii) the long-term ABA concentration on a fresh weight basis rather than on a dry weight basis is likely to be responsible for structural or physiological changes in stomata during leaf growth.     

Optimization of biological sulfide removal in a CSTR bioreactor

In this study, biological sulfide removal from natural gas in a continuous bioreactor is investigated for estimation of the optimal operational parameters. According to the carried out reactions, sulfide can be converted to elemental sulfur, sulfate, thiosulfate, and polysulfide, of which elemental sulfur is the desired product. A mathematical model is developed and was used for investigation of the effect of various parameters on elemental sulfur selectivity. The results of the simulation show that elemental sulfur selectivity is a function of dissolved oxygen, sulfide load, pH, and concentration of bacteria. Optimal parameter values are calculated for maximum elemental sulfur selectivity by using genetic algorithm as an adaptive heuristic search. In the optimal conditions, 87.76% of sulfide loaded to the bioreactor is converted to elemental sulfur.     

Phytoseiid mites (Acari: Mesostigmata) associated with tea gardens in north of Iran

Predator mites of Phytoseiidae family are among the most important biocontrol agents in the world. These beneficial mites are considered as natural enemies of many pests and herbivore mites, and can feed on different growth stages of pests (egg, larva or nymph). Five species of Phytoseiidae mites were found during a survey conducted on tea plants, Camellia sinensis (Theaceae), in the Mazandaran and Guilan Provinces in the north of Iran, on the coast of the Caspian Sea, the major tea-growing region of Iran. Some of these species are recorded for the first time in tea gardens of Iran.     

Siliciclastic input and sedimentation rate as controls on paleoecological distribution of Lower Miocene benthic carbonate producers in a fan–delta: Zagros foreland basin,Iran

This paper aimed to study Lower Miocene (Burdigalian) mixed carbonate–siliciclastic deposits within an Upper Cenozoic synorogenic conglomerate–dominated succession in north of Shalamzar in the Zagros foreland basin, Iran. The deposits are composed of nine facies: foraminiferal mudstone, silty mudstone, sandy mudstone, fossiliferous sandy mudstone, fossiliferous argillaceous mudstone, fossiliferous calclithite, coral limestone, calcareous claystone and hybrid sandstone. The facies represent a mixed carbonate– siliciclastic shelf–type fan–delta. The subenvironments of the fan–delta include muddy pro–delta, sandy delta– front, clastic proximal mouth bar and a subordinate delta plain. Siliciclastic input and sedimentation rate controlled the paleoecological distribution of different benthic carbonate–producing fauna in the fan–delta during its progradation into a shelf marine environment. Input of siliciclastic deposits and sedimentation rate limited the diversity and development of corals and controlled their colonization and growth morphologies in the sandy delta–front. Siliciclastic input (including plant materials and coal debris) and sedimentation rate controlled the trophic habitats of many gastropods and their abundance and distribution in the sandy delta– front and clastic proximal mouth bar. Also, increased siliciclastic input favored abundance of larger benthic foraminifera in most parts of the fan–delta with the exception of the muddy pro–delta.