Anti-inflammatory,Antioxidant and Analgesic Amides

The synthesis of some new aryl acetic acids and amides and a pharmacochemical study and quantitative structure-activity relationships (QSAR) on them are described. The compounds were screened for their biological activity using the carrageenin induced rat paw oedema model and a significant inhibition of oedema occurred (44.1–80.1%) at a concentration of 0.01?mmol/1?kg. The analgesic activity, based on the inhibition of acetic acid-induced writhing in rats was also found to be significant. The compounds were found to interact with the stable free radical 1,1-diphenyl-hydrazyl DPPH and with DMSO (for hydroxyl radicals). The compounds were screened for radical scavenging activity with the xanthine/xanthine oxidase system for O₂^-? and for inhibition of soybean lipoxygenase (LOX). The results are discussed in terms of the structural and physicochemical characteristics of the compounds.     

Nutrient Sensing by Histone Marks: Reading the Metabolic Histone Code Using Tracing,Omics, and Modeling

Several metabolites serve as substrates for histone modifications and communicate changes in the metabolic environment to the epigenome. Technologies such as metabolomics and proteomics have allowed us to reconstruct the interactions between metabolic pathways and histones. These technologies have shed light on how nutrient availability can have a dramatic effect on various histone modifications. This metabolism–epigenome cross talk plays a fundamental role in development, immune function, and diseases like cancer. Yet, major challenges remain in understanding the interactions between cellular metabolism and the epigenome. How the levels and fluxes of various metabolites impact epigenetic marks is still unclear. Discussed herein are recent applications and the potential of systems biology methods such as flux tracing and metabolic modeling to address these challenges and to uncover new metabolic–epigenetic interactions. These systems approaches can ultimately help elucidate how nutrients shape the epigenome of microbes and mammalian cells.     

Formulation of a novel oxybenzone-loaded nanostructured lipid carriers (NLCs)

The objective of the current study was to formulate oxybenzone into nanostructured lipid carriers (NLCs) to enhance its sunscreening efficacy and safety. NLCs of oxybenzone were prepared by the solvent diffusion method. A complete 2(3) factorial design was used for the evaluation of the prepared oxybenzone NLCs. The study design involves the investigation of the effect of three independent variables namely liquid lipid type (Miglyol 812 and oleic acid), liquid lipid concentration (15% and 30%), and oxybenzone concentration (5% and 10% with respect to total lipids) on the particle size (p.s.) , the entrapment efficiency (EE%) and the in vitro drug release after 8 h. The prepared NLCs were spherical in overall shape and were below 0.8 microm. Miglyol 812 and 30% liquid lipid were found to significantly decrease the p.s. and increase the EE% when compared to oleic acid and 15% liquid lipid. Increasing oxybenzone concentration increased significantly the p.s. but did not affect the EE%. NLCs prepared using Miglyol 812, 15% liquid lipid, and 10% oxybenzone showed slower drug release when compared to those prepared using oleic acid, 30% liquid lipid, and 5% oxybenzone, respectively. The candidate oxybenzone-loaded NLC dispersion was then formulated into gel. The incorporation of oxybenzone into NLCs greatly increased the in vitro sun protection factor and erythemal UVA protection factor of oxybenzone more than six- and eightfold, respectively, while providing the advantage of overcoming side effects of free oxybenzone as evidenced by very low irritation potential.     

Possible involvement of some secondary metabolites in salt tolerance of sugarcane

Accumulation of toxic ions in plant tissues modulates the levels of primary and secondary metabolites, which may be related to salinity tolerance. In this study two sugarcane clones, CP-4333 (tolerant) and HSF-240 (sensitive), were exposed to salinity levels at the formative stage, and evaluated three times at 10-day intervals. Although net rate of photosynthesis (Pn), leaf area, length and dry weight of shoots were decreased in both clones, the CP-4333 showed less reduction compared to HSF-240. Both clones displayed a general tendency to accumulate Na+ and Cl- and little K+, though CP-4333 accumulated less Na+ and more K+ compared to HSF-240, and thus showed a higher K+:Na+ ratio. The carotenoid (CAR) content remained steady, while total chlorophyll (CHL) was slightly reduced in the tolerant clone and significantly reduced in HSF-240. In contrast, soluble phenolics (PHE), anthocyanins (ANT) and flavones (FLA) levels were 2.5, 2.8 and 3.0 times greater in CP-4333 in comparison with HSF-240. The decrease in Pn and most secondary metabolites demonstrated by the sensitive clone, but not evidenced in the tolerant clones, suggest that the presence of those metabolites is related to increased salt tolerance of sugarcane. The increased synthesis of PHE, ANT and FLA seems to protect sugarcane from ion-induced oxidative stress, probably due to a common structural skeleton, the phenyl group, of those metabolites. CAR, as components of the light harvesting center (LHC) and biosynthesized in chloroplasts, may confer resistance to this organelle. The PHE, ANT and FLA synthesized in the cytosol may protect cells from ion-induced oxidative damage by binding the ions and thereby showing reduced toxicity on cytoplasmic structures.     

Slm1 and slm2 are novel substrates of the calcineurin phosphatase required for heat stress-induced endocytosis of the yeast uracil permease

The Ca2+/calmodulin-dependent phosphatase calcineurin promotes yeast survival during environmental stress. We identified Slm1 and Slm2 as calcineurin substrates required for sphingolipid-dependent processes. Slm1 and Slm2 bind to calcineurin via docking sites that are required for their dephosphorylation by calcineurin and are related to the PXIXIT motif identified in NFAT. In vivo, calcineurin mediates prolonged dephosphorylation of Slm1 and Slm2 during heat stress, and this response can be mimicked by exogenous addition of the sphingoid base phytosphingosine. Slm proteins also promote the growth of yeast cells in the presence of myriocin, an inhibitor of sphingolipid biosynthesis, and regulation of Slm proteins by calcineurin is required for their full activity under these conditions. During heat stress, sphingolipids signal turnover of the uracil permease, Fur4. In cells lacking Slm protein activity, stress-induced endocytosis of Fur4 is blocked, and Fur4 accumulates at the cell surface in a ubiquitinated form. Furthermore, cells expressing a version of Slm2 that cannot be dephosphorylated by calcineurin display an increased rate of Fur4 turnover during heat stress. Thus, calcineurin may modulate sphingolipid-dependent events through regulation of Slm1 and Slm2. These findings, in combination with previous work identifying Slm1 and Slm2 as targets of Mss4/phosphatidylinositol 4,5-bisphosphate and TORC2 signaling, suggest that Slm proteins integrate information from a variety of signaling pathways to coordinate the cellular response to heat stress.     

Contribution of whole blood to the control of plasma asymmetrical dimethylarginine

The endogenous nitric oxide (NO) synthase (NOS) inhibitor asymmetrical dimethylarginine (ADMA) is elevated in many patients and may contribute to the initiation and progression of their disease. While some mechanistic pathways have been identified, tissue-specific contributions to ADMA control remain unclear. We sought to determine if whole blood (WB) could participate in ADMA control ex vivo. Anesthetized male Sprague-Dawley rats underwent exsanguinations, and WB preparations were incubated at 37 degrees C for 5 h. ADMA and symmetrical dimethylarginine were analyzed by high-pressure liquid chromatography. Incubation of lysed red blood cell (RBC) supernatant yielded a significant decrease in ADMA that was blocked by 4124W, a synthetic inhibitor of dimethylarginine dimethylaminohydrolase, the only reported enzyme to hydrolyze ADMA. Hydrolysis of ADMA was diminished by addition of physiologically relevant concentrations of zinc (i.e., 20 microM). Conversely, when rat WB or WB supernatant was incubated at 37 degrees C, it liberated quantities of free ADMA (1-2 microM) that in vivo would likely have pathological consequences. Addition of arginine methyltransferase inhibitors to these incubations did not reduce ADMA release, indicating no dominant role for active protein methylation during these incubations. This ADMA liberation was significantly reduced by addition of protease inhibitors, indicating a dependence on peptide bond hydrolysis. Total ADMA (protein incorporated plus free) was determined by acid hydrolysis and found to be 43.18 +/- 4.79 microM in WB with approximately 95% of this in RBCs. These ex vivo data demonstrate the potential of blood to control the NO-NOS system by modulating free ADMA.     

The In Vitro Mass-Produced Model Mycorrhizal Fungus,Rhizophagus irregularis,Significantly Increases Yields of the Globally Important Food Security Crop Cassava

The arbuscular mycorrhizal symbiosis is formed between arbuscular mycorrhizal fungi (AMF) and plant roots. The fungi provide the plant with inorganic phosphate (P). The symbiosis can result in increased plant growth. Although most global food crops naturally form this symbiosis, very few studies have shown that their practical application can lead to large-scale increases in food production. Application of AMF to crops in the tropics is potentially effective for improving yields. However, a main problem of using AMF on a large-scale is producing cheap inoculum in a clean sterile carrier and sufficiently concentrated to cheaply transport. Recently, mass-produced in vitro inoculum of the model mycorrhizal fungus Rhizophagus irregularis became available, potentially making its use viable in tropical agriculture. One of the most globally important food plants in the tropics is cassava. We evaluated the effect of in vitro mass-produced R. irregularis inoculum on the yield of cassava crops at two locations in Colombia. A significant effect of R. irregularis inoculation on yield occurred at both sites. At one site, yield increases were observed irrespective of P fertilization. At the other site, inoculation with AMF and 50% of the normally applied P gave the highest yield. Despite that AMF inoculation resulted in greater food production, economic analyses revealed that AMF inoculation did not give greater return on investment than with conventional cultivation. However, the amount of AMF inoculum used was double the recommended dose and was calculated with European, not Colombian, inoculum prices. R. irregularis can also be manipulated genetically in vitro, leading to improved plant growth. We conclude that application of in vitro R. irregularis is currently a way of increasing cassava yields, that there is a strong potential for it to be economically profitable and that there is enormous potential to improve this efficiency further in the future.     

Size and genetic composition of the colonizing propagules in a butterfly metapopulation

The amount and spatial distribution of genetic variation that is maintained in a metapopulation depends critically on the colonization process. Here, we use molecular markers to determine the number and genetic relatedness of individuals establishing new local populations in a large metapopulation of the Glanville fritillary butterfly Melitaea cinxia. The empirical results are compared with the predictions of a dispersal model based on a diffusion approximation of correlated random walk, which serves as a base‐line hypothesis about the rate and pattern of colonization. The results show that half of the new local populations consisted of a single larval group of full sibs and hence necessarily of the offspring of a single female. If the colonization involved two or more larval groups, these were usually oviposited by two different females that were unrelated to each other. The pattern of colonizations is thus intermediate between the propagule pool and the migrant pool models. These results elucidate the generation of genetic stochasticity, which may influence the dynamics of small populations. The dispersal model predicted well the pattern of habitat occupancy and the pattern of colonizations in relation to landscape structure, though which particular habitat patches became colonized was influenced also by measures of habitat quality not included in the model.