DNA hypomethylating agents increase activation and cytolytic activity of CD8+ T cells

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Evaluation of Bacillus subtilis (JN032305) biofungicide to control chilli anthracnose in pot controlled conditions

Colletotrichum gloeosporioides (Penz.) causing anthracnose is a potent pathogen of chilli resulting in significant yield loss. The in vitro root colonisation study showed an increase in root bacterial count by 10 × 10⁵ colony forming units/cm root for Bacillus subtilis after 15 days of germination. Population level of the antagonist was stable in talc till the 180th day (30°C – 1.6 × 10⁸; 4°C – 1.9 × 10⁸) and in lignite till the 150th day (30°C – 1.5 × 10⁸; 4°C – 1.3 × 10⁸). Combined application of B. subtilis and carbendazim enhanced all biometric parameters with reduction in disease incidence. Soil, seed, root dip and foliar spray treatment significantly enhanced the growth parameters of chilli in B. subtilis inoculated treatments in comparison to the untreated control. Seed application resulted in highest plant fresh weight (76.84 g) and dry weight (34.17 g) compared to the untreated control (50 g and 21 g fresh and dry weight, respectively). Highest plant height ranging from 70 cm (soil application) to 77 cm (dip treatment) with Bacillus inoculation was comparable with carbendazim treatment (61 cm with soil application) and 78 cm (dip treatment) and significantly higher than the untreated control (58.2 cm with soil and 61 cm with application, respectively). Dip treatment resulted in significant increase in root length with B. subtilis (33 cm) and carbendazim (32.5 cm) in comparison to untreated control (15 cm). Co-inoculation of pathogen with B. subtilis (singly and with carbendazim) not only reduced the disease incidence but also improved all the biometric parameters in comparison to challenge inoculation. Root dip application was effective in promoting growth while seed application was effective in disease control.     

C-terminal fragments of parathyroid hormone-related protein,PTHrP-(107-111) and (107-139), and the N-terminal PTHrP-(1-40) fragment stimulate membrane-associated protein kinase C activity in rat spleen lymphocytes

Membrane-associated protein kinase C (PKC) activity in lymphocytes freshly isolated from rat spleen was stimulated by the C-terminal parathyroid hormonerelated protein fragments, PTHrP-(107–111) and PTHrP-(107–139), at concentrations from 10^?3 to 10⁴ pM. By contrast, the same concentrations of PTHrP-(120–139), Without the 107–111 TRSAW (-Thr-Arg-Ser-Ala-Trp-) sequence of the other C terminal fragments, did not stimulate spleen lymphocyte PKC. Low concentrations of the N-terminal PTHrP-(1–40) fragment also stimulated membrane-associated PKC activity in the spleen lymphocytes. These results suggest that PTHrP might be an important physiological regulator of the immune response. Published 1994 Wiley-Liss, Inc.     

Identification and characterization of Ixodes scapularis antigens that elicit tick immunity using yeast surface display

Repeated exposure of rabbits and other animals to ticks results in acquired resistance or immunity to subsequent tick bites and is partially elicited by antibodies directed against tick antigens. In this study we demonstrate the utility of a yeast surface display approach to identify tick salivary antigens that react with tick-immune serum. We constructed an Ixodes scapularis nymphal salivary gland yeast surface display library and screened the library with nymph-immune rabbit sera and identified five salivary antigens. Four of these proteins, designated P8, P19, P23 and P32, had a predicted signal sequence. We generated recombinant (r) P8, P19 and P23 in a Drosophila expression system for functional and immunization studies. rP8 showed anti-complement activity and rP23 demonstrated anti-coagulant activity. Ixodes scapularis feeding was significantly impaired when nymphs were fed on rabbits immunized with a cocktail of rP8, rP19 and rP23, a hall mark of tick-immunity. These studies also suggest that these antigens may serve as potential vaccine candidates to thwart tick feeding.     

Polyanhydride Nanoparticle Delivery Platform Dramatically Enhances Killing of Filarial Worms

Filarial diseases represent a significant social and economic burden to over 120 million people worldwide and are caused by endoparasites that require the presence of symbiotic bacteria of the genus Wolbachia for fertility and viability of the host parasite. Targeting Wolbachia for elimination is a therapeutic approach that shows promise in the treatment of onchocerciasis and lymphatic filariasis. Here we demonstrate the use of a biodegradable polyanhydride nanoparticle-based platform for the co-delivery of the antibiotic doxycycline with the antiparasitic drug, ivermectin, to reduce microfilarial burden and rapidly kill adult worms. When doxycycline and ivermectin were co-delivered within polyanhydride nanoparticles, effective killing of adult female Brugia malayi filarial worms was achieved with approximately 4,000-fold reduction in the amount of drug used. Additionally the time to death of the macrofilaria was also significantly reduced (five-fold) when the anti-filarial drug cocktail was delivered within polyanhydride nanoparticles. We hypothesize that the mechanism behind this dramatically enhanced killing of the macrofilaria is the ability of the polyanhydride nanoparticles to behave as a Trojan horse and penetrate the cuticle, bypassing excretory pumps of B. malayi, and effectively deliver drug directly to both the worm and Wolbachia at high enough microenvironmental concentrations to cause death. These provocative findings may have significant consequences for the reduction in the amount of drug and the length of treatment required for filarial infections in terms of patient compliance and reduced cost of treatment.     

The LUX Score: A Metric for Lipidome Homology

A lipidome is the set of lipids in a given organism, cell or cell compartment and this set reflects the organism’s synthetic pathways and interactions with its environment. Recently, lipidomes of biological model organisms and cell lines were published and the number of functional studies of lipids is increasing. In this study we propose a homology metric that can quantify systematic differences in the composition of a lipidome. Algorithms were developed to 1. consistently convert lipids structure into SMILES, 2. determine structural similarity between molecular species and 3. describe a lipidome in a chemical space model. We tested lipid structure conversion and structure similarity metrics, in detail, using sets of isomeric ceramide molecules and chemically related phosphatidylinositols. Template-based SMILES showed the best properties for representing lipid-specific structural diversity. We also show that sequence analysis algorithms are best suited to calculate distances between such template-based SMILES and we adjudged the Levenshtein distance as best choice for quantifying structural changes. When all lipid molecules of the LIPIDMAPS structure database were mapped in chemical space, they automatically formed clusters corresponding to conventional chemical families. Accordingly, we mapped a pair of lipidomes into the same chemical space and determined the degree of overlap by calculating the Hausdorff distance. We named this metric the ‘Lipidome jUXtaposition (LUX) score’. First, we tested this approach for estimating the lipidome similarity on four yeast strains with known genetic alteration in fatty acid synthesis. We show that the LUX score reflects the genetic relationship and growth temperature better than conventional methods although the score is based solely on lipid structures. Next, we applied this metric to high-throughput data of larval tissue lipidomes of Drosophila. This showed that the LUX score is sufficient to cluster tissues and determine the impact of nutritional changes in an unbiased manner, despite the limited information on the underlying structural diversity of each lipidome. This study is the first effort to define a lipidome homology metric based on structures that will enrich functional association of lipids in a similar manner to measures used in genetics. Finally, we discuss the significance of the LUX score to perform comparative lipidome studies across species borders.