New biscoumarin derivatives-cytotoxicity and enzyme inhibitory activities

Biscoumarin derivatives 1-27 were tested for their inhibition of snake venom and human nucleotide pyrophosphatase phosphodiesterase-1 enzymes. Lineweaver-Burk and Dixon plots and their secondary replots showed that these compounds are pure non-competitive inhibitors of both the enzymes. Ki and IC50 values of biscoumarins were found to be in the range of 50 to 1000 and 164 to > 1000 microM, respectively, against human recombinant phosphodiesterase 1 enzyme and 8.0 to 1150 and 9.44 to > 1000 microM, respectively, against snake venom phosphodiesterase. Compounds 1, 3, 4, 6, 7, 17, 26, and 30 were found to be non-competitive and non-cytotoxic upto a concentration of 200 microg/mL as evident by less than 10% cell death after 3 h of incubation.     

Plant growth promoting potential of free-living diazotrophs and other rhizobacteria isolated from Northern Indian soil

The viable count of free-living diazotrophic bacteria in different crop rhizospheres varied from 1.11 x 10(4) to 8.5 x 10(5) CFU/g of soil. The majority of the diazotrophs phenotypically belong to either Azotobacter chroococcum, non-A. chroococcum type and to a heterogenous group tentatively named putative nitrogen-fixing (PNF) bacteria. In this study, 25 isolates of the PNF group were screened for their multiple plant growth-promoting (PGP) traits and grouped into 5 PGP types. An isolate, PNF(11) showed promising PGP potential in vitro and was characterized as a species of Achromobacter by 16S rRNA analysis. The isolate PNF(11) along with three other previously isolated PGP bacteria, Azotobacter sp. (AZS(3)), fluorescent pseudomonas (Ps(5)), Bacillus sp. (Bc(1)) were selected for crop inoculation response in green house experiment on Vigna radiata var.T44. Plants from inoculated and control pots were sampled and analyzed at 30, 45 and 60 days after sowing for various vegetative, nodule-related data and yield parameters. The findings indicated that selected isolate of PNF bacteria, and other PGP isolates with multiple activities significantly improve the plant growth parameters, yield parameters of Vigna radiata T44 over control and also show good compatibility with Bradyrhizobium inoculation.     

Ethnopharmacological Survey of Plants Used for the Treatment of Stomach,Diabetes, and Ophthalmic Diseases in Sudhan Gali,Kashmir , Pakistan

The present paper represents the ethnopharmacological survey of Sudhan Gali, Kashmir, Pakistan. The study revealed that 12 plant species belonging to 11 families were used for the treatment of stomach, diabetes and ophthalmic diseases by the local people in Sudhan Gali. Achillea millefolium , Aconitum heterophyllum, Berberis lycium, Polygonum amplexicaule, Mentha longifolia, Paeonia emodi, Plantago lanceolata were locally used for stomach related problems treatment; Berberis lycium, Skimmia lareola, Solanum dulcamara for diabetes and Geranium wallichianum, Artemisia vulgaris, Solanum dulcamara, and Corydalis crassifolia used for the treatment of ophthalmic diseases. Two species Berberis lycium and Solanum dulcamara have multipurpose value. Former is used to treat stomach as well as diabetes while latter is used to treat not only to diabetes but also ophthalmic diseases. According to IUCN categories , out of these 12 plant species collected and marketed, Polygonum amplexicaule and Paeonia emodi are endangered, Aconitum heterophyllum; Berberis lycium species are vulnerable while Plantago lanceolata and Skimmia lareola species are rare.The availability of these medicinal plants has decreased during the past 20 years and these are facing a drastic biotic pressure due to their extensive usage and non-scientific methods of collection. It is quite evident that these valuable native medicinal plants species are going to decline in number and ultimately will become extinct if no timely proper conservation strategies are adopted.     

Disease-drug pairs revealed by computational genomic connectivity mapping on GBA1 deficient, Gaucher disease mice

We have reported that, in addition to recapitulating the classical human Gaucher disease (GD1) phenotype, deletion of the glucocerebrosidase (GBA1) gene in mice results in the dysfunction of a diverse population of immune cells. Most of immune-related, non-classical features of GD1, including gammopathies and autoimmune diathesis, are resistant to macrophage-directed therapies. This has prompted a search for newer agents for human GD1. Here, we used high-density microarray on splenic and liver cells from affected GBA1(-/-) mice to establish a gene "signature", which was then utilized to interrogate the Broad Institute database, CMAP. Computational connectivity mapping of disease and drug pairs through CMAP revealed several highly enriched, non-null, mimic and anti-mimic hits. Most notably, two compounds with anti-helminthic properties, namely albendazole and oxamniquine, were identified; these are particularly relevant for future testing as the expression of chitinases is enhanced in GD1.     

Length–weight,length–length relationships and feeding habits of wild Indus Mahseer,Tor macrolepis,from Attock,Pakistan

In this study the length–weight (LWR) and length–length relationships (LLR) were carried out for Indus Mahseer, Tor macrolepis, from the Haro River and Nalah Kala, Attock, Pakistan. A total of 118 specimens were used to estimate the relationship parameters. The results of LWR (W = a TL^b) from five different sites indicated W = 0.0044 TL^3.14, W = 0.0054 TL^3.08, W = 0.0059 TL^3.21, W = 0.0076 TL^3.12, and W = 0.0107 TL^2.99, respectively, with an overall value of W = 0.0100 TL^2.94. All regressions for LLR were highly significant (P ≤ 0.001), with coefficient of determination (r²) values of > 0.90. All relationships for LWR and LLR were found to be isometric. T. macrolepis is principally a herbivorous bottom feeder, mainly feeding on aquatic plants and algae, supplemented by insects.     

Analyzing the significance of defoliation in growth, photosynthetic compensation and source-sink relations

Leaf canopy plays a determining role influencing source-sink relations as any change in source activity (photosynthesis) affects sink metabolism. Defoliation (removal of leaves) influences growth and photosynthetic capacity of plants, remobilizes carbon and nitrogen reserves and accelerates sink metabolism, leading to improved source-sink relations. The response of plants to defoliation could be used to manipulate source-sink relations by removing lower and senescing leaves to obtain greatest photosynthetic capacity and efficient carbon and nitrogen metabolism under optimal and stressful environments. The present work enhances our current understanding on the physiological responses of plants to defoliation and elaborates how defoliation influences growth, photosynthetic capacity and source-sink relations under optimal and changing environmental conditions.     

Role of ethylene in alleviation of cadmium-induced photosynthetic capacity inhibition by sulphur in mustard

Sulphur (S) assimilation leads to the formation of glutathione (GSH) and alleviation of cadmium (Cd) stress. GSH is synthesized from its immediate metabolite cysteine, which also serves as a metabolite for ethylene formation through S‐adenosyl methionine. To assess the role of ethylene in S‐induced alleviation of Cd stress on photosynthesis, the effects of S or ethephon (ethylene source) on GSH and ethylene were examined in mustard (Brassica juncea L. cv. Varuna). Sufficient‐S at 100 mg S kg^?1 soil alleviated Cd‐induced photosynthetic inhibition more than excess‐S (200 mg S kg^?1 soil) via ethylene by increased GSH. Under Cd stress, plants were less sensitive to ethylene, despite high ethylene evolution, and showed photosynthetic inhibition. Ethylene sensitivity of plants increased with ethephon or sufficient‐S, triggering the induction of an antioxidant system, and leading to increased photosynthesis even under Cd stress. The effects of ethephon and S under Cd stress were similar. The effects of S were reversed by ethylene biosynthesis inhibitor, aminoethoxyvinylglycine (AVG), suggesting that ethylene plays an important role in S‐induced alleviation of Cd stress on photosynthesis.     

<Emphasis Type="Italic">O</Emphasis>-GlcNAc modification of the anti-malarial vaccine candidate <Emphasis Type="Italic">Pf</Emphasis>AMA1: <Emphasis Type="Italic">in silico</Emphasis>-defined structural changes and potential to generate a better vaccine

The complex life cycle of plasmodial parasites makes the selection of a single subunit protein a less than optimal strategy to generate an efficient vaccinal protection against malaria. Moreover, the full protection afforded by malarial proteins carried by intact parasites implies that immune responses against different antigens expressed in different phases of the cycle are required, but also suggests that native malarial antigens are presented to the host immune system in a manner that recombinant proteins do not achieve. The malarial apical membrane antigen 1 (AMA1) represents a suitable vaccine candidate because AMA1 is expressed on sporozoites and merozoites and allows them to invade hepatocytes and erythrocytes, respectively. Anti-AMA1 antibodies and cytotoxic T-cells are therefore expected to interfere both with the primary invasion of hepatocytes by sporozoites and with the later propagation of merozoites in erythrocytes, and thus efficiently counteract parasite development in its human host. AMA1 bears potential glycosylation sites and the human erythrocytic O-linked N-acetylglucosamine transferase (OGT) could glycosylate AMA1 through combinatorial metabolism. This hypothesis was tested in silico by developing binding models of AMA1 with human OGT complexed with UDP-GlcNc, and followed by the binding of O-GlcNAc with the hydroxyl group of AMA1 serine and threonine residues. Our results suggests that AMA1 shows potential for glycosylation at Thr517 and Ser498 and that O-GlcNAc AMA1 may constitute a conformationally more appropriate antigen for developing a protective anti-malarial immune response.     

A comparison of two different techniques for the detection of blood parasite, Theileria annulata, in cattle from two districts in Khyber Pukhtoon Khwa Province (Pakistan)

The present study was carried out to determine the prevalence of Theileria annulata in large ruminants from two districts, Peshawar and Kohat, in Khyber Pukhtoon Khwa (Pakistan). Blood samples were collected from 95 cattle. Data on the characteristics of animals and herds were collected through questionnaires. No significant risk factors were found associated with the spread of tropical theileriosis in the study area. Two different parasite detection techniques, PCR amplification and screening of Giemsa stained slides, were compared and it was found that PCR amplification is a more sensitive tool (33.7% parasite detection), as compared to smear scanning (5.2% parasite detection) for the detection of Theileria annulata. 32 out of 95 animals, from both districts, produced the 721-bp fragment specific for Theileria annulata.